Publications by authors named "Ashraf Mohamadkhani"

55 Publications

Seroprevalence of Immunoglobulin M and G Antibodies against SARS-CoV-2 Virus: A Systematic Review and Meta-Analysis Study.

Iran J Immunol 2021 Mar;18(1):34-46

Student Research Committee, Faculty of Medicine, Shahid Beheshti University of MedicalSciences, Tehran, Iran.

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new global health threat.

Objectives: to analyze the effectiveness of the measurement of specific antibodies to SARS-CoV2 (IgM and IgG) for the diagnosis of COVID-19 and to analyze the rate of SARS-CoV2 seroprevalence in the population.

Methods: 11 relevant studies, published before June 5, 2020, were included in this meta-analysis. These studies were identified by searching the MEDLINE and Scopus databases. The final selected studies were analyzed using STATA version 14. Publication bias was examined using both Egger's test and Funnel plots. Moreover, the I² statistic has been used to evaluate and verify heterogeneity.

Results: The 11 relevant studies selected for the present meta-analysis cover a total of 996 infection cases. According to the results, the average rate of positive cases for IgM (AU/mL) was 2.10 (95% CI: 1.65-2.55; I2=92.2%), and the sensitivity in individuals with positive IgM test was 63% (95% CI: 47-79; I2=94.9%). In addition, the average rate of positive cases for IgG (AU/mL) was 67.44 (95% CI: 28.79-106.09; I2=99.4%), and the sensitivity in individuals with positive IgG test was 79% (95% CI: 67-90; I2=89.5%).

Conclusions: According to this analysis, detection of anti-SARS-CoV-2 IgM and IgG antibodies may assist early detection of SARS-CoV2 infection. Whether antibodies against SARS-CoV-2 confer protective immunity warrants further studies.
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http://dx.doi.org/10.22034/iji.2021.87723.1824DOI Listing
March 2021

The prognostic value of comorbidity for the severity of COVID-19: A systematic review and meta-analysis study.

PLoS One 2021 16;16(2):e0246190. Epub 2021 Feb 16.

Department of Family Medicine, Shiraz University of Medical Science, Fars, IR Iran.

Background And Objectives: With the increase in the number of COVID-19 infections, the global health apparatus is facing insufficient resources. The main objective of the current study is to provide additional data regarding the clinical characteristics of the patients diagnosed with COVID-19, and in particular to analyze the factors associated with disease severity, lack of improvement, and mortality.

Methods: 102 studies were included in the present meta-analysis, all of which were published before September 24, 2020. The studies were found by searching a number of databases, including Scopus, MEDLINE, Web of Science, and Embase. We performed a thorough search from early February until September 24. The selected papers were evaluated and analyzed using Stata software application version 14.

Results: Ultimately, 102 papers were selected for this meta- analysis, covering 121,437 infected patients. The mean age of the patients was 58.42 years. The results indicate a prevalence of 79.26% for fever (95% CI: 74.98-83.26; I2 = 97.35%), 60.70% for cough (95% CI: 56.91-64.43; I2 = 94.98%), 33.21% for fatigue or myalgia (95% CI: 28.86-37.70; I2 = 96.12%), 31.30% for dyspnea (95% CI: 26.14-36.69; I2 = 97.67%), and 10.65% for diarrhea (95% CI: 8.26-13.27; I2 = 94.20%). The prevalence for the most common comorbidities was 28.30% for hypertension (95% CI: 23.66-33.18; I2 = 99.58%), 14.29% for diabetes (95% CI: 11.88-16.87; I2 = 99.10%), 12.30% for cardiovascular diseases (95% CI: 9.59-15.27; I2 = 99.33%), and 5.19% for chronic kidney disease (95% CI: 3.95-6.58; I2 = 96.42%).

Conclusions: We evaluated the prevalence of some of the most important comorbidities in COVID-19 patients, indicating that some underlying disorders, including hypertension, diabetes, cardiovascular diseases, and chronic kidney disease, can be considered as risk factors for patients with COVID-19 infection. Furthermore, the results show that an elderly male with underlying diseases is more likely to have severe COVID-19.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246190PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886178PMC
February 2021

Existing antiviral options against SARS-CoV-2 replication in COVID-19 patients.

Future Microbiol 2020 12 6;15:1747-1758. Epub 2021 Jan 6.

Department of Nutrition, Nutrition Research Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 28081, USA.

COVID-19 caused by SARS-CoV-2, is an international concern. This infection requires urgent efforts to develop new antiviral compounds. To date, no specific drug in controlling this disease has been identified. Developing the new treatment is usually time consuming, therefore using the repurposing broad-spectrum antiviral drugs could be an effective strategy to respond immediately. In this review, a number of broad-spectrum antivirals with potential efficacy to inhibit the virus replication via targeting the virus spike protein (S protein), RNA-dependent RNA polymerase (RdRp), 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro) that are critical in the pathogenesis and life cycle of coronavirus, have been evaluated as possible treatment options against SARS-CoV-2 in COVID-19 patients.
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http://dx.doi.org/10.2217/fmb-2020-0120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789744PMC
December 2020

Critical complications of COVID-19: A descriptive meta-analysis study.

Rev Cardiovasc Med 2020 09;21(3):433-442

Student research committee, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, 198571743, Tehran, IR Iran.

