Gastroenterology and Hepatology from Bed to Bench

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Aim: Since interactome analysis of diseases can provide candidate biomarker panel related to the diseases, in this research, protein-protein interaction (PPI) network analysis is used to introduce the involved crucial proteins in Gastric adenocarcinoma (GA). 

Background: Gastric adenocarcinoma (GA) is the most common type of stomach cancer. There is no efficient diagnostic molecular method for GA.

Method: Applying Cytoscape software 3.4.0 and String Database, the PPI network was constructed for 200 genes. Based on centrality parameters, the critical nodes were screened. Gene ontology of the key proteins for pathway analysis and molecular function processing were done and the highlighted pathways and activities were discussed.

Results: The results indicated that among 200 initial genes, 141 one were included in a main connected network. Seven crucial proteins including tumor protein p53, epidermal growth factor receptor, albumin, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian), v-akt murine thymoma viral oncogene homolog 1, v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) and catenin (cadherin-associated protein), beta 1, 88kDa , and Myogenic differentiation 1, were introduced as key nodes of the network. These identified proteins are mostly involved in pathways and activities related to cancer.

Conclusion:  In conclusion, the finding is corresponding to the significant roles of these introduced proteins in GA disease. This protein panel may be a useful probe for diagnostic proposes in management of GA. 

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Background: There is an accumulating evidence indicating that the inadequate immune responses are responsible for HBV persistency. Therefore, polymorphisms in genes encoding the cytokines, which are responsible for regulation of the immune response, can affect the course and outcome of the infection. The IFN-? +874 T/A polymorphism affects the expression of IFN-?, which shown to be crucial to HBV clearance. The Aim: This study aimed to investigate the association of IFN- ? +874 (T/A) Polymorphism with the HBV infection outcome in Syrian population. Patients and Methods: In this prospective cross-sectional study, 113 samples were collected (43 healthy individuals, 69 chronic HBV patients). Genomic DNA was isolated. Sequencing and ARMS-PCR were performed to genotype the IFN-? +874 T/A polymorphism. Results: Results of this study showed an association between IFN- ? +874 T/A polymorphism with the chronic HBV infection (P < 0.05). In addition, results showed that the AA genotype increased the risk of chronicity (OR = 4.15, 95% CI = 1.39 – 12.4), whereas the AT genotype reduced the risk of chronicity (OR = 0.41, 95% CI = 0.18 – 0.90). Conclusion: Results of this study might conclude that the IFN- ? +874 T/A polymorphism is associated with the chronic HBV infection, according to the genetic model AA vs. AT&TT.

Introduction: Chronic hepatitis B infection (CHB) is a major global health problem. Hepatitis B e antigen (HBeAg)-negative is a common type of CHB in Iran. Liver damage in HBeAg-negative CHB leads to progressive form of the liver disease with poor prognosis. Therefore, it seems necessary to perform a comprehensive evaluation of different spectrum of laboratory measurements accompanying histological findings. The aim of this study was to evaluate the association between the biochemical, virologic and histologic features in HBeAg-negative CHB. Furthermore, we assessed the application of new cut-off values for alanine aminotransferase in HBeAg-negative CHB patients.

Materials and methods: HBeAg- negative CHB patients referring to hepatology clinics at Ghaem and Imam Reza hospitals during two years period were enrolled. Patients with alcohol consumption, liver mass, fatty liver and whom with positive results of Anti HDV, Anti HCV or Anti HIV were excluded. Liver enzymes were requested and Hepatitis B viral loads were measured by real time polymerase chain reaction (RT-PCR) in all patients. Liver biopsies were assessed by two expert pathologists. The relationship between viral loads, liver enzymes and histopathological features was analyzed using descriptive and analytic statistical methods.

Results: One hundred and fifty HBeAg-negative and HBe Ab-positive CHB patients (males=110, mean age=38.44±11.34 years) were assessed. Serum ALT levels had a significant relation with the logarithm of serum HBV-DNA levels (P<0.0001), grade and stage on liver biopsy (P<0.001, P=0.034, respectively). Serum viral load, AST and ALT levels were independent predictors of histological grade, but age was the only independent predictor of the stage of liver fibrosis. There was a significant relationship between serum ALT levels and stage of liver fibrosis (P<0.0001) when the new cutoff values for ALT were taken into account.

