ISSN: 2008-2258

Systematic Review and Meta-Analysis


Prognostic value of microRNA-125a/b family in patients with gastric cancer: A meta-analysis

Nasrin Amiri-Dashatan, Mehdi Koushki, Mohsen Naghi –Zadeh, Mohammad Reza Razzaghi, Hamid Mohaghegh

Gastroenterology and Hepatology from Bed to Bench, , 30 December 2021
https://doi.org/10.22037/ghfbb.vi.2279

Background: miR-125 family (including miR-125a, miR-125b) have been reported as pivotal prognostic biomarkers of gastric cancer (GC). However, there is controversy about the role of miR-125 family in progression prediction of GC.


Aim: We design this meta-analysis to reassess the prognostic and clinicopathologic values of microRNA-125 family in GC patients.


Methods: Studies were systemically searched from electronic databases of PubMed, ISI Web of Science, Scopus and Cochrane library. The overall hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI) was calculated to evaluate the association between miR-125 family expression with prognosis and susceptibility to gastric cancer. The quality of evidence was evaluated using Newcastle-Ottava Scale (NOS).


Results: Totally 1203 GC patients in ten studies were analyzed in this meta-analysis. The results showed a high significant association between the ratio of low/high expression of miR-125a (HR= 1.7; 95% CI: 1.38 to 2.08; P< 0.001) and poor OS in patients with GC, while, this ratio for miR-125b (HR= 1.16; 95% CI: 0.71 to 1.89; P= 0.53) was not significant. Further, low miR-125 family expression was associated with clinicopathological features of liver metastasis (OR= 6.3; 95% CI: 1.1 to 36.3; P= 0.03). The sensitivity analysis shows that our results were completely powerful and stable. No potential publication bias was observed using Begg’s (P = 0.72) and Egger’s (P = 0.95) tests.


Conclusion: The low expression of miR-125 family predicts poor OS in GC patients. Thus, miR-125 family may be helpful as a potential biomarker for the prognosis of gastric cancer.

Review Article


Non-coding RNAs as novel circulating biomarkers of liver diseases; a narrative review

Fedra Mokhtary, Seyed Reza Mohebbi, Afsaneh Sharifian, Marzieh Ramandi, Mohammad Reza Razzaghi

Gastroenterology and Hepatology from Bed to Bench, , 30 December 2021
https://doi.org/10.22037/ghfbb.vi.2415

The liver plays a principal role in the human body as a metabolic and detoxifying unit. Liver diseases are the world’s major health problems and affect millions of people worldwide. Early detection of liver diseases is certainly effective in timely treatment and prevention of their progression. Liver injury is associated with significant alterations in immune responses and various tissues related genes expressions and cytokines production pattern changes. Increasing or decreasing the specific spectrum of non-coding RNAs in different phases of liver disease can be a criterion for diagnosis. Novel diagnostic biomarkers are needed for liver diseases. Currently, micro RNAs (miRNAs) are known to play important roles in the diagnosis of liver disease. Circulating biomarkers such as miRNAs-assisted diagnosis can be conceivably helpful for the early treatment of liver diseases. In this review, we looked at miRNAs and their potential applications in liver diseases as diagnostic biomarkers.

Gut microbiota, Angiotensin-converting enzyme, celiac disease and risk of COVID-19 infection; a review

Fahimeh Sadat Gholam-Mostafaei, Tina Didari, Marzieh Ramandi, Reza Vafaee, Mohammad Rostami Nejad

Gastroenterology and Hepatology from Bed to Bench, , 30 December 2021
https://doi.org/10.22037/ghfbb.vi.2487

Celiac disease (CD) is an autoimmune disorder of the gastrointestinal tract in a genetically susceptible person. However, gluten is the most crucial trigger factor for CD, environmental factors such as microbiota and opportunistic infection risk its pathogenesis.


Coronavirus disease 19 (COVID-19) spread rapidly and became one of the health care system problems worldwide. Moreover, there is little known about the risk of severe covid-19 and the role of dysbiosis among patients with CD. There is a lack of knowledge in CD gut microbiota effects on COVID 19 infection. Therefore, in the current review we discussed the relationship between CD and risk factors such as microbiota for susceptibility to COVID19.

