Review Article

Virus in the pathogenesis of inflammatory bowel disease: role of Toll-like receptor 7/8/3

Hamid Asadzadeh Aghdaei, Negar Jamshidi, Vahid Chaleshi, Nazanin Jamshidi, Amir Sadeghi , Mohsen Norouzinia, Mohammad Reza Zali

Gastroenterology and Hepatology from Bed to Bench, Vol. 14 No. 4 (2021), 23 Shahrivar 2021,

Inflammatory bowel disease (IBD) pathogenesis is influenced by immune system malfunction, particularly innate immune receptors such toll-like receptors. Furthermore, due to the extreme close association between viruses and IBD incidence, it is critical to further investigation between the virus and IBD. TLRs 3, 5, and 7 are three members of TLRs family that are involved in antiviral immune responses. Finding a relationship between TLR related virus and IBD is important not only for disease pathogenesis but also for therapeutic effectiveness. Furthermore, it has been shown that influenza expresses severe in patients with IBD who use immune system inhibitors, and the influenza vaccine is less effective in these patients. In dendritic cells, TLR7 and TLR8 regulate the production of interferons (IFNs) and inflammatory mediators. COVID-19 causes the production of IL-6, which could be due to the induction of TLR pathways. TLR activation by SARS-CoV-2 causes inflammation and IL-1 production, which induces IL-6 to be produced. Understanding the TLR associated viruses’ molecular mechanism can greatly help improve the quality of life of people with IBD. Therefore, the present study aimed to review the role of TLR7, 8 and 3 in inflammatory bowel disease, their association with viral infections and to evaluate different antagonists for the treatment of IBD.

Original Article

Adult celiac disease with persistent IBS-type symptoms: a pilot study of an adjuvant FODMAP diet

Nick Trott, Dr Anupam Rej, Sarah Coleman, Professor David Sanders

Gastroenterology and Hepatology from Bed to Bench, Vol. 14 No. 4 (2021), 23 Shahrivar 2021,

Background and Aims

Patients with biopsy proven adult celiac disease (CD) may have on-going gastrointestinal symptoms despite adherence to the gluten-free diet (GFD). Functional gut symptoms including Irritable Bowel Syndrome (IBS) is one cause of persisting symptoms in CD patients. This pilot study assessed the benefit of an adjuvant low FODMAP diet (LFD) in adult CD patients established on GFD who had a normal remission biopsy.


Twenty-five adult CD patients who were adherent to the GFD were recruited. These patients had histologically normal villi on their remission biopsy. A specialist dietitian then offered an adjuvant LFD. Symptom response was assessed using the Gastrointestinal Symptom Rating Scale (GSRS) from baseline to follow up.


Of the 25 CD patients in remission with concurrent IBS 9 patients did not wish to pursue the LFD, 1 patient had incomplete data. Fifteen patients completed a minimum of four weeks on the LFD (mean age 44 ± 17.3; median duration of follow-up 7.2 years; range 43.2 years). Global symptom relief of gut symptoms was reported by 8/15 patients (53% P = 0.007). Significant reductions in abdominal pain (P <0.01) distension (P < 0.02) and flatulence (P <0.01) were demonstrated.


This is the first study to demonstrate an adjunct LFD is an effective dietary treatment for concurrent IBS in adult CD patients with biopsy-confirmed remission. Such patients should be seen by a specialist dietitian to ensure nutritional adequacy and appropriate reintroduction of FODMAP containing foods.

Determination of allograft fibrosis by measurement of liver stiffness using transient elastography in children after liver transplantation at Shiraz Organ Transplant Center

Seyed Mohsen Dehghani, Maryam Ataollahi, seyyed Bozorgmehr Hedayati, Fateme Parooie, Iraj Shahramian

Gastroenterology and Hepatology from Bed to Bench, Vol. 14 No. 4 (2021), 23 Shahrivar 2021,

Introduction: Liver stiffness (LS) assessment using fibro-scanning (transient elastography-TE) is a non-invasive method for the evaluation of liver fibrosis. The aim of this study was to determine allograft fibrosis by measuring LS using TE in children after liver transplantation at Shiraz Organ Transplant Center.

Methods: All children undergoing liver transplant from 2012 to 2016 were included in the study. Demographic data, graft type, immunosuppressive drugs, as well as clinical and paraclinical data were obtained from patients’ records. TE was performed to determine LS in all patients. Liver fibrosis was also confirmed based on Metavir score.

