2025
Endothelial CLEC5A drives barrier dysfunction and vascular leakage responsible for lung injury in bacterial pneumonia and sepsis
Zhang T, Huang X, Goodwin J, Wen R, Liu Y, Yang Y, Zhang T, Zheng Y, Chen A, Hao P, Tong X, Yang N, Liu C. Endothelial CLEC5A drives barrier dysfunction and vascular leakage responsible for lung injury in bacterial pneumonia and sepsis. Science Advances 2025, 11: eadt7589. PMID: 40498836, PMCID: PMC12154197, DOI: 10.1126/sciadv.adt7589.Peer-Reviewed Original ResearchConceptsVascular leakagePuncture (CLP)-induced polymicrobial sepsisRegulating endothelial barrier functionCLP-challenged miceEndothelial barrier dysfunctionTrans-endothelial electrical resistanceEndothelial barrier functionLipopolysaccharide (LPS)-induced endotoxemiaVascular endothelial cellsPattern recognition receptorsSurvival benefitMultiorgan failurePolymicrobial sepsisTrans-endothelial migrationCecal ligationBacterial pneumoniaLung injuryBarrier dysfunctionVascular injurySingle-cell RNA sequencingDecreased mortalityInflammatory stormBacterial infectionsHeterogeneity of vascular endothelial cellsSepsisEarly detection of lung injury and matrix metalloproteinase activation in ARDS could improve diagnostic and therapeutic strategies?
Cho S, Jang S, Heerdt P, Thorn S, Sinusas A. Early detection of lung injury and matrix metalloproteinase activation in ARDS could improve diagnostic and therapeutic strategies? Expert Review Of Respiratory Medicine 2025, ahead-of-print: 1-3. PMID: 40462542, DOI: 10.1080/17476348.2025.2515993.Peer-Reviewed Original ResearchLower Respiratory Tract C. Albicans Induces Lung Injury in Mice and Associates With Lung Injury Endpoints in Humans
Tolman N, Choi W, Alder J, Tabary M, Qin S, Wang X, Zhang Y, Tu Y, Sharma L, Bon J, Robinson K, Snyder M, Dela Cruz C, Nguyen M, Morris A, Biswas P, Bain W, Kitsios G. Lower Respiratory Tract C. Albicans Induces Lung Injury in Mice and Associates With Lung Injury Endpoints in Humans. American Journal Of Respiratory And Critical Care Medicine 2025, 211: a2825-a2825. DOI: 10.1164/ajrccm.2025.211.abstracts.a2825.Peer-Reviewed Original ResearchLung injuryInjury endpointsProteomics, Redox Proteomics, and Metabolomics Profiling of Phosgene-induced Lung Injury in a Murine Model
Clair G, Day N, Daly J, Ushakumary M, Jordt S, Achanta S, Lin V. Proteomics, Redox Proteomics, and Metabolomics Profiling of Phosgene-induced Lung Injury in a Murine Model. American Journal Of Respiratory And Critical Care Medicine 2025, 211: a2448-a2448. DOI: 10.1164/ajrccm.2025.211.abstracts.a2448.Peer-Reviewed Original ResearchVEGF-D, unlike VEGF-A, improves vascular integrity in the lung and exerts a protective effect during acute lung injury
Yuan Y, Sharma L, Tang W, Yoon Y, Kirk S, Birukov K, Kaminski N. VEGF-D, unlike VEGF-A, improves vascular integrity in the lung and exerts a protective effect during acute lung injury. Physiology 2025, 40: 0734. DOI: 10.1152/physiol.2025.40.s1.0734.Peer-Reviewed Original ResearchAcute lung injuryAcute respiratory distress syndromeImmune cell infiltrationVEGF-DIdiopathic pulmonary fibrosisChronic obstructive pulmonary diseaseVEGF-AVascular integrityMicrovascular nicheAnti-inflammatory propertiesLung injuryCell infiltrationTNF-aLung tissueParacrine signalingPulmonary vascular integrityBarrier functionLung injury indexLevels of pro-inflammatory markersRespiratory distress syndromeTherapeutic targetTumor necrosis factor-aEffects of VEGF-ABronchoalveolar lavage fluidImproving vascular integrityYou know my NAMs
Ghosh S, Rothlin C. You know my NAMs. Immunity 2025, 58: 1179-1181. PMID: 40367920, DOI: 10.1016/j.immuni.2025.04.025.Peer-Reviewed Original ResearchIn vivo synergistic enhancement of MIF‐mediated inflammation in acute lung injury by the plant ortholog Arabidopsis MDL1
