Losartan enhances the suppressive effect of pirfenidone on the bleomycin-induced epithelial-mesenchymal transition and oxidative stress in A549 cell line

Objective(s): Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease. Despite the promising anti-fibrotic effect, the toleration of pirfenidone (PFD) by the patients in full dose is low. Combination therapy is a method for enhancing the therapeutic efficiency of PFD and decreasing its dose. Therefore, the present study evaluated the effect of a combination of losartan (LOS) and PFD on oxidative stress parameters and the epithelial-mesenchymal transition (EMT) process induced by bleomycin (BLM) in human lung adenocarcinoma A549 cells. Materials and Methods: The non-toxic concentrations of BLM, LOS, and PFD were assessed by the MTT assay. Malondialdehyde (MDA) and anti-oxidant enzyme activity including catalase (CAT) and superoxide dismutase (SOD) were assessed after co-treatment. Migration and western blot assays were used to evaluate EMT in BLM-exposed A549 after single or combined treatments. Results: The combination treatment exhibited a remarkable decrease in cellular migration compared with both single and BLM-exposed groups. Furthermore, the combination treatment significantly improved cellular anti-oxidant markers compared with the BLM-treated group. Moreover, combined therapy markedly increased epithelial markers while decreasing mesenchymal markers. Conclusion: This in vitro study revealed that the combination of PFD with LOS might be more protective in pulmonary fibrosis (PF) than single therapy because of its greater efficacy in regulating the EMT process and oxidative stress. The current results might offer a promising therapeutic strategy for the future clinical therapy of lung fibrosis

INVESTIGATION THE ROLE OF MEPXH1 (HIS139ARG) POLYMORPHISM ON NUMBER OF EXACERBATIONS AND DISEASE SEVERITY IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE IN A SMOKER POPULATION

The purpose of this study was to examine investigation the role of mEPXH1 (His139Arg) polymorphisms on number of exacerbations and disease severity in chronic obstructive pulmonary disease in a smoker population. Chronic obstructive pulmonary disease (COPD) has become the fourth most common single cause of morbidity, and its prevalence is increasing worldwide. It is a syndrome composed of chronic bronchitis, small airways disease (bronchiolitis), and emphysema, in varying proportions between affected individuals. The study was performed cohort and prospectively. The population consist of 213 patients with COPD disease. Genotyping of mEPXH1 was performed using multiplex PCR. Data analysis included, Pearson’s r correlations, regression analysis, ANOVA analyses, Tukey, test for comparison and SPSS software (package of Spss / pc + + ver18). The results showed that there is not relationship between polymorphisms of mEPXH1 and number of exacerbations. According the results, there is not significant relationship between polymorphisms of mEPXH1 and disease severity. Also there is not significant relationship between mEPXH1 and disease in COPD patients on basis parameters of spirometery and oxidative stress in COPD patients

Boosting therapeutic efficacy of mesenchymal stem cells in pulmonary fibrosis: The role of genetic modification and preconditioning strategies

Pulmonary fibrosis (PF) is the end stage of severe lung diseases, in which the lung parenchyma is replaced by fibrous scar tissue. The result is a remarkable reduction in pulmonary compliance, which may lead to respiratory failure and even death. Idiopathic pulmonary fibrosis (IPF) is the most prevalent form of PF, with no reasonable etiology. However, some factors are believed to be behind the etiology of PF, including prolonged administration of several medications (e.g., bleomycin and amiodarone), environmental contaminant exposure (e.g., gases, asbestos, and silica), and certain systemic diseases (e.g., systemic lupus erythematosus). Despite significant developments in the diagnostic approach to PF in the last few years, efforts to find more effective treatments remain challenging. With their immunomodulatory, anti-inflammatory, and anti-fibrotic properties, stem cells may provide a promising approach for treating a broad spectrum of fibrotic conditions. However, they may lose their biological functions after long-term in vitro culture or exposure to harsh in vivo situations. To overcome these limitations, numerous modification techniques, such as genetic modification, preconditioning, and optimization of cultivation methods for stem cell therapy, have been adopted. Herein, we summarize the previous investigations that have been designed to assess the effects of stem cell preconditioning or genetic modification on the regenerative capacity of stem cells in PF