Genetic Association of VDR gene Apa1 and Taq1 Variants with Scleroderma in an Iranian Northeast Population.

BACKGROUND: Despite vigorous research efforts, the etiology of scleroderma (systemic sclerosis (SSc)) remains still unclear and both genetic and environmental factors clearly contribute to the pathogenesis of scleroderma. Reports of aberrant vitamin D status in scleroderma patients suggest a need for considering the genotype and allele frequencies of VDR gene polymorphisms. This case-control study aimed to investigate the possible association of two common polymorphisms of the VDR gene (ApaI, and TaqI) with susceptibility to scleroderma in an Iranian population. METHODS: Using polymerase chain reaction and restriction fragment length polymorphism (PCRRFLP), ApaI and TaqI polymorphisms in the VDR region were genotyped in 51 patients with scleroderma and 50 healthy controls. Logistic regression analysis was performed to calculate the genotypes odds ratios (ORs) as a measure of association with the presence of scleroderma. Haplotype and linkage disequilibrium analyses were also performed on the detected genotypes. RESULTS: No significant differences were found for the allelic and genotype distributions of ApaI and TaqI polymorphisms between patients with scleroderma and healthy controls (p>0.05). In haplotype analysis, three haplotypes TA, CA, and TC, with a frequency greater than 1% were identified. However, none of them was associated with the risk of scleroderma. CONCLUSION: Our preliminary study showed no evidence of an association between ApaI and TaqI polymorphisms and scleroderma. As the association between VDR polymorphisms and autoimmune diseases varies across the different ethnic populations, further large cohort studies are necessary to confirm the results.

Serum lysyl oxidase concentration increases in long-standing systemic sclerosis: Can lysyl oxidase change over time?

Objectives: This study aims to investigate the association of serum lysyl oxidase (LOX) levels with systemic sclerosis (SSc), to examine the relationship between LOX and disease onset, and to evaluate the probable effects of hyperlipidemia on the circulating levels of LOX among patients with SSc. Patients and methods: Between May 2017 and November 2018, a total of 39 patients with SSc (2 males, 37 females; mean age: 46.6±12.3 years; range, 18 to 65 years) and 35 healthy controls (4 males, 31 females; mean age: 43.1±14.1 years; range, 18 to 65 years) were included. Serum LOX concentration was measured using the enzyme-linked immunoassay in triplicate. Results: We found higher levels of serum LOX in patients with SSc compared to healthy controls. There was a significant relationship between serum LOX levels and disease onset. Patients with long-standing disease demonstrated increased levels of LOX in the blood compared to the recent-onset group. Hyperlipidemia did not have a significant effect on circulating levels of LOX. There was a significant negative correlation between LOX levels and modified Rodnan Skin Score in the subgroup of patients with skin involvement only and in patients without gastrointestinal involvement. Conclusion: Our study findings show an increased level of LOX protein level in the blood of patients diagnosed with SSc. Hyperlipidemia seems not to affect the concentrations of LOX in the peripheral blood of patients with SSc.

Vitamin D Levels in Patients with Behcet's Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: Behcet's disease (BD) is a chronic multisystem inflammatory disease classified as Variable Vessel Vasculitis with unclear etiology. We designed this systematic review and meta-analysis to evaluate vitamin D status in Behcet's disease patients with this background. METHODS: We performed this systematic review and meta-analysis according to PRISMA guidelines. We included all observational studies in humans published in English, evaluating the association of 25(OH)D concentrations in Behcet's patients. Two reviewers (HRK and AE) independently searched the databases and screened articles based on their titles and abstracts. A third reviewer resolved all disagreements. We performed analysis using Cochrane Program Review Manager Version 5.3. The protocol for this review was registered on PROSPERO (CRD42020197426). RESULTS: A total of 341 publications were initially identified according to the search strategy. Finally, 12 publications were included in the meta-analysis. We performed this meta-analysis on 1265 participants from different studies with a sample size ranging from 63 to 224 individuals. In studies comparing active and inactive subgroups of patients with Behcet's disease, we found a significantly lower serum level of vitamin D in patients with Active BD (-0.4; 95% CI: -0.61, -0.25; p<0.001). We found that the serum level of vitamin D in Behcet's disease is significantly higher than in health controls (0.5; 95% CI: 0.15, 0.50; p=0.001). CONCLUSION: We demonstrated that the existing evidence is consistent with the hypothesis that an increased serum level of vitamin D would be associated with a substantially lower risk of active Behcet's disease.

