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3-Chloro-1,2-Propanediol Exposure Induces Cardiotoxicity and Behavioural Abnormalities in zebrafish Embryos

Environmental Toxicology 2025年第4期40卷 664-673页

作者： Wang, Jing Yuan, Qiang Hu, Weitao Ye, Zhijun Zhang, Li Wang, Zhipeng Liu, Jiejun Huang, Ling Liu, Fasheng Liao, Xinjun Xiao, Juhua Zhang, Shouhua Cao, Zigang Affiliated Hospital of Jinggangshan University Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases Jiangxi Key Laboratory of Developmental Biology of Organs and Epigenetics Clinical Research Center of Affiliated Hospital of Jinggangshan University College of Life Sciences Jinggangshan University Ji'an China Affiliated Hospital of Jinggangshan University Clinical Research Center of Affiliated Hospital of Jinggangshan University Jiangxi Province Ji'an China Department of Ultrasound Jiangxi Provincial Maternal and Child Health Hospital Jiangxi Nanchang China Department of General Surgery Jiangxi Provincial Children's Hospital Jiangxi Nanchang China

Numerous contemporary diseases are linked to food contamination. Pathogenic agents might stem from certain food ingredients or result from pollution stemming from food processing or packaging. One such contaminant is 3-Chloro-1,2-propanediol (3-MCPD), it has been previously reported to be produced during the preparation of chemical sauces, as well as during the heating of baked goods. Yet, uncertainty surrounds its potential to induce embryonic developmental toxicity. In this study, zebrafish were employed as the focal point to assess the impact of 3-MCPD on initial embryonic development, heart functionality, and behavior. The research unveiled that exposure of zebrafish embryos to 18, 36, and 54 mM 3-MCPD led to cardiac anomalies, including pericardial edema, reduced heart rate, and elongated SV-BA distance. Additionally, 3-MCPD exposure triggered aberrations in cardiac-related gene expression and an elevation in oxidative stress. Notably, behavioral changes were observed in 3-MCPD-exposed zebrafish embryos, while vascular development appeared unaffected. This study introduces a novel basis for comprehensive exploration of 3-MCPD toxicity. © 2024 Wiley Periodicals LLC.

关键词： Heart

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Dimethyl sulfate induces zebrafish embryo cardiotoxicity and behavioral disturbances by upregulating oxidative stress levels

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Chemico-Biological Interactions 2025年 416卷

作者： Liu, Jiejun Wang, Jing Yuan, Qiang Wang, Zhipeng Liu, Fasheng Liao, Xinjun Li, Huiming Zhang, Shouhua Xiao, Juhua Cao, Zigang Affiliated Hospital of Jinggangshan University Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases Jiangxi Key Laboratory of Developmental Biology of Organs and Epigenetics Key Laboratory of Jiangxi Province for Biological Invasion and Biosecurity Clinical Research Center of Jinggangshan University School of Life Sciences Jinggangshan University Ji'an 343009 China Department of Ultrasound Jiangxi Provincial Maternal and Child Health Hospital Jiangxi Nanchang 330006 China Department of General Surgery Jiangxi Provincial Children's Hospital Jiangxi Nanchang 330006 China

Dimethyl sulfate (DMS) is a versatile chemical compound used in various industries, including pharmaceuticals, pesticides, dyes, and fragrances. Due to the widely application of Dimethyl sulfate (DMS), it is necessary to study its potential toxicity. According to ecological data analysis, DMS has been identified as a potential environmental hazard, particularly in water bodies. However, its toxicity to aquatic organisms remains largely unexplored. In this study, using zebrafish embryos as a model system, we evaluated the toxicity of DMS for the first time and uncovered significant adverse effects on early embryonic development, characterized by extensive cardiac damage and neurotoxicity. DMS inhibited the activity of antioxidant enzymes, resulting in excessive production of reactive oxygen species (ROS) and subsequent apoptosis of myocardial cells, along with pericardial edema, bradycardia, and elongated SV-BA distance. Additionally, DMS directly induced oxidative stress and altered the activity of acetylcholinesterase (ACHE) and adenosine triphosphatase (ATPase), thereby disrupting the expression of genes involved in neural development and neurotransmission. These findings may contribute to the DMS-induced behavioral abnormalities, such as reduced and unbalanced locomotion in larvae and altered swimming behavior. Importantly, astaxanthin, an antioxidant carotenoid, was able to rescue the embryonic cardiac and neurotoxic effects triggered by DMS exposure, suggesting that DMS primarily induces zebrafish cardiac and neural developmental toxicity through upregulation of oxidative stress. Overall, our study demonstrates the potential of DMS to induce cardiac and neurotoxicity in zebrafish embryos, suggesting toxicity risks to other aquatic organisms and even humans. These findings provide a basis for a comprehensive assessment of DMS toxicity and serve as an early warning for its environmental presence and product residues. © 2025

