Gastroenterology and Hepatology from Bed to Bench

Celiac disease (CD) is an autoimmune disorder of the small intestinal mucosa in genetically susceptible subjects consuming gluten. Gluten in wheat, rye and barley is harmful for some individuals and leads to various symptoms. Research has shown that treatment with probiotics in CD patients could improve the symptoms by the gluten hydrolysis. For this purpose, different databases such as Medline, PubMed, Scopus, and Google Scholar were searched using the following keywords: Celiac disease, Wheat flour, Gluten, glutamine, Probiotic, Bifidobacterium, Lactobacillus, Enzymes, Wheat allergy, Immune system, T cells, HLA-DQ2, HLA-DQ8, Gluten-free diet, Proteolysis, α2-gliadin fragment, Gliadin, 33-mer peptide, and Zonulin. The search aimed to retrieve the articles published during 2000-2019. Today, a gluten-free diet (GFD) is the only celiac disease treatment. Biotechnological strategy based on probiotic treatment could degrade gluten. Research has shown that combination of the probiotic enzyme is more effective than single probiotic on gluten hydrolysis. The result of different studies showed that probiotic mixture has the capacity to hydrolyze a considerable concentration of the 33-mer of gliadin completely. The present study was aimed to investigate associations between the capacities of probiotics on gluten hydrolysis.

Keywords: Celiac disease, Gliadin, Gluten-free diet, Probiotics, Wheat.

(Please cite as: Ramedani N, Sharifan A, Gholam-Mostafaei FS, Rostami-Nejad M, Yadegar A, Moham Ehsani-Ardakani MJ. The potentials of probiotics on gluten hydrolysis; a review study. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S1-S7).

Gastrointestinal bleeding is an overwhelming complication of patients taking antithrombotic agents. These drugs pose a challenge to physicians in the management of bleeding to establish hemostasis without putting these patients at a higher risk for thromboembolism. This study aims to propose an algorithmic approach to four major groups of patients receiving antithrombotic agents (single antiplatelet agents, dual antiplatelet agents, anticoagulants and direct oral anticoagulants) to decide when and how these drugs should be held or restarted to offset between the risk of re-bleeding and thromboembolism. Four case-based algorithms are proposed in this article based on some relevant articles. Having designed four case-based algorithms, we are hoping to guide physicians who face a dilemma on the management of patients receiving antithrombotics when gastrointestinal bleeding occurs. Patients using antithrombotics referred for gastrointestinal bleeding were stratified into four groups based on the medication which is used as an antithrombotic agent and four algorithms were designed which are presented here. We have made an attempt to have a stepwise approach to four cases relevant to the study and have an evaluation on the management of their antithrombotic agents during an episode of gastrointestinal bleeding. It is widely accepted that antithrombotic agents should be restarted as soon as possible after the establishment of hemostasis in a patient taking antithrombotics referring for gastrointestinal bleeding. The time for resuming these drugs is different based on the severity of bleeding, the probability of thromboembolic events, and the nature of the antithrombotic medication which is used by the patient.

Keywords: Algorithms, Gastrointestinal bleeding, Thromboembolic events, Antithrombotic agents.

(Please cite as: Sadeghi A, Zali MR, Mohaghegh Shalmani H, Ketabi Moghadam P, Rajabnia Chenari M, Karimi MA, et al. An algorithmic approach to gastrointestinal bleeding in patients receiving antithrombotic agents. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S8-S17).

Colorectal cancer (CRC) is a heterogeneous disease with various genetic and epigenetic factors leading to difficulties in response to both the therapy and drug resistance. Moreover, even in tumors with similar histopathological characteristics, different responses and molecular features could be observed because of the genetic basis and its interactions with the living environment. Through personalized medicine, we can classify patients into separate groups according to their genetic and epigenetic features and their susceptibility for a specific disease which could help with choosing the best therapeutic approach. In this review, genetic and epigenetic factors that cause heterogeneity in colorectal cancer are evaluated and proper drug administration in both chemotherapy and target therapy are suggested.

Keywords: Colorectal cancer, Personalized medicine, Biomarker, Targeted therapy, Chemotherapy.

(Please cite as: Vaseghi Maghvan P, Jeibouei SH, Akbari ME, Niazi V, Karami F, Rezvani, AR, et al. Personalized medicine in colorectal cancer. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S18-S28).

Liver cancer is the third cause of cancer-related deaths in the world. It is primarily divides into two main types, namely hepatocellular carcinoma (HC) and cholangiocarcinoma (IC). Due to the increasing number of patients with liver cancer and the high mortality rate, early diagnosis of the disease can be helpful in treatment, but most patients are diagnosed atlate stages of HC. The aim of this study is to screen and provide an overview on candidate biomarkers related to primary liver cancer to introduce the critical ones. In this study, various biomarkers related to the diagnosis of primary liver cancer have been studied. Accordingly, biomarkers are divided into different groups as blood biomarkers classified as serum and plasma biomarkers, tissue biomarkers, microRNA biomarkers, proteomic biomarkers and altered genes. Previous researches have focused on liver cells and bile ducts, the surround cellular environment, how cells differentiate, and the types of genes expressed in liver cancer. Some even have focused on the origin of tumor cells and how they differentiate and develop. In all these studies, the expression of specific proteins and genes in liver cancer has been considered. Based on available sources, biomarkers can be considered as candidates to diagnose and prognosis of various types of primary liver cancer, from sources such as blood, tissue, mic-RNA, proteome and genes. However, more investigations are required to introduce a biomarker for precise detection of early liver cancer.

