فهرست مطالب

  • Volume:12 Issue:4, 2019
  • تاریخ انتشار: 1398/09/16
  • تعداد عناوین: 24
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  • Mohammad Rostami Nejad, Mostafa Rezaei Tavirani, Vahid Mansoori, Saeed Abdi, Zahra Akbari Pages 1-7

    Gastric cancer is one of the epidemics diseases with a high mortality rate in different countries. It causes many health problems in the world every year. It affects the digestive tract, and in advanced cases, its treatment has many difficulties. Early detection of cancer in different parts of the gastrointestinal tract can be accompanied by inexpensive treatment. As cancer cells make different biomarkers during different stages of the disease, researchers are looking for different biomarkers for gastrointestinal cancers detection. On the other hand, with the advent of advanced techniques such as proteomics and the discovery of a large number of proteins related to gastrointestinal cancer, finding the role of these proteins is essential. Indeed, the function of large amounts of these proteins has remained unknown.Data from databases such as genes and proteins associated with gastrointestinal cancers were collected and the proteomic data of these databases were analyzed to find a clear perspective of the impact of proteomics in gastric cancer management.The role of heat shock proteins, metabolic proteins, membrane binding proteins, galectins, prohibitins, S100 proteins, and many different types of proteins in gastric cancer was highlighted. This article reviewed proteomic researches in cancer-related areas of the gastric cancer in order to evaluate the findings of researchers.Keywords: Gastric cancer, Biomarker, Proteomic.(Please cite as: Rostami-Nejad M, Rezaei-Tavirani M, Mansouri V, Akbari Z, Abdi S. Impact of proteomics investigations on gastric cancer treatment and diagnosis. Gastroenterol Hepatol Bed Bench 2019;12(Suppl. 1):S1-S7).

    Keywords: Gastric cancer, Biomarker, Proteomic
  • Sama Rezasoltani*, Amir Sadeghi, Ebrahim Radinnia, Ali Naseh, Zahra Gholamrezaei, Mehdi Azizmohammad Looha, Abbas Yadegar Pages 8-13

    Gut microbiota play critical roles in maintaining the human health in several aspects. Bile acids (BAs) are endogenous cholesterol-derived molecules that can be modified by the gut microbiota and act as signaling molecules in the regulation of host metabolic and physiology processes. Gut microbiota release many enzymes that are capable to perform considerable modifications on BAs such as bile salt hydrolases (BSH), 7?-dehydroxylase (CYP7A), and hydroxysteroid dehydrogenase (HSDH). These enzymatic roles can change in the gut microbiota composition, cause alteration in BAs profile and metabolism and even gallstone formation. Patients with 15 years of asymptomatic gallstone have increased risk for colorectal cancer (CRC), which may be related to altered gut microbiota, changes in bile metabolism, as well as cellular and molecular effects in the proximal colon. In gallstone-associated CRC patients, the association between consensus molecular subtypes of CRC should be clarified to identify if specific pathways are related.Keywords: Gut microbiota, Cholesterol gallstones, Colorectal cancer.(Please cite as: Rezasoltani S, Sadeghi A, Radinnia E, NasehA, Gholamrezaei Z, Looha A, et al. The association between gut microbiota, cholesterol gallstones and colorectal cancer. Gastroenterol Hepatol Bed Bench 2019;12(Suppl.1):S8-S13).

    Keywords: Gut microbiota, Cholesterol gallstones, Colorectal cancer
  • Nesa Kazemifard*, Amir Sadeghi, Behnaz Varaminian, Hamid Rezvani, Ahmad Ayadi, Ramin Talaie, Arfa Moshiri Pages 14-21

    Colorectal cancer is the third most common cancer worldwide. New cancer treatment strategies such as monoclonal antibodies against growth factor and angiogenesis receptors improved the overall survival (OS) and progression-free survival (PFS) in metastatic colorectal cancer (mCRC) patients. However, acquired resistance could happen after these therapies. Circulating tumor DNA (ctDNA) is the DNA fraction derived from tumor cells and could be applied as a non-invasive method for detecting tumor mutations before, during, and after therapies. Here, we reviewed most of the studies on the application of ctDNA as treatment monitoring in mCRC patients who receive different target therapies. Also, we compared ctDNA with other existing cancer-treatment monitoring methods.

    Keywords: Circulating tumor DNA, Colorectal cancer, Treatment monitoring
  • Reza Ranjbar, Somayeh Mohammadpour, Amir Torshizi Esfahani*, Sina Namazian, Mohammad Yaghob, Taleghani, Kaveh Baghaei, Seyed Abdolreza Mortazavi Tabatabaei, Leila Pasharavesh, Ehsan Nazemalhosseini Mojarad Pages 22-29
    Aim

    This study aimed to evaluate the distribution of PIK3CA E545K mutation in Iranian CRC patients and explored its roles in disease prognosis.

    Background

    Deregulation of the phosphoinositide 3-kinase (PI3K) pathway contributes to the progression of tumors. The p110a (PIK3CA), a catalytic subunit of PIK3, is mutated in many types of cancers. Exon 9 (E545K) is the most frequently mutated hotspot in PIK3CA in colorectal cancer (CRC). However, the prognostic role of PIK3CA E545K mutation needs to be elucidated.

    Methods

    Tumors from 187 CRC patients were retrospectively collected from the Taleghani and Shohada Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran, between 2010 and 2017. PIK3CA E545K status was detected in Formalin-fixed paraffin-embedded (FFPE) tissues using PCR-RFLP methods, and validated by pyrosequencing. Correlations between PIK3CA E545K mutation clinicopathological features were analyzed.

