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Prenatal cadmium exposure impairs neural tube closure via inducing excessive apoptosis in neuroepithelium

Journal of Environmental Sciences 2024年第4期138卷 572-584页

作者： Shiyong Zhu Xuenan Li Xueyan Dai Jinlong Li College of Veterinary medicine Northeast Agricultural UniversityHarbin 150030China key laboratory of the Provincial Education Department of Heilongjiang for Common Animal disease Prevention and Treatment Northeast Agricultural UniversityHarbin 150030China Heilongjiang key laboratory for laboratory Animals and comparative medicine Northeast Agricultural UniversityHarbin 150030China

Birth defects have become a public health concern.The hazardous environmental factors exposure to embryos could increase the risk of birth defects.Cadmium,a toxic environmental factor,can cross the placental barrier during pregnancy.Pregnant woman may be subjected to cadmium before taking precautionary protective actions.However,the link between birth defects and cadmium remains obscure.Cadmium exposure can induce excessive apoptosis in neuroepithelium during embryonic development progresses.Cadmium exposure activated the p53 via enhancing the adenosine 5‘-monophosphate(AMP)-activated protein kinase(AMPK)and reactive oxygen species'(ROS)level.And cadmium decreases the level of Paired box 3(Pax3)and murine double minute 2(Mdm2),disrupting the process of p53 ubiquitylation.And p53 accumulation induced excessive apoptosis in neuroepithelium during embryonic development progresses.Excessive apoptosis led to the failure of neural tube closure.The study emphasizes that environmental materials may increase the health risk for embryos.Cadmium caused the failure of neural tube closure during early embryotic day.Pregnant women may be exposed by cadmium before taking precautionary protective actions,because of cadmium concentration-containing foods and environmental tobacco smoking.This suggests that prenatal cadmium exposure is a threatening risk factor for birth defects.

关键词： Cadmium Neural tube closure Excessive apoptosis p53 Embryogenesis

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The protective effects of Xuebijing injection on intestinal injuries of mice exposed to irradiation

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Animal Models and Experimental medicine 2022年第6期5卷 565-574页

作者： Yinping Dong YuanYang Zhang Xinyue Wang Wenxuan Li Junling Zhang Lu Lu Hui Dong Saijun Fan Aimin Meng Deguan Li Tianjin key laboratory of Radiation medicine and Molecular Nuclear medicine Institute of Radiation MedicineChinese Academy of Medical Science&Peking Union Medical CollegeTianjinChina Key Laboratory of Human Disease Comparative Medicine Ministry of HealthBeijing Engineering Research Center for Laboratory Animal Models of Human Critical DiseasesNational Human Diseases Animal Model Resource CenterInstitute of Laboratory Animal SciencesChinese Academy of Medical Sciences(CAMS)and Peking Union Medical College(PUMC)BeijingChina

Background:Gastrointestinal(GI)injury is one of the most common side effects of radiotherapy.However,there is no ideal therapy method except for symptomatic treatment in the clinic.Xuebijing(XBJ)is a traditional Chinese medicine,used to treat sepsis by injection.In this study,the protective effects of XBJ on radiation-i nduced intestinal injury(RⅢ)and its mechanism were explored.Methods:The effect of XBJ on survival of irradiated C57BL/6 mice was monitored.Histological changes including the number of crypts and the length of villi were evaluated by H&E.The expression of Lgr5^(+)intestinal stem cells(ISCs),Ki67^(+)cells,villin and lysozymes were examined by immunohistochemistry.The expression of cytokines in the intestinal crypt was detected by RT-PCR.DNA damage and apoptosis rates in the small intestine were also evaluated by immunofluorescence.Results:In the present study,XBJ improved the survival rate of the mice after 8.0and 9.0 Gy total body irradiation(TBI).XBJ attenuated structural damage of the small intestine,maintained regenerative ability and promoted proliferation and differentiation of crypt cells,decreased apoptosis rate and reduced DNA damage in the intestine.Elevation of IL-6 and TNF-α was limited,but IL-1,TNF-β and IL-10 levels were increased in XBJ-treated group after irradiation.The expression of Bax and p53 were decreased after XBJ treatment.Conclusions:Taken together,XBJ provides a protective effect on RⅢby inhibiting inflammation and blocking p53-related apoptosis pathway.

