Oxidative stress and age-related changes in T cells: Is thalassemia a model of accelerated immune system aging?

Iron overload in β-thalassemia major occurs mainly due to blood transfusion, an essential treatment for β-thalassemia major patients, which results in oxidative stress. It has been thought that oxidative stress causes elevation of immune system senescent cells. Under this condition, cells normally enhance in aging, which is referred to as premature immunosenescence. Because there is no animal model for immunosenescence, most knowledge on the immunosenescence pattern is based on induction of immunosenescence. In this review, we describe iron overload and oxidative stress in β-thalassemia major patients and how they make these patients a suitable human model for immunosenescence. We also consider oxidative stress in some kinds of chronic virus infections, which induce changes in the immune system similar to β-thalassemia major. In conclusion, a therapeutic approach used to improve the immune system in such chronic virus diseases, may change the immunosenescence state and make life conditions better for β-thalassemia major patients. © 2016 Termedia Sp. z o.o. All rights reserved

Effect of snake venom on prostate cancer: a systematic review

Introduction: Prostate cancer is the second deadly cancer in men. One way to deal with tumor resistance is using natural sources like snake venoms that contain a wide spectrum of anti-cancer components. The aim of this study was to review the anti-neoplastic property of snake venom against prostate cancer. Methods and Results: In this systematic review, based on PRISMA guidelines, two persons independently searched MeSH and other relevant terms like “snake venom”, “prostatic neoplasms” and 3 others in databases including PubMed, Medline, Scopus, Sciverse( Elsevier, ScienceDirect), Cochrane library, Sid, Magiran, and iranmedex up to October 2017, and all articles with considered inclusion criteria were added to the study. 82 articles were obtained by primary searching and after removing irrelevant and duplicate articles 14 articles with all inclusion criteria were added to this study. Many snake venoms’ components are effective on prostate cancer; some of them changed gene expression of tumor cells while others like enzymes have a direct effect on cancer cells. Although there are many compounds with anti-cancer property in snake venoms there are some with carcinogenic effect. For example Prokineticins and Hyaluronidase in some venoms induced angiogenesis and growth of the tumor. Walterinnesia aegyptia venom alone and its combination with silica nanoparticles, Rhodostomin, a proteinase from Vipera lebetina, Vipera lebetina turanica venom, cysteine-rich secretory proteins, Disintegrins, lectin and many other components had wide range of anti-cancer properties like inhibiting cancer cells’ invasion, migration, growth, and their adhesion to the extracellular matrix, inducing apoptosis by down-regulated antiapoptotic proteins like Bcl-2 and increasing the expression of proapoptotic proteins like Bcl-2-binding component 3, Bax, caspase-3, caspase-9 and other mechanisms. Conclusions: Snake venoms are good sources for treating prostate cancer but application of nanoparticles in combination with venoms could make the results more efficient. However, their side effects must be considered

Evaluation of Enterovirus infection in people with type 1 diabetes in Chaharmahal and Bakhtiari province compared to healthy subjects

