Benchmark Dose Assessment for Coke Oven Emissions-Induced Mitochondrial DNA Copy Number Damage Effects / 生物医学与环境科学（英文）

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 is 0.002 mg/m 3. This value will provide a benchmark for determining possible OELs.

Relationships between blood leukocyte mitochondrial DNA copy number and inflammatory cytokines in knee osteoarthritis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

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.

Relationships between blood leukocyte mitochondrial DNA copy number and inflammatory cytokines in knee osteoarthritis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

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.

Effects of resveratrol on mitochondrial DNA copy in retinal vascular endothelial cells cultured under high glucose conditions and its mechanism / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate effects of resveratrol on mitochondrial DNA copy in retinal vascular endothelial cells cultured under high glucose conditions and its mechanism.METHODS:Human retinal vascular endothelial cells were cultured in low glucose or high glucose medium,the genomic DNA was extracted and copy number of mitochondrial DNA was detected by real-time PCR.Effects of resveratrol on the mitochondrial DNA copy in retinal vascular endothelial cells cultured under high glucose medium were studied.The expression of mitochondrial transcription factor A (TFAM) and acetylated proliferator-activated receptor coactivator-1 alpha (PGC-1α) were analyzed by Western blot and coimmunoprecipitation.RESULTS:High glucose inhibited the copy number of mitochondrial DNA in retinal vascular endothelial cells.However,resveratrol decreased the level of acetylated PGC-1α in retinal vascular endothelial cells,increased the expression of TFAM and the copy number of mitochondrial DNA.CONCLUSION:Resveratrol may improve mitochondrial function of retinal vascular endothelial cells exposed to a high glucose environment via activation of the PCG-1α-TFAM signaling pathway.

Relationship Between Mitochondrial DNA Related Factors and Traditional Chinese Medical Syndrome Types in Primary Osteoporosis Patients / 广州中医药大学学报

Objective To investigate the biological characteristics of primary osteoporosis syndrome types from the perspective of mitochondrial DNA ( mtDNA) , thus to reveal the nature of osteoporosis and its traditional Chinese medical syndrome types. Methods A total of 210 osteoporosis women patients meeting the diagnostic criteria, inclusion criteria and exclusion criteria were collected from July of 2011 to October of 2013. The osteoporosis patients were differentiated into the syndrome types of yin deficiency of liver and kidney ( N=67) , yang deficiency of spleen and kidney ( N=70) and qi stagnation and blood stasis ( N=73) . And a total of 69 age-matched post-menopause non-osteoporosis patients were chosen as the control group, which were classified into the syndrome of harmony of Qi and blood. The peripheral blood was sampled for detecting mtDNA copy number with fluorescent quantitatitation PCR and for examining 8-hydroxy-2’-deoxyguanosine ( 8-OHdG) content by enzyme-linked immunosorbent assay (ELISA) . Statistical methods was used to analyze the correlation of bone mineral density (BMD) with mtDNA copy number and 8-OHdG content in different groups. Results The difference of mtDNA copy number was significant between the osteoporosis patients and non-osteoporosis patients (P<0.05), and was also significant among the three syndrome types of osteoporosis patients (P<0.05) . And 8-OHdG content showed the same features between the osteoporosis patients and non-osteoporosis patients (P<0.05) and among the three syndrome types of osteoporosis patients (P<0.05) . The correlation analysis results showed that mtDNA copy number was positively correlated with BMD, while 8-OHdG was negatively correlated with BMD in each group. Conclusion The mtDNA copy number and 8-OHdG content are correlated with the syndrome types of primary osteoporosis patients, and close correlation is shown between spleen-kidney yang deficiency and 8-OHdG, and between liver-kidney yin deficiency and mtDNA copy number.