Cigarette smoking and risk of adult-onset Still disease: a propensity score matching analysis.

BACKGROUND: Environmental factors play an important role in the pathogenesis of rheumatic diseases. Smoking is thought to be a risk factor for autoimmune rheumatic diseases. AIMS: The purpose of the present study was to assess the association between smoking and adult-onset Still disease (AOSD) and the effect of smoking on outcomes of this disease. METHODS: In this case-control study, patients with AOSD who met the Yamaguchi criteria, were older than 16 years at the disease onset and were in follow-up for at least 12 months were consecutively enrolled in the study. The outcome of AOSD was assessed by acquiring remission on treatment, remission off treatment, time to remission and rate of flare. The smoking status of participants was defined by direct or phone interviews. Individuals who had smoked daily for at least 6 months were defined as a smoker. We performed propensity score matching analyses by using four parameters, including age, sex, educational status and marital status. RESULTS: Propensity score matching resulted in 72 patients with AOSD and 216 matched controls. The number of ever smokers in the AOSD and control groups were 11 (15.3%) and 25 (11.6%) respectively. There was no significant increase in the risk of AOSD in multivariate analysis after adjustment for age, sex, marital status and educational level. There were no significant differences in the outcomes of AOSD between ever and never smokers. CONCLUSIONS: Smoking probably is not a risk factor for AOSD and did not affect the response to treatment.

Randomized double-blinded controlled trial on the effect of synbiotic supplementation on IL-17/IL-23 pathway and disease activity in patients with axial spondyloarthritis.

BACKGROUND: Interleukin 17 (IL17)-expressing CD4+ T cells and IL-17/IL-23 pathway play a key role in the pathogenesis of axial spondyloarthritis (axSpA). Synbiotics have been suggested due to their immunomodulatory effects in the treatment of autoimmune diseases. This randomized double-blind, placebo-controlled trial was designed to assess the effects of synbiotic supplement on IL-17/IL-23 pathway and disease activity in patients with axSpA. METHODS: Forty-eight axSpA patients were randomly allocated to use one synbiotic capsule or placebo daily for 12 weeks. Disease activity was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and ASAS-endorsed disease activity score-C-reactive protein (ASDAS-CRP). The secondary outcome was proportion of IL17-expressing CD4+ T cells, IL-17 and IL-23 gene expression, and supernatant levels of IL-17 and IL-23, which were measured at the baseline and end of the trial. RESULTS: A total of 48 patients were randomized into the synbiotic and placebo groups. Thirty-eight patients completed the study. Synbiotic supplementation significantly reduced the proportion of IL17-expressing CD4+ T cells (4.88 ± 2.47 vs. 2.16 ± 1.25), gene expression of IL-17 (1.03 ± 0.24 vs. 0.65 ± 0.26) and IL-23 (1.01 ± 0.13 vs. 0.68 ± 0.24) and serum IL-17 (38.22 ± 14.40 vs. 24.38 ± 11.68) and IL-23 (51.77 ± 17.40 vs. 32.16 ± 12.46) compared with baseline. Significant differences between groups were noticed only in the proportion of IL17-expressing CD4+ T cells, and IL-17 and IL-23 gene expression. Synbiotic supplementation did not significantly alter BASDAI and ASDAS-CRP compared with baseline and placebo group at the end of trial. CONCLUSION: Present study indicated beneficial effect of synbiotic supplement on IL-17/IL-23 pathway without improving disease activity in axSpApatients.HighlightsSynbiotic supplementation reduced IL17-expressing CD4+ T cells proportion in axSpA.Synbiotic supplementation decreased IL-17 and IL-23 gene expression in axSpA.Synbiotic supplementation did not change disease activity score in axSpA.

Effects of N-acetylcysteine supplementation on disease activity, oxidative stress, and inflammatory and metabolic parameters in rheumatoid arthritis patients: a randomized double-blind placebo-controlled trial.