زمینه و هدف: دیابت نوع 1، یک بیماری خود ایمنی چندعاملی بوده که برهمکنش عوامل ژنتیکی و محیطی می‌تواند سبب بروز آن شود. ویروس‌ها، ازجمله انتروویروس ها، از مهم‌ترین عوامل محیطی در پاتوژنز دیابت نوع 1 هستند. به‌منظور تعیین ارتباط میان انتروویروس ها و دیابت نوع 1 در جمعیت بیماران ایرانی، به بررسی میزان عفونت انتروویروسی در سرم بیماران مبتلا به دیابت نوع 1 پرداخته شد. روش بررسی: در این مطالعه‌ی مورد- شاهدی، برای تشخیص وجود RNA انتروویروسی، از تست Nested-PCR و برای تعیین کلاس‌های مختلف از آنتی بادی‌های ضد انتروویروسی نیز از تست الایزا استفاده شد. آزمون‌های آماری مورد استفاده در این مطالعه شامل آزمون دقیق فیشر و کای اسکوئر بود. یافته ها: از 35 نمونه سرمی جمع‌آوری‌شده از بیماران مبتلا به دیابت نوع 1، در سرم 12 بیمار (2/34) عفونت انتروویروسی به روش Nested-PCR مثبت شد، درحالی‌که تنها در یک مورد از افراد سالم مثبت بود (8/2) که اختلاف معنی داری را میان دو گروه نشان می دهد (05/0P<). آنتی‌بادی IgG ضد انتروویروسی در سرم 13 بیمار (1/37) و این آنتی‌بادی از کلاس IgA، در سرم 10 بیمار (5/28) یافت شد. این میزان در افراد سالم به ترتیب 3 (5/8) و 2 (7/5) نفر بود (برای هر دو آنتی بادی 05/0P<). آنتی بادی ضد انتروویروسی از کلاس IgM، در سرم هیچ‌یک از بیماران و افراد کنترل یافت نشد (1=P). نتیجه گیری: نتایج بدست آمده از این مطالعه نشان می‌دهد میزان شیوع عفونت انتروویروسی بیماران ایرانی مبتلا به دیابت نوع 1 به شکل معنی‌داری بالاتر از افراد سالم است. این مطالعه نوعی ارتباط میان انتروویروس ها و بیماری دیابت نوع 1 را در جمعیت مورد مطالعه نشان می‌دهد

Effect of Low-level Laser Therapy on Bone Defect Repair in Diabetic and Osteoporotic Rats using the Real-Time PCR Technique

Introduction: Bone formation is disturbed in type 1 diabetes followed by changes in the bone microstructure. The most important metabolic disorder in diabetes is osteoporosis, which is characterized by bone loss and bone structure degradation. This study aimed to determine the effect of lowpower laser on bone defect repair in the experimental model of diabetes and osteoporosis. Materials & Methods: A total of 30 fourmonth-old female Wistar rats weighing 190-220 g were selected and randomly divided into six groups, including 1: non-diabetic control (Co.), 2: non-diabetic laser (L.), 3: diabetic control (Co.D.), 4: diabetic laser (L.D.), 5: diabetic alendronate (A.D.), and 6: diabetic laser + alendronate (L.A.D.).Diabetes was induced in groups 3, 4, 5, and 6. All groups underwent ovariectomy and partial bone defect. In the laser group, a lowlevel laser (890nm, 80 Hz, 1/5J / cm 2) was radiated to 3 points at the defect location. Tibia bones were collected, and Real-time PCR was performed after a month. The data were analyzed using ANOVA. A p-value less than P<0.05 was considered statistically significant. Ethics code: 13237-91-1-1393- 10397 Findings: The t-test showed a significant decrease in tibia bone density in diabetic and osteoporotic rats, compared to the nondiabetic control group. Moreover, analysis of gene expression data (ANOVA, P<0.05) revealed a significant difference between the group of diabetic laser + alendronate and other groups in terms of Runx2 gene expression and Osteocalcin. Discussions & Conclusions: According to the findings, laser therapy combined with alendronate can accelerate the repair of partial bone defect in the experimental model of diabetes and osteoporosis. Keywords: Low-level laser, Osteoporosis, Partial bone defect, Real-time PCR, Type 1 diabete

Alteration in CD8+T cell subsets in enterovirus-infected patients: An alarming factor for type 1 diabetes mellitus

Type 1 diabetes is a multi-factorial disease that can develop due to the combination of genetic and environmental factors. Viruses, particularly enteroviruses, are major environmental candidates in the pathogenesis of type 1 diabetes, even though the mechanisms of pathogenicity of these viruses and their effects on the immune system have not been understood very well yet. Previous studies show that any imbalance in the population of different lymphocyte subsets could develop autoimmune diseases. Our theory is that enteroviral infection causes an impairment in the distribution of lymphocyte subtypes and consequently results in the diabetes onset in some individuals. Therefore, in this project, we evaluated the distribution of T CD8+ lymphocytes and their subsets in type 1 diabetes patients. This study was conducted to investigate the relationship between enteroviral infection and type 1 diabetes mellitus in an Iranian population, and suggestion a predicting approach for susceptible subjects. © 201

