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Arsenic-related oxidative stress and resultant diseases have attracted global concern, while longitudinal studies are scarce. To assess the relationship between arsenic exposure and systemic oxidative damage, we performed two repeated measures among 5236 observations (4067 participants) in the Wuhan-Zhuhai cohort at the baseline and follow-up after 3 years. Urinary total arsenic, biomarkers of DNA oxidative damage (8-hydroxy-2'-deoxyguanosine (8-OHdG)), lipid peroxidation (8-isoprostaglandin F2alpha (8-isoPGF2α)), and protein oxidative damage (protein carbonyls (PCO)) were detected for all observations. Here we used linear mixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage. Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions. After adjusting for potential confounders, arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners. In cross-sectional analyses, each 1% increase in arsenic level was associated with a 0.406% (95% confidence interval (CI): 0.379% to 0.433%), 0.360% (0.301% to 0.420%), and 0.079% (0.055% to 0.103%) increase in 8-isoPGF2α, 8-OHdG, and PCO, respectively. More importantly, arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α (β: 0.147; 95% CI: 0.130 to 0.164), 8-OHdG (0.155; 0.118 to 0.192), and PCO (0.050; 0.035 to 0.064) in the longitudinal analyses. Our study suggested that arsenic exposure was not only positively related with global oxidative damage to lipid, DNA, and protein in cross-sectional analyses, but also associated with annual increased rates of these biomarkers in dose-dependent manners., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Cadmium (Cd) exposure has become a growing public health issue and the level of urinary Cd is commonly used as the internal biomarker of overall Cd exposure. There has been raised a concern whether the level of Cd in a single spot urine actually reflects individual internal exposure over a long-term period. We aimed to examine the variability of urinary Cd levels over three years. Levels of urinary Cd were determined repeatedly in 2238 general adults during a follow-up of three-year from a community-based prospective study. We estimated the intra-class correlation coefficients (ICCs) of urinary Cd level over three years using the three-level random-effects mixed models to assess their variations. We found that the Pearson correlations for urinary Cd over three years were 0.521 for uncorrected Cd, 0.632 for creatinine (Cr)-corrected Cd, and 0.551 for specific gravity (SG)-corrected Cd, respectively (all P < 0.001). Moderate reproducibility was obtained for urinary Cd over three years, where ICCs of the three methods all exceeded 0.50. Of note, Cr-corrected urinary Cd levels achieved high reproducibility [0.773, 95%CI (0.750-0.794)]. Additionally, positive dose-response associations of smoking amount with Cr-corrected urinary Cd level were observed (P trend <0.05). Our findings suggest that Cr-corrected urinary Cd level in a single measurement was a credible biomarker for the relatively long-term levels of urinary Cd in the general population and cigarette smoking plays a part of urinary Cd exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Short-term effects of fine particulate matter (PM 2.5 ) exposure on lung function have been reported. However, few studies have assessed PM 2.5 exposure on the personal level, and the mechanism underlying the effects of PM 2.5 exposure on lung function remains less clear., Objectives: To evaluate the association between personal PM 2.5 exposure and lung function alteration in general population and to explore the roles of systematic inflammation and oxidative damage in this association., Methods: A total of 7685 lung function tests were completed among 4697 urban adults in Wuhan, China. Plasma C-reactive protein (CRP), urinary 8-iso-prostaglandin-F 2α (8-iso-PGF 2α ) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were measured. Personal PM 2.5 exposure levels were estimated using an estimation model from the actual measurements of individual PM 2.5 levels in 191 participants. Mixed linear models were used to evaluate the association between personal PM 2.5 exposure and lung function. Mediation analyses were conducted to investigate the roles of CRP, 8-iso-PGF 2α and 8-OHdG in above associations., Results: After adjusting for confounders, each 10 μg/m 3 increase in the previous-day personal PM 2.5 exposure was associated with 2.94 mL, 2.02 mL and 16.14 mL/s decreases in forced vital capacity (FVC), forced expiration volume in 1 s (FEV 1 ) and peak expiratory flow, respectively. The associations were more obvious among never smokers compared with current smokers. Cumulative 7-day exposure to PM 2.5 led to the strongest adverse effects on lung function. Among never smokers with high PM 2.5 exposure levels, a positive relationship was observed between personal PM 2.5 level and urinary 8-iso-PGF 2α , and 8-iso-PGF 2α meditated 4.69% and 12.30% of the association between the 7-day moving PM 2.5 concentration and FVC and FEV 1 , respectively. We did not observe a significant positive association between PM 2.5 exposure and plasma CRP or urinary 8-OHdG., Conclusion: Short-term personal exposure to PM 2.5 is associated with reduced pulmonary ventilation function. Urinary 8-iso-PGF 2α partly mediates these associations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Exposure to heavy metals was reported to be associated with heart rate variability (HRV) alteration. However, possible pathway of such association remains unclear. In this research, we investigated the possible role of lipid peroxidation in the associations between urinary heavy metals and HRV. We performed a cross-sectional study using baseline data of Wuhan-Zhuhai cohort. Urinary heavy metals (including lead, barium, antimony, cadmium, zinc, copper, iron and manganese), urinary 8-iso-prostaglandin-F2α levels (common biomarker for lipid peroxidation) and HRV indices (SDNN, r-MSSD, low frequency, high frequency and total power) were measured among 3022 participants. We conducted multivariable linear regression models to quantify associations between urinary 8-iso-prostaglandin-F2α (8-iso-PGF2α) and heavy metals or HRV indices. The potential role of 8-iso-PGF2α in the association of urinary heavy metals with HRV was evaluated through mediation