BAFF promotes regulatory T-cell apoptosis and blocks cytokine production by activating B cells in primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology. A number of questions regarding its etiology are unclear. CD4+CD25+ regulatory T cells (Tregs) play a critical role in self-tolerance and, for unknown reasons, their relative number is reduced in PBC patients. B-cell-activating factor (BAFF) is a key survival factor during B-cell maturation and its concentration is increased in peripheral blood of PBC patients. It has been reported that activated B cells inhibit Treg cell proliferation and there are no BAFF receptors on Tregs. Therefore, we speculated that excessive BAFF may result in Treg reduction via B cells. To prove our hypothesis, we isolated Tregs and B cells from PBC and healthy donors. BAFF and IgM concentrations were then analyzed by ELISA and CD40, CD80, CD86, IL-10, and TGF-β expression in B cells and Tregs were measured by flow cytometry. BAFF up-regulated CD40, CD80, CD86, and IgM expression in B cells. However, BAFF had no direct effect on Treg cell apoptosis and cytokine secretion. Nonetheless, we observed that BAFF-activated B cells could induce Treg cell apoptosis and reduce IL-10 and TGF-β expression. We also showed that BAFF-activated CD4+ T cells had no effect on Treg apoptosis. Furthermore, we verified that bezafibrate, a hypolipidemic drug, can inhibit BAFF-induced Treg cell apoptosis. In conclusion, BAFF promotes Treg cell apoptosis and inhibits cytokine production by activating B cells in PBC patients. The results of this study suggest that inhibition of BAFF activation is a strategy for PBC treatment

Association between drinking water quality and mental health and the modifying role of diet: a prospective cohort study

Abstract Background Environmental factors play an important role in developing mental disorders. This study aimed to investigate the associations of metal and nonmetal elements in drinking water with the risk of depression and anxiety and to assess whether diets modulate these associations. Methods We conducted a prospective cohort study including 24,285 participants free from depression and anxiety from the Yinzhou Cohort study in the 2016–2021 period. The exposures were measured by multiplying metal and nonmetal element concentrations in local pipeline terminal tap water samples and total daily drinking water intakes. Cox regression models adjusted for multi-level covariates were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (95%CIs). Results During an average follow-up period of 4.72 and 4.68 years, 773 and 1334 cases of depression and anxiety were identified, respectively. A 1 standard deviation (SD) increase in manganese exposure reduced the incidence of depression by 8% (HR 0.92, 95%CI 0.88 to 0.97). In contrast, with a 1 SD increase in copper and cadmium exposure, the incidence of depression increased by 6% (HR 1.06, 95%CI 1.01 to 1.11) and 8% (HR 1.08, 95%CI 1.00 to 1.17), respectively. The incidence of anxiety increased by 39% (HR 1.39, 95%CI 1.20 to 1.62), 33% (HR 1.33, 95%CI 1.03 to 1.71), and 14% (HR 1.14, 95%CI 1.03 to 1.25) respectively for a 1 SD increase in manganese, iron, and selenium exposure. Diets have a moderating effect on the associations of metal and nonmetal elements with the risk of anxiety. Stronger associations were observed in older, low-income groups and low-education groups. Conclusions We found significant associations between exposure to metal and nonmetal elements and depression and anxiety. Diets regulated the associations to some extent

The association between exposure to PM2.5 components from coal combustion and mortality in female breast cancer patients

PM _2.5 components may promote the development of breast cancer and increase the risk of mortality. This study aims to investigate the associations between long-term exposure to PM _2.5 components and multiple causes of mortality among women with breast cancer living in Inner Mongolia, China. We constructed an Inner Mongolia cohort of 33 952 breast cancer patients from 2012 to 2021 using data from the Inner Mongolia Regional Health Information Platform. We assessed each patient’s exposure to PM _2.5 components using the Tracking Air Pollution in China database. Cox regression models were used to estimate adjusted hazard ratios and 95% confidence intervals (95% CIs). A total of 3295 deaths were identified. For each interquartile increase in concentration in the 5 years before diagnosis, the all-cause mortality increased significantly by 5% (HR: 1.05, 95%CI: 1.00–1.10) for black carbon and by 4% (HR: 1.04, 95%CI: 1.00–1.09) for sulfate (SO _4 ^2− ), and decreased by 7% (HR: 0.93, 95%CI: 0.88–0.98) for nitrate (NO _3 ^− ). An association between organic matter and an increased all-cause mortality was also observed. Similar results were found for associations with risk of death from breast cancer-specific causes, cardio-cerebrovascular disease (CCVD) causes, and respiratory causes. Stronger associations were observed in older age groups and in Han Chinese patients. Our results showed that long-term exposure to black carbon, organic matter, and SO _4 ^2− were more responsible for the increased risk of death from all causes, breast cancer-specific causes, CCVD causes, and respiratory causes. This suggests that more effective measures to control coal combustion emissions in Inner Mongolia are urgently needed. The elderly and Han Chinese populations may be at high risk

Additional file 1 of Association between drinking water quality and mental health and the modifying role of diet: a prospective cohort study

Additional file 1: Table S1. Baseline characteristics of study participants stratified by the levels of Manganese in tap water. Table S2. Baseline characteristics of study participants stratified by the levels of Zinc in tap water. Table S3. Baseline characteristics of study participants stratified by the levels of Copper in tap water. Table S4. Baseline characteristics of study participants stratified by the levels of Iron in tap water. Table S5. Baseline characteristics of study participants stratified by the levels of Aluminum in tap water. Table S6. Baseline characteristics of study participants stratified by the levels of Cadmium in tap water. Table S7. Baseline characteristics of study participants stratified by the levels of Selenium in tap water. Table S8. Baseline characteristics of study participants stratified by the levels of Fluorine in tap water. Table S9. Subgroup analysis for the prospective association between metal, nonmetal elements exposure and onset of depression. Table S10. Subgroup analysis for the prospective association between metal, nonmetal elements exposure and onset of anxiety. Table S11. Sensitive analysis of association between long term exposure to metal and nonmetal elements and risk of depression and anxiety onset. Table S12. E-value for point estimates and the lower 95% confidence intervals of the Hazard. Fig. S1. Directed acyclic graph for water exposure and depression, anxiety