Publications by authors named "Ramazan Rezaei"

18 Publications

  • Page 1 of 1

Tumor-Derived Exosomes Enriched by miRNA-124 Promote Anti-tumor Immune Response in CT-26 Tumor-Bearing Mice.

Front Med (Lausanne) 2021 27;8:619939. Epub 2021 Apr 27.

Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Exosomes have been introduced as a new alternative delivery system for the transmission of small molecules. Tumor-derived exosomes (TEXs) not only contain tumor-associated antigens to stimulate antitumor immune responses but also act as natural carriers of microRNAs. The aim of the current study was to evaluate the efficacy of miR-124-3p-enriched TEX (TEXomiR) as cell-free vaccine in the induction of antitumor immune responses in a mouse model of colorectal cancer. Briefly, the exosomes were isolated from cultured CT-26 cell line, and modified calcium chloride method was used to deliver miR-124-3p mimic into the exosomes. We used a CT-26-induced BALB/c mouse model of colorectal cancer and analyzed the effect of TEXomiR on survival, tumor size, spleen and tumor-infiltrated lymphocytes, and splenocyte proliferation. Furthermore, intra-tumor regulatory T cells, cytotoxic activity of the splenocytes, and cytokine secretion was also evaluated to describe the anti-tumor immune response. When the tumor size reached 100 mm, the mice were injected with TEXomiR, TEX, and/or phosphate-buffered saline (PBS) subcutaneously three times with 3-day interval, and then tumor size was monitored every 2 days. The results indicated that TEXs could efficiently deliver functional miR-124-3p mimic. The evaluation in tumor-bearing mice showed that treatment with TEXomiR can elicit a stronger anti-tumor immune response than unloaded TEX and PBS. Significant tumor growth inhibition and increased median survival time was achieved in tumor-bearing mice treated with TEXomiR. A significant decrease in CD4/CD8 and Treg/CD8 ratio in tumor tissue was demonstrated. Moreover, increased cytotoxicity and proliferation of splenocytes in the TEXomiR group compared to the TEX and PBS groups were identified. Taken together, our data demonstrated that tumor-derived exosomes efficiently deliver miR-124-3p mimic, and TEXomiR promotes anti-tumor immune responses.
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http://dx.doi.org/10.3389/fmed.2021.619939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110712PMC
April 2021

FAS-670A>G gene polymorphism and the risk of allograft rejection after organ transplantation: a systematic review and meta-analysis.

Blood Res 2021 Mar;56(1):17-25

Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

The association between the risk of allograft rejection after organ transplantation and FAS gene polymorphism has been evaluated previously. However, inconsistent results have been reported. Hence, we conducted the most up-to-date meta-analysis to evaluate this association. All eligible studies reporting the association between FAS-670A>G polymorphism and the risk of allograft rejection published up to December 2019 were extracted using a comprehensive systematic database search in the Web of Science, Scopus, and PubMed. The pooled odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated to determine the association strength. This meta-analysis included six case-control studies with 277 patients who experienced allograft rejection and 1,001 patients who did not experience allograft rejection (controls) after organ transplantation. The overall results showed no significant association between FAS-670A>G polymorphism and the risk of allograft rejection in five genetic models (dominant model: OR=0.81, 95% CI=0.58‒1.12; recessive model: OR=0.10, 95% CI=0.80‒1.53; allelic model: OR=0.96, 95% CI=0.79‒1.18; GG vs. AA: OR=0.92, 95% CI=0.62‒1.36; and AG vs. AA: OR=0.75, 95% CI=0.52‒1.08). Moreover, subgroup analysis according to ethnicity and age did not reveal statistically significant results. Our findings suggest that FAS-670A>G polymorphism is not associated with the risk of allograft rejection after organ transplantation.
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http://dx.doi.org/10.5045/br.2021.2020201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987476PMC
March 2021

Exosome-mediated delivery of functionally active miRNA-375-3p mimic regulate epithelial mesenchymal transition (EMT) of colon cancer cells.

Life Sci 2021 Mar 13;269:119035. Epub 2021 Jan 13.

Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Aims: EMT is the process by which a polarized epithelial cell undergoes several changes leading to highly invasive and fibroblast-like morphology. It has been described that miR-375 is inversely associated with EMT in cancerous patients and can effectively inhibit invasion and migration of tumor cells. Here, we investigate whether miR-375 mimic delivered by tumor-derived exosomes could reverse EMT process.

