Synthesis of 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-]quinazolinones through a cyclized dearomatization and trichloromethylation cascade strategy.

A variety of 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-]quinazolinones were prepared in moderate to good yields with high regioselectivity through intramolecular 6- cyclization and trichloromethylation of 3-alkynyl-2-pyridinyl-tethered quinazolinones in chloroform. Mechanistic studies revealed that chloroform might serve as a trichloromethyl anion precursor. Furthermore, the reaction could be easily performed on gram scales and an estrone-derived 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-]quinazolinone was prepared over five steps.

Electrophysiological evaluation of an anticancer drug gemcitabine on cardiotoxicity revealing down-regulation and modification of the activation gating properties in the human rapid delayed rectifier potassium channel.

Gemcitabine is an antineoplastic drug commonly used in the treatment of several types of cancers including pancreatic cancer and non-small cell lung cancer. Although gemcitabine-induced cardiotoxicity is widely recognized, the exact mechanism of cardiac dysfunction causing arrhythmias remains unclear. The objective of this study was to electrophysiologically evaluate the proarrhythmic cardiotoxicity of gemcitabine focusing on the human rapid delayed rectifier potassium channel, hERG channel.

Effect of Nrf2 on Phenotype Changes of Macrophages in the Anterior Vaginal Wall of Women With Pelvic Organ Prolapse.

Objective: The aim of this study was to observe the effect of nuclear factor-erythroid 2-related factor 2 (Nrf2) on the phenotype changes of macrophages in the anterior vaginal wall of patients with pelvic organ prolapse (POP).

Methods: The tissues of the anterior vaginal wall of the control group (n = 30) and POP groups (n = 60) were collected during operation. The expressions of Nrf2, iNOS (representative factor of M1 macrophages), and CD206 (representative factor of M2 macrophages) were determined by immunohistochemical staining and Western blot.

Nitric oxide down-regulates voltage-gated Na channel in cardiomyocytes possibly through S-nitrosylation-mediated signaling.

Nitric oxide (NO) is produced from endothelial cells and cardiomyocytes composing the myocardium and benefits cardiac function through both vascular-dependent and-independent effects. This study was purposed to investigate the possible adverse effect of NO focusing on the voltage-gated Na channel in cardiomyocytes. We carried out patch-clamp experiments on rat neonatal cardiomyocytes demonstrating that NOC-18, an NO donor, significantly reduced Na channel current in a dose-dependent manner by a long-term application for 24 h, accompanied by a reduction of Nav1.

Disruption of asparagine-linked glycosylation to rescue and alter gating of the Na1.5-Na channel.

SCN5A gene encodes the voltage-gated sodium channel Na1.5 which is composed of a pore-forming α subunit of the channel. Asparagine (N)-linked glycosylation is one of the common post-translational modifications in proteins.