Alzheimer＇s disease, the leading cause of dementia in the elderly, is a complex neurodegenerative disorder which leads to a progressive decline in cognitive functions. A rapid screening model is highly demanded for i...Alzheimer＇s disease, the leading cause of dementia in the elderly, is a complex neurodegenerative disorder which leads to a progressive decline in cognitive functions. A rapid screening model is highly demanded for identification and evaluation of novel anti-Alzheimer＇s disease drugs from a large numbers of compounds. Until now, numerous studies utilized zebrafish model for drug discovery. Since aluminum can induce a similar biological activity in zebrafish as in Alzheimer patients, in this study, we developed a novel animal model using 3 to 5 day post-fertilization larval zebrafish by optimizing the doses and duration of aluminum chloride exposure. Six anti-Alzheimer＇s disease drugs with a variety of mechanisms were tested to validate the newly developed zebrafish model. Importantly, Rivastigmine, ThT, Flurbiprofen and AM-117 could increase the value of Dyskinesia Recovery Rate by 53.4-64%, 169.4-200%, 54.5-96% and 70.9-121%, respectively. Rivastigmine, Memantine, ThT, Flurbiprofen, Rosiglitazone and AM-117 improved the value of Response Efficiency by 86.6-175.1%, 28.2-66.6%, 127.2-236.5%, 118.3-323.7%, 26.6-140.8% and 70.2-161.4%, respectively. Our results suggest that the zebrafish model developed in this study could be a useful tool for high throughput screening of potential novel anti-Alzheimer＇s disease leading compounds targeting acetylcholinesterase, N-methyl-D-aspartic acid receptor, γ-secretase, peroxisome proliferator-activated receptor-γand amyloid-β.展开更多
OBJECTIVE To assess the efficancy of Yangxue Qingnao granules on simvastatininduced vascular injury model in zebrafish.METHODS Since statins can inhibit vascular development in zebrafish,in this study,we developed a n...OBJECTIVE To assess the efficancy of Yangxue Qingnao granules on simvastatininduced vascular injury model in zebrafish.METHODS Since statins can inhibit vascular development in zebrafish,in this study,we developed a novel animal model using 1 to 3 day post-fertilization larval zebrafish by optimizing the doses and duration of simvastatin exposure.Five pro-angiogenic drugs with a variety of mechanisms were tested to validate the newly developed zebrafish model.Zebrafish was treated with different concentration of Yangxue Qingnao granules(62.5,125 and 250 μg·mL-1) for 2 d then tested for the area of subintestinal vein vessels.RESULTS Vascular regeneration promoting effect of five pro-angiogenic drugs(calycosin,astragaloside,chlorogenic acid,ferulic acid and Panax Notoginseng Saponins) were 8-48%,24-51%,35-58%,28-75% and 37-69%,respectively.In 62.5,125 and 250 μg·mL-1 Yangxue Qingnao granules group,vascular regeneration promoting effect were 21%(P>0.05),84%(P<0.01) and 53%(P<0.01).CONCLUSION Our results demonstrate that the zebrafish vascular injury model validated in this study could be used for in vivo angiogenesis studies and drug screening and for assessing pro-angiogenic drugs with different mechanisms.Yangxue Qingnao granules could promote the vascular regeneration in zebrafish.展开更多
Triclosan(TCS)has garnered significant attention due to its widespread use and associated endocrine-disrupting effects.However,its impact on the neuroendocrine system and underlying mechanisms remain poorly understood...Triclosan(TCS)has garnered significant attention due to its widespread use and associated endocrine-disrupting effects.However,its impact on the neuroendocrine system and underlying mechanisms remain poorly understood.Here,we established correlations between TCS exposure and serum sex hormone levels in participants of the National Health and Nutrition Examination Survey(NHANES).Additionally,we investigated TCS’s influence on the neuroendocrine system using adult zebrafish exposed to environmentally relevant concentrations of TCS(0.361–48.2μg/L)for 21 days.Assessment of reproductive and neurotoxicity included histopathological examination and behavioral tests.Transcriptomics,proteomics analyses,and biochemical detection were employed to elucidate mechanisms underlying TCS-induced neuroendocrine disruption.Significant correlations