Considering the importance of inflammation and oxidative stress in the development of rheumatoid arthritis (RA) as well as anti-inflammatory and antioxidant features of N-acetylcysteine (NAC), this study was conducted to evaluate the effect of NAC supplementation on disease activity, oxidative stress, and inflammatory and metabolic parameters in RA patients. In a randomized double-masked placebo-controlled trial, 74 RA subjects were chosen and randomly divided into two groups to take 600 mg of NAC or placebo twice daily for 3 months. Before and after the study, disease activity was assessed via disease activity score-28 (DAS-28), and serum malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione peroxidase (GPX) activity, nitric oxide (NO), high-sensitivity C-reactive protein (hs-CRP), fasting blood sugar (FBS), lipid profile, and erythrocyte sedimentation rate (ESR) were measured. Seventy patients completed the trial. Compared to baseline, NAC significantly reduced morning stiffness (P < 0.001), DAS-28 (P < 0.001), ESR (P = 0.004), MDA (P < 0.001), NO (P < 0.001), hs-CRP (P = 0.006), FBS (P < 0.001), and low-density lipoprotein cholesterol (LDL-C) (P = 0.023) and significantly increased GPx activity (P = 0.015) and high-density lipoprotein cholesterol (HDL-C) level (P = 0.001). After treatment, remarkable differences were only seen between the two groups in serum NO (P = 0.003), FBS (P = 0.010), and HDL-C (P < 0.001) adjusted for baseline measures. There were no significant changes in morning stiffness, DAS-28, ESR, hs-CRP, MDA, TAC, GPx activity, triglyceride, total cholesterol, and LDL-C levels compared to the placebo group. In conclusion, NAC did not improve RA disease activity, but reduced NO and FBS and increased HDL-C levels. It appears that NAC should not be consumed as a replacement for routine medications prescribed in RA therapy, but it can be used as an adjunctive therapy.

Effects of nanocurcumin supplementation on T-helper 17 cells inflammatory response in patients with Behcet's disease: a randomized controlled trial.

OBJECTIVE: Present research was performed to assess the effects of nanocurcumin supplementation on T-helper 17 (Th17) cells inflammatory response in patients with Behcet's disease (BD). METHODS: In this randomized double-blind, placebo-controlled trial, 36 BD subjects were randomly placed into two groups to take 80 mg/day nanocurcumin or placebo for eight weeks. Disease activity, frequency of Th17 cells and expression of related parameters including retinoic acid-related orphan receptor γ (RORγt) transcription factor messenger RNA (mRNA), related microRNAs (miRNAs) such as miRNA-155, miRNA-181, and miRNA-326 as well as proinflammatory cytokines including interleukin (IL)-17 and IL-23 were evaluated. RESULTS: Thirty-two patients (17 in the nanocurcumin and 15 in the placebo groups) completed the trial. Number of Th17 cells decreased significantly in the nanocurcumin group compared to baseline (p = .012) and placebo (p = .047). Moreover, RORγt, IL-17, IL-23, miRNA-155, miRNA-181, and miRNA-326 mRNA expression decreased significantly in the nanocurcumin group compared with baseline (p = .004, p = .009, p < .001, p < .001, p < .001, p < .001, respectively) and placebo (p = .002, p = .021, p = .006, p = .035, p < .001, p = .017, respectively). Significant reductions in IL-17 and IL-23 were seen in nanocurcumin group compared with baseline (p = .017 and p = .015) and placebo (p = .047 and p = .048, respectively). Significant reduction in disease activity was observed in nanocurcumin group compared with placebo group (p = .035). CONCLUSION: Nanocurcumin supplementation had favorable effects in improving inflammatory factors and disease activity in BD patients. Additional studies are warranted to suggest nanocurcumin as a safe complementary therapy in BD.HighlightsNanocurcumin supplementation decreased Th17 cells frequency significantly compared with baseline and placebo group.Nanocurcumin supplementation decreased mRNA expression of RORγt, IL-17, IL-23, miRNA-155, miRNA-181, and miRNA-326 significantly compared to baseline and placebo group.Nanocurcumin supplementation decreased cell supernatant IL-17 and IL-23 significantly compared to baseline and placebo group.Nanocurcumin supplementation decreased disease activity significantly compared to placebo group.

