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Decabromodiphenyl ether induces the chromosome association disorders of spermatocytes and deformation failures of spermatids in mice

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Journal of Environmental Sciences 2024年第4期138卷 531-542页

作者： Jinglong Xue Xiangyang Li Yafei Chi Leqiang Gao Yue Zhang Yan Wang Moxuan Zhao Jialiu Wei Zhixiong Shi Xianqing Zhou Department of Toxicology and hygienic chemistry School of Public HealthCapital Medical UniversityBeijing 100069China Beijing Key laboratory of Environmental Toxicology Capital Medical UniversityBeijing 100069China laboratory Animal Center Capital Medical UniversityBeijing 100069China Key laboratory of Cardiovascular Epidemiology&Department of Epidemiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

The environmental presence of decabromodiphenyl ether(BDE-209),which is toxic to the male reproductive system,is *** current study investigated its mechanism of toxicity in *** results showed,that BDE-209 induced DNA damage,decreased the expression of the promoter of meiosis spermatogenesis-and oogenesis-specific basic helix-loop-helix 1(Sohlh1),meiosis related-factors Lethal(3)malignant brain tumor like 2(L3MBTL2),PIWI-like protein 2(MILI),Cyclin-dependent kinase 2(CDK2),Cyclin A,synaptonemal complex protein 1(SYCP1)and synaptonemal complex protein 3(SYCP3),and caused spermatogenic cell apoptosis,resulting in a decrease in sperm quantity and ***,BDE-209 downregulated the levels of anaphase-promoting complex/cyclosome(APC/C),increased the expression of PIWI-like protein 1(MIWI)in the cytoplasm of elongating spermatids,and decreased the nuclear levels of RING finger protein 8(RNF8),ubiquitinated(ub)-H2A/ub-H2B,and Protamine 1(PRM1)/Protamine 2(PRM2),while increasing H2A/H2B nuclear levels in *** reproductive toxicity was persistent for 50 days following the withdrawal of BDE-209 *** results suggested that BDE-209 inhibits the initiation of meiosis by decreasing the expression of ***,the reduced expression of L3MBTL2 inhibited the formation of chromosomal synaptonemal complexes by depressing the expression of meiosis regulators affecting the meiotic progression and also inhibited histone ubiquitination preventing the replacement of histones by protamines,by preventing RNF8 from entering nuclei,which affected the evolution of spermatids into mature sperm.

关键词： BDE-209 Meiosis L3MBTL2 Sperm RNF8 Histone ubiquitination

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Direct and rapid detection of serum amino acid and monoamine neurotransmitters to assist the diagnosis of panic disorder

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Science China chemistry 2024年

作者： Shiwen Liu Xuerui Wan Meng Zhao Jiaqi Wang Weilan Wu Linlin You Yonggui Yuan Qian Xu Rong Gao Key laboratory of Environmental Medicine Engineering Ministry of Education School of Public Health Southeast University Key laboratory of Modern Toxicology of Ministry of Education Department of Hygienic Analysis and Detection School of Public HealthNanjing Medical University Department of Psychosomatics and Psychiatry Zhongda Hospital School of Medicine Southeast University

The measurement of amino acid and monoamine neurotransmitters（NTs） in serum plays a central role in the identification and monitoring of clinical panic disorder（PD）. However, the strong polarity and chemical heterogeneity of NTs make direct extraction and rapid detection extremely challenging. Herein, we developed a strategy that integrated solid phase extraction based on magnetic Fe3O4coated with polydopamine（Fe3O4@PDA） and direct analysis of mass spectrometry in real time（DART-MS） for quantification of 10 NTs. We systematically investigated the optimal conditions of this strategy to achieve good accuracy and precision. Compared with existing magnetic solid phase extraction methods for NTs detection in biological samples, this strategy could adsorb more targets while having similar adsorption efficiencies, and the total process time was reduced by an average of 69.42%. We rapidly determined the metabolic abnormality of 6 types of NTs in the serum of PD patients and demonstrated their diagnostic accuracy. In addition, an outstanding feature of PD in which tryptophan was more metabolized by the KYN pathway and the 5-hydroxytryptamine pathway was inhibited could be elucidated by this strategy. Our results highlighted the potential ability of Fe3O4@PDA coupled with DART-MS to assist in the clinical diagnosis of PD.