analyses. After adjusting for potential confounders, urinary manganese, iron, copper, zinc, cadmium, antimony and barium were identified to be negatively associated with one or more HRV parameters. Each one-unit growth of log-transformed levels of urinary manganese, iron, copper, zinc, antimony and barium was associated with a 1.9%, 1.5%, 4.7%, 4.0%, 2.7% and 1.3% decrease in SDNN, respectively. We observed positive dose-response relationships between all eight urinary heavy metals and 8-iso-PGF2α, as well as negative association of urinary 8-iso-PGF2α with SDNN and total power (all P trend<0.05). The proportions mediated by 8-iso-PGF2α on SDNN were 4.6% for manganese, 9.3% for iron, 19.8% for antimony and 11.0% for barium. The proportions mediated by 8-iso-PGF2α on total power were 6.9% for manganese and 10.1% for cadmium (all P value < 0.05). This study suggested that urinary manganese, iron, copper, zinc, cadmium, antimony and barium were negatively associated with HRV indices. Lipid peroxidation may partly mediate the associations of urinary manganese, iron, cadmium, antimony and barium with specific HRV indices., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Exposure to fine particulate matter (PM 2.5 ) have been associated with adverse respiratory outcomes, but long-term effect of personal exposure on lung function remains largely unknown. We conducted a panel study of 158 adult residents with 394 measurements of personal PM 2.5 concentration and lung function within six years to investigate the long-term association. Linear mixed models were used to identify the associations between lung function changes in relation to different levels of persistent personal PM 2.5 exposure in three or six years. We further attempted to validate resident areas (city) and smoking status as potential predictors of the long-term PM 2.5 exposure levels (persistently high/ persistently low) by generating ROC curves. Compared with subjects who had persistently low exposure level, those with persistently high levels of personal PM 2.5 exposure had an additional 3.63 % decline in FEV 1 /FVC in three years (-3.63 [-7.25, -0.02]), while 7.15 % decline in six years (-7.15 [-14.27, -0.03]). BMI can modify the association. The AUCs were 0.68 (95 %CI: 0.54, 0.82), 0.75 (0.64, 0.86), and 0.82 (0.71, 0.93) for models including smoking status, resident areas, and smoking status combining resident areas respectively. These findings provide new evidence for the long-term effect of personal PM 2.5 exposure on lung function decline., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) is related to decreased lung function. However, whether oxidative damage is involved in this relationship remains unclear. This study was aimed to explore the potential mediating role of oxidative DNA or lipid damage in the association between PAH exposure and lung function., Methods: The urinary levels of monohydroxy polycyclic aromatic hydrocarbon metabolites (OH-PAHs) and lung function parameters were measured among 3367 participants from the baseline of the Wuhan-Zhuhai cohort. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane (8-iso-PGF2α) were determined to evaluate the individuals' oxidative DNA and lipid damage degrees, respectively. Linear mixed models were used to investigate the associations of urinary OH-PAHs, 8-OHdG and 8-iso-PGF2α with lung function parameters. Mediation analysis was further conducted to assess the potential role of oxidative damage in the association between urinary OH-PAHs and lung function., Results: Each one-percentage increase in the sum of urinary OH-PAHs, high-molecular-weight or low-molecular-weight OH-PAHs (ƩOH-PAHs, ƩHMW OH-PAH or ƩLMW OH-PAHs, respectively) was associated with a 0.2152-, 0.2076- or 0.1985- ml decrease in FEV 1 , and a 0.1891-, 0.2195- or 0.1634- ml decrease in FVC, respectively. Additionally, significantly positive dose-response relationships of ƩOH-PAHs, ƩHMW OH-PAH and ƩLMW OH-PAHs with urinary 8-OHdG or 8-iso-PGF2α, as well as an inverse dose-response relationship between urinary 8-OHdG and FVC, were observed (all P for trend < 0.05). Mediation analysis indicated that urinary 8-OHdG mediated 14.22% of the association between ƩHMW OH-PAH and FVC., Conclusion: Higher levels of oxidative DNA damage might be involved in the decreased levels of FVC caused by high-molecular-weight PAH exposure.

Objective: Acrylamide exposure from daily-consumed food has raised global concern. We aimed to assess the exposure-response relationships of internal acrylamide exposure with oxidative DNA damage, lipid peroxidation, and fasting plasma glucose (FPG) alteration and investigate the mediating role of oxidative DNA damage and lipid peroxidation in the association of internal acrylamide exposure with FPG., Research Design and Methods: FPG and urinary biomarkers of oxidative DNA damage (8-hydroxy-deoxyguanosine [8-OHdG]), lipid peroxidation (8-iso-prostaglandin-F2α [8-iso-PGF2α]), and acrylamide exposure (N-acetyl-S-[2-carbamoylethyl]-l-cysteine [AAMA], N-acetyl-S-[2-carbamoyl-2-hydroxyethyl]-l-cysteine [GAMA]) were measured for 3,270 general adults from the Wuhan-Zhuhai cohort. The associations of urinary acrylamide metabolites with 8-OHdG, 8-iso-PGF2α, and FPG were assessed by linear mixed models. The mediating roles of 8-OHdG and 8-iso-PGF2α were evaluated by mediation analysis., Results: We found significant linear positive dose-response relationships of urinary acrylamide metabolites with 8-OHdG, 8-iso-PGF2α, and FPG (except GAMA with FPG) and 8-iso-PGF2α with FPG. Each 1-unit increase in log-transformed level of AAMA, AAMA + GAMA (ΣUAAM), or 8-iso-PGF2α was associated with a 0.17, 0.15, or 0.23 mmol/L increase in FPG, respectively ( P and/or P trend < 0.05). Each 1% increase in AAMA, GAMA, or ΣUAAM was associated with a 0.19%, 0.27%, or 0.22% increase in 8-OHdG, respectively, and a 0.40%, 0.48%, or 0.44% increase in 8-iso-PGF2α, respectively ( P and P trend < 0.05). Increased 8-iso-PGF2α rather than 8-OHdG significantly mediated 64.29% and 76.92% of the AAMA- and ΣUAAM-associated FPG increases, respectively., Conclusions: Exposure of the general adult population to acrylamide was associated with FPG elevation, oxidative DNA damage, and lipid peroxidation, which in turn partly mediated acrylamide-associated FPG elevation., (© 2020 by the American Diabetes Association.)