Keywords: Hepatocellular carcinoma, Biomarker, Diagnosis, Prognosis, Proteomics.

(Please cite as: Mansouri V, Razzaghi MR, Nikzamir A, Ahmadzadeh AR, Iranshahi M, Haghazali M, et al. Assessment of liver cancer biomarkers. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S29-S39).

Aim: The aim of this study was to estimate the standardized incidence rate (SIR) and also the relative risk (RR) of colorectal cancer (CRC) in Iran and to determine the distribution of CRC risk in a map after adjusting socioeconomic risk factors.

Background: The growth of CRC incidence rate in Iran is a major public health problem and identifying high-risk regions is essential for further intervention.

Methods: For this cross-sectional study, all CRC cases that occurred in 30 Iranian provinces between 2005 and 2008 were collected according to the International Classification of Diseases (ICD-10). In addition, socioeconomic information was extracted from statistical center of Iran. Bayesian and Poison regression models were fitted to identify significant covariates. For RR estimating, the spatial analysis using GIS technique was carried out.

Results: The Bayesian method with increasing precision of the parameter estimates had a better fit. According to spatial model,  East Azerbaijan province had a high (11.14) and South Khorasan province had a low  (0.22) risk of CRC in the period of study. SIR for the male population was 1.92 ± 3.25, and for the female population it was 1.85 ± 3.37.

Conclusion: There is a non-uniform spatial pattern of CRC risk in Iran. According to the results, North, Northwest and some parts of West and Central provinces of Iran are identified as high-risk areas; thus, it is recommended that health policymakers, especially in these areas, have more intervention measures. Further studies are needed to map the RR adjusted for nutrition factors.

Keywords: Colorectal Cancer, Relative risk, Bayesian model, Poisson regression, Spatial analysis.

(Please cite as: Pourhoseingholi MA, Najafimehr H, Kavousi A, Pasharavesh L, Khanabadi B. The spatial distribution of colorectal cancer relative risk in Iran: a nationwide spatial study. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S40-S46).

Aim: Here, we evaluated the VEGF gene -2578C/A polymorphism as a potential susceptibility factor in colorectal cancer (CRC) occurrence amongst Iranian CRC patients.

Background: Vascular endothelial growth factor (VEGF) is a key regulatory factor in angiogenesis which plays essential roles in the development of malignancy in colorectal cancer (CRC), as the third most prevalent cancer worldwide.

Methods: VEGF -2578C/A polymorphism was evaluated in 200 CRC patients and 200 healthy control subjects via restriction fragment length polymorphism analysis.

Results: The frequencies of CC, AC and AA genotypes among CRC patients were 22.5%, 51% and 26.5%, respectively, with their respective genotype frequencies at 16%, 54% and 30% in control cohorts (P=0.247). The A allele frequency among the case group was 52% and for control group, it was 57%. C allele frequency in case and control groups was 48% and 43%, respectively (p=0.156). No significant association was observed (p=0.990) between this polymorphism and CRC stage.

Conclusion: Our findings provide limited support for the hypothesis that the -2578C/A VEGF are associated with increased risk of colorectal cancer in Iranian colorectal cancer patients and suggest instead that meta data studies, which have previously relied upon populations definitions such as ‘Asian’, should more specifically take into account country of origin when associating prognostic value to a given genotype.

Keywords: Colorectal cancer, Angiogenesis, VEGF, Single nucleotide polymorphism, Vascular endothelial growth factor.

(Please cite as: Savabkar S, Zali N, Hadizadeh M, Tavangarroosta SH, Young CH, Shojaeian F, et al. Lack of association between VEGF -2578C/A polymorphism and risk of colorectal cancer in an Iranian population Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S47-S52).

Aim: This study was aimed at gene assessment of Crohn's disease (CD) through protein-protein interaction (PPI) network analysis to find crucial genes.

Background: CD is a major subtype of inflammatory bowel diseases (IBD), which affects gastrointestinal tract. PPI network analysis is a suitable tool to clarify a critical gene as a drug target or diagnostic biomarker for these types of diseases.

Methods: Gene expression profile GSE126124 of 20 CD patients and 20 healthy controls was obtained from the Gene Expression Omnibus (GEO) database. RNA profile of peripheral blood mononuclear cells (PBMCs) and colon biopsy samples of the studied groups was investigated. Crucial genes were selected and analyzed via the PPI network by Cytoscape software. Gene ontology enrichment for the hubs, bottlenecks, and hub-bottlenecks was performed via CluGO plugin of Cytoscape software.

Results: Eighty-one differentially expressed genes (DEGs) among 250 initial DEGs were highlighted as significant by FC>2 and p-value ≤ 0.05, and 69 significant DEGs were used for PPI network construction. The network was characterized by poor connections, so 20 top neighbors were added to form a scale-free network. The main connected component included 39 query DEGs and 20 added first neighbors. Three clusters of biological processes associated with crucial genes were identified and discussed.

