The Experts below are selected from a list of 1056 Experts worldwide ranked by ideXlab platform
Bing Shao - One of the best experts on this subject based on the ideXlab platform.
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Mechanism of Bisphenol AF-induced progesterone inhibition in human chorionic gonadotrophin-stimulated mouse Leydig tumor cell line (mLTC-1) cells.
Environmental toxicology, 2018Co-Authors: Yixing Feng, Zhihao Jiao, Jiachen Shi, Hejun Duan, Bing ShaoAbstract:Bisphenol AF (BPAF) has been shown to inhibit testicular steroidogenesis in male rats. However, the precise mechanisms related to the toxic effects of BPAF on reproduction remain poorly understood. In the present study, a mouse Leydig tumor cell line (mLTC-1) was used as a model to investigate the mechanism of steroidogenic inhibition and to identify the molecular target of BPAF. Levels of progesterone and the concentration of cyclic adenosine monophosphate (cAMP) in cells exposed to BPAF were detected, and expression of key genes and proteins in steroid biosynthesis was assessed. The results showed that BPAF exposure decreased human chorionic gonadotrophin (hCG)-stimulated progesterone production in a dose-dependent manner. The 24-h IC50 (half maximal inhibitory concentration) value for BPAF regarding progesterone production was 70.2 µM. A dramatic decrease in cellular cAMP concentration was also observed. Furthermore, BPAF exposure inhibited expression of genes and proteins involved in cholesterol transport and progesterone biosynthesis. Conversely, the protein levels of steroidogenic acute regulatory protein (StAR) were not altered, and those of progesterone were still decreased upon 22R-hydroxycholesterol treatment of cells exposed to higher doses of BPAF. Together, these data indicate that BPAF exposure inhibits progesterone secretion in hCG-stimulated mLTC-1 cells by reducing expression of scavenger receptor class B type I (SR-B1) and cytochrome P450 (P450scc) due to the adverse effects of cAMP. However, StAR might not be the molecular target in this process.
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Gestational and lactational exposure to Bisphenol AF in maternal rats increases testosterone levels in 23-day-old male offspring.
Chemosphere, 2016Co-Authors: Nan Sheng, Yixing Feng, Bing Shao, Ruina Cui, Xuejiang Guo, Hongxia Zhang, Jiayin DaiAbstract:Abstract During prenatal and postnatal development, exposure to environmental chemicals with estrogenic activity, such as Bisphenol AF (BPAF), may result in reproductive disorders. Currently, the mechanisms behind such disorders in male offspring induced by gestational and lactational exposure to BPAF remain poorly understood. Here, female rats from gestational day (GD) 3–19 were exposed to 100 mg BPAF/kg/day by oral gavage. On the day of birth (postnatal day (PD) 0), cross-fostering took place between treated and control litters, and cross-fostered mother rats were given BPAF 100 mg/kg/day during the postnatal period (PD 3 to PD 19). HPLC-MS/MS analysis showed that BPAF was transferred via cord blood and lactation, finally bio-accumulating in the offspring testes. Pups exposed to BPAF both prenatally and postnatally showed a significant increase in testis testosterone levels compared with that of the control, while all pups exposed to BPAF showed a significant decrease in testis inhibin B (INHB) levels. Compared with the control, RNA-seq revealed that 279 genes were significantly differentially expressed in the testes of pups exposed to BPAF both prenatally and postnatally, including genes involved in cell differentiation and meiosis. These results indicate that gestational and lactational exposure to BPAF in the mother can impair reproductive function in male offspring.
