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

Application of Deep Neural Network to Predict the High-Cycle Fatigue Life of AISI 1045 Steel Coated by Industrial Coatings

In this study, deep learning approach was utilized for fatigue behavior prediction, analysis, and optimization of the coated AISI 1045 mild carbon steel with galvanization, hardened chromium, and nickel materials with different thicknesses of 13 and 19 mu m were used for coatings and afterward fatigue behavior of related specimens were achieved via rotating bending fatigue test. Experimental results revealed fatigue life improvement up to 60% after applying galvanization coat on untreated material. Obtained experimental data were used for developing a Deep Neural Network (DNN) modelling and accuracy of more than 99%.was achieved. Predicted results have a fine agreement with experiments. In addition, parametric analysis was carried out for optimization which indicated that coating thickness of 10-15 mu m had the highest effects on fatigue life improvement

Potential application of mesh-free SPH method in turbulent river flows

A comprehensive review has been completed on the simulation of turbulent flow over rough beds using mesh-free particle models. Based on the outcomes of this review, an improved Smoothed Particle Hydrodynamics (SPH) method has been developed for open channel flows over a rough bed, in which a mixing length model is used for modeling the 2D turbulence and a drag force equation is proposed for treating the boundary shear. The proposed model was applied to simulate a depth-limited open channel flow over a rough bed surface. The results of the velocity profile and shear stress distribution show a good agreement with the experimental data and existing analytical solutions. This work reveals that in order to correctly model turbulent open channel flow over a rough bed, the treatment of both flow turbulence and bed roughness effect is equally important

Cathelicidin (LL-37) and its correlation with pro-oxidant, antioxidant balance and disease activity in systemic lupus erythematosus: A cross-sectional human study

Background Cathelicidin (LL-37), an endogenous antimicrobial peptide, has recently been involved in the pathogenesis of autoimmune diseases. To assess whether LL-37 reflects disease activity, we measured serum levels of it in systemic lupus erythematosus (SLE) patients with active and inactive disease compared to healthy controls. LL-37 was also compared between new and old cases. Moreover, the correlation of LL-37 and pro-oxidant, antioxidant balance (PAB) was measured. Methods The study population consisted of 50 SLE patients and 28 healthy controls. Of those, 39 patients had active and 11 patients had inactive disease. Serum levels of LL-37 were measured by ELISA and PAB values by a special method. Results There was no difference in levels of LL-37 between patients and healthy controls (50.9 ± 20.8 vs. 67.7 ± 43.3 ng/ml, P = 0.31). LL-37 did not correlate with SLEDAI and its items in total patients. LL-37 had a positive correlation with SLEDAI in active patients (P = 0.01, r = 0.4). In active patients (78% of patients), multivariate regression analysis showed significant negative correlation between LL-37 and C3 (P = 0.01, standardized beta -0.50). No difference was found in levels of PAB between patients and controls (90.4 ± 34.1 vs. 86.9 ± 25.6 HK, P = 0.4).There was no difference in the levels of PAB between patients with active and inactive disease (93.2 ± 34.1 vs. 80.2 ± 33.7 HK, P = 0.27). No correlation was found between levels of PAB and SLEDAI items and total score. However, a positive correlation between the levels of LL-37 and PAB in SLE patients was found (r = 0.3, P < 0.01). Conclusion Based on this study, serum LL-37 and PAB did not increase in lupus compared with healthy individuals. LL-37 serum values rose in parallel with SLEDAI in active disease. Positive correlation between serum PAB and LL-37 could be a great achievement of this study that may suggest the role of antioxidants in controlling NETosis. © 2016 SAGE Publications

Additional effect of etanercept or infliximab on the liver function tests of patients with rheumatoid arthritis: a cohort study