    Results

    The frequency of PIK3CA E545K gene mutations in CRC patients was 10.7%. Significant correlations were observed in PIK3CA E545K mutation with tumor differentiation and TNM stage (p < 0.042 and p = 0.033, respectively). Kaplan–Meier analysis showed a worse prognosis in overall survival (OS) in patients with PIK3CA E545K mutation (p < 0.001). Multivariate analysis indicated that PIK3CA E545K mutation was a detrimental factor for OS (HR = 6.497, 95% CI: 2.859-14.768, p < 0.021).

    Conclusion

    A high frequency of PIK3CA E545K mutation was detected in Iranian CRC patients. The results of the present study suggested that PIK3CA E545K mutation may be associated with poor prognosis. These findings require further confirmation via prospective studies with larger samples.Keywords: PIK3CA, Mutation, Prognosis, Colorectal cancer.(Please cite as: Ranjbar R, Mohammadpour S, Torshizi Esfahani A, Namazian S, Yaghob-Taleghani M, Baghaei K, et al. Prevalence and prognostic role of PIK3CA E545K mutation in Iranian colorectal cancer patients. Gastroenterol Hepatol Bed Bench 2019;12(Suppl.1):22-29).

    Keywords: PIK3CA, Mutation, Prognosis, Colorectal cancer
  • Somayeh Mohammadpour, Amir Torshizi Esfahani, Raana Karimpour, Farbod Bakhshian, Seyed Abdolreza Mortazavi Tabatabaei, Asma Laleh, Ehsan Nazemalhosseini Mojarad Pages 30-36
    Aim

    This study aimed to determine the link between Snail1 expression and CRC patients’ survival as well as its significant association with EMAST status.

    Background

    Snail1 is an evolutionary preserved zinc-finger transcription protein which contributes to Epithelial-to-mesenchymal transition (EMT). EMT initiates invasion and proliferation in many tumors. Elevated microsatellite alteration at selected tetranucleotide repeats (EMAST) is a marker of poor prognosis in patients with colorectal cancer (CRC). We hypothesized that Snail1 overexpression is an important mediator of metastasis and decreased survival in CRCs that characteristically have EMAST phenotype.

    Methods

    Quantitative real-time polymerase chain reactions were carried out to analyze the expression levels of Snail1 in both normal and tumor specimens from a total of 122 paraffin-embedded tissues (FFPE) of CRC sample with known EMAST status. The correlation between Snail1 expression and clinicopathological characteristics, survival, and EMAST status were examined.

    Results

    Snail1 overexpression was detected in tumor tissues in 32% of all examined patients and its positive expression was related to metastasis (p=0.001) and EMAST+ phenotype (P=0.017). Further, positive Snail1 expression correlates with poor overall survival in CRC patients (P=0.01).

    Conclusion

    Our findings suggest that Snail1 overexpression is not only associated with EMAST but also with clinicopathological variables of poor prognosis. These results indicate that Snail1 expression levels may be useful for establishing novel therapeutic strategies and could help survival improvement in CRC patients.Keywords: Snail1, Elevated microsatellite alteration at selected tetranucleotide repeats (EMAST), Survival, Colorectal cancer.(Please cite as: Mohammadpour S, Torshizi Esfahani A, KarimpourR, BakhshianF, Mortazavi TabatabaeiSA, LalehA, et al. High expression of Snail1 is associated with EMAST and poor prognosis in CRC patients. Gastroenterol Hepatol Bed Bench 2019;12(Suppl.1):S30-S36).

    Keywords: Snail1, Elevated microsatellite alteration at selected tetranucleotide repeats (EMAST), Survival, Colorectal cancer
  • Farzaneh Amanpour, Setareh Akbari, Mehdi Azizmohammad Looha, Mohammad Abdehagh, Mohammad Amin Pourhoseingholi Pages 37-43
    Aim

    We used mixture cure mode to separately investigate the risk factors for long-term and short-term survival of colorectal cancer patients.

    Background

    Colorectal cancer (CRC) is the second most common cancer worldwide. In cancer studies, patients’ survival is the most important indicator of patients’ status. Classical methods in analyzing the survival data usually apply Cox proportional hazard regression.

    Methods

    The study was performed on 1121 patients diagnosed with colorectal cancer. Mixture cure model with Weibull distribution and logit link function was fitted to data.

    Results

    Odds of long-term survival for rectum cancer patients were lower than for colon cancer patients (OR=0.29(0.09, 0.9)). Also, patients with the advanced stage of the disease had lower odds of long-term survival compared to early-stage patients (OR=0.24(0.06, 0.86)).In the short-term, the hazard of death for people with normal BMI was lower than the underweight group (HR=0.4(0.21, 0.76)). The short-term hazard of death for rectum cancer was about half of the short-term hazard for colon cancer (HR=0.49(0.29, 0.81)). Further, people with moderately (HR=2.11(1.26, 3.55)) and poorly (HR=4.04(2.03, 8.03)) differentiated tumor grade had a higher short-term hazard of death compared to people with well-differentiated grade.

    Conclusion

    Predictive variables of colorectal cancer survival showed different effects in short- and long -terms. Site topography was a prognosis for both long-term and short-term survival; BMI and tumor grade were short-term predictors of survival while stage was a long-term predictor of survival.Keywords: Mixture cure model, Colorectal cancer, Survival.(Please cite as: Amanpour F, Akbari S, Azizmohammad Looha M, Abdehagh M, Pourhoseingholi MA. Mixture cure model for estimating short-term and long-term colorectal cancer survival. Gastroenterol Hepatol Bed Bench 2019;12(Suppl.1):S37-S43).

