Azilsartan Modulates HMGB1/NF-κB/p38/ERK1/2/JNK and Apoptosis Pathways during Renal Ischemia Reperfusion Injury

Renal ischemia/reperfusion (IR) injury is characterized by an unexpected impairment of blood flow to the kidney. Azilsartan is an angiotensin receptor blocker that is approved for the management of hypertension. The present study aimed to investigate, on molecular basics, the nephroprotective activity of azilsartan on renal IR injury in rats. Rats were assigned into four groups: (1) Sham group, (2) Azilsartan group, (3) IR group, and (4) IR/Azilsartan-treated group. Histological examination and renal function were evaluated. Levels of KIM-1, HMGB1, caspase 3, GPX, SOD, NF-κB, and p53 proteins were investigated using ELISA. mRNA levels of IL-1β, IL6, IL10, TNF-α, NF-κB, p53, and bax were assessed by qRT-PCR. Expression of p38, JNK, and ERK1/2 proteins was investigated by Western blotting. IR injury resulted in tissue damage, elevation of creatinine, BUN, KIM-1, HMGB1, caspase 3, NF-κB, and p53 levels, decreasing GPX and SOD activities, and up-regulation of NF-κB, IL-1β, IL6, TNF-α, p53, and bax genes. Furthermore, it up-regulated the expression of phosphorylated/total ratio of p38, ERK1/2, and JNK proteins. Interestingly, treatment of the injured rats with azilsartan significantly alleviated IR injury-induced histopathological and biochemical changes. It reduced the creatinine, BUN, KIM-1, HMGB1, caspase-3, NF-κB, and p53 levels, elevated GPX and SOD activities, down-regulated the expression of NF-κB, IL-1β, IL6, TNF-α, p53, and bax genes, and up-regulated IL10 gene expression. Furthermore, it decreased the phosphorylated/total ratio of p38, ERK1/2, and JNK proteins. Azilsartan exhibited nephroprotective activity in IR-injured rats via its antioxidant effect, suppression of inflammation, attenuation of apoptosis, and inhibition of HMGB1/NF-κB/p38/ERK1/2/JNK signaling pathway

Latent tuberculosis infection among patients with coronary artery stenosis: A case–Control study

Background: The activation of the cell-mediated immune responses by Mycobacterium tuberculosis can promote atherogenesis. Aims: The aim of this study is to determine the frequency of latent tuberculosis infection (LTBI) among patients with coronary artery stenosis (CAS) and to explore the association between LTBI and development of CAS. We conducted a case–control study which included 183 patients′ who underwent percutaneous coronary angiography (121 patients with CAS and 62 patients without as a control group). Methods: For all the study population, clinical evaluation, tuberculin skin test (TST), imaging studies (including chest radiography and echocardiography), laboratory investigations, and electrocardiography were carried out. Only for the patients with positive TST, QuantiFERON-TB Gold test was performed. Predictors of CAS were identified using univariate analyses (Yates' corrected Chi-square test or Fischer's exact test) followed by multivariate analysis (binary logistic regression). Results: Among 29.5% of the study population, LTBI was detected, and among patients with CAS, 56.2% of patients had advanced CAS. After multivariate analysis, it was found that metabolic syndrome (MS) (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.5–22.6, P = 0.022) and LTBI (OR 2.5, 95% CI 1.2–17.3, P = 0.018) were the predictors of CAS among the study population, while only diabetes mellitus (DM) (OR 1.9, 95% CI 1.1–11.7, P = 0.031) was the predictor of advanced CAS. Conclusion: LTBI is associated with the development of CAS. In addition, MS is associated with CAS, while its related disorder, DM, is associated with advanced CAS