Disease Markers http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. A Comparison of KL-6 and Clara Cell Protein as Markers for Predicting Bronchopulmonary Dysplasia in Preterm Infants Wed, 27 Aug 2014 11:53:19 +0000 http://www.hindawi.com/journals/dm/2014/736536/ Objectives. To evaluate the predictive characteristics of KL-6 and CC16 for bronchopulmonary dysplasia (BPD) in preterm infants, either independently or in combination. Study Design. This prospective cohort study was performed from 2011 to 2013 with preterm neonates of gestational age ≤32 weeks and birth weight ≤1500 g. Serum KL-6 and CC16 levels were determined 7 and 14 days after birth. Results. Seventy-three preterm infants were studied. BPD was identified in 24 of these infants. After adjusting for potential confounders, serum KL-6 concentrations were found to be elevated in BPD infants at both time points relative to non-BPD infants, while serum CC16 concentrations were lower at 14 days. At both 7 d and 14 d of life the predictive power of KL-6 levels exceeded that of CC16 (area under receiver operating characteristic curve: at 7 d, 0.91 cf. 0.73, ; at 14 d, 0.95 cf. 0.85, ). The combination of these markers enhanced the sensitivity further. Conclusions. Serum KL-6 levels higher than 79.26 ng/mL at 14 days postpartum in preterm infants predict the occurrence of BPD. CC16 was less predictive than KL-6 at this time point, but KL-6 and CC16 together enhanced the prediction. Keyi Wang, Xianmei Huang, Hui Lu, and Zhiqun Zhang Copyright © 2014 Keyi Wang et al. All rights reserved. Two Polymorphisms in the Fractalkine Receptor CX3CR1 Gene Influence the Development of Atherosclerosis: A Meta-Analysis Tue, 26 Aug 2014 06:08:28 +0000 http://www.hindawi.com/journals/dm/2014/913678/ Background. The associations between the Fractalkine receptor (CX3CR1) gene T280M (rs3732378) and V249I (rs3732379) polymorphisms and atherosclerosis (AS) risk are conflicting. The aim of this meta-analysis was undertaken to assess their associations. Methods. PubMed, Embase, Web of Science, Medline, Cochrane database, and CNKI were searched to get the genetic association studies. All statistical analyses were done with Stata 11.0. Results. Twenty-five articles involving 49 studies were included in the final meta-analysis. The analysis showed that the 280M allele carriers of the CX3CR1 T280M polymorphism decreased the risk of AS and coronary artery disease (CAD) in the heterozygous state but increased the risk of ischemic cerebrovascular disease (ICVD) in the homozygote state. The 249I allele carriers of the CX3CR1 V249I polymorphism decreased the risk of AS and CAD in the heterozygous state. The V249I-T280M combined genotype VITM and IITM also decreased the risk of AS. Conclusions. The present meta-analysis suggests that the CX3CR1 T280M and V249I polymorphisms are associated with the susceptibility to AS. However, the results should be interpreted with caution because of the high heterogeneity in the meta-analysis. Jian Wu, Rui-Xing Yin, Quan-Zhen Lin, Tao Guo, Guang-Yuan Shi, Jia-Qi Sun, Shao-Wen Shen, and Qing Li Copyright © 2014 Jian Wu et al. All rights reserved. Lead Exposure: A Summary of Global Studies and the Need for New Studies from Saudi Arabia Tue, 19 Aug 2014 06:09:49 +0000 http://www.hindawi.com/journals/dm/2014/415160/ Lead poisoning (plumbism) can cause irreversible genetic and reproductive toxicity, hematological effects, neurological damage, and cardiovascular effects. Despite many efforts to minimize lead poisoning, it continues to be a major health concern in many developing and developed countries. Despite efforts to control lead exposure and toxicity, serious cases of lead poisoning increasingly occur as a result of higher vehicular traffic and industrialization. The biomarkers for identification of genetic susceptibility to a particular disease are useful to identify individuals who are at risk for lead poisoning. Although many such studies have been taken up elsewhere, very few studies were performed in Saudi Arabia to assess susceptibility to lead poisoning. This indicates an urgent need for testing of susceptible individuals. The present paper was planned to understand the genetic susceptibility to lead toxicity in the various population studies conducted worldwide and also to correlate it with the current scenario in Saudi Arabia. Such studies are necessary for appropriate precautions in terms of diet and avoiding exposure to be used in order to prevent adverse health effects. A. P. Shaik, S. A. Sultana, and A. H. Alsaeed Copyright © 2014 A. P. Shaik et al. All rights reserved. Association of the Three Common SNPs of Cyclooxygenase-2 Gene (rs20417, rs689466, and rs5275) with the Susceptibility of Breast Cancer: An Updated Meta-Analysis Involving 34,590 Subjects Mon, 18 Aug 2014 06:29:16 +0000 http://www.hindawi.com/journals/dm/2014/484729/ Several single nucleotide polymorphisms have been identified in cyclooxygenase-2 (COX-2) genes (e.g., −765 G>C (rs20417), −1195G>A (rs689466), and 8473 C>T (rs5275)). The association of these SNPs with the risk of different cancer types is still controversial. This study aims to evaluate the correlation between these SNPs and breast cancer risk in different ethnic groups. We have searched PubMed, Web of Knowledge, and Embase for relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the associations. A total of 13 studies (15,330 cases and 19,260 controls) were eligible for meta-analysis. This meta-analysis showed that COX-2 rs20417 polymorphism was correlated with an increased risk of breast cancer in Caucasians, while rs689466 was associated with a decreased risk of breast cancer in Caucasians. The rs5275 polymorphism