关键词： Behavioural changes Cardiotoxicity DMS zebrafish

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Isolation and characterization of a new diketopiperazine from Cephalotrichum sp. RD-ZLM03 isolated in Jinlun cave

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Journal of Asian natural products research 2025年 1-8页

作者： Yi Hao Pei-Hai Li Rong-Xiang Wu Cai-Xia Wei Ting Shu Fan-Dong Kong Pei Wang Li-Man Zhou School of Chemistry and Chemical Engineering Guangxi Minzu University Nanning530006 China. Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province Biology Institute Qilu University of Technology (Shandong Academy of Sciences) Jinan250103 China. Key Laboratory of Chemistry and Engineering of Forest Products State Ethnic Affairs Commission Guangxi Key Laboratory of Chemistry and Engineering of Forest Products Guangxi Minzu University Nanning530006 China.

A new diketopiperazine, spirotryprostatin C (), as well as nine known compounds (-), were isolated from the fermentation broth of the karst cave derived fungus sp. RD-ZLM03. Their structures were determined based on spectroscopic and X-ray diffraction analysis. Compounds , , , , , , and showed significant proangiogenic activities at the concentration of 25 μM in the zebrafish model.

关键词： Cave fungus Cephalotrichum sp diketopiperazine proangiogenic activities spirotryprostatin C

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Bexarotene regulates zebrafish embryonic development by activating Wnt signaling pathway

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Life Sciences 2025年 373卷

作者： Zha, Wenwen Wang, Ziang Hu, Weitao Ge, Chenkai Yuan, Wenbin Shen, Qinyuan Li, Weirong Chen, Wanqing Tang, Jingrong Xiao, Zhonghao Meng, Yunlong Huang, Lirong Zhong, Zilin Li, Tao-Sheng Chen, Jianjun Cao, Zigang Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases Jiangxi Key Laboratory of Developmental Biology of Organs and Epigenetics Clinical Research Center of Affiliated Hospital of Jinggangshan University Key Laboratory of Jiangxi Province for Biological Invasion and Biosecurity College of Chinese Medicine Jinggangshan University Ji'an 343009 China Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases Jiangxi Key Laboratory of Development Biology of Organs and Epigenetics Key Laboratory of Jiangxi Province for Biological Invasion and Biosecurity Clinical Research Center of Affiliated Hospital of Jinggangshan University College of Life Sciences Jinggangshan University Ji'an 343009 China Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation Clinical Research Center for Anesthesiology and Perioperative Medicine Translational Research Institute of Brain and Brain-Like Intelligence Department of Pediatrics Shanghai Fourth People's Hospital School of Medicine Tongji University Shanghai 200434 China Institute of Medical Genetics Department of Big Data in Health Science School of Public Health and General Medicine Tongji University School of Medicine Tongji University Shanghai 200331 China Department of Stem Cell Biology Atomic Bomb Disease Institute of Biomedical Sciences Nagasaki University Nagasaki Japan

