Iron oxide nanoparticles(IONPs)have wide applications in the biomedical field due to their outstanding physical and chemical properties.However,the potential adverse effects and relatedmechanisms of IONPs in human org...Iron oxide nanoparticles(IONPs)have wide applications in the biomedical field due to their outstanding physical and chemical properties.However,the potential adverse effects and relatedmechanisms of IONPs in human organs,especially the lung,are still largely ignored.In this study,we found that group-modified IONPs(carboxylated,aminated and silica coated)induce slight lung cell damage(in terms of the cell cycle,reactive oxygen species(ROS)production,cell membrane integrity and DNA damage)at a sublethal dosage.However,aminated IONPs could release more iron ions in the lysosome than the other two types of IONPs,but the abnormally elevated iron ion concentration did not induce ferroptosis.In-triguingly,amino-modified IONPs aggravated the accumulation of intracellular peroxides induced by the ferroptosis activator RSL3 and thus caused ferroptosis in vitro,and the coadministration of amino-modified IONPs and RSL3 induced more severe lung injury in vivo.Therefore,our data revealed that the surface functionalization of IONPs plays an important role in determining their potential pulmonary toxicity,as surface modification influences their degradation behavior.These results provide guidance for the design of future IONPs and the corresponding safety evaluations and predictions.展开更多
Metal may affect maternal immune function,but few epidemiological studies have reported the associations between multiple-metal exposure and maternal immunoglobulin(Ig)levels.Based on the Hangzhou Birth Cohort Study,1...Metal may affect maternal immune function,but few epidemiological studies have reported the associations between multiple-metal exposure and maternal immunoglobulin(Ig)levels.Based on the Hangzhou Birth Cohort Study,1059 participants were included,and eleven metals in whole blood samples and serum IgA,IgG,IgE and IgM levels were measured.Linear regression,quantile-based g-computation(QGC),and Bayesian kernel machine regression(BKMR)models were used to evaluate the associations.Compared with the first tertile of metal levels,arsenic(As)was negatively associated with IgE(β=-0.25,95%confidence interval(CI)=-0.48 to-0.02).Moreover,significant associations of manganese(Mn)with IgA,IgG and IgM were demonstrated(β=0.10,95%CI=0.04 to 0.18;β=0.07,95%CI=0.03 to 0.12;β=0.10,95%CI=0.03 to 0.18,respectively).Cadmium(Cd)were associated with higher levels of IgM.QGC models showed the positive association of the metalmixtures with IgA and IgG,with Mn playing amajor role.Mn and Cd had positive contributions to IgM,while As had negative contributions to IgE.In the BKMR models,the latent continuous outcomes of IgA and IgG showed a significant increase when all the metals were at their 60th percentile or above compared to those at their 50th percentile.Therefore,exposure to metals was associated with maternal Igs,and mainly showed that Mn was associated with increased levels of IgA,IgG and IgM,and As was associated with low IgE levels.展开更多
Growing evidences showed that heavy metals exposure may be associated with metabolic diseases.Nevertheless,themechanism underlying arsenic(As)exposure and metabolic syndrome(MetS)risk has not been fully elucidated.So ...Growing evidences showed that heavy metals exposure may be associated with metabolic diseases.Nevertheless,themechanism underlying arsenic(As)exposure and metabolic syndrome(MetS)risk has not been fully elucidated.So we aimed to prospectively investigate the role of serum uric acid(SUA)on the association between blood As exposure and incident MetS.A sample of 1045 older participants in a community in China was analyzed.We determined As at baseline and SUA concentration at follow-up in the Yiwu Elderly Cohort.MetS events were defined according to the criteria of the International Diabetes Federation(IDF).Generalized linear model with log-binominal regression model was applied to estimate the association of As with incident MetS.To investigate the role of SUA in the association between As andMetS,amediation analysiswas conducted.In the fully adjusted log-binominal model,per interquartile range increment of As,the risk of MetS increased 1.25-fold.Compared with the lowest quartile of As,the adjusted relative risk(RR)of MetS in the highest quartile was 1.42(95%confidence interval,CI:1.03,2.00).Additionally,blood As was positively associated with SUA,while SUA had significant association with MetS risk.Further mediation analysis demonstrated that the association of As and MetS risk was mediated by SUA,with the proportion of 15.7%.Our study found higher As was remarkably associated with the elevated risk of MetS in the Chinese older adults population.Mediation analysis indicated that SUA might be a mediator in the association between As exposure and MetS.展开更多
基金supported by the National Natural Science Foundation of China(Nos.22076212 and 22222611)the Youth Innovation Promotion Association of CAS(No.2021040).
