Yulang Chi

Fine particulate matter 2.5 exerted its toxicological effect by regulating a new layer, long non-coding RNA

Fine particulate matter (PM2.5) exposure, especially to its organic components, induces adverse health effects on the respiratory system. However, the molecular mechanisms have still not been fully elucidated. Long non-coding RNA (lncRNA) is involved in various physio-pathological processes. In this study, the roles of lncRNA were investigated to reveal the toxicology of PM2.5. Organic extracts of PM2.5 from Nanjing and Shanghai cities were adopted to treat human bronchial epithelial cell lines (BEAS-2B and A549). RNA sequencing showed that the lncRNA functioned as antisense RNA, intergenic RNA and pre-miRNA. The mRNA profiles were also altered after exposure. PM2.5 from Nanjing showed a more serious impact than that from Shanghai. In detail, higher expression of n405968 was positively related to the elevated mRNA levels of inflammatory factors (IL-6 and IL-8). Increasing levels of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) were positively associated with the induced epithelial-mesenchymal transition (EMT) process. Similar response was observed between both cell lines. The higher content of polycyclic aromatic hydrocarbons (PAHs) is likely to contribute to higher toxicity of PM2.5 from Nanjing than that from Shanghai. Antagonism of aryl hydrocarbon receptor (AHR) or inhibition of CYP1A1 diminished the effects stimulated by PM2.5. Our results indicated that lncRNAs could be involved in the toxicology of PM2.5 through regulating the inflammation and EMT process.

The Inflammation Response to DEHP through PPARγ in Endometrial Cells

Epidemiological studies have shown the possible link between phthalates and endometrium-related gynecological diseases, however the molecular mechanism(s) behind this is/are still unclear. In the study, both primary cultured endometrial cells and an endometrial adenocarcinoma cell line (Ishikawa) were recruited to investigate the effects of di-(2-ethylhexyl) phthalate (DEHP) at human-relevant concentrations. The results showed that DEHP did not affect the viability of either type of cell, which showed different responses to inflammation. Primary cultured cells showed stronger inflammatory reactions than the Ishikawa cell line. The expression of inflammatory factors was induced both at the mRNA and protein levels, however the inflammation did not induce the progress of epithelial-mesenchymal transition (EMT) as the protein levels of EMT markers were not affected after exposure to either cell type. Further study showed that the mRNA levels of peroxisome proliferator-activated receptor gamma (PPARγ) wereup-regulated after exposure. In all, our study showed that human-relevant concentrations of DEHP could elicit the inflammatory response in primary cultured endometrial cells rather than in Ishikawa cell line. PPARγ may act as the mediating receptor in the inflammation reaction.

Different effects of bisphenol a and its halogenated derivatives on the reproduction and development of Oryzias melastigma under environmentally relevant doses

Bisphenol A (BPA) and its halogenated compounds (H-BPAs) are widely detected in the environmental media and organisms. However, their toxicological effects, especially chronic exposure at low doses, have not been fully compared. In this study, the effects of BPA and H-BPAs on the reproduction and development of Oryzias melastigma were systematically assessed and compared at various developmental stages. BPA and its derivatives tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) elicited the acceleration of embryonic heartbeat. BPA did not show any significant impact on the hatching time and rate of embryos. In contrast, both TBBPA and TCBPA led to the delayed hatching and decreased hatching rate. Accordingly, the expressions of hatching enzyme significantly decreased upon exposure and TCBPA was found to be more toxic than TBBPA. The body weight and gonadsomatic index (GSI) of the treated fish were relatively lower than the control fish upon long-term (four months from larvae to adult) exposure to BPA rather than H-BPAs. Slowed oocyte development occurred in the ovary, and the estrogen level decreased after exposure to BPA rather than H-BPAs. In male fish, no significant alteration was observed in the testis for all groups. The concentration of testosterone significantly decreased upon exposure to BPA rather than H-BPAs. The effects of these three chemicals on the estrogen-related gene expressions were different under various developmental stages. Our study indicated the importance of considering both the exposure stages and structure-activity relationship when assessing the eco-toxicological impact of pollutants.

Metabolomics approach reveals metabolic disorders and potential biomarkers associated with the developmental toxicity of tetrabromobisphenol A and tetrachlorobisphenol A.