    Keywords: Mixture cure model, Colorectal cancer, Survival
  • Mohsen Norouzinia, Mona Zamanian Azodi, Diba Najafgholizadeh Seyfi, Ali Kardan, Ali Naseh, Zahra Akbari Pages 44-50
    Aim

    The main goal of this investigation was to provide an overview on H.pylori effect on gastric tissue via bioinformatics analysis of microarray-identified miRNAs and its target genes.

    Background

    MicroRNAs which control about 30 to 60% of gene expression in human body play a critical role in different cell growth stages. Expression modification of non-coding (NC) RNAs in H.pylori infections requires further investigations to provide better understanding of their roles in the body.

    Methods

    GSE54397, the microRNA microarray dataset, was analyzed by GEO2R, the online GEO database for detection of differentially expressed microRNAs and lastly the potential target genes as well as their associated pathways.

    Results

    A total of 244 miRNAs were detected as differentially expressed (p<0.05 and FC>2) in non-cancerous tissue of gastric with H.pylori infection in comparison with tissues without H.pylori infection. The findings indicated that hub microRNAs and target genes of up-regulated network are KIF9, DCTN3, and CA5BP1 along with hsa-miR-519d, hsa-miR-573, hsa-miR-646, hsa-miR-92a-1, hsa-miR-186, and hsa-miR-892a, respectively. For the down-regulated network, genes of RABGAP1, HSPB11 and microRNAs of hsa-miR-620, hsa-miR-19b-2, hsa-miR-555, and hsa-let-7f-2 were hubs. Most of the up-regulated microRNAs are involved in gastric cancer development while there is no evidence for the down-regulated ones. Yet, all of the hub down-regulated miRNAs are reported to have associations with different kinds of cancer.

    Conclusion

    The introduced hub miRNAs and genes may serve as feasible markers in the mechanisms of H.pylori infection for different kinds of gastric diseases, in particular gastric cancer. However, their role requires further investigations.Keywords: MicroRNA, Helicobacter pylori, Regulatory network, Target genes, Hubs, Functional analysis.(Please cite as: Norouzinia M, Zamanian Azodi M, Najafgholizadeh Seyfi D, Kardan A, Naseh A, Akbari Z. Comparison of Predication of hub target genes of differentially expressed microRNAs contributing in Helicobacter pylori infection in gastric non-cancerous tissue. Gastroenterol Hepatol Bed Bench 2019;12(Suppl.1):S44-S50).

    Keywords: MicroRNA, Helicobacter pylori, Regulatory network, Target genes, Hubs, Functional analysis
  • Parisa Azizi, Sogol Mazhari, Samaneh Tokhanbigli, Fatemeh Naderi Noukabadi, Elahe Daskar Abkenar, Esmaeil Shamsafzali, Kaveh Baghaei Pages 51-57
    Aim

    Given the high similarity of phenotypical and secretory properties of mesenchymal stem cells and fibroblasts, this study investigated the possibility of inducing EMT process by mesenchymal stem cells.

    Background

    Annually, more than 13% of deaths worldwide occur due to cancer. One of the main reasons for the high mortality rate is due to the metastasis of cancer stem cells. Induction of metastasis occurs during the EMT process, which can also be stimulated by fibroblast cells.

    Methods

    Mesenchymal stem cells (MSCs) were isolated and sub-cultured until passage 3 or 4. AGS cells were co-cultured with MSCs for 4 days. As the positive control group, AGS cells were treated with TGF-? (10ng/ml) for 48h. Finally, the mRNA expression level of Vimentin, ?-catenin, Snail, and E-cadherin as the EMT pattern, were evaluated by RT-PCR technique.

    Results

    Our findings indicated that AGS cells’ crosstalk with MSCs significantly upregulated fibroblast markers including Vimentin and Snail expression. However, no significant changes were identified for ?-catenin gene expression. Additionally, AGS treatment with MSCs resulted in diminished E-cadherin in the targeted cells.

    Conclusion

    Based on the results, the AGS cells crosstalk with MSCs activates induction of epithelial mesenchymal transition, which is confirmed through the elevation of Vimentin and Snail expression and reduction of E-cadherin expression as a specific epithelial marker. However, it seems that MSc was not effective on Wnt/ ?-catenin signal gastric cancer cell line.Keywords: Gastric Cancer, Epithelial mesenchymal transition, Mesenchymal stem cells.(Please cite as: Azizi P, Mazhari S, Tokhanbigli S, Naderi NoukabadiF, Daskar AbkenarE, Shamsafzali E, et al. Paracrine signals of mesenchymal stem cells induce epithelial to mesenchymal transition in gastric cancer cells. Gastroenterol Hepatol Bed Bench 2019;12(Suppl.1):S51-S57).

    Keywords: Gastric Cancer, Epithelial mesenchymal transition, Mesenchymal stem cells
  • Vahid Chaleshi*, Shiva Irani, Masoud Alebouyeh, Reza Mirfakhraie, Hamid Asadzadeh Aghdaei Pages 58-65
    Background

    Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is one of the long non-coding RNAs that plays an important role in invasion, cell proliferation and metastasis of various cancers. However, insufficient information on the association of MALAT1 with the methylation process and its role in the development of colorectal cancer is not yet fully available. This study set out to determine the effect of methylation on MALAT1 gene in primary colorectal lesions and tumors to gain further knowledge about the diagnostic and prognostic value of MALAT1.

    Materials and methods

    Methylation Pattern of MALAT1 promoter determined by Methylation-Specific Polymerase Chain Reaction (MSP) in 86 colorectal primary lesions, tumors and normal specimens. MALAT1 methylation pattern was compared in tumor and polyp tissue. In order to obtain more accurate results, we investigated the association of MALAT1 promoter methylation pattern with clinicopathologic factors in patients.

