2025
Secretory leukocyte protease inhibitor influences periarticular joint inflammation in Borrelia burgdorferi-infected mice
Yu Q, Tang X, Hart T, Homer R, Belperron A, Bockenstedt L, Ring A, Nakamura A, Fikrig E. Secretory leukocyte protease inhibitor influences periarticular joint inflammation in Borrelia burgdorferi-infected mice. ELife 2025, 14: rp104913. PMID: 40392222, PMCID: PMC12092001, DOI: 10.7554/elife.104913.Peer-Reviewed Original ResearchConceptsSecretory leukocyte protease inhibitorJoint inflammationC57BL/6 miceHigher infection loadTick-borne infectionsWild-type control miceClinical manifestations of infectionDevelopment of Lyme arthritisElevated serum levelsExcessive pro-inflammatory responsesManifestations of infectionProtease inhibitorsPro-inflammatory responseAnkle joint tissueInfection loadPromote tissue repairAnti-inflammatory effectsSerum levelsPeriarticular swellingClinical manifestationsControl miceTibiotarsal jointMMP-8Lyme diseaseIL-6Optimism moderates the relationship between inflammatory polygenic risk and major depressive disorder in U.S. Military veterans
Fischer I, Overstreet C, Cabrera-Mendoza B, Qiu D, Krystal J, Polimanti R, Gelernter J, Pietrzak R. Optimism moderates the relationship between inflammatory polygenic risk and major depressive disorder in U.S. Military veterans. The World Journal Of Biological Psychiatry 2025, 26: 189-198. PMID: 40343713, DOI: 10.1080/15622975.2025.2498352.Peer-Reviewed Original ResearchConceptsMajor depressive disorderU.S. military veteransPolygenic risk scoresDepressive disorderMilitary veteransMajor depressive disorder riskPsychosocial moderatorsMDD screeningLow optimismPolygenic riskHigher optimismNationally representative sampleTrauma burdenPredisposition to inflammationStandard deviation increaseUK BiobankGenetic riskPathway-based analysisVeteransIncreased oddsRepresentative sampleRisk scoreMedical conditionsInflammatory biomarkersChronic inflammationIdentification of Distinct Biological Groups of Patients With Cryptogenic NORSE via Inflammatory Profiling
Guillemaud M, Chavez M, Kobeissy F, Vezzani A, Jimenez A, Basha M, Batra A, Demeret S, Eka O, Eschbach K, Foreman B, Gaspard N, Gerard E, Gofton T, Haider H, Hantus S, Howe C, Jongeling A, Kalkach-Aparicio M, Kandula P, Kazazian K, Kim M, Lai Y, Marois C, Mellor A, Mohamed W, Morales M, Pimentel C, Ramirez A, Steriade C, Struck A, Taraschenko O, Torcida Sedano N, Wainwright M, Yoo J, Wang K, Navarro V, Hirsch L, Hanin A. Identification of Distinct Biological Groups of Patients With Cryptogenic NORSE via Inflammatory Profiling. Neurology Neuroimmunology & Neuroinflammation 2025, 12: e200403. PMID: 40334176, PMCID: PMC12063244, DOI: 10.1212/nxi.0000000000200403.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCytokinesDrug Resistant EpilepsyFemaleHumansInflammationMaleMiddle AgedStatus EpilepticusYoung AdultConceptsCryptogenic new-onset refractory status epilepticusClusters of patientsCytokine profileInflammatory markersNew-onset refractory status epilepticusTarget specific inflammatory pathwaysInitiation of immunotherapyResponse to immunotherapyRefractory status epilepticusPersonalized therapeutic strategiesGroup of patientsStatistically significant elevationTime of administrationProtein pathway analysisInflammatory subgroupsMultiple immunotherapiesDifferential treatment responseRefractory SEC patientsImprove patient outcomesAutoimmune mechanismsImmune dysregulationClinical featuresCytokine levelsAutoimmune processMyeloperoxidase impacts vascular function by altering perivascular adipocytes’ secretome and phenotype in obesity
