Jinlong Li

Background: Lifestyles are associated with age‐related diseases through chronic inflammation, yet the mediating pathways remain unclear. Immunoglobulin G (IgG) regulates inflammation by altering N‐glycans. However, it lacks evidence on the mediating effect of IgG N‐glycosylation linking lifestyles with age‐related diseases. Methods: A two‐step Mendelian randomization (MR) design was conducted in East Asian and European populations to evaluate the mediating role of IgG N‐glycosylation linking lifestyles with age‐related diseases. In European populations, 32 lifestyles were selected as exposures, 23 glycan direct traits as candidate mediators, and 25 age‐related diseases were considered in the MR analyses. For East Asian populations, 13 lifestyles, 24 candidate mediators, and 14 outcomes were analyzed. We used inverse‐variance weighting as the primary method, supplemented by sensitivity analyses. Results: Mediation MR analyses were conducted on three pathways in which IgG N‐glycans were considered potential mediators among European ancestry. We observed the suggested mediating role of glycan peak (GP) 10 linking ground coffee consumption with rheumatoid arthritis (RA) ( β = −1.614, p = 0.023), but not for GP15 ( β = 1.385, p = 0.069). No mediating effect of GP22 was observed between dried fruit consumption and cognitive function ( β = 0.063, p = 0.092). Additionally, fortified wine consumption showed no mediating effect on Alzheimer’s disease via N‐glycans, including those of GP7, GP19, GP23, and GP24 (all ps > 0.05). No mediating pathways were detected in East Asian populations. Conclusion: The mediation MR analysis provides suggestive evidence that GP10 may play a role in the association between ground coffee consumption and RA. Further prospective cohort studies and mechanistic experiments are warranted to explore the potential underlying pathways.

Silicosis is an occupational lung disease characterized by silicotic nodules and progressive pulmonary fibrosis, caused by long-term excessive inhalation of free silica. So far, no effective methods have been developed to delay or cure silicotic fibrosis. Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-Exos), which possess functions of intercellular communication, tissue repair and regeneration, offering a potential strategy for the treatment of silicosis. In this study, exosomes were extracted from human umbilical cord mesenchymal stem cells (huc-MSCs) using differential centrifugation and characterized for subsequent experiments. A silica-induced silicosis mouse model was established. Lung CT scans were performed to assess pulmonary lesions, while blood oxygenation status was monitored. Histopathological analysis of lung tissues was conducted, and Western blot was used to evaluate inflammatory and fibrotic markers, aiming to investigate the therapeutic effects of hucMSCs and their exosomes on silicotic mice. High-throughput transcriptome sequencing of lung tissues was employed to screen differentially expressed genes and signaling pathways in the two treatment groups, followed by in vitro validation of the proposed mechanisms. Our findings demonstrate that hucMSC-Exos alleviate pulmonary inflammation, slow lung fibrosis, inhibit macrophage pyroptosis, activate the actin cytoskeleton signaling pathway, and maintain plasma membrane integrity in silicotic mice. This study provides possible therapeutic targets and molecular mechanisms for silicosis, establishing a link among silicosis, cytoskeleton, and pyroptosis, while validating the protective effect of hucMSC-Exos on the lungs of silicotic mice.

Inorganic arsenic is a well-known environmental toxicant and carcinogen, and there is overwhelming evidence for an association between this metalloid poisoning and hepatic diseases. However, the biological mechanism involved is not well characterized. In the present study, we probed how inorganic arsenic modulates the hepatic polarization of macrophages, as well as roles of PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy participates in regulating the metalloid-mediated macrophage polarization. Our results indicate that acute arsenic exposure induced macrophage polarization with up-regulated gene expression of inducible nitric oxide synthase (Inos) and arginase-1 (Arg1), monocyte chemotactic protein-1 (Mcp-1) and macrophage inflammatory protein-2 (Mip-2), tumor necrosis factor (Tnf)-α, interleukin (Il)-1β and Il-6, as well as anti-inflammatory factors Il-4 and Il-10. In parallel, we demonstrated the disrupted hepatic redox balance typically characterized by the up-regulation of hydrogen peroxide (H₂O₂) and glutathione (GSH), and activation of PINK1/Parkin-mediated mitophagy in the livers of acute arsenic-exposed mice. In addition, our results demonstrate that it might be the PINK1/Parkin-mediated mitophagy that renders hepatic macrophage refractory to arsenic-induced up-regulation of the genes Inos, Mcp-1, Mip-2, Tnf-α, Il-1β, Il-6 and Il-4. In this regard, this is the first time the protective effects of PINK1/Parkin-mediated mitophagy in inorganic arsenic-induced hepatic macrophage polarization in vivo have been reported. These findings add novel insights into the arsenical immunotoxicity and provide a basis for the preve.ntive and therapeutic potential of PINK1/Parkin-mediated mitophagy in arsenic poisoning.

Background: Previous studies, predominantly in Western individuals, have reported weight gain or weight loss are related to the increased depressive symptoms at all ages, but no study of depressive symptoms has examined its relation to actual (not just self-reported) weight changes in the middle-aged and older adults. Evidence of the relationship in older Asian individuals remains sparse. The study aimed to examine the relationship between weight changes and incidence of depressive symptoms in a nationally representative sample of community-dwelling older Asians. Method: Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which included 17,284 adults aged 45 years. Participants were followed every two years using a face-to-face, computer-aided personal interview (CAPI) and structured questionnaire. We excluded participants with no follow-up data. The numbers of individuals who completed both the baseline and follow-up surveys were 3118 for the short-term (two years from 2011–2013) and the long-term (four years from 2011–2015). Additionally, to associate weight change with subsequent depressive symptoms, we also included 2472 participants without depressive symptom in 2013 and observed the incidence of depressive symptom in 2015 (subsequent term from 2013–2015). Finally, weight changes were classified as loss > -3%, stable-3–3%, gain3-6%, gain6-9%, and gain > 9%. Multivariable-adjusted cox regression in the study were used to assess the hazard ratios (HRs) of each weight change category. Results: The incidence of depressive symptoms was 20.72% in the 2011–2013, 27.04% in the 2011–2015, and 23.02% in 2013–2015. Weight loss > 3% for all intervals was associated with higher depressive symptoms than stable weight during the 2011–2013 [1.305(1.031,1.651)] among the total populations. When stratified by sex, the results in males and females were different from those in the total population [females:1.389(0.997, 1.935); males:1.263(0.902, 1.767)]. Weight loss > 3% for intervals was associated with higher depressive symptoms than stable weight during the 2013–2015[1.643(1.140, 2.368)] among the males and its effect was also stronger for the total in 2011–2013. Moreover, there was no significant association between weight gain and incident depressive symptom, and no significant interaction effect in terms of the sex*weight changes. Conclusion: Our findings could inform health promotion interventions to body-weight management aimed at improving the health of the middle-aged and older adults, particularly in the total people with short-term weight loss and males with subsequent term weight loss.