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cD4^(+)T cells produce IFN-I to license cDc1s for induction of cytotoxic T-cell activity in human tumors

cellular & Molecular Immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël c.de Groot Marij J.P.Welters Tom de Wit Ellen Schrama Hans van Eenennaam Saskia J.Santegoets Timo Oosenbrug Annemarthe van der Veen Joris L.Vos charlotte L.Zuur Noel F.c.c.de Miranda Heinz Jac.bs Sjoerd H.van der burg Jannie borst Yanling Xiao Department of Immunology Leiden University Medical CenterLeidenThe Netherlands Oncode Institute Leiden University Medical CenterLeidenThe Netherlands Department of Tumor biology and Immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS b.V. OssThe Netherlands Division of Medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Otorhinolaryngology Leiden University Medical center LeidenThe Netherlands Department of Pathology Leiden University Medical CenterLeidenThe Netherlands

cD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDc1s)to induce cD8^(+)cytotoxic T lymphocyte(cTL)anticancer responses,as proven in mouse *** recently identified cDc1s with a transcriptomic imprint of cD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting ***,we delineate the mechanism of cDc1 licensing by cD4^(+)T cells in *** cD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHc-I antigen(cross-)presentation by cDc1s and thereby improves their ability to induce cTL anticancer *** cooperation with cD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDc1s required for cTL response ***-I-producing cD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to cTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDcs and tumor-reactive cD8^(+)T *** agreement with this scenario,the presence of IFN-I-producing cD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关键词： cD4^(+)T-cell help cDc1 licensing IFN-I signaling cD40 costimulation (cross-)presentation cTL priming Tumor control

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Inflammatory Factor IL1αInduces Aberrant Astrocyte Proliferation in Spinal cord Injury Through the Grin2c/ca^(2+)/caMK2b Pathway

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Neuroscience bulletin 2024年第4期40卷 421-438页

作者： Yu Xia Lu Ding changlin Zhang Qi Xu Ming Shi Tianshun Gao Feng-Quan Zhou David Y.b.Deng Scientific Research center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Department of Gynecology The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Pelvic Floor Disorders center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China big Data center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Sir Run Run Shaw Hospital Zhejiang University School of MedicineHangzhou310016China Orthopaedic and Neurological Repair center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China

Spinal cord injury(ScI)is one of the most devastating traumas,and the aberrant proliferation of astrocytes usually causes neurological ***,the mechanism underlying astrocyte over-proliferation after ScI is ***2c(glutamate ionotropic receptor type 2c)plays an essential role in cell *** bioinformatic analysis indicated that Grin2c and ca^(2+)transport functions were inhibited in astrocytes after *** of Grin2c stimulated astrocyte proliferation by inhibiting the ca^(2+)/calmodulin-dependent protein kinase 2b(caMK2b)pathway in *** screening different inflammatory factors,interleukin 1α(IL1α)was further found to inhibit Grin2c/ca^(2+)/caMK2b and enhance astrocyte proliferation in an oxidative damage *** of IL1αusing neutralizing antibody resulted in increased Grin2c expression and the inhibition of astrocyte proliferation ***,this study suggests that IL1αpromotes astrocyte proliferation by suppressing the Grin2c/ca^(2+)/caMK2b pathway after ScI,revealing a novel pathological mechanism of astrocyte proliferation,and may provide potential targets for ScI repair.

关键词： IL1α Grin2c Astrocyte Spinal cord injury

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clinical-based phenotypes in children with pediatric post-cOVID-19 condition

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World Journal of Pediatrics 2024年第7期20卷 682-691页