had no association with breast cancer risk. Zhi-Jun Dai, Yong-Ping Shao, Xiao-Bin Ma, Dan Xu, Wei Tang, Hua-Feng Kang, Shuai Lin, Meng Wang, Hong-Tao Ren, and Xi-Jing Wang Copyright © 2014 Zhi-Jun Dai et al. All rights reserved. The Serum Glycome to Discriminate between Early-Stage Epithelial Ovarian Cancer and Benign Ovarian Diseases Tue, 12 Aug 2014 09:37:11 +0000 http://www.hindawi.com/journals/dm/2014/238197/ Epithelial ovarian cancer (EOC) is the sixth most common cause of cancer deaths in women because the diagnosis occurs mostly when the disease is in its late-stage. Current diagnostic methods of EOC show only a moderate sensitivity, especially at an early-stage of the disease; hence, novel biomarkers are needed to improve the diagnosis. We recently reported that serum glycome modifications observed in late-stage EOC patients by MALDI-TOF-MS could be combined as a glycan score named GLYCOV that was calculated from the relative areas of the 11 N-glycan structures that were significantly modulated. Here, we evaluated the ability of GLYCOV to recognize early-stage EOC in a cohort of 73 individuals comprised of 20 early-stage primary serous EOC, 20 benign ovarian diseases (BOD), and 33 age-matched healthy controls. GLYCOV was able to recognize stage I EOC whereas CA125 values were statistically significant only for stage II EOC patients. In addition, GLYCOV was more sensitive and specific compared to CA125 in distinguishing early-stage EOC from BOD patients, which is of high relevance to clinicians as it is difficult for them to diagnose malignancy prior to operation. Karina Biskup, Elena Iona Braicu, Jalid Sehouli, Rudolf Tauber, and Véronique Blanchard Copyright © 2014 Karina Biskup et al. All rights reserved. Association of Tagging SNPs in the MTHFR Gene with Risk of Type 2 Diabetes Mellitus and Serum Homocysteine Levels in a Chinese Population Wed, 06 Aug 2014 11:42:24 +0000 http://www.hindawi.com/journals/dm/2014/725731/ Diabetes is a global public health crisis, and the prevalence is increasing rapidly. Folate supplementation is proved to be effective in reducing the risk of diabetes or improving its symptoms. Methylenetetrahydrofolate reductase is an important enzyme involved in folate metabolism. The aim of this study is to examine whether polymorphisms in the MTHFR gene are associated with risk of type 2 diabetes mellitus (T2DM) and fasting total serum homocysteine (tHcy) levels. We genotyped nine tagging SNPs in the MTHFR gene in a case-control study, including 595 T2DM cases and 681 healthy controls in China. We found that C allele of rs9651118 had significant decreased risk of T2DM (adjusted odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.55–0.87, ) compared with T allele. Haplotype analysis also showed that MTHFR CTCCGA haplotype (rs12121543-rs13306553-rs9651118-rs1801133-rs2274976-rs1801131) had significant reduced risk of T2DM (adjusted OR = 0.71, 95% CI: 0.58–0.87, ) compared with CTTTGA haplotype. Besides, the MTHFR rs1801133 was significantly associated with serum levels of tHcy in healthy controls (). These associations were still significant after Bonferroni corrections (). These findings suggest that variants in the MTHFR gene may influence the risk of T2DM and tHcy levels. Han Wang, Cong Hu, Shu-Hui Xiao, and Bin Wan Copyright © 2014 Han Wang et al. All rights reserved. Antineutrophil Cytoplasmic Antibody Frequency in Chronic Hepatitis B Patients Tue, 05 Aug 2014 09:41:37 +0000 http://www.hindawi.com/journals/dm/2014/982150/ Background. Chronic hepatitis B (CHB) is a viral disease, common across the world, and associated with several extraintestinal manifestations including vasculitis. Antineutrophil cytoplasmic antibodies (ANCAs) are sensitive and specific markers for vasculitides. There is limited data available in the literature on whether ANCA formation is stimulated by CHB infection. In the present study we aimed to identify the frequency of ANCA in CHB patients. Methods. A total of 174 subjects were included in the study (87 CHB patients, 87 control subjects). Perinuclear-ANCA (P-ANCA), cytoplasmic-ANCA (C-ANCA), myeloperoxidase ANCA (MPO-ANCA), and proteinase 3-ANCA (PR3-ANCA) were studied. IFA was used for P-ANCA and C-ANCA assays, and ELISA was used for MPO-ANCA and PR3-ANCA assays. Results. ANCA positivity was high in both groups (31% in the CHB group and 26% among controls). There were no significant differences between the groups for P-ANCA and MPO-ANCA (P = 0.6 and P = 0.6, resp.). Frequency of borderline positive C-ANCA and all positive PR3-ANCA (positive + borderline positive) was significantly higher in the CHB group (P = 0.009 and P = 0.005, resp.). Conclusions. In the present study, the frequency of ANCA was high in both groups. The CHB group had a relatively higher frequency of ANCA positivity compared to controls. Borderline positive C-ANCA and positive PR3-ANCA were significantly higher in the CHB group. These results suggest that ANCA may have a high prevalence in Turkey. Patients with CHB should be evaluated particularly for C-ANCA and PR3-ANCA in the presence of vasculitic complaints and lesions. Turan Calhan, Abdurrahman Sahin, Resul Kahraman, Mustafa Erhan Altunoz, Fatma Ozbakır, Kamil Ozdil, and Hacı Mehmet Sokmen Copyright © 2014 Turan Calhan et al. All rights reserved. miR-146a Expression Level as a Novel Putative Prognostic Marker for Acute Promyelocytic Leukemia Tue, 05 Aug 2014 07:48:47 +0000 http://www.hindawi.com/journals/dm/2014/150604/ Background. Although the curative rate for acute promyelocytic leukemia (APL) has been improved over decades, long-term prognosis is still poor. The genetic pathways that regulated cell lineage fate during the development