Profiling inflammatory cytokines following zinc supplementation: a systematic review and meta-analysis of controlled trials.

Chronic inflammation has been considered as the main cause of chronic diseases. Zn has anti-inflammatory effects by decreasing the expression of inflammatory markers. The present systematic review and meta-analysis study aims to evaluate the impact of Zn supplementation on inflammation. PubMed (Medline), Scopus, Web of Science, and Embase databases were searched up to 10 December 2020. Controlled trials which have investigated the effects of Zn supplementation on serum/plasma levels of inflammatory cytokines in subjects aged >15 years were included. A pooled meta-analysis was performed using a random effect model. Sensitivity analysis was performed to determine the robustness of the observed effect sizes. A total of twelve studies was included in meta-analysis. Zn could decrease IL-6 levels (standardised mean difference (SMD) = -0·76 pg/ml; 95 % CI -1·28, -0·24; P = 0·004). There was no significant change in TNF-α (SMD = 0·42 pg/ml; 95 % CI -0·31, 1·16; P = 0·257) and IL-2 levels (SMD = 1·64 pg/ml; 95 % CI -1·31, 4·59; P = 0·277) following Zn supplementation. However, Zn could increase IL-2 significantly after the deletion of one arm in sensitivity analysis (SMD = 2·96 pg/ml; 95 % CI 2·03, 3·88; P < 0·05). Conclusively, Zn supplementation can decrease the IL-6 level. Zn increased IL-2 level after the sensitivity analysis. Zn supplementation has not ameliorative effects on TNF-α.

Treatment of palindromic rheumatism: A systematic review.

OBJECTIVES: Palindromic rheumatism (PR) characterised by self-resolving attacks of arthritis and peri-arthritis that may progress to other autoimmune connective tissue diseases (CTDs). The aim of this systematic review was to analyse the effectiveness of different treatments on PR. METHODS: Articles were collected from Cochrane, PubMed, Science Direct, Scopus, ProQuest, Ebsco, Google Scholar, MEDLINE and EMBASE. Search keywords were "palindromic rheumatism," "palindromic rheumatism and remission," "palindromic rheumatism and course," "palindromic rheumatism and prognosis," "palindromic rheumatism and treatment" and "palindromic rheumatism and therapy." The studies that were included met the following criteria: (a) adult patients aged ≥16 with PR; (b) being on treatment with medications defined as those that were developed for the treatment of inflammatory arthritis and (c) including outcome measures to evaluate the efficacy of the treatment including remission rate and progression to other diseases. RESULTS: Twenty-four studies met the inclusion criteria. Although case series and retrospective studies showed that conventional disease-modifying antirheumatic drugs (DMARDs) can control attacks of the disease, 15%-70% of patients with PR evolve to autoimmune CTDs during several years, despite treatment with DMARDs. A retrospective study showed that tight control strategy could control attacks of the disease and prevent its progression to RA. The evidence provided from available studies is insufficient to determine that DMARDs can prevent the progression of PR to autoimmune CTDs. CONCLUSION: Although case series and retrospective studies showed that DMARDs can control attacks of the disease, our review suggests that randomised clinical trials and prospective studies with adequate sample size are needed to prove that DMARDs can prevent progression of PR to autoimmune CTDs and which DMARDs are preferred for the treatment of PR.

Long-term remission in patients with systemic lupus erythematosus.

