Gastroenterology and Hepatology from Bed to Bench

As a chronic immune complication, celiac disease has a broad spectrum of clinical manifestations and gluten ingestion as an external trigger will induce the onset of this disease in genetically predisposed individuals. Because of the complex nature of celiac disease and various cascades of immunological pathways, therapies which are tend to target a single pathway or factor, often have unsatisfactory results. Thus, it should be considered that the new emerging area of cellular therapy by targeting multiple pathways may hold the key for treating celiac affected patients with complicated forms of this disease. The aim of this review is to discuss different pathways which are affected by celiac disease and to compare how various strategies, mainly cellular therapies, can regulate these pathways.

Aim: In the present study, a protein-protein interaction network construction is conducted for IBD.

Background: Inflammatory bowel diseases as serious chronic gastrointestinal disorders attracted many molecular investigations. Diverse molecular information is present for IBD. However, these molecular findings are not highlighted based on interactome analysis. On the other hand, PPI network analysis is a powerful method for study of molecular interactions in the protein level that provide useful information for highlighting the desired key proteins.

Methods: Cytoscape is the used software with its plug-ins for detailed analysis. Two centrality parameters including degree and betweenness are determined and the crucial proteins based on these parameters are introduced.

Results: The 75 proteins among 100 initial proteins are included in the network of IBD. Seventy-five nodes and 260 edges constructed the network as a scale free network. The findings indicate that there are seven hub-bottleneck proteins in the IBD network.

Conclusion: More examination revealed the essential roles of these key proteins in the integrity of the network. Finally, the indicator panel including NFKB1, CD40, TNFA, TYK2, NOD2, IL23R, and STAT3 is presented as a possible molecular index for IBD. Keywords: Inflammatory bowel diseases (IBD), Protein-protein interaction (PPI) network analysis, Hub-bottlenecks, Protein clusters

Aim: In the current study, we analysised only the articles that investigate serum proteome profile of cirrhosis patients or HCC patients versus healthy controls.

Background: Increased understanding of cancer biology has enabled identification of molecular events that lead to the discovery of numerous potential biomarkers in diseases. Protein-protein interaction networks is one of aspect that could elevate the understanding level of molecular events and protein connections that lead to the identification of genes and proteins associated with diseases.

Methods: Gene expression data, including 63 gene or protein names for hepatocellular carcinoma and 29 gene or protein names for cirrhosis, were extracted from a number of previous investigations. The networks of related differentially expressed genes were explored using Cytoscape and the PPI analysis methods such as MCODE and ClueGO. Centrality and cluster screening identified hub genes, including APOE, TTR, CLU, and APOA1 in cirrhosis.

Results: CLU and APOE belong to the regulation of positive regulation of neurofibrillary tangle assembly. HP and APOE involved in cellular oxidant detoxification. C4B and C4BP belong to the complement activation, classical pathway and acute inflammation response pathway. Also, it was reported TTR, TFRC, VWF, CLU, A2M, APOA1, CKAP5, ZNF648, CASP8, and HSP27 as hubs in HCC. In HCC, these include A2M that are corresponding to platelet degranulation, humoral immune response, and negative regulation of immune effector process. CLU belong to the reverse cholesterol transport, platelet degranulation and human immune response. APOA1 corresponds to the reverse cholesterol transport, platelet degranulation and humoral immune response, as well as negative regulation of immune effector process pathway.

Conclusion: In conclusion, this study suggests that there is a common molecular relationship between cirrhosis and hepatocellular cancer that may help with identification of target molecules for early treatment that is essential in cancer therapy.

Aim: The corresponding proteins are important for network mapping since the interaction analysis can provide a new interpretation about disease underlying mechanisms as the aim of this study.

Backgroud: Nonalcoholic steatohepatitis (NASH) is one of the main causes of liver disease in the world. It has been known with many susceptible proteins that play essential role in its pathogenesis.

Methods: In this paper, protein-protein interaction (PPI) network analysis of fatty liver disease retrieved from STRING db by the application of Cytoscape Software. ClueGO analyzed the associated pathways for the selected top proteins.

