Objective To investigate whether exposure to particulate matter of diameter equal to or less than 2.5μm(PM2.5)alters the response of lung epithelial cells to extrinsic regulation by globally profiling cell surface li...Objective To investigate whether exposure to particulate matter of diameter equal to or less than 2.5μm(PM2.5)alters the response of lung epithelial cells to extrinsic regulation by globally profiling cell surface ligands and quantifying their binding activity.Methods Human A549 lung epithelial cells(LECs)were treated with or without PM2.5.Ligandomic profiling was applied to these cells for the global identification of LEC-binding ligands with simultaneous quantification of binding activity.Quantitative comparisons of the entire ligandome profiles systematically identified ligands with increased or decreased binding to PM2.5-treated LECs.Results We found 143 ligands with increased binding to PM2.5-treated LECs and 404 ligands with decreased binding.Many other ligands showed no change in binding activity.For example,apolipoprotein E(ApoE),Notch2,and growth arrest-specific 6(Gas6)represent ligands with increased,decreased,or unchanged binding activity,respectively.Both ApoE and Gas6 are phagocytosis ligands,suggesting that phagocytic receptors on LECs after stimulation with PM2.5 were differentially upregulated by PM2.5.Conclusion These results suggest that the newly-developed ligandomics is a valuable approach to globally profile the response of LECs to PM2.5 in terms of regulating the expression of cell surface receptors,as quantified by ligand binding activity.This quantitative ligandome profiling will provide indepth understanding of the LEC molecular response on the cell surface to particulate matter air pollution.展开更多
Exposure to particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5) may increase risk of lung cancer. The repetitive and broad-area coverage of satellites may allow atmospheric remote sensing to o...Exposure to particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5) may increase risk of lung cancer. The repetitive and broad-area coverage of satellites may allow atmospheric remote sensing to offer a unique opportunity to monitor air quality and help fill air pollution data gaps that hinder efforts to study air pollution and protect public health. This geographical study explores if there is an association between PM2.5 and lung cancer mortality rate in the conterminous USA. Lung cancer (ICD-10 codes C34- C34) death count and population at risk by county were extracted for the period from 2001 to 2010 from the U.S. CDC WONDER online database. The 2001-2010 Global Annual Average PM2.5 Grids from MODIS and MISR Aerosol Optical Depth dataset was used to calculate a 10 year average PM2.5 pollution. Exploratory spatial data analyses, spatial regression (a spatial lag and a spatial error model), and spatially extended Bayesian Monte Carlo Markov Chain simulation found that there is a significant positive association between lung cancer mortality rate and PM2.5. The association would justify the need of further toxicological investigation of the biological mechanism of the adverse effect of the PM2.5 pollution on lung cancer. The Global Annual Average PM2.5 Grids from MODIS and MISR Aerosol Optical Depth dataset provides a continuous surface of concentrations of PM2.5 and is a useful data source for environmental health research.展开更多