    Results

    The results indicated that the MALAT1 promoter methylation pattern in tumor tissue, primary lesions tissue and normal was not significant difference (p=0.430). Moreover, compared, the MALAT1 promoter methylation pattern between polyp types and tumor tissue groups was not significant (p=0.437). Surprisingly, the methylation frequency of MALAT1 methylation was significantly higher in colon lesions in comparison with their rectum lesion, p = 0.035. In addition, significant hypermethylation of MALAT1 was not observed between the other patients’ clinicopathological data at both polyps 46/66 and tumor tissue 20/66.

    Conclusion

    This study suggests that the MALAT1 promoter methylation pattern in patients with colorectal primary lesions and tumors compared with normal tissue as not a significant risk factor for colorectal cancer. Moreover, clearance the significantly higher methylation frequency in colon lesions in comparison with their rectum lesion need to be further explored.

    Keywords: long non-coding RNAs, colorectal cancer, colonic polyps, metastasis-associated lung adenocarcinoma transcript 1, MALAT1, DNA Methylation
  • Mohammad Reza Zali, Mona Zamanian Azodi, Zahra Razzaghi, Mohammad Hossain Heydari Pages 66-73
    Aim

    Identifying the critical genes in that differentiate gall bladder cancer from the normal gall bladder and the related biological terms are the aim of this study.

    Background

    Molecular mechanism underlying gall bladder cancer (GBC) trigger and developments still requires investigations. Potential therapeutic biomarkers can be identified through protein-protein interaction network prediction of proteome as a complementary study.

    Methods

     Here, a literature review of proteomics studies of Gall bladder cancer from 2010 to 2019 was handled to screen differentially expressed proteins in this cancer. A network of 27 differentially expressed proteins (DEPs) via Cytoscape 3.7.1 and its plug-ins was constructed and analyzed.

    Results

    Ten proteins were introduced as hub-bottlenecks that among them four were from DEPs. The gene ontology analysis also indicated that Positive regulation of multi-organism process and regulation of response to biotic stimulus are the most disrupted biological processes of GBC considering their relationships with the DEPs.

    Conclusion

    ACTG, ALB, GGH, and DYNC1H1 and relative biological terms were introduced as drug targets and possible diagnostic biomarker.

    Keywords: Gallbladder cancer, Protein-protein interaction network analysis, Hub-bottleneck proteins, Biological process
  • Somayeh Jahani Sherafat*, Masoumeh Azimirad, Hajieh Ghasemian Safaei, Hadi Ahmadi Amoli, Sharareh Moghim, Ghazal Sherkat, Esmaeil Shamsafzali, Mohammad Reza Zali Pages 74-79
    Aim

    The aim of this study was to evaluate the effect of intestinal microbiota metabolites in colorectal cancer patients on HT29 cell line using MTT assay.

    Background

    Colorectal cancer is one of the most common malignant tumors, Human guts harbor abundant microbes that adjust many aspects of host physiology.  Increasing studies show that gut microbiota plays a significant role in the incidence and expansion of CRC, as a result of virulence factors, bacterial metabolites, or inflammatory pathways.

    Materials and Methods

    In this cross sectional study, 60 biopsy samples including 30 cancerous and 30 adjacent healthy tissues were collected from patients with CRC during 2017. Biopsy samples first cultured on Thioglycollate broth medium for 24hr and then microbiota metabolites were filtered and stored at -20 C° for further evaluation. HT29 cells were treated by microbiota metabolites in different time (3, 6, 12, 18h) and its viability was assessed by MTT assay.

    Results

    Treated cells with microbiota metabolites showed increased viability and proliferation in time-dependent analysis by MTT assay but there was not any significant differences between two groups.

    Conclusion

    It seems that microbial metabolites are able to induce proliferation and increase cell viability and therefore induction of colorectal cancer.

    Keywords: Metabolites, Cell line, MTT, Colorectal cancer
  • Mahsa Ghorbaninejad*, Raheleh Heydari, Parvaneh Mohammadi, Shabnam Shahrokh, Mehrdad Haghazali, Binazir Khanabadi, Anna Meyfour Pages 80-86
    Aim

    The aim of this study was to determine gene expression levels of TNF-?, NOTCH1 and HES1 in patients with UC.

    Background

    Intestinal inflammation and epithelial injury are the leading actors of inflammatory bowel disease (IBD), causing an excessive pro-inflammatory cytokines expression such as TTNF-?. Also, target genes of NOTCH signaling are involved in the regulation of intestinal homeostasis. Previous studies demonstrated that TNF-? increases in ulcerative colitis (UC) patients but the relationship between TNF-? and NOTCH signaling pathway in UC etiopathology needs to further study.  

    Methods

     Twelve active UC patients and twelve healthy controls were enrolled into this study. RNA was extracted and the mRNA expression levels of TNF-?, NOTCH1 and HES1 were examined using real-time PCR analyses. Moreover, transcriptome data deposited in Gene Expression Omnibus (GEO) database were analyzed to detect the differential expression of TNF superfamily and NOTCH1gene in IBD patients. Finally, the interaction of TNF-? and NOTCH signaling was obtained from The SIGnaling Network Open Resource 2.0 (SIGNOR 2.0) database.

    Results

    The transcription level of TNF-?, NOTCH1 and HES1 genes were significantly increased in UC patients compared with control (p < 0.05). In addition, GEO results confirmed our expression results. SIGNOR analysis showed TNF-? interacts with NOTCH signaling components.

    Conclusion

    Based on our data, we showed that NOTCH1 and HES1 in co-operation of TNF-?, may play an important role in pathogenesis of UC. The members of NOTCH signaling pathway can be ideal candidates to target therapy of IBD.