Original Article


SMAD4 mutations identified in Iranian patients with colorectal cancer and polyp.

Rouhallah Najjarsadeghi, Nastaran saeedi , Negar sahba, Amir Sadeghi

Gastroenterology and Hepatology from Bed to Bench, , 30 December 2021
https://doi.org/10.22037/ghfbb.vi.1925

Background: Colorectal cancer is one of the five prevalent cancers among the Iranian population. However, its molecular mechanisms is not fully understood, while the vast majority of CRCs arise from neoplastic polyp. Methods: Colorectal cancer and polyp lesions with matched normal tissues from patients who had undergone colonoscopy in Taleghani Hospital (January 2009 – November 2010) were included in the study. DNA extraction and PCR-sequencing for exons 5-11 of the SMAD-4 gene was carried out on 39 and 30 specimens of polyp and adenocarcinoma.


Results: 33.3% of cancer and 28.2% of polyp specimens were mutated for Smad-4. Missense mutations, especially in the MH2 domain (63.6% and 68.75) were the prominent alterations. In cancer, codon 435 and in polyp, codons 435 and 399 were the most prevalent mutations. Unlike cancer specimens, in polyp, transversion was the most frequent substitutions (56.25 vs. 35.7%). CG>TA transition was about 18.75 and 14.3% in cancer and polyp samples. Mutations of codon 264 and C.483-4 were seen both in cancer and neoplastic polyps.


Conclusion: As the frequent alterations, missense mutations are presumably selected during tumorigenesis and polyposis due to their structural impacts on SMAD4 functions and TGF-ß signaling pathway. The lower frequency of CG>TA can be attributed to the global genome hypomethylation. Presumably, SMAD4 mutations had occurred in the primary polyps, and some of these mutated cells then developed to carcinoma. On the other hand, polyp-specific mutations may lower the risk of CRC.

Identification of Key Candidate Genes and Pathways Associated with Colorectal Aberrant Crypt Foci-to-Adenoma-to-Carcinoma Progression

Setareh Fayazfar, Afsaneh Arefi, Akram Safaei, Hakimeh Zali , Ehsan Nazemalhosseini Mojarad

Gastroenterology and Hepatology from Bed to Bench, , 30 December 2021
https://doi.org/10.22037/ghfbb.vi.2205

Introduction: Although colorectal cancer (CRC) is the third most common type of cancer, the involved signaling pathways, and driver-genes are largely unclear. CRC begins with the malignant transformation of precancerous lesions including aberrant crypt foci (ACF) and benign adenomatous polyp or adenoma. We aim to detect key candidate genes and pathways involved in colorectal aberrant crypt foci-to-adenoma-to-carcinoma progression.


Methods: We provided a list of formerly reported ACF, adenoma, and CRC-associated proteins from GeneCards and then analyzed data in online David Bioinformatics Resources. The protein-protein interactions were surveyed utilizing the String database and Cytoscape software. After the recognition of hubs and bottlenecks, the key genes and pathways were identified through different bioinformatical analysis.


Results: The most important pathways associated with colorectal aberrant crypt foci-to-adenoma progression were attributed to “pathways in cancer” and “Chemokine signaling pathway” and those in adenoma-to-carcinoma progression were related to “pathways in cancer”, “Chemokine signaling pathway” and “Ras signaling pathway”. The genes participating in these pathways are the key important genes. Furthermore, PRKACB, CUL2, and GSK3B were important genes as the seed in the clusters related to adenoma and GNB1, RALBP1, ROCK1, and IKBKG in the clusters related to cancer.


Conclusion: By integrated bioinformatical analysis, the key candidate genes and pathways in progress CRC formed precursor lesions were identified. This could lead to our better understanding of the cause and underlying molecular events as well as the detection of therapeutic targets for CRC.

Assessment of colon cancer molecular mechanism: A System Biology Approach

Babak Arjmand , Mahmood khodadost, Somayeh Jahani Sherafat, Mostafa Rezaei –Tavirani, Maryam Hamzeloo Moghadam, Sina Rezaei Tavirani, Majid Iranshahi

Gastroenterology and Hepatology from Bed to Bench, , 30 December 2021
https://doi.org/10.22037/ghfbb.vi.2368

Background: Colorectal cancer is known as the third most common kind of cancer which is introduced as the second important reason of global cancer-related mortality rates. There are many documents about colon cancer molecular mechanism.