Bexarotene (Bex) is a selective retinoid X receptor (RXR) agonist and is commonly used as an anti-tumor drug in the clinic to treat patients with cutaneous T-cell lymphoma (CTCL). With the widespread use of this drug, people are increasingly concerned about its side effects and safety of use. At present, the effects of bexarotene drugs on the health of organisms remain uncertain, but retinoid drugs are generally biologically active and may pose potential risks to them. Therefore, in this study, we used a zebrafish model to evaluate the effects of Bex on embryonic development. Six hours after fertilization, we exposed zebrafish embryos to 3 μg/L, 6 μg/L, and 9 μg/L bexarotene. At 96 hpf, compared with the control group, zebrafish embryos exposed to bexarotene showed obvious heart and liver development defects, including reduced hatching rate, pericardial enlargement, heart rate disorder, yolk sac edema, small liver area and abnormal photo-optical motor responses. Transcriptome and qPCR results showed abnormal expression of genes related to heart and liver development was induced by Bexarotene. Mechanistically, bexarotene induced a significant upregulation of the transcriptional expression levels of genes related to the Wnt signaling pathway, and IWR-1 was able to effectively rescue the heart and liver developmental defects of zebrafish caused by bexarotene. Therefore, our study showed that bexarotene may cause zebrafish embryonic developmental defects by upregulating the Wnt signaling pathway, revealing the side effects and associated novel mechanisms of bexarotene, and providing a theoretical basis for its safe and effective use in the treatment of clinically related diseases. © 2025

关键词： Bexarotene Embryonic development Wnt signaling pathway zebrafish

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Toxic effects and mechanisms of monometallic bismuth nanoparticles on early stages of zebrafish (Danio rerio)

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Science of the Total Environment 2025年 983卷 179702页

作者： Ding, Yiwei Wang, Songtao Qi, Guilin Hu, Yangyang Huang, Jiaolong Zhang, Ying Lian, Kai Li, Zhiyong Li, Xinyu Kong, Weimeng Liu, Ying Duan, Peng Yu, Hui Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Xiangyang City Xiangyang No. 1 People's Hospital Hubei University of Medicine Xiangyang 441000 China School of Public Health Hubei University of Medicine Shiyan 442000 China Hubei Provincial Clinical Research Center for Accurate Fetus Malformation Diagnosis Department of Obstetrics and Gynecology Xiangyang No. 1 People's Hospital Hubei University of Medicine Xiangyang 441000 China

Bismuth nanoparticles (Bi NPs) have shown great potential in the fields of biomedical applications due to their favourable properties. However, the impacts and toxic mechanisms of monometallic Bi NPs on vertebrates remain poorly explored. In the present study, we utilised zebrafish (Danio rerio) as a model to evaluate the toxic effects of acute exposure to Bi NPs on early life stages. Bi NPs–treated embryos exhibited an increase in the number of malformations and decreased hatching. Exposure to 5 mg/L Bi NPs induced embryonic developmental abnormalities, including lipid transport, behavioural, and craniofacial deformities. Moreover, exposure to 25 mg/L Bi NPs caused embryonic developmental defects, including behavioural dysfunction, skeletal deformity, cardiac teratogenesis, and ocular abnormalities. Based on transcriptomics, we identified a total of 859 differentially expressed genes. Of these, 338 upregulated genes are mainly related to skeletal system development, circadian rhythm, and oxidative stress, while 519 downregulated genes are associated with visual perception and heart contraction. Furthermore, the carbon metabolism and peroxisome proliferator–activated receptor (PPAR) signalling pathways, which are essential for embryonic development, were significantly dysregulated by exposure to Bi NPs. This study innovatively focused on evaluating the embryonic developmental toxicities of monometallic Bi NPs on zebrafish and unveiled the underlying toxic mechanisms, highlighting the potential hazard and risk posed by Bi NPs and raising concerns regarding adverse impacts on aquatic organisms. © 2025

关键词： Bismuth nanoparticles Nanotoxicity Transcriptomic zebrafish

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An overview of chronic myeloid leukemia and its animal models

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Science China(Life Sciences) 2015年第12期58卷 1202-1208页

作者： MA WeiXu MA Ning CHEN XiaoHui ZHANG YiYue ZHANG WenQing Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes Department of Developmental Biology Institute of Genetic Engineering School of Basic Medical Sciences Southern Medical University