Hof A, Landerer M, Peitsmeyer P, Herzog R, Alber J, Ahdab M, Nettersheim F, Mehrkens D, Geißen S, Braumann S, Guthoff H, von Stein P, Nemade H, Picard F, Braun R, Hoyer F, Brüning J, Pfeifer A, Hildebrand S, Winkels H, Baldus S, Adam M, Schäkel J, Mollenhauer M. Myeloperoxidase impacts vascular function by altering perivascular adipocytes’ secretome and phenotype in obesity. Cell Reports Medicine 2025, 6: 102087. PMID: 40252642, PMCID: PMC12147848, DOI: 10.1016/j.xcrm.2025.102087.Peer-Reviewed Original ResearchConceptsPerivascular adipose tissueVascular functionEndothelial functionObesity-related cardiovascular diseaseImmune cell frequenciesAdipose tissuePerivascular adipose tissue inflammationReduced arterial stiffnessInflammatory cytokine releaseHuman white adipocytesInfluence vascular functionObese patientsAdipocyte marker expressionMyeloid cellsCardiovascular morbidityImmune cellsCytokine releaseEndothelial dysfunctionIncreased inflammationAdipocyte secretomeCell frequencyMarker expressionMPO levelsConsumption in vivoNitrotyrosine formationThe inflammatory and genetic mechanisms underlying the cumulative effect of co-occurring pain conditions on depression
Jiang R, Geha P, Rosenblatt M, Wang Y, Fu Z, Foster M, Dai W, Calhoun V, Sui J, Spann M, Scheinost D. The inflammatory and genetic mechanisms underlying the cumulative effect of co-occurring pain conditions on depression. Science Advances 2025, 11: eadt1083. PMID: 40173244, PMCID: PMC11964001, DOI: 10.1126/sciadv.adt1083.Peer-Reviewed Original ResearchConceptsDepression riskChronic pain conditionsPain conditionsPrevalence of comorbid depressionPain scoresUK Biobank participantsPain-free individualsComposite pain scoresHigh-risk individualsPain screeningMendelian randomizationBiobank participantsPain sitesDepression incidenceComorbid depressionIncreased riskBody sitesDepressionC-reactive proteinPainCausal inferenceFollow-upScoresRiskInflammatory markersIn 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 microscopyMIFInjuryImpact of body weight on IVF: pathophysiology, outcomes, and clinical considerations
Sekula N, Basar M, Pal L. Impact of body weight on IVF: pathophysiology, outcomes, and clinical considerations. Current Opinion In Obstetrics & Gynecology 2025, 37: 130-140. PMID: 40172001, DOI: 10.1097/gco.0000000000001023.Peer-Reviewed Original ResearchConceptsIVF outcomesExcess weightIVF cycle outcomesIVF treatment cyclesLive birth rateCycle outcomesImpact of excess weightAssociation of excess weightImpact of body weightClinical pregnancyExcess body weightBirth rateBody weightIVFAdverse implicationsUterine receptivityDetrimental implicationsWeight excessTreatment cyclesInflammatory processInsulin resistancePathogenic mechanismsClinical considerationsOutcomesDNA repairAdding insult to injury: the spectrum of tubulointerstitial responses in acute kidney injury
