BioMed Research International: Gastroenterology The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Proteobacteria: A Common Factor in Human Diseases Thu, 02 Nov 2017 00:00:00 +0000 Microbiota represents the entire microbial community present in the gut host. It serves several functions establishing a mutualistic relation with the host. Latest years have seen a burst in the number of studies focusing on this topic, in particular on intestinal diseases. In this scenario, Proteobacteria are one of the most abundant phyla, comprising several known human pathogens. This review highlights the latest findings on the role of Proteobacteria not only in intestinal but also in extraintestinal diseases. Indeed, an increasing amount of data identifies Proteobacteria as a possible microbial signature of disease. Several studies demonstrate an increased abundance of members belonging to this phylum in such conditions. Major evidences currently involve metabolic disorders and inflammatory bowel disease. However, more recent studies suggest a role also in lung diseases, such as asthma and chronic obstructive pulmonary disease, but evidences are still scant. Notably, all these conditions are sustained by various degree of inflammation, which thus represents a core aspect of Proteobacteria-related diseases. G. Rizzatti, L. R. Lopetuso, G. Gibiino, C. Binda, and A. Gasbarrini Copyright © 2017 G. Rizzatti et al. All rights reserved. Reduced Transferrin Levels in Active Inflammatory Bowel Disease Tue, 31 Oct 2017 12:05:57 +0000 Inflammatory bowel disease (IBD) is an inflammatory disease of unclear etiopathogenesis and challenging diagnosis, frequently complicated by anemia and malnutrition. C-reactive protein (CRP) remains the only biochemical marker of clinical relevance. The aim of this study was to test hypothesis that transferrin, coinfluenced by inflammation, malnutrition, anemia, and oxidative stress, may better reflect global IBD patient’s condition than any other more specific index. Transferrin and other indices of inflammation, anemia, malnutrition, and oxidative stress were measured in 137 IBD patients (Crohn’s disease (CD): and ulcerative colitis (UC): ) and 97 controls. Transferrin is reduced in active CD and UC and negatively correlates with the disease activity scores (CD: ; UC: ). In UC, transferrin correlates negatively with CRP, erythrocyte sedimentation rate (ESR), leukocytes, platelets, interleukin-6, interleukin-10, and TNF-α and positively with albumins, cholesterol, hemoglobin, hematocrit, erythrocytes, iron, and paraoxonase-1. In CD, transferrin correlates negatively with CRP, leukocytes, platelets, interleukin-1, and interleukin-6 and positively with albumins, iron, catalase, glutathione peroxidase-1, superoxide dismutase-1, and paraoxonase-1. The associations with inflammation and anemia/malnutrition were more pronounced in UC and with oxidative stress in CD. As UC activity marker, transferrin outperforms ESR and hemoglobin, indices used in calculating the disease clinical severity score. Malgorzata Matusiewicz, Katarzyna Neubauer, Paulina Lewandowska, Andrzej Gamian, and Malgorzata Krzystek-Korpacka Copyright © 2017 Malgorzata Matusiewicz et al. All rights reserved. Effect of Glycine, Pyruvate, and Resveratrol on the Regeneration Process of Postischemic Intestinal Mucosa Thu, 19 Oct 2017 00:00:00 +0000 Background. Intestinal ischemia is often caused by a malperfusion of the upper mesenteric artery. Since the intestinal mucosa is one of the most rapidly proliferating organs in human body, this tissue can partly regenerate itself after the onset of ischemia and reperfusion (I/R). Therefore, we investigated whether glycine, sodium pyruvate, and resveratrol can either support or potentially harm regeneration when applied therapeutically after reperfusion injury. Methods. I/R of the small intestine was initiated by occluding and reopening the upper mesenteric artery in rats. After 60 min of ischemia and 300 min of reperfusion, glycine, sodium pyruvate, or resveratrol was administered intravenously. Small intestine regeneration was analyzed regarding tissue damage, activity of saccharase, and Ki-67 positive cells. Additionally, systemic parameters and metabolic ones were obtained at selected periods. Results. Resveratrol failed in improving the outcome after I/R, while glycine showed a partial beneficial effect. Sodium pyruvate ameliorated metabolic acidosis, diminished histopathologic tissue injury, and increased cell proliferation in the small intestine. Conclusion. While glycine could improve in part regeneration but not proliferation, sodium pyruvate seems to be a possible therapeutic agent to facilitate proliferation and to support mucosal regeneration after I/R injury to the small intestine. Lisa Brencher, Frank Petrat, Katrin Stych, Tim Hamburger, and Michael Kirsch Copyright © 2017 Lisa Brencher et al. All rights reserved. Exclusive Enteral Nutrition Induces Remission in Pediatric Crohn’s Disease via Modulation of the Gut Microbiota Mon, 16 Oct 2017 00:00:00 +0000 Exclusive enteral nutrition (EEN) has been proven to be effective and safe in treating pediatric Crohn’s disease (CD). EEN induces pediatric CD remission possibly through three pathways: (1) direct anti-inflammatory effects, (2) improved epithelial barrier function, and (3) modulation of the gut microbiota. Recent studies have demonstrated that modulation of the gut microbiota plays a major role in EEN-induced remission. Variations of microbial components, which directly influence the diversity and metabolic functions of the gut microbiota, are closely associated with the immunological conditions of the gut and the susceptibility to diseases. The reduction of proinflammatory microbial components and harmful microbial metabolites after EEN treatment greatly decreases the inflammatory injuries of the gut. Dawei Gong, Xinjuan Yu, Lili Wang, Lingling Kong, Xiaojie Gong, and Quanjiang Dong Copyright © 2017 Dawei Gong et al. All rights reserved. Gastrointestinal Motility, Mucosal Mast Cell, and Intestinal Histology in Rats: Effect of Prednisone Tue, 19 Sep 2017 08:38:12 +0000 Our aim was to verify the effects of prednisone related to gastrointestinal motility, intestinal histology, and mucosal mast cells in rats. Two-month-old male Wistar rats were randomly assigned to control group (vehicle) animals receiving saline 0.9% () or treated orally with 0.625 mg/kg/day of prednisone () or 2.5 mg/kg/day of prednisone () during 15 days. Mast cells and other histologic analyses were performed in order to correlate to gastric emptying, cecum arrival, and small intestine transit evaluated by Alternating Current Biosusceptometry. Results showed that prednisone in adult rats increased the frequency of gastric contractions, hastened gastric emptying, slowed small intestinal transit, and reduced mucosal mast cells. Histologically, the treatment with both doses of prednisone decreased villus height, whereas longitudinal and circular muscles and crypt depth were not affected. These findings indicate an impairment of intestinal absorption which may be linked to several GI dysfunctions and symptoms. The relationship between gastrointestinal motor disorders and cellular immunity needs to be clarified in experimental studies since prednisone is one of the most prescribed glucocorticoids worldwide. Maysa Bruno de Lima, Loyane Almeida Gama, Andrieli Taise Hauschildt, Denize Jussara Rupolo Dall’Agnol, Luciana Aparecida Corá, and Madileine Francely Americo Copyright © 2017 Maysa Bruno de Lima et al. All rights reserved. Colonic Transit Time and Gut Peptides in Adult Patients with Slow and Normal Colonic Transit Constipation Thu, 07 Sep 2017 07:56:53 +0000 Purpose. To investigate whether pathophysiological differences exist among healthy controls (HC) and patients with slow and normal transit constipation (STC and NTC), we evaluated () gastrointestinal (GI) symptoms using validated questionnaires; () circulating concentrations of neurotensin, motilin, corticotrophin-releasing factor (CRF), and somatostatin; and () possible differences in frequency distribution of the neurotensin rs1800832 A/G and Neurotensin Receptor 1 rs6090453 C/G SNPs. Methods. Fifty-one patients with severe functional constipation and 20 HC completed the study. Symptoms were evaluated by GSRS and Constipaq scoring system. Plasma concentrations of GI peptides were evaluated by ELISA on fasting and six sequential blood samples after a standard meal. Genotyping was performed by PCR and endonuclease digestion. Results. Symptom profiles largely overlapped between NTC and STC patients. As for peptide profiles, neurotensin showed lower concentrations at 60 and 90 min in STC versus HC, and motilin showed throughout the curve 85% and 82% lower levels in STC than HC and NTC, respectively. Finally, neurotensin polymorphism resulted in being associated with the peptide levels. Conclusions. Symptom profile is not a reliable tool to discriminate STC, whilst the GI peptide profiles might help in identifying it. Giuseppe Riezzo, Guglielmina Chimienti, Caterina Clemente, Benedetta D’Attoma, Antonella Orlando, Caterina Mammone Rinaldi, and Francesco Russo Copyright © 2017 Giuseppe Riezzo et al. All rights reserved. Comparative Evaluation between Sulfasalazine Alone and in Combination with Herbal Medicine on DSS-Induced Ulcerative Colitis Mice Wed, 06 Sep 2017 08:21:47 +0000 The present study aimed to investigate the comparative evaluation of pharmacological efficacy between sulfasalazine alone and sulfasalazine in combination with herbal medicine on dextran sodium sulfate- (DSS-) induced UC in mice. Balb/c mice received 5% DSS in drinking water for 7 days to induce colitis. Animals were divided into five groups (): Group I (normal group), Group II (DSS control group), Group III (DSS + sulfasalazine (30 mg/kg)), Group IV (DSS + sulfasalazine (60 mg/kg)), and Group V (DSS + sulfasalazine (30 mg/kg) Cinnamomi Cortex and Bupleuri Radix mixture (30 mg/kg) (SCB)). Colonic pathological changes were analyzed using hematoxyline/eosin staining. The antioxidant, inflammatory, and apoptotic protein levels were determined using western blotting. SCB supplementation, as well as sulfasalazine, suppressed colonic length and mucosal inflammatory infiltration. In addition, SCB treatment significantly reduced the expression of proinflammatory signaling molecules through suppression of both mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-B) signaling pathways and prevented the apoptosis of the colon. Moreover, SCB administration significantly led to the upregulation of antioxidant enzymes including SOD and catalase. Taken together, SCB treatment might offer a better treatment for human UC than sulfasalazine alone or may be useful as an alternative therapeutic strategy against UC, without any evidence of side effects. Mi-Rae Shin, Kyeong Jo Kim, Soo Hyun Kim, Su Ji Kim, Bu-Il Seo, Hyo-Jin An, and Seong-Soo Roh Copyright © 2017 Mi-Rae Shin et al. All rights reserved. High-Density Lipoprotein Cholesterol, Blood Urea Nitrogen, and Serum Creatinine Can Predict Severe Acute Pancreatitis Tue, 22 Aug 2017 00:00:00 +0000 Background and Aims. Early prediction of disease severity of acute pancreatitis (AP) would be helpful for triaging patients to the appropriate level of care and intervention. The aim of the study was to develop a model able to predict Severe Acute Pancreatitis (SAP). Methods. A total of 647 patients with AP were enrolled. The demographic data, hematocrit, High-Density Lipoprotein Cholesterol (HDL-C) determinant at time of admission, Blood Urea Nitrogen (BUN), and serum creatinine (Scr) determinant at time of admission and 24 hrs after hospitalization were collected and analyzed statistically. Results. Multivariate logistic regression indicated that HDL-C at admission and BUN and Scr at 24 hours (hrs) were independently associated with SAP. A logistic regression function (LR model) was developed to predict SAP as follows: −2.25–0.06 HDL-C (mg/dl) at admission + 0.06 BUN (mg/dl) at 24 hours + 0.66 Scr (mg/dl) at 24 hours. The optimism-corrected c-index for LR model was 0.832 after bootstrap validation. The area under the receiver operating characteristic curve for LR model for the prediction of SAP was 0.84. Conclusions. The LR model consists of HDL-C at admission and BUN and Scr at 24 hours, representing an additional tool to stratify patients at risk of SAP. Wandong Hong, Suhan Lin, Maddalena Zippi, Wujun Geng, Simon Stock, Vincent Zimmer, Chunfang Xu, and Mengtao Zhou Copyright © 2017 Wandong Hong et al. All rights reserved. New Frontiers in Genetics, Gut Microbiota, and Immunity: A Rosetta Stone for the Pathogenesis of Inflammatory Bowel Disease Wed, 02 Aug 2017 09:42:17 +0000 Inflammatory bowel disease (IBD), which encompasses ulcerative colitis (UC) and Crohn’s disease (CD), is a complicated, uncontrolled, and multifactorial disorder characterized by chronic, relapsing, or progressive inflammatory conditions that may involve the entire gastrointestinal tract. The protracted nature has imposed enormous economic burdens on patients with IBD, and the treatment is far from optimal due to the currently limited comprehension of IBD pathogenesis. In spite of the exact etiology still remaining an enigma, four identified components, including personal genetic susceptibility, external environment, internal gut microbiota, and the host immune response, are responsible for IBD pathogenesis, and compelling evidence has suggested that IBD may be triggered by aberrant and continuing immune responses to gut microbiota in genetically susceptibility individuals. The past decade has witnessed the flourishing of research on genetics, gut microbiota, and immunity in patients with IBD. Therefore, in this review, we will comprehensively exhibit a series of novel findings and update the major advances regarding these three fields. Undoubtedly, these novel findings have opened a new horizon and shed bright light on the causality research of IBD. Mingxia Zhou, Jing He, Yujie Shen, Cong Zhang, Jiazheng Wang, and Yingwei Chen Copyright © 2017 Mingxia Zhou et al. All rights reserved. Sustainability of Endovenous Iron Deficiency Anaemia Treatment: Hospital-Based Health Technology Assessment in IBD Patients Thu, 06 Jul 2017 05:56:16 +0000 Iron deficiency anaemia (IDA) is the main extraintestinal manifestation affecting patients with inflammatory bowel disease (IBD). The Health Technology Assessment approach was applied to evaluate the sustainability of intravenous (IV) iron formulations in the Italian hospital setting, with particular focus on ferric carboxymaltose. Data on the epidemiology of IBD and associated IDA, in addition to the efficacy and safety of IV iron formulations currently used in Italy, were retrieved from scientific literature. A hospital-based cost-analysis of the outpatient delivery of IV iron treatments was performed. Organizational and ethical implications were discussed. IDA prevalence in IBD patients varies markedly from 9 to 73%. IV iron preparations were proven to have good efficacy and safety profiles, and ferric carboxymaltose provided a fast correction of haemoglobin and serum ferritin levels in iron-deficient patients. Despite a higher price, ferric carboxymaltose would confer a beneficial effect to the hospital, in terms of reduced cost related to individual patient management and additionally to the patient by reducing the number of infusions and admissions to healthcare facilities. Ethically, the evaluation is appropriate due to its efficacy and compliance. This assessment supports the introduction of ferric carboxymaltose in the Italian outpatient setting. A. Poscia, J. Stojanovic, F. Kheiraoui, E. M. Proli, F. Scaldaferri, M. Volpe, M. L. Di Pietro, A. Gasbarrini, L. Fabrizio, S. Boccia, and C. Favaretti Copyright © 2017 A. Poscia et al. All rights reserved. A Measure of Suffering in relation to Anxiety and Quality of Life in IBS Patients: Preliminary Results Tue, 04 Jul 2017 06:39:44 +0000 Irritable bowel syndrome (IBS) is a chronic gastrointestinal (GI) disorder with a severe impact on quality of life (QoL). We explored the relationship of a visual measure of suffering, the PRISM-RII, with quality of life (QoL) and anxiety measures in IBS patients. Participants were 44 IBS patients who completed several questionnaires and kept a symptom diary for two weeks. The measures used were PRISM-RII (self-illness separation (SIS); illness perception measure (IPM)); IBS-36 (IBS health related QoL); SF-36 (physical and mental health related QoL); State-Trait Anxiety Inventory (STAI-T); Visceral Sensitivity Index (VSI; GI-specific anxiety); and a symptom diary. SIS was negatively correlated to VSI, while IPM was negatively correlated to SIS and the physical component of SF-36 and positively to VSI and symptom severity. We found significant differences between participants who perceive their illness as small and those who perceive it as medium in SIS, symptom severity, VSI, and the mental component of SF-36. Participants, who perceived their illness as small, represented their illness as more distant, showed lower average symptom severity, and had lower GI-specific anxiety and higher QoL. The results indicate that IPM and SIS can be useful in discriminating patients with more prominent psychological difficulties and QoL impairment. Sanda Pletikosić Tončić and Mladenka Tkalčić Copyright © 2017 Sanda Pletikosić Tončić and Mladenka Tkalčić. All rights reserved. Corrigendum to “Safety and Efficacy of Small Bowel Examination by Capsule Endoscopy for Patients before Liver Transplantation” Mon, 03 Jul 2017 07:05:17 +0000 Seiji Kawano, Akinobu Takaki, Masaya Iwamuro, Tetsuya Yasunaka, Yoshiyasu Kono, Kou Miura, Toshihiro Inokuchi, Yoshiro Kawahara, Yuzo Umeda, Takahito Yagi, and Hiroyuki Okada Copyright © 2017 Seiji Kawano et al. All rights reserved. Downregulation of miR-214-3p May Contribute to Pathogenesis of Ulcerative Colitis via Targeting STAT6 Sun, 02 Jul 2017 07:46:43 +0000 MicroRNAs (miRs) are small noncoding RNA molecules and recently have demonstrated that altered expression and functions are their tight association with ulcerative colitis (UC). Previous microarray study reported that miR-214 was downregulated in the sigmoid colon of patients with active UC, but the roles of miR-214 in the pathogenesis of UC remain to be elucidated. In this study, significant lower level of miR-214-3p and higher level of STAT6 in the intestinal mucosa of active UC patients compared with the health controls were confirmed by quantitative real-time PCR. Results of luciferase reporter assays and western blot demonstrated that miR-214-3p directly targets STAT6 and negatively regulates the expression of STAT6 at the posttranscriptional level. Furthermore, the expression of miR-214-3p was decreased in TNF-α treated HT29 cells and STAT6 protein level was increased in a time-dependent manner. Silenced STAT6 and upregulation of miR-214-3p could decrease the level of INF-γ in TNF-α treated HT29 cells. Additionally, the results of the present study indicate that miR-214-3p and STAT6 axis may be a novel therapeutic target for intestinal inflammation of patients with active UC. Jin-an Li, Yong-duo Wang, Kui Wang, Zhen-lan Wang, Dao-yong Jia, Bi-ying Yang, and Chang-bing Xiong Copyright © 2017 Jin-an Li et al. All rights reserved. The Effects of Melatonin on Elevated Liver Enzymes during Statin Treatment Mon, 29 May 2017 00:00:00 +0000 Taking statins can cause increase in the level of aspartate and alanine aminotransferase. The aim of this study was to assess the usefulness of melatonin in counteracting the adverse hepatic events from statins. Methods. The research program included 60 patients (aged 47–65 years, 41 women and 19 men) with hyperlipidemia taking atorvastatin or rosuvastatin at a dose of 20–40 mg daily. The patients were randomly allocated in two groups. Group I () was recommended to take the same statin at a standardized daily dose of 20 mg together with melatonin at a dose of  mg. Group II () patients took statin with placebo at the same dose and time of the day. Follow-up laboratory tests (AST, ALT, GGT, and ALP) were evaluated after 2, 4, and 6 months of treatment. Results. In Group I the levels of all enzymes decreased after 6 months, particularly AST,  U/L versus  U/L (); ALT,  U/L versus  U/L (); and GGT,  U/L versus 59,6 U/L (). Conclusion. Melatonin exerts a hepatoprotective effect in patients taking statins. Cezary Chojnacki, Aleksandra Błońska, and Jan Chojnacki Copyright © 2017 Cezary Chojnacki et al. All rights reserved. Appendectomy as a Risk Factor for Bacteremic Biliary Tract Infection Caused by Antibiotic-Resistant Pathogens Mon, 15 May 2017 07:54:27 +0000 Background/Aims. Recent evidence has suggested that appendix plays a pivotal role in the development and preservation of intestinal immune system. The aim of this study is to examine whether prior appendectomy is associated with an increased risk for the development of antibiotic-resistant bacteria in bacteremia from biliary tract infection (BTI). Methods. Charts from 174 consecutive cases of bacteremia derived from BTI were retrospectively reviewed. Using multivariate analysis, independent risk factors for development of antibiotic-resistant bacteria were identified among the clinical parameters, including a history of appendectomy. Results. In total, 221 bacteria strains were identified from 174 BTI events. Of those, 42 antibiotic-resistant bacteria were identified in 34 patients. Multivariate analysis revealed that prior appendectomy (Odds ratio (OR), 3.02; 95% confidence interval (CI), 1.15–7.87; ), antibiotic use within the preceding three months (OR, 3.06; 95% CI, 1.26–7.64; ), and bilioenteric anastomosis or sphincterotomy (OR, 3.77; 95% CI, 1.51–9.66; ) were independent risk factors for antibiotic-resistant bacteria. Conclusions. Prior appendectomy was an independent risk factor for the development of antibiotic-resistant bacteria in bacteremia from BTI. Koki Kawanishi, Jun Kinoshita, Hiroko Abe, Tetsuhiro Kakimoto, Yuko Yasuda, Takeshi Hara, and Jun Kato Copyright © 2017 Koki Kawanishi et al. All rights reserved. Colorectal Cancer: From the Genetic Model to Posttranscriptional Regulation by Noncoding RNAs Wed, 10 May 2017 08:23:07 +0000 Colorectal cancer is the third most common form of cancer in developed countries and, despite the improvements achieved in its treatment options, remains as one of the main causes of cancer-related death. In this review, we first focus on colorectal carcinogenesis and on the genetic and epigenetic alterations involved. In addition, noncoding RNAs have been shown to be important regulators of gene expression. We present a general overview of what is known about these molecules and their role and dysregulation in cancer, with a special focus on the biogenesis, characteristics, and function of microRNAs. These molecules are important regulators of carcinogenesis, progression, invasion, angiogenesis, and metastases in cancer, including colorectal cancer. For this reason, miRNAs can be used as potential biomarkers for diagnosis, prognosis, and efficacy of chemotherapeutic treatments, or even as therapeutic agents, or as targets by themselves. Thus, this review highlights the importance of miRNAs in the development, progression, diagnosis, and therapy of colorectal cancer and summarizes current therapeutic approaches for the treatment of colorectal cancer. María Antonia Lizarbe, Jorge Calle-Espinosa, Eva Fernández-Lizarbe, Sara Fernández-Lizarbe, Miguel Ángel Robles, Nieves Olmo, and Javier Turnay Copyright © 2017 María Antonia Lizarbe et al. All rights reserved. Weekday of Surgery Affects Postoperative Complications and Long-Term Survival of Chinese Gastric Cancer Patients after Curative Gastrectomy Tue, 18 Apr 2017 06:45:49 +0000 Many factors have been reported to affect the long-term survival of gastric carcinoma patients after gastrectomy; the present study took the first attempt to find out the potential role of weekday carried out surgery in the postoperative prognosis of gastric cancer patients. 463 gastric cancer patients have been followed up successfully. Pearson test was used for univariate analyses. Survival curves were constructed by using Kaplan-Meier method and evaluated by using the log-rank test. The Cox proportional hazard regression model was used to find out the risk factors, and subgroup analysis was conducted to rule out confounding factors. We found that the patients who underwent gastrectomy on the later weekday (Wednesday–Friday) more easily suffered from a higher postoperative morbidity. Weekday of surgery was one of the independent indicators for the prognosis of patients after gastric cancer surgery. However, the role of weekday of surgery was significantly weakened in the complications group. In conclusion, surgery performed in the later weekday was more likely to lead to increased postoperative complications and an unfavorable role in prognosis of Chinese gastric cancer patients after curative gastrectomy. Rong Li, Ai-min Leng, Ting Liu, Yan-wu Zhou, Jun-xian Zeng, Xiao-ming Liu, Ting-zi Hu, Xiao-xia Jiang, Lin-fang Zhang, and Can-xia Xu Copyright © 2017 Rong Li et al. All rights reserved. Negative Correlation between miR-200c and Decorin Plays an Important Role in the Pathogenesis of Colorectal Carcinoma Sun, 16 Apr 2017 07:44:41 +0000 Aim. To demonstrate the regulatory role of miRNA in colorectal carcinoma (CRC) and reveal the transcript markers that may be associated with CRC clinical outcomes. Method. Herein, we analyzed both mRNA and miRNA gene expression profiles of 255 CRC tumor samples from The Cancer Genome Atlas project to reveal the regulatory association between miRNA and mRNA. Also, the potential role of gene coexpression network in CRC has been explored. Results. The negative correlation between miR-200c and DCN (Decorin) was calculated in CRC, indicating that DCN could be a potential target of miR-200c. Clinical features indicated that colon polyp history and overall survival were significantly related to the expression level of miR-200c. Three coexpression networks have been constructed, and genes involved in the networks are related to cell cycle, NOTCH, and mTOR signaling pathways. Conclusion. Our result provides a new insight into cancer related mRNA coexpression network in CRC research. Ren-Yi Tang, Zun Wang, Hong-Qi Chen, and Si-Bo Zhu Copyright © 2017 Ren-Yi Tang et al. All rights reserved. Corrigendum to “Quantitative Evaluation and Selection of Reference Genes for Quantitative RT-PCR in Mouse Acute Pancreatitis” Thu, 13 Apr 2017 00:00:00 +0000 Zhaoping Yan, Jinhang Gao, Xiuhe Lv, Wenjuan Yang, Shilei Wen, Huan Tong, and Chengwei Tang Copyright © 2017 Zhaoping Yan et al. All rights reserved. Meta-Analysis of the Relationship between NM23 Expression to Gastric Cancer Risk and Clinical Features Thu, 16 Mar 2017 00:00:00 +0000 The prognostic value of reduced NM23 expression for gastric cancer (GC) patients is still contradictory. Thus, we conducted a meta-analysis to quantitatively evaluate the association of NM23 expression with GC risk and clinical features by analyzing 27 publications. The result of our meta-analysis indicated that NM23 expression is markedly reduced in gastric cancer tissues (OR = 3.15; 95% CI = 1.97–5.03; ). Furthermore, NM23 expression was negatively correlated with N stage, TNM stage, and histological grade. However, NM23 expression was not correlated with T stage, lymphatic invasion, vascular invasion, and 5-year overall survival rate. In conclusion, reduced NM23 expression correlated with gastric cancer risk, but its association with GC clinical features remains inconclusive. Therefore, large-scale and well-designed studies, which use uniform antibody and criterion of NM23 positive expression, are required to further validate the role of the NM23 in predicting GC progression. Min Fang, Yifeng Tao, Zhimin Liu, Hao Huang, Min Lao, Lingsha Huang, and Bo Zhu Copyright © 2017 Min Fang et al. All rights reserved. Banhasasim-Tang Treatment Reduces the Severity of Esophageal Mucosal Ulcer on Chronic Acid Reflux Esophagitis in Rats Thu, 02 Mar 2017 06:52:04 +0000 The present study was conducted to evaluate both antioxidant and anti-inflammatory activity of Banhasasim-tang (BHSST) on chronic acid reflux esophagitis (CRE) model. Rat CRE model was established operatively and then treated with BHSST (1 g/kg body weight per day) for 15 days Esophageal pathological changes were analyzed using macroscopic examination and hematoxylin/eosin staining. The antioxidant and inflammatory protein levels were determined using Western blotting. The administration of BHSST significantly reduced both the overexpression of serum reactive oxygen species (ROS) and an excessive formation of thiobarbituric acid-reactive substances (TBARS) in esophagus tissue. Thus, the severity of esophageal ulcer was lower in BHSST treated rats than control rats on the gross and histological evaluation. Nuclear factor-erythroid 2-related factor 2 (Nrf2) led to the upregulation of antioxidant enzyme including SOD, GPx-1/2, and HO-1 by binding to antioxidant response element (ARE). Moreover, BHSST administration markedly reduced the expression of inflammatory proteins through mitogen-activated protein kinase- (MAPK-) related signaling pathways and decreased significantly the protein expressions of inflammatory mediators and cytokines by inhibition of nuclear factor-kappa B (NF-κB) activation. Taken together, these results support the fact that BHSST administration can suppress the development of esophageal mucosal ulcer via regulating inflammation through the activation of the antioxidant pathway. Mi-Rae Shin, Bu-Il Seo, Chang Gue Son, Seong-Soo Roh, and Hyo-Jin An Copyright © 2017 Mi-Rae Shin et al. All rights reserved. Lack of Clinical Relevance of ANA and ASMA Positivity in Patients with Liver Transplantation without a History of Autoimmune Diseases Mon, 27 Feb 2017 12:02:28 +0000 The relevance of isolated autoimmunity elevation in orthotopic liver transplantation (OLT) patients is unknown. Our aim was to analyse how serum autoantibodies change in time and to evaluate their clinical relevance in OLT patients. Patients were invited to provide samples to evaluate ANA, AMA, ASMA, and LKM at the time of enrolment (0), after 6 months (6), and after 12 months (12). We included 114 patients in the study (76% males, median age 62.5 years), finding isolated elevation of at least one serum antibody in up to 80% of them. We described fluctuating positive autoantibodies in the one year of observation, with only 45.6% of patients positive for ANA and less than 2% positive for ASMA, at all three times. Isolated elevation of tissue antibodies was not related to gender, age, HCC at transplant, early rejection, cause of transplantation, immunotherapy taken, and age at the time of the study. We did not detect a higher prevalence of positive autoimmunity in patients with signs of liver injury. ANA and ASMA evaluation in patients with liver transplantation and no history of autoimmune disease has no clinical relevance, since it varies in time and is not related to any risk factors or liver injury. Routine autoimmunity evaluation should be avoided. Lucienne Pellegrini, Gianpaolo Parrilli, Antonella Santonicola, Luigi Cinquanta, Cesare Caputo, Carolina Ciacci, and Fabiana Zingone Copyright © 2017 Lucienne Pellegrini et al. All rights reserved. Exploring the Potential of Anticipated Regret as an Emotional Cue to Improve Bowel Cancer Screening Uptake Thu, 02 Feb 2017 07:55:06 +0000 Objective. Bowel cancer is currently the second leading cause of cancer-related death in Australia and screening participation is suboptimal. This study examined the role of emotion in the form of anticipated regret (AR) and its relationship to screening intentions. Methods. persons aged 45 to 80 years completed a survey measuring demographic variables, readiness to screen, relative importance of health by comparison to other life priorities, satisfaction with current health, and AR if not participating in future bowel cancer screening. Results. AR was a significant predictor of future screening intentions. Those with higher levels of AR were seven times more likely (OR = 7.18) to intend to screen in the future compared to those with lower AR. This relationship was not compromised when controlling for other variables including gender and satisfaction with one’s health. AR levels were significantly lower in people who had been screened previously and in those with full health insurance. Conclusions. These results demonstrate that AR is uniquely related to future bowel cancer screening intentions. Future studies should continue to consider this as a useful target for behavioural interventions and identify new ways of delivering these interventions to improve their reach. Ian T. Zajac, Amy Duncan, Suzana Freegard, Carlene Wilson, Ingrid Flight, and Deborah Turnbull Copyright © 2017 Ian T. Zajac et al. All rights reserved. Increased Expression of Toll-Like Receptors 4, 5, and 9 in Small Bowel Mucosa from Patients with Irritable Bowel Syndrome Sun, 29 Jan 2017 00:00:00 +0000 The aim of our study was to compare patients with irritable bowel syndrome (IBS) and healthy controls regarding the expression of toll-like receptors 2, 4, 5, and 9 (TLR2, TLR4, TLR5, and TLR9), the primary mucosal receptors of bacterial components, in small and large bowel mucosa. Methods. We analysed biopsies from jejunum and sigmoid colon of 22 patients (17 females) with IBS aged 18–66 (median: 39) years and 14 healthy volunteers (12 females) aged 22–61 (median: 42) years. Eight patients had constipation-predominant IBS (C-IBS), 7 had diarrhoea-predominant IBS (D-IBS), and 7 had IBS without predominance of constipation or diarrhoea. We analysed mRNA levels for TLRs using quantitative PCR and distribution of TLRs in mucosa using immunohistochemistry. Results. We found increased mRNA expression of TLR4 (mean fold change versus ; ), TLR5 ( versus ; ) and TLR9 ( versus ; ) but not of TLR2 in the small bowel mucosa from patients with IBS compared to the controls. There was no significant difference in mRNA levels for TLRs in colon mucosa between patients and controls. Conclusion. Upregulation of TLR4, TLR5, and TLR9 suggests the involvement of bacteria or dysregulation of the immune response to commensal flora in small bowel mucosa in IBS patients. Aldona Dlugosz, Katherina Zakikhany, Nathalie Acevedo, Mauro D’Amato, and Greger Lindberg Copyright © 2017 Aldona Dlugosz et al. All rights reserved. The Interaction between GSTT1, GSTM1, and GSTP1 Ile105Val Gene Polymorphisms and Environmental Risk Factors in Premalignant Gastric Lesions Risk Sun, 15 Jan 2017 13:00:01 +0000 The study investigated the possible influence of GSTM1, GSTT1, and GSTP1 gene polymorphisms as predisposing factors for premalignant gastric lesions as well as their interaction with H. pylori infection, gastrotoxic drugs, smoking, and alcohol consumption. In this study, 270 patients with a complet set of gastric biopsies and successfully genotyped were finally included. The GSTM1 gene polymorphism had significant contribution in mild/severe endoscopic lesions () as well as in premalignant lesions (). The GSTM1 null genotype increased the risk for mucosal defects in H. pylori-negative patients (OR = 2.27, 95% CI: 1.20–4.37) and the risk for premalignant lesions in patients with no alcohol consumption (OR = 2.13, 95% CI: 1.19–3.83). The GSTT1 deleted polymorphism did not significantly increase the risk for premalignant lesions in the absence of gastrotoxic drugs (OR = 1.82, 95% CI: 0.72–4.74). The combined GSTT1T1 and GSTM1 null polymorphisms were borderline correlated with an increased risk for premalignant lesions (OR = 1.72, 95% CI: 1.00–2.97). The wild-type GSTP1 Ile/Ile genotype versus the variant genotypes Ile/Val + Val/Val was significantly associated with a decreased risk of gastric atrophy/intestinal metaplasia (OR = 0.60, 95% CI: 0.37–0.98). In conclusion, the GSTM1 and GSTT1 null genotypes increased the risk for premalignant and endoscopic gastric lesions, modulated by H. pylori, alcohol, or gastrotoxic drug consumption, while the presence of the GSTP1Val allele seemed to reduce the risk for premalignant lesions. Anca Negovan, Mihaela Iancu, Valeriu Moldovan, Simona Mocan, and Claudia Banescu Copyright © 2017 Anca Negovan et al. All rights reserved. Safety and Efficacy of Small Bowel Examination by Capsule Endoscopy for Patients before Liver Transplantation Wed, 11 Jan 2017 08:44:30 +0000 Background and Aims. Gastrointestinal surveillance is a requirement prior to liver transplantation (LT), but small intestine examination is not generally undertaken. The aim of the present study was to evaluate the safety and efficacy of capsule endoscopy (CE) for patients with end-stage liver disease. Methods. 