Tetrabromobisphenol A and tetrachlorobisphenol A are halogenated bisphenol A (H-BPA), and has raised concerns about their adverse effects on the development of fetuses and infants, however, the molecular mechanisms are unclear, and related metabolomics studies are limited. Accordingly, a metabolomics study based on gas chromatography-mass spectrometry was employed to elucidate the molecular developmental toxicology of H-BPA using the marine medaka (Oryzias melastigmas) embryo model. Here, we revealed decreased synthesis of nucleosides, amino acids and lipids, and disruptions in the TCA (tricarboxylic acid) cycle, glycolysis and lipid metabolism, thus inhibiting the developmental processes of embryos exposed to H-BPA. Unexpectedly, we observed enhanced neural activity accompanied by lactate accumulation and accelerated heart rates due to an increase in dopamine pathway and a decrease in inhibitory neurotransmitters following H-BPA exposure. Notably, disorders of the neural system, and disruptions in glycolysis, the TCA cycle, nucleoside metabolism, lipid metabolism, glutamate and aspartate metabolism induced by H-BPA exposure were heritable. Furthermore, lactate and dopa were identified as potential biomarkers of the developmental toxicity of H-BPA and related genetic effects. This study has demonstrated that the metabolomics approach is a useful tool for obtaining comprehensive and novel insights into the molecular developmental toxicity of environmental pollutants.

Epithelial-mesenchymal transition effect of fine particulate matter from the Yangtze River Delta region in China on human bronchial epithelial cells

Epidemiological studies have demonstrated that fine particulate matter (PM2.5) exposure causes airway inflammation, which may lead to lung cancer. The activation of epithelial-mesenchymal transition (EMT) is assumed to be a crucial step in lung tumor metastasis and development. We assessed the EMT effect of low concentrations (0, 0.1, 1.0, and 5.0μg/mL) of PM2.5 organic extract on a human bronchial epithelial cell line (BEAS-2B). PM2.5 samples were collected from three cities (Shanghai, Ningbo, and Nanjing) in the Yangtze River Delta (YRD) region in autumn 2014. BEAS-2B cells were exposed to the PM2.5 extract to assess cell viability, invasion ability as well as the relative mRNA and protein expressions of EMT markers. Our findings revealed that BEAS-2B cells changed from the epithelial to mesenchymal phenotype after exposure. In all groups, PM2.5 exposure dose-dependently decreased the expression of E-cadherin and increased the expression of Vimentin. The key transcription factors, including ZEB1 and Slug, were significantly up-regulated upon exposure. These results indicated that the PM2.5 organic extract induced different degrees of EMT progression in BEAS-2B cells. The cell invasion ability increased in a concentration-dependent manner after 48hr of treatment with the extract. This study offers a novel insight into the effects of PM2.5 on EMT and the potential health risks associated with PM2.5 in the YRD region.

In situ combined chemical and biological assessment of estrogenic pollution in a water recycling system

Estrogenic pollution and its control in aquatic systems have drawn substantial attention around the world. The chemical and biological assessment approaches currently utilized in the laboratory or field cannot give an integrated assessment of the pollution when used separately. In this study, in situ chemical and biological methods were combined to detect pollution in a water recycling system. Data for the water quality index (WQI) demonstrated that the water treatment resulted in the decline of pollution from upstream to downstream. Wild male Nile tilapia, Oreochromis niloticus, was sampled in June and September. The concentrations of four common endocrine disrupting chemicals (EDCs) were determined in the tilapia liver by chromatographic analysis methods. The level of 17β-estradiol (E2) declined from upstream to downstream in both months. In contrast, the levels of bisphenol A (BPA), di-(2-ethylhcxyl) phthalate (DEHP), and perfluorooctane sulfonate (PFOS) did not display this declining tendency. The highest relative expression of vitellogenin 1 (VTG1) was observed in tilapia from upstream, then the level significantly decreased along the water system. The relative expression levels of CYP1A1 in the water system were also significantly higher than that of the control. However, no declining trend could be observed along the water system. The change of VTG1 expression corresponded well with that of E2 levels in the tilapia liver. Overall, our study assessed the pollution by endocrine disruptors using chemical and biological data with good correspondence. This study also demonstrated the effectiveness of the water recycling system in eliminating estrogen pollution in municipal sewage.

PCBs-high-fat diet interactions as mediators of gut microbiota dysbiosis and abdominal fat accumulation in female mice

