Wenjun Yin

Tris(2-chloroethyl)phosphate-induced cell growth arrest via attenuation of SIRT1-independent PI3K/Akt/mTOR pathway

Tris(2‐chloroethyl)phosphate (TCEP) as an organophosphorus flame retardant and plasticizer has been widely used in industrial and household products. It not only was detected in residential indoor air and dust, surface and drinking water, but also in human plasma and breast milk, and tissue samples of liver, kidneys and brain from rodents. TCEP is classified as carcinogenic category 2 and toxic for reproduction category 1B. Sufficient evidence from experimental animals indicated carcinogenicity of TCEP in the liver, and kidneys as well as cell loss in the brain. However, the underlying mechanisms of TCEP‐induced hepatotoxicity are mostly unknown. We investigated the in vitro effects of TCEP as well as TCEP‐induced cell growth in the L02 and HepG2 cells through the PI3K/Akt/mTOR pathway. We found that TCEP reduced cell viability of these cell lines, induced the cell growth arrest, upregulated mRNA and protein levels of SIRT1, and attenuated the PI3K/Akt/mTOR pathway. However, growth arrest of the L02 and HepG2 cells were aggravated after inhibiting the SIRT1 expression with EX‐527. The findings above suggested that TCEP induced the cell growth arrest of L02 and HepG2 cells via attenuation of the SIRT1‐independent PI3K/Akt/mTOR pathway. Copyright

Association of individual-level concentrations and human respiratory tract deposited doses of fine particulate matter with alternation in blood pressure

Fine particulate matter (PM2.5) contributes to the risk of cardiovascular events, partially owing to its deposition in the human respiratory tract. To investigate short-term effects of ambient PM2.5 exposure on alternation of blood pressure (BP), this study was conducted during the winter-summer period between 2014 and 2015. The study included 106 community residents in Wuhan city, China. We repeatedly monitored the household and outdoor PM2.5 concentrations as well as individual-level PM2.5 in each season, and then assessed personal PM2.5 exposure (including deposited doses of PM2.5 in the human respiratory tract) by using different methodology (such as using a dosimetry model). All participants took part in the physical examination, including the inflammatory indicators, BP and lung function parameters measurements. Subsequently, we assessed the health damage of exposure to PM2.5 using generalized additive models. We observed increased BP at 2-day lag for an interquartile range increase in ambient fixed-site, households, individual-level PM2.5 exposure and the corresponding lung deposited doses of each exposure concentration (pxa0<xa00.05), decreased BP at 3-day lag for an interquartile range increase in ambient fixed-site, households PM2.5 and the corresponding lung deposited doses of each exposure concentration (pxa0<xa00.05). The estimated deposited doses of PM2.5 by the deposition fractions in this study and the referenced deposition fractions by previous reported method were equivalent associated with alternation in BP. In conclusion, lung deposited dose of PM2.5 as a quantitative indicator may be used to assess adverse cardiovascular effects following the systemic inflammation. However, we require careful assessment of acute adverse cardiovascular effects using ambient fixed-site PM2.5 after short-term PM2.5 exposure.

Combined effect of urinary monohydroxylated polycyclic aromatic hydrocarbons and impaired lung function on diabetes.

Associations of type 2 diabetes with exposure to polycyclic aromatic hydrocarbons and reduced lung function have been reported. The aim of the present study was to investigate effect of reduced lung function and exposure to background PAHs on diabetes. A total of 2730 individuals were drawn from the Wuhan-Zhuhai (WHZH) Cohort Study (n=3053). Participants completed physical examination, measurement of lung function and urinary monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs). Risk factors for type 2 diabetes were identified by multiple logistic regression analysis, and the presence of additive interaction between levels of urinary OH-PAHs and lower lung function was evaluated by calculation of the relative excess risk due to interaction (RERI) and attributable proportion due to interaction (AP). Urinary OH-PAHs levels was positively associated with type 2 diabetes among individuals with impaired lung function (p<0.05). Forced expiratory volume in one second (FEV1, odd ratio (OR): 0.664, 95% confidence interval (CI): 0.491-0.900) and forced vital capacity (FVC, OR: 0.693, 95% CI: 0.537-0.893) were negatively associated with diabetes among individuals. Additive interaction of higher urinary levels of OH-PAHs and lower FVC (RERI: 0.679, 95% CI: 0.120-1.238); AP: 0.427, 95% CI: 0.072-0.782) was associated with diabetes. Exposure to background PAHs was related to diabetes among individuals with lower lung function. Urinary levels of OH-PAHs and reduced lung function had an additive effect on diabetes.

