Astragaloside IV protects cardiomyocytes from hypoxic injury by regulating endoplasmic reticulum stress via eIF2α/CHOP signaling pathway.

Endoplasmic reticulum stress (ER stress) is suggested to promote cardiomyocyte apoptosis and ultimately lead to ischemic injury. Inhibition of ER stress-induced apoptosis may be a therapeutic strategy for MI injury. Astragaloside-IV (AST) from Astragalus membranaceus (Fisch) Bge, was reported to have cardioprotective properties. In this study, we investigated the protective effect of AST on cardiomyocytes against hypoxia injury by regulating ER stress and inhibiting apoptosis. H9c2 cardiomyocytes were divided into three groups, normal group, hypoxia group and AST group. Cell viability was determined by CCK-8 assay. Intracellular reactive oxygen species (ROS) production was detected by DCFH-DA (2,7- dichloro-dihydrofluorescein diacetate) florescent staining. The study showed that AST treatment could significantly increase the cell viability of H9c2 cells exposed to hypoxia. Furthermore, AST could restrain cell apoptosis and decrease the production of ROS. Compared with normal group, the protein levels of Bax, caspase-3, caspase-9, GRP78, p-eIF2α, and CHOP were enhanced in the hypoxia group, whereas the protein level of Bcl-2 was dramatically reduced. Compared with hypoxia group, AST markedly inhibited the phosphorylation of eIF2α and the expression of caspase-3, caspase-9 and CHOP, and promoted the protein expression of Bcl-2. Thus, AST can inhibit the ER stress-mediated apoptosis, partly through the eIF2α/CHOP pathway suppression to inhibit ER stress.

MiR-199a-5p enhances neuronal differentiation of neural stem cells and promotes neurogenesis by targeting Cav-1 after cerebral ischemia.

AIMS: MicroRNAs (miRs) are involved in endogenous neurogenesis, enhancing of which has been regarded as a potential therapeutic strategy for ischemic stroke treatment; however, whether miR-199a-5p mediates postischemic neurogenesis remains unclear. This study aims to investigate the proneurogenesis effects of miR-199a-5p and its possible mechanism after ischemic stroke. METHODS: Neural stem cells (NSCs) were transfected using Lipofectamine 3000 reagent, and the differentiation of NSCs was evaluated by immunofluorescence and Western blotting. Dual-luciferase reporter assay was performed to verify the target gene of miR-199a-5p. MiR-199a-5p agomir/antagomir were injected intracerebroventricularly. The sensorimotor functions were evaluated by neurobehavioral tests, infarct volume was measured by toluidine blue staining, neurogenesis was detected by immunofluorescence assay, and the protein levels of neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), caveolin-1 (Cav-1), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF) were measured by Western blotting. RESULTS: MiR-199a-5p mimic enhanced neuronal differentiation and inhibited astrocyte differentiation of NSCs, while a miR-199a-5p inhibitor induced the opposite effects, which can be reversed by Cav-1 siRNA. Cav-1 was through the dual-luciferase reporter assay confirmed as a target gene of miR-199a-5p. miR-199a-5p agomir in rat stroke models manifested multiple benefits, such as improving neurological deficits, reducing infarct volume, promoting neurogenesis, inhibiting Cav-1, and increasing VEGF and BDNF, which was reversed by the miR-199a-5p antagomir. CONCLUSION: MiR-199a-5p may target and inhibit Cav-1 to enhance neurogenesis and thus promote functional recovery after cerebral ischemia. These findings indicate that miR-199a-5p is a promising target for the treatment of ischemic stroke.

Lianhua Qingwen prescription for Coronavirus disease 2019 (COVID-19) treatment: Advances and prospects.

BACKGROUND: An outbreak of Coronavirus Disease 2019 (COVID-19) which was infected by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is still spreading and has led to unprecedented health emergency over the world. Though no specific drug has been developed so far, emerging agents have been confirmed effective or potentially beneficial to restrain it. Lianhua Qingwen (LHQW) is a commonly used Chinese medical preparation to treat viral influenza, including in the fight against SARS in 2002-2003 in China. Recent data also showed that LHQW played a vigorous role in COVID-19 treatment. PURPOSE: This review will elucidate the pre-clinical and clinical evidence of LHQW in lung protection and antiviral activities, and provide timely data delivery for the exploration of effective treatment strategies in the therapy of COVID-19. STUDY DESIGN AND METHOD: The research data were obtained from the academic databases (up to August 8, 2020) including Pubmed, CNKI and Web of Science, on ethnobotany and ethno medicines. The search keywords for screening the literature information were "virus", "COVID-19", or "SARS-CoV-2", and "Lianhua Qingwen". The documents were filtered and summarized for final evaluation. RESULTS: The collected evidence demonstrated that LHQW exhibited benefits against COVID-19. Impressively, LHQW in conjunction with conventional treatment could significantly improve COVID-19 patients as a synergetic strategy. The mechanisms were mainly involved the antiviral activity, and regulation of inflammation response as well as immune function. CONCLUSION: Although the data were far from adequate, the latest advances had shown the benefits of LHQW in COVID-19, especially in combination with other antiviral drugs. This review provides comprehensive evidence of LHQW as a complementary strategy for treating COVID-19. Nevertheless, imperious researches should be conducted to clarify the unconfirmed effects, regulatory mechanisms and adverse reactions of LHQW in treating COVID-19 by means of well designed randomized controlled trials.

Expression of microRNA-21 in ovarian epithelial carcinoma and its clinical significance / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of microRNA-21(miR-21) in ovarian epithelial carcinoma and its association with the clinicopathological features.</p><p><b>METHODS</b>The expression of miR-21 was detected by Stem-loop real-time RT-PCR in 48 cases of ovarian epithelial carcinomas, 24 cases of benign ovarian epithelial tumors and 15 cases of normal ovarian tissues.</p><p><b>RESULTS</b>The relative expression level of miR-21(2-(DeltaDelta)CT) was 4.849-/+1.813 in the ovarian epithelial carcinomas, significantly higher than that in the benign ovarian tumors and normal ovarian tissues (P<0.01), but comparable between the latter two groups. The expression of miR-21 was not correlated to the histological type, but increased significantly with the progression of the clinical stages and histological grading (P<0.01), showing a close correlation to lymphatic metastasis.</p><p><b>CONCLUSION</b>MiR-21 might play a role as an oncogene in the tumorigenesis and development of ovarian epithelial carcinoma, and is possibly correlated to the progression and prognosis of ovarian epithelial carcinoma.</p>