Global, regional, and national burden of stroke attributable to extreme low temperatures, 1990-2019: A global analysis.

BACKGROUND: Extreme ambient temperatures have been linked to increased risks of stroke morbidity and mortality. However, global estimates of the burden of stroke due to extreme low temperatures are not well-defined. AIMS: This study aimed to determine the global burden of stroke due to extreme low temperatures and its spatiotemporal trend from 1990 to 2019. METHODS: Based on the Global Burden of Disease Study 2019, we obtained global, regional, and national data on deaths, disability-adjusted life years (DALYs), age-standardized mortality rate (ASMR), and age-standardized rate of DALYs (ASDR) of stroke attributed to extreme low temperatures, further stratified by age, sex, and sociodemographic index (SDI). RESULTS: Globally, in 2019, an estimated 474,000 stroke deaths with the corresponding ASMR (6.2 (95% uncertainty interval (UI): 4.6-7.9)) and ASDR (103.9 (95% UI: 77.0-134.5)) per 100,000 population, were attributable to extreme low temperatures. The most significant burden was observed in Central Asia, followed by Eastern Europe and East Asia. From 1990 to 2019, the global burden of stroke and its subtypes (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) attributable to extreme low temperatures exhibited a decrease in both ASMR and ASDR. Significant decreases in stroke burden occurred in the high-SDI regions, high-income Asia Pacific, and subarachnoid hemorrhage cases. Moreover, the ASMR and ASDR increased with age and were higher in males than females. CONCLUSION: The global stroke burden due to extreme low temperatures remains high despite a decreasing trend over the past three decades. The stroke burden due to extreme low temperatures was more notable for Central Asia, older people, and the male sex.

The role of N6-methyladenosine methylation in PAHs-induced cancers.

Polycyclic aromatic hydrocarbons (PAHs), which are a wide range of environmental toxicants, may act on humans through inhalation, ingestion, and skin contact, resulting in a range of toxic reactions. Epidemiological studies showed that long-term exposure to PAHs in the occupational and living environment results in a substantial rise in the incidence rate of many cancers in the population, so the prevention and treatment of these diseases have become a major worldwide public health problem. N6-methyladenosine (m6A) modification greatly affects the metabolism of RNA and is implicated in the etiopathogenesis of many kinds of diseases. In addition, m6A-binding proteins have an important role in disease development. The abnormal expression of these can cause the malignant proliferation, migration, invasion, and metastasis of cancers. Furthermore, a growing number of studies revealed that environmental toxicants are one of the cancer risk factors and are related to m6A modifications. Exposure to environmental toxicants can alter the methylation level of m6A and the expression of the m6A-binding protein, thus promoting the occurrence and development of cancers through diverse mechanisms. m6A may serve as a biomarker for early environmental exposure. Through the study of m6A, we can find the health injury early, thus providing a new sight for preventing and curing environmental health-related diseases.

MEG3 polymorphisms associated with peripheral blood leukocyte mitochondrial DNA copy number in PAHs-exposure workers.

BACKGROUND: Epidemiological studies have shown that exposure to Polycyclic aromatic hydrocarbons (PAHs) is associated with reduced mitochondrial DNA copy number (mtDNA-CN). Long non-coding RNA maternally expressed gene 3 (MEG3) is involved in mitochondrial function regulation. However, it is unknown whether single-nucleotide polymorphisms in the MEG3 can regulate the mtDNAcn in PAHs exposed populations. The aim of this study was to examine the effect of MEG3 genetic polymorphisms on the mtDNA-CN in PAHs exposed populations. MATERIALS AND METHODS: We recruited 544 coke oven workers and 238 controls using random cluster sampling. High-performance liquid chromatography was used to detect the concentrations of four OH-PAHs (1-hydroxypyrene [1-OHPyr], 1-hydroxynathalene [1-OHNap], 2-hydroxynathalene [2-OHNap], and 3-hydroxyphenanthrene [3-OHPhe]) in urine. The mtDNA-CN of peripheral blood leukocytes was measured using the quantitative polymerase chain reaction method. Sequenom Mass ARRAY matrix-assisted laser desorption/ionization-time of flight mass spectrometry platform was used to detect ten polymorphisms in MEG3. RESULTS: The OH-PAHs levels in the exposure group were significantly higher than those in the control group (P < 0.001). The mtDNA-CN in the exposure group was significantly lower than that in the control group (P < 0.001). A linear regression model revealed that PAHs-exposure (ß [95% confidence interval, CI], -0.428 [-0.475, -0.381], P < 0.001), male gender (-0.052 [-0.098, -0.005], P = 0.029), genotype TT for MEG3 rs11859 (-0.088 [-0.142, -0.035], P = 0.001), and genotype GG for MEG3 rs7155428 (-0.114 [-0.210, -0.017], P = 0.021) were associated with decreased mtDNA-CN. CONCLUSION: PAHs-exposure, male gender, genotype TT for rs11859, and genotype GG for rs7155428 were risk factors for mtDNA-CN.

