Influence of 1 Alpha, 25-Dihydroxyvitamin D3 on T helper 17 cells and related cytokines in systemic lupus erythematosus

Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Emerging data suggests that T helper 17 (Th17) cells play a pathogenic role in SLE and the increased number of these cells correlates with disease activity. In recent years, 1α, 25-dihydroxyvitamin D3 (1,25VitD3) has been considered as an immunomodulatory factor. Objective: To investigate the effect of 1,25VitD3 on Th17 cells and on the expression of related cytokines in SLE patients. Method: Thirty SLE patients (newly diagnosed or in remission) were sampled for 10 ml whole blood to isolate peripheral blood mononuclear cells (PBMCs) using Ficoll-Hypaque density gradient centrifugation. Isolated cells were cultured in the presence and absence of 50 nM 1,25VitD3. After incubation, cells were harvested and stimulated for 4-5 hours with phorbol myristate acetate (PMA) and ionomycin in the presence of brefeldin A. IL-17 secreting cells were analyzed by flowcytometry. RNA was extracted from cultured cells, cDNA was synthesized, and the expression levels of IL-6, IL-17, IL-23 and TGF-β genes were assessed by real-time PCR. Results: The percentage of Th17 cells (CD3+CD8- IL-17+ T cells) decreased significantly in 1,25VitD3-treated cells (3.67 ± 2.43%) compared to untreated cells (4.65 ± 2.75%) (p=0.003). The expression of TGF-β up regulated (1.38-fold) and the expression of IL-6 (50%), IL-17 (27%) and IL-23 (64%) down regulated after 1,25VitD3 treatment. Conclusion: This study showed that 1,25VitD3 modulates Th17 related pathways in SLE patients and revealed the immunomodulatory effect of 1,25VitD3 on the Th17 mediated autoimmunity. © 2015, Shiraz University of Medical Sciences. All rights reserved

Correlated Factors with Back Pain in Patients after Coronary Angiography

Background and Objective: Cardiac angiography, which is widely used in Iran, is a diagnostic and therapeutic procedure for cardiac diseases. The patients suffer from back pain due to complete bed rest after angiography. Thus, this study aimed at determining the correlated factors with the severity of back pain after cardiac angiography in Dr. Ganjavian Hospital of Dezful, 2011. Material and Methods: In this correlational study, 140 candidates of cardiac angiography were selected via convenience sampling. We used a checklist to collect the data about age, sex, body mass index(BMI), smoking, high blood pressure, diabetes and duration of angiography, which are the influential factors of the severity of back pain. Then, the severity of back pain was measured at first, second, fourth and sixth hour after angiography, using a numerical scale of pain assessment.To analyze the data, we used descriptive statistic, Mann Whitney and Spearman correlation. Results:The subjects are males (N=67), females (N=64) and smokers (12%). The mean age is 55.7±7.7, and body mass index is 27.6±3.07. None of them has history of back pain and previous angiography. Based on Spearman, there is no significance correlation between back pain of 1, 2, 4, and 6 hours after angiography and factors such as age, BMI and duration of angiography. Man Whitney test indicates a statistical significance between gender and severity of pain in the first hour (Z=-2.17) and sixth hour (Z=-2.4) after angiography, whereas there is no statistical significance in the second, fourth and fifth hour after angiography. As well, there is no significant correlation between back pain and variables such as smoking, diabetes and hypertension. Conclusion:The findings showthat the nurses by being aware of related factors to back pain severity can try to reduce the pain and promote the patients’ convenience. Keywords: Coronary angiography, Back pain, Correlated Factor

IL10 Low-Frequency Variants in Behçet's Disease Patients

To explain the missing heritability after the genome-wide association studies era, sequencing studies allow the identification of low-frequency variants with a stronger effect on disease risk. Common variants in the interleukin 10 gene (IL10) have been consistently associated with Behçet's disease (BD) and the goal of this study is to investigate the role of low-frequency IL10 variants in BD susceptibility

Expression of Regulatory Platelet MicroRNAs in Patients with Sickle Cell Disease

Background: Increased platelet activation in sickle cell disease (SCD) contributes to a state of hypercoagulability and confers a risk of thromboembolic complications. The role for post-transcriptional regulation of the platelet transcriptome by microRNAs (miRNAs) in SCD has not been previously explored. This is the first study to determine whether platelets from SCD exhibit an altered miRNA expression profile. Methods and Findings: We analyzed the expression of miRNAs isolated from platelets from a primary cohort (SCD = 19, controls = 10) and a validation cohort (SCD = 7, controls = 7) by hybridizing to the Agilent miRNA microarrays. A dramatic difference in miRNA expression profiles between patients and controls was noted in both cohorts separately. A total of 40 differentially expressed platelet miRNAs were identified as common in both cohorts (p-value 0.05, fold change>2) with 24 miRNAs downregulated. Interestingly, 14 of the 24 downregulated miRNAs were members of three families - miR-329, miR-376 and miR-154 - which localized to the epigenetically regulated, maternally imprinted chromosome 14q32 region. We validated the downregulated miRNAs, miR-376a and miR-409-3p, and an upregulated miR-1225-3p using qRT-PCR. Over-expression of the miR-1225-3p in the Meg01 cells was followed by mRNA expression profiling to identify mRNA targets. This resulted in significant transcriptional repression of 1605 transcripts. A combinatorial approach using Meg01 mRNA expression profiles following miR-1225-3p overexpression, a computational prediction analysis of miRNA target sequences and a previously published set of differentially expressed platelet transcripts from SCD patients, identified three novel platelet mRNA targets: PBXIP1, PLAGL2 and PHF20L1. Conclusions: We have identified significant differences in functionally active platelet miRNAs in patients with SCD as compared to controls. These data provide an important inventory of differentially expressed miRNAs in SCD patients and an experimental framework for future studies of miRNAs as regulators of biological pathways in platelets. © 2013 Jain et al