Exposure to polycyclic aromatic hydrocarbons and central obesity enhanced risk for diabetes among individuals with poor lung function

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 (nxa0=xa02716) 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 (pxa0<xa00.05 for all). Among individuals with poor lung function, the RERI between urinary ΣOH-PAHs and waist circumstance (WC, RERI: 0.866, 95% CI:xa0-0.431, 2.164, pxa0=xa00.192) or waist-to-height ratio (WHtR, RERI: 1.091, 95% CI:xa0-0.124, 2.305, pxa0=xa00.078) was found; the AP due to the interaction between urinary ΣOH-PAHs and WC or WHtR was 0.383 (95% CI:xa0-0.07, 0.80, pxa0=xa00.086) or 0.465 (95% CI: 0.019, 0.912, pxa0=xa00.04). The results indicated that central obesity may enhance the effect of exposure to background PAHs on diabetes in individuals with poor lung function.

Associations between urinary monohydroxy polycyclic aromatic hydrocarbons metabolites and Framingham Risk Score in Chinese adults with low lung function

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.

Estimated individual inhaled dose of fine particles and indicators of lung function: A pilot study among Chinese young adults

Fine particle (PM2.5)-related lung damage has been reported in most studies regarding environmental or personal PM2.5 concentrations. To assess effects of personal PM2.5 exposures on lung function, we recruited 20 postgraduate students and estimated the individual doses of inhaled PM2.5 based on their microenvironmetal PM2.5 concentrations, time-activity patterns and refereed inhalation rates. During the period of seven consecutive days in each of the four seasons, we repeatedly measured the daily lung function parameters and airway inflammation makers such as fractional exhaled nitric oxide (FeNO) as well as systemic inflammation markers including interleukin-1β on the final day. The high individual dose (median (IQR)) of inhaled PM2.5 was 957 (948) μg/day. We observed a maximum FeNO increase (9.1% (95%CI: 2.2-15.5)) at lag 0 day, a maximum decrease of maximum voluntary ventilation (11.8% (95% CI: 4.6-19.0)) at lag 5 day and a maximum interleukin-1β increase (103% (95% CI: 47-159)) at lag 2 day for an interquartile range increase in the individual dose of inhaled PM2.5 during the four seasons. Short-term exposure to PM2.5 assessed by the individual dose of inhaled PM2.5 was associated with higher airway and systemic inflammation and reduced lung function. Further studies are needed to understand better underlying mechanisms of lung damage following acute exposure to PM2.5.

Tris (2-chloroethyl) phosphate induces senescence-like phenotype of hepatocytes via the p21Waf1/Cip1-Rb pathway in a p53-independent manner

Tris (2-chloroethyl) phosphate (TCEP) has been widely used as a plasticizer and flame retardant. TCEP as a potential carcinogen is often detected in the occupational and nature environments. To investigate effects of TCEP on human hepatocytes, we assessed cell growth rate, cellular membrane integrity, senescence-associated β-galactosidase (SA-β-Gal) activity and analyzed expression of regulators involved in the p53-p21Waf1/Cip1-Rb pathway in TCEP-treated L02 cells. The results showed TCEP increased the percentage of SA-β-Gal positive cells, decreased IL-6 levels, down-regulated the regulators of p38MAPK-NF-κB pathways, but up-regulated the regulators of p21Waf1/Cip1-Rb pathway in L02 cells. Furthermore, we measured the SA-β-Gal activity and expression of regulators involved in the p53-p21Waf1/Cip1-Rb pathway in L02-p53 cells and p53-null Hep3B cells. Similar results were found in L02-p53 cells and Hep3B cells. The findings demonstrated that TCEP induced senescence-like growth arrest via the p21Waf1/Cip1-Rb pathway in a p53-independent manner, without activation of the IL-6/IL6R, p38MAPK-NF-κB pathways in hepatocytes.

Obesity mediated the association of exposure to polycyclic aromatic hydrocarbon with risk of cardiovascular events