Main Methods: The exosomes were isolated from HT-29 and SW480. Subsequently, exosomes were loaded with miR-375-3p mimic applying modified calcium chloride method. Quantitative real-time PCR was used for evaluation of the loading efficiency of miR-375 mimic in the exosomes. The effects of miR-375 loaded tumor exosomes (TEXomiR) on EMT process investigated using flow cytometry, cell morphology, and invasion and migration assay.

Key Findings: The in vitro results showed that the tumor derived exosomes can efficiently deliver miR-375 mimic to reduce the expression of β-catenin, vimentin, ZEB1, and snail. In contrast, TEXomiR significantly increased the expression of E- cadherin in EMT process. Furthermore, the migration and invasion abilities of HT-29 and SW480 cells were inhibited by TEXomiR. The expression of CD44 and CD133 are increased in EMT process. Flow cytometry evaluation demonstrated that treatment with TEXomiR significantly decreased the expression of CD44 and CD133 in SW480 cell line.

Significance: Our results imply that colon cancer cells-derived exosomes could be used as an effective nonvehicle to deliver miR-375-3p mimic. Moreover, TEXomiR may be a potent therapeutic agent for the treatment of metastatic colorectal cancer.
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http://dx.doi.org/10.1016/j.lfs.2021.119035DOI Listing
March 2021

Interleukin-4 gene polymorphism (C33T) and the risk of the asthma: a meta-analysis based on 24 publications.

BMC Med Genet 2020 11 23;21(1):232. Epub 2020 Nov 23.

Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Previous studies evaluated the association of IL-4 C33T polymorphism and risk of bronchial asthma but failed to establish a consistent conclusive association. In the present meta-analysis, we intend to define a more reliable estimate of the association in the presence of filling published literature.

Methods: An exhaustive search in Web of Science, Scopus, and PubMed databases was performed to identify all relevant publications before September 2020, and 24 publications (28 studies) with 6587 cases and 8408 controls were included in final analysis. The association between polymorphism and risk of asthma were measured by Odd ratios (ORs) and 95% confidence intervals (CIs). Moreover, Cochran's Q and the I statistics were used to evaluate the degree of heterogeneity between studies.

Results: In the overall study populations, a significant positive association was detected under all genotype models and announced the IL-4 C33T polymorphism as a potential risk factor in the pathogenesis of asthma. In the subgroup analysis by age, a significant association between IL-4 C33T polymorphism and risk of asthma in different age groups was identified in allelic model, which highlighted the predisposing role of the T allele for the asthma risk in all three age groups. Furthermore, the results of subgroup analysis by continent were heterogenous. Accordingly, IL-4 C33T polymorphism was a risk factor in Europeans (all models except heterozygote comparison), Americans (all models except recessive and homozygote comparison) and Asians (just recessive and allelic model). Finally, the ethnicity-specific analysis disclosed a significant association between IL-4 C33T polymorphism and asthma risk in Caucasians (all genotype models except heterozygote comparison), while this association was not significant in African-Americans.

Conclusions: This study suggests that IL-4 C33T polymorphism potentially acts as a risk factor for asthma in different ethnicities and age groups.
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http://dx.doi.org/10.1186/s12881-020-01169-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686752PMC
November 2020

Vitamin D Receptor Gene Polymorphisms and the Risk of Metabolic Syndrome (MetS): A Meta-Analysis.

Endocr Metab Immune Disord Drug Targets 2020 Aug 4. Epub 2020 Aug 4.

Department of immunology, school of public health, Tehran university of medical sciences, Tehran. Iran.

Introduction: Several studies have assessed the association between the vitamin D receptor (VDR) polymorphism and risk of metabolic syndrome (MetS). However, the results were inconsistent and inconclusive. Therefore, we conducted a meta-analysis to clarify the exact association between the vitamin D receptor (VDR) polymorphisms and the risk of MetS.

Methods: All accessible studies reporting the association between the FokI (rs2228570) or / and TaqI (rs731236) or/and BsmI (rs1544410) or/and ApaI (rs7975232 polymorphisms of the Vitamin D Receptor and susceptibility to MetS published prior to February 2019 were systematically searched in Web of Science, Scopus, and PubMed. After that, Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were estimated to evaluate the strength of the association in five genetic models.