MEG3 polymorphisms associated with leukocyte telomere length in workers exposed to polycyclic aromatic hydrocarbons.

Long non-coding RNA maternally expressed gene 3 (MEG3) has been revealed to be involved in telomere length (TL) maintenance and homeostasis. However, it is unknown whether single-nucleotide polymorphisms (SNPs) in MEG3 could regulate TL in populations exposed to polycyclic aromatic hydrocarbons (PAHs). This study aimed to explore the effect of MEG3 genetic polymorphisms on TL in PAH-exposed populations. This study recruited 544 coke oven workers and 238 controls using random cluster sampling. The concentrations of four urinary OH-PAHs were measured by employing high-performance liquid chromatography. TL was measured by a quantitative polymerase chain reaction assay. The MEG3 genetic polymorphisms were detected using a Sequenom MassARRAY matrix-assisted laser desorption/ionization-time of flight mass spectrometry platform. The concentrations of four urinary OH-PAHs in the exposure group were significantly higher than those in the control group (P < 0.001). TL in the exposure group (4.57 ± 0.84) was significantly lower than in the control (5.00 ± 0.75), and TL had a negative correlation with OH-PAHs. The generalized linear model found that PAH exposure [ß(95% CI) = -0.409(-0.537, -0.282), P < 0.001] and the CT+TT genotype in MEG3 rs10132552 [ß(95% CI) = -0.299(-0.582, -0.017), P = 0.038] were associated with the decreased TL. In conclusion, PAH exposure and the CT+TT genotype in MEG3 rs10132552 may be the risk factors for TL reduction.

Association of frailty with health service use among older Chinese adults: analysis of population-based panel data.

Background: Frailty is a common syndrome characterized by rapid growth in the aging population that has an impact on healthcare systems. This study aimed to investigate the impact of frailty on health service use and whether this effect varies with chronic diseases and socioeconomic status among older individuals in China. Methods: A balanced panel data analysis was conducted on 3,306 older individuals who completed follow-ups for the three waves of the China Health and Retirement Longitudinal Study (CHARLS) in 2011, 2013, and 2015. The Physical Frailty Phenotype (PFP) Scale was used to assess frailty status. Negative binomial regression was used to test the associations between frailty status, outpatient visits in the past 4 weeks, and annual inpatient hospital days. Results: Compared with robust individuals, individuals with pre-frail or frail status were likely to report a higher number of outpatient visits [pre-frail: incidence rate ratio (IRR) = 1.28, 95% CI = 1.16-1.41; frail: IRR = 1.45, 95% CI = 1.23-1.71], and inpatient hospital days (pre-frail: IRR = 1.40, 95% CI = 1.24-1.58; frail: IRR = 2.17, 95% CI = 1.81-2.60) after controlling for all covariates. All five frailty components (weight loss, exhaustion, low physical activity, slowness, and weakness) were associated with a higher number of inpatient hospital days, and two components (weight loss and exhaustion) were associated with a higher number of outpatient visits. The effect of frailty on inpatient hospital stays persisted in different socioeconomic groups, across all health insurance programmes and physical comorbidities. Conclusion: Frailty is associated with greater health service use among older individuals. Effective screening, prevention, intervention, and management of frailty may be important to reduce health service use.