Chronic myeloid leukemia(CML) is a form of leukemia characterized by the presence of clonal bone marrow stem cells with the proliferation of mature granulocytes(neutrophils, eosinophils, and basophils) and their precursors. CML is a type of myeloproliferative disease associated with a characteristic chromosomal translocation called the Philadelphia(Ph) chromosome or t(9;22) translocation(BCR-ABL). CML is now usually treated with targeted drugs called tyrosine kinase inhibitors(TKIs). The mechanism and natural history of CML is still unclear. Here, we summarize the present CML animal disease models and compare them with each other. Meanwhile, we propose that it is a very wise choice to establish zebrafish(Danio rerio) CML model mimics clinical CML. This model could be used to learn more about the mechanism of CML, and to aid in the development of new drugs to treat CML.

关键词： chronic myeloid leukemia（CML） animal disease model zebrafish

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Quantity versus quality： the sperm war

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Asian Journal of Andrology 2016年第6期18卷 900-901页

作者： Shan Xiao Laixin Xia Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes Department of Cell Biology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China

The evolution of sperm traits manifests itself prolifically across species, andpostcopulatory sexual selection （PSS）, as executed by the female, accompanies this process. The adaptive significance of some sperm traits （for example, the shape and number of sperms） is well understood. However, the evolution of germ size has not been fully exploited. The most recent study by Lfipold et al.1 reveals that the evolution of longer sperm is driven by the female seminal receptacle and mating frequency in Drosophila, which, in turn, increases the benefits to females. These findings provide a comprehensive interpretation regarding the evolution of sperm size.

关键词： @@

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Tripterygium wilfordii multiglycoside-induced hepatotoxicity via inflammation and apoptosis in zebrafish

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Chinese Journal of Natural Medicines 2021年第10期19卷 750-757页

作者： DUAN Xiu-Ying MA Rui-Jiao HSIAO Chung-Der JIANG Zhen-Zhou ZHANG Lu-Yong ZHANG Yun LIU Ke-Chun Biology Institute Qilu University of Technology(Shandong Academy of Sciences)Jinan 250103China Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province Jinan 250103China Department of Bioscience Technology Chung Yuan Christian UniversityTaoyuan 32023China Jiangsu Key Laboratory of Drug Screening China Pharmaceutical UniversityNanjing 210009China

Tripterygium wilfordii multiglycoside(GTW)is a commonly used compound for the treatment of rheumatoid arthritis(RA)and immune diseases in clinical ***,it can induce liver injury and the mechanism of hepatotoxicity is still not *** study was designed to investigate GTW-induced hepatotoxicity in zebrafish larvae and explore the mechanism *** 72 hpf(hours post fertilization)zebrafish larvae were administered with different concentrations of GTW for three days and their mortality,malformation rate,morphological changes in the liver,transaminase levels,and histopathological changes in the liver of zebrafish larvae were *** reverse transcription-polymerase chain reaction(RT-PCR)was used to examine the levels of microRNA-122(miR-122)and genes related to inflammation,apoptosis,cell proliferation and liver *** results showed that GTW increased the mortality of zebrafish larvae,while significant malformations and liver damage *** main manifestations were elevated levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST),significant liver atrophy,vacuoles in liver tissue,sparse cytoplasm,and unclear hepatocyte ***-PCR results showed that the expression of miR-122 significantly decreased by GTW;the mRNA levels of inflammation-related genes il1β,il6,tnfα,il10,cox2 and ptges significantly increased;the mRNA level of tgfβsignificantly decreased;the mRNA levels of apoptosis-related genes,caspase-8 and caspase-9,significantly increased;the mRNA level of bcl2 significantly decreased;the mRNA levels of cell proliferation-related genes,top2αand uhrf1,significantly reduced;the mRNA levels of liver function-related genes,alr and cyp3c1,significantly increased;and the mRNA level of cyp3a65 significantly *** zebrafish,GTW can cause increased inflammation,enhanced apoptosis,decreased cell proliferation,and abnormal expression of liver function-related genes,leading to abnormal liver structure and funct

