Protease-activated receptors (PARs) are a family of G protein-coupled receptors with a unique activation mechanism involving proteolytic cleavage of the extracellular N-terminal domain of the receptor. PAR2 has a contractile effect on esophageal smooth muscle. We investigate the signaling pathways of the PAR2-activating peptide (PAR2-AP) induced contraction in cat esophageal smooth muscle cells. The length of freshly isolated smooth muscle cells and permeabilized cells from feline esophagus were measured by scanning micrometry, and by confirming molecular basis via western blot analysis. The responses to PAR2-AP were initial and sustained contractions, depending on time. The maximum contraction of the initial phase occurred at 60 s. The PAR2-AP-induced contraction was mediated by Gαi1, Gαi3, and Gαq protein activation, leading to phospholipase-c (PLC) and myosin light chain kinase (MLCK) activation. 20 kDa myosin light chain (MLC20) was phosphorylated by PAR2-AP. Rho kinase-2 (ROCK-2), an activator of 17 kDa C-kinase potentiated Protein phosphatase-1 Inhibitor (CPI-17), was increased by PAR2 receptor activation. In conclusion, PAR2-AP produced an initial contraction mediated by Gαi1, Gαi3, and Gαq protein activation, resulting in PLC and MLCK activation. The sustained contraction by PAR2-AP was mediated by the Rho/Rho kinase-dependent pathway.
Background and aims: The new visceral adiposity index (NVAI) is an indirect marker of visceral adipose tissue recently developed using a Korean population. Here we examined the association of NVAI with coronary artery calcification and arterial stiffness in asymptomatic Korean patients. Methods and results: We analyzed data from 60,938 asymptomatic Korean adults. Odds ratios and 95% confidence intervals (CIs) for coronary artery calcification score (CACS) > 100 and brachial eankle pulse wave velocity (baPWV) !14 m/s were calculated across NVAI tertiles using multiple logistic regression analysis. Receiver operating characteristic (ROC) and area under the curve (AUC) analyses were used to assess the ability of NVAI to predict moderate to high risk of cardiovascular disease. The prevalence of moderate and high risk of cardiovascular disease increased significantly as the NVAI tertile increased. The odds ratio (95% CI) of the highest NVAI tertile for CACS >100 was 5.840 (5.101e6.686) for men and 18.916 (11.232e31.855) for women, after adjusting for confounders. All NVAI AUC values were significantly higher than the AUC values for other visceral adiposity markers. Conclusions: This study provides the evidence that NVAI is independently and positively associated with coronary calcification and arterial stiffness in asymptomatic Korean adults.
This study investigated effect of extract containing quercetin-3-O-β-D-glucuronopyranoside from Rumex Aquaticus Herba (ECQ) against chronic gastritis in rats. To produce chronic gastritis, the animals received a daily intra-gastric administration of 0.1 ml of 0.15% iodoacetamide (IA) solution for 7 days. Daily exposure of the gastric mucosa to IA induced both gastric lesions and significant reductions of body weight and food and water intake. These reductions recovered with treatment with ECQ for 7 days. ECQ significantly inhibited the elevation of the malondialdehyde levels and myeloperoxidase activity, which were used as indices of lipid peroxidation and neutrophil infiltration. ECQ recovered the level of glutathione, activity of superoxide dismutase (SOD), and expression of SOD-2. The increased levels of total NO concentration and iNOS expression in the IA-induced chronic gastritis were significantly reduced by treatment with ECQ. These results suggest that the ECQ has a therapeutic effect on chronic gastritis in rats by inhibitory actions on neutrophil infiltration, lipid peroxidation and various steps of reactive oxygen species (ROS) generation.
Purpose: Stroke prevention in patients with atrial fibrillation (AF) is influenced by many factors. Using a contemporary registry, we evaluated variables associated with the use of warfarin or direct oral anticoagulants (OACs). Materials and Methods: In the prospective multicenter CODE-AF registry, 10529 patients with AF were evaluated. Multivariate analyses were performed to identify variables associated with the use of anticoagulants. Results: The mean age of the patients was 66.9±14.4 years, and 64.9% were men. The mean CHA2DS2-VASc and HAS-BLED scores were 2.6±1.7 and 1.8±1.1, respectively. In patients with high stroke risk (CHA2DS2-VASc ≥2), OACs were used in 83.2%, including direct OAC in 68.8%. The most important factors for non-OAC treatment were end-stage renal disease [odds ratio (OR) 0.27; 95%
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