Exposure to 1-bromopropane (1-BP) has been reported to cause glutathione depletion and increase the level of oxidative damage, which play critical roles in diabetes. However, the possible associations or mechanisms of the exposure of 1-BP with the plasma glucose level and the risk of diabetes are unclear. In this study, we explored the relationships of the urinary 1-BP metabolite N-Acetyl-S-(n-propyl)-l-cysteine (BPMA) with fasting plasma glucose (FPG) levels and the risk of diabetes, and the mediating role of oxidative damage in the above relationships in 3678 urban adults from the Wuhan-Zhuhai cohort in China. We found a significant dose-response relationship between BPMA and FPG levels with a β of 0.09 (95 % CI: 0.04, 0.14). In addition, mediating effect of urinary BPMA on FPG levels was observed depending on elevated 8-isoprostane level, with a median proportion of 32.06 %. Furthermore, we observed a significant association between urinary BPMA and the risk of diabetes, with an adjusted odds ratio of 1.34 (1.18, 1.52) for all participants. These results indicated that urinary 1-BP metabolites were positively associated with FPG levels and the risk of diabetes among urban adults in this cross-sectional study. Lipid peroxidation partially mediated the association between urinary 1-BP metabolites and FPG levels., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

MicroRNAs (miRNAs) are a class of small, non-coding RNAs with a post-transcriptional regulatory function on gene expression and cell processes, including proliferation, apoptosis and differentiation. In recent decades, miRNAs have attracted increasing interest to explore the role of epigenetics in response to air pollution. Air pollution, which always contains kinds of particulate matters, are able to reach respiratory tract and blood circulation and then causing epigenetics changes. In addition, extensive studies have illustrated that miRNAs serve as a bridge between particulate matter exposure and health-related effects, like inflammatory cytokines, blood pressure, vascular condition and lung function. The purpose of this review is to summarize the present knowledge about the expression of miRNAs in response to particulate matter exposure. Epidemiological and experimental studies were reviewed in two parts according to the size and source of particles. In this review, we also discussed various functions of the altered miRNAs and predicted potential biological mechanism participated in particulate matter-induced health effects. More rigorous studies are worth conducting to understand contribution of particulate matter on miRNAs alteration and the etiology between environmental exposure and disease development., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Urinary polycyclic aromatic hydrocarbon (PAH) metabolites, biomarkers of internal PAH exposure, are commonly used to explore the effects of PAH on human health. However, the correlation between environmental PAH exposure and the species or levels of urinary PAH metabolites remains unclear. We collected detailed information on PAH exposure sources, including cigarette smoking, cooking, traffic and diet habits via structured questionnaires, and determined 12 urinary monohydroxylated PAH metabolites (OH-PAHs) among 4092 participants from the Wuhan-Zhuhai cohort. Linear mixed models and generalized linear models were conducted to explore the associations of urinary metabolite levels with single or multiple PAH exposure sources. We also calculated the standardized regression coefficients to further compare the contributions of different sources to urinary OH-PAH levels. Our results showed that increasing levels of urinary 1-, 2-hydroxynaphthalene (1-, 2- OHNa) and 2-hydroxyfluorene (2-OHFlu) were significantly correlated with tobacco smoking (all P < 0.01). The concentrations of 1-, 2- OHNa and 9-hydroxyfluorene (9-OHFlu) were positively correlated with dietary intake (all P < 0.05). Individuals who spent a long time in traffic showed elevated levels of 9-OHFlu and 1-hydroxyphenanthrene (1-OHPh) compared with individuals who spent a short time in traffic (all P < 0.05). Self-cooking was associated only with elevated 1-hydroxypyrene (1-OHP) levels. Moreover, good kitchen ventilation resulted in significantly decreased urinary low-molecular-weight OH-PAH levels. These findings suggested that cigarette smoking, self-cooking, high dietary PAH intake and a long time spent in traffic were associated with increased levels of specific urinary PAH metabolites, and good kitchen ventilation effectively reduced the exposure to low-molecular-weight PAHs in self-cooking participants., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Cadmium (Cd) is a toxic heavy metal that is widely distributed in the environment. However, the mechanisms linking Cd exposure and type 2 diabetes risks are not completely elucidated. In this study, we aim to investigate the roles of C-reactive protein (CRP) on the association between urinary Cd and type 2 diabetes risk. We determined urinary Cd and plasma CRP concentrations among 3,140 adults from Wuhan-Zhuhai cohort. Dose-response relationships between urinary Cd, plasma CRP, and type 2 diabetes were explored using multivariate logistic regression and linear mixed regression models. Mediation analysis was performed to investigate the role of plasma CRP in the associations between urinary Cd and type 2 diabetes risk. With adjustment for potential confounders, the odds ratios (ORs) of type 2 diabetes showed an upward trend when urinary Cd concentration gradually increased (P trend <0.01). Significantly positive dose-response relationships were observed between urinary Cd and plasma CRP, as well as between plasma CRP and type 2 diabetes risk. Compared to those when both Cd and CRP levels were low, the adjusted ORs (95%CI) of type 2 diabetes was the highest [2.053(1.395-3.020)] in individuals with high levels of urinary Cd and plasma CRP. Mediation analysis estimated that plasma CRP mediated 4.01% of the association between