ABSTRACT
ACE2 is a major receptor for cell entry of SARS-CoV-2. Despite advances in targeting ACE2 to inhibit SARS-CoV-2s binding, how to efficiently and flexibly control ACE2 levels for prevention of SARS-CoV-2 infection has not been explored. Here, we revealed Vitamin C (VitC) administration as an effective strategy to prevent SARS-CoV-2 infection. VitC reduced ACE2 protein levels in a dose-dependent manner, while partial reduction of ACE2 can greatly restrict SARS-CoV-2 infection. Further studies uncovered that USP50 is a crucial regulator of ACE2 protein levels, and VitC blocks the USP50-ACE2 interaction, thus promoting K48-linked polyubiquitination at Lys788 and degradation of ACE2, without disrupting ACE2 transcriptional expression. Importantly, VitC administration reduced host ACE2 and largely blocked SARS-CoV-2 infection in mice. This study identified an in vivo ACE2 balance controlled by both USP50 and an essential nutrient VitC, and revealed a critical role and application of VitC in daily protection from SARS-CoV-2 infection. HighlightsO_LIVitC reduces ACE2 protein levels in a dose-dependent manner C_LIO_LIVitC and USP50 regulate K48-linked ubiquitination at Lys788 of ACE2 C_LIO_LIVitC blocks the interaction between USP50 and ACE2 C_LIO_LIVitC administration lowers host ACE2 and prevents SARS-CoV-2 infection in vivo C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/499651v1_ufig1.gif" ALT="Figure 1"> View larger version (60K): org.highwire.dtl.DTLVardef@196682borg.highwire.dtl.DTLVardef@190f14dorg.highwire.dtl.DTLVardef@d22b59org.highwire.dtl.DTLVardef@1c0faa_HPS_FORMAT_FIGEXP M_FIG C_FIG The deubiquitinase USP50 controls ACE2 protein stability and levels, while Vitamin C blocks the USP50-ACE2 interaction and therefore results in ACE2 degradation, offering a flexible and efficient approach to protection of the host from SARS-CoV-2 infection.
ABSTRACT
Objective:To assess the clinical effectiveness and safety of Runing granule for hyperplasia of mammary gland.Methods:The databases such as the CNKI, Wanfang Data, VIP, CBM, Cochrane Library, Embase, PubMed and Web of Science are searched from the date of their establishment to June 2020. The main outcome measures were effective rate and incidence of adverse events. All randomized control trial (RCT) about the clinical effectiveness and safety of Runing granule single (single group) or combined with other treatment (combined group)/ other treatment (control group) for hyperplasia of mammary gland were included. Endnote software was used to manage literature, Excel software was used to extract data, quality assessment was conducted according to the methods of Cochrane Reviewers′ Handbook 5.1 recommend by the Cochrane Collaboration and Revman 5.3 software was used to perform Meta-analysis.Results:Twelve RCT were included with total 2 447 patients. In terms of efficiency, Meta-analysis showed single group was better than control group ( RR=1.17, 95% CI: 1.00-1.36, P=0.04), combined group was better than control group ( RR=1.35, 95% CI: 1.10-1.67, P=0.005). In terms of adverse event rate, single group was lower than control group ( RR=0.18, 95% CI: 0.09-0.34, P<0.01), combined group was better than control group( RR=0.33, 95% CI: 0.20-0.56, P<0.01). Conclusion:The usage of Runing granule single or combined with other treatment in the treatment of hyperplasia of mammary gland is more effective and the adverse reaction is lower.