作者： Lieke c.E.Noij Jelle M.blankestijn coen R.Lap Marlies A.van Houten Giske biesbroek Anke-Hilse Maitland-van der Zee Mahmoud I.Abdel-Aziz Johannes b.van Goudoever Mattijs W.Alsem caroline L.H.brackel Kim J.Oostrom Simone Hashimoto Suzanne W.J.Terheggen-Lagro Department of Pediatric Pulmonology and Allergy Amsterdam UMCLocation AMCEmma Children’s HospitalAmsterdam University Medical CenterRoom G2-222Meibergdreef 91105AZAmsterdamThe Netherlands Department of Pulmonary Medicine Amsterdam UMCAmsterdamThe Netherlands Department of Pediatrics Spaarne GasthuisHoofddorpThe Netherlands Department of Pediatrics Emma Children’s HospitalAmsterdam University Medical CenterAmsterdamThe Netherlands Department of Rehabilitation Medicine Amsterdam Movement SciencesMeibergdreef 9AmsterdamThe Netherlands Department of Paediatric Pulmonology Department of PaediatricsTergooi MCHilversumThe Netherlands Department of child and Adolescent Psychiatry and Psychosocial care Amsterdam UMCAmsterdam Reproduction and DevelopmentAmsterdamThe Netherlands

background Pediatric post coronavirus disease 2019(cOVID-19)condition(PPcc)is a heterogeneous syndrome,which can significantly affect the daily lives of *** study aimed to identify clinically meaningful phenotypes in children with PPcc,to better characterize and treat this *** Participants were children with physician-diagnosed PPcc,referred to the academic hospital Amsterdam UMc in the Netherlands between November 2021 and March *** factors and information on post-cOVID symptoms,comorbidities,and impact on daily life were *** clusters were identified using an unsupervised and unbiased approach for mixed data *** Analysis of 111 patients(aged 3–18 years)revealed three distinct clusters within *** 1(n=62,median age=15 years)predominantly consisted of girls(74.2%).These patients suffered relatively more from exercise intolerance,dyspnea,and smell *** 2(n=33,median age=13 years)contained patients with an even gender distribution(51.5%girls).They suffered from relatively more sleep problems,memory loss,gastrointestinal symptoms,and *** 3(n=16,median age=11 years)had a higher proportion of boys(75.0%),suffered relatively more from fever,had significantly fewer symptoms(median of 5 symptoms compared to 8 and 10 for clusters 1 and 2 respectively),and experienced a lower impact on daily *** This study identified three distinct clinical PPcc phenotypes,with variations in sex,age,symptom patterns,and impact on daily *** findings highlight the need for further research to understand the potentially diverse underlying mechanisms contributing to post-cOVID symptoms in children.

关键词： Adolescents clusters Long cOVID Pediatric Phenotypes Post-cOVID syndrome

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Exosomes derived from tumor adjacent fibroblasts efficiently target pancreatic tumors

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Acta Pharmaceutica Sinica b 2024年第7期14卷 3009-3026页

作者： Saini Setua Shabia Shabir Poornima Shaji Ana Martinez bulnes Anupam Dhasmana Swathi Holla Nivesh K.Mittal Nirakar Sahoo Tripti Saini Francesco Giorgianni Mohammad Sikander Andrew E.Massey bilal b.Hafeez Manish K.Tripathi Vincent P.Diego Meena Jaggi Junming Yue Nadeem Zafar Murali M.Yallapu Stephen W.behrman Sheema Khan Subhash c.chauhan Department of Pharmaceutical Sciences College of Pharmacyand College of MedicineUniversity of Tennessee Health Science Center(UTHSC)MemphisTN 36163USA Department of computer Science Islamic University of Science and TechnologyAwantiporaJ&K 192122India Department of Immunology and Microbiology School of MedicineUniversity of Texas Rio Grande ValleyMcAllenTX 78504USA South Texas center of Excellence in cancer Research School of Medicinethe University of Texas Rio Grande ValleyMcAllenTX 78504USA Himalayan School of biosciences and cancer Research Institute Himalayan Institute of Medical SciencesSwami Rama Himalayan UniversityDehradun 248016India Plough center for Sterile Drug Delivery Solutions UTHSCMemphisTN 38104USA Department of biology College of SciencesUTRGVMcAllenTX 78539USA National Institute of biomedical Imaging and bioengineering(NIbIb) National Institutes of HealthBethesdaMD 20892USA South Texas Diabetes and Obesity Institute UTRGVMcAllenTX 78504USA Dept.of Laboratory Medicine&Pathology University of WashingtonSeattleWA 98195USA Department of Surgery Baptist Memorial Medical EducationBaptist Memorial HospitalMemphisTN 38120USA baptist Health Sciences University MemphisTN 38104USA

