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Neural Regeneration Research 2021年第7期16卷 1417-1418页

作者： Chaoling Dong Aarti Choudhary Eroboghene E.Ubogu neuromuscular Immunopathology Research laboratory Division of Neuromuscular DiseaseDepartment of NeurologyUniversity of Alabama at BirminghamBirminghamALUSA

Peripheral nerves coordinate signal transduction from the periphery to the central nervous system for processing and transmission back as required for normal mammalian *** nerves and nerve roots are structurally divided into three compartments:the outermost epineurium,inner perineurium that surrounds nerve fascicles and the innermost endoneurium(Mizisin and Weerasuriya,2011).

关键词： function. barrier coordinate

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 ***,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 ***,the permeability of the infected vessel was in ***,disin tegrity of BBB was discovered in the infected hamsters by administration of Evans ***,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 *** an in vitro BBB model that comprises primary BMECs with astrocytes,SARS-CoV-2 was found to infect and cross through the *** 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 ***,inflammatory responses including vasculitis,glial activation,and upregulated inflammatory factors occurred after SARS-CoV-2 ***,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

Sequential infection with H1N1 and SARS-CoV-2 aggravated COVID-19 pathogenesis in a mammalian model, and covaccination as an effective method of prevention of COVID-19 and influenza

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Signal Transduction and Targeted Therapy 2021年第6期6卷 1876-1883页

作者： Linlin Bao Wei Deng Feifei Qi Qi Lv Zhiqi Song Jiangning Liu Hong Gao Qiang Wei Pin Yu Yanfeng Xu Yajin Qu Fengdi Li Jing Xue Shuran Gong Mingya Liu Guanpeng Wang Shunyi Wang Binbin Zhao Bin Cong Chuan Qin Beijing Key laboratory for Animal Models of Emerging and Remerging Infectious diseases NHC Key Laboratory of Human Disease Comparative MedicineInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina Hebei Medical University ShijiazhuangChina

Influenza A virus may circulate simultaneously with the SARS-CoV-2 virus,leading to more serious respiratory diseases during this ***,the influence of these viruses on disease outcome when both influenza A and SARS-CoV-2 are present in the host remains *** a mammalian model,sequential infection was performed in ferrets and in K18-MCE2 mice,with SARS-CoV-2 infection following *** found that co-infection with H1N1 and SARS-CoV-2 extended the duration of clinical manifestation of COVID-19,and enhanced pulmonary damage,but reduced viral shedding of throat swabs and viral loads in the lungs of ***,mortality was increased in sequentially infected mice compared with single-infection *** with singlevaccine inoculation,co-inoculation of PiCoVacc(a SARS-CoV-2 vaccine)and the flu vaccine showed no significant differences in neutralizing antibody titers or virus-specific immune *** immunization effectively protected K18-MCE2 mice against both H1N1 and SARS-CoV-2 *** findings indicated the development of systematic models of co-infection of H1N1 and SARS-CoV-2,which together notably enhanced pneumonia in ferrets and mice,as well as demonstrated that simultaneous vaccination against HINT and SARS-CoV-2 may be an effective prevention strategy for the coming winter.

关键词： prevention H1N1 influenza

Dhcr24 activates the PI3K/Akt/HKII pathway and protects against dilated cardiomyopathy in mice

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Animal Models and Experimental Medicine 2018年第1期1卷 40-52页

作者： Wei Dong Fei-fei Guan Xu Zhang Shan Gao Ning Liu Wei Chen Lian-feng Zhang Dan Lu Key laboratory of Human disease comparative Medicine NHFPC Institute of Laboratory Animal Science Chinese Academy of Medical Sciences & Comparative Medical Center Peking Union Medical College

Background: 24-dehydrocholesterol reductase(Dhcr24) catalyzes the last step of cholesterol biosynthesis, which is required for normal development and antiapoptotic activities of tissues. We found that Dhcr24 expression decreased in the cTnTR141 Wdilated cardiomyopathy(DCM) transgenic mice. Therefore, we tested whether rescued expression of Dhcr24 could prevent the development of DCM and its possible ***: Heart tissue specific transgenic overexpression mice of Dhcr24 was generated, then was crossed to c TnTR141 Wmouse to obtain the double transgenic mouse(DTG). The phenotypes were demonstrated by the survival, cardiac geometry and function analysis, as well as microstructural and ultrastructural observations based on echocardiography and histology examination. The pathway and apoptosis were analysed by western blotting and TUNEL assay in vivo and in ***: We find that Dhcr24 decreased in hearts tissues of cTnTR141 Wand LMNAE82 KDCM mice. The transgenic overexpression of Dhcr24 significantly improves DCM phenotypes in cTnTR141 Wmice, and activates PI3K/Akt/HKII pathway, followed by a reduction of the translocation of Bax and release of cytochrome c, caspase-9 and caspase-3 activation and myocyte apoptosis. Knockdown the expression of Dhcr24 reduces the activation of PI3K/Akt/HKII pathway and inhibition of the mitochondrial-dependent apoptosis. The anti-apoptotic effect of Dhcr24 could be completely removed by the inhibition of PI3K pathway and partly removed by the HKII inhibitor in H9c2 cell ***: Compensatory expression of Dhcr24 protect against DCM through activated PI3K/Akt/HKII pathway and reduce Bax translocation. This is the first investigation for the molecular mechanism of Dhcr24 participate in development of DCM.