    Keywords: Ulcerative colitis, TNF-?, NOTCH signaling, HES1
  • Hedieh Balaii, Meysam Olfatifar, Sepideh Olianasab Narab, Asghar Arab Hosseini, Ali Seyed Salehi, Shabnam Shahrokh Pages 87-93
    Aim

    We conducted this study to estimate the direct medical cost of the Iranian IBD patients.

    Background

    In the economic evaluation setting, descriptive epidemiological studies can provide substantial information for health system policymakers in taking accountable decisions for diseases such as Inflammatory Bowel Disease (IBD).

    Methods

    To do so, we used a self-designed checklist to collect demographic and medical cost information for IBD patients. We also tried to have a national estimation of IBD costs.

    Results

    The mean annual medical cost of IBD was 18354.52 PPP$. Crohn's disease (CD) vs. ulcerative colitis (UC) and UC township patients vs. Tehran residents patients had higher medical costs (31160.79 PPP$; P<0.001) and (20840.23 PPP$, P<0.025). The most spent medical cost in both IBD subtypes (CD/UC) was attributed to biological agents, especially in UC patients. We estimated that the mean annual cost of IBD in Iran for 2017 was 746315864 (602964172, 964685749) PPP$(constant incidence) and 862776811 (697055402, 1115222835) PPP$(increment incidence) respectively. If we assume the constant incidence from 2012 to 2017 the prevalence and subsequently mean annual cost of IBD in 2017 were 66.95 per 100000 and 746315864(602964172, 964685749) PPP$. The prevalence and mean annual cost of IBD for another scenario were 77.39 per 100000 and 862776811(697055402, 1115222835) PPP$ respectively. 

    Conclusion

    Our results suggest that to the management of IBD patient's policymakers should consider shifting the medical costs to biological agents, the higher cost of CD and the impact of underlying factors on the distribution of these medical costs.

    Keywords: Inflammatory bowel disease, Medical cost, Crohn's disease, Ulcerative colitis
  • Shaghayegh Baradaran Ghavami*, Fateme Kabiri, Mahyar Nourian, Hedieh Balaii, Shabnam Shahrokh, Vahid Chaleshi, Ghazal Sherkat, Farzaneh Shalileh, Hamid Asadzadeh Aghdaei Pages 94-100
    Aim

    In the present study, two main variants of ATG16L1 gene, rs2241880 T300A and rs2241879 C/T were evaluated in IBD patients and in remission and flare up phase between Iranian population for the first time.

    Background

    Inflammatory bowel disease (IBD) has increased a global incidence and prevalence in recently years the world and especially in pediatric. ATG16L1 is the major gene that regulates autophagy pathway. Autophagy pathway also effects on dybiosis.

    Materials and methods

    Genomic DNA was isolated from peripheral blood samples following salting out extraction method. The genotypes of ATG16L1 polymorphisms rs2241880 T300A and rs2241879 C/T were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

    Results

    In this case control study, a total of 101 IBD patients (75 ulcerative colitis [UC] and 26 Crohn’s disease [CD]) and 99 healthy controls were evaluated. In the present study, a significant association was found between rs2241879 single nucleotide polymorphism on ATG16L1 gene and increased risk of IBD between Iranian population (P=0.01). There was no statistically significant relationship between rs2241880 and IBD risk (P= 0.42). Also,the effect on these two variants was investigated in relapse and flare up phase and it was not significant, but in CD, rs2241879 and rs2241880 were a trend for a difference in relapse phase.

    Conclusion

    The results showed that ATG16L1 gene rs2241879 has significant relationship with increased risk of IBD between Iranian population. Individuals with C allele showed a significant relationship with 1.68-fold increased risk of IBD (P=0.01; adjusted OR=1.68; 95% CI=1.13-2.50).*Corresponding Author: Hamid Asadzadeh Aghdaei, Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Tel: +98-2122432525, Fax: +98-2122432514, E-mail: hamid.assadzadeh@gmail.com     Abstract

    Introduction

    Inflammatory bowel disease (IBD) is on the increase in the world and the number of pediatric cases is increasing.  ATG16L1 is the major gene that regulates autophagy pathway. Autophagy pathway also effects on gut microbiota. In the present study, two main variants of ATG16L1 gene, rs2241880 T300A and rs2241879 C/T were evaluated in IBD patients and in remission and flare up phase between Iranian population for the first time.

    Materials and methods

    Genomic DNA was isolated from peripheral blood samples following salting out extraction method. The genotypes of ATG16L1 polymorphisms rs2241880 T300A and rs2241879 C/T were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

    Results

    In this case control study, a total of 101 IBD (75 ulcerative colitis [UC] and 26 Crohn’s disease [CD]) and 99 healthy controls were evaluated. In the present study, a significant association was found between rs2241879 single nucleotide polymorphism on ATG16L1 gene and risk of IBD in Iranian population (P=0.01). There was no statistically significant relationship between rs2241880 and IBD risk (P= 0.42). The effect of these two variants was investigated in relapse and flare up phase and it was not significant, but in CD, rs2241879 and rs2241880 were a trend for a difference in relapse phase.

    Discussion

    The results showed that ATG16L1 gene rs2241879 has significant relationship with increased risk of IBD in Iranian diseases status. Individuals with C allele showed a significant relationship with 1.68-fold increased risk of IBD (P=0.01; adjusted OR=1.68; 95% CI=1.13-2.50). Key words: Autophagy, ATG16L1, inflammatory bowel disease (IBD), diseases status.