31 patients who needed LT were enrolled, and 139 patients who underwent CE over the same period of time acted as controls. Results. Frequency of successful achievement of evaluation of the full length of the small bowel, the mean gastric transit time, and the mean small bowel transit time were not significantly different between the two groups. Abnormalities in the small bowel were found in 26 patients. Comparative analysis revealed that history of EV rupture, history of EV treatment, red color sign of EV, and presence of PHG or HCC were significantly associated with patients with >2 two such findings (high score group). Conclusions. Small bowel examination by CE in patients before liver transplantation could be performed safely and is justified by the high rate of abnormal lesions detected particularly in patients with history of EV therapy or bleeding, red color sign, and presence of PHG or HCC. This study was registered in the UMIN Clinical Trial Registry (UMIN 000008672). Kawano Seiji, Takaki Akinobu, Iwamuro Masaya, Yasunaka Tetsuya, Kono Yoshiyasu, Miura Kou, Inokuchi Toshihiro, Kawahara Yoshiro, Umeda Yuzo, Yagi Takahito, and Okada Hiroyuki Copyright © 2017 Kawano Seiji et al. All rights reserved. Metastatic Crohn’s Disease: An Approach to an Uncommon but Important Cutaneous Disorder Tue, 03 Jan 2017 08:26:47 +0000 Objective. To provide physicians with a clinical approach to metastatic Crohn’s disease (MCD). Main Message. Metastatic Crohn’s disease, defined as skin lesions present in areas noncontiguous with the gastrointestinal tract, is the rarest cutaneous manifestation of Crohn’s disease. MCD lesions vary in morphology and can arise anywhere on the skin. MCD presents equally in both sexes and across age groups. Cutaneous findings may precede, develop concurrently with, or follow gastrointestinal involvement. A detailed history and thorough physical examination including a full-skin exam may help to exclude other dermatoses, as MCD can mimic other common disorders. A biopsy is required for a definitive diagnosis. Treatment options for MCD remain underwhelming due to the lack of randomized control studies and varying responses of reported therapeutic methods. Topical, intralesional, and systemic corticosteroids, antibiotics, traditional immunosuppressants, and surgery have shown mixed results. Recently, biologics have shown promise, even with refractory cases of MCD. Conclusion. MCD is an important cutaneous manifestation of this inflammatory disorder. Although a rare entity, early recognition can provide opportunity for successful therapeutic intervention. Babak Aberumand, Jessica Howard, and John Howard Copyright © 2017 Babak Aberumand et al. All rights reserved. Aspirin Protects against Acinar Cells Necrosis in Severe Acute Pancreatitis in Mice Thu, 29 Dec 2016 09:22:30 +0000 Aspirin has a clear anti-inflammatory effect and is used as an anti-inflammatory agent for both acute and long-term inflammation. Previous study has indicated that aspirin alleviated acute pancreatitis induced by caerulein in rat. However, the role of aspirin on severe acute pancreatitis (SAP) and the necrosis of pancreatic acinar cell are not yet clear. The aim of this study was to determine the effects of aspirin treatment on a SAP model induced by caerulein combined with Lipopolysaccharide. We found that aspirin reduced serum amylase and lipase levels, decreased the MPO activity, and alleviated the histopathological manifestations of pancreas and pancreatitis-associated lung injury. Proinflammatory cytokines were decreased and the expression of NF-κB p65 in acinar cell nuclei was suppressed after aspirin treatment. Furthermore, aspirin induced the apoptosis of acinar cells by TUNEL assay, and the expression of Bax and caspase 3 was increased and the expression of Bcl-2 was decreased. Intriguingly, the downregulation of critical necrosis associated proteins RIP1, RIP3, and p-MLKL was observed; what is more, we additionally found that aspirin reduced the COX level of pancreatic tissue. In conclusion, our data showed that aspirin could protect pancreatic acinar cell against necrosis and reduce the severity of SAP. Clinically, aspirin may potentially be a therapeutic intervention for SAP. Guotao Lu, Zhihui Tong, Yanbing Ding, Jinjiao Liu, Yiyuan Pan, Lin Gao, Jianfeng Tu, Yuhui Wang, George Liu, and Weiqin Li Copyright © 2016 Guotao Lu et al. All rights reserved. Prognostic Factors and Clinical Characteristics of Patients with Primary Duodenal Adenocarcinoma: A Single-Center Experience from China Tue, 27 Dec 2016 14:22:33 +0000 Aim. To evaluate the clinical risk factors influencing overall survival of patients with duodenal adenocarcinoma after potentially curative resection. Methods. A series of 201 patients with primary duodenal adenocarcinoma who underwent surgery from 1999 to 2014 at Chinese Medical Academic Cancer Hospital were studied by retrospective chart review and subsequent telephone follow-up. Results. Resectional surgery was performed in 138 of the 201 patients to attempt curative treatment, while 63 patients were treated with palliative surgery. Median survival of patients who underwent resectional operation was 57 months, whereas that of patients who had palliative surgery was shorter, 7 months (). For patients who underwent radical resection, the overall 1-, 3-, and 5-year survival rates were 87.3, 59.1, and 44.1%, respectively. Multivariate Cox regression analysis revealed that lymph node metastasis (HR 31.76, 2.14 to 470.8; ) and vascular invasion (HR 3.75, 1.24 to 11.38; ) were independent prognostic factors negatively associated with survival in patients undergoing curative resection. There was no survival difference between the groups treated by the pancreaticoduodenectomy () and limited resection () for early-stage duodenal adenocarcinoma (). Conclusions. Duodenal adenocarcinoma is a rare disease. Curative resection is the best treatment for appropriate patients. Lymph node metastases and vascular invasion are negative prognostic factors. Qing-Long Jiang, Xiang-Hui Huang, Ying-Tai Chen, Jian-Wei Zhang, and Cheng-Feng Wang Copyright © 2016 Qing-Long Jiang et al. All rights reserved. Comparative Genomics of H. pylori and Non-Pylori Helicobacter Species to Identify New Regions Associated with Its Pathogenicity and Adaptability Sun, 18 Dec 2016 13:55:32 +0000 The genus Helicobacter is a group of Gram-negative, helical-shaped pathogens consisting of at least 36 bacterial species. Helicobacter pylori (H. pylori), infecting more than 50% of the human population, is considered as the major cause of gastritis, peptic ulcer, and gastric cancer. However, the genetic underpinnings of H. pylori that are responsible for its large scale epidemic and gastrointestinal environment adaption within human beings remain unclear. Core-pan genome analysis was performed among 75 representative H. pylori and 24 non-pylori Helicobacter genomes. There were 1173 conserved protein families of H. pylori and 673 of all 99 Helicobacter genus strains. We found 79 genome unique regions, a total of 202,359bp, shared by at least 80% of the H. pylori but lacked in non-pylori Helicobacter species. The operons, genes, and sRNAs within the H. pylori unique regions were considered as potential ones associated with its pathogenicity and adaptability, and the relativity among them has been partially confirmed by functional annotation analysis. However, functions of at least 54 genes and 10 sRNAs were still unclear. Our analysis of protein-protein interaction showed that 30 genes within them may have the cooperation relationship. De-Min Cao, Qun-Feng Lu, Song-Bo Li, Ju-Ping Wang, Yu-Li Chen, Yan-Qiang Huang, and Hong-Kai Bi Copyright © 2016 De-Min Cao et al. All rights reserved. Ultrasound for Appendicitis: Performance and Integration with Clinical Parameters Thu, 01 Dec 2016 09:10:18 +0000 Objective. To evaluate the performance of ultrasound in pediatric appendicitis and the integration of US with the pediatric appendicitis score (PAS) and C-reactive protein (CRP). Method. An institution-based, retrospective study of children who underwent abdominal US for suspected appendicitis between 2012 and 2015 at a tertiary pediatric surgery center. US results were dichotomized, with a nonvisualized appendix considered as a negative examination. Results. In total, 438 children were included (mean 8.5 years, 54% boys), with an appendicitis rate of 29%. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for US were 82%, 97%, 92%, and 93%, respectively, without significant age or gender differences. Pediatric radiologists had significantly higher sensitivity compared to general radiologists, 88% and 71%, respectively (), but no differences were seen for specificity, PPV, and NPV. The sensitivity, NPV, and negative likelihood ratio for the combination of negative US, PAS < 5, and CRP < 5 mg/L were 98%, 98%, and 0.05 (95% CI 0.03–0.15). Conclusion. US may be a useful tool for evaluating children with suspected appendicitis, regardless of age or gender, and should be the first choice of imaging modalities. Combining US with PAS and CRP may reduce several unnecessary admissions for in-hospital observation. Fanny Löfvenberg and Martin Salö Copyright © 2016 Fanny Löfvenberg and Martin Salö. All rights reserved. Role of BKCa in Stretch-Induced Relaxation of Colonic Smooth Muscle Mon, 28 Nov 2016 11:34:51 +0000 Stretch-induced relaxation has not been clearly identified in gastrointestinal tract. The present study is to explore the role of large conductance calcium-activated potassium channels (B) in stretch-induced relaxation of colon. The expression and currents of B were detected and the basal muscle tone and contraction amplitude of colonic smooth muscle strips were measured. The expression of B in colon is higher than other GI segments (P < 0.05). The density of B currents was very high in colonic smooth muscle cells (SMCs). B in rat colonic SMCs were sensitive to stretch. The relaxation response of colonic SM strips to stretch was attenuated by charybdotoxin (ChTX), a nonspecific B blocker (P < 0.05). After blocking enteric nervous activities by tetrodotoxin (TTX), the stretch-induced relaxation did not change (P > 0.05). Still, ChTX and iberiotoxin (IbTX, a specific B blocker) attenuated the relaxation of the colonic muscle strips enduring stretch (P < 0.05). These results suggest stretch-activation of B in SMCs was involved in the stretch-induced relaxation of colon. Our study highlights the role of mechanosensitive ion channels in SMCs in colon motility regulation and their physiological and pathophysiological significance is worth further study. Jie Ren, Fang Xin, Ping Liu, Hai-Yan Zhao, Si-Tao Zhang, Peng Han, Hai-Xia Huang, and Wei Wang Copyright © 2016 Jie Ren et al. All rights reserved. Lower Level of Bacteroides in the Gut Microbiota Is Associated with Inflammatory Bowel Disease: A Meta-Analysis Thu, 24 Nov 2016 07:05:33 +0000 Background and Aims. Multiple studies have reported associations between inflammatory bowel disease (IBD) and the flora disequilibrium of Bacteroides. We performed a meta-analysis of the available data to provide a more precise estimate of the association between Bacteroides level in the gut and IBD. Methods. We searched PubMed/MEDLINE, EMBASE, Cochrane Library, Wiley Library, BIOSIS previews, Web of Science, CNKI, and ScienceDirect databases for published literature on IBD and gut microbiota from 1990 to 2016. Quality of all eligible studies was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). We compared the level of Bacteroides in IBD patients with that in a control group without IBD, different types of IBD patients, and IBD patients with active phase and in remission. Results. We identified 63 articles, 9 of which contained sufficient data for evaluation. The mean level of Bacteroides was significantly lower in Crohn’s disease (CD) and ulcerative colitis (UC) patients in active phase than in normal controls. The level of Bacteroides in remission CD and UC patients was much lower than patients in the control group. Bacteroides level was even lower in patients with CD and UC in active phase than in remission. Conclusions. This analysis suggests that lower levels of Bacteroides are associated with IBD, especially in active phase. Yingting Zhou and Fachao Zhi Copyright © 2016 Yingting Zhou and Fachao Zhi. All rights reserved. hsa-miR-376c-3p Regulates Gastric Tumor Growth Both In Vitro and In Vivo Mon, 14 Nov 2016 11:05:51 +0000 Background. In recent studies, aberrant expression of various microRNAs (miRNAs) is reported to be associated with gastric cancer metastasis. Method. Overexpression construct and inhibitor of hsa-miR-376c-3p were expressed in human gastric adenocarcinoma cell line SGC-7901. The expression level of tumor related genes was detected by qPCR, western blot, and immunostaining. Cell apoptosis was determined by flow cytometry. Xenograft of SGC-7901 cells was used to elucidate the function of hsa-miR-376c-3p in gastric tumor growth in vivo. Result. Expression of hsa-miR-376c-3p was detected in SGC-7901 cells. Downregulation of hsa-miR-376c-3p increased the expression level of BCL-2 and decreased the expression of smad4 and BAD. On the contrary, overexpression of hsa-miR-376c-3p increased the expression of BAD and smad4, while it led to the decreasing expression level of BCL-2. Overexpression of hsa-miR-376c-3p also promoted cell apoptosis in vitro and inhibited gastric tumor growth in vivo. Furthermore, the expression of BCL-2 was higher and expression of smad4 and BAD was lower in tumor tissue than the tissue adjacent to tumor from gastric cancer patients. Conclusion. This study demonstrated that hsa-miR-376c-3p plays an important role in the inhibition of gastric tumor growth and tumor related gene expression both in vitro and in vivo. Lin Tu, Enhao Zhao, Wenyi Zhao, Zizhen Zhang, Defeng Tang, Yeqian Zhang, Chaojie Wang, Chun Zhuang, and Hui Cao Copyright © 2016 Lin Tu et al. All rights reserved. The Efficacy of Infliximab Monotherapy versus Infliximab-Azathioprine Sequential Treatment in Crohn’s Disease: Experience from a Tertiary Medical Center in China Tue, 08 Nov 2016 09:07:06 +0000 Objective. To evaluate the efficacy of infliximab (IFX) monotherapy versus infliximab-azathioprine sequential treatment in Crohn’s disease (CD) patients. Methods. Patients newly diagnosed with CD using IFX as induction therapy were enrolled. After 6 times of IFX infusions, they were divided into IFX monotherapy group and IFX-AZA sequential therapy group. Clinical remission rates were assessed at weeks 57, 84, 111, and 138 while endoscopic remission rates were assessed at weeks 84 and 138 to evaluate the efficacy of these two groups. Results. A total of seventy-nine patients had accomplished 138-week follow-up. At weeks 84 and 138, the deep remission rate (18/22 and 17/22) of IFX monotherapy group was significantly higher compared to IFX-AZA sequential therapy group (26/57 and 21/57) ( and 0.001, resp.). Similar findings were found in complete endoscopic remission rate. The clinical remission rates of IFX monotherapy group were similar to that of IFX-AZA sequential therapy group (). At weeks 84 and 138, the endoscopic remission rate and the endoscopic improvement rate between these two groups displayed no significant difference (). Conclusion. IFX monotherapy provides higher deep remission rate compared with IFX-AZA sequential therapy in two-year maintenance therapy. For patients who could not receive prolonged IFX therapy, IFX-AZA sequential therapy is acceptable, though long-term efficacy remains to be seen. Tianyu Zhang, Zhengting Wang, Rong Fan, Maochen Zhang, Yun Lin, Liwen Hong, Xiaolin Zhou, Shurong Hu, Mengmeng Cheng, and Jie Zhong Copyright © 2016 Tianyu Zhang et al. All rights reserved. Advances in Colorectal Cancer Sun, 06 Nov 2016 06:38:47 +0000 Nikolaos I. Nikiteas, Markus Weber, Anthony Antoniou, and Dimitrios Dimitroulis Copyright © 2016 Nikolaos I. Nikiteas et al. All rights reserved. Gene Expression Profile of Colon Mucosa after Cytotoxic Insult in wt and Apc-Mutated Pirc Rats: Possible Relation to Resistance to Apoptosis during Carcinogenesis Thu, 20 Oct 2016 09:47:55 +0000 Apc-mutated Pirc rats, spontaneously developing intestinal tumours, are resistant to 1,2-dimethylhydrazine- (DMH-) induced colon apoptosis. To understand this phenomenon, we analyzed the expression of genotoxic stress-related genes Mgmt, Gsta1, and Gstp1 in the colon of wt and Pirc rats in basal conditions and 24 h after DMH; plasmatic oxidant/antioxidant status was also evaluated. After DMH, Mgmt expression was increased in both genotypes but significantly only in wt rats; Gsta1 expression was significantly increased in both genotypes. Gstp1 expression did not vary after DMH but was lower in Pirc rats. Moreover, for each genotype, we studied by microarray technique whole gene expression profile after DMH. By unsupervised cluster analysis, 28 genes were differentially modulated between the two genotypes. Among them were interferon-induced genes Irf7, Oas1a, Oasl2, and Isg15 and the transcription factor Taf6l, overexpressed in DMH-treated wt rats and unchanged in Pirc rats. RT-PCR confirmed their overexpression in DMH-treated wt rats and showed a slighter variation in DMH-treated Pirc rats. Taken together, despite a blunted induction of Irf7, Oas1a, and Mgmt, defective apoptosis in Pirc rats 24 h after DMH is not mirrored by major differences in gene expression compared with wt rats. Angelo Pietro Femia, Cristina Luceri, Maura Lodovici, Stefania Crucitta, and Giovanna Caderni Copyright © 2016 Angelo Pietro Femia et al. All rights reserved. Comparison and Prognostic Analysis of Adjuvant Radiotherapy versus Salvage Radiotherapy for Treatment of Radically Resected Locally Advanced Esophageal Squamous Cell Carcinoma Sun, 16 Oct 2016 13:32:27 +0000 Objective. To compare adjuvant radiotherapy and salvage radiotherapy after radical resection for treatment of esophageal squamous cell carcinoma (ESCC). Methods. Data from 155 patients with locally advanced ESCC who underwent radical resection and received postoperative radiotherapy from 2005 to 2011 were reviewed. Seventy-nine patients received adjuvant radiotherapy and 76 received salvage radiotherapy after locoregional recurrence. Results. The median disease-free survival (DFS) and overall survival (OS) were significantly higher in the adjuvant radiotherapy group than the salvage radiotherapy group (DFS 25.73 months versus 10.73 months, ; OS 33.33 months versus 26.22 months, ). The independent prognostic factors for DFS were performance status (PS) before radiotherapy and pathological stage in the adjuvant radiotherapy group, compared with lymph node metastasis, tumor location, and adjuvant chemotherapy in the salvage radiotherapy group. The independent prognostic factors for OS were age and PS in both groups. No differences in median DFS and OS between the groups were observed in patients aged > 65 years or with PS ≥ 2. Conclusion. Compared to salvage radiotherapy, postoperative adjuvant radiotherapy can prolong DFS and OS for patients with radically resected local advanced ESCC but cannot improve survival for patients aged > 65 years or with PS ≥ 2. Xin Xu, Hua-Ying Xie, Di Zhou, Ren-Hua Huang, Yong-Rui Bai, Jun Yuan, and Ming Ye Copyright © 2016 Xin Xu et al. All rights reserved. A Randomized, Double-Blind, Placebo-Controlled Trial: The Efficacy of Multispecies Probiotic Supplementation in Alleviating Symptoms of Irritable Bowel Syndrome Associated with Constipation Tue, 09 Aug 2016 15:28:12 +0000 Background and Aim. The efficacy of supplementation treatment with two multispecies probiotic formulates on subjects diagnosed with IBS-C and the assessment of their gut microbiota were investigated. Methods. A randomized, double-blind, three-arm parallel group trial was carried out on 150 IBS-C subjects divided into three groups (F_1, F_2, and F_3). Each group received a daily oral administration of probiotic mixtures (for 60 days) F_1 or F_2 or placebo F_3, respectively. Fecal microbiological analyses were performed by species-specific qPCR to assess the different amount of probiotics. Results. The percentage of responders for each symptom was higher in the probiotic groups when compared to placebo group during the treatment period () and was maintained quite similar during the follow-up period (). Fecal analysis demonstrated that probiotics of the formulations increased during the times of treatment only in fecal DNA from subjects treated with F_1 and F_2 and not with F_3, and the same level was maintained during the follow-up period. Conclusions. Multispecies probiotic supplementations are effective in IBS-C subjects and induce a different assessment in the composition of intestinal microbiota. This clinical study is registered with the clinical study registration number ISRCTN15032219. Valerio Mezzasalma, Enrico Manfrini, Emanuele Ferri, Anna Sandionigi, Barbara La Ferla, Irene Schiano, Angela Michelotti, Vincenzo Nobile, Massimo Labra, and Patrizia Di Gennaro Copyright © 2016 Valerio Mezzasalma et al. All rights reserved. Use of the Biphasic 13C-Sucrose/Glucose Breath Test to Assess Sucrose Maldigestion in Adults with Functional Bowel Disorders Mon, 08 Aug 2016 16:26:43 +0000 Sucrase insufficiency has been observed in children with of functional bowel disorders (FBD) and symptoms of dietary carbohydrate intolerance may be indistinguishable from those of FBD. A two-phase 13C-sucrose/13C-glucose breath test (13C-S/GBT) was used to assess sucrase activity because disaccharidase assays are seldom performed in adults. When 13C-sucrose is hydrolyzed to liberate monosaccharides, oxidation to 13CO2 is a proportional indicator of sucrase activity. Subsequently, 13C-glucose oxidation rate was determined after a secondary substrate ingestion (superdose) to adjust for individual habitus effects (Phase II). 13CO2 enrichment recovery ratio from 13C-sucrose and secondary 13C-glucose loads reflect the individualized sucrase activity [Coefficient of Glucose Oxidation for Sucrose (CGO-S)]. To determine if sucrase insufficiency could be a factor in FBD, 13C-S/GBT was validated using subjects with known sucrase gene mutation status by comparing 13CO2-breath enrichment with plasma 13C-glucose enrichment. 13C-S/GBT was used to assess sucrose digestion in FBD patients and asymptomatic controls. 13CO2-breath enrichment correlated with the appearance of 13C-sucrose-derived glucose in plasma (). Mean, control group CGO-S-enrichment outcomes were 1.01 at 60′, 0.92 at 75′, and 0.96 at mean 60′–75′ with normal CGO-S defined as >0.85 (95% C.I.). In contrast, FBD patients demonstrated lower CGO-S values of 0.77 at 60′, 0.77 at 75′, and 0.76 at mean 60′–75′ (Chi Square: 6.55; ), which points to sucrose maldigestion as a cause of FBD. Antone R. Opekun, Albert M. Balesh, and Harold T. Shelby Copyright © 2016 Antone R. Opekun et al. All rights reserved. Therapeutic Strategies in HCC: Radiation Modalities Wed, 03 Aug 2016 07:16:28 +0000 Patients with hepatocellular carcinoma (HCC) comply with an advanced disease and are not eligible for radical therapy. In this distressed scenario new treatment options hold great promise; among them transarterial chemoembolization (TACE) and transarterial metabolic radiotherapy (TAMR) have shown efficacy in terms of both tumor shrinking and survival. External radiation therapy (RTx) by using novel three-dimensional conformal radiotherapy has also been used for HCC patients with encouraging results while its role had been limited in the past for the low tolerance of surrounding healthy liver. The rationale of TAMR derives from the idea of delivering exceptional radiation dose locally to the tumor, with cell killing intent, while preserving normal liver from undue exposition and minimizing systemic irradiation. Since the therapeutic efficacy of TACE is being continuously disputed, the TAMR with 131I Lipiodol or 90Y microspheres has gained consideration providing adequate therapeutic responses regardless of few toxicities. The implementation of novel radioisotopes and technological innovations in the field of RTx constitutes an intriguing field of research with important translational aspects. Moreover, the combination of different therapeutic approaches including chemotherapy offers captivating perspectives. We present the role of the radiation-based therapies in hepatocellular carcinoma patients who are not entitled for radical treatment. R. Gallicchio, A. Nardelli, P. Mainenti, A. Nappi, D. Capacchione, V. Simeon, C. Sirignano, F. Abbruzzi, F. Barbato, M. Landriscina, and G. Storto Copyright © 2016 R. Gallicchio et al. All rights reserved. Predictive Biomarkers in Colorectal Cancer: From the Single Therapeutic Target to a Plethora of Options Mon, 01 Aug 2016 14:28:45 +0000 Colorectal cancer (CRC) is one of the most frequent cancers and is a leading cause of cancer death worldwide. Treatments used for CRC may include some combination of surgery, radiation therapy, chemotherapy, and targeted therapy. The current standard drugs used in chemotherapy are 5-fluorouracil and leucovorin in combination with irinotecan and/or oxaliplatin. Most recently, biologic agents have been proven to have therapeutic benefits in metastatic CRC alone or in association with standard chemotherapy. However, patients present different treatment responses, in terms of efficacy and toxicity; therefore, it is important to identify biological markers that can predict the response to therapy and help select patients that would benefit from specific regimens. In this paper, authors review CRC genetic markers that could be useful in predicting the sensitivity/resistance to chemotherapy. Daniela Rodrigues, Adhemar Longatto-Filho, and Sandra F. Martins Copyright © 2016 Daniela Rodrigues et al. All rights reserved. Chemopreventive Properties and Toxicity of Kelulut Honey in Sprague Dawley Rats Induced with Azoxymethane Mon, 25 Jul 2016 10:01:28 +0000 Ethnopharmacological Relevance. Colon cancer has been a major problem worldwide. Kelulut honey (KH) is produced by the stingless bees from Trigona species and has strong antioxidant activities that could be one of the potential chemopreventive agents from natural resources. Aim of This Study. This study investigated the chemopreventive properties and toxicity of KH in Sprague Dawley rats induced with azoxymethane (AOM). Material and Method. Twenty-four male Sprague Dawley rats aged 5 weeks were divided into 4 groups: (G1) untreated group not induced with AOM, (G2) untreated group induced with AOM, (G3) treated group induced with AOM, and (G4) treated group not induced with AOM. Injection of AOM (15 mg/kg) was via intraperitoneal route once a week for two subsequent weeks. The treatment groups were given oral administration of KH (1183 mg/kg body weight) twice daily for 8 weeks. Results. Treatment with KH significantly reduced the total number of aberrant crypt foci (ACF) and aberrant crypts (AC) and crypt multiplicity. KH was not toxic to the animals since the level of blood profile parameters, liver enzymes, and kidney functions was in normal range. Conclusions. The current finding shows that KH has chemopreventive properties in rats induced with colorectal cancer and also was found not toxic towards the animals. Latifah Saiful Yazan, Muhamad Firdaus Shyfiq Muhamad Zali, Razana Mohd Ali, Nurul Amira Zainal, Nurulaidah Esa, Sarah Sapuan, Yong Sze Ong, Yin Sim Tor, Banulata Gopalsamy, Fui Ling Voon, and Sharifah Sakinah Syed Alwi Copyright © 2016 Latifah Saiful Yazan et al. All rights reserved. Downregulation of ADAMTS8 by DNA Hypermethylation in Gastric Cancer and Its Clinical Significance Thu, 14 Jul 2016 16:03:59 +0000 A disintegrin and metallopeptidase with thrombospondin motif type 8 (ADAMTS8), a member of the ADAMTS family, was discovered as a novel angiogenesis inhibitor. We analyzed the expression and methylation of ADAMTS8 in primary gastric tumors and gastric cancer cell lines. We also examined the relationship between ADAMTS8 expression and methylation and clinicopathologic features. The results showed that the significant downregulation of ADAMTS8 mRNA expression was observed in gastric cancer cell lines and tissues, and its expression was related to invasive depth and lymph node metastasis. CpG was hypermethylated in gastric cancer cell lines MKN45, MGC803, and BGC823, as well as primary gastric cancer specimens. ADAMTS8 mRNA expression was significantly lower in methylated primary gastric tumors. A significant association was found between ADAMTS8 methylation status and lymph node metastasis in primary gastric cancer. Moreover, ADAMTS8 expression was upregulated in the gastric cancer cell lines MGC803, BGC823, and MKN45 after treatment with 5-aza-2′-deoxycytidine. Thus, our results demonstrate that expression of ADAMTS8 mRNA is significantly decreased and DNA methylation is frequent in gastric cancer. ADAMTS8 hypermethylation is associated with decreased expression in gastric cancer and may play an important role in the invasion and metastasis of gastric cancer. Jing Chen, Jiakui Zhang, Xin Li, Chundong Zhang, Hongbin Zhang, Junzhe Jin, and Dongqiu Dai Copyright © 2016 Jing Chen et al. All rights reserved. Lactate Dehydrogenase in Hepatocellular Carcinoma: Something Old, Something New Sun, 29 May 2016 14:27:26 +0000 Hepatocellular carcinoma (HCC) is the most common primary liver tumour (80–90%) and represents more than 5.7% of all cancers. Although in recent years the therapeutic options for these patients have increased, clinical results are yet unsatisfactory and the prognosis remains dismal. Clinical or molecular criteria allowing a more accurate selection of patients are in fact largely lacking. Lactic dehydrogenase (LDH) is a glycolytic key enzyme in the conversion of pyruvate to lactate under anaerobic conditions. In preclinical models, upregulation of LDH has been suggested to ensure both an efficient anaerobic/glycolytic metabolism and a reduced dependence on oxygen under hypoxic conditions in tumour cells. Data from several analyses on different tumour types seem to suggest that LDH levels may be a significant prognostic factor. The role of LDH in HCC has been investigated by different authors in heterogeneous populations of patients. It has been tested as a potential biomarker in retrospective, small, and nonfocused studies in patients undergoing surgery, transarterial chemoembolization (TACE), and systemic therapy. In the major part of these studies, high LDH serum levels seem to predict a poorer outcome. We have reviewed literature in this setting trying to resume basis for future studies validating the role of LDH in this disease. Luca Faloppi, Maristella Bianconi, Riccardo Memeo, Andrea Casadei Gardini, Riccardo Giampieri, Alessandro Bittoni, Kalliopi Andrikou, Michela Del Prete, Stefano Cascinu, and Mario Scartozzi Copyright © 2016 Luca Faloppi et al. All rights reserved. Validation of an Endoscopic Fibre-Optic Pressure Sensor for Noninvasive Measurement of Variceal Pressure Mon, 23 May 2016 06:29:04 +0000 In this study, the authors have developed endoscopic fibre-optic pressure sensor to detect variceal pressure and presented the validation of in vivo and in vitro studies, because the HVPG requires catheterization of hepatic veins, which is invasive and inconvenient. Compared with HVPG, it is better to measure directly the variceal pressure without puncturing the varices in a noninvasive way. Bin Sun, De-Run Kong, Su-Wen Li, Dong-Feng Yu, Ging-Jing Wang, Fang-Fang Yu, Qiong Wu, and Jian-Ming Xu Copyright © 2016 Bin Sun et al. All rights reserved. Simultaneous Minimally Invasive Treatment of Colorectal Neoplasm with Synchronous Liver Metastasis Sun, 15 May 2016 09:51:58 +0000 Purpose. To analyse perioperative and oncological outcomes of minimally invasive simultaneous resection of primary colorectal neoplasm with synchronous liver metastases. Methods. A Medline revision of the current published literature on laparoscopic and robotic-assisted combined colectomy with hepatectomy for synchronous liver metastatic colorectal neoplasm was performed until February 2015. The specific search terms were “liver metastases”, “hepatic metastases”, “colorectal”, “colon”, “rectal”, “minimally invasive”, “laparoscopy”, “robotic-assisted”, “robotic colorectal and liver resection”, “synchronous”, and “simultaneous”. Results. 