We also found that age had a significant relation with histological grade but it showed a reverse relation with alanine aminotransferase (ALT) levels (P=0.009).

Conclusions: In HBeAg-negative CHB patients, serum AST levels had a better predicting value for liver necrosis and inflammation. Moreover, age could be regarded as an independent predictor of the stage of liver fibrosis. This study revealed that the new cutoff values for ALT had superiority over the conventional values to identify patients with a higher risk of liver fibrosis.

Keywords: Hepatitis B, HBeAg, grade, stage, viral load, AST, ALT

Aim: The aim of present study was to evaluate the different doses of Butyric acid (BA) and Arsenic (As) on mouse liver mitochondria oxidative stress and pancreatic islets insulin secretion.

Background: BA is found in many foods and As is a toxic metal in drinking water. They can induce oxidative stress in some tissue.

Materials and Methods:  In this experimental study, Liver mitochondria were isolated by administration of different centrifugation method and pancreatic islets of mice were isolated by a collagenase method. Mitochondria by BA (35, 75, 150, 300 ?M) and As (20, 50, 100, 200 ?M) and the islets were incubated by BA (250, 500, 1000, 1500 ?M) and As (0, 50, 100, 200 ?M) for 1 hour. At the end of experiment mitochondrial viability and membrane potential, ROS, MDA, GSH and islets insulin secretion were measured by their specific methods.

Results: BA and As administration increased mitochondrial levels of ROS, MDA and decreased GSH and pancreatic islet insulin secretion in a dose dependent manner (p < 0.05). The exact mitochondria toxic concentrations were 75 ?M for BA and 100 ?M for As. Also, the doses of 1000 ?M for BA and 100 ?M for As were consider as reducing concentrations for islets insulin secretion. Additionally, coadministration of these doses of BA and As revealed an additive effect on their own tissues variables.

Conclusion: Alone or in combination administration of BA and As induced oxidative stress in liver mitochondria and decreased insulin secretion of pancreatic islets.

Aim: The aim of this study was to assess the association between survival of patients with colorectal cancer and prognostic factors in a competing risks parametric model using Weibull distribution.

Background: The prognosis of colorectal cancer is relatively good in terms of survival time. In many prognostic studies, patients may be exposed to several types of competing events. These different causes of death are called competing risks.

Methods: Data recorded from 372 patients with colorectal cancer who registered in Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences (Tehran, Iran) from 2004 to 2015 in a retrospective study. Analysis was performed using competing risks model and Weibull distribution. Software used for data analysis was R, and significance level was regarded as 0.05.

Results: The result indicated that, at the end of follow-up, 111 (29.8%) death was from colorectal cancer and 14 (3.8%) death was due to other diseases. The average body mass index (BMI) was 24.61(SD 3.98). The mean survival time for a patient in 372 was 62.05(SD 48.78) month with median equals to 48 months. According to competing-risks method, only stageIII ( HR, 1.69; 95% CI, 1.246-2.315 ), stageIV( HR, 4.51; 95% CI,2.91-6.99 ) and BMI( HR, 0.96; 95% CI, 0.96-0.975)  have a significant effect on patient’s survival time.

Conclusion: This study indicated pathologic stage(III,IV) and BMI as the prognosis, using Weibull model with competing risks analysis, while other model without the competing events leads to significant predictors which may due to over-estimation.

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It is not clear in guidelines whether it would be is necessary to organise a CT angiogram (CTA) prior to these procedures in patients with an acute lower GI bleed. While there are studies which recommend the use of a CTA, there are other studies against using CTA in these circumstances. Here we present a case of a patient with an acute lower GI bleed who became haemodynamically unstable. We show in this case study, the catheter angiogram not being able to identify the site of bleeding without the aid of the CTA prior.

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