Aim: Assessment and comparison of colon cancer dysregulated genes from GEO and STRING is aim of this study.


Methods: From STRING database, numbers of 100 differentially expressed proteins which are related to colon cancers were retrieved and analyzed via network analysis. The central nodes of the network were assessed via gene ontology. Finding was compared with a GSE from GEO.


Results: Based on data from STRING database, TP53, EGFR, HRAS, MYC, AKT1, GAPDH, KRAS, ERBB2, PTEN, and VEGFA were identified as central genes. The central nodes were not included in the significant DEGs of the analyzed GSE.


Conclusion: Combination of different database sources in system biology investigations, provide useful information about the studied diseases.

Association study on IL-22 and IL-22RA1 genes variants in Iranian patients with colorectal cancer

Seyed Reza Mohebbi, Khatoon Karimi, Fatemeh Rostami, Shabnam Kazemian, Pedram Azimzadeh, Hanieh Mirtalebi, Ehsan Nazemalhosseini-Mojarad, Hamid Asadzadeh Aghdaei, Reza Vafaee, Mohammad Hossain Heydari

Gastroenterology and Hepatology from Bed to Bench, , 30 December 2021
https://doi.org/10.22037/ghfbb.vi.2423

Aim and background: The important role of pro-inflammatory cytokines during tumorigenesis is well-established. In recent years, IL-22 has been linked with colorectal cancer (CRC) through a number of mechanistic and observational studies. We hypothesized that single nucleotide polymorphisms (SNPs) in regulatory region of the IL-22 signaling pathway genes including IL-22 and IL-22RA1 variants may be associated with CRC susceptibility.


Materials and methods: We studied the association of four novel polymorphisms in IL-22 gene (rs1179251 and rs1179246) and IL-22RA1 gene (rs4648936 and rs10794665) with CRC risk using a case-control design with 304 cases and 345 controls from the Iranian population. All 649 subjects were evaluated by PCR – RFLP method.


Results: No significant difference was found in genotype and allele frequencies between the cases and controls for the IL-22 and IL-22RA1 gene variants and CRC risk before or after adjusting for confounders.


Conclusion: These findings do not present any significant evidence for associations between variants in IL-22 signaling pathway genes and CRC. Complementary studies with greater sample size may be necessary to fully elucidate the nature of these associations.

Description of the inflammatory bowel disease natural history in Tehran province, Iran: Mixed panel approaches

Meysam Olfatifar, Hamid Asadzadeh Aghdaei, Mohamad Amin Pourhoseingholi, Hedieh Balaii, Saeed Hashemi Nazari, Shabnam Shahrokh, Siamak Sabour, Maria Ivanchuk, Pavlo Ivanchuk, Soheila Khodakarim, Mohammad Reza Zali, Pejman Rohani, Gholamhossein Mehralian

Gastroenterology and Hepatology from Bed to Bench, , 30 December 2021
https://doi.org/10.22037/ghfbb.vi.2354

Background: Inflammatory bowel disease (IBD) is a non-homogenous condition with an unpredictable natural history that affects the patient's quality of life in their lifetime. Hence, it is very crucial to provide evidence for optimal patient management.


Methods: In this retrospective cohort study, we included 198 IBD patients who have been visited at least three times routinely from Oct 2015 to May 2020. Then we applied two panel-based approaches Multi-State Model (MSM) and random-effect ordered logistic to elucidate the clinical course of IBD, comprising remission, mild, moderate to severe, and surgery states.


Results: For ulcerative colitis (UC), women had a slightly poor condition for remission but better for moderate to severe (faster transition to mild) compared to men. For Crohn's disease (CD), they had a better condition for remission but a slightly poor condition for the severe state. The biological agent's user had a better condition with better sojourn time, transition rate, or/and odds states than UC, especially for CD. Oral 5-ASA had better efficacy for people with remission or/and mild states but not for moderate to severe states, especially in CD. Immunosuppressive drugs were better for patients with lower disease severity, especially for UC.