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Bisphenol AF-Induced Endogenous Transcription Is Mediated by ERa and ERK1/2 Activation in Human Breast Cancer
2016Co-Authors: Jing Guo, Jing Zhang, Wenhui Gao, Xiaoyu Han, Bing ShaoAbstract:Bisphenol AF (BPAF)-induced transcriptional activity has been evaluated by luciferase reporter assay. However, the molecular mechanism of BPAF-induced endogenous transcription in human breast cancer cells has not been fully elucidated. In the present study, we investigated the effect and mechanism of BPAF-induced endogenous transcription detected by real-time PCR in human breast cancer cells. We found that BPAF stimulated transcription of estrogen responsive genes, such as trefoil factor 1 (TFF1), growth regulation by estrogen in breast cancer 1 (GREB1) and cathepsin D (CTSD), through dose-dependent and time-dependent manners in T47D and MCF7 cells. Gene-silencing of ERa, ERb and G protein-coupled estrogen receptor 1 (GPER) by small interfering RNA revealed that BPAF-induced endogenous transcription was dependent on ERa and GPER, implying both genomic and nongenomic pathways might be involved in the endogenous transcription induced by BPAF. ERa-mediated gene transcription was further confirmed by inhibition of ER activity using ICI 182780 in ERa-positive T47D and MCF7 cells as well as overexpression of ERa in ERa-negative MDA-MB-231 breast cancer cells. Moreover, we utilized Src tyrosine kinase inhibitor PP2 and two MEK inhibitors PD98059 and U0126 to elucidate the rapid nongenomic activation of Src/MEK/ERK1/2 cascade on endogenous transcription. Our data showed that BPAF-induced transcription could be significantly blocked by PP2, PD98059 and U0126, suggesting activation of ERK1/2 was also required to regulate endogenous transcription. Taken together, these results indicate that BPAF-induced endogenous transcriptio
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Uptake, depuration and bioconcentration of Bisphenol AF (BPAF) in whole-body and tissues of zebrAFish (Danio rerio).
Ecotoxicology and environmental safety, 2016Co-Authors: Jiachen Shi, Jing Zhang, Yixing Feng, Yunjia Yang, Bing ShaoAbstract:Abstract Bisphenol AF (BPAF) is an analog of Bisphenol A (BPA) and is widely used as a raw material in the plastics industry. However, an understanding of the potential risks posed by BPAF in the aquatic environment is lacking. The bioconcentration factor (BCF) is a measure used to assess the secondary poisoning potential as well as risks to human health. In this work we measured the accumulation and elimination of BPAF in the whole-body and in liver, muscle and gonad tissues of zebrAFish. BPAF uptake was relatively rapid with equilibrium concentrations reached AFter 24–72 h of exposure. We observed gender differences both in whole-body and in tissue accumulation. Muscle was the primary BPAF storage tissue during the uptake phase in this study. In the elimination phase, BPAF concentrations declined rapidly during depuration, especially during the initial 2 h, and the rate of elimination in males was faster than females from the whole-body and from tissues. The appearance of BPAF glucuronide (BPAF-G) at the start of the uptake phase indicated the rapid biotransformation of BPAF to BPAF-G in vivo. The high lipid content of female gonad could act to delay the diffusion of the xenobiotic within the body in a contaminated environment, but it also acts to delay xenobiotic elimination from the body.
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Bisphenol AF-Induced Endogenous Transcription Is Mediated by ERα and ERK1/2 Activation in Human Breast Cancer Cells
PloS one, 2014Co-Authors: Jing Guo, Jing Zhang, Wenhui Gao, Xiaoyu Han, Bing ShaoAbstract:Bisphenol AF (BPAF)-induced transcriptional activity has been evaluated by luciferase reporter assay. However, the molecular mechanism of BPAF-induced endogenous transcription in human breast cancer cells has not been fully elucidated. In the present study, we investigated the effect and mechanism of BPAF-induced endogenous transcription detected by real-time PCR in human breast cancer cells. We found that BPAF stimulated transcription of estrogen responsive genes, such as trefoil factor 1 (TFF1), growth regulation by estrogen in breast cancer 1 (GREB1) and cathepsin D (CTSD), through dose-dependent and time-dependent manners in T47D and MCF7 cells. Gene-silencing of ERα, ERβ and G protein-coupled estrogen receptor 1 (GPER) by small interfering RNA revealed that BPAF-induced endogenous transcription was dependent on ERα and GPER, implying both genomic and nongenomic pathways might be involved in the endogenous transcription induced by BPAF. ERα-mediated gene transcription was further confirmed by inhibition of ER activity using ICI 182780 in ERα-positive T47D and MCF7 cells as well as overexpression of ERα in ERα-negative MDA-MB-231 breast cancer cells. Moreover, we utilized Src tyrosine kinase inhibitor PP2 and two MEK inhibitors PD98059 and U0126 to elucidate the rapid nongenomic activation of Src/MEK/ERK1/2 cascade on endogenous transcription. Our data showed that BPAF-induced transcription could be significantly blocked by PP2, PD98059 and U0126, suggesting activation of ERK1/2 was also required to regulate endogenous transcription. Taken together, these results indicate that BPAF-induced endogenous transcription of estrogen responsive genes is mediated through both genomic and nongenomic pathways involving the ERα and ERK1/2 activation in human breast cancer cells.