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Amelioration effects of traditional Chinese medicine on alcohol-induced fatty liver

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World Journal of Gastroenterology 2005年第35期11卷 5512-5516页

作者： Hyun-Jeong Kwon Yun-Young Kim Se-Young Choung Department of hygienic chemistry College of Pharmacy Kyung Hee University Seoul 130-701 South Korea

AIM： To examine the effects of traditional Chinese medicine （TCM） on alcohol-induced fatty liver in rats. TCM consists of Astragalus membranaceus, Morus alba, Crataegus pinnatifida, Alisma orientale, Salvia miltiorrhiza, and Pueraria lobata. METHODS： The rats were separated randomly into five groups. One （the CD group） was fed a control diet for 10 wk, another （the ED group） fed an ethanol-containing isocaloric liquid diet for 10 wk, and the last three （the TCM group） were fed an ethanol-containing isocaloric liquid diet for 10 wk and dosed orally with TCM （222 mg/kg.d, TCM222; 667 mg/kg·d, TCM667; and 2 000 mg/kg.d, TCM2000, respectively） weekly during the last 4 wk. RESULTS： ED group developed fatty liver according to lipid profile and liver histological findings. Compared with the control group, liver/body weight, serum triglyceride （TG） and total cholesterol （TC）, liver TG and TC, serum alanine aminotransferase （ALT） and aspartic aminotransferase （AST） significantly increased in the ED group. Whereas, in the rats administered with TCM, liver/body weight, serum TG and TC, liver TG and TC, serum ALT and AST were significantly decreased, and the degree of hepatic lipid droplets was markedly improved compared with those in the ED group. CONCLUSION： TCM treatment causes significant reduction in alcohol-induced lipid hepatic accumulation, reversing fatty liver and liver damage, and can be used as a remedy for alcoholic fatty liver.

关键词： Fatty liver Alcohol Astragalus membranaceus,Horus alba Crataegus pinnatifida Alisma orientale Salvia miltiorrhiza Pueraria Iobata

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Screening of agonistic activities against four nuclear receptors in wastewater treatment plants in Japan using a yeast two-hybrid assay

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Journal of Environmental Sciences 2011年第1期23卷 125-132页

作者： Daisuke Inoue Koki Nakama Kazuko Sawada Taro Watanabe Hisae Matsui Kazunari Sei Tsuyoshi Nakanishi Michihiko Ike Division of Sustainable Energy and Environmental Engineering Osaka University2-1 YamadaokaSuitaOsaka 565-0871Japan laboratory of hygienic chemistry and Molecular Toxicology Gifu Pharmaceutical University5-6-1 Mitahora-higashiGifu 502-8585Japan

To assess the potential endocrine disruptive effects through multiple nuclear receptors （NRs）, especially non-steroidal NRs, in municipal wastewater, we examined the agonistic activities on four NRs （estrogen receptor α, thyroid hormone receptor α, retinoic acid receptor ct and retinoid X receptor α） of untreated and treated wastewater from municipal wastewater treatment plants （WWTPs） in Japan using a yeast two-hybrid assay. Investigation of the influent and effluent of seven WWTPs revealed that agonistic activities against steroidal and non-steroidal NRs were always detected in the influents and partially remained in the effluents. Further investigation of four WWTPs employing conventional activated sludge, pseudo-anoxic-oxic, anoxic-oxic and anaerobic-anoxic-oxic processes revealed that the ability to reduce the agonistic activity against each of the four NRs varies depending on the treatment process. These results indicated that municipal wastewater in Japan commonly contains endocrine disrupting chemicals that exert agonistic activities on steroidal and non-steroidal NRs, and that some of these chemicals are released into the natural aquatic environment. Although the results obtained in yeast assays suggested that measured levels of non-steroidal NR agonists in the effluent of WWTPs were not likely to cause any biological effect, further study is required to assess their possible risks in detail.

