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Diabetes and pulmonary infection:how hyperglycaemia shapes the immune system

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signal Transduction and Targeted Therapy 2024年第4期9卷 1245-1246页

作者： Christian Herder Michael Roden Nicolas Venteclef Institute for Clinical Diabetology German Diabetes CenterLeibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf40225DüsseldorfGermany German Center for Diabetes Research(DZD) Partner Düsseldorf85764München-NeuherbergGermany Department of Endocrinology and Diabetology Medical Faculty and University Hospital DüsseldorfHeinrich Heine University Düsseldorf40225DüsseldorfGermany Institut Necker-Enfants Malades(INEM) UniversitéParis CitéINSERM UMR-S1151CNRS UMR-S8253ParisFrance

In a recent study published in Nature,Nobs and colleagues aimed to identify novel mechanisms that may explain why diabetes is associated with an increased susceptibility to viral respiratory infections.Their analyses revealed a central role of lung dendritic cells(DC)which exhibited several functional defects induced by hyperglycaemia and consequently result in impaired antiviral immune responses.

关键词： impaired lung respiratory

Development of NK cell-based cancer immunotherapies through receptor engineering

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Cellular & Molecular Immunology 2024年第4期21卷 315-331页

作者： Audrey Page Nicolas Chuvin Jenny Valladeau-Guilemond stéphane Depil Centre de Recherche en Cancérologie de Lyon UMR INSERM U1052 CNRS 5286Centre Léon BérardLyonFrance ErVimmune LyonFrance Centre Léon Bérard LyonFrance UniversitéClaude Bernard Lyon 1 LyonFrance

Natural killer(NK)cell-based immunotherapies are attracting increasing interest in the field of cancer treatment.Early clinical trials have shown promising outcomes,alongside satisfactory product efficacy and safety.Recent developments have greatly increased the therapeutic potential of NK cells by endowing them with enhanced recognition and cytotoxic capacities.This review focuses on surface receptor engineering in NK cell therapy and discusses its impact,challenges,and future directions.Most approaches are based on engineering with chimeric antigen receptors to allow NK cells to target specific tumor antigens independent of human leukocyte antigen restriction.This approach has increased the precision and potency of NK-mediated recognition and elimination of cancer cells.In addition,engineering NK cells with T-cell receptors also mediates the recognition of intracellular epitopes,which broadens the range of target peptides.Indirect tumor peptide recognition by NK cells has also been improved by optimizing immunoglobulin constant fragment receptor expression and signaling.Indeed,engineered NK cells have an improved ability to recognize and destroy target cells coated with specific antibodies,thereby increasing their antibodydependent cellular cytotoxicity.The ability of NK cell receptor engineering to promote the expansion,persistence,and infiltration of transferred cells in the tumor microenvironment has also been explored.Receptor-based strategies for sustained NK cell functionality within the tumor environment have also been discussed,and these strategies providing perspectives to counteract tumor-induced immunosuppression.Overall,receptor engineering has led to significant advances in NK cell-based cancer immunotherapies.As technical challenges are addressed,these innovative treatments will likely reshape cancer immunotherapy.

关键词： NK cells Cell therapy Receptor engineering CAR

severe asthma exacerbation:Changes in patient characteristics,management,and outcomes from 1997 to 2016 in 40 ICUs in the greater Paris area

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Journal of Intensive Medicine 2024年第2期4卷 209-215页

作者： Romy Younan Jean Loup Augy Bertrand Hermann Bertrand Guidet Philippe Aegerter Emmanuel Guerot Ana Novara Caroline Hauw-Berlemont Amer Hamdan Clotilde Bailleul Francesca santi Jean-Luc Diehl Nicolas Peron Nadia Aissaoui Intensive Care Unit AP-HPGeorges Pompidou European HospitalUniversitéde ParisParisFrance Intensive Care Unit AP-HPSaint Antoine HospitalUniversités de SorbonneUniversitéPierre et Marie CurieParisFrance inserm U1136 ParisFrance Versailles saint-Quentin-en-Yvelines University INSERM U1018Groupe Interrégional de Recherche Clinique et d'InnovationÎle-de-FranceFrance Respiratory Medicine Department AP-HPGeorges Pompidou European HospitalUniversitéde ParisParisFrance Innovative Therapies in Hemostasis INSERM UMR-S1140Universitéde ParisParisFrance Intensive Care Unit and Biosurgical Research Lab(Carpentier Foundation) AP-HPGeorges Pompidou European HospitalParisFrance Paris-Cardiovascular-Research-Center INSERM U970ParisFrance