BACKGROUND: Remission has been introduced as a desirable outcome and the primary target of treatment in systemic lupus erythematosus (SLE). The purpose of this study was to identify the number of patients in remission and the long-term outcome of the disease and their predictors. METHOD: Of the 379 patients in our SLE Database, a total of 193 patients fulfilled the inclusion criteria. Remission was definition according to the definitions of remission in SLE. Three levels of remission were defined, including remission on-treatment, remission off-treatment and complete remission. In addition, we have defined a sustained remission for each level of remission in which the remission should last at least 5 years. RESULTS: During a median follow-up of 96 months, remission on-treatment and off-treatment, and complete remission were obtained in 49.2%, 38.9% and 19.2% of patients, respectively. Predictors of remission on-treatment in multivariate regression analysis were adherence to therapy and remission induction during 6 months after treatment. Predictors of remission off-treatment were age ≥40 at the time of analysis and remission induction during 6 months after treatment. Poor outcome (SLE Damage Index ≥1) was observed in 28% of the patients. Age at disease onset <30, kidney and nervous system involvement and SLEDAI-2K ≥ 11 at the cohort entry were the risk factors of poor outcome in multivariate analysis. However, sustained remission on-treatment had a negative association with poor outcome. CONCLUSION: Treatment with glucocorticoids, antimalarials, immunosuppressants and biologics in sequential or in combination may cause durable remission. Patients with durable remission have significantly lower organ damage.

Effects of melatonin supplementation on serum oxidative stress markers and disease activity in systemic lupus erythematosus patients: A randomised, double-blind, placebo-controlled trial.

BACKGROUND: Considering pathological significance of oxidative stress in systemic lupus erythematosus (SLE), current research aimed to evaluate the effects of melatonin supplementation on oxidative stress markers and disease activity in SLE. METHOD: In this randomised double-blind, placebo-controlled trial, 32 SLE females were selected and randomly assigned into two groups to take 10 mg/day melatonin or placebo for 12 weeks. Before and after trial, serum malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured and disease activity was determined by Systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K). RESULTS: Twenty-five patients (13 in the melatonin and 12 in the placebo groups) completed the trial. Melatonin supplementation caused significant reduction in serum MDA compared with baseline (P = .003) and placebo group (P = .004). Serum TAC level did not change significantly in the melatonin group compared with baseline and placebo group (P > .05). Furthermore, melatonin supplementation did not cause significant change in disease activity compared to baseline and placebo group (P > .05). CONCLUSION: This study demonstrated affirmative effects of melatonin in decreasing oxidative stress in SLE patients without any effect on disease activity. Further investigations are required to affirm these primitive findings and to achieve concise conclusions.What's known Free radical damage and oxidative stress has a remarkable function in systemic lupus erythematosus (SLE) pathogenesis. Products derived from oxidative modification cascades are found in biological fluids and their redundancy has a correlation with disease activity and organ damage in SLE. Dietary supplements, which decrease oxidative stress, would be useful in managing SLE. Melatonin is a potent antioxidant and has anti-inflammatory and immunomodulatory characteristics. Limited in vitro and animal studies are available indicating desirable effects of melatonin in preventing from SLE organ damage, thereby opening a new area of investigation that can contribute to using melatonin as a therapy or co-therapy for SLE. What's new Melatonin supplementation caused significant reduction in serum MDA compared with baseline and placebo group. Serum TAC level did not change significantly in the melatonin group compared with baseline and placebo group. Furthermore, melatonin supplementation did not cause significant change in disease activity compared to baseline and placebo group.

Cholinergic anti-inflammatory pathway and connective tissue diseases.

Connective tissue diseases (CTDs) consist of an extensive range of heterogeneous medical conditions, which are caused by immune-mediated chronic inflammation and influences the various connective tissues of the body. They include rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, vasculitis, Sjögren's syndrome, Behcet's disease, and many other autoimmune CTDs. To date, several anti-inflammatory approaches have been developed to reduce the severity of inflammation or its subsequent organ manifestations. As a logical mechanism to harnesses the undesired inflammation, some studies investigated the role of the intrinsic cholinergic anti-inflammatory pathway (CAP) in the modulation of chronic inflammation. Many different experimental and clinical models have been developed to evaluate the therapeutic significance of the CAP in CTDs. On the other hand, an issue that is less emphasized in this regard is the presence of autonomic neuropathy in CTDs, which influences the efficiency of CAP in such clinical settings. This condition occurs during CTDs and is a well-known complication of patients suffering from them. The advantages and limitations of CAP in the control of inflammatory responses and its possible therapeutic benefits in the treatment of CTDs are the main subjects of the current study. Therefore, this narrative review article is provided based on the recent findings of the complicated role of CAP in CTDs which were retrieved by searching Science Direct, PubMed, Google Scholar, and Web of Science. It seems that delineating the complex influences of CAP would be of great interest in designing novel surgical or pharmacological therapeutic strategies for CTDs therapy.