目的研究不同剂量直径≤2.5μm的细颗粒物(PM2.5)诱导卵清蛋白(OVA)致哮喘小鼠肺损伤的程度。方法雄性BALB/c小鼠被随机分为正常对照组、OVA哮喘组、(1、5、15)mg/m L PM2.5处理的OVA哮喘组。收集支气管肺泡灌洗液(BALF)进行Gimsa染色...目的研究不同剂量直径≤2.5μm的细颗粒物(PM2.5)诱导卵清蛋白(OVA)致哮喘小鼠肺损伤的程度。方法雄性BALB/c小鼠被随机分为正常对照组、OVA哮喘组、(1、5、15)mg/m L PM2.5处理的OVA哮喘组。收集支气管肺泡灌洗液(BALF)进行Gimsa染色观察白细胞数量,ELISA检测小鼠血清γ干扰素(IFN-γ)、白细胞介素17(IL-17)和IL-10的含量;实时定量PCR进行外周血单个核细胞(PBMC)Toll样受体4(TLR4)、核因子κB(NF-κB)的mRNA水平;Western blot法检测T细胞表达的T盒(T-bet)、维甲酸相关孤核受体γt(RORγt)和叉头盒P3(FOXP3)蛋白水平;HE染色观察小鼠肺组织病变情况。结果与对照组相比,OVA哮喘组小鼠的肺泡间隔增厚,肺泡腔增大,且出现较明显的炎性细胞浸润,BALF中与炎症反应相关的白细胞数目增多;与OVA哮喘组相比,15 mg/m L PM2.5诱导的哮喘小鼠上述变化极其明显。与对照组相比,OVA哮喘组小鼠血清中IFN-γ、IL-10显著降低,而IL-17显著增加;与OVA哮喘组相比,15 mg/m L PM2.5处理的OVA哮喘组IFN-γ、IL-10含量显著减少,而IL-17含量显著增加。与对照组相比,OVA哮喘组小鼠PBMC中TLR4、NF-κB表达量明显增加,与OVA哮喘组相比,15 mg/m L PM2.5处理OVA哮喘组TLR4、NF-κB表达量显著增加。与对照组相比,OVA哮喘组小鼠T-bet和FOXP3蛋白水平明显降低,RORγt蛋白水平明显升高;与OVA哮喘组相比,15 mg/m L PM2.5处理OVA哮喘组小鼠T-bet和FOXP3蛋白水平极显著降低,而RORγt蛋白水平显著增加。结论 15 mg/m L PM2.5通过激活TLR4/NF-κB信号通路促进OVA诱发的哮喘和肺损伤。展开更多
目的探讨HMGA2基因缺失对PM2.5暴露致大鼠肺损伤和心功能不全的影响。方法将野生型(WT)大鼠按体重用随机数字表法分为对照组和PM2.5组,每组5只大鼠;将HMGA2^(-/-)大鼠按体重用随机数字表法分为HMGA2^(-/-)组和HMGA2^(-/-)+PM2.5组,每组...目的探讨HMGA2基因缺失对PM2.5暴露致大鼠肺损伤和心功能不全的影响。方法将野生型(WT)大鼠按体重用随机数字表法分为对照组和PM2.5组,每组5只大鼠;将HMGA2^(-/-)大鼠按体重用随机数字表法分为HMGA2^(-/-)组和HMGA2^(-/-)+PM2.5组,每组5只大鼠。对照组和HMGA2^(-/-)组大鼠每天气管滴注0.3 ml 0.9%氯化钠溶液,PM2.5组和HMGA2^(-/-)+PM2.5组每天气管滴注0.3 ml PM2.5混悬液,连续4周后对大鼠的心功能[左心室射血分数(LVEF)、左心室缩短分数(LVFS)]和肺功能[肺活量(FVC)、最大通气量(MVV)]进行评价,检测大鼠血清中白介素-6(IL-6)、肿瘤坏死因子α(TNF-α)、3-硝基酪氨酸(3-NT)和4-羟基壬烯醛(4-HNE)水平,同时检测肺和心脏组织中高迁移率族蛋白A2(HMGA2)、核转录因子-κB(NF-κB)和过氧化物还原判酶5(PRDX5)蛋白水平。结果HMGA2^(-/-)组和HMGA2^(-/-)+PM2.5组大鼠肺和心脏组织中HMGA2无表达;与对照组比较,PM2.5组肺和心脏组织中HMGA2表达降低,差异有统计学意义(P<0.05);与对照组比较,HMGA2^(-/-)组各指标差异无统计学意义(P>0.05);与对照组比较,PM2.5组和HMGA2^(-/-)+PM2.5组大鼠FVC、MVV、LVEF和LVFS降低,IL-6、TNF-α、3-NT和4-HNE增加,肺和心脏组织中NF-κB和PRDX5降低(P<0.05);与PM2.5组比较,HMGA2^(-/-)+PM2.5组大鼠FVC、MVV、LVEF和LVFS降低,IL-6、TNF-α、3-NT和4-HNE增加,肺和心脏组织中NF-κB增加、PRDX5降低(P<0.05)。结论HMGA2基因敲除能加重PM2.5暴露致大鼠肺损伤和心功能不全,其机制可能与炎症和氧化应激有关。展开更多
This study is focused on the linkage between lung cancer incidence rates and PM2.5 pollution. Researches conducted by leading research organizations in U.S. and Europe were reviewed and analyzed, and strong evidence e...This study is focused on the linkage between lung cancer incidence rates and PM2.5 pollution. Researches conducted by leading research organizations in U.S. and Europe were reviewed and analyzed, and strong evidence exists that elevated fine particulate air pollution exposures are associated with significant increases in lung cancer mortality. The linkage between fine particulate air pollution and lung cancer motility is observed even after controlling for cigarette smoking, occupational exposure, and other risk factors. This finding is in alignment with observations in China which show an upward trend of lung cancer incidences coupled with a downward trend in the number of smokers. Currently, China lacks systematic research on the effect of PM2.5 on lung cancer. As a result, this paper investigated studies on the linkage between pollution and lung cancer incidence from decades of research conducted in the U.S. and Europe. One important step in solving this issue in China is through classifying PM2.5 pollution as a human cacinogen. Adequate government regulation, public awareness, regional collaboration and industrial compliance are also key to the successful control of PM2.5 pollution and smog.展开更多