The coronavirus disease 2019 (COVID-19) is a novel coronavirus infection that has rapidly spread worldwide, causing a pandemic. The main objective of this meta-analysis was to evaluate the prevalence of the most common symptoms and complications of COVID-19. All relevant studies on the clinical complications of COVID-19 have been identified by searching two web databases (i.e., PubMed and Scopus). Afterward, the relevant data were extracted from the selected studies, and then analyzed by the STATA (Version 14) random-effects model. The 30 studies selected for our meta-analysis covered 6,389 infected patients. The prevalence rates of the most common symptoms were as follows: fever: 84.30% (95% CI: 77.13-90.37; I2 = 97.74%), cough: 63.01% (95% CI: 57.63-68.23; I2 = 93.73%), dyspnea: 37.16% (95% CI: 27.31-47.57%; I2 = 98.32%), fatigue: 34.22% (95% CI: 26.29-42.62; I2 = 97.29%), and diarrhea: 11.47% (95% CI: 6.96-16.87; I2 = 95.58%). Moreover, the most prevalent complications were found to be acute respiratory distress syndrome (ARDS) with 33.15% (95% CI: 23.35-43.73; I2 = 98.56%), arrhythmia with 16.64% (95% CI: 9.34-25.5; I2 = 92.29%), acute cardiac injury with 15.68% (95% CI: 11.1-20.97; I2 = 92.45%), heart failure with 11.50% (95% CI: 3.45-22.83; I2 = 89.48%), and acute kidney injury (AKI) with 9.87% (95% CI: 6.18-14.25; I2 = 95.64%). In this study, we assessed the prevalence of the main clinical complications of COVID-19, and found that following respiratory complications, cardiac and renal complications are the most common clinical complications of COVID-19.
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http://dx.doi.org/10.31083/j.rcm.2020.03.129DOI Listing
September 2020

Circulating plasma fatty acids and risk of pancreatic cancer: Results from the Golestan Cohort Study.

Clin Nutr 2021 Apr 15;40(4):1897-1904. Epub 2020 Sep 15.

Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background & Aims: Pancreatic cancer (PC) with a dismal prognosis is considered as a fatal malignancy, attracting the scientists' attention to study its causes and pathogenesis pathways. Given the lack of enough evidence and conflicting findings about the association of PC risk with plasma fatty acids, we aimed to explore the associations of circulating plasma fatty acids with the risk of PC in a cohort study.

Methods: From about 50,000 subjects participated in this cohort study in 2004-2008, fifty incident cases of PC were recruited and 150 controls matched by age, sex and residence place (urban/rural) were randomly selected. The plasma fatty acids composition was measured by gas chromatography with Flame Ionization Detector (GC-FID) in plasma samples collected at the baseline of cohort study. Multivariable conditional logistic regression was used to estimate OR (with 95% CI) of PC risk associated with plasma levels of fatty acids considering known potential risk factors for PC.

Results: Our findings showed that total saturated fatty acids and total industrial trans fats were not associated with the risk of PC; whereas, statistically significant inverse associations were found between high plasma levels of total mono-unsaturated fatty acids (MUFAs), omega-3 and ruminant trans fatty acids with the risk of PC [OR = 0.31 (0.11-0.89), OR  = 0.30 (0.10-0.91) and OR = 0.15 (0.04-0.49), respectively]. Omega-6 fatty acids especially high plasma levels of Arachidonic acid was positively associated with the risk of PC [OR = 11.07 (3.50-35.02)].

Conclusion: Except for the plasma circulating whole fats, the levels of different classes of fats may significantly change pancreatic cancer susceptibility. Unsaturated fatty acids including omega-3-PUFA and MUFA are considered as protective biomarkers in PC prevention. On the contrary, omega-6-fatty acids are positively associated with the risk of PC.
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http://dx.doi.org/10.1016/j.clnu.2020.09.002DOI Listing
April 2021

Heritability for stroke: Essential for taking family history.

Caspian J Intern Med 2020 May;11(3):237-243

Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background: There are many well-established factors that influence the risk of stroke including blood pressure, diabetes, low socioeconomic status and smoking, however, the shared genetic resource in members of a family effect on stroke predisposition. Genome-wide association studies (GWAS) have demonstrated evidence of a shared genetic source in stroke risk. This review considered the influence of family history as one of the main risk factors in stroke according to the literature.

Methods: Literature review was obtained by searching for the key words "stroke", "family history" and "stroke gene" in PubMed. An overview has been made on the topics: relevance of stroke family history, family history assessment tools and specific candidate genes for stroke.

Results: Family history of stroke is an important risk factor for the development of cerebrovascular diseases in addition to stroke subtypes in relatives who have reached the questionnaire and pedigree. While variation in a small number of loci showed Mendelian inheritance of stroke phenotypes, the genetic variations in several stroke risk loci are shared with multiple related vascular traits.

Conclusion: This study highlighted the importance of family history in stroke phenotypes and current related genetics information. Increasing awareness of the importance of family history in stroke has the advantage of preventing exposure to stroke with health care.
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http://dx.doi.org/10.22088/cjim.11.3.237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442467PMC
May 2020

Metabolomics analysis of the saliva in patients with chronic hepatitis B using nuclear magnetic resonance: a pilot study.

Iran J Basic Med Sci 2019 Sep;22(9):1044-1049

Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran.

Objectives: Hepatitis B virus infection causes chronic disease such as cirrhosis and hepatocellular carcinoma. The metabolomics investigations have been demonstrated to be related to pathophysiologic mechanisms in many disorders such as hepatitis B infection. The aim of this study was to investigate the saliva metabolic profile of patients with chronic hepatitis B infection and to identify underlying mechanisms as well as potential biomarkers associated with the disease.

Materials And Methods: Saliva from 16 healthy subjects and 20 patients with chronic hepatitis B virus were analyzed by nuclear magnetic resonance (NMR). Then, multivariate statistical analysis was performed to identify discriminative metabolites between two groups.

Results: A set of metabolites were detected, including propionic acid, putrescine, acetic acid, succinic acid, tyrosine, lactic acid, butyric acid, pyruvic acid, 4-pyridoxic acid and 4-hydroxybenzoic acid, which in combination with one another could accurately distinguish patients from healthy controls. Our results clearly demonstrated altered metabolites are involved in nine metabolic pathways.

Conclusion: Metabolomics has the potential to be considered as a novel clinical tool for hepatitis B diagnosis while contributing to a comprehensive understanding of disease mechanisms.
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http://dx.doi.org/10.22038/ijbms.2019.36669.8733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880533PMC
September 2019

Oral microbial community composition is associated with pancreatic cancer: A case-control study in Iran.

Cancer Med 2020 01 21;9(2):797-806. Epub 2019 Nov 21.