关键词： Xuebijing injection Intestinal injury Total body irradiation Inflammation Apoptosis

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LasDB: A collective database for laboratory animal strain resources

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Animal Models and Experimental medicine 2018年第4期1卷 266-271页

作者： Qi Kong Chuan Qin Institute of laboratory Animal Science Chinese Academy of Medical Sciences(CAMS) and Comparative Medicine CenterPeking Union Medical College (PUMC) NHC Key Laboratory of Human Disease Comparative Medicine Key Laboratory of Human Diseases Animal Model State Administration of Traditional Chinese Medicine Beijing key laboratory for Animal Models of Emerging and Reemerging Infectious diseases Beijing Engineering Research Center for Experimental Animal Models of human Critical diseases

Background: With the aim of establishing the most comprehensive database of laboratory animal strains, the "laboratory animal strain resources database"(LasDB)was constructed as a searchable online database of all laboratory animal strains,stocks and mutant embryonic stem-cell lines available worldwide, including inbred,outbred, mutant and genetically engineered strains.Methods: MySQL database software was used to construct the LasDB, offering an easy-to-use interface.Results: To date, LasDB has a collection covering data for 21 596 mouse strains,2062 rat strains, 13 monkey strains, 2 hamster strains, 5 dog strains, 5 rabbit strains and more than 50 other laboratory animal strains. LasDB will be continually improved with regular updates of new laboratory animal strains from all over the world.Conclusion: To the best of our knowledge, this is the first database that attempts to systematically integrate all available laboratory animal strain data with the aim of supporting open usage and full resource sharing.

关键词： comparative medicine database laboratory animal resource strain

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Distinct neuronal excitability alterations of medial prefrontal cortex in early-life neglect model of rats

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Animal Models and Experimental medicine 2022年第3期5卷 274-280页

作者： Yu Zhang Xiuping Sun Changsong Dou Xianglei Li Ling Zhang Chuan Qin NHC Key Laboratory of Human Disease Comparative Medicine Institute of Laboratory Animal SciencesChinese Academy of Medical Sciences(CAMS)Comparative Medicine CenterPeking Union Medical College(PUMC)BeijingChina National human diseases Animal Model Resource Center BeijingChina Beijing Engineering Research Center for Experimental Animal Models of human Critical diseases BeijingChina International Center for Technology and Innovation of animal model BeijingChina Changping National laboratory(CPNL) BeijingChina

Object:Early-life neglect has irreversible emotional effects on the central nervous system.In this work,we aimed to elucidate distinct functional neural changes in me-dial prefrontal cortex(mPFC)of model rats.Methods:Maternal separation with early weaning was used as a rat model of early-life neglect.The excitation of glutamatergic and GABAergic neurons in rat mPFC was recorded and analyzed by whole-cell patch clamp.Results:Glutamatergic and GABAergic neurons of mPFC were distinguished by typi-cal electrophysiological properties.The excitation of mPFC glutamatergic neurons was significantly increased in male groups,while the excitation of mPFC GABAergic neurons was significant in both female and male groups,but mainly in terms of rest membrane potential and amplitude,respectively.Conclusions:Glutamatergic and GABAergic neurons in medial prefrontal cortex showed different excitability changes in a rat model of early-life neglect,which can contribute to distinct mechanisms for emotional and cognitive manifestations.

关键词： early-life neglect model GABAergic glutamatergic maternal separation with early weaning medial prefrontal cortex neuronal excitability

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Combined superposition effect of hypertension and dyslipidemia on left ventricular hypertrophy

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Animal Models and Experimental medicine 2022年第3期5卷 227-238页

作者： Xueyao Zhang Guangxiao Li Chuning Shi Dongyuan Zhang Yingxian Sun Department of Cardiology First Hospital of China Medical UniversityShenyangChina Department of Medical Record Management First Hospital of China Medical UniversityShenyangChina NHC Key Laboratory of Human Disease Comparative Medicine Institute of Laboratory Animal SciencesChinese Academy of Medical Sciences(CAMS)Comparative Medicine CenterPeking Union Medical College(PUMC)BeijingChina