urinary Cd and type 2 diabetes risk [mediating effect: OR (95%CI) = 1.019(1.002-1.057)]. Individuals with high levels of urinary Cd and plasma CRP had a much higher risk of type 2 diabetes. Plasma CRP may serve as a mediator in the association between urinary Cd and type 2 diabetes risk, providing clues for further study on the biological pathway for type 2 diabetes related to Cd exposure., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Polychlorinated dibenzo-dioxins and polychlorinated dibenzo-furans (PCDD/Fs) have been reported to induce reactive oxygen species and oxidative stress, but the dose-response relationships have not been explored in molecular epidemiological studies. In this study, a total of 602 participants were recruited, comprising of 215 foundry workers, 171 incineration workers and 216 residents living more than 5 km away from the plants as the reference group. Individual PCDD/Fs exposures were estimated according to PCDD/Fs levels of working and living ambient air and daily foods. Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-iso-prostaglandin-F2α (8-isoPGF2α) were determined to reflect oxidatively generated damage to DNA and lipid. Generalized linear models were used to access the associations between PCDD/Fs exposure and oxidative stress biomarkers. We found that PCDD/Fs exposure and urinary oxidative stress biomarkers of workers were all higher than those of the reference group. Significantly positive exposure-response relationships between individual PCDD/Fs exposures and urinary 8-oxodG and 8-iso-PGF2α were found. Each 1-unit increase in ln-transformed levels of PCDD/Fs exposure generated a 0.78 nmol/mmol creatinine increase in ln-transformed 8-oxodG and a 0.50 ng/mmol creatinine increase in ln-transformed 8-isoPGF2α in foundry workers, a 0.49 nmol/mmol creatinine increase in ln-transformed 8-oxodG and a 0.26 ng/mmol creatinine increase in ln-transformed 8-isoPGF2α in incineration workers, compared with the reference group. And such associations were not modified by tobacco use. Our findings could help to understand the dose-response relationships between PCDD/Fs and oxidatively generated damage to DNA and lipid, and provide an epidemiologic basis for conducting research on the carcinogenesis and other toxicity mechanisms of PCDD/Fs., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The relations of polycyclic aromatic hydrocarbons (PAHs) exposure with platelet indices remain unclear. Based on the baseline data from the Wuhan-Zhuhai Cohort Study, we used generalized linear model, multivariate logistic regression analysis and restricted cubic splines (RCS) to assess linear and nonlinear relationship of PAHs exposure with platelet indices. The results showed that among Wuhan individuals, there were the non-linear relations between total hydroxynaphthalene (ΣOHNa) and mean platelet volume (MPV) or ratio of mean platelet volume to platelet count (MPVP), total hydrophenanthrene (ΣOHPh) and MPV or platelet distribution width (PDW), the sum concentration of urinary monohydroxylated metabolites of PAHs (ΣOH-PAHs) and ratio of platelet count to lymphocyte count (PLR) or MPVP, 1-hydropyrene (1-OHP) and PLR or PDW. But among Zhuhai individuals, neither linear nor non-linear relations were found between each of OH-PAHs or ΣOH-PAHs and platelet indices. The findings indicate that serum MPV and MPVP may be independent biomarkers of effects of exposing to environmental PAHs on human bodies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Previous publications have indicated that some metals are associated with an increased prevalence of type 2 diabetes mellitus (T2DM); however, the mechanisms remain largely unknown. This study aimed to quantify the associations of oxidative DNA damage with urinary metals and prevalence of T2DM among the general population, and further to assess the role of oxidative DNA damage in mediating the association of urinary metals with prevalence of T2DM. Diagnoses of T2DM were performed clinically or by measuring fasting levels of plasma glucose ≥7.0mmol/L. Concentrations of urinary metals and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in 2127 participants were measured using inductively coupled plasma-mass spectrometry and high-performance liquid chromatography. Relationships among urinary metals, 8-OHdG (a biomarker for oxidative DNA damage), and prevalence of T2DM were analyzed using mediation analysis. After adjusting for covariates, we found that the log-transformed levels of urinary copper, arsenic, selenium, molybdenum, and antimony were positively associated with prevalence of T2DM. Urinary 8-OHdG was not only positively correlated with copper, arsenic, selenium, and antimony in an upwardly trending, dose-responsive manner but was also positively associated with prevalence of T2DM (odds ratio (OR): 1.95; 95% CI: 1.17-3.24). Mediation analysis estimated that urinary 8-OHdG mediated 13.22% and 8.84% of associations between prevalence of T2DM and concentrations of urinary arsenic and antimony, respectively (all P value<0.05). Our findings suggested that urinary arsenic and antimony concentrations were associated with an increased prevalence of T2DM by a mechanism partly involving oxidative DNA damage., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Inflammation may play an important role in the association between exposure to polycyclic aromatic hydrocarbons (PAHs) and atherosclerotic cardiovascular disease (ASCVD) risk. However, the underlying mechanisms remain unclear., Objectives: To investigate the association of PAHs exposure with ASCVD risk and effects of mean platelet volume (MPV) or Club cell secretory protein (CC16) on the association., Methods: A total of 2022 subjects (689 men and 1333 women) were drawn from the baseline Wuhan residents of the Wuhan-Zhuhai Cohort study. Data on demography and the physical examination were obtained from each participant. Urinary monohydroxy PAH metabolites (OH-PAHs) levels were measured by a gas chromatography-mass spectrometry. We estimated the