Baker M, Cantley L. Adding insult to injury: the spectrum of tubulointerstitial responses in acute kidney injury. Journal Of Clinical Investigation 2025, 135: e188358. PMID: 40091836, PMCID: PMC11910233, DOI: 10.1172/jci188358.Peer-Reviewed Original ResearchConceptsAcute kidney injuryTubular epithelial cellsKidney injuryTubular cellsCases of acute kidney injuryImmune-mediated processPersistence of inflammationBiphasic immune responseChronic kidney diseaseCell deathTubular cell injuryLymphocyte subsetsTubular repairCell cycle arrestOutflow obstructionTEC differentiationPreclinical findingsLymphocytic infiltrationProinflammatory macrophagesKidney diseaseModulate inflammationImmune responseActivated macrophagesMetabolic reprogrammingTubular castsp53 enhances DNA repair and suppresses cytoplasmic chromatin fragments and inflammation in senescent cells
Miller K, Li B, Pierce-Hoffman H, Patel S, Lei X, Rajesh A, Teneche M, Havas A, Gandhi A, Macip C, Lyu J, Victorelli S, Woo S, Lagnado A, LaPorta M, Liu T, Dasgupta N, Li S, Davis A, Korotkov A, Hultenius E, Gao Z, Altman Y, Porritt R, Garcia G, Mogler C, Seluanov A, Gorbunova V, Kaech S, Tian X, Dou Z, Chen C, Passos J, Adams P. p53 enhances DNA repair and suppresses cytoplasmic chromatin fragments and inflammation in senescent cells. Nature Communications 2025, 16: 2229. PMID: 40044657, PMCID: PMC11882782, DOI: 10.1038/s41467-025-57229-3.Peer-Reviewed Original ResearchConceptsCytoplasmic chromatin fragmentsDNA repairGenome integrityChromatin fragmentsNuclear DNA damage signalsGenomic instabilitySenescent cellsActivation of p53Controlling DNA repairATM-dependent mannerDNA damage signalingSignatures of agingAge-associated accumulationActivate p53P53 activationHallmarks of agingDamage signalingAge-associated diseasesSignaling circuitsP53Molecular circuitsEnhanced DNA repairGenomePharmacological inhibitionAge-associated inflammationMulti-Scale Multi-Cell Computational Model of Inflammation-Mediated Aortic Remodeling in Hypertension
Estrada A, Humphrey J. Multi-Scale Multi-Cell Computational Model of Inflammation-Mediated Aortic Remodeling in Hypertension. Annals Of Biomedical Engineering 2025, 53: 1014-1023. PMID: 39904866, PMCID: PMC12067544, DOI: 10.1007/s10439-025-03685-3.Peer-Reviewed Original ResearchBuprenorphine induces human fetal membrane sterile inflammation
Lynn T, Kelleher M, Georges H, McCauley E, Logan R, Yonkers K, Abrahams V. Buprenorphine induces human fetal membrane sterile inflammation. Journal Of Reproductive Immunology 2025, 168: 104445. PMID: 39914058, PMCID: PMC11890952, DOI: 10.1016/j.jri.2025.104445.Peer-Reviewed Original ResearchConceptsOpioid-use disorderPreterm birthToll-like receptor 4Prostaglandin E2Sterile inflammationRate of preterm birthAssociated with pregnancy complicationsInnate immune toll-like receptor 4Maternal-fetal interfaceNeutrophil chemokine IL-8Induce sterile inflammationM-opioid receptorCytokines IL-1bInflammatory cytokines IL-6Chemokine IL-8Cytokines IL-6Maternal morbidityPregnancy complicationsOpioid useOpioid-usersHuman FMInflammatory profileMembrane weakeningIL-1BPretermTime-restricted feeding reduces inflammatory markers and downregulates JAG1 and NICD protein levels in the liver of aged mice
