Embarking on a new journey,exploring infinite possibilities-Welcoming the 2025 edition of Animal Models and Experimental Medicine

Against the backdrop of a new era that commands the attention of scholars worldwide,and on a scientific research journey filled with both hope and challenges,Animal Models and Experimental Medicine(AMEM),as a beacon guiding innovation and rigorous research in the field of animal models and experimental medicine,has once again shone brightly in 2024.With an impact factor of 3.8,a JCI and JCR Q2 ranking,and a CiteScore of 6.3,the journal has demonstrated a continuous rise in its influence and academic status.

The transcriptome of MHV-infected RAW264.7 cells offers an alternative model for macrophage innate immunity research

Background:Macrophages are the primary innate immune cells encountered by the invading coronaviruses,and their abilities to initiate inflammatory reactions,to main-tain the immunity homeostasis by differential polarization,to train the innate immune system by epigenic modification have been reported in laboratory animal research.Methods:In the current in vitro research,murine macrophage RAW 264.7 cell were infected by mouse hepatitis virus,a coronavirus existed in mouse.At 3-,6-,12-,24-,and 48-h post infection(hpi.),the attached cells were washed with PBS and harvested in Trizol reagent.Then The harvest is subjected to transcriptome sequencing.Results:The transcriptome analysis showed the immediate(3 hpi.)up regulation of DEGs related to inflammation,like Il1b and Il6.DEGs related to M2 differential po-larization,like Irf4 showed up regulation at 24 hpi.,the late term after viral infection.In addition,DEGs related to metabolism and histone modification,like Ezh2 were de-tected,which might correlate with the trained immunity of macrophages.Conclusions:The current in vitro viral infection study showed the key innated im-munity character of macrophages,which suggested the replacement value of viral infection cells model,to reduce the animal usage in preclinical research.

High expression of SULF1 is associated with adverse prognosis in breast cancer brain metastasis

Background:Breast cancer is the most common cancer in women,and in advanced stages,it often metastasizes to the brain.However,research on the biological mechanisms of breast cancer brain metastasis and potential therapeutic targets are limited.Methods:Differential gene expression analysis(DEGs)for the datasets GSE43837 and GSE125989 from the GEO database was performed using online analysis tools such as GEO2R and Sangerbox.Further investigation related to SULF1 was conducted using online databases such as Kaplan-Meier Plotter and cBioPortal.Thus,expression levels,variations,associations with HER2,biological processes,and pathways involv-ing SULF1 could be analyzed using UALCAN,cBioPortal,GEPIA2,and LinkedOmics databases.Moreover,the sensitivity of SULF1 to existing drugs was explored using drug databases such as RNAactDrug and CADSP.Results:High expression of SULF1 was associated with poor prognosis in advanced breast cancer brain metastasis and was positively correlated with the expression of HER2.In the metastatic breast cancer population,SULF1 ranked top among the 16 DEGs with the highest mutation rate,reaching 11%,primarily due to amplification.KEGG and GSEA analyses revealed that the genes co-expressed with SULF1 were positively enriched in the‘ECM-receptor interaction’gene set and negatively enriched in the‘Ribosome’gene set.Currently,docetaxel and vinorelbine can act as treatment options if the expression of SULF1 is high.Conclusions:This study,through bioinformatics analysis,unveiled SULF1 as a poten-tial target for treating breast cancer brain metastasis(BM).

Single-cell sequencing reveals the features of adaptive immune responses in the liver of a mouse model of dengue fever