Background Despite advances in asthma treatments,severe asthma exacerbation(sAE)remains a life-threatening condition in adults,and there is a lack of data derived from adult patients admitted to intensive care units(ICUs)for sAE.The current study investigated changes in adult patient characteristics,management,and outcomes of sAE over a 20-year period in 40 ICUs in the greater Paris area.Methods In this retrospective observational study,admissions to 40 ICUs in the greater Paris area for sAE from January 1,1997,to December 31,2016 were analyzed.The primary outcome was the proportion of ICU admissions for sAE during 5-year periods.secondary outcomes were ICU and hospital mortality,and the use of mechanical ventilation and catecholamine.Multivariate analysis was performed to assess factors associated with ICU mortality.Results A total of 7049 admissions for sAE were recorded.For each 5-year period,the proportion decreased over time,with sAE accounting for 2.84%of total ICU admissions(n=2841)between 1997 and 2001,1.76%(n=1717)between 2002 and 2006,1.05%(n=965)between 2007 and 2011,and 1.05%(n=1526)between 2012 and 2016.The median age was 46 years(interquartile range[IQR]:32–59 years),55.41%were female,the median simplified Acute Physiology score II was 20(IQR:13–28),and 19.76%had mechanical ventilation.The use of mechanical ventilation remained infrequent throughout the 20-year period,whereas the use of catecholamine decreased.ICU and hospital mortality rates decreased.Factors associated with ICU mortality were renal replacement therapy,catecholamine,cardiac arrest,pneumothorax,acute respiratory distress syndrome,sepsis,and invasive mechanical ventilation(IMV).Non-survivors were older,had more severe symptoms,and were more likely to have received IMV.Conclusion ICU admission for sAE remains uncommon,and the proportion of cases decreased over time.Despite a slight increase in symptom severity during a 20-year period,ICU and hospital mortality decreased.Patients requiring IMV had a higher mortality rate.

关键词： Epidemiology Intensive care unit Mechanical ventilation severe asthma exacerbation

Perspectives in human brain plasticity sparked by glioma invasion:from intraoperative(re)mappings to neural reconfigurations

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Neural Regeneration Research 2024年第5期19卷 947-948页

作者： sam Ng Hugues Duffau Guillaume Herbet Department of Neurosurgery Gui de Chauliac HospitalMontpellier University Medical CenterMontpellierFrance Institute of Functional Genomics University of MontpellierCNRSINSERMMontpellierFrance Praxiling Laboratory UMR5267CNRSPaul Valéry-Montpellier 3 UniversityMontpellierFrance

Exploring the aptitude of the human brain to compensate functional consequences of a lesion damaging its structural architecture is a key challenge to improve patient care in various neurological diseases,to optimize neuroscientifically-informed strategies of postlesional rehabilitation,and ultimately to develop innovative neuro-regenerative therapies.The term‘plasticity’,initially referring to the intrinsic propensity of neurons to modulate their synaptic transmission in a learning situation,was progressively transposed to brain injury research and clinical neurosciences.Indeed,in the event of brain damage,adaptive mechanisms of compensation allow a partial reshaping of the structure and activities of the central nervous system,thus permitting to some extent the maintenance of brain functions.