Chain-mediating effect of interaction between telomeres and mitochondria under oxidative stress in coke oven workers.

Coke oven emissions (COEs) exposure leads to oxidative stress, an imbalance between oxidant production and antioxidant defence in the body, which then leads to shortened relative telomere length (RTL) and reduced mitochondrial DNA copy number (mtDNAcn), ultimately leading to ageing and disease. By analysing the relationship among COEs, oxidative stress, RTL and mtDNAcn, we investigated the chain-mediating effects of oxidative stress and telomeres on mitochondrial damage and mitochondria on telomere damage in coke oven workers. A total of 779 subjects were included in the study. Cumulative COEs exposure concentrations were estimated, and the RTL and mtDNAcn of peripheral blood leukocytes were measured using real-time fluorescence quantitative PCR. Total antioxidant capacity (T-AOC) was measured to reflect the level of oxidative stress. The data were statistically analysed using SPSS 21.0 software and discussed using mediation effect analysis. After adjusting for age, sex, smoking, drinking and BMI, generalised linear model revealed dose-response associations between COEs and T-AOC, RTL and mtDNAcn, respectively. (Ptrend < 0.05). The results of chain-mediating effect showed that the proportion of the chain-mediating effect of "CED-COEs→T-AOC→ RTL→mtDNAcn" was 0.82% (ß = -0.0005, 95% CI = [-0.0012, -0.0001]), and the proportion of the chain-mediating effect of "CED-COEs→T-AOC→ mtDNAcn → RTL ″ was 2.64% (ß = -0.0013, 95% CI = [-0.0025, -0.0004]). After oxidative stress is induced by COEs, mitochondria and telomeres may interact with each other while leading further to potential bodily damage. This study provides clues to explore the association between mitochondria and telomeres.

Effect and interaction of TNKS genetic polymorphisms and environmental factors on telomere damage in COEs-exposure workers.

Coke oven emissions (COEs) contain many carcinogenic polycyclic aromatic hydrocarbons (PAHs). Telomere damage is an early biological marker reflecting long-term COEs-exposure. Whereas, whether the genetic variations of telomere-regulated gene TNKS have an effect on the COEs-induced telomere damage is unknown. So we detected the environmental exposure levels, relative telomere length (RTL), and TNKS genetic polymorphisms among 544 COEs-exposure workers and 238 healthy participants. We found that the RTL of the wild homozygous GG genotype in rs1055328 locus was statistically shorter compared with the CG+CC genotype for the healthy participants using covariance analysis(P = 0.008). In the Generalized linear model (GLM) analysis, TNKS rs1055328 GG could accelerate telomere shortening (P = 0.011); and the interaction between TNKS rs1055328 GG and COEs-exposure had an effect on RTL (P = 0.002). In conclusion, this study was the first to discover the role of TNKS rs1055328 locus in COEs-induced telomere damage, and proved that chromosomal damage was a combined consequence of environmental and genetic factors.

Association of Depressive Symptoms With Health Service Use and Catastrophic Health Expenditure Among Middle-Aged and Older Chinese Adults: Analysis of Population-Based Panel Data.

OBJECTIVES: To determine the impact of depressive symptoms on health service use and catastrophic health expenditure, and whether it varied by per-capita household consumption, health insurance schemes, and physical comorbidities. DESIGN: Population-based panel data analysis. SETTING AND PARTICIPANTS: Participants were 8585 adults aged 45 years and older in 2011, and had completed a follow-up survey in 2013, 2015, and 2018 from the China Health and Retirement Longitudinal Study (CHARLS). METHODS: Depressive symptoms were assessed using the short form of the Center for Epidemiologic Studies Depression Scale. The number of outpatient visits and inpatient hospital days were used as proxies for health service use. When households' out-of-pocket spending on health was 40% or above its total expenditure, it was defined as a catastrophic health expenditure. With the panel data approach, random-effects negative binomial regression and logistic regression were used to analyze the effect of depressive symptoms on health service use and health care expenditure, respectively. RESULTS: Depressive symptoms were associated with increased number of outpatient visits (incidence rate ratio 1.52; 95% CI 1.44-1.60) and days spent in the hospital as an inpatient (1.52; 1.43-1.62). Depressive symptoms were also associated with a significantly increased likelihood of catastrophic health expenditure (odds ratio 1.54; 95% CI 1.43-1.66). Their effect on outpatient visits, inpatient hospital days, and catastrophic health expenditure persisted in different age, per-capita household consumption, and physical comorbidities groups, and across all health insurance programs. CONCLUSIONS AND IMPLICATIONS: Depressive symptoms were risk indicators that can drive health service use and household financial stress. Given the rapidly aging population in China, there is an urgent need to integrate mental health care into routine physical examinations to alleviate the economic impacts of depressive symptoms on individuals in China. specifically for individuals with physical comorbidities and in poorer socioeconomic conditions.