Conclusion: The results of this study indicated that GATA3 has a key role in CD pathogenesis and could be a possible drug target or diagnostic biomarker for Crohn’s disease.

Keywords: Crohn’s disease, Genes, Gene ontology, GATA3 transcription factor.

(Please cite as: Rezaei-Tavirani S, Asri N, Emamhadi MA, Jahani-Sherafat S, Salehi AS, Gholamrezaei Z, et al. Introducing GATA3 as a prominent player in Crohn’s disease. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S53-S59).

Aim: this study was conducted to investigate expression of the genes associated with CD in the target tissue in order to estimate contribution of each single gene to development of immune response. Then, the same set of genes was evaluated in peripheral blood mononuclear cells  (PBMCs).

Background: Celiac disease (CD) is a chronic systemic autoimmune disease of the small intestine occurring in genetically-susceptible individuals. There are several genes related to immune response.

Methods: For this purpose, the genes related to CD were extracted from public databases (documents of proteomics and microarray-based techniques) and were organized in a protein-protein interaction network using the search tool for retrieval of interacting genes/proteins (STRING) database as a plugin of Cytoscape software version 3.6.0. The main genes were introduced and enriched via ClueGO to find the related biochemical pathways. The network was analyzed, and the most important genes were introduced based on central indices.

Results: Among 20 CD genes as hub and bottleneck nodes, there were 7 genes with common expression in blood and intestinal tissue (C-X-C motif chemokine 11(CXCL11), granzyme B (GZMB), interleukin 15(IL-15), interleukin 17(IL-17A), interleukin 23(IL-23A), t-box transcription factor 21(TBX21), and tumor necrosis factor alpha-induced protein 3(TNFAIP3)).

Conclusion: The enriched biological process related to the central nodes of celiac network indicated that most of hub-bottleneck genes are the well-known ones involved in different types of autoimmune and inflammatory diseases.

Keywords: Celiac Disease, PBMC, Intestinal Tissue, Autoimmune, Inflammatory.

(Please cite as: Khalkhal E, Nobakht F, Haidari MH, Razaghi Z, Ghasemzad M, Sheikhan M, et al. Evaluation of expression of common genes in the intestine and peripheral blood mononuclear cells (PBMC) associated with celiac disease. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S60-S67).

Aim: The aim of this study is to assess the molecular profile of gastroesophageal reflux disease (GERD) via Protein-protein interaction (PPI) network analysis and gene ontology (GO) investigation.

Background: GERD which affects the life of about 30% of people is associated with high costs in the human papulation. Several risk factors such as smoking, eating habits, BMI, and dysfunction of lower esophageal sphincter have been reported to contribute to the onset and progression of GERD. The roles of some types of interleukins and inflammatory factors as molecular features of GERD are investigated.

Methods: Genes related to GERD were analyzed by Cytoscape v.3.7.2 and the corresponding plug-ins. ClueGO and CluePedia assessed the gene ontology and action type properties for the central nodes.

Results: The results indicated that there are 12 hub-bottlenecks almost all of which except ALB are dispersed in the network clusters 1 and 2. Il17 signaling pathway among 7 identified biochemical pathways was also detected as a most related annotation for these central genes.

Conclusion: Numbers of 11 critical genes and one pathway (IL17 signaling pathway) were highlighted as the deregulate genes and pathway in GERD. Common molecular features of GERD and cancer appeared.

Keywords: Gastroesophageal reflux disease, Protein-protein interaction network analysis, Gene ontology, Biomarker.

(Please cite as: Zamanian Azodi M, Razzaghi MR, Malekpour H, Rezaei-Tavirani M, Rezaei-Taviran M5, Heidari MH, et al. Highlighted role of “IL17 signaling pathway” in gastroesophageal reflux disease. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S68-S74).

Aim: The aim of this study is to assess the molecular profile of gastroesophageal reflux disease (GERD) via Protein-protein interaction (PPI) network analysis and gene ontology (GO) investigation.

Background: GERD which affects the life of about 30% of people is associated with high costs in the human papulation. Several risk factors such as smoking, eating habits, BMI, and dysfunction of lower esophageal sphincter have been reported to contribute to the onset and progression of GERD. The roles of some types of interleukins and inflammatory factors as molecular features of GERD are investigated.

Methods: Genes related to GERD were analyzed by Cytoscape v.3.7.2 and the corresponding plug-ins. ClueGO and CluePedia assessed the gene ontology and action type properties for the central nodes.

Results: The results indicated that there are 12 hub-bottlenecks almost all of which except ALB are dispersed in the network clusters 1 and 2. Il17 signaling pathway among 7 identified biochemical pathways was also detected as a most related annotation for these central genes.

Conclusion: Numbers of 11 critical genes and one pathway (IL17 signaling pathway) were highlighted as the deregulate genes and pathway in GERD. Common molecular features of GERD and cancer appeared.

Keywords: Gastroesophageal reflux disease, Protein-protein interaction network analysis, Gene ontology, Biomarker.

(Please cite as: Zamanian Azodi M, Razzaghi MR, Malekpour H, Rezaei-Tavirani M, Rezaei-Taviran M5, Heidari MH, et al. Highlighted role of “IL17 signaling pathway” in gastroesophageal reflux disease. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S68-S74).