Spiller L, Zhang L, Gerra S, Stoppe C, Scheiermann P, Calandra T, Lolis E, Panstruga R, Bernhagen J, Hoffmann A. In vivo synergistic enhancement of MIF‐mediated inflammation in acute lung injury by the plant ortholog Arabidopsis MDL1. The FASEB Journal 2025, 39: e70489. PMID: 40134325, PMCID: PMC11937861, DOI: 10.1096/fj.202403301r.Peer-Reviewed Original ResearchConceptsAcute lung injuryLung injuryPulmonary infiltration of neutrophilsAdministered to C57BL/6 miceAcute respiratory distress syndromeParameters of lung injuryRespiratory distress syndromeInfiltration of neutrophilsPro-inflammatory cytokine genesPulmonary inflammationDistress syndromeC57BL/6 miceLeukocyte infiltrationArabidopsis thaliana proteinsInflammatory mediatorsHuman MIFMouse modelCytokine genesCombined treatmentFlow cytometryMonocytic cellsInflammationImmunofluorescence microscopyMIFInjuryEffects of Lung Expansion on Global and Regional Pulmonary Blood Volume in a Sheep Model of Acute Lung Injury
Zang M, Zeng C, Lagier D, Leng N, Grogg K, Motta-Ribeiro G, Laine A, Winkler T, Melo M. Effects of Lung Expansion on Global and Regional Pulmonary Blood Volume in a Sheep Model of Acute Lung Injury. Anesthesiology 2025, 142: 1071-1084. PMID: 39946655, PMCID: PMC12074886, DOI: 10.1097/aln.0000000000005412.Peer-Reviewed Original ResearchPositive end-expiratory pressurePulmonary blood volumeLung expansionBlood volumeLung injurySystemic endotoxemiaMechanical ventilationRespiratory-gated positron emission tomographyVentilator-induced lung injuryModel of acute lung injuryDistribution of blood volumeAcute lung injuryLow-volume mechanical ventilationLung injury modelEnd-expiratory pressureQuantify blood volumePulmonary capillary blood volumeLow blood volumeRegional blood volumePositron emission tomographyVascular blood volumeCapillary blood volumeLung blood volumeCapillary closureEnd-inspirationDamage sensing through TLR9 regulates inflammatory and antiviral responses during influenza infection
Kim J, Yuan Y, Agaronyan K, Zhao A, Wang V, Gau D, Toosi N, Gupta G, Essayas H, Kaminski A, McGovern J, Yu S, Woo S, Lee C, Gandhi S, Saber T, Saleh T, Hu B, Sun Y, Ishikawa G, Bain W, Evankovich J, Chen L, Yun H, Herzog E, Dela Cruz C, Ryu C, Sharma L. Damage sensing through TLR9 regulates inflammatory and antiviral responses during influenza infection. Mucosal Immunology 2025, 18: 537-548. PMID: 39884393, PMCID: PMC12205908, DOI: 10.1016/j.mucimm.2025.01.008.Peer-Reviewed Original ResearchToll-like receptor 9Anti-influenza immunityToll-like receptor 9 activationImpaired viral clearanceViral clearanceMyeloid cellsTissue injuryInflammatory responseInfluenza infectionPersistent inflammationLung injuryTissue damageToll-like receptor 9 deficiencyReceptor 9Toll-like receptor 9 signalingToll-like receptor 9 ligandInfection of immune cellsInfluenza-infected individualsPersistent lung injuryTLR9-/- miceInfected myeloid cellsInflammatory lung injurySensing tissue damageUnmethylated CpG DNA sequencesMitochondrial DNAThe fungal microbiota modulate neonatal oxygen-induced lung injury
Martin I, Silverberg M, Abdelgawad A, Tanaka K, Halloran B, Nicola T, Myers E, Desai J, White C, Karabayir I, Akbilgic O, Tipton L, Gentle S, Ambalavanan N, Peters B, Vu L, Jain V, Lal C, Cormier S, Pierre J, Jilling T, Talati A, Willis K. The fungal microbiota modulate neonatal oxygen-induced lung injury. Microbiome 2025, 13: 24. PMID: 39871397, PMCID: PMC11773857, DOI: 10.1186/s40168-025-02032-x.Peer-Reviewed Original ResearchConceptsBronchopulmonary dysplasiaLung injury severityLung injuryDevelopment of bronchopulmonary dysplasiaSeverity of lung injuryAugmented lung injuryMorbidities of prematurityVery preterm infantsOxygen-induced lung injuryChronic lung diseaseIntestinal microbiomeMicrobiome of infantsPotential therapeutic strategyPreterm infantsNeonatal microbiomePremature infantsPremature neonatesInjury severityMurine modelNeonatal healthLung diseaseMouse modelTherapeutic strategiesLoss of function approachesFungal communities