关键词： plasticity figuration consequences

Preclinical and clinical evidence of the association of colibactinproducing Escherichia coli with anxiety and depression in colon cancer

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World Journal of Gastroenterology 2024年第21期30卷 2817-2826页

作者： Fabien Rondepierre Maëva Meynier Johan Gagniere Vincent Deneuvy Anissa Deneuvy Gwenaelle Roche Elodie Baudu Bruno Pereira Richard Bonnet Nicolas Barnich Frédéric Antonio Carvalho Denis Pezet Mathilde Bonnet Isabelle Jalenques service de Psychiatrie de l’Adulte A et Psychologie Médicale CHU Clermont-FerrandClermont-Ferrand 63000France M2isH UMR 1071INSERMUniversity of Clermont AuvergneINRAE USC 1382Clermont-Ferrand 63001France NeuroDol UMR 1107INSERMUniversity of Clermont AuvergneClermont-Ferrand 63001France Department of Digestive surgery CHU de Clermont-FerrandClermont-Ferrand 63001France Biostatistics Unit Department of Clinical Research and InnovationCHU Clermont-FerrandClermont-Ferrand 63000France Department of Bacteriology CHU de Clermont-FerrandClermont-Ferrand 63001France UniversitéClermont Auvergne INPCNRSClermont Auvergne Institut PascalClermont-Ferrand 63000France

BACKGROUND The association between the intestinal microbiota and psychiatric disorders is becoming increasingly apparent.The gut microbiota contributes to colorectal carcinogenesis(CRC),as demonstrated with colibactin-producing Escherichia coli(CoPEC).AIM To evaluate the association between CoPEC prevalence and anxiety-and depressive-like behaviors with both preclinical and clinical approaches.METHODs Patients followed after a CRC surgery and for whom the prevalence of CoPEC has been investigated underwent a psychiatric interview.Results were compared according to the CoPEC colonization.In parallel C57BL6/J wild type mice and mice with a CRC susceptibility were chronically infected with a CoPEC strain.Their behavior was assessed using the Elevated Plus Maze test,the Forced swimming Test and the Behavior recognition system PhenoTyper®.REsULTs In a limited cohort,all patients with CoPEC colonization presented with psychiatric disorders several years before cancer diagnosis,whereas only one patient(17%)without CoPEC did.This result was confirmed in C57BL6/J wildtype mice and in a CRC susceptibility mouse model(adenomatous polyposis colimultiple intestinal neoplasia/+).Mice exhibited a significant increase in anxiety-and depressive-like behaviors after chronic infection with a CoPEC strain.CONCLUsION This finding provides the first evidence that CoPEC infection can induce microbiota-gut-brain axis disturbances in addition to its procarcinogenic properties.

关键词： Colorectal cancer Colibactin Escherichia coli Colibactin-producing Escherichia coli Inflammation Anxiety Depression Behavior

systematic review of risk factors,prognosis,and management of colorectal signet-ring cell carcinoma

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2141-2158页

作者： Frederiek Nuytens Vincent Drubay Clarisse Eveno Florence Renaud Guillaume Piessen Department of Digestive and Oncological surgery University LilleClaude Huriez University HospitalLille 59000France Department of Digestive and Hepatobiliary/Pancreatic surgery AZ GroeningeKortrijk 8500Belgium Cambrai Hospital Center and sainte Marie Group of Hospitals of The Catholic Institute of LilleCambrai 59400France CNRs InsermUMR9020-U1277-CANTHER-CancerUniversity LilleCHU LilleLille 59000France

BACKGROUND Colorectal signet-ring cell carcinoma(CsRCC)is a rare clinical entity which accounts for approximately 1%of all colorectal cancers.Although multiple studies concerning this specific topic have been published in the past decades,the pathogenesis,associated risk factors,and potential implications on treatment are still poorly understood.Besides the low incidence,historically confusing histological criteria have resulted in confusing data.Nevertheless,the rising incidence of CsRCC along with relatively young age at presentation and associated dismal prognosis,highlight the actual interest to synthesize the known literature regarding CsRCC.AIM To provide an updated overview of risk factors,prognosis,and management of CsRCC.METHODs A literature search in the MEDLINE/PubMed database was conducted with the following search terms used:‘signet ring cell carcinoma’and‘colorectal’.studies in English language,published after January 1980,were included.studies included in the qualitative synthesis were evaluated for content concerning epidemiology,risk factors,and clinical,diagnostic,histological,and molecular features,as well as metastatic pattern and therapeutic management.If possible,presented data was extracted in order to present a more detailed overview of the literature.REsULTs In total,67 articles were included for qualitative analysis,of which 54 were eligible for detailed data extraction.CsRCC has a reported incidence between 0.1%-2.4%and frequently presents with advanced disease stage at the time of diagnosis.CsRCC is associated with an impaired overall survival(5-year Os:0%-46%)and a worse stagecorrected outcome compared to mucinous and not otherwise specified adenocarcinoma.The systematic use of exploratory laparoscopy to determine the presence of peritoneal metastases has been advised.surgery is the mainstay of treatment,although the rates of curative resection in CsRCC(21%-82%)are lower compared to those in other histological types.In case of peritoneal metastasis,cytoreductive surgery with hyperther

