Publications by authors named "Hamidreza Mahmoudzadeh-Sagheb"

41 Publications

Withania coagulans extract attenuates oxidative stress-mediated apoptosis of cerebellar purkinje neurons after ischemia/reperfusion injury.

Metab Brain Dis 2021 May 10. Epub 2021 May 10.

Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, IR, Iran.

Cerebral ischemia/reperfusion (I/R) is known to increase reactive oxygen species (ROS) generation, consequences of oxidative stress (OS), and neuronal death in the susceptible brain areas including the cerebellum. Newly, remarkable attention has been paid to a natural diet with the capability to scavenge ROS. Withania coagulans root extract (WCE) is rich in components with antioxidants properties. Therefore, this study aimed to evaluate the effect of WCE on cerebellar Purkinje cells (PCs) against OS-mediated apoptosis after I/R injury. In this experimental study 64 male adult Wistar rats were randomly divided into 4 groups (n = 16) as follows: control, sham, I/R, and WCE 1000 + I/R. I/R animals were pretreated with daily administration of hydro-alcoholic WCE (1000 mg/kg) or distilled water as a vehicle for 30 days before I/R injury. After 72 h, the animals were sacrificed, the cerebellum tissue was removed and used for biochemical (CAT, SOD, GPx, and MDA levels) and histopathological (Nissl and TUNEL staining) assays. Findings showed that the MDA level and the number of apoptotic neurons significantly increased and viable Purkinje neurons decreased in I/R injury (p < 0.05). Administration of 1000 mg/kg WCE reduced MDA level and enhanced antioxidants activity including CAT, SOD, and GPx significantly. In addition, intact surviving PCs increased. At the same time, TUNEL-positive neurons decreased significantly in the WCE pre-treated group (p < 0.05). These findings suggest that WCE can counteract cerebral I/R-induced OS and associated neuronal death by enhancement of ROS scavenging and antioxidant capacity. It appears that pre-treatment with 1000 mg/kg WCE for thirty days can protect PCs against OS-mediated apoptosis after I/R injury.
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http://dx.doi.org/10.1007/s11011-021-00745-0DOI Listing
May 2021

Cannabinoid receptor type-1 and its correlation with CB1 gene polymorphism-1359G/A in ectopic pregnancy compared to the control group.

J Obstet Gynaecol Res 2021 Apr 28;47(4):1256-1264. Epub 2021 Jan 28.

Department of Obstetrics and Gynecology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.

Aim: Ectopic pregnancy (EP) is one of the most important causes of maternal mortality. This study aimed to evaluate the immunohistochemical (IHC) expression of the cannabinoid receptor type-1 (CB1) and its association with CB1-1359G/A gene polymorphism (rs1049353) in the fallopian tubes in EP compared to controls.

Methods: In this case-control study, 100 women with EP (cases) and 100 women that underwent abdominal surgery due to the hysterectomy or uterine tubal ligation (healthy controls) were included. Genotyping of CB1-1359G/A polymorphism, tissue expression of CB1 at the protein and mRNA levels were studied using restriction fragment length polymorphism, IHC method, and quantitative real-time polymerase chain reaction (qRT-PCR) analysis.

Results: Genotyping showed that in EP, the frequency of AA, AA+AG genotypes, and A allele was significantly higher than healthy control subjects (p = 0.001). Also, patients with EP had significantly increased IHC expression of CB-1 compared to the control samples (p = 0.016). Patients with AA and AG genotypes had a significantly higher IHC expression of CB-1 compared to the GG genotype. qRT-PCR analysis showed that patients with EP had significantly increased expression of CB-1 compared to the control samples (p < 0.001). Patients with AA and AG genotypes had higher significant mRNA expression of CB-1 compared to the GG genotype.

Conclusions: CB1 is likely to be effective in creating innate immunity in humans and can affect the process of EP in the fallopian tube. CB1 is also a pathological valuable factor in identifying the pathway of inflammation during ectopic implantation.
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http://dx.doi.org/10.1111/jog.14688DOI Listing
April 2021

Elevated immunoexpression of interferon-gamma in placenta tissue samples from pregnancies complicated with preeclampsia compared to the placenta previa.

Pregnancy Hypertens 2020 Oct 11;22:175-180. Epub 2020 Sep 11.

Infectious Diseases and Tropical Medicine Research Center, Zahedan University of Medical Sciences, Zahedan, Iran; Department of Histology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran. Electronic address:

Aim: The present study aimed to compare the immunohistochemical expression of interferon-gamma (IFN-γ) in placentas from pregnancies complicated with preeclampsia (PE) and placenta previa (PP) and normal healthy placentas.

Methods: Placentas were collected from cases of PE, PP and normal pregnancies as a control group (10 placentas in each group). All the deliveries were at full-term (37-42 weeks) by cesarean section and newborns were without any complications or diseases. Expression of IFN-γ in the placenta was determined using immunohistochemical methods and findings were compared. Statistical analysis was performed by Mann-Whitney and Kruskal-Wallis tests for comparing the mean values of IFN-γ expression in the placentas from PE, PP and control groups. Our results showed that the immunoexpression of IFN-γ in syncytiotrophoblast cells, extravillous trophoblast cells, vascular endothelium and basal plate of the placenta from PE group were more than control and PP groups (P < 0.05) and in PP group were more than the control group (P < 0.05).

Conclusion: We concluded that the immunoexpression of IFN-γ was increased significantly in placenta tissue samples of the PE group compared to the PP group and normal pregnancies. It is proposed that IFN-γ has an important role in the different mechanisms of PE and PP progression.
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http://dx.doi.org/10.1016/j.preghy.2020.08.003DOI Listing
October 2020

Interferon gamma gene polymorphisms and chronic hepatitis B infections in an Iranian population.

Turk J Gastroenterol 2020 07;31(7):515-521

Infectious Diseases and Tropical Medicine Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran; Department of Histology, Zahedan University of Medical Sciences, Zahedan, Iran.

Background And Aims: Chronic hepatitis B is an important health problem in all countries. I Interferon gamma is a pro-inflammatory Th1 cytokines, which can exert antiproliferative and antitumor activity. Some SNPs in IFN-γ and IFN-γR1 genes may influence the susceptibility to HBV. Here, we evaluated the impact of interferon gamma (+874 T/A) and its receptor (-611A/G, +189G/C and +95C/T) polymorphisms and the risk of HBV in Iranian patients.

