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Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models

Zoological Research 2024年第4期45卷 747-766页

作者： Hong-Yi Zheng Tian-Zhang Song Yong-Tang Zheng State Key laboratory of Genetic Evolution&Animal Models KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesCenter for Biosafety Mega-ScienceKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China National Resource Center for Non-human Primates National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China

The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019(COVID-19)immunobiology,often resulting in a lack of reproducibility when extrapolated to the whole ***,developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** review summarizes current progress related to COVID-19 animal models,including non-human primates(NHPs),mice,and hamsters,with a focus on their roles in exploring the mechanisms of immunopathology,immune protection,and long-term effects of SARS-CoV-2 infection,as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 *** among these animal models and their specific applications are also highlighted,as no single model can fully encapsulate all aspects of *** effectively address the challenges posed by COVID-19,it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and *** animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic,serving as a robust resource for future emerging infectious diseases.

关键词： SARS-CoV-2 COVID-19 Animal models Infection immunology Immunotherapy

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Chemical compounds as well as antioxidant and litholytic activities of Arbutus unedo L. leaves against calcium oxalate stones

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Journal of Integrative Medicine 2019年第6期17卷 430-437页

作者： Rabie Kachkoul Tarik Squalli Housseini Mohamed Mohim Radouane El Habbani Youssef Miyah Anissa Lahrichi laboratory of Biochemistry Faculty of Medicine and PharmacyUniversity Sidi Mohammed Ben AbdellahBP 1893FezMorocco Faculty of Science and Technology University Sidi Mohammed Ben AbdellahBP 2202FezMorocco laboratory of molecular bases in human pathology and therapeutic tools Faculty of Medicine and PharmacyUniversity Sidi Mohammed Ben AbdellahBP 1893FezMorocco Department of Nephrology University Hospital HassanⅡBP 1835AtlasFezMorocco

Objective: The present study aimed to quantify and identify the bioactive compounds of the Arbutus unedo L. leaves in order to evaluate both their antioxidant properties and litholytic activities against calcium oxalate ***: This survey was carried out using hydroalcoholic extract(***) and infusion(***) of A. unedo leaves. The quantification of phenolic compounds, flavonoids, flavonols and anthocyanins was done by spectrophotometric methods and identification of chemical components was performed by ultraperformance liquid chromatography with photodiode array and electrospray ionization tandem mass spectrometry. Antioxidant activity was measured using the 1,1-diphenyl-2-picrylhydrazyl(DPPH)method and by the ferric reducing/antioxidant power(FRAP) assay. Litholytic activity of *** and *** was studied using a special model that resembles circuitry of the urinary ***: *** showed greater antioxidant efficacy than ***(P < 0.05). Its higher efficiency was shown via the values of median inhibitory concentration, which was close to(76.14 ± 0.91) mg/mL for *** versus(202.64 ± 5.77) lg/mL for *** using the DPPH method, and(53.77 ± 0.81) lg/mL for *** versus(236.86 ± 31.90) lg/mL for ***, using FRAP method. *** exhibited significantly higher litholytic activity compared to ***(P < 0.05), with dissolution values of 31.03% ± 0.63% versus 14.55% ± 0.65%, ***: Overall, the results suggest that the A. unedo is rich in bioactive compounds, and possesses antioxidant and litholitic abilities that are worthy of further study.