Polychlorinated biphenyls (PCBs), one type of lipophilic pollutant, are ubiquitous in daily life. PCBs exposure has been implicated in the alterations of gut microbial community which is profoundly associated with diverse metabolic disorders, including obesity. High-fat diet (H) is a dietary pattern characterized by a high percentage of fat. According to the theory that similarities can be easily solvable in each other, PCBs and H exposures are inevitably and objectively coexistent in a real living environment, prompting great concerns about their individual and combined effects on hosts. However, the effects of PCBs-H interactions on gut microbiota and obesity are still incompletely understood. In the present study, the effects of PCBs and/or H on the gut microbiota alteration and obesity risk in mice were examined and the interactions between PCBs and H were investigated. Obtained results showed that PCBs and/or H exposure induced prominent variations in the gut microbiota composition and diversity. Exposure to PCBs also resulted in higher body fat percentage, greater size of abdominal subcutaneous adipocytes and increased expression of proinflammatory cytokines including TNF-α, iNOS and IL-6. Such PCBs-induced changes could be further enhanced upon the co-exposure of H, implying that obese individuals may be vulnerable to PCBs exposure. Taken together, the present study is helpful for a better understanding of the gut microbiota variation influenced by PCBs and/or H exposure, and furthermore, provides a novel insight into the mechanism of PCBs-H interactions on host adiposity.

Evaluation of Volatile Organic Compounds and Carbonyl Compounds Present in the Cabins of Newly Produced, Medium- and Large-Size Coaches in China.

An air-conditioned coach is an important form of transportation in modern motorized society; as a result, there is an increasing concern of in-vehicle air pollution. In this study, we aimed to identify and quantify the levels of volatile organic compounds (VOCs) and carbonyl compounds (CCs) in air samples collected from the cabins of newly produced, medium- and large-size coaches. Among the identified VOCs and CCs, toluene, ethylbenzene, xylene, formaldehyde, acetaldehyde, acrolein/acetone, and isovaleraldehyde were relatively abundant in the cabins. Time was found to affect the emissions of the contaminants in the coaches. Except for benzaldehyde, valeraldehyde and benzene, the highest in-vehicle concentrations of VOCs and CCs were observed on the 15th day after coming off the assembly line, and the concentrations exhibited an approximately inverted U-shaped pattern as a function of time. Interestingly, this study also showed that the interior temperature of the coaches significantly affected the VOCs emissions from the interior materials, whereas the levels of CCs were mainly influenced by the relative humidity within the coaches. In China, guidelines and regulations for the in-vehicle air quality assessment of the coaches have not yet been issued. The results of this study provide further understanding of the in-vehicle air quality of air-conditioned coaches and can be used in the development of both specific and general rules regarding medium- and large-size coaches.

New insights into the metabolism and toxicity of bisphenol A on marine fish under long-term exposure

Bisphenol A (BPA) exposure receives great ecotoxicological concern. However, gaps in knowledge, such as metabolism of BPA and inconsistent reports on reproductive toxicity, still exist. In this study, a marine fish model (Oryzias melastigma) was exposed to serial concentrations of BPA throughout its whole life cycle. The level of BPA-glucuronide (BPAG) dramatically increased throughout the embryonic stage since 4 dpf. Accordingly, the mRNA level and enzymatic activity of UDP-glucuronosyltransferases (UGTs) increased across the embryonic stage. The mRNA level of UGT2 subtype rather than UGT1 or UGT5 showed a concentration dependent response to BPA exposure. BPA exposure led to the morphological disruption of the chorion and villi as shown by scanning electron microscopy; however, the hatchability was not significantly influenced after exposure. Newly hatching larvae were continuously exposed to BPA for 120 days. Lower mRNA levels of hormone metabolism-related genes, decreased ratio of E2/T, slower ovary development and decreased egg production confirmed the inhibitory effect of BPA on reproduction. Overall, our results showed the conjugation of BPA into BPAG by UGT2 at the embryonic stage and convinced the reproductive toxicity from multiple levels after whole life exposure to BPA.

Enantiomeric resolution, stereochemical assignment and toxicity evaluation of TPA enantiomers.

Tetrahydro-α-(1-methylethyl)-2-oxo-1(2H)-pyrimidineacetic acid (TPA) is a critical intermediate in the synthesis of HIV protease inhibitors. A simple and efficient method for the separation and determination of TPA enantiomers was developed. The TPA was separated into its enantiomers with an enantiomeric purity of 99% using an HPLC system equipped with a Chiralpak OD-H column. Semi-preparative HPLC enantioseparations were carried out for further enrichment of the enantiomers. The validity of this method was evaluated on the basis of its precision, accuracy, linearity and recovery. The method was observed to be suitable for the rapid separation and semi-preparation of TPA isomers. The separated enantiomers were identified by optical rotation and high-resolution electrospray ionization mass spectrometry. Furthermore, the stereochemical structures of the TPA enantiomers were definitively confirmed using a combination of experimental and calculated electronic circular dichroism spectra. The toxicity of the separated pure enantiomers against Oryzias melastigma was evaluated using the median lethal concentration (LC50 ) values. The results indicated that (S)-(-)-TPA is ~2.5 times more toxic than its enantiomorphism.