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This study investigated the effects of constant light exposure on polycystic ovary syndrome (PCOS)-like endocrine and metabolic changes in high-fat diet (HFD)-fed rats and to elucidate the related microbiotic mechanisms.A total of 32 female Sprague-Dawley rats were divided into four groups (n = 8 each): rats on a normal chow diet with standard light-dark cycle, rats on a normal chow diet with constant light exposure, rats on an HFD with standard light-dark cycle, and rats on an HFD with constant light exposure. After 16 weeks of treatment, changes in anthropometric parameters, estrous cycle, hormone profiles, ovarian pathology, and gut microbiota and short-/medium-chain fatty acids in colon contents were assessed.Constant light exposure aggravated PCOS-like phenotypes in HFD-fed rats, such as hyperandrogenism, disrupted estrous cycle, and polycystic ovaries. Additionally, constant light exposure and an HFD synergized to decrease α-diversity of gut microbiota, create a reduced abundance of Ruminococcus genus, and create an increased abundance of Firmicutes and the Firmicutes/Bacteroidetes ratio. In HFD-fed rats, the group with constant light exposure had an increase in propionate acid and a decrease in total medium-chain fatty acids in colon contents compared with the standard light-dark cycle group.Constant light exposure causes gut dysbiosis, alters production of short- and medium-chain fatty acids, and aggravates PCOS-like traits in HFD-fed rats.

Although excess adiposity has been linked with various cancers, association between body composition and some cancers remains unclear, like lung and prostate cancers. We investigated associations of body composition with risk of overall cancer and major site-specific cancers in a prospective cohort of 454,079 cancer-free participants from UK-Biobank. Body composition was measured with bioimpedance analysis. We evaluated hazard ratio (HR) and 95% confidence interval (CI) with multivariate Cox linear and nonlinear models in men and women separately. We identified 27,794 cancers over 7.6 years of follow-up. Multivariable adjusted models including fat-free mass (FFM) and fat mass (FM) showed that FFM was positively associated with overall cancer risk in men and women (HR 1.03, 95% CI 1.01-1.04 and 1.07, 1.04-1.10, respectively); while the association between FM and overall cancer disappeared after adjusting for FFM. FFM was associated with higher risks of obesity-related cancers combined, stomach (women only), malignant melanoma, postmenopausal breast, corpus uteri, prostate, kidney (men only), and blood cancers, and lower risk of lung cancer. FM was associated with higher risks of obesity-related cancers combined, esophageal, colon, lung (men only), postmenopausal breast (at the lower end of FM range), and corpus uteri cancers, and lower risks of rectal, malignant melanoma (women only), prostate and blood cancers. FFM and FM seemed to have different effects on cancer risk, and the effects varied substantially by cancer type, in both direction and size. Higher FM/FFM ratio was also associated with some cancers risk, and might be a useful predictor of cancer risk. This article is protected by copyright. All rights reserved.

Objective To investigate the effect of paraquat (PQ) exposure on gene expression in neural stem cells as well as structures and functions of vascular endothelial cells. Methods RNA-Seq was used to explore the differentially expressed genes in human umbilical cord blood-neural stem cells (HUCB-NSCs) at different stages (eg, proliferation, early and late differentiation) in the presence of PQ. The effects of PQ on human umbilical vein endothelial cells (HUVECs), including cell proliferation, apoptosis, cytokines secretion, and expression of tight junction proteins, were assessed with CCK-8, flow cytometry, ELISA, and western blot analysis, individually. Results A total of 53 genes were up-regulated and 61 genes were down-regulated in PQ treated HUCB-NSCs, including seven genes associated with the differentiation of neural stem cells, for example, Gfap, S100B, Oct4, Gdf3, Sox1, Pax6, and Ngn1. PQ treatment significantly reduced the proliferation of HUVECs, inhibited cytokines secretion (VEGF, BFGF) and expressions of tight junction-associated protein (Claudin 1, Occludin, ZO-1), as well as induced significant apoptosis. Conclusion Our study suggests that PQ impairs the development of nervous system by regulating the expression of genes associated with neural stem cell differentiation, as well as the structure and function of vascular endothelial cells, which together lead to abnormality in the nervous system.

