Role of thioredoxin in chronic obstructive pulmonary disease (COPD): a promising future target.

INTRODUCTION: Thioredoxin (Trx) is a secretory protein that acts as an antioxidant, redox regulator, anti-allergic, and anti-inflammatory molecule. It has been used to treat dermatitis and inflammation of the digestive tract. In the lungs, Trx has a significant anti-inflammatory impact. On the other hand, Chronic Obstructive Pulmonary Disease (COPD) is one of the significant causes of death in the developed world, with a tremendous individual and socioeconomic impact. Despite new initiatives and endless treatment trials, COPD incidence and death will likely escalate in the coming decades. AREAS COVERED: COPD is a chronic inflammatory disease impacting the airways, lung parenchyma, and pulmonary vasculature. Oxidative stress and protease-antiprotease imbalances are thought to be involved in the process. The most popular respiratory inflammatory and allergic disorders therapies are corticosteroids and ß-receptor agonists. These medications are helpful but have some drawbacks, such as infection and immunosuppression; thus, addressing Trx signalling treatments may be a viable COPD treatment approach. This review shall cover the pathophysiology of COPD, the pharmacognosy of anti-COPD drugs, including the assets and liabilities of each, and the role and mechanism of Trx in COPD treatment. EXPERT OPINION: Limited research has targeted the thioredoxin system as an anti-COPD drug. Spectating the increase in the mortality rates of COPD, this review article would be an interesting one to research.

Association of IL4RA and IL-8 polymorphism in predicting susceptibility towards tuberculosis.

Mycobacterium tuberculosis is an infectious bacterial disease frequently affecting the lungs. With two fatalities from tuberculosis (TB) occurring every three minutes, India has the highest disease burden. The aetiology of tuberculosis has been linked to IL-8 and IL-4RA. Thus, the impact of the IL4RAQ576R and IL8 gene polymorphism on TB susceptibility was assessed. 301 healthy and 301 TB patients participated in a cross-sectional study. PCR RFLP was performed to identify the genotype of the IL4RAQ576R and IL-8 +781C/T gene polymorphism. The odds ratio and 95% confidence intervals were calculated using logistic regression to evaluate the risk of TB with IL4RAQ576R and IL-8 +781C/T polymorphism. A significant association was found between IL-4RA (p=0.04) and IL-8 +781 C/T (p= 0.03) in tuberculosis. Further, when clinical symptoms were compared with both polymorphisms, two of them, i.e., cough in IL-4RA576R (p=0.04) and breathlessness (p=0.01) in IL-8 +781C/T, showed a significant association. Moreover, different combinations of the SNPS were made, and the 3 risk allele shows a significant protective role (p=0.02). There is considerable evidence which shows that M. tuberculosis causes TB, an infectious disease that is genetically predisposed. The results of our study also showed that IL-4 RA Q576R and IL-8 +781 C/T played a significant protective function against tuberculosis, confirming the claim mentioned earlier. However, only the cough in IL-4RA576R and the dyspnea in IL-8 +781C/T exhibited a significant co-relation in TB patients when symptoms were examined. Additionally, the combined effects of the two SNPs were investigated, and it was discovered that the 3-risk allele has a strong association with tuberculosis. Therefore, the polymorphisms mentioned earlier, which may also be influenced by ethnicity, may significantly impact the chance of developing tuberculosis.

Genetic variations in the antioxidant genes and their role in modulating susceptibility towards chronic obstructive pulmonary disease in the North Indian population.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a persistent inflammatory lung condition characterized by an obstruction in removing oxygen from the lungs. Oxidant and antioxidant imbalance have long been hallmarks of COPD development, where the amount of antioxidants produced is less than that of oxidants. Here, polymorphism in the antioxidant enzymes like Catalase, Superoxide dismutase and Glutathione peroxidase plays an essential role in regulating the levels of oxidants. METHODS: 1000 subjects, including 500 COPD cases and 500 controls, have been recruited and genotyped to assess the correlation between COPD and the particular SNPS of antioxidant genes. Logistic regression was used to compute odds ratios (ORs) and 95 % confidence intervals (CIs) to assess the association between SNPs and COPD risk. The relationship between spirometry value and COPD for all SNPs has been analyzed using Kruskal Wallis's. Haplotype analysis has also been performed. The effect of SNP interactions on COPD risk was assessed through the Multifactor Dimensionality Reduction (MDR) approach, a nonparametric test for overcoming some of the limitations of the logistic regression for detecting and characterizing SNP interactions. RESULTS: Our findings indicated a strong association between COPD and the variations in the CAT rs7943316 (OR = 0.61, Pc = 0.0001), SOD2 rs4880 (OR = 2.07, Pc = 0.0006), and GPx rs1050450 (OR = 0.60, Pc = 0.0018). Furthermore, SOD2 rs4880 was associated with forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) of COPD patients. Our study found that the triple combination of SOD1 (rs2234694), SOD1 (rs36232792) and SOD2 (rs4880) was found to be elevating the risk of COPD (OR = 2.83, Pc = 0.006). SOD2 rs4880 and GPx rs1050450 are also linked to cough and mucus production. The Haplotype study reveals a substantial relationship between CAT (rs7943316 and rs1001179) and SOD (rs2234694 and rs4880), which increases the risk of COPD. The three-locus model (CAT rs794331, CAT rs1101179, and GPx rs1050450) was the most effective for COPD risk assessment based on the MDR findings, which were statistically significant (p < 0.0001). CONCLUSION: This study shows that rs7943316, rs4880, and rs1050450 are associated with the risk of COPD in the north Indian population and have the potential to enhance our knowledge of COPD at the molecular level, which in turn might pave the way for earlier detection, treatment, and preventive efforts.

Correlation of Serum Selenium in Asthma Patients with Severity of the Disorder.

Asthma is characterized by reversible airway obstruction, increased bronchial hyper-responsiveness and chronic inflammation, as well as higher levels of oxidative stress mainly due to decreased antioxidant defenses. Our primary aim was to investigate the correlation of serum selenium (Se) levels with the severity of asthma across gender, age, family history, and prevalence from childhood. Selenium levels in blood samples in 103 asthmatic patients and 103 healthy individuals were evaluated. The obtained data indicated that the mean serum Se levels in asthma patients were found to be twofold lower as compared to the controls (p < 0.001). However, there were no significant differences in the asthmatic patients when gender and age were considered. Patients characterized by family history of asthma and inhaler usage had 8% and 7% lower serum Se concentrations, although the difference was only border significant (p = 0.05). Multiple regression analysis demonstrated a significant inverse association of inhaler usage (ß = - 0.226; p < 0.001) with serum Se levels even after adjustment for asthma severity (ß = - 0.644; p < 0.001). While this report clearly necessitates a more detailed study, it is plausible that Se deficiency leads to impaired immune response, and therefore, Se supplementation might modulate oxidative stress in the lung and could potentially alleviate asthma pathophysiology.