20 clinical reports including 150 patients who underwent minimally invasive one-stage procedure were retrospectively analysed. No randomized trials were found. The approach was laparoscopic in 139 patients (92.7%) and robotic in 11 cases (7.3%). The rectum was the most resected site of primary neoplasm (52.7%) and combined liver procedure was in 89% of cases a minor liver resection. One patient (0.7%) required conversion to open surgery. The overall morbidity and mortality rate were 18% and 1.3%, respectively. The most common complication was colorectal anastomotic leakage. Data concerning oncologic outcomes were too heterogeneous in order to gather definitive results. Conclusion. Although no prospective randomized trials are available, one-stage minimally invasive approach seems to show advantages over conventional surgery in terms of postoperative short-term course. On the contrary, more studies are required to define the oncologic values of the minimally invasive combined treatment. Stefano Garritano, Federico Selvaggi, and Marcello Giuseppe Spampinato Copyright © 2016 Stefano Garritano et al. All rights reserved. Cost-Effectiveness between Double and Single Fecal Immunochemical Test(s) in a Mass Colorectal Cancer Screening Thu, 07 Apr 2016 12:29:18 +0000 This study investigated the cost-effectiveness between double and single Fecal Immunochemical Test(s) (FIT) in a mass CRC screening. A two-stage sequential screening was conducted. FIT was used as a primary screening test and recommended twice by an interval of one week at the first screening stage. We defined the first-time FIT as FIT1 and the second-time FIT as FIT2. If either FIT1 or FIT2 was positive (+), then a colonoscopy was recommended at the second stage. Costs were recorded and analyzed. A total of 24,419 participants completed either FIT1 or FIT2. The detection rate of advanced neoplasm was 19.2% among both FIT1+ and FIT2+, especially high among men with age ≥55 (27.4%). About 15.4% CRC, 18.9% advanced neoplasm, and 29.9% adenoma missed by FIT1 were detected by FIT2 alone. Average cost was $2,935 for double FITs and $2,121 for FIT1 to detect each CRC and $901 for double FITs and $680 for FIT1 to detect each advanced neoplasm. Double FITs are overall more cost-effective, having significantly higher positive and detection rates with an acceptable higher cost, than single FIT. Double FITs should be encouraged for the first screening in a mass CRC screening, especially in economically and medically underserved populations/areas/countries. Shan-Rong Cai, Hong-Hong Zhu, Yan-Qin Huang, Qi-Long Li, Xin-Yuan Ma, Su-Zhan Zhang, and Shu Zheng Copyright © 2016 Shan-Rong Cai et al. All rights reserved. Advances of Targeted Therapy in Treatment of Unresectable Metastatic Colorectal Cancer Tue, 05 Apr 2016 06:52:16 +0000 Despite being one of the most frequently diagnosed cancers worldwide, prognosis of metastatic colorectal cancer (CRC) was poor. Development and introduction of biologic agents in treatment of patients with metastatic CRC have brought improved outcomes. Monoclonal antibodies directing epidermal growth factor receptors and vascular endothelial growth factor are main biologic agents currently used in treatment of metastatic CRC. Encouraged by results from many clinical trials demonstrating efficacy of those monoclonal antibodies, the combination therapy with those targeted agents and conventional chemotherapeutic agents has been established as the standard therapy for patients with metastatic CRC. However, emergency of resistance to those target agents has limited the efficacy of treatment, and strategies to overcome the resistance are now being investigated by newly developed biological techniques clarifying how to acquire resistance. Here, we introduce mechanisms of action of the biologic agents currently used for treatment of metastatic CRC and several landmark historical clinical studies which have changed the main stream of treatment. The mechanism of resistance to those agents, one of serious problems in treatment metastatic CRC, and ongoing clinical trials to overcome the limitations and improve treatment outcomes will also be presented in this review. Suk-young Lee and Sang Cheul Oh Copyright © 2016 Suk-young Lee and Sang Cheul Oh. All rights reserved. Expression of Migration-Related Genes in Human Colorectal Cancer and Activity of a Disintegrin and Metalloproteinase 17 Sun, 27 Mar 2016 11:50:25 +0000 Introduction. The ability to form metastases which depends on the mechanisms of cell migration is an important element of the progression of cancer. In the present study we analyzed the genes involved in the regulation of migration in colon cancer cells. Materials and Methods. A total of 20 pairs of surgically removed tumoral and healthy (marginal) tissues samples from colorectal cancer patients at clinical stages I-II and III-IV were analyzed. The isolation of RNA from CRC and normal tissues and its subsequent molecular analysis were performed according to manufacturer’s instructions. Microarray data analysis was performed using the GeneSpring 11.5 platform and Significance Analysis of Microarrays (SAM). In SAM analysis to identify significantly differentially expressed genes score and -value parameters were used. Results. The largest increase in expression of genes was shown by MMP9, ADAM17, EphA2, and TIMP. Conclusions. Presented genes, especially ADAM17, MMP9, EphA2, TIMP1, ICAM 11, and CD4, may be used as prognostic markers of advanced stages of colorectal cancer, contributing to the development of new lines of therapy focused on reducing metastasis of the primary tumor. Katarzyna Walkiewicz, Paweł Kozieł, Martyna Bednarczyk, Adam Błażelonis, Urszula Mazurek, and Małgorzata Muc-Wierzgoń Copyright © 2016 Katarzyna Walkiewicz et al. All rights reserved. Lactulose Hydrogen Breath Test Result Is Associated with Age and Gender Thu, 17 Mar 2016 16:28:42 +0000 Small intestinal bacterial overgrowth (SIBO) is associated with chronic gastrointestinal diseases and structural/functional abnormalities of the gastrointestinal tract. SIBO’s association with clinical characteristics is unclear. This study investigates the association between clinical factors and SIBO according to lactulose hydrogen breath test (LHBT) result. Methods. A cross-sectional study in a university-based gastroenterology practice was performed. Data was abstracted from the medical records of subjects undergoing LHBT from 6/1/2009 to 6/1/2013. Logistic regression analysis was performed to determine the association between predictor variables: age, sex, body mass index (BMI), and positive LHBT, the outcome of interest. Results. LHBT was performed in 791 subjects. Fifty-four percent had a positive LHBT. There was no statistically significant difference between the LHBT results according to age or BMI. In females, the likelihood of a positive LHBT increased with age (OR 1.02; 95% CI: 1.01–1.03). In males, the likelihood of a positive LHBT result decreased with age (OR 0.98; 95% CI: 0.97–1.00). Conclusion. There was an association between age, with respect to sex, and a positive LHBT. With increased age in females, the odds of a positive LHBT increased, while, in men, the odds of a positive LHBT decreased with age. Carolyn Newberry, Ann Tierney, and Octavia Pickett-Blakely Copyright © 2016 Carolyn Newberry et al. All rights reserved. Quantitative Evaluation and Selection of Reference Genes for Quantitative RT-PCR in Mouse Acute Pancreatitis Wed, 16 Mar 2016 07:52:49 +0000 The analysis of differences in gene expression is dependent on normalization using reference genes. However, the expression of many of these reference genes, as evaluated by quantitative RT-PCR, is upregulated in acute pancreatitis, so they cannot be used as the standard for gene expression in this condition. For this reason, we sought to identify a stable reference gene, or a suitable combination, for expression analysis in acute pancreatitis. The expression stability of 10 reference genes (ACTB, GAPDH, 18sRNA, TUBB, B2M, HPRT1, UBC, YWHAZ, EF-1α, and RPL-13A) was analyzed using geNorm, NormFinder, and BestKeeper software and evaluated according to variations in the raw Ct values. These reference genes were evaluated using a comprehensive method, which ranked the expression stability of these genes as follows (from most stable to least stable): RPL-13A, YWHAZ > HPRT1 > GAPDH > UBC > EF-1α > 18sRNA > B2M > TUBB > ACTB. RPL-13A was the most suitable reference gene, and the combination of RPL-13A and YWHAZ was the most stable group of reference genes in our experiments. The expression levels of ACTB, TUBB, and B2M were found to be significantly upregulated during acute pancreatitis, whereas the expression level of 18sRNA was downregulated. Thus, we recommend the use of RPL-13A or a combination of RPL-13A and YWHAZ for normalization in qRT-PCR analyses of gene expression in mouse models of acute pancreatitis. Zhaoping Yan, Jinhang Gao, Xiuhe Lv, Wenjuan Yang, Shilei Wen, Huan Tong, and Chengwei Tang Copyright © 2016 Zhaoping Yan et al. All rights reserved. Concomitant Thyroid Disorders and Inflammatory Bowel Disease: A Literature Review Thu, 03 Mar 2016 13:29:30 +0000 The aim of this report was to review and summarize the literature on cases of concomitant inflammatory bowel disease (IBD) and thyroid diseases. We included the following previous case reports of concomitant IBD and thyroid diseases: 16 cases of ulcerative colitis (UC) and Graves’ disease (GD), 3 cases of Crohn’s disease (CD) and GD, 10 cases of CD and Hashimoto’s thyroiditis (HT), 4 cases of IBD and subacute thyroiditis (SAT) or SAT-like symptoms, and 13 cases of IBD (12/13 cases were CD) and amyloid goiter. There might be no obvious differences of prevalence of thyroid dysfunction (hyper- or hypothyroidism), GD, and thyroid cancer between IBD patients and general populations. However, concomitant UC and HT might be relatively common in patients with multiple autoimmune disorders, and AG is one of the complications with CD patients. There might be no obvious differences of fatal prognoses between IBD patients with thyroid diseases and patients with thyroid diseases without IBD. Toru Shizuma Copyright © 2016 Toru Shizuma. All rights reserved. Dehydroabietic Acid Derivative QC4 Induces Gastric Cancer Cell Death via Oncosis and Apoptosis Mon, 29 Feb 2016 13:03:01 +0000 Aim. QC4 is the derivative of rosin’s main components dehydroabietic acid (DHA). We investigated the cytotoxic effect of QC4 on gastric cancer cells and revealed the mechanisms beneath the induction of cell death. Methods. The cytotoxic effect of QC4 on gastric cancer cells was evaluated by CCK-8 assay and flow cytometry. The underlying mechanisms were tested by administration of cell death related inhibitors and detection of apoptotic and oncosis related proteins. Cytomembrane integrity and organelles damage were confirmed by lactate dehydrogenase (LDH) leakage assay, mitochondrial function test, and cytosolic free Ca2+ concentration detection. Results. QC4 inhibited cell proliferation dose- and time-dependently and destroyed cell membrane integrity, activated calpain-1 autolysis, and induced apoptotic protein cleavage in gastric cancer cells. The detection of decreased ATP and mitochondrial membrane potential, ROS accumulation, and cytosolic free Ca2+ elevation confirmed organelles damage in QC4-treated gastric cancer cells. Conclusions. DHA derivative QC4 induced the damage of cytomembrane and organelles which finally lead to oncosis and apoptosis in gastric cancer cells. Therefore, as a derivative of plant derived small molecule DHA, QC4 might become a promising agent in gastric cancer therapy. Dongjun Luo, Qing Ni, Anlai Ji, Wen Gu, Junhua Wu, and Chunping Jiang Copyright © 2016 Dongjun Luo et al. All rights reserved. Does the Gadoxetic Acid-Enhanced Liver MRI Impact on the Treatment of Patients with Colorectal Cancer? Comparison Study with 18F-FDG PET/CT Sun, 28 Feb 2016 16:41:16 +0000 Objectives. We evaluated the value of Gadoxetic acid-enhanced liver MRI in the preoperative staging of colorectal cancer and estimated the clinical impact of liver MRI in the management plan of liver metastasis. Methods. We identified 108 patients who underwent PET/CT and liver MRI as preoperative evaluation of colorectal cancer, between January 2011 and December 2013. We evaluated the per nodule sensitivity of PET/CT and liver MRI for liver metastasis. Management plan changes were estimated for patients with metastatic nodules newly detected on liver MRI, to assess the clinical impact. Results. We enrolled 131 metastatic nodules (mean size 1.6 cm) in 41 patients (mean age 65 years). The per nodule sensitivities of PET/CT and liver MRI were both 100% for nodules measuring 2 cm or larger but were significantly different for nodules measuring less than 2 cm (59.8% and 95.1%, resp., ). At least one more metastatic nodule was detected on MRI in 16 patients. Among these, 7 patients indicated changes of management plan after performing MRI. Conclusions. Gadoxetic acid-enhanced liver MRI detected more metastatic nodules compared with PET/CT, especially for small (<2 cm) nodules. The newly detected nodules induced management plan change in 43.8% (7/16) of patients. Ji-Won Oh, Soon Nam Oh, Joon Il Choi, Moon Hyung Choi, Ie Ryung Yoo, Myung Ah Lee, Young-Kyung Yoo, and Seong Taek Oh Copyright © 2016 Ji-Won Oh et al. All rights reserved. The Protective Effects of 18β-Glycyrrhetinic Acid on Helicobacter pylori-Infected Gastric Mucosa in Mongolian Gerbils Wed, 24 Feb 2016 07:58:26 +0000 18β-Glycyrrhetinic acid (GRA), a major component of Glycyrrhiza glabra, is widely used therapeutically in clinic. In this study, the effect of GRA on Helicobacter pylori- (H. pylori-) infected gastritis was investigated in Mongolian gerbils in vivo. The gerbils were randomly divided into groups: uninfected; H. pylori-infected; H. pylori + antibiotics (clarithromycin, amoxicillin, and esomeprazole); and H. pylori + GRA. The gastric intraluminal pH value, histopathological changes, and the expression levels of inflammation-related cytokines (IL-1β, TNF-α, COX-2, and iNOS) were investigated. The results showed that, in the H. pylori + GRA group, the intraluminal gastric pH value was lower ( versus , ), erosion and hyperplasia were alleviated, the infiltration of neutrophils and mononuclear cells was attenuated (), and the expression levels of TNF-α, IL-1β, COX-2, and iNOS were decreased () compared with the H. pylori-infected group. There was no significant difference in results between the H. pylori + GRA group and the H. pylori + antibiotics group. This study indicated that GRA significantly attenuated H. pylori-infected gastritis in gerbils and has the potential to be developed as a new therapeutic drug. Donghui Cao, Jing Jiang, Lili You, Zhifang Jia, Tetsuya Tsukamoto, Hongke Cai, Shidong Wang, Zhen Hou, Yue-er Suo, and Xueyuan Cao Copyright © 2016 Donghui Cao et al. All rights reserved. Novel Topics in Inflammatory Bowel Disease Tue, 23 Feb 2016 13:05:03 +0000 Atsushi Sakuraba, Alessandro Armuzzi, Kian Keyashian, and Makoto Naganuma Copyright © 2016 Atsushi Sakuraba et al. All rights reserved. Treating Small Bowel Obstruction with a Manual Physical Therapy: A Prospective Efficacy Study Thu, 18 Feb 2016 12:13:04 +0000 Small bowel obstructions (SBOs) caused by adhesions are a common, often life-threatening postsurgical complication with few treatment options available for patients. This study examines the efficacy of a manual physical therapy treatment regimen on the pain and quality of life of subjects with a history of bowel obstructions due to adhesions in a prospective, controlled survey based study. Changes in six domains of quality of life were measured via ratings reported before and after treatment using the validated Small Bowel Obstruction Questionnaire (SBO-Q). Improvements in the domains for pain (), overall quality of life (), and pain severity () were significant when average scores before treatment were compared with scores after treatment. The gastrointestinal symptoms () domain was marginally significant. There was no statistically significant improvement identified in the diet or medication domains in the SBO-Q for this population. Significant improvements in range of motion in the trunk (), often limited by adhesions, were also observed for all measures. This study demonstrates in a small number of subjects that this manual physical therapy protocol is an effective treatment option for patients with adhesive small bowel obstructions as measured by subject reported symptoms and quality of life. Amanda D. Rice, Kimberley Patterson, Evette D. Reed, Belinda F. Wurn, Bernhard Klingenberg, C. Richard King III, and Lawrence J. Wurn Copyright © 2016 Amanda D. Rice et al. All rights reserved. Confocal Laser Endomicroscopy in Gastrointestinal and Pancreatobiliary Diseases: A Systematic Review and Meta-Analysis Wed, 17 Feb 2016 14:02:49 +0000 Confocal laser endomicroscopy (CLE) is an endoscopic-assisted technique developed to obtain histopathological diagnoses of gastrointestinal and pancreatobiliary diseases in real time. The objective of this systematic review is to analyze the current literature on CLE and to evaluate the applicability and diagnostic yield of CLE in patients with gastrointestinal and pancreatobiliary diseases. A literature search was performed on MEDLINE, EMBASE, Scopus, and Cochrane Oral Health Group Specialized Register, using pertinent keywords without time limitations. Both prospective and retrospective clinical studies that evaluated the sensitivity, specificity, or accuracy of CLE were eligible for inclusion. Of 662 articles identified, 102 studies were included in the systematic review. The studies were conducted between 2004 and 2015 in 16 different countries. CLE demonstrated high sensitivity and specificity in the detection of dysplasia in Barrett’s esophagus, gastric neoplasms and polyps, colorectal cancers in inflammatory bowel disease, malignant pancreatobiliary strictures, and pancreatic cysts. Although CLE has several promising applications, its use has been limited by its low availability, high cost, and need of specific operator training. Further clinical trials with a particular focus on cost-effectiveness and medicoeconomic analyses, as well as standardized institutional training, are advocated to implement CLE in routine clinical practice. Alessandro Fugazza, Federica Gaiani, Maria Clotilde Carra, Francesco Brunetti, Michaël Lévy, Iradj Sobhani, Daniel Azoulay, Fausto Catena, Gian Luigi de’Angelis, and Nicola de’Angelis Copyright © 2016 Alessandro Fugazza et al. All rights reserved. Optimizing Human Bile Preparation for Two-Dimensional Gel Electrophoresis Thu, 04 Feb 2016 08:48:31 +0000 Aims. Bile is an important body fluid which assists in the digestion of fat and excretion of endogenous and exogenous compounds. In the present study, an improved sample preparation for human bile was established. Methods and Material. The method involved acetone precipitation followed by protein extraction using commercially available 2D Clean-Up kit. The effectiveness was evaluated by 2-dimensional electrophoresis (2DE) profiling quality, including number of protein spots and spot distribution. Results. The total protein of bile fluid in benign biliary disorders was 0.797 ± 0.465 μg/μL. The sample preparation method using acetone precipitation first followed by 2D Clean-Up kit protein extraction resulted in better quality of 2DE gel images in terms of resolution as compared with other sample preparation methods. Using this protocol, we obtained approximately 558 protein spots on the gel images and with better protein spots presentation of haptoglobin, serum albumin, serotransferrin, and transthyretin. Conclusions. Protein samples of bile prepared using acetone precipitation followed by 2D Clean-Up kit exhibited high protein resolution and significant protein profile. This optimized protein preparation protocol can effectively concentrate bile proteins, remove abundant proteins and debris, and yield clear presentation of nonabundant proteins and its isoforms on 2-dimensional electrophoresis gel images. Hao-Tsai Cheng, Sen-Yung Hsieh, Chang-Mu Sung, Betty Chien-Jung Pai, Nai-Jen Liu, and Carl PC Chen Copyright © 2016 Hao-Tsai Cheng et al. All rights reserved. Diagnostic Methods of Helicobacter pylori Infection for Epidemiological Studies: Critical Importance of Indirect Test Validation Tue, 19 Jan 2016 10:31:41 +0000 Among the methods developed to detect H. pylori infection, determining the gold standard remains debatable, especially for epidemiological studies. Due to the decreasing sensitivity of direct diagnostic tests (histopathology and/or immunohistochemistry [IHC], rapid urease test [RUT], and culture), several indirect tests, including antibody-based tests (serology and urine test), urea breath test (UBT), and stool antigen test (SAT) have been developed to diagnose H. pylori infection. Among the indirect tests, UBT and SAT became the best methods to determine active infection. While antibody-based tests, especially serology, are widely available and relatively sensitive, their specificity is low. Guidelines indicated that no single test can be considered as the gold standard for the diagnosis of H. pylori infection and that one should consider the method’s advantages and disadvantages. Based on four epidemiological studies, culture and RUT present a sensitivity of 74.2–90.8% and 83.3–86.9% and a specificity of 97.7–98.8% and 95.1–97.2%, respectively, when using IHC as a gold standard. The sensitivity of serology is quite high, but that of the urine test was lower compared with that of the other methods. Thus, indirect test validation is important although some commercial kits propose universal cut-off values. Muhammad Miftahussurur and Yoshio Yamaoka Copyright © 2016 Muhammad Miftahussurur and Yoshio Yamaoka. All rights reserved. Immunohistochemical Studies on Galectin Expression in Colectomised Patients with Ulcerative Colitis Mon, 18 Jan 2016 07:37:56 +0000 Introduction. The aetiology and pathogenesis of ulcerative colitis (UC) are essentially unknown. Galectins are carbohydrate-binding lectins involved in a large number of physiological and pathophysiological processes. Little is known about the role of galectins in human UC. In this immunohistochemical exploratory study, both epithelial and inflammatory cell galectin expression were studied in patients with a thoroughly documented clinical history and were correlated with inflammatory activity. Material and Methods. Surgical whole intestinal wall colon specimens from UC patients () and controls () were studied. Clinical history, pharmacological treatment, and modified Mayo-score were recorded. Tissue inflammation was graded, and sections were stained with antibodies recognizing galectin-1, galectin-2, galectin-3, and galectin-4. Results. Galectin-1 was undetectable in normal and UC colonic epithelium, while galectin-2, galectin-3, and galectin-4 were strongly expressed. A tendency towards diminished epithelial expression with increased inflammatory grade for galectin-2, galectin-3, and galectin-4 was also found. In the inflammatory cells, a strong expression of galectin-2 and a weak expression of galectin-3 were seen. No clear-cut correlation between epithelial galectin expression and severity of the disease was found. Conclusion. Galectin expression in patients with UC seems to be more dependent on disease focality and individual variation than on degree of tissue inflammation. Mattias Block, Johan Mölne, Hakon Leffler, Lars Börjesson, and Michael E. Breimer Copyright © 2016 Mattias Block et al. All rights reserved. Validation of Urine Test for Detection of Helicobacter pylori Infection in Indonesian Population Mon, 28 Dec 2015 14:01:26 +0000 We measured the accuracy of the urine test (RAPIRUN) for detection of Helicobacter pylori infection in Indonesia (Jakarta, Pontianak, and Jayapura) using histology confirmed by immunohistochemistry and/or culture as gold standards. We also used immunohistochemistry to identify CagA phenotype and analyzed H. pylori CagA diversity in Indonesia. The overall prevalence of H. pylori infection in 88 consecutive dyspeptic patients based on the urine test was 15.9% (14/88), 38.1% for patients in Jayapura that had higher prevalence of H. pylori infection than that in Jakarta (9.7%, ) and Pontianak (8.3%, ). Overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of RAPIRUN were 83.3%, 94.7%, 71.4%, 97.3%, and 93.2%, respectively. All of the H. pylori-positive patients were immunoreactive for anti-CagA antibody but not immunoreactive for East Asian specific anti-CagA antibody in all H. pylori-positive subjects. We confirmed the high accuracy of RAPIRUN in Indonesian population. In general, we found less virulent type of H. pylori in Indonesia, which partly explained the low incidence gastric cancer in Indonesia. Ari Fahrial Syam, Muhammad Miftahussurur, Willy Brodus Uwan, David Simanjuntak, Tomohisa Uchida, and Yoshio Yamaoka Copyright © 2015 Ari Fahrial Syam et al. All rights reserved. The Influence of Ghrelin on the Development of Dextran Sodium Sulfate-Induced Colitis in Rats Wed, 02 Dec 2015 14:21:50 +0000 Ghrelin has protective and therapeutic effects in the gut. The aim of present studies was to investigate the effect of treatment with ghrelin on the development of colitis evoked by dextran sodium sulfate (DSS). Methods. Studies have been performed on rats. Colitis was induced by adding 5% DSS to the drinking water for 5 days. During this period animals were treated intraperitoneally twice a day with saline or ghrelin given at the dose of 8 nmol/kg/dose. On the sixth day, animals were anesthetized and the severity of colitis was assessed. Results. Treatment with ghrelin during administration of DSS reduced the development of colitis. Morphological features of colonic mucosa exhibited a reduction in the area and deep of mucosal damage. Ghrelin reversed the colitis-induced decrease in blood flow, DNA synthesis, and superoxide dismutase activity in colonic mucosa. These effects were accompanied by a decrease in the colitis-evoked increase in mucosal concentration of interleukin-1β and malondialdehyde. Treatment with ghrelin reversed the DSS-induced reduction in body weight gain. Conclusions. Administration of ghrelin exhibits the preventive effect against the development of DSS-induced colitis. This effect seems to be related to ghrelin’s anti-inflammatory and antioxidative properties. Aleksandra Matuszyk, Dagmara Ceranowicz, Zygmunt Warzecha, Piotr Ceranowicz, Krzysztof Fyderek, Krystyna Gałązka, Jakub Cieszkowski, Joanna Bonior, Jolanta Jaworek, Małgorzata Pihut, and Artur Dembiński Copyright © 2015 Aleksandra Matuszyk et al. All rights reserved. Incidence Trends and Geographical Variability of Pediatric Inflammatory Bowel Disease in Slovenia: A Nationwide Study Tue, 24 Nov 2015 07:38:55 +0000 Background. The aims of the study were to determine the incidence rate of pediatric inflammatory bowel disease (PIBD) and its trends for the period of 2002–2010 and to assess the geographical distribution of PIBD in Slovenia. Materials and Methods. Medical records of patients (0–18 years) with newly diagnosed IBD during the study period were retrospectively reviewed. Results. The mean incidence rate for IBD in 2002–2010 was 7.6 per 100,000 children and adolescents per year, 4.5 for Crohn’s disease (CD), 2.9 for ulcerative colitis (UC), and 0.2 for IBD-unclassified, respectively. The incidence rate increased from 5.8 per 100,000 per year in 2002–2004 to 8.6 in 2005–2007 and remained stable afterwards. Statistically significant difference in the incidence rate between the Northeastern and Southwestern parts of the country was observed (). Conclusion. This nationwide study demonstrates that Slovenia is among the European countries with the highest PIBD incidence. During the study period a substantial rise of PIBD incidence was observed during the first half of the study and it seems to have stabilized in the second half. The significant difference in PIBD incidence between Northeastern and Southwestern parts of the country merits further exploration of the possible environmental factors. Darja Urlep, Rok Blagus, and Rok Orel Copyright © 2015 Darja Urlep et al. All rights reserved. Management of Nonceliac Gluten Sensitivity by Gastroenterology Specialists: Data from an Italian Survey Thu, 19 Nov 2015 15:57:10 +0000 Background and Aim. Nonceliac gluten sensitivity is syndrome characterized by symptoms disappearing after a gluten-free diet. Its existence is still argument of discussion among specialists. Our aim was to evaluate the knowledge about nonceliac gluten sensitivity among gastroenterology specialists. Methods. During October 2013 a questionnaire was sent through a medical newsletter to Italian gastroenterologists. Twelve questions investigated their knowledge on nonceliac gluten sensitivity, including their diagnostic and therapeutic approach. Results. A total of 212 gastroenterologists filled in the questionnaire. The 98.6% were aware of the existence of a syndrome called “nonceliac gluten sensitivity” and 77% believe in its existence. However, only 56% gave a correct definition of the term. The majority of specialists diagnosed gluten sensitive patients and the number of diagnoses was not statistically different from that of celiac disease. Moreover, a gluten-free diet was prescribed by 64% of the specialists and among them the 73% noted an increase of gluten sensitive patients attending their outpatient services. Conclusions. Our study indicated that most of the specialists recognize nonceliac gluten sensitivity and prescribe gluten-free diet, although 44% of the specialists are not able to give its correct definition; underlining the necessity of medical education on this topic is needed. Federica Branchi, Francesca Ferretti, Lorenzo Norsa, Leda Roncoroni, Dario Conte, Maria Teresa Bardella, and Luca Elli Copyright © 2015 Federica Branchi et al. All rights reserved. Genetic Polymorphisms of IL-17F and TRAF3IP2 Could Be Predictive Factors of the Long-Term Effect of Infliximab against Crohn’s Disease Mon, 19 Oct 2015 07:57:51 +0000 Background. We aimed to identify certain genes related to response to infliximab (IFX) and biomarkers to predict the IFX effect for Japanese Crohn’s disease (CD) patients by performing an association study of single nucleotide polymorphisms (SNPs) in candidate genes in the interleukin- (IL-) 17 signaling pathway with response to IFX after 1 year of treatment. Methods. A total of 103 patients were divided into two groups, responders and nonresponders. Twenty-eight tag SNPs in 5 genes were genotyped. The frequencies of alleles and genotypes of each SNP were compared between responders and nonresponders in three different inheritance models. A genetic test was performed using a combination of the associated SNPs as biomarkers. Results. Multivariate logistic regression analysis indicated that the four variable factors, concomitant use of immunomodulators, penetrating disease, a G/G genotype of rs766748 in IL-17F, and a C/C or C/A genotype of rs1883136 in TRAF3IP2, independently contributed to response to IFX after 1 year of treatment. Genetic test using the polymorphisms of these genes perfectly predicted the responder and nonresponder CD patients with both concomitant use of immunomodulators and penetrating disease. Conclusion. IL17F and TRAF3IP2 are one of IFX-related genes, useful as biomarkers of IFX response, and may be target molecules for new therapeutic drugs. Shigetoshi Urabe, Hajime Isomoto, Tetsuya Ishida, Kazumi Maeda, Tatsuo Inamine, Shinji Kondo, Norihide Higuchi, Kayoko Sato, Ryohei Uehara, Hiroyuki Yajima, Haruhisa Machida, Chun Chuan Chen, Yasuhiro Fukuda, Fuminao Takeshima, Kazuhiko Nakao, and Kazuhiro Tsukamoto Copyright © 2015 Shigetoshi Urabe et al. All rights reserved. Immunohistochemical Expression of Ornithine Decarboxylase, Diamine Oxidase, Putrescine, and Spermine in Normal Canine Enterocolic Mucosa, in Chronic Colitis, and in Colorectal Cancer Thu, 15 Oct 2015 08:03:55 +0000 We compared the immunohistochemical expression of putrescine (PUT), spermine (SPM), ornithine decarboxylase (ODC), and diamine oxidase (DAO) in bioptic samples of canine colonic mucosa with chronic inflammation (i.e., granulomatous colitis and lymphoplasmacytic colitis) or neoplasia. Single and total polyamines levels were significantly higher in neoplastic tissue than in normal samples. Samples with different degrees of inflammation showed a general decrease expression of ODC if compared to controls; SPM was practically not expressed in control samples and very low in samples with chronic-granulomatous inflammation. In carcinomatous samples, the ODC activity was higher with respect to controls and samples with inflammation. This is the first description of polyamines expression in dog colonic mucosa in normal and in different pathological conditions, suggesting that the balance between polyamine degradation and biosynthesis is evidently disengaged during neoplasia. Giacomo Rossi, Matteo Cerquetella, Graziano Pengo, Subeide Mari, Emilia Balint, Gabrio Bassotti, and Nicolae Manolescu Copyright © 2015 Giacomo Rossi et al. All rights reserved. Actions of Probiotics on Trinitrobenzenesulfonic Acid-Induced Colitis in Rats Tue, 13 Oct 2015 11:44:43 +0000 We investigated the actions of probiotics, Streptococcus faecalis 129 BIO 3B (SF3B), in a trinitrobenzenesulfonic acid- (TNBS-) induced colitis model in rats. After TNBS was administered into the colons of rats for induction of colitis, the rats were divided into two groups: one group was given a control diet and the other group was given a diet containing SF3B for 14 days. There were no apparent differences in body weight, diarrhea period, macroscopic colitis score, and colonic weight/length ratio between the control group and SF3B group, suggesting that induction of colitis was not prevented by SF3B. Next, we investigated whether SF3B-containing diet intake affects the restoration of enteric neurotransmissions being damaged during induction of colitis by TNBS using isolated colonic preparations. Recovery of the nitrergic component was greater in the SF3B group than in the control group. A compensatory appearance of nontachykininergic and noncholinergic excitatory components was less in the SF3B group than in the control group. In conclusion, the present study suggests that SF3B-containing diet intake can partially prevent disruptions of enteric neurotransmissions induced after onset of TNBS-induced colitis, suggesting that SF3B has therapeutic potential. Takahiko Shiina, Takeshi Shima, Kiyotada Naitou, Hiroyuki Nakamori, Yuuki Sano, Kazuhiro Horii, Masaki Shimakawa, Hiroshi Ohno, and Yasutake Shimizu Copyright © 2015 Takahiko Shiina et al. All rights reserved. The Demographic and Clinical Characteristics of Ulcerative Colitis in a Northeast Brazilian Population Mon, 05 Oct 2015 13:14:20 +0000 Introduction. The purpose of this study was to describe the clinical and demographic characteristics of UC in Bahia, a Brazilian state, and to identify the variables associated with extensive colitis, steroid therapy, immunosuppression, and colectomy. Methods. In this cross-sectional study UC patients were interviewed, and additional information was collected from the medical records. Descriptive statistics and multivariate Poisson regression analysis were used. Results. This study included 267 individuals, the mean age of whom was 39.4 years at diagnosis. There was a predominance of females and left-side colitis. Extensive colitis was positively associated with male gender, diarrhea, weight loss, and a younger age at diagnosis. In contrast, active smoking and a family history of IBD were negatively associated with extensive colitis. Positive associations were observed between steroid therapy and diarrhea, weight loss, urban patients, extraintestinal manifestations (EIMs), and hospitalization. Younger age and weight loss at diagnosis, a family history of IBD, extensive colitis, EIMs, hospitalization, and steroid therapy were all positively associated with immunosuppression. In contrast, Caucasian individuals, smokers, patients with rectal bleeding, and rural patients areas were all observed to have a decreased likelihood of immunosuppression. Conclusions. Our results corroborate the association between higher prevalence of extensive colitis and younger age at diagnosis. An association between steroid therapy and clinical presentation at diagnosis was observed. The observation that white individuals and rural patients use less immunosuppressive drugs highlights the need to study the influence of environmental and genetic factors on the behavior of UC in this population. Bruno César da Silva, Andre Castro Lyra, Carlos Maurício Cardeal Mendes, Camila Paula Oliveira Ribeiro, Sonyara Rauedys Oliveira Lisboa, Mariana Tinoco Lordello de Souza, Renata Cavalcanti Portela, and Genoile Oliveira Santana Copyright © 2015 Bruno César da Silva et al. All rights reserved. Gene Expression-Genotype Analysis Implicates GSDMA, GSDMB, and LRRC3C as Contributors to Inflammatory Bowel Disease Susceptibility Mon, 21 Sep 2015 13:51:03 +0000 To investigate the biological foundation of the inflammatory bowel disease (IBD), ulcerative colitis and Crohn’s disease, susceptibility locus rs2872507, we have investigated the expression of 13 genes using ileal and colonic biopsies from patients with IBD (inflamed and noninflamed mucosa) or from individuals without IBD (noninflamed mucosa). The susceptibility allele was consistently associated with reduced expression of GSDMB ( = 4.1 × 10−3–7.2 × 10−10). The susceptibility allele was also associated with the increased expression of GSDMA ( = 1.6 × 10−4) and LRRC3C ( = 7.8 × 10−6) in colon tissue from individuals without IBD and with the reduced expression of PGAP3 (IBD; = 2.0 × 10−3) and ZPBP2 (Crohn’s disease; = 7.7 × 10−4) in noninflamed ileum. Inflammation resulted in the reduced colonic expression of ERBB2, GRB7, MIEN1, and PGAP3 ( = 1.0 × 10−4–1.0 × 10−9) and the increased colonic expression of IKZF3 and CSF3 ( = 2.4 × 10−7–3.5 × 10−8). Based on our results and published findings on GSDMA, GSDMB, LRRC3C, and related proteins, we propose that this locus in part affects IBD susceptibility via effects on apoptosis and cell proliferation and believe this hypothesis warrants further experimental investigation. Jan Söderman, Linda Berglind, and Sven Almer Copyright © 2015 Jan Söderman et al. All rights reserved. Tetramethylpyrazine Inhibits Activation of Hepatic Stellate Cells through Hedgehog Signaling Pathways In Vitro Mon, 24 Aug 2015 08:38:25 +0000 Background and Aim. Tetramethylpyrazine (TMP), a major alkaloid isolated from Ligusticum chuanxiong, has been reported in hepatic fibrosis models. However, the action mechanism remains unclear. In the present study, effects of tetramethylpyrazine (TMP) against hepatic stellate cell (HSC) activation as well as the possible mechanisms were evaluated. Methods. Western blot assay was used to detect TMP effects on protein expression of Smo, Patched, Hhip, and Gli and to investigate the effects of TMP on Cyclin D1, Cyclin E1, CDK2, Bcl-2, Bax, and caspase expression with cyclopamine supplementation. Results. Our results showed that TMP significantly inhibits the expression of Cyclin D1, Cyclin E1, and Cyclin-dependent kinase CDK2 and changes the HSC cycle by inhibiting the proliferation of HSC. Moreover, TMP has also been shown to decrease the expression of Bcl-2 and increase the expression of Bax in HSC-T6 cells. Furthermore, TMP can inhibit the expression of connective tissue growth factor (CTGF), and the inhibitory effect was intensified after the application of joint treatment with TMP and cyclopamine. Conclusion. TMP may be an effective Hh signaling pathway inhibitor for hepatic fibrosis treatment. Jue Hu, Gang Cao, Xin Wu, Hao Cai, and Baochang Cai Copyright © 2015 Jue Hu et al. All rights reserved. A New Era of Laparoscopic Revision of Kasai Portoenterostomy for the Treatment of Biliary Atresia Wed, 22 Jul 2015 06:59:17 +0000 Purpose. Kasai portoenterostomy is the standard therapy for biliary atresia (BA). If Kasai is unsuccessful, there is controversy over whether revision of Kasai restores adequate biliary drainage. Although there are several reports of laparoscopic Kasai (Lap-Kasai), none has described laparoscopic revision (Lap-revision). The purposes of this study were to evaluate the feasibility and efficacy of Lap-revision. Methods. 