关键词： Antioxidant activity Arbutus unedo L Litholytic activity Phenolic compounds Liquid chromatography Photodiode array Electrospray ionization tandem Mass spectrometry

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Dynamic m6A-ncRNAs association and their impact on cancer pathogenesis, immune regulation and therapeutic response

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Genes & Diseases 2023年第1期10卷 135-150页

作者： Yuanliang Yan Jinwu Peng Qiuju Liang Xinxin Ren Yuan Cai Bi Peng Xi Chen Xiang Wang Qiaoli Yi Zhijie Xu Department of Pharmacy Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of pathology Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of pathology Xiangya Changde HospitalChangdeHunan 415000China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China Center for molecular Medicine Xiangya HospitalKey Laboratory of Molecular Radiation Oncology of Hunan ProvinceCentral South UniversityChangshaHunan 410008China

Several types of modifications have been proven to participate in the metabolism and processing of different RNA types,including non-coding RNAs(ncRNAs).N-6-methyladenosine(m6A)is a dynamic and reversible RNA modification that is closely involved in the ncRNA homeostasis,and serves as a crucial regulator for multiple cancer-associated signaling *** ncRNAs usually regulate the epigenetic modification,mRNA transcription and other biological processes,displaying enormous roles in human *** this review,we summarized the significant implications of m6A-ncRNA interaction in various types of *** particular,the interplay between m6A and ncRNAs in cancer pathogenesis and therapeutic resistance are being widely *** also discussed the relevance of m6A-ncRNA interaction in immune regulation,followed by the interference on cancer immunotherapeutic *** addition,we briefly highlighted the computation tools that could identify the accurate features of m6A methylome among *** summary,this review would pave the way for a better understanding of the biological functions of m6A-ncRNA crosstalk in cancer research and treatment.

关键词： Cancer Immune regulation N-6-Methyladenosine Non-coding RNAs therapeutic response

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Modeling human gastric cancers in immunocompetent mice

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Cancer Biology & Medicine 2024年第7期21卷 553-570页

作者： Weihong Zhang Shilong Wang Hui Zhang Yan Meng Shi Jiao Liwei An Zhaocai Zhou Department of Stomatology Department of Medical UltrasoundShanghai Tenth People's HospitalTongji University Cancer CenterTongji University School of MedicineShanghai 200072China State Key laboratory of Genetic Engineering School of Life SciencesZhongshan HospitalFudan UniversityShanghai 200032China Collaborative Innovation Center for Cancer Personalized Medicine School of Public HealthNanjing Medical UniversityNanjing 211166China

Gastric cancer(GC)is a major cause of cancer-related mortality *** is determined by multiple(epi)genetic and environmental factors;can occur at distinct anatomic positions of the stomach;and displays high heterogeneity,with different cellular origins and diverse histological and molecular *** heterogeneity has hindered efforts to fully understand the pathology of GC and develop efficient *** the past decade,great progress has been made in the study of GC,particularly in molecular subtyping,investigation of the immune microenvironment,and defining the evolutionary path and *** mouse models,particularly immunocompetent models that mimic the cellular and molecular features of human GC,in combination with organoid culture and clinical studies,have provided powerful tools for elucidating the molecular and cellular mechanisms underlying GC pathology and immune evasion,and the development of novel therapeutic ***,we first briefly introduce current progress and challenges in GC study and subsequently summarize immunocompetent GC mouse models,emphasizing the potential application of genetically engineered mouse models in antitumor immunity and immunotherapy studies.

关键词： Gastric cancer heterogeneity mouse model GEMM immunocompetent

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Targeting growth hormone function: strategies and therapeutic applications

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Signal Transduction and Targeted Therapy 2019年第1期4卷 614-624页

作者： Man Lu Jack U.Flanagan Ries J.Langley Michael P.Hay Jo K.Perry Liggins Institute University of AucklandAucklandNew Zealand Auckland Cancer Society Research Centre School of Medical SciencesUniversity of AucklandAucklandNew Zealand Maurice Wilkins Centre for molecular Biodiscovery AucklandNew Zealand Department of molecular Medicine and pathology School of Medical SciencesUniversity of AucklandAucklandNew Zealand

human growth hormone(GH)is a classical pituitary endocrine hormone that is essential for normal postnatal growth and has pleiotropic effects across multiple physiological *** is also expressed in extrapituitary tissues and has localized autocrine/paracrine effects at these *** adults,hypersecretion of GH causes acromegaly,and strategies that block the release of GH or that inhibit GH receptor(GHR)activation are the primary forms of medical therapy for this *** of GH has also been linked to cancer and the microvascular complications that are associated with ***,studies to investigate the therapeutic potential of GHR antagonism in these diseases have been limited,most likely due to difficulty in accessing therapeutic tools to study the pharmacology of the receptor in *** review will discuss current and emerging strategies for antagonizing GH function and the potential disease indications.