The expression analysis of Fra-1 gene and IL-11 protein in Iranian patients with ulcerative colitis

Abstract Background: Fra-1 (fosl1) belongs to the activator protein1 (AP-1) family inducing IL-11 expression in oxidative stress condition. IL-11 plays a pivotal role in protecting epithelial barriers integrity. In this study, we investigated the Fra-1 gene expression in the inflamed mucosa of patients with ulcerative colitis (UC) as well as its relation to IL-11 expression. Materials and methods: We enrolled 20 patients and 20 healthy controls with definite UC based on the clinical criteria. Fra-1 gene expression in inflamed and non-inflamed colonic biopsies was determined by real-time polymerase chain reaction (RT-PCR). The IL-11 protein concentration was measured by Enzyme-Linked Immunosorbent Assay (ELISA) method. Pearson correlation was applied to calculate the relation between Fra-1 and IL-11. Results: An increased level of Fra-1 gene expression was observed in patients with mild ulcerative colitis. The protein concentration of IL-11 was also increased in mild UC patients. Conversely, a significant decrease of IL-11 protein level was detected in severe UC patients compared to control group. Conclusion: Oxidative stress in inflamed intestinal biopsies can induce fra-1 gene expression. Our findings suggest that Fra-1 transcription factor leads to the production of IL-11 protein in UC patients

The regulatory role of Nrf2 in antioxidants phase2 enzymes and IL-17A expression in patients with ulcerative colitis

Background: Reactive oxygen species (ROS) is one of the pathogenic factors responsible for intestinal injury in Ulcerative colitis (UC). Nuclear factor erythroid-2 related factor 2 (Nrf2) plays a critical role against ROS factors to conserve epithelial integrity. This study aimed to localize Nrf2 and IL-17A protein in the inflamed mucosa of patients with ulcerative colitis. The gene expression of Nrf2 was also correlated with GST-A4 and PRDX1. Materials and methods: A total of 20 patients and 20 healthy controls with definite UC based on the clinical criteria were enrolled for this study. The expression pattern of Nrf2 and IL-17A protein was compared in inflamed and non-inflamed colonic biopsies by immunohistochemical staining. Nrf2, GST-A4 and PRDX1 gene expression were determined by real-time polymerase chain reaction (RT-PCR). Results: In inflamed colonic biopsies, an increased level of Nrf2 protein factor was detected in epithelial cells. Conversely, IL-17A protein was presented more in mononuclear cells in mucosa and lamina propria regions. A significant increase of Nrf2, GST-A4 gene expression was observed in both mild and severe patients with ulcerative colitis. GST-A4 gene expression indicated a high exponential rate in logistic regression. Conclusion: Oxidative stress in inflamed colonic tissue can induce Nrf2 gene expression. The performance of Nrf2 transcription factor may lead to the induction of GST-A4 and PRDX1. IL-17A is less detected in intestinal inflammation, presenting Nrf2 factor. The present findings suggest that Nrf2 function in the gut plays a role in arresting both inflammatory response and oxidative damages of UC

An evaluation of the effect of pulsed wave low-level laser therapy on the biomechanical properties of the vertebral body in two experimental osteoporosis rat models.