Results: INS, PPARA, LEP, SREBF1, and ALB are the introduced biomarker panel for fatty liver disease.

Conclusion: It seems that pathways related to insulin have a prominent role in fatty liver disease. Therefore, investigation in this case is required to confirm the possible linkage of introduced panel and involvement of insulin pathway in the disease.

Aim: Chronic Hepatitis C infection is a critical health problem worldwide, which caused by hepatitis C virus (HCV). Interleukin 28B (IL28B) is a determinant factor in disease progression and also susceptibility to chronic HCV infection.

Background: The most significant aim of this study is to analyze the association between IL28B gene polymorphisms with susceptibility to chronic HCV infection in Iranian population.

Methods: This study follows a case- control study design, in which, 288 patients with chronic hepatitis C and 250 healthy individuals were genotyped for IL28B polymorphisms (rs12979860 C/T and rs8099917 G/T). Studied population collected from Taleghani Haospital, Tehran. Genotyping of IL28B gene polymorphisms were performed using PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) method. 10 percent of the studied population was sequenced to validate the results.

Results: rs8099917 G/T and rs12979860 C/T were differently distributed in hepatitis C patients and healthy controls in the female gender. TT, TG and GG genotypes distribution in the female gender were 56.7%, 39.8% and 4.5% in cases and 67%, 31.6% and 1.4% in controls (p=0.54). Also CC, CT and TT genotypes distribution were 31.8%, 61.4% and 6.8% in cases and 51.7%, 44.9% and 3.4% in controls (p=0.2). However, there was no significant difference in the allelic frequency and genotype distribution of rs12979860 C/T and rs8099917 T/G in both HCV patients with genotype 1a and 3a

Aim: The aim of this study is to survey the effect of Helicobacter Pylori on metabolic syndrome parameters in diabetic patients. Background: Helicobacter pylori (HP) infection is the most common infection in developing countries. Some studies showed the association between HP infection and insulin resistance. Insulin resistance is a major mechanism in the development of metabolic syndrome (MetS) and it is said that MetS is more prevalent among HP infected subjects. Also, some studies have shown that MetS is common among patients with type 2 diabetes mellitus. In this study, we aimed to investigate the prevalence of MetS in diabetic patients and its association with HP. Methods: This cross-sectional study was carried out from May to December 2014 on 211 diabetic patients. For each patient, the following data were collected: age, gender, diabetes duration, weight, body mass index (BMI), waist circumference, blood pressure (BP), HDL, cholesterol, triglyceride (TG), total cholesterol, and HbA1c. The lipid profile was performed on fasting samples. Anti- HP IgG antibody was measured and serum titer >30AU/mL was considered positive. MetS was diagnosed by The National Cholesterol Education Program’s Adult Treatment Panel III report (NCEP-ATPIII) and IDF criteria.

Results: Totally 139 patients (65.9%) were HP+ and 72 patients (34.1%) were HP-. Age, gender and diabetes duration were not significantly different in both groups. BMI was significantly lower in HP+ women (29.05±5.26 vs. 31.45±4.8, p=0.02). Although the waist circumference of men was not different between the two groups but it was significantly lower in HP+ women (102.04±12.37 vs. 97.3±10, p=0.03). Although BP and TG levels were not statistically different in HP+ and HP- patients, but HP+ patients had lower HDL level (p=0.037) which was due to lower HDL in men (58.2±26.6 vs. 72.48±28.1, p=0.012). The prevalence of MetS according to the IDF criteria among HP+ and HP- patients was 76.6% vs. 69.8% (p=0.27). Also, the prevalence of MetS according to NCEP-ATP III criteria among HP+ and HP- patients was 90.4% vs. 87.2% (p=0.5). Duration of diabetes did not affect the prevalence of metabolic syndrome among HP+ and HP- patients.

Conclusion: It seems that HP infection increases the prevalence of metabolic syndrome through an increase in insulin resistance. According to NCEP-ATPIII criteria, the increase in the prevalence of metabolic syndrome in HP+ patients is almost significant, however more complete studies is recommended to investigate this relationship.