Exposure to polycyclic aromatic hydrocarbons (PAHs) could cause high blood pressure (BP) and increased risk for atherosclerotic cardiovascular disease (ASCVD). However, the mechanisms underlying the relationship between them were unclear. We investigated potential mediation effect of obesity on the association of exposure to PAHs with high BP and increased risk for ASCVD. In the repeated measures study, 106 community-dwelling residents in Wuhan, China finished the physical examination in the winter and summer seasons, eight urinary PAHs metabolites were measured. Associations of urinary PAHs with high BP and increased risk for ASCVD were assessed using either linear mixed effect models or generalized estimating equations models. Mediation analysis was performed to evaluate the mediating effect of obesity on the association of urinary PAHs metabolites with high BP or increased risk of ASCVD. We observed the positive association between urinary PAHs metabolites and BP or the odds ratios for high BP (all P<0.05). Additionally, each one-unit increase in ln-transformed urinary levels of 4-hydroxyphenanthrene or the total of PAH metabolites was associated with a 12.63% or 11.91% increase in the estimated 10-year ASCVD risk (both P<0.05). The waist-to-height ratio mediated 29.0% of the association of urinary 4-hydroxyphenanthrene with increased risk of ASCVD (P<0.05). The findings suggest that PAHs exposure may be associated with elevated BP and an increased risk of ASCVD. Obesity may partially mediate the association between PAHs exposure and higher BP or increased risk of ASCVD.

Environmental exposure to polycyclic aromatic hydrocarbons, kitchen ventilation, fractional exhaled nitric oxide, and risk of diabetes among Chinese females

Diabetes is related to exposure to polycyclic aromatic hydrocarbons (PAHs), inflammation in the body, and housing characters. However, associations of urinary monohydroxy-PAHs (OH-PAHs) or fractional exhaled nitric oxide (FeNO) with diabetes risk in relation to housing characters are unclear. In this study, 2645 individuals were drawn from the baseline survey of the Wuhan-Zhuhai Cohort Study. Associations of diabetes with urinary OH-PAHs or FeNO among cooking participants were estimated using logistic regression models. Among women with self-cooking meals, urinary OH-PAH levels were positively associated with diabetes risk (Pxa0<xa0.05); the cooking women with high FeNO (≥25xa0ppb) had a 59% increase in the risk of diabetes (OR: 1.59, 95% CI: 1.06, 2.38), compared with those with low FeNO (<25xa0ppb). The cooking women with use of kitchen exhaust fans/hoods had a 52% decrease in the risk of diabetes (OR: 0.48, 95% CI: 0.27, 0.84), compared with those with nonuse of kitchen exhaust fans/hoods. The results indicated that the cooking women had an elevated risk of diabetes, which may be partly explained by an increase in the PAH body burden and higher inflammatory responses. Use of kitchen exhaust fan/hood can be associated with a lower risk of diabetes.

Dose-response relationships between urinary phthalate metabolites and serum thyroid hormones among waste plastic recycling workers in China

Background Exposure to phthalates may affect thyroid hormone status. However, there were inconsistent observations for the associations of phthalates exposure with altered thyroid hormones. Objectives The aim of this study was to investigate effects of urinary excretion of phthalate metabolites on the levels of thyroid hormones among workers engaged in waste plastic recycling in China. Methods We measured serum levels of thyroid hormones and urinary levels of eight phthalate metabolites among 317 participants (165 workers engaged in waste plastic recycling and 152 farmers), analyzed relationships between urinary phthalate metabolites and thyroid function parameters by multivariate linear regression analysis and structural equation modelling as well as assessed the dose‐response relationships between them by restricted cubic spline functions. Results Maximum urinary values of eight phthalate metabolites in the occupational exposed workers were higher than the controls. Compared with the controls, the workers had higher levels of urinary monobenzyl phthalate (MBzP, 1.12 vs. 0.92 &mgr;g/g creatinine), mono (2‐ethyl‐5‐hydroxyhexyl) phthalate (MEHHP, 38.84 vs. 32.55 &mgr;g/g creatinine), mono‐n‐octyl phthalate (MOP, .11 vs. 0.09 &mgr;g/g creatinine), serum total triiodothyronine (T3, 1.04 vs. 0.92 ng/mL) and the T3 to thyroxine (T4) ratio (1.44 vs. 1.09) (all P < 0.05). The results from structural equation modelling analysis showed that phthalates metabolites were positively associated with total T3 (&bgr; = 0.044, SE = 0.021, P < 0.05) or the T3/T4 ratio (&bgr; = 0.053, SE = 0.022, P < 0.05) among all participants. Among the workers, there were the non‐monotonic dose‐response associations between urinary monomethyl phthalate (MMP) and serum total T3 or the T3/T4 ratio, as well as between urinary monoethyl phthalate (MEP) and the T3/T4 ratio (all P < 0.05). Conclusions The dose‐response relationships between urinary phthalate metabolites and thyroid hormone parameters may be non‐monotonic among the workers. Further investigations are needed to corroborate these findings. HighlightsMaximum urinary phthalate levels of the workers are higher than those of controls.A non‐linear association of urinary MMP with total T3 was found among the workers.The workers showed a non‐linear association of urinary MMP with the T3/T4 ratio.The workers exhibited a non‐linear association of urinary MEP with the T3/T4 ratio.