Association of Genetic Polymorphisms of TERT with Telomere Length in Coke Oven Emissions-Exposed Workers.

We explored the association between variations in the telomere maintenance genes and change in telomere length (TL) in workers. The TL of peripheral blood leukocytes from 544 coke oven workers and 238 controls were detected using the Real-time PCR method. Variations in four genes were then detected using the PCR based restriction fragment length polymorphism. The effects of environmental and genetic factors on TL were subsequently analyzed through covariance analysis and a generalized linear model .The TL of subjects with GG genotypes were longer than those with AG genotype in the TERT rs2736098 locus amongst the controls (P = .032). The combined effect of COEs exposure and AG+AA genotypes had a significant effect on TL (P < .001). The interaction between the COEs exposure factor and the rs2736098AG+AA genotypes had a significant effect on the TL (P < .05). The TL in coke oven workers is associated with the interactions between TERT rs2736098 AG+AA and COEs exposure.

The polymorphisms in cGAS-STING pathway are associated with mitochondrial DNA copy number in coke oven workers.

OBJECTIVE: To evaluate the interaction effects of Polycyclic aromatic hydrocarbons (PAHs) exposure and variants in cGAS-STING genes on mitochondrial DNA copy number (mtDNAcn) in workers. METHODS: The mtDNAcn was determined by real-time quantitative polymerase-chain reaction in 544 PAHs-exposed workers and 238 office workers. The polymorphisms were detected by flight mass spectrometry. RESULTS: The mtDNAcn in PAHs exposure group was significantly lower than non-occupational exposure population (P < 0.00). The cGAS rs610913 CA+AA had significant interaction effects with STING rs11554776 GG+GA (P = 0.035), rs7380824 CC+CT (P = 0.026), and rs78233829 GC+CC (P = 0.034) on mtDNAcn. The generalized linear model results showed that the influencing factors of mtDNAcn include PAHs exposure (P < 0.001) and the interaction of PAHs exposure and cGAS rs 311678 AA+AG (P = 0.047). CONCLUSION: The influencing factors of mtDNAcn include PAHs exposure and the interaction of PAHs exposure and cGAS rs 311678 AA+AG.

Relationship between miRNAs polymorphisms and peripheral blood leukocyte DNA telomere length in coke oven workers: A cross-sectional study.

OBJECTIVE: The purpose of this study was to investigate the factors affecting telomere length (TL) in coke oven workers by analyzing the interaction between miRNAs polymorphisms and coke oven emissions (COEs) exposure. METHODS: A total of 544 coke oven workers and 238 healthy controls were recruited. Peripheral blood was collected from the subjects, genomic DNA was extracted, leukocyte TL was detected by real-time quantitative polymerase chain reaction, and fifteen polymorphisms of eight miRNAs were genotyped by flight mass spectrometry. RESULTS: Statistical analysis showed that the peripheral blood DNA TL in the exposure group was shorter than that in the control group (P < 0.001). Generalized linear model found that COEs-exposure [ß (95%CI) = -0.427 (-0.556, -0.299), P < 0.001], genotype CC+CT for miR-612 rs1144925 [ß (95%CI) = -0.367 (-0.630, -0.104), P = 0.006], and the interaction of miR-181B1 rs12039395 TT genotype and COEs-exposure [ß (95% CI) = 0.564 (0.108, 1.020), P = 0.015] were associated with the shortened TL. CONCLUSION: COEs-exposure and miR-612 rs1144925 TT could promote telomere shortening in coke oven workers. The interaction of miR-181B1 rs12039395 TT genotype and COEs-exposure could protect telomere. This provides clues for further mechanistic studies between miRNA and telomere damage.