association between each OH-PAHs and the 10-year ASCVD risk or coronary heart disease (CHD) risk using logistic regression models, and further analyze the mediating effect of MPV or plasma CC16 on the association by using structural equation modeling., Results: The results of multiple logistic regression models showed that some OH-PAHs were positively associated with ASCVD risk but not CHD risk, including 2-hydroxyfluoren (β = 1.761; 95% CI: 1.194-2.597), 9-hydroxyfluoren (β = 1.470; 95% CI: 1.139-1.898), 1-hydroxyphenanthrene (β = 1.480; 95% CI: 1.008-2.175) and ΣOH-PAHs levels (β = 1.699; 95% CI: 1.151-2.507). The analysis of structural equation modeling shows that increased MPV and increased plasma CC16 levels contributed 13.6% and 15.1%, respectively, to the association between PAHs exposure and the 10-year ASCVD risk (p < 0.05)., Conclusions: Exposure to PAHs may increase the risk of atherosclerosis, which was partially mediated by MPV or CC16., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Previous studies have reported an association of exposure to polycyclic aromatic hydrocarbons (PAHs) with lung function decline or cardiovascular diseases, or reduced lung function with 10-year cardiovascular (CV) risk. We analyzed risk factors for the 10-year Framingham CV risk using multiple logistic regression, and examined the mediational effect of reduced lung function on the association between exposure to PAHs and FRS using the post-exploratory structural equation modeling. Participants (n = 2268) were drawn from the Wuhan residents at baseline from the Wuhan-Zhuhai Cohort Study. They completed the physical examination, measurements of lung function and urinary monohydroxylated-PAHs (OH-PAHs). In all individuals, we found a dose-response relationship of PAHs exposure, forced expiratory volume in 1s (FEV1) or forced vital capacity (FVC) with the 10-year CV risk. The proportions of FEV1 and FVC mediation effects in association of PAH exposure with the10-year CV risk were 35% and 24%, respectively. The findings indicated that PAHs exposure or reduced lung function increased the 10-year CV risk. Impaired lung function may partly contribute to increase in the 10-year CV risk regarding exposure to PAHs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Some studies have shown an association between obesity or exposure to polycyclic aromatic hydrocarbons (PAHs) and the risk of diabetes. This study aimed to investigate the interaction of obesity and urinary monohydroxy-PAHs (OH-PAHs) on diabetes. Individuals (n = 2716) were drawn from the baseline survey of the Wuhan-Zhuhai Cohort Study. They completed the physical examination, measurements of lung function, biochemical indices and urinary OH-PAHs levels. Additive effect of obesity and urinary ΣOH-PAHs levels on diabetes was assessed by calculating the relative excess risk due to interaction (RERI) and the attributable proportion (AP) due to interaction. Several urinary OH-PAHs were positively associated with diabetes in individuals with central obesity or normal weight (p < 0.05 for all). Among individuals with poor lung function, the RERI between urinary ΣOH-PAHs and waist circumstance (WC, RERI: 0.866, 95% CI: -0.431, 2.164, p = 0.192) or waist-to-height ratio (WHtR, RERI: 1.091, 95% CI: -0.124, 2.305, p = 0.078) was found; the AP due to the interaction between urinary ΣOH-PAHs and WC or WHtR was 0.383 (95% CI: -0.07, 0.80, p = 0.086) or 0.465 (95% CI: 0.019, 0.912, p = 0.04). The results indicated that central obesity may enhance the effect of exposure to background PAHs on diabetes in individuals with poor lung function., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Global DNA methylation levels can be determined by environmental and genetic factors. There are emerging evidences that methylation status can be modified as exposed to environmental factors such as PM 2.5 , but the genetic determinants are still largely unknown. To explore whether genetic variants contribute to global DNA methylation levels with consideration of environmental exposures, we systematically evaluated the association between genetic variants and global DNA methylation levels in 301 subjects from three cities in southern, central and northern China with different PM 2.5 exposure levels (Zhuhai, Wuhan and Tianjin, respectively). Personal 24-h PM 2.5 exposure levels and global DNA methylation levels for each subject were evaluated. Using Illumina Human Exome BeadChip, 241,305 SNVs was genotyped and assessed for their association with global DNA methylation levels. We found that after adjusting for age, gender, PM 2.5 exposure level, pack-years of smoking and BMI, 14 SNVs were consistently associated with global DNA methylation levels with pooled P≤1.00×10 -4 after meta-analysis of three cohorts, in which 8 SNVs together with age were independent factors modifying global DNA methylation levels. Joint analysis of these identified SNVs showed a significant allele-dosage association between the number of variants and global DNA methylation levels (P=1.82×10 -23 ). In particular, we detected a significant multiplicative interaction between rs4344916 on chromosome 2p22.3 and PM 2.5 exposure on global DNA methylation level (P=0.0095). Our findings indicate that genetic variants alone or in combination with PM 2.5 play an important role in modifying individual global DNA methylation levels., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Health conditions may greatly modify the association between particulate matter (PM) and heart rate variability (HRV), but whether the modification of PM effect by coronary artery disease (CAD) risk status depends on the PM levels remains unknown. We investigated the associations between personal exposures to PM with aerodynamic diameter of ≤10μm (PM10) and ≤2.5μm (PM2.5) and concurrent HRV, and whether the effect of PM on HRV was modified by Framingham risk score (FRS) in healthy subjects with different PM exposure levels. Personal exposures to PM10 and PM2.5 were measured for 24h in 152 volunteers of