2024
Factors Associated with Pediatric Drowning-Associated Lung Injury
Shenoi R, Crowe J, Dorfman S, Bergmann K, Mistry R, Hariharan S, Tavarez M, Wai S, Jones J, Langhan M, Ward C, McCallin T, Sethuraman U, Shah N, Mendez D, Wolpert K, Santos-Malave C, Ruttan T, Quayle K, Okada P, Bubolz B, Buscher J, McKee R, Mangold K, Wendt W, Thompson A, Hom J, Brayer A, Blackstone M, Brennan C, Russell W, Agarwal M, Khanna K, Louie J, Sheridan D, Camp E, Committee P. Factors Associated with Pediatric Drowning-Associated Lung Injury. The Journal Of Pediatrics 2024, 279: 114459. PMID: 39736377, DOI: 10.1016/j.jpeds.2024.114459.Peer-Reviewed Original ResearchConceptsRisk factorsEmergency departmentCross-sectional study of childrenEmergency medical servicesPediatric emergency departmentCross-sectional studyAbnormal respiratory rateLung injuryPrehospital dataSpine injuriesAbnormal chest radiographic findingsED presentationsDrowning deathsMedical servicesPatient dispositionStudy of childrenChest radiographic findingsED courseAbnormal heart rateLogistic regressionShort-term outcomesAbnormal lung auscultationChest radiograph reportsRadiographic reportsOlder ageContext‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuries
Feng J, Kim J, Wang V, Chang D, Liu H, Bain W, Robinson K, Jie Z, Kotenko S, Dela Cruz C, Sharma L. Context‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuries. Physiological Reports 2024, 12: e70104. PMID: 39455422, PMCID: PMC11511623, DOI: 10.14814/phy2.70104.Peer-Reviewed Original ResearchConceptsIII interferon signalingType III interferon signalingLung injuryInterferon SignalingBleomycin-induced weight lossInflammatory responseModel of lung injuryBacterial pathogen Pseudomonas aeruginosaAcute lung injuryPathogen Pseudomonas aeruginosaBacterial endotoxin LPSChemotherapeutic agent bleomycinType III interferonsAnti-inflammatory roleIncreased inflammatory signalingLate time pointsBleomycin modelKnockout miceEndotoxin LPSIII interferonsAntiviral cytokinesDay 3Inflammatory signalingEarly injuryImpaired recoveryPathophysiology and Prevention of Manual-Ventilation-Induced Lung Injury (MVILI)
White L, Conrad S, Alexander J. Pathophysiology and Prevention of Manual-Ventilation-Induced Lung Injury (MVILI). Pathophysiology 2024, 31: 583-595. PMID: 39449524, PMCID: PMC11503381, DOI: 10.3390/pathophysiology31040042.Peer-Reviewed Original ResearchManual ventilationLung injuryManual hyperventilationOperator-dependent skillsShort-term ventilationMechanism of injuryManikin-based studyBag valve maskAmerican Heart AssociationEuropean Resuscitation CouncilHyperventilated patientsMechanical ventilationHemodynamic alterationsHealthcare providersHeart AssociationPatient populationResuscitation effortsGastric regurgitationResuscitation CouncilCardiopulmonary resuscitationVentilation parametersPatientsInjury processAcute barotraumaVentilationProtective mechanical ventilation in critically ill patients after surgery
Zorrilla-Vaca A, Arevalo J, Grant M. Protective mechanical ventilation in critically ill patients after surgery. Current Opinion In Critical Care 2024, 30: 679-683. PMID: 39503212, DOI: 10.1097/mcc.0000000000001215.Peer-Reviewed Original ResearchIntensive care unitVentilator-induced lung injuryLung protective strategyCritically ill patientsMechanical ventilationCare unitLung injurySurgical patientsFast-track extubation protocolOpen-lung ventilation strategyIll patientsRisk of ventilator-induced lung injuryHigh-flow nasal cannulaHigh-risk surgical patientsOpen lung ventilationOperating roomNoninvasive ventilation supportProtective mechanical ventilationPositive-end expiratory pressureAcute lung injuryMechanically Ventilated PatientsStandard of careThoracic surgeryNasal cannulaRetrospective studyChitinase 3-like-1 Inhibits Innate Antitumor and Tissue Remodeling Immune Responses by Regulating CD47-SIRPα- and CD24-Siglec10-Mediated Phagocytosis.
