Tanshinol alleviates ischemia-induced myocardial fibrosis via targeting ERK2 and disturbing the intermolecular autophosphorylation of ERK2Thr188.

Myocardial fibrosis is the fundamental remodeling process in myocardial ischemia (MI) and also the major contributor of heart failure and death. Tanshinol (Danshensu in Chinese, DSS), a major ingredient of salvia mitiorrhiza Bunge (Lamiaceae) root, exerted significant cardio protection effects. In this study, we aimed to identify the action target and then uncover the mechanism of DSS alleviating myocardial fibrosis. The pharmacological activities of DSS protecting ischemic cardiac was assessed and the myocardial proteomics was carried out. To identify the target of DSS, a cellular thermal shift assay combined with LC-MS identification was conducted. Surface plasmon resonance assay, molecular dynamics simulation and pharmacological and molecular biology approaches were adopted to explore the action mechanisms of DSS. Our results revealed that DSS effectively alleviated MI-induced left ventricle dysfunctions and the increasements of circulating myocardial markers. Besides, DSS significantly reversed the proteomic profile related to myocardial fibrotic processes and the ERK2 was identified as a crucial cellular target of DSS. DSS abated the temperature-dependent denaturation of ERK2 in a dose-dependent manner and the KD value of DSS and ERK2 was 60.19 µM. After Ang II stimulation, DSS suppressed the phosphorylation of Thr188 rather than the classic residues in TEY motif. DSS interfered the ERK2 homo-dimerization and then blocked the intermolecular autophosphorylation at Thr188 site. Thereout, DSS inhibited the nuclear translocation of ERK2 and the expression of downstream fibrotic biomolecules. Collectively, our results demonstrated that DSS targeted ERK2 and suppressed the intermolecular autophosphorylation at Thr188 residue, thus protecting ischemic myocardia from fibrosis remodeling.

A cross-sectional study of olfactory and taste disorders among COVID-19 patients in China.

To determine the prevalence and clinical features of olfactory and taste disorders among coronavirus disease 2019 (COVID-19) patients in China. A cross-sectional study was performed in Wuhan from April 3, 2020 to April 15, 2020. A total of 187 patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) completed face-to-face interviews or telephone follow-ups. We found that the prevalence of olfactory and taste disorders was significantly lower in the Chinese cohort than in foreign COVID-19 cohorts. Females were more prone to olfactory and taste disorders. In some patients, olfactory and taste disorders precede other symptoms and can be used as early screening and warning signs.

miR21 is Associated with the Cognitive Improvement Following Voluntary Running Wheel Exercise in TBI Mice.

Recent evidences revealed that the alteration of microRNAs (miRNAs) might be associated with neuroplasticity induced by voluntary running wheel (RW) exercise in mice suffered from traumatic brain injury (TBI). In the present study, we explored the possible role of miR21 involved in the cognitive improvement following voluntary RW in TBI mice. Firstly, in situ hybridization and quantitative real-time PCR (qRT-PCR) were employed to determine the hippocampal expression and location of miR21 in TBI mice with or without spontaneous RW. Either miR21-mimics/plenti-miR21 or miR21-agomir/miR21-sponge was employed to regulate the miR21 expression in vivo and in vitro. Acquisition of spatial learning and memory retention was assessed by Morris Water Maze (MWM) test. Golgi stain was also performed to evaluate the alteration of hippocampal dendrite. Our finding confirmed that the elevated miR21 level in hippocampal post-TBI was significantly reduced by spontaneous RW. Overexpression of miR21 in TBI mice with spontaneous RW induced deteriorations in spatial learning and memory retention by significant decreases in the somata size and branch points of the hippocampus neurons. In vitro transduction with miR21 also reduced the neurite extension and the area of cultured hippocampal neuron. However, miR21 down-regulation reversed these effects. The present data strongly suggest that miR21 is an important molecule that has been involved in neuroprotection induced by voluntary RW exercise post-TBI.