Objective To estimate the lung cancer burden that may be attributable to ambient fine particulate matter （PM2.5） pollution in Guangzhou city in China from 2005 to 2013. Methods The data regarding PM2.5 exposure were...Objective To estimate the lung cancer burden that may be attributable to ambient fine particulate matter （PM2.5） pollution in Guangzhou city in China from 2005 to 2013. Methods The data regarding PM2.5 exposure were obtained from the ＆#39;Ambient air pollution exposure estimation for the Global Burden of Disease 2013＇ dataset at 0.1° ×0.1° spatial resolution. Disability-adjusted life years （DALYs） were estimated based on the information of mortality and incidence of lung cancer. Comparative risk analysis and integrated exposure-response function were used to estimate attributed disease burden. Results The population-weighted average concentration of PM2.5 was increased by 34.6% between 1990 and 2013, from 38.37 μg/m3 to 51.31 μg/m^3. The lung cancer DALYs in both men and women were increased by 36.2% from 2005 to 2013. The PM2.5 attributed lung cancer DALYs increased from 12105.0 （8181.0 for males and 3924.0 for females） in 2005 to 16489.3 （11291.7 for males and 5197.6 for females） in 2013. An average of 23.1% lung cancer burden was attributable to PM2.5 pollution in 2013. Conclusion PM2.5 has caused serious but under-appreciated public health burden in Guangzhou and the trend deteriorates. Effective strategies are needed to tackle this major public health problem.展开更多
基金supported by the National Institute of Health under Grant#R01EY027749-01A1,#R24EY028764-01A1,#R21EY027065-02,#R41EY027665-01A1 to LW,and#P30-EY014801The American Diabetes Association under Grant#1-18-IBS-172 to LW+1 种基金An institutional grant from Research to Prevent BlindnessThe National Natural Science Foundation of China under Grant#81573112 and#81373030 to WWD.
文摘Objective To investigate whether exposure to particulate matter of diameter equal to or less than 2.5μm(PM2.5)alters the response of lung epithelial cells to extrinsic regulation by globally profiling cell surface ligands and quantifying their binding activity.Methods Human A549 lung epithelial cells(LECs)were treated with or without PM2.5.Ligandomic profiling was applied to these cells for the global identification of LEC-binding ligands with simultaneous quantification of binding activity.Quantitative comparisons of the entire ligandome profiles systematically identified ligands with increased or decreased binding to PM2.5-treated LECs.Results We found 143 ligands with increased binding to PM2.5-treated LECs and 404 ligands with decreased binding.Many other ligands showed no change in binding activity.For example,apolipoprotein E(ApoE),Notch2,and growth arrest-specific 6(Gas6)represent ligands with increased,decreased,or unchanged binding activity,respectively.Both ApoE and Gas6 are phagocytosis ligands,suggesting that phagocytic receptors on LECs after stimulation with PM2.5 were differentially upregulated by PM2.5.Conclusion These results suggest that the newly-developed ligandomics is a valuable approach to globally profile the response of LECs to PM2.5 in terms of regulating the expression of cell surface receptors,as quantified by ligand binding activity.This quantitative ligandome profiling will provide indepth understanding of the LEC molecular response on the cell surface to particulate matter air pollution.