Long-term outcome and predictors of remission in Behçet's disease in daily practice.

BACKGROUND: Many factors can influence the response to treatment and prognosis of Behçet's disease (BD). Identifying the predictors of response to treatment can improve the quality and decrease the cost of medical care. This analytical study was performed to identify factors affecting the remission and outcome in BD patients with long-term follow-up. METHODS: A total of 245 BD patients aged over 16 years were followed for at least 12 months and visited at least three times a year were included. The outcome was assessed by the number of patients who were in sustained and long-term remission, had lost the primary criteria of BD for at least 12 months, were asymptomatic, and developed the sequela of disease or deceased. Sustained remission was defined as being in remission for at least six months. Long-term remission was defined as remission for ≥ 5 years. RESULTS: Mean age and mean duration of follow-up were 35.1 ± 10.7 years and 92.3 months, respectively. At the end of follow-up, 63.2% of the patients lost the criteria of BD, 51.8% of the cases were in sustained remission, and 36.2% of them were asymptomatic. Predictors of sustained remission were adherence to therapy and treatment for more than six years. Having genital ulcers and treatment with methotrexate were associated with non-remission. Predictor of long-term remission was remission induction in the first two years of the treatment. Treatment with methotrexate was associated with non-remission. Poor outcome was observed in 31.8% of patients. Male sex, obesity, and having severe disease were the risk factors of poor outcome. CONCLUSION: Achieving remission in BD is not inaccessible. Treatment with conventional and biologic disease-modifying antirheumatic drugs may cause sustained and long-term remission. Adherence to treatment, remission induction during the two years after the diagnosis and treatment for at least six years have significant role.

Evaluation of DNA methylation status of toll-like receptors 2 and 4 promoters in Behcet's disease.

BACKGROUND: Altered innate immune function plays an important role in the initiation of inflammatory response in Behcet's disease (BD). Toll-like receptors (TLRs) are the master regulators of the innate immune system. Because the role of TLRs remains unknown in the pathogenesis of BD, the present study aimed to evaluate the expression levels and methylation status of the TLR2 and TLR4 promoters in patients with BD. METHODS: In the present study, Iranian Azeri BD patients (n = 47) with an active (n = 22) and inactive (n = 25) period, and healthy controls (n = 61), were matched according to age, sex and ethnicity. TLR2 and TLR4 genes promoter CpG islands were predicted with the Eukaryotic Promoter Database (https://epd.vital-it.ch). Methylated DNA immunoprecipitation (MeDIP) was conducted. RESULTS: The results showed that mRNA of TLR4 was significantly increased in the peripheral blood mononuclear cells (PBMCs) of BD patients with an active phase compared to the control group. Differences in mRNA of TLR4 between the inactive BD and control groups were not significant. Differences in TLR2 mRNA levels in the PBMCs of the active and inactive phase BD and control groups were not significant. The methylation rate of TLR4 gene promoter was significantly lower in the active and inactive BD groups compared to the control group. The difference between the active and inactive BD groups was not significant. There was no significant difference in the methylation rates of the TLR2 gene between studied groups. CONCLUSIONS: Our preliminary findings suggest that the hypomethylation of TLR4 gene may be involved in the pathogenesis of BD via increasing TLR4 expression.

Interleukin-17 mRNA expression and serum levels in Behçet's disease.