Aim: Since, contradictory data have been reported about the effect of diverse variants of H. pylori virulence factors on IL-8 induction, we aimed to analyze the effect of this diversity on levels of IL-8 secretion in AGS cell line.

Background: Helicobacter pylori colonizes the human stomach and induces the activation of inflammatory cytokines, including interleukin (IL)-8, in the gastric mucosa. This induction promotes neutrophil and monocyte recruitment that causes gastric tissue damage.

Methods: To determine whether different strains of H. pylori and their CagA variants have possible roles on IL-8 induction, polarized

AGS cell line was infected with CagA+ H. pylori strains carrying different EPIYA motifs (ABCCC and ABC) and CagA- strain for 24 hours. Difference in stimulation of IL-8 was measured by ELISA.

Results: IL-8 secretion was elevated in the treated cells with CagA encoding strains compared with the negative one. Furthermore, a noticeably increased level of IL-8 induction was measured by the CagA-EPIYA type ABCCC encoding strain in compare to that carried EPIYA type ABC

Conclusion: Results of this study provide new evidence about different effects of H. pylori strains and possible roles of their CagA variants on IL-8 induction. It seems that not only carriage of cagA and its expression, but also diversity in EPIYA motif be involved in IL-8 induction in the gastric epithelial cells.

Aim: The purpose of this study was to determine the antibiotic susceptibility pattern and distribution of integron in H. pylori isolates collected from patients referred to private health care centers in Tehran, Iran.

Background: Antibiotic resistance is the main reason for failure of Helicobacter pylori therapy. Integrons as genetic reservoirs play main roles in the dissemination of antimicrobial resistance gene.

Methods: During a 12-month cross-sectional study period, 65 H. pylori isolates were recovered from 124 biopsy specimens. Isolates were subjected to susceptibility testing using by Epsilometer test according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guideline. PCR was used to detect different types of integrons.

Results: Antimicrobial susceptibility testing revealed that 73.8% of isolates were resistant to metronidazole, 43.1% to clarithromycin, 29.2% to tetracycline, 27.7% to amoxicillin, 23.1% to rifampicin and 13.4% to levofloxacin. Frequency of multidrug resistance among

H. pylori isolates was 26.1%. The most predominant resistance profiles among our isolates were included resistance to clarithromycin and metronidazole (20%). Class 1 and 2 integrons were detected in 8 (12.3%) and 15 (23.1%) of the isolates, respectively. Conclusions: The high prevalence of multidrug resistance and frequency of class 2 integron in this survey can be a warning for clinicians. Continuous surveillance is necessary for the development of new treatment protocols to prevent the treatment failures and also further spread of resistant isolates.

Aim: We aimed to present clinical and genetic guidelines of colorectal cancer screening for risk assessment of populations at risk. Background: National guidelines can be used as a guide for choosing the method of screening for each individual. These guidelines facilitate decision making and support the delivery of cancer screening service.

Methods: In the first step, a comparative study was performed by using secondary data extracted from the literature review. Three countries (Canada, Australia and United States) were selected from 25 countries that are member in the International Cancer Screening Network (ICSN). The second step of study was qualitative survey. The study was based on the grounded theory approach. Study tool was semi-structured interview. Interviewing involves asking questions and getting answers from participants. 22 expert’s perspectives about guidelines of colorectal cancer screening were surveyed.

Results: Screening program of selected countries was compared. Countries were surveyed by number of risk groups and subgroups, criteria for risk assessment, beginning age, recommendations, screening approaches and intervals. Australia and United States have three risk groups and Canada has two risk groups. Four risk groups were defined in the national guideline, including high risk, increased risk, average and low risk group. The high risk group comprises of 8 subgroups, increased risk group comprises of 3 subgroups and average risk group contain 4 subgroups. Approved clinical criteria for hereditary syndromes and the roadmap of genetic and pathologic survey were designed. Conclusions: Guidelines and pathways have a vital role in the quality improvement of CRC screening program. National guidelines were refined according to the environmental and genetic criteria of colorectal cancer in Iran. These guidelines provide evidence-based recommendations by risk groups. National pathways as a risk assessment tool can evaluate and improve the processes and outcomes of cancer screening in practice. One of the suggestions for future research is the designing expert system for real-time decision making during a clinical interaction.

