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Neutralizing antibodies could be antivirals against COVID-19 pandemics. Here, we report the isolation of four human-origin monoclonal antibodies from a convalescent patient in China. All of these isolated antibodies display neutralization abilities in vitro. Two of them (B38 and H4) block the binding between RBD and vial cellular receptor ACE2. Further competition assay indicates that B38 and H4 recognize different epitopes on the RBD, which is ideal for a virus-targeting mAb-pair to avoid immune escape in the future clinical applications. Moreover, therapeutic study on the mouse model validated that these two antibodies can reduce virus titers in the infected mouse lungs. Structure of RBD-B38 complex revealed that most residues on the epitope are overlapped with the RBD-ACE2 binding interface, which explained the blocking efficacy and neutralizing capacity. Our results highlight the promise of antibody-based therapeutics and provide the structural basis of rational vaccine design. One Sentence SummaryA pair of human neutralizing monoclonal antibodies against COVID-19 compete cellular receptor binding but with different epitopes, and with post-exposure viral load reduction activity.
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The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, December 2019, and continuously poses a serious threat to public health. Our previous study has shown that cytokine storm occurred during SARS-CoV-2 infection, while the detailed role of cytokines in the disease severity and progression remained unclear due to the limited case number. In this study, we examined 48 cytokines in the plasma samples from 53 COVID-19 cases, among whom 34 were severe cases, and the others moderate. Results showed that 14 cytokines were significantly elevated upon admission in COVID-19 cases. Moreover, IP-10, MCP-3, and IL-1ra were significantly higher in severe cases, and highly associated with the PaO2/FaO2 and Murray score. Furthermore, the three cytokines were independent predictors for the progression of COVID-19, and the combination of IP-10, MCP-3 and IL-1ra showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations. Serial detection of IP-10, MCP-3 and IL-1ra in 14 severe cases showed that the continuous high levels of these cytokines were associated with disease deterioration and fatal outcome. In conclusion, we report biomarkers that closely associated with disease severity and outcome of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, providing novel therapeutic targets and strategy.
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<p><b>OBJECTIVE</b>To investigate the distribution of CSF1PO, TPOX and TH01 in 5 minority populations only resided in Yunnan province.</p><p><b>METHODS</b>DNA extraction from bloods and multiplex amplification of CSF1PO, TPOX and TH01 were carried out. The technique of denaturing polyacrylamide gel electrophoresis and silver staining method were used.</p><p><b>RESULTS</b>The data on the distribution of allele frequencies of 3 loci(CSF1PO, TPOX and TH01) in Achang Deang Bulang Pumi and Jino were collected and analyzed.</p><p><b>CONCLUSION</b>The allele distribution of the loci were in good agreement with the Hardy-Weinberg equibrium. A satisfactory result was obtained and some significant genetics differences were noticed in different populations.</p>
Assuntos
Feminino , Humanos , Masculino , Alelos , China , Frequência do Gene , Genótipo , Sequências de Repetição em Tandem , GenéticaRESUMO
AIM:To study the effect of Hirudo on level of Endothelin-1(ET-1),kidney structure and function in diabetic nephyropathy(DN) rats. METHODS: STZ-induced DN rats were randomly divided into four groups: model group,Hirudo(17.5 g/kg,8.75 g/kg) treatment group,and captopril group,in addition,normal rats for control group.All rats were given by ig for 6 weeks.Kidney function and kidney index(kidney weight/body weight) were determined,the level of ET-1 was determined by Radioimmunoassay,the expression of ET-1 in the kidney tissue by immunohistochemicai,and kidney tissue was observed by lightmicroscope and transmission electron microscope. RESULTS: The level and expression of ET-1,kidney index in DN rats significantly increased.The level and expression of ET-1 markedly decreased in Hirudo treatment group,and kidney pathologic changes of DN rats in Hirudo treatment group were improved. CONCLUSION: Hirudo can ameliorate early kidney hyperdynamic abnormality in DN rats,possess protective effect on kidney of DN rats,whose mechanism may be associated partly with a down-regulation of levels and expression of ET-1.
