Perfluoroalkyl substances promote breast cancer progression via ERα and GPER mediated PI3K/Akt and MAPK/Erk signaling pathways.

Perfluoroalkyl substances (PFASs) are a classic environmental endocrine disruptor with carcinogenic risk. Epidemiological studies have shown that PFASs contamination is associated with breast cancer development, but the mechanism remains largely unknown. This study first obtained complex biological information about PFASs-induced breast cancer through the comparative toxicogenomics database (CTD). The Protein-Protein Interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis were utilized to investigate molecular pathways. The ESR1 and GPER expression levels at different pathological stages and the prognosis of Breast Cancer patients were confirmed using the Cancer Genome Atlas (TCGA) database. Furthermore, we verified this by cellular experiments and the results showed breast cancer cell migration and invasion were promoted by PFOA. Two estrogen receptors (ER), ERα and G protein-coupled estrogen receptor (GPER), mediated the promoting effects of PFOA by activating MAPK/Erk and PI3K/Akt signaling pathways. These pathways were regulated by ERα and GPER in MCF-7 cells or independently by GPER in MDA-MB-231 cells. Overall, our study provides a better overview of the mechanisms associated with PFASs-induced breast cancer development and progression.

Impacts of heatwaves and cold spells on glaucoma in rural China: a national cross-sectional study.

China faces increasing health risks from climate change. The structure and function of the eye and vision were affected by extreme heat and cold. The study aimed to evaluate the impacts of heatwaves and cold spells on glaucoma. A national cross-sectional study of the Rural Epidemiology for Glaucoma (REG-China) was conducted in ten provinces of China, and 36,081 adults aged 40 years or more were included. Glaucoma signs were assessed via a standard examination. A total of 15 heatwave definitions, based on intensity (95th to 99th percentiles of temperature distribution) and duration (≥2 days, 3 days, and 4 days), were used to quantify heatwave effects, and 6 cold spell definitions were defined based on threshold temperature percentile (5th and 10th) and duration (3 days, 5 days, and 9 days). Multivariable-adjusted logistic regression models paired with interaction analysis were performed to investigate the impacts of heatwaves and cold spells on glaucoma, and the dose-response relationships were assessed using a restricted cubic spline (RCS) model. Subgroup analysis was conducted stratified by gender, age, smoking status, occupation, and family history of glaucoma. The overall prevalence of glaucoma was 2.1% (95% CI 1.94-2.25%). Higher heatwaves were significantly correlated with higher OR of glaucoma, with the OR (95% CI) ranging from 1.014 (1.009, 1.018) to 1.090 (1.065, 1.115) by different definitions. Glaucoma was affected by heatwaves more strongly than by cold spells. The effects of both heatwaves and cold spells were higher in males than females and in smokers than nonsmokers. These results of the present study evoked the attention of prospective research to elucidate the relationship between extreme temperatures and eye diseases.

Breast adipose metabolites mediates the association of tetrabromobisphenol a with breast cancer: A case-control study in Chinese population.

Studies exploring the association of tetrabromobisphenol A (TBBPA) with breast cancer and related mechanisms are limited. To investigate the relationship between TBBPA levels in breast adipose and breast cancer, we carried out case-control research. As well as further examine the mediating role of adipose metabolites between TBBPA and breast cancer using the metabolomics approach. In this study, the concentration of TBBPA was determined utilizing ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) after a solid phase extraction (SPE) pretreatment. High-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was employed to analyze adipose metabolomics. Evaluation of metabolites linked to TBBPA exposure and breast cancer was performed utilizing mediation analysis. With an estimated OR (95%CI) of 1.153 (1.023, 1.299), TBBPA was firmly linked with breast cancer. We also used propensity score matching analysis and sensitivity analysis to reduce the effect of confounding factors on the results. Metabolomics of adipose suggested significant perturbation in the linoleic acid metabolism pathway. In addition, for PC (16:0/16:0) as phospholipids, a mediation effect on the associations of TBBPA exposure with breast cancer risks was observed (estimated mediation percentage: 56.58%). Understanding the relationship between TBBPA exposure and the risk of breast cancer may be facilitated by the findings, which point to potential mediation metabolites.