Background:Dengue fever,an acute insect-borne infectious disease caused by the dengue virus(DENV),poses a great challenge to global public health.Hepatic involve-ment is the most common complication of severe dengue and is closely related to the occurrence and development of disease.However,the features of adaptive immune responses associated with liver injury in severe dengue are not clear.Methods:We used single-cell sequencing to examine the liver tissues of mild or se-vere dengue mice model to analyze the changes in immune response of T cells in the liver after dengue virus infection,and the immune interaction between macrophages and T cells.Flow cytometry was used to detect T cells and macrophages in mouse liver and blood to verify the single-cell sequencing results.Results:Our result showed CTLs were significantly activated in the severe liver injury group but the immune function-related signal pathway was down-regulated.The rea-son may be that the excessive immune response in the severe group at the late stage of DENV infection induces the polarization of macrophages into M2 type,and the macrophages then inhibit T cell immunity through the TGF-βsignaling pathway.In ad-dition,the increased proportion of Treg cells suggested that Th17/Treg homeostasis was disrupted in the livers of severe liver injury mice.Conclusions:In this study,single-cell sequencing and flow cytometry revealed the characteristic changes of T cell immune response and the role of macrophages in the liver of severe dengue fever mice.Our study provides a better understanding of the pathogenesis of liver injury in dengue fever patients.

The characteristics of hDPP4 transgenic mice subjected to aerosol MERS coronavirus infection via an animal nose-only exposure device

Background: Middle East respiratory syndrome coronavirus(MERS-Co V), which is not fully understood in regard to certain transmission routes and pathogenesis and lacks specific therapeutics and vaccines, poses a global threat to public health.Methods: To simulate the clinical aerosol transmission route, h DPP4 transgenic mice were infected with MERS-Co V by an animal nose-only exposure device and compared with instillation-inoculated mice. The challenged mice were observed for 14 consecutive days and necropsied on days 3, 5, 7, and 9 to analyze viral load, histopathology, viral antigen distribution, and cytokines in tissues.Results: MERS-Co V aerosol-infected mice with an incubation period of 5-7 days showed weight loss on days 7-11, obvious lung lesions on day 7, high viral loads in the lungs on days 3-9 and in the brain on days 7-9, and 60% survival. MERS-Co V instillation-inoculated mice exhibited clinical signs on day 1, obvious lung lesions on days 3-5, continuous weight loss, 0% survival by day 5, and high viral loads in the lungs and brain on days 3-5. Viral antigen and high levels of proinflammatory cytokines and chemokines were detected in the aerosol and instillation groups. Disease, lung lesion, and viral replication progressions were slower in the MERS-Co V aerosol-infected mice than in the MERS-Co V instillation-inoculated mice.Conclusion: h DPP4 transgenic mice were successfully infected with MERS-Co V aerosols via an animal nose-only exposure device, and aerosol-and instillation-infected mice simulated the clinical symptoms of moderate diffuse interstitial pneumonia. However, the transgenic mice exposed to aerosol MERS-Co V developed disease and lung pathology progressions that more closely resembled those observed in humans.

Deepen the understanding and communication of animal models and experimental medicine research studies

At the first issue of the year 2021,I would like to extend my sincere gratitude for your continued support and attention to Animal Models and Experimental Medicine(AMEM)journal.On behalf of AMEM,I would like to wish you a Happy New Year and all the best!AMEM is an international,open access academic journal dedicated to establish an international platform for academic exchange in the field of experimental animal sciences.AMEM is jointly founded by Chinese Association for Laboratory Animal Sciences(CALAS),Asian Federation of Laboratory Animal Science Associations(AFLAS),the International Council for Laboratory Animal Science(ICLAS)and Institute of Laboratory Animal Sciences(ILAS),Chinese Academy of Medical Sciences&Peking Union Medical College.Since its first publication in 2018,it has now entered into its fourth year.

LasDB: A collective database for laboratory animal strain resources

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.

Era of the 4D animal model

Revealing the entire dynamics of pathogenesis is critical for understanding,preventing and treating human disease but is limited by systematic clinical sampling.This drawback can be overcome with animal model studies.Recent advances in phenotyping,omics and bioinformatics technologies promote the development of the 4D animal model to simulate and digitally display the spatiotemporal landscapes of phenotypes and molecular dynamics in human diseases and reveal novel targets for diagnosis and therapy.In this commentary,the origin,supporting technologies,content,function and application,and advantages of 4D animal models over clinical studies and traditional animal models,as well as their limitations,are presented.