Aim: The purpose of this study was to investigate the effect of biofeedback therapy on constipation to improve sexual function among the female population with pelvic floor hypertonicity.

Background: It appears that pelvic floor disorder could lead to sexual complaints. Unfortunately, there are few data on the correlation between pelvic floor-related constipation and sexual disorders. The biofeedback role as a conservative method in improving the health status in these patients is conflicting.

Methods: Forty-two eligible women were included in the study. The exclusion criteria were not being sexually active, not having functional constipation according to Rome IV criteria, and having other psychiatric issues, according to DSM4TR criteria. All participants were treated using biofeedback in eight sessions, during two months. Before and after the treatment, they were analyzed by pelvic floor impact questionnaire, pelvic floor Distress Inventory, and Short Scale Personal Experiences Questionnaire (SPE Q).

Results: Biofeedback significantly improved orgasm, arousal, and dyspareunia (respectively P = 0.001, P = 0.001, P = 0.001). However, there was no significant improvement in libido and partner satisfaction domains (respectively P = 0.132, P = 0.341). Significant negative correlations were detected between the age and sexual function. On the other hand, there was no negative relationship between vaginal delivery as well as cesarean delivery and different components of sexual function.

Conclusion: It seems the improvement in pelvic floor muscle hypertonicity leads to sexual satisfaction. Nevertheless, more data are required to prove this correlation.

Keywords: Sexual dysfunction, Biofeedback, Pelvic floor disorder, Constipation.

(Please cite as: Banihashem SSH, Chalakinia N, Eslami P, Mahdavi Roshan M, Kheradmandn A, Abdi S, et al. Impact of biofeedback therapy for pelvic floor-related constipation to improve sexual function. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S75-S80).

Aim: The main complication of Endoscopic retrograde cholangiopancreatography (ERCP) is post-ERCP pancreatitis (PEP).

Background: Based on demographic characteristics and underlying issues and ERCP indication, patients are categorized as high risk or low risk. There have been no studies on the synergistic effects of NSAIDS and hydration therapy, separately sorted by the risk assessment of PEP in different groups of patients.

Methods: This study included 281 eligible participants after exclusion. According to demographic characteristics and co-morbidities, the patients were divided to high risk and low risk. The high-risk group was divided randomly into two subgroups and both of them received NSAIDs (100 mg rectal Diclofenac). One group received standard hydration (1.5mg/kg/hr), another the other received aggressive hydration (3mg/kg/h). The low-risk group received standard hydration. One of its subgroups received NSAIDs, while others did not. The efficacy of these preventions was compared across 4 subgroups.

Results: The mean age was 59.85±17.17. Eight hours after ERCP, the amylase and lipase were significantly higher in the high-risk group with standard hydration (P=0.00). Amylase, lipase 8 hours, between two low risk subgroups, NSAIDs had no significant effect (P=0.38, P=0.95, respectively).  After adjustment based on cannulation, manipulation and duration of time, the results had no change (P=0.64, P=0.19, P=0.61).

Conclusion: The aggressive hydration could significantly decrease the risk of PEP. However, the low-risk group was exposed to the lowest risk of PEP. NSAIDs could not help to decrease the rate PEP in the low-risk groups alone. Overall, it seems hydration and NSAIDs therapy had synergistic outcome in high-risk patients.

Keywords: Endoscopic retrograde cholangiopancreatography (ERCP), post ERCP pancreatitis.

(Please cite as: Aghajanpoor Pasha M, Eslami p, Dooghaie Moghadam A, Moazzami B, shojaee S, Almasi F, et al. The synergistic impact of NSAIDs and aggressive hydration therapy on the rate of post-ERCP pancreatitis in high -risk and low -risk patients. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S81-S88).

Aim: This study was designed to perform network analysis of Alzheimers҆ disease and diabetes and to find their correlation with each other and other diseases/pathways.

Background: Alzheimer’s disease (AD) as a neurodegenerative disease and diabetes as a metabolic disease are two major health problems in the recent years. The recent studies have reported their correlation and same spreading pathways of these two diseases together, but details of this relation are not well known yet at molecular level..

Methods: In thermal proteome profiling (TPP) technique, after treatment of the extracted proteins by heat and drug concentration, the resulting proteins were analyzed by mass spectrometry. Enrichment analysis of these proteins led to development of AD and diabetes. First, corresponding genes for each disease were extracted from DisGeNET database and then, protein-protein interaction network was constructed for each of them using the search tool for retrieval of interacting genes and proteins (STRING). After analyzing these networks, hub-bottleneck nodes of networks were evaluated. Also, common nodes between two networks were extracted and used for further analysis.

Results: High correlation was found between AD and diabetes based on the existence of 40 common genes. Results of analyses revealed 14 genes in AD and 12 genes in diabetes as hub-bottleneck 7 of which were common including caspase 3 (CASP3), insulin-like growth factor 1 (IGF1), catalase (CAT), tumor necrosis factor (TNF), leptin (LEP), vascular endothelial growth factor A (VEGFA), and interleukin 6 ( IL-6).

Conclusion: Our results revealed a direct correlation between AD and diabetes and also a correlation between these two diseases and non-alcoholic fatty liver disease (NAFLD), suggesting that a small change in each of these three diseases can lead to development of any other diseases in the patients. Also, the enrichments exhibited the existence of common pathways between AD, diabetes, NAFLD, and male infertility.