Glaucoma in rural China (the Rural Epidemiology for Glaucoma in China (REG-China)): a national cross-sectional study.

OBJECTIVE: This study aimed to investigate the prevalence of glaucoma with associated factors in the rural populations of 10 provinces in China. DESIGN: A population-based cross-sectional study. METHODS: All participants aged 6 years or older from 10 provinces completed visual acuity testing, slit-lamp examination, ophthalmoscopy and non-contact tonometry. Glaucoma suspects underwent fundus photography, Goldmann applanation tonometry, visual field testing and gonioscopy. Glaucoma was determined according to the International Society of Geographical and Epidemiological Ophthalmology classification scheme. Associations of demographics and medical factors with glaucoma were assessed using multiple logistic regression models. RESULTS: From June 2017 to October 2018, 48 398 of 52 041 participants were included in the final analyses. The age-standardised prevalence of glaucoma was 1.7% (95% CI 1.55% to 1.78%) among the participants older than 6 years, which was 2.1% (95% CI 1.93% to 2.23%) in participants aged over 40 years. The constituent ratios of glaucoma were: 44.4% primary angle-closure glaucoma (PACG), 34.7% primary open-angle glaucoma, 2.6% congenital glaucoma and 18.3% other types of glaucoma. Increasing age, smoking, cerebral stroke, type 2 diabetes, higher education (college or more) and higher personal income were significant risk factors for PACG. The unilateral and bilateral blindness rates in the entire study population were 4.692% and 1.068%, respectively. A family history of glaucoma was a significant risk factor for the prevalence of glaucoma and blindness in at least one eye. CONCLUSIONS: Rural populations have a high prevalence of glaucoma, which should be included in chronic disease management programmes in China for long-term care.

Breast microbiome associations with breast tumor characteristics and neoadjuvant chemotherapy: A case-control study.

Background: Commensal microbiota have been proven to colonize the mammary gland, but whether their composition is altered in patients with breast cancer (BC) remains elusive. This study intends to explore the breast microbiome differences between benign and malignant diseases and to investigate the impact of neoadjuvant chemotherapy (NAC) on the breast microbiota in patients with BC. Methods: Breast normal adipose tissues (NATs) were collected from 79 patients with BC and 15 controls between July 2019 and November 2021. The BC group consisted of 29 patients who had received NAC and 50 who were non-NAC patients. Participants diagnosed with benign breast disease were recruited as controls. 16S rRNA gene sequencing was used to analyze the bacterial diversity of NATs. Results: The community structure of the NAT microbiome was significantly different between the BC and control groups. Proteobacteria decreased (47.40% versus 39.74%), whereas Firmicutes increased (15.71% versus 25.33%) in patients with BC when compared with that in control tissues. Nine genera were enriched in BC NATs, and four genera levels increased in the control group. The associations between differential bacterial genera and breast tumor grade were calculated by Spearman's correlation. The results showed that tumor grade was positively associated with the relative abundance of Streptococcus and negatively related to Vibrio, Pseudoalteromonas, RB41, and Photobacterium. Moreover, menopause was associated with the microbiota composition change of non-NAC BC patients and related to the significant reduction in the abundance level of Pseudoalteromonas, Veillonella, and Alcaligenes. In addition, NAC was related to the beta diversity of patients with BC and associated with the decrease of Clostridium_sensu_stricto_7 and Clostridium_sensu_stricto_2 in postmenopausal patients. Of note, Tax4Fun functional prediction analysis revealed that the metabolic state was more exuberant in the BC group with upregulating of multiple metabolism-related pathways. Conclusion: Our results offer new insight into the relationship between NAC and breast microbiota and help to better characterize the breast microbial dysbiosis that occurs in patients with BC. Further epidemiological studies with larger sample size and well-designed animal experiments are required to elucidate the role of breast microbiota in the therapeutic outcome of BC.