Materials And Methods: SNPs of interferon gamma and its receptor genotypes were determined in 221 infected patients with HBV and 200 people without HBV using ARMS-PCR and PCR- RFLP method.

Results: In this study, we showed an obvious relationship between IFN-γ SNPs and susceptibility to chronic HBV. Our findings suggest that IFN-γ-874A allele increases the risk of disease and carriers of the T allele have reduced susceptibility to infection. In addition, there was not any relationship between the -611A/G, +189G/C and +95C/T regions of IFN-γ R1 and HBV.

Conclusions: Our observations demonstrate +874 T/A SNP as a predicting factor in patients who have the risk of HBV.
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http://dx.doi.org/10.5152/tjg.2020.181024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480198PMC
July 2020

Hepatocyte paraffin 1 and arginase-1 are effective panel of markers in HBV-related HCC diagnosis in fine-needle aspiration specimens.

BMC Res Notes 2020 Aug 20;13(1):388. Epub 2020 Aug 20.

Infectious Diseases and Tropical Medicine Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran.

Objective: In order to make successful treatment for HBV-related hepatocellular carcinoma, an early diagnosis is necessary. In this research we aimed to evaluate the IHC staining pattern of Hepatocyte paraffin 1 and arginase-1 and their performance in early diagnosis of HCC. The incidence of HepPar-1 and Arg-1 were evaluated by IHC in 121 patients (HBV, HCC, HBV + HCC) and 30 healthy subjects.

Results: Arg-1 had significantly increased sensitivity in identification of HBV + HCC patients compared to HepPar-1 (P < 0.001). The sensitivity of arginase-1 is 96.3% whereas, the sensitivity of HepPar-1 is 72.7%. Arg-1 had higher specificity in identification of HBV + HCC patients compared to HepPar-1 (P < 0.05). With one positive marker, the sensitivity, the specificity and the positive predictive values and negative predictive value were 84.3%, 82.4%, 88.6% and 85.4% respectively. Also with one positive marker, the sensitivity and negative predictive value were significantly higher compared to the both 2 positive combinations. It was concluded that Arg-1 can improves the ability to detect HBV + HCC patients when compared with HepPar-1. When, both markers being positive, the specificity and PPVs of this combination were fairly higher. Concurrent use of these two proteins may be one of the best HCC detection patterns in needle specimens.
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http://dx.doi.org/10.1186/s13104-020-05230-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450594PMC
August 2020

Upregulation of elafin expression in the fallopian tube of ectopic tubal pregnancies compared to the normal tubes.

J Reprod Immunol 2020 09 21;141:103136. Epub 2020 May 21.

Department of Histology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran; Infectious Diseases and Tropical Medicine Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran. Electronic address:

Background: Ectopic pregnancy is one of the most important causes of maternal deaths and fallopian tubes are the location of 95% of ectopic pregnancies. Elafin is a natural antimicrobial molecule that plays an important role as an anti-inflammatory agent in mucosal surfaces and has been found in the female reproductive tract.

Objectives: The aim of this study was to investigate elafin expression, in the fallopian tube mucosa of ectopic pregnancies compared to the normal tubes using immunohistochemistry (IHC) techniques and quantitative reverse transcription (qRT)-PCR.

Methods: In this case-control study, uterine tube samples were obtained from patients with an indication for surgical removal of the tubes. The case group (n = 20) consisted of patients who were undergoing salpingectomy due to an ectopic pregnancy, the control group (n = 20) included patients who had a salpingectomy and hysterectomy. Using qRT-PCR and IHC, the expression of elafin was investigated in both study groups.

Results: Immunohistochemical expression of elafin in the epithelium and connective tissue was significantly increased in the implantation site of the patients in comparison with the control group (P < 0.001). The level of elafin mRNA increased in the mucous membrane of the fallopian tube from patients with the ectopic pregnancy compared to the normal mucosa (P < 0.001).

Conclusion: Increasing expression of elafin during an ectopic pregnancy may be a mechanism for enhancing innate immune response and be involved in related pathological conditions such as infection and ectopic implantation.
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http://dx.doi.org/10.1016/j.jri.2020.103136DOI Listing
September 2020

Structural changes in the brain of patients with relapsing-remitting multiple sclerosis compared to controls: a MRI-based stereological study.

Ir J Med Sci 2020 Nov 20;189(4):1421-1427. Epub 2020 May 20.

Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Background: Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system characterized by demyelination, inflammation, gliosis, and axonal loss. Nowadays, increasing scientific reports have focused on neurodegenerative processes and structural changes of the disease underlying pathogenesis.

Aim: The aim of this study is a structural analysis of brain magnetic resonance images (MRIs) in patients with relapsing-remitting multiple sclerosis (RRMS) comparing with normal individuals.

Methods: This case-control study was carried out on MRIs of 20 patients with RRMS and 20 healthy controls in Zahedan, Iran. MR images with 4-mm slice thickness and 0.5-mm intervals in three anatomical planes (coronal, sagittal, axial) were acquired. Then, stereological parameters, including volume and volume density of different parts of the brain, based on Cavalries' point counting method were measured in both groups. Data analyses were performed using Mann-Whitney U and Pearson's correlation tests.

Results: The results of the study showed that there were no significant differences in total brain, hemispheres, gray matter, and basal nuclei volume and volume density between the two groups (p ˃ 0.05). However, the left hemisphere, cerebellum, lateral ventricles, brainstem, corpus callosum, and white matter volume in RRMS patients were significantly lower than those in controls (p ˂ 0.05).

Conclusion: The findings showed that quantitative assessments based on stereological method on brain MRIs facilitate clarifying neuropathology of the disease. Also, it can be helpful as a simple index for following up the clinical situation and assessing therapeutic efficiency in MS patients. It may provide a precise treatment approach and justification of symptoms in patients with MS.
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http://dx.doi.org/10.1007/s11845-020-02253-zDOI Listing
November 2020

Polymorphisms of Gene is Associated with Chronic HBV Infection in Iranian Population.