关键词： apoptosis Dhcr24 dilated cardiomyopathy gene expression and regulation

Progress,implications,and challenges in using humanized immune system mice in CAR-T therapy-Application evaluation and improvement

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Animal Models and Experimental Medicine 2024年第1期7卷 3-11页

作者： Hanwei Yue Lin Bai NHC Key laboratory of Human disease comparative Medicine Institute of Laboratory Animal SciencesCAMS and PUMCChao-yang DistrictBeijingChina

In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient *** better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor *** exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and *** believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient *** characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid *** study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development.

关键词： antitumor antiviral CAR-T humanized immune system model humanized mice preclinical research

Effectiveness and mechanisms of adiposederived stem cell therapy in animal models of Parkinson’s disease:a systematic review and meta-analysis

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Translational Neurodegeneration 2021年第2期10卷 166-177页

作者： Keya Li Xinyue Li Guiying Shi Xuepei Lei Yiying Huang Lin Bai Chuan Qin NHC Key laboratory of Human disease comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijing 100021China

Animal models provide an opportunity to assess the optimal treatment way and the underlying mechanisms of direct clinical application of adipose-derived stem cells(ADSCs).Previous studies have evaluated the effects of primitive and induced ADSCs in animal models of Parkinson’s disease(PD).Here,eight databases were systematically searched for studies on the effects and in vivo changes caused by ADSC *** assessment was conducted using a 10-item risk of bias *** the subsequent meta-analysis,study characteristics were extracted and effect sizes were *** out of 2324 published articles(n=169 animals)were selected for further *** ADSC therapy,the rotation behavior(10 experiments,n=156 animals)and rotarod performance(3 experiments,n=54 animals)were improved(P<0.00001 and P=0.0003,respectively).The rotation behavior test reflected functional recovery,which may be due to the neurogenesis from neuronally differentiated ADSCs,resulting in a higher pooled effect size of standard mean difference(SMD)(−2.59;95%CI,−3.57 to−1.61)when compared to that of primitive cells(−2.18;95%CI,−3.29 to−1.07).Stratified analyses by different time intervals indicated that ADSC intervention exhibited a long-term *** the transplantation of ADSCs,tyrosine hydroxylase-positive neurons recovered in the lesion area with pooled SMD of 13.36[6.85,19.86].Transplantation of ADSCs is a therapeutic option that shows long-lasting effects in animal models of *** potential mechanisms of ADSCs involve neurogenesis and neuroprotective *** standardized induction of neural form of transplanted ADSCs can lead to a future application in clinical practice.

关键词： Parkinson’s disease Adipose-derived stem cells Animal model Stem cell therapy Meta-analysis Neurogenesis Neuroprotection

Rehmannia glutinosa exhibits anti-aging effect through maintaining the quiescence and decreasing the senescence of hematopoietic stem cells

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Animal Models and Experimental Medicine 2018年第3期1卷 194-202页

作者： Lin Bai Gui-ying Shi Ya-jun Yang Wei Chen Lian-feng Zhang Chuan Qin Key laboratory of Human disease comparative Medicine Ministry of HealthInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medical Center Peking Union Medical College

Background: The time-related decline in regenerative capacity and organ homeostasis is a major feature of aging. Rehmannia glutinosa and Astragalus membranaceus have been used as traditional Chinese herbal medicines for enhanced immunity and prolonged life. However, the mechanism by which this herbal medicine slows aging is unknown. In this study, we investigated the mechanism of the herbal anti-aging ***: Mice were fed diets supplemented with R. glutinosa or A. membranaceus for 10 months; the control group was fed a standard diet. The phenotypes were evaluated using a grading score system and survival analysis. The percentages of the senescence phenotypes of hematopoietic stem cells(HSCs) were determined by fluorescence-activated cell sorting analysis. The function and the mechanism of HSCs were analyzed by clonogenic assay and the real-time polymerase chain ***: The anti-aging effect of R. glutinosa is due to the enhanced function of HSCs. Mice fed with R. glutinosa displayed characteristics of a slowed aging process,including decreased senescence and increased rate of survival. Flow cytometry analysis showed decreased numbers of Lin–Sca1^+c-kit–(LSK) cells, long-term HSCs(LT-HSCs) and short-term HSCs(ST-HSCs) in the R. glutinosa group. In vitro, clonogenic assays showed increased self-renewal ability of LT-HSCs from the R. glutinosa group as well as maintaining LSK quiescence through upregulated p18 expression. The R. glutinosa group also showed decreased reactive oxygen species levels and the percentage of β-gal^+ cells through downregulation of the cellular senescence-associated protein p53 and ***: Rehmannia glutinosa exerts anti-aging effects by maintaining the quiescence and decreasing the senescence of HSCs.