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Oral microbiota may be related to pancreatic cancer risk because periodontal disease, a condition linked to multiple specific microbes, has been associated with increased risk of pancreatic cancer. We evaluated the association between oral microbiota and pancreatic cancer in Iran.

Methods: A total of 273 pancreatic adenocarcinoma cases and 285 controls recruited from tertiary hospitals and a specialty clinic in Tehran, Iran provided saliva samples and filled out a questionnaire regarding demographics and lifestyle characteristics. DNA was extracted from saliva and the V4 region of the 16S rRNA gene was PCR amplified and sequenced on the MiSeq. The sequencing data were processed using the DADA2 plugin in QIIME 2 and taxonomy was assigned against the Human Oral Microbiome Database. Logistic regression and MiRKAT models were calculated with adjustment for potential confounders.

Results: No association was observed for alpha diversity with an average of 91.11 (standard deviation [SD] 2.59) sequence variants for cases and 89.42 (SD 2.58) for controls. However, there was evidence for an association between beta diversity and case status. The association between the Bray-Curtis dissimilarity and pancreatic cancer was particularly strong with a MiRKAT P-value of .000142 and specific principal coordinate vectors had strong associations with cancer risk. Several specific taxa were also associated with case status after adjustment for multiple comparisons.

Conclusion: The overall microbial community appeared to differ between pancreatic cancer cases and controls. Whether these reflect differences evident before development of pancreatic cancer will need to be evaluated in prospective studies.
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http://dx.doi.org/10.1002/cam4.2660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970053PMC
January 2020

An Increased Level of Aryl Hydrocarbon Receptor in Patients with Pancreatic Cancer.

Middle East J Dig Dis 2019 Jan 4;11(1):38-44. Epub 2018 Oct 4.

Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

BACKGROUND Aryl-carbon receptor (AhR), a ligand-activated transcription factor, is best known for its ability to mediate the effects of environmental toxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin. AhR is expressed in several tumor cells and regulates the expression of genes in the signal transduction pathways. In this study, we examined the soluble levels of AhR in patients with pancreatic cancer. METHODS 123 samples, including 59 (48%) samples of pancreatic ductal adenocarcinoma based on histological evidence and 64 (52%) healthy control samples, were evaluated to determine plasma levels of AhR by Enzyme-linked immunoassay. RESULTS The median of AhR among patients was 0.280 ng/mL, which differed considerably from 0.07 ng/mL in the control group ( < 0.001). Significant differences of the AhR were observed between the plasma samples of the patients compared with the healthy group, with respect to male sex ( < 0.001), age groups ( = 0.001), diabetic status ( < 0.001), body mass index (BMI) categories ( = 0.035), and constantly smokers ( < 0.001). We also observed significant differences between the level of AhR expression between men and women ( = 0.01) and ever to never smokers ( = 0.009) in the case group. In addition, the age of 65 and a BMI of 25 or less were significant factors in plasma AhR levels ([1.61 95%CI 1.08-2.38] and [1.84 95%CI 1.22-2.77], respectively). CONCLUSION The results of this study can add diagnostic information to pancreatic cancer involving AhR and the potential efficacy of this receptor in therapeutic strategies.
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http://dx.doi.org/10.15171/mejdd.2018.126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488497PMC
January 2019

Gut Microbiota and Fecal Metabolome Perturbation in Children with Autism Spectrum Disorder.

Middle East J Dig Dis 2018 Oct 21;10(4):205-212. Epub 2018 Jul 21.

Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

The brain-intestinal axis concept describes the communication between the intestinal microbiota as an ecosystem of a number of dynamic microorganisms and the brain. The composition of the microbial community of the human gut is important for human health by influencing the total metabolomic profile. In children with autism spectrum disorder (ASD), the composition of the fecal microbiota and their metabolic products has a different configuration of the healthy child. An imbalance in the metabolite derived from the microbiota in children with ASD affect brain development and social behavior. In this article, we review recent discoveries about intestinal metabolites derived from microbiota based on high-yield molecular studies in children with ASD as part of the "intestinal brain axis".
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http://dx.doi.org/10.15171/mejdd.2018.112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488507PMC
October 2018

The Effect of Vitamin D on Serum Asymmetric Dimethylarginine in Patients with Mild to Moderate Ulcerative Colitis.

Int J Vitam Nutr Res 2020 Jan 15;90(1-2):17-22. Epub 2019 Apr 15.

Digestive Diseases Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

: In inflammatory bowel disease increased asymmetric dimethylarginine (ADMA) levels could inhibit nitric oxide (NO) synthase. Vitamin D may increase activity and expression of endothelial NO synthase, which could be done through its possible mechanism of decreasing ADMA levels. The aim of this study is to investigate the possible effect of Vitamin D3 on serum ADMA levels in ulcerative colitis (UC) patients. Ninety mild to moderate UC patients were randomized. Each patient received one single muscular injection of 300,000 IU (7500 μg) Vitamin D3 (Vitamin D group) or 1 ml normal saline (Placebo group). At baseline and 90 days after the intervention measurements were done. Data were analyzed using independent t-test and analysis of covariance. Baseline correlations were assessed by Pearson and Spearman correlation coefficients. Following data analysis of 86 participants (40 in placebo and 46 in vitamin D group), there was no correlation between baseline ADMA with baseline vitamin D, ESR and hs-CRP at baseline (p = 0.77) and at the end of study (p = 0.82). Serum ADMA levels were not statistically different between two groups. Adjustment for baseline ADMA levels and baseline body mass index (BMI) did not change the results. With subgroup analyses based on gender and vitamin D level no statistical differences in ADMA levels between two groups were found. In this study, we found no significant changes in serum ADMA levels 3 months following a high dose vitamin D administration in mild to moderate UC patients. Further studies in vitamin D deficient patients are needed.
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http://dx.doi.org/10.1024/0300-9831/a000303DOI Listing
January 2020

Vitamin D Decreases Beck Depression Inventory Score in Patients with Mild to Moderate Ulcerative Colitis: A Double-Blind Randomized Placebo-Controlled Trial.

