Search

Rheumatoid arthritis (RA) is an autoimmune disease that significantly impacts quality of life by disrupting CD4+ T cell immune homeostasis. The identification of a low-side-effect drug for RA treatment is urgently needed. Our previous study suggests that Trichinella spiralis paramyosin (Ts-Pmy) has immunomodulatory effects, but its potential effect on CD4+ T cell response in RA remains unclear. In this study, we used a murine model to investigate the role of rTs-Pmy in regulating CD4+ T cell differentiation in collagen-induced arthritis (CIA). Additionally, we assessed the impact of rTs-Pmy on CD4+ T cell differentiation towards the Th1 and Th17 phenotypes, which are associated with inflammatory responses in arthritis, using in vitro assays. The results demonstrated that rTs-Pmy administration reduced arthritis severity by inhibiting Th1 and Th17 response while enhancing Treg response. Prophylactic administration of Ts-Pmy showed superior efficacy on CIA compared to therapeutic administration. Furthermore, in vitro assays demonstrated that rTs-Pmy could inhibit the differentiation of CD4+ T cells into Th1 and Th17 while inducing the production of Tregs, suggesting a potential mechanism underlying its therapeutic effects. This study suggests that Ts-Pmy may ameliorate CIA by restoring the immune balance of CD4+ T cells and provides new insights into the mechanism through which helminth-derived proteins exert their effects on autoimmune diseases. [ABSTRACT FROM AUTHOR]

Objectives: To explore the relationship between estradiol (E2) and the incidence of hyperuricemia (HUA) in adult women and to explore whether glucolipid metabolism disorders play a mediating role in mediating this relationship., Methods: A total of 2,941 participants aged 20-65 years were included in the National Health and Nutrition Examination Survey (NHANES) 2013-2016. Multivariate logistic regression analysis was performed to evaluate the correlations of E2 with HUA. Multivariate linear regression analysis was performed to evaluate the associations between E2 and triglyceride (TG), total cholesterol (TC), and the triglyceride-glucose index (TyG). The restricted cubic spline (RCS) model was used to further explore the association between E2 and HUA and between TG, TC, and TyG and HUA. Mediation analyses were performed to examine whether TC, TG, and TyG mediated the relationship between E2 and HUA., Results: After adjusting for covariates, logistic regression revealed that ln(E2) was significantly associated with HUA in the female subgroup ( p = 0.035) and that the incidence of HUA tended to increase with decreasing ln(E2) ( p for trend = 0.026). Linear regression showed that E2 was significantly associated with TC ( p = 0.032), TG ( p = 0.019), and TyG ( p = 0.048). The RCS model showed that ln(E2) was linearly correlated with the incidence of HUA ( p -overall = 0.0106, p -non-linear = 0.3030). TC and TyG were linearly correlated with HUA (TC: p -overall = 0.0039, p -non-linear = 0.4774; TyG: p -overall = 0.0082, p -non-linear = 0.0663), whereas TG was non-linearly correlated with HUA. Mediation analyses revealed that TC, TG, and TyG significantly mediated the relationship between ln(E2) and HUA (TC, indirect effect: -0.00148, 7.5%, p = 0.008; TG, indirect effect: -0.00062, 3.1%, p = 0.004; TyG, indirect effect: -0.00113, 5.6%, p = 0.016)., Conclusion: In conclusion, this study demonstrated that compared with women aged 20-45 years, women aged 45-55 years and 55-65 years had lower E2 levels and a greater incidence of HUA. E2 levels and the incidence of HUA were negatively associated in female individuals but not in male individuals. In addition, TC, TG, and TyG, which are markers of glucolipid metabolism, played a mediating role in the association between E2 and HUA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Qian, Cui, Li, Cheng and Gao.)