Macêdo A, de Sousa Neto I, Antonio G, Gaspar R, de Lima R, Dias L, Vieira R, Muñoz V, Brunelli D, da Silva A, Cintra D, Ropelle E, Pauli J. Time-restricted feeding reduces inflammatory markers and downregulates JAG1 and NICD protein levels in the liver of aged mice. Nutrition 2025, 133: 112691. PMID: 39983606, DOI: 10.1016/j.nut.2025.112691.Peer-Reviewed Original ResearchConceptsRNA-seq datasetsNotch1 intracellular domainMitochondrial respirationTime-restricted feedingAged miceInflammatory markersAd libitum dietIntracellular domainHepatic mitochondrial respirationATP productionLiver mitochondrial respirationCellular longevityLiver of aged miceLibitum dietDisease Activity ScoreCompared to adult animalsNotch1 signalingProtein contentTime-restricted feeding protocolsUpregulation of Notch1Investigated metabolic parametersProtein levelsNotch1Adult miceCollagen fibersCFTR dictates monocyte adhesion by facilitating integrin clustering but not activation
Younis D, Marosvari M, Liu W, Pulikkot S, Cao Z, Zhou B, Vella A, McArdle S, Hu L, Chen Y, Gan W, Yu J, Bruscia E, Fan Z. CFTR dictates monocyte adhesion by facilitating integrin clustering but not activation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2412717122. PMID: 39813254, PMCID: PMC11760921, DOI: 10.1073/pnas.2412717122.Peer-Reviewed Original ResearchConceptsIntegrin clusteringCF transmembrane conductance regulatorCystic fibrosisAdhesion defectsPathogenesis of cystic fibrosisClinically relevant disease modelsMembrane recruitmentTransmembrane conductance regulatorIntegrin activationTherapeutic strategy designRelevant disease modelsIntegrinCF monocytesCell adhesionMonocyte dysfunctionPatients' monocytesTissue infectionsConductance regulatorSuperresolution microscopyCortex formationLeukocyte-dependent inflammationInflammatory pathogenesisLeukocyte adhesionMonocytesInflammationAnti-Syndecan 2 Antibody Treatment Reduces Edema Formation and Inflammation of Murine Laser-Induced CNV.
Corti F, Locri F, Plastino F, Perrotta P, Zsebo K, Ristori E, Yin X, Song E, André H, Simons M. Anti-Syndecan 2 Antibody Treatment Reduces Edema Formation and Inflammation of Murine Laser-Induced CNV. Translational Vision Science & Technology 2025, 14: 10. PMID: 39792057, PMCID: PMC11730891, DOI: 10.1167/tvst.14.1.10.Peer-Reviewed Original ResearchConceptsAge-related macular degenerationLaser-induced choroidal neovascularizationAnti-VEGF therapyTransendothelial electrical resistanceVEGF-A activityChoroidal neovascularizationIntravitreal injectionRetinal lesionsLong-term anti-VEGF therapyMurine laser-induced choroidal neovascularizationNeovascular age-related macular degenerationWet age-related macular degenerationAlteration of visual acuityIntravitreal anti-VEGF therapySide effectsLocal intravitreal injectionReduced edema formationSuppression of edemaRelated side effectsPermeability in vitroEndothelial cell junctionsNeovascular AMDVisual acuityAssessed in vitroMacular degenerationMultiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature
Bosticardo M, Dobbs K, Delmonte O, Martins A, Pala F, Kawai T, Kenney H, Magro G, Rosen L, Yamazaki Y, Yu H, Calzoni E, Lee Y, Liu C, Stoddard J, Niemela J, Fink D, Castagnoli R, Ramba M, Cheng A, Riley D, Oikonomou V, Shaw E, Belaid B, Keles S, Al-Herz W, Cancrini C, Cifaldi C, Baris S, Sharapova S, Schuetz C, Gennery A, Freeman A, Somech R, Choo S, Giliani S, Güngör T, Drozdov D, Meyts I, Moshous D, Neven B, Abraham R, El-Marsafy A, Kanariou M, King A, Licciardi F, Cruz-Muñoz M, Palma P, Poli C, Adeli M, Algeri M, Alroqi F, Bastard P, Bergerson J, Booth C, Brett A, Burns S, Butte M, Padem N, de la Morena M, Dbaibo G, de Ravin S, Dimitrova