J Diet Suppl 2019 29;16(5):541-549. Epub 2018 Jun 29.

Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences , Tehran , Iran.

The prevalence of depression in inflammatory bowel disease (IBD) is significantly more than in controls. Some studies assessed the link between vitamin D and depression. The aim of this study was to assess the effect of vitamin D on Beck Depression Inventory (BDI) score in ulcerative colitis (UC) patients. In this double-blind randomized controlled trial, 90 mild to moderate UC patients were assigned to receive a single injection of 300,000 IU vitamin D3 or 1 ml normal saline as placebo. At baseline and 3 months later, measurements of BDI score and serum 25-OH-vitamin D3 were done. Data were compared by independent sample test, Mann-Whitney U test, and analysis of covariance (ANCOVA). Baseline BDI scores were not statistically different between the two groups ( = .4); scores decreased in the vitamin D group after the intervention ( = .023). Further subgroup analysis regarding baseline serum vitamin D levels and adjusted for baseline BDIs revealed lowering effect of vitamin D on BDI scores only in subgroup with baseline serum vitamin D levels equal to or higher than 30 ng/ml ( < .001). In this study, there was a statistically significant reduction in BDI score in mild to moderate UC patients 3 months after 300,000 IU vitamin D3 injection. Subgroup analysis showed that patients with sufficient baseline vitamin D may benefit from supplementation more than vitamin D-deficient patients, which indicates that higher serum vitamin D levels may be needed for its antidepressant effect.
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http://dx.doi.org/10.1080/19390211.2018.1472168DOI Listing
February 2020

Mutations in Known and Novel cancer Susceptibility Genes in Young Patients with Pancreatic Cancer.

Arch Iran Med 2018 06 1;21(6):228-233. Epub 2018 Jun 1.

Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background: Pancreatic cancer is the fourth most common cause of mortality due to cancer, globally. It has a poor prognosis and is usually diagnosed at later stages when tumor resection is not possible. Heritability for pancreatic cancer is relatively high and clinically significant.

Methods: A group of 24 pancreatic cancer patients with young age at onset, from a referral hospital in Tehran University of Medical Sciences were screened for mutations in 710 cancer relevant genes using next generation sequencing technology.

Results: Two patients had pathogenic mutations in known pancreatic cancer susceptibility genes, BRCA1/2. Two other patients also had potentially pathogenic mutations in 2 novel candidate genes including PARP4 and EXO1.

Conclusion: BRCA1/2 genes are the most commonly mutated pancreatic cancer susceptibility genes that should be considered in all pancreatic cancer cases with young age at onset or a family history of cancer. PARP4 and EXO1 also are potential candidate genes for susceptibility to pancreatic cancer. Identifying the hereditary cases of pancreatic cancer will help to offer more targeted treatments to the patients and also to prevent cancer in family members who might be a mutation carrier.
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June 2018

On the potential role of intestinal microbial community in hepatocarcinogenesis in chronic hepatitis B.

Cancer Med 2018 May 15. Epub 2018 May 15.

Liver and Pancreatobiliary Disease Research Center, Digestive Disease Research institute, Shariati Hospital, Tehran University of Medical Science, Tehran, Iran.

The chronic infection of hepatitis B virus (HBV) is the most potent risk factor for the development of cirrhosis and hepatocellular carcinoma (HCC). The association of intestinal microbiota alteration with progressive liver disease has been investigated in recent studies. Overgrowth of potentially pathogenic bacteria of gram-negative species and, in particular, a significant increase in the fecal count of Escherichia coli (E. coli) are characterized in the presence of HCC. This study was conducted to describe the characteristics of the intestinal microbiota related to the presence of HCC in HBV-carrier patients. The available literature indicates the colonization of E. coli as principal source of portal vein lipopolysaccharide (LPS), in the gut may contribute to the carcinogenesis process by inducing chronic inflammation. This understanding could help to predict the clinical outcomes in HBV-carrier patients and innovative strategies to reduce the virulence of liver disease from intestinal dysbiosis.
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http://dx.doi.org/10.1002/cam4.1550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051233PMC
May 2018

Significant SNPs Related to Telomere Length and Hepatocellular Carcinoma Risk in Chronic Hepatitis B Carriers

Asian Pac J Cancer Prev 2018 Mar 27;19(3):585-590. Epub 2018 Mar 27.

Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. Email:

Chronic hepatitis B virus (HBV) infection increases the risk of developing cirrhosis and hepatocellular carcinoma (HCC) with suspected interactions between virus replication and host immune responses. A number of reports have suggested that telomerase function may be involved in chronic hepatitis B (CHB) pathogenesis, but positive or negative associations with HCC risk remain for discussion. Mean telomere length is an indicator of biological aging and it has been reported that reduction in NBV carriers compared to normal individuals. In somatic cells, telomeres contain simple, tandemly repeated G-rich sequences that frequently are reduced by 50 to 200 base pairs at each cell division. Several genome-wide association studies (GWAS) in diverse ethnic populations have revealed eleven single nucleotide polymorphisms (SNPs) linked to telomere length. Two of these, rs398652 and rs621559, have prognostic value and could be used as genetic markers. This review describes current knowledge concerning telomerase activity and telomere length as well as significant polymorphisms in HBV-related HCC patients. In particular, to cast light on genotype-phenotype interactions, we used SNPnexus to evaluate effects of the two SNPs on risk of disease and complex disorders.
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http://dx.doi.org/10.22034/APJCP.2018.19.3.585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980828PMC
March 2018

Kaempferol increases apoptosis in human acute promyelocytic leukemia cells and inhibits multidrug resistance genes.

J Cell Biochem 2018 02 20;119(2):2288-2297. Epub 2017 Oct 20.

Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Acute promyelocytic leukemia (APL) is one of the most life-threatening hematological malignancies. Defects in the cell growth and apoptotic pathways are responsible for both disease pathogenesis and treatment resistance. Therefore, pro-apoptotic agents are potential candidates for APL treatment. Kaempferol is a flavonoid with antioxidant and anti-tumor properties. This study was designed to investigate the cytotoxic, pro-apoptotic, and differentiation-inducing effects of kaempferol on HL-60 and NB4 leukemia cells. Resazurin assay was used to determine cell viability following treatment with kaempferol (12.5-100 μM) and all-trans retinoic acid (ATRA; 10 μM; used as a positive control). Apoptosis and differentiation were also detected using propidium iodide and NBT staining techniques, respectively. Furthermore, the expression levels of genes involved in apoptosis (PI3 K, AKT, BCL2, BAX, p53, p21, PTEN, CASP3, CASP8, and CASP9), differentiation (PML-RAR and HDAC1), and multi-drug resistance (ABCB1 and ABCC1) were determined using quantitative real-time PCR. The protein expressions of Bax/Bcl2 and casp3 were confirmed using Western blot. The results showed that kaempferol decreased cell viability and increased subG1 population in the tested leukemic cells. This effect was associated with decreased expression of Akt, BCL2, ABCB1, and ABCC1 genes, while the expression of CASP3 and BAX/BCL-2 ratio were significantly increased at both gene and protein levels. Kaempferol promoted apoptosis and inhibited multidrug resistance in a concentration-dependent manner, without any differential effect on leukemic cells. In conclusion, this study suggested that kaempferol may be utilized as an appropriate alternative for ATRA in APL patients.
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http://dx.doi.org/10.1002/jcb.26391DOI Listing
February 2018

Pancreatic Cancer is Associated with Peripheral Leukocyte Oxidative DNA Damage

Asian Pac J Cancer Prev 2017 05 1;18(5):1349-1355. Epub 2017 May 1.

Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. Email:

Background: DNA damage accumulation has been linked to the cancer phenotype. The purpose of this study was to compare the levels of DNA base 8-hydroxy-2′-deoxyguanosine (8-OHdG) and C-reactive protein (CRP) inflammatory markers in healthy controls and pancreatic cancer patients from a hospital-based case-control study. Materials and Methods: Fifty-five pancreatic cancer patients and 55 healthy controls were enrolled from a pool of patients referred to the Endoscopic Ultrasound (EUS) center. Analysis of DNA content of peripheral blood cells was conducted for 8-OHdG with the 32P-postlabelling assay. Serum CRP levels were measured by high-sensitivity assays and demographic data for comparison were collected from individual medical records. Results: The group of cases showed significant increased median (IQR) 8-OHdG DNA adducts/106 nucleotides and CRP compared to the controls (208.8 (138.0-340.8) vs 121.8 (57.7-194.8) RAL value; P<0.001) and (3.5 (1.5-8.6) vs 0.5 (0.2-1.5) mg/L P<0.001). A number of conditional regression models confirmed associations of pancreatic cancer with oxidative DNA damage in peripheral leukocytes.Conclusions: Our findings suggest the importance of leukocyte 8-OHdG adducts as an indicator for systemic oxidative DNA damage in pancreatic cancer patients. In addition to increase in the CRP inflammatory marker, this supports the impact of inflammation in the occurrence of pancreatic cancer as well as inflammatory responses during cancer development.
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http://dx.doi.org/10.22034/APJCP.2017.18.5.1349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555546PMC
May 2017

Kaempferol increases apoptosis in human cervical cancer HeLa cells via PI3K/AKT and telomerase pathways.

Biomed Pharmacother 2017 May 1;89:573-577. Epub 2017 Mar 1.

Research Center for Non Communicable Diseases, Jahrom University of Medical Sciences, Motahari Avenue, Jahrom, Iran. Electronic address:

Cervical cancer is one of the most frequent cancers in women worldwide. Defects in the apoptotic pathways are responsible for both the disease pathogenesis and its therapy resistance. It is thus a good candidate for treatment by pro-apoptotic agents. Kaempferol as a flavonoid has antioxidant and anti-tumor properties. Kaempferol has been shown to induce apoptosis and cell death in cancer cells. However, due to the problems in the treatment of cervical cancer, this study is designed to investigate the molecular mechanism by which kaempferol suppresses the growth of cervical cancer HeLa cell as compared with HFF cells (normal cells). Cells treated with kaempferol (12-100μM) and 5-FU (1-10μM), as the positive control, up to 72h. Cell viability was determined by MTT assay and real time PCR was used to investigate apoptosis and telomerase genes expression. The results showed that kaempferol decreased cell viability as concentration- and time-dependently. IC values were 10.48μM for HeLa and 707.00μM for HFF cells, as compared with 1.40μM and 16.38μM for 5-FU after 72h treatment, respectively. Also, kaempferol induced cellular apoptosis and aging through down-regulating the PI3K/AKT and hTERT pathways. This study suggests that kaempferol may be a useful adjuvant therapeutic agent in the treatment of cervical cancer.
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http://dx.doi.org/10.1016/j.biopha.2017.02.061DOI Listing
May 2017

Expression Analysis of Previously Verified Fecal and Plasma Dow-regulated MicroRNAs (miR-4478, 1295-3p, 142-3p and 26a-5p), in FFPE Tissue Samples of CRC Patients.

Arch Iran Med 2017 Feb;20(2):92-95

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-related mortality worldwide. Early diagnosis of this neoplasm is critical and may reduce patients' mortality. MicroRNAs are small non-coding RNA molecules whose expression pattern can be altered in various diseases such as CRC.

Methods: In this study, we evaluated the expression levels of miR-142-3p, miR-26a-5p (their reduced expression in plasma samples of CRC patients was previously confirmed), miR-4478 and miR-1295-3p (their reduced expression in stool samples of CRC patients was previously confirmed) in tissue samples of CRC patients in comparison to healthy subjects. To achieve this purpose, total RNA including small RNA was extracted from 53 CRC and 35 normal subjects' Formalin-fixed, Paraffin-embedded (FFPE) tissue samples using the miRNeasy FFPE Mini Kit. The expression levels of these four selected miRNAs were measured using quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR).