Perfluoroalkyl substances (PFASs) as risk factors for breast cancer: a case-control study in Chinese population.

BACKGROUND: Perfluoroalkyl substances (PFASs) are a large family of synthetic chemicals, some of which are mammary toxicants and endocrine disruptors. Recent studies have implicated exposure to PFASs as a risk factor for breast cancer in Europe and America. Little is known about the role of PFASs with respect to breast cancer in the Chinese population. METHODS: Participants who were initially diagnosed with breast cancer at Tianjin Medical University Cancer Institute and Hospital between 2012 and 2016 were recruited as cases. The controls were randomly selected from the participants with available blood samples in the Chinese National Breast Cancer Screening Program (CNBCSP) cohort. Ultimately, we enrolled 373 breast cancer patients and 657 controls. Plasma PFASs were measured by an ultra-performance liquid chromatography (UPLC) system coupled to a 5500 Q-Trap triple quadrupole mass spectrometer. A logistic regression model with least absolute shrinkage and selection operator (LASSO) regularization was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the relationships between PFASs and breast cancer. The three most predictive variables in the LASSO model were selected from 17 PFASs, which was based on the optimal penalty coefficient (λ = 0.0218) identified with the minimum criterion. Additionally, Bayesian kernel machine regression (BKMR) and quantile g-computation models were applied to evaluate the associations between separate and mixed exposure to PFASs and breast cancer. RESULTS: Perfluorooctanesulfonic acid (PFOS) exhibited the highest concentration in both the cases and controls. Perfluorooctanoic acid (PFOA) and perfluoro-n-decanoic acid (PFDA) were positively associated with breast cancer, and perfluoro-n-tridecanoic acid (PFTrDA) was negatively associated with breast cancer according to both the continuous-PFASs and the quartile-PFASs logistic regression models. Of note, PFOA was associated with the occurrence of estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-positive breast cancer (ORER+ = 1.47, 95% CI: 1.19, 1.80; ORPR+ = 1.36, 95% CI: 1.09, 1.69; ORHER2 = 1.62, 95% CI: 1.19, 2.21). CONCLUSIONS: Overall, we observed that PFASs were associated with breast cancer in Chinese women. Prospective cohort studies and mechanistic experiments are warranted to elucidate whether these associations are causal.

TCDD-induced antagonism of MEHP-mediated migration and invasion partly involves aryl hydrocarbon receptor in MCF7 breast cancer cells.

Evidence has shown that the activation of AhR (aryl hydrocarbon receptor) can promote cancer cell metastasis. However, limited studies have been carried out on mixed exposure to endocrine-disrupting chemicals (EDCs), especially in human breast cancer. Therefore, using MCF7 human breast cancer cells, we investigated the effects of coexposure to MEHP (mono 2-ethylhexyl phthalate) and TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) on cell migration and invasion, as well as the roles of AhR and the MMP/slug pathway. Our data suggest that MEHP or TCDD can induce migration and invasion in MCF7 cells, and the promotion is partly AhR dependent. We also observed that MEHP antagonized TCDD to reduce AhR-mediated CYP1A1 expression. Subsequently, we revealed that MEHP recruited AhR to dioxin response element (DRE) sequences and decreased TCDD-induced AhR-DRE binding in CYP1A1 genes. Overall, MEHP is a potential AHR agonist, capable of decreasing TCDD-induced AhR-DRE binding in CYP1A1 genes. The antagonizing effect of coexposure led to the inhibition of the epithelial-mesenchymal transition (EMT) in MCF7 cells. Our study provides new evidence for the potential mechanisms involved in EDCs exposure and their interactions in EMT.

BDE-47 Decreases Progesterone Levels in BeWo Cells by Interfering with Mitochondrial Functions and Genes Related to Cholesterol Transport.