Keywords: NAFLD, Alzheimer's disease, Diabetes mellitus, Type II, Male infertility, Bioinformatics.

(Please cite as: Gholizadeh E, Khaleghian A, Najafgholi Seyfi D, Karbalaei R. Showing NAFLD, as a key connector Disease between Alzheimer’s disease and diabetes via analysis of systems biology. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S89-S97).

Aim: Evaluation of deregulated genes after long-term consuming of omeprazole via network analysis.

Background: Proton pump inhibitors (PPIs) are used to inhibit gastric high rate of acid secretion in patients. Omeprazole as a PPI is a common drug in this regard. Evaluation of long-term consumption of omeprazole is studied in the present study via its effects on the gene expression of “human coronary artery endothelial cells”.

Methods: Net effect of the presence of omeprazole on gene expression profiles of “human coronary artery endothelial cells” was evaluated through data from gene expression omnibus (GEO). Results of protein-protein interaction (PPI) network analysis were assessed via biological process examination to find the critical deregulated genes after long-term consumption of omeprazole.

Results: “Negative regulation of muscle cell apoptotic process”, “negative regulation of DNA binding”, “telencephalon cell migration”, “forebrain cell migration” “response to cadmium ion”, “cell-cell recognition”, “positive regulation of protein targeting to mitochondrion”, and “central nervous system neuron development” were the clusters of biological processes that were associated to the long -term presence of omeprazole. The final critical deregulated genes were JAK2, PTK2, and NRG1.

Conclusion: It can be concluded that cell cycle, proliferation, and apoptosis and several essential biological processes are affected and nervous system is a possible target related to the long-term consumption of omeprazole.

Keywords: Omeprazole, Long term consumption, Gene expression.

(Please cite as: Nikzamir AR, Rezaei-Tavirani M, Razzaghi MR, Rezaei Tavirani S, Hamzeloo-Moghadam M, Esmaeili S, et al. Evaluation of long-term consumption of omeprazole disadvantages: a network analysis. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S98-S105).

Aim: The present study was conducted to determine the genes with common expression in blood and appendix tissue samples in order to introduce them as possible diagnostic biomarkers.

Background: Diagnosis of acute appendicitis (AA) without applying computed tomographytomography (CT), subjecting the patient to significant radiation, can be surprisingly difficult. Blood circulation may have conscious alterations in its RNA, protein, or metabolite composition.

Methods: The genes related to appendix tissue and blood samples of the patients with AA were extracted from public databases. Fold change (FC) ≥ 2 in blood and FC ≥ 5 in appendix tissue samples were considered to screen differentially expressed genes (DEGs). A protein-protein interaction network was organized using the search tool for retrieval of interacting genes and proteins (STRING) database as a plugin of Cytoscape software version 3.6.0. The main genes were enriched by DAVID Bioinformatics Resources to find the related biochemical pathways.

Results: Among the DEGs in blood and appendix tissue samples, C-X-C motif chemokine receptor 1(CXCR1), leukocyte immunoglobulin-like receptor A3 (LILRA3), low-affinity immunoglobulin gamma Fc region receptor III (FCGR3), and superoxide dismutase 2(SOD2) were common in both sources. CXCR1 was found as only hub gene upregulated in both blood and tissue of the patients with AA compared to controls and those with other abdominal pain.

Conclusion: CXCR1, FCGR3, LILRA3, and SOD2 were determined as a suitable possible biomarker panel for diagnosis of AA disease.

Keywords: Acute appendicitis; Biomarker, Diagnosis.

(Please cite as: Khalkhal E, Razzaghi Z, Akbarzadeh Baghban AR, Naderi N,  Rezaei-Tavirani M, Rezaei-Tavirani M. Evaluation of CXCR1 as a possible diagnostic biomarker in acute appendicitis. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S106-S112).

Aim: We aimed to carry out proteomic assessment of long-term effects of hepatitis C on liver.

Background: Cirrhosis is a condition where liver is damaged and loses its efficiency, and has the high rate of mortality in the world. Proteome profiling may help to identify important proteins and find the pathogenesis Cirrhosis is a condition where liver is damaged and loses its efficiency, and has the high rate of mortality in the world. Proteome profiling may help to identify important proteins and find the pathogenesis.

Methods: Here, by the application of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), combined with (MALDI-TOF-TOF MS), proteome profile of decompensated HCV cirrhosis is determined compared to healthy matched controls. Furthermore, Cytoscape has used network analysis. The proteome comparison between two groups identified proteins with significant expression changes (p<0.05 and fold change ≥ 1.5).

Results: We found upregulation of IGHA1, C3, A1BG, IGKC and one isoform of HP. Also, lower expression of APOA4 and the other spot of HP in advanced cirrhosis patients were revealed based on HCV compared to matched controls. According to network analysis, ALB has been introduced as a key protein, which may play an important role in pathogenesis.

Conclusion: Integration of the proteomics with protein interaction data led to the identification of several novel key proteins related to the immune system that may reflect the long-term effects of hepatitis C virus on the liver, and can introduce as therapeutic targets for advanced HCV- cirrhosis.