Aim: We aimed to compare the effectiveness and safety of sleeve gastrectomy versus gastric bypass at one-year.

Background: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the two most commonly performed bariatric procedures worldwide.

Methods: Patients from a prospectively collected database who presented to a specialized bariatric center and underwent a primary bariatric procedure between March 2013 and April 2015 were included and compared regarding major and minor complication rates and weight loss parameters at 6 and 12 months.

Results: A total of 513 patients with a mean age of 37.5±12.5, 82.6 % female and mean body mass index (BMI) of 44.1±6.3  kg/m2

were included in our analysis: 73.3% underwent SG and 26.7% underwent RYGB. Major and minor complication rates were 7.1 and 2.6% for SG vs. 9.5 and 2.2% for the RYGB, respectively (P=NS). The operative and anesthesia time in SG patients were significantly shorter than in RYGB patients (P<0.001). SG and RYBG patients achieved similar excess weight loss at one year (75.4±20.5% vs. 71.8±26.3%, respectively, P=NS). Baseline BMI was the only predictive factor for weight loss at one year (OR: 0.901, CI: 0.827-0.982, P<0.017).

Conclusion: RYGB and SG both showed similar one-year safety and effectiveness. Long-term studies are needed to complement these findings.

Aim: The present study was aimed to evaluate E. granulosus genotypes isolated from goats using HRM analysis in Isfahan province. Background: Cystic echincoccosis, so-called hydatidosis, is widespread infection caused by the larval stage of Echinococcus granulosus. This is an important zoonotic disease worldwide, especially in the developing countries such as Iran. To date, molecular studies mainly based on the mitochondrial DNA sequences have identified distinct genotypes termed G1-G10 which can differ in some characteristics such as the growth and infectivity to different intermediate hosts or the survival rate in the definitive hosts that are important for the development of control strategies.

Methods: From August to December 2014, 1341 goats were investigated and hydatid cysts were collected from the liver and lungs of 43 infected goats in Isfahan province abattoirs, Isfahan, Iran. Total genomic DNA was extracted from each sample, amplified for the presence of polymorphism of mitochondrial gene coding for cytochrome c oxidase subunit 1 (CO1), using high resolution melting curve (HRM) method.

Results: the results of HRM analysis using the sequence of CO1 gene for 43 Echinococcus granulosus isolates from goats showed 31, 2 and 10 isolates were identified as G1, G2, and G3 genotypes, respectively.

Conclusion: G1 is the predominant genotype in the isolated goat samples in Isfahan province, and the presence of G2 strain was reported for the first time in goat in Iran.

Aim: The aim of the present study was to determine the prevalence of intestinal parasites and their relation with socio-demographic data in referred individuals to the medical centers in Tonekabon, Mazandaran province, 2015.

Background: Due to the climatic and ecological conditions in Mazandaran province, determination of the status of intestinal parasites among referred individuals to the medical centers of Tonekabon city can help researchers and healthcare services to prevent and/or control of parasitic infection in this region.

Methods: This cross sectional study was conducted with  randomized  sampling  in 2015  on 820 stool  samples.  Stool samples were assessed using direct slide smear with saline and Lugol, formalin-ether concentration, Ziehl-Neelsen and trichrome staining. Polymerase Chain Reaction (PCR) using specific primers was conducted for the samples suspected for Entamoeba histolytica/E. dispar and Cryptosporidium spp. One Cryptosporidium positive sample in this study was submitted for sequencing.

Results: A total of 444 (54.1%) and 376 (45.9%) were male and female, respectively. Furthermore, 495 (60.4%) and 325 (39.6%) of participants had lived in the urban and rural areas, respectively. Overall, 222 participants (27.1%) were infected with at least one intestinal parasites. Prevalence of pathogenic protozoa (Giardia lamblia and Cryptosporidium spp.) and helminthes parasites was calculated as 3.1 and 1.2%, respectively. The most common intestinal parasites in this area were: Blastocystis 153 (18.7%), Endolymax nana 44 (5.4%), Entamoeba coli 40 (4.9%), Giardia lamblia 25 (3%), Iodamoeba butschlii 22 (2.7%), Ascaris 5 (0.6%), Enterobius

vermicularis 4 (0.5%), Trichostrongylus 1 (0.1%) and Cryptosporidium 1 (0.1%). By sequencing of the positive Cryptosporidium isolate using Gp60 gene, Cryptosporidium parvum subtype ?aA16G2R1 was diagnosed.