Conclusions: Panel approaches have potential efficacy to tackle the unpredictable clinical course of IBD (UC/CD). Hence, we highly recommend that our findings be included in the Iranian routine clinical environment of IBD and/or that related studies be conducted in Iran and other regions to gain a better understanding of the natural history of IBD.

High Viral Load Detection of Human Cosavirus in Iranian Pediatric Patients with Acute Gastroenteritis

Sadaf Khoshbazan, Zahra Evani, Seyed Dawood Mousavi Nasab, Nayeb Ali Ahmadi, Aynaz Parhiz, Bahman Khalesi, Mohammad Hasan Firouzjani, Mostafa Ghaderi, Maryam Barati, Mohammad Javad Ehsani Ardakani

Gastroenterology and Hepatology from Bed to Bench, , 30 December 2021
https://doi.org/10.22037/ghfbb.vi.2400

Aim: The present study was implemented an RT-qPCR assay for detection and quantification of human Cosavirus in stool specimens among pediatric patients involved in acute gastroenteritis.


Background: Human Cosavirus is a newly recognized virus that seems to be partly related to acute gastroenteritis in pediatric patients. However, the relationship between human Cosavirus and diseases in humans is unclear.


Methods: In this study, a total of 160 stool samples from January 2018 to December 2019 were collected from presenting pediatric patients with acute gastroenteritis in a Karaj hospital, Iran. After viral RNA extraction, the RT-qPCR was performed to amplify the 5’UTR region of the human Cosavirus genome and viral load was analyzed.


Results: Out of the 160 samples tested, the human Cosavirus genomic RNA was detected in 4/160 (2.5%) of stool samples. The maximum viral load was determined to be 4.6×106 copies/ml in one sample obtained from 4 years’ patient.


Conclusion:


As a new member of Picornaviridae family, for the first time occurrence of human Cosavirus illustrated in fecal samples of pediatric patients with acute gastroenteritis in Iran.

Common and Differential Features of Liver and Pancreatic Cancers: Molecular Mechanism Approach

Kourosh Saki, Vahid Mansouri, Nastaran Asri, Mohammad Fathi, Zahra Razzaghi

Gastroenterology and Hepatology from Bed to Bench, , 30 December 2021
https://doi.org/10.22037/ghfbb.vi.2437

Aim: Liver is affected by metastatic disease in pancreatic cancer. The aim of this study is to introduce biomarkers commonly involved in pancreatic cancer metastasis to liver


Methods: Two cancer biomarkers were distinguished via STRING database protein query. Dysregulated proteins of two cancers included in 2 networks drawn by Cytoscape software v 3.2.7. 20 top nodes achieved by Network analyzer application of Cytoscape based on degree value. The common hub nodes were determined and action map were analyzed.


Results: Among 20 hubs of each studied cancers, 18 common hub nodes (90% of hubs) were identified. The common hub nodes were screened by action maps and four proteins including AKT1, CDKN2A, ERBB2, and IL6 were determined as common central proteins related to the two studied diseases.


Conclusions: AKT1, CDKN2A, ERBB2, and IL6 are introduced as common protein core of liver and pancreatic cancer while STAT3, CASP3, NOTCH1, and CTNNB1 are possible differential proteins to discriminate these cancers.

Assessment of Common and Differentially Expressed Proteins between Diabetes Mellitus and Fatty Liver Disease: A Network Analysis

Kourosh Saki, Vahid Mansouri, Saeed Abdi , Mohammad Fathi, Zahra Razzaghi, Mehrdad Haghazali

Gastroenterology and Hepatology from Bed to Bench, , 30 December 2021
https://doi.org/10.22037/ghfbb.vi.2426

Back ground: Nonalcoholic fatty liver disease (NFLD) is a chronic hepatic failure with broad range of hepatic disorders. NFLD and diabetes type 2 coexist regularly to drive adverse outcome as hepatocellular carcinoma and vascular complications.
Aim: This study aimed to introduce main biomarkers related to NFLD and diabetes II to find out common pathogenic and metabolite factors linked NFLD to diabetes II
Methods: The related proteins to NFDL and diabetes mellitus extracted from String database. Proteins related to each disease were included in protein-protein interaction network via Cytoscape software. Obtained networks were analyzed via Cytoscape network analyzer. The central nodes were determined as top hubs based on degree value. Top hubs related to NFLD and diabetes melliteswere compared.

