Investigating the causal associations between five anthropometric indicators and nonalcoholic fatty liver disease: Mendelian randomization study.

BACKGROUND: Although the etiology of nonalcoholic fatty liver disease (NAFLD) has not been thoroughly understood, the emerging roles of anthropometric indicators in assessing and predicting the risk of NAFLD have been highlighted by accumulating evidence. AIM: To evaluate the causal relationships between five anthropometric indicators and NAFLD employing Mendelian randomization (MR) design. METHODS: The Anthropometric Consortium provided genetic exposure data for five anthropometric indicators, including hip circumference (HC), waist circumference (WC), waist-to-hip ratio (WHR), body mass index (BMI), and body fat percentage (BF). Genetic outcome data for NAFLD were obtained from the United Kingdom Biobank and FinnGen Consortium. Genome-wide significant single nucleotide polymorphisms were chosen as instrumental variables. Univariable MR (UVMR) and multivariable MR (MVMR) designs with analytical approaches, including inverse variance weighted (IVW), MR-Egger, weighted median (WM), and weighted mode methods, were used to assess the causal relationships between anthropometric indicators and NAFLD. RESULTS: Causal relationships were revealed by UVMR, indicating that a higher risk of NAFLD was associated with a per-unit increase in WC [IVW: odds ratio (OR) = 2.67, 95%CI: 1.42-5.02, P = 2.25 × 10-3], and BF was causally associated with an increased risk of NAFLD (WM: OR = 2.23, 95%CI: 1.07-4.66, P = 0.033). The presence of causal effects of WC on the decreased risk of NAFLD was supported by MVMR after adjusting for BMI and smoking. However, no causal association between BF and NAFLD was observed. In addition, other causal relationships of HC, WHR (BMI adjusted), and BMI with the risk of NAFLD were not retained after FDR correction. CONCLUSION: This study establishes a causal relationship, indicating that an increase in WC is associated with a higher risk of NAFLD. This demonstrates that a suitable decrease in WC is advantageous for preventing NAFLD.

Mecanismo de células dendríticas derivadas de sangre periférica humana en la regulación de la autofagia en células de carcinoma / Mechanism of human peripheral blood-derived dendritic cells in the regulation of autophagy in carcinoma cells

Resumen Introducción: Las células dendríticas (CD) están involucradas en el reconocimiento, respuesta y modulación inmunológicos relacionados con la aparición del cáncer. Objetivo: Explorar el mecanismo de las CD en la inhibición de la autofagia de las células del hepatoma. Métodos: Células mononucleares de sangre periférica humana se aislaron mediante centrifugación en gradiente de densidad de Ficoll y se indujeron en CD, las cuales fueron cocultivadas con células HepG2 por ensayo de migración Transwell. La actividad de las células HepG2 se determinó mediante ensayo CCK8. La expresión del índice de autofagia LC3 se midió con análisis de transferencia Western y la expresión y secreción de citocinas mediante qRT-PCR y ELISA. Resultados: En el sistema de cocultivo, las CD redujeron la viabilidad de HepG2; la expresión de IL-2, IL-12, IL-10 e IFN-γ en CD también se inhibió significativamente, si bien IL-2 e IFN-γ aún se expresaron 0.6 y 0.53 más que en el grupo de control. Conclusión: Las CD pueden regular la autofagia de las células del carcinoma hepatocelular. El mecanismo puede estar relacionado con la síntesis y liberación de citocinas como IL-2, IL-12 e IFN-γ por parte de las CD.

Abstract Introduction: Dendritic cells (DC) are involved in immune recognition, response and immunomodulation mechanisms related to the onset of cancer. Objective: To explore DCs mechanism in the inhibition of autophagy in hepatoma cells. Methods: Human peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation and induced into DCs, which were co-cultured with HepG2 cells by Transwell migration assay. HepG2 cell activity was determined using the CCK8 assay. LC3 autophagy index expression was measured with Western blot analysis, and the expression and secretion of cytokines, with qRT-PCR and ELISA. Results: In the co-culture system, DCs were able to reduce HepG2 cells viability; IL-2, IL-12, IL-10 and IFN-γ expression in DCs was also significantly inhibited, although IL-2 and IFN-γ were still expressed 0.6 and 0.53 more than in the control group. Conclusion: DCs can regulate autophagy in hepatocellular carcinoma cells. The mechanism may be related to the synthesis and release of cytokines such as IL-2, IL-12 and IFN-γ by DCs.

Mechanism of human peripheral blood-derived dendritic cells in the regulation of autophagy in carcinoma cells.

INTRODUCTION: Dendritic cells (DC) are involved in immune recognition, response and immunomodulation mechanisms related to the onset of cancer. OBJECTIVE: To explore DCs mechanism in the inhibition of autophagy in hepatoma cells. METHODS: Human peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation and induced into DCs, which were co-cultured with HepG2 cells by Transwell migration assay. HepG2 cell activity was determined using the CCK8 assay. LC3 autophagy index expression was measured with Western blot analysis, and the expression and secretion of cytokines, with qRT-PCR and ELISA. RESULTS: In the co-culture system, DCs were able to reduce HepG2 cells viability; IL-2, IL-12, IL-10 and IFN-γ expression in DCs was also significantly inhibited, although IL-2 and IFN-γ were still expressed 0.6 and 0.53 more than in the control group. CONCLUSION: DCs can regulate autophagy in hepatocellular carcinoma cells. The mechanism may be related to the synthesis and release of cytokines such as IL-2, IL-12 and IFN-γ by DCs.

INTRODUCCIÓN: Las células dendríticas (CD) están involucradas en el reconocimiento, respuesta y modulación inmunológicos relacionados con la aparición del cáncer. OBJETIVO: Explorar el mecanismo de las CD en la inhibición de la autofagia de las células del hepatoma. MÉTODOS: Células mononucleares de sangre periférica humana se aislaron mediante centrifugación en gradiente de densidad de Ficoll y se indujeron en CD, las cuales fueron cocultivadas con células HepG2 por ensayo de migración Transwell. La actividad de las células HepG2 se determinó mediante ensayo CCK8. La expresión del índice de autofagia LC3 se midió con análisis de transferencia Western y la expresión y secreción de citocinas mediante qRT-PCR y ELISA. RESULTADOS: En el sistema de cocultivo, las CD redujeron la viabilidad de HepG2; la expresión de IL-2, IL-12, IL-10 e IFN-γ en CD también se inhibió significativamente, si bien IL-2 e IFN-γ aún se expresaron 0.6 y 0.53 más que en el grupo de control. CONCLUSIÓN: Las CD pueden regular la autofagia de las células del carcinoma hepatocelular. El mecanismo puede estar relacionado con la síntesis y liberación de citocinas como IL-2, IL-12 e IFN-γ por parte de las CD.