65 patients underwent open Kasai between November 2001 and November 2013, and 12 patients underwent Lap-Kasai between December 2013 to January 2015. The indications for revision included bile flow cessation and recurrent cholangitis. Clinical data were compared between open and laparoscopic revisions of Kasai. Results. Open revision of Kasai was performed in 20 patients after open Kasai, and Lap-revision was performed in 4 patients after Lap-Kasai. Lap-revision was completed without conversion or major complication in any patient. The bilirubin level was normalized by Lap-revision in all four patients, and three of them were alive with their native liver. Open and laparoscopic revisions of Kasai were comparable in terms of the operation time, blood loss, and surgical outcomes. Conclusion. Lap-revision is a feasible and effective method for the treatment of BA and might herald a new era for the treatment of this disease. Naruhiko Murase, Hiroo Uchida, Yasuyuki Ono, Takahisa Tainaka, Kazuki Yokota, Akihide Tanano, Chiyoe Shirota, and Ryo Shirotsuki Copyright © 2015 Naruhiko Murase et al. All rights reserved. Endoscopic Management of Foreign Bodies in the Upper Gastrointestinal Tract of Adults Wed, 15 Jul 2015 06:20:52 +0000 Background. Foreign object ingestion and food bolus impaction are a common clinical problem. We report our clinical experiences in endoscopic management for adults, foreign body ingestion, and food bolus impaction. Method. A retrospective chart review study was conducted on adult patients with foreign body ingestion and food bolus impaction between January 2011 and November 2014. Patients with incomplete medical records were excluded. Results. A total of 198 patients (226 incidents) were included in the study (male/female: 1.54/1; age 57 ± 16 years). Among them, 168 foreign bodies were found successfully (74.3%). 75.6% of the foreign bodies were located in the esophagus. Food bolus impaction was most common (41.6%). 93.5% of foreign bodies in current study cohort were successfully extracted and 5 patients required surgical interventions. Comparisons between symptomatic and asymptomatic patients revealed that locations of foreign bodies in the pharynx and esophagus were the significant relevant factors (). Shorter time taken to initiate endoscopic interventions increased detection rate (289.75 ± 465.94 versus 471.06 ± 659.93 minutes, ). Conclusion. Endoscopic management is a safe and highly effective procedure in extracting foreign body ingestion and food bolus impaction. Prompt endoscopic interventions can increase the chance of successful foreign bodies’ detection. Chih-Chien Yao, I-Ting Wu, Lung-Sheng Lu, Sheng-Chieh Lin, Chih-Ming Liang, Yuan-Hung Kuo, Shih-Cheng Yang, Cheng-Kun Wu, Hsing-Ming Wang, Chung-Huang Kuo, Shue-Shian Chiou, Keng-Liang Wu, Yi-Chun Chiu, Seng-Kee Chuah, and Wei-Chen Tai Copyright © 2015 Chih-Chien Yao et al. All rights reserved. Inguinal Hernias Represent the Most Frequent Surgical Complication after Kasai in Biliary Atresia Infants Thu, 09 Jul 2015 07:49:06 +0000 Biliary atresia (BA) is an orphan medical condition of the newborn, resulting in end-stage liver cirrhosis due to obliterative cholangiopathy of the extrahepatic bile duct. Although Kasai’s hepatoportoenterostomy (KPE) is the well-established first-line therapy, little is known about its surgical complications. 153 patients receiving open KPE treated at a single center between 1994 and 2014 were analysed retrospectively regarding short-term complications and survival with the native liver. In brief, 40.5% of patients suffered from 1–3 surgical complications, inguinal hernias (IH) being most prevalent (40.0%). In BA patients, incidence of IH was associated with male gender (), the syndromic form of BA (), and percutaneous drainage for ascites (). No association was found with prematurity () or birth weight () in our study. In conclusion, IH frequently develops after open KPE of BA patients, but this complication does not negatively affect the patient’s outcome. Nevertheless, inspection of the internal inguinal ring and prophylactic closure of inapparent hernias should be discussed in order to prevent secondary surgical procedures. Omid Madadi-Sanjani, Nathalie Carl, Thomas Longerich, Claus Petersen, and Julia H. K. Andruszkow Copyright © 2015 Omid Madadi-Sanjani et al. All rights reserved. Triphala Extract Suppresses Proliferation and Induces Apoptosis in Human Colon Cancer Stem Cells via Suppressing c-Myc/Cyclin D1 and Elevation of Bax/Bcl-2 Ratio Wed, 17 Jun 2015 10:03:06 +0000 Colon cancer is the second leading cause of cancer related deaths in the USA. Cancer stem cells (CSCs) have the ability to drive continued expansion of the population of malignant cells. Therefore, strategies that target CSCs could be effective against colon cancer and in reducing the risk of relapse and metastasis. In this study, we evaluated the antiproliferative and proapoptotic effects of triphala, a widely used formulation in Indian traditional medicine, on HCT116 colon cancer cells and human colon cancer stem cells (HCCSCs). The total phenolic content, antioxidant activity, and phytochemical composition (LC-MS-MS) of methanol extract of triphala (MET) were also measured. We observed that MET contains a variety of phenolics including naringin, quercetin, homoorientin, and isorhamnetin. MET suppressed proliferation independent of p53 status in HCT116 and in HCCSCs. MET also induced p53-independent apoptosis in HCCSCs as indicated by elevated levels of cleaved PARP. Western blotting data suggested that MET suppressed protein levels of c-Myc and cyclin D1, key proteins involved in proliferation, and induced apoptosis through elevation of Bax/Bcl-2 ratio. Furthermore, MET inhibited HCCSCs colony formation, a measure of CSCs self-renewal ability. Anticancer effects of triphala observed in our study warrant future studies to determine its efficacy in vivo. Ramakrishna Vadde, Sridhar Radhakrishnan, Lavanya Reddivari, and Jairam K. P. Vanamala Copyright © 2015 Ramakrishna Vadde et al. All rights reserved. Ethnomedicinal Evaluation of Medicinal Plants Used against Gastrointestinal Complaints Sun, 31 May 2015 07:13:56 +0000 Aim of the present study was to document ethnomedicinal plants used against gastrointestinal complaints in five selected remote regions of Pakistan and to select potential medicinal plants for further in vitro and in vivo investigation. Data on ethnomedicinal plants and ethnographic profile of respondents was documented using semistructured questionnaires. The present study revealed utilization of 52 medicinal plants for the treatment of different gastrointestinal infections in studied regions. Apiaceae was the most dominant family reported to be used for the treatment of these infections (4 plants). Among all the plant parts fruit (24%), whole plants and leaves (23% each) were the most preferred plant parts used by the healers. Dosage of recipe was found to be related with the age of the patient. Highest degree of informant consensus was reported for vomiting, nausea (0.92 each), abdominal pain (0.9), and diarrhea (0.89). Withania coagulans scored highest FL value (86%) followed by Mentha longifolia and Melia azadirachta ranked second with FL value (75% each). Young generation was found to possess little traditional knowledge about utilizing plant recipes against these infections. Plants with high Fic and FL values should be subjected for further phytochemical and pharmacological investigation for scientific validation. Akash Tariq, Sakina Mussarat, Muhammad Adnan, E. F. Abd_Allah, Abeer Hashem, Abdulaziz Abdullah Alqarawi, and Riaz Ullah Copyright © 2015 Akash Tariq et al. All rights reserved. The Sea Lamprey as an Etiological Model for Biliary Atresia Tue, 26 May 2015 11:59:09 +0000 Biliary atresia (BA) is a progressive, inflammatory, and fibrosclerosing cholangiopathy in infants that results in obstruction of both extrahepatic and intrahepatic bile ducts. It is the most common cause for pediatric liver transplantation. In contrast, the sea lamprey undergoes developmental BA with transient cholestasis and fibrosis during metamorphosis, but emerges as a fecund adult with steatohepatitis and fibrosis in the liver. In this paper, we present new histological evidence and compare the sea lamprey to existing animal models to highlight the advantages and possible limitations of using the sea lamprey to study the etiology and compensatory mechanisms of BA and other liver diseases. Understanding the signaling factors and genetic networks underlying lamprey BA can provide insights into BA etiology and possible targets to prevent biliary degeneration and to clear fibrosis. In addition, information from lamprey BA can be used to develop adjunct treatments for patients awaiting or receiving surgical treatments. Furthermore, the cholestatic adult lamprey has unique adaptive mechanisms that can be used to explore potential treatments for cholestasis and nonalcoholic steatohepatitis (NASH). Yu-Wen Chung-Davidson, Chu-Yin Yeh, and Weiming Li Copyright © 2015 Yu-Wen Chung-Davidson et al. All rights reserved. Helicobacter pylori Infection Thu, 21 May 2015 07:11:25 +0000 Ping-I Hsu, Yoshio Yamaoka, Khean-Lee Goh, Marco Manfredi, Deng-Chyang Wu, and Varocha Mahachai Copyright © 2015 Ping-I Hsu et al. All rights reserved. Biofilm Formation by Helicobacter pylori and Its Involvement for Antibiotic Resistance Tue, 19 May 2015 11:42:19 +0000 Bacterial biofilms are communities of microorganisms attached to a surface. Biofilm formation is critical not only for environmental survival but also for successful infection. Helicobacter pylori is one of the most common causes of bacterial infection in humans. Some studies demonstrated that this microorganism has biofilm forming ability in the environment and on human gastric mucosa epithelium as well as on in vitro abiotic surfaces. In the environment, H. pylori could be embedded in drinking water biofilms through water distribution system in developed and developing countries so that the drinking water may serve as a reservoir for H. pylori infection. In the human stomach, H. pylori forms biofilms on the surface of gastric mucosa, suggesting one possible explanation for eradication therapy failure. Finally, based on the results of in vitro analyses, H. pylori biofilm formation can decrease susceptibility to antibiotics and H. pylori antibiotic resistance mutations are more frequently generated in biofilms than in planktonic cells. These observations indicated that H. pylori biofilm formation may play an important role in preventing and controlling H. pylori infections. Therefore, investigation of H. pylori biofilm formation could be effective in elucidating the detailed mechanisms of infection and colonization by this microorganism. Hideo Yonezawa, Takako Osaki, and Shigeru Kamiya Copyright © 2015 Hideo Yonezawa et al. All rights reserved. Seven-Day Nonbismuth Containing Quadruple Therapy Could Achieve a Grade “A” Success Rate for First-Line Helicobacter pylori Eradication Tue, 19 May 2015 08:20:55 +0000 This prospective study was to assess the efficacy of nonbismuth containing quadruple therapy as first-line H. pylori treatment and to determine the clinical factors influencing patient outcome. We enrolled 200 H. pylori-infected naïve patients. They were prescribed either a 7-day nonbismuth containing quadruple therapy group (EACM, esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, metronidazole 500 mg twice daily, and clarithromycin 500 mg twice daily) or a 7-day standard triple therapy group (EAC, esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily). Follow-up studies to assess treatment responses were carried out 8 weeks later. The eradication rates attained by EACM and EAC groups were 95.6% (95% confidence interval [CI] = 89.4%–98.3%) and 79.3% (95% CI = 70%–86.4%) in the per-protocol analysis (P < 0.001) and 88% (95% CI = 80.2%–93.0%) and 73% (95% I = 63.6%–80.3%) in the intention-to-treat analysis (P = 0.007). Clarithromycin resistance, metronidazole resistance, and dual clarithromycin and metronidazole resistances were the clinical factors influencing H. pylori eradication in EACM group. Clarithromycin resistance and dual clarithromycin and metronidazole resistances were the influential factor for EAC treatment. In conclusion, the results suggest that 7-day nonbismuth containing quadruple therapy could achieve a grade “A” report card for first-line H. pylori treatment. Wei-Chen Tai, Chih-Ming Liang, Chen-Hsiang Lee, Chien-Hua Chiu, Ming-Luen Hu, Lung-Sheng Lu, Yuan-Hung Kuo, Chung-Mou Kuo, Yi-Hao Yen, Chung-Huang Kuo, Shue-Shian Chiou, Keng-Liang Wu, Yi-Chun Chiu, Tsung-Hui Hu, and Seng-Kee Chuah Copyright © 2015 Wei-Chen Tai et al. All rights reserved. Helicobacteraceae in Bulk Tank Milk of Dairy Herds from Northern Italy Mon, 18 May 2015 14:13:47 +0000 Helicobacter pylori is responsible for gastritis and gastric adenocarcinoma in humans, but the routes of transmission of this bacterium have not been clearly defined. Few studies led to supposing that H. pylori could be transmitted through raw milk, and no one investigated the presence of other Helicobacteraceae in milk. In the current work, the presence of Helicobacteraceae was investigated in the bulk tank milk of dairy cattle herds located in northern Italy both by direct plating onto H. pylori selective medium and by screening PCR for Helicobacteraceae, followed by specific PCRs for H. pylori, Wolinella spp., and “Candidatus Helicobacter bovis.” Three out of 163 bulk milk samples tested positive for Helicobacteraceae, but not for the subsequent PCRs. H. pylori was not isolated in any case. However, given similar growth conditions, Arcobacter butzleri, A. cryaerophilus, and A. skirrowii were recovered. In conclusion, the prevalence of Helicobacteraceae in raw milk was negligible (1.8%), and H. pylori was not identified in any of the positive samples, suggesting that, at least in the farming conditions of the investigated area, bovine milk does not represent a potential source of infection. Valentina Bianchini, Camilla Recordati, Laura Borella, Valentina Gualdi, Eugenio Scanziani, Elisa Selvatico, and Mario Luini Copyright © 2015 Valentina Bianchini et al. All rights reserved. The Prevalence of Helicobacter pylori Virulence Factors in Bhutan, Vietnam, and Myanmar Is Related to Gastric Cancer Incidence Mon, 18 May 2015 12:07:53 +0000 Gastric cancer is a significant health problem in Asia. Although the prevalence of Helicobacter pylori infection is similar in Bhutan, Vietnam, and Myanmar, the incidence of gastric cancer is highest in Bhutan, followed by Vietnam and Myanmar. We hypothesized that H. pylori virulence factors contribute to the differences. The status of cagA, vacA, jhp0562, and β-(1,3)galT(jhp0563) was examined in 371 H. pylori-infected patients from Bhutan, Vietnam, and Myanmar. Each virulence factor could not explain the difference of the incidence of gastric cancer. However, the prevalence of quadruple-positive for cagA, vacA s1, vacA m1, and jhp0562-positive/β-(1,3)galT-negative was significantly higher in Bhutan than in Vietnam and Myanmar and correlated with gastric cancer incidence. Moreover, gastritis-staging scores measured by histology of gastric mucosa were significantly higher in quadruple-positive strains. We suggest that the cagA, vacA s1, vacA m1, and jhp0562-positive/β-(1,3)galT-negative genotype may play a role in the development of gastric cancer. Tran Thi Huyen Trang, Seiji Shiota, Miyuki Matsuda, Tran Thanh Binh, Rumiko Suzuki, Ratha-korn Vilaichone, Varocha Mahachai, Lotay Tshering, Ho D. Q. Dung, Tomohisa Uchida, Osamu Matsunari, Thein Myint, Vu Van Khien, and Yoshio Yamaoka Copyright © 2015 Tran Thi Huyen Trang et al. All rights reserved. Comparison of Second-Line Quadruple Therapies with or without Bismuth for Helicobacter pylori Infection Mon, 18 May 2015 10:08:40 +0000 The bismuth-based quadruple regimen has been applied in Helicobacter pylori rescue therapy worldwide. The non-bismuth-based quadruple therapy or “concomitant therapy” is an alternative option in first-line eradication but has not been used in second-line therapy. Discovering a valid regimen for rescue therapy in bismuth-unavailable countries is important. We conducted a randomized controlled trial to compare the efficacies of the standard quadruple therapy and a modified concomitant regimen. One hundred and twenty-four patients were randomly assigned into two groups: RBTM (rabeprozole 20 mg bid., bismuth subcitrate 120 mg qid, tetracycline 500 mg qid, and metronidazole 250 mg qid) and RATM (rabeprozole 20 mg bid., amoxicillin 1 g bid., tetracycline 500 mg qid, and metronidazole 250 mg qid) for 10 days. The eradication rate of the RBTM and RATM regimen was 92.1% and 90.2%, respectively, in intention-to-treat analysis. Patients in both groups had good compliance (~96%). The overall incidence of adverse events was higher in the RATM group (42.6% versus 22.2%, ), but only seven patients (11.5%) experienced grades 2-3 events. In conclusion, both regimens had good efficacy, compliance, and acceptable side effects. The 10-day RATM treatment could be an alternative rescue therapy in bismuth-unavailable countries. Guang-Hong Jheng, I-Chen Wu, Hsiang-Yao Shih, Meng-Chieh Wu, Fu-Chen Kuo, Huang-Ming Hu, Chung-Jung Liu, Wen-Hung Hsu, Chi-Tan Hu, Ming-Jong Bair, Chao-Hung Kuo, Deng-Chyang Wu, and Ping-I Hsu Copyright © 2015 Guang-Hong Jheng et al. All rights reserved. Correlation between Gastric Mucosal Morphologic Patterns and Histopathological Severity of Helicobacter pylori Associated Gastritis Using Conventional Narrow Band Imaging Gastroscopy Mon, 18 May 2015 09:47:19 +0000 Background and Aim. Identifying specific gastric mucosal morphologic patterns useful for detecting Helicobacter pylori associated gastritis and correlation with histopathological severity. Methods. The endoscopists classified the C-NBI gastroscopic findings into 5 gastric mucosal morphologic patterns as follows: type 1: regular arrangement of collecting venules, type 2: cone-shaped gastric pits, type 3: rod-shaped gastric pits with prominent sulci, type 4: ground glass-like morphology, and type 5: dark brown patches with bluish margin and irregular border. Biopsies of all of the cases were then evaluated by 5 pathologists for definitive Helicobacter pylori diagnosis. Result. Type 1 and type 2 patterns were statistically significant in predicting Helicobacter pylori negative status (58/60, ). Type 3, type 4, and type 5 patterns were statistically significant in predicting Helicobacter pylori positive status (132/140, ). Furthermore, the sensitivity, specificity, and positive and negative predictive values of type 3, 4, or 5 morphologies for predicting Helicobacter pylori positive were 94.28%, 96.66%, 98.50%, and 87.87%, respectively, correlated well with inflammation grading according to the Sydney classification (). Conclusion. Our study suggests that gastric mucosal morphologic patterns in the Helicobacter pylori infected gastric mucosa can be reliably identified using C-NBI gastroscopy with good correlation with inflammation grading. Taweesak Tongtawee, Soraya Kaewpitoon, Natthawut Kaewpitoon, Chavaboon Dechsukhum, Ryan A. Loyd, and Likit Matrakool Copyright © 2015 Taweesak Tongtawee et al. All rights reserved. Inhibitory Effect of Various Breads on DMH-Induced Aberrant Crypt Foci and Colorectal Tumours in Rats Thu, 14 May 2015 12:23:30 +0000 Bread is rich in dietary fibre and many phytochemical compounds, which may influence chemoprevention of colon cancer. In the present study, we evaluated the effect of three kinds of bread on DMH-induced colorectal tumours in F344 rats. F344 rats were divided into four groups (Steinmetz Three-Grain bread, Steinmetz Country bread, White bread, and MF). All groups were injected with 1,2-dimethylhydrazine (DMH, 20 mg/kg body weight) once a week for 8 consecutive weeks from 5 weeks of age. To investigate the antioxidant effect of bread, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging rate of bread and the serum levels of 8-hydroxy-deoxyguanosine (8-OHdG) in rats were examined. The number of colorectal aberrant crypt foci (ACF) and the incidence of colorectal tumours were studied after 34 weeks of DMH treatment. The Steinmetz Three-Grain and Steinmetz Country bread groups had higher scavenging rates of the DPPH free radical and lower serum levels of 8-OHdG and incidence of ACF, adenomas, and adenocarcinomas of colon than the White bread and MF group. Steinmetz Three-Grain bread and Steinmetz Country bread have various ingredient combinations that may inhibit colorectal cancer progression. Guangying Qi, Sien Zeng, Tiri Takashima, Koichiro Nozoe, Megumi Shobayashi, Koji Kakugawa, Kaori Murakami, Hiroshi Jikihara, Lihua Zhou, and Fumio Shimamoto Copyright © 2015 Guangying Qi et al. All rights reserved. The Characteristics of Antioxidant Activity after Liver Transplantation in Biliary Atresia Patients Tue, 12 May 2015 13:53:59 +0000 Purpose. Cholestatic liver injury is associated with a high production of free radicals. The pathogenesis of liver injury in biliary atresia (BA) patients is largely undefined. The goal of the present study was to clarify the oxidative damage and the changes in antioxidant enzyme activities that occur during the development of BA and after liver transplantation (LT). Methods. We enrolled BA patients and control subjects and collected their clinical information. The activities of antioxidant enzymes in BA patients before LT (BA group) and after LT (LT group) were analyzed. Results. The number of mitochondrial DNA copies had increased in the LT group compared with the BA group. Similarly, the activity of glutathione peroxidase had increased in the LT group compared with the BA group. The level of glutathione was higher in the LT group than in the BA group. Malondialdehyde levels were decreased in the LT group compared with the BA group. Conclusions. These data indicate that LT is associated with increased antioxidant enzyme activities and decreased malondialdehyde levels in BA patients. The manipulation of mitochondria-associated antioxidative activity might be an important future management strategy for BA. Chih-Jen Chen, Kuo-Shu Tang, Ying-Hsien Huang, Chao-Long Chen, Li-Tung Huang, Jiin-Haur Chuang, and Mao-Meng Tiao Copyright © 2015 Chih-Jen Chen et al. All rights reserved. Helicobacter pylori-Induced Signaling Pathways Contribute to Intestinal Metaplasia and Gastric Carcinogenesis Sun, 10 May 2015 06:24:39 +0000 Helicobacter pylori (H. pylori) induces chronic gastric inflammation, atrophic gastritis, intestinal metaplasia, and cancer. Although the risk of gastric cancer increases exponentially with the extent of atrophic gastritis, the precise mechanisms of gastric carcinogenesis have not been fully elucidated. H. pylori induces genetic and epigenetic changes in gastric epithelial cells through activating intracellular signaling pathways in a cagPAI-dependent manner. H. pylori eventually induces gastric cancer with chromosomal instability (CIN) or microsatellite instability (MSI), which are classified as two major subtypes of gastric cancer. Elucidation of the precise mechanisms of gastric carcinogenesis will also be important for cancer therapy. Soichiro Sue, Wataru Shibata, and Shin Maeda Copyright © 2015 Soichiro Sue et al. All rights reserved. Rebamipide Improves Chronic Inflammation in the Lesser Curvature of the Corpus after Helicobacter pylori Eradication: A Multicenter Study Tue, 28 Apr 2015 09:39:39 +0000 Background and Aim. Although many epidemiologic studies have shown that Helicobacter pylori eradication has prophylactic effects on gastric cancer, it does not completely eliminate the risk of gastric cancer. We aimed to investigate the changes in histological gastritis in patients receiving rebamipide treatment after H. pylori eradication. Methods. 206 patients who had undergone H. pylori eradication were evaluated. Of these, 169 patients who achieved successful eradication were randomly allocated to 2 groups: the rebamipide group (n = 82) and the untreated group (n = 87). The primary endpoints were histopathological findings according to the updated Sydney system at the start of the study and after 1 year. Results. Final assessment for histological gastritis was possible in 50 cases from the rebamipide group and 53 cases from the untreated group. The activity and atrophy improved in both the rebamipide and untreated groups, and no significant intergroup differences were observed. Chronic inflammation affecting the lesser curvature of the corpus was significantly improved in the rebamipide group compared to in the untreated group ( versus ; P = 0.043). Conclusions. Rebamipide treatment after H. pylori eradication alleviated chronic inflammation in the lesser curvature of the corpus compared to that in the untreated group. This trial is registered with UMIN000002369. Tomoari Kamada, Motonori Sato, Tadashi Tokutomi, Tetsuo Watanabe, Takahisa Murao, Hiroshi Matsumoto, Noriaki Manabe, Masanori Ito, Shinji Tanaka, Kazuhiko Inoue, Akiko Shiotani, Takashi Akiyama, Jiro Hata, and Ken Haruma Copyright © 2015 Tomoari Kamada et al. All rights reserved. The Influence of Metabolic Factors for Nonalcoholic Fatty Liver Disease in Women Mon, 20 Apr 2015 09:57:30 +0000 Background/Aims. Women after menopause have increased insulin resistance and visceral fat, which may increase the prevalence of nonalcoholic fatty liver disease (NAFLD). However, the pathogenesis of NAFLD in women has not been clearly defined. In this study, we aimed to determine the risk factors for NAFLD in women. Methods. A retrospective cohort study was conducted. Women who underwent abdominal ultrasonography and blood sampling for routine health check-ups were recruited. Results. Among 1,423 subjects, 695 women (48.9%) were in a menopausal state. The prevalence of NAFLD was higher in postmenopausal women than in premenopausal women (27.2% versus 14.4%, ). In premenopausal women, low HDL-cholesterol, central obesity, and homeostasis model assessment-estimated insulin resistance showed a significant association with the increased risk of NAFLD in multivariate analysis. In postmenopausal women, the presence of diabetes, triglyceridemia, and central obesity showed a significant association with the risk of NAFLD. The presence of menopause and hormone replacement therapy in postmenopausal women were not risk factors for NAFLD. Conclusions. Our findings showed different metabolic factors for NAFLD in pre- and postmenopausal women. However, the key issues are the same: central obesity and insulin resistance. These results reemphasize the importance of metabolic factors irrespective of menopausal status in the pathogenesis of NAFLD in women. Goh Eun Chung, Jeong Yoon Yim, Donghee Kim, Seon Hee Lim, Jong In Yang, Young Sun Kim, Sun Young Yang, Min-Sun Kwak, Joo Sung Kim, and Sang-Heon Cho Copyright © 2015 Goh Eun Chung et al. All rights reserved. Factors Influencing the Eicosanoids Synthesis In Vivo Wed, 11 Mar 2015 11:58:07 +0000 External factors activate a sequence of reactions involving the reception, transduction, and transmission of signals to effector cells. There are two main phases of the body’s reaction to harmful factors: the first aims to neutralize the harmful factor, while in the second the inflammatory process is reduced in size and resolved. Secondary messengers such as eicosanoids are active in both phases. The discovery of lipoxins and epi-lipoxins demonstrated that not all arachidonic acid (AA) derivatives have proinflammatory activity. It was also revealed that metabolites of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) such as resolvins, protectins, and maresins also take part in the resolution of inflammation. Knowledge of the above properties has stimulated several clinical trials on the influence of EPA and DHA supplementation on various diseases. However, the equivocal results of those trials prevent the formulation of guidelines on EPA and DHA supplementation. Prescription drugs are among the substances with the strongest influence on the profile and quantity of the synthesized eicosanoids. The lack of knowledge about their influence on the conversion of EPA and DHA into eicosanoids may lead to erroneous conclusions from clinical trials. Jarosław Szefel, Wiesław Janusz Kruszewski, and Ewa Sobczak Copyright © 2015 Jarosław Szefel et al. All rights reserved. The Role of Enteral Nutrition in Patients with Inflammatory Bowel Disease: Current Aspects Sun, 22 Feb 2015 16:28:14 +0000 Enteral nutrition (EN) is considered to be of great importance in patients with inflammatory bowel disease (IBD) and nutritional problems. This comprehensive review is aiming to provide the reader with an update on the role of EN in IBD patients. EN can reduce Crohn’s disease (CD) activity and maintain remission in both adults and children. Nutritional support using liquid formulas should be considered for CD patients and in serious cases of ulcerative colitis (UC), especially for those who may require prolonged cycles of corticosteroids. Given that the ultimate goal in the treatment of CD is mucosal healing, this advantage of EN over corticosteroid treatment is valuable in therapeutic decision-making. EN is indicated in active CD, in cases of steroid intolerance, in patient’s refusal of steroids, in combination with steroids in undernourished individuals, and in patients with an inflammatory stenosis of the small intestine. No differences between the efficiency of elemental diets and nonelemental formulas have been noticed. EN must be the first choice compared to TPN. EN has a restricted value in the treatment of patients with large bowel CD. In conclusion, it seems important not to underestimate the role of nutrition as supportive care in patients with IBD. John K. Triantafillidis, Costas Vagianos, and Apostolos E. Papalois Copyright © 2015 John K. Triantafillidis et al. All rights reserved. Endoscopic Sphincterotomy with Large Balloon Dilation versus Endoscopic Sphincterotomy for Bile Duct Stones: A Systematic Review and Meta-Analysis Tue, 10 Feb 2015 09:01:47 +0000 The safety and efficacy of endoscopic sphincterotomy with large balloon dilation (EPLBD) are unclear. This study compares the safety and efficacy between EPLBD and endoscopic sphincterotomy (EST). Patients and Methods. Literatures were searched for randomized controlled trials in PUBMED, EMBASE, and Cochrane Library. Outcome measurements included adverse events; stone removal rate; requirement of mechanical lithotripsy. Results. Four RCTs with a total of 596 patients were included. Three RCTs compared EPLBD versus EST alone for stone removal; one RCT compared EPLBD versus EST plus mechanical lithotripsy for stone removal. Pooled data from three RCTs showed that there was no significant difference in the adverse event of ERCP. A significantly higher cholangitis rate was seen in patients who received EST plus mechanical lithotripsy, compared to those treated with EPLBD (13.3% versus 0.0, ). No statistical difference was found between EPLBD and EST for stone removal rate. Significant differences in requirement of mechanical lithotripsy were seen with removal of large stones (>15 mm), with EPLBD reducing the use of mechanical lithotripsy (RR: 0.73; 95% CI: 0.54–0.99). Conclusions. EPLBD and EST have similar efficacy and safety for bile duct stones clearance. With larger stones, EPLBD can reduce requirement of mechanical lithotripsy. Lei Xu, Moe Htet Kyaw, Yee Kit Tse, and James Yun Wong Lau Copyright © 2015 Lei Xu et al. All rights reserved. A Randomized Study on the Effectiveness of Prophylactic Clipping during Endoscopic Resection of Colon Polyps for the Prevention of Delayed Bleeding Tue, 03 Feb 2015 12:49:23 +0000 Backgrounds. The efficacy of clipping for preventing the delayed bleeding after the removal of colon polyps is still controversial. In order to clarify this efficacy, a randomized controlled study was performed. Methods. One hundred and fifty-six patients with colon neoplasms (288 lesions) were enrolled in the study. The patients were randomly divided into two groups: clipping or nonclipping groups using a sealed envelope method before the endoscopic resections. Eight specialists and nine residents were invited to perform this procedure. The risk factors and the rates of delayed bleeding after the endoscopic resections in each group were investigated. Results. There were no significant differences in the bleeding rate between the clipping and nonclipping groups, while the length of the procedure was significantly longer and the cost was higher in the clipping group than in the nonclipping group. The rate of bleeding was significantly higher in cases with polyps 2 cm or larger and with a longer procedure time, while none of the other factors affected the bleeding rate. Conclusions. This randomized controlled study revealed no significant effect of prophylactic clipping for preventing delayed bleeding after the endoscopic resection of colon polyps. Tatsuya Dokoshi, Mikihiro Fujiya, Kazuyuki Tanaka, Aki Sakatani, Yuhei Inaba, Nobuhiro Ueno, Shin Kashima, Takuma Goto, Junpei Sasajima, Motoya Tominaga, Takahiro Ito, Kentaro Moriichi, Hiroki Tanabe, Katsuya Ikuta, Takaaki Ohtake, and Yutaka Kohgo Copyright © 2015 Tatsuya Dokoshi et al. All rights reserved. Association of Polymorphisms in X-Ray Repair Cross Complementing 1 Gene and Risk of Esophageal Squamous Cell Carcinoma in a Chinese Population Sun, 01 Feb 2015 13:51:33 +0000 Objectives. To investigate the association between three single nucleotide polymorphisms (SNPs) in the X-ray repair cross complementing 1 gene (XRCC1) and the risk of esophageal squamous cell carcinoma (ESCC) in Chinese population. Methods. A case-control study including 381 primary ESCC patients recruited from hospital and 432 normal controls matched with patients by age and gender from Chinese Han population was conducted. The genotypes of three XRCC1 polymorphisms at −77T>C (T-77C), codon 194 (Arg194Trp), and codon 399 (Arg399Gln) were studied by means of polymerase chain reaction-restriction fragment length polymorphism techniques (PCR-RFLP). Unconditional logistic regression model and haplotype analysis were used to estimate associations of these three SNPs in XRCC1 gene with ESCC risk. Results. Polymorphisms at these three sites in XRCC1 gene were not found to be associated with risk for developing ESCC; however the haplotype was significantly associated with reduced risk of ESCC (OR: 0.62, 95% CI: 0.40–0.96) upon haplotype analysis. Conclusion. These results suggested that the gene-gene