Investigating the effect of polymerase inhibitors on cellular proliferation: Computational studies, cytotoxicity, CDK1 inhibitory potential, and LC‐MS/MS cancer cell entrapment assays

Chemical Biology & Drug Design, Journal Year: 2024, Volume and Issue: 103(3)

Published: March 1, 2024

Abstract Directly acting antivirals (DAAs) are a breakthrough in the treatment of HCV. There controversial reports on their tendency to induce hepatocellular carcinoma (HCC) HCV patients. Numerous have concluded that HCC is attributed patient‐related factors while others inclined attribute this as DAA side‐effect. This study aims investigate effect polymerase inhibitor DAAs, especially daclatasivir (DLT) cellular proliferation compared ribavirin (RBV). The interaction DAAs with variable cell‐cycle proteins was studied silico. binding affinities multiple targets were investigated and molecular dynamics assessed. vitro selected candidate DLT cancer cell determined CDK1 inhibitory potential evaluated. Finally, entrapment candidates assessed by an in‐house developed validated LC‐MS/MS method. results indicated antiviral agents, DLT, may exert anti‐proliferative against lines. showed be achieved via targets, including CDK1, resulting halting proliferation. exhibited remarkable permeability liver line which permits adequate targets. In conclusion, reveal cells. These pose therapeutic choice for patients suffering from liable development.

Language: Английский

High-intensity interval training attenuates renal injury induced by myocardial ischemia-reperfusion in rats

Journal of the Chinese Medical Association, Journal Year: 2024, Volume and Issue: 88(2), P. 126 - 137

Published: Oct. 22, 2024

Background: High-intensity interval training (HIIT) has been recognized as an effective form of short-duration exercise. The purpose this study was to assess whether HIIT could reduce renal injury induced by myocardial ischemia-reperfusion (MIR) in rats. Methods: Male Sprague-Dawley rats were randomly assigned the Sham (SHAM), coronary artery occlusion (CAO), HIIT, and ischemic precondition (IPC) groups. Rats underwent 40 minutes left anterior descending CAO under anesthesia, followed 3 hours reperfusion, induce MIR. Postsurgery, sacrificed, their blood, heart, kidney tissues examined. group 4 weeks before surgery. Results: intervention significantly reduced after MIR concentrations blood urea nitrogen (BUN) creatinine (CRE) serum. Moreover, proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, decreased, while anti-inflammatory cytokine IL-10 increased Additionally, suppressed expression FoxO1, Bax/Bcl-2 ratio, TNF-α, cleaved-caspase-3/caspase-3 ratio tissues, ultimately reducing cell apoptosis. Conclusion: This is first demonstrate that effects similar IPC, regulates production cytokines inhibits apoptosis, thereby occurrence cardiorenal syndrome.

Language: Английский