关键词： agonistic activity endocrine disrupting chemicals non-steroidal nuclear receptor wastewater treatment plants

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DNA methylation changes induced by BDE-209 are related to DNA damage response and germ cell development in GC-2spd

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Journal of Environmental Sciences 2021年第11期33卷 161-170页

作者： Xiangyang Li Yue Zhang Xiaomin Dong Guiqing Zhou Yujian Sang Leqiang Gao Xianqing Zhou Zhiwei Sun Department of Toxicology and hygienic chemistry School of Public HealthCapital Medical UniversityBeijing 100069China Beijing Key laboratory of Environmental Toxicology Capital Medical UniversityBeijing 100069China Experimental Center for basic medical teaching Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Decabrominated diphenyl ether(BDE-209)is generally utilized in multiple polymer materials as common brominated flame ***-209 has been listed as persistent organic pollutants(POPs),which was considered to be reproductive toxin in the *** it still remains unclear about the effects of BDE-209 on DNA methylation and the inducedmale reproductive *** to the extensive epigenetic regulation in germ line development,we hypothesize that BDE-209 exposure impacts the statue of DNA methylation in spermatocytes in ***,the mouse GC-2spd(GC-2)cells were used for the genome wide DNA methylation analysis after treated with 32μg/mL BDE-209 for 24 *** results showed that BDE-209 caused genomic methylation changes with 32,083 differentially methylated CpGs in GC-2 cells,including 16,164(50.38%)hypermethylated and 15,919(49.62%)hypomethylated *** integrated analysis ofDNAmethylation data and functional enrichment,we found that BDE-209 might affect the functional transcription in cell growth and sperm development by differential gene ***-PCR validation demonstrated the involvement of p53-dependent DNA damage response in the GC-2 cells after BDE-209 *** general,our findings indicated that BDE-209-induced genome wide methylation changes could be interrelated with reproductive *** study might provide new insights into the mechanisms of male reproductive toxicity under the environmental exposure to BDE-209.

关键词： Decabrominated diphenyl ether (BDE-209) DNA methylation Functional enrichment DNA damage response Germ cell development GC-2spd

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FKBP23 in ER binds to BiP specifically

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Science China chemistry 2004年第1期47卷 17-23页

作者： ZHANG Wanqi, LI Hui, ZHANG Xiaobin, SHEN Ye, WANG Yinong, Ml Huaifeng & HE BinglinState Key laboratory of Functional Polymer Materials for Adsorption and Separation, Chemical School of Nankai University, Tianjin 300071, China hygienic School of Tianjin Medical University, Tianjin 300071, China Medical School of Nankai University, Tianjin 300071, China State Key laboratory of Functional Polymer Materials for Adsorption and Separation Chemical School of Nankai University Tianjin China hygienic School of Tianjin Medical University Tianjin China Medical School of Nankai University Tianjin China

FKBP23 was found in mouse endoplasmic reticulum (ER) in 1998. It consists of an N-terminal peptidyl-prolyl cis-trans isomerase (PPlase) domain and a C-terminal domain with Ca2+ binding sites. The fusion protein of mouse FKBP23 and glutathione S-transferase (GST), GST-FKBP23, and the fusion protein of BiP, a member of heat shock protein 70 (Hsp 70) in ER, and GST, GST-BiP, were subcloned in E. coli, expressed and purified. The fusion proteins were restrictively digested by Factor Xa (FaXa) to obtain the free cloned proteins FKBP23 and BiP. With the assay of adsorption of free FKBP23 or BiP with GST-BiP or GST-FKBP23 attached to the Glutathione-Sepharose 4B, the adsorbed FKBP23 or BiP could be detected by Immunoblot. It means that FKBP23 binds to BiP. Furthermore, BiP in leukocyte ER-extract can be adsorbed with GST-FKBP23 attached to the glutathione-Sepharose 4B. It shows that FKBP23 binds to natural BiP in ER, too. These experiments show that a PPIase binds to a molecular chaperone of the Hsp70 family.

关键词： peptidyl-prolyl cis/trans isomerase, FKBP23, BiP, endoplasmic reticulum, specific binding.

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Nitro-PAH exposures of occupationally-exposed traffic workers and associated urinary 1-nitropyrene metabolite concentrations

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Journal of Environmental Sciences 2016年第11期28卷 213-221页

作者： Justin P.Miller-Schulze Michael Paulsen Takayuki Kameda Akira Toriba Kazuichi Hayakawa Brandon Cassidy Luke Naeher Manuel Aguilar Villalobos Christopher D.Simpson Department of chemistry University of Washington WA 98195-1700 USA. Department of Environmental and Occupational Health Sciences University of Washington WA 98195 Seattle USA laboratory of hygienic chemistry Instkute of Medical Pharmaceutical and Health Sciences Faculty of Pharmacy Kanazawa UniversityKakurna-machi Kanazawa Ishikawa 920-1192 Japan Graduate School of Natural Science and Technology Kanazawa University Kakma-machi Kanazawa Ishikawa 920-1192 Japan Department of Enuironmental Health Sciences University of Georgia Athens CA 30602-2102 USA Asociacion del Aire Ambiental Lima Peru

The assessment of occupational exposure to diesel exhaust（DE） is important from an epidemiological perspective. Urinary biomarkers of exposure have been proposed as a novel approach for measuring exposure to DE. In this study, we measured the concentrations of two urinary metabolites of 1-nitropyrene（1NP）, a nitrated polycyclic aromatic hydrocarbon that has been suggested as a molecular marker of diesel particulate matter. These two metabolites, 6-hydroxy-1-nitropyrene and 8-hydroxy-1-nitropyrene, were determined in urine samples（10 m L） from a small group of workers who were occupationally-exposed to vehicle exhaust in Trujillo, Peru, before and after their workshifts. Workshift exposures to1 NP, as well as PM_（2.5）, 2-nitropyrene and 2-nitrofluoranthene, were also *** to 1NP were similar in all studied workers, averaging 105 ± 57.9 pg/m^3（±standard deviation）. Median urinary concentrations of the average of the pre- and post-exposure samples for 6-hydroxy-1-nitropyrene and 8-hydroxy-1-nitropyrene, were found to be 3.9 and 2.3 pg metabolite/mg creatinine, respectively in the group of occupationally-exposed subjects（n = 17） studied. A direct relationship between workshift exposure to 1NP and urinary 1NP metabolites concentrations was not observed. However,the 1NP exposures and the creatinine-corrected urinary concentrations of the hydroxynitropyrene metabolites in these Peruvian traffic workers were similar to occupationally-exposed taxi drivers in Shenyang, China, and were higher than biomarker levels in office workers from Trujillo without occupational exposure to vehicle *** study provides further evidence that urinary metabolites of 1NP are associated with exposure to DE and may serve as a useful exposure biomarker.

关键词： Urinary biomarkers 1-Nitropyrene Diesel particulate matter

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Decabromodiphenyl ether induces the chromosome association disorder of spermatocytes and deformation failure of spermatids in mice

Decabromodiphenyl ether induces the chromosome association d...

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中国毒理学会第十次全国毒理学大会

作者： Jinglong Xue Xiangyang Li Leqiang Gao Yue Zhang Yan Wang Moxuan Zhao Xianqing Zhou Department of Toxicology and hygienic chemistry School of Public Health Capital Medical University Beijing Key laboratory of Environmental Toxicology Capital Medical University

PURPOSE Decabromodiphenyl ether(BDE-209) as a common brominated flame retardant is widespread in the environment. Although BDE-209 has been shown to induce male reproductive toxicity, the exact mechanism is unclear. This study aimed to investigate the mechanisms of male reproductive toxicity caused by BDE-209. MATERIALS and METHODS 48 male mice were divided into two groups after a week of acclimation. The treatment group was given 75 mg/kg/d BDE-209 by gastric gavage for 50 days, and the control group was given the same amount of corn oil. After the 50-day exposure period, 12 mice were randomly selected from each group, sacrificed under deep anesthesia;the remaining male mice were continued to be raised for 50 days without any treatment, and then they were sacrificed. Morphological change of testis tissues structure was determined using the Periodic Acid-Schiff stain(PAS). The protein expressions were determined using Western Blot and *** experimental data were analyzed using the SPSS 25.0 program, and the independent samples T-test was used to compare the significant differences between the two groups. RESULTS BDE-209 induced DNA damage, decreased the expression of the promoter of meiosis Sohlh1, meiosis related-factors L3MBTL2, MILI, CDK2, and Cyclin A, and synaptonemal complex elements SYCP1 and SYCP3, and caused spermatogenic cell apoptosis, resulting in a decrease in sperm quantity and ***, BDE-209 downregulated the levels of ubiquitin ligases APC/C, increased the expression of MIWI in the cytoplasm of elongating spermatids, and decreased the nuclear levels of RNF8, ubiquitinated(ub)-H2A/ub-H2B, and PRM1/PRM2, while increasing H2A/H2B nuclear levels in *** reproductive toxicity was persistent for 50 days following the withdrawal of BDE-209 *** The results suggested that BDE-209 inhibits the initiation of meiosis by decreasing the expression of Sohlh1. Furthermore, the reduced expression of L3MBTL2 in