The Association Between Polymorphisms in Cell-Cycle Genes and Mitochondrial DNA Copy Number in Coke Oven Workers.

The mitochondrial DNA (mtDNA) copy number is a vital component in maintaining normal mitochondrial function. It is affected by environmental and occupational exposures, as well as polymorphisms in nuclear genes. Nonetheless, the specific roles of polymorphisms in cell-cycle genes and mtDNA copy number are still unknown. This study enrolled a sample of 544 coke oven workers and 238 non-exposed controls so as to assess the effect of exposure of coke oven emissions (COEs) and polymorphisms in cell-cycle genes on the mtDNA copy number. We found that the mtDNA copy number in the exposed group (0.60 ± 0.29) was significantly lower than that in the control group (1.03 ± 0.31) (t =18.931, P < 0.001). The analysis of covariance showed that both the rs1801270 (CA+CC) and the rs1059234 (CT+CC) in p21 gene were associated with lower mtDNA copy number in the exposed group (P = 0.001). Generalized linear models indicated COEs-exposure (ß = -0.432, P < 0.001) and rs1059234 (CT+CC) in p21 gene (ß = -0.060, P = 0.024) were the factors in mtDNA copy number reduction. In conclusion, this study suggests that the decrease of the mtDNA copy number is associated with COEs-exposure and the rs1059234 (CT+CC) in the p21 gene.

m6A demethylase FTO promotes tumor progression via regulation of lipid metabolism in esophageal cancer.

BACKGROUND: Epitranscriptomics studies have contributed greatly to the development of research on human cancers. In recent years, N6-methyladenosine (m6A), an RNA modification on the N-6 position of adenosine, has been found to play a potential role in epigenetic regulation. Therefore, we aimed to evaluate the regulation of cancer progression properties by m6A. RESULTS: We found that m6A demethylase fat mass and obesity-associated protein (FTO) was highly expressed in esophageal cancer (EC) stem-like cells, and that its level was also substantially increased in EC tissues, which was closely correlated with a poor prognosis in EC patients. FTO knockdown significantly inhibited the proliferation, invasion, stemness, and tumorigenicity of EC cells, whereas FTO overexpression promoted these characteristics. Furthermore, integrated transcriptome and meRIP-seq analyses revealed that HSD17B11 may be a target gene regulated by FTO. Moreover, FTO promoted the formation of lipid droplets in EC cells by enhancing HSD17B11 expression. Furthermore, depleting YTHDF1 increased the protein level of HSD17B11. CONCLUSIONS: These data indicate that FTO may rely on the reading protein YTHDF1 to affect the translation pathway of the HSD17B11 gene to regulate the formation of lipid droplets in EC cells, thereby promoting the development of EC. The understanding of the role of epitranscriptomics in the development of EC will lay a theoretical foundation for seeking new anticancer therapies.

Genetic variants in telomerase-associated protein 1 are associated with telomere damage in PAH-exposed workers.

Telomeres are functional complexes at the ends of linear chromosomes, and telomerase aids in their maintenance and replication. Additionally, accumulating evidence suggests that telomerase-associated protein 1 (TEP1) is a component of the telomerase ribonucleoprotein complex and is responsible for catalyzing the addition of new synthetic telomere sequences to chromosome ends. In our previous study, we found that genetic variants of the TERT gene participated in the regulation of telomere length. Exposure to particulate matter, environmental pollutants, oxidative stress, and pesticides is associated with shortening of telomere length. However, it is unknown whether genetic variants in the TEP1 gene may affect telomere length (TL) in polycyclic aromatic hydrocarbon (PAH)-exposed workers. Therefore, we measured the peripheral leukocyte TL and genotyped the polymorphism loci in the TEP1 gene among 544 PAH-exposed workers and 238 healthy controls. Covariance analysis showed that the individuals carrying TEP1 rs1760903 CC and TEP1 rs1760904 TT had longer TL in the control group (P < 0.05). In the generalized linear model, we found that rs1760903 CC was a protective factor against TL shortening, and PAH exposure could promote telomere shortening (P < 0.05). Thus, this study reinforces the roles of environmental factors and genetic variations in telomere damage, and provides a theoretical foundation for the early detection of susceptible populations and the establishment of occupational standards.