Background : Hypertension and dyslipidemia are considered reversible risk factors for cardiovascular disease. The purpose of this study was to explore the impact of traditional and nontraditional blood lipid profiles on the risk of left ventricular hypertrophy(LVH) and to explore the superposition effect of dyslipidemia combined with hypertension.Methods : Data on 9134 participants(53.5 ±10.3 years old) from the Northeast China Rural Cardiovascular Health Study(NCRCHS) were statistically analyzed. The blood lipid profile was measured by total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), total glyceride(TG), and calculated nontraditional blood lipid indices including non-HDL-C, atherosclerosis index(AI), TC/HDL-C, and residual cholesterol(RC).Results : After the adjustment of age and gender, the odds ratios(ORs) of LVH in patients with hypertension, high LDL-C, high non-HDL-C, high AI, and high TC/HDL-C were 3.97(3.31– 4.76), 1.27(1.02– 1.59), 1.21(1.04– 1.39), 1.33(1.15– 1.53), and 1.42(1.22– 1.65), respectively. After full adjustment of potential confounding factors, high AI and TC/HDL-C were associated with LVH rather than traditional blood lipid indices.The combination of hypertension and nontraditional dyslipidemia(defined by high AI and TC/HDL-C) was associated with the highest risk of LVH, especially in participants under 45 years of age. The risk was more significant in men, 5.09-fold and 6.24-fold,respectively, compared with 3.66-fold and 4.01-fold in women.Conclusions : People with dyslipidemia defined by nontraditional blood lipid indices(high AI and high TC/HDL-C) and hypertension were more likely to develop LVH.

关键词： atherosclerosis dyslipidemia hypertension l eft ventricular hypertrophy

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Animal models and experimental medicine and the Nobel Prize in Physiology or medicine 2021-TRPV and PIEZO receptors for temperature and touch sensation

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Animal Models and Experimental medicine 2021年第4期4卷 297-299页

作者： Yu Zhang Dongyuan Zhang Chuan Qin Institute of laboratory Animal Sciences Chinese Academy of Medical SciencesBeijingChina comparative medicine Center Peking Union Medical CollegeBeijingChina NHC Key Laboratory of Human Disease Comparative Medicine BeijingChina Beijing Engineering Research Center for Experimental Animal Models of human Critical diseases BeijingChina Chinese Association for laboratory Animal Sciences BeijingChina

1|INTRODUCTION For decades,experimental animal models have been powerful tools for biomedical research and have supported most of the physiological or medical achievements recognized by Nobel Prizes,including the research that won this year's Physiology or medicine Prize.On 4th October 2021,the Nobel Prize in Physiology or medicine 2021 was awarded jointly to David Julius and Ardem Patapoutian"for their discoveries of receptors for temperature and touch."1 Their discoveries have profoundly changed our view of how we sense the world around us2.

关键词： jointly Nobel sensation

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Lgr5^+ intestinal stem cell sorting and organoid culture

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Animal Models and Experimental medicine 2019年第2期2卷 132-135页

作者： Ruixue Liu Haifeng Li Juan Cai Qiang Wei Xiaonan Han Key Laboratory of Human Disease Comparative Medicine The Ministry of Health Institute of Laboratory Animal Science (ILAS) Chinese Academy of Medical Science (CAMS) and Peking Union Medical College (PUMC)

Intestinal epithelial stem cells (IESCs) are one of the most rapidly self‐renewing and proliferating adult stem cells. The IESCs reside at the bottom of intestinal and colonic crypts, giving rise to all intestinal epithelial lineages and maintaining intestinal epithelial replenishment. The technique of three‐dimensional culture based upon intestinal stem cell biology has been recently developed to study gastrointestinal development and disease pathogenesis. Here, we summarize the techniques used to isolate Lgr5‐ positive IESCs to form the enteroids from intestine or colonoids from colon, and present the means to examine these organoid functions. This study will provide a simple and practical way for producing intestinal tissues in the laboratory.

关键词： colonoids enteroids Lgr5 intestinal stem cells organoid culture

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Screening for urinary markers predicting hematopoietic stem cell injury induced by busulfan using genetically diverse mice

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Animal Models and Experimental medicine 2023年第2期6卷 146-154页

作者： Yuhang Sun Bowen Guan Xing Liu Lingyan Zhang Xinpei Wang Aimin Meng Ran Gao National human diseases Animal Model Resource Center NHC Key Laboratory of Human Disease Comparative MedicineBeijing Engineering Research Center for Experimental Animal Models of Human Critical DiseasesInstitute of Laboratory Animal Sciences Chinese Academy of Medical Sciences(CAMS)and Peking Union Medical College(PUMC)National Center of Technology Innovation for Animal ModelBeijingChina

Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor cells.The susceptibility of HSCs to BU injury plays an important role in the myeloablative efficacy of BU.Different susceptibilities were demonstrated in genetically diverse(GD)mice in our preliminary research.Methods:Three strains of GD mice with different susceptibilities to BU-i nduced HSC injury were used for screening biological markers of HSC injury susceptibility in urine.The urine proteins were analyzed using liquid chromatography coupled with tandem mass spectrometry to screen for differentially expressed proteins.Screening for possible biomarkers based on differences in protein expression abundance was validated using enzyme-l inked immunoassay(ELISA).Results:Functional analysis showed that the differential proteins were all involved in a series of biological pathways related to cellular senescence,apoptosis,and angiogenesis;whereas the differential proteins of the high-susceptible strain were enriched for the regulation of bone marrow microenvironment pathways,those of low-susceptible strain were enriched for the proapoptotic effect of GTPase pathways.Based on protein abundance differences,several urinary proteins that may be indicative of susceptibility were screened,and ELISA validation results showed that angiotensin-converting enzyme may be a potential biomarker predicting HSC susceptibility for BU conditioning.Conclusions:This study indicates that urinary protein levels can reflect differences in susceptibility to BU-i nduced HSC injury.Using GD mice to construct genetic difference models will provide preclinical data for screening BU-related biological markers.

关键词： angiotensin I converting enzyme busulfan hematopoietic stem cell injury inbred genetic diversity mice urinary marker

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Morphine analgesia in male inbred genetic diversity mice recapitulates the among-individual variance in response to morphine in humans

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Animal Models and Experimental medicine 2022年第3期5卷 288-296页

作者： Yin Yang Bowen Guan Qiang Wei Wei Wang Aimin Meng Key Laboratory of Human Disease Comparative Medicine Ministry of HealthBeijing Engineering Research Center for Laboratory Animal Models of Human Critical DiseasesInstitute of Laboratory Animal SciencesChinese Academy of Medical Sciences(CAMS)and Peking Union Medical College(PUMC)BeijingChina Department of Physiology and Neurobiology School of Basic Medical SciencesZhengzhou UniversityZhengzhouChina

Morphine is a widely used analgesic, but its use in clinical precision medicine is limited by the variance in response among individuals. Although previous studies have shown that individual differences in morphine can be explained in terms of pharmacodynamics and pharmacokinetics, genetic polymorphisms also play an important role. However, the genetic basis of different sensitivity and tolerance susceptibility to morphine remains ambiguous. Using 15 strains of inbred Genetic Diversity(GD) mice,a new resource with wide genetic and phenotypic variation, we demonstrated great variance in sensitivity to morphine analgesia and susceptibility to morphine tolerance between different GD strains. Among-i ndividual variance in response to morphine analgesia in the population can be modeled in GD mice. Two loci respectively may be associated with the among-i ndividual variance in morphine sensitivity and tolerance,confirming the role of genetic factors in among-i ndividual different responses to morphine. These results indicate that GD mice may be a potential tool for the identification of new biomarkers to improve the clinical administration of morphine.

关键词： inbred genetic diversity mice morphine analgesia morphine tolerance quantitative trait loci mapping

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SARS-CoV-2 crosses the blood-brain barrier accompanied with basement membrane disruption without tight junctions alteration

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Signal Transduction and Targeted Therapy 2021年第10期6卷 3062-3073页

作者： Ling Zhang Li Zhou Linlin Bao Jiangning Liu Hua Zhu Qi Lv Ruixue Liu Wei Chen Wei Tong Qiang Wei Yanfeng Xu Wei Deng-Hong Gao Jing Xue Zhiqi Song Pin Yu Yunlin Han Yu Zhang Xiuping Sun Xuan Yu Chuan Qin NHC Key Laboratory of Human Disease Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina

SARS-CoV-2 has been reported to show a capacity for invading the brains of humans and model animals.However,it remains undear whether and how SARS-CoV-2 crosses the blood-brain barrier(BBB).Herein,SARS-CoV-2 RNA was occasionally detected in the vascular wall and perivascular space,as well as in brain microvascular endothelial cells(BMECs)in the infected K18-hACE2 transgenic mice.Moreover,the permeability of the infected vessel was in creased.Furthermore,disin tegrity of BBB was discovered in the infected hamsters by administration of Evans blue.Interestingly,the expression of claudin5,ZO-1,occludin and the ultrastructure of tight junctions(TJs)showed unchanged,whereas,the basement membrane was disrupted in the infected animals.Using an in vitro BBB model that comprises primary BMECs with astrocytes,SARS-CoV-2 was found to infect and cross through the BMECs.Consistent with in vivo experiments,the expression of MMP9 was increased and collagen IV was decreased while the markers for TJs were not altered in the SARS-CoV-2-infected BMECs.Besides,inflammatory responses including vasculitis,glial activation,and upregulated inflammatory factors occurred after SARS-CoV-2 infection.Overall,our results provide evidence supporting that SARS-CoV-2 can cross the BBB in a transcellular pathway accompanied with basement membrane disrupted without obvious alteration of TJs.

关键词： basement alteration barrier

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