interactions might play vital roles in the progression on esophageal cancer in Chinese Han population and it would be necessary to confirm these findings in a large and multiethnic population. Yu-Xia Yun, Li-Ping Dai, Peng Wang, Kai-Juan Wang, Jian-Ying Zhang, and Wei Xie Copyright © 2015 Yu-Xia Yun et al. All rights reserved. High Pressure Air Jet in the Endoscopic Preparation Room: Risk of Noise Exposure on Occupational Health Sun, 01 Feb 2015 13:21:26 +0000 After high-level disinfection of gastrointestinal endoscopes, they are hung to dry in order to prevent residual water droplets impact on patient health. To allow for quick drying and clinical reuse, some endoscopic units use a high pressure air jet (HPAJ) to remove the water droplets on the endoscopes. The purpose of this study was to evaluate the excessive noise exposure with the use of HPAJ in endoscopic preparation room and to investigate the risk to occupational health. Noise assessment was taken during 7 automatic endoscopic reprocessors (AERs) and combined with/without HPAJ use over an 8-hour time-weighted average (TWA). Analytical procedures of the NIOSH and the ISO for noise-induced hearing loss were estimated to develop analytic models. The peak of the noise spectrum of combined HPAJ and 7 AERs was significantly higher than that of the 7 AERs alone ( versus  dBA, ). The risk of hearing loss (HL > 2.5 dB) was 2.15% at 90 dBA, 11.6% at 95 dBA, and 51.3% at 100 dBA. The odds ratio was 49.1 (95% CI: 11.9 to 203.6). The noise generated by the HPAJ to work over TWA seriously affected the occupational health and safety of those working in an endoscopic preparation room. King-Wah Chiu, Lung-Sheng Lu, and Cheng-Kun Wu Copyright © 2015 King-Wah Chiu et al. All rights reserved. Anemia in Inflammatory Bowel Disease Outpatients: Prevalence, Risk Factors, and Etiology Sun, 01 Feb 2015 09:34:21 +0000 Anemia is common in inflammatory bowel disease (IBD). However, epidemiological studies of nonwestern IBD populations are limited and may be confounded by demographic, socioeconomic, and disease-related influences. This study evaluated the prevalence, risk factors, and etiology of anemia in Brazilian outpatients with IBD. Methods. In this cross-sectional study, 100 Crohn’s disease (CD) patients and 100 ulcerative colitis (UC) subjects were assessed. Anemia workup included complete blood count, ferritin, transferrin saturation, serum levels of folic acid and vitamin B12, and C-reactive protein (CRP) concentration. Results. The overall prevalence of anemia in IBD was 21%. There was no significant difference in the prevalence of anemia between CD subjects (24%) and UC (18%). Moderate disease activity (OR: 3.48, 95% CI, 1.95–9.64, ) and elevated CRP levels (OR: 1.8, 95% CI, 1.04–3.11, ) were independently associated with anemia. The most common etiologies of anemia found in both groups were iron deficiency anemia (IDA; 10% on CD and 6% on UC) followed by the anemia of chronic disease (ACD; 6% for both groups). Conclusions. In Brazilian IBD outpatients, anemia is highly concurrent condition. Disease moderate activity as well as increased CRP was strongly associated with comorbid anemia. IDA and/or ACD were the most common etiologies. Carla Valéria de Alvarenga Antunes, Abrahão Elias Hallack Neto, Cristiano Rodrigo de Alvarenga Nascimento, Liliana Andrade Chebli, Ivana Lúcia Damásio Moutinho, Bruno do Valle Pinheiro, Maycon Moura Reboredo, Carla Malaguti, Antonio Carlos Santana Castro, and Júlio Maria Fonseca Chebli Copyright © 2015 Carla Valéria de Alvarenga Antunes et al. All rights reserved. Endoscopic Ultrasound-Guided Therapies in Pancreatic Neoplasms Sat, 31 Jan 2015 14:07:06 +0000 Endoscopic ultrasound (EUS) has evolved from being primarily a diagnostic modality into an interventional endoscopic tool for the management of both benign and malignant gastrointestinal illnesses. EUS-guided therapy has garnered particular interest as a minimally invasive approach for the treatment of pancreatic cancer, a disease often complicated by its aggressive course and poor survival. The potential advantage of an EUS-guided approach revolves around real-time imaging for targeted therapy of a difficult to reach organ. In this review, we focus on EUS-guided therapies for pancreatic neoplasms. Dennis Yang and Christopher J. DiMaio Copyright © 2015 Dennis Yang and Christopher J. DiMaio. All rights reserved. Label-Free Quantitative Mass Spectrometry Reveals a Panel of Differentially Expressed Proteins in Colorectal Cancer Wed, 28 Jan 2015 09:32:37 +0000 To identify potential biomarkers involved in CRC, a shotgun proteomic method was applied to identify soluble proteins in three CRCs and matched normal mucosal tissues using high-performance liquid chromatography and mass spectrometry. Label-free protein profiling of three CRCs and matched normal mucosal tissues were then conducted to quantify and compare proteins. Results showed that 67 of the 784 identified proteins were linked to CRC (28 upregulated and 39 downregulated). Gene Ontology and DAVID databases were searched to identify the location and function of differential proteins that were related to the biological processes of binding, cell structure, signal transduction, cell adhesion, and so on. Among the differentially expressed proteins, tropomyosin-3 (TPM3), endoplasmic reticulum resident protein 29 (ERp29), 18 kDa cationic antimicrobial protein (CAMP), and heat shock 70 kDa protein 8 (HSPA8) were verified to be upregulated in CRC tissue and seven cell lines through western blot analysis. Furthermore, the upregulation of TPM3, ERp29, CAMP, and HSPA8 was validated in 69 CRCs byimmunohistochemistry (IHC) analysis. Combination of TPM3, ERp29, CAMP, and HSPA8 can identify CRC from matched normal mucosal achieving an accuracy of 73.2% using IHC score. These results suggest that TPM3, ERp29, CAMP, and HSPA8 are great potential IHC diagnostic biomarkers for CRC. Nai-Jun Fan, Jiang-Ling Gao, Yan Liu, Wei Song, Zhan-Yang Zhang, and Chun-Fang Gao Copyright © 2015 Nai-Jun Fan et al. All rights reserved. A Prospective Randomized Controlled Trial of AJG522 versus Standard PEG + E as Bowel Preparation for Colonoscopy Thu, 22 Jan 2015 14:20:16 +0000 Polyethylene glycol- (PEG-) based bowel preparations for colonoscopies are often poorly tolerated due to the large volumes of fluid intake required. We compared low-volume “modified” PEG + ascorbic acid (AJG522) with standard PEG with electrolytes (PEG + E) in addition to a stimulant laxative and an agent to improve bowel function for the bowel cleansing before colonoscopy to evaluate its efficacy, safety, and acceptability. Outpatients scheduled to undergo colonoscopy were randomized to receive either AJG522 or PEG + E. Bowel cleansing conditions were assessed via macroscopic fecal findings by blinded and independent investigators. A survey of the patients’ feedback regarding the preparation was conducted by questionnaire. Successful cleansing was achieved in all cases, except for 4 cases in the PEG + E group, at 3 hours after taking the preparation. The fecal properties were significantly clearer in the AJG522 group than in the PEG + E group at 2 hours after taking each preparation . Although the total liquid volume of the bowel preparation was not reduced, the AJG522 preparation could significantly reduce the required volume of the preparation . Moreover, the patients in the AJG522 group had better acceptability . There were no significant differences in the safety profiles between groups (UMIN000013892). Toshihiko Sagawa, Ken Sato, Taku Tomizawa, Masafumi Mizuide, Hidetoshi Yasuoka, Yasuyuki Shimoyama, Shiko Kuribayashi, Satoru Kakizaki, Osamu Kawamura, Motoyasu Kusano, and Masanobu Yamada Copyright © 2015 Toshihiko Sagawa et al. All rights reserved. Correlation of Serum Levels of Endostatin with Tumor Stage in Gastric Cancer: A Systematic Review and Meta-Analysis Mon, 19 Jan 2015 07:39:31 +0000 Background. We performed a systematic review and meta-analysis to study the association between serum endostatin levels and gastric cancer (GC) progression. Method. We searched the MEDLINE, Science Citation Index, Cochrane Library, PubMed, Embase, Current Contents Index, and several Chinese databases for published studies relevant to our study topic. Carefully selected studies were pooled and SMD and its corresponding 95% CI were calculated. Version 12.0 STATA software was used for statistical analysis. Results. Serum endostatin levels were analyzed in 12 case-control studies (736 GC patients and 350 controls). Significant differences in serum endostatin levels were observed between GC patients and the healthy controls (SMD = 1.418, 95% CI = 1.079~1.757, ). Importantly, significantly lower levels of serum endostatin were found in I-II grade patients compared to those with III-IV grade tumors (). Further, higher serum endostatin levels were observed in the LN invasion-positive GC subjects in comparison with LN invasion-negative subjects (). Conclusion. Patients with GC exhibited elevated levels of serum endostatin than controls and its level showed a statistical correlation with the more aggressive type of GC, exhibiting invasion and LN metastasis. Thus, serum levels of endostatin being a useful prognostic biomarker for GC patients warrants further investigation. Zheng-Hua Wang, Zhi-Tu Zhu, Xu-Yang Xiao, and Jin Sun Copyright © 2015 Zheng-Hua Wang et al. All rights reserved. Peptic Ulcer Diseases: Genetics, Mechanism, and Therapies Sun, 28 Dec 2014 06:14:33 +0000 Seng-Kee Chuah, Deng-Chyang Wu, Hidekazu Suzuki, Khean-Lee Goh, John Kao, and Jian-Lin Ren Copyright © 2014 Seng-Kee Chuah et al. All rights reserved. Therapeutic Efficacy of pH-Dependent Release Formulation of Mesalazine on Active Ulcerative Colitis Resistant to Time-Dependent Release Formulation: Analysis of Fecal Calprotectin Concentration Tue, 18 Nov 2014 07:43:14 +0000 Purpose. Few reports have compared the clinical efficacy of a pH-dependent release formulation of mesalazine (pH-5-ASA) with a time-dependent release formulation (time-5-ASA). We examined whether pH-5-ASA is effective for active ulcerative colitis (UC) in patients resistant to time-5-ASA. Methods. We retrospectively and prospectively analyzed the efficacy of pH-5-ASA in mildly to moderately active UC patients in whom time-5-ASA did not successfully induce or maintain remission. The clinical efficacy of pH-5-ASA was assessed by clinical activity index (CAI) before and after switching from time-5-ASA. In addition, the efficacy of pH-5-ASA on mucosal healing (MH) was evaluated in a prospective manner by measuring fecal calprotectin concentration. Results. Thirty patients were analyzed in a retrospective manner. CAI was significantly reduced at both 4 and 8 weeks after switching to pH-5-ASA. In the prospective study (), administration of pH-5-ASA also significantly reduced CAI scores at 4 and 8 weeks in these patients who were resistant to time-5-ASA. In addition, fecal calprotectin concentration was significantly decreased along with improvement in CAI after switching to pH-5-ASA. Conclusions. Our results suggest that pH-5-ASA has clinical efficacy for mildly to moderately active patients with UC in whom time-5-ASA did not successfully induce or maintain remission. Kousaku Kawashima, Shunji Ishihara, Takafumi Yuki, Koji Onishi, Yoshinori Kushiyama, Hirofumi Fujishiro, Youichi Miyaoka, Mika Yuki, Yoshinori Komazawa, Takashi Tanimura, Hiroki Sonoyama, Yasumasa Tada, Ryusaku Kusunoki, Akihiko Oka, Nobuhiko Fukuba, Naoki Oshima, Ichiro Moriyama, and Yoshikazu Kinoshita Copyright © 2014 Kousaku Kawashima et al. All rights reserved. Comparison of Proton Pump Inhibitor and Histamine-2 Receptor Antagonist in the Prevention of Recurrent Peptic Ulcers/Erosions in Long-Term Low-Dose Aspirin Users: A Retrospective Cohort Study Thu, 11 Sep 2014 00:00:00 +0000 Background. Proton pump inhibitor and histamine-2 receptor antagonist can prevent aspirin-related ulcers/erosions but few studies compare the efficacy of these two agents. Aims. We evaluated the efficacy of omeprazole and famotidine in preventing recurrent ulcers/erosions in low-dose aspirin users. Methods. The 24-week clinical outcomes of the patients using low-dose aspirin for cardiovascular protection with a history of ulcers/erosions and cotherapy of omeprazole or famotidine were retrospectively reviewed. The incidence of gastrointestinal symptoms, recurrent ulcers/erosions, erosive esophagitis, gastrointestinal bleeding, and thromboembolic events was analyzed. Results. A total of 104 patients (famotidine group, 49 patients; omeprazole group, 55 patients) were evaluated. Famotidine group had more gastrointestinal symptoms episodes than omeprazole group (46.9% versus 23.6%, . Fifteen famotidine group patients and 5 omeprazole group patients had recurrent ulcers/erosions (30.6% versus 9.1%, . Lanza scale was significantly lower in omeprazole group than in famotidine group versus . Only 1 famotidine group patient had ulcer bleeding. The incidences of erosive esophagitis and thromboembolic events were comparable between both groups. Conclusions. Omeprazole was superior to famotidine with less gastrointestinal symptoms and recurrent ulcers/erosions in patients using 24-week low-dose aspirin. The risk of erosive esophagitis, gastrointestinal bleeding, and thromboembolic events was similar between both groups. Wen-Chi Chen, Yun-Da Li, Po-Hung Chiang, Feng-Woei Tsay, Hoi-Hung Chan, Wei-Lun Tsai, Tzung-Jiun Tsai, E-Ming Wang, Jin-Shiung Cheng, and Kwok-Hung Lai Copyright © 2014 Wen-Chi Chen et al. All rights reserved. Quinolone-Containing Therapies in the Eradication of Helicobacter pylori Thu, 28 Aug 2014 09:30:25 +0000 Fluoroquinolones, especially levofloxacin, are used in the eradication of Helicobacter pylori worldwide. Many consensus guidelines recommend that the second-line rescue therapy for H. pylori eradication consists of a proton pump inhibitor, a quinolone, and amoxicillin as an option. Unfortunately, quinolone is well associated with a risk of developing bacterial resistance. In this paper, we review quinolone-containing H. pylori eradication regimens and the challenges that influence the efficacy of eradication. It is generally suggested that the use of levofloxacin should be confined to “rescue” therapy only, in order to avoid a further rapid increase in the resistance of H. pylori to quinolone. The impact of quinolone-containing H. pylori eradication regimens on public health issues such as tuberculosis treatment must always be taken into account. Exposure to quinolone is relevant to delays in diagnosing tuberculosis and the development of drug resistance. Extending the duration of treatment to 14 days improves eradication rates by >90%. Tailored therapy to detect fluoroquinolone-resistant strains can be done by culture-based and molecular methods to provide better eradication rates. Molecular methods are achieved by using a real-time polymerase chain reaction to detect the presence of a gyrA mutation, which is predictive of treatment failure with quinolones-containing triple therapy. Seng-Kee Chuah, Wei-Chen Tai, Chen-Hsiang Lee, Chih-Ming Liang, and Tsung-Hui Hu Copyright © 2014 Seng-Kee Chuah et al. All rights reserved. Impact of Blood Type, Functional Polymorphism (T-1676C) of the COX-1 Gene Promoter and Clinical Factors on the Development of Peptic Ulcer during Cardiovascular Prophylaxis with Low-Dose Aspirin Wed, 27 Aug 2014 08:25:41 +0000 Aims. To investigate the impact of blood type, functional polymorphism (T-1676C) of the COX-1 gene promoter, and clinical factors on the development of peptic ulcer during cardiovascular prophylaxis with low-dose aspirin. Methods. In a case-control study including 111 low-dose aspirin users with peptic ulcers and 109 controls (asymptomatic aspirin users), the polymorphism (T-1676C) of the COX-1 gene promoter was genotyped, and blood type, H pylori status, and clinical factors were assessed. Results. Univariate analysis showed no significant differences in genotype frequencies of the COX-1 gene at position -1676 between the peptic ulcer group and control group. Multivariate analysis revealed that blood type O, advanced age, history of peptic ulcer, and concomitant use of NSAID were the independent risk factors for the development of peptic ulcer with the odds ratios of the 2.1, 3.1, 27.6, and 2.9, respectively. Conclusion. The C-1676T polymorphism in the COX-1 gene promoter is not a risk factor for ulcer formation during treatment with low-dose aspirin. Blood type O, advanced age, history of peptic ulcer, and concomitant use of NSAID are of independent significance in predicting peptic ulcer development during treatment with low-dose aspirin. Pin-Yao Wang, Hsiu-Ping Chen, Angela Chen, Feng-Woei Tsay, Kwok-Hung Lai, Sung-Shuo Kao, Wen-Chi Chen, Chao-Hung Kuo, Nan-Jing Peng, Hui-Hwa Tseng, and Ping-I Hsu Copyright © 2014 Pin-Yao Wang et al. All rights reserved. Different Clinical Utility of Oropharyngeal Bacterial Screening prior to Percutaneous Endoscopic Gastrostomy in Oncological and Neurological Patients Wed, 27 Aug 2014 07:09:32 +0000 Background. The aim of this study was to monitor oropharyngeal bacterial colonization in patients indicated for percutaneous endoscopic gastronomy (PEG). Methods. Oropharyngeal swabs were obtained from patients prior to PEG placement. A development of peristomal infection was evaluated. The analysis of oropharyngeal and peristomal site pathogens was done. Results. Consecutive 274 patients referred for PEG due to neurological disorder or cancer completed the study. Oropharyngeal colonization with pathogens was observed in 69% (190/274), dominantly in the neurologic subgroup of patients (P < 0.001). Peristomal infection occurred in 30 (10.9%) of patients and in 57% of them the correlation between oropharyngeal and peristomal agents was present. The presence of oropharyngeal pathogens was assessed as an important risk factor for the development of peristomal infection only in oncological patients (OR = 8.33, 95% CI: 1.66–41.76). Despite a high prevalence of pathogens in neurological patients, it did not influence the risk of peristomal infection with the exception for methicillin resistant Staphylococcus aureus (MRSA) carriers (OR 4.5, 95% CI: 1.08–18.76). Conclusion. During oropharyngeal microbial screening prior to the PEG insertion, the detection of pathogens may be a marker of the increased risk of peristomal infection in cancer patients only. In neurological patients the benefit of the screening is limited to the detection of MRSA carriers. Radek Kroupa, Jana Jurankova, Milan Dastych, Michal Senkyrik, Tomas Pavlik, Jitka Prokesova, Marketa Jecmenova, Jiri Dolina, and Ales Hep Copyright © 2014 Radek Kroupa et al. All rights reserved. The Relationship between Helicobacter pylori and Beta-2 Microglobulin in Humans Wed, 27 Aug 2014 06:00:42 +0000 H. pylori is related to various gastrointestinal diseases. Microglobulin (M) is an intrinsic element of major histocompatibility complex (MHC I). Serum M level may increase in inflammatory states. The aim of current study is to evaluate the relationship between M and H. pylori bearing CagA strains. Methods. H. pylori status was determined by histopathology of samples taken from stomach. CagA status and M level were measured from blood samples of patients. Eradication therapy was administered to the patients with H. pylori infection. Microglobulin levels were measured before and after treatment. Results. 35 (29.2%) H. pylori(−) patients and 85 (70.8%) H. pylori (+) patients were included in the study. There were 52 (43.3%) patients with CagA negative and 33 (27.5%) patients with CagA positive H. pylori infection. The mean serum M level was 1.83 mg/L in H. pylori (−) group, 1.76 mg/L in H. pylori (+) CagA (−) group, and 1.93 mg/L in H. pylori and CagA (+) group (). Serum M levels (1.82 versus 1.64 mg/L ) were decreased after eradication. Conclusion. H. pylori and CagA status did not affect M level. Relationship between low grade systematic inflammation and H. pylori should be investigated to find out new predictors for diseases associated with inflammation. Abdullah Özgür Yeniova, Metin Kucukazman, Naim Ata, Kursat Dal, Ayşe Kefeli, Sebahat Başyiğit, Bora Aktaş, Kadir Okhan Akın, and Yaşar Nazlıgül Copyright © 2014 Abdullah Özgür Yeniova et al. All rights reserved. Comparison of Hemostatic Efficacy of Argon Plasma Coagulation with and without Distilled Water Injection in Treating High-Risk Bleeding Ulcers Wed, 27 Aug 2014 00:00:00 +0000 Background. Argon plasma coagulation (APC) is useful to treat upper gastrointestinal bleeding, but its hemostatic efficacy has received little attention. Aims. This investigation attempted to determine whether additional endoscopic injection before APC could improve hemostatic efficacy in treating high-risk bleeding ulcers. Methods. From January 2007 to April 2011, adult patients with high-risk bleeding ulcers were included. This investigation compared APC plus distilled water injection (combined group) to APC alone for treating high-risk bleeding ulcers. Outcomes were assessed based on initial hemostasis, surgery, blood transfusion, hospital stay, rebleeding, and mortality at 30 days posttreatment. Results. Totally 120 selected patients were analyzed. Initial hemostasis was accomplished in 59 patients treated with combined therapy and 57 patients treated with APC alone. No significant differences were noted between these groups in recurred bleeding, emergency surgery, 30-day mortality, hospital stay, or transfusion requirements. Comparing the combined end point of mortality plus the failure of initial hemostasis, rebleeding, and the need for surgery revealed an advantage for the combined group . Conclusions. Endoscopic therapy with APC plus distilled water injection was no more effective than APC alone in treating high-risk bleeding ulcers, whereas combined therapy was potentially superior for patients with poor overall outcomes. Yuan-Rung Li, Ping-I Hsu, Huay-Min Wang, Hoi-Hung Chan, Kai-Ming Wang, Wei-Lun Tsai, Hsien-Chung Yu, and Feng-Woei Tsay Copyright © 2014 Yuan-Rung Li et al. All rights reserved. Rhubarb Tannins Extract Inhibits the Expression of Aquaporins 2 and 3 in Magnesium Sulphate-Induced Diarrhoea Model Mon, 18 Aug 2014 11:10:52 +0000 Tannins, a group of major active components of Chinese rhubarb and widely distributed in nature, have a significant antidiarrhoeal activity. Aquaporins (AQPs) 2 and 3 play important roles in regulating water transfer during diarrhoea. The present study aims to determine the effect of the total tannins extract of rhubarb on aquaporins (AQPs) 2 and 3 in diarrhoea mice and HT-29 cells both induced by magnesium sulphate (MgSO4). Our results showed that rhubarb tannins extract (RTE) significantly decreased the faecal water content in colon and evaluation index of defecation of diarrhoea mice. Interestingly, RTE could markedly reduce the mRNA and protein expression levels of AQPs 2 and 3 in apical and lateral mucosal epithelial cells in the colons of diarrhoea mice and HT-29 cells both induced by MgSO4 in a dose-dependent manner. Furthermore, RTE suppressed the production of cyclic monophosphate- (cAMP-) dependent protein kinase A catalytic subunits α (PKA C-α) and phosphorylated cAMP response element-binding protein (p-CREB, Ser133) in MgSO4-induced HT-29 cells. Our data showed for the first time that RTE inhibit AQPs 2 and 3 expression in vivo and in vitro via downregulating PKA/p-CREB signal pathway, which accounts for the antidiarrhoeal effect of RTE. Chunfang Liu, Yanfang Zheng, Wen Xu, Hui Wang, and Na Lin Copyright © 2014 Chunfang Liu et al. All rights reserved. Consensus on Control of Risky Nonvariceal Upper Gastrointestinal Bleeding in Taiwan with National Health Insurance Thu, 14 Aug 2014 00:00:00 +0000 Background and Aims. To compose upper gastrointestinal bleeding (UGIB) consensus from a nationwide scale to improve the control of UGIB, especially for the high-risk comorbidity group. Methods. The steering committee defined the consensus scope to cover preendoscopy, endoscopy, postendoscopy, and overview from Taiwan National Health Insurance Research Database (NHIRD) assessments for UGIB. The expert group comprised thirty-two Taiwan experts of UGIB to conduct the consensus conference by a modified Delphi process through two separate iterations to modify the draft statements and to vote anonymously to reach consensus with an agreement ≥80% for each statement and to set the recommendation grade. Results. The consensus included 17 statements to highlight that patients with comorbidities, including liver cirrhosis, end-stage renal disease, probable chronic obstructive pulmonary disease, and diabetes, are at high risk of peptic ulcer bleeding and rebleeding. Special considerations are recommended for such risky patients, including raising hematocrit to 30% in uremia or acute myocardial infarction, aggressive acid secretory control in high Rockall scores, monitoring delayed rebleeding in uremia or cirrhosis, considering cycloxygenase-2 inhibitors plus PPI for pain control, and early resumption of antiplatelets plus PPI in coronary artery disease or stroke. Conclusions. The consensus comprises recommendations to improve care of UGIB, especially for high-risk comorbidities. Bor-Shyang Sheu, Chun-Ying Wu, Ming-Shiang Wu, Cheng-Tang Chiu, Chun-Che Lin, Ping-I Hsu, Hsiu-Chi Cheng, Teng-Yu Lee, Hsiu-Po Wang, and Jaw-Town Lin Copyright © 2014 Bor-Shyang Sheu et al. All rights reserved. The Utilization of a New Immunochromatographic Test in Detection of Helicobacter pylori Antibody from Maternal and Umbilical Cord Serum Thu, 07 Aug 2014 07:02:17 +0000 Background. Helicobacter pylori (H. pylori) was linked with several extragastrointestinal diseases, including preeclampsia and intrauterine growth restriction of fetus. One of the signals which can be transferred from mother to fetus is the H. pylori IgG antibody. Aims. We utilized a commercial immunochromatographic kit to detect the antibody in maternal and cord serum. Methods. Three hundred and forty-six females were enrolled and the blood samples were collected on antenatal examination and on delivery. The maternal H. pylori infection was determined by stool H. pylori antigen test. Results. One hundred and five females (30.3%) were H. pylori-infected, and the prevalence was higher in immigrants (43.5%) than in Taiwanese (28.7%, ). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the kit were 77.1%, 88.0%, 73.6%, 89.8%, and 84.7%, respectively. This kit also had similar performance in cord serum. Comparing to the maternal result on delivery, this kit offered a consistent performance in antenatal maternal serum (kappa coefficient 0.92) and in cord serum (kappa coefficient 0.88). Conclusions. H. pylori IgG antibody can be transferred through the placenta into the fetal circulation. However, accuracy of the test kit needs to be evaluated before utilization in screening. Fu-Chen Kuo, Chien-Yi Wu, Chao-Hung Kuo, Chia-Fang Wu, Chien-Yu Lu, Yen-Hsu Chen, Chiao-Yun Chen, Yi-Ching Lo, Ming-Tsang Wu, and Huang-Ming Hu Copyright © 2014 Fu-Chen Kuo et al. All rights reserved. Novel Targets and Small Molecular Interventions for Liver Cancer Mon, 04 Aug 2014 06:59:51 +0000 Chunping Jiang, Youmin Wu, Jian Zhou, and Jingmin Zhao Copyright © 2014 Chunping Jiang et al. All rights reserved. Predicting the Progress of Caustic Injury to Complicated Gastric Outlet Obstruction and Esophageal Stricture, Using Modified Endoscopic Mucosal Injury Grading Scale Mon, 04 Aug 2014 06:55:04 +0000 Severe caustic injury to the gastrointestinal tract carries a high risk of luminal strictures. The aim of this retrospective study was to identify predicting factors for progress of caustic injury to gastric outlet obstruction (GOO) and esophageal strictures (ES), using modified endoscopic mucosal injury grading scale. We retrospectively reviewed medical records of patients with caustic injuries to the gastrointestinal tract in our hospital in the past 7 years. We enrolled 108 patients (49 male, 59 female, mean age 50.1 years, range 18–86) after applying strict exclusion criteria. All patients received early upper gastrointestinal endoscopy within 24 hours of ingestion. Grade III stomach injuries were found in 58 patients (53.7%); 43 (39.8%) esophageal, and 13 (12%) duodenal. Of the 108 patients, 10 (9.3%) died during the acute stage. Age over 60 years (OR 4.725, ) was an independent risk factor of mortality for patients after corrosive injury. Among the 98 survivors, 36 developed luminal strictures (37.1%): ES in 18 patients (18.6%), GOO in 7 (7.2%), and both ES and GOO in 11 (11.3%). Grade III esophageal (OR 3.079, ) or stomach (OR 18.972, ) injuries were independent risk factors for obstructions. Age ≥60 years was the independent risk factor for mortality after corrosive injury of GI tract. Grade III injury of esophagus was the independent risk factor for development of ES. Grade III injury of stomach was the independent risk factor for development of GOO. Lung-Sheng Lu, Wei-Chen Tai, Ming-Luen Hu, Keng-Liang Wu, and Yi-Chun Chiu Copyright © 2014 Lung-Sheng Lu et al. All rights reserved. Human Umbilical Cord Perivascular Cells Exhibited Enhanced Migration Capacity towards Hepatocellular Carcinoma in Comparison with Bone Marrow Mesenchymal Stromal Cells: A Role for Autocrine Motility Factor Receptor Wed, 23 Jul 2014 11:11:00 +0000 Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Unfortunately, the incidence and mortality associated with HCC are increasing. Therefore, new therapeutic strategies are urgently needed and the use of mesenchymal stromal cells (MSCs) as carrier of therapeutic genes is emerging as a promising option. Different sources of MSCs are being studied for cell therapy and bone marrow-derived cells are the most extensively explored; however, birth associated-tissues represent a very promising source. The aim of this work was to compare the in vitro and in vivo migration capacity between bone marrow MSCs (BM-MSCs) and human umbilical cord perivascular cells (HUCPVCs) towards HCC. We observed that HUCPVCs presented higher in vitro and in vivo migration towards factors released by HCC. The expression of autocrine motility factor (AMF) receptor, genes related with the availability of the receptor on the cell surface (caveolin-1 and -2) and metalloproteinase 3, induced by the receptor activation and important for cell migration, was increased in HUCPVCs. The chemotactic response towards recombinant AMF was increased in HUCPVCs compared to BM-MSCs, and its inhibition in the conditioned medium from HCC induced higher decrease in HUCPVC migration than in BM-MSC. Our results indicate that HUCPVCs could be a useful cellular source to deliver therapeutic genes to HCC. Juan Bayo, Esteban Fiore, Jorge B. Aquino, Mariana Malvicini, Manglio Rizzo, Estanislao Peixoto, Laura Alaniz, Flavia Piccioni, Marcela Bolontrade, Osvaldo Podhajcer, Mariana G. Garcia, and Guillermo Mazzolini Copyright © 2014 Juan Bayo et al. All rights reserved. Decreased Gastric Motility in Type II Diabetic Patients Wed, 23 Jul 2014 07:15:01 +0000 Background. To differentiate gastric motility and sensation between type II diabetic patients and controls and explore different expressions of gastric motility peptides. Methods. Eleven type II diabetic patients and health volunteers of similar age and body mass index were invited. All underwent transabdominal ultrasound for gastric motility and visual analogue scales. Blood samples were taken for glucose and plasma peptides (ghrelin, motilin, and glucacon-like peptides-1) by ELISA method. Results. Gastric emptying was significantly slower in diabetic patients than controls (T50: 46.3 (28.0–52.3) min versus 20.8 (9.6–22.8) min, ) and less antral contractions in type II diabetic patients were observed . Fundus dimensions did not differ. There were a trend for less changes in gastrointestinal sensations in type II diabetic patients especially abdomen fullness, hunger, and abdominal discomfort. Although the serum peptides between the two groups were similar a trend for less serum GLP-1in type II diabetic patients was observed . Conclusion. Type II diabetic patients have delayed gastric emptying and less antral contractions than controls. The observation that there were lower serum GLP-1 in type II diabetic patients could offer a clue to suggest that delayed gastric emptying in diabetic patients is not mainly influenced by GLP-1. Yi-Chun Chiu, Ming-Chun Kuo, Christopher K. Rayner, Jung-Fu Chen, Keng-Liang Wu, Yeh-Pin Chou, Wei-Chen Tai, and Ming-Luen Hu Copyright © 2014 Yi-Chun Chiu et al. All rights reserved. Ablative Therapy for Esophageal Dysplasia and Early Malignancy: Focus on RFA Mon, 21 Jul 2014 10:31:17 +0000 Ablative therapies have been utilized with increasing frequency for the treatment of Barrett’s esophagus with and without dysplasia. Multiple modalities are available for topical ablation of the esophagus, but radiofrequency ablation (RFA) remains the most commonly used. There have been significant advances in technique since the introduction of RFA. The aim of this paper is to review the indications, techniques, outcomes, and most common complications following esophageal ablation with RFA. Rebecca Tuttle, Steven J. Nurkin, and Steven N. Hochwald Copyright © 2014 Rebecca Tuttle et al. All rights reserved. Genome-Wide Uncovering of STAT3-Mediated miRNA Expression Profiles in Colorectal Cancer Cell Lines Sun, 13 Jul 2014 09:14:34 +0000 Colorectal cancer (CRC) is one of the most common malignancies resulting in high mortality worldwide. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor which is frequently activated and aberrantly expressed in CRC. MicroRNAs (miRNAs) are a class of small noncoding RNAs which play important roles in many cancers. However, little is known about the global miRNA profiles mediated by STAT3 in CRC cells. In the present study, we applied RNA interference to inhibit STAT3 expression and profiled the miRNA expression levels regulated by STAT3 in CRC cell lines with deep sequencing. We found that 26 and 21 known miRNAs were significantly overexpressed and downexpressed, respectively, in the STAT3-knockdown CRC cell line SW480 (SW480/STAT3-siRNA) compared to SW480 transfected with scrambled siRNAs (SW480/siRNA-control). The miRNA expression profiling was then validated by quantitative real-time PCR for selected known miRNAs. We further predicted the putative target genes for the dysregulated miRNAs and carried out functional annotation including GO enrichment and KEGG pathway analysis for selected miRNA targets. This study directly depicts STAT3-mediated miRNA profiles in CRC cells, which provides a possible way to discover biomarkers for CRC therapy. Jufeng Zhang, Xia Luo, Huiming Li, Ling Deng, and Ying Wang Copyright © 2014 Jufeng Zhang et al. All rights reserved. Dehydroabietic Acid Derivative QC2 Induces Oncosis in Hepatocellular Carcinoma Cells Sun, 06 Jul 2014 07:34:37 +0000 Aim. Rosin, the traditional Chinese medicine, is reported to be able to inhibit skin cancer cell lines. In this report, we investigate the inhibitory effect against HCC cells of QC2, the derivative of rosin’s main components dehydroabietic acid. Methods. MTT assay was used to determine the cytotoxicity of QC2. Morphological changes were observed by time-lapse microscopy and transmission electron microscopy and the cytoskeleton changes were observed by laser-scanning confocal microscopy. Cytomembrane integrity and organelles damage were confirmed by detection of the reactive oxygen (ROS), lactate dehydrogenase (LDH), and mitochondrial membrane potential (Δψm). The underlying mechanism was manifested by Western blotting. The oncotic cell death was further confirmed by detection of oncosis related protein calpain. Results. Swelling cell type and destroyed cytoskeleton were observed in QC2-treated HCC cells. Organelle damage was visualized by transmission electron microscopy. The detection of ROS accumulation, increased LDH release, and decreased ATP and Δψm confirmed the cell death. The oncotic related protein calpain was found to increase time-dependently in QC2-treated HCC cells, while its inhibitor PD150606 attenuated the cytotoxicity. Conclusions. Dehydroabietic acid derivative QC2 activated oncosis related protein calpain to induce the damage of cytomembrane and organelles which finally lead to oncosis in HCC cells. Guang Zhang, Chunping Jiang, Zhongxia Wang, Weibo Chen, Wen Gu, and Yitao Ding Copyright © 2014 Guang Zhang et al. All rights reserved. The Role of Hypoxia Inducible Factor-1 in Hepatocellular Carcinoma Wed, 02 Jul 2014 11:49:41 +0000 Hypoxia is a common feature of many solid tumors, including hepatocellular carcinoma (HCC). Hypoxia can promote tumor progression and induce radiation and chemotherapy resistance. As one of the major mediators of hypoxic response, hypoxia inducible factor-1 (HIF-1) has been shown to activate hypoxia-responsive genes, which are involved in multiple aspects of tumorigenesis and cancer progression, including proliferation, metabolism, angiogenesis, invasion, metastasis and therapy resistance. It has been demonstrated that a high level of HIF-1 in the HCC microenvironment leads to enhanced proliferation and survival of HCC cells. Accordingly, overexpression, of HIF-1 is associated with poor prognosis in HCC. In this review, we described the mechanism by which HIF-1 is regulated and how HIF-1 mediates the biological effects of hypoxia in tissues. We also summarized the latest findings concerning the role of HIF-1 in the development of HCC, which could shed light on new therapeutic approaches for the treatment of HCC. Dongjun Luo, Zhongxia Wang, Junyi Wu, Chunping Jiang, and Junhua Wu Copyright © 2014 Dongjun Luo et al. All rights reserved. Outcome of Holiday and Nonholiday Admission Patients with Acute Peptic Ulcer Bleeding: A Real-World Report from Southern Taiwan Tue, 01 Jul 2014 11:54:25 +0000 Background. Recent findings suggest that patients admitted on the weekend with peptic ulcer bleeding might be at increased risk of adverse outcomes. However, other reports found that there was no “holiday effect.” The purpose of this study was to determine if these findings hold true for a real-life Taiwanese medical gastroenterology practice. Materials and Methods. We reviewed the medical files of hospital admissions for patients with peptic ulcer bleeding who received initial endoscopic hemostasis between January 2009 and March 2011. A total of 744 patients were enrolled (nonholiday group, ; holiday group, ) after applying strict exclusion criteria. Holidays were defined as weekends and national holidays in Taiwan. Results. Our results showed that there was no significant difference in baseline characteristics between the two groups. We also observed that, compared to the nonholiday group, patients in the holiday group received earlier endoscopy treatment (12.20 hours versus 16.68 hours, ), needed less transfused blood (4.8 units versus 6.6 units, ), shifted from intravenous to oral proton-pump inhibitors (PPIs) more quickly (5.3 days versus 6.9 days, ), and had shorter hospital stays (13.05 days versus 17.36 days, ). In the holiday and nonholiday groups, the rebleeding rates were 17.8% and 23.41% (), the mortality rates were 11.63% versus 13.66% (), and surgery was required in 2.11% versus 4.66% (), respectively. Conclusions. Patients who presented with peptic ulcer bleeding on holidays did not experience delayed endoscopy or increased adverse outcomes. In fact, patients who received endoscopic hemostasis on the holiday had shorter waiting times, needed less transfused blood, switched to oral PPIs quicker, and experienced shorter hospital stays. Tsung-Chin Wu, Seng-Kee Chuah, Kuo-Chin Chang, Cheng-Kun Wu, Chung-Huang Kuo, Keng-Liang Wu, Yi-Chun Chiu, Tsung-Hui Hu, and Wei-Chen Tai Copyright © 2014 Tsung-Chin Wu et al. All rights reserved. Diagnosis, Treatment, and Outcome in Patients with Bleeding Peptic Ulcers and Helicobacter pylori Infections Mon, 30 Jun 2014 11:56:09 +0000 Upper gastrointestinal (UGI) bleeding is the most frequently encountered complication of peptic ulcer disease. Helicobacter pylori (Hp) infection and nonsteroidal anti-inflammatory drug (NSAID) administration are two independent risk factors for UGI bleeding. Therefore, testing for and diagnosing Hp infection are essential for every patient with UGI hemorrhage. The presence of the infection is usually underestimated in cases of bleeding peptic ulcers. A rapid urease test (RUT), with or without histology, is usually the first test performed during endoscopy. If the initial diagnostic test is negative, a delayed 13C-urea breath test (UBT) or serology should be performed. Once an infection is diagnosed, antibiotic treatment is advocated. Sufficient evidence supports the concept that Hp infection eradication can heal the ulcer and reduce the likelihood of rebleeding. With increased awareness of the effects of Hp infection, the etiologies of bleeding peptic ulcers have shifted to NSAID use, old age, and disease comorbidity. Ting-Chun Huang and Chia-Long Lee Copyright © 2014 Ting-Chun Huang and Chia-Long Lee. All rights reserved. Neuroendocrine Differentiation Is a Prognostic Factor for Stage II Poorly Differentiated Colorectal Cancer Sun, 29 Jun 2014 08:31:49 +0000 Neuroendocrine differentiation (NED) in colorectal cancer is an indistinct phenomenon and may define a new cancer subtype, especially in the poorly differentiated colorectal cancer (PDCRC). The clinical features of PDCRC with NED remain controversial, thus confusing the implementation of individualized treatment. This study included 171 patients who underwent surgery from 2000 to 2011 and had pathology-confirmed PDCRC. Each sample was examined by immunohistochemistry for the biological markers of NED, synaptophysin (Syn), and chromogranin (CgA). Patients with Syn(+) and/or CgA(+) cells were classified as NED(+); otherwise, they were NED(−). Data were collected for patients who were followed up for at least two years. NED(+) staining was present in 71 (41.5%) patients. The median survival time was 36.9 months. No survival differences existed between the NED(−) and NED(+) groups . However, stage II NED(+) patients had a significantly worse prognosis than NED(−) patients . For the NED(+) group, the median survival was 38.56 months, and the 5-year survival was 65%. For the NED(−) group, the median survival was 53.18 months, and the 5-year survival was 90%. NED is a common event in primary PDCRC. For stage II PDCRC, NED(+) indicates a poor prognosis. Yue Liu, Jinghong Xu, Yurong Jiao, Yeting Hu, Chenghao Yi, Qiong Li, Zhou Tong, Xiaowei Wang, Lifeng Hu, Qian Xiao, Jun Li, and Kefeng Ding Copyright © 2014 Yue Liu et al. All rights reserved. Ablative Therapies for Colorectal Polyps and Malignancy Thu, 26 Jun 2014 00:00:00 +0000 Endoscopic techniques are gaining popularity in the management of colorectal polyps and occasionally superficial cancers. While their use is in many times palliative, they have proven to be curative in carefully selected patients with polyps or malignancies, with less morbidity than radical resection. However, one should note that data supporting local and ablative therapies for colorectal cancer is scarce and may be subject to publication bias. Therefore, for curative intent, these techniques should only be considered in highly select cases as higher rates of local recurrences have also been reported. The aim of this review is to explain the different modalities of local and ablative therapies specific to colorectal neoplasia and explain the indications and circumstances where they have been most successful. Jacqueline Oxenberg, Steven N. Hochwald, and Steven Nurkin Copyright © 2014 Jacqueline Oxenberg et al. All rights reserved. The Effect of Helicobacter pylori Eradication on the Levels of Essential Trace Elements Thu, 26 Jun 2014 00:00:00 +0000 Objective. This study was designed to compare the effect of Helicobacter pylori (H. pylori) infection treatment on serum zinc, copper, and selenium levels. Patients and Methods. We measured the serum zinc, copper, and selenium levels in H. pylori-positive and H. pylori-negative patients. We also evaluated the serum levels of these trace elements after H. pylori eradication. These serum copper, zinc, and selenium levels were determined by inductively coupled plasma mass spectrometry. Results. Sixty-three H. pylori-positive patients and thirty H. pylori-negative patients were studied. Serum copper, zinc, and selenium levels had no significant difference between H. pylori-positive and H. pylori-negative groups. There were 49 patients with successful H. pylori eradication. The serum selenium levels were lower after successful H. pylori eradication, but not significantly (). There were 14 patients with failed H. pylori eradication. In this failed group, the serum selenium level after H. pylori eradication therapy was significantly lower than that before H. pylori eradication therapy (). The serum zinc and copper levels had no significant difference between before and after H. pylori eradication therapies. Conclusion. H pylori eradication regimen appears to influence the serum selenium concentration (IRB number: KMUH-IRB-20120327). Meng-Chieh Wu, Chun-Yi Huang, Fu-Chen Kuo, Wen-Hung Hsu, Sophie S. W. Wang, Hsiang-Yao Shih, Chung-Jung Liu, Yen-Hsu Chen, Deng-Chyang Wu, Yeou-Lih Huang, and Chien-Yu Lu Copyright © 2014 Meng-Chieh Wu et al. All rights reserved. Hepatic Stellate Cell Coculture Enables Sorafenib Resistance in Huh7 Cells through HGF/c-Met/Akt and Jak2/Stat3 Pathways Wed, 25 Jun 2014 11:44:57 +0000 Purpose. Tumor microenvironment confers drug resistance to kinase inhibitors by increasing RKT ligand levels that result in the activation of cell-survival signaling including PI3K and MAPK signals. We assessed whether HSC-LX2 coculture conferred sorafenib resistance in Huh7 and revealed the mechanism underlying the drug resistance. Experimental Design. The effect of LX2 on sorafenib resistance was determined by coculture system with Huh7 cells. The rescue function of LX2 supernatants was assessed by MTT assay and fluorescence microscopy. The underlying mechanism was tested by administration of pathway inhibitors and manifested by Western blotting. Results. LX2 coculture significantly induced sorafenib resistance in Huh7 by activating p-Akt that led to reactivation of p-ERK. LX2 secreted HGF into the culture medium that triggered drug resistance, and exogenous HGF could also induce sorafenib resistance. The inhibition of p-Akt blocked sorafenib resistance caused by LX2 coculture. Increased phosphorylation of Jak2 and Stat3 was also detected in LX2 cocultured Huh7 cells. The Jak inhibitor tofacitinib reversed sorafenib resistance by blocking Jak2 and Stat3 activation. The combined administration of sorafenib and p-Stat3 inhibitor S3I-201 augmented induced apoptosis even in the presence of sorafenib resistance. Conclusions. HSC-LX2 coculture induced sorafenib resistance in Huh7 through multiple pathways: HGF/c-Met/Akt pathway and Jak2/Stat3 pathway. A combined administration of sorafenib and S3I-201 was able to augment sorafenib-induced apoptosis even in the presence of LX2 coculture. Weibo Chen, Junhua Wu, Hua Shi, Zhongxia Wang, Guang Zhang, Yin Cao, Chunping Jiang, and Yitao Ding Copyright © 2014 Weibo Chen et al. All rights reserved. Maintenance Therapy with Partially Hydrolyzed Guar Gum in the Conservative Treatment of Chronic Anal Fissure: Results of a Prospective, Randomized Study Wed, 25 Jun 2014 08:07:06 +0000 Purpose. This study was designed to evaluate the role of maintenance therapy with partially hydrolyzed guar gum (PHGG) after topical application of glyceryl trinitrate (GTN) in the conservative treatment of chronic anal fissure (CAF). Methods. From all the patients with CAF observed during the study period, 165 subjects with healed CAF after standard therapy with topical GTN 0.4% ointment were randomized to receive (group II) or not (group I) maintenance therapy with PHGG for 10 months. Clinical and manometric followup was carried out 6 and 12 months after treatment. Results. At six-month followup, median visual analogue scale score was significantly higher in group I if compared with group II. The success and recurrence rate at 12-month followup were, respectively, 38.3% (28/73) in group I versus 58.5% (41/70) in group II (; Fisher’s exact test) and 30.2% (13/43) in group I versus 14.5% (7/48) in group II (; Fisher’s exact test). Conclusion. The maintenance therapy with PHGG in patients with healed CAF after chemical sphincterotomy by topical application of GTN 0.4% ointment seems associated with a significant reduction of recurrence rate and with a significant increase of success rate at 12-month followup. Antonio Brillantino, Francesca Iacobellis, Giuseppe Izzo, Natale Di Martino, Roberto Grassi, and Adolfo Renzi Copyright © 2014 Antonio Brillantino et al. All rights reserved. Hepatocellular Carcinoma: Novel Molecular Targets in Carcinogenesis for Future Therapies Wed, 25 Jun 2014 07:25:56 +0000 Background. Hepatocellular carcinoma is one of the most common and lethal malignant tumors worldwide. Over the past 15 years, the incidence of HCC has more than doubled. Due to late diagnosis and/or advanced underlying liver cirrhosis, only limited treatment options with marginal clinical benefit are available in up to 70% of patients. During the last decades, no effective conventional cytotoxic systemic therapy was available contributing to the dismal prognosis in patients with HCC. A better knowledge of molecular hepatocarcinogenesis provides today the opportunity for targeted therapy. Materials and Methods. A search of the literature was made using cancer literature, the PubMed, Scopus, and Web of Science (WOS) database for the following keywords: “hepatocellular carcinoma,” “molecular hepatocarcinogenesis,” “targeted therapy,” and “immunotherapy.” Discussion and Conclusion. Treatment decisions are complex and dependent upon tumor staging, presence of portal hypertension, and the underlying degree of liver dysfunction. The knowledge of molecular hepatocarcinogenesis broadened the horizon for patients with advanced HCC. During the last years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. In the future, new therapeutic options will be represented by a blend of immunotherapy-like vaccines and T-cell modulators, supplemented by molecularly targeted inhibitors of tumor signaling pathways. Gaetano Bertino, Shirin Demma, Annalisa Ardiri, Maria Proiti, Salvatore Gruttadauria, Adriana Toro, Giulia Malaguarnera, Nicoletta Bertino, Michele Malaguarnera, Mariano Malaguarnera, and Isidoro Di Carlo Copyright © 2014 Gaetano Bertino et al. All rights reserved. Strontium Chloride: Can It Be a New Treatment Option for Ulcerative Colitis? Wed, 18 Jun 2014 10:29:04 +0000 Background/Aims. Patients with ulcerative colitis still need effective therapy without major side effects. It has been found that strontium can suppress NFκB activation induced by TNF-α. This opens a gate to a new anti-TNF agent which is cheap and can be given orally. We for the first time aimed to investigate the effect of strontium chloride (SrCl2) on inflammation in experimental colitis. Methods. Thirty female Wistar albino rats were divided into 5 groups each containing 6 rats. The rats in groups 1 and 2 served as the healthy control and colitis group, respectively. The rats in groups 3, 4, and 5 had colitis and received 40 mg/kg SrCl2, 160 mg/kg SrCl2, and 1 mg/kg prednisolone by oral gavage, respectively. The rats were sacrificed for histological evaluation and determination of serum neopterin, TNF-α, and IFN-γ levels. Results. The neopterin, TNF-α and IFNγ levels of group 2 was significantly higher than the other groups. The neopterin, TNF-α, and IFN-γ levels of controls and other treatment groups were comparable. There were a significant difference in macroscopic and microscopic healing between group 2 and other groups histologically. But there was not a significant difference within treatment receiving groups. Conclusion. SrCl2 had comparable therapeutic efficiency with prednisolone. Firdevs Topal, Ozlem Yonem, Nevin Tuzcu, Mehmet Tuzcu, Hilmi Ataseven, and Melih Akyol Copyright © 2014 Firdevs Topal et al. All rights reserved. Pepsinogen II Can Be a Potential Surrogate Marker of Morphological Changes in Corpus before and after H. pylori Eradication Tue, 17 Jun 2014 06:56:04 +0000 Background. The aim of this investigation is to study the relationship between gastric morphology and serum biomarkers before and after Helicobacter pylori eradication. Methods. First-degree relatives of gastric cancer patients underwent gastroscopy before and 2.5 years after H. pylori eradication. The morphological changes in two categories (normal to mild and moderate to severe) were compared with level of pepsinogens I and II before eradication (), after eradication (), and in those with persistent infection (). Results: After eradication, pepsinogen I decreased to 70% and pepsinogen II to 45% of the previous values. Unlike pepsinogen II and pepsinogen I to II ratio that were affected by the severity of inflammation and atrophy in corpus in all groups, pepsinogen I generally did not change. After eradication, subjects with high mononuclear infiltration in corpus had lower pepsinogen I (54 versus 77.1 μ/mL), higher pepsinogen II (9.4 versus 6.9 μ/mL), and lower ratio (7.9 versus 11.6) than those without (). Conclusion. Pepsinogen II is a good marker of corpus morphological changes before and after H. pylori eradication. Sadegh Massarrat, Arghavan Haj-Sheykholeslami, Ashraf Mohamadkhani, Nasrin Zendehdel, Ali Aliasgari, Naser Rakhshani, Manfred Stolte, and Seyed Mehdi Shahidi Copyright © 2014 Sadegh Massarrat et al. All rights reserved. Differential Expression of Cholecystokinin A Receptor in Gallbladder Cancer in the Young and Elderly Suggests Two Subsets of the Same Disease? Sun, 15 Jun 2014 11:39:18 +0000 Background. Cholecystokinin type A receptor (CCKAR) is known to be overexpressed in variety of human malignancies but information regarding its expression in gallbladder cancer (GBC) is limited. Attempts were now made to investigate expression pattern of CCKAR mRNA and protein in controls and GBC patients and correlate it with various clinicopathological parameters following surgical resection. Materials and Methods. Gallbladder tissue samples from 64 subjects (GBC: 39; control: 25) were studied. Expression of CCKAR mRNA was evaluated by reverse transcriptase-polymerase chain reaction and confirmed using real-time polymerase chain reaction. Protein expression was studied by enzyme-linked immunosorbent assay. Results. Significantly higher expression of CCKAR mRNA and protein was observed in GBC tissues. Overexpression was also observed for stage III and in moderately and poorly differentiated tumors. When the clinicopathological parameters were compared, we found age dependent decrease in CCKAR expression. Relatively higher expression of CCKAR was observed in younger patients (age < 45 years) having more aggressive disease when compared with elderly ones (age ≥ 45 years). Conclusions. Age related differential expression of CCKAR in GBC may suggest two possible variants of the disease in this endemic belt. Hasan Raza Kazmi, Abhijit Chandra, Kavita Baghel, Anshuman Singh, Jaya Nigam, Devendra Parmar, Abbas Ali Mahdi, Sudhir K. Goel, and Sandeep Kumar Copyright © 2014 Hasan Raza Kazmi et al. All rights reserved. A Critical Role for ZDHHC2 in Metastasis and Recurrence in Human Hepatocellular Carcinoma Mon, 09 Jun 2014 00:00:00 +0000 It has been demonstrated that loss of heterozygosity (LOH) was frequently observed on chromosomes 8p22-p23 in hepatocellular carcinoma (HCC) and was associated with metastasis and prognosis of HCC. However, putative genes functioning on this chromosomal region remain unknown. In this study, we evaluated LOH status of four genes on 8p22-p23 (MCPH1, TUSC3, KIAA1456, and ZDHHC2). LOH on ZDHHC2 was associated with early metastatic recurrence of HCC following liver transplantation and was correlated with tumor size and portal vein tumor thrombi. Furthermore, our results indicate that ZDHHC2 expression was frequently decreased in HCC. Overexpression of ZDHHC2 could inhibit proliferation, migration, and invasion of HCC cell line Bel-7402 in vitro. These results suggest an important role for ZDHHC2 as a tumor suppressor in metastasis and recurrence of HCC. Chuanhui Peng, Zhijun Zhang, Jian Wu, Zhen Lv, Jie Tang, Haiyang Xie, Lin Zhou, and Shusen Zheng Copyright © 2014 Chuanhui Peng et al. All rights reserved. Alterations in Lipid Mediated Signaling and Wnt/β-Catenin Signaling in DMH Induced Colon Cancer on Supplementation of Fish Oil Thu, 05 Jun 2014 08:57:44 +0000 Ceramide mediates inhibition of cyclooxygenase-2 (COX-2) which catalyzes formation of prostaglandin further activating peroxisome proliferator-activated receptorγ (PPARγ) and Wnt/β-catenin pathway; and hence plays a critical role in cancer. Therefore, in current study, ceramide, COX-2, 15-deoxy prostaglandin J2(15-deoxy PGJ2), PPARγ, and β-catenin were estimated to evaluate the effect of fish oil on lipid mediated and Wnt/β-catenin signaling in colon carcinoma. Male Wistar rats in Group I received purified diet while Groups II and III received modified diet supplemented with FO : CO(1 : 1) and FO : CO(2.5 : 1), respectively. These were further subdivided into controls receiving ethylenediaminetetraacetic acid and treated groups receiving dimethylhydrazine dihydrochloride (DMH)/week for 4 weeks. Animals sacrificed 48 hours after last injection constituted initiation phase and those sacrificed after 16 weeks constituted postinitiation phase. Decreased ceramide and increased PPARγ were observed in postinitiation phase only. On receiving FO+CO(1 : 1)+DMH and FO+CO(2.5 : 1)+DMH in both phases, ceramide was augmented whereas COX-2, 15-deoxy PGJ2, and nuclear translocation of β-catenin were reduced with respect to cancerous animals. Decrease was more significant in postinitiation phase with FO+CO(2.5 : 1)+DMH. Treatment with oils increased PPARγ in initiation phase but decreased it in postinitiation phase. Hence, fish oil altered lipid mediated signalling in a dose and time dependent manner so as to inhibit progression of colon cancer. Shevali Kansal, Kim Vaiphei, and Navneet Agnihotri Copyright © 2014 Shevali Kansal et al. All rights reserved. Levofloxacin-Amoxicillin/Clavulanate-Rabeprazole versus a Standard Seven-Day Triple Therapy for Eradication of Helicobacter pylori Infection Thu, 05 Jun 2014 07:52:32 +0000 The resistance rates of Helicobacter pylori to amoxicillin and metronidazole therapy are higher in eastern Taiwan as compared to national and worldwide rates. The high resistance rate in this territory justified a search for a better eradication regimen. We conducted an open-labeled, prospective, randomized, and controlled study in a tertiary referral hospital in eastern Taiwan. Between December 2007 and December 2009, a total of 153 Helicobacter pylori-positive, therapy-naïve patients with a positive rapid urease test were recruited for random assignment to two seven-day treatment groups: levofloxacin (500 mg), amoxicillin/clavulanate (875 mg/125 mg), and rabeprazole (20 mg) twice per day (LAcR) or clarithyromicin (500 mg), amoxicillin (1000 mg), and rabeprazole (20 mg) twice per day (CAR). Helicobacter pylori eradication was assessed using the 13C-urea breath test or rapid urease test performed at least 4 weeks after the end of treatment. After exclusion, 146 patients were enrolled and allocated in the study. The Helicobacter pylori eradication rates analyzed by both intention to treat (78.1% versus 57.5%, ) and perprotocol (80.9% versus 61.8%, ) were significantly higher for the LAcR group. In conclusion, the seven-day LAcR regimen provided improved Helicobacter pylori eradication efficacy when compared with the standard CAR triple therapy in eastern Taiwan. Ming-Cheh Chen, Wei-Yi Lei, Jen-Shung Lin, Chih-Hsun Yi, Deng-Chyang Wu, and Chi-Tan Hu Copyright © 2014 Ming-Cheh Chen et al. All rights reserved. The Best Choice of Treatment for Acute Colonic Diverticulitis with Purulent Peritonitis Is Uncertain Tue, 03 Jun 2014 09:36:11 +0000 Severe stages of acute, colonic diverticulitis can progress into intestinal perforations with peritonitis. In such cases, urgent treatment is needed, and Hartmann’s procedure is the standard treatment for cases with fecal peritonitis. Peritoneal lavage may be an alternative to resection for acute diverticulitis with purulent peritonitis, but ongoing randomized trials are awaited to clarify this. Line Hupfeld, Jakob Burcharth, Hans-Christian Pommergaard, and Jacob Rosenberg Copyright © 2014 Line Hupfeld et al. All rights reserved. Baicalein Induces Apoptosis and Autophagy via Endoplasmic Reticulum Stress in Hepatocellular Carcinoma Cells Tue, 03 Jun 2014 07:24:11 +0000 Background. Hepatocellular carcinoma (HCC) remains a disastrous disease and the treatment for HCC is rather limited. Separation and identification of active compounds from traditionally used herbs in HCC treatment may shed light on novel therapeutic drugs for HCC. Methods. Cell viability and colony forming assay were conducted to determine anti-HCC activity. Morphology of cells and activity of caspases were analyzed. Antiapoptotic Bcl-2 family proteins and JNK were also examined. Levels of unfolded protein response (UPR) markers were determined and intracellular calcium was assayed. Small interfering RNAs (siRNAs) were used to investigate the role of UPR and autophagy in baicalein-induced cell death. Results. Among four studied flavonoids, only baicalein exhibited satisfactory inhibition of viability and colony formation of HCC cells within water-soluble concentration. Baicalein induced apoptosis via endoplasmic reticulum (ER) stress, possibly by downregulating prosurvival Bcl-2 family, increasing intracellular calcium, and activating JNK. CHOP was the executor of cell death during baicalein-induced ER stress while eIF2α and IRE1α played protective roles. Protective autophagy was also triggered by baicalein in HCC cells. Conclusion. Baicalein exhibits prominent anti-HCC activity. This flavonoid induces apoptosis and protective autophagy via ER stress. Combination of baicalein and autophagy inhibitors may represent a promising therapy against HCC. Zhongxia Wang, Chunping Jiang, Weibo Chen, Guang Zhang, Dongjun Luo, Yin Cao, Junhua Wu, Yitao Ding, and Baorui Liu Copyright © 2014 Zhongxia Wang et al. All rights reserved. Gastrointestinal Hemorrhage in Warfarin Anticoagulated Patients: Incidence, Risk Factor, Management, and Outcome Thu, 29 May 2014 11:37:32 +0000 Background. Warfarin reduces the incidence of thromboembolism but increases the risk of gastrointestinal bleeding (GIB). GIB during warfarin anticoagulation is rarely evaluated in Asian patients. Aims. This study aimed at investigating the incidence, risk factors, management, and outcome of GIB in Taiwanese patients treated with warfarin. Methods. We analyzed a cohort of warfarin anticoagulated patients between July 1993 and May 2012. Clinical data were retrieved in a chart-reviewing manner. Results. A total of 401 warfarin anticoagulated patients were enrolled. The incidence of GIB was 3.9% per patient-years. Multivariate analysis with Cox regression showed that age >65 years old (RR: 2.5, 95% CI: 1.2–5.5), a mean international normalized ratio >2.1 (RR: 2.1, 95% CI: 1.0–4.2), a history of GIB (RR: 5.1, 95% CI: 1.9–13.5), and cirrhosis (RR: 6.9, 95% CI: 2.0–24.5) were independent factors predicting GIB. 27.3% of the GIB patients had rebleeding after restarting warfarin while thromboembolic events were found in 16.7% of the patients discontinuing warfarin therapy. Conclusions. Warfarin was associated with a significant incidence of GIB in Taiwanese patients. The intensity of anticoagulation should be monitored closely during warfarin therapy, especially in patients with risk factors of GIB. Wen-Chi Chen, Yan-Hua Chen, Ping-I Hsu, Feng-Woei Tsay, Hoi-Hung Chan, Jin-Shiung Cheng, and Kwok-Hung Lai Copyright © 2014 Wen-Chi Chen et al. All rights reserved. Monocolonization of Germ-Free Mice with Bacteroides fragilis Protects against Dextran Sulfate Sodium-Induced Acute Colitis Thu, 29 May 2014 07:52:31 +0000 Ulcerative colitis is inflammatory conditions of the colon caused by interplay of genetic and environmental factors. Previous studies indicated that the gut microflora may be involved in the colonic inflammation. Bacteroides fragilis (BF) is a Gram-negative anaerobe belonging to the colonic symbiotic. We aimed to investigate the protective role of BF in a colitis model induced in germ-free (GF) mice by dextran sulfate sodium (DSS). GF C57BL/6JNarl mice were colonized with BF for 28 days before acute colitis was induced by DSS. BF colonization significantly increased animal survival by 40%, with less reduction in colon length, and decreased infiltration of inflammatory cells (macrophages and neutrophils) in colon mucosa following challenge with DSS. In addition, BF could enhance the mRNA expression of anti-inflammatory-related cytokine such as interleukin 10 (IL-10) with polymorphism cytokine IL-17 and diminish that of proinflammatory-related tumor necrosis factor α with inducible nitric oxide synthase in the ulcerated colon. Myeloperoxidase activity was also decreased in BF-DSS mice. Taking these together, the BF colonization significantly ameliorated DSS-induced colitis by suppressing the activity of inflammatory-related molecules and inducing the production of anti-inflammatory cytokines. BF may play an important role in maintaining intestinal immune system homeostasis and regulate inflammatory responses. Chien-Chao Chiu, Yung-Hao Ching, Yu-Chih Wang, Ju-Yun Liu, Yen-Peng Li, Yen-Te Huang, and Hsiao-Li Chuang Copyright © 2014 Chien-Chao Chiu et al. All rights reserved. Nutrition in Pelvic Radiation Disease and Inflammatory Bowel Disease: Similarities and Differences Wed, 28 May 2014 10:49:36 +0000 Due to the intestinal inflammation, tissue damage, and painful abdominal symptoms restricting dietary intake associated with both diseases, patients with intestinal pelvic radiation disease (PRD) or inflammatory bowel disease (IBD) are at increased risk to develop protein calorie malnutrition and micronutrient deficiencies. In the current paper, we review the nutritional management of both diseases, listing the similar approaches of nutritional management and the nutritional implications of intestinal dysfunction of both diseases. Malnutrition is prevalent in patients with either disease and nutritional risk screening and assessment of nutritional status are required for designing the proper nutritional intervention plan. This plan may include dietary management, oral nutritional supplementation, and enteral and/or parenteral nutrition. In addition to managing malnutrition, nutrients exert immune modulating effects during periods of intestinal inflammation and can play a role in mitigating the risks associated with the disease activity. Consistently, exclusive enteral feeding is recommended for inducing remission in pediatric patients with active Crohn’s disease, with less clear guidelines on use in patients with ulcerative colitis. The field of immune modulating nutrition is an evolving science that takes into consideration the specific mechanism of action of nutrients, nutrient-nutrient interaction, and preexisting nutritional status of the patients. Tiffany DeWitt and Refaat Hegazi Copyright © 2014 Tiffany DeWitt and Refaat Hegazi. All rights reserved. Effects of Exogenous Lactase Administration on Hydrogen Breath Excretion and Intestinal Symptoms in Patients Presenting Lactose Malabsorption and Intolerance Sun, 25 May 2014 13:04:02 +0000 Objective. To establish whether supplementation with a standard oral dose of Beta-Galactosidase affects hydrogen breath excretion in patients presenting with lactose malabsorption. Methods. Ninety-six consecutive patients positive to H2 Lactose Breath Test were enrolled. Mean peak H2 levels, the time to reach the peak H2, the time to reach the cut-off value of 20 ppm, the cumulative breath H2 excretion, the areas under the curve, and a Visual Analogical 10-point Scale for symptoms were calculated. Genotyping of the C/T-13910 variant was carried out. Results. Following the oral administration of Beta-Galactosidase, in 21.88% of the cases, H2 Lactose Breath Test became negative (Group A), while mean peak H2 levels (74.95 ppm versus 7.85), , in 17.71% (Group B) were still positive, with the H2 level 20 ppm above the baseline, but the peak H2 levels were significantly lower than those observed at the baseline test (186.7 ppm versus 66.64), , while in 60.41% (Group C) they were still positive with the peak H2 levels similar to those observed at the baseline test (94.43 versus 81.60 ppm). All 96 individuals tested presented the C/C-13910 genotype nonpersistence. Conclusions. The response to oral administration of Beta-Galactosidase in patients with symptoms of lactose malabsorption presents a significant variability. Ivan Ibba, Agnese Gilli, Maria Francesca Boi, and Paolo Usai Copyright © 2014 Ivan Ibba et al. All rights reserved. Microencapsulated Bifidobacterium longum subsp. infantis ATCC 15697 Favorably Modulates Gut Microbiota and Reduces Circulating Endotoxins in F344 Rats Thu, 22 May 2014 10:53:31 +0000 The gut microbiota is a bacterial bioreactor whose composition is an asset for human health. However, circulating gut microbiota derived endotoxins cause metabolic endotoxemia, promoting metabolic and liver diseases. This study investigates the potential of orally delivered microencapsulated Bifidobacterium infantis ATCC 15697 to modulate the gut microbiota and reduce endotoxemia in F344 rats. The rats were gavaged daily with saline or microencapsulated B. infantis ATCC 15697. Following 38 days of supplementation, the treated rats showed a significant (P < 0.05) increase in fecal Bifidobacteria (4.34 ± 0.46 versus 2.45 ± 0.25% of total) and B. infantis (0.28 ± 0.21 versus 0.52 ± 0.12 % of total) and a significant (P < 0.05) decrease in fecal Enterobacteriaceae (0.80 ± 0.45 versus 2.83 ± 0.63% of total) compared to the saline control. In addition, supplementation with the probiotic formulation reduced fecal (10.52 ± 0.18 versus 11.29 ± 0.16 EU/mg; P = 0.01) and serum (0.33 ± 0.015 versus 0.30 ± 0.015 EU/mL; P = 0.25) endotoxins. Thus, microencapsulated B. infantis ATCC 15697 modulates the gut microbiota and reduces colonic and serum endotoxins. Future preclinical studies should investigate the potential of the novel probiotic formulation in metabolic and liver diseases. Laetitia Rodes, Shyamali Saha, Catherine Tomaro-Duchesneau, and Satya Prakash Copyright © 2014 Laetitia Rodes et al. All rights reserved. Impaired Intestinal Mucosal Barrier upon Ischemia-Reperfusion: “Patching Holes in the Shield with a Simple Surgical Method” Wed, 14 May 2014 14:16:53 +0000 Mesenteric ischemia-reperfusion (IR) is associated with impairment of the gut barrier function and the initiation of a proinflammatory cascade with life-threatening results. Therefore methods directed to ameliorate IR injury are of great importance. We aimed at describing the effects of postconditioning (PC) on the alterations of the intestinal mucosal function and the inflammatory response upon mesenteric IR. Methods. Male Wistar rats were gavaged with green fluorescent protein-expressing E. coli suspensions. Animals were randomized into three groups (), sham-operated, IR-, and PC-groups, and underwent 60 minutes of superior mesenteric artery occlusion, followed by 6 hours of reperfusion. Postconditioning was performed at the onset of reperfusion. Blood and tissue samples were taken at the end of reperfusion, for histological, bacteriological, and plasma examinations. Results. The PC-group presented a more favorable claudin-2, claudin-3, claudin-4, and zonula occludens-1 membrane expression profile, and significantly lower rates of bacterial translocation to distant organs and plasma D-lactate levels compared to the IR-group. Histopathological lesions, plasma I-FABP, IL-6, and