2025
Improvements in hearing loss with bone-targeted enzyme replacement therapy are associated with corrected hypomineralization and osteocyte properties of auditory ossicles in Enpp1-deficient mice
Ocokoljic A, Srivastava S, von Kroge S, Stabach P, Busse B, Weise K, Oheim R, Rolvien T, Braddock D. Improvements in hearing loss with bone-targeted enzyme replacement therapy are associated with corrected hypomineralization and osteocyte properties of auditory ossicles in Enpp1-deficient mice. Journal Of Bone And Mineral Research 2025, zjaf082. PMID: 40495691, DOI: 10.1093/jbmr/zjaf082.Peer-Reviewed Original ResearchEnzyme replacement therapyHearing lossReplacement therapyENPP1 deficiencyAuditory brainstem response thresholdsAutosomal recessive hypophosphatemic rickets type 2Markers of mineral metabolismArterial calcification of infancyBrainstem response thresholdsElevated hearing thresholdsPrevent hearing lossWild-type miceImpairment of hearingAuditory ossiclesHearing thresholdsHearing functionHearing deficitsArtery calcificationDose-dependentlyMiddle earMouse modelOssicular chainBone propertiesMineral metabolismEffective treatmentUremic toxin receptor NR1H3 contributes to hyperlipidemia- and chronic kidney disease-accelerated vascular inflammation, which is partially suppressed by novel YBX2 anti-ROS pathway
Lu Y, Sun Y, Saaoud F, Xu K, Shao Y, Han B, Jiang X, Martinez L, Vazquez-Padron R, Mohsin S, Zhao H, Wang H, Yang X. Uremic toxin receptor NR1H3 contributes to hyperlipidemia- and chronic kidney disease-accelerated vascular inflammation, which is partially suppressed by novel YBX2 anti-ROS pathway. Redox Biology 2025, 85: 103724. PMID: 40505347, PMCID: PMC12182350, DOI: 10.1016/j.redox.2025.103724.Peer-Reviewed Original ResearchChronic kidney diseaseReactive oxygen speciesROS regulationNephrectomy-induced chronic kidney diseaseVascular inflammationRNA-binding proteinsReactive oxygen species regulationPromote vascular inflammationPromotion of inflammationCellular ROS levelsTrained immunityDisease progressionKidney diseaseMouse modelCytokine genesMouse aortaProinflammatory genesTranscription factorsRisk factorsRegulating inflammationHyperlipidemiaCardiovascular diseaseInflammationNegative feedback mechanismYBX2Separation of telomere protection from length regulation by two different point mutations at amino acid 492 of RTEL1
Smoom R, May C, Lichtental D, Bar-Ness K, Rangel R, Khoury J, Nachmani D, Avrahami D, Ahangari F, Skordalakes E, Kaminski N, Kaestner K, Tzfati Y. Separation of telomere protection from length regulation by two different point mutations at amino acid 492 of RTEL1. Nucleic Acids Research 2025, 53: gkaf507. PMID: 40530700, PMCID: PMC12203905, DOI: 10.1093/nar/gkaf507.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsDisease Models, AnimalDNA DamageDNA HelicasesDyskeratosis CongenitaFetal Growth RetardationGrowth DisordersHematopoiesisHumansIntellectual DisabilityLimb Deformities, CongenitalLungMiceMicrocephalyPoint MutationTelomereTelomere HomeostasisX-Linked Intellectual DisabilityConceptsHoyeraal-Hreidarsson syndromeTelomere protectionLength regulationTelomere length regulationTelomere-related diseasesTelomere biology disordersDNA helicaseMouse genomeGenome stabilityMouse modelMouse telomeresAberrant hematopoiesisGenomic instabilityPoint mutationsHouse miceTelomeric DNA damageAnaphase bridgesRTEL1Amino acidsTelomereMechanistic rolesDNA damageMutationsIsoleucine mutationGenomeDevelopment of Mouse Models for Ménétrier's Disease.
