A novel fermented Yi traditional medicine efficiently suppresses the replication of SARS-CoV-2 in vitro

Currently, the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a worldwide epidemic, causing more than 80 million infections and more than 1.7 million deaths. The pandemic has led to the closure of enterprises and schools in many countries, resulting in serious disruption of the global economy and social activities. Remdesivir is currently approved by the FDA for the treatment of COVID-19, but the WHO declared that Remdesivir is almost ineffective against COVID-19. The research and development of vaccines has made great progress, but it will take at least several months for safe and effective vaccines to be widely used clinically. Clinical studies revealed that some Traditional Chinese Medicines, such as Lianhua Qingwen Capsule and Huoxiang Zhengqi Water, exhibited excellent therapeutic effect on COVID-19. However, until now, there is still no cure for COVID-19. Therefore, there is an urgent need to find medicines that can effectively fight against the SARS-CoV-2. In this study, JIE BEN No. 10 (JB10), a fermentation broth produced by Yi traditional medicine fermentation technology, was explored for its anti-coronavirus activity. The in vitro data showed that JB10 could significantly suppresses the replication of the SARS-CoV-2 with an EC50 of 769.1 times dilution and a selection index of 42.68. Further studies indicated that JB10 had significant anti-inflammatory and antioxidant activities. The analysis of active components suggested that JB10 contained a large amount of superoxide dismutase (SOD), flavones, polyphenols, crude polysaccharide, etc. which may explain the anti-coronavirus activity, anti-inflammatory and antioxidant effects. Our study provides a new potentially therapeutic strategy for COVID-19.

Prediction of the Epidemic of COVID-19 Based on Quarantined Surveillance in China

Backgroud and ObjectiveTo predict the epidemic of COVID-19 based on quarantined surveillance from real world in China by modified SEIR model different from the previous simply mathematical model. Design and MethodsWe forecasted the epidemic of COVID-19 based on current clinical and epidemiological data and built a modified SEIR model to consider both the infectivity during incubation period and the influence on the epidemic from strict quarantined measures. ResultsThe peak time of the curve for the infected newly diagnosed as COVID-19 should substantially present on Feb. 5, 2020 (in non-Hubei areas) and Feb. 19, 2020 (in Hubei). It is estimated that the peak of the curve of the cumulative confirmed cases will appear in non-Hubei areas on Mar. 3, 2020 and in Hubei province on Mar. 10, 2020, and the total number of the patients diagnosed as COVID-19 is 18,000 in non-Hubei areas and 78,000-96,000 in Hubei. The Chinese COVID-19 epidemic can be completetly controlled in May, 2020. ConclusionsCOVID-19 is only a local outbreak in Hubei Province, China. It can be probably avoided the pandemic of global SARS-CoV-2 cases rise with the great efforts by Chinese government and its people.

Memantine Improves Cognitive Function and Alters Hippocampal and Cortical Proteome in Triple Transgenic Mouse Model of Alzheimer's Disease

Memantine is a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist clinically approved for moderate-to-severe Alzheimer's disease (AD) to improve cognitive functions. There is no report about the proteomic alterations induced by memantine in AD mouse model yet. In this study, we investigated the protein profiles in the hippocampus and the cerebral cortex of AD-related transgenic mouse model (3×Tg-AD) treated with memantine. Mice (8-month) were treated with memantine (5 mg/kg/bid) for 4 months followed by behavioral and molecular evaluation. Using step-down passive avoidance (SDA) test, novel object recognition (NOR) test and Morris water maze (MWM) test, it was observed that memantine significantly improved learning and memory retention in 3xTg-AD mice. By using quantitative proteomic analysis, 3301 and 3140 proteins in the hippocampus and the cerebral cortex respectively were identified to be associated with AD abnormalities. In the hippocampus, memantine significantly altered the expression levels of 233 proteins, among which PCNT, ATAXIN2, TNIK, and NOL3 were up-regulated, and FLNA, MARK 2 and BRAF were down-regulated. In the cerebral cortex, memantine significantly altered the expression levels of 342 proteins, among which PCNT, PMPCB, CRK, and MBP were up-regulated, and DNM2, BRAF, TAGLN 2 and FRY1 were down-regulated. Further analysis with bioinformatics showed that memantine modulated biological pathways associated with cytoskeleton and ErbB signaling in the hippocampus, and modulated biological pathways associated with axon guidance, ribosome, cytoskeleton, calcium and MAPK signaling in the cerebral cortex. Our data indicate that memantine induces higher levels of proteomic alterations in the cerebral cortex than in the hippocampus, suggesting memantine affects various brain regions in different manners. Our study provides a novel view on the complexity of protein responses induced by memantine in the brain of AD.

Effect of TRPC1 depletion on survival of cerebral nerve cells / 中国病理生理杂志

AIM:To study the effect of transient receptor potential channel 1 ( TRPC1) on the survival of hip-pocampal neurons in mice.METHODS:TRPC1 knockout mice and the control mice (6 months old) were used in this study.Immunofluorescence staining of neuron-specific marker NeuN, Nissl staining and TUNEL staining were performed to measure the changes of the neurons in hippocampal CA1, CA3 and dentate gyrus (DG).Western blot analysis was used to detect the levels of pro-apoptotic protein C/EBP homologous protein ( CHOP) and cleaved caspase-3.RESULTS:Immuno-fluorescence staining and Nissl staining showed that the number of neuronal cells was significantly decreased in hippocampal CA1, CA3 and DG of TRPC1 knockout mice compared with the control mice.TUNEL staining showed that the apoptosis neuronal cell number of the above areas in TRPC1 knockout mice was significantly increased compared with the control mice.The results of Western blot revealed that the levels of CHOP and cleaved caspase-3 were significantly increased in the hippocampus of TRPC1 knockout mice relative to the control mice.CONCLUSION:The depletion of TRPC1 induces neu-ronal loss through a mechanism of TRPC1-mediated apoptosis.