Results: A total of 9 articles based on four gene variations, and comprising 3348 participants with 1779 metabolic syndrome patients were included. The overall results suggested a significant association between BsmI (rs1544410) polymorphism and MetS susceptibility in recessive model (OR, 0.72, 95% CI, 0.55-0.95, fixed effect model), allelic model (OR, 0.83, 95% CI, 0.72-0.95, fixed effect model), and bb vs BB (OR, 0.65, 95% CI, 0.46-0.93, fixed effect). However, no significant association was identified between TaqI (rs731236) polymorphism, ApaI (rs7975232) polymorphism, and FokI (rs2228570) polymorphism and MetS.

Conclusion: This meta-analysis suggested an association between the BsmI (rs1544410) polymorphism and MetS. Indeed, BsmI (rs1544410) acts as a protective factor in the MetS. As a result, the VDR gene could be regarded as a promising pharmacological and physiological target in prevention or treatment of the MetS.
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http://dx.doi.org/10.2174/1871530320666200805101302DOI Listing
August 2020

Transforming growth factor beta 1 (TGFβ1) polymorphisms and unexplained infertility: A genetic association study.

Syst Biol Reprod Med 2020 Aug 31;66(4):267-280. Epub 2020 Jul 31.

Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences , Tehran, Iran.

The prevalence of infertility is increasing and worrisome. About 10 to 30% of infertility is classified as idiopathic or unexplained infertility (UI). is multifunctional and immunoregulatry cytokine which regulates both implantation and adhesion of trophoblasts to the extracellular matrix during pregnancy. The aim of the current study was to investigate the association between two polymorphisms rs1800470 (C29T) and rs1800471 (G74C) of the gene in Iranian patients with unexplained infertility. A total of 250 UI patients and 484 healthy individuals with no history of infertility were included in the study. The amplification and sequencing of target DNA fragments were done using PCR and automated sequencing methods, respectively. The effects of these polymorphisms on both structure and function of mRNA and protein were analyzed using new in-silico tools. The frequency distribution of the alleles, genotypes, and haplotypes of both rs1800470 and rs1800471 polymorphisms had a statistically significant difference between subjects and controls. CC genotype of TGF-β1 rs1800470 (29C→T) increase the risk of UI in male UI patients. Moreover, C alleles of TGF-β1 rs1800471 was associated with increased risk of UI in female UI patients. Couples, subgroup analysis revealed a significant association between TGF-β1 polymorphisms (rs1800470, rs1800471) and the risk of UI in male, female, and all UI patients. The frequency of TG and CG haplotypes were statistically different in both UI and healthy subjects group (P < 0.05). RS1800471 polymorphisms changed the secondary structure of mRNA and resulted in the removal of one mRNA arm and creation of two new arms. Taken together, the results of the current study suggest that functional polymorphisms may play an important role in the susceptibility to UI in Iranian population. According to in silico analysis, polymorphisms in TGF-β1 can reduce mRNA half-life and, therefore, reduced expression. .
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http://dx.doi.org/10.1080/19396368.2020.1773575DOI Listing
August 2020

Vitamin D receptor gene polymorphisms and susceptibility to urolithiasis: a meta-regression and meta-analysis.

BMC Nephrol 2020 07 10;21(1):263. Epub 2020 Jul 10.

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

Background: The currently available data with respect to the association between vitamin D receptor (VDR) gene polymorphism and risk to urolithiasis are inconclusive and inconsistent. Hence, an exhaustive meta-analysis can solve the discrepancies and provide a hint for upcoming investigations. Herein, a meta-analysis was carried out to attain a conclusive estimate of the association between VDR gene single nucleotide polymorphisms (SNPs) and urolithiasis risk.

Methods: The major databases, including ISI Web of science, Scopus, and PubMed/MEDLINE were searched systematically from until June 2020 to retrieve all relevant studies. Association between VDR gene polymorphisms, including FokI (rs2228570), TaqI (rs731236), BsmI (rs1544410), and ApaI (rs7975232), and urolithiasis risk was evaluated using pooled odds ratio (OR) and their corresponding 95% confidence interval (CI). Additionally, to seek for the potential source of heterogeneity, meta-regression analyses were exerted.