Indian J Clin Biochem 2020 Apr 2;35(2):158-168. Epub 2019 Jan 2.

1Infectious Diseases and Tropical Medicine Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.

Survivin can affect the progression of infection and is considered as a marker of various malignancies. The aim of the study was to investigate the possible association of gene polymorphisms of survivin (-, -, -, -, -, -) and chronic hepatitis B infection in Iranian patients. The genotypes of survivin SNPs were investigated by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method using 100 chronic HBV infected patients (HBV), 40 spontaneously recovered HBV subjects and 100 healthy controls (C). Serum level of survivin was determined using ELISA method. The -, -, - and - alleles were associated with increased susceptibility to chronic hepatitis B infection ( = 0.001,  < 0.001,  = 0.003 and  < 0.001 respectively). Chronic HBV patients with -, - and - genotypes had higher levels of survvin. Survivin -, -, - and - gene polymorphisms may be associated with chronic HBV susceptibility in Iranian HBV patients.
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http://dx.doi.org/10.1007/s12291-018-0805-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093622PMC
April 2020

CCR5, MCP-1 and VDR Gene Polymorphisms Are Associated with the Susceptibility to HBV Infection.

Indian J Clin Biochem 2019 Oct 27;34(4):407-417. Epub 2018 Jun 27.

1Infectious Diseases and Tropical Medicine Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.

Genetic variants of chemokine and regulatory cytokines play functional roles in chronic HBV infection. The objective of the study, was to evaluate the association between the , -/, --/, -/, -/C SNPs and HBV susceptibility, in samples of Iranian populations. The , -/, -/, -/, -/ polymorphisms were analyzed by polymerase chain reaction and PCR-RFLP using 100 chronic HBV infected (HBV) patients, 40 spontaneously recovered HBV (SR) subjects and 100 healthy controls (C). Also, serum levels of protein were monitored. The study showed that the existence of -, - and - alleles significantly increased risk of chronic HBV infection. In addition, haplotype had a higher frequency in HBV patients than C and SR groups and might relate to the natural history of the infection. Statistical analysis indicated positive correlations between -/, -/, -/, -/ genotypes and serum levels of the CCR5, MCP-1 and VDR in HBV patients. According to the statistical analysis, significant associations with susceptibility to chronic HBV infection was observed with -/, -/, -/, -/ polymorphisms. In addition, no association of the SNP with the disease was found.
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http://dx.doi.org/10.1007/s12291-018-0772-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801280PMC
October 2019

Meta-analysis and systematic review of prognostic significance of Glypican-3 in patients with hepatitis B-related hepatocellular carcinoma.

Virusdisease 2019 Jun 28;30(2):193-200. Epub 2019 Mar 28.

1Infectious Diseases and Tropical Medicine Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.

Hepatocellular carcinoma (HCC) is a common malignant cancer and the second cause of cancer-related death worldwide. Glypican-3 () is established as an important prognostic factor for HCC but the results are still controversial. Moreover, its utility as an immunohistochemical marker for HCC is not conclusive. Herein we aimed to find the prognostic significance of in HCC patients. The PubMed, Web of Science, EMBASE, SCOPUS and Cochrane library databases were searched and eligible studies based on the expression and survival outcome of HCC (odds ratios or hazard ratios) included in the current meta-analysis. The STATA 12.0 and RevMan 5.3 software were used for statistical evaluations. 17 articles contained 2618 patients, were included in the recent meta-analysis. Our findings revealed a significant association between tumor stage, higher tumor grade, presence of vascular invasion, shorter overall survival, shorter disease-free survival and high expression of . The subgroup analyses based on sample size, cutoffs and follow-up period were also conducted to examine the association between and OS and also to increase the homogeneity of study. Current study found a significant association between expression and poor prognosis of HCC and specially related to the HCC invasion and progression. It was recommended to design more prospective studies based on the relationship between and HCC to confirm our results.
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http://dx.doi.org/10.1007/s13337-019-00517-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531550PMC
June 2019

Effects of gestational diabetes mellitus on stereological parameters and extravillous trophoblast cells of placenta compared to the control group.

J Obstet Gynaecol 2019 Oct 7;39(7):928-933. Epub 2019 May 7.

Department of Histology, School of Medicine, Zahedan University of Medical Sciences , Zahedan , Iran.

The quantitative changes of extravillous trophoblast cells (EVTs) in placenta of gestational diabetes mellitus (GDM) patients were investigated compared to healthy controls using stereological methods. The volumetric parameters of the placenta and EVTs were estimated using Cavalieri's principle and Physical Disector stereological methods. The placental volume and weight in the GDM group increased compared to the control group ( < .05). The difference in the total volume of intervillous space and blood vessels of the placenta between GDM and control groups was statistically significant ( < .05). In addition, there was a significant difference in the volume density of blood vessels and syncytiotrophoblast between the GDM group and the control group ( < .05). The total volume of the EVTs, nucleus and cytoplasm diameter, volume of the nucleus and cytoplasm, nucleus to cytoplasm ratio (N/C) of EVTs and the total number of EVTs per unit volume of the placenta in the GDM group showed a significant increase compared to the controls ( < .05). Impact statement It is reported that extravillous trophoblast cells (EVTs) played an important role in pregnancy complications. There are limited studies on the quantitative changes of EVTs in the placental bed of GDM patients. The results showed that volumetric parameters and number of EVTs were significantly altered in GDM placentas. These changes can be associated with disturbances in trophoblastic invasion in GDM pregnancies and may affect the development and survival of the embryo. In the present study, there is a new insight to placenta structure that probably could be useful to understanding possible mechanisms of pregnancy complications and the achievement of new therapeutic strategies. Further investigation on the molecular biology of these cells in pregnancy complications will be needed to clarify this hypothesis.
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http://dx.doi.org/10.1080/01443615.2019.1578948DOI Listing
October 2019

Immunomodulatory factors gene polymorphisms in chronic periodontitis: an overview.

BMC Oral Health 2019 02 12;19(1):29. Epub 2019 Feb 12.

Infectious Diseases and Tropical Medicine Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.

Background: Chronic periodontitis (CP), defines as destruction of the supporting tissues of the teeth and resorption of the alveolar bone. It is widespread in human populations and represent an important problem for public health. CP results from inflammatory mechanisms created by the interaction between environmental and host genetic factors that confer the individual susceptibility to the disease.