Keywords: Proteomic, liver cirrhosis, hepatitis C, Two-dimensional gel electrophoresis (2DE), Protein –protein interaction.

(Please cite as: Safaei A, Arefi Oskouie A, Mohebbi SR, Razaghi Z, Nejadi N. Proteomic study of advanced cirrhosis based on HCV to reveal potential biomarkers. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S113-S121).

Aim: This study aimed to determine the prevalence of Human Astroviruses (HAstVs), enteric Adenoviruses (HAdVs), and Sapoviruses (SaVs) in acute diarrhea patients, as well as their relation to age, sex, and season.

Background: Acute gastroenteritis is one of the most common diseases affecting children <5 years old and viral agents with approximately >75% are the major causative agent of acute infectious diarrhea. After Rotavirus and Norovirus, the greater viral agents of acute gastroenteritis include HAstVs, HAdVs, and SaVs. To the best of our knowledge, there are sparse studies in Iran detecting at least three enteric viruses as causative agents of diarrhea simultaneously.

Methods: The sample was collected from children referring to pediatric medical centers in Tehran, Iran; they were tested for Astrovirus, enteric Adenovirus, and Sapovirus by conventional PCR method. The association of incidence of viral enteric agents was evaluated with age, sex and seasonal pattern in children <5 years old.

Results: The positive case number among acute gastroenteritis patients was 17/120 (14.1%). Patients ranged in age within 1–60 months, but 52.9% were aged ≤ 12 months. Males comprised the majority (70.6), and the male: female ratio was 2.4. HAstV was the most frequently detected virus (6.7%), while SaVs were detected only in 2.5% of cases. Mixed infections were not detected in these samples. The highest rate of HAstV was identified in winter (66.7%), HAdV in fall (66.7%), and SaV in winter (33.3%).

Conclusion: These findings underscore the importance of monitoring the epidemiology of HAstV, HAdV, and SaV as causative agents of viral diarrhea infections.

Keywords: Gastroenteritis virus, Astrovirus, Adenovirus, Sapovirus, Polymerase chain reaction.

(Please cite as: Mousavi Nasab SD, Zali F, Kaghazian H, Aghasadeghi MR, Mardani R, Gachkar L, et al. Prevalence of astrovirus, adenovirus, and sapovirus infections among Iranian children with acute gastroenteritis. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S122-S127).

Aim: The aim of the study is to estimate the burden of Rotavirus gastroenteritis as well as predominant genotypes of Rotavirus among children less than 5 years of age referring to Pediatric University Hospital in Qom, Iran.

Background: Gastroenteritis is the fourth most common cause of death and accounts for 16% of all deaths in children <5 years of age worldwide.

Methods: During two years, 130 patients referring to a pediatric hospital were enrolled in this study. After RNA extraction, Rotaviruses were detected by the VP6 gene. Then, G-typing (G1, G2, G3, G4, G8, G9, and G12) and P-typing (P4, P6, and P8) were performed using RT-PCR and specific primers.

Results: The results of the PCR revealed that from a total of 130 patients, 22 cases (16.9%) showed positive VP6 by RT-PCR. G1 was mostly the predominant serotype (27%), accounting for 22% of all VP7-positive isolates, followed by G9 (18%),G2 (9%), G3 (9%), and G4 (9%). None of the strains revealed the presence of G8 genotype (0%), and 5 specimens (23%) were non-typable.

The frequency of P typing was P8 (50%), P6 (23%), P4 (14%), and 3 samples were P-non-typable (13%), respectively. The dominant G-P combination was G1 [8] (32%).

Conclusion: Such studies based on typing methods assists in the Rotavirus vaccine introduction by policymakers and design of new effective vaccines.

Keywords: Diarrhea, Rotavirus, Genotyping, Acute gastroenteritis, Vaccine, Iran.

(Please cite as: Shams S, Mousavi Nasab SD, Heydari H, Tafaroji J, Ahmadi NA, Shams Afzali E. Detection and Characterization of Rotavirus G and P Types from children with acute gastroenteritis in Qom, central Iran. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S128-S133).

Aim: To estimate the epidemiological parameters related to the Covid-19 outbreak in Iran.

Background: Estimating the epidemiological parameters of new public health threat (COVID-19) is essential to support and inform public health decision-making in different communities including Iran.

Methods: We established a mathematical model to estimate the epidemiological parameters from 19 Feb to 15 March based on daily COVID-19 confirmed cases in Iran. Then, we estimated the effect of early traffic restriction on our estimation.

Results: We estimated the R0 at 2.11 (95% CI, 1.87-2.50) and the infected number at 92,260 (95% CI: 59,263 -152,212) by 15 March. Our estimate for the ascertainment rate was about 1.2% (95% CI: 1.1-1.4). The latent period estimation was 4.24 (95% CI: 2.84-6.65). We observed a decline in our estimate after considering the traffic restriction.

Conclusion: Our results suggest that health authorities in Iran must take impactful strategies to control the COVID-19 outbreak to reach R0<1. Therefore, the establishment of complementary, multilateral, and cost-effective measures for the treatment of symptomatic and early diagnosis and isolation of asymptomatic cases/contacts are strongly recommended because of low ascertainment rate and large number of infected cases. We additionally recommend that traffic restriction be combined with other controlling measures.