were found between TCS exposure and estradiol,testosterone,and sex hormone-binding globulin levels in NHANES participants.In addition,TCS exposure inhibited ovary development and spermatogenesis in zebrafish.Transcriptomics and proteomics analysis revealed gender-specific key signaling and metabolism-related pathways implicated in TCS-induced reproductive toxicity.Moreover,TCS exposure induced nervous system impairment,as evidenced by histological changes and altered motor behavior,possibly associated with oxidative damage.Correlation analysis further highlighted the potential connection between endocrine system disruption and nervous system impairment following TCS exposure.Overall,this study provided evidence supporting TCS-induced endocrine disruption and offered insights into its underlying mechanisms.展开更多
Radix Sophorae tonkinensis(RST) is a widely used herb in Traditional Chinese Medicine(TCM) for treating infectious and inflammatory diseases. However, the toxicity data for RST are limited. The aim of this work is to ...Radix Sophorae tonkinensis(RST) is a widely used herb in Traditional Chinese Medicine(TCM) for treating infectious and inflammatory diseases. However, the toxicity data for RST are limited. The aim of this work is to assess and compare the toxicity of the whole RST extract and its five active fractions using the zebrafish model. Five active fractions of RST were prepared using five different types of solvents, which included dealkalized water, ethanol, n-butyl ethanol, dichloromethane, and diethyl ether. The chemical profiles of the active fractions were determined by high-performance liquid chromatography(HPLC), and the toxicity observed in the zebrafish model was confirmed using mouse models. In the zebrafish model, cardiovascular toxicity was observed for the fraction extracted using diethyl ether, and hepatotoxicity was observed for the whole RST extract and the fractions extracted using water and ethanol, whereas both cardiovascular and hepatic toxicities were observed for the fractions extracted using n-butyl ethanol and dichloromethane. The hepatotoxicity of the fractions extracted using n-butyl ethanol and dichloromethane was also observed in mice. Our findings provide the toxicity data for RST and its five active fractions through modeling in a zebrafish, and indicate that the different fractions may each have a different toxicity, which is helpful for the optimal use of RST in clinical practice.展开更多
基金Acknowledgments The authors thank the National Natural Science Foundation of China （81302646）, Natural Science Foundation of Zhejiang Province （LQ13H300002）, Science Technology Department of Zhejiang Province （2015F50015） and Health and Family Planning commission of Zhejiang Province （XKQ-010-001 and 2013KYB070） for financial support.
文摘Alzheimer＇s disease, the leading cause of dementia in the elderly, is a complex neurodegenerative disorder which leads to a progressive decline in cognitive functions. A rapid screening model is highly demanded for identification and evaluation of novel anti-Alzheimer＇s disease drugs from a large numbers of compounds. Until now, numerous studies utilized zebrafish model for drug discovery. Since aluminum can induce a similar biological activity in zebrafish as in Alzheimer patients, in this study, we developed a novel animal model using 3 to 5 day post-fertilization larval zebrafish by optimizing the doses and duration of aluminum chloride exposure. Six anti-Alzheimer＇s disease drugs with a variety of mechanisms were tested to validate the newly developed zebrafish model. Importantly, Rivastigmine, ThT, Flurbiprofen and AM-117 could increase the value of Dyskinesia Recovery Rate by 53.4-64%, 169.4-200%, 54.5-96% and 70.9-121%, respectively. Rivastigmine, Memantine, ThT, Flurbiprofen, Rosiglitazone and AM-117 improved the value of Response Efficiency by 86.6-175.1%, 28.2-66.6%, 127.2-236.5%, 118.3-323.7%, 26.6-140.8% and 70.2-161.4%, respectively. Our results suggest that the zebrafish model developed in this study could be a useful tool for high throughput screening of potential novel anti-Alzheimer＇s disease leading compounds targeting acetylcholinesterase, N-methyl-D-aspartic acid receptor, γ-secretase, peroxisome proliferator-activated receptor-γand amyloid-β.