Yunjia Yang - One of the best experts on this subject based on the ideXlab platform.
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Uptake, depuration and bioconcentration of Bisphenol AF (BPAF) in whole-body and tissues of zebrAFish (Danio rerio).
Ecotoxicology and environmental safety, 2016Co-Authors: Jiachen Shi, Jing Zhang, Yixing Feng, Yunjia Yang, Bing ShaoAbstract:Abstract Bisphenol AF (BPAF) is an analog of Bisphenol A (BPA) and is widely used as a raw material in the plastics industry. However, an understanding of the potential risks posed by BPAF in the aquatic environment is lacking. The bioconcentration factor (BCF) is a measure used to assess the secondary poisoning potential as well as risks to human health. In this work we measured the accumulation and elimination of BPAF in the whole-body and in liver, muscle and gonad tissues of zebrAFish. BPAF uptake was relatively rapid with equilibrium concentrations reached AFter 24–72 h of exposure. We observed gender differences both in whole-body and in tissue accumulation. Muscle was the primary BPAF storage tissue during the uptake phase in this study. In the elimination phase, BPAF concentrations declined rapidly during depuration, especially during the initial 2 h, and the rate of elimination in males was faster than females from the whole-body and from tissues. The appearance of BPAF glucuronide (BPAF-G) at the start of the uptake phase indicated the rapid biotransformation of BPAF to BPAF-G in vivo. The high lipid content of female gonad could act to delay the diffusion of the xenobiotic within the body in a contaminated environment, but it also acts to delay xenobiotic elimination from the body.
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simultaneous determination of Bisphenol a Bisphenol AF tetrachloroBisphenol a and tetrabromoBisphenol a concentrations in water using on line solid phase extraction with ultrahigh pressure liquid chromatography tandem mass spectrometry
International Journal of Environmental Analytical Chemistry, 2014Co-Authors: Yunjia Yang, Yi Yang, Jing Zhang, Bing ShaoAbstract:An on-line solid-phase extraction (SPE) ultrahigh-pressure liquid chromatography tandem mass spectrometry method was developed and validated for the simultaneous determination of the Bisphenol A, Bisphenol AF, tetrachloroBisphenol A, and tetrabromoBisphenol A concentrations in water samples. The on-line SPE system used a 10 µm particle size SPE column to concentrate the analytes and was coupled with a 1.7 µm particle size chromatographic column for analysis. The total analysis time for each sample using this process was only 12 min, and the method limit of quantification (MLOQ) ranged from 1.5 to 53 ng/L for different water matrices when a 2.5 mL sample was injected. Isotopic internal standard calibration was used to compensate for matrix effects in the trace-level analysis using mass spectrometry. The method has good precision (RSD < 14.1%) and accuracy (spiked recoveries ranging from 85.1% to 110.8% at three spiking levels). Finally, this method was successfully used to analyse real environmental water ...