Polybrominated diphenyl ethers (PBDEs) have been reported to exert reproductive endocrine toxicity, but the mechanisms for this process remain unclear. Currently available studies have concentrated on the enzymatic reactions during steroidogenesis, but the results are not consistent. In this study, we explored the effects of 2,2',4,4'-tertrabromodiphenyl ether (BDE-47) on progesterone biosynthesis and the potential mechanisms in human placental choriocarcinoma cells. The results showed that BDE-47 decreased progesterone production in a dose-dependent manner but had no effect on key enzymes (Cyp11a1 and 3ß-HSD). BDE-47 exposure depolarized the mitochondrial membrane potential and downregulated adenosine triphosphate levels. The gene expression levels of Mfn2, Tspo, Atad3, Vdac1, Fis1, and Drp1, which are involved in mitochondrial dynamics and cholesterol transport, were disturbed. The demethylation of some CpG loci of mitochondrial biomarkers (Drp1, Opa1, Vdac2, and Atad3) was induced in the 1 µM BDE-47 exposure group, but no methylation change was observed with 50 µM treatment. Our findings unveiled that the reduction of progesterone synthesis induced by BDE-47 might be associated with cholesterol transportation, mitochondrial dynamics, and mitochondrial functions. These findings provide substantial data on the reproductive endocrine toxicity of PBDEs.

Psychosocial stress is associated with benign breast disease in young Chinese women: results from Project ELEFANT.

PURPOSE: Psychosocial stress, including bereavement and work-related stress, is associated with the risk of breast cancer. However, it is unknown whether it may also be linked with increased risk of benign breast disease (BBD). METHODS: Our study leveraged 61,907 women aged 17-55 years old from the Project ELEFANT study. BBD was diagnosed by clinician. Self-reported data on psychosocial stress over a 10-year period was retrospectively collected from questionnaires and categorised by cause (work, social and economic) and severity (none, low and high). Odd ratios (ORs) for the development of BBD were estimated using logistic regression. The model was adjusted for age, BMI, TSH levels, smoking, alcohol consumption, family history, age of menarche, oral contraceptive usage, education and occupation. RESULTS: Within our study, 8% (4,914) of participants were diagnosed with BBD. Work-related stress [OR 1.57, 95% confidence interval (CI) 1.46-1.69] and financial stress (OR 1.34, 95% CI 1.24-1.44) were significantly associated with BBD incidence, with a smaller but still significant association with social stress (OR 1.11, 95% CI 1.01-1.21). The associations remained significant after exclusion of participants with first- and second-degree family history of breast disease. The presence of multiple forms of stress did not synergistically increase risk. The neutrophil-lymphocyte ratio (NLR), a marker of systemic inflammation and prognostic marker for breast cancer, was not associated with BBD. CONCLUSIONS: Psychosocial stress, particularly work-related and financial stress, is associated with increased risk of benign breast disease among young Chinese women.

Age at menarche and prevention of hypertension through lifestyle in young Chinese adult women: result from project ELEFANT.