Benchmark dose analysis for PAHs hydroxyl metabolites in urine based on mitochondrial damage of peripheral blood leucocytes in coke oven workers in China.

OBJECTIVES: The aim was to explore the dose-response relationship between occupational polycyclic aromatic hydrocarbons (PAHs) exposure and mitochondrial damage in coke oven plants workers. METHODS: 544 workers and 238 healthy people were recruited. The ultra-high performance liquid chromatography was used to determine the level of 1-hydroxypyrene, 1-hydroxynaphthalene, 2-hydroxynaphthalene and 3-hydroxyphenanthrene. The real-time fluorescence quantitative polymerase chain reaction was used to determine the mitochondrial DNA copy number (mtDNAcn). The benchmark dose software was used to analyze the benchmark dose. RESULTS: The mtDNAcn in the exposure group was lower than that in the control group. The concentrations of 1-hydroxypyrene, 1-hydroxynaphthalene, 2-hydroxynaphthalene and 3-hydroxyphenanthrene in the exposure group were higher than those in the control group. There is a dose-response relationship between 1-hydroxypyrene, 3-hydroxyphenanthrene and mitochondrial DNA damage. The benchmark dose lower confidence limit (BMDL) of 1-hydroxypyrene were 0.045, 0.004, and 0.058 pg/µg creatinine in the total, male, and female population, respectively. The BMDL of 3-hydroxyphenanthrene were 5.142, 6.099, and 2.807 pg/µg creatinine in the total, male, and female population, respectively. CONCLUSIONS: The BMDL of 1-hydroxypyrene and 3-hydroxyphenanthrene initially explored can provide a reference to establish occupational exposure biological limits.

Tumor microenvironment characterization in cervical cancer identifies prognostic relevant gene signatures.

OBJECTIVE: The aim of this study is to systematically analyze the transcriptional sequencing data of cervical cancer (CC) to find an Tumor microenvironment (TME) prognostic marker to predict the survival of CC patients. METHODS: The expression profiles and clinical follow-up information of CC were downloaded from the TCGA and GEO. The RNA-seq data of TCGA-CESC samples were used for CIBERSORT analysis to evaluate the penetration pattern of TME in 285 patients, and construct TMEscore. Other data sets were used to validate and evaluate TMEscore model. Further, survival analysis of TMEscore related DEGs was done to select prognosis genes. Functional enrichment and PPI networks analysis were performed on prognosis genes. RESULTS: The TMEscore model has relatively good results in TCGA-CESC (HR = 2.47,95% CI = 1.49-4.11), TCGA-CESC HPV infection samples (HR = 2.13,95% CI = 1-4.51), GSE52903 (HR = 2.65, 95% CI = 1.06-6.6), GSE44001 (HR = 2.1, 95% CI = 0.99-4.43). Patients with high/low TMEscore have significant difference in prognosis (log-rank test, P = 0.00025), and the main difference between high TMEscore subtypes and low TMEscore subtypes is immune function-related pathways. Moreover, Kaplan-Meier survival curves found out a list of identified prognosis genes (n = 86) which interestingly show significant enrichment in immune-related functions. Finally, PPI network analysis shows that highly related nodes such as CD3D, CD3E, CD8A, CD27 in the module may become new targets of CC immunotherapy. CONCLUSIONS: TMEscore may become a new prognostic indicator predicting the survival of CC patients. The prognostic genes (n = 86) may help provide new strategies for tumor immunotherapy.