Results: Literature search led to finally finding of 33 studies evaluating the VDR gene SNPs and urolithiasis risk. It was observed that none of the four SNPs were significantly associated with urolithiasis predisposition. However, subgroup analysis confirmed higher risk of urolithiasis in East-Asian and Caucasian population with ApaI and TaqI gene polymorphism. The analyses of sensitivity acknowledged the results stability.

Conclusion: Although this meta-analysis did not support the association of FokI, TaqI, BsmI, and ApaI in the overall polled analysis, it suggests that ApaI and TaqI SNPs is associated with increased risk of urolithiasis in East-Asian and Caucasians populations.
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http://dx.doi.org/10.1186/s12882-020-01919-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350604PMC
July 2020

Association between vitamin D receptor (VDR) polymorphisms and the risk of multiple sclerosis (MS): an updated meta-analysis.

BMC Neurol 2019 Dec 26;19(1):339. Epub 2019 Dec 26.

Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, 14194, Iran.

Background: The association between the Vitamin D Receptor (VDR) gene polymorphism and the risk of Multiple sclerosis (MS) has been evaluated in several researches. However, the findings were inconsistent and inconclusive. Therefore, we set out a meta-analysis of all eligible published case-control studies to obtain an exact evaluation of the association between VDR gene polymorphisms and MS.

Method: All relevant studies reporting the association between the VDR gene FokI (rs2228570), or/and TaqI (rs731236) or/and BsmI (rs1544410) or/and ApaI (rs7975232) polymorphisms and susceptibility to MS published up to May, 2019 were identified by comprehensive systematic search in the electronic database of web of science, Scopus, and PubMed. After that, the strength of association between VDR gene polymorphisms and susceptibility to MS was evaluated by odds ratio (OR) and 95% confidence interval (CI).

Results: A total of 30 case-control studies were included in the meta-analysis. The overall results suggested a significant association between TaqI polymorphism and MS risk under heterozygote genetic model (OR = 1.27, 95%CI = 1.01-1.59, random effect). Moreover, the pooled results of subgroup analysis declined presence of significant association under all defined genetic model. In subgroup analysis, BsmI polymorphisms was associated with increased risk of MS under recessive model in Asian populations. On the other hand, ApaI polymorphism was associated with decreased risk of MS under recessive and aa vs. AA model in Asian populations.

Conclusion: This meta-analysis suggested a significant association between TaqI polymorphism and MS susceptibility. Furthermore, BsmI polymorphism was associated with increased risk of MS in Asian populations. In contrast, ApaI polymorphism was associated with decreased risk of MS in Asian populations. Future large-scale studies on gene-environment and gene-gene interactions are required to estimate risk factors and assist early diagnosis of patients at high risk for MS.
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http://dx.doi.org/10.1186/s12883-019-1577-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933912PMC
December 2019

Cancer stem cells: A review from origin to therapeutic implications.

J Cell Physiol 2020 02 8;235(2):790-803. Epub 2019 Jul 8.

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

Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are elucidated as cells that can perpetuate themselves via autorestoration. These cells are highly resistant to current therapeutic approaches and are the main reason for cancer recurrence. Radiotherapy has made a lot of contributions to cancer treatment. However, despite continuous achievements, therapy resistance and tumor recurrence are still prevalent in most patients. This resistance might be partly related to the existence of CSCs. In the present study, recent advances in the investigation of different biological properties of CSCs, such as their origin, markers, characteristics, and targeting have been reviewed. We have also focused our discussion on radioresistance and adaptive responses of CSCs and their related extrinsic and intrinsic influential factors. In summary, we suggest CSCs as the prime therapeutic target for cancer treatment.
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http://dx.doi.org/10.1002/jcp.29044DOI Listing
February 2020

Myeloid-derived suppressor cells and tumor: Current knowledge and future perspectives.