文摘Iron oxide nanoparticles(IONPs)have wide applications in the biomedical field due to their outstanding physical and chemical properties.However,the potential adverse effects and relatedmechanisms of IONPs in human organs,especially the lung,are still largely ignored.In this study,we found that group-modified IONPs(carboxylated,aminated and silica coated)induce slight lung cell damage(in terms of the cell cycle,reactive oxygen species(ROS)production,cell membrane integrity and DNA damage)at a sublethal dosage.However,aminated IONPs could release more iron ions in the lysosome than the other two types of IONPs,but the abnormally elevated iron ion concentration did not induce ferroptosis.In-triguingly,amino-modified IONPs aggravated the accumulation of intracellular peroxides induced by the ferroptosis activator RSL3 and thus caused ferroptosis in vitro,and the coadministration of amino-modified IONPs and RSL3 induced more severe lung injury in vivo.Therefore,our data revealed that the surface functionalization of IONPs plays an important role in determining their potential pulmonary toxicity,as surface modification influences their degradation behavior.These results provide guidance for the design of future IONPs and the corresponding safety evaluations and predictions.
基金supported by the National Natural Science Foundation of China(No.U22A20358)Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents(No.2020-18).
文摘Metal may affect maternal immune function,but few epidemiological studies have reported the associations between multiple-metal exposure and maternal immunoglobulin(Ig)levels.Based on the Hangzhou Birth Cohort Study,1059 participants were included,and eleven metals in whole blood samples and serum IgA,IgG,IgE and IgM levels were measured.Linear regression,quantile-based g-computation(QGC),and Bayesian kernel machine regression(BKMR)models were used to evaluate the associations.Compared with the first tertile of metal levels,arsenic(As)was negatively associated with IgE(β=-0.25,95%confidence interval(CI)=-0.48 to-0.02).Moreover,significant associations of manganese(Mn)with IgA,IgG and IgM were demonstrated(β=0.10,95%CI=0.04 to 0.18;β=0.07,95%CI=0.03 to 0.12;β=0.10,95%CI=0.03 to 0.18,respectively).Cadmium(Cd)were associated with higher levels of IgM.QGC models showed the positive association of the metalmixtures with IgA and IgG,with Mn playing amajor role.Mn and Cd had positive contributions to IgM,while As had negative contributions to IgE.In the BKMR models,the latent continuous outcomes of IgA and IgG showed a significant increase when all the metals were at their 60th percentile or above compared to those at their 50th percentile.Therefore,exposure to metals was associated with maternal Igs,and mainly showed that Mn was associated with increased levels of IgA,IgG and IgM,and As was associated with low IgE levels.
基金supported by the Fundamental Research Funds for the Central Universities(Nos.2021FZZX001-39 and 2020QNA7018)the Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province(No.20220204)the Medical Science and Technology Project of Zhejiang Province(No.2023RC037).
文摘Growing evidences showed that heavy metals exposure may be associated with metabolic diseases.Nevertheless,themechanism underlying arsenic(As)exposure and metabolic syndrome(MetS)risk has not been fully elucidated.So we aimed to prospectively investigate the role of serum uric acid(SUA)on the association between blood As exposure and incident MetS.A sample of 1045 older participants in a community in China was analyzed.We determined As at baseline and SUA concentration at follow-up in the Yiwu Elderly Cohort.MetS events were defined according to the criteria of the International Diabetes Federation(IDF).Generalized linear model with log-binominal regression model was applied to estimate the association of As with incident MetS.To investigate the role of SUA in the association between As andMetS,amediation analysiswas conducted.In the fully adjusted log-binominal model,per interquartile range increment of As,the risk of MetS increased 1.25-fold.Compared with the lowest quartile of As,the adjusted relative risk(RR)of MetS in the highest quartile was 1.42(95%confidence interval,CI:1.03,2.00).Additionally,blood As was positively associated with SUA,while SUA had significant association with MetS risk.Further mediation analysis demonstrated that the association of As and MetS risk was mediated by SUA,with the proportion of 15.7%.Our study found higher As was remarkably associated with the elevated risk of MetS in the Chinese older adults population.Mediation analysis indicated that SUA might be a mediator in the association between As exposure and MetS.