community residents who were free of cardiovascular disease in two cities (Zhuhai and Wuhan) that differ in air quality. Simultaneously, 24h HRV indices were obtained from 3-channel Holter monitor. FRS was calculated based on age, sex, lipid profiles, blood pressure, diabetes, and smoking status. Linear regression models were constructed after adjusting for potential confounders. We found significant decrease in total power (TP) and low power (LF) with increased PM10 concentrations (P for trend<0.05) in the high PM levels city (Wuhan) and total population, but not in the low PM levels city (Zhuhai). We also observed significant modification of FRS on PM10 effect in Wuhan. Interestingly, elevated PM10 was associated in a greater decreased HRV in the low FRS subgroup, but not in the high FRS subgroup. However, we did not find any significant main effects of PM2.5 or PM2.5-FRS interactions on HRV in city-specified or city-combined analyses. Overall, the findings indicate that individual coronary risk profiles may modulate the association between particulate air pollution and HRV in high PM exposure levels., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Epidemiological studies have suggested an association between external estimates of exposure to metals in air particles and altered heart rate variability (HRV). However, studies on the association between internal assessments of metals exposure and HRV are limited., Objectives: The purpose of this study was to examine the potential association between urinary metals and HRV among residents of an urban community in Wuhan, China., Methods: We performed a cross-sectional analysis of 23 urinary metals and 5-min HRV indices (SDNN, standard deviation of normal-to-normal intervals; r-MSSD, root mean square of successive differences in adjacent normal-to-normal intervals; LF, low frequency; HF, high frequency; TP, total power) using baseline data on 2,004 adult residents of Wuhan., Results: After adjusting for other metals, creatinine, and other covariates, natural log-transformed urine titanium concentration was positively associated with all HRV indices (all p < 0.05). Moreover, we estimated negative associations between cadmium and r-MSSD, LF, HF, and TP; between lead and r-MSSD, HF, and TP; and between iron, copper, and arsenic and HF, SDNN, and LF, respectively, based on models adjusted for other metals, creatinine, and covariates (all p < 0.10). Several associations differed according to cardiovascular disease risk factors. For example, negative associations between cadmium and r-MSSD were stronger among participants ≤ 52 years of age (vs. > 52), current smokers (vs. nonsmokers), body mass index < 25 kg/m2 (vs. ≥ 25), and among those who were not hypertensive., Conclusions: Urine concentrations of several metals were associated with HRV parameters in our cross-sectional study population. These findings need replication in other studies with adequate sample sizes.

The incidence of diabetes is increasing rapidly in Chinese population, and it has been postulated that environmental factors may play a role in the etiology of diabetes. Therefore, we aimed to investigate the association between PAHs exposure and risk of diabetes in a community-based population of 2824 participants with completed questionnaires, measurements of biochemical indices, and urinary PAHs metabolites. We found that elevated urinary PAHs metabolites were associated, in a dose-dependent manner, with increased risk of diabetes. Particularly, these associations were more evident in subjects who were female, less than 55 years old, nonsmokers, and normal weight. In addition, there was a modest improvement in diabetes discrimination of prediction models when incorporating certain PAHs metabolites into conventional risk factors (CRF). Overall, our data suggested that there may be a dose-dependent relationship between PAHs metabolites and risk of diabetes among general Chinese population., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Particulate air pollution has been recognized to be associated with a wide range of adverse health effects, including increased mortality, morbidity, exacerbation of respiratory conditions. However, earlier physiological or pathological changes or long-term bodies' reaction to air pollutants have not been studied in depth in China. The Wuhan-Zhuhai (WHZH) cohort study is designed to investigate the association between air pollutants exposure and physiological or pathological reactions on respiratory and cardiovascular system., Methods/design: The cohort is a community-based prospective study that includes 4812 individuals aged 18-80 years. The collections of data were conducted from April to May 2011 in Wuhan city and in May 2012 in Zhuhai city. At baseline, data on demographic and socioeconomic information, occupational history, family disease history, lifestyle, cooking mode, daily travel mode, physical activity and living condition have been collected by questionnaires. Participants underwent an extensive physical examination, including anthropometry, spirometry, electrocardiography, and measurements of blood pressure, heart rate, exhaled nitric oxide and carbon monoxide. Potential conditions in the lung, heart, liver, spleen, and skin were synchronously performed. In addition, samples of morning urine, fasting blood serum and plasma were collected during physical health examination. DNA were extracted and were stored at -80°C. Environment concentrations of particulate matter and chemicals were determined for 15 days in each of four seasons. Participants are followed for physiological or pathological changes or incidence of cardiopulmonary diseases every 3 years., Discussion: The results obtained in WHZH cohort study may increase a better understanding of the relationship between particulate air pollution and its components and possible health damages. And the potential mechanisms underlying the development of cardiopulmonary diseases has implications for the development of prevention and treatment strategies.