Results: During this period more than 400 liver Tx were done in children but just 54 were available and willing to this study .54 patients including 20 (37%) girls and 34 (63%) boys who underwent liver transplantation were studied. The mean age of the patients was 12.96 ±5.32 years. Correlations between FS score (LS) and AST (P = 0.01), total bilirubin (P = 0.002), albumin (P = 0.001), PT (P = 0.03), and INR (P = 0.001) were significant. There was no significant relationship between FS score (LS) and type of allograft (P = 0.79) and underlying disease (P = 0.36). Positive and significant correlations were observed between Metavir score and AST (P = 0.01), total bilirubin (P = 0.01), INR (P = 0.004) and cholesterol (P = 0.001). The severity of fibrosis significantly and negatively correlated with albumin (P = 0.004) and glucose (P = 0.003). Also, there was no significant relationship between Metavir score and allograft type (P = 0.7).

Conclusion: Our study demonstrated that 14.9% of LT patients had a METAVIR ≥ F2. The time between LT and TE was significantly correlated with LS, and the degree of liver fibrosis based on Metavir score. However, there was no significant relationship between LS with allograft type as well as underlying liver disease

Introducing physical exercise as a potential strategy in liver cancer prevention and development

Mona Zamanian, Sakineh khatoon Hajisayah, Mohammadreza Razzaghi, Mostafa Rezaei Tavirani

Gastroenterology and Hepatology from Bed to Bench, Vol. 14 No. 4 (2021), 23 Shahrivar 2021,

Background. There are many evidences about benefits of physical activity which are mostly related to the metabolism regulation and body health. Deeper investigation deals with other features of physical activity such as anticancer property.

Aim. In this study, anticancer property of physical activity investigates via network analysis in the trained rats.

Methods. To investigate proteome profile of rats’ liver subjected to physical activity via bioinformatics, protein-protein interaction network analysis was applied. For this reason, a number of 12 differentially expressed proteins were searched and analyzed by Cytoscape 3.7.2 and its plug-ins. The network was analyzed to identify hub-bottleneck nodes. The action map was constructed for the central proteins.

Results. The findings indicate that among the queried proteins, Eno1 and Pgm1 were only assigned as hubs by Network Analzyer.  Gpi, Pkm, Aldoa, and Aldoart2 also were identified ad central nodes among the first neighbors of network elements. Furthermore, glycolytic process, carbohydrate catabolic process, and glucose metabolic process are the enrichment of key elements that could be imperative in the mechanism of exercise in liver function. Anticancer property of the central nodes was highlighted.

Conclusion. Our network findings point out the anticancer properties of physical activity, which was also supported by the previous investigations.   

Background: Modulation of the acetylation status of histones, histones modification, plays an important role in regulating gene transcription and expression. Histone deacetylation controlled by histone deacetylases (HDACs) leads to gene downregulation. Histone deacetylase inhibitors (HDACIs) are an emerging class of therapeutics with potential anticancer effects. They can induce apoptosis through the activation of both extrinsic and intrinsic apoptotic pathways. The current study was assigned to investigate the effect of trichostatin A (TSA) on mitochondrial/intrinsic [pro- (Bax, Bak, and Bim) and anti- (Bcl-2, Bcl-xL, and Mcl-1) apoptotic genes] and cytoplasmic/extrinsic (DR4, DR5, FAS, FAS-L, and TRAIL genes) pathways, histone deacetylase 1, 2, and 3, p53, p73, cell viability, and apoptosis in hepatocellular carcinoma (HCC) HCCLM3, MHCC97H, and MHCC97L cell lines. Methods: The HCCLM3, MHCC97H, and MHCC97L cells were cultured and treated with TSA. To determine viability, apoptosis, and the relative expression level of the mentioned genes, MTT assay, cell apoptosis assay, and qRT-PCR were done respectively. Results: TSA up-regulated the Bax, Bak, Bim, DR4, DR5, FAS, FAS-L, TRAIL, p53, and p73 and down-regulated Bcl-2, Bcl-xL, Mcl-1, histone deacetylases 1, 2, and 3 significantly resulting in apoptosis induction. Maximal and minimal apoptosis was seen in MHCC97H and HCCLM3 cell line (93.94 and 39.68 %) respectively after 24 and 48 h. Therefore, the MHCC97H cell line was more sensitive to TSA. Conclusion: Our findings demonstrated that HDAC inhibitor TSA can induce apoptosis and inhibit cell growth through both mitochondrial/intrinsic and cytoplasmic/extrinsic apoptotic pathways in hepatocellular carcinoma HCCLM3, MHCC97H, and MHCC97L cell lines.

