Objective The study aimed to estimate the benchmark dose(BMD)of coke oven emissions(COEs)exposure based on mitochondrial damage with the mitochondrial DNA copy number(mtDNAcn)as a biomarker.Methods A total of 782 subj...Objective The study aimed to estimate the benchmark dose(BMD)of coke oven emissions(COEs)exposure based on mitochondrial damage with the mitochondrial DNA copy number(mtDNAcn)as a biomarker.Methods A total of 782 subjects were recruited,including 238 controls and 544 exposed workers.The mtDNAcn of peripheral leukocytes was detected through the real-time fluorescence-based quantitative polymerase chain reaction.Three BMD approaches were used to calculate the BMD of COEs exposure based on the mitochondrial damage and its 95%confidence lower limit(BMDL).Results The mtDNAcn of the exposure group was lower than that of the control group(0.60±0.29 vs.1.03±0.31;P<0.001).A dose-response relationship was shown between the mtDNAcn damage and COEs.Using the Benchmark Dose Software,the occupational exposure limits(OELs)for COEs exposure in males was 0.00190 mg/m^(3).The OELs for COEs exposure using the BBMD were 0.00170 mg/m^(3)for the total population,0.00158 mg/m^(3)for males,and 0.00174 mg/m^(3)for females.In possible risk obtained from animal studies(PROAST),the OELs of the total population,males,and females were 0.00184,0.00178,and 0.00192 mg/m^(3),respectively.Conclusion Based on our conservative estimate,the BMDL of mitochondrial damage caused by COEs is0.002 mg/m^(3).This value will provide a benchmark for determining possible OELs.展开更多
Osteoarthritis(OA)is a degenerative articular disorder manifested by cartilage destruction,subchondral sclerosis,osteophytes,and synovitis,resulting in chronic joint pain and physical disability in the elderly.The pur...Osteoarthritis(OA)is a degenerative articular disorder manifested by cartilage destruction,subchondral sclerosis,osteophytes,and synovitis,resulting in chronic joint pain and physical disability in the elderly.The purpose of this study was to investigate mitochondrial DNA copy number(mtDNACN)and inflammatory cytokines in primary knee OA patients and healthy volunteers.A total of 204 knee OA patients and 169 age-matched healthy volunteers were recruited.Their relative blood leukocyte mtDNACN was assessed by quantitative real-time polymerase chain reaction(qRT-PCR),and ten inflammatory cytokines in their plasma were detected by multiplex immunoassay.Blood leukocyte mtDNACN in the OA group was significantly lower than that in the control group.Leukocyte mtDNACN in the control group was negatively correlated with their age(r=−0.380,P<0.0001),whereas mtDNACN in the OA group was positively correlated with their age(r=0.198,P<0.001).Plasma interleukin-4(IL-4)and IL-6 were significantly higher in the knee OA group than in the control group.The plasma IL-6 level was positively correlated with blood leukocyte mtDNACN in the OA group(r=0.547,P=0.0014).IL-5 showed as a major factor(coefficient 0.69)in the second dimension of principle components analysis(PCA)-transformed data and was significantly higher in the OA group(P<0.001)as well as negatively correlated with mtDNACN(r=−0.577,P<0.001).These findings suggest that elevation of plasma IL-4 and IL-6 and a relative reduction in mtDNACN might be effective biomarkers for knee OA.IL-5 is a plausible factor responsible for decreasing blood leukocyte mtDNACN in knee OA patients.展开更多
基金supported by the National Natural Science Foundation of China[grant numbers:NSFC81872597,81001239]。
文摘Objective The study aimed to estimate the benchmark dose(BMD)of coke oven emissions(COEs)exposure based on mitochondrial damage with the mitochondrial DNA copy number(mtDNAcn)as a biomarker.Methods A total of 782 subjects were recruited,including 238 controls and 544 exposed workers.The mtDNAcn of peripheral leukocytes was detected through the real-time fluorescence-based quantitative polymerase chain reaction.Three BMD approaches were used to calculate the BMD of COEs exposure based on the mitochondrial damage and its 95%confidence lower limit(BMDL).Results The mtDNAcn of the exposure group was lower than that of the control group(0.60±0.29 vs.1.03±0.31;P<0.001).A dose-response relationship was shown between the mtDNAcn damage and COEs.Using the Benchmark Dose Software,the occupational exposure limits(OELs)for COEs exposure in males was 0.00190 mg/m^(3).The OELs for COEs exposure using the BBMD were 0.00170 mg/m^(3)for the total population,0.00158 mg/m^(3)for males,and 0.00174 mg/m^(3)for females.In possible risk obtained from animal studies(PROAST),the OELs of the total population,males,and females were 0.00184,0.00178,and 0.00192 mg/m^(3),respectively.Conclusion Based on our conservative estimate,the BMDL of mitochondrial damage caused by COEs is0.002 mg/m^(3).This value will provide a benchmark for determining possible OELs.
基金Project supported by the 90th Anniversary of Chulalongkorn University(No.RA61/104)the Research Chair Grant from the National Science and Technology Development Agency+1 种基金the 100th Anniversary of Chulalongkorn University Fund for Doctoral Scholarshipthe Overseas Research Experience Scholarship for Graduate Student,Thailand and China Scholarship Council,China
文摘Osteoarthritis(OA)is a degenerative articular disorder manifested by cartilage destruction,subchondral sclerosis,osteophytes,and synovitis,resulting in chronic joint pain and physical disability in the elderly.The purpose of this study was to investigate mitochondrial DNA copy number(mtDNACN)and inflammatory cytokines in primary knee OA patients and healthy volunteers.A total of 204 knee OA patients and 169 age-matched healthy volunteers were recruited.Their relative blood leukocyte mtDNACN was assessed by quantitative real-time polymerase chain reaction(qRT-PCR),and ten inflammatory cytokines in their plasma were detected by multiplex immunoassay.Blood leukocyte mtDNACN in the OA group was significantly lower than that in the control group.Leukocyte mtDNACN in the control group was negatively correlated with their age(r=−0.380,P<0.0001),whereas mtDNACN in the OA group was positively correlated with their age(r=0.198,P<0.001).Plasma interleukin-4(IL-4)and IL-6 were significantly higher in the knee OA group than in the control group.The plasma IL-6 level was positively correlated with blood leukocyte mtDNACN in the OA group(r=0.547,P=0.0014).IL-5 showed as a major factor(coefficient 0.69)in the second dimension of principle components analysis(PCA)-transformed data and was significantly higher in the OA group(P<0.001)as well as negatively correlated with mtDNACN(r=−0.577,P<0.001).These findings suggest that elevation of plasma IL-4 and IL-6 and a relative reduction in mtDNACN might be effective biomarkers for knee OA.IL-5 is a plausible factor responsible for decreasing blood leukocyte mtDNACN in knee OA patients.
