BioMed Research International: Gastroenterology The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . 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. Underestimating the Toxicological Challenges Associated with the Use of Herbal Medicinal Products in Developing Countries Thu, 19 Sep 2013 10:16:59 +0000 Various reports suggest a high contemporaneous prevalence of herb-drug use in both developed and developing countries. The World Health Organisation indicates that 80% of the Asian and African populations rely on traditional medicine as the primary method for their health care needs. Since time immemorial and despite the beneficial and traditional roles of herbs in different communities, the toxicity and herb-drug interactions that emanate from this practice have led to severe adverse effects and fatalities. As a result of the perception that herbal medicinal products have low risk, consumers usually disregard any association between their use and any adverse reactions hence leading to underreporting of adverse reactions. This is particularly common in developing countries and has led to a paucity of scientific data regarding the toxicity and interactions of locally used traditional herbal medicine. Other factors like general lack of compositional and toxicological information of herbs and poor quality of adverse reaction case reports present hurdles which are highly underestimated by the population in the developing world. This review paper addresses these toxicological challenges and calls for natural health product regulations as well as for protocols and guidance documents on safety and toxicity testing of herbal medicinal products. Vidushi S. Neergheen-Bhujun Copyright © 2013 Vidushi S. Neergheen-Bhujun. 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. Molecular Profiling Predicts the Existence of Two Functionally Distinct Classes of Ovarian Cancer Stroma Thu, 09 May 2013 11:38:28 +0000 Although stromal cell signaling has been shown to play a significant role in the progression of many cancers, relatively little is known about its importance in modulating ovarian cancer development. The purpose of this study was to investigate the process of stroma activation in human ovarian cancer by molecular analysis of matched sets of cancer and surrounding stroma tissues. RNA microarray profiling of 45 tissue samples was carried out using the Affymetrix (U133 Plus 2.0) gene expression platform. Laser capture microdissection (LCM) was employed to isolate cancer cells from the tumors of ovarian cancer patients (Cepi) and matched sets of surrounding cancer stroma (CS). For controls, ovarian surface epithelial cells (OSE) were isolated from the normal (noncancerous) ovaries and normal stroma (NS). Hierarchical clustering of the microarray data resulted in clear separations between the OSE, Cepi, NS, and CS samples. Expression patterns of genes encoding signaling molecules and compatible receptors in the CS and Cepi samples indicate the existence of two subgroups of cancer stroma (CS) with different propensities to support tumor growth. Our results indicate that functionally significant variability exists among ovarian cancer patients in the ability of the microenvironment to modulate cancer development. Loukia N. Lili, Lilya V. Matyunina, L. DeEtte Walker, Benedict B. Benigno, and John F. McDonald Copyright © 2013 Loukia N. Lili 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.