Behçet's disease (BD) was considered a T-helper 1 (Th1)-mediated autoimmune disease, but with the introduction of Th17 cells, their role in the pathogenesis of BD was also addressed. Despite studies on IL-17 in BD, the prognostic value of this cytokine in BD is unclear. The aim of this study is to determine the IL-17 mRNA expression rate and serum levels in patients with BD and its correlation with clinical manifestations and activity of BD. Forty-six BD patients in the active phase of the disease and 70 healthy controls were recruited in this study. BD activity was measured by Behçet's disease current activity form (BDCAF), Iranian Behçet's disease dynamic activity measure (IBDDAM) and total inflammatory activity index (TIAI). The IL-17 mRNA expression and serum levels were significantly higher in the BD patients compared with the healthy controls. These parameters in the BD patients aged <25 at disease onset, positive pathergy test, and positive HLA-B5 and HA-B51 were significantly higher than the healthy controls (P < 0.05). The IL-17 serum level in the patients with active uveitis was lower than the patients with in-active uveitis. There was no association between other clinical manifestations of BD and these parameters. No significant correlation was found between BDCAF and IBDDAM with IL-17 mRNA expression and serum levels. However, TIAI had a significant and negative correlation with the serum levels of IL-17.

The methylation status of TNF-α and SOCS3 promoters and the regulation of these gene expressions in patients with Behçet's disease.

Introduction: The aim of this study was to evaluate the methylation status of TNF-α and SOCS3 promoters in patients with BD and compare them with a healthy group.Method: This was a case-control study, in which 47 subjects with BD and 61 individuals as the control participated. Blood samples were collected from all the participants. Then, PBMCs were isolated using the Ficoll method and methylation of considered sites was investigated using the qMS-PCR technique after DNA extraction by the rapid genomic DNA extraction method and its analysis with Nano-drop.Results: The methylation and expression of TNF-α showed that the methylation level significantly declined in the patient in comparison with the healthy (p < 0.05). Moreover, the results on the mean expression showed that it significantly increased in the patient group, as compared with the healthy group (p < 0.05). In addition, the expression of the SOCS3 gene was not significantly different between the patients and healthy subjects while the level of SOCS3 methylation was significantly higher in the patient group than that in the healthy group (p < 0.05).Discussion: The present study revealed that the gene expression of TNF-alpha increased in BD patients, suggesting that TNF-alpha likely has a role in the pathogenesis of BD.

Tuberculin skin test conversion in patients under treatment with anti-tumor necrotizing factor alpha agents.

BACKGROUND: Despite successful clinical outcomes of biologic medications in patients with chronic rheumatic diseases, some considerable adverse effects such as infections remain a major concern. Possibility of tuberculosis (TB) reactivation over treatment with anti-tumor necrotizing factor (TNF) alpha agents has necessitated a screening test before initiation of treatment. However, screening over the course of treatment is not recommended in those patients with negative baseline screening tests. This study aimed to evaluate the efficacy of tuberculin skin test (TST) before treatment in patients with chronic rheumatologic diseases who were indicated to receive anti-TNF-alpha therapy and the necessity of repeating this test over the course of treatment. METHODS: In this prospective study, patients with chronic rheumatologic diseases receiving anti-TNF-alpha agents were studied in a two-year period. TST was performed before treatment and those with positive results were excluded from the study. Thereafter, treatment with anti-TNF-alpha agents was initiated with the indicated dose. TST was repeated before administration of biologic treatment until TST became positive or 16 weeks after the initiation of treatment with anti-TNF-alpha. RESULTS: A total of 51 cases were studied, of whom one patient (1.9%) was excluded due to positive TST before treatment. All participants received infliximab and the TST test became positive in one patient (2%) 2 weeks after receiving the first dose. Also, the results of further tests at weeks 6, 10, and 14 were all negative for the remaining patients. CONCLUSION: Due to the possibility of TST conversion after administration of anti-TNF-alpha therapy, it is important to consider TB monitoring in patients under treatment with these agents using available methods such as TST.

Promoter methylation of Bax and Bcl2 genes and their expression in patients with Behcet's disease.

