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Compartmentalization of the inflammatory response during bacterial sepsis and severe COVID-19

Journal of Intensive Medicine 2024年第3期4卷 326-340页

作者： Jean-Marc Cavaillon Benjamin G.Chousterman Tomasz Skirecki Institut Pasteur ParisFrance department of Anesthesia and Critical Care Lariboisière University HospitalDMU ParabolAPHP NordParisFrance inserm u942 University of ParisParisFrance department of Translational Immunology and Experimental Intensive Care Centre of Postgraduate Medical EducationWarsawPoland

Acute infections cause local and systemic disorders which can lead in the most severe forms to multi-organ failure and eventually to death. The host response to infection encompasses a large spectrum of reactions with a concomitant activation of the so-called inflammatory response aimed at fighting the infectious agent and removing damaged tissues or cells, and the anti-inflammatory response aimed at controlling inflammation and initiating the healing process. Fine-tuning at the local and systemic levels is key to preventing local and remote injury due to immune system activation. Thus, during bacterial sepsis and Coronavirus disease 2019 (COVID-19), concomitant systemic and compartmentalized pro-inflammatory and compensatory anti-inflammatory responses are occurring. Immune cells (e.g., macrophages, neutrophils, natural killer cells, and T-lymphocytes), as well as endothelial cells, differ from one compartment to another and contribute to specific organ responses to sterile and microbial insult. Furthermore, tissue-specific microbiota influences the local and systemic response. A better understanding of the tissue-specific immune status, the organ immunity crosstalk, and the role of specific mediators during sepsis and COVID-19 can foster the development of more accurate biomarkers for better diagnosis and prognosis and help to define appropriate host-targeted treatments and vaccines in the context of precision medicine.

关键词： Acute respiratory distress syndrome Bone marrow Cytokines Lungs Mucosa Vaccines

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Cardiac differentiation is modulated by anti-apoptotic signals in murine embryonic stem cells

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World Journal of Stem Cells 2024年第5期16卷 551-559页

作者： Amani Yehya Joseph Azar Mohamad Al-Fares Helene Boeuf Wassim Abou-Kheir Dana Zeineddine Ola Hadadeh department of Anatomy Cell Biology and Physiological SciencesAmerican University of BeirutBeirut 1107-2020Lebanon inserm BiotisU1026University BordeauxBordeaux F-33000France Rammal Rammal Lab Physio-Toxicity Environmental TeamFaculty of SciencesLebanese UniversityNabatieh 0000Lebanon

BACKGROuND Embryonic stem cells(ESCs)serve as a crucial ex vivo model,representing epiblast cells derived from the inner cell mass of blastocyst-stage *** exhibit a unique combination of self-renewal potency,unlimited proliferation,and *** latter is evident by the ability of the isolated cells to differ-entiate spontaneously into multiple cell lineages,representing the three primary embryonic germ *** regulatory networks guide ESCs,directing their self-renewal and lineage-specific ***,or programmed cell death,emerges as a key event involved in sculpting and forming various organs and structures ensuring proper embryonic ***-ever,the molecular mechanisms underlying the dynamic interplay between diffe-rentiation and apoptosis remain poorly *** To investigate the regulatory impact of apoptosis on the early differentiation of ESCs into cardiac cells,using mouse ESC(mESC)models-mESC-B-cell lym-phoma 2(BCL-2),mESC-PIM-2,and mESC-metallothionein-1(MET-1)-which overexpress the anti-apoptotic genes Bcl-2,Pim-2,and Met-1,*** mESC-T2(wild-type),mESC-BCL-2,mESC-PIM-2,and mESC-MET-1 have been used to assess the effect of potentiated apoptotic signals on cardiac *** hanging drop method was adopted to generate embryoid bodies(EBs)and induce terminal differentiation of *** size of the generated EBs was measured in each condition compared to the wild *** the functional level,the percentage of cardiac differentiation was measured by calculating the number of beating cardiomyocytes in the manipulated mESCs compared to the *** the molecular level,quantitative reverse transcription-polymerase chain reaction was used to assess the mRNA expression of three cardiac markers:Troponin T,GATA4,and ***,troponin T protein expression was evaluated through immunofluorescence and western blot *** Our findings showed that the upregulation of Bcl-

关键词： Mouse embryonic stem cells Self-renewal Apoptosis Cardiac differentiation B-cell lymphoma 2 PIM-2 Metallothionein-1

