Let-7g improves multiple endothelial functions through targeting transforming growth factor-beta and SIRT-1 signaling.

Objectives: The present study aimed to explore the role of microribonucleic acid (miRNA) Let-7g in regulating endothelial functions.

Background: Derangement of miRNAs is implicated in the pathogenesis of cardiovascular diseases. Because the transforming growth factor (TGF)-β pathway plays a regulatory role in endothelial functions, miRNAs targeted at TGF-β signal cascade might affect vascular health.

Inhibition of ATR-dependent signaling by protoapigenone and its derivative sensitizes cancer cells to interstrand cross-link-generating agents in vitro and in vivo.

DNA damage caused during cancer treatment can rapidly activate the ataxia telangiectasia-mutated (ATM) and ATM and Rad3-related (ATR)-dependent phosphorylation of Chk2 and Chk1 kinases, which are hallmarks of the DNA damage response (DDR). Pharmacologic inhibition of ATR causes a synthetic lethal effect on ATM- or p53-defective cancers, suggesting that such inhibition is an effective way to improve the sensitivity of cancers to DNA-damaging agents. Here, both the natural compound protoapigenone (WYC02) and its synthetic derivative WYC0209 exhibited cytotoxic effects on various cancer cell lines.