TNF-α levels were significantly lower in the PC-group compared to the IR-group. Conclusion. The use of postconditioning improved the integrity of the intestinal mucosal barrier upon mesenteric IR, and thus reduced the incidence of bacterial translocation and development of a systemic inflammatory response. Olivér Rosero, Péter Ónody, Tibor Kovács, Dávid Molnár, Gábor Lotz, Szilárd Tóth, Zsolt Turóczi, András Fülöp, Dávid Garbaisz, László Harsányi, and Attila Szijártó Copyright © 2014 Olivér Rosero et al. All rights reserved. Coexpression of SFRP1 and WIF1 as a Prognostic Predictor of Favorable Outcomes in Patients with Colorectal Carcinoma Wed, 14 May 2014 09:28:58 +0000 Colorectal tumorigenesis is ascribed to the activity of Wnt signaling pathway in a ligand-independent manner mainly through APC and CTNNB1 gene mutations and in a ligand-dependent manner through low expression of Wnt inhibitors such as WNT inhibitory factor 1 (WIF1) and secreted frizzled related protein 1 (SFRP1). In this study we found that WIF1 protein expression was increased and SFRP1 was decreased significantly in CRC tissue versus normal tissue, and high expression of WIF1 was associated with big tumor diameters and deep invasion, and loss of SFRP1 expression was associated with the left lesion site, deep invasion, and high TNM stage. Among the four expression patterns (WIF+/SFRP1+, WIF+/SFRP1−, WIF−/SFRP1+, and WIF−/SFRP1−) only coexpression of WIF1 and SFRP1 (WIF+/SFRP1+) was associated with favorable overall survival, together with low TNM stage, as an independent prognostic factor as shown in a multivariate survival model. The results indicated that WIF1 seemed to play an oncogenic role, while SFRP1 seemed to play an oncosuppressive role although both of them are secreted Wnt antagonists. Coexpression of SFRP1 and WIF1, rather than SFRP1 or WIF1 alone, could be used, together with low TNM stage, as a prognostic predictor of favorable outcomes in CRC. Shiyong Huang, XiaoMing Zhong, Jun Gao, Rongfeng Song, Hongyu Wu, Shuming Zi, Shijie Yang, Peng Du, Long Cui, Chun Yang, and Zikang Li Copyright © 2014 Shiyong Huang et al. All rights reserved. BAG3 and HIF-1α Coexpression Detected by Immunohistochemistry Correlated with Prognosis in Hepatocellular Carcinoma after Liver Transplantation Thu, 08 May 2014 16:15:09 +0000 Objective. The objective is to determine the effects of BAG3 and HIF-1α expression on the prognosis of HCC patients after liver transplantation. Methods. Samples from 31 patients with HCC receiving liver transplantation were collected for this study. The immunohistochemistry was used to detect the expression of BAG3 and HIF-1α of HCC samples. Results. According to the immunohistochemistry results, BAG3 and HIF-1α staining were significantly associated with tumor TNM stage (, ). A significant association between high BAG3/HIF-1α levels and a shorter overall survival was detected, so as the combined BAG3 and HIF-1α analysis. Conclusion. The results suggested that the expression level of BAG3 and HIF-1α is efficient prognostic parameters in patients with HCC after liver transplantation. Heng Xiao, Rongliang Tong, Shaobing Cheng, Zhen Lv, Chaofeng Ding, Chengli Du, Haiyang Xie, Lin Zhou, Jian Wu, and Shusen Zheng Copyright © 2014 Heng Xiao et al. All rights reserved. Plasmid Transfer of Plasminogen K1-5 Reduces Subcutaneous Hepatoma Growth by Affecting Inflammatory Factors Thu, 08 May 2014 13:17:59 +0000 There is evidence that plasminogen K1-5 (PlgK1-5) directly affects tumour cells and inflammation. Therefore, we analysed if PlgK1-5 has immediate effects on hepatoma cells and inflammatory factors in vitro and in vivo. In vitro, effects of plasmid encoding PlgK1-5 (pK1-5) on Hepa129, Hepa1-6, and HuH7 cell viability, apoptosis, and proliferation as well as VEGF and TNF-alpha expression and STAT3-phosphorylation were investigated. In vivo, tumour growth, proliferation, vessel density, and effects on vascular endothelial growth factor (VEGF) and tumour necrosis factor alpha (TNF-alpha) expression were examined following treatment with pK1-5. In vivo, pK1-5 halved cell viability; cell death was increased by up to 15% compared to the corresponding controls. Proliferation was not affected. VEGF, TNF-alpha, and STAT3-phosphorylation were affected following treatment with pK1-5. In vivo, ten days after treatment initiation, pK1-5 reduced subcutaneous tumour growth by 32% and mitosis by up to 77% compared to the controls. Vessel density was reduced by 50%. TNF-alpha levels in tumour and liver tissue were increased, whereas VEGF levels in tumours and livers were reduced after pK1-5 treatment. Taken together, plasmid gene transfer of PlgK1-5 inhibits hepatoma (cell) growth not only by reducing vessel density but also by inducing apoptosis, inhibiting proliferation, and triggering inflammation. Lea A. Koch, Volker Schmitz, Christian P. Strassburg, and Esther Raskopf Copyright © 2014 Lea A. Koch et al. All rights reserved. The Role of Hemoclips Reinforcement in the Ligation-Assisted Endoscopic Enucleation for Small GISTs in Gastric Fundus Wed, 07 May 2014 06:50:11 +0000 Background. Endoscopic ultrasonography- (EUS-) assisted band ligation has been proven to be a safe and effective procedure for the treatment of small gastrointestinal stromal tumors (GISTs) apart from the relatively high risk of the postligation perforation of the gastric fundus. The aim of this study is to investigate the efficacy of hemoclip reinforcement in treating small GISTs in the gastric fundus. Method. During a standard endoscopy, a transparent cap attached to the endoscopic tip was placed over the lesion to exert sustained maximal aspiration before a rubber band was released. Once a definite ligation was confirmed by EUS, the tumor was enucleated. Four to 6 hemoclips were placed on the folds around the ligation band to reduce the tension of the ligation site. Results. The small GISTs were resected completely in 192 patients. Two cases of delayed perforation were found 72 hours after the procedure and successfully treated with an ordinary conservative method. Conclusion. Hemoclip-reinforced endoscopic band ligation with systematic follow-up using EUS appears to be a simple and effective technique for the resection of small GISTs in the gastric fundus. Ge Nan, Sun Siyu, Wang Sheng, Liu Xiang, and Guo Jintao Copyright © 2014 Ge Nan et al. All rights reserved. Effect of Mesalamine and Prednisolone on TNBS Experimental Colitis, following Various Doses of Orally Administered Iron Sun, 04 May 2014 13:54:31 +0000 Background. Experimental data suggest that oral iron (I.) supplementation can worsen colitis in animals. Aim. To investigate the influence of various concentrations of orally administered I. in normal gut mucosa and mucosa of animals with TNBS colitis, as well as the influence of Mesalamine (M.) and Prednisolone (P.) on the severity of TNBS colitis following orally administered I. Methods and Materials. 156 Wistar rats were allocated into 10 groups. Colitis was induced by TNBS. On the 8th day, all animals were euthanatized. Activity of colitis and extent of tissue damage were assessed histologically. The levels of tissue tumor necrosis factor-α (t-TNF-α) and tissue malondialdehyde (t-MDA) were estimated in all animal groups. Results. Moderate and high I. supplementation induced inflammation in the healthy colon and increased the activity of the experimentally induced TNBS colitis. Administration of M. on TNBS colitis following moderate iron supplementation (0.3 g/Kg diet) resulted in a significant improvement in the overall histological score as well as in two individual histological parameters. M. administration, however, did not significantly reduce the t-TNF-α levels ( versus , ), although it significantly reduced the t-MDA levels ( versus , ). Administration of M. on TNBS colitis following high iron supplementation (3.0 g/Kg diet) did not improve the overall histological score and the individual histological parameters, neither reduced the levels of t-TNF-α ( versus , ). However, M. significantly reduced the t-MDA levels ( versus , ). Administration of P. on TNBS colitis after moderate iron supplementation resulted in a significant improvement in the overall histological score as well as in three individual histological parameters. P. also resulted in a significant reduction in the t-TNF-α levels ( versus , ) and the t-MDA levels ( versus , ). Administration of P on TNBS colitis after high I. supplementation resulted in a significant improvement of the overall histological score and three individual histological parameters and significantly reduced the levels of t-TNF-α ( versus , ). Conclusion. I. can induce colonic inflammation and aggravate TNBS colitis. M. and P. can significantly improve the inflammatory process in the colonic mucosa in TNBS colitis aggravated by orally administered I. P. has a stable anti-TNF-α effect. These findings suggest that the harmful. John K. Triantafillidis, Georgia Douvi, George Agrogiannis, Efstratios Patsouris, Aristofanis Gikas, and Apostolos E. Papalois Copyright © 2014 John K. Triantafillidis et al. All rights reserved. Evolving Ablative Therapies for Hepatic Malignancy Tue, 29 Apr 2014 12:05:15 +0000 The liver is a common site for both primary and secondary malignancy. Hepatic resection and transplantation are the two treatment modalities that have been shown to achieve complete cure, but only 10 to 20% of patients are candidates for these treatments. For the remaining patients, tumor ablation has emerged as the most promising alternative modality. In addition to providing local control and improving survival outcomes, tumor ablation also helps to down stage patients for potential curative treatments, both alone as well as in combination with other treatments. While tumor ablation can be achieved in multiple ways, the introduction of newer ablative techniques has shifted the focus from palliation to potentially curative treatment. Because the long-term safety and survival benefits are not substantive at present, it is important that we strive to evaluate the results from these studies using appropriate comparative outcome methodologies. Smit Singla, Steven N. Hochwald, and Boris Kuvshinoff Copyright © 2014 Smit Singla et al. All rights reserved. Association between Two Common Polymorphisms and Risk of Hepatocellular Carcinoma: Evidence from an Updated Meta-Analysis Thu, 17 Apr 2014 16:55:31 +0000 Background. Recent studies suggested that two common polymorphisms, miR-146a G>C and miR-196a2 C>T, may be associated with individual susceptibility to hepatocellular carcinoma (HCC). However, the results remain conflicting rather than conclusive. Object. The aim of this study was to assess the association between miR-146a G>C and miR-196a2 C>T polymorphisms and the risk of HCC. Methods. A meta-analysis of 17 studies (10938 cases and 11967 controls) was performed. Odds ratios and 95% confidence intervals were used to evaluate the strength of the association. Results. For miR-146a G>C, the variant genotypes were associated with a decreased risk of HCC (CC versus GG: OR = 0.780 and 95% CI 0.700–0.869; GC/CC versus GG: OR = 0.865 and 95% CI 0.787–0.952; CC versus GC/GG: OR = 0.835 and 95% CI 0.774–0.901). For miR-196a2 C>T, significant association was also observed (TT versus CC: OR = 0.783, 95% CI: 0.649–0.943, and ; CT versus CC: OR = 0.831, 95% CI 0.714–0.967, and ; CT/TT versus CC: OR = 0.817, 95% CI 0.703–0.949, and ). Conclusion. The two common polymorphisms miR-146a G>C and miR-196a2 C>T were associated with decreased HCC susceptibility, especially in Asian population. Zhaoming Wang, Lei Zhang, Xuesong Shi, Huayu Xu, Ting Wang, and Jianmin Bian Copyright © 2014 Zhaoming Wang et al. All rights reserved. Does Long-Term Use of Silver Nanoparticles Have Persistent Inhibitory Effect on H. pylori Based on Mongolian Gerbil’s Model? Thu, 17 Apr 2014 13:32:32 +0000 Background. It is urgent to find alternative agents due to increasing failure rate of Helicobacter pylori (H. pylori) eradication. The study surveyed the long-term effect of silver nanoparticles (AgNP) on H. pylori based on Mongolian gerbil’s model. Materials and Methods. Fifty gerbils were randomly allocated to six groups (A–F). Group (Gr) A: the gerbils were fed with broth; Gr B and D: the gerbils were fed with AgNP/clay complex (0.1% of weight); Gr C and E: the gerbils were fed with AgNP/clay complex(1% of weight); and Gr D, E, and F: the gerbils were inoculated with H. pylori. At the 20th experimental week, the gerbils were sacrificed. Histology was evaluated according to the classification of the Sydney system. was considered to be statistically significant. Results. The AgNP/clay has more obvious inhibitory effect on H. pylori in vitro. There was a trend of higher concentrations of AgNP with stronger inhibitory effect on H. pylori growth . There were no significant differences of inflammation among groups D, E, and F Conclusion. AgNP/clay would be a potential and safe agent for inhibiting H. pylori. It should be helpful for eradication of H. pylori infection. Chao-Hung Kuo, Chien-Yu Lu, Yuan-Chieh Yang, Chieh Chin, Bi-Chuang Weng, Chung-Jung Liu, Yen-Hsu Chen, Lin-Li Chang, Fu-Chen Kuo, Deng-Chyang Wu, and Hong-Lin Su Copyright © 2014 Chao-Hung Kuo et al. All rights reserved. Quantitative Diagnosis of Colorectal Polyps by Spectral Domain Optical Coherence Tomography Wed, 09 Apr 2014 13:47:06 +0000 The principal aim of this study is to investigate the scattering coefficient of colorectal polyp tissues using an optical coherence tomography (OCT) technique. It combines the existing scattering coefficient model and spectral domain OCT to achieve method of early diagnosis of colorectal polyp in hospitals. Seventeen patients were studied, and a total of 1456 data points were extracted by curve-fitting the OCT signals into a confocal single-backscattering model. The results show that the mean scattering coefficient value for colorectal polyps is 1.91 mm−1 (std: ±0.54 mm−1), which is between the values for normal and malignant tissues. In addition, we studied the difference between adenomatous polyps () and inflammatory polyps () quantitatively and found that the adenomatous tissues had lower scattering coefficients than the inflammatory ones. The quantitative measurements confirmed that OCT can be used in primary diagnosis to compensate for the deficiencies in methods of pathological diagnosis, with a great potential for early diagnosis of tissues. Chen Wang, Qinqin Zhang, Xiaojing Wu, Tao Tang, Hong Liu, S. W. Zhu, Bruce Z. Gao, and X.-C. Yuan Copyright © 2014 Chen Wang et al. All rights reserved. MicroRNA-24 Modulates Aflatoxin B1-Related Hepatocellular Carcinoma Prognosis and Tumorigenesis Tue, 08 Apr 2014 08:41:27 +0000 MicroRNA-24 (miR-24) may be involved in neoplastic process; however, the role of this microRNA in the hepatocellular carcinoma (HCC) related to aflatoxin B1 (AFB1) has not been well elaborated. Here, we tested miR-24 expression in 207 pathology-diagnosed HCC cases from high AFB1 exposure areas and HCC cells. We found that miR-24 was upregulated in HCC tumor tissues relative to adjacent noncancerous tissue samples, and that the high expression of miR-24 was significantly correlated with larger tumor size, higher microvessel density, and tumor dedifferentiation. Additionally, this microRNA overexpression modified the recurrence-free survival (relative hazard ratio [HR], 4.75; 95% confidence interval [CI], 2.66–8.47) and overall survival (, 95% CI = 2.34–5.46) of HCC patients. Furthermore, we observed some evidence of joint effects between miR-24 and AFB1 exposure on HCC prognosis. Functionally, miR-24 overexpression progressed tumor cells proliferation, inhibited cell apoptosis, and developed the formation of AFB1-DNA adducts. These results indicate for the first time that miR-24 may modify AFB1-related HCC prognosis and tumorigenesis. Yi-Xiao Liu, Xi-Dai Long, Zhi-Feng Xi, Yun Ma, Xiao-Ying Huang, Jin-Guang Yao, Chao Wang, Tian-Yu Xing, and Qiang Xia Copyright © 2014 Yi-Xiao Liu et al. All rights reserved. Therapy of Helicobacter pylori: Present Medley and Future Prospective Tue, 01 Apr 2014 12:29:12 +0000 The increasing prevalence of antimicrobial resistance has warned clinicians to adopt new strategies for dealing with the H. pylori infection. The success of various therapeutic regimens has recently declined to unacceptable levels. To date, first line therapies (including concomitant therapy and hybrid therapy), second line therapies (including bismuth-containing quadruple therapy and levofloxacin-containing therapy), and third line therapy (culture-guided therapy) had been introduced. In the near future, treatment of H. pylori is entering into a completely new resistance era. In this setting, despite the recent progress, we may only be targeting the patients with problematic H. pylori. Local preference for antibiotic selection should be an inevitable article in each therapeutic regimen worldwide. Meanwhile, improving the patients’ compliance protocols and observed side effects in suggested therapeutic regimens should be considered cautiously. The new strategies in treatment should be adopted based upon local resistance patterns, which requires physician’s resistance about the recommended guidelines. Designing new therapeutic regimen, which contains most effective available antibiotics with less possible side effects and high patient compliance, represents a challenging task in treatment of H. pylori infections. Amin Talebi Bezmin Abadi Copyright © 2014 Amin Talebi Bezmin Abadi. All rights reserved. MicroRNAs 146a and 147b Biomarkers for Colorectal Tumor’s Localization Sun, 30 Mar 2014 09:46:23 +0000 The recently identified class of microRNAs (miRs) provided a new insight into cancer research, since abnormalities of members of microRNAs family have been found in various types of cancer. However, the relationship between five miRNAs (miR146a, miR155, miR21, miR135a, and miR147b) and colorectal cancer remains unclear. In the present study, we examined expression of these miRNAs in 25 pair-matched colon cancer tissues and normal colon mucosa. The expression levels of miR146a, miR155, miR21, miR135a, and miR147b were quantified by real-time PCR. We found that miR21, miR146a, and miR135a were all expressed at higher levels in colon tumors. On the other hand, miR146a and miR147b expressions are significantly higher in left colon compared to right colon. These two miRs, especially miR146a, seemed to be markers for the left colon tumors. Moreover, significant proportional and inverse correlations were found between miR expressions in tumor and healthy tissue, and the correlations profiles were different depending on cancer localization. Taken together, these results lead us to suggest the presence of different mechanisms regulating miRs expression and consequently their target genes in left and right colon. So the pathway of colorectal carcinogenesis would be different according to the site of the tumor. Inés Omrane, Nadia Kourda, Nejla Stambouli, Maud Privat, Imen Medimegh, Amira Arfaoui, Nancy Uhrhammer, Karim Bougatef, Olfa Baroudi, Hassen Bouzaienne, Raja Marrakchi, Yves-Jean Bignon, and Amel Benammar-Elgaaied Copyright © 2014 Inés Omrane et al. All rights reserved. Gastroprotective Effect of Ethanolic Extract of Curcuma xanthorrhiza Leaf against Ethanol-Induced Gastric Mucosal Lesions in Sprague-Dawley Rats Mon, 24 Mar 2014 14:14:03 +0000 Herbal medicines appeared promising in prevention of many diseases. This study was conducted to investigate the gastroprotective effect of Curcuma xanthorrhiza leaf in the rats induced gastric ulcer by ethanol. Normal and ulcer control received carboxymethycellulose (5 mL/kg) orally, positive control was administered with 20 mg/kg omeprazole (reference drug) and 2 groups were received 250 mg/kg and 500 mg/kg of the leaf extract, respectively. To induce of gastric ulcers formation, ethanol (5 mL/kg) was given orally to all groups except normal control. Gross ulcer areas, histology, and amount of prostaglandin E2, superoxide dismutase and malondialdehyde were assessed to determine the potentiality of extract in prevention against gastric ulcers. Oral administration of extract showed significant gastric protection effect as the ulcer areas was remarkably decreased. Histology observation showed less edema and leucocytes infiltration as compared with the ulcer control which exhibited severe gastric mucosa injury. Furthermore, the leaf extract elevated the mucus weight, level of prostaglandin E2 and superoxide dismutase. The extract also reduced malondialdehyde amount significantly. Results showed leaf extract of Curcuma xanthorrhiza can enhanced the gastric protection and sustained the integrity of gastric mucosa structure. Acute toxicity test did not showed any sign of toxicity (2 g/kg and 5 g/kg). Nurhidayah Ab. Rahim, Pouya Hassandarvish, Shahram Golbabapour, Salmah Ismail, Saad Tayyab, and Mahmood Ameen Abdulla Copyright © 2014 Nurhidayah Ab. Rahim et al. All rights reserved. Autophagy in Hepatic Fibrosis Sun, 23 Mar 2014 09:38:41 +0000 Hepatic fibrosis is a leading cause of morbidity and mortality worldwide. Hepatic fibrosis is usually associated with chronic liver diseases caused by infection, drugs, metabolic disorders, or autoimmune imbalances. Effective clinical therapies are still lacking. Autophagy is a cellular process that degrades damaged organelles or protein aggregation, which participates in many pathological processes including liver diseases. Autophagy participates in hepatic fibrosis by activating hepatic stellate cells and may participate as well through influencing other fibrogenic cells. Besides that, autophagy can induce some liver diseases to develop while it may play a protective role in hepatocellular abnormal aggregates related liver diseases and reduces fibrosis. With a better understanding of the potential effects of autophagy on hepatic fibrosis, targeting autophagy might be a novel therapeutic strategy for hepatic fibrosis in the near future. Yang Song, Yingying Zhao, Fei Wang, Lichan Tao, Junjie Xiao, and Changqing Yang Copyright © 2014 Yang Song et al. All rights reserved. A Two-Tube Multiplex Reverse Transcription PCR Assay for Simultaneous Detection of Viral and Bacterial Pathogens of Infectious Diarrhea Mon, 10 Mar 2014 07:38:15 +0000 Diarrhea caused by viral and bacterial infections is a major health problem in developing countries. The purpose of this study is to develop a two-tube multiplex PCR assay using automatic electrophoresis for simultaneous detection of 13 diarrhea-causative viruses or bacteria, with an intended application in provincial Centers for Diseases Control and Prevention, China. The assay was designed to detect rotavirus A, norovirus genogroups GI and GII, human astrovirus, enteric adenoviruses, and human bocavirus (tube 1), and Salmonella, Vibrio parahaemolyticus, diarrheagenic Escherichia coli, Campylobacter jejuni, Shigella, Yersinia, and Vibrio cholera (tube 2). The analytical specificity was examined with positive controls for each pathogen. The analytical sensitivity was evaluated by performing the assay on serial tenfold dilutions of in vitro transcribed RNA, recombinant plasmids, or bacterial culture. A total of 122 stool samples were tested by this two-tube assay and the results were compared with those obtained from reference methods. The two-tube assay achieved a sensitivity of 20–200 copies for a single virus and 102-103 CFU/mL for bacteria. The clinical performance demonstrated that the two-tube assay had comparable sensitivity and specificity to those of reference methods. In conclusion, the two-tube assay is a rapid, cost-effective, sensitive, specific, and high throughput method for the simultaneous detection of enteric bacteria and virus. Ji Wang, Ziqian Xu, Peihua Niu, Chen Zhang, Jingyun Zhang, Li Guan, Biao Kan, Zhaojun Duan, and Xuejun Ma Copyright © 2014 Ji Wang et al. All rights reserved. Toxic Damage Increases Angiogenesis and Metastasis in Fibrotic Livers via PECAM-1 Thu, 06 Mar 2014 11:24:15 +0000 Excessive ethanol consumption is one of the main causes of liver fibrosis. However, direct effects of ethanol exposure on endothelial cells and their contribution to fibrogenesis and metastasis were not investigated. Therefore we analysed whether ethanol directly affects endothelial cells and if this plays a role during fibrogenesis and metastasis in the liver. Murine and human endothelial cells were exposed to ethanol for up to 72 hours. In vitro, effects on VEGF, HIF-1alpha, PECAM-1, and endothelial cell functions were analysed. In vivo, effects of continuous liver damage on blood vessel formation and metastasis were analysed by PECAM-1 immunohistochemistry. Ethanol increased HIF-1alpha and VEGF levels in murine and human endothelial cells. This resulted in enhanced intracellular signal transduction, and PECAM-1 expression as well as tube formation and wound healing. In vivo, toxic liver damage increased angiogenesis during fibrogenesis. Metastasis was also enhanced in fibrotic livers and located to PECAM-1 positive blood vessels compared to nonfibrotic mice. In conclusion, ethanol had strong effects on endothelial cells, which—at least in part—led to a profibrotic and prometastatic environment mediated by PECAM-1. Blockade of increased PECAM-1 expression could be a promising tool to inhibit fibrogenesis and metastasis in the liver. Esther Raskopf, Maria Angeles Gonzalez Carmona, Christina Jay Van Cayzeele, Christian Strassburg, Tilman Sauerbruch, and Volker Schmitz Copyright © 2014 Esther Raskopf et al. All rights reserved. Durable Expression of Minicircle DNA-Liposome-Delivered Androgen Receptor cDNA in Mice with Hepatocellular Carcinoma Thu, 06 Mar 2014 08:31:06 +0000 Background. The most common gene-based cancer therapies involve the suppression of oncogenic molecules and enhancement of the expression of tumor-suppressor genes. Studies in noncancer disease animal models have shown that minicircle (MC) DNA vectors are easy to deliver and that the proteins from said MC-carrying DNA vectors are expressed over a long period of time. However, delivery of therapeutic genes via a liposome-mediated, MC DNA complex has never been tested in vascular-rich hepatocellular carcinoma (HCC). Liposome-mediated DNA delivery exhibits high in vivo transfection efficiency and minimal systemic immune response, thereby allowing for repetitive interventions. In this study, we evaluated the efficacy of delivering an MC-liposome vector containing a 3.2 kb androgen receptor (AR; HCC metastasis suppressor) cDNA into Hepatitis B Virus- (HBV-) induced HCC mouse livers. Results. Protein expression and promoter luciferase assays revealed that liposome-encapsulated MC-AR resulted in abundant functional expression of AR protein (100 kD) for up to two weeks. The AR cDNA was also successfully delivered into normal livers and diseased livers, where it was persistently expressed. In both normal livers and livers with tumors, the expression of AR was detectable for up to 60 days. Conclusion. Our results show that an MC/liposome delivery system might improve the efficacy of gene therapy in patients with HCC. Tian-You Chang, Chin-Ying Chung, Wei-Min Chuang, Long-Yuan Li, Long-Bin Jeng, and Wen-Lung Ma Copyright © 2014 Tian-You Chang et al. All rights reserved. Reexpression of Let-7g MicroRNA Inhibits the Proliferation and Migration via K-Ras/HMGA2/Snail Axis in Hepatocellular Carcinoma Tue, 04 Mar 2014 13:07:58 +0000 Let-7 family microRNAs have been reported to be downregulated in human hepatocellular carcinoma in comparison with normal hepatic tissues. Among them, let-7g was identified as the lowest expression using real-time RT-PCR. However, the mechanism by which let-7g works in hepatocellular carcinoma remains unknown. Here, in our present study, we have had let-7g reexpressed in vitro in hepatocellular carcinoma cell lines MHCC97-H and HCCLM3 via transfection. The proliferation after reexpression of let-7g was assayed using MTT method; the migration and invasion after restoration were detected by wound-healing and Transwell assay, respectively. We found using Western-blotting that let-7g can regulate epithelial-mesenchymal transition (EMT) by downregulating K-Ras and HMGA2A after reexpresssion. Xenografted nude mice were used to observe whether or not reexpression of let-7g could have potential therapeutic ability. In vivo, to observe the association with let-7g expression and overall prognosis, 40 paired cases of hepatocellular carcinoma were analyzed using in situ hybridization (ISH). It was found that reexpression of let-7g can inhibit the proliferation, migration, and invasion significantly, and that low expression of let-7g was significantly associated with poorer overall survival. Taken together, let-7g could be used as a promising therapeutic agent in vivo in the treatment of hepatocellular carcinoma at the earlier stage. Ke-ji Chen, Ying Hou, Kui Wang, Jun Li, Yong Xia, Xiao-yu Yang, Gang Lv, Xiang-Lei Xing, and Feng Shen Copyright © 2014 Ke-ji Chen et al. All rights reserved. Antisecretory Effect of Hydrogen Sulfide on Gastric Acid Secretion and the Involvement of Nitric Oxide Mon, 24 Feb 2014 08:15:51 +0000 The present study was designed to investigate the effect of H2S on distention-induced gastric acid secretion. Fifty-two rats were randomly assigned to seven experimental groups. The gastric acid secretion was stimulated by gastric distention. Two groups of rats received L-cysteine or saline for 5 days before stimulation of the gastric acid secretion. Two groups of animals also received NaHS or saline just prior to stimulation of the gastric acid secretion. The effect of L-NAME and propargylglycine was also investigated. The mucosal levels of the gene expression of cyclooxygenase-2 (COX-2), endothelial nitric oxide synthase (eNOS), and H+/K+-ATPase α-subunit were quantified by qPCR and luminal concentrations of NO were determined. NaHS and L-cysteine decreased the gastric acid output in response to distention. The mRNA expression of H+/K+-ATPase α-subunit decreased by NaHS and L-cysteine as compared with the control group while gene expression of eNOS and COX-2 was upregulated. The inhibitory effect of NaHS on distention-induced gastric acid secretion was mitigated by pretreatment of L-NAME. These findings suggest the involvement of NO in mediating the antisecretory effect of H2S. Seyyed Ali Mard, Hasan Askari, Niloofar Neisi, and Ali Veisi Copyright © 2014 Seyyed Ali Mard et al. All rights reserved. Endoscopic and Pathologic Changes of the Upper Gastrointestinal Tract in Crohn’s Disease Mon, 03 Feb 2014 08:18:11 +0000 Background. Crohn’s disease (CD) may involve any part of the gastrointestinal tract. We assessed the prevalence and features of upper gastrointestinal (UGI) lesions in CD. Methods. This was a retrospective study that included 138 CD patients that underwent esophagogastroduodenoscopy (EGD). The rate of Crohn’s specific endoscopic lesions in the esophagus, stomach, and duodenum was assessed, and immunohistochemical analysis was performed. Changes in the UGI lesions were assessed in those who had two or more EGD. Results. Of 138 patients, 51.3% had Crohn’s specific UGI lesions. The rates of Crohn’s specific lesion in the esophagus, upper-to-middle stomach, lower stomach, duodenal bulb, and 2nd portion of the duodenum were 6.5%, 47.8%, 24.6%, 31.9%, and 18.1%, respectively. Granulomas were detected in 6.1%, 25.0%, and 11.4% in the upper-to-middle stomach, lower stomach, and duodenal bulb, respectively, but none in the esophagus and 2nd portion of the duodenum. Thirty-seven were analyzed for Helicobacter pylori and 4 were positive (10.8%). Improvements of UGI lesions were seen in 14 out of 49 (28.5%) and were unchanged in 59.2% and worsened in 12.2%. Conclusions. The prevalence of Crohn’s specific UGI lesions was common in our case series, and immunohistochemical studies suggested that the majority was unrelated to Helicobacter pylori infection. Worsening of UGI lesions over the course was rare. Atsushi Sakuraba, Yasushi Iwao, Katsuyoshi Matsuoka, Makoto Naganuma, Haruhiko Ogata, Takanori Kanai, and Toshifumi Hibi Copyright © 2014 Atsushi Sakuraba et al. All rights reserved. Animal Model of Acid-Reflux Esophagitis: Pathogenic Roles of Acid/Pepsin, Prostaglandins, and Amino Acids Sun, 02 Feb 2014 16:24:37 +0000 Esophagitis was induced in rats within 3 h by ligating both the pylorus and transitional region between the forestomach and glandular portion under ether anesthesia. This esophageal injury was prevented by the administration of acid suppressants and antipepsin drug and aggravated by exogenous pepsin. Damage was also aggravated by pretreatment with indomethacin and the selective COX-1 but not COX-2 inhibitor, whereas PGE2 showed a biphasic effect depending on the dose; a protection at low doses, and an aggravation at high doses, with both being mediated by EP1 receptors. Various amino acids also affected this esophagitis in different ways; L-alanine and L-glutamine had a deleterious effect, while L-arginine and glycine were highly protective, both due to yet unidentified mechanisms. It is assumed that acid/pepsin plays a major pathogenic role in this model of esophagitis; PGs derived from COX-1 are involved in mucosal defense of the esophagus; and some amino acids are protective against esophagitis. These findings also suggest a novel therapeutic approach in the treatment of esophagitis, in addition to acid suppressant therapy. The model introduced may be useful to test the protective effects of drugs on esophagitis and investigate the mucosal defense mechanism in the esophagus. Koji Takeuchi and Kenji Nagahama Copyright © 2014 Koji Takeuchi and Kenji Nagahama. All rights reserved. Changes in the Mucus Barrier during Cisplatin-Induced Intestinal Mucositis in Rats Mon, 23 Dec 2013 11:39:26 +0000 Aim. Gastrointestinal mucositis is a frequent complication of antineoplastic chemotherapy, but the effects of chemotherapy on mucosal defense mechanisms remain poorly understood. We studied the effects of cisplatin on mucin, one of the principal defense factors of the gastrointestinal mucosa, and evaluated the efficacy of two different types of H2-receptor antagonists against cisplatin-induced mucositis. Methods. Cisplatin (6 mg/kg) was administered intravenously to rats (day 0). The rats were sacrificed 1, 3, 7, and 11 days after treatment, and their stomach, jejunum, ileum, and colon were removed. Immunoreactivity of the mucosa was compared with the use of anti-mucin monoclonal antibody. To evaluate the efficacy of H2-receptor antagonists, either famotidine (3 mg/kg) or lafutidine (30 mg/kg) was given orally once daily on days 0, 1, and 2. Histological and biochemical findings were compared among the groups to assess effects on cisplatin-induced injury. Results. Cisplatin significantly altered the immunoreactivity and content of mucin in the small intestinal mucosa, especially in the ileum. Lafutidine protected against cisplatin-induced mucosal injury and attenuated decreased mucin accumulation. Conclusion. Cisplatin appears to alter the mucus barrier function in the intestinal mucosa. Lafutidine might effectively prevent chemotherapy-induced mucositis by activating intestinal mucus cells. Hajime Yamamoto, Kazuhiko Ishihara, Yuko Takeda, Wasaburo Koizumi, and Takafumi Ichikawa Copyright © 2013 Hajime Yamamoto et al. All rights reserved. Trends in Dietary Patterns, Alcohol Intake, Tobacco Smoking, and Colorectal Cancer in Polish Population in 1960–2008 Thu, 28 Nov 2013 12:37:27 +0000 The study examined the relationships between long-term trends in food consumption, alcohol intake, tobacco smoking, and colorectal cancer (CRC) incidence. Data on CRC incidence rates were derived from the National Cancer Registry, on food consumption from the national food balance sheets; data on alcohol and tobacco smoking reflected official statistics of the Central Statistical Office. It was shown that CRC incidence rates were increasing between 1960 and 1995, which could have been affected by adverse dietary patterns (growing consumption of edible fats, especially animal fats, sugar, red meat, and declining fibre and folate intake), high alcohol consumption, and frequent tobacco smoking noted until the end of the 1980s. Since 1990, the dietary pattern changed favourably (decrease in consumption of red meat, animal fats, and sugar, higher vitamin D intake, increase in vegetables and fruit quantities consumed, and decline in tobacco smoking). These changes could contribute to the stabilisation of CRC incidence among women seen after 1996 and a reduction in the rate of increase among men. Mirosław Jarosz, Włodzimierz Sekuła, and Ewa Rychlik Copyright © 2013 Mirosław Jarosz et al. All rights reserved. Infliximab Extends the Duration until the First Surgery in Patients with Crohn’s Disease Tue, 26 Nov 2013 14:34:13 +0000 Background/Aims. While biological drugs are useful for relieving the disease activity and preventing abdominal surgery in patients with Crohn’s disease (CD), it is unclear whether the use of biological drugs in CD patients with no history of abdominal surgery is appropriate. We evaluated the effects of infliximab and other factors on extending the duration until the first surgery in CD patients on a long-term basis. Methods. The clinical records of 104 CD patients were retrospectively investigated. The cumulative nonoperation rate until the first surgery was examined with regard to demographic factors and treatments. Results. The 50% nonoperative interval in the 104 CD patients was 107 months. The results of a univariate analysis revealed that a female gender, the colitis type of CD, and the administration of corticosteroids, immunomodulators, or infliximab were factors estimated to improve the cumulative nonoperative rate. A multivariate analysis showed that the colitis type and administration of infliximab were independent factors associated with a prolonged interval until the first surgery in the CD patients with no history of abdominal surgery. Conclusions. This study suggests that infliximab treatment extends the duration until the first surgery in CD patients with no history of abdominal surgery. The early use of infliximab before a patient undergoes abdominal surgery is therefore appropriate. Aki Sakatani, Mikihiro Fujiya, Takahiro Ito, Yuhei Inaba, Nobuhiro Ueno, Shin Kashima, Motoya Tominaga, Kentaro Moriichi, Kotaro Okamoto, Hiroki Tanabe, Katsuya Ikuta, Takaaki Ohtake, Toru Kono, Hiroyuki Furukawa, Toshifumi Ashida, and Yutaka Kohgo Copyright © 2013 Aki Sakatani et al. All rights reserved. HBV Genotype B/C and Response to Lamivudine Therapy: A Systematic Review Tue, 19 Nov 2013 09:58:17 +0000 A number of nucleoside analogues such as lamivudine (LAM), actually used for the treatment of chronic hepatitis B, can suppress HBV DNA replication, improve transaminase level and liver histology, and enhance the rate of hepatitis B e antigen (HBeAg) clearance. The responses to LAM therapy involve HBeAg clearance and HBV DNA conversion of negative. However, the associations between HBV genotype B/C and response to LAM therapy remain ambiguous. The aim of this meta-analysis is to determine more precise estimations of the relationship. All the publications on the associations between HBV genotype B/C and response to LAM (HBeAg clearance and HBV DNA conversion of negative) through June 2013 were collected. Relative risk (RR) with 95% confidence intervals (95% CI) was calculated in fixed or random model, was calculated to examine heterogeneity, and funnel plots were plotted to examine small study effects with Stata 11 software. Overall, for HBeAg clearance and genotype B/C, the RR (95% CI) was 1.27 (0.94–1.71), while for HBV DNA conversion of negative and genotype B/C, the RR (95% CI) was 1.07 (0.98–1.17). HBV genotype B/C shows no significance associations with response to lamivudine therapy (HBeAg clearance and HBV DNA conversion of negative). Xiu-Li Chen, Man Li, and Xiao-Lan Zhang Copyright © 2013 Xiu-Li Chen et al. All rights reserved. Appendicostomy in Preschool Children with Anorectal Malformation: Successful Early Bowel Management with a High Frequency of Minor Complications Mon, 23 Sep 2013 14:37:27 +0000 Aim. The aim of this study is to evaluate postoperatively bowel symptoms of antegrade colon enema through appendicostomies in preschool children with anorectal malformation (ARM). Method. 