文摘OBJECTIVE To assess the efficancy of Yangxue Qingnao granules on simvastatininduced vascular injury model in zebrafish.METHODS Since statins can inhibit vascular development in zebrafish,in this study,we developed a novel animal model using 1 to 3 day post-fertilization larval zebrafish by optimizing the doses and duration of simvastatin exposure.Five pro-angiogenic drugs with a variety of mechanisms were tested to validate the newly developed zebrafish model.Zebrafish was treated with different concentration of Yangxue Qingnao granules(62.5,125 and 250 μg·mL-1) for 2 d then tested for the area of subintestinal vein vessels.RESULTS Vascular regeneration promoting effect of five pro-angiogenic drugs(calycosin,astragaloside,chlorogenic acid,ferulic acid and Panax Notoginseng Saponins) were 8-48%,24-51%,35-58%,28-75% and 37-69%,respectively.In 62.5,125 and 250 μg·mL-1 Yangxue Qingnao granules group,vascular regeneration promoting effect were 21%(P>0.05),84%(P<0.01) and 53%(P<0.01).CONCLUSION Our results demonstrate that the zebrafish vascular injury model validated in this study could be used for in vivo angiogenesis studies and drug screening and for assessing pro-angiogenic drugs with different mechanisms.Yangxue Qingnao granules could promote the vascular regeneration in zebrafish.
基金Science and Technology Project of Guangdong Province,China(2022A0505050035)National Natural Science Foundation of China(82273656,82304177,82073519)+5 种基金Guangdong Basic Applied Basic Research Foundation(2022A1515010610,Guangdong-Dongguan Joint grant 2022A1515111098,Guangdong-Guangzhou Joint grant 2023A1515110373)Chinese Postdoctoral Science Foundation(2023M741553,2022M721486,2023T160295)Postdoctoral Fellowship Program of CPSF(GZC20231055)National Training Program of Innovation and Entrepreneurship for Undergraduates(202212121034,S202312121124)Guangdong Provincial Key Laboratory of Tropical Disease Research(2017B030314035)NMPA Key Laboratory for Safety Evaluation of Cosmetics,and the GDMPA Project of Scientific and Technological Innovation(2024ZDZ09).
文摘Triclosan(TCS)has garnered significant attention due to its widespread use and associated endocrine-disrupting effects.However,its impact on the neuroendocrine system and underlying mechanisms remain poorly understood.Here,we established correlations between TCS exposure and serum sex hormone levels in participants of the National Health and Nutrition Examination Survey(NHANES).Additionally,we investigated TCS’s influence on the neuroendocrine system using adult zebrafish exposed to environmentally relevant concentrations of TCS(0.361–48.2μg/L)for 21 days.Assessment of reproductive and neurotoxicity included histopathological examination and behavioral tests.Transcriptomics,proteomics analyses,and biochemical detection were employed to elucidate mechanisms underlying TCS-induced neuroendocrine disruption.Significant correlations were found between TCS exposure and estradiol,testosterone,and sex hormone-binding globulin levels in NHANES participants.In addition,TCS exposure inhibited ovary development and spermatogenesis in zebrafish.Transcriptomics and proteomics analysis revealed gender-specific key signaling and metabolism-related pathways implicated in TCS-induced reproductive toxicity.Moreover,TCS exposure induced nervous system impairment,as evidenced by histological changes and altered motor behavior,possibly associated with oxidative damage.Correlation analysis further highlighted the potential connection between endocrine system disruption and nervous system impairment following TCS exposure.Overall,this study provided evidence supporting TCS-induced endocrine disruption and offered insights into its underlying mechanisms.
基金Project supported by the National Science and Technology Major Project of China(Nos.2012ZX09505001-002 and 2015ZX09501004-002-002)the Zhejiang Provincial Science and Technology Planning Project of China(No.2014C03009)
文摘Radix Sophorae tonkinensis(RST) is a widely used herb in Traditional Chinese Medicine(TCM) for treating infectious and inflammatory diseases. However, the toxicity data for RST are limited. The aim of this work is to assess and compare the toxicity of the whole RST extract and its five active fractions using the zebrafish model. Five active fractions of RST were prepared using five different types of solvents, which included dealkalized water, ethanol, n-butyl ethanol, dichloromethane, and diethyl ether. The chemical profiles of the active fractions were determined by high-performance liquid chromatography(HPLC), and the toxicity observed in the zebrafish model was confirmed using mouse models. In the zebrafish model, cardiovascular toxicity was observed for the fraction extracted using diethyl ether, and hepatotoxicity was observed for the whole RST extract and the fractions extracted using water and ethanol, whereas both cardiovascular and hepatic toxicities were observed for the fractions extracted using n-butyl ethanol and dichloromethane. The hepatotoxicity of the fractions extracted using n-butyl ethanol and dichloromethane was also observed in mice. Our findings provide the toxicity data for RST and its five active fractions through modeling in a zebrafish, and indicate that the different fractions may each have a different toxicity, which is helpful for the optimal use of RST in clinical practice.