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Fine particulate matters inducing reproductive impairment by causing cell cycle arrest and activating mitochondrial apoptosis pathway in male rats and spermatocyte cells

Fine particulate matters inducing reproductive impairment by...

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中国生理学会内分泌代谢、比较生理与应激生理学术会议

作者： Jianhui Liu Lihua Ren Jialiu Wei Jin Zhang Yannan Zhang Hejing Hu Junchao Duan Zhiwei Sun Xianqing Zhou Department of Toxicology and hygienic chemistry School of Public HealthCapital Medical University Beijing Key laboratory of Environmental Toxicology Capital Medical University

Fine particulate matters(PM2.5) have been shown to induce male reproductive toxicity,but the mechanism is *** explore the toxic mechanism of PM2.5,32 male Sprague-Dawley(SD)rats were treated to normal saline(control group) or PM2.5 with the doses of 1.8,5.4 and 16.2 mg/*** intratracheal instillation every 3 days for 30 *** 30 days,the rats were sacrificed for tissue *** vitro,GC-2 spd cells were treated to various concentrations(12.5,25,50 μg/mL) of PM2.5 for 24 *** results showed that PM2.5 obviously decreased sperm quality,increased sperm abnormality rate and damaged testicular tissue in male ***2.5 induced oxidative stress and DNA damage in ***,PM2.5 significantly increased the expression of BAX,cytochrome C,Caspase-9,Caspase-3 on the 30 th *** vitro,GC-2 cells treated with PM2.5 displayed mitochondria swelling and cristae ***2.5 induced S-phase cell cycle arrest and apoptosis in GC-2 spd *** results suggest that PM2.5 might induce apoptosis by up-regulating the expressions of mitochondrial apoptosis pathway factors through causing DNA damage and cell cycle arrest resulting from oxidative stress,and cause a decrease in the quantity and quality of sperms.

关键词： Fine particulate matters oxidative stress cell cycle arrest mitochondrial apoptosis pathway male reproduction

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Silica nanoparticles induce abnormal mitosis and apoptosis by balance and regulation of PKC mediated positive and negative signaling pathways

Silica nanoparticles induce abnormal mitosis and apoptosis b...

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第六届中国毒理学会免疫毒理专业委员会换届及学术会议

作者： Jin Zhang Lihua Ren Lianshuang Zhang Jialiu Wei Liu jianhui Zhiwei Sun Xianqing Zhou Department of Toxicology and hygienic chemistry School of Public HealthCapital Medical University Beijing Key laboratory of Environmental Toxicology Capital Medical University

Researches had shown mat SiNPs could damage seminiferous epithelium and reduce the quantity and quality of sperms,but little is known about the toxicity mechanism of SiNPs on male reproductive *** investigate toxic mechanism of SiNPs,male germ cell lines(GC-2spd) were exposed to 0,6.25,12.5,25 or 50μg/mL SiNPs for 24 h,*** results showed that SiNPs resulted in a dose-dependent reduction in cell viability,as well as increases in the LDH release and cell apoptosis *** can lead to DNA strand breaks and abnormal *** addition,SiNPs induced cell cycle arrest in the GO/Gl phase and proliferation *** could simultaneously activate negative signaling pathway(PKC-5/p53/p21) by PKC-5 and positive signaling pathway(PKC-α/MAPK) by PKC-α.However the lower expressions of cyclin E and CDK2 indicated that negative signaling pathway mediated by PKC-8 played a dominant role in the process of cell *** results suggested that SiNPs might activate PKC-8 mediated negative signaling due to DNA strand breaks resulting from *** activity PKC-8mediated negative signaling arrested GC-2 cells at GO/Gl phase,resulting in abnormal mitosis and cell apoptosis.

关键词： Silica nanoparticles mitosis GC-2spd cells Cell cycle PKC

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