BACKGROUND: Early and late age at menarche are associated with risk of hypertension, but little is known whether modifiable lifestyle can reduce this risk. METHODS: Our study leverages 60,135 healthy young Chinese women from the Environmental and LifEstyle FActors iN metabolic health throughout life-course Trajectories (ELEFANT) study. Menarche age and lifestyle factors were assessed by self-reported questionnaires and hypertension was diagnosed by physicians. We estimated the odds ratios (ORs) of hypertension associated with menarche age using multivariable logistic regression. We further investigated whether modifiable lifestyles (body mass index, BMI; psychological stress; passive smoking; and imbalanced diet) increased risk in joint analyses. RESULTS: The association between age at menarche and hypertension was U-shaped, with age ≤ 12 at menarche giving the highest OR (1.46, 95% confidence interval [CI], 1.27-1.69) and ≥ 16 the second highest (OR = 1.36, 95% CI = 1.15-1.62). Simultaneous analysis of lifestyle risk factors and age of menarche showed that having one or more modifiable risk factors increased the menarche age-hypertension association. The risk of hypertension among participants with menarche age ≤ 12 decreased from OR 13.21 (95% CI = 5.17-29.36) with four high-risk lifestyle factors to 12.36 (95% CI = 9.51-16.05) with three high-risk factors, 5.24 (95% CI = 4.11-6.69) with two, and 2.76 (95% CI = 2.09-3.60) with one, in comparison to individuals with no high-risk lifestyle factors and menarche age 14. CONCLUSIONS: Our results suggest that modification of lifestyle, including maintenance of normal weight and a balanced diet, are associated with substantially reduce the risk of hypertension in high-risk individuals. Early and late age at menarche are risk factors for the development of hypertension in Western populations, and there is limited evidence that this is also true of Chinese populations. Targeted prevention of hypertension in vulnerable populations would be highly beneficial in efforts to reduce the incidence of cardiovascular disease, but it is not currently known whether lifestyle intervention could reduce hypertension risk. In this study, we analysed the risk of hypertension by age at menarche and four modifiable lifestyle factors (BMI, diet, psychological stress, and smoking tobacco) in a cohort of 60,135 young adult Chinese women (mean age 29). We identified that early and late age at menarche are associated with increased risk of hypertension in young Chinese women. There was joint effects between age at menarche and lifestyles on hypertension only participants with age at menarche ≤12 and being overweight or obese. Modification of lifestyle, including maintenance of normal weight and a balanced diet, can substantially reduce the risk of hypertension in high-risk individuals. In conclusion, our study has revealed that early and late menarche age are associated with the development of hypertension in young Chinese women, and that this risk is modified by healthy lifestyle traits.

Increased risk of nonalcoholic fatty liver disease with occupational stress in Chinese policemen: A 4-year cohort study.

Nonalcoholic fatty liver disease (NAFLD) and occupational stress have been recognized as major public health concerns. We aimed to explore whether occupational stress was associated with NAFLD in a police population.A total of 6559 male police officers were recruited for this prospective study in April 2007. Among them, 2367 eligible subjects participated in follow-up from 2008 to 2011. NAFLD was diagnosed based on standard criteria. Occupational stress was evaluated by Occupational Stress Inventory-Revised scores.The incidence of NAFLD was 31.2% in the entire police. After adjusting for traditional risk factors, moderate occupational stress (MOS), high occupational stress (HOS), and high personal strain (HPS) were risk factors (MOS: hazard ratio [HR] = 1.237, 95% confidence interval [CI] = 1.049-1.460; HOS: HR = 1.727, 95% CI = 1.405-2.124; HPS: HR = 3.602, 95% CI = 1.912-6.787); and low occupational stress (LOS) and low personal strain (LPS) were protective factors (LOS: HR = 0.366, 95% CI = 0.173-0.776; LPS: HR = 0.490, 95% CI = 0.262-0.919) for NAFLD in the entire police cohort. HOS and HPS remained robust among traffic police.HOS and HPS were independent predictors for the development of NAFLD in a Chinese police population. Additional future prospective investigations are warranted to validate our findings.

Long-term exposure to urban air pollution and lung cancer mortality: A 12-year cohort study in Northern China.

Cohort evidence that links long-term exposures to air pollution and mortality comes largely from the United States and European countries. We investigated the relationship between long-term exposures to particulate matter <10µm in diameter (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) and mortality of lung cancer in Northern China. A cohort of 39,054 participants were followed during 1998-2009. Annual average concentrations for PM10, NO2, and SO2 were determined based on data collected from central monitoring stations. Lung cancer deaths (n=140) were obtained from death certificates, and hazard ratios (HRs) were estimated using Cox proportional hazards models, adjusting for age, gender, BMI, education, marital status, smoking status, passive smoking, occupation, alcohol consumption, etc. Each 10mg/m(3) increase in PM10 concentrations was associated with a 3.4%-6.0% increase in lung cancer mortality in the time-varying exposure model and a 4.0%-13.6% increase in the baseline exposure model. In multi-pollutant models, the magnitude of associations was attenuated, most strongly for PM10. The association was different in men and women, also varying across age categories and different smoking status. Substantial differences exist in the risk estimates for participants based on assignment method for air pollution exposure.