Aim: The aim of the current study was to explore and summarize some functional biomarkers that are associated with CP susceptibility.

Methods: CP is considered to be a multifactorial disease. The pathogenesis of multifactorial diseases is characterized by various biological pathways. The studies revealed that polymorphisms were associated with susceptibility to periodontal diseases. In other word, genetic variations can change the development of CP. However, there are some conflicting results, because there are different variations in frequency of some alleles in any populations. Therefore, we conducted the current review to completely understanding the special biomarkers for CP.

Results: There is some evidence that SNPs in the IL-1α, IL-1β, IL1RN, IL-6, IL-10, TNF-α, TGF-β1, IFN-γ and VDR may be associated with CP susceptibility.

Conclusion: In conclusion, numerous studies have reported the host genetic factors associated with CP susceptibility and related traits. Therefore, it is prevail to study the multiple SNPs and their effects to find the useful diagnosis methods. The current study will investigate the relationship between polymorphisms in cytokine genes and the susceptibility to the chronic periodontitis.
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http://dx.doi.org/10.1186/s12903-019-0715-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373099PMC
February 2019

Study of liver in HBV-related hepatocellular carcinoma: Stereology shows quantitative differences in liver structure.

Eur J Histochem 2018 Sep 18;62(3). Epub 2018 Sep 18.

Zahedan University of Medical Sciences, Infectious Diseases and Tropical Medicine Research Center, and Department of Histology.

Hepatocellular carcinoma is one of the main consequences of liver chronic disease. Hepatocellular carcinoma-related changes may be seen in patients with chronic hepatitis B. The aim of the current study was to quantitate liver tissue elements by stereological technique in patients with hepatitis B-related cancer and compare the results with control and only hepatitis B group. Needle liver biopsies from 40 patients with only chronic hepatitis B infection, from 41 patients with only early hepatocellular carcinoma, from 40 patients with early hepatitis B-related cancer and 30 healthy subjects (control group) were analyzed by stereological method using systematic uniform random sampling method. Haematoxylin and eosin stained sections were used. The numerical density of hepatocytes, hepatocyte volume, numerical density of Kupffer cells, volume density of the connective tissue in the portal space, and volume density of the connective tissue were assessed. Quantitative analysis of liver samples indicated that there were statistically significant differences in the numerical density of hepatocytes, hepatocyte volume, numerical density of Kupffer cells, volume density of the connective tissue in the portal space, and volume density of the connective tissue between control and hepatitis B-related cancer and hepatitis B groups. Quantitative, stereological technique is simple and reliable for evaluating HCC in chronic hepatitis B. It is useful for assessing the liver tissue parameters. Stereology is recommended for the diagnosis of people prone to cancer in patients with chronic hepatitis B.
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http://dx.doi.org/10.4081/ejh.2018.2950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166574PMC
September 2018

The relationship between L-leucine-7-amido-4-methyl coumarin 1 gene polymorphism and susceptibility to the chronic hepatitis B virus infection in an Iranian population.

J Res Med Sci 2018 26;23:62. Epub 2018 Jul 26.

Department of Biology, School of Biology, Damghan University, Damghan, Iran.

Background: Lamnin has important effects on human immunity system. The current study aimed to assess the role of L-leucine-7-amido-4-methyl coumarin 1 gene polymorphisms on hepatitis B virus (HBV) susceptibility.

Materials And Methods: The , and polymorphisms were analyzed using polymerase chain reaction (PCR) and PCR-reaction-restriction fragment-length polymorphism and amplification-refractory mutation system-PCR using three different groups including chronic HBV-infected patients, HBV patients who were resolved their infection spontaneously and healthy volunteers. Laminin concentrations were also measured in the blood of these individuals.

Results: People with , and alleles have an increased risk of HBV infection. Moreover, we found that CGTAT haplotype was more frequent in chronically infected people who could affect the mechanism of disease. Furthermore, there was a significant relationship between laminin concentration and , and genotypes in patients.

Conclusion: According to the statistical analysis, polymorphisms probably, related to the chronic HBV infection. In addition, no association of the single nucleotide polymorphisms with the disease was found.
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http://dx.doi.org/10.4103/jrms.JRMS_372_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091139PMC
July 2018

Evaluation of immunohistochemical expression of survivin and its correlation with -31G/C gene polymorphism in colorectal cancer.

Med Mol Morphol 2019 Jun 20;52(2):82-89. Epub 2018 Aug 20.

Infectious Diseases and Tropical Medicine Research Center, Zahedan University of Medical Sciences, Zahedan, Islamic Republic of Iran.

Colorectal cancer (CRC) placed among the most common neoplasm. Survivin is a member of the inhibitor apoptosis gene family. This gene could be associated with aggressive behavior in numerous types of cancers. The aim of the present study was to evaluate the immunohistochemical expression of survivin gene and its correlation with -31G/C polymorphism in CRC patients. This case-control study was performed on 90 cases: 30 adenocarcinoma, 30 adenomatous polyp, and 30 normal colon. Immunohistochemical expression of survivin evaluated on formalin-fixed paraffin-embedded tissue and -31G/C polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis. Results showed that the subjects carrying C/C genotype with 43.3% (p = 0.002' OR = 12.188, CI = 2.530-58.720) and G/C genotype with 43.3% (p = 0.032' OR = 4.432, CI = 1.133-17.341) significantly had increased risk of CRC compared with subjects carrying GG genotype. Allelic frequencies showed statistically significant difference (p = 0.001) among adenocarcinoma (G = 35%, C = 65%), adenomatous (G = 43.3, C = 56.7), and normal group (G = 68.3, C = 31.7). Immunohistological evaluation showed nuclear survivin protein expression in patients with the CC genotype higher than in patient with the GG and GC genotypes (p = 0.002). The results suggest that C allele of - 31G/C polymorphism in survivin might be cooperative in CRC development.
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http://dx.doi.org/10.1007/s00795-018-0204-0DOI Listing
June 2019

Concomitant use of heat-shock protein 70, glutamine synthetase and glypican-3 is useful in diagnosis of HBV-related hepatocellular carcinoma with higher specificity and sensitivity.