Objectives: To investigate the effects of the urinary metabolite profiles of background exposure to the atmospheric pollutants polycyclic aromatic hydrocarbon (PAH) and Framingham risk score (FRS), which assesses an individual's cardiovascular disease risk, on heart rate variability (HRV)., Methods: The study conducted from April to May 2011 in Wuhan, China, included 1978 adult residents with completed questionnaires, physical examinations, blood and urine samples, and 5-min HRV indices (including SD of all normal to normal intervals (SDNN), root mean square successive difference (rMSSD), low frequency (LF), high frequency (HF) and their ratio (LF/HF), and total power) obtained from 3-channel Holter monitor. 12 urinary PAH metabolites were measured by gas chromatography-mass spectrometry. FRS was calculated by age, sex, lipid profiles, blood pressure, diabetes and smoking status. Linear regression models were constructed after adjusting for potential confounders., Results: Elevated total concentration of hydroxynaphthalene (ΣOHNa) was significantly associated, in a dose-responsive manner, with decreased SDNN and LF/HF (ptrend=0.014 and 0.007, respectively); elevated total concentration of hydroxyfluorene (ΣOHFlu) was significantly associated with reduced SDNN, LF and LF/HF (ptrend=0.027, 0.003, and <0.0001, respectively); and elevated total concentration of all PAH metabolites (ΣOH-PAHs) was associated with decreased LF and LF/HF (ptrend=0.005 and <0.0001, respectively). Moreover, increasing quartiles of FRS were significantly associated with decreased HRV indices, except LF/HF (all ptrend<0.0001). Interestingly, individuals in low-risk subgroups had greater decreases in SDNN, LF and LF/HF in relation to ΣOH-PAHs, ΣOHNa and ΣOHFlu than those in high-risk subgroups (all p<0.05)., Conclusions: Environmental PAH exposure may differentially affect HRV based on individual coronary risk profiles.

Environmental pyrethroids are concerning due to their widespread residues and potential implications on human health. We aimed to assess the association of pyrethroid exposure with glucose homeostasis and examine the interaction between obesity and pyrethroid exposure. A total of 4233 US general adults from the National Health and Nutrition Examination Survey with measured urinary pyrethroid metabolites, fasting plasma glucose (FPG), fasting insulin (FINS), and glycated hemoglobin A1c (HbA1c) were included in the study. The homeostasis model assessment (HOMA2) calculator was utilized to assess insulin resistance (HOMA2-IR), insulin sensitivity (HOMA2-IS), and beta-cell function (HOMA2-β). We estimated the associations of pyrethroid metabolites with glucose homeostasis parameters (FPG, FINS, HbA1c, HOMA2-IR, HOMA2-IS, and HOMA2-β) using multivariate linear regression models and restricted cubic spline models and further assessed the interaction between obesity and pyrethroid metabolites on glucose dyshomeostasis. Urinary 3-phenoxybenzoic acid (3-PBA) was the most detected pyrethroid metabolite (81%) with a median concentration of 0.43 (interquartile range 0.20–1.01) μg/g urinary creatinine. Compared with the participants in the lowest quartile, those in the highest quartile of 3-PBA had a 1.93% (95% confidence interval: 0.46%, 3.42%), 6.69% (1.96%, 11.64%), 1.60% (0.64%, 2.57%), 7.06% (2.33%, 12.01%), −6.59% (−10.72%, −2.28%), and 1.10% (−2.69%, 5.04%) alteration in FPG, FINS, HbA1c, HOMA2-IR, HOMA2-IS, and HOMA2-β, respectively. The restricted cubic spline model displayed a linear positive association between 3-PBA and FPG, FINS, HbA1c, and HOMA2-IR, and a negative association with HOMA2-IS (all P for overall <0.05 and P for non-linear >0.05). Additionally, the association between urinary 3-PBA and FPG was modified by general obesity (P for interaction <0.05), with a more pronounced association observed in obese participants than in non-obese participants. Our findings suggested that pyrethroid exposure was associated with glucose dyshomeostasis. General obesity significantly heightened the association between pyrethroid exposure and increased FPG level. [Display omitted] • We assessed the link with glucose homeostasis of pyrethroids in US general adults. • Urinary pyrethroid metabolite 3-PBA was associated with glucose dyshomeostasis. • The relationship of urinary 3-PBA with FPG was modified by general obesity. • Obesity exacerbated the increased FPG associated with urinary 3-PBA. [ABSTRACT FROM AUTHOR]

Crystalline silica has been classified as a human carcinogen by the International Agency for Research on Cancer (Lyon, France); however, few previous studies have provided quantitative data on silica exposure, silicosis, and/or smoking. We investigated a cohort in China (in 1960–2003) of 34,018 workers without exposure to carcinogenic confounders. Cumulative silica exposure was estimated by linking a job-exposure matrix to work history. Cox proportional hazards model was used to conduct exposure-response analysis and risk assessment. During a mean 34.5-year follow-up, 546 lung cancer deaths were identified. Categorical analyses by quartiles of cumulative silica exposure (using a 25-year lag) yielded hazard ratios of 1.26, 1.54, 1.68, and 1.70, respectively, compared with the unexposed group. Monotonic exposure-response trends were observed among nonsilicotics (P for trend < 0.001). Analyses using splines showed similar trends. The joint effect of silica and smoking was more than additive and close to multiplicative. For workers exposed from ages 20 to 65 years at 0.1 mg/m3 of silica exposure, the estimated excess lifetime risk (through age 75 years) was 0.51%. These findings confirm silica as a human carcinogen and suggest that current exposure limits in many countries might be insufficient to protect workers from lung cancer. They also indicate that smoking cessation could help reduce lung cancer risk for silica-exposed individuals. [ABSTRACT FROM PUBLISHER]