of APL remain unclear. Methods. We investigated the correlations of miR-146a expression with its target gene Smad4 and the biological behaviors of NB4 cells. We also analyzed their expression in clinical samples from APL patients. Results. miR-146a influenced apoptosis and proliferation in NB4 cells. miR-146a influenced endogenous Smad4 protein levels in APL cells. miR-146a expression levels were positively correlated with white cell counts and PML/RARα fusion protein expression. miR-146a expression levels were negatively correlated with Smad4 protein and the helper T cell (Th)/the suppressor T cell (Ts) ratio in these patients. Conclusions. These findings indicated that miR-146a played an important role in the development of APL in part through the repression on Smad4 protein expression. miR-146a functioned as an oncogene and may be a novel prognostic biomarker in APL. Lan Xu, Hua Zhong, Haixia Wan, Fang-yuan Chen, Jihua Zhong, Fei Xiao, Jia Liu, and Lijing Shen Copyright © 2014 Lan Xu et al. All rights reserved. Levels of Human Erythrocyte Membrane-Bound and Cytosolic Glycohydrolases Are Associated with Oxidative Stress in Erectile Dysfunction Patients Tue, 05 Aug 2014 00:00:00 +0000 http://www.hindawi.com/journals/dm/2014/485917/ Oxidative stress (OS) and production of NO, by endothelium nitric oxide synthetase (eNOS), are involved in the pathophysiology of erectile dysfunction (ED). Moreover, OS induces modifications of the physicochemical properties of erythrocyte (RBC) plasma membranes and of the enzyme content of the same membranes. Due to their role in signalling early membrane alterations in OS-related pathologies, several plasma membrane and cytosolic glycohydrolases of human RBC have been proposed as new markers of cellular OS. In RBC, NOS can be activated and deactivated by phosphorylation/glycosylation. In this regulatory mechanism O-β-N-AcetylGlucosaminidase is a key enzyme. Cellular levels of O-GlcNAcylated proteins are related to OS; consequently dysfunctional eNOS O-GlcNAcylation seems to have a crucial role in ED. To elucidate the possible association between RBC glycohydrolases and OS, plasma hydroperoxides and antioxidant total defenses (Lag-time), cytosolic O-β-N-AcetylGlucosaminidase, cytosolic and membrane Hexosaminidase, membrane β-D-Glucuronidase, and α-D-Glucosidase have been studied in 39 ED patients and 30 controls. In ED subjects hydroperoxides and plasma membrane glycohydrolases activities are significantly increased whereas Lag-time values and cytosolic glycohydrolases activities are significantly decreased. These data confirm the strong OS status in ED patients, the role of the studied glycohydrolases as early OS biomarker and suggest their possible use as specific marker of ED patients, particularly in those undergoing nutritional/pharmacological antioxidant therapy. L. Massaccesi, G. V. Melzi d’Eril, G. M. Colpi, G. Tettamanti, G. Goi, and A. Barassi Copyright © 2014 L. Massaccesi et al. All rights reserved. The Role of Haptoglobin Genotypes in Chagas Disease Thu, 24 Jul 2014 00:00:00 +0000 http://www.hindawi.com/journals/dm/2014/793646/ Although the number of people infected with T. cruzi is on the rise, host genetic and immune components that are crucial in the development of the Chagas disease have been discovered. We investigated the frequency of polymorphisms in the gene encoding haptoglobin of patients with chronic Chagas disease. The results suggest that while the HP1-1 genotype may confer protection against infection and the development of chronic Chagas disease due to the rapid metabolism of the Hp1-1-Hb complex and its anti-inflammatory activity, the presence of HP2-2 genotype may increase susceptibility towards a chronic condition of the disease due to a slow metabolism of the Hp2-2-Hb complex, lower antioxidant activity, and increased inflammatory reactivity, which lead to cell damage and a deterioration of the cardiac function. Finally, correlations between HP genotypes in different age groups and cardiac manifestations suggest that HP polymorphism could influence the prognosis of this infectious disease. This study shows some of the relevant aspects of the haptoglobin gene polymorphism and its implications in the T. cruzi infection. Ninomar Mundaray Fernández and Mercedes Fernández-Mestre Copyright © 2014 Ninomar Mundaray Fernández and Mercedes Fernández-Mestre. All rights reserved. Recipients with In Utero Induction of Tolerance Upregulated MHC Class I in the Engrafted Donor Skin Sun, 20 Jul 2014 12:11:47 +0000 http://www.hindawi.com/journals/dm/2014/531092/ The alterations in MHC class I expression play a crucial step in immune evasion of cancer or virus-infected cells. This study aimed to examine whether tolerized grafts modified MHC class I expression. FVB/N mice were rendered tolerant of C57BL/6 alloantigens by in utero transplantation of C57BL/6 marrows. Postnatally, engrafted donor skins and leukocytes were examined for their MHC expression by quantitative real-time PCR and flow cytometry. Engrafted donor skins upregulated their MHC class I related gene transcripts after short-term (1~2 weeks) or long-term (>1 month) engraftment. This biological phenomenon was simultaneously associated with upregulation of TAP1 gene transcripts, suggesting an important role of TAP1 in the regulation of MHC class I pathway. The surface MHC class I molecules of H-2 in engrafted donor leukocytes consistently showed overexpression. Conclusively, the induction of allograft tolerance involved biological modifications of donor transplants. The overexpression of MHC class I within engrafted transplants of tolerant mice might be used as the tolerance biomarkers for identifying a state of graft