Gabriel T, Park J, Madala S, Coffey R, Huh W. Development of Mouse Models for Ménétrier's Disease. Journal Of Visualized Experiments 2025 PMID: 40549725, DOI: 10.3791/67981.Peer-Reviewed Original ResearchConceptsSpasmolytic polypeptide-expressing metaplasiaLoss of parietal cellsMouse modelFeatures of MDMouse linesFoveolar hyperplasiaParietal cellsEGF receptorTransforming growth factor-aEGFR-neutralizing antibodyChief cellsDevelopment of mouse modelsChief cell differentiationDecreased acid secretionGiant rugal foldsTransgenic mouse linesInducible mouse modelGrowth factor AModel of MDIn vivo modelsMist1 expressionHistological remissionClinical improvementHistopathological featuresTreatment optionsImpact of peritoneal macrophage depletion on endometriotic lesion development in a mouse model
Stratopoulou C, Cacciottola L, Gawde N, Ngombo A, Brusa D, Donnez J, Taylor H, Dolmans M. Impact of peritoneal macrophage depletion on endometriotic lesion development in a mouse model. Journal Of Endometriosis And Uterine Disorders 2025, 10: 100113. DOI: 10.1016/j.jeud.2025.100113.Peer-Reviewed Original ResearchMacrophage depletionEndometriotic lesionsTreated miceMacrophage accumulationMouse modelVascular endothelial growth factor immunostainingEndometriosis developmentQuantification of immune cellsFlow cytometryMouse model of endometriosisClodronate-containing liposomesKi67-positive proliferating cellsNovel therapeutic optionsRate of fibrosisModel of endometriosisTUNEL-positive apoptotic cellsLevels of fibrosisPathogenesis of endometriosisReproductive-age womenMasson's trichrome stainingEndometriotic lesion developmentEnhanced cell deathPlacebo-controlledUterine fragmentsT cellsTargeted inhibition of pathobiont virulence factor mitigates alcohol-associated liver disease
Yang Y, Duan Y, Lang S, Fondevila M, Schöler D, Harberts A, Cabré N, Chen S, Shao Y, Vervier K, Miyamoto Y, Zhang X, Chu H, Yang L, Tan C, Eckmann L, Bosques-Padilla F, Verna E, Abraldes J, Brown R, Vargas V, Altamirano J, Caballería J, Shawcross D, Louvet A, Lucey M, Mathurin P, Garcia-Tsao G, Bataller R, Stärkel P, Lawley T, Schnabl B. Targeted inhibition of pathobiont virulence factor mitigates alcohol-associated liver disease. Cell Host & Microbe 2025, 33: 957-972.e6. PMID: 40441146, PMCID: PMC12162233, DOI: 10.1016/j.chom.2025.05.003.Peer-Reviewed Original ResearchConceptsEthanol-induced liver diseaseAlcohol-associated liver diseaseAlcohol-associated hepatitisLiver diseaseGenome of Escherichia coliE. coliMetagenomic sequencing of fecal samplesInternational cohort of patientsGenetic manipulation of bacteriaGnotobiotic mouse modelOutcomes of patientsManipulation of bacteriaCohort of patientsScavenger receptor MARCOGlobal health burdenVirulence factorsMetagenomic sequencingGut microbiotaGenetic manipulationDisease progressionMouse modelKupffer cellsKpsMBacterial spreadInternational cohortIL‐6 signaling regulates the inflammatory response without impacting pathogen burden during influenza‐associated pulmonary aspergillosis
Sharma L, Singh R, Tolman N, Ngeow C, Duray A, Naghshtabrizi N, Ahmad A, Bain W, Robinson K. IL‐6 signaling regulates the inflammatory response without impacting pathogen burden during influenza‐associated pulmonary aspergillosis. Physiological Reports 2025, 13: e70372. PMID: 40420617, PMCID: PMC12106949, DOI: 10.14814/phy2.70372.Peer-Reviewed Original ResearchConceptsAF infectionAspergillus fumigatusInterleukin-6IL-6 signalingLung inflammationInfluenza-associated pulmonary aspergillosisInterleukin-6 knockout miceNeutrophilic lung inflammationBronchoalveolar lavage fluidEpithelial cell damageLung capillary permeabilitySusceptibility to opportunistic pathogensPulmonary aspergillosisClinical courseLavage fluidKnockout miceOpportunistic pathogenRAGE levelsEpithelial integrityMouse modelIL-6Pathological inflammationTissue injuryInflammatory responseViral infectionIndole-3-lactic acid suppresses colorectal cancer via metabolic reprogramming
Zhou S, Wang K, Huang J, Xu Z, Yuan Q, Liu L, Wang Z, Miao J, Wang H, Wang T, Guan W, Ding C. Indole-3-lactic acid suppresses colorectal cancer via metabolic reprogramming. Gut Microbes 2025, 17: 2508949. PMID: 40409349, PMCID: PMC12118437, DOI: 10.1080/19490976.2025.2508949.Peer-Reviewed Original ResearchConceptsIndole-3-lactic acidColorectal cancer patientsColorectal cancerAryl hydrocarbon receptorDownregulated glucose metabolismPotential clinical therapeutic targetsAnti-apoptotic capabilityInfluence tumor progressionGut microbiota metabolismTumor cell proliferationMetagenomic sequencingPhosphorylation sitesXenograft mouse modelGut microbiotaClinical therapeutic targetMetabolic reprogrammingMicrobiota metabolismP-STAT3Tumor progressionTumor malignancyMouse modelTryptophan metabolismCancer cellsIn vitro experimentsCRC developmentcGAS Expression is enhanced in systemic sclerosis associated interstitial lung disease and stimulates inflammatory myofibroblast activation.
Yu S, Hu B, Sun Y, Peng X, Lee C, Woo S, McGovern J, Zielonka J, Saber T, Ghincea A, Gandhi S, Walia A, Pivarnik T, Ishikawa G, Shao S, Sun H, Gunes B, Kujawski S, Perez S, Odell W, Hinchcliff M, Varga J, Feghali-Bostwick C, Sauler M, Gomez J, Ryu C, Herzog E. cGAS Expression is enhanced in systemic sclerosis associated interstitial lung disease and stimulates inflammatory myofibroblast activation. European Respiratory Journal 2025, 2401564. PMID: 40374521, DOI: 10.1183/13993003.01564-2024.Peer-Reviewed Original ResearchPrecision cut lung slicesSSc-ILD lung tissuesType 1 interferonSSc-ILDProduction of cytokinesBronchoalveolar lavageHuman precision cut lung slicesLung tissueLung fibroblastsLungs of patientsInterstitial lung diseasePulmonary fibrosis modelBleomycin mouse modelIsolated lung fibroblastsCultured fibroblastsPerturbs innate immunityFibrotic stimuliSingle cell RNA sequencing datasetsSystemic sclerosisHuman lung fibroblastsLung diseaseMouse modelCyclic GMP-AMP synthaