The role of progesterone in cellular apoptosis of skin and lung in a bleomycin-injured mouse model

Systemic sclerosis is a female predominant, a fibrotic autoimmune disease in which disturbance in tissue homeostasis and cell turnover including cell apoptosis are central events in pathogenesis. Sex hormones are known as the important players in sexual dimorphism of autoimmune diseases and in tissue homeostasis. Progesterone influences autoimmune disease via its immunomodulatory effect or by its direct action on parenchymal cell function. On the other hand, this hormone impacts tissue homeostasis by acting on cell apoptosis in a different situation. The objective of this study was to examine the effect of progesterone on cellular apoptosis of skin and lung tissues in a mouse model of scleroderma. Four group of mice were involved in this study with 10 mice in each. The fibrotic model was induced by daily subcutaneous injection of bleomycin for 28 days. One week after initiation of fibrosis induction, mice received subcutaneous progesterone alone or with bleomycin for 21 days. Control group received only Phosphate buffered saline PBS. After 28 days, under lethal anesthesia skin and lung tissues were harvested for histological assessment and hydroxyproline measurement. Apoptosis in tissue sections was detected by TUNEL assay technique. Bleomycin administration induced fibrosis in skin and lung tissues. Severe apoptosis was seen in skin and lung tissues of the bleomycin-treated group (p0.05) or in the lung (p>0.05) did not alter apoptosis in bleomycin-treated animals. Our data confirm the role of apoptosis in the pathogenesis of fibrosis in this model; however, progesterone does not affect cellular apoptosis in skin and lung tissues of bleomycin-injured animals. Copyright© February 2019, Iran J Allergy Asthma Immunol. All rights reserved

Genetic Variants of Cytochrome b-245, Alpha Polypeptide Gene and Premature Acute Myocardial Infarction Risk in An Iranian Population

Background: Oxidative stress induced by superoxide anion plays critical roles in the pathogenesis of coronary artery disease (CAD) and hence acute myocardial infarction (AMI). The major source of superoxide production in vascular smooth muscle and endothelial cells is the NADPH oxidase complex. An essential component of this complex is p22phox, that is encoded by the cytochrome b-245, alpha polypeptide (CYBA) gene. The aim of this study was to investigate the association of CYBA variants (rs1049255 and rs4673) and premature acute myocardial infarction risk in an Iranian population. Methods: The study population consisted of 158 patients under the age of 50 years, with a diagnosis of premature AMI, and 168 age-matched controls with normal coronary angiograms. Genotyping of the polymorphisms was performed by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Results: There was no association between the genotypes and allele frequencies of rs4673 polymorphism and premature acute myocardial infarction (P>0.05). A significant statistical association was observed between the genotypes distribution of rs1049255 polymorphism and AMI risk (P=0.037). Furthermore, the distribution of AA+AG/GG genotypes was found to be statistically significant between the two groups (P=0.011). Conclusions: Our findings indicated that rs1049255 but not rs4673 polymorphism is associated with premature AMI

Gelatinases Increase in Bleomycin-induced Systemic Sclerosis Mouse Model

Systemic sclerosis is a fibrotic autoimmune disease in which aberrant remodeling of the extracellular matrix in organs disturbs their functionalities. The aim of this study was to investigate the expression of gelatinases on systemic sclerosis. Consequently, a mouse model of systemic sclerosis was employed and the gelatinolytic activity of gelatinases was evaluated on the fibrotic tissues of this model. Two groups of ten mice were considered in this work: a group of systemic sclerosis model and control group. For the generation of systemic sclerosis model, mice received bleomycin, while the control group was subjected to phosphate buffered saline (PBS) reception. Mice were tested for fibrosis by using trichrome staining, hydroxyproline measurement and α-SMA detection in tissue sections. Additionally, the gelatinolytic activity of matrix metalloproteinase 2 and matrix metalloproteinase 9 were measured using gelatin zymography in lungs and skin tissue homogenates. The obtained results indicated that subcutaneous injection of bleomycin-induced fibrosis in skin and lung tissues of mice. Pro and active forms of matrix methaloproteinase 9 were increased in fibrotic lung tissues (p<0.05 and p<0.01, respectively), while, the gelatinolytic activity of MMP2 was unaffected in these tissues. Additionally, in skin tissues of bleomycin-treated animals, both pro and active forms of MMP9 and MMP2 were increased (p<0.05). Pro and active forms of gelatinases increase differently in skin and lung tissues of bleomycin-induced scleroderma

Human leukocyte antigen class I (A, B) and class II (DRB1) allele and haplotype frequencies in Iranian patients with Buerger's disease

Objective: The aim of this study was to investigate the human leukocyte antigen (HLA) class I (HLA-A and HLA-B) and II (HLA-DRB1) allele and haplotype frequencies in a group of Iranian patients with Buerger's disease (BD) in comparison with a normal healthy control group. Methods: A total of 70 unrelated male patients and 100 healthy controls from Sina Hospital, Tehran, Iran, belonging to the same ethnic background, were enrolled in this case-control study. HLA-A, B, and DRB1 typing were performed by polymerase chain reaction with sequence-specific primers (PCR-SSP). Results: The results of this case-control study showed that the frequency of the HLA-A*03:01 (odds ratio (OR) = 2.88, P value (Pv) =.002), HLA-A*29:01 (OR = 15.31, Pv <.001), HLA-DRB1*04:02 (OR = 3.41, Pv <.001), and HLA-DRB1*16:01 (OR = 8.16, Pv <.001) was significantly higher in BD patients compared with healthy controls, whereas the frequency of the HLA-DRB1*01:01 (OR = 0.03, Pv <.001) was significantly lower in BD patients. The most frequent extended haplotypes in our patients were HLA-A*02:01-B*55:01-DRB1*04:03. Conclusion: This study is the first study evaluating an association between the HLA pattern and BD in the patients with BD from North West and North Iran. © 2020 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Lt

Oxidative discolouration in whole-head and cut lettuce: biochemical and environmental influences on a complex phenotype and potential breeding strategies to improve shelf-life

Lettuce discolouration is a key post-harvest trait. The major enzyme controlling oxidative discolouration has long been considered to be polyphenol oxidase (PPO) however, levels of PPO and subsequent development of discolouration symptoms have not always correlated. The predominance of a latent state of the enzyme in plant tissues combined with substrate activation and contemporaneous suicide inactivation mechanisms are considered as potential explanations for this phenomenon. Leaf tissue physical properties have been associated with subsequent discolouration and these may be influenced by variation in nutrient availability, especially excess nitrogen and head maturity at harvest. Mild calcium and irrigation stress has also been associated with a reduction in subsequent discolouration, although excess irrigation has been linked to increased discolouration potentially through leaf physical properties. These environmental factors, including high temperature and UV light intensities, often have impacts on levels of phenolic compounds linking the environmental responses to the biochemistry of the PPO pathway. Breeding strategies targeting the PALand PPOpathway biochemistry and environmental response genes are discussed as a more cost-effective method of mitigating oxidative discolouration then either modified atmosphere packaging or post-harvest treatments, although current understanding of the biochemistry means that such programs are likely to be limited in nature and it is likely that they will need to be deployed alongside other methods for the foreseeable future

Novel inhibitors of the calcineurin/NFATc hub - alternatives to CsA and FK506?

The drugs cyclosporine A (CsA) and tacrolimus (FK506) revolutionized organ transplantation. Both compounds are still widely used in the clinic as well as for basic research, even though they have dramatic side effects and modulate other pathways than calcineurin-NFATc, too. To answer the major open question - whether the adverse side effects are secondary to the actions of the drugs on the calcineurin-NFATc pathway - alternative inhibitors were developed. Ideal inhibitors should discriminate between the inhibition of (i) calcineurin and peptidyl-prolyl cis-trans isomerases (PPIases; the matchmaker proteins of CsA and FK506), (ii) calcineurin and the other Ser/Thr protein phosphatases, and (iii) NFATc and other transcription factors. In this review we summarize the current knowledge about novel inhibitors, synthesized or identified in the last decades, and focus on their mode of action, specificity, and biological effects

Patient sources for drug information in Iran: A questionnaire-based survey

Objectives: To identify sources used by patients to obtain drug-related information and to find which portion of patients study the Patient Information Leaflet (PIL). Methods: A cluster random sampling was used to select 19 community pharmacies in Shiraz, Iran, from 192 pharmacies registered by Food and Drug Office of Shiraz University of Medical Sciences. Using a questionnaire, an independent assessor surveyed outpatients immediately after their prescriptions were dispensed. Results were subjected to statistical analysis. Results: Total of 671 patients were interviewed, of which 188 patients (28) reported they received no information from pharmacists or physicians and 169 patients (25) received their medications without prescription. Nearly half of the patients (46) were informed on the frequency of use and dose of their medications. Very few patients (6) were appropriately informed about the frequency of use, dosage, duration of treatment, and potential side effects, allergies and drug interactions. Patients with college education used PILs as a source of information more than those with lower education levels. Conclusion: A significant portion of patients obtained medicines without a prescription. Only a few portion of patients in Shiraz received adequate drug information from their physician or pharmacist. A considerable portion of patients did not study PILs. © 2008 Springer Science+Business Media B.V