D, Djidjik R, Dorna M, Dutmer C, Elfeky R, Facchetti F, Fuleihan R, Geha R, Gonzalez-Granado L, Haljasmägi L, Ale H, Hayward A, Hifanova A, Ip W, Kaplan B, Kapoor N, Karakoc-Aydiner E, Kärner J, Keller M, Dávila Saldaña B, Kiykim A, Kuijpers T, Kuznetsova E, Latysheva E, Leiding J, Locatelli F, Alva-Lozada G, McCusker C, Celmeli F, Morsheimer M, Ozen A, Parvaneh N, Pasic S, Plebani A, Preece K, Prockop S, Sakovich I, Starkova E, Torgerson T, Verbsky J, Walter J, Ward B, Wisner E, Draper D, Myint-Hpu K, Truong P, Lionakis M, Similuk M, Walkiewicz M, Klion A, Holland S, Oguz C, Bogunovic D, Kisand K, Su H, Tsang J, Kuhns D, Villa A, Rosenzweig S, Pittaluga S, Notarangelo L, Ghosh R, Siefert B, Tokita M, Yan J, Jodarski C, Kamen M, Gore R, Reynolds-Lallement N, Lewis K, Bannon S, Borges A, Gentile N. Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature. Science Immunology 2025, 10: eadq1697. PMID: 39792639, PMCID: PMC12087669, DOI: 10.1126/sciimmunol.adq1697.Peer-Reviewed Original ResearchConceptsRAG deficiencyRecombination-activating geneImmune dysregulationInflammatory signaturePattern of immune dysregulationT helper 2B cell developmentType I interferonOmenn syndromeImmunological phenotypeImmune profileSelf-antigensB cellsClinical managementDefective TI interferonCellular indicesImmunopathologyPatientsMultiomics approachPhenotypeHypomorphic formDysregulationLineage-specific contributionsDeficiencyRNA sensing at the crossroads of autoimmunity and autoinflammation
Williams S, Sim S, Wolin S. RNA sensing at the crossroads of autoimmunity and autoinflammation. RNA 2025, 31: rna.080304.124. PMID: 39779213, PMCID: PMC11874990, DOI: 10.1261/rna.080304.124.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoimmune DiseasesAutoimmunityHumansImmunity, InnateInflammationInterferon Type IRNAConceptsRNA sensorsInnate immune system's abilityImmune systemAutoinflammatory diseasesHost defense systemRNA homeostasisForeign RNAHost RNAType I interferon-stimulated genesPathogen recognitionInnate immune systemI interferon-stimulated genesRNA sensingImmune-mediated diseasesImmune system's abilityRNAAdaptive immune systemHuman immune systemTumor surveillanceViral counterpartsSenescent cellsGenesHomeostatic processesViral infectionPathogensGenetic Associations Among Inflammation, White Matter Architecture, and Extracellular Free Water
Rodrigue A, Knowles E, Mollon J, Mathias S, Peralta J, Leandro A, Fox P, Kochunov P, Olvera R, Almasy L, Curran J, Blangero J, Glahn D. Genetic Associations Among Inflammation, White Matter Architecture, and Extracellular Free Water. Human Brain Mapping 2025, 46: e70101. PMID: 39757975, PMCID: PMC11702472, DOI: 10.1002/hbm.70101.Peer-Reviewed Original ResearchConceptsGenetic correlationsDiffusion tensor imagingCirculating cytokine levelsPeripheral inflammatory responseWhite matter architectureFA measurementsCytokine levelsCytokine measurementsWhite matter integrityProinflammatory cytokinesSingle-compartment modelIL-8Inflammatory processInflammatory responseFree water volumeFree waterGenetic relationshipsWhite matterWhite matter microstructureExtracellular free waterGenetic association
2024
Efficacy of GABA aminotransferase inactivator OV329 in models of neuropathic and inflammatory pain without tolerance or addiction