Results: We found that the expression levels of miR-4478 and miR-1295b-3p (two previously down-regulated fecal miRNAs) were significantly decreased in FFPE samples of CRC patients compared to healthy controls. On the other hand, no significant differences were seen in expression levels of miR-142-3p and miR-26a-5p (two previously down-regulated circulating miRNAs) in FFPE samples between these two groups.

Conclusion: Regarding current findings, it may be concluded that to diagnose CRC patients based on the miRNAs approach, stool samples are more likely preferable to plasma samples; nevertheless, additional studies with more samples are needed to confirm the results.
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http://dx.doi.org/0172002/AIM.006DOI Listing
February 2017

The Relationship between Zinc Levels and Autism: A Systematic Review and Meta-analysis.

Iran J Child Neurol 2016 ;10(4):1-9

Research Committee, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran.

Objective: Autism is a complex behaviorally defined disorder.There is a relationship between zinc (Zn) levels in autistic patients and development of pathogenesis, but the conclusion is not permanent.

Materials & Methods: The present study conducted to estimate this probability using meta-analysis method. In this study, Fixed Effect Model, twelve articles published from 1978 to 2012 were selected by searching Google scholar, PubMed, ISI Web of Science, and Scopus and information were analyzed. I² statistics were calculated to examine heterogeneity. The information was analyzed using R and STATA Ver. 12.2.

Results: There was no significant statistical difference between hair, nail, and teeth Zn levels between controls and autistic patients: -0.471 [95% confidence interval (95% CI): -1.172 to 0.231]. There was significant statistical difference between plasma Zn concentration and autistic patients besides healthy controls: -0.253 (95% CI: 0.498 to -0.007). Using a Random Effect Model, the overall Integration of data from the two groups was -0.414 (95% CI: -0.878 to -0.051).

Conclusion: Based on sensitivity analysis, zinc supplements can be used for the nutritional therapy for autistic patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100031PMC
January 2016

Opium use, cigarette smoking, and alcohol consumption in relation to pancreatic cancer.

Medicine (Baltimore) 2016 Jul;95(28):e3922

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran Digestive Disease Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran Department of Public Health Analysis, School of Community Health and Policy, Morgan State University, Baltimore, MD Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences Gastrointestinal and Liver Disease Research Center, Firoozgar Hospital, Iran University of Medical Sciences Sasan Alborz Biomedical Research Center, Masoud Gastroenterology and Hepatology Clinic, Tehran, Iran Division of Gastroenterology and Hepatology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD American Cancer Society, Atlanta, GA Institute for Transitional Epidemiology and the Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY.

Background And Aims: Although several studies have suggested opium as a risk factor for cancers of the esophagus, stomach, larynx, lung, and bladder, no previous study has examined the association of opium with pancreatic cancer. We aimed to study the association between opium use and risk of pancreatic cancer in Iran, using a case-control design. We also studied the association of cigarette smoking and alcohol consumption with pancreatic cancer, for which little information was available from this population.

Methods: Cases and controls were selected from patients who were referred to 4 endoscopic ultrasound centers in Tehran, Iran. We recruited 316 histopathologically (all adenocarcinoma) and 41 clinically diagnosed incident cases of pancreatic cancer, as well as 328 controls from those with a normal pancreas in enodosonography from January 2011 to January 2015. We used logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: After adjustment for potential confounders, opium use (OR 1.91; 95% CI 1.06-3.43) and alcohol consumption (OR 4.16; 95% CI 1.86-9.31) were significantly associated with an increased risk of pancreatic cancer. We did not find an association between ever tobacco smoking and pancreatic cancer risk (OR 0.93; 95% CI 0.62-1.39).

Conclusion: In our study, opium use and alcohol consumption were associated with an increased risk of pancreatic cancer, whereas cigarette smoking was not.
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http://dx.doi.org/10.1097/MD.0000000000003922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4956779PMC
July 2016

Inverse Association of Plasma Level of Glutathione Peroxidase with Liver Fibrosis in Chronic Hepatitis B: Potential Role of Iron.

Middle East J Dig Dis 2016 Apr;8(2):122-30

Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

BACKGROUND Oxidative stress has a major pathogenic role for liver damage following chronic hepatitis B. Glutathione peroxidase (Gpx) is necessary in oxidative state mechanism that is generally down-regulated by Hepatitis B virus (HBV) infection. On the other hand, disorders of iron homeostasis have been found out in HBV infected patients. Therefore, the objective of this study was to assess the interplay of Gpx and serum iron on clinical and virological features of patients with chronic HBV infection. METHODS One hundred and fifty adult, treatment-naïve, patients with chronic hepatitis B were randomly designated from an ongoing cohort of patients with HBV. Plasma Gpx1 concentration and HBV DNA quantity were measured. Liver stiffness was measured by transient elastography. RESULTS Serum iron had a positive association with HBV DNA count in the total population. Serum iron was not associated with liver stiffness. However, HBV DNA was significantly associated with liver stiffness only in male patients. Serum Gpx was inversely associated with liver stiffness. Serum iron and Gpx had indirect effects on liver stiffness via HBV DNA count. We observed dissimilar effects of serum iron on HBV DNA and Gpx on liver stiffness in male and female patients. CONCLUSION We identified interplay of serum iron and Gpx1 in relation to level of liver fibrosis in patients with chronic hepatitis B. Our results propose that oxidative stress and serum iron are differentially implicated in the progression of chronic hepatitis B in male and female patients.
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http://dx.doi.org/10.15171/mejdd.2016.17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885611PMC
April 2016

Downregulation of Plasma MiR-142-3p and MiR-26a-5p in Patients With Colorectal Carcinoma.

Iran J Cancer Prev 2015 May 22;8(3):e2329. Epub 2015 May 22.

Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, IR Iran.

Background: Colorectal cancer is one of the most commonly diagnosed cancers and cancer- related death worldwide. Identification of new specific biomarkers could be helpful to detection of this malignancy. Altered plasma microRNA expression has been identified in many cancers, including colorectal cancer.