Genetic polymorphisms of metabolic enzyme genes associated with leukocyte mitochondrial DNA copy number in PAHs exposure workers.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) exposure had been reported to be a risk factor of mtDNAcn in our early study. However, the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs-Exposure workers has not been fully evaluated. AIM: The aim of the study was to explore the effect of metabolic enzymes' genetic polymorphisms on mtDNAcn in PAHs-Exposure. METHODS AND RESULTS: We investigated the effects of metabolic enzymes' genetic polymorphisms on mtDNAcn among 544 coke oven workers and 238 office staffs. The mtDNAcn of peripheral blood leukocytes was measured using the Real-time quantitative polymerase chain reaction (PCR) method. PCR and restriction fragment length was used to detect five polymorphisms in GSTT1, GSTM1, GSTP1 rs1695, CYP2E1 rs6413432, and CYP2E1 rs3813867. The mtDNAcn in peripheral blood leukocytes was significantly lower in the exposure group than that in the control group (p < .001). The 1-OHPYR had an increasing trend with the genotypes AA→AG → GG of GSTP1 rs1695 in the control group. Generalized linear model indicated that the influencing factors of mtDNAcn were PAHs-exposure [ß (95% CI) = -0.420 (-0.469, -0.372), p < .001], male [ß (95% CI) = -0.058 (-0.103, -0.012), p = .013], and AA genotype for GSTP1 rs1695 [ß (95% CI) = -0.051 (-0.095, -0.008), p = .020]. CONCLUSION: The individuals carrying the AA genotype of GSTP1 rs1695 may have a lower mtDNAcn due to their weaker detoxification of PAHs.

Estimations of benchmark dose for urinary metabolites of coke oven emissions among workers.

Coke oven emissions (COEs), usually composed of polycyclic aromatic hydrocarbons (PAHs) and so on, may alter the relative telomere length of exposed workers and have been linked with adverse health events. However, the relevant biological exposure limits of COEs exposure has not been evaluated from telomere damage. The purpose of this study is to estimate benchmark dose (BMD) of urinary PAHs metabolites from COEs exposure based on telomere damage with RTL as a biomarker. A total of 544 exposed workers and 238 controls were recruited for participation. High-performance liquid chromatography and qPCR were used to detect concentrations of urinary mono-hydroxylated PAHs and relative telomere length in peripheral blood leukocytes for all subjects. The benchmark dose approach was used to estimate benchmark dose (BMD) and its lower 95% confidence limit (BMDL) of urinary OH-PAHs of COEs exposure based on telomere damage. Our results showed that telomere length in the exposure group (0.75 (0.51, 1.08)) was shorter than that in the control group (1.05 (0.76,1.44))(P < 0.05), and a dose-response relationship was shown between telomere damage and both 1-hydroxypyrene and 3-hydroxyphenanthrene in urine. The BMDL of urinary 1-hydroxypyrene from the optimal model for telomere damage was 1.96, 0.40, and 1.01 (µmol/mol creatinine) for the total, males, and females group, respectively. For 3-hydroxyphenanthrene, the BMDL was 0.94, 0.33, and 0.49 (µmol/mol creatinine) for the total, males, and females. These results contribute to our understanding of telomere damage induced by COEs exposure and provide a reference for setting potential biological exposure limits.

Association between genetic polymorphisms of telomere pathway genes and hydrogen peroxide level in omethoate exposure workers.

OBJECTIVE: The aim of this study was to explore the association between genetic variations in telomere pathway genes and the level of hydrogen peroxide (H2O2) in omethoate exposure workers. METHODS: A total of 180 omethoate exposure workers and 115 healthy controls were recruited. The level of H2O2 in plasma was determined with molybdenic acid colorimetry. Polymerase chain reaction and restriction fragment length was used to detect polymorphisms in POT1 rs1034794, POT1 rs10250202, TERF1 rs3863242, and TERT rs2736098. RESULTS: The level of H2O2 in exposure group (4.26 ± 0.71) was significantly higher than that in control group (3.29 ± 0.46). Generalized linear models indicated that risk factors for the increase H2O2 level were exposure [ß(95 % CI) = 0.951 (0.806, 1.096), P < 0.001] and AA + AT genotype in POT1 rs034794 [ß(95 % CI) = 0.397 (0.049, 0.745), P = 0.025]. CONCLUSION: The increase H2O2 level was associated with omethoate exposure and AA + AT genotypes in POT1 gene rs1034794. It provided a new idea that polymorphisms in telomere pathway genes may indirectly regulate telomere length by influencing oxidative stress.