Osteoporosis (OP) increases vertebral fragility as a result of the biomechanical effects of diminished bone structure and composition. This study has aimed to assess the effects of pulsed wave low-level laser therapy (PW LLLT) on cancellous bone strength of an ovariectomized (OVX-d) experimental rat model and a glucocorticoid-induced OP (GIOP) experimental rat model. There were four OVX-d groups and four dexamethasone-treated groups. A group of healthy rats was used for baseline evaluations. The OVX-d rats were further subdivided into the following groups: control rats with OP, OVX-d rats that received alendronate, OVX-d rats treated with PW LLLT, and OVX-d rats treated with alendronate and PW LLLT. The remaining rats received dexamethasone and were divided into four groups: control, alendronate-treated rats, laser-treated rats, and laser-treated rats with concomitant administration of alendronate. PW LLLT (890 nm, 80 Hz, 0.972 J/cm(2)) was performed on the spinal processes of the T12, L1, L2, and L3 vertebras. We extracted the L1 vertebrae and submitted them to a mechanical compression test. Biomechanical test findings showed positive effects of the PW LLLT and alendronate administration on increasing bending stiffness and maximum force of the osteoporotic bones compared to the healthy group. However, laser treatment of OVA-d rats significantly increased stress high load compared to OVA-d control rats. PW LLLT preserved the cancellous (trabecular) bone of vertebra against the detrimental effects of OV-induced OP on bone strength in rats compared to control OV rats

Edaravone leads to proteome changes indicative of neuronal cell protection in response to oxidative stress

Neuronal cell death, in neurodegenerative disorders, is mediated through a spectrum of biological processes. Excessive amounts of free radicals, such as reactive oxygen species (ROS), has detrimental effects on neurons leading to cell damage via peroxidation of unsaturated fatty acids in the cell membrane. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has been used for neurological recovery in several countries, including Japan and China, and it has been suggested that Edaravone may have cytoprotective effects in neurodegeneration. Edaravone protects nerve cells in the brain by reducing ROS and inhibiting apoptosis. To gain further insight into the cytoprotective effects of Edaravone against oxidative stress condition we have performed comparative two-dimensional gel electrophoresis (2DE)-based proteomic analyses on SH-SY5Y neuroblastoma cells exposed to oxidative stress and in combination with Edaravone. We showed that Edaravone can reverse the cytotoxic effects of H2O2 through its specific mechanism. We observed that oxidative stress changes metabolic pathways and cytoslceletal integrity. Edaravone seems to reverse the H2O2-mediated effects at both the cellular and protein level via induction of Peroxiredoxin-2. (C) 2015 Elsevier Ltd. All rights reserved

Designing a novel multi‑epitope vaccine against Ebola virus using reverse vaccinology approach

Ebola virus (EBOV) is a dangerous zoonotic infectious disease. To date, more than 25 EBOV outbreaks have been documented, the majority of which have occurred in Central Africa. The rVSVG-ZEBOV-GP vaccine (ERVEBO), a live attenuated vaccine, has been approved by the US Food and Drug Administration (FDA) to combat EBOV. Because of the several drawbacks of live attenuated vaccines, multi-epitope vaccines probably appear to be safer than live attenuated vaccines. In this work, we employed immunoinformatics tools to design a multi-epitope vaccine against EBOV. We collected sequences of VP35, VP24, VP30, VP40, GP, and NP proteins from the NCBI database. T-cell and linear B-cell epitopes from target proteins were identified and tested for antigenicity, toxicity, allergenicity, and conservancy. The selected epitopes were then linked together in the vaccine's primary structure using appropriate linkers, and the 50S ribosomal L7/L12 (Locus RL7 MYCTU) sequence was added as an adjuvant to the vaccine construct's N-terminal. The physicochemical, antigenicity, and allergenicity parameters of the vaccine were all found to be satisfactory. The 3D model of the vaccine was predicted, refined, and validated. The vaccine construct had a stable and strong interaction with toll-like receptor 4 (TLR4) based on molecular docking and molecular dynamic simulation (MD) analysis. The results of codon optimization and in silico cloning revealed that the proposed vaccine was highly expressed in Escherichia coli (E. coli). The findings of this study are promising; however, experimental validations should be carried out to confirm these findings