tolerance. Jeng-Chang Chen, Liang-Shiou Ou, Hsiu-Yueh Yu, Ming-Ling Kuo, Pei-Yeh Chang, and Hsueh-Ling Chang Copyright © 2014 Jeng-Chang Chen et al. All rights reserved. K-ras Mutational Status in Cytohistological Tissue as a Molecular Marker for the Diagnosis of Pancreatic Cancer: A Systematic Review and Meta-Analysis Wed, 16 Jul 2014 12:14:36 +0000 http://www.hindawi.com/journals/dm/2014/573783/ Background. More clinically meaningful diagnostic tests are needed in pancreatic cancer (PC). K-ras mutations are the most frequently acquired genetic alteration. Methods. Original research articles involving the diagnostic accuracy of K-ras mutation detection in PC were selected. Data were presented as forest plots and summary receiver operating characteristic (SROC) curve analysis was used to summarize the overall test performance. Results. We assessed 19 studies from 16 published articles. The reports were divided into three groups according to the process used to obtain the test material. The summary estimates for detecting K-ras status using an invasive method (fine needle aspiration (FNA), endoscopic retrograde cholangiopancreatography (ERCP), or surgery) were better than cytology: the pooled sensitivity was 77% (95% confidence interval (CI): 74–80%) versus 54% (95% CI: 47–61%); specificity was 88% (95% CI: 85–91%) versus 91% (95% CI: 83–96%); and diagnostic odds ratio (DOR) was 20.26 (11.40–36.03) versus 7.52 (95% CI: 2.80–20.18), respectively. When two procedures were combined, the diagnostic accuracy was markedly improved. Conclusions. The analysis of K-ras mutations in pancreatic tissue has a promising diagnostic significance in PC. Further valuable studies are needed. Jing Yang, Jingjing Li, Rong Zhu, Huawei Zhang, Yuanyuan Zheng, Weiqi Dai, Fan Wang, Miao Shen, Kan Chen, Ping Cheng, Yan Zhang, Chengfen Wang, Junshan Wang, Yujing Xia, Jie Lu, Yingqun Zhou, and Chuanyong Guo Copyright © 2014 Jing Yang et al. All rights reserved. Serum Interleukin 17 Levels in Patients with Crohn’s Disease: Real Life Data Wed, 16 Jul 2014 10:23:17 +0000 http://www.hindawi.com/journals/dm/2014/690853/ The aim of this study was to investigate serum IL17 levels in patients with Crohn’s disease (CD) and to investigate the relationship between serum IL17 levels with disease activity. Methods. Fifty patients with CD and sex- and age-matched 40 healthy controls were included in the study. The serum IL17 levels, complete blood count, blood chemistry, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were measured, and Crohn’s disease activity was calculated using Crohn’s disease activity index (CDAI). Results. The mean serum IL17 level of CD patients did not differ from those of healthy controls (). There was no difference between the mean serum IL levels of active CD patients and of quiescent CD patients (). However, the mean IL17 level of active patients was lower than of control subjects (). Serum IL17 was not correlated with inflammatory markers (ESR, CRP, white blood count, platelet count, and albumin) and CDAI. Conclusions. Peripheral blood serum IL17 levels of CD patients were not higher than of healthy controls, and also, serum IL17 level was not correlated with clinical disease activity. Peripheral IL17 measurement is not a useful tool for detecting and monitoring Crohn’s disease which is understood to have complex etiopathogenesis. Abdurrahman Sahin, Turan Calhan, Mustafa Cengiz, Resul Kahraman, Kubra Aydin, Kamil Ozdil, May Korachi, and H. Mehmet Sokmen Copyright © 2014 Abdurrahman Sahin et al. All rights reserved. Comparison of Different Blood Collection, Sample Matrix, and Immunoassay Methods in a Prenatal Screening Setting Tue, 15 Jul 2014 13:07:04 +0000 http://www.hindawi.com/journals/dm/2014/509821/ We compared how measurements of pregnancy-associated plasma protein A (PAPP-A) and the free beta subunit of human chorionic gonadotropin (fβ-hCG) in maternal blood are influenced by different methods for blood collection, sample matrix, and immunoassay platform. Serum and dried blood spots (DBS) were obtained by venipuncture and by finger prick of 19 pregnant women. PAPP-A and fβ-hCG from serum and from DBS were measured by conventional indirect immunoassay on an AutoDELFIA platform and by antibody microarray. We compared methods based on the recoveries for both markers as well as marker levels correlations across samples. All method comparisons showed high correlations for both marker concentrations. Recovery levels of PAPP-A from DBS were 30% lower, while those of fβ-hCG from DBS were 50% higher compared to conventional venipuncture serum. The recoveries were not affected by blood collection or immunoassay method. The high correlation coefficients for both markers indicate that DBS from finger prick can be used reliably in a prenatal screening setting, as a less costly and minimally invasive alternative for venipuncture serum, with great logistical advantages. Additionally, the use of antibody arrays will allow for extending the number of first trimester screening markers on maternal and fetal health. Jeroen L. A. Pennings, Jacqueline E. Siljee, Sandra Imholz, Sylwia Kuc, Annemieke de Vries, Peter C. J. I. Schielen, and Wendy Rodenburg Copyright © 2014 Jeroen L. A. Pennings et al. All rights reserved. Prognostic Value of VEGF in Patients Submitted to Percutaneous Coronary Intervention Mon, 07 Jul 2014 09:00:19 +0000 http://www.hindawi.com/journals/dm/2014/135357/ We examined the longitudinal changes of VEGF levels after percutaneous coronary intervention for predicting major adverse cardiac events (MACE) in coronary artery disease (CAD) patients. VEGF was measured in 94 CAD patients’ serum before revascularization, 1-month and 1-year