    Keywords: Autophagy, ATG16L1, inflammatory bowel disease (IBD), diseases status
  • Hadis Najafimehr*, Hosein Yadegari, Hamed Taherinejad, Khosrow Manhoie, Seyed Ramin Rasooli, Abbas Moradi, Mohammad Javad Akbariju, Hosein Mohseni, Sabah Ghadimi, Hamid Mohaghegh Shalmani Pages 101-107
    Aim

    The aim of present study is to evaluate the factor associated with functional constipation (FC) and determine a normal range of bowel movement (BM) in an Iranian Auto factory’s worker.  

    Background

    The digestive system may be affected by workplace condition.  Some occupational conditions can effect on bowel habit and FC.

    Materials and methods

    In this cross -sectional study, 3590 workers who worked in Tehran suburb in 2017 were evaluated. The workers were working at morning or rotatory shifts and in the official and non- official sections. In addition to demographic and stool frequency questions, workers were asked to complete the Rome IV Questionnaire.

    Results

    The normal range of BM frequency was determined between one and three per day. The BM frequency had a significant association with age (P=0.002), marital status (P=0.024), education (P=0.011), expose to chemical materials (P<0.001) and work section (P<0.001). The total prevalence of FC was 9.7% and among rotatory shift working, was more than the only morning shift working, (10% vs 6%; P=0.02). Independent factors associated with FC were found as age (for 30- 40 years old: OR=1.88; 95% CI (1.20, 3.03) and for ?41 years old: OR=1.91; 95% CI (1.12,3.17)), smoking (OR=1.52; 95% CI (1.20,1.93)) and work section (for Paint section: OR=0.33; 95% CI (0.12,0.87), for Montage section: OR=0.44; 95% CI (0.18,1.10), for Press & Platform section: OR=0.12; 95% CI (0.05,0.37)).

    Conclusions

    Occupational condition probably makes difference in bowel habit. Rotatory shift, official working and smoking may increase the risk of constipation.

    Keywords: Bowel movement, Constipation, Work shift, Auto factory
  • Ensieh Khalkhal*, Zahra Razaghi, Hakimeh Zali, Ayad Bahadorimonfared, Majid Iranshahi, Mohammad Rostami Nejad Pages 108-116
    Aim

    The aim of this study is to explore the expression of genes associated to celiac disease (CD) in the target tissue and peripheral blood monocytes (PBMC) or serum to introduce possible potential biomarkers.

    Background

    Celiac disease (CD) is an autoimmune disease induced by gluten ingestion in genetically predisposed individuals. Despite technological progress, small intestine biopsy still is gold standard to diagnosis of CD.

    Methods

    CD data were collected from public databases (proteomics and microarray-based techniques documents). Differentially expressed genes (DEGs) in PBMC or serum and small intestinal biopsies from celiac patients compared to normal were collected and analyzed to introduce common individuals. Gene ontology was done to identify the involved biological terms.

    Results

    Among 598 CD genes in biopsies and 260 genes in PBMC or serum, 32 common genes with similar expression pattern in the both of source were identified. Numbers of 48 biological terms were introducing which were involved in the CD via the determined DEGs. “Cytokine activity” was the most expanded one of the biological terms.

    Conclusion

    In this analysis it was concluded that 32 potential biomarkers of CD can be assessed by complementary research to introduce effective and available biomarkers in biopsy and blood.

    Keywords: Celiac disease, PBMs, gene expression, intestine biopsy
  • Maryam Naserinejad, Sadjad Shojaee, Mehdi Ghobakhlou, Sara Ashtari, Elena Lak, Pegah Eslami, Mohammad Amin Pourhoseingholi Pages 117-122
    Aim

    Present study aimed to evaluate association between serum levels of interleukin (IL)-1, IL-6, IL-8, IL-15 genes and interferon (IFN)-? and the risk of celiac disease (CD).

    Background

    The role of serum cytokine levels in the pathophysiology of CD is still an open field to be explored.

    Methods

    This case-control study was performed on 110 patients with CD and 46 healthy controls referred to Taleghani Hospital, Tehran, Iran. Expression levels of IL-1, IL-6, IL-8, IL-15 and IFN-? were assessed by enzyme-linked immunosorbent assay (ELISA) kits.

    Results

    The Bayesian intervention odds ratio (OR) and Highest Posterior Density (HPD) interval were 1.133 (95% credible interval 1.018- 1.269), 0.947 (95% credible interval 0.898 - 0.996) and 1.004 (95% credible interval 1.001- 1.009) for IL-1, IL-6, and IL-8 respectively.

    Conclusion

    Serum levels of IL-15 and IFN-? have no effect on the risk of CD and its symptoms, but given the OR and the HPD interval obtained for serum levels of IL-1, IL-6 and IL-8, one unit increase in IL-1 serum, the risk of CD 1.13 times more likely and one unit increase in IL-6 serum reduces risk of CD by 15% and about IL-8, the risk of CD increases 0.004 times with a unit increase in IL-8 serum.

    Keywords: Celiac disease, Cytokines, Bayesian Logistic regression model
  • Sina Rezaei Tavirani*, Mohammad Rostami Nejad, Reza Vafaee, Enseih Khalkhal, Aliasghar Keramatinia, Mohammad Javad Ehsani Ardakani, Mohammadreza Razzaghi Pages 123-129
    Aim

    This study was aimed to screen the common genes between celiac disease (CD) and type 1 diabetes mellitus to find critical ones.

    Background

    Celiac disease as a chronic autoimmune disorder that is correlated to type 1 diabetes mellitus (T1DM) in several molecular pathways. Achieve to the clear common molecular mechanism of the both diseases is attracted attention of scientists.