164 children with ARM operated on with posterior sagittal anorectal plasty were included. The malformations were classified according to Krickenbeck classification. Seventeen children in preschool age had an appendicostomy. The bowel symptoms according to the Krickenbeck follow-up were analysed pre- and postoperatively. All complications were registered. A questionnaire on the use of the appendicostomy was answered. Results. The median age (range) at the time of the appendicostomy was 4 (1–6) years. The observation time was 5 (0.5–14) years. The main indications for appendicostomy were incontinence and noncompliance to rectal enemas. Postoperatively there was a significant decrease in soiling and constipation (). The total complication rate was 43% with infections (29%), stenosis (12%), and retrograde leakage (0). The median time required for giving enema in the appendicostomy was 45 minutes (range: 15–120) once a day varying from 2 times/week to 3 times/day. And: complications are less frequent than in older children. Conclusion. Appendicostomy in preschool children with ARM is a way to achieve fecal cleanness before school start. The infection rate was high, but other complications are less frequent than in older children. Pernilla Stenström, Christina Granéli, Martin Salö, Kristine Hagelsteen, and Einar Arnbjörnsson Copyright © 2013 Pernilla Stenström et al. All rights reserved. Alkaline Phosphatase: The Next Independent Predictor of the Poor 90-Day Outcome in Alcoholic Hepatitis Tue, 17 Sep 2013 09:48:07 +0000 Aim. Determination of risk factors relevant to 90-day prognosis in AH. Comparison of the conventional prognostic models such as Maddrey’s modified discriminant function (mDF) and Child-Pugh-Turcotte (CPT) score with newer ones: the Glasgow Alcoholic Hepatitis Score (GAHS); Age, Bilirubin, INR, Creatinine (ABIC) score, Model for End-Stage Liver Disease (MELD), and MELD-Na in the death prediction. Patients and Methods. The clinical and laboratory variables obtained at admission were assessed. The mDF, CPT, GAHS, ABIC, MELD, and MELD-Na scores’ different areas under the curve (AUCs) and the best threshold values were compared. Logistic regression was used to assess predictors of the 90-day outcome. Results. One hundred sixteen pts fulfilled the inclusion criteria. Twenty (17.4%) pts died and one underwent orthotopic liver transplantation (OLT) within 90 days of follow-up. No statistically significant differences in the models‘ performances were found. Multivariate logistic regression identified CPT score, alkaline phosphatase (AP) level higher than 1.5 times the upper limit of normal (ULN), and corticosteroids (CS) nonresponse as independent predictors of mortality. Conclusions. The CPT score, AP > 1.5 ULN, and the CS nonresponse had an independent impact on the 90-day survival in AH. Accuracy of all studied scoring systems was comparable. Beata Kasztelan-Szczerbinska, Maria Slomka, Krzysztof Celinski, and Mariusz Szczerbinski Copyright © 2013 Beata Kasztelan-Szczerbinska et al. All rights reserved. Anti-Actin IgA Antibodies Identify Celiac Disease Patients with a Marsh 3 Intestinal Damage among Subjects with Moderate Anti-TG2 Levels Thu, 05 Sep 2013 11:54:16 +0000 A new diagnostic tool (algorithm-1) for coeliac disease (CD) permitting the diagnosis without performing the duodenal biopsy has been recently proposed by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). It combines symptoms associated with CD, high anti-transglutaminase type 2 antibody (anti-TG2) levels, anti-endomysium-IgA antibodies (EMA), and at-risk HLA. Our aims were (i) to evaluate retrospectively in 227 individuals (149 CD patients and 78 controls) the algorithm-1, (ii) to reduce the number of duodenal biopsies among CD patients for whom algorithm-1 is not applicable through the addition of antiactin IgA antibodies (AAA-IgA), and (iii) to evaluate prospectively algorithm-1 and AAA-IgA in 50 patients with suspected CD. Algorithm-1 identified 70 out of 149 CD patients with Marsh 3 lesions. Adding AAA-IgA to the remaining patients with anti-TG2 levels comprised between 4 and 10 times upper limit of normal (ULN) allowed the detection of further 20 patients with a Marsh 3 damage. In our prospective study, algorithm-1 identified 23 out of 50 patients, whilst further 7 were recognized adding AAA-IgA. We confirm that algorithm-1 may avoid the duodenal biopsy in many CD patients and underscores the usefulness of AAA-IgA in reducing the number of duodenal biopsies in patients with moderate anti-TG2 levels. Enrico Schirru, Fabrice Danjou, Lucia Cicotto, Rossano Rossino, Maria Doloretta Macis, Rosanna Lampis, Rita-Désirée Jores, and Mauro Congia Copyright © 2013 Enrico Schirru et al. All rights reserved. Metabolism, Physiological Role, and Clinical Implications of Sphingolipids in Gastrointestinal Tract Thu, 05 Sep 2013 11:14:52 +0000 Sphingolipids in digestive system are responsible for numerous important physiological and pathological processes. In the membrane of gut epithelial cells, sphingolipids provide structural integrity, regulate absorption of some nutrients, and act as receptors for many microbial antigens and their toxins. Moreover, bioactive sphingolipids such as ceramide or sphingosine-1-phosphate regulate cellular growth, differentiation, and programmed cell death—apoptosis. Although it is well established that sphingolipids have clinical implications in gastrointestinal tumorigenesis or inflammation, further studies are needed to fully explore the role of sphingolipids in neoplastic and inflammatory diseases in gastrointestinal tract. Pharmacological agents which regulate metabolism of sphingolipids can be potentially used in the management of colorectal cancer or inflammatory bowel diseases. The aim of this work is to critically the review physiological and pathological roles of sphingolipids in the gastrointestinal tract. Krzysztof Kurek, Bartłomiej Łukaszuk, Dominika M. Piotrowska, Patrycja Wiesiołek, Anna Małgorzata Chabowska, and Małgorzata Żendzian-Piotrowska Copyright © 2013 Krzysztof Kurek et al. All rights reserved. FOXP3+ T Regulatory Cell Modifications in Inflammatory Bowel Disease Patients Treated with Anti-TNF Agents Mon, 26 Aug 2013 08:40:51 +0000 Treg modulation has been hypothesized as one of the mechanisms by which antitumor necrosis factor α (TNFα) agents exert their action in rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). However, data in IBD are still conflicting. We evaluated CD4+CD25+FOXP3+ (Tregs) by flow cytometry in peripheral blood from 32 adult IBD patient before (T0) and after the induction of anti-TNFα therapy (T1). Eight healthy controls (HCs) were included. We also evaluated the number of FOXP3+ cells in the lamina propria (LP) in biopsies taken in a subset of patients and controls. Treg frequencies were significantly increased in peripheral blood from our patients after anti-TNFα therapy compared to T0. T1 but not T0 levels were higher than HC. The increase was detectable only in clinical responders to the treatment. A negative correlation was found among delta Treg levels and the age of patients or disease duration and with the activity score of Crohn’s disease (CD). No significant differences were found in LP FOXP3+ cells. Our data suggest the possibility that in IBD patients the treatment with anti-TNFα may affect Treg percentages and that Treg modifications may correlate with clinical response, but differently in early versus late disease. Luisa Guidi, Carla Felice, Annabella Procoli, Giuseppina Bonanno, Enrica Martinelli, Manuela Marzo, Giammarco Mocci, Daniela Pugliese, Gianluca Andrisani, Silvio Danese, Italo De Vitis, Alfredo Papa, Alessandro Armuzzi, and Sergio Rutella Copyright © 2013 Luisa Guidi et al. All rights reserved. Quality of Life after Stapled Hemorrhoidopexy: A Prospective Observational Study Thu, 22 Aug 2013 11:47:33 +0000 Objective. The objective of the study was to assess the change in quality of life (QOL) of patients undergoing stapled hemorrhoidopexy (SH) using WHO Quality of Life-BREF (WHOQOL-BREF) questionnaire. Methods. The study sample comprised patients with symptomatic II, III, and IV degree hemorrhoids, undergoing SH. The patients were asked to complete WHOQOL-BREF questionnaire before and one month following the surgery. Result. There were 20 patients in the study group. The postoperative pain score measured by visual analogue scale at six hours postoperatively was at 24 hours. The items in the WHOQOL-BREF had high-internal consistency or reliability as shown by high Cronbach's alpha coefficient which was 0.82 and 0.90 for pre- and postoperative questionnaires. There was significant improvement in the overall perception of QOL and health, and in physical and psychological domains. There was modest improvement in environmental domain, while no change was noted in social domain. Conclusion. SH improved the quality of life of patients treated for hemorrhoids. Pankaj Kumar Garg, Gopal Kumar, Bhupendra Kumar Jain, and Debajyoti Mohanty Copyright © 2013 Pankaj Kumar Garg et al. All rights reserved. Effect of Perilla frutescens Fixed Oil on Experimental Esophagitis in Albino Wistar Rats Tue, 20 Aug 2013 13:25:35 +0000 The present study was undertaken to elucidate the effect of Perilla frutescens fixed oil on experimental esophagitis in albino rats. A group of rats (), treated with control vehicle (0.9% NaCl in double distilled water, 3 mL/kg, i.p.) and Perilla frutescens fixed oil (100%) (1, 2, and 3 mL/kg, i.p.), or pantoprazole (30 mg/kg, i.p.), were subjected to pylorus and forestomach ligation. Animals were sacrificed after 6 h and evaluated for the gastric pH, volume of gastric juices, total acidity, esophagitis index and free acidity. Esophageal tissues were further subjected to estimations of TBARS, GSH, catalase, and SOD. Treatment with fixed oil significantly inhibited the gastric secretion, total acidity, and esophagitis index. The oil also helped to restore the altered levels of oxidative stress parameters to normal. The present study also makes evident the in vitro antihistaminic and anticholinergic activity of alpha linolenic acid (ALA) (18 : 3, ) on isolated rat ileum preparation. The lipoxygenase inhibitory, histamine antagonistic, antisecretory (anticholinergic), and antioxidant activity of the oil was attributed for its efficacy in reflux esophagitis. Ekta Arya, Sudipta Saha, Shubhini A. Saraf, and Gaurav Kaithwas Copyright © 2013 Ekta Arya et al. All rights reserved. Detection of Gastric Cancer with Fourier Transform Infrared Spectroscopy and Support Vector Machine Classification Tue, 13 Aug 2013 09:20:22 +0000 Early diagnosis and early medical treatments are the keys to save the patients' lives and improve the living quality. Fourier transform infrared (FT-IR) spectroscopy can distinguish malignant from normal tissues at the molecular level. In this paper, programs were made with pattern recognition method to classify unknown samples. Spectral data were pretreated by using smoothing and standard normal variate (SNV) methods. Leave-one-out cross validation was used to evaluate the discrimination result of support vector machine (SVM) method. A total of 54 gastric tissue samples were employed in this study, including 24 cases of normal tissue samples and 30 cases of cancerous tissue samples. The discrimination results of SVM method showed the sensitivity with 100%, specificity with 83.3%, and total discrimination accuracy with 92.2%. Qingbo Li, Wei Wang, Xiaofeng Ling, and Jin Guang Wu Copyright © 2013 Qingbo Li et al. All rights reserved. Gut Microbial Flora, Prebiotics, and Probiotics in IBD: Their Current Usage and Utility Wed, 07 Aug 2013 14:03:59 +0000 Inflammatory bowel diseases are chronic diseases affecting the gastrointestinal tract, whose major forms are represented by Crohn’s disease (CD) and ulcerative colitis (UC). Their etiology is still unclear, although several factors have been identified as major determinants for induction or relapses. Among these, the role of the “forgotten organ”, gut microbiota, has become more appreciated in recent years. The delicate symbiotic relationship between the gut microbiota and the host appears to be lost in IBD. In this perspective, several studies have been conducted to assess the role of prebiotics and probiotics in gut microbiota modulation. This is a minireview aimed to address in an easy format (simple questions-simple answers) some common issues about the theme. An update on the role of selected constituents of gut microbiota in the pathogenesis of IBD is presented together with the analysis of the efficacy of gut microbiota modulation by prebiotics and probiotics administration in the management of IBD. Franco Scaldaferri, Viviana Gerardi, Loris Riccardo Lopetuso, Fabio Del Zompo, Francesca Mangiola, Ivo Boškoski, Giovanni Bruno, Valentina Petito, Lucrezia Laterza, Giovanni Cammarota, Eleonora Gaetani, Alessandro Sgambato, and Antonio Gasbarrini Copyright © 2013 Franco Scaldaferri et al. All rights reserved. Inflammatory Bowel Disease Therapies and Gut Function in a Colitis Mouse Model Tue, 06 Aug 2013 13:37:10 +0000 Background. Exclusive enteral nutrition (EEN) is a well-established approach to the management of Crohn’s disease. Aim. To determine effects of EEN upon inflammation and gut barrier function in a colitis mouse model. Methods. Interleukin-10-deficient mice (IL-10−/−) were inoculated with Helicobacter trogontum and then treated with EEN, metronidazole, hydrocortisone, or EEN and metronidazole combination. Blood and tissue were collected at 2 and 4 weeks with histology, mucosal integrity, tight junction integrity, inflammation, and H. trogontum load evaluated. Results. H. trogontum induced colitis in IL-10−/− mice with histological changes in the cecum and colon. Elevated mucosal IL-8 mRNA in infected mice was associated with intestinal barrier dysfunction indicated by decreased transepithelial electrical resistance and mRNA of tight junction proteins and increased short-circuit current, myosin light chain kinase mRNA, paracellular permeability, and tumor necrosis factor-α and myeloperoxidase plasma levels ( for all comparisons). EEN and metronidazole, but not hydrocortisone, treatments restored barrier function, maintained gut barrier integrity, and reversed inflammatory changes along with reduction of H. trogontum load (versus infected controls ). Conclusion. H. trogontum infection in IL-10−/− mice induced typhlocolitis with intestinal barrier dysfunction. EEN and metronidazole, but not hydrocortisone, modulate barrier dysfunction and reversal of inflammatory changes. Lily Nahidi, Steven T. Leach, Hazel M. Mitchell, Nadeem O. Kaakoush, Daniel A. Lemberg, John S. Munday, Karina Huinao, and Andrew S. Day Copyright © 2013 Lily Nahidi et al. All rights reserved. The Effects of Bariatric Procedures versus Medical Therapy for Obese Patients with Type 2 Diabetes: Meta-Analysis of Randomized Controlled Trials Sun, 21 Jul 2013 09:19:00 +0000 Objective. To assess the effects of bariatric surgery versus medical therapy for type 2 diabetes mellitus. Methods. The Cochrane library, PubMed, Embase, Chinese biomedical literature database, and Wanfang database up to February 2012 were searched. The literature searches strategies contained terms (“diabetes*”, “surg*”, and “medic*” were used), combined with the medical subject headings. Randomized controlled trails (RCTs) of frequently used bariatric surgery for obese patients with type 2 diabetes were included. Study selection, data extraction, quality assessment, and data analyses were performed according to the Cochrane standards. Results. Three randomized controlled trials (RCTs) involving 170 patients in the bariatric surgery groups and 100 patients in the medical therapy group were selected. Compared with medical therapy, bariatric surgery for type 2 diabetes can significantly decrease the levels of HbA1c, FBG, weight, triglycerides, and the dose of hypoglycemic, antihypertensive, and lipid-lowering medicine, while increasing the rate of diabetes remission (RR = 9.74, 95%CI, (1.36, 69.66)) and the levels of high-density lipoprotein. However, there are no statistical differences in serious adverse events between the surgical and medical groups (RR = 1.23, 95%CI, (0.80, 1.87)). Conclusions. Surgical procedures were more likely to help patients achieve benefits than medical therapy alone. Further intensive RCTs of high-quality, multiple centers and long-term followup should be carried out to provide more reliable evidence. Xiaohu Guo, Xiaoyan Liu, Mancai Wang, Fengxian Wei, Yawu Zhang, and Youcheng Zhang Copyright © 2013 Xiaohu Guo et al. All rights reserved. Reduced T Cell Receptor Excision Circle Levels in the Colonic Mucosa of Microscopic Colitis Patients Indicate Local Proliferation rather than Homing of Peripheral Lymphocytes to the Inflamed Mucosa Sun, 14 Jul 2013 09:17:27 +0000 Dysregulated T cell responses in the intestine may lead to chronic bowel inflammation such as collagenous colitis (CC) and lymphocytic colitis (LC), together known as microscopic colitis (MC). Having demonstrated increased local T cell responses in the intestinal mucosa of MC patients, we investigated the recent thymic emigrants by measuring T cell receptor excision circle (TREC) levels in the colonic biopsies from CC (), LC (), and CC or LC patients in histopathological remission (CC-HR, ) (LC-HR, ), non-inflamed diarrhoea patients (), and controls () by real-time PCR. We observed lower median TREC levels in both CC and LC patients as well as in LC-HR patients compared to controls. In contrast to MC patients, non-inflamed diarrhoea patients presented with enhanced TREC levels compared to controls. None of the recorded differences did, however, reach statistical significance. A trend towards increased relative expression of CD3 was noted in all MC subgroups examined and reached statistical significance in LC patients compared to controls. In conclusion, reduced TRECs level in the colonic mucosa, together with our previously demonstrated enhanced expression of Ki67+ T cells, suggests local expansion of resident T lymphocytes in the inflamed mucosa of MC patients. Ashok Kumar Kumawat, Kristina Elgbratt, Curt Tysk, Johan Bohr, and Elisabeth Hultgren Hörnquist Copyright © 2013 Ashok Kumar Kumawat et al. All rights reserved. Expression of Melatonin Synthesizing Enzymes in Helicobacter pylori Infected Gastric Mucosa Wed, 10 Jul 2013 09:07:52 +0000 Helicobacter pylori colonization of gastric mucosa causes pain of unknown etiology in about 15–20% of infected subjects. The aim of the present work was to determine the level of expression of enzymes involved in the synthesis of melatonin in gastric mucosa of asymptomatic and symptomatic H. pylori infected patients. To diagnose H. pylori infection, histological analysis and the urea breath test (UBT C13) were performed. The levels of mRNA expression of arylalkylamine-N-acetyltransferase (AA-NAT) and acetylserotonin methyltransferase (ASMT) were estimated in gastric mucosa with RT-PCR. The level of AA-NAT expression and AMST was decreased in H. pylori infected patients and was increased after H. pylori eradication. We conclude that decreased expression of melatonin synthesizing enzymes, AA-NAT and ASMT, in patients with symptomatic H. pylori infection returns to normal level after H. pylori eradication. Cezary Chojnacki, Tomasz Popławski, Janusz Blasiak, Jan Chojnacki, Russel J. Reiter, and Grazyna Klupinska Copyright © 2013 Cezary Chojnacki et al. All rights reserved. Ethanol Extract of Cordyceps militaris Grown on Germinated Soybeans Attenuates Dextran-Sodium-Sulfate- (DSS-) Induced Colitis by Suppressing the Expression of Matrix Metalloproteinases and Inflammatory Mediators Wed, 12 Jun 2013 09:49:47 +0000 The effect of Cordyceps militaris (CM) grown on germinated soybeans (GSC) in the inflammatory bowel disease (IBD) model was studied. To demonstrate the preventive effect of GSC extract in a dextran-sodium-sulfate- (DSS-) induced acute colitis mouse model, GSC was administered 2 days before DSS coadministration. GSC significantly suppressed DSS-induced disease activity index (DAI) as well as histopathological scores, compared to control or CM-treated group. To elucidate the anti-IBD activity of GSC, we checked the level of matrix metalloproteinases (MMPs) and inflammatory mediators. GSC extract decreased the level of MMP-3 and -9 mRNAs and p53 proteins. The level and activity of LPS-induced MMP-9 were reduced in GSC-treated RAW264.7 cells. It also attenuated the level of inducible nitric oxide synthase (iNOS) and tumor necrosis factor- (TNF-) α mRNAs both in colon tissue and in macrophage cells. These results suggest that GSC can be applied as a protective agent against IBDs. Dong Ki Park and Hye-Jin Park Copyright © 2013 Dong Ki Park and Hye-Jin Park. All rights reserved. Acute Toxicity and Gastroprotective Role of M. pruriens in Ethanol-Induced Gastric Mucosal Injuries in Rats Tue, 28 May 2013 08:57:00 +0000 The investigation was to evaluate gastroprotective effects of ethanolic extract of M. pruriens leaves on ethanol-induced gastric mucosal injuries in rats. Forty-eight rats were divided into 8 groups: negative control, extract control, ulcer control, reference control, and four experimental groups. As a pretreatment, the negative control and the ulcer control groups were orally administered carboxymethylcellulose (CMC). The reference control was administered omeprazole orally (20 mg/kg). The ethanolic extract of M. pruriens leaves was given orally to the extract control group (500 mg/kg) and the experimental groups (62.5, 125, 250, and 500 mg/kg). After 1 h, CMC was given orally to the negative and the extract control groups. The other groups received absolute ethanol. The rats were sacrificed after 1 h. The ulcer control group exhibited significant mucosal injuries with decreased gastric wall mucus and severe damage to the gastric mucosa. The extract caused upregulation of Hsp70 protein, downregulation of Bax protein, and intense periodic acid schiff uptake of glandular portion of stomach. Gastric mucosal homogenate showed significant antioxidant properties with increase in synthesis of PGE2, while MDA was significantly decreased. The ethanolic extract of M. pruriens leaves was nontoxic (<5 g/kg) and could enhance defensive mechanisms against hemorrhagic mucosal lesions. Shahram Golbabapour, Maryam Hajrezaie, Pouya Hassandarvish, Nazia Abdul Majid, A. Hamid A. Hadi, Noraziah Nordin, and Mahmood A. Abdulla Copyright © 2013 Shahram Golbabapour et al. All rights reserved. Electrogastrography in Adults and Children: The Strength, Pitfalls, and Clinical Significance of the Cutaneous Recording of the Gastric Electrical Activity Sat, 25 May 2013 17:36:04 +0000 Cutaneous electrogastrography (EGG) is a non-invasive technique to record gastric myoelectrical activity from the abdominal surface. Although the recent rapid increase in the development of electrocardiography, EGG still suffers from several limitations. Currently, computer analysis of EGG provides few reliable parameters, such as frequency and the percentage of normal and altered slow wave activity (bradygastria and tachygastria). New EGG hardware and software, along with an appropriate arrangement of abdominal electrodes, could detect the coupling of the gastric slow wave from the EGG. At present, EGG does not diagnose a specific disease, but it puts in evidence stomach motor dysfunctions in different pathological conditions as gastroparesis and functional dyspepsia. Despite the current pitfalls of EGG, a multitasking diagnostic protocol could involve the EGG and the 13C-breath testing for the evaluation of the gastric emptying time—along with validated gastrointestinal questionnaires and biochemical evaluations of the main gastrointestinal peptides—to identify dyspeptic subgroups. The present review tries to report the state of the art about the pathophysiological background of the gastric electrical activity, the recording and processing methodology of the EGG with particular attention to multichannel recording, and the possible clinical application of the EGG in adult and children. Giuseppe Riezzo, Francesco Russo, and Flavia Indrio Copyright © 2013 Giuseppe Riezzo et al. All rights reserved. Diet, Microbiome, and the Intestinal Epithelium: An Essential Triumvirate? Sun, 17 Mar 2013 16:14:02 +0000 The intestinal epithelium represents a critical barrier protecting the host against diverse luminal noxious agents, as well as preventing the uncontrolled uptake of bacteria that could activate an immune response in a susceptible host. The epithelial monolayer that constitutes this barrier is regulated by a meshwork of proteins that orchestrate complex biological function such as permeability, transepithelial electrical resistance, and movement of various macromolecules. Because of its key role in maintaining host homeostasis, factors regulating barrier function have attracted sustained attention from the research community. This paper will address the role of bacteria, bacterial-derived metabolism, and the interplay of dietary factors in controlling intestinal barrier function. Javier Rivera Guzman, Victoria Susan Conlin, and Christian Jobin Copyright © 2013 Javier Rivera Guzman et al. All rights reserved. Prevention of Chronic Experimental Colitis Induced by Dextran Sulphate Sodium (DSS) in Mice Treated with FR91 Sun, 12 Feb 2012 15:45:00 +0000 One of the main treatments currently used in humans to fight cancer is chemotherapy. A huge number of compounds with antitumor activity are present in nature, and many of their derivatives are produced by microorganisms. However, the search for new drugs still represents a main objective for cancer therapy, due to drug toxicity and resistance to multiple chemotherapeutic drugs. In animal models, a short-time oral administration of dextran sulfate sodium (DSS) induces colitis, which exhibits several clinical and histological features similar to ulcerative colitis (UC). However, the pathogenic factors responsible for DSS-induced colitis and the subsequent colon cancer also remain unclear. We investigated the effect of FR91, a standardized lysate of microbial cells belonging to the Bacillus genus which has been previously shown to have significant immunomodulatory effects, against intestinal inflammation. Colitis was induced in mice during 5 weeks by oral administration 2% (DSS). Morphological changes in the colonic mucosa were evaluated by hematoxylin-eosin staining and immunohistochemistry methods. Adenocarcinoma and cryptal cells of the dysplastic epithelium showed cathenin-β, MLH1, APC, and p53 expression, together with increased production of IFN-γ. In our model, the optimal dose response was the 20% FR91 concentration, where no histological alterations or mild DSS-induced lesions were observed. These results indicate that FR91 may act as a chemopreventive agent against inflammation in mice DSS-induced colitis. Valter R. M. Lombardi, Ignacio Etcheverría, Iván Carrera, Ramón Cacabelos, and Antonio R. Chacón Copyright © 2012 Valter R. M. Lombardi et al. All rights reserved. Higher Molecular Weight Polyethylene Glycol Increases Cell Proliferation While Improving Barrier Function in an In Vitro Colon Cancer Model Sat, 01 Oct 2011 12:56:55 +0000 Polyethylene glycol (PEG) has been previously shown to protect against enteric pathogens and prevent colon cancer invasion. To determine if PEG could indeed protect against previously observed pro-invasive effects of commensal E. coli and EPEC, Caco-2 cells grown in an in vitro model of colon cancer were infected with strains of human commensal E. coli or EPEC and treated with 10% PEG 3350, PEG 8000, and PEG 20,000, respectively. At 24 hours after infection, MMP-1 and MMP-13 activities, cell cluster thickness, depth of invasion, and proliferation were determined using standard molecular biology techniques and advanced imaging. We found that higher molecular weight PEG, especially PEG 8000 and 20,000, regardless of bacterial infection, increased proliferation and depth of invasion although a decrease in cellular density and MMP-1 activity was also noted. Maximum proliferation and depth of invasion of Caco-2 cells was observed in scaffolds treated with a combination of commensal E. coli strain, HS4 and PEG 8000. In conclusion, we found that PEG 8000 increased cell proliferation and led to the preservation of cell density in cells treated with commensal bacteria. This is important, because the preservation of a proliferative response in colon cancer results in a more chemo-responsive tumor. Shruthi Bharadwaj, Ramana Vishnubhotla, Sun Shan, Chinmay Chauhan, Michael Cho, and Sarah C. Glover Copyright © 2011 Shruthi Bharadwaj et al. All rights reserved. Cytotoxic T Cells in H. pylori-Related Gastric Autoimmunity and Gastric Lymphoma Tue, 22 Jun 2010 09:01:19 +0000 Helicobacter pylori infection is the major cause of gastroduodenal pathologies, but only a minority of infected patients develop gastric B-cell lymphoma, gastric autoimmunity, or other life threatening diseases, as gastric cancer or peptic ulcer. The type of host immune response against H. pylori, particularly the cytolytic effector functions of T cells, is crucial for the outcome of the infection. T cells are potentially able to kill a target via different mechanisms, such as perforins or Fas-Fas ligand interaction. In H. pylori-infected patients with gastric autoimmunity cytolytic T cells, that cross-recognize different epitopes of H. pylori proteins and H+K+-ATPase autoantigen, infiltrate the gastric mucosa and lead to gastric atrophy via long-lasting activation of Fas ligand-mediated appotosis and perforin-induced cytotoxicity. On the other hand, gastric T cells from MALT lymphoma exhibit defective perforin- and Fas-Fas ligand-mediated killing of B cells, with consequent abnormal help for B-cell proliferation, suggesting that deregulated and exhaustive H. pylori-induced T cell-dependent B-cell activation can support both the onset and the promotion of low-grade B-cell lymphoma. Mathijs P. Bergman and Mario M. D'Elios Copyright © 2010 Mathijs P. Bergman and Mario M. D'Elios. All rights reserved. Rotavirus-Like Particles: A Novel Nanocarrier for the Gut Tue, 13 Apr 2010 10:48:03 +0000 The delivery of bioactive molecules directly to damaged tissues represents a technological challenge. We propose here a new system based on virus-like particles (VLP) from rotavirus, with a marked tropism for the gut to deliver bio-active molecules to intestinal cells. For this, nonreplicative VLP nanoparticles were constructed using a baculovirus expression system and used to deliver an exogenous biomolecule, the green fluorescent protein (GFP), into either MA104 cells or intestinal cells from healthy and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-treated mice. Our results show that expression of rotavirus capsid proteins in baculovirus led to the auto assembly of VLP that display similar properties to rotavirus. In vitro experiments showed that VLP were able to enter into MA104 cells and deliver the reporter protein. Intragastric administration of fluorescent VLP in healthy and TNBS-treated mice resulted in the detection of GFP and viral proteins in intestinal samples. Our results demonstrate an efficient entry of non-replicative rotavirus VLP into the epithelial cell line MA104 and provide the first in vivo evidence of the potential of these nanoparticles as a promising safe candidate for drug delivery to intestinal cells. Naima G. Cortes-Perez, Catherine Sapin, Loïc Jaffrelo, Sabine Daou, Jean Pierre Grill, Philippe Langella, Philippe Seksik, Laurent Beaugerie, Serge Chwetzoff, and Germain Trugnan Copyright © 2010 Naima G. Cortes-Perez et al. All rights reserved.