With the immense economic growth and social development, China has gained worldwide attention. With the quick growth of industrialization, several international professionals are gaining interest in occupational management system and in the role of the Chinese Government in protecting the worker's health. The Law on Prevention and Control of Occupational Diseases and the Work Safety Law are the two most important laws in China, which highlight the responsibilities of the employer, employee, governmental agencies, authorized occupational health service agency, and other stakeholders. The State Council comprises two departments, namely, the State Administration on Work Safety (SAWS) and the National Health and Family Planning Commission (NHFPC), which are responsible for governing the occupational health work. A series of regulations and standards have been promulgated by the Chinese Government to encourage or instruct the employers to fulfill their responsibility; however, several issues persist related to occupational health work, including administrative, technological, and sociocultural aspects. At present, the Chinese Government wants to enhance the reform in both economic and administrative structures, and the adjustments for modifying and/or improving the occupational health regulatory system are expected. Notably, the occupational health work in China must be altered for better.

The developing brain is uniquely vulnerable to toxic chemical exposures. Studies indicate that neural stem cell (NSC) self-renewal is susceptible to oxidative stress caused by xenobiotics. However, the impact of antioxidants on NSC self-renewal and the potential mechanisms remain elusive. In this study, primary murine neural progenitor cells (mNPCs) from the subventricular zone were used as a research model. In addition, paraquat (PQ) was used to elicit oxidative stress and N-acetylcysteine (NAC) was used as a powerful antioxidant. mNPCs were treated with 80 μm PQ for 24 hours with or without 4 hours of NAC pretreatment. Our results showed that PQ treatment increased intracellular reactive oxygen species production, decreased cell viability and DNA synthesis, and promoted cell apoptosis. Meanwhile, pretreatment with NAC alleviated PQ-induced cytotoxicity in mNPCs. To elucidate the mechanisms further, we found that NAC pretreatment prevented PQ-induced reactive oxygen species production, mitochondrial fragmentation and autophagy in mNPCs. NAC-pretreated cells showed increased anti-apoptotic protein Bcl-2 and decreased pro-apoptotic protein Bax expression. Similarly, NAC pretreatment increased p-mTOR and decreased LC3B-II protein expression. Moreover, NAC decreased mitophagy related mRNA Pink1 and Parkin expression. Taken together, our results suggested that the antioxidant NAC treatment significantly attenuated PQ-induced mNPC self-renewal disruption through decreasing autophagy and salvaging mitochondrial morphology. These findings revealed a potential mechanism for neurological treatment relating to antioxidant and suggested potentially relevant implications for PQ-related neurodegenerative disorders. Thus, our study also provided insight into therapeutic strategies for the neurotoxic effects of oxidative stress-associated toxicants.

A precise, high-throughput and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed for the determination of fluorochloridone (FLC) in rat plasma. The extraction of analytes from plasma samples was carried out by protein precipitation procedure using acetonitrile prior to UPLC-MS/MS analysis. Verapamil was proved as a proper internal standard (IS) among many candidates. The chromatographic separation based on UPLC was well optimized. Multiple reaction monitoring in positive electrospray ionization was used with the optimized MS transitions at: m/z 312.0 → 292.0 for FLC and m/z 456.4 → 165.2 for IS. This method was well validated with good linear response (r(2) > 0.998) observed over the investigated range of 3-3000 ng/mL and with satisfactory stability. This method was also characterized with adequate intra- and inter-day precision and accuracy (within 12%) in the quality control samples, and with high selectivity and less matrix effect observed. Total running time was only 1.5 min. This method has been successfully applied to a pilot FLC pharmacokinetic study after oral administration. Copyright © 2016 John Wiley & Sons, Ltd.

