Emerging synthetic or derivative chemicals have drawn global concern due to their potential endocrine-disrupting effects,either as agonists or antagonists or through indirect effects on enzymes of signal transduction ...Emerging synthetic or derivative chemicals have drawn global concern due to their potential endocrine-disrupting effects,either as agonists or antagonists or through indirect effects on enzymes of signal transduction pathways.Currently,in vitro screening models are limited to poor tolerance,robustness,high cost and need for sphisticated equipment or complex procedures that require high levels of expertise.Herein,a multiplex analysis platform based on autobioluminescent yeast strains,including BLYhERaS,BLYhERbS,BLYhPRS,BLYhARS,BLYhMRS,and BLYhGRS,was developed for use in easy,rapid,robust,and sensitive screening for potential modulation of endocrine systems.Methods were applied to assess endocrine-disrupting effects of Bisphenol A(BPA)and its alternatives.Disrupting activities of bisphenols(BPs)varied greatly,and some BPA substitutes exerted more potent activities than those of BPA.Most BPs were primarily agonists of ERa and ERb,while others were antagonists to AR,PR,GR,and MR.BPP and BPM exhibited non-monotonic dose-response relationships toward ERa and ERb,and BHPF and BPG displayed converse disrupting activities to ERa and ERb.Overall,the bioassay system provides an efficient tool for comprehensive evaluation of endocrine-disrupting activities of emerging contaminants.展开更多
基金supported by the National Key Research and Development Program of China(NO.2023YFD1301505,No.2017YFC1600303)the Agricultural Science and Technology Innovation Program of CAAS(CAAS-ASTIP-IQSTAP-04)Prof.Giesy was supported by the Canada Research Chair program,the 2012"High Level Foreign Experts"(#GDT20143200016)program,funded by the State Administration of Foreign Experts Affairs,the P.R.China to Nanjing University and the Einstein Professor Program of the Chinese Academy of Sciences and a Distinguished Visiting Professorship in the Department of Environmental Sciences,Baylor University in Waco,TX,USA.
文摘Emerging synthetic or derivative chemicals have drawn global concern due to their potential endocrine-disrupting effects,either as agonists or antagonists or through indirect effects on enzymes of signal transduction pathways.Currently,in vitro screening models are limited to poor tolerance,robustness,high cost and need for sphisticated equipment or complex procedures that require high levels of expertise.Herein,a multiplex analysis platform based on autobioluminescent yeast strains,including BLYhERaS,BLYhERbS,BLYhPRS,BLYhARS,BLYhMRS,and BLYhGRS,was developed for use in easy,rapid,robust,and sensitive screening for potential modulation of endocrine systems.Methods were applied to assess endocrine-disrupting effects of Bisphenol A(BPA)and its alternatives.Disrupting activities of bisphenols(BPs)varied greatly,and some BPA substitutes exerted more potent activities than those of BPA.Most BPs were primarily agonists of ERa and ERb,while others were antagonists to AR,PR,GR,and MR.BPP and BPM exhibited non-monotonic dose-response relationships toward ERa and ERb,and BHPF and BPG displayed converse disrupting activities to ERa and ERb.Overall,the bioassay system provides an efficient tool for comprehensive evaluation of endocrine-disrupting activities of emerging contaminants.
文摘目的探讨股密葆方对大鼠激素性股骨头坏死的血管生成修复的影响,以揭示其作用的部分机制。方法 176只动物随机分为空白对照组、模型组、股密葆方高、中、低剂量组,共5组,每组8只,雌雄各半。后4组参照Okazaki等人应用大肠杆菌内毒素联合激素注射的造模方法构建大鼠激素性股骨头坏死模型。造模成功后,股密葆方高、中、低剂量组分别灌服股密葆混悬液,空白对照组和模型组均灌服等量的生理盐水。分别选取药物干预后4、8、12 w 3个时间点,每组随机处死4只大鼠行VEGF免疫组化染色、透射电镜观察。分析每组各时间点相关指标的变化情况及各组之间的差异。结果 HE染色及透射电镜观察证实股骨头坏死动物模型建立成功,股密葆方各组VEGF表达增强,逐渐恢复至正常水平,与模型组比较,差别具有统计学意义(P<0.05),其中以股密葆方低剂量组表达最强。结论股密葆方可以加速股骨头内的正常修复速度,促进新生血管生成,使骨形成加快。