关键词： Colorectal cancer signet-ring cell histology Poorly cohesive cells systematic review Risk factors Prognosis Therapeutic management

The germline genetics of mild-to-moderate penetrance:An intriguing role of PRAME in multiple carcinogenesis

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Genes & Diseases 2024年第3期11卷 7-10页

作者： Diaddin Hamdan Van Tai Nguyen Justine Paris Christophe Leboeuf Morad El Bouchtaoui Marc Espie Anne Janin Geraldine Falgarone Melanie Di Benedetto Guithem Bousquet Universite de Paris Cite INSERMUMR_S942MASCOTParis F-75006France Hopital La Porte Verte Versailles F-78004France National Cancer Hospital Cancer Research and Clinical Trials CenterHaNoi100000VietNam AP-HP-Hopital saint Louis Centre de Maladies du SeinParisF-75010France Universite sorbonne Paris Nord Bobigny F-93000France AP-HP-Hopital Avicenne Unite de Medecine AmbulatoireBobigny F-93000France

Germline genetics of high penetrance such as BRCA genes,mutations might be sufficient for carcinogenesis,but this only explains fewer than 10%of cancers.We assume that most cancers are the result of germline mutations of low to moderate penetrance,combined with acquired mutations due to external carcinogenic stressors.With their accumulation over time,aging is associated with an increased risk of multiple cancer development in a given individual.For decades,germline genetics have been based on familial linkage studies enabling most high-penetrance genes to be identified.More recently,population-wide studies have led to the identification of considerable numbers of polymorphisms associated with cancer risk.However,most of them are of unknown functional value,thus limiting their translational application.

关键词： carcinogenesis BRCA linkage

In vivo astrocyte reprogramming following spinal cord injury

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Neural Regeneration Research 2024年第3期19卷 487-488页

作者： Yannick N.Gerber Florence E.Perrin MMDN University of MontpellierEPHEINSERMMontpellierFrance Institut Universitaire de France(IUF) ParisFrance

Harmful and helpful roles of astrocytes in spinal cord injury(sCI):sCI induce gradable sensory,motor and autonomic impairments that correlate with the lesion severity and the rostro-caudal location of the injury site.The absence of spontaneous axonal regeneration after injury results from neuron-intrinsic and neuron-extrinsic parameters.Indeed,not only adult neurons display limited capability to regrow axons but also the injury environment contains inhibitors to axonal regeneration and a lack of growth-promoting factors.Amongst other cell populations that respond to the lesion,reactive astrocytes were first considered as only detrimental to spontaneous axonal regeneration.Indeed,astrocytes.

关键词： injury impairment programming

Activity-dependent mechanisms of neuroprotection:promising avenues against dementia

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Neural Regeneration Research 2024年第7期19卷 1409-1410页

作者： Davide Tampellini U1195 inserm-UniversitéParis-saclay Le Kremlin-BicêtreFrance Institut Professeur Baulieu Le Kremlin-BicêtreFrance

The study of the brain and its complex functions is highly fascinating and,at the same time,extremely important.Indeed,furthering our understanding of the biology of neurons and synapses is a prerequisite to uncover the mechanisms involved in memory formation and the coordination of movement as well as their alterations occurring in several neurological disorders.

关键词： alterations mechanisms neurological