Eur J Histochem 2018 Jan 29;62(1):2859. Epub 2018 Jan 29.

Zahedan University of Medical Sciences.

Hepatocellular carcinoma is the third leading cause of cancer-related death worldwide and late diagnosis is the main cause of death in HCC patients. In this study expression patterns of HSP70, GPC3 and GS and their relationships with pathogenesis of HCC in Iranian patients were investigated. The expression of HSP70, GPC3 and GS were determined by immunohistochemistry and quantitative real-time PCR (q-PCR) methods, using 121 cases from patients with HBV alone, HCC without HBV, HBV+HCC and 30 normal tissues as control group. HSP70, GPC3 and GS were expressed in higher levels in HBV-related HCC samples compared to HBV alone group. The results showed that the labeling index of HSP70, GPC3 and GS are correlated with immunohistochemical and molecular expressions of HSP70, GPC3 and GS. The sensitivity and specificity for HCC diagnosis were 43.4% and 89.7% for HSP70, 64.3% and 90.4% for GPC3, and 60.7% and 94.3% for GS, respectively. The sensitivity and specificity of the panels with 3, 2 and 1 positive markers, regardless of which one, were 21.6% and 100%, 51.3% and 100% and 93.4% and 80.5% respectively. The current study demonstrated an association between HSP70, GPC3 and GS expressions and HBV-related HCC in our population. It was concluded that HSP70, GPC3 and GS expressions could be useful biomarkers for increasing the specificity and sensitivity of HCC diagnosis to acceptable level. Also, proper combinations of these 3 markers could improve diagnostic accuracy.
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http://dx.doi.org/10.4081/ejh.2018.2859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806503PMC
January 2018

Analysis of interleukin-10 gene polymorphisms in patients with chronic periodontitis and healthy controls.

Dent Res J (Isfahan) 2018 Jan-Feb;15(1):71-79

Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Background: Interleukin-10 (IL-10) is an anti-inflammatory cytokine that has important roles in the periodontal diseases. The IL10-1082, -819, and -592 polymorphisms in the promoter region of IL-10 gene have been associated with various IL-10 expressions. The aim of this study was to investigate the association between these gene polymorphisms with chronic periodontitis in a sample of Iranian populations from Southeast of Iran.

Materials And Methods: IL-10 single nucleotide polymorphisms were analyzed in 210 patients with chronic periodontitis (CP) and 100 individuals without CP by polymerase chain reaction-restriction fragment length polymorphism method. Statistical analysis of data was performed using the Chi-square test. The risk associated with single alleles, genotypes, and haplotypes were calculated by performing a multiple logistic regression analysis to estimate the odds ratio (OR) and 95% confidence interval (CI). < 0.05 for statistical significance.

Results: The prevalences of AG and GG genotypes of IL10-1082 were significantly different between CP and control groups in comparison to AA genotype (OR = 2.671; CI = 1.482-4.815; = 0.001 for AG vs. AA, OR = 4.151; CI = 2.128-8.097; < 0.001 for GG vs. AA). In addition, subjects with at least one IL10-1082-G allele were significantly had an increased risk for CP (OR = 2.157; CI = 1.531-3.038; < 0.001). The distribution of the IL10-819 and IL10-592 genotypes was not different between CP and control subjects ( = 0.109 and = 0.139, respectively). The combination of different genotypes showed that GCC haplotype was significantly different between groups (OR = 4.379; CI = 1.077-17.807; = 0.039).

Conclusion: The results demonstrated that IL10-1082 polymorphism was a putative risk factor for chronic periodontitis and associated with increased susceptibility to CP.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806433PMC
http://dx.doi.org/10.4103/1735-3327.223614DOI Listing
March 2018

Placenta structural changes in heavy smoking mothers: a stereological aspect.

Curr Med Res Opin 2018 11 20;34(11):1893-1897. Epub 2018 Mar 20.

b Department of Histology, School of Medicine , Zahedan University of Medical Sciences Zahedan , Iran.

Objective: Smoking during pregnancy is able to alter the structure and function of the placenta. In the present study, quantitative changes of the placenta in smoking mothers were investigated compared to healthy controls by Cavalieri's point counting method.

Methods: Twenty placentas from heavy smoking mothers and non-smoker controls (n = 10 in each group) were selected. Systematic uniform random sampling (SURS) was used for sample selection and tissue sectioning. Quantitative parameters of the placenta in the selected sections were estimated after Masson's trichrome staining. Differences between the two groups were determined by the Mann Whitney U test and the significance level was set at p < .05.

Results: Results showed that there was a significant difference in the placental weight, total volume of placenta, intervillous space, fibrin and syncytiotrophoblast between the heavy smoker group and the control group (p < .05). The differences in the volume density of fibrin and blood vessels between the smoker and control groups were statistically significant (p < .05).

Conclusions: Our findings suggested that quantitative parameters of the placenta significantly changed in placentas from the smoker group compared to controls. These changes can probably be associated with pregnancy complications in smoking mothers and may affect the development and survival of the fetus and even its future life.
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http://dx.doi.org/10.1080/03007995.2018.1444590DOI Listing
November 2018

Association of macrophage migration inhibitory factor gene polymorphisms with chronic periodontitis in a South Eastern Iranian population.

Dent Res J (Isfahan) 2017 Nov-Dec;14(6):395-402

Department of Histology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.

Background: Macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator. It plays a vital role in immune response against the oral disease. MIF is a regulator of innate immunity, and bacterial antigens can stimulate serum level of this protein. In experimental gingivitis, the expression level of MIF increases and this increment positively correlates with oral plaque index. The single nucleotide polymorphisms in the gene encoding the MIF protein can control the function of MIF. The aim of the present study was a clarification of the associations between G/C, 95 bp, and 189 bp insertion/deletion (I/D) polymorphisms and chronic periodontitis (CP) compared with healthy controls.

Materials And Methods: This case-control study was carried out on 210 CP patients and 100 normal subjects. G/C and 95 bp and 189 bp I/D polymorphisms were genotyped, using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) and PCR, respectively. Allele and genotype frequencies of the variants were compared between patients and controls using Chi-square. test. The value of < 0.05 was considered statistically significant.