Objectives: The main objective of this study was to identify the circulating microRNAs with the most expression changes in colorectal cancer patients compared with neoplasm free healthy individuals.

Materials And Methods: MicroRNA expression profiling was performed on plasma samples of 37 colorectal cancer patients and 8 normal subjects using microRNA microarray. Quantitative real-time reverse transcription polymerase chain reaction was used to validate the two selected altered microR NAs. Plasma samples from 61 colorectal cancer patients and 24 normal subjects were used in our validation study.

Results: In profiling study we found a panel of six plasma microRNAs with significant downregulation. MicroRNA-142-3p and microRNA-26a-5p were selected and validated by polymerase chain reaction. Our results demonstrated that expression levels of plasma microRNA-142-3p and microRNA-26a-5p were significantly downregulated in patients with colorectal cancer when compared to control group.

Conclusions: Our findings suggest that downregulation of plasma microRNA-142-3p and microRNA-26a-5p might serve as novel noninvasive biomarkers in the diagnosis of colorectal cancer, although more studies are needed to highlight the theoretical strengths.
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http://dx.doi.org/10.17795/ijcp2329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581368PMC
May 2015

The possible impact of sortilin in reducing HBsAg expression in chronic hepatitis B.

J Med Virol 2016 Apr 8;88(4):647-52. Epub 2015 Sep 8.

Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Hepatitis B virus (HBV) infection is a major global health problem. Chronically infected people are at risk for progressive hepatic fibrosis and consequent cirrhosis. Hepatitis B surface antigen (HBsAg) level in serum is a complementary marker for intrahepatic HBV DNA and covalently closed circular DNA (cccDNA). Sortilin-1 (SORT1) has been reported to be involved in the post-Golgi vesicle trafficking of Apo lipoproteins degradation pathways. This study was designed to evaluate the hepatic and serum expression of HBsAg and its association with hepatic SORT1 gene expression in patients with chronic HBV. Thirty chronic hepatitis B patients with histological examination results were enrolled in this study. Liver biopsies were analyzed for hepatic HBsAg and SORT1 gene expression by immunohistochemistry and quantitative real time PCR (qRT-PCR), respectively. Twenty seven out of 30 (90%) liver biopsies had positive staining for HBsAg and showed a significant inverse association with hepatic SORT1 fold change gene expression (β = -0.5, P = 0.042). There was significant association between HBV DNA levels and HBsAg expression in hepatocyte or serum titer of HBsAg (r = 0.39, P = 0.029; r = 0.39, P = 0.032 respectively). Serum ALT was also correlated with hepatic activity index (HAI) score (β = 0.6, P = 0.001). Inverse association between hepatic SORT1 gene expression and hepatic HBsAg expression indicates the possible role of sortilin in HBsAg particle formation.
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http://dx.doi.org/10.1002/jmv.24367DOI Listing
April 2016

Central Obesity and Advanced Liver Stiffness in Hepatitis B: Result from Golestan Hepatitis B Cohort Study.

Arch Iran Med 2015 Sep;18(9):562-6

Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Background: Chronic infection with the hepatitis B virus and obesity may both contribute synergistically to liver disease, although relatively few studies have investigated this hypothesis. Therefore, in this study, we evaluated the relationship between central obesity and the liver stiffness in the Golestan Hepatitis B cohort study (GHBCS).

Methods: Our study included 304 chronic hepatitis B (CHB) patients enrolled from GHBCS. Liver stiffness measurement (LSM) and laboratory tests were performed after a follow-up of 4 years (2012). The hepatitis B viral load was measured at the baseline and follow-up using the real-time PCR method. Waist circumference ≥ 102 cm in men and ≥ 89 cm in women (central obesity) was considered to be abnormal. Advanced liver stiffness (ALS) was defined as LSM ≥ 8 KPa. Statistical analysis was performed using SPSS-V17. Logistic regression was used to test predictors of advanced liver stiffness (LSM ≥ 8 KPa). Linear regression was used to test the predictive value of variables in ALT (as a continuous variable). P-value of less than 0.05 was considered statistically significant.

Results: Among these CHB patients, 19 (7.4%) cases with a mean (±SD) age of 49.5 (±6.3) developed ALS after 4 years of follow-up. Multivariate analysis showed a significant predictive role of central obesity and viral load in ALS.

Conclusions: Central obesity is related to the liver stiffness in chronic hepatitis B patients.
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http://dx.doi.org/0151809/AIM.003DOI Listing
September 2015

Negative Association of Plasma Levels of Vitamin D and miR-378 With Viral Load in Patients With Chronic Hepatitis B Infection.

Hepat Mon 2015 Jun 23;15(6):e28315. Epub 2015 Jun 23.

Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, IR Iran.

Background: Chronic Hepatitis B (CHB) is accompanied by inflammation of liver because of infection with Hepatitis B Virus (HBV). Previous studies revealed an inverse association between vitamin D and HBV DNA levels.

Objectives: The current study aimed to investigate the levels of 25 (OH) D3 (the steady form of vitamin D), miR-378 and HBV DNA in the patients with CHB.

Patients And Methods: One hundred and seventy three patients with HBeAg negative CHB were recruited for the study. Plasma levels of HBVDNA and 25 (OH) D3 were quantified. The expression level of miR-378 in plasma was measured by a relative quantitative Real Time Polymerase Chain Reaction (qRT-PCR) assay.

Results: In the pathway regression analysis, the plasma level of 25 (OH) D3 showed a significant inverse correlation with plasma levels of HBV DNA (-0.198, P = 0.008) and direct correlation with miR-378 (0.188, P = 0.013). Similarly plasma level of miR-378 had inverse association with HBV DNA level (-0.177, P = 0.020).

Conclusions: These results suggest that vitamin D could involve in a miRNA- mediated regulatory pathway in control of HBV replication. Further studies are recommended to understand the effects of miR-378 and anti-infective action of vitamin D on Hepatitis B Virus.
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http://dx.doi.org/10.5812/hepatmon.28315v2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533027PMC
June 2015

Repository of Human Blood Derivative Biospecimens in Biobank: Technical Implications.