All blood cells are differentiated from hematopoietic stem and progenitor cells (HSPCs), a process known as hematopoiesis that can be influenced by a variety of environmental factors. In this unit, we introduce a couple of protocols including phenotypic analysis, mixed bone marrow (BM) chimera and rescue assays, colony-forming unit (CFU), and in vitro OP9 stromal cell differentiation assays for evaluating HSPCs in the BM of mice, and provide some examples of their implications in mouse models treated with heavy metals. The protocols for evaluating hematopoietic stem cells (HSCs) comprise phenotypic analysis and functional transplantation assays. The protocols for assessing hematopoietic progenitor cells (HPCs) consist of phenotypic analysis and in vitro differentiation assays. The main techniques applied in these protocols include flow cytometry (phenotypic analysis and sorting), irradiation, transplantation, and cell culture. © 2018 by John Wiley & Sons, Inc.

Chronic exposure to Paraquat (PQ) may result in progressive pulmonary fibrosis and subsequent chronic obstructive pulmonary malfunction. Connective tissue growth factor (CTGF) has been proposed as a key determinant in the development of lung fibrosis. We investigated thus whether knock down of CTGF can prevent human lung fibroblasts (MRC-5) activation and proliferation with the subsequent inhibition of PQ-induced fibrosis. MRC-5 was transfected with CTGF-siRNAs and exposed to different concentrations of PQ. The siRNA-silencing efficacy was evaluated using western blotting analyses, qRT-PCR and flow cytometry. Next, the viability and migration of MRC-5 was determined. MMP-2, MMP-9, and TIMP-1 accumulation were quantified to evaluate the lung fibrosis exposure to PQ. Over expression of CTGF mRNA was observed in human MRC-5 cell as early as 6 h following PQ stimulation. CTGF gene expression in MRC-5 cells was substantially reduced by RNAi, which significantly suppressed the expression of the lung fibrosis markers such as tissue inhibitor of metalloproteinase-2 (TIMP-2), Matrix metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9) that were stimulated by PQ. Inhibition of CTGF expression suppressed impeded the proliferation and migration ability of MRC-5 cells and resulted in cell-extracellular matrix (ECM) protein accumulation in cells. Our results suggest that CTGF promoted the development of PQ-induced lung fibrosis in collaboration with transforming growth factor β1 (TGFβ1). Furthermore, the observed arresting effects of CTGF knock down during this process suggested that CTGF is the potential target site for preventing PQ-induced pulmonary fibrosis. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1620-1626, 2016.

Summary Background The monitoring of cosmetic adverse reactions (CARs) in China has progressed to a new stage of development because of government institutional reforms. Objective To discuss and formulate an appropriate model for CAR monitoring in China. Methods The formulation of a new CAR-monitoring model under the administration of the Food and Drug Supervision Department is discussed on the basis of China's current national conditions and with reference to the previous CAR-monitoring and drug-monitoring models of the organization formerly known as the Ministry of Health of the People's Republic of China. Results The preliminary design of the CAR-monitoring model is considered to be a long-term development goal of CAR monitoring. The monitoring model at this stage was developed on the basis of China's national conditions; specifically, the development of a two-level (national and provincial agencies) monitoring system that relies on CAR-monitoring sentinels, and reports that cover CARs with definite causal associations. Conclusion This model is developed on both theoretical and practical foundations, and can function as a proper monitoring model at the initial stage of current CAR monitoring through an appropriate pilot programme, exploration, and improvement.