Background: Crystalline silica is considered as one of the most common and serious occupational hazards to workers' health. Although its association with lung cancer has been studied for many decades, the conclusion remains somewhat controversial. Our objectives are to review and summarize the epidemiological evidence on the relationship between occupational silica exposure and risk of lung cancer and to provide an update on this major occupational health concern.Methods: Eligible studies up to 29 April 2016 were identified. Pooled effect estimates were calculated according to the reported outcome and the study design. Cohort, case control and proportional mortality studies were examined separately. Studies reporting results according to silicotic status were grouped together and analyzed. Due to the significant amount of heterogeneity expected, random effects models were implemented. Subgroup and meta-regression analyses (both univariate and multivariate) were performed in an attempt to explain heterogeneity. Studies which had adequate exposure characterization were selected to find out whether there was an exposure-response relationship between silica and lung cancer.Results: The risk of lung cancer was found to be elevated in both silicotics and non-silicotics. The pooled standardized mortality ratio (SMR) was 2.32 with a 95 % confidence interval (95 % CI) of 1.91-2.81 and 1.78 (95 % CI 1.07-2.96) respectively. The pooled standardized incidence ratio (SIR) was 2.49 (95 % CI 1.87-3.33) and 1.18 (95 % CI 0.86-1.62) respectively. Subgroup analysis showed that workers in the mining industry had the highest risk of lung cancer with a pooled SMR of 1.48 (95 % CI 1.18-1.86) and the weakest association was seen in potteries with a pooled SMR of 1.14 (95 % CI 1.05-1.23). A positive exposure-response relation was found between cumulative silica exposure and risk of lung cancer.Conclusion: The results of our meta-analysis supported the carcinogenic role of silica on the lungs, which was more pronounced at higher levels of exposure, in the presence of silicosis and in the mining industry. Further research is needed to evaluate whether non-silicotics are truly at risk, whether a predisposing factor would explain this potential risk, and to determine the mechanism of carcinogenicity of silica in humans. [ABSTRACT FROM AUTHOR]

Silica particles are commonly encountered in natural and industrial activities. Long-term environmental exposure to silica can result in silicosis, which is characterized by chronic inflammation and abnormal tissue repair in lung. To uncover the role of m6A modification in silica-induced pulmonary inflammation, we conducted this study using established mouse and macrophage models. In this study, the aerodynamic diameter of silica particles was approximately 1–2 µm. We demonstrated that silica exposure in mice caused pulmonary inflammation and increased global m6A modification levels, the downregulation of alkB homolog 5 (ALKBH5) might contribute to this alteration. Besides, we found that F4/80, a macrophage-specific biomarker, was co-expressed with ALKBH5 through dual immunofluorescent staining. In vitro studies using MeRIP assays suggested that Slamf7 was a target gene regulated by m6A modification, and specific inhibition of ALKBH5 increased Slamf7 expression. Mechanistically, ALKBH5 promoted m6A modification of Slamf7, which decreased Slamf7 mRNA stability in an m6A-dependent manner, ultimately regulating Slamf7 expression. In addition, silica exposure activated PI3K/AKT and induced macrophage autophagy. Inhibition of Slamf7 promoted autophagy, reduced the secretion of pro-inflammatory cytokines, and improved silica-induced pulmonary inflammation. In summary, ALKBH5 can regulate silica-induced pulmonary inflammation by modulating Slamf7 m6A modification and affecting the function of macrophage autophagy. [Display omitted] • Silica-caused pulmonary inflammation was accompanied by increased m6A modification. • ALKBH5 regulated the alteration of m6A modification induced by silica exposure. • Slamf7 was a target gene in silica-induced inflammation modulated by ALKBH5. • Macrophage autophagy regulated by Slamf7 was associated with pulmonary inflammation. [ABSTRACT FROM AUTHOR]

Abstract: Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) have been reported as possible carcinogenic hazards to humans. However, epidemiological studies on their carcinogenic roles are limited. The current study was designed to determine the concentrations and characteristics of PCDD/Fs and evaluate their association with cancer mortality in exposed workers in one automobile foundry factory. PCDD/F levels in factory and surrounding environment were analyzed through air and settling dust sampling. The cancer mortalities among workers in this foundry factory were calculated using data from a cohort study. The results showed that the PCDD/F concentrations of air in workplace ranged 0.36–2.25pgWorld Health Organization-Toxic Equivalent (WHO-TEQ) Nm−3 (average 1.01pgWHO-TEQNm−3), which were 1.16–7.26 times higher than those outside the factory. The PCDD/F concentrations of settling dust in the workplace ranged 3.34–18.64pgWHO-TEQg−1 (average 8.25pgWHO-TEQg−1), which were lower than those just outside the factory (average 16.13pgWHO-TEQg−1). Furthermore, a cohort study of workers in this factory with average follow-up of 24.52years showed that cancer was the leading cause of death, with significant elevated mortality (standardized mortality ratio (SMR)=1.70, 95% confidence interval (CI): 1.35–2.13) among workers, when compared with Chinese national mortality. The cancer mortality among front-line workers was increased significantly (adjusted relative risk (RR)=1.73, 95% CI: 1.14–2.60), particularly among melting and casting workers, when compared with that among assistant workers. Our results indicated that there was a dose–response relationship between PCDD/F exposure and cancer mortality among foundry workers. [Copyright &y& Elsevier]