(20S) Ginsenoside Rh2 Inhibits STAT3/VEGF Signaling by Targeting Annexin A2.

Signal transducers and activators of transcription 3 (STAT3) acts as a transcriptional signal transducer, converting cytokine stimulation into specific gene expression. In tumor cells, aberrant activation of the tyrosine kinase pathway leads to excessive and continuous activation of STAT3, which provides further signals for tumor cell growth and surrounding angiogenesis. In this process, the tumor-associated protein Annexin A2 interacts with STAT3 and promotes Tyr705 phosphorylation and STAT3 transcriptional activation. In this study, we found that (20S) ginsenoside Rh2 (G-Rh2), a natural compound inhibitor of Annexin A2, inhibited STAT3 activity in HepG2 cells. (20S) G-Rh2 interfered with the interaction between Annexin A2 and STAT3, and inhibited Tyr705 phosphorylation and subsequent transcriptional activity. The inhibitory activity of STAT3 leaded to the negative regulation of the four VEGFs, which significantly reduced the enhanced growth and migration ability of HUVECs in co-culture system. In addition, (20S)G-Rh2 failed to inhibit STAT3 activity in cells overexpressing (20S)G-Rh2 binding-deficient Annexin A2-K301A mutant, further proving Annexin A2-mediated inhibition of STAT3 by (20S)G-Rh2. These results indicate that (20S)G-Rh2 is a potent inhibitor of STAT3, predicting the potential activity of (20S)G-Rh2 in targeted therapy applications.

Early diagnosis and population prevention of coronavirus disease 2019.

PURPOSE OF REVIEW: To discuss the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by nucleic acid and antibody testing as well as its contribution to mitigating the spread of coronavirus disease 2019. RECENT FINDINGS: Nucleic acid testing (NAT) is the firstly developed and most widely used diagnostic technique for SARS-CoV-2 infection. However, the sensitivity of SARS-CoV-2 RNA NAT assays is always unsatisfactory, mainly due to insufficient viral RNA in samples, especially when upper respiratory samples were used. Compared with NAT assays, serological tests are more convenient and less dependent on the quality of sample collection. But the sensitivity of antibody assays varies largely to test samples collected at different time after onset of symptoms. The diagnostic sensitivity can be significantly improved by combination of RNA and antibody testing. Due to the lack of effective drugs and vaccines, population prevention results mainly from timely triage and quarantine of SARS-CoV-2 infected individuals. Thus, extensive testing with NAT and antibody assays simultaneously is very important to constrain coronavirus disease 2019 epidemic. SUMMARY: Viral RNA testing combining with serological testing could improve the early diagnosis of SARS-CoV-2 infection, which has great value for clinical practice and public health.

Serology characteristics of SARS-CoV-2 infection after exposure and post-symptom onset.

BACKGROUND: Timely diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a prerequisite for treatment and prevention. The serology characteristics and complement diagnosis value of the antibody test to RNA test need to be demonstrated. METHOD: Serial sera of 80 patients with PCR-confirmed coronavirus disease 2019 (COVID-19) were collected at the First Affiliated Hospital of Zhejiang University, Hangzhou, China. Total antibody (Ab), IgM and IgG antibodies against SARS-CoV-2 were detected, and the antibody dynamics during the infection were described. RESULTS: The seroconversion rates for Ab, IgM and IgG were 98.8%, 93.8% and 93.8%, respectively. The first detectible serology marker was Ab, followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 days post exposure (d.p.e.) or 9, 10 and 12 days post onset (d.p.o.), respectively. The antibody levels increased rapidly beginning at 6 d.p.o. and were accompanied by a decline in viral load. For patients in the early stage of illness (0-7 d.p.o), Ab showed the highest sensitivity (64.1%) compared with IgM and IgG (33.3% for both; p<0.001). The sensitivities of Ab, IgM and IgG increased to 100%, 96.7% and 93.3%, respectively, 2 weeks later. When the same antibody type was detected, no significant difference was observed between enzyme-linked immunosorbent assays and other forms of immunoassays. CONCLUSIONS: A typical acute antibody response is induced during SARS-CoV-2 infection. Serology testing provides an important complement to RNA testing in the later stages of illness for pathogenic-specific diagnosis and helpful information to evaluate the adapted immunity status of patients.