Polychlorinated biphenyls and breast cancer: A congener-specific meta-analysis.

The incidence of breast cancer is related to various risk factors, especially that the environmental and lifestyle factors account for major contribution at the rate of 70% to 95% over all. However, there still remains some controversy over the epidemiological evidence regarding the effects of environmental carcinogens on the risk of breast cancer. We conducted a quantitative meta-analysis aiming at full evaluation of the effects of polychlorinated biphenyls (PCBs) on breast cancer in a congener-specific fashion. Four online literature databases were systematically searched before 1st January 2015, for studies stating correlation between PCB congeners and breast cancer. The Newcastle-Ottawa Scale was used to evaluate the quality of the studies that were included in our analysis. Sixteen studies were included in our final meta-analysis after screening based on the priori inclusion criteria. Nine PCB congeners were reported by more than two studies and they were presented in detail. The pooled Odds Ratios (ORs) showed a significant increase in the risk of breast cancer in individuals with higher plasma/fat levels of PCB 99 (OR: 1.36; 95% CI: 1.02 to 1.80), PCB 183 (OR: 1.56; 95% CI: 1.25 to 1.95) and PCB 187 (OR: 1.18; 95% CI: 1.01 to 1.39). Besides, the outcomes did not support a relationship between dioxin-like PCB congeners and the risk of breast cancer. The results of our meta-analysis imply that PCB 99, PCB 183 and PCB 187 would increase the risk of breast cancer. The mechanism of this increased risk may be by the induction of the CYP2B family in cytochrome P450 enzymes.

Effects of di(n-butyl) and monobutyl phthalate on steroidogenesis pathways in the murine Leydig tumor cell line MLTC-1.

Di(n-butyl) phthalate (DBP) and its active metabolite monobutyl phthalate (MBP) have been shown to disrupt reproductive organ growth. The objective of this study was to evaluate the effects of DBP/MBP on steroidogenesis in the murine Leydig tumor cell line MLTC-1 in vitro. MLTC-1 cells were incubated with various concentrations of DBP (100, 1, 0.01, and 0µmol/l in DMSO) and MBP (1000, 10, 0.1, and 0µmol/l in DMSO) for 24h. Testosterone secretion was stimulated at the lowest doses and inhibited at higher treatment doses of DBP and MBP. The mRNA levels of the side-chain cleavage enzyme (P450scc), cytochrome p450c17 (P450c17) and 3ß-hydroxy-steroid dehydrogenase (3ßHSD) were significantly reduced in the phthalate-exposed groups, whereas, the transcription and translation of insulin-like hormone 3 (INSL3) was affected by DBP and MBP. Alterations of the steroidogenic enzymes and INSL3 in MLTC-1 cells may be involved in the biphasic effects of DBP/MBP on androgen production.

[Effects of dibutyl phthalate and monobutyl phthalate on testosterone secretion and insulin-like factor 3 expression of Leydig tumor cells in mice].