Side effects of Omeprazole: a System Biology study

Maryam Hamzeloo-Moghadam, Mostafa Rezaei –Tavirani, Somayeh Jahani-Sherafat, Sina Rezaei Tavirani, Somayeh Esmaeili, Mojtaba Ansari, Alireza Ahmadzadeh

Gastroenterology and Hepatology from Bed to Bench, Vol. 14 No. 4 (2021), 23 Shahrivar 2021,

Background: Omeprazole as a proton pump inhibitor has a widespread consumption to inhibit gastric acid secretion. Assessment of omeprazole effects on human cardiovascular system is the main aim of this study.

Methods: Gene expression profiles of “human coronary artery endothelial cells” in the absence and presence of omeprazole is downloaded from gene expression omnibus (GEO). The differentially expressed genes (DEGs) are interacted as an interactome and the hub nodes are determined. The DEGs are enriched via gene ontology (GO) analysis. The critical hubs are identified based on GO finding.

Results: Among 103 queried DEGs 61 individuals were included in the main connected component. CTNNB1, HNRNPA1, SRSF4, TRA2A, SFPQ, and RBM5 genes are identified as critical hub genes. Six clusters of biological terms were introduced as deregulated elements in the presence of omeprazole.

Conclusion: In conclusion, long time consumption of omeprazole may be accompanied with undesirable effects, however more evidences are required.

Introduction/Aim  : 

Helicobacter pylorus is a widespread infection in India. Resistance to commonly used antibiotics against Helicobacter pylori increases rapidly, leading to traditional triple therapy's lower success. So, a search for a new regimen is needed.

In this study, we compared the efficacy of  14-day triple therapy with a novel ten-day LOAD regimen to eradicate Helicobacter pylori infection in India .


 In this randomized trial, patients with Helicobacter pylori infection were randomized to LOAD therapy (levofloxacin 250 mg OD, omeprazole 40 mg BD,  nitazoxanide 500mg BD, and doxycycline  100 mg OD) for ten days and standard triple therapy ( pantoprazole 80 mg, amoxicillin 2000 mg, and clarithromycin 1000 mg daily in divided doses for 14 days ). Gastric biopsy/RUT  was done 10–12 weeks after completing therapy to confirm Helicobacter pylori eradication.

Result :

The eradication rates with LOAD regimen  were significantly greater than with standard triple therapy on both intention-to-treat analysis (82.75 % vs. 60.26 %, p = 0.001; difference, 22.49 % [95 % CI, 8.5-18 %] and per-protocol analysis (83.3 % vs. 62.75 %, p = 0.002; difference, 20.55 % [95 % CI, 7.1-22.5 %]). Both the treatment regimens were well tolerated.

Conclusion :

Although the rate of eradication of H. pylori infection with the LOAD regimen was significantly higher than that with triple therapy, the efficacy was still suboptimal. It may be due to fluoroquinolone resistance or a short course of treatment.

Candida colonization of the esophagus and gastric mucosa; a comparison of patients taking proton pump inhibitors and those taking histamine receptor antagonist drugs

Batoul Mottaghi, Mohammad Hassan Emami, Padideh Riahi, Alireza Fahim, Hojjatolah Rahimi, Rasoul Mohammadi

Gastroenterology and Hepatology from Bed to Bench, Vol. 14 No. 4 (2021), 23 Shahrivar 2021,

Aim: Investigation of Candida colonization of the esophagus and gastric mucosa in patients taking proton pump inhibitors in comparison to those taking histamine-2 receptor antagonists.

Background: Candida species are normal flora of alimentary tract can cause infection of the esophagus and gastro-intestinal tract in immunocompromised patients. Consumption of proton pump inhibitors, and histamine-2 receptor antagonists have shown to alter the gastric pH which may predispose to floral transmission and colonization of the esophagus and stomach.

Patients and methods: Two hundred and forty-five clinical specimens were obtained from 91 patients underwent endoscopy from September 2019 to February 2020. Direct microscopy with KOH 10% and subculture on sabouraud dextrose agar containing chloramphenicol used as primary screening. PCR with ITS primers was performed to amplify ITS1-5.8SrDNA-ITS2 region and MspI restriction enzyme used for RFLP to identify clinical isolates.