Keywords: COVID-19, Iran, Outbreak, Epidemiological parameters.

(Please cite as: Olfatifar M, WQ, HR, Pourhoseingholi MA, Babaee E, Seifollahi R, et al. Early estimation of the epidemiological parameters of novel coronavirus disease (COVID-2019) outbreak in Iran: 19 Feb-15 March, 2020. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S134-S138).

Aim: To acquire a deeper perception of EMT, we evaluated the expression of some candidate extra cellular matrix (ECM) proteins including THBS2, OSMR and CHI3L1 which were collected from RNA-seq bioinformatic analyses.

Background: Gastric cancer (GC) is a major incident gastrointestinal cancer with a high rate of mortality. Metastasis is a challenging issue in gastric cancer treatment. Epithelial mesenchymal transition (EMT) of cancer cells is a complicated process controlled by different cells and molecular pathways regarded as an important step at the onset of metastasis.

Methods: AGS gastric cancer cell line was cultured and treated by TGF-β. EMT induction was verified by measuring the expression of E-cadherin, Snail, β-catenin and Vimentin genes by real time PCR. Then, following our previous study, we evaluated the expression of THBS2, OSMR and CHI3L1 genes in EMT induced cells by real time PCR.

Results: Downregulation of E-cadherin and upregulation of Snail, β-catenin and Vimentin genes were verified in AGS treated cells in comparison with none-treated cells (P-value = 0.0355, P-value = 0.007, P-value = 0.0059, P-value = 0.0206 respectively). Also, upregulation of THBS2, OSMR and CHI3L1 were validated in these cells after EMT induction (P-value = 0.0147, P-value = 0.05, P-value = 0.05 respectively).

Conclusion: Our morphological and molecular results validated EMT induction by TGF- β cytokine in AGS gastric cancer cell line. Furthermore, significant upregulation of candidate genes including THBS2, OSMR and CHI3L1 verified the role of these proteins in gastric cancer invasiveness. However, further studies are needed for the validation of prognostic value of these markers.

Keywords: Gastric cancer (GC), Epithelial mesenchymal transition (EMT), TGF- β cytokine, THBS2, OSMR and CHI3L1.

(Please cite as: Abed Kahnamouei Sh, Baghaei K, Pakzad P, Hashemi M, Zali MR. The role of extracellular matrix proteins in gastric cancer development via epithelial-mesenchymal transition. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S139-S144).

Hydatid disease is an ongoing issue in endemic areas. Hydatid cysts can be seen in any organ but, liver is one of the most common involved organs. Cystobiliary communication as an overwhelming complication of hepatic hydatid cysts can contribute to the obstructive jaundice, cholangitis, sepsis and even biliary cirrhosis if left untreated. The patient we are trying to present is a 61-year-old farmer who presented with obstructive jaundice, multiple common bile duct stones and biliary cirrhosis attributed to a long-lasting untreated hepatic hydatid cyst. Portal hypertension is introduced to be an uncommon presentation of hydatid cyst. Extrinsic compression of the porta hepatis and obstruction of inferior vena cava are amongst major causes of hydatidosis leading up to portal hypertension as reported in the literature. Portal hypertension in the presented case is proposed to emerge from long-lasting cystobiliary communication ending in biliary cirrhosis.

Keywords: Hepatic, Hydatid cyst, Biliary cirrhosis.

(Please cite as: Asadzadeh-Aghdaei H, Moshari MR, Zandi R, Karimi MA, Salari S, Ketabi Moghadam P. An uncommon presentation of hepatic hydatid cyst leading to biliary cirrhosis and portal hypertension. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S145-S148).

  [1] A 37-year-old man, Iranian resident in Zanjan, presented to the gastroenterology clinic of Taleghani Hospital; a teaching referral hospital in Tehran, Iran, with chief complaint of a significant weight loss about 20 kg in recent 4 months. He denied any concomitant systemic signs and symptoms except for a generalized malaise. He did not mention any change in bowel habit and eating pattern but a slight decrease in appetite without nausea and vomiting. He denied smoking and use of any illicit drug or alcohol. His past medical history was negative. He was admitted for further work regarding his unexplained weight loss. On admission, he was well with stable vital signs. His blood pressure was 110/70 mmHg, body temperature: 36.5 ^o C, heart rate: 84 bites per minute, and respiratory rate: 13 per minute all within normal limits. His physical exam was only notable for a mild epigastric and right upper quadrant (RUQ) tenderness. His laboratory tests were normal except for a normochromic normocytic anemia with a hemoglobin concentration of 12 mg/dl. Serum iron level was 37 mcg/dl with a total iron binding capacity (TIBC) level of 275 mcg/dl and a ferritin level of 10 mcg/l revealing an iron deficient erythropoiesis. Further laboratory tests evaluating tumor markers, thyroid function tests, liver function tests, serum bilirubin level, urine analysis and stool examination were all normal. We decided to proceed with an upper gastrointestinal endoscopy and colonoscopy in the next step of the management of the patient with significant weight loss. Total colonoscopy was unremarkable and esophagogastroduodenoscopy demonstrated a sessile polyp in antrum pathologically consistent with hyperplastic polyp. His spiral chest CT scan was normal but an abdominopelvic CT scan revealed dilation of intrahepatic ducts disseminated all over the liver prominently in the periphery of the right hepatic lobe. Periductal parenchyma was enhanced in some parts indicative of infective or neoplastic processes. Scattered celiac and mesentric lymph nodes with maximum diameter of 6 mm were also detected (figure 1). To have a better visualization of extrahepatic ducts besides intrahepatic ducts, an endoscopic ultrasound (EUS) was performed. As reflected in figure-2, findings of EUS were unremarkable except for 3 hypoechoic and round hilar lymph nodes with the largest diameter of 21mm, most probably indicative of reactive lymph nodes. This patient’s signs and symptoms continued to remain stable, so he was discharged and was advised to follow other diagnostic modalities in the outpatient clinic. Some months later, he referred to the gastroenterology clinic with similar complaints of inability to weight gain and anorexia. Given the previous history of intrahepatic duct dilation, an MRCP was demanded which revealed heterogeneity of the liver parenchyma due to multiple masses or microabscesses in the liver. Laboratory results were negative for infectious, helminthic and parasitic disorders for this kind of liver involvement, and imaging reports were unable to rule out a neoplastic process and give a definite diagnosis. This made us proceed with a liver biopsy.