关键词： therapeutic pituitary diseases

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Targeting tight junctions during epithelial to mesenchymal transition in human pancreatic cancer

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World Journal of Gastroenterology 2014年第31期20卷 10813-10824页

作者： Daisuke Kyuno Hiroshi Yamaguchi Tatsuya Ito Tsuyoshi Kono Yasutoshi Kimura Masafumi Imamura Takumi Konno Koichi Hirata Norimasa Sawada Takashi Kojima Department of Surgery Sapporo Medical University School of Medicine Department of Cell Science Research Institute for Frontier Medicine Sapporo Medical University School of Medicine Department of pathology Sapporo Medical University School of Medicine

Pancreatic cancer continues to be a leading cause of cancer-related death worldwide and there is an urgent need to develop novel diagnostic and therapeutic strategies to reduce the mortality of patients with this disease. In pancreatic cancer, some tight junction proteins, including claudins, are abnormally regulated and therefore are promising molecular targets for diagnosis, prognosis and therapy. Claudin-4 and-18 are overexpressed in human pancreatic cancer and its precursor lesions. Claudin-4 is a high affinity receptor of Clostridium perfringens enterotoxin(CPE). The cytotoxic effects of CPE and monoclonal antibodies against claudin-4 are useful as novel therapeutic tools for pancreatic cancer. Claudin-18 could be a putative marker and therapeutic target with prognostic implications for patients with pancreatic cancer. Claudin-1,-7, tricellulin and marvelD3 are involved in epithelial to mesenchymal transition(EMT) of pancreatic cancer cells and thus might be useful as biomarkers during disease. Protein kinase C is closely related to EMT of pancreatic cancer and regulates tight junctions of normal human pancreatic duct epithelial cells and the cancer cells. This review focuses on the regulation of tight junctions via protein kinase C during EMT in human pancreatic cancer for the purpose of developing new diagnostic and therapeutic modalities for pancreatic cancer.

关键词： Tight junctions Claudins Tricellulin MarvelD3 Normal human pancreatic duct epithelial cells Pancreatic cancer Protein kinase C Epithelial to mesenchymal transition

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Translational research case studies:Development of antibodies for cancer diagnosis and therapy

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Journal of Nanjing Medical University 2007年第6期21卷 385-385页

作者： Brian Cao Antibody Technology laboratory Van Andel Research InstituteUSA 49506

Antibodies are primary tools in several areas of biomedical sciences, including basic research, diagnostics, and molecular therapeutics. Antibodies are widely used in diagnostic applications for clinical medicine. Analysis of cells and tissues in pathology laboratories includes the use of antibodies on tissue sections. Further, antibodies are making rapid inroads into medical therapeutics, driven by technological evolution from chimeric and humanized to fully human antibodies. The therapeutic antibody market has the potential to reach $30 billion by 2010. Our lab has developed a monoclonal antibody, named Met4 that was raised against the extracellular domain of Met specifically with the goal of measuring Met in FFPE tissues. The Met receptor kinase is expressed on the cell surface of a significant number and variety of human primary solid tumors and in their metastases. The characterization of the Met4 antibody suggests it should possess adequate performance for quantification of Met expression in clinical specimens. We have also generated a fully human Fab fragment against EGFR; conjugated it to taxol as an immuno-chemotherapy agent; and investigated its in vitro antitumor efficacy on EGFR positive A431 epidermoid carcinoma cells.

关键词： monoclonal antibody cancer diagnosis and therapy Met 4

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