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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 *** 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 *** 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 *** primary outcome was the proportion of ICu admissions for SAE during 5-year *** outcomes were ICu and hospital mortality,and the use of mechanical ventilation and *** analysis was performed to assess factors associated with ICu *** A total of 7049 admissions for SAE were *** 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 *** 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 *** use of mechanical ventilation remained infrequent throughout the 20-year period,whereas the use of catecholamine *** and hospital mortality rates *** 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 *** ICu admission for SAE remains uncommon,and the proportion of cases decreased over *** a slight increase in symptom severity during a 20-year period,ICu and hospital mortality *** requirin

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

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Prevention of ventilator-associated pneumonia with inhaled antibiotics

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World Journal of Emergency Medicine 2024年第3期15卷 165-168页

作者： Stephan Ehrmann Jie Li Intensive Care Medicine INSERM CIC 1415CRICS-TriggerSep FCRIN research networkUniversity Hospital Center in ToursTours 37044France Respiratory pathology Research Center National Institute of Health and Medical ResearchTours 37000France department of Cardiopulmonary Sciences Division of Respiratory CareRush UniversityChicago 60612USA

The direct delivery of inhaled antibiotics to the respiratory tract has been a subject of enduring interest among medical practitioners and researchers due to the associated favorable *** interest has been particularly pronounced in the context of critically illpatients,wherehealthcare-associatedpulmonary infections represent a significant challenge,driving continued exploration of inhaled antibiotics for intubated *** high-level evidence has shown a very promising application in the field of ventilator-associated pneumonia (VAP) prevention.^([1]).

关键词： pneumonia ventilator respiratory

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New insights into astrocyte diversity from the lens of transcriptional regulation and their implications for neurodegenerative disease treatments

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Neural Regeneration Research 2024年第11期19卷 2335-2336页

作者： Ibrahim Olabayode Saliu Guoyan Zhao department of Genetics Washington University School of MedicineSt.LouisMOUSA department of Neurology Department of Pathology and ImmunologyWashington University School of MedicineSt.LouisMOUSA

Astrocytes are a major glial cell type in the central nervous system,and they provide trophic and metabolic support to *** addition to these roles,they play crucial roles in modulating synaptic functions,development,and pruning(Brandebura et al.,2023).Astrocytes become reactive(activated)by undergoing morphological,molecular,and functional alterations in response to neuropathology such as in injuries and neurodegenerative diseases(NDs)(Escartin et al.,2021).

关键词： degenerative injuries

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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 *** 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 *** the low incidence,historically confusing histological criteria have resulted in confusing ***,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 *** To provide an updated overview of risk factors,prognosis,and management of *** 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 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 *** possible,presented data was extracted in order to present a more detailed overview of the *** In total,67 articles were included for qualitative analysis,of which 54 were eligible for detailed data *** has a reported incidence between 0.1%-2.4%and frequently presents with advanced disease stage at the time of *** is associated with an impaired overall survival(5-year OS:0%-46%)and a worse stagecorrected outcome compared to mucinous and not otherwise specified *** systematic use of exploratory laparoscopy to determine the presence of peritoneal metastases has been *** is the mainstay of treatment,although the rates of curative resection in CSRCC(21%-82%)are lower compared to those in other histological *** case of peritoneal

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

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Adult neurogenesis:a real hope or a delusion?

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Neural Regeneration Research 2024年第1期19卷 6-15页

作者： Ghulam Hussain Rabia Akram Haseeb Anwar Faiqa Sajid Tehreem Iman Hyung Soo Han Chand Raza Jose-Luis Gonzalez De Aguilar Neurochemicalbiology and Genetics Laboratory(NGL) Department of PhysiologyFaculty of Life SciencesGovernment College UniversityFaisalabadPunjabPakistan department of Physiology School of MedicineClinical Omics InstituteKyungpook National UniversityDaeguKorea department of Zoology Faculty of Chemistry and Life SciencesGovernment College UniversityLahorePakistan inserm U1118Mécanismes Centraux et Péripheriques de la NeurodégénérescenceStrasbourgFranceUniversitéde StrasbourgStrasbourgFrance

Adult neurogenesis,the process of creating new neurons,involves the coordinated division,migration,and differentiation of neural stem *** process is restricted to neurogenic niches located in two distinct areas of the brain:the subgranular zone of the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricle,where new neurons are generated and then migrate to the olfactory *** has been thought to occur only during the embryonic and early postnatal stages and to decline with age due to a continuous depletion of neural stem ***,recent years have seen tremendous progress in our understanding of adult brain neurogenesis,bridging the knowledge gap between embryonic and adult ***,we discuss the current status of adult brain neurogenesis in light of what we know about neural stem *** this notion,we talk about the importance of intra cellular signaling molecules in mobilizing endogenous neural stem cell prolife *** on the current understanding,we can declare that these molecules play a role in targeting neurogenesis in the mature ***,to achieve this goal,we need to avoid the undesired proliferation of neural stem cells by controlling the necessary checkpoints,which can lead to tumorigenesis and prove to be a curse instead of a blessing or hope.