What is your diagnosis?

What is the next step?

Received: 24 September 2020  Accepted: 8 December 2020

Reprint or Correspondence: Saeed Abdi, MD. Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

E-mail:  saeedabdi75@yahoo.com

ORCID ID: 0000-0002-2375-3748

1. [1] A 29-year-old man was admitted to the emergency department of Taleghani hospital; a teaching referral hospital in Tehran, Iran, with an acute upper gastrointestinal (GI) bleeding. On admission, he was found to have severe hematemesis since 6 hours before his arrival following an episode of intractable nausea and vomiting. He was single, residing in Tehran, Iran. He had a history of a 10 pack-year smoking, opium addiction and social alcohol consumption but denied usage of other illicit drugs, other medications including NSAIDs and other over-the-counter drugs.  He had a history of stab wound 5 years ago leading to pneumohemothorax requiring a chest tube insertion. He did not mention any melena, defecation and gas passing since 2 days ago. He was not found to have any significant abdominal pain on admission. Four hours post admission, he was still conscious and oriented to the questions we were asking and he was still complaining about severe nausea. He had a temperature of 37.8o C. His blood pressure was 110/75mmHg. He had tachycardia of about 100 beats per minute. Resuscitation with IV fluids started. His physical examination was notable for a mild tenderness in left upper quadrant of the abdomen, dullness to percussion in the left thorax and decreased lung sounds on auscultation in the left lung but the examination of other organs was unremarkable. NG (nasogastric) tube was inserted and fresh bleeding was detected in the tube. His laboratory tests revealed an Hb of 12 gr/dl which was significantly lower than his previous Hb which was documented 18 gr/dl. No leukocytosis and thrombocytopenia was detected. His VBG was within normal limits. Kidney function tests, serum electrolytes, liver function tests, pancreatic enzymes and other biochemical tests were all unremarkable. Being hemodynamically stable but with an ongoing blood loss which demonstrated a serious risk for making him unstable in the near future, an emergent upper GI endoscopy was performed which revealed a completely congested and inflamed mucosa of fundus unable to be inflated in retroflex view. No active bleeding and source of bleeding was detected. Scope could not be passed into the distal part of stomach (figure-1). Abnormal auscultation of the lungs urged evaluation of thoracic field. Chest x ray (figure-2) and thoracic spiral CT scan (figure-3) were demanded.  Six hours post admission, he was found to have tachypnea and shortness of breath. He spiked a heart rate of 120.  

   What is your diagnosis?

   What is the next step?

    

   Received: 28 May 2020   Accepted: 18 July 2020

   Reprint or Correspondence: Pardis Ketabi Moghadam, MD. Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

   E-mail: ketabimoghadam.p@gmail.com

   ORCID ID: 0000-0001-7110-2950

.

Although most subepithelial lesions are benign, the malignant forms could present as serious life-threating cancers. Their accurate diagnosis depends on complete surgical resection. Different endoscopic methods have been recommended for the resection. Recently, the EMR has been considered as a safe and effective technique, while various revised EMR techniques have been introduced. In this study, a new version of EMR has been evaluated in two patients. Two middle-aged cases with gastric subepithelial tumors were admitted to Taleghani gastrointestinal department. The polyps were resected via our new Endoscopic Mucosal Resection (EMR) technique. In this technique, the needle knife was used for un-roofing the mucosal surface. Then, the polyps were resected with hot snares. The hemoclips were applied for ligation too. We found no early or delayed complications. Furthermore, the microscopic margins of the lesions were free. Our study represented a safe and cost-beneficial technique for subepithelial lesions and no complications was found and the margins were free. However, further investigations are required for confirming the validity of this new EMR technique.

Keywords: Subepithelial Tumor, Endoscopic Mucosal Resection.

(Please cite as: Asadzadeh Aghdaei H, Sadeghi A, Ghorbanpour Nouri A, Nouri GHR, Dooghaie Moghadam A, Azizi MR, et al. A new endoscopic submucosal resection –ligation technique for gastric tumors. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S149-S153).