BCL2 and BAX genes are a group of signalling inducer and inhibitor genes playing a key role in the process of cellular physiological death (apoptosis). These genes, through the JAK/STAT signalling pathway, affect different cytokines on cell function and subsequently lead to the pathophysiology of diseases, especially autoimmune diseases. In addition, altering the methylation of genes can affect their expression. Since the aetiology and pathology of Behcet's disease is not fully understood, the aim of this study was to determine the methylation pattern of BCL2 and BAX genes in patients with Behcet's disease and compare it with those of control group. This was a case-control study on 51 patients with Behcet and 61 control subjects. Blood samples were received from all subjects. Subsequently, the peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll method and the methylation of the sites was investigated using quantitative methylation specific PCR (qMS-PCR) technique after extraction of DNA by salting out method and its examination with Nano drop. The results of methylation and expression of Bax gene suggest that the methylation level in the patient group significantly increased compared to the healthy individuals (p-value < .05). Furthermore, the results related to Bax gene expression revealed that the mean of gene expression in the patient group has decreased compared to the healthy group, and this decrease was statistically significant (p-value < .05). The rate of expression and methylation of Bcl2 did not indicate any change in the two patient and healthy groups. Given the results of this study, it can be guessed that perhaps DNA methylation is involved in certain conditions of the disease and it may result in regulation of the expression of the involved genes such as Bax gene, in the pathogenesis of the disease.

A Systematic Review of the Potential Effects of Nigella sativa on Rheumatoid Arthritis.

Considering the different untoward effects of the drugs prescribed for the treatment of rheumatoid arthritis (RA), there has been an increasing interest in adjuvant therapies devoid of such unfavorable reactions. Although the beneficial effects of Nigella sativa (N. sativa) on RA have been established, it seems that its mechanisms of action have not still been reviewed. The present review is designed to evaluate the effects of N. sativa on RA systematically. We searched these electronic databases until April 2019: PubMed, Scopus, ISI Web of Science, Cochrane Library, Embase, Ovid, ProQuest, and Google scholar. No restriction was conducted based on language or publication date. We selected all of the related clinical, animal, and in vitro studies. Review papers, abstracts in conferences, book chapters, and papers regarding the effects of N. sativa combined with other herbs, as well as articles regarding the effects of N. sativa on other diseases, were excluded. Each article was assessed critically for the possible risk of bias. Nineteen articles were reviewed. Animal and in vitro investigations supported the favorable effects of N. sativa on clinical, inflammatory, oxidative, and immunologic parameters on RA, whereas results of limited clinical studies did not illustrate any change or improvement of inflammatory and oxidative biomarkers in RA. N. sativa could control RA via multiple ways such as decreasing inflammation, inhibiting oxidative stress, and modulating the immune system. This paper provides persuasive clues to defend the efficacy of N. sativa in RA and justifies the significance of subsequent clinical trials.

The association between serum levels of growth differentiation factor-15 and rheumatoid arthritis activity.

BACKGROUND: Macrophages play a crucial role in the pathogenesis of rheumatoid arthritis (RA). Growth differentiation factor-15 (GDF-15) acts as an autocrine regulator of macrophage activation. OBJECTIVE: The aim of this study was to assess serum level of GDF-15 as a potential biomarker for detecting RA activity. METHOD: A total of 100 female RA patients and 55 age and weight matched healthy control females were enroled. The serum level of GDF-15 was measured using enzyme-linked immunosorbent assay. RESULTS: Serum levels of GDF-15 in RA patients with high, moderate, low and no disease activity were 989.0 ± 161.9, 505.6 ± 220.5, 349.2 ± 155.9 and 349.0 ± 144.0 pg/mL, respectively. GDF-15 with a cut-off value higher than 705 pg/mL was indicative of high RA activity with sensitivity of 96% and specificity of 92%. CONCLUSION: GDF-15 serum levels may be used as a biomarker to predict high RA disease activity.