Bisphenol A (BPA) is an endocrine disruptor with potentially harmful effects on humans. However, epigenetic mechanisms that modulate the effects of BPA remain unclear. Methylation of long interspersed nucleotide elements (LINE-1) is a marker of genome-wide methylation status. This study aims to examine whether BPA exposure was associated with LINE-1 methylation changes in men. Male factory workers in Hunan, China (N = 149) were studied, 77 with BPA exposure in workplace (BPA-exposed group) and 72 without BPA exposure in workplace (control group). Pre-shift and post-shift urine samples were collected from the BPA-exposed group and spot urine samples were collected from the control group. Urine samples were assessed for BPA. In addition, blood and semen samples were collected from both groups for LINE-1 methylation analysis. In multivariate analysis adjusted for age, education, smoking habits and alcohol consumption, sperm LINE-1 methylation level was significantly lower in BPA exposed workers (p

The postoperative respiratory and analgesic effects of dexmedetomidine and morphine have not been compared in children with sleep apnoea having adenotonsillectomy. In a randomised double-blind study we recruited 60 children, aged 2-13 years, who received either intravenous dexmedetomidine 1 μg.kg(-1) or morphine 100 μg.kg(-1) on anaesthetic induction. End-tidal carbon dioxide, Children's Hospital of Eastern Ontario Pain Scale score and supplementary morphine administration were recorded every 15 min for 60 min postoperatively. Over 60 min, mean (SD) end-tidal carbon dioxide was consistently lower with dexmedetomidine compared with morphine (5.4 (0.7) kPa vs 6.0 (0.6) kPa, respectively; p = 0.001). Mean (SD) pain scores were higher with dexmedetomidine (8.1 (2.0) immediately postoperatively and 6.7 (1.0) at 60 min vs 7.6 (1.8) and 6.3 (0.7), respectively, with morphine (p = 0.023)). More patients required supplementary morphine with dexmedetomidine (13/30 (43%) vs 21/30 (70%); p = 0.037). Postoperatively, dexmedetomidine produced less respiratory depression than morphine, but less effective analgesia.

BACKGROUND Bisphenol-A (BPA) is an endocrine disruptor with widespread human exposure. The effect of in utero BPA exposure on human offspring remains largely unknown. METHODS Anogenital distance (AGD) of sons of workers who did or did not have occupational BPA exposure during pregnancy were compared in an occupational cohort study. Parental BPA exposure level during the index pregnancy was estimated through a job-exposure matrix based on personal air sampling measurement. Maternal exposure was considered direct in utero exposure to the fetus, whereas paternal exposure was considered indirect in utero exposure. RESULTS A total of 153 boys were included in the final analysis, among them 56 with parental occupational exposure during pregnancy and 97 without. After controlling for the boys' ages and weights using linear regression, parental occupational exposure to BPA during pregnancy was associated with shortened AGD in male offspring. The association was stronger for maternal exposure (p < 0.01). There was also a dose-response relationship with increased BPA exposure levels in pregnancy associated with greater magnitude of shortened AGD in male offspring, with a statistically significant trend for the association (p = 0.008). CONCLUSION Our findings provide the first epidemiologic evidence that in utero BPA exposure may adversely affect male genital development. Birth Defects Research (Part A) 91:867–872, 2011. © 2011 Wiley-Liss, Inc.

In this study, we investigated the time-course changes of hormone levels and sperm numbers in male Sprague–Dawley (SD) rats after neonatal exposure to 3,3′,4,4′,5,5′-hexachlorobiphenyl (PCB169). Neonatal rats were given (through oral gavages) doses of 0, 0.025, 0.25, or 0.5 mg/kg-day of PCB169 in corn oil from postnatal day 1 (PND1) to PND7. The rats were sacrificed at PND8, PND21, and PND90. PCB169 exposure was confirmed by the marked induction of liver CYP1A1 mRNA expression at these three time points. The testicular daily sperm production and the sperm counts of the epididymis cauda significantly decreased at PND90 compared to that of control. Although reductions in serum thyroxine and triiodothyronine levels occurred at all these three time points and at both PND21 and PND90, respectively, the mRNA expression of testicular thyroid hormone receptor α1 was suppressed significantly only at PND8. The serum and testicular testosterone (T) levels declined markedly at PND90 compared to the controls, but there was no effect at PND21. The mRNA expression of testicular steroidogenic factor 1 was inhibited markedly at the three time points, whereas those of StAR, P450c17, P450scc, and 3β-HSD were suppressed significantly only at PND90 relative to the controls. PCB169 treatment had no effects on pituitary follicle-stimulating hormone and luteinizing hormone levels and on their receptors' expression in the testes. These results indicate that neonatal exposure to PCB169 damages hormone levels and testicular function in the long-term, resulting in persistent hypothyroidism and decreases in adult T levels and sperm counts. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2011.