after. Independently of clinical presentation, patients had lower VEGF concentration than a cohort of healthy subjects (median, IQ: 15.9, 9.0–264 pg/mL versus 419, 212–758 pg/mL; ) at baseline. VEGF increased to 1-month (median, IQ: 276, 167–498 pg/mL; ) and remained steady to 1-year (median, IQ: 320, 173–497 pg/mL; ) approaching control levels. Drug eluting stent apposition and previous medication intake produced a less steep VEGF evolution after intervention (). Baseline VEGF concentration <40.8 pg/mL conveyed increased risk for MACE in a 5-year follow-up. Results reflect a positive role of VEGF in recovery and support its importance in CAD prognosis. Catarina Ramos, Patrícia Napoleão, Mafalda Selas, Cláudia Freixo, Ana Maria Viegas Crespo, Miguel Mota Carmo, Rui Cruz Ferreira, and Teresa Pinheiro Copyright © 2014 Catarina Ramos et al. All rights reserved. Haplotype Map of Sickle Cell Anemia in Tunisia Wed, 02 Jul 2014 11:48:48 +0000 http://www.hindawi.com/journals/dm/2014/938301/ β-Globin haplotypes are important to establish the ethnic origin and predict the clinical development of sickle cell disease patients (SCD). To determine the chromosomal background of Tunisian sickle cell patients, in this first study in Tunisia, we have explored four polymorphic regions of β-globin cluster on chromosome 11. It is the 5′ region of β-LCR-HS2 site, the intervening sequence II (IVSII) region of two fetal ( and ) genes and the 5′ region of β-globin gene. The results reveal a high molecular diversity of a microsatellite configuration describing the sequences haplotypes. The linkage disequilibrium analysis showed various haplotype combinations giving 22 “extended haplotypes”. These results confirm the utility of the β-globin haplotypes for population studies and contribute to knowledge of the Tunisian gene pool, as well as establishing the role of genetic markers in physiopathology of SCD. Imen Moumni, Maha Ben Mustapha, Sarra Sassi, Amine Zorai, Ikbel Ben Mansour, Kais Douzi, Dorra Chouachi, Fethi Mellouli, Mohamed Bejaoui, and Salem Abbes Copyright © 2014 Imen Moumni et al. All rights reserved. The Clinicopathological Significance of miR-133a in Colorectal Cancer Tue, 01 Jul 2014 00:00:00 +0000 http://www.hindawi.com/journals/dm/2014/919283/ This study determined the expression of microRNA-133a (MiR-133a) in colorectal cancer (CRC) and adjacent normal mucosa samples and evaluated its clinicopathological role in CRC. The expression of miR-133a in 125 pairs of tissue samples was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and correlated with patient’s clinicopathological data by statistical analysis. Endogenous expression levels of several potential target genes were determined by qRT-PCR and correlated using Pearson’s method. MiR-133a was downregulated in 83.2% of tumors compared to normal mucosal tissue. Higher miR-133a expression in tumor tissues was associated with development of distant metastasis, advanced Dukes and TNM staging, and poor survival. The unfavorable prognosis of higher miR-133a expression was accompanied by dysregulation of potential miR-133a target genes, LIM and SH3 domain protein 1 (LASP1), Caveolin-1 (CAV1), and Fascin-1 (FSCN1). LASP1 was found to possess a negative correlation (), whereas CAV1 exhibited a significant positive correlation (), and a stronger correlation was found in patients who developed distant metastases (). In addition, a negative correlation of FSCN1 was only found in nonmetastatic patients. In conclusion, miR-133a was downregulated in CRC tissues, but its higher expression correlated with adverse clinical characteristics and poor prognosis. Timothy Ming-Hun Wan, Colin Siu-Chi Lam, Lui Ng, Ariel Ka-Man Chow, Sunny Kit-Man Wong, Hung-Sing Li, Johnny Hon-Wai Man, Oswens Siu-Hung Lo, Dominic Foo, Alvin Cheung, Thomas Yau, Jensen Tung-Chung Poon, Ronnie Tung-Ping Poon, Wai-Lun Law, and Roberta Wen-Chi Pang Copyright © 2014 Timothy Ming-Hun Wan et al. All rights reserved. A New Susceptibility Locus for Myocardial Infarction, Hypertension, Type 2 Diabetes Mellitus, and Dyslipidemia on Chromosome 12q24 Thu, 26 Jun 2014 12:10:03 +0000 http://www.hindawi.com/journals/dm/2014/291419/ We examined the role of hepatic nuclear factor-1 alpha (HNF1a) gene polymorphism on coronary artery disease (CAD) traits in 4631 Saudi angiographed individuals (2419 CAD versus 2212 controls) using TaqMan assay on ABI Prism 7900HT sequence detection system. Following adjustment for confounders, the rs2259820_CC (1.19 (1.01–1.42); ), rs2464196_TT (1.19 (1.00–1.40); ), and rs2259816_T (1.13 (1.01–1.26); ) were associated with MI. The rs2259820_T (1.14 (1.03–1.26); ) and rs2464196_C (1.12 (1.02–1.24); ) were associated with type 2 diabetes mellitus (T2DM), while the rs2393791_T (1.14 (1.01–1.28); ), rs7310409_G (1.16 (1.03–1.30); ), and rs2464196_AG+GG (1.25 (1.05–1.49); ) were implicated in hypertension. Hypertriglyceridemia was linked to the rs2393791_T (1.14 (1.02–1.27); ), rs7310409_G (1.12 (1.01–1.25); ), rs1169310_G (1.15 (1.04–1.28); ), and rs1169313_CT+TT (1.24 (1.06–1.45); ) and high low density lipoprotein-cholesterol levels were associated with rs2259820_T (1.23 (1.07–1.41); ), rs2464196_T (1.22 (1.06–1.39); ), and rs2259816_T (1.18 (1.02–1.36); ). A 7-mer haplotype CATATAC (; ), constructed from the studied SNPs, was associated with MI, and CATATA implicated in T2DM (; ). Hypertriglyceridemia was linked to TGCGGG (; ), and obesity to ACGGGT (; ). Our results suggest that the HNF1a is a common susceptibility gene for MI, T2DM, hypertension, and dyslipidemia. Salma M. Wakil, Nzioka P. Muiya, Asma I. Tahir, Mohammed Al-Najai, Batoul Baz, Editha Andres, Nejat Mazhar, Nada Al Tassan, Maie Alshahid, Brian