Wirt J, Ferreira L, Jesus C, Woodward T, Oliva I, Xu Z, Crystal J, Pepin R, Silverman R, Hohmann A. Efficacy of GABA aminotransferase inactivator OV329 in models of neuropathic and inflammatory pain without tolerance or addiction. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 122: e2318833121. PMID: 39793055, PMCID: PMC11725897, DOI: 10.1073/pnas.2318833121.Peer-Reviewed Original ResearchConceptsComplete Freund's adjuvantInflammatory painMechanical hypersensitivityAntinociceptive efficacyGlutamate levelsInjection of complete Freund's adjuvantConditioned place preference assayPaclitaxel-induced mechanical hypersensitivitySpinal site of actionSide effectsEnhancement of GABAergic transmissionChemotherapeutic agent paclitaxelPaclitaxel-induced increaseCompared to morphineLumbar spinal cordIncreased endogenous GABA levelsReduced glutamate levelsNeuropathic nociceptionSite of actionGABAergic transmissionAnalgesic strategiesPathological painGABAergic inhibitionSpinal sitesAbuse liabilityMalate initiates a proton-sensing pathway essential for pH regulation of inflammation
Chen Y, Shi R, Xiang Y, Fan L, Tang H, He G, Zhou M, Feng X, Tan J, Huang P, Ye X, Zhao K, Fu W, Li L, Bian X, Chen H, Wang F, Wang T, Zhang C, Zhou B, Chen W, Liang T, Lv J, Kang X, Shi Y, Kim E, Qin Y, Hettinghouse A, Wang K, Zhao X, Yang M, Tang Y, Piao H, Guo L, Liu C, Miao H, Tang K. Malate initiates a proton-sensing pathway essential for pH regulation of inflammation. Signal Transduction And Targeted Therapy 2024, 9: 367. PMID: 39737965, PMCID: PMC11683149, DOI: 10.1038/s41392-024-02076-9.Peer-Reviewed Original ResearchConceptsL-malateInflammatory responseCytosolic pHBind BiPTCA intermediatesSensing pathwaysRegulation of inflammatory responsesBiological informationAnti-inflammatory metabolitesAnti-inflammatory proteinPro-inflammatory macrophagesRegulation of inflammationSignaling modalitiesPhysiological adaptationsAnti-inflammatory effectsIRF2BP2BiPPH regulationCarboxylate metaboliteChemical languageIn vivoIn vitroMacrophagesPathwayPH reductionDiverse NKT cells regulate early inflammation and neurological outcomes after cardiac arrest and resuscitation
Tamura T, Cheng C, Villaseñor-Altamirano A, Yamada K, Ikeda K, Hayashida K, Menon J, Chen X, Chung H, Varon J, Chen J, Choi J, Cullen A, Guo J, Lin X, Olenchock B, Pinilla-Vera M, Manandhar R, Sheikh M, Hou P, Lawler P, Oldham W, Seethala R, Baron R, Bohula E, Morrow D, Blumberg R, Chen F, Merriam L, Weissman A, Brenner M, Chen X, Ichinose F, Kim E, Sohn H, Rolland T, Weil B. Diverse NKT cells regulate early inflammation and neurological outcomes after cardiac arrest and resuscitation. Science Translational Medicine 2024, 16: eadq5796. PMID: 39630883, PMCID: PMC11792709, DOI: 10.1126/scitranslmed.adq5796.Peer-Reviewed Original ResearchConceptsOut-of-hospital cardiac arrestCohort of patientsNeurological outcomeT cellsImmune cellsCardiac arrestNatural killer (NK) cellsAssociated with good neurological outcomesDiverse T cell receptor repertoireNeurological injuryT cell receptor repertoireAssociated with poor neurological outcomeIncreased inflammatory chemokineInnate T cellsPoor neurological outcomeWild-type micePost-cardiac arrestAccumulation of macrophagesIncreased neuronal injuryBrains of miceNKT cellsTreated miceReceptor repertoireInflammatory chemokinesCytokine expression
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