The effect of vitamin D on GATA3 gene expression in peripheral blood mononuclear cells in allergic asthma.

INTRODUCTION: Asthma is becoming a major health problem in many countries. Immune responses in allergic asthma, as the most prevalent asthmatic phenotype, are mediated mostly by a subtype of T lymphocytes referred to as the effector lineage of Type 2 Th cells (Th2). The development of Th2 cells is mainly governed by a zinc finger transcription factor, i.e., GATA-binding protein 3 (GATA3). Allergic asthma is a complex disease, and vitamin D deficiency has been named as a non-genetic risk factor for its development. Vitamin D, a steroid hormone belonging to the family of nuclear receptors, has shown significant immunosuppressive effects in previous studies. In this study, given its immunomodulatory properties, we aimed to investigate the effects of different concentrations of vitamin D on GATA3 gene expression in peripheral blood mononuclear cells (PBMCs), including Th2 cells, and compare GATA3 expression levels between PBMCs taken from allergic asthmatic patients and healthy controls. RESULTS: The total sample size was 40 and the quantitative real-time PCR (qPCR) procedure was applied to assess the mRNA expression levels of GATA3 in different groups. Collectively, our results demonstrated that the expression of GATA3 in PBMCs taken from patients with allergic asthma is lower than in that from healthy controls. In addition, in the control group, cells co-cultured with vitamin D had a significantly increased GATA3 expression. However, in the patient group, such an increase was only observed in cells treated with 10⁻7M-vitamin D. By contrast, incubation with vitamin D at the concentration of 10-6 M slightly decreased the expression of GATA3 among patients. CONCLUSION: In summary, it is likely that vitamin D should regulate GATA3 gene expression in the PBMCs in a dose-dependent manner. The impacts of this steroid hormone can also differ between the status of health and allergic asthma in either extent or direction.

Efficacy of botulinum toxin type A injection for Raynaud's phenomenon and digital ulcers in patients with systemic sclerosis.

Introduction: Systemic sclerosis (SSc) is an autoimmune, connective tissue disorder of unknown etiology which causes vasculopathy and fibrosis. Raynaud's phenomenon (RP) is a common complication of SSc, which leads to ischemia and gangrenes. Treatment of RP is a clinical problem and often remains insufficient.This study aimed to evaluate the therapeutic efficacy of local injections of botulinum toxin type A (BTX-A) in improving the symptoms of Raynaud's phenomenon (RP) secondary to scleroderma. Material and methods: This parallel single-blinded, placebo-controlled clinical trial enrolled 29 patients with scleroderma. Participants received BTX-A in the first, 2nd, 3rd, and 4th dorsal web spaces and the base of the thumb and small finger of the non-dominant hand and 2.5 ml of sterile normal saline in the opposite hand. Pre-injection measurements and post-injection follow-up evaluations at months 1 and 4 were performed. We compared the outcomes using the paired Student's t-test. Results: The change in pain severity between pre-injection and month 1 follow-up was significantly larger in the BTX-A group (p-value = 0.04). Between pre-injection and month 1 and month 4, the changes in the Raynaud's condition score (RCS) (p-value = 0.02, 0.004, respectively) and the number of Raynaud's attacks (p-value = 0.006, 0.001, respectively) were significantly greater in the BTX-A group. No significant difference was found in terms of paresthesia, skin thickening, upper extremity function, ulcer diameter, number of ulcers, or Raynaud's attack duration between the two groups (p-value > 0.05). In time, the decrease in pain severity, paresthesia, RCS, number of ulcers, and ulcer diameter, and the increase in upper extremity function were significantly greater in the BTX-A group as compared to the placebo group (p < 0.05). Conclusions: Our study showed that local injection of BTX-A is safe and has beneficial therapeutic effects on RP and RP-related digital ulcers in SSc patients.

A comparative study of anti-leukemic effects of kaempferol and epigallocatechin-3-gallate (EGCG) on human leukemia HL-60 cells.

OBJECTIVE: Acute promyelocytic leukemia (APL) is among the most threatening hematological malignant cancers. Defects in cell growth and apoptotic pathways lead to the pathogenesis of the disease as well as its resistance to therapy; therefore, it is a good model for examining pro-apoptotic agents. The present study compared the molecular mechanism induced by kaempferol and epigallocatechin gallate (EGCG) as well as all-trans retinoic acid (ATRA), in HL-60 leukemia cells during five days. MATERIALS AND METHODS: Cell viability was determined by resazurin assay following treatment with ATRA (10 µM), EGCG, and kaempferol (12.5-100 µM), and apoptosis was detected by the ANX V/PI kit. Moreover, the levels of genes involved in apoptosis (PI3K, AKT, BCL2, BAX, P21, PTEN, CASP3, CASP8, and CASP9) and multi-drug resistance (MDR, ABCB1 and ABCC1) were assessed by using real-time PCR test. RESULTS: Based on the findings, kaempferol decreased cell viability and increased apoptosis in HL60 cells more than EGCG. Apoptosis was induced via extrinsic and intrinsic pathways in HL60 cells by kaempferol and EGCG. In addition, kaempferol and EGCG increased apoptosis and inhibited MDR in a concentration- and time-dependent manner. CONCLUSION: Kaempferol at high concentrations can be taken into consideration for treating patients with APL as compared with EGCG.

Inflammation, diet, and type 2 diabetes: a mini-review.

Inflammation is a common feature of type 2 diabetes (T2D). Inflammatory cytokines increase in patients with type 2 diabetes, metabolic syndrome, and heart disease. Various types of cells can produce inflammatory cytokines and then release them into the bloodstream, where their complex interactions with target tissues raise a tissue-specific immune response. This review focused on C-reactive protein (CRP), tumor necrosis factor (TNF)-α as an inflammatory cytokine, and adiponectin produced by adipose tissues. Despite the major role of cytokines in the development of T2D, further studies are required to investigate the possible effects of the macronutrient composition of diet on these cytokines.

Therapeutic Potency of PI3K Pharmacological Inhibitors of Gastrointestinal Cancer.

Therapeutic targeting of phosphatidyl-inositol 3-kinase (PI3K) is considered as a possible strategy in several types of cancer, including gastrointestinal ones. In vitro and in vivo studies indicated the significance of proapoptotic and antiproliferative inhibition of PI3K. Although there are many phase 1 and 2 clinical trials on PI3K inhibitors in patients with gastrointestinal cancer, the molecular mechanism of PI3K targeting PI3K/ mTOR pathway is not clear. Panclass I, isoformselective, and dual PI3K/mTOR inhibitors are under investigation. This review aimed to indicate PI3K-dependent targeting mechanisms in gastrointestinal cancer and the evaluation of related clinical data.

Subcutaneous Emphysema, Pneumomediastinum and Pneumothorax in a Patient with Dermatomyositis.

INTRODUCTION: Spontaneous pneumomediastinum, pneumothorax, and subcutaneous emphysema are rare, but serious complications of inflammatory myopathies and occur more commonly in DM than PM. complications of dermatomyositis (DM) and polymyositis (PM), both of which can be fatal. CASE REPORT: A 20-year-old woman was admitted with neck pain, dyspnea, cough, and fever. She had been diagnosed with dermatomyositis 21 months prior. A thorax computed tomography (CT) scan revealed ground glass opacities in her lungs, pneumomediastinum, pneumothorax, and subcutaneous emphysema. Despite intensive immunosuppressive therapy, clinical deterioration and radiological progression were observed, ultimately the patient died. CONCLUSION: During the care for a patient with dermatomyositis, the otorhinolaryngologist should be cautious of rapidly progressive and fatal neck subcutaneous emphysema. For a patient with dermatomyositis and with normal bronchoscopy and esophagoscopy, the main treatment is control of dermatomyositis with medical therapy. Therefore, a tracheostomy and/or mechanical ventilation may not be necessary.