Results: The study findings showed that G/C polymorphism, especially the C allele increased the risk of CP. The 95-bp I/D polymorphism was not associated with CP and the 185-bp I/D variant was not polymorphic in our population.

Conclusion: Therefore, -137 G/C variant increased the risk of CP in the South East of the Iranian population. In other words, polymorphisms in MIF gene influence clinical outcome of CP infection and influence the susceptibility to disease. Further studies with larger sample sizes and different ethnicities are required to validate our findings.
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http://dx.doi.org/10.4103/1735-3327.218563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713063PMC
December 2017

P16ink4a Subcellular Expression Patterns in Colorectal Adenocarcinoma, Adenoma and Non-Neoplastic Tissue Samples

Asian Pac J Cancer Prev 2017 11 26;18(11):3049-3054. Epub 2017 Nov 26.

Infectious Diseases and Tropical Medicine Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.

Background: Colorectal cancer (CRC) is one of the most common neoplasms with high mortality at advanced stages worldwide. Thus diagnosis of CRC at an early stage with sensitive molecular methods is a high priority. The aim of this study was to evaluate P16ink4a subcellular expression patterns in colorectal adenocarcinoma, adenoma and non-neoplastic tissue samples. Methods: A total of 137 colorectal formalin fixed paraffin-embedded tissue blocks from the pathology archives of Ali-Ebne-Abitaleb central hospital, Zahedan, Iran, were examined in three groups: adenocarcinoma (n= 63), adenoma (n= 38) and non-neoplastic (n= 36). The subcellular expression pattern was determined by immunocytochemistry. Data analysis was performed using Kruskal-Wallis and Fisher exact tests with the significance level set as p˂0.05. Results: P16ink4a subcellular localization was observed in three different patterns, nuclear+cytoplasmic (73.33%), cytoplasmic (13.33%) and nuclear (13.33%). In most samples, nuclear+cytoplasmic was the predominant subcellular pattern. However, a significant difference in P16ink4a subcellular expression patterns was observed along the non-neoplastic, adenoma, adenocarcinoma sequence (p˂0.001). An association with the histological tumor type was also noted (p=0.021). Conclusion: Considering variation in localization of P16ink4a under different pathological conditions, P16ink4a night be sensitive prognostic biomarker for benign colon lesions. Its use may improve strategies for screening, prognostic assessment and management of patients with CRC. Further studies are recommended in this field.
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http://dx.doi.org/10.22034/APJCP.2017.18.11.3049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773790PMC
November 2017

Quantitative changes of gastric mucosa during carcinogenesis using stereological methods.

J BUON 2017 Jul-Aug;22(4):905-910

Infectious Diseases and Tropical Medicine Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.

Purpose: To investigate the effects of helicobacter pylori (H. pylori) infection on the quantitative changes of gastric mucosa in cancerous and precancerous lesions using stereological methods.

Methods: One hundred and twenty-two gastric samples were studied. After determination of H. pylori infection, 42 gastric tissues of intestinal metaplasia (IM) patients, 38 specimens from dysplasia (DYS), and 42 specimens from gastric cancer (GC) types were selected from the pathology archive of Imam Ali Hospital, Zahedan, Iran. Gastric tissues were sectioned and stained with p53 and Ki-67 immunohistochemical (IHC) method and haematoxylin/eosin (H&E). Then, the numerical density (NV) of p53-positive, Ki-67-positive cells, eosinophil and polymorphonuclear (PMN) cells were estimated using dissector counting technique in IM, DYS and GC lesions.

Results: In IM, DYS and GC specimens, the NV of p53-positive cells in the presence of H. pylori infection (H. pylori+) was significantly higher than in H. pylori absence (H. pylori-). The NV of Ki-67- positive cells only in DYS specimens, showed significant difference between H. pylori+ and H. pylori- groups. The NV of eosinophil cells in DYS and GC specimens in H. pylori+ groups were significantly higher than in H. pylori- groups and the NV of polymorphonuclear cells in IM specimens showed significant difference between H. pylori+ and H. pylori- groups.

Conclusion: The results showed that H. pylori infection could cause significant quantitative changes in the cellular structure of gastric mucosa that might be influential on gastric carcinogenesis.
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July 2019

Quantitative changes of extravillous trophoblast cells in heavy smoker mothers compared with healthy controls.

Reprod Fertil Dev 2018 Jan;30(2):409-414

Department of Histology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, 9816743175, Iran.

Maternal smoking during pregnancy can induce structural and functional changes in the placenta. Placentas from heavy smoker (>20 cigarettes per day) mothers and non-smoker healthy controls (n=10 in each group) were enrolled in the present case-control study. Sample selection and sectioning were performed by systematic uniform random sampling (SURS). Selected sections were stained using Masson's trichrome to estimate quantitative parameters of placental extravillous trophoblast cells (EVTs) and the number of EVTs. Differences between groups were evaluated using the Mann-Whitney U-test, with significance set at P<0.05. There was a significant difference in placental weight and the total volume of the placenta between the heavy smoker and control groups (P<0.05). The total volume of EVTs, nucleus diameter, cytoplasm diameter, the volume of the nucleus and cytoplasm and the nucleus to cytoplasm ratio of EVTs were significantly greater in the heavy smoker compared with control group (P<0.05 for all). In placentas from heavy smokers, the total number of EVTs per unit volume of placental bed were significantly greater than in the control group (P<0.05 for both). In conclusion, the findings suggest that maternal smoking could affect fetal health by changing the quantitative parameters of the placenta, and likely the invasive properties of EVTs.
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http://dx.doi.org/10.1071/RD17041DOI Listing
January 2018

The association between interleukin-28B gene polymorphisms as a potential biomarker and the risk of chronic Periodontitis in an Iranian population.

Head Face Med 2017 Jun 27;13(1):16. Epub 2017 Jun 27.

Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Background: Chronic Periodontitis (CP) is a common inflammatory disease affects supporting tissues of the teeth and can lead to tooth loss. The objective of this study was to determine the relationship between polymorphisms in the IL-28B gene and chronic periodontitis in an Iranian population.

Methods: Two hundred and ten CP patients and one hundred healthy subjects were enrolled in the present case-control study. The rs12979860 and rs8099917 SNPs were identified using RFLP and T-ARMS-PCR methods respectively.