Results: Seventy cultures out of 245 specimens were positive for Candida colonization (28.5%). Colonization of Candida species in gastric acid and gastric tissue biopsies of patients who took PPIs and H2 blockers was significantly higher than those were in control group (p = 0.001). The use of ranitidine, pantoprazole and omeprazole increased the risk of gastric candidiasis by 10.60, 9.20, and 12.99 times, respectively (p < 0.05).

Conclusion: The use of PPIs and H2 blockers, ageing, and consumption of vegetables were main risk factors for gastric infection in the present survey, and some other variables such as Candida species, cigarette smoking, drinking alcohol, etc. were not implicated in the development of gastroesophageal lesions. We need further investigations to know how these predisposing factors change the host defenses mechanisms and increase colonization of fungi at mucosal surfaces.

Brief Report

Melatonin effect on platelet count in patients with liver disease

Ayda Esmaeili, Mohssen Nassiri Toosi, Mohammad Taher, jaleh bayani, Soha Namazi

Gastroenterology and Hepatology from Bed to Bench, Vol. 14 No. 4 (2021), 23 Shahrivar 2021,


Thrombocytopenia occurs by exacerbating severity of liver disease. Reduction in the secretion of thrombopoetin, as an intrinsic hormone mainly produced by liver, plays an important role in this complication induced by liver disease. A positive effect of melatonin on platelet count in the patients with chronic liver disease was reported in the current study.



 Design of this study was a double-blind, cross-over, placebo-controlled pilot study. The patients with liver disease were given two 5 mg pearls of melatonin or placebo for two weeks and after 2 weeks wash out period, we switched their groups. The liver function test and platelets count were assessed once at the beginning and once at the end of each phase of the study.


In the current study, 40 patients with eligible criteria were included. The average platelet count has significantly increased by melatonin in comparison with placebo (from 175.67±92.84 to 191.10±98.82 vs from 185.22±98.39 to 176.45±91.45) (p-value <0.001). Also, melatonin significantly reduced ALT, AST, total bilirubin, and direct and MELD scores in the patients with liver disease (p-value<0.05).


Melatonin may increase platelet count and inhibit thrombocytopenia in the patients with liver disease; however, more investigations are needed to confirm the obtained result.

Case Report

Delayed dysphagia following foreign body swallowing: case report

Gholam Reza Mohajeri, Hamid Talebzadeh

Gastroenterology and Hepatology from Bed to Bench, Vol. 14 No. 4 (2021), 23 Shahrivar 2021,


The prevalence of foreign body swallowing is high in both children and adults. Different types of objects can be ingested. In older individuals denture ingestion is common. They may be left in the esophagus after being swallowed and then repelled.

  Materials and methods

  We present a case of a 62-year-old man who attended clinic due to dysphagia lasting for 5 years with an endoscopy report of a foreign body in his esophagus.  


There are a few reports of the presence of these objects in the esophagus for a long time.


Chronic remaining foreign bodies may be associated with complications, so extraction of the foreign body, especially in elderly, should be made promptly following diagnosis.

Case Series

Non-celiac gluten sensitivity as a rare cause of growth retardation in children: a case series study

Hedyeh Saneifard, Ali Sheikhy, Fereshteh Karbasian, Golnaz Eslamian, Marjan Shakiba, Delara Babaie

Gastroenterology and Hepatology from Bed to Bench, Vol. 14 No. 4 (2021), 23 Shahrivar 2021,

Background: non-celiac gluten sensitivity (NCGS) is a condition characterized by gastrointestinal and extra-intestinal symptoms which triggered by ingestion of Gluten contained compounds i.e., wheat, rye, and barley, in subjects without celiac disease or wheat allergy.

Case presentation: hereby we present five children and adolescents with final diagnosis of NCGS. All patients had failure to thrive and abdominal pain. Following gluten free diet, clinical symptoms reduced and we detected significant weight and height gain after 1 month of diet.

Conclusion: relationship between failure to thrive and NCGS is still unknown, hence according to mentioned cases, NCGS may be one of the main causes of FTT, which can be prevented by gluten free diets.

Photo Quiz

An uncommon cause of intermittent dysphagia

Saeed Abdi, Mehran Mahdavi Roshan, Naghmeh Salarieh

Gastroenterology and Hepatology from Bed to Bench, Vol. 14 No. 4 (2021), 23 Shahrivar 2021,

A 42 year old woman admitted to the gastrointestinal department of Taleghani hospital; a teaching referral hospital in Tehran; Iran with epigastric pain; fever and dysphagia. She complained of intermittent dysphagia; regurgitation and epigastric pain( without any benefit from PPI treatment)  one month in each year from five years before admission.