Characteristics of animal models for COVID-19

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the causative agent of coronavirus disease 2019(COVID-19),the most consequential pandemic of this century,threatening human health and public safety.SARS-CoV-2 has been continuously evolving through mutation of its genome and variants of concern have emerged.The World Health Organization R&D Blueprint plan convened a range of expert groups to develop animal models for COVID-19,a core requirement for the prevention and control of SARS-CoV-2 pandemic.The animal model construction techniques developed during the SARS-CoV and MERS-CoV pandemics were rapidly deployed and applied in the establishment of COVID-19 animal models.To date,a large number of animal models for COVID-19,including mice,hamsters,minks and nonhuman primates,have been established.Infectious diseases produce unique mani-festations according to the characteristics of the pathogen and modes of infection.Here we classified animal model resources around the infection route of SARS-CoV-2,and summarized the characteristics of the animal models constructed via transnasal,localized,and simulated transmission routes of infection.

Focus on cutting-edge research to improve the influence of Animal Models and Experimental Medicine

The year 2022 marks the fifth year of the publication of Animal Models and Experimental Medicine( AMEM). We are intensely proud of the publication of each paper, because we recognize that all our efforts are worthwhile to provide a platform for communication and sharing of outstanding scientific results and reinforce the discipline position of animal models and experimental medicine.

Forty years of research in animal models of human diseases and outstanding achievements in supporting human life and health

The 2nd Longtan Science Conference and the 40th anniversary of the Institute of Laboratory Animal Sciences,Chinese Academy of Medical Sciences&Comparative Medicine Center,Peking Union Medical College.On November 19-20,2020,the 2nd Longtan Science Conference and the 40th anniversary celebrations of the Institute of Laboratory Animal Sciences,Chinese Academy of Medical Sciences&Comparative Medicine Center,Peking Union Medical College(hereinafter referred to as"ILAS")were held in Beijing.The conference was jointly organized by the Institute and the Chinese Association for Laboratory Animal Sciences.

Summary of animal models of myelodysplastic syndrome

Myelodysplastic syndrome(MDS)is a malignant tumor of the hematological system characterized by long-term,progressive refractory hemocytopenia.In addition,the risk of leukemia is high,and once it develops,the course of acute leukemia is short with poor curative effect.Animal models are powerful tools for studying human diseases and are highly effective preclinical platforms.Animal models of MDS can accurately show genetic aberrations and hematopoietic clone phenotypes with similar cellular features(such as impaired differentiation and increased apoptosis),and symptoms can be used to assess existing treatments.Animal models are also helpful for understanding the pathogenesis of MDS and its relationship with acute leukemia,which helps with the identification of candidate genes related to the MDS phenotype.This review summarizes the current status of animal models used to research myelodysplastic syndrome(MDS).

Announcing the launch of a new journal: Animal Models andExperimental Medicine

In the Chinese Year of the Dog,we are pleased to present to you the first issue of the new journal we have organized:Animal Models and Experimental Medicine(AMEM).Why do we need a new journal in this area?Laboratory animal sciences is an emerging interdisciplinary subject,which integrates theories and methods from many disciplines,including biology,medicine,pharmacy,veterinary,bioengineering,biomedical engineering,etc.In recent years,many outstanding papers based on laboratory animals have been published around the world,highlighting how laboratory animal sciences has,among other things,provided systematic biological materials and pertinent technologies for the development of related disciplines;integration into many frontier disciplines;development of new disciplines such as comparative medicine,experimental animal medicine,and comparative biology;and supported development in fields such as life sciences,medicine,food,environment and aerospace.However,there are very few specialized journals in this field,and their impact is very limited.Therefore,it is urgent to establish a professional English-language journal to meet the need of all researchers in this important field.

Message from animal models and experimental medicine for 2024-Striving for excellence with distinctive features

Since its inception,Animal Models and Experimental Medicine(AMEM)has received 632 articles in total from 52 countries and regions includ-ing China,Iran,the United States,India,Nigeria,Israel,Germany,Iraq,Italy,Japan,Australia,Bangladesh,Belgium,Brazil,and Canada,among others.AMEM has become an important international exchange plat-form for innovative research achievements in the field of laboratory animal science and basic medicine.