Conclusion: Protozoa were more abundant than helminthes and Giardia lamblia was the most common protozoan pathogen. In this study, no significant association was found between the prevalence and the variables of socio-demographic data. Adequate knowledge and periodic surveillance of the prevalence of parasites and the socio-demographic variables that affect their frequency is important for effective control of parasitic infections.

Aim: Prevalence and risk factors associated with intestinal parasites among children ? 12 years old in Nahavand county western Iran, was the objective of this search.

Background: Intestinal parasites (IPs) are important health problems among most societies.

Methods: This cross sectional study was carried out during 6 months from April to September 2014 in Nahavand County western Iran. Fecal samples were collected from 500 children suffering from gastrointestinal disorders (GIDs) and examined by macroscopy and microscopic (using saline and iodine wet mount, formalin-ether sedimentation, Trichrome and modified Ziehl Neelsen staining) methods. Finally, data was analyzed using Chi-square (Chi2) test and Fisher’s exact test as well as logistic regression.

Results: 21.8% (109/500) of the samples were infected by one or more IPs. The most common parasites were Blastocystis sp. (16.2%), followed by Cryptosporidium spp. (2.6%), Giardia lamblia (1.6%), and Entamoeba coli (1.6%). Prevalence of intestinal parasite infections were significantly associated with age (OR= 2.280; CI 95% = 1.375-3.830; P<0.002), gender (OR= 0551; CI 95% = 0.348-0.875; P<0.011), contact with domestic animal or soil (OR= 0.492; CI 95% = 0.282-0.860; P<0.013) and seasons (OR= 2.012; CI 95% = 1.254-3.227; P<0.004). There was a significant correlation between IPs with diarrhea (OR= 3.027; CI 95% = 1.712-5.345; P<0.001) and nausea or vomiting (OR= 3.261; CI 95% = 1.281-8.175; P<0.013).

Conclusion: Blastocystis sp. was the most prevalent parasites among children in Nahavand County and Helminthes infection have been dramatically decreased. Our finding shown that gender, age, season and contact with domestic animals or soil polluted are main predictive factors for intestinal parasite infections among children in this region. Moreover, IPs infection among children with gastrointestinal disorders were significantly associated with diarrhea and vomiting or nausea signs.

Hepatobiliary cystadenomas (HBC) is a rare neoplasm which comprising less than one percent of liver cystic neoplasms. Although it’s known as a benign tumor, but they have a potential for neoplastic transformation. Making a proper diagnosis and ruling out of other differential diagnosis is important because of different treatment. In the present study, we described a case of HBC manifested as idiopathic dominant biliary stricture in common hepatic duct (CHD), on the basis of spiral CT scan and MRI, and elevated CA19-9. With a probable diagnosis of malignant biliary stricture, she underwent ERCP and cholangioscopy that were non-diagnostic and final diagnosis was made surgically. HBCs usually found incicentally as a cystic lesion and biliary stricture without visible cyst in imaging like that seen in cholangiocarcinoma is very unlikely. In truth, this patient is an unusual manifestation of one rare disease.

Lipomas of the colon are relatively rare benign soft tissue tumors derived from mature adipocytes of mesenchymatic origin. During colonoscopy, surgery or autopsy they are generally discovered incidentally. Most cases are asymptomatic, with a small tumor size, and do not need any special treatment. However, in the cases with larger in size of tumor some symptoms such as anemia, abdominal pain, constipation, diarrhea, bleeding, or intussusception may be presented. We reported a 47-year-old woman with colonic intussusception in the descending colon caused by colonic lipoma and diagnosed after surgical exploration for obstructive colonic mass.