关键词： adult neurogenesis aging brain-derived neurotrophic factor dentate gyrus hippocampus neural stem cells neurotrophic factors Notch oxidative stress stem cells subgranular zone

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pathology of hepatic iron overload

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World Journal of Gastroenterology 2007年第35期13卷 4755-4760页

作者： Yves Deugnier Bruno Turlin Liver unit and CIC inserm 0203 Pontchaillou University HospitalRennes 35033France department of pathology and inserm u 522 Pontchaillou University HospitalRennes 35033France

Although progress in imaging and genetics allow for a noninvasive diagnosis of most cases of genetic iron overload, liver pathology remains often useful （1） to assess prognosis by grading fibrosis and seeking for associated lesions and （2） to guide the etiological diagnosis, especially when no molecular marker is available. Then, the type of liver siderosis （parenchymal, mesenchymal or mixed） and its distribution throughout the Iobule and the liver are useful means for suggesting its etiology： HLA-linked hemochromatosis gene （HFE） hemochromatosis or other rare genetic hemochromatosis, nonhemochromatotic genetic iron overload （ferroportin disease, aceruloplasminemia）, or iron overload secondary to excessive iron supply, inflammatory syndrome, noncirrhotic chronic liver diseases including dysmetabolic iron overload syndrome, cirrhosis, and blood disorders.

关键词： Iron Liver Biopsy Hemochromatosis Ferroportin HLA-linked hemochromatosis gene Hepcidin Metabolic syndrome

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Decoding the nexus:branched-chain amino acids and their connection with sleep,circadian rhythms,and cardiometabolic health

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Neural Regeneration Research 2025年第5期20卷 1350-1363页

作者： Hui Li Laurent Seugnet department of Neurology Xijing HospitalXi’anShaanxi ProvinceChina Centre de Recherche en Neurosciences de Lyon Integrated Physiology of the Brain Arousal Systems(WAKING)UniversitéClaude Bernard Lyon 1INSERM U1028CNRS UMR 5292BronFrance

The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular *** the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other *** these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral *** the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of ***-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared *** their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy ***,they impact GABAergic neurons and the excitation/inhibition *** rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock *** mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully *** sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory *** mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these *** this context,the Drosophila model,though underutilized,holds promise in shedding new light on these *** findings indicate its po

关键词： branched-chain amino acids cardiovascular health circadian clock drosophila insulin metabolism sleep γ-aminobutyric acid

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ATM Activation is Key in Vasculogenic Mimicry Formation by Glioma Stem-like Cells

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Biomedical and Environmental Sciences 2024年第8期37卷 834-849页

作者： Jing Xie Jiaxin Tang Yuan Li Xue Kong Wei Wang Haibo Wu department of pathology the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230036AnhuiChina Intelligent pathology Institute Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230036AnhuiChina

Objective Vasculogenic mimicry(VM)is a novel vasculogenic process integral to glioma stem cells(GSCs)in glioblastoma(GBM).However,the relationship between VM and ataxia-telangiectasia mutated(ATM)serine/threonine kinase activation,which confers chemoradiotherapy resistance,remains *** We investigated VM formation and phosphorylated ATM(pATM)levels by CD31/GFAPperiodic acid-Schiff dual staining and immunohistochemical staining in 145 GBM *** stem-like cells(GSLCs)derived from the formatted spheres of u87 and u251 cell lines and their pATM level and VM formation ability were examined using western blot and three-dimensional *** the examination of the function of pATM in VM formation by GSLCs,ATM knockdown by shRNAs and deactivated via ATM phosphorylation inhibitor Ku55933 were *** VM and high pATM expression occurred in 38.5% and 41.8% of tumors,respectively,and were significantly associated with reduced progression-free and overall *** with VM-positive GBMs exhibited higher pATM levels(r_(s)=0.425,P=0.01).The multivariate analysis established VM as an independent negative prognostic factor(P=0.002).Furthermore,GSLCs expressed high levels of pATM and formed vascular-like networks in *** inactivation or knockdown hindered VM-like network formation concomitant with the downregulation of pVEGFR-2,VE-cadherin,and laminin *** VM may predict a poor GBM prognosis and is associated with pATM *** propose that pATM promotes VM through extracellular matrix modulation and VE-Cadherin/pVEGFR-2 activation,thereby highlighting ATM activation as a potential target for enhancing anti-angiogenesis therapies for GBM.

关键词： Glioblastoma Vasculogenic mimicry Ataxia-telangiectasia mutated(ATM) Glioma stem-like cell

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