Results: SNP analysis revealed that the G allele of rs8099917 SNP and T allele of rs12979860 SNP increased susceptibility to CP compared to the A allele and C allele (p < 0.0001, OR = 2.712, CI = 1.783-4.126; p < 0.0001, OR = 2.538, CI = 1.784-3.613 respectively). In addition, the CT/GT, TT/GG and TT/GT haplotypes were predominant in CP patients and significantly associated with the increased risk of CP.

Conclusion: IL-28B polymorphisms may be useful predictive factors for chronic periodontitis and correlated to the susceptibility to CP infection in our population.
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http://dx.doi.org/10.1186/s13005-017-0148-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485623PMC
June 2017

Quantitative changes of extravillous trophoblast cells in placentas of systemic lupus erythematosus patients.

J Obstet Gynaecol 2017 Aug 11;37(6):746-751. Epub 2017 Apr 11.

b Department of Histology , School of Medicine, Zahedan University of Medical Sciences Zahedan , Iran.

In the present study, quantitative changes of extravillous trophoblast cells (EVTs) in the placentas of SLE patients were investigated compared to healthy controls using stereological methods. Volumetric parameters and number of EVTs per unit volume of the placenta were estimated respectively, using Cavalieri's principle and Physical Disector stereological methods. Placental volume in the SLE group was increased compared to the control group, but this increase was not statistically significant (p > .05). Placental weight in the patient group showed a significant decrease compared to controls (p < .05). Total volume of EVTs, diameter and volume of the nucleus and cytoplasm and the N/C ratio of EVTs in the SLE group showed a significant increase compared to the controls (p < .05). In SLE placentas the total number of EVTs per unit volume of the placenta was increased significantly compared to the control group (p < .05). Impact statement In the present study, there is a new insight to placenta structure that may be useful in understanding possible mechanisms of pregnancy complications and the achievement of new therapeutic strategies. In the present study, for the first time quantitative changes of extravillous trophoblast cells (EVTs) in the placental bed of SLE patients were investigated compared to healthy controls using stereological methods. Results showed that volumetric parameters and number of EVTs were significantly altered in SLE placentas. These changes can be associated with disturbances in trophoblastic invasion in SLE pregnancies and may affect the development and survival of the embryo. Further investigation on the molecular biology of these cells in pregnancy complications will be needed to clarify this hypothesis.
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http://dx.doi.org/10.1080/01443615.2017.1306695DOI Listing
August 2017

Quantitative Parameters of Interdental Gingiva in Chronic Periodontitis Patients with IFN-γ Gene Polymorphism.

Prague Med Rep 2017;118(1):37-48

Department of Histology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.

Chronic periodontitis (CP), an infectious disease resulting in inflammation within the periodontal tissue, is the main cause of adult tooth loss. CP is a multi-factorial disorder and the interaction between multiple genetic and environmental factors results in the manifestation of this disease. Recent researches in periodontitis has focused on cytokine gene polymorphisms that play important role in periodontal inflammation, but few studies investigated histological change that occur during CP in the supporting tissue of teeth. The aims of this study were to investigate the association of IFN-γ +874 A/T polymorphisms and quantitative parameters of interdental gingiva in CP patients. The study samples were interdental gingiva biopsies from 60 individuals including 38 patients and 22 healthy subjects. After determination of IFN-γ +874 A/T gene polymorphism by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), patients were divided in three subgroups: 10 AA, 18 AT and 10 TT. After slides preparation, quantitative parameters were estimated by Cavalieri's point-counting method. Statistical analyses were performed using Mann-Whitney and Kruskal-Wallis test to compare differences between groups. The volume density (Vv) of epithelium, connective tissue and its components were significantly different between the control and CP groups (P<0.05). Statistically significant differences in the Vv of collagenous and non-collagenous matrix of interdental gingiva between AA, AT and TT groups were found (P<0.05). Result of present study shows that IFN-γ +874 A/T is strongly associated with some quantitative parameters of connective tissue constituents of interdental papilla in CP patients.
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http://dx.doi.org/10.14712/23362936.2017.4DOI Listing
July 2017

Association of TNF-α Gene Polymorphisms with Production of Protein and Susceptibility to Chronic Hepatitis B Infection in the South East Iranian Population.

Hepat Mon 2016 Nov 30;16(11):e41984. Epub 2016 Oct 30.

Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Background: The host genetic background regulates the natural history of chronic hepatitis B virus (HBV) infection.

Objectives: The aim of this study was to investigate the association between TNF-α gene polymorphism in the promoter region and susceptibility to chronic hepatitis B virus infection.

Methods: Four polymorphisms of TNF-α gene including -238 A/G, -308 A/G, -857 C/T, and -863 A/C were analyzed by PCR-RFLP in 100 chronic HBV infected patients (HBV group), 40 spontaneously recovered HBV subjects (SR group), and 100 healthy controls (C group). Also, serum levels of protein were monitored.

Results: The study showed that the existence of -308 G, -857 C, and -863 A alleles significantly increased susceptibility to chronic HBV infection. In addition, GGCA haplotype had a higher frequency in HBV patients than C and SR groups that might be related to the natural history of the infection. Chronic HBV patients with -308 GG, -857 CC, and -863 AA genotypes had lower serum levels of TNF-α compared to those with other genotypes.

Conclusions: The results indicated that there was a positive association between susceptibility to chronic HBV infection and TNF-α polymorphism. In addition, HBV patients carrying -308 GG, -857 CC, and -863 AA genotypes with lower serum levels of TNF-α had an increased risk of infection.
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http://dx.doi.org/10.5812/hepatmon.41984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5203729PMC
November 2016

Immunohistochemical Expression of Myeloperoxidase in Placental Samples of Systematic Lupus Erythematosus Pregnancies.

J Family Reprod Health 2016 Jun;10(2):64-70

Department of Histology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.

Objective: Reports of increased level of Myeloperoxidase (MPO) in plasma and placental extracts of Systematic Lupus Erythematosus (SLE) has been proposed that MPO may have an important role in this pregnancy complication. In present study immunohistochemical MPO expression was investigated in placental samples of SLE women compared with normal controls.