    Methods

    The related genes to the CD and T1DM were obtained from disease query of STRING and included in two separated PPI networks by Cytoscape software version 3.7.1. The networks were analyzed by network analyzer and the hub nodes were determined. The common hubs between the two networks were selected for more analysis and enriched via gene ontology by using ClueGO plugin of Cytoscape software and action map was provided by Cluepedia application of Cytoscape software.

    Results

    Two separated networks of 2000 and 430 genes related to T1DM and CD, respectively were constructed. Numbers of 84 and 28 hubs were determined for T1DM and CD, respectively. There are 11 common hubs between the two networks. The first top hubs of Type 1 Diabetes Mellitus and CD networks were insulin (INS) and tumor necrosis factor (TNF), respectively. Number of 77 biological terms and pathways (in five clusters) were related to the common hubs. Action map revealed near relationship between hubs.

    Conclusion

    The result of this study indicated that TNF is key mediator of immune reactions in celiac disease and type 1 diabetes mellitus.

    Keywords: Celiac disease, Type 1 Diabetes Mellitus, TNF, Insulin
  • Hamid Asadzadeh, Aghdaei, Mohammad, Mehdi Zadeh, Esmaeel, Somayeh Esmaeili, Mostafa Rezaei –Tavirani, Sina Rezaei –Tavirani, Vahid Mansouri, Fatemeh Montazer Pages 130-135
    AIM

    Evaluation of high fat medium (HFM) effect on gene expression profile human Sk-hep1 cells and determination of critical differential proteins are the aim of this study.

    Background

    There is correlation between high fat diet (HFD), obesity, and non-alcoholic fatty liver disease. Despite of wide range of investigations, molecular mechanism understanding of HFD of onset and progression of NAFLD implies more examination. In this study network analysis is applied to obtain a clear perspective about HFD effects and NAFLD. 

    Methods

    Gene expression profiles of human Sk-hep1 cells treated with HFM versus controls were extracted from GEO. Data was analyzed by GEO2R and the significant and characterized DEGs were included in the PPI network. Numbers of 10 top nodes of query DEGs based on four centrality parameters were selected to determine central nodes. The common hub nodes with at least other one central group were identified as central nodes. Action map was provided for the introduced central nodes.

    Results

    Heterogeneous nuclear ribonucleoprotein family including A1, A2/B1, D, R, and D-like, and five proteins (PRPF40A, SRSF1, PCF11, LSM8, and HSP90AA1) were introduced as differentially proteins.

    Conclusion

    mRNA processing and several biological terms including hypoxia and oxidative stress, apoptosis, regulation of cell morphology and cytoskeletal organization, and differentiation of micro tubes were introduced as dysregulated terms under HFM condition.

    Keywords: Liver, fat, network, gene
  • Sajad Shojaee*, Farid Zayeri, Maryam Nasserinejad, Ali Ghasemzadeh, Saeedeh Sadat Beheshti Shirazi, Mahsa Khodadoostan Pages 136-144
    Aim

    The aim of this research was to estimate the changing rate of odds ratio (OR) by varying degrees of hepatitis B virus (HBV) underreporting.

    Background

    Data registering is usually associated with much errors such as misclassification, under-reporting, missing data due to lack of co-operation, error prone factor, and also in medical studies due to inadequate diagnosis of physician or low accuracy of laboratory tests. In the present study, which discuss about the actual impact of vaccination on HBV prevention, exposure and response were prone to various errors. Furthermore, some people in the community possibly infected to virus while were not reported in the count of patients with HBV infected.

    Methods

    This was a Case control study. Cases include patients with HBV who were referred to the gastroenterology and liver disease research center. Control group include patients without HBV who were performed a fatty liver test at Taleghani hospital laboratory. Bayesian approach and Gibbs sampling algorithm were used to estimate OR.

    Results

    According to results, misclassification rate was mild in raw data but with an increase in degree of underreporting for 50 and 500 of unreported cases, OR increased about half and more than double, respectively, while sensitivity decreased strikingly.

    Conclusion

    Our analysis asserted that knowing the degree of underreporting is essential to accurately calculate OR and sensitivity. In addition, despite varying OR in the different samples, overall results were similar according to the pattern of exposure and response association.Key Words: Vaccination, Hepatitis B virus, Misclassification, Underreporting, Bayesian adjustment

    Keywords: Vaccination, Hepatitis B virus, Misclassification, Underreporting, Bayesian adjustment
  • Sara Ashtari*, Afsaneh Sharifian, Behzad Hatami, Seyed Reza Mohebbi, GholamReza Nouri, Monireh Bazdar, Nosratollah Naderi Pages 145-148
    Aims

    The aim of this study was to compare the different phases of chronic Hepatitis B virus (HBV) infection with different values for normal ALT. 

    Background

    For many years upper limit of 40 IU was considered normal for ALT for both sexes, but in recent years this value is challenged and some guidelines have lowered their limit. 

    Methods

    In this cross-sectional study, 2000 HBsAg positive patients who were referred to Taleghani Hospital, Tehran, Iran, from 2011 through 2018 were classified in four groups according to American Association of the study of the liver disease (AASLD), European Association of the study of the liver (EASL) /Asian-Pacific Association of the study of the liver (APASL) and American Collage of Gastroenterology (ACG) guidelines. Frequency of each group based on 3 different guidelines was compared.

    Results

    In HBeAg positive patients (n=100), percentage of immune tolerance phase was 43% according to AASLD cutoff for normal ALT (35 IU for men, 25 IU for women) while it was 68% and 28% with regard to EASL/APASL and ACG (30 IU for men, 19 IU for women) cutoffs respectively. In HBeAg negative patients (n=1900), 66.68% were inactive carriers according to AASLD but the percentage changed to 82.89% and 52.42% considering EASL/APASL and ACG values, respectively.