Ma B, Kamle S, Sadanaga T, Lee C, Lee J, Yee D, Zhu Z, Silverman E, DeMeo D, Choi A, Lee C, Elias J. Chitinase 3-like-1 Inhibits Innate Antitumor and Tissue Remodeling Immune Responses by Regulating CD47-SIRPα- and CD24-Siglec10-Mediated Phagocytosis. The Journal Of Immunology 2024, 213: 1279-1291. PMID: 39291933, DOI: 10.4049/jimmunol.2400035.Peer-Reviewed Original ResearchImmune checkpoint moleculesChronic obstructive pulmonary diseaseInhibit adaptive immune responsesAdaptive immune responsesInnate immune responseImmune responseInhibition of innate immune responsesInhibits T cell costimulationGeneration of adaptive immune responsesMacrophage phagocytosisInhibit innate immune responsesChitinase 3-like 1T cell costimulationEpithelial cell deathObstructive pulmonary diseaseCheckpoint moleculesPoor prognosisLung injuryInhibit macrophagesPulmonary diseaseCHI3L1Inflammation pathwaysCancerSHP-2 phosphataseCell deathCasRx-based Wnt activation promotes alveolar regeneration while ameliorating pulmonary fibrosis in a mouse model of lung injury
Shen S, Wang P, Wu P, Huang P, Chi T, Xu W, Xi Y. CasRx-based Wnt activation promotes alveolar regeneration while ameliorating pulmonary fibrosis in a mouse model of lung injury. Molecular Therapy 2024, 32: 3974-3989. PMID: 39245939, PMCID: PMC11573616, DOI: 10.1016/j.ymthe.2024.09.008.Peer-Reviewed Original ResearchWnt/b-catenin signalingStem cell activityLung epitheliumAlveolar regenerationPulmonary fibrosisLung fibrosisWnt signalingCell activationMouse models of lung injuryModel of lung injuryWnt activityAlveolar type II cell proliferationBleomycin-induced injuryAmeliorated pulmonary fibrosisActivation of Wnt signalingType II cell proliferationInhibit lung fibrosisRegenerative medicineAnti-fibrotic effectsTreating pulmonary fibrosisActivated Wnt signalingLung injuryMouse modelFibrosisWnt/b-cateninAdjunctive N-Acetylcysteine and Lung Function in Pulmonary Tuberculosis.