Relationship between vitamin D level and Bechcet's disease activity: A systematic review and meta-analysis.

Aim: In the present study, the evidence about the association between vitamin D deficiency and Behcet's disease activity was systematically reviewed and meta-analyzed. Method: We searched the English and Persian databases of Medline (Ovid), CINHAL, Scopus, Proquest, the Cochrane library and SID, IranDoc, Magiran, Iran Medex for articles published up until May 2018 with the keywords were related to serum vitamin D and active and inactive Behcet's disease in adults. Meta-analysis was done using the CMA software. Results: A total of 138 titles were retrieved and reduced to 80 titles after deletion of duplicates and finally after close assessing of titles and abstracts eight eligible studies including a total of 939 participants were identified for systematic review and meta-analysis. According to the results of the meta-analysis, the pooled effect size of the differences in the serum level of vitamin D in patients with inactive Behçet's Disease and healthy controls was [OR:-0.05; 95% CI:-2.05, 1.94; p = 0.95]. The serum vitamin D level was significantly lower in active patients compared with healthy controls [OR:1.21; 95%CI: -0.12, 2.31; p = 0.03]. The pooled effect size of the differences in the serum level of vitamin D in active and inactive Behçet's Disease was [OR:-0.71; 95%CI: -1.41, -0.007; p = 0.04] Conclusion: There is an association between vitamin D deficiency and active Behçet's Disease. Future studies investigating the association of vitamin D deficiency and Behçet's Disease needs to involve following information: dietary intake of calcium and vitamin D, measuring of sun exposure, report of drug consumption and physical activity level.

Clinical characteristics and long-term outcome of Takayasu arteritis in Iran: a multicentre study

Background/aim: This study aimed to evaluate the demographic, clinical, angiographic and prognostic characteristics of Takayasu arteritis (TA) in Iran. Materials and methods: A total of 75 patients with TA based on the American College of Rheumatology 1990 criteria for TA classification referred to the Rheumatology Centres, were followed-up from 1989 to 2019. Demographic, clinical, angiographic and prognostic characteristics were collected at baseline and last visit. Results: The mean age was 31.9 ± 9.8 years at the disease onset. Female to male ratio was 14. The median latency in diagnosis was 24 months. Pulse discrepancy in the arms, blood pressure discrepancy in the arms, limb claudication, hypertension and constitutional symptoms were the most common clinical features. The most common angiographic type at the time of diagnosis was Type I (42.7%). The most frequent arterial lesion was stenosis (89.4%). Subclavian, carotid and aortic arteries were the most commonly involved arteries. New lesions developed in 28.6% of patients during the 5.25-year follow-up. Vasculitis-induced chronic damage was observed in all patients. Disease activity decreased and vascular damage remained stable throughout the follow-up period. Conclusions: The clinical features and angiographic type of TA in Iran are different from most Asian countries. Differences in angiographic and clinical features may lead to delayed diagnosis. The issue of delay in diagnosis should create awareness among health care providers that TA is not a very rare disease in Iranians and failure to pay attention to warning symptoms may delay the diagnosis.

Survivin modulatory role in autoimmune and autoinflammatory diseases.

Baculoviral IAP repeat containing 5 (BIRC5) gene encodes the important protein as survivin, a multifunctional protein, which is involved in cellular and molecular networks, progression of cell cycle, homeostasis, developmental morphogenesis, and apoptosis. The proximal BIRC5 promoter possesses specific binding sites for key transcription factors such as nuclear factor κB and signal transducer and activator of transcription 3. Upregulation of survivin exacerbates the autoimmune diseases (AIDs) including multiple sclerosis and myasthenia gravis by reducing the activity threshold of survivin-specific cytotoxic T cells. DNA damage along with upregulation or downregulation of survivin have been demonstrated in initiation and pathogenesis of cancers and AIDs. However, detailed mechanism of survivin function in pathogenesis of AIDs is not well understood. This review focuses on the structure, specificity, regulation, and function of survivin in physiologic conditions and pathogenesis of AIDs.