关键词：
biomaterials;cartilage tissue engineering;functionalization of polymers;ginsenoside Rg1;PHBV fibrous scaffold
摘要：
Inflammatory environment in the end-stage osteoarthritis (OA) cartilage defects greatly limits the effectiveness of engineered cartilage. It is critical that developing scaffolds intend to be applied in cartilage tissue engineering (CTE) under this pathological condition. In this study, poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) (PHBV) fibrous scaffolds modified by ginsenoside Rg1 could be able to alleviate the dedifferentiation of articular chondrocytes caused by interleukin-1 beta (IL-1 beta), a key inflammatory factor in the pathogenesis of OA. Followed by 5-day incubation with culture media containing IL-1 beta, articular chondrocytes cultured with ginsenoside Rg1-modified PHBV fibrous scaffolds (PHBV-g-Rg1) displayed typical chondrocytic morphology compared with those cultured with PHBV fibrous scaffolds. By employing real-time quantitative polymerase chain reaction assay, it demonstrated that PHBV-g-Rg1 fibrous scaffold reduced IL-1 beta-caused dedifferentiation to articular chondrocytes via enhancing the transcription of chondrocytic phenotype-related genes and reducing the transcription of matrix degradation-related genes. It suggests that ginsenoside Rg1-modified PHBV fibrous scaffold would be potentially applied in CTE to treat cartilage defects under IL-1 beta threat. (c) 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 48378.
摘要：
Background Epidemiological studies have suggested an association between Helicobacter pylori (H pylori) infection and atherosclerosis through undefined mechanisms. Endothelial dysfunction is critical to the development of atherosclerosis and related cardiovascular diseases. The present study was designed to test the hypothesis that H pylori infection impaires endothelial function through exosome-mediated mechanisms. Methods and Results Young male and female patients (18-35 years old) with and without H pylori infection were recruited to minimize the chance of potential risk factors for endothelial dysfunction for the study. Endothelium-dependent flow-mediated vasodilatation of the brachial artery was evaluated in the patients and control subjects. Mouse infection models with CagA(+) H pylori from a gastric ulcer patient were created to determine if H pylori infection-induced endothelial dysfunction could be reproduced in animal models. H pylori infection significantly decreased endothelium-dependent flow-mediated vasodilatation in young patients and significantly attenuated acetylcholine-induced endothelium-dependent aortic relaxation without change in nitroglycerin-induced endothelium-independent vascular relaxation in mice. H pylori eradication significantly improved endothelium-dependent vasodilation in both patients and mice with H pylori infection. Exosomes from conditioned media of human gastric epithelial cells cultured with CagA(+) H pylori or serum exosomes from patients and mice with H pylori infection significantly decreased endothelial functions with decreased migration, tube formation, and proliferation in vitro. Inhibition of exosome secretion with GW4869 effectively preserved endothelial function in mice with H pylori infection. Conclusions H pylori infection impaired endothelial function in patients and mice through exosome-medicated mechanisms. The findings indicated that H pylori infection might be a novel risk factor for cardiovascular diseases.
摘要：
CGRP, known as the most potent vasodilator substance, plays an important role in hypertension initiation and development. TRPV1 and TRPA1 are critical in promoting the synthesis and release of CGRP, thereby regulating the cardiovascular tone. Rutaecarpine exhibits potent vasodilator and hypertensive effects by stimulating CGRP synthesis and release via activation of TRPV1. And NO has been shown to react with H2S in vivo to form HNO, thereby activating HNO-TRPA1-CGRP pathway. Inspired by combination therapy, 11 rutaecarpine-furoxan hybrids were designed, synthesized and evaluated. The results demonstrated that most hybrids exerted comparable or improved vasodilator activities. Among which, 13a is the most potent both ex vivo (EC50=13.1nM) and in vivo. Mechanistic studies revealed that the vasodilator and anti-hypertensive effects of the hybrids might involve the promotion of CGRP release via dual activation of TRPV1 and TRPA1. This work suggests that dual-targeted hybrids might be an effective and promising approach to discover and develop novel anti-hypertensive drugs.
摘要：
Objective: By establishing the acute myocardial ischemia (AMI) model, to investigate the effects of Xintongtai granule on new blood vessels density, the expression of Notch1, D114 protein in rats with AMI. Methods: The rats were randomly divided into six groups, except for the 10 rats in sham -operation group, the other rats were ligatured left anterior of coronary artery to establish the rat models of AML Then randomly di-vided into the model group, high-, medium- and low-dose of Xintongtai groups, and Shexiang Baoxin pill (麝香保心丸)group, which were treated separately with distilled water, high-dose, medium-dose and low-dose of Xin-tongtai and Shexiang Baoxin pill by gavaged for 2 weeks, the new blood vessels density in myocardial tissue, the expression of Notch1 and D114 protein in myocardial tissue was tested using immunohistochemical method. Results: The expression of Notch1 and D114 in ischemic myocardium and the microvessel density of ischemic myocardium in model group were higher than those in sham-operated group (P<0.05), and the expression of Notch1 and D114 in ischemic myocardium in Xintongtai group and Shexiang Baoxin Pill group were higher than those in model group (P<0.05). Conclusion: Xintongtai has protective effect on ischemic myocardium, which may-be related to its activation of Notch signaling pathway, up-regulation of Notch1 and D114 protein expression in ischemic area and promotion of angiogenesis.