Influencing factors and solution strategies of chimeric antigen receptor T-cell therapy(CAR–T)cell immunotherapy

Chimeric antigen receptor T-cesll therapy(CAR–T)has achieved groundbreaking advancements in clinical application,ushering in a new era for innovative cancer treatment.However,the challenges associated with implementing this novel targeted cell therapy are increasingly significant.Particularly in the clinical management of solid tumors,obstacles such as the immunosuppressive effects of the tumor microenvironment,limited local tumor infiltration capability of CAR–T cells,heterogeneity of tumor targeting antigens,uncertainties surrounding CAR–T quality,control,and clinical adverse reactions have contributed to increased drug resistance and decreased compliance in tumor therapy.These factors have significantly impeded the widespread adoption and utilization of this therapeutic approach.In this paper,we comprehensively analyze recent preclinical and clinical reports on CAR–T therapy while summarizing crucial factors influencing its efficacy.Furthermore,we aim to identify existing solution strategies and explore their current research status.Through this review article,our objective is to broaden perspectives for further exploration into CAR–T therapy strategies and their clinical applications.

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

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 years.Methods: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 virus.RNA sequencing analysis was used to screen the differentially expressed genes(DEGs)after CA10 infection.Coxsackievirus A 16(CA16)and enterovirus 71(EV71)infections were also compared with CA10.Results:After CA10 virus infection,the mice showed paralysis of the hind limbs at 3 days post infection and weight loss at 5 days post infection.We observed viral replication in various tissues and severe inflammatory cell infiltration in skeletal muscle.The 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 pathways.Compared with CA16 and EV71 infection,CA10 may have an inhibitory effect on T helper(Th)cell differentiation and cell growth.Additionally,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 pathway.Conclusions:Our findings revealed a group of genes that coordinate in response to CA10 infection,which increases our understanding of the pathological mechanism of HFMD.

Polypyrimidine Tract-Binding Protein Enhances Zika Virus Translation by Binding to the 5'UTR of Internal Ribosomal Entry Site

Objectives To identify the 5'untranslated region of Zika virus(ZIKV 5'UTR)RNA-binding proteins and to investigate the impact of the binding protein on the activity of internal ribosomal entry site(IRES)located in ZIKV 5'UTR and virus production.Methods Interacting proteins in U251 cells were captured using tRSA-tagged ZIKV 5'UTR RNA and tRSA-ZIKV 5'UTR RNA-binding proteins were visualized by SDS-PAGE silver staining,Subsequently,liquid chromatographytandem mass spectrometry(LC-MS/MS),bioinformatics analysis,and Western blot were used to identify the candidate proteins binding to ZIKV 5'UTR.Dicistronic expression assay and plaque forming assay were performed to analyze the effect of the binding protein on ZIKV IRES activity and ZIKV production,respecitvely.Results tRSA RNA pull-down assay,LC-MS/MS,and Western blot analysis showed that polypyrimidine tractbinding protein(PTB)bound to the ZIKV 5'UTR.Furthermore,dual luciferase reporter assay revealed that overexpression of PTB significantly enhanced the IRES activity of ZIKV(t=10.220,P<0.001),while PTB knockdown had the opposite effect(t=4.897,P<0.01).Additionally,virus plaque forming assay demonstrated that up-regulation of PTB expression significantly enhanced viral titer(t=6.400,P<0.01),whereas reducing PTB expression level weakened virus infectivity(t=5.055,P<0.01).Conclusion PTB positively interacts with the ZIKV 5'UTR and enhances IRES activity and virus production.