Superiority of laterally elevated wedged insoles to neutrally wedged insoles in medial knee osteoarthritis symptom relief.

AIM: Knee osteoarthritis (OA), is the most common degenerative joint disease. Several non-pharmacological interventions have been used for this purpose such as insoles. There are contradictory data about the superiority and effectiveness of laterally wedged compared with neutrally wedged insoles. This study was designed to compare the effectiveness of laterally and neutrally wedged insoles in management of knee OA. METHODS: In this double-blind, parallel treatment trial, 118 patients with knee OA according to American College of Rheumatology (ACR) criteria were enrolled and were followed for 2 months. Patients were randomly divided into two groups. Fifty-seven of them were treated with 5° laterally elevated wedged insoles (group A) and 61 patients were treated with neutrally wedged insoles (group B). Edinburg Knee Functional Scale (EKFS) was used to evaluate knee function before and after interventions. At the end of 2 months, severity of knee pain during the previous 2 days, numbers of non-steroid anti inflammatory drugs (NSAIDs) used for pain relief within the last 2 weeks and EKFS were assessed. RESULTS: Severity of knee pain decreased in both groups after intervention. The mean difference in groups A (laterally wedged insole) and B (neutrally wedged insole) were 29.3 (95% confidence interval [95% CI]: 25.12, 33.55) and 6.25 (95% CI: 3.09, 9.4), respectively (P < 0.001 for both). In addition, at the end of the study, EKFS improved significantly in group A (mean: 7.54, 95% CI: 6.3, 8.8; P < 0.001), while in group B we could not find significant improvement (mean: 0.54, 95% CI: -0.41, 1.5; P = 0.166). Numbers of NSAIDs used during the two final weeks of the study significantly decreased compared with baseline in group A (P = 0.001; mean: 2.6, 95% CI: 1.3, 3.9); while in group B this was not shown (P = 0.9; mean: 0.05, 95% CI:-0.87, 0.97). CONCLUSION: This study suggests that laterally elevated wedged insoles are more effective than neutrally wedged insoles, in pain relief of knee OA.

Plasma levels of leptin and visfatin in rheumatoid arthritis patients; is there any relationship with joint damage?

OBJECTIVE S: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder, primarily targeting the synovium and articular cartilage that leads to joint damage. Recent reports have suggested the role of adipocytokines in mediating joint damage; however it still is a matter of debate. The purpose of this study was to evaluate the association between serum values of adiopocytokines (leptin, visfatin) and radiographic joint damage in patients with RA. MATERIALS AND METHODS: Fifty-four patients diagnosed with RA, based on Revised ACR Criteria 2010, with 1-5 year disease duration since diagnosis, were enrolled. Twenty-nine of patients had erosion in radiographic studies and 25patients had no erosion. Radiographic joint damages were defined according to Larsen Score. Additionally, serum levels of adipocytokines were measured and cross-sectional associations with radiographic damage were explored, adjusting for pertinent confounders. RESULTS: The serum level of visfatin were significantly higher in patients with radiographic joint damage compared with patients with no joint damage (P=0.013). This difference remained significant after adjustment for C-reactive protein levels (P=0.008), but not after adjustment for disease duration (P=0.247). The mean leptin serum levels were not different between these two groups (P=0.903). There was a positive correlation between leptin levels and BMI (r=0.494, P<0.001). However, after adjustment for BMI, leptin levels had no difference between two groups (P=0.508). CONCLUSION: This study revealed that visfatin levels were significantly higher in patients with radiographic joint damage dependently to disease duration. Therefore, it seems that adipocytokine may be a valuable factor in therapeutic targets in the future.