J Cell Physiol 2019 07 7;234(7):9966-9981. Epub 2018 Dec 7.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

The immunosuppressive features of tumor lesions participate not only as one of the major players inducing cancer progression but also a big challenge for effective immunotherapy. It has been found that immunosuppression associated with chronic inflammatory factors, such as growth factors, cytokines, and chemokines is generated by stroma and tumor cells. Chronic and exhaustive secretion of these mediators triggers the generation of myeloid-derived suppressor cells (MDSCs) demonstrating one of the key players engaged in tumor immunosuppression. In point of fact, direct cell-to-cell contact is a prerequisite for immunosuppressive functions of MDSCs. From the clinical perspective, the frequency of peripheral blood MDSCs is correlated with clinical stage and therapeutic response in various cancers. Furthermore, MDSCs are involved in chemoresistant settings. Altogether, it is a rational therapeutic approach to block the fierce cycle in which MDSCs are developed and infiltrated to favor cancer progression. In this review, we will summarize recent findings of MDSCs in tumor progression and discuss potential therapeutic strategies that could be evaluated in future clinical trials.
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http://dx.doi.org/10.1002/jcp.27923DOI Listing
July 2019

Association study between killer immunoglobulin-like receptor polymorphisms and ankylosing spondylitis disease: An updated meta-analysis.

Int J Rheum Dis 2018 Oct 5;21(10):1746-1755. Epub 2018 Nov 5.

Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Several genetic studies have assessed the association between polymorphisms in killer immunoglobulin-like receptors (KIR) genes and susceptibility of individuals to ankylosing spondylitis (AS), but the findings have been inconclusive and incongruous. Therefore, we conducted this meta-analysis of all case-control studies meeting the inclusion criteria for obtaining an exact conclusion of the effect of KIR polymorphisms on the risk of AS.

Methods: A systematic literature search was conducted in electronic databases, including Scopus web of science, ScienceDirect, and PubMed to find all eligible studies exploring the association between KIR polymorphisms and the risk of AS, prior to June 2017. Pooled odds ratios (OR) and their corresponding 95% CIs were used to evaluate the strength of the association between KIR polymorphisms and the risk of AS.

Results: A total of 16 case-control studies, encompassed in 12 papers, with 1770 cases and 2907 healthy subjects were included in the meta-analysis. This meta-analysis revealed three significant positive associations of 2DS1, 2DS5, and 3DS1 with susceptibility to AS, while two significant negative associations of 2DL2 and 2DS2 with susceptibility to AS were identified. In the subgroup analysis based on human leukocyte antigen (HLA)-B*27 positive patients and healthy subjects, results indicated that there were four significant positive associations between 2DL5, 2DS4, 2DS5, 3DS1 polymorphisms and susceptibility to AS in HLA-B*27-positive patients; a significant negative association of 3DL1 in HLA-B*27-positive patients was found.

Conclusions: While 2DS1, 2DS5, and 3DS1 polymorphisms increased AS risk, 2DL2 and 2DS2 polymorphisms were associated with reduced AS susceptibility.
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http://dx.doi.org/10.1111/1756-185X.13408DOI Listing
October 2018

Genetic implications in the pathogenesis of systemic sclerosis.

Int J Rheum Dis 2018 Aug;21(8):1478-1486

Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Systemic sclerosis (SSc) is a chronic autoimmune disease of the connective tissues of unknown etiology, characterized mainly by fibrosis of the skin, vascular abnormalities, and systemic involvement of other organs, such as gastrointestinal tract, kidneys, lungs, and heart. SSc has been associated with a complex etiology with the involvement of both environmental and genetic factors in the onset and outcome of the disease. Although several major histocompatibility complex (MHC) and non-MHC genes have been associated with the disease risk, there are several questions to answer. This article's purpose was to provide an extensive overview of the identified genetic factors in the etiopathogenesis of SSc.
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http://dx.doi.org/10.1111/1756-185X.13344DOI Listing
August 2018

Atherosclerosis and autoimmunity: a growing relationship.

Int J Rheum Dis 2018 May 19;21(5):908-921. Epub 2018 Apr 19.

Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Atherosclerosis is regarded as one of the leading causes of mortality and morbidity in the world. Nowadays, it seems that atherosclerosis cannot be defined merely through the Framingham traditional risk factors and that autoimmunity settings exert a remarkable role in its mechanobiology. Individuals with autoimmune disorders show enhanced occurrence of cardiovascular complications and subclinical atherosclerosis. The mechanisms underlying the atherosclerosis in disorders like rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, systemic sclerosis and Sjögren's syndrome, seem to be the classical risk factors. However, chronic inflammatory processes and abnormal immune function may also be involved in atherosclerosis development. Autoantigens, autoantibodies, infectious agents and pro-inflammatory mediators exert a role in that process. Being armed with the mechanisms underlying autoimmunity in the etiopathogenesis of atherosclerosis in rheumatic autoimmune disorders and the shared etiologic pathway may result in substantial developing therapeutics for these patients.
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http://dx.doi.org/10.1111/1756-185X.13309DOI Listing
May 2018

Evaluation of ITGB2 (CD18) and SELL (CD62L) genes expression and methylation of ITGB2 promoter region in patients with systemic sclerosis.