The application of extracellular vesicles,particularly exosomes(EXs),is rapidly expanding in the field of medicine,owing to their remarkable properties as natural carriers of biological *** study investigates utilization of exosomes derived from stromal cells of tumor adjacent normal tissues(NAF-EXs)for personalized medicine,which can be derived at the time of diagnosis by endoscopic ***,we show that exosomes(EXs)derived from NAFs demonstrate differential bio-physical characteristics,efficient cellular internalization,drug loading efficiency,pancreatic tumor targeting and delivery of ***-derived EXs(NAF-EXs)were used for loading ormeloxifene(ORM),a potent anti-cancer and desmoplasia inhibitor as a model *** found that ORM maintains normal fibroblast cell phenotype and renders them incompatible to be triggered for a cAF-like phenotype,which may be due to regulation of ca^(2+) influx in fibroblast ***-EXs-ORM effectively blocked oncogenic signaling pathways involved in desmoplasia and epithelial mesenchymal transition(EMT)and repressed tumor growth in xenograft mouse *** conclusion,our data suggests preferential tropism of NAF-EXs for PDAc tumors,thus imply feasibility of developing a novel personalized medicine for PDAc patients using autologous NAF-EXs for improved therapeutic outcome of anti-cancer ***,it provides the opportunity of utilizing this biological scaffold for effective therapeutics in combination with standard therapeutic regimen.

关键词： Pancreatic cancer Tumor adjacent normal tissue fibroblasts(NAF) Desmoplasia Extracellular vesicles Exosomes Tumor targeting Ormeloxifene Personalized medicine

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cancer-associated fibroblasts express cD1d and activate invariant natural killer T cells under cellular stress

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cellular & Molecular Immunology 2024年第1期21卷 91-94页

作者： Shengduo Pei Jonas Sjölund Yueyun Pan Kristian Pietras Mikael c.I.Karlsson Department of Microbiology Tumor and Cell BiologyKarolinska InstitutetStockholmSweden Division of Translational cancer Research Department of Laboratory MedicineLund University Cancer CentreLund UniversityLundSweden

Invariant natural killer T(iNKT)cells are part of the family of unconventional T cells,and they recognize glycolipid antigens presented on the MHc class I like molecule cD1^([1]).In humans there are five cD1 molecules named cD1a to cD1e,whereas mice use only cD1d for lipid ***,iNKT cells can elicit both cytotoxicity similarly to conventional cD8 T cells and secrete cytokines that influence the adaptive immune response including providing direct T cell help to b cells^([2]).In the context of tumors,they can use both release of granzyme b and use Fas-mediated mechanisms for killing of tumor *** iNKT cells use a restricted TcR repertoire and cD1 molecules are non-heterogenous the risk of graft vs host disease is limited and thus these T cells have been an attractive option for off the shelf immunotherapy to treat cancer^([3]).

关键词： killer cD1d cancer

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应用钆布醇的稳态MR血管成像评估股骨头缺血性坏死病人的血供变化

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国际医学放射学杂志 2024年第1期 129-130页

作者： Z.H.Liao c.Liu b.Wu c.Ma b.Ming Q.Zhou 陈莉

摘要目的探讨应用钆布醇行稳态（SS）MR血管成像（MRA）评价股骨头坏死（ONFH）血供变化的可行性。方法前瞻性纳入2021年12月—2022年5月招募的参与者。比较

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continuous Expression of Interferon Regulatory Factor 4 Sustains cD8^(+)T cell Immunity against Tumor

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Research 2024年第3期2023卷 433-444页

作者： Anze Yu Jinfei Fu Zheng Yin Hui Yan Xiang Xiao Dawei Zou Xiaolong Zhang Xiongbing Zu Xian c.Li Wenhao chen Immunobiology and Transplant Science center Department of SurgeryHouston Methodist Research Institute and Institute for Academic MedicineHouston Methodist HospitalHoustonTXUSA Department of Urology First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongChina Systems Medicine and bioengineering Department Houston Methodist Neal Cancer CenterHoustonTXUSA Department of Radiology Houston Methodist HospitalWeill Cornell MedicineHoustonTXUSA Department of Urology Xiangya HospitalCentral South UniversityChangshaHunanChina Department of Surgery Weill Cornell MedicineCornell UniversityNew YorkNYUSA.

