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Current evidence suggests that amyloid beta (Aβ) peptides may play a major role in the pathogenesis of Alzheimer's disease in part by eliciting oxidative stress. Puerarin, a major isoflavone glycoside from Kudzu root (Pueraria lobata), has been reported to exert estrogen-like and antioxidant activities. The central hypothesis guiding this study is that puerarin will prevent or at least markedly attenuate Aβ(25-35)-induced excess production of reactive oxygen species (ROS) by interrupting glycogen synthase kinase-3β (GSK-3β) signaling. In this study, we demonstrate that pretreatment of primary hippocampal neurons with puerarin significantly reduced Aβ(25-35)-induced oxidative stress characterized by scavenging of ROS and inhibiting lipid peroxidation. Puerarin induced expression of nuclear Nrf2 protein, but not in the Nrf2 mRNA level, and increased heme oxygenase-1 (HO-1) levels at levels of transcription and translation. Puerarin-induced Serine 9 phosphorylation of GSK-3β was blocked by lithium chloride treatment in primary hippocampal neurons, indicating the participation of the GSK-3β inactivation. This protective effect was partially reversed when GSK-3β were blocked by the chemical inhibitors such as lithium chloride. These results suggest puerarin as a phytoestrogen with potential of a possible therapeutic agent in neurodegenerative diseases involving oxidative stress.

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Background The outbreak of COVID-19 has led to international concern. We aimed to establish an effective screening strategy in Shanghai, China, to aid early identification of patients with COVID-19. MethodsWe did a multicentre, observational cohort study in fever clinics of 25 hospitals in 16 districts of Shanghai. All patients visiting the clinics within the study period were included. A strategy for COVID-19 screening was presented and then suspected cases were monitored and analysed until they were confirmed as cases or excluded. Logistic regression was used to determine the risk factors of COVID-19. Findings We enrolled patients visiting fever clinics fromJan 17 to Feb 16, 2020. Among 53 617 patients visiting fever clinics, 1004 (1•9%) were considered as suspected cases, with 188 (0•4% of all patients, 18•7% of suspected cases) eventually diagnosed as confirmed cases. 154 patients with missing data were excluded from the analysis. Exposure history (odds ratio [OR] 4•16, 95% CI 2•74-6•33; p<0•0001), fatigue (OR 1•56, 1•01-2•41; p=0•043), white blood cell count less than 4 × 10⁹ per L (OR 2•44, 1•28-4•64; p=0•0066), lymphocyte count less than 0•8 × 10⁹ per L (OR 1•82, 1•00-3•31; p=0•049), ground glass opacity (OR 1•95, 1•32-2•89; p=0•0009), and having both lungs affected (OR 1•54, 1•04-2•28; p=0•032) were independent risk factors for confirmed COVID-19.Interpretation The screening strategy was effective for confirming or excluding COVID-19 during the spread of this contagious disease. Relevant independent risk factors identified in this study might be helpful for early recognition of the disease.