Proteomic analysis and identification reveal the anti-inflammatory mechanism of clofazimine on lipopolysaccharide-induced acute lung injury in mice.

BACKGROUND AND OBJECTIVE: Acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS) was increasingly recognized as one of the most severe acute hyperimmune response of coronavirus disease 2019 (COVID-19). Clofazimine (CFZ) has attracted attention due to its anti-inflammatory property in immune diseases as well as infectious diseases. However, the role and potential molecular mechanism of CFZ in anti-inflammatory responses remain unclear. METHODS: We analyze the protein expression profiles of CFZ and LPS from Raw264.7 macrophages using quantitative proteomics. Next, the protective effect of CFZ on LPS-induced inflammatory model is assessed, and its underlying mechanism is validated by molecular biology analysis. RESULTS: LC-MS/MS-based shotgun proteomics analysis identified 4746 (LPS) and 4766 (CFZ) proteins with quantitative information. The key proteins and their critical signal transduction pathways including TLR4/NF-κB/HIF-1α signaling was highlighted, which was involved in multiple inflammatory processes. A further analysis of molecular biology revealed that CFZ could significantly inhibit the proliferation of Raw264.7 macrophages, decrease the levels of TNF-α and IL-1ß, alleviate lung histological changes and pulmonary edema, improve the survival rate, and down-regulate TLR4/NF-κB/HIF-1α signaling in LPS model. CONCLUSION: This study can provide significant insight into the proteomics-guided pharmacological mechanism study of CFZ and suggest potential therapeutic strategies for infectious disease.

Factors Influencing Post-traumatic Stress Symptoms in Chinese Adolescents During the COVID-19 Pandemic.

To investigate the prevalence of post-traumatic stress symptoms (PTSSs) and analyze the influencing factors of PTSS among adolescents in a large sample study during the COVID-19 pandemic, we did a cross-sectional study by collecting demographic data and mental health measurements from a large group of 175,318 adolescents in 32 Chinese provinces and autonomous regions, using the Impact of Event Scale-Revised (IES-R) that was used to measure the PTSS of the participants. The results showed that the prevalence of PTSS was 35.7% in Chinese adolescents during the COVID-19 pandemic. Binary logistic regression analysis showed that, for the personal risk factors, the older age, female gender, the personality domains of extroversion, the irregular sleep schedule, the lack of aerobic exercise, and the lack of peer support were associated with the higher levels of PTSS. The family subjective and objective factors were associated with higher levels of PTSS. Our findings suggested that family factors are the most important factors that affect Chinese adolescents' PTSS due to the longtime home quarantine.

Psychological Impact of COVID-19 Epidemic on Adolescents: A Large Sample Study in China.

Background: The COVID-19 pandemic is a major public health emergency. However, little is known about the psychological impact of this pandemic on adolescents. We aim to assess the prevalence and influencing factors of depression, anxiety, and posttraumatic growth (PTG) among adolescents in a large sample study. Methods: This cross-sectional study collected demographic data and mental health measurements from 175,416 adolescents covering 31 provinces, centrally administered municipalities, and autonomous regions in mainland China from February 23 to March 8, 2020. The status of depression, anxiety, and PTG was assessed by the nine-item Patient Health Questionnaire, seven-item generalized anxiety disorder questionnaire, and post-traumatic growth inventory. Results: The prevalence of depression, anxiety, and PTG in adolescents was 35.9, 28.0, and 45.6%, respectively. The prevalence of depression and anxiety in the slight or severe epidemic areas was similar. Regression analysis showed that female sex and older age were associated with higher levels of depression, anxiety, and lower levels of PTG. Symptoms related to COVID-19, excessive attention to epidemic information, living in urban or severe epidemic areas, and conflicts with parents during home quarantine were risk factors for depression, anxiety, and PTG. Frequent communication with peers, exercise, and receiving public welfare psychological assistance were protective factors. Poor family economic status was a significant risk factor for depression and PTG. Conclusion: Our findings suggested that positive and negative psychological reactions coexist in adolescents faced with the pandemic. The factors associated with psychological problems and PTG provide strategic guidance for maintaining adolescents' mental health in China and worldwide during any pandemic such as COVID-19.