T-cell-based immunotherapy is gaining momentum in cancer treatment;however,our comprehension of the transcriptional regulation governing T cell antitumor activity remains *** objective of this study was to explore the function of interferon regulatory factor 4(IRF4)in antitumor cD8^(+)T cells using the TRAMP-c1 prostate cancer and b16F10 melanoma *** achieve this,we generated an Irf4^(GFP-DTR) mouse strain and discovered that cD8^(+)tumor-infiltrating lymphocytes(TILs)expressing high levels of *** exhibited a more differentiated PD-1high cell *** administering diphtheria toxin to tumor-bearing Irf4^(GFP-DTR) mice,we partially depleted ***^(+)TILs and observed an accelerated tumor *** specifically explore the function of IRF4 in antitumor cD8^(+)T cells,we conducted 3 adoptive cell therapy(AcT)***,depleting ***^(+)cD8^(+)TILs derived from AcT significantly accelerated tumor growth,emphasizing their crucial role in controlling tumor ***,deleting the Irf4 gene in antitumor cD8^(+)T cells used for AcT led to a reduction in the frequency and effector differentiation of cD8^(+)TILs,completely abolishing the antitumor effects of ***,we performed a temporal deletion of the Irf4 gene in antitumor cD8^(+)T cells during AcT,starting from 20 days after tumor implantation,which significantly compromised tumor ***,sustained expression of IRF4 is essential for maintaining cD8^(+)T cell immunity in the melanoma model,and these findings carry noteworthy implications for the advancement of more potent immunotherapies for solid tumors.

关键词： sustained immunity implantation

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Stress enhances expression of calcium-binding proteins and NMDAR subunit genes in the rat hippocampus

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Neuroprotection 2024年第2期2卷 167-178页

作者： Aravind Parthasarathy Ramesha Hanumanthappa Sarojini R.bulbule Kiran P.c. Hemalatha Nanjaiah Gopinath G. Siddaiah b.M. David Muniswamy Devaraju Kuramkote Shivanna Neurochemistry Lab Department of BiochemistryKarnatak UniversityDharwadIndia Department of Microbiology and Immunology University of Maryland School of MedicineBaltimoreMarylandUSA Department of Zoology Karnatak UniversityDharwadIndia

backgrounds:Oxidative stress impairs the function of calcium-binding proteins and deregulates calcium signaling in living *** have previously explored the overexpression of calcium-binding protein genes in a reactive oxygen and nitrogen species-induced in vitro cell model of stress that leads to ***,in in vivo models,low levels of stress leads to depressive-like ***,we aimed to analyze gene expression of major calcium-binding proteins(calcineurin,calmodulin,calsyntenin,synaptotagmin,and calreticulin)and N-methyl-D-aspartic acid(NMDA)receptor subunits(glutamate receptor ionotropic[GluN]GluN1,GluN2A,and GluN2b)in the hippocampus of stress-induced ***:Six-week-old male Wistar rats were assigned to two stress induction groups and a control group without stress(n=6).Stress was induced by using H_(2)O_(2)(3%in water)or by immobilization(using a sticky mat)over a period of 30 *** of calcium-binding protein genes in the hippocampus,antioxidant assays,structural alterations in hippocampal neurons,and depressive-like behavior were ***:Expression of genes encoding calcium-binding proteins calcineurin,calsyntenin,synaptotagmin and NMDA receptor subunit GluN1 was enhanced in both chemical and physical stress-induced rats compared with control rats(4.25±0.05 vs.1.03±0.02,pced rats,neurons in the cA2 region of the hippocampus were fewer and appeared disorganized compared with control ***,stressinduced rats showed decreased mobility and lower sucrose preference in behavioral studies compared with control ***:Lower levels of reactive oxygen and nitrogen species(RONS)can also lead to stress in rats by affecting their calcium signaling,buffering capacity in the neurons leading to depressive symptoms.