文摘Exposure to particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5) may increase risk of lung cancer. The repetitive and broad-area coverage of satellites may allow atmospheric remote sensing to offer a unique opportunity to monitor air quality and help fill air pollution data gaps that hinder efforts to study air pollution and protect public health. This geographical study explores if there is an association between PM2.5 and lung cancer mortality rate in the conterminous USA. Lung cancer (ICD-10 codes C34- C34) death count and population at risk by county were extracted for the period from 2001 to 2010 from the U.S. CDC WONDER online database. The 2001-2010 Global Annual Average PM2.5 Grids from MODIS and MISR Aerosol Optical Depth dataset was used to calculate a 10 year average PM2.5 pollution. Exploratory spatial data analyses, spatial regression (a spatial lag and a spatial error model), and spatially extended Bayesian Monte Carlo Markov Chain simulation found that there is a significant positive association between lung cancer mortality rate and PM2.5. The association would justify the need of further toxicological investigation of the biological mechanism of the adverse effect of the PM2.5 pollution on lung cancer. The Global Annual Average PM2.5 Grids from MODIS and MISR Aerosol Optical Depth dataset provides a continuous surface of concentrations of PM2.5 and is a useful data source for environmental health research.
文摘目的研究不同剂量直径≤2.5μm的细颗粒物(PM2.5)诱导卵清蛋白(OVA)致哮喘小鼠肺损伤的程度。方法雄性BALB/c小鼠被随机分为正常对照组、OVA哮喘组、(1、5、15)mg/m L PM2.5处理的OVA哮喘组。收集支气管肺泡灌洗液(BALF)进行Gimsa染色观察白细胞数量,ELISA检测小鼠血清γ干扰素(IFN-γ)、白细胞介素17(IL-17)和IL-10的含量;实时定量PCR进行外周血单个核细胞(PBMC)Toll样受体4(TLR4)、核因子κB(NF-κB)的mRNA水平;Western blot法检测T细胞表达的T盒(T-bet)、维甲酸相关孤核受体γt(RORγt)和叉头盒P3(FOXP3)蛋白水平;HE染色观察小鼠肺组织病变情况。结果与对照组相比,OVA哮喘组小鼠的肺泡间隔增厚,肺泡腔增大,且出现较明显的炎性细胞浸润,BALF中与炎症反应相关的白细胞数目增多;与OVA哮喘组相比,15 mg/m L PM2.5诱导的哮喘小鼠上述变化极其明显。与对照组相比,OVA哮喘组小鼠血清中IFN-γ、IL-10显著降低,而IL-17显著增加;与OVA哮喘组相比,15 mg/m L PM2.5处理的OVA哮喘组IFN-γ、IL-10含量显著减少,而IL-17含量显著增加。与对照组相比,OVA哮喘组小鼠PBMC中TLR4、NF-κB表达量明显增加,与OVA哮喘组相比,15 mg/m L PM2.5处理OVA哮喘组TLR4、NF-κB表达量显著增加。与对照组相比,OVA哮喘组小鼠T-bet和FOXP3蛋白水平明显降低,RORγt蛋白水平明显升高;与OVA哮喘组相比,15 mg/m L PM2.5处理OVA哮喘组小鼠T-bet和FOXP3蛋白水平极显著降低,而RORγt蛋白水平显著增加。结论 15 mg/m L PM2.5通过激活TLR4/NF-κB信号通路促进OVA诱发的哮喘和肺损伤。
文摘目的探讨HMGA2基因缺失对PM2.5暴露致大鼠肺损伤和心功能不全的影响。方法将野生型(WT)大鼠按体重用随机数字表法分为对照组和PM2.5组,每组5只大鼠;将HMGA2^(-/-)大鼠按体重用随机数字表法分为HMGA2^(-/-)组和HMGA2^(-/-)+PM2.5组,每组5只大鼠。对照组和HMGA2^(-/-)组大鼠每天气管滴注0.3 ml 0.9%氯化钠溶液,PM2.5组和HMGA2^(-/-)+PM2.5组每天气管滴注0.3 ml PM2.5混悬液,连续4周后对大鼠的心功能[左心室射血分数(LVEF)、左心室缩短分数(LVFS)]和肺功能[肺活量(FVC)、最大通气量(MVV)]进行评价,检测大鼠血清中白介素-6(IL-6)、肿瘤坏死因子α(TNF-α)、3-硝基酪氨酸(3-NT)和4-羟基壬烯醛(4-HNE)水平,同时检测肺和心脏组织中高迁移率族蛋白A2(HMGA2)、核转录因子-κB(NF-κB)和过氧化物还原判酶5(PRDX5)蛋白水平。结果HMGA2^(-/-)组和HMGA2^(-/-)+PM2.5组大鼠肺和心脏组织中HMGA2无表达;与对照组比较,PM2.5组肺和心脏组织中HMGA2表达降低,差异有统计学意义(P<0.05);与对照组比较,HMGA2^(-/-)组各指标差异无统计学意义(P>0.05);与对照组比较,PM2.5组和HMGA2^(-/-)+PM2.5组大鼠FVC、MVV、LVEF和LVFS降低,IL-6、TNF-α、3-NT和4-HNE增加,肺和心脏组织中NF-κB和PRDX5降低(P<0.05);与PM2.5组比较,HMGA2^(-/-)+PM2.5组大鼠FVC、MVV、LVEF和LVFS降低,IL-6、TNF-α、3-NT和4-HNE增加,肺和心脏组织中NF-κB增加、PRDX5降低(P<0.05)。结论HMGA2基因敲除能加重PM2.5暴露致大鼠肺损伤和心功能不全,其机制可能与炎症和氧化应激有关。