Materials And Methods: Ten patients with SLE were recruited as case group. Control group was selected from mothers with normal uncomplicated pregnancies. A monoclonal antibody specific for MPO was used for immunohistochemical staining and then the staining was quantified and differences between groups were compared using Mann-Whitney U test.

Results: There were significant differences in the expression levels of MPO in the syncytiotrophoblast cells and the extravillous trophoblast cells between the control and SLE groups (p < 0.05). There were no significant differences in the expression level of MPO in the vascular endothelium and the relative number of the MPO-positive leukocytes in placental tissue between SLE and control groups (p > 0.05).

Conclusion: The present study showed that MPO expression is increased in syncytiotrophoblast cells and the extravillous trophoblast cells of SLE placentas compared to healthy subjects. It seems that these changes are able to impress structure and function of placenta and survival of the fetus.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026670PMC
June 2016

Neuroprotective effects of Withania coagulans root extract on CA1 hippocampus following cerebral ischemia in rats.

Avicenna J Phytomed 2016 Jul-Aug;6(4):399-409

Department of Anatomy, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.

Objective: Oxygen free radicals may be implicated in the pathogenesis of ischemia reperfusion damage. The beneficial effects of antioxidant nutrients, as well as complex plant extracts, on cerebral ischemia-reperfusion injuries are well known. This study was conducted to determine the effects of the hydro-alcoholic root extract of Withania coagulans on CA1 hippocampus oxidative damages following global cerebral ischemia/reperfusion in rat.

Materials And Methods: Male Wistar rats were randomly divided in five groups: control, sham operated, Ischemia/ Reperfiusion (IR), and Withania Coagulans Extract (WCE) 500 and 1000mg/kg + I/R groups. Ischemia was induced by ligation of bilateral common carotid arteries for 30 min after 30 days of WCE administration. Three days after, the animals were sacrificed, their brains were fixed for histological analysis (NISSL and TUNEL staining) and some samples were prepared for measurement of malondialdehyde (MDA) level and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity in hippocampus.

Results: WCE showed neuroprotective activity by significant decrease in MDA level and increase in the SOD, CAT and GPx activity in pretreated groups as compared to I/R groups (p<0.001). The number of intact neurons was increased while the number of TUNEL positive neurons in CA1 hippocampal region in pretreated groups were decreased as compared to I/R group (p<0.001).

Conclusion: WCE showed potent neuroprotective activity against oxidative stress-induced injuries caused by global cerebral ischemia/ reperfusion in rats probably by radical scavenging and antioxidant activities.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967835PMC
August 2016

Impact of host gene polymorphisms on susceptibility to chronic hepatitis B virus infection.

Infect Genet Evol 2016 10 23;44:94-105. Epub 2016 Jun 23.

Infectious Diseases and Tropical Medicine Research Center, Zahedan University of Medical Sciences, Zahedan, Iran; Department of Histology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran. Electronic address:

Hepatitis B virus (HBV) infection can result in a number of different clinical conditions, including asymptomatic HBV carriers to chronic hepatitis and primary hepatocellular carcinoma. Variations in cytokine genes have been discussed to affect the natural history of HBV infection. These cytokines may involve in the viral binding to the cells, modulating the host immune response to infection and pathological changes in the liver, and affecting the antiviral therapies. Various studies reveal that SNPs play an important role in pathogenesis of HBV. On the other hand, various outcomes of infection cannot be completely shown by genetic factors because these studies have inconsistent results with regard to the possible impacts of host genetic polymorphisms on susceptibility to infection. Therefore, to identify the real effects of host genetic factors in HBV susceptibility and natural history of the disease, studies with large sample size will be needed. In addition, due to the complex interactions of genetic factors it is better to identify synergies of several SNPs. Such studies can provide better insights into the novel methods of diagnosis and treatment. Current review will discuss significant genetic variations in cytokine genes that may affect the susceptibility to the chronic HBV infection.
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http://dx.doi.org/10.1016/j.meegid.2016.06.043DOI Listing
October 2016

The Correlation Between Interferon Lambda 3 Gene Polymorphisms and Susceptibility to Hepatitis B Virus Infection.

Hepat Mon 2016 Mar 5;16(3):e34266. Epub 2016 Mar 5.

Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, IR Iran; Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, IR Iran.

Background: Cytokines are proteins that mediate innate and adaptive immunity responses. It is hypothesized that interferon lambda 3 (IFNL3) levels can influence the outcome of chronic hepatitis B virus (HBV) infection. Polymorphisms in IFN genes have been associated with response to infection.

Objectives: This study was carried-out to investigate the association of IFNL3 gene polymorphisms (rs12979860 and rs8099917) with HBV susceptibility, in chronic HBV-infected patients.

Patients And Methods: In this case-control study, we determined IFNL3 single nucleotide polymorphisms (SNPs) (rs12979860 and rs8099917) in 221 individuals, with chronic HBV infection, and 200 healthy individuals, who were voluntary blood donors, with negative test for HBV. Alleles and genotypes analyses were performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods.

Results: The frequencies of the rs12979860 and rs8099917 genotypes were not significantly different between the HBV-infected and the control groups (CC:CT:TT of 30.3%:48.0%:21.7% vs. 33.0%:49.0%:18.0%, P > 0.05, and GG:GT:TT of 5.8%:39.4%:54.8% vs. 5.0%:41.0%:54.0%, P > 0.05, respectively). Also, the frequencies of the alleles were not significantly different between both groups (C:T of 54.3%:45.7% vs. 57.5%:42.5%, P > 0.05, and G:T of 25.6%:74.4% vs. 25.5%:74.5%, P > 0.05, respectively) and the chronic HBV infection. There were no significant differences between patients, with at least one rs12979860C and or rs8099917T alleles compared to the healthy controls (rs12979860: CT + CC:TT, OR = 1.26, 95%CI = 0.78 - 2.04, P = 0.341 and rs8099917: GT + TT:GG, OR = 1.03, 95%CI = 0.70 - 1.51, P = 0.877, respectively).

Conclusions: Our study showed no correlation between rs12979860 and rs8099917 SNPs and chronic HBV infection. Further studies, with larger sample sizes and different ethnicities, are necessary to validate our findings.
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http://dx.doi.org/10.5812/hepatmon.34266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4875561PMC
March 2016