Middle East J Dig Dis 2015 Apr;7(2):61-8

Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Human biorepositories are collection of biological samples and health information from a large number of participants generally in the cohort studies. The main purpose of established biobanks is organization of biomedical research for upgrading the knowledge of human disorders from cancer to infectious and rare disease. The studies of generation relationships and understanding the preclinical stages of ageing are also from the solution of bitobank. This review overview the significance and storage condition of biospecimens including whole blood, red blood cells (RBC), buffy coat, plasma, serum, DNA and RNA that derived from blood in human biobanks. These biological samples provide valuable information on the prevalence of germline mutations, epigenetic modifications or interaction between genes and proteins in associated with the development of certain types of disease. The quality of biospecimen in biobanks is a powerful tool for valid identification of biomarkers. Therefore optimum qualities of human biological samples in long time storage that have been assessed in several studies also indicate in this review.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430793PMC
April 2015

Association of Mutations in the Basal Core Promoter and Pre-core Regions of the Hepatitis B Viral Genome and Longitudinal Changes in HBV Level in HBeAg Negative Individuals: Results From a Cohort Study in Northern Iran.

Hepat Mon 2015 Feb 21;15(2):e23875. Epub 2015 Feb 21.

Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, IR Iran.

Background: Although certain HBV mutations are known to affect the expression of Hepatitis e antigen, their association with HBV viral level or clinical outcomes is less clear.

Objectives: We evaluated associations between different mutations in the Basal Core promoter (BCP) and Pre-core (PC) regions of HBV genome and subsequent changes in HBV viral DNA level over seven years in a population of untreated HBeAg negative chronic hepatitis B (CHB) participants in Northeast of Iran.

Materials And Methods: Participants in the current study were drawn from the Golestan Hepatitis B Cohort Study (GHBCS), a cohort of approximately 2590 HBsAg positive subjects (living in Gonbad city) embedded in the Golestan Cohort Study (GCS). At baseline, HBsAg was measured in all participants and revealed 2590 HBsAg positive cases. We randomly selected 304 participants who their blood sample were taken at both baseline and seven years later in follow-up and had not been treated for HBV during this time. HBV viral load were assessed at baseline and at year 7. The BCP and PC regions of the HBV DNA, at baseline, were amplified via hemi-nested PCR and sequenced by cycle sequencing. At year 7, liver stiffness was assessed by fibroscan; also, other parameters of liver disease were assessed following standard clinical protocols. Associations were assessed via tabulation, chi-square, t-tests and logistic regression. P values < 0.05 were considered statistically significant and all tests were two-sided.

Results: Among 304 HBsAg positive participants, 99 had detectable HBV DNA at study baseline. Of these, 61.6% had PC mutations (48.5% A1896 and 25.2% G1899). In contrast to other mutations, A1896 was associated with a higher proportion of detectable HBV DNA at year 7 (39.6%) compared to patients with the wild type (13.7%) (OR: 4.36, CI95% = 1.63-11.70; P Value = 0.002). Although participants with the A1896 mutation had higher year-7 HBV viral load than participants with G1896 (2.30 ± 1.66 IU/mL vs. 1.76 ± 1 IU/mL among patients with detectable HBV; P value = 0.052), no association was observed with either serum level ALT or liver stiffness. Interestingly, mutations in the basal core promoter (BCP) region had no significant effect on virus DNA detection.

Conclusions: In this population with chronic HBeAg negative hepatitis B, an association was observed between the G1896A mutation in the Pre-core region of HBV and subsequent level of HBV DNA seven years later, which indicated that mutations in this region of HBV genome may contribute to disease progression in these patients and play an important role in HBV natural course of disease.
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http://dx.doi.org/10.5812/hepatmon.23875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350247PMC
February 2015

Direct Sequencing of Cyclooxygenase-2 (COX-2) Revealed an Intronic Variant rs201231411 in Iranian Patients with Pancreatic Cancer.

Middle East J Dig Dis 2015 Jan;7(1):14-8

1. Liver and Pancreatobiliary Diseases Research Institute, Digestive Diseases.

BACKGROUND There are hoarding documents for the biological importance of cyclooxygenase-2 (COX-2) in pancreatic carcinogenesis. We aimed to thoroughly investigate the DNA sequence variations of whole COX-2 exons in a large case-control study of pancreatic cancer by direct sequencing. METHODS The entire exonic regions of COX-2 including 10 exons were sequenced in the germline DNA of 96 patients with pancreatic cancer. Selected variants within exons six to seven (E6E7) amplicon from the test panel were genotyped in 96 controls. RESULTS The COX-2 gene was demonstrated to be genetically conserved. Four missense mutations were found in three cases. However the common variant c.724-10_724-7delATTT (rs201231411) that is located in intron 6, showed significant difference between cases and controls (21 [21.9%] vs 11 [%11.5], p=0.05). CONCLUSION This study determined that COX-2 has a conservative sequence, which is required for its enzymatic activity and supports the important role of this enzyme's expression in pancreatic cancer rather than any changes in its activity. The effect of intronic variant rs201231411 on COX-2 expression could be analyzed in future studies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4293795PMC
January 2015

Immune-Regulatory Events in the Clearance of HBsAg in Chronic Hepatitis B: Focuses on HLA-DP.

Middle East J Dig Dis 2015 Jan;7(1):5-13

1. Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Successful clearance of hepatitis B virus (HBV) is a promising event in which host's immune system will attempt to get rid of the virus. The immunological events of HBsAg seroclearance have attracted great attention in both natural history investigations and therapeutic trials. Recent genome-wide association studies (GWAS) has confirmed polymorphisms in the human leukocyte antigen (HLA)-DP locus associated with spontaneous HBV clearance. In this review the impact of host immune response in declining HBsAg during the natural history of the infection has been discussed.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4293802PMC
January 2015