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Biotransformation of Bisphenol AF to Its Major Glucuronide Metabolite Reduces Estrogenic Activity
PloS one, 2013Co-Authors: Yunjia Yang, Yi Yang, Jing Zhang, Yixing Feng, Jie Yin, Bing ShaoAbstract:Bisphenol AF (BPAF), an endocrine disrupting chemical, can induce estrogenic activity through binding to estrogen receptor (ER). However, the metabolism of BPAF in vivo and the estrogenic activity of its metabolites remain unknown. In the present study, we identified four metabolites including BPAF diglucuronide, BPAF glucuronide (BPAF-G), BPAF glucuronide dehydrated and BPAF sulfate in the urine of Sprague-Dawley (SD) rats. BPAF-G was further characterized by nuclear magnetic resonance (NMR). AFter treatment with a single dose of BPAF, BPAF was metabolized rapidly to BPAF-G, as detected in the plasma of SD rats. Biotransformation of BPAF to BPAF-G was confirmed with human liver microsomes (HLM), and Vmax of glucuronidation for HLM was 11.6 nmol/min/mg. We also found that BPAF glucuronidation could be mediated through several human recombinant UDP-glucuronosyltransferases (UGTs) including UGT1A1, UGT1A3, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15 and UGT2B17, among which UGT2B7 showed the highest efficiency of glucuronidation. To explain the biological function of BPAF biotransformation, the estrogenic activities of BPAF and BPAF-G were evaluated in ER-positive breast cancer T47D and MCF7 cells. BPAF significantly stimulates ER-regulated gene expression and cell proliferation at the dose of 100 nM and 1 μM in breast cancer cells. However, BPAF-G did not show any induction of estrogenic activity at the same dosages, implying that formation of BPAF-G is a potential host defense mechanism against BPAF. Based on our study, biotransformation of BPAF to BPAF-G can eliminate BPAF-induced estrogenic activity, which is therefore considered as reducing the potential threat to human beings.
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Simultaneous determination of Bisphenol A, Bisphenol AF, tetrachloroBisphenol A, and tetrabromoBisphenol A concentrations in water using on-line solid-phase extraction with ultrahigh-pressure liquid chromatography tandem mass spectrometry
International Journal of Environmental Analytical Chemistry, 2013Co-Authors: Yunjia Yang, Yi Yang, Jing Zhang, Bing ShaoAbstract:An on-line solid-phase extraction (SPE) ultrahigh-pressure liquid chromatography tandem mass spectrometry method was developed and validated for the simultaneous determination of the Bisphenol A, Bisphenol AF, tetrachloroBisphenol A, and tetrabromoBisphenol A concentrations in water samples. The on-line SPE system used a 10 µm particle size SPE column to concentrate the analytes and was coupled with a 1.7 µm particle size chromatographic column for analysis. The total analysis time for each sample using this process was only 12 min, and the method limit of quantification (MLOQ) ranged from 1.5 to 53 ng/L for different water matrices when a 2.5 mL sample was injected. Isotopic internal standard calibration was used to compensate for matrix effects in the trace-level analysis using mass spectrometry. The method has good precision (RSD
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Determination of Bisphenol AF (BPAF) in tissues, serum, urine and feces of orally dosed rats by ultra-high-pressure liquid chromatography-electrospray tandem mass spectrometry.
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2012Co-Authors: Yunjia Yang, Yi Yang, Jing Zhang, Jie Yin, Naiyuan Zhou, Bing ShaoAbstract:As a homologue of Bisphenol A (BPA), there is concern about the potential reproductive and developmental toxicity of Bisphenol AF (BPAF) based on in vitro tests. In this study, a simple and universal analytical method was developed for the determination of trace BPAF in various tissues and excreta of rats AFter they were orally dosed. The samples were hydrolyzed with glucuronidase/arylsulfatase followed by ultrasonic extraction with acetonitrile. The crude extract was purified with a mixed-mode anion exchange (Oasis MAX) solid-phase extraction (SPE) cartridge. Separation and quantification was then conducted by ultra-high-pressure liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) in negative ionization mode. The recoveries at three fortification levels in different biological samples were from 71.0% to 102.3% with relative standard deviations no more than 13.2% (n=6). The quantification limits of the method were from 0.5 μg/kg to 3 μg/kg depending on the matrix. This method was successfully applied to the determination of BPAF in tissues, serum, urine and feces of orally dosed rats.
Jing Zhang - One of the best experts on this subject based on the ideXlab platform.