关键词： anti-aging hematopoietic stem cells quiescence Rehmannia glutinosa

Therapeutic efficacy of Pudilan Xiaoyan Oral Liquid(PDL)for COVID-19 in vitro and in vivo

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1875-1877页

作者： Wei Deng Yanfeng Xu Qi Kong Jing Xue Pin Yu Jiangning Liu Qi Lv Fengdi Li Qiang Wei Linlin Bao 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

Dear Editor,Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),has rapidly swept through the worldwide,with more than 3 million confirmed *** now,no vaccine or effective therapeutic measures are provided to prevent the SARS-CoV-2 *** medicines have some strong advantages on pharmacokinetics,known side effects,safety and dosing regimens.1 Although remdesivir and chloroquine could effectively inhibit the replication of SARS-CoV-2 in vitro,2 no medicine candidates have been evaluated in vivo by using animal models with SARS-CoV-2 infection.

关键词： vivo fir COV

Interaction between the gut microbiome and mucosal immune system

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Military Medical Research 2017年第3期4卷 170-177页

作者： Na Shi Na Li Xinwang Duan Haitao Niu Institute of laboratory Animal Sciences Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center Peking Union Medical Collage (PUMC) Key Laboratory of Human Disease Comparative Medicine Ministry of Health Department of Rheumatology the Second Affiliated Hospital of Nanchang University

The gut microbiota, the largest symbiotic ecosystem with the host, has been shown to play important roles in maintaining intestinal homeostasis. Dysbiosis of the gut microbiome is caused by the imbalance between the commensal and pathogenic microbiomes. The commensal microbiome regulates the maturation of the mucosal immune system, while the pathogenic microbiome causes immunity dysfunction, resulting in disease *** gut mucosal immune system, which consists of lymph nodes, lamina propria and epithelial cells, constitutes a protective barrier for the integrity of the intestinal tract. The composition of the gut microbiota is under the surveillance of the normal mucosal immune system. Inflammation, which is caused by abnormal immune responses,influences the balance of the gut microbiome, resulting in intestinal diseases. In this review, we briefly outlined the interaction between the gut microbiota and the immune system and provided a reference for future studies.

关键词： Microbiome Immunity Inflammation

Pathogenicity and transcriptomic profiling reveals immunology molecular hallmarks after CA10 virus infection

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Animal Models and Experimental Medicine 2024年第5期7卷 717-731页

作者： Wanjun Peng Jing Wu Binbin Zhao Lihong Zhang Xin Chen Xiaohui Wei Na Rong Yunlin Han Jiangning Liu 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

Background:Hand,foot and mouth disease(HFMD)is a common infectious disease caused by viral infection by a variety of enteroviruses,with coxsackievirus A 10(CA10)having become more prevalent in recent ***:In this study,models of CA10 infection were established in 7-day-old Institute of Cancer Research(ICR)mice by intraperitoneal injection to analyze the pathogenicity of the *** sequencing analysis was used to screen the differentially expressed genes(DEGs)after CA10 *** A 16(CA16)and enterovirus 71(EV71)infections were also compared with ***:After CA10 virus infection,the mice showed paralysis of the hind limbs at 3 days post infection and weight loss at 5 days post *** observed viral replication in various tissues and severe inflammatory cell infiltration in skeletal *** RNA-sequencing analysis showed that the DEGs in blood,muscle,thymus and spleen showed heterogeneity after CA10 infection and the most upregulated DEGs in muscle were enriched in immune-related *** with CA16 and EV71 infection,CA10 may have an inhibitory effect on T helper(Th)cell differentiation and cell ***,the common DEGs in the three viruses were most enriched in the immune system response,including the Toll-l ike receptor pathway and the nucleotide-binding and oligomerization domain(NOD)-l ike ***:Our findings revealed a group of genes that coordinate in response to CA10 infection,which increases our understanding of the pathological mechanism of HFMD.

关键词： CA10 HFMD RNA-Seq