Wallis R, Sabi I, Lalashowi J, Bakuli A, Mapamba D, Olomi W, Siyame E, Ngaraguza B, Chimbe O, Charalambous S, Rachow A, Ivanova O, Zurba L, Myombe B, Kunambi R, Hoelscher M, Ntinginya N, Churchyard G. Adjunctive N-Acetylcysteine and Lung Function in Pulmonary Tuberculosis. NEJM Evidence 2024, 3: evidoa2300332. PMID: 39189858, DOI: 10.1056/evidoa2300332.Peer-Reviewed Original ResearchConceptsWhole blood glutathione levelsLung functionN-acetylcysteinePulmonary tuberculosisCulture conversionSecondary outcomesGlutathione levelsEffect of N-acetylcysteineTuberculosis treatment outcomesOutcome of lung functionOral N-acetylcysteineRecovery of lung functionAdjunctive N-acetylcysteineAssociated with improved recoveryN-acetylcysteine treatmentPermanent lung injuryFar-advanced tuberculosisSputum cultureStandard therapyNAC administrationAdverse eventsLung injuryGlobal health concernCohort studyClinical evaluationMechanical ventilation guided by driving pressure optimizes local pulmonary biomechanics in an ovine model
Lagier D, Zeng C, Kaczka D, Zhu M, Grogg K, Gerard S, Reinhardt J, Ribeiro G, Rashid A, Winkler T, Vidal Melo M. Mechanical ventilation guided by driving pressure optimizes local pulmonary biomechanics in an ovine model. Science Translational Medicine 2024, 16: eado1097. PMID: 39141699, DOI: 10.1126/scitranslmed.ado1097.Peer-Reviewed Original ResearchConceptsPositive end-expiratory pressureMechanical ventilationFour-dimensional computed tomographyParenchymal strainsVentilator-induced lung injuryAcute respiratory distress syndromeRespiratory system driving pressureManagement of mechanical ventilationPositive end-expiratory pressure valuesRespiratory distress syndromeTidal overdistensionEnd-expiratory pressureAssociated with mortalityPulmonary complicationsLung biomechanicsLung massDistress syndromeClinical outcomesLung injuryComputed tomographyClinical managementGeneral anesthesiaLung collapseDriving pressureLungRecruited atypical Ly6G+ macrophages license alveolar regeneration after lung injury
Ruscitti C, Abinet J, Maréchal P, Meunier M, de Meeûs C, Vanneste D, Janssen P, Dourcy M, Thiry M, Bureau F, Schneider C, Machiels B, Hidalgo A, Ginhoux F, Dewals B, Guiot J, Schleich F, Garigliany M, Bellahcène A, Radermecker C, Marichal T. Recruited atypical Ly6G+ macrophages license alveolar regeneration after lung injury. Science Immunology 2024, 9: eado1227-eado1227. PMID: 39093958, PMCID: PMC7616420, DOI: 10.1126/sciimmunol.ado1227.Peer-Reviewed Original ResearchConceptsLung injuryAlveolar regenerationGranulocyte-macrophage colony-stimulating factorColony-stimulating factorType 2 epithelial cellsAlveolar type 2 epithelial cellsPopulation of macrophagesModels of injuryImmune cellsSuspected pneumoniaA virusAlveolar damageEpithelial regenerationInterleukin-4Lung damageMacrophage subsetsReceptor signalingLungPerilesional areaRepair responseMacrophagesTherapeutic targetInjuryCellsAirborne pathogensLung Epithelium Releases Growth Differentiation Factor 15 in Response to Pathogen-mediated Injury
Shah F, Bahudhanapati H, Jiang M, Tabary M, van der Geest R, Tolman N, Kochin M, Xiong Z, Al-Yousif N, Sayed K, Benos P, Raffensperger K, Evankovich J, Neal M, Snyder M, Eickelberg O, Ray P, Dela Cruz C, Bon J, McVerry B, Straub A, Jurczak M, Suber T, Zhang Y, Chen K, Kitsios G, Lee J, Alder J, Bain W. Lung Epithelium Releases Growth Differentiation Factor 15 in Response to Pathogen-mediated Injury. American Journal Of Respiratory Cell And Molecular Biology 2024, 70: 379-391. PMID: 38301257, PMCID: PMC11109583, DOI: 10.1165/rcmb.2023-0429oc.Peer-Reviewed Original ResearchConceptsLung injuryPlasma levelsLung epitheliumGDF15 levelsAssociated with plasma levelsAcute respiratory distress syndromeGrowth differentiation factor 15Acute respiratory failureRespiratory distress syndromeWild-type miceLung cytokine levelsHuman lung epitheliumAcute lung injuryDifferentiation factor 15Levels of GDF15Critically ill humansPrognostic of mortalitySARS-CoV-2 infectionCirculating GDF15 levelsRespiratory tract levelRespiratory failureDistress syndromeCytokine profileStress cytokinesCytokine levels
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