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Bisphenol AF and Bisphenol B Exert Higher Estrogenic Effects than Bisphenol A via G Protein-Coupled Estrogen Receptor Pathway
Environmental science & technology, 2017Co-Authors: Lin-ying Cao, Jing Zhang, Xiao-min Ren, Wei-ping Qin, Yu Yang, Bin Wan, Liang-hong GuoAbstract:Numerous studies have indicated estrogenic disruption effects of Bisphenol A (BPA) analogues. Previous mechanistic studies were mainly focused on their genomic activities on nuclear estrogen receptor pathway. However, their non-genomic effects through G protein-coupled estrogen receptor (GPER) pathway remain poorly understood. Here, using a SKBR3 cell-based fluorescence competitive binding assay, we found six BPA analogues bound to GPER directly, with Bisphenol AF (BPAF) and Bisphenol B (BPB) displaying much higher (~9-fold) binding AFfinity than BPA. Molecular docking also demonstrated the binding of these BPA analogues to GPER. By measuring calcium mobilization and cAMP production in SKBR3 cells, we found the binding of these BPA analogues to GPER lead to the activation of subsequent signaling pathways. Consistent with the binding results, BPAF and BPB presented higher agonistic activity than BPA with the lowest effective concentration (LOEC) of 10 nM. Moreover, based on the results of Boyden chamber an...
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Bisphenol AF and Bisphenol B Exert Higher Estrogenic Effects than Bisphenol A via G Protein-Coupled Estrogen Receptor Pathway
2017Co-Authors: Lin-ying Cao, Jing Zhang, Xiao-min Ren, Wei-ping Qin, Yu Yang, Bin Wan, Liang-hong GuoAbstract:Numerous studies have indicated estrogenic disruption effects of Bisphenol A (BPA) analogues. Previous mechanistic studies were mainly focused on their genomic activities on nuclear estrogen receptor pathway. However, their nongenomic effects through G protein-coupled estrogen receptor (GPER) pathway remain poorly understood. Here, using a SKBR3 cell-based fluorescence competitive binding assay, we found six BPA analogues bound to GPER directly, with Bisphenol AF (BPAF) and Bisphenol B (BPB) displaying much higher (∼9-fold) binding AFfinity than BPA. Molecular docking also demonstrated the binding of these BPA analogues to GPER. By measuring calcium mobilization and cAMP production in SKBR3 cells, we found the binding of these BPA analogues to GPER lead to the activation of subsequent signaling pathways. Consistent with the binding results, BPAF and BPB presented higher agonistic activity than BPA with the lowest effective concentration (LOEC) of 10 nM. Moreover, based on the results of Boyden chamber and wound-healing assays, BPAF and BPB displayed higher activity in promoting GPER mediated SKBR3 cell migration than BPA with the LOEC of 100 nM. Overall, we found two BPA analogues BPAF and BPB could exert higher estrogenic effects than BPA via GPER pathway at nanomolar concentrations
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Bisphenol AF-Induced Endogenous Transcription Is Mediated by ERa and ERK1/2 Activation in Human Breast Cancer
2016Co-Authors: Jing Guo, Jing Zhang, Wenhui Gao, Xiaoyu Han, Bing ShaoAbstract:Bisphenol AF (BPAF)-induced transcriptional activity has been evaluated by luciferase reporter assay. However, the molecular mechanism of BPAF-induced endogenous transcription in human breast cancer cells has not been fully elucidated. In the present study, we investigated the effect and mechanism of BPAF-induced endogenous transcription detected by real-time PCR in human breast cancer cells. We found that BPAF stimulated transcription of estrogen responsive genes, such as trefoil factor 1 (TFF1), growth regulation by estrogen in breast cancer 1 (GREB1) and cathepsin D (CTSD), through dose-dependent and time-dependent manners in T47D and MCF7 cells. Gene-silencing of ERa, ERb and G protein-coupled estrogen receptor 1 (GPER) by small interfering RNA revealed that BPAF-induced endogenous transcription was dependent on ERa and GPER, implying both genomic and nongenomic pathways might be involved in the endogenous transcription induced by BPAF. ERa-mediated gene transcription was further confirmed by inhibition of ER activity using ICI 182780 in ERa-positive T47D and MCF7 cells as well as overexpression of ERa in ERa-negative MDA-MB-231 breast cancer cells. Moreover, we utilized Src tyrosine kinase inhibitor PP2 and two MEK inhibitors PD98059 and U0126 to elucidate the rapid nongenomic activation of Src/MEK/ERK1/2 cascade on endogenous transcription. Our data showed that BPAF-induced transcription could be significantly blocked by PP2, PD98059 and U0126, suggesting activation of ERK1/2 was also required to regulate endogenous transcription. Taken together, these results indicate that BPAF-induced endogenous transcriptio
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Uptake, depuration and bioconcentration of Bisphenol AF (BPAF) in whole-body and tissues of zebrAFish (Danio rerio).