Rheumatol Int 2018 Mar 22;38(3):489-498. Epub 2018 Jan 22.

Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.

Systemic sclerosis (SSc), an autoimmune disease of connective tissue, is characterized by inflammation, fibrosis, and vessel endothelial damage. Products of Integrin subunit beta 2 (ITGB2) and selectin L (SELL) genes participate in several functional pathways of immune system. The aim of this investigation was to survey the transcript level of ITGB2 and SELL genes as well as methylation status of CpG sites in promoter region of differently expressed gene in PBMCs of SSc patients. PBMCs were isolated from whole blood of 50 SSc patients and 30 healthy controls. Total RNA and DNA contents of PBMCs were extracted. Gene expression was analyzed by real-time PCR using the SYBR Green PCR Master Mix. To investigate the methylation status of CpG sites, DNA samples were treated by bisulfite, amplified through nested PCR, and sequenced through Sanger difficult sequencing method. ITGB2 gene in PBMCs of SSc patients was overexpressed significantly in comparison to healthy controls. However, no altered SELL expression was observed. Three CpG sites of 12, 13 and 14 were significantly hypomethylated in patients group, despite overall methylation status of ITGB2 gene promoter revealed no significant difference between study groups. There was no statistically significant correlation between methylation status of ITGB2 promoter and the gene expression in patients. Regarding to lack of correlation of increased expression of ITGB2 with its promoter hypomethylation in SSc patients, our study suggests that upregulation of ITGB2 in PBMCs from SSc patients is probably due to another mechanism other than methylation alteration.
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http://dx.doi.org/10.1007/s00296-017-3915-yDOI Listing
March 2018

Association Between IL6-174 G/C Polymorphism and Graves' Disease: A Systematic Review and Meta-Analysis.

Acta Med Iran 2017 Nov;55(11):665-671

Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran. AND Rheumatology Expert Group (REG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.

Several studies have evaluated the association between interleukin-6 (IL-6) -174 G/C polymorphism and Graves' disease (GD); however, the results have been inconsistent. In the current study, a meta-analysis was performed to assess the association of IL6 -174 G/C polymorphism with Graves' disease. Medline, EMBASE, and Web of Science databases were searched to identify all eligible studies published before August 2016. Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated to assess the strength of association in dominant, recessive, allelic, homozygotes contrast, and heterozygotes contrast models. A total of four case-control studies with 554 GD cases and 1201 healthy controls were included in this meta-analysis. In the combined analysis, the results showed significant association between the IL6 -174 G/C polymorphism and the risk for GD in dominant model (OR=1.39, 95% CI: 1.07-1.80), recessive model (OR=2.75, 95% CI: 1.01-7.55) and homozygote contrast model (OR=3.25, 95% CI: 1.1-9.58). No publication bias was found in the current study (all P>0.05). The meta-analysis results suggested that the IL6 -174 G/C polymorphism was indicated to be associated with the risk of GD. Further studies are warranted to confirm these results.
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November 2017

Th17/Treg immunoregulation and implications in treatment of sulfur mustard gas-induced lung diseases.

Expert Rev Clin Immunol 2017 12 23;13(12):1173-1188. Epub 2017 Oct 23.

a Chemical Injuries Research Center , Baqiyatallah University of Medical Sciences , Tehran , Iran.