    Conclusion

    By using ACG and to a lesser extend AASLD cutoff for ALT, many patients shift from immune tolerance and inactive carrier state into immune active phase. Therefore more patients are candidates for treatment or intensive workup to determine extent of liver injury.

    Keywords: Chronic hepatitis B, ALT level, CHB phases, Iran
  • Afsaneh Sharifian*, Sara Ashtari, Behzad Hatami, Seyed Reza Mohebbi, Nosratollah Naderi Pages 149-155
    Aims

    To investigate routes of transmission, demographic characteristics and frequency of different phases of chronic hepatitis B (CHB) in 2000 Iranian patients.

    Background

    Knowledge about the most frequent risk factors of CHB and its different phases is very important for optimal prevention and management policy making.

    Methods

    In this cross-sectional study, 2000 HBsAg positive patients who were referred to Taleghani Hospital from 2011 through 2018 were enrolled. ELISA method was employed to detect serological markers of CHB. Taking into account the HBV DNA and ALT levels and HBeAg status, patients were classified in four groups, according to AASLD 2017 guideline.

    Results

    Male and female patients had nearly equal frequencies in our study and 82.5 % of them aged more than 20 years. A great number of our patients (95%) were HBeAg negative and the most frequent risk factors of HBV infection were positive periodontal and family history (40.3% and 24.9%, respectively). Majority of our patients were inactive carriers (63.35%) while minority of them were in immune tolerant group (2.15 %).

    Conclusion

    Immune tolerance phase group had lowest members in our study and most of them were above 20 years old.This can be due to the mass vaccination of neonates since 1993. Most of CHB patients were in inactive carrier group. Although it is recommended not to treat these patients, but performing periodic liver function tests and disease severity assesment is warranted, especially in patients above 40 years old.

    Keywords: Chronic hepatitis B, Risk factors, Natural history, Iran
  • Seyed Dawood Mousavi Nasab*, Abbas Ahmadi Vasmehjani, Homan Kaghazian, Rajab Mardani, Fatemeh Zali, Nayeb Ali Ahmadi, Mohsen Norouzinia, Mohammadreza Razzaghi Pages 156-162
    Aim

    The present study was designed to evaluate the correlation of interleukin 28B (IL28B, IFNL3) rs12979860 mRNA levels, viral load and liver function among hepatitis C virus (HCV) patients genotype 1a.

    Background

    HCV is considered essentially hepatotropic, and is a major health problem around the world.Patients and

    methods

    This study included 100 HCV-infected patients with HCV genotype1a (G1a) and rs12979860 CC genotype. These patients were divided into two groups according to HCV treatment. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and HCV Load were measured and recorded for each patient. IL28B mRNA levels were determined using real-time polymerase chain reaction assay, and their correlation with clinical data were analyzed. STRING applied to construct a network and identify interactions between IL28B (IFNL3) and its significant neighbor proteins.

    Results

    The results showed a significant relationship between the ALT and ALP levels with IL28B rs12979860 mRNA expression level in men, and also with aged >50 years. In the treated group, AST level and HCV load have a significant relationship with IL28B mRNA expression level. Results showed the level of ALP and AST decreased significantly with increased IL28B mRNA expression level in the treated and untreated group, respectively. STRING database showed that IL28B (IFNL3) interacted with ten important neighbor proteins and some of these proteins are involved in signal transduction pathway activating antiviral response.

    Conclusion

    This study indicates that rs12979860CC genotype could predict IL28B mRNA expression level in HCV-infected patients with G1a. Furthermore, IL28B mRNA expression level may serve as a useful marker for the development of G1a HCV-associated outcomes.Keywords: HCV patients, Interleukin 28B, IFNL3, mRNA levels, Liver enzyme.

    Keywords: HCV patients, Interleukin 28B, IFNL3, mRNA levels, Liver enzyme
  • Farahnaz Sadat Shayegan Mehr, Masoumeh Azimirad, Seyedeh Nazanin Mansouri Gilani, Ayub Ghafurian, Abbas Yadegar Page 163
    Aim

    To investigate the effect of sub-minimum inhibitory concentration (sub-MIC) of metronidazole, ciprofloxacin and imipenem on growth and toxin production in Clostridioides difficile.

    Background

    C. difficile is the most common causative agent of hospital-acquired diarrhea. Toxin production in C. difficile appears to be critical process for induction of the disease. Several factors such as antibiotics can facilitate growth and toxin production in in C. difficile.

    Methods

    Five C. difficile strains were grown with and without sub-MIC concentrations of metronidazole; ciprofloxacin; imipenem (0.5x MIC) and bacterial growth was measured by density at OD620 nm in 0, 4, 8, 12 and 24 h after inoculation. Toxin production was detected using ELISA in culture supernatants and also in cell pellet.

    Results

    The five strains showed minor growth variations in the presence and absence of antibiotic sub-MIC values, except for metronidazole, in which the sub-MIC concentration decreased the growth rate of the resistant isolate in comparison with the control without antibiotic. There were no significant variations was observed in the levels of toxin production with the sub-MIC values of antibiotics examined in comparison with antibiotic-free controls. However, the amount of toxin production in the culture supernatant was greater than cell pellet.

    Conclusion

    The findings of this study suggested that sub-MIC concentrations of antibiotics may have little effects on bacterial growth and toxin production of C. difficile. Taken together, these findings suggest that, presence of antimicrobial agents, increased expression levels of certain genes, particularly virulence genes, may help C. difficile to survive.

    Keywords: Clostridium difficile, Toxin production, Bacterial growth, Antibiotics