Ecotoxicology and environmental safety, 2016Co-Authors: Jiachen Shi, Jing Zhang, Yixing Feng, Yunjia Yang, Bing ShaoAbstract:Abstract Bisphenol AF (BPAF) is an analog of Bisphenol A (BPA) and is widely used as a raw material in the plastics industry. However, an understanding of the potential risks posed by BPAF in the aquatic environment is lacking. The bioconcentration factor (BCF) is a measure used to assess the secondary poisoning potential as well as risks to human health. In this work we measured the accumulation and elimination of BPAF in the whole-body and in liver, muscle and gonad tissues of zebrAFish. BPAF uptake was relatively rapid with equilibrium concentrations reached AFter 24–72 h of exposure. We observed gender differences both in whole-body and in tissue accumulation. Muscle was the primary BPAF storage tissue during the uptake phase in this study. In the elimination phase, BPAF concentrations declined rapidly during depuration, especially during the initial 2 h, and the rate of elimination in males was faster than females from the whole-body and from tissues. The appearance of BPAF glucuronide (BPAF-G) at the start of the uptake phase indicated the rapid biotransformation of BPAF to BPAF-G in vivo. The high lipid content of female gonad could act to delay the diffusion of the xenobiotic within the body in a contaminated environment, but it also acts to delay xenobiotic elimination from the body.
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Direct interactions in the recognition between the environmental estrogen Bisphenol AF and human serum albumin.
Journal of molecular recognition : JMR, 2015Co-Authors: Lijun Yang, Xin Wang, Jing Zhang, Tingting Zhang, Zhenzhen Zhang, Lei ZhangAbstract:Bisphenol AF (BPAF) was used as a model compound to investigate the binding mechanism between the endocrine disrupting compound and human serum albumin (HSA) using multispectroscopic techniques and molecular modeling method at the protein level. The results indicated that BPAF was indeed bound to HSA and located in the hydrophobic pocket of HSA on subdomain IIA through hydrogen bond and van der Waals interactions. The fluorescence quenching data showed that the binding of BPAF and HSA quenched the intrinsic fluorescence of HSA, and the static quenching constants were acquired. Copyright © 2015 John Wiley & Sons, Ltd.
Yi Yang - One of the best experts on this subject based on the ideXlab platform.
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Transformation of Bisphenol AF and Bisphenol S by manganese dioxide and effect of iodide.
Water Research, 2018Co-Authors: Su–yan Pang, Yang Zhou, Shaofang Sun, Lihong Wang, Zhen Wang, Yuan Gao, Yi Yang, Jin JiangAbstract:Abstract In this work, transformation of Bisphenol A (BPA) alternatives Bisphenol AF (BPAF) and Bisphenol S (BPS) by manganese dioxide (MnO2) and the effect of iodide (I−) during these processes were investigated in comparison with BPA for the first time. These three Bisphenols showed appreciable reactivity towards MnO2 with the half-lives of their loss following the order of BPA
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simultaneous determination of Bisphenol a Bisphenol AF tetrachloroBisphenol a and tetrabromoBisphenol a concentrations in water using on line solid phase extraction with ultrahigh pressure liquid chromatography tandem mass spectrometry
International Journal of Environmental Analytical Chemistry, 2014Co-Authors: Yunjia Yang, Yi Yang, Jing Zhang, Bing ShaoAbstract:An on-line solid-phase extraction (SPE) ultrahigh-pressure liquid chromatography tandem mass spectrometry method was developed and validated for the simultaneous determination of the Bisphenol A, Bisphenol AF, tetrachloroBisphenol A, and tetrabromoBisphenol A concentrations in water samples. The on-line SPE system used a 10 µm particle size SPE column to concentrate the analytes and was coupled with a 1.7 µm particle size chromatographic column for analysis. The total analysis time for each sample using this process was only 12 min, and the method limit of quantification (MLOQ) ranged from 1.5 to 53 ng/L for different water matrices when a 2.5 mL sample was injected. Isotopic internal standard calibration was used to compensate for matrix effects in the trace-level analysis using mass spectrometry. The method has good precision (RSD < 14.1%) and accuracy (spiked recoveries ranging from 85.1% to 110.8% at three spiking levels). Finally, this method was successfully used to analyse real environmental water ...