Gene Expression Profiling and Association Studies Implicate the Neuregulin Signaling Pathway in Behçet's Disease Susceptibility

Behçet's disease (BD) is a complex disease with genetic and environmental risk factors implicated in its etiology; however, its pathophysiology is poorly understood. To decipher BD's genetic underpinnings, we combined gene expression profiling with pathway analysis and association studies. We compared the gene expression profiles in peripheral blood mononuclear cells (PBMCs) of 15 patients and 14 matched controls using Affymetrix microarrays and found that the neuregulin signaling pathway was over-represented among the differentially expressed genes. The Epiregulin (EREG), Amphiregulin (AREG), and Neuregulin-1 (NRG1) genes of this pathway stand out as they are also among the top differentially expressed genes. Twelve haplotype tagging SNPs at the EREG-AREG locus and 15 SNPs in NRG1 found associated in at least one published BD genome-wide association study were tested for association with BD in a dataset of 976 Iranian patients and 839 controls. We found a novel association with BD for the rs6845297 SNP located downstream of EREG, and replicated three associations at NRG1 (rs4489285, rs383632, and rs1462891). Multifactor dimensionality reduction analysis indicated the existence of epistatic interactions between EREG and NRG1 variants. EREG-AREG and NRG1, which are members of the epidermal growth factor (EGF) family, seem to modulate BD susceptibility through main effects and gene–gene interactions. These association findings support a role for the EGF/ErbB signaling pathway inBD pathogenesis that warrants further investigation and highlight the importance of combining genetic and genomic approaches to dissect the genetic architecture of complex diseases

Status of Total Antioxidant Capacity and Malondialdehyde Level in Methamphetamine Addicts: A Cross Sectional Study

Background: Methamphetamine (MA) is an illegal amphetamine-like which stimulate the central nervous system. In recent years, MA has been widely abused worldwide. Previous studies have suggested that oxidative stress (OS) plays an important role in MA-induced toxicity. From this view, antioxidant therapy could be considered as a potential drug therapy in MA abusers. Therefore, the objective of this study was to evaluate OS status in MA abusers.Methods: This was a cross-sectional study conducted on 21 MA abusers who referred to Iranian National Center for Addiction Studies and Congress 60 Humane Revivification Society, and 15 healthy males as a control group. The demographic data and peripheral blood sampling was obtained from both groups. The serum malondialdehyde (MDA) level as a marker of plasma lipid peroxidation and total antioxidant capacity (TAC) of plasma were analyzed.Results: Significant decrease in plasma TAC in case group was observed (101.85±12.5 vs. 130.7±16.12 mmol/L). No significant increase in MDA serum level was detected in case group in comparison with control (27.35±2.6 vs. 26.67±2.22 µmol/L, respectively). Neither the serum MDA levels nor the plasma TAC were significantly correlated with the duration and amount of MA abuse.Conclusion: It seems that, MA abuse is associated with prooxidant-antioxidant imbalance, which suggests evaluation the role of antioxidants administration for the prevention and treatment of MA-induced toxicity

A qualitative study on personal information management (PIM) in clinical and basic sciences faculty members of a medical university in Iran

Background: Personal Information Management (PIM) refers to the tools and activities to save and retrieve personal information for future uses. This study examined the PIM activities of faculty members of Iran University of Medical Sciences (IUMS) regarding their preferred PIM tools and four aspects of acquiring, organizing, storing and retrieving personal information. Methods: The qualitative design was based on phenomenology approach and we carried out 37 interviews with clinical and basic sciences faculty members of IUMS in 2014. The participants were selected using a random sampling method. All interviews were recorded by a digital voice recorder, and then transcribed, codified and finally analyzed using NVivo 8 software. Results: The use of PIM electronic tools (e-tools) was below expectation among the studied sample and just 37 had reasonable knowledge of PIM e-tools such as, external hard drivers, flash memories etc. However, all participants used both paper and electronic devices to store and access information. Internal mass memories (in Laptops) and flash memories were the most used e-tools to save information. Most participants used "subject" (41.00) and "file name" (33.7 ) to save, organize and retrieve their stored information. Most users preferred paper-based rather than electronic tools to keep their personal information. Conclusion: Faculty members had little knowledge about PIM techniques and tools. Those who organized personal information could easier retrieve the stored information for future uses. Enhancing familiarity with PIM tools and training courses of PIM tools and techniques are suggested