Evaluating the immunity against hepatitis B virus among Yasuj University of Medical Sciences students-2014

Background & Aim: &nbsp;Hepatitis B virus vaccination, Ab titer of particular importance in health care workers is high. Due to the fact that the rate of immunization against the disease is not directly measurable, the presence of detectable levels of antibody in the serum of the vaccinated individual, the individual's immunity against disease is considered to be equivalent. The aim of this study was to evaluating the immunity against hepatitis B virus among Yasuj University of Medical Sciences students. Methods: In this cross - sectional study using purposive sampling 120 students input 2007-2010 were selected. After completing a questionnaire including demographic information and immunization records 5 ml of blood was taken. After separating serum using an ELISA kit specific antibody levels were measured against hepatitis B virus. The data collected was analyzed using descriptive statistics, chi-square test and analysis of variance. Results: In 74.16% of students the specific IgG Ab against the hepatitis B virus surface Ag were more than 20 IU/L, which is secure and in 19.16% of&nbsp; them the Ab titer was below 10 IU/L which is non immune and&nbsp; in 6.68% of students the Ab titer was between 10-20 IU/L that were borderline. Also in those who had received complete vaccination, immunization rates were &nbsp;&nbsp;&nbsp;&nbsp;96.67 %. Conclusion: This study showed if vaccination against hepatitis B was complete, would be a high degree of immunity

EFFECT OF TOOL ROTATION RATE IN FRICTION STIR SPOT WELDING ON LIQUATION CRACKING OF AZ91 ALLOY

Cast AZ91 alloy is one of the most used magnesium alloys, which is sensitive to liquation in the fusion weld method,s and friction stir spot welding due to low eutectic temperature and the presence of the intermetallic compound in eutectic temperature. In this research, the liquation behavior of AZ91 alloy during friction stir spot welding was investigated. The process was carried out at two rotation speeds of 1000 and 2500 rpm and a dwell time of 1 second on the plate of AZ91 with a 10 mm thickness. Microstructural characterization was carried out using optical and scanning electron microscopes. The results showed that at low rotation speed (1000 rpm), mechanical grinding redistribution and dissolution of -Mg17Al12 precipitates occurred. While at high rotation speed (2500 rpm), the predominant phenomenon was liquation. In this condition, the liquation initiated around the phase, and then the liquid re-solidified, leading to the typical eutectic structure instead of initial precipitates. Moreover, the liquation intensified by approaching the stirred zone. Also, the presence of liquid film along grain boundaries resulted in decreased grain boundary strength and liquation cracking

Direct immunomodulatory influence of IFN-β on human astrocytoma cells

Astrocytes actively play a pivotal role in inflammatory disease intensity of central nervous system especially multiple sclerosis (MS). Although IFN-β is a selective therapy for MS but the role of IFN-β in stimulating the astrocytes to produce cytokines is not clearly revealed. Therefore, it is encouraging to assess the modulatory role of IFN-β on astrocytes of brain tissue. The aim of our study was to analyze the molecular mechanisms of recombinant IFN-β 1a directly affecting IL-10, iNOS, MMP-9 and TIMP-1 expression in central nervous system for the first time. In this way, in vitro procedures conducted by human astrocytoma A172 and 1321N1 cell lines as a model system. The total RNA from A172 and 1321N1 cells treated with IFN-β and LPS/IFN-γ/IFN-β and untreated cells were extracted and evaluated for IL-10, iNOS, MMP-9 and TIMP-1 expression by real-time RT-PCR. We found a significant dose-dependent increase in IL-10 gene expression in A172 and 1321N1 cells treated with IFN-β or LPS/IFN-γ/IFN-β. Moreover, a significant decrease was observed in iNOS expression suggesting a similar mechanism of action for both cells. Eventually there were no significant changes concerning the modulation of the MMP-9 and TIMP-1 in response to IFN-β treatment. In part, the immunomodulatory effect of IFN-β may be due to increase of IL-10 and suppression of iNOS expression in astrocytes of brain tissue. © 2015 Informa Healthcare USA, Inc. All rights reserved