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Biotransformation of Bisphenol AF to Its Major Glucuronide Metabolite Reduces Estrogenic Activity
PloS one, 2013Co-Authors: Yunjia Yang, Yi Yang, Jing Zhang, Yixing Feng, Jie Yin, Bing ShaoAbstract:Bisphenol AF (BPAF), an endocrine disrupting chemical, can induce estrogenic activity through binding to estrogen receptor (ER). However, the metabolism of BPAF in vivo and the estrogenic activity of its metabolites remain unknown. In the present study, we identified four metabolites including BPAF diglucuronide, BPAF glucuronide (BPAF-G), BPAF glucuronide dehydrated and BPAF sulfate in the urine of Sprague-Dawley (SD) rats. BPAF-G was further characterized by nuclear magnetic resonance (NMR). AFter treatment with a single dose of BPAF, BPAF was metabolized rapidly to BPAF-G, as detected in the plasma of SD rats. Biotransformation of BPAF to BPAF-G was confirmed with human liver microsomes (HLM), and Vmax of glucuronidation for HLM was 11.6 nmol/min/mg. We also found that BPAF glucuronidation could be mediated through several human recombinant UDP-glucuronosyltransferases (UGTs) including UGT1A1, UGT1A3, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15 and UGT2B17, among which UGT2B7 showed the highest efficiency of glucuronidation. To explain the biological function of BPAF biotransformation, the estrogenic activities of BPAF and BPAF-G were evaluated in ER-positive breast cancer T47D and MCF7 cells. BPAF significantly stimulates ER-regulated gene expression and cell proliferation at the dose of 100 nM and 1 μM in breast cancer cells. However, BPAF-G did not show any induction of estrogenic activity at the same dosages, implying that formation of BPAF-G is a potential host defense mechanism against BPAF. Based on our study, biotransformation of BPAF to BPAF-G can eliminate BPAF-induced estrogenic activity, which is therefore considered as reducing the potential threat to human beings.
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Simultaneous determination of Bisphenol A, Bisphenol AF, tetrachloroBisphenol A, and tetrabromoBisphenol A concentrations in water using on-line solid-phase extraction with ultrahigh-pressure liquid chromatography tandem mass spectrometry
International Journal of Environmental Analytical Chemistry, 2013Co-Authors: Yunjia Yang, Yi Yang, Jing Zhang, Bing ShaoAbstract:An on-line solid-phase extraction (SPE) ultrahigh-pressure liquid chromatography tandem mass spectrometry method was developed and validated for the simultaneous determination of the Bisphenol A, Bisphenol AF, tetrachloroBisphenol A, and tetrabromoBisphenol A concentrations in water samples. The on-line SPE system used a 10 µm particle size SPE column to concentrate the analytes and was coupled with a 1.7 µm particle size chromatographic column for analysis. The total analysis time for each sample using this process was only 12 min, and the method limit of quantification (MLOQ) ranged from 1.5 to 53 ng/L for different water matrices when a 2.5 mL sample was injected. Isotopic internal standard calibration was used to compensate for matrix effects in the trace-level analysis using mass spectrometry. The method has good precision (RSD
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Determination of Bisphenol AF (BPAF) in tissues, serum, urine and feces of orally dosed rats by ultra-high-pressure liquid chromatography-electrospray tandem mass spectrometry.