关键词： Tripterygium wilfordii multiglycoside zebrafish Hepatotoxicity Inflammation Apoptosis

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Kunxian Capsule Extract Inhibits Angiogenesis in zebrafish Embryos via PI3K/AKT-MAPK-VEGF Pathway

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Chinese Journal of Integrative Medicine 2023年第2期29卷 137-145页

作者： MA Rui-jiao Maharajan Kannan XIA Qing ZHANG Shan-shan TU Peng-fei LIU Ke-chun ZHANG Yun Biology Institute Qilu University of Technology(Shandong Academy of Sciences)Jinan 250103China Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province Jinan 250103China State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China

Objective: To investigate the anti-angiogenic activity of Kunxian Capsule(KX) extract and explore the underlying molecular mechanism using zebrafish. Methods: The KX extract was prepared with 5.0 g in 100 mL of 40% methanol followed by ultrasonication and freeze drying. Freeze dried KX extract of 10.00 mg was used as test stock solution. Triptolide and icariin, the key bioactive compounds of KX were analyzed using ultra-high performance liquid chromatography. The transgenic zebrafish Tg(flk1:GFP) embryos were dechorionated at 20-h post fertilization(hpf) and treated with PTK 787, and 3.5, 7, 14 and 21 μg/m L of KX extract, *** 24-h post exposure(hpe), mortality and malformation(%), intersegmental vessels(ISV) formation, and m RNA expression level of angiogenic pathway genes including phosphoinositide 3-kinase(PI3K), protein kinase B(AKT),extracellular signal-regulated kinases(ERKs), mitogen-activated protein kinase(MAPK), vascular endothelial growth factor(VEGF) and fibroblast growth factor(FGF-2) were determined. Further, the embryos at 72 hpf were treated with KX extract to observe the development of sub-intestinal vein(SIV) after 24 hpe. Results: The chromatographic analysis of test stock solution of KX extract showed that triptolide and icariin was found as 0.089 mg/g and 48.74 mg/g, respectively, which met the requirements of the national drug standards. In zebrafish larvae experiment, KX extract significantly inhibited the ISV(P<0.01) and SIV formation(P<0.05). Besides, the m RNA expression analysis showed that KX extract could significantly suppress the expressions of PI3K and AKT,thereby inhibiting the m RNA levels of ERKs and MAPK. Moreover, the downstream signaling cascade affected the expression of VEGF and its receptors(VEGFR and VEGFR-2). FGF-2, a strong angiogenic factor, was also downregulated by KX treatment in zebrafish larvae. Conclusion: KX extract exhibited anti-angiogenic effects in zebrafish embryos by regulating PI3K/AKT-MAPK-VE

关键词： angiogenesis rheumatoid arthritis synovial inflammation osteoporosis Chinese medicine

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Large-Scale Forward Genetic screening Analysis of Development of Hematopoiesis in zebrafish

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Journal of Genetics and Genomics 2012年第9期39卷 473-480页

作者： Kun Wang Zhibin Huang Lingfeng Zhao Wei Liu Xiaohui Chen Ping Meng Qing Lin Yali Chi Mengchang Xu Ning Ma Yiyue Zhang Wenqing Zhang Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes Department of Cell Biology School of Basic Medical Sciences Southern Medical University Guangzhou 510515 China

zebrafish is a powerful model for the investigation of *** order to isolate novel mutants with hematopoietic defects, large-scale mutagenesis screening of zebrafish was *** scoring specific hematopoietic markers,52 mutants were identified and then classified into four types based on specific phenotypic *** mutant represented a putative mutation of a gene regulating the relevant aspect of hematopoiesis,including early macrophage development,early granulopoiesis,embryonic myelopoiesis,and definitive erythropoiesis/*** method should be applicable for other types of genetic screening in *** addition,further study of the mutants we identified may help to unveil the molecular basis of hematopoiesis.

关键词： zebrafish Large-scale screening Hematopoiesis

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