RESUMO
BACKGROUND: Interferon-alpha (IFNα) is a common treatment for chronic hepatitis B virus (HBV) infection, but its efficacy varies widely among patients. GTPASE, an interferon-stimulated gene (ISG), has recently been identified as a factor in antiviral immunity, though its role in HBV infection is not fully understood. OBJECTIVE: This study investigates the role of GTPASE in enhancing the antiviral effects of IFNα against HBV and elucidates its mechanism of action. METHODS: We analyzed the impact of GTPASE overexpression and silencing on HBV replication and clearance in HBV-infected cells. Molecular docking studies assessed the interaction between GTPASE and HBV surface antigens (HBs). Clinical samples from HBV patients undergoing Peg-IFNα treatment were also evaluated for GTPASE expression and its correlation with treatment efficacy. RESULTS: Overexpression of GTPASE led to significant inhibition of HBV replication, increased HBeAg seroconversion, and enhanced HBsAg clearance. GTPASE directly bound to HBs proteins, reducing their levels and affecting viral particle formation. Silencing GTPASE reduced these effects, while combined treatment with Peg-IFNα and GTPASE overexpression further improved antiviral outcomes. Mutational analysis revealed that specific sites in GTPASE are crucial for its antiviral activity. CONCLUSIONS: GTPASE acts as a positive regulator in IFNα-induced antiviral immunity against HBV. It enhances the therapeutic efficacy of IFNα by targeting HBs and modulating viral replication. GTPASE levels may serve as a predictive biomarker for response to Peg-IFNα therapy, highlighting its potential for improving individualized treatment strategies for chronic HBV infection.
Assuntos
Antivirais , GTP Fosfo-Hidrolases , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Hepatite B Crônica , Interferon-alfa , Replicação Viral , Humanos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Replicação Viral/efeitos dos fármacos , Antivirais/farmacologia , Antivirais/uso terapêutico , Interferon-alfa/farmacologia , Interferon-alfa/uso terapêutico , GTP Fosfo-Hidrolases/metabolismo , GTP Fosfo-Hidrolases/genética , Antígenos de Superfície da Hepatite B/metabolismo , Simulação de Acoplamento Molecular , Adulto , Masculino , Antígenos E da Hepatite B/metabolismo , Células Hep G2 , Feminino , Resultado do TratamentoRESUMO
As a result of the implementation of the "double carbon" strategy, the issue of how to encourage green behaviour has become a prominent one in society. According to the cognitive-affective processing system theory, this study constructs two paths through which green inclusive leadership influences employee green behaviours: the cognitive pathway mediated by pro-environmental goals clarity and the affective way mediated by green organization identification. Data analysis of 372 employees in chemical enterprises reveals that first, employees' perception of green inclusive leadership positively affects employee green behaviour; second, green inclusive leadership enhances employee awareness of environmental goals and green organization identification so that employees are more likely to behave environmentally; furthermore, green HRM practices positively moderate the relationship between green inclusive leadership and pro-environmental goals clarity, as well as positively moderate the relationship between green inclusive leadership and green organization identification. This study aims to provide theoretical and practical insight into how to promote the green development of organizations from the perspective of leadership style to facilitate green development.
Assuntos
Liderança , Local de Trabalho , Humanos , Local de Trabalho/psicologia , Conservação dos Recursos Naturais , CarbonoRESUMO
The contribution of gut-liver signaling to the development of non-alcoholic hepatic steatosis (NHS) in non-diabetic adults remains unclear. We therefore performed comprehensive 16S ribosomal RNA sequencing and fecal metabolomics analyses in 32 controls and 59 non-diabetic adults with NHS and performed fecal microbiota transplantation into germ-free mice using controls and NHS patients as donors. Compared to controls, the abundance of the genera Collinsella and Acinetobacter were higher, while that of Lachnospira was lower, in NHS subjects. Fecal metabolomics analysis showed decreased L-tryptophan levels and increased abundance of the tryptophan metabolite kynurenine in individuals with NHS. Correlation analysis showed that kynurenine levels positively associated with the abundance of Collinsella and Acinetobacter. ROC analysis demonstrated that the combination of tryptophan and kynurenine could discriminate NHS patients from controls with good statistical power [P < 0.05; AUC = 0.833 (95% CI, 0.747 to 0.918)]. Supporting a key role of dysbiotic gut microbiota in NHS development, incipient hepatic steatosis and increased kynurenine levels were observed in GF mice colonized with samples from NHS patients. These results indicate that enhanced kynurenine production resulting from altered gut microbiota composition contributes to NHS in nondiabetic adults and suggest the relevance of tryptophan metabolites as diagnostic biomarkers.