1.Genistein protects PC12 cells from Aβ(25-35)-induced apoptosis via JNK signaling and regulation of Fas pathway
Jingrong CHEN ; Yaojie ZHENG ; Fuling YOU ; Hong YANG
Chinese Pharmacological Bulletin 2015;(2):175-180
Aim To investigate the effect of genistein ( GEN) against Aβ( 25 -35 )-induced PC12 cells in regulation of Fas pathway through the activation of JNK. Methods Aβ( 25 -35 )-induced PC12 cells model was established. MTT and fluorescence activated cell sorting to analyze cell viability and apoptotic rate. Fluorescence quantitative PCR was used to detect Fas apoptotic pathways related gene Fas, FasL, caspase-3 and caspase-8 mRNA relative expression. Spectropho-tometry was used to detect caspase-3 and caspase-8 en-zyme activity. Western blot was adopted to detect JNK and p-JNK protein expression level changes. Results GEN attenuated Aβ( 25-35 )-induced upregulation of Fas and FasL, caspase-3 and caspase-8 mRNA lev-el, caspase-3 and caspase-8 enzyme activity, and sig-nificantly reduced Aβ(25-35) induced JNK phospho-rylation level. Conclusion GEN can protect PC12 cells from Aβ(25-35)-induced apoptosis via reducing Aβ( 25 -35 )-induced phosphorylation of JNK activa-tion, and then inhibit the JNK dependent Fas apoptotic pathway.
2.Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19.
Xiaoyan LIU ; Zhe LI ; Shuai LIU ; Jing SUN ; Zhanghua CHEN ; Min JIANG ; Qingling ZHANG ; Yinghua WEI ; Xin WANG ; Yi-You HUANG ; Yinyi SHI ; Yanhui XU ; Huifang XIAN ; Fan BAI ; Changxing OU ; Bei XIONG ; Andrew M LEW ; Jun CUI ; Rongli FANG ; Hui HUANG ; Jincun ZHAO ; Xuechuan HONG ; Yuxia ZHANG ; Fuling ZHOU ; Hai-Bin LUO
Acta Pharmaceutica Sinica B 2020;10(7):1205-1215
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) , which suppressed SARS-CoV-2 replication . In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers ( < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.