Results: 200 proteins related to NFDL and diabetes mellitus were found via String database separately and connected via undirected edges in individual networks. Central nodes based on degree value were determined for each disease. 10 percent of top nodes were selected based on degree value as 20 top hubs for each disease. Target common hub proteins between NFDL and diabetes mellitus are:  INS, AKT1, ALB, PPARG, IL6, GPDPH, LEP, TNF, ADIPOQ, IGF1, TP53, MAPK3, and SIRT1


Conclusions:


According to the results, 13 common and 14 discriminatory central dysregulated proteins were determined for NAFLD and diabetes mellitus.

Predictors of Metabolic-Associated Fatty Liver Disease (MAFLD) in Adults: A Population-Based Study in Northeastern Iran

Ehsaneh Taheri, Alireza Moslem, Alireza Mousavi-jarrahi, Behzad Hatami, Mohammad Amin Pourhosseingholi, Hamid Asadzadeh aghdaei, Mohammad reza Zali

Gastroenterology and Hepatology from Bed to Bench, , 30 December 2021
https://doi.org/10.22037/ghfbb.vi.2447

Aim: The current study was designed to determine the predictive risk factors of metabolic
dysfunction-associated fatty liver disease (MAFLD) among Iranian population.
Background: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease has renamed
to the new terminology of MAFLD. While there is no approved treatment for fatty liver diseases,
identifying the risk factors of MAFLD is more important than other non-communicable diseases.
Methods: This nested case-control study was performed based on the Persian Sabzevar Cohort
Study (PSCS) consisting of 4,242 participants in northeastern Iran with an age range of 35 to 70
years. We recruited 968 MAFLD cases and 964 age and sex- matched controls. We collected
data including demographic, lifestyle, anthropometric, biochemical, dietary habits, and sleep
information.
Results: The mean age of the participants was 49.2 ± 8.8 years, and 39.9% of them were male.
The prevalence of MAFLD in the studied population was 22.8%. Increase in body mass index
(BMI) (OR [odds ratios] 5.51, 95% CI [confidence interval] 2.73 – 11.10), waist circumference
(WC) (OR 1.85, 95% CI 1.44 – 2.38), triglyceride (TG) (OR 1.10, 95% CI 1.06 – 1.15), total
cholesterol (TC) (OR 1.02, 95% CI 1.003 – 1.04), and AST (OR 1.10, 95% CI 1.05 – 1.16) were
statistically significantly associated with higher risk of MAFLD (P <0.05 for all). Furthermore,
the risk of having MAFLD was 43% higher in subjects who sleep less than five compared to
those with more than 7-hour sleep/day (OR 1.43; 95% CI 1.07 – 1.92, P = 0.01)
Conclusion: In our study, BMI, WC, plasma levels of TG, total cholesterol, and AST are the
best predictors of MAFLD. Sleeping ≤ 5 relative to more than 7 hours/day increases the MAFLD
risk.

Comparison of endoscopic balloon dilatation potency using balloons size more or less than 15 mm in the treatment of large bile duct stones; a clinical trial study

Amir Sadeghi, arash dooghaie moghadam, Shaghayegh Jamshidizade, Mohsen Norouzinia , Negin Jamshidfar , Parna Hosseini

Gastroenterology and Hepatology from Bed to Bench, , 30 December 2021
https://doi.org/10.22037/ghfbb.vi.2288

Abstract


Background: The present study was performed on patients with large bile duct stones to compare clinical outcomes and complications of balloon dilatation treatment between two sizes of balloons, < 15 mm and ≥ 15 mm.