OBJECTIVE: To observe the effects of dibutyl phthalate (DBP) and monobutyl phthalate (MBP) on the mRNA and protein expression of insulin-like factor 3 (INSL3) in the Leydig tumor cells (MA-10) of mice and the level of testosterone secreted from MA-10 cells. METHODS: The MA-10 cells of mice, used as a cellular model, were exposed to DBP and MBP. The content of testosterone in the supernatant medium was measured by enzyme-linked immunosorbent assay; the mRNA and protein expression levels of INSL3 in MA-10 cells were measured by quantitative PCR and Western Blot. RESULTS: Compared with the control group, MA-10 cells showed increased synthesis of testosterone when exposed to low concentrations of DBP and MBP (10(-9) ∼ 10(-6) mol/L) and inhibited synthesis of testosterone when exposed to high concentrations of DBP and MBP (10(-3) mol/L), and the typical two-way effects became more significant as the time went one and the concentrations increased (P < 0.05). Compared with the control group, MA-10 cells showed significantly lower mRNA and protein expression levels of INSL3 when exposed to 10(-6) and 10(-4) mol/L DBP (P < 0.05); MA-10 cells showed increased protein expression of INSL3 when exposed to 10(-7) mol/L MBP, and the mRNA and protein expression levels of INSL3 decreased as the concentration of MBP increased. CONCLUSION: DBP and MBP can inhibit the secretion of testosterone from MA-10 cells at high concentrations, but stimulate the secretion of testosterone at low concentrations. Both DBP and MBP have inhibitory effects on the mRNA and protein expression of INSL3 in MA-10 cells.

Effects of low concentrations of di-(2-ethylhexyl) and mono-(2-ethylhexyl) phthalate on steroidogenesis pathways and apoptosis in the murine leydig tumor cell line MLTC-1.

The aim of this study was to evaluate the effects of low concentrations of DEHP and MEHP on steroidogenesis in a murine Leydig tumor cell line (MLTC-1) in vitro. The result of flow cytometry analysis revealed that the proportion of apoptotic cells was significantly increased after the exposure to DEHP. All three genes (P450scc, P450c17, and 3ßHSD) under study showed an increased expression following exposure to DEHP or MEHP, although some insignificant inhibitory effects appeared in the 10 µmol/L treatment group as compared with the controls. It was also found that compared with the controls. It was also found that DEHP or MEHP stimulated INSL3 mRNA and protein especially in the 0.001 µmol/L treatment group. Testosterone secretions were stimulated after the exposure to DEHP or MEHP. Alternations of steroidogenic enzymes and INSL3 in MLTC-1 cells might be involved in the biphasic effects of DEHP/MEHP on androgen production.

[Correlation between atmospheric polycyclic aromatic hydrocarbons exposure and urinary hydroxyl metabolites of polycyclic aromatic hydrocarbons in elderly population in Tianjin, China].

OBJECTIVE: To identify suitable hydroxyl polycyclic aromatic hydrocarbons (OH-PAHs) for co-evaluation of internal exposure level of PAHs by simultaneous determination of a variety of OH-PAHs in urine. METHODS: The 24-h individual particulate matter and morning urine samples of 112 subjects were collected during June 2011. PAHs carried by individual particulate matter samples and OH-PAHs in urine samples were detected by gas chromatography-mass spectrometry. RESULTS: Seven OH-PAHs were detected in urine samples, among which 1-hydroxy-naphthalene (1-OHNap) concentration was the highest [(20.54 ± 28.94) µmol/mol Cr], while 1-hydroxy-pyrene (1-OHP) concentration was the lowest [(0.73 ± 0.63) µmol/mol Cr]. The concentrations of these seven OH-PAHs decreased in the following order: 1-hydroxy-naphthalene (1-OHNap) > 9-hydroxy-fluorene (9-OHFlu) > 2-hydroxy-naphthalene (2-OHNap) > 3-hydroxy-fluorene (3-OHFlu) > 2-hydroxy-fluorene (2-OHFlu) > 6-hydroxy-chrysene (6-OHChr) > 1-hydroxy-pyrene (1-OHP). The effects of gender and smoking upon the contents of OH-PAHs in urine samples were not significant. There was a good correlation between total hydroxy-naphthalene (ΣOHNap) and 1-OHNap (r = 0.948), and a good correlation was also showed between total hydroxy-fluorene (ΣOHFlu) and 9-OHFlu (r = 0.975). Naphthalene carried by atmospheric particulate matters demonstrated better correlation with 1-OHNap than 2-OHNap, while fluorene carried by atmospheric particulate matters showed better correlation with 9-OHFlu than 3-OHFlu and 2-OHFlu. The correlation coefficients of ΣOHNap, ΣOHFlu and 6-OHChr with 1-OHP were 0.427, 0.543 and 0.655, respectively, and the correlations were not strong. CONCLUSION: It cannot reflect internal exposure level of PAHs to use 1-OHP as the only biomarker, while 1-OHNap and 9-OHFlu can be well predictive of the exposure levels of corresponding total OH-PAHs, suggesting that simultaneous determination of 1-OHNap, 9-OHFlu and 1-OHP can be more accurate and comprehensive in evaluating the internal exposure level of PAHs.

