Wogonin inhibits latent HIV-1 reactivation by downregulating histone crotonylation.

BACKGROUND: Wogonin, a flavone isolated from Scutellaria baicalensis Georgi, is a commonly used phytochemical with anti-inflammatory and antitumor properties. However, the antiviral activity of wogonin against human immunodeficiency virus type 1 (HIV-1) has not been reported. PURPOSE: The current study aimed to explore whether wogonin can suppress latent HIV-1 reactivation and the mechanism of wogonin in inhibiting proviral HIV-1 transcription. METHODS: We assessed the effects of wogonin on HIV-1 reactivation using flow cytometry, cytotoxicity assay, quantitative PCR (qPCR), viral quality assurance (VQA), and western blot analysis. RESULTS: Wogonin, a flavone isolated from S. baicalensis, significantly inhibited the reactivation of latent HIV-1 in cellular models and in primary CD4+ T cells from antiretroviral therapy (ART)-suppressed individuals ex vivo. Wogonin exhibited low cytotoxicity and long-lasting inhibition of HIV-1 transcription. Triptolide is a latency-promoting agent (LPA) that inhibits HIV-1 transcription and replication; wogonin had a stronger ability to inhibit HIV-1 latent reactivation than triptolide. Mechanistically, wogonin inhibited the reactivation of latent HIV-1 by inhibiting the expression of p300, a histone acetyltransferase, and decreasing the crotonylation of histone H3/H4 in the HIV-1 promoter region. CONCLUSION: Our study found that wogonin is a novel LPA that can inhibit HIV-1 transcription by HIV-1 epigenetic silencing, which could bear promising significance for future applications of HIV-1 functional cure.

Hospitalization, interpersonal and personal factors of social anxiety among COVID-19 survivors at the six-month follow-up after hospital treatment: the minority stress model.

Background: As a highly infectious disease with human-to-human transmission characteristics, COVID-19 has caused panic in the general public. Those who have recovered from COVID-19 may experience discrimination and internalized stigma. They may be more likely to worry about social interaction and develop social anxiety. Objectives: This study investigated the associations among hospitalization factors, social/interpersonal factors, personal factors, and social anxiety to reveal the mechanism of social anxiety in COVID-19 survivors. Methods: A cross-sectional, multicenter telephone survey was conducted from July to September 2020 in five Chinese cities (i.e. Wuhan, Nanning, Shenzhen, Zhuhai, and Dongguan); adult COVID-19 survivors were recruited 6 months after they were discharged from the hospital. Linear regressions and path analysis based on the minority stress model were conducted to test the relationships among hospitalization, social/interpersonal factors, personal factors, and social anxiety. Results: The response rate was 74.5% (N = 199, 55.3% females). Linear regression analyses showed that various hospitalization, social/interpersonal, and personal factors were statistically significantly associated with social anxiety. Path analysis showed that the proposed model fit the data well (χ2(df) = 3.196(3), p = .362, CFI = .999, NNFI = .996, RMSEA = .018). Internalized stigma fully mediated the association between perceived discrimination/social support and social anxiety, while it partially mediated the association between perceived affiliate stigma and social anxiety. Conclusions: The results suggest that social/interpersonal and personal factors have a stronger association with social anxiety than hospitalization factors and highlight the importance of internalized stigma in understanding the mechanisms of these relationships. Clinical psychologists can refer to these modifiable psychosocial factors to develop efficient interventions for mental health promotion.

Antecedentes: Como una enfermedad altamente infecciosa con características de transmisión de persona a persona, el COVID-19 ha causado pánico en el público en general. Aquellos que se han recuperado del COVID-19 pueden experimentar discriminación y estigma internalizado. Es más probable que se preocupen por la interacción social y desarrollen ansiedad social.Objetivos: Este estudio investigó las asociaciones entre factores de hospitalización, factores sociales /interpersonales, factores personales y ansiedad social para revelar el mecanismo de ansiedad social en sobrevivientes de COVID-19.Métodos: Se realizó una encuesta telefónica transversal multicentro de julio a septiembre de 2020 en cinco ciudades chinas (es decir, Wuhan, Nanning, Shenzhen, Zhuhai y Dongguan). Se reclutaron sobrevivientes adultos de COVID-19 seis meses después de ser dados de alta del hospital. Se realizaron regresiones lineales y análisis de ruta basados en el modelo de estrés de minoría para probar las relaciones entre la hospitalización, los factores sociales/interpersonales, los factores personales y la ansiedad social.Resultados: La tasa de respuesta fue del 74,5% (N = 199, 55,3% mujeres). Los análisis de regresión lineal mostraron que varios factores de hospitalización, sociales/interpersonales y personales se asociaron de manera estadísticamente significativa con la ansiedad social. El análisis de ruta mostró que el modelo propuesto se ajustaba bien a los datos (χ2 (df) = 3.196 (3), p = .362, CFI = .999, NNFI = .996, RMSEA = .018). El estigma internalizado medió completamente la asociación entre discriminación/apoyo social percibido y ansiedad social, mientras que medió parcialmente la asociación entre el estigma percibido de afiliados y ansiedad social.Conclusiones: Los resultados sugieren que los factores sociales/interpersonales y personales tienen una asociación más fuerte con la ansiedad social que los factores de hospitalización y resaltan la importancia del estigma internalizado en la comprensión de los mecanismos de estas relaciones. Los psicólogos clínicos pueden referirse a estos factores psicosociales modificables para desarrollar intervenciones eficientes para la promoción de la salud mental.