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2012Co-Authors: Yunjia Yang, Yi Yang, Jing Zhang, Jie Yin, Naiyuan Zhou, Bing ShaoAbstract:As a homologue of Bisphenol A (BPA), there is concern about the potential reproductive and developmental toxicity of Bisphenol AF (BPAF) based on in vitro tests. In this study, a simple and universal analytical method was developed for the determination of trace BPAF in various tissues and excreta of rats AFter they were orally dosed. The samples were hydrolyzed with glucuronidase/arylsulfatase followed by ultrasonic extraction with acetonitrile. The crude extract was purified with a mixed-mode anion exchange (Oasis MAX) solid-phase extraction (SPE) cartridge. Separation and quantification was then conducted by ultra-high-pressure liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) in negative ionization mode. The recoveries at three fortification levels in different biological samples were from 71.0% to 102.3% with relative standard deviations no more than 13.2% (n=6). The quantification limits of the method were from 0.5 μg/kg to 3 μg/kg depending on the matrix. This method was successfully applied to the determination of BPAF in tissues, serum, urine and feces of orally dosed rats.
Yan Wang - One of the best experts on this subject based on the ideXlab platform.
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use of embryonic stem cell derived cardiomyocytes to study cardiotoxicity of Bisphenol AF via the gper cam enos pathway
Toxicology, 2020Co-Authors: Shoufei Yang, Wei Cheng, Fan Liang, Ren Zhou, Hui Wang, Yan Feng, Yan WangAbstract:Bisphenol AF (BPAF) is a derivative of Bisphenol A (BPA) that is widely used in fluorinated polymers, fluorinated rubber, electronic equipment, plastic optical fibers, etc. Studies have shown that BPAF exposure is associated with a number of diseases; however, little is known about the effects of BPAF on cardiomyocytes. We investigated the impact of chronic exposure to BPAF on cardiomyocytes derived from embryonic stem cells (ESCs). The present study showed that chronic exposure to various concentrations of BPAF (0, 8, 200 and 1000 ng/ml) induces cardiomyocyte hypertrophy. The ratios of microfilaments to mitochondrial length and the ratio of microfilaments to cell nuclei and MYH7b levels indicate that BPAF exposure alters the morphology of the cells and mitochondria. Furthermore, BPAF exposure at concentrations from 8 to 1000 ng/ml results in an increase in G protein-coupled estrogen receptor (GPER) expression. Additionally, our results suggest that these effects of BPAF mediate cardiomyocyte hypertrophy apparently due to an increase in the production of reactive nitrogen species (RNS) via an increase in endothelial NO synthase (eNOS). These results imply that ESC-based myocardial differentiation can be an excellent cellular model to study BPAF-induced cardiotoxicity at the cellular and molecular levels.
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Use of embryonic stem cell-derived cardiomyocytes to study cardiotoxicity of Bisphenol AF via the GPER/CAM/eNOS pathway.
Toxicology, 2020Co-Authors: Shoufei Yang, Wei Cheng, Fan Liang, Ren Zhou, Hui Wang, Yan Feng, Yan WangAbstract:Bisphenol AF (BPAF) is a derivative of Bisphenol A (BPA) that is widely used in fluorinated polymers, fluorinated rubber, electronic equipment, plastic optical fibers, etc. Studies have shown that BPAF exposure is associated with a number of diseases; however, little is known about the effects of BPAF on cardiomyocytes. We investigated the impact of chronic exposure to BPAF on cardiomyocytes derived from embryonic stem cells (ESCs). The present study showed that chronic exposure to various concentrations of BPAF (0, 8, 200 and 1000 ng/ml) induces cardiomyocyte hypertrophy. The ratios of microfilaments to mitochondrial length and the ratio of microfilaments to cell nuclei and MYH7b levels indicate that BPAF exposure alters the morphology of the cells and mitochondria. Furthermore, BPAF exposure at concentrations from 8 to 1000 ng/ml results in an increase in G protein-coupled estrogen receptor (GPER) expression. Additionally, our results suggest that these effects of BPAF mediate cardiomyocyte hypertrophy apparently due to an increase in the production of reactive nitrogen species (RNS) via an increase in endothelial NO synthase (eNOS). These results imply that ESC-based myocardial differentiation can be an excellent cellular model to study BPAF-induced cardiotoxicity at the cellular and molecular levels.