Introduction: Sulfur mustard (SM) is an extremely toxic gas used in chemical warfare to cause massive lung injury and death. Victims exposed to SM gas acutely present with inhalational lung injury, but among those who survive, some develop obstructive airway diseases referred to as SM-lung syndrome. Pathophysiologically, SM-lung shares many characteristics with smoking-induced chronic obstructive pulmonary disease (COPD), including airway remodeling, goblet cell metaplasia, and obstructive ventilation defect. Some of the hallmarks of COPD pathogenesis, which include dysregulated lung inflammation, neutrophilia, recruitment of interleukin 17A (IL -17A) expressing CD4T cells (Th17), and the paucity of lung regulatory T cells (Tregs), have also been described in SM-lung. Areas covered: A literature search was performed using the MEDLINE, EMBASE, and Web of Science databases inclusive of all literature prior to and including May 2017. Expert commentary: Here we review some of the recent findings that suggest a role for Th17 cell-mediated inflammatory changes associated with pulmonary complications in SM-lung and suggest new therapeutic approaches that could potentially alter disease progression with immune modulating biologics that can restore the lung Th17/Treg balance.
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http://dx.doi.org/10.1080/1744666X.2017.1389646DOI Listing
December 2017

IRF7 gene expression profile and methylation of its promoter region in patients with systemic sclerosis.

Int J Rheum Dis 2017 Oct 26;20(10):1551-1561. Epub 2017 Sep 26.

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

Objective: The aim of the current study was to evaluate if methylation status of CpG sites of interferon regulatory factor 7 (IRF7) promoter in peripheral blood mononuclear cells (PBMCs) of systemic sclerosis (SSc) patients is involved in pathogenesis of the disease.

Methods: PBMCs were isolated from whole blood of 50 SSc patients and 30 controls. After the extraction of total RNA and DNA contents from PBMCs, complementary DNA (cDNA) was synthesized. Afterwards, quantitative analysis of IRF7 messenger RNA (mRNA) was conducted by real-time polymerase chain reaction (PCR). To evaluate the methylation status of the promoter region of IRF7 gene, PCR products of bisulfite-treated DNA from SSc patients and controls were sequenced.

Results: The mRNA expression of IRF7 in PBMCs from patients compared with controls was significantly upregulated. While limited cutaneous SSc patients expressed the mRNA of IRF7 higher than controls, the diffuse cutaneous SSc group did not demonstrate significantly increased expression in comparison to controls. Insignificant promoter hypomethylation of IRF7 was observed in SSc patients compared with the control group. However, CpG2 hypomethylation was significantly associated with increased SSc risk. Furthermore, overall promoter methylation and mRNA level of IRF7 were significantly correlated with each other. Nonetheless, none of them correlated with Rodnan score of SSc patients. There was significant difference in IRF7 mRNA expression between CpG8 methylated and unmethylated SSc patients. Moreover, the difference of methylation and expression was not significant between anti-nuclear antibody (ANA)-positive and ANA-negative SSc patients.

Conclusions: It is suggested that hypomethylation of the IRF7 promoter might play a role in SSc pathogenesis, probably through promoting the IRF7 expression in PBMCs of patients with SSc.
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http://dx.doi.org/10.1111/1756-185X.13175DOI Listing
October 2017

Association of chronic hepatitis B infection with metabolic syndrome and its components: Meta-analysis of observational studies.

Diabetes Metab Syndr 2017 Dec 3;11 Suppl 2:S939-S947. Epub 2017 Jul 3.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.

Introduction: Observational studies evaluating the association between chronic hepatitis B (CHB) and risk of metabolic syndrome (MetS) have yielded inconclusive results.

Objective: The current meta-analysis was conducted to identify whether CHB infection plays a role in the risk of MetS and its components.

Methods: The electronic search of MEDLINE, PubMed Central, and EMBASE databases was systematically performed from their inception until February 2017 to identify all eligible studies. The most adjusted risk estimates and their corresponding 95% confidence intervals (CIs) for the associations of chronic hepatitis B with MetS and its components were collected and analyzed.

Results: A total of 13 studies, with a total sample size of 138,994,999 subjects and 35,481,231 individuals with MetS were included in this Meta-analysis. The results of pooled analysis revealed that CHB infection is related to reduced risk of MetS (OR=0.83, 95%CI=0.71-0.79, random effects), with evidence of significant heterogeneity (I2=89%, P<0.001). This association was an age, gender, and ethnicity-dependent relationship. Moreover, CHB was associated with reduced risk of elevated blood pressure, reduced HDL-cholesterol, increased fasting glucose, and, most strongly with increased triglycerides in some subgroups. The sensitivity analyses confirmed the stability of the results.

Conclusions: This meta-analysis suggests that CHB is associated with decreased risk of MetS and some of its single components.
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http://dx.doi.org/10.1016/j.dsx.2017.07.020DOI Listing
December 2017