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1.
Int J Mol Sci ; 25(12)2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38928413

ABSTRACT

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.


Subject(s)
Arthritis, Experimental , CD4-Positive T-Lymphocytes , Cell Differentiation , Th17 Cells , Trichinella spiralis , Tropomyosin , Animals , Trichinella spiralis/immunology , Arthritis, Experimental/immunology , Arthritis, Experimental/pathology , Arthritis, Experimental/drug therapy , Mice , Cell Differentiation/drug effects , Tropomyosin/immunology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Th17 Cells/immunology , Th17 Cells/metabolism , Th1 Cells/immunology , Male , Helminth Proteins/pharmacology , Helminth Proteins/therapeutic use , Helminth Proteins/immunology , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/drug therapy , T-Lymphocytes, Regulatory/immunology , Disease Models, Animal , Mice, Inbred DBA
2.
Cureus ; 10(5): e2651, 2018 May 18.
Article in English | MEDLINE | ID: mdl-30034973

ABSTRACT

This study explores the effect of diuretics use on metabolic markers (i.e., the lipid profile) since thiazide diuretics are extensively used to treat cardiac patients with hypertension (HTN) and other comorbidities. The Embase and PubMed databases were searched for relevant English-language peer-reviewed articles. Different search terms and medical subject headings (MesH) terms were used to find the relevant articles. Our study included randomized controlled trials with hypertensive adult patients in the intervention group receiving thiazide diuretics; controls receiving any other diuretic or any other intervention for HTN where an intention to treat analysis was performed. We collected the demographic details, baseline lipid profile values, and end-of-study lipid profile values of all the participants in the studies along with the standard deviation of each value to calculate the net change effect. Five studies were included. We used the Q-test and I2 index for heterogeneity and the inverse variance method for weighting. We used the fixed effects model for total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) because TC and LDL-C had no heterogeneity (I2 was 0%). We used a random-effects model for triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C), which showed moderate heterogeneity (I2 was 57.2% and 59.5%, respectively). We used the Cochrane quality assessment to assess the quality level of the included studies. We used a funnel plot to avoid publication bias. Diuretics have a significant effect on lipid profiles. However, because this conclusion is supported by a low number of studies, further research is needed, and physicians are advised to use their best clinical judgment until the relationship between diuretics and lipid profiles seen in this study can be further supported by additional studies.

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