F. Meyer, and Nduna Dzimiri Copyright © 2014 Salma M. Wakil et al. All rights reserved. Urinary N-Acetyl-beta-D-glucosaminidase as an Early Marker for Acute Kidney Injury in Full-Term Newborns with Neonatal Hyperbilirubinemia Tue, 24 Jun 2014 12:12:46 +0000 http://www.hindawi.com/journals/dm/2014/315843/ Purpose. To investigate renal function estimated by markers in full-term newborns with hyperbilirubinemia. Methods. A total of 332 full-term newborns with hyperbilirubinemia and 60 healthy full-term newborns were enrolled. Total serum bilirubin, serum creatinine (Cr), serum blood urea nitrogen (BUN), serum cystatin C (Cys-C), urinary beta-2-microglobulin (β2MG) index, and urinary N-acetyl-beta-D-glucosaminidase (NAG) index were measured before and after treatment. All newborns were divided into three groups according to total serum bilirubin levels: group 1 (221-256), group 2 (256-342), and group 3 (>342). Results. The control group and group 1 did not differ significantly in regard to serum Cr, serum BUN, serum Cys-C, urinary β2MG index, and urinary NAG index. Urinary NAG index in group 2 was significantly higher than that in control group (). Between control group and group 3, serum Cys-C, urinary β2MG index, and urinary NAG index differed significantly. The significant positive correlation between total serum bilirubin and urinary NAG index was found in newborns when total serum bilirubin level was more than 272 μmol/L. Conclusions. High unconjugated bilirubin could result in acute kidney injury in full-term newborns. Urinary NAG might be the suitable marker for predicting acute kidney injury in full-term newborns with hyperbilirubinemia. Bangning Cheng, Yulian Jin, Guanghui Liu, Zhiheng Chen, Hongmei Dai, and Min Liu Copyright © 2014 Bangning Cheng et al. All rights reserved. Serum Levels of Resistin, Adiponectin, and Apelin in Gastroesophageal Cancer Patients Tue, 24 Jun 2014 06:49:28 +0000 http://www.hindawi.com/journals/dm/2014/619649/ The aim of the study was the investigation of relationship between cachexia syndrome and serum resistin, adiponectin, and apelin in patients with gastroesophageal cancer (GEC). Material and Methods. Adipocytokines concentrations were measured in sera of 85 GEC patients and 60 healthy controls. They were also evaluated in tumor tissue and appropriate normal mucosa of 38 operated cancer patients. Results. Resistin and apelin concentrations were significantly higher in GEC patients than in the controls. The highest resistin levels were found in cachectic patients and in patients with distant metastasis. Serum adiponectin significantly decreased in GEC patients with regional and distant metastasis. Serum apelin was significantly higher in cachectic patients than in the controls. Apelin was positively correlated with hsCRP level. Resistin and apelin levels increased significantly in tumor tissues. Weak positive correlations between adipocytokines levels in serum and in tumor tissue were observed. Conclusions. Resistin is associated with cachexia and metastasis processes of GEC. Reduction of serum adiponectin reflects adipose tissue wasting in relation to GEC progression. Correlation of apelin with hsCRP can reflect a presumable role of apelin in systemic inflammatory response in esophageal and gastric cancer. Dorota Diakowska, Krystyna Markocka-Mączka, Piotr Szelachowski, and Krzysztof Grabowski Copyright © 2014 Dorota Diakowska et al. All rights reserved. Immunophenotypes and Immune Markers Associated with Acute Promyelocytic Leukemia Prognosis Thu, 19 Jun 2014 08:29:55 +0000 http://www.hindawi.com/journals/dm/2014/421906/ CD2+, CD34+, and CD56+ immunophenotypes are associated with poor prognoses of acute promyelocytic leukemia (APL). The present study aimed to explore the role of APL immunophenotypes and immune markers as prognostic predictors on clinical outcomes. A total of 132 patients with de novo APL were retrospectively analyzed. Immunophenotypes were determined by flow cytometry. Clinical features, complete remission (CR), relapse, and five-year overall survival (OS) rate were assessed and subjected to multivariate analyses. The CD13+CD33+HLA-DR-CD34− immunophenotype was commonly observed in patients with APL. Positive rates for other APL immune markers including cMPO, CD117, CD64, and CD9 were 68.7%, 26%, 78.4%, and 96.6%, respectively. When compared with patients with CD2− APL, patients with CD2+ APL had a significantly higher incidence of early death (50% versus 15.7%; ), lower CR rate (50% versus 91.1%; ), and lower five-year OS rate (41.7% versus 74.2%; ). White blood cell (WBC) count before treatment was found to be the only independent risk factor of early death, CR failure, and five-year mortality rate. Flow cytometric immunophenotype analysis can facilitate prompt APL diagnosis. Multivariate analysis has demonstrated that WBC count before treatment is the only known independent risk factor that predicts prognosis for APL in this study population. Fang Xu, Chang-Xin Yin, Chun-Li Wang, Xue-Jie Jiang, Ling Jiang, Zhi-Xiang Wang, Zheng-Shan Yi, Kai-Kai Huang, and Fan-Yi Meng Copyright © 2014 Fang Xu et al. All rights reserved. Clinical Usefulness of Novel Serum and Imaging Biomarkers in Risk Stratification of Patients with Stable Angina Thu, 19 Jun 2014 00:00:00 +0000 http://www.hindawi.com/journals/dm/2014/831364/ Inflammatory mediators appear to be the most intriguing yet confusing subject, regarding the management of patients with acute coronary syndromes (ACS). The current inflammatory concept of atherosclerotic coronary artery disease (CAD) led many investigators to concentrate on systemic markers of inflammation, as well as imaging techniques, which may be helpful in