关键词： calcineurin H_(2)O_(2) hippocampus immobilization NMDA receptors

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Added value of molecular karyotype in childhood acute lymphoblastic leukemia

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cancer Innovation 2023年第6期2卷 513-523页

作者： Margaux camuset baptiste Le calvez Olivier Theisen catherine Godon Audrey Grain caroline Thomas Marie-Laure couec Marie c.béné Fanny Rialland Marion Eveillard Pediatric Oncology CHU NantesNantes UniversitéUniv AngersINSERMCNRSCRCI2NANantesFrance Hematology biology CHU NantesNantes UniversitéUniv AngersINSERMCNRSCRCI2NANantesFrance

background:Thanks to an improved therapeutic regimen in childhood b-cell precursor acute lymphoblastic leukemia(bcP-ALL),5 year-overall survival now exceeds 90%.Unfortunately,the 25%of children who relapse have an initial poor prognosis,potentially driven by pre-existing or emerging molecular *** latter are initially and essentially identified by ***,some subtle alterations are not visible through ***:Single nucleotide polymorphisms(SNP)array is an alternative way of chromosomal analysis allowing for a more in-depth evaluation of chromosomal modifications such as the assessment of copy number alterations(cNA)and loss of heterozygosity(LOH).This method was applied here in retrospective diagnosis/relapse paired samples from seven children with bcP-ALL and in a prospective cohort of 38 newly diagnosed childhood ***:In the matched study,compared to the initial karyotype,SNP array analysis reclassified two patients as poor prognosis *** during relapse was seen for 4 cNA and 0.9 *** the prospective study,SNP reclassified the 10 patients with intermediate karyotype as 7 good prognosis and 3 poor ***,in all the children tested,SNP array allowed to identify additional anomalies compared to conventional karyotype,refine its prognostic value and identify some druggable anomalies that could be used for precision ***,the anomalies detected could be segregated in four groups respectively involved in b-cell development,cell proliferation,transcription and molecular ***:SNP therefore appears to be a method of choice in the integrated diagnosis of bcP ALL,especially for patients initially classified as intermediate *** complementary method of both cytogenetics and high throughput sequencing allows to obtain further classified information and can be useful in case of failure of these techniques.

关键词： bcP-ALL karyotype pediatric patients prognosis SNP array

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Association between Mental Disorders and Subsequent Medical conditions

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四川生理科学杂志 2024年第4期46卷 217-217页

作者： Natalie c Momen National center for Register-based Research School of Business and Social Sciences at Aarhus Uni versity 8210 Aarhus V Denmark. center for Integrated Register-based Research the Departments of Biomedicine-Human Genetics and Public Health the Center for Integrative Sequencing and the Big Data Center for Environment and Health Aarhus University. Lundbeck Foundation Initiative for Integrative Psychiatric Research the center for Genomics and Personalized Medicine the Department of Neurology and the Research Unit Department of Psychosis Aarhus University Hospital and the Research Unit for General Practice Aarhus the Copenhagen Research Center for Mental Health Mental Health Center Copenhagen Copenhagen University Hospital Psychiatric Center Copenhagen. Department of Health care Policy Harvard Medical School Boston the Neurogenomics Division Translational Genomics Research Institute Phoenix AZ the Department of Psychological Medicine Dunedin School of Medicine University of Otago Dunedin New Zealand Sievert Consulting Minneapolis and the Institute for Health Metrics and Evaluation University of Washington Seattle. Faculty of Health and Medical Sciences the Department of clinical Medicine and the Lundbeck Foundation GeoGenetics Center GLOBE Institute University of Copenhagen Copenhagen and the Institute of Biological Psychiatry Mental Health Center Sankt Hans Mental Health Services Capital Region Roskilde Denmark the National Drug and Alcohol Research Centre University of New South Wales Sydney. Departments of Psychology and Developmental Psychology Heymans Institute and the Interdisciplinary Center Psychopathology and Emotion Regulation University of Groningen Groningen the Netherlands. Department of General Practice Melbourne Medical School University of Melbourne Melbourne VIC and the Queensland Brain Institute Queensland Centre for Mental Health Research the Park Centre for Mental Health and the School of Public Health Faculty of Medicine University of Queensland

background:Persons with mental disorders are at a higher risk than the general population for the subsequent development of certain medical ***:We used a population-based cohort from Danish national registries that included data on more than 5.9 million persons born in Denmark from 1900 through 2015 and followed them from 2000 through 2016,for a total of 83.9 million person-years.

关键词： conditions milli population

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