Background Recent studies indicate that lead may exert actions both directly on osteoblast and osteoclast function, and indirectly via kidney dysfunction on bone turnover. The main focus of this study was to investigate whether occupational lead exposure is associated with low bone mass in a population working in a storage battery plant. Methods Monophoton absorptiometry was used to measure bone mineral density (BMD) in the population and the Z score was introduced to define osteoporosis (Z score

Background The aim of the present study is to determine the long-term testicular effects of neonatal exposure to PCB153. Methods Sprague-Dawley (SD) rats were treated by oral gavage with PCB153 in corn oil at doses of 0, 0.025, and 2.5 mg/kg per day from postnatal day 3 (PND 3) to PND7. The rats were sacrificed on PND 8 and PND 77. TUNEL in situ detection for testis apoptosis, immunohistochemical staining of thyroid gland for thyroxine (T4), semi-quantitative RT-PCR for mRNA expression, and radioimmunoassay (RIA) for serum hormone levels were performed. Results Neonatal treatment with PCB153 at both doses had no obvious effects on body weight, testis weight, testis histology, and germ cell apoptosis, but decreased T4 staining in thyroid gland was observed on PND 8. On PND 77, neonatal treatment with 2.5 mg/kg per day of PCB153 significantly reduced daily sperm product (DSP). Serum levels of thyroxine (T4) and free thyroxine (FT4) decreased, but there were no differences in thyroid-stimulating hormone (TSH) level between the control and exposed groups. Gap junction connexin43 (CX43) and cyclin-dependent kinase inhibitor (CDKI) P27kip1 mRNA expression, which was associated with Sertoli cell differentiation, was significantly reduced after PCB153 treatment on PND 8 but not on PND 77. Androgen-binding protein (ABP) and androgen receptor (AR) mRNA expression, which indicates Sertoli cell maturation, was suppressed on PND 77 after neonatal PCB153 exposure. Conclusions The findings in this study suggest that neonatal exposure to PCB153 induces persistent T4 reduction, which disturbs Sertoli cell function, and subsequently results in alterations in adult spermatogenesis. Birth Defects Res (Part B) 89:18-25, 2010. (c) 2009 Wiley-Liss, Inc.

Effect of Chlordimeform on Cardiovascular Function in Occupational Exposures: Zhijun ZHOU, et al. Department of Occupational Health, Shanghai Medical University—To understand the possible effects of an insecticide, chlordimeform, on the human cardiovascular system, this work was carried out. Pre- and post- exposure, the medical examinations, especially cardiovascular functions, were meticulously done in farmers spraying 0.125% solution of chlordimeforme for 3 consecutive days and packers packing chlordimeform for one month. The exposure level was measured by means of the urinary excretion of chlordimeform and its main metabolite, 4-chlor-o-tolumidine, as well as the air concentration in the work place and skin contamination by using a regional proportional sampling strategy. The alterations, though mild and diverse, were significant compared to their own pre-exposure background. The changes in heart rate, blood pressure and some EKG parameters, such as T wave, P wave, PR interval and Qt interval were noticed. The cardiovascular functional changes were usual and sensitive findings in the exposed persons, and their importance in health surveillance needs to be emphasized. (J Occup Health 1999; 41: 59-61)