risk stratification and prognosis assessment for cardiovascular events. In this review, we try to depict many of the recently studied markers regarding stable angina (SA), their clinical usefulness, and possible future applications in the field. George Tsaknis, Iraklis Tsangaris, Ignatios Ikonomidis, and Argirios Tsantes Copyright © 2014 George Tsaknis et al. All rights reserved. Comparative Plasma Protein Profiling of Hemoglobin H Disease Sun, 15 Jun 2014 12:36:17 +0000 http://www.hindawi.com/journals/dm/2014/340214/ HbH and HbH-constant spring (HbH-CS) are the most common forms of α-thalassemia detected in the Thai population. The accumulation of excess β globin chains in these diseases results in increased red cell hemolysis, and patients with HbH-CS normally have a more severe clinical presentation than patients with HbH disease. This study aimed to detect alterations in the expression of plasma proteins of HbH and HbH-CS patients as compared to normal plasma. Platelet poor plasma was separated from HbH and HbH-CS and normal subjects and differential plasma proteins were detected using two-dimensional gel electrophoresis and identified using LC/MS/MS. A total of 14 differentially expressed proteins were detected of which 5 proteins were upregulated and 9 were downregulated. Most of the differentially expressed proteins are liver secreted proteins involved in hemolysis, oxidative stress response, and hemoglobin degradation. Seven proteins were found to be differentially expressed between HbH and HbH-CS. Levels of haptoglobin, a hemoglobin scavenging protein, were significantly increased in HbH patients as compared to HbH-CS patients. The identification of differentially expressed proteins may lead to a better understanding of the biological events underlying the clinical presentation of HbH and HbH-CS patients and can have application as hemolytic markers or severity predictors. Kamonlak Leecharoenkiat, Wannapa Sornjai, Kornpat Khungwanmaythawee, Atchara Paemanee, Chartchai Chaichana, Sittiruk Roytrakul, Suthat Fucharoen, Saovaros Svasti, and Duncan R. Smith Copyright © 2014 Kamonlak Leecharoenkiat et al. All rights reserved. Erratum to “Molecular Targeted Approaches for Advanced BRAF V600, N-RAS, c-KIT, and GNAQ Melanoma” Mon, 02 Jun 2014 09:06:01 +0000 http://www.hindawi.com/journals/dm/2014/246751/ Giovanni Ponti, Giovanni Pellacani, Aldo Tomasi, Pietro Loschi, Gabriele Luppi, Fabio Gelsomino, and Caterina Longo Copyright © 2014 Giovanni Ponti et al. All rights reserved. Study of Leptin and Adiponectin as Disease Markers in Subjects with Obstructive Sleep Apnea Thu, 29 May 2014 06:16:29 +0000 http://www.hindawi.com/journals/dm/2014/706314/ Background. Published studies showed conflicting results of the associations between adiponectin and leptin levels and obstructive sleep apnoea (OSA). In obese patients, plasma leptin is elevated and adiponectin is decreased, and we postulate that these adipokines could be potential markers of clinical and metabolic perturbations in patients with OSA. Methods. 147 patients with suspected OSA had polysomnography to determine the Respiratory Disturbance Index (RDI). We measured fasting plasma glucose (FPG), fasting serum insulin, plasma leptin, adiponectin, and full lipid profile. Patients were classified on the basis of the RDI, degree of adiposity, and insulin resistance (IR) (homeostasis model assessment of insulin resistance (HOMAIR)). Results. 28.6% of subjects had normal polysomnography, 34.8% had mild OSA, 19.6% had moderate OSA, and 17% had severe OSA. Obesity was more prevalent in subjects with moderate-severe OSA (47%). Adiponectin decreased significantly with increasing severity of OSA. Though BMI was significantly higher in subjects with severe OSA, paradoxically, leptin was lowest in those subjects independent of gender dimorphism. Conclusions. Adiponectin is an independent marker of disease severity in patients with OSA. The paradoxical decrease in circulating leptin, which suggests impaired secretion, deserves further studies as a potential marker of severe OSA. Sana Al Mutairi, Olusegun A. Mojiminiyi, Alia Al Alawi, Tahani Al Rammah, and Nabila Abdella Copyright © 2014 Sana Al Mutairi et al. All rights reserved. Proteome Changes in the Plasma of Myelodysplastic Syndrome Patients with Refractory Anemia with Excess Blasts Subtype 2 Sun, 25 May 2014 11:03:07 +0000 http://www.hindawi.com/journals/dm/2014/178709/ The goal of this study was to explore the plasma proteome of myelodysplastic syndrome (MDS) patients with refractory anemia with excess blasts subtype 2 (RAEB-2) in comparison to healthy controls. 20 plasma samples were separated with 2D electrophoresis and statistically processed with Progenesis SameSpots software. 47 significantly differing () spots were observed, and 27 different proteins were identified by nano-LC-MS/MS. Mass spectrometry-based relative label-free quantification showed a 2-fold increase of the leucine-rich alpha-2-glycoprotein (LRAG) peptide levels in the RAEB-2 group. Changes in the fragments of the inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) protein were observed. Western blot analysis showed no differences in albumin and ITIH4 levels, while increased expression was observed for LRAG in the RAEB-2 group. Quantification using ELISA showed decreased plasma level of alpha-2-HS glycoprotein in the RAEB-2 group. In conclusion, this is the first time that alpha-2-HS glycoprotein and LRAG were proposed as new biomarkers of RAEB-2 and advanced MDS, respectively. Alpha-2-HS glycoprotein, a protein involved in the bone marrow development and previously proposed as a MDS biomarker candidate, was significantly decreased in RAEB-2. Increased