Methods: Patients with large bile duct stones admitted to Taleghani hospital from December 2018 to December 2019 who were the candidates for balloon dilation with limited sphincterotomy. Patients were randomly divided into two groups. In group B, a ≥ 15 mm balloon was used, and in group A, a balloon <15 mm was used. The clinical results of balloon dilation and its complications were recorded and compared


Results: Most patients had 1 or 2 large bile duct stones, and there was no significant difference in the number of stones. Extraction was successful in 92.8% of group B and 85.7% of group A without significant differences (P = 0.8). Pancreatitis, hemorrhage, cholangitis, and perfusion occurred in 8%, 4.2%, 1.4%, and 2.8% of group B subjects and also in 10%, 2.8%, 0%, and 1.4% of group A subjects, respectively, and the difference between the two groups was not significant.


 Conclusion: Generally, this study results showed that balloon size did not have a significant effect on the success rate of bile duct stones. Moreover, considering the lack of significant association between balloon dilatation size and the occurrence of post-endoscopic complications such as pancreatitis, it seems that large-size dilatation has no serious clinical risk.

C-Reactive Protein Is a Possible Marker Relative to severity and mortality of COVID-19 Infection

Noorollah Tahery, Mahmood Khodadost, Somayeh Jahani Sherafat3 Jahani Sherafat, Mostafa Rezaei –Tavirani, Nayebali Ahmadi, Fatemeh Montazer, Majid Rezaei Tavirani6 Rezaei Tavirani, Nosratollah Naderi

Gastroenterology and Hepatology from Bed to Bench, , 30 December 2021
https://doi.org/10.22037/ghfbb.vi.2388

Introduction: COVID-19 pandemic changed life style of human in recent years and appeared as a complicated health problem. Clinical finding indicates to mild, sever, and fatal condition of this disease. Prediction of disease severity is a significant point in managing COVID-19 infection. In the present study it is tried to introduce possible biomarker to differentiate the sever and fatal condition of disease.


Methods: Number of 195 differentially genes that discriminate the fatal patients from the patient with sever condition were extracted from literature and screen to find the significant differentially genes (DEGs). The significant DEGs plus added 90 first neighbors from STRING database were included in interactome by using Cytoscape software v 3.7.2. The central nodes of the analyzed network were identified and assessed.


Results: Number of 10 significant DEGs were candidate to be assessed which 9 individuals were recognized by STRING database. IL6, ALB, TNF, CRP, INS, MPO, C3, CXCL8, TTR, and TLR4 were determined as central nodes. IL6, CRP, and TTR are highlighted as the critical genes related to severity of COVID-19 infection.


Conclusion: CRP was pointed as the best possible biomarker which its levels are related to the severity and fatality of COVID-19 infection.

Brief Report


Efficacy of infliximab and adalimumab therapy in very early onset ulcerative colitis

Pejman Rohani, Hosein Alimadadi, Fatemeh Abdollah Gorji, Shabnam Shahrokh, Mohammad Reza Zali

Gastroenterology and Hepatology from Bed to Bench, , 30 December 2021
https://doi.org/10.22037/ghfbb.vi.2392

Objective: Children with very early onset inflammatory bowel disease (IBD) are patients with diagnosis of IBD before 6 years of age. This multicenter study is the first one on Iranian children with very early onset ulcerative colitis (UC) and one of the few studies about the effect of biological therapy in children with UC under 7 years of age.


Method: Study was performed on 14 children under 7 years of age with severe UC. Children with severe UC who had failed therapy with corticosteroid and azathioprine as conventional treatment were treated with infliximab (IFX) and later with adalimumab (ADA).


Results: A total of 6 (43%) patients were female. The mean age was 4.9 years (3–7 years) and the mean age of diagnosis was 3.4 years (1.5–6 years). The mean duration of illness was 1.5 years. At the end of 54 weeks of therapy with IFX, 2 (14%) patients were in remission, 2 (14%) patients were mild, and 4 (29%) patients were moderate, with no secondary treatment failure (during the maintenance phase). A total of 6 (43%) patients had primary treatment failure (no response after 14 weeks of therapy). These patients had treatment with ADA. At the end of 52 weeks of therapy, out of those 6 (100%) patients, 3 (50%) patients were referred to colectomy, 1 (17%) patient had remission, and 2 (33%) patients had mild severity.


Conclusions: Our study has shown that IFX is safe and an effective therapy in children with very early onset UC. ADA may be effective in the treatment of children with UC who are refractory to IFX.

Abstract Meeting