Saeed Akhlaghi,1 Maryam Sahebari,2 Mahmoud Mahmoodi,1 Mehdi Yaseri,1 Mohammad Ali Mansournia,1 Houshang Rafatpanah,3 Hojjat Zeraati1 1Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; 2Rheumatic Diseases Research Center (RDRC), Mashhad University of Medical Sciences, Mashhad, Iran; 3Inflammation and Inflammatory Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Purpose: One of the most important long-term side effects of therapy for rheumatoid arthritis (RA) is the elevation of liver function tests, with earlier studies reporting an elevation of more than 1&times; the upper limit of normal (&gt;1 &times; ULN). The current study expands the literature by comparing the trends of transaminase changes caused by conventional and biologic disease-modifying antirheumatic drugs (DMARDs).Patients and methods: The drug categories examined were methotrexate (MTX) and all other nonbiologic DMARDs. Where RA patients exhibited inadequate response to conventional DMARDs (cDMARDs), we added biologic DMARDs (bDMARDs) to the treatment. We compared the trend of changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the patients receiving MTX with the trend observed in the patients whose treatment encompassed both bDMARDs and MTX. The comparison was conducted using random intercept models, which are a type of linear mixed effects model.Results: This work involved 512 RA patients (MTX: 450, MTX + infliximab [INF]: 26, MTX + etanercept [ETA]: 36), whose ALT and/or AST levels were measured in 1,786 visits (MTX: 1,543, MTX + INF: 107, MTX + ETA: 136). ALT and/or AST elevations greater than 1 &times; ULN were observed in 344 (19.3%) visits (MTX: 295 [19.1%], MTX + INF/ETA: 49 [20.2%]). In this study, the trends of ALT and AST changes increased when receiving MTX, while the INF/ETA addition decreased these trends. The random intercept models indicated that changes in the mean ALT levels were significantly different over the time for MTX and MTX + INF/ETA groups (&beta; [SE] =-0.190 [0.093], P= 0.040) but changes in the mean AST levels were nonsignificantly different over the time for such groups (&beta; [SE] =-0.099 [0.064], P=0.120).Conclusion: Despite a higher incidence of elevated transaminases during the use of MTX + INF/ETA, the combination of INF/ETA with MTX reduced transaminase levels and returned ALT levels to normal concentrations. Keywords: longitudinal, ALT, AST, DMARDs, biologic DMARDs, MT

The Relationship between Serum Pro‐Brain Natriuretic Peptide (Pro‐BNP) Levels and Pulmonary Arterial Hypertension (PAH) in Patients with Limited Scleroderma

Introduction: Pulmonary arterial hypertension (PAH) is a late progressive sclerodermarelated complication, which can lead to right heart failure and cor pulmonale. Given that cardiac catheterization is a diagnostic method of choice for PAH, and considering the high risks of this method, the purpose of this study was to evaluate the relationship between serum Pro‐Brain natriuretic peptide (Pro‐BNP) Levels and PAH in patients with limited scleroderma. Materials and Methods: In this cross sectional study , during June 2011‐ Dec 2013, referring patients to two major educational hospitals, Mashhad‐ Iran, with scleroderma, who were afflicted with the disease for at least two years (or more), were enrolled in the study if they met the inclusion and exclusion criteria. All the patients underwent echocardiography to determine the pulmonary artery pressure (PAP). Afterwards, the subjects were referred to a lung center for performing body plethysmography, carbon monoxide diffusing capacity (DLCO), and 6‐ minute walk test (6MWT). Pro‐BNP Serum level was determined using flourescent immune assay method. Results: The present study included 20 patients (18 female subjects) with the mean age of 43.28±9.56 yrs, and the mean pro‐BNP level of 138 pg/ml. The logarithmic correlation between PAP values, Forced Vital Capacity /DLCO ratio, and pro‐BNP level, which was measured using Pearson's correlation coefficient, showed a significant association among these variables( respectively, r=0.76, P0.001; r=0.677, P=0.011). Moreover, the DLCO decrease was associated with increasing pro‐BNP level, though this relationship was not significant. Conclusion: This study showed that there was a significant relationship between the serum levels of pro‐BNP marker and increased PAP in the echocardiography, DLCO reduction, and FVC/DLCO increase. In fact, this serum marker can be used in patients with systemic scleroderma (SSc) to evaluate the status of PAH