Abnormal expression of MAPK, EGFR, CK17 and TGk in the skin lesions of chloracne patients exposed to dioxins.

OBJECTIVE: Chloracne is one of the most sensitive and specific hallmark of dioxin intoxication. Although its clinical features are clearly described, poor understanding of the molecular pathways of dioxin-induced chloracne hampers a rational approach to therapy. The aim of the present study was to investigate the role of EGFR, MAPK, CK17, and TGk in the pathogenesis of chloracne related to dioxin exposures. METHODS: Epidermal tissues of twelve chloracne patients exposed to dioxins were compared with tissues from 12 healthy controls. These skin tissues were obtained by punch biopsies. p-EGFR and p-MAPK were examined by immunofluorescence. The mRNA and protein levels of CK17 and TGk were examined by fluorescence in situ hybridization and immunohistochemistry, respectively. RESULTS: p-EGFR and p-MAPK were found in all chloracne tissues, whereas no expression was found in the controls. CK17 mRNA and protein were also found in all chloracne lesions, but none in controls (P=0.000). TGk mRNA and protein were detected in both groups, but the distribution was distinct. The positive signals in the controls were mainly in the stratum granulosum, while in the chloracne tissues, the positive signals were found more significantly in the stratum granulosum and stratum spinosum. CONCLUSIONS: The results demonstrate that in the human skin the activation of mitogen-activated protein kinase pathway and up-regulation of CK17 and TGK may play roles in the pathogenesis of chloracne related to dioxin exposures.

[A matched case-control study on the risk factors of metabolic syndrome among policemen].

OBJECTIVE: To investigate the life style, genetic and occupational risk factors of metabolic syndrome (MS) among policemen. METHODS: 1:4 matched case-control study was used, based on physical examination data of Tianjin Policemen in 2010, 708 patients with MS were randomly selected as cases, which were matched with 2832 healthy controls on the basis of sex and age (+/- 1 year). An epidemiological investigations on the past exposure status of several possible risk factors was conducted, and the data were analyzed with conditional logistic regression. RESULTS: Fifteen factors related to exposure were identified for MS through univariate conditional logistic regression analysis. Multivariate conditional logistic regression analysis suggested that, seven factors, such as family history of hypertension (OR = 2.406, 95% CI: 1.946-2.975), family history of diabetes (OR = 1.301, 95% CI: 1.043-1.623), smoking (OR = 1.357, 95%CI: 1.010-1.823), snoring (OR = 1.268, 95% CI: 1.043-1.543), work intensity (OR = 4.603, 95% CI: 3.767-5.623), occupational stressful events (OR = 1.524, 95% CI: 1.209-1.922), security policemen (OR = 1.453, 95% CI: 1.127-1.872) and criminal investigation policemen (OR = 2.792, 95% CI: 2.168-3.596), could significantly increase the risk of disease development, but dairy products (OR = 0.782, 95% CI: 0.619-0.989) was a protect factor for MS. The results from population attributable risk factors analysis showed that the control of smoking, snoring, work intensity, occupational stressful events can decreased the risk of MS to 16.26%, 11.71%, 56.87% and 8.97%, respectively. CONCLUSION: Metabolic syndrome has became a significant public health problem among policemen, it's necessary to take measures on life style, occupational risk factors for reducing the incidence of MS, and improving the health level among policemen.