文摘This study is focused on the linkage between lung cancer incidence rates and PM2.5 pollution. Researches conducted by leading research organizations in U.S. and Europe were reviewed and analyzed, and strong evidence exists that elevated fine particulate air pollution exposures are associated with significant increases in lung cancer mortality. The linkage between fine particulate air pollution and lung cancer motility is observed even after controlling for cigarette smoking, occupational exposure, and other risk factors. This finding is in alignment with observations in China which show an upward trend of lung cancer incidences coupled with a downward trend in the number of smokers. Currently, China lacks systematic research on the effect of PM2.5 on lung cancer. As a result, this paper investigated studies on the linkage between pollution and lung cancer incidence from decades of research conducted in the U.S. and Europe. One important step in solving this issue in China is through classifying PM2.5 pollution as a human cacinogen. Adequate government regulation, public awareness, regional collaboration and industrial compliance are also key to the successful control of PM2.5 pollution and smog.
基金supported by the Centre for Health Statistics Information,National Health and Family Planning Commission of the People’s Republic of China
文摘Objective To estimate the lung cancer burden that may be attributable to ambient fine particulate matter （PM2.5） pollution in Guangzhou city in China from 2005 to 2013. Methods The data regarding PM2.5 exposure were obtained from the ＆#39;Ambient air pollution exposure estimation for the Global Burden of Disease 2013＇ dataset at 0.1° ×0.1° spatial resolution. Disability-adjusted life years （DALYs） were estimated based on the information of mortality and incidence of lung cancer. Comparative risk analysis and integrated exposure-response function were used to estimate attributed disease burden. Results The population-weighted average concentration of PM2.5 was increased by 34.6% between 1990 and 2013, from 38.37 μg/m3 to 51.31 μg/m^3. The lung cancer DALYs in both men and women were increased by 36.2% from 2005 to 2013. The PM2.5 attributed lung cancer DALYs increased from 12105.0 （8181.0 for males and 3924.0 for females） in 2005 to 16489.3 （11291.7 for males and 5197.6 for females） in 2013. An average of 23.1% lung cancer burden was attributable to PM2.5 pollution in 2013. Conclusion PM2.5 has caused serious but under-appreciated public health burden in Guangzhou and the trend deteriorates. Effective strategies are needed to tackle this major public health problem.
