We have previously shown that PPAR-γ agonist 15d-PGJ2 inhibited neuronal autophagy after cerebral ischemia/reperfusion injury. However, the underlying mechanism of its regulatory role in neuronal autophagy remains unclear. This study was designed to test the hypothesis that 15d-PGJ2 upregulated Bcl-2 which binds to Beclin 1, and thereby inhibits autophagy. We performed cell viability assay, cytotoxicity assay, western blot, and co-immunoprecipitation to analyze autophagy activities in vitro model of oxygen-glucose deprivation/reoxygenation (OGD/R). OGD/R induced autophagy in cultured cortical neurons. 15d-PGJ2 treatment significantly decreased LC3-II/LC3-I ratio and Beclin 1 expression, but increased p62 expression. Autophagic inhibitor 3-methyladenine decreased LC3-II levels, increased neuronal cell viability, and mimicked some protective effect of 15d-PGJ2 against OGD/R injury. OGD/R-induced autophagy coincided with decreases in Bcl-2 expression and increases in Beclin 1 expression. 15d-PGJ2 treatment upregulated Bcl-2 expression and decreased Beclin 1 expression, and inhibit the dissociation of Beclin1 from Bcl-2 significantly. Bcl-2 siRNA abrogated the effect of 15d-PGJ2 on Beclin 1, LC3-II and p62, and influence cell viability and LDH level, while scRNA did not. PPAR-γ agonist 15d-PGJ2 exerts neuroprotection partially via inhibiting neuronal autophagy after OGD/R injury. The inhibition of autophagy by 15d-PGJ2 is mediated through upregulation of Bcl-2.
Introduction
Influenza has been linked to the crowding in emergency departments (ED) across the world. The impact of the Coronavirus Disease 2019 (COVID-19) pandemic on China EDs has been quite different from those during past influenza outbreaks. Our objective was to determine if COVID-19 changed ED visit disease severity during the pandemic.
Methods
This was a retrospective cross sectional study conducted in Nanjing, China. We captured ED visit data from 28 hospitals. We then compared visit numbers from October 2019 to February 2020 for a month-to-month analysis and every February from 2017 to 2020 for a year-to-year analysis. Inter-group chi-square test and time series trend tests were performed to compare visit numbers. The primary outcome was the proportion of severe disease visits in the EDs.
Results
Through February 29
th
2020, there were 93 laboratory-confirmed COVID-19 patients in Nanjing, of which 40 cases (43.01%) were first seen in the ED. The total number of ED visits in Nanjing in February 2020, were dramatically decreased (
n
= 99,949) in compared to January 2020 (
n
= 313,125) and February 2019 (
n
= 262,503). Except for poisoning, the severe diseases in EDs all decreased in absolute number, but increased in proportion both in year-to-year and month-to-month analyses. This increase in proportional ED disease severity was greater in higher-level referral hospitals when compared year by year.
Conclusion
The COVID-19 outbreak has been associated with decreases in ED visits in Nanjing, China, but increases in the proportion of severe ED visits.
Ginkgolide B (GB) has been shown to exert neuroprotective effects against cerebral ischemia/reperfusion (I/R) injury. However, the underlying mechanism by which GB prevents ischemic cell death remains unclear. Lysosomal proteases, including cathepsins B and L, have been implicated in ischemic cell death following reperfusion. Therefore, in the present study, we investigated the role of GB with respect to cathepsin-mediated cell death following I/R. Both the expression and enzymatic activity of cathepsins B and L were significantly increased in the ischemic cortex following cerebral I/R injury. We found that GB treatment markedly decreased the activity and expression of cathepsins B and L following I/R. Moreover, GB reduced necrotic and apoptotic cell death following I/R. These data strongly suggest that GB prevents cathepsin-mediated cell death following focal cerebral I/R injury, and they might provide new insights into the mechanism of the neuroprotective effects of GB.
Restenosis is a major complication of percutaneous transluminal coronary angioplasty (PTCA) and is characterized by increased superoxide formation and accumulation of smooth muscle cells (SMCs). The mechanisms through which peroxisome proliferator-activated receptor-gamma (PPAR-gamma) modulates the pathological process are incompletely defined. In this study, balloon injury of porcine coronary arteries in vivo and cell scraping model in vitro were used to elucidate the pathway via this molecule. PPAR-gamma and NADPH oxidase expression significantly increased both in neointimal hyperplasia after balloon injury or in the cultured SMCs after scraping injury. In vitro, PPAR-gamma agonist 15-deoxy-Delta(12,14)-prostagladlin J(2) (15d-PGJ2) decreased cell-scraping-induced superoxide generation through suppression of NADPH oxidase activity via down-regulation of p22(phox) and gp91(phox). Furthermore, 15d-PGJ2 could suppress scraping-stimulated proliferation of SMCs. These data demonstrate that upregulation of PPAR-gamma and NADPH oxidases are involved in restenosis and activation of PPAR-gamma can inhibit the NADPH oxidase-dependent superoxide generation in SMCs after injury. These findings will provide a new potential drug target for restenosis after balloon injury.
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