expression and changes in modification(s) were observed for LRAG, a protein involved in granulocytic and neutrophil differentiation, and angiogenesis. Pavel Majek, Zuzana Riedelova-Reicheltova, Jiri Suttnar, Klara Pecankova, Jaroslav Cermak, and Jan E. Dyr Copyright © 2014 Pavel Majek et al. All rights reserved. Gene Expression Profiling of Colorectal Tumors and Normal Mucosa by Microarrays Meta-Analysis Using Prediction Analysis of Microarray, Artificial Neural Network, Classification, and Regression Trees Mon, 19 May 2014 12:12:30 +0000 http://www.hindawi.com/journals/dm/2014/634123/ Background. Microarray technology shows great potential but previous studies were limited by small number of samples in the colorectal cancer (CRC) research. The aims of this study are to investigate gene expression profile of CRCs by pooling cDNA microarrays using PAM, ANN, and decision trees (CART and C5.0). Methods. Pooled 16 datasets contained 88 normal mucosal tissues and 1186 CRCs. PAM was performed to identify significant expressed genes in CRCs and models of PAM, ANN, CART, and C5.0 were constructed for screening candidate genes via ranking gene order of significances. Results. The first screening identified 55 genes. The test accuracy of each model was over 0.97 averagely. Less than eight genes achieve excellent classification accuracy. Combining the results of four models, we found the top eight differential genes in CRCs; suppressor genes, CA7, SPIB, GUCA2B, AQP8, IL6R and CWH43; oncogenes, SPP1 and TCN1. Genes of higher significances showed lower variation in rank ordering by different methods. Conclusion. We adopted a two-tier genetic screen, which not only reduced the number of candidate genes but also yielded good accuracy (nearly 100%). This method can be applied to future studies. Among the top eight genes, CA7, TCN1, and CWH43 have not been reported to be related to CRC. Chi-Ming Chu, Chung-Tay Yao, Yu-Tien Chang, Hsiu-Ling Chou, Yu-Ching Chou, Kang-Hua Chen, Harn-Jing Terng, Chi-Shuan Huang, Chia-Cheng Lee, Sui-Lun Su, Yao-Chi Liu, Fu-Gong Lin, Thomas Wetter, and Chi-Wen Chang Copyright © 2014 Chi-Ming Chu et al. All rights reserved. Biomarkers of Inflammatory Bowel Disease Mon, 19 May 2014 10:51:21 +0000 http://www.hindawi.com/journals/dm/2014/710915/ Inflammatory bowel disease (IBD) is a chronic disease mostly involved with intestine with unknown etiology. Diagnosis, evaluation of severity, and prognosis are still present as challenges for physicians. An ideal biomarker with the characters such as simple, easy to perform, noninvasive or microinvasive, cheap, rapid, and reproducible is helpful for patients and clinicians. Currently biomarkers applied in clinic include CRP, ESR, pANCA, ASCA, and fecal calprotectin. However, they are far from ideal. Lots of studies are focused on seeking for ideal biomarker for IBD. Herein, the paper reviewed recent researches on biomarkers of IBD to get advances of biomarkers in inflammatory bowel disease. Yi Fengming and Wu Jianbing Copyright © 2014 Yi Fengming and Wu Jianbing. All rights reserved. Hypertrophy of Ligamentum Flavum in Lumbar Spine Stenosis Is Associated with Increased miR-155 Level Sun, 18 May 2014 09:38:08 +0000 http://www.hindawi.com/journals/dm/2014/786543/ Hypertrophy of ligamentum flavum (LF) contributes to lumbar spinal stenosis (LSS) and is caused mainly by fibrosis. Recent data indicate that miR-155 plays a crucial role in the pathogenesis of different fibrotic diseases. This study aimed to test the hypothesis that miR-155 exerts effects on LF thickness by regulating collagen expression. We found that LF thickness and the expression of collagen I and, collagen III were higher in LF from LSS patients than in LF from lumbar disc herniation (LDH) patients (). The expression of miR-155 was significantly higher in LF from LSS group than in LF from LDH group (). miR-155 level was positively correlated with LF thickness (, ), type I collagen level (, ), and type III collagen level (, ). miR-155 mimic increased mRNA and protein expression of collagen I and collagen III in fibroblasts isolated from LF, while miR-155 sponge decreased mRNA and protein expression of collagen I and III in fibroblasts. In conclusions, miR-155 is a fibrosis-associated miRNA and may play important role in the pathogenesis of LF hypertrophy. Jianwei Chen, Zude Liu, Guibin Zhong, Lie Qian, Zhanchun Li, Zhiguang Qiao, Bin Chen, and Hantao Wang Copyright © 2014 Jianwei Chen et al. All rights reserved. Beta2-Microglobulin as a Diagnostic Marker in Cerebrospinal Fluid: A Follow-Up Study Thu, 08 May 2014 07:21:49 +0000 http://www.hindawi.com/journals/dm/2014/495402/ Beta2-Microglobulin (β2-m) is a low molecular weight protein occurring in all body fluids. Its concentration increases in various pathologies. Increased values in cerebrospinal fluid (CSF) are ascribed to an activation of immune system. Using immunoturbidimetry, we examined concentrations of beta2-microglobulin in cerebrospinal fluid in a large group of 6274 patients with defined neurological diseases. Cell counts, total protein, albumin, glucose, lactic acid, immunoglobulins concentrations, and isofocusing (IEF) were also evaluated. We found substantial changes of CSF β2-m concentrations in purulent meningitis, leptomeningeal metastasis, viral meningitis/encephalitis, and neuroborreliosis, while in multiple sclerosis these changes were not significant. Intrathecal synthesis and immune activation were present in these clinical entities. A new normative study enables better understanding of beta2-microglobulin behavior in CSF. Jana Svatoňová, Klára Bořecká, Pavel Adam, and Věra Lánská Copyright © 2014 Jana Svatoňová et al. All rights reserved.