P-selectin glycoprotein ligand 1 deficiency prevents development of acute pancreatitis by attenuating leukocyte infiltration

BACKGROUND Acute pancreatitis(AP) is rapid-onset pancreatic inflammation that causes local and systemic inflammatory response syndrome(SIRS) with high morbidity and mortality, but no approved therapies are currently available. P-selectin glycoprotein ligand 1(PSGL-1) is a transmembrane glycoprotein to initiate inflammatory responses. We hypothesized that PSGL-1 may be involved in the development of AP and would be a new target for the treatment of AP.AIM To investigate the role and mechanism of PSGL-1 in the development of AP.METHODS The PSGL-1 expression on leukocytes was detected in peripheral blood of AP patients and volunteers. Pancreatic injury, inflammatory cytokines expression, and inflammatory cell infiltration was measured in AP mouse models induced with PSGL-1 knockout(PSGL-1-/-) and wild-type(PSGL-1+/+) mice. Leukocyteendothelial cell adhesion was measured in a peripheral blood mononuclear cell(PBMC)-endothelial cell coculture system.RESULTS The expression of PSGL-1 on monocytes and neutrophils was significantly increased in AP patients. Compared with PSGL-1+/+ mice, PSGL-1-/-AP mice induced by caerulein exhibited lower serum amylase, less Interleukin-1 beta(IL-1 beta) and Interleukin-6(IL-6) expression, less neutrophil and macrophage infiltration, and reduced peripheral neutrophil and monocyte accounts. PSGL-1 deficiency alleviated leukocyte-endothelial cell adhesion via IL-6 but not IL-1 beta.CONCLUSION PSGL-1 deficiency effectively inhibits the development of AP by preventing leukocyte-endothelial cell adhesion via IL-6 stimulation and may become a potential therapeutic target for treating AP.

Disease Progression Patterns of SHIV-KB9 in Rhesus Macaques of Chinese Origin in Comparison with Indian Macaques

Objective To develop a model of SHIV-KB9/Chinese origin rhesus （Ch Rh） macaques for vaccine research and to compare the pathogenesis of SHIV-KB9 in Ch Rh macaques with that reported in Indian rhesus （Ind Rh） macaques. Methods Seven mamu-A＊01 negative Ch Rh macaques were inoculated intravenously with 1-10000 MID50 of SHIV-KB9. The monkeys were monitored for viral load, CD4, CDS, SHIV-specific antibody and virus genetic variation. The results were compared with those previously observed in Ind Rh macaques. Results As compared to that observed in Ind Rh macaques, SHIV-KB9 in Ch Rh macaques displayed three identical disease progression patterns. However, the primary pattern was not identical between the two subspecies. The level of plasma viremia differed in SHIV-KB9-infected Ch Rh macaques which exhibited different outcomes from those in Ind Rh macaques. Generally, the values of viral load and the maintenance of CD4^＋ T cells were associated with humoral responses. Otherwise, the viral genetic distances （divergence, diversity） were larger in animals （M419, M425） with their CD4^＋ T cells profoundly depleted. Conclusion The model of SHIV-KB9/Ch Rh macaques displays a relatively slow progression to AIDS compared with Ind Rh macaques, which may more accurately reflect the potential of candidate vaccines in humans.

Microarray microRNA profiling of urinary exosomes in a 5XFAD mouse model of Alzheimer’s disease

Background:Alzheimer's disease(AD)is an incurable and irreversible neurodegen-erative disease,without a clear pathogenesis.Therefore,identification of candidates before amyloid-βplaque(Aβ)deposition proceeds is of major significance for earlier intervention in AD.Methods:To explore the potential noninvasive earlier biomarkers of AD in a 5XFAD mouse model,microRNAs(miRNAs)from urinary exosomes in 1-month-old pre-Aβaccumulation 5XFAD mice models and their littermate controls were profiled by mi-croarray analysis.The differentially expressed miRNAs were further analyzed via droplet digital PCR(ddPCR).Results:Microarray analysis demonstrated that 48 differentially expressed miRNAs(18 upregulated and 30 downregulated),of which six miRNAs-miR-196b-5p,miR-339-3p,miR-34a-5p,miR-376b-3p,miR-677-5p,and miR-721-were predicted to display gene targets and important signaling pathways closely associated with AD pathogenesis and verified by ddPCR.Conclusions:Urinary exosomal miRNAs showing differences in expression prior to Aβ-plaque deposition were identified.These exosomal miRNAs represent potential noninvasive biomarkers that may be used to prevent AD in clinical applications.