Maintaining a balanced bile acids (BAs) metabolism is essential for lipid and cholesterol metabolism, as well as fat intake and absorption. The development of obesity may be intricately linked to BAs and their conjugated compounds. Our study aims to assess how BAs influence the obesity indicators by Mendelian randomization (MR) analysis. Instrumental variables of 5 BAs were obtained from public genome-wide association study databases, and 8 genome-wide association studies related to obesity indicators were used as outcomes. Causal inference analysis utilized inverse-variance weighted (IVW), weighted median, and MR-Egger methods. Sensitivity analysis involved MR-PRESSO and leave-one-out techniques to detect pleiotropy and outliers. Horizontal pleiotropy and heterogeneity were assessed using the MR-Egger intercept and Cochran Q statistic, respectively. The IVW analysis revealed an odds ratio of 0.94 (95% confidence interval: 0.88, 1.00; P = .05) for the association between glycolithocholate (GLCA) and obesity, indicating a marginal negative causal association. Consistent direction of the estimates obtained from the weighted median and MR-Egger methods was observed in the analysis of the association between GLCA and obesity. Furthermore, the IVW analysis demonstrated a suggestive association between GLCA and trunk fat percentage, with a beta value of −0.014 (95% confidence interval: −0.027, −0.0004; P = .04). Our findings suggest a potential negative causal relationship between GLCA and both obesity and trunk fat percentage, although no association survived corrections for multiple comparisons. These results indicate a trend towards a possible association between BAs and obesity, emphasizing the need for future studies.

Although studies have indicated causality between brisk walking and various diseases, the relationships between walking pace and respiratory diseases lack thorough investigation. The underlying relationships between walking pace and various respiratory diseases were examined through univariable Mendelian randomization (MR) analyses. Furthermore, we performed multivariable MR analyses to observe whether relationships between walking pace and respiratory diseases change after adjustment of body mass index (BMI). The genome-wide association study data of self-reported walking pace, BMI, and 42 respiratory diseases were retrieved from publicly available datasets. We employed the inverse-variance weighted, weighted median, and MR-Egger methods for MR analysis. Using the inverse-variance weighted method in univariable MR, we identified statistically significant negative causal associations between self-reported walking pace and 4 respiratory traits, including chronic lower respiratory diseases (odds ratio [OR], 0.27 [95% confidence interval [CI], 0.18–0.41]), asthma (OR, 0.23 [95% CI, 0.14–0.38]), chronic obstructive pulmonary disease (OR, 0.15 [95% CI, 0.08–0.30]), and diseases of the respiratory system (OR, 0.54 [95% CI, 0.41–0.70]). Similar results were observed with the MR-Egger and weighted median methods. These associations remained significant, though slightly attenuated, after adjusting for BMI. A brisk walking pace may significantly benefit respiratory health and aid in disease prevention and risk stratification.

Toxoplasma gondii ( T. gondii ) is an apicomplexan parasite that infects most warm-blooded animals, including approximately one-third of the human population worldwide. Dense granule proteins (GRAs), secreted from specialized organelles and trafficked to multiple compartments, including the parasitophorous vacuole (PV), parasitophorous vacuole membrane (PVM), host cytosol, and host cell nucleus following host cell invasion, have emerged as critical mediators of host–parasite interactions. This review provides a comprehensive analysis of our current knowledge of GRA proteins in toxoplasmosis pathogenesis and establishes a framework for developing novel interventions against this globally significant parasitic disease. Key GRA proteins form pore complexes that regulate PVM permeability, while GRA effectors manipulate host immunity to evade invasion. GRA proteins are essential for tissue cyst formation and bradyzoite differentiation, enabling lifelong chronic infection. The exceptional immunogenicity of GRA antigens has positioned them as promising candidates for diagnostic applications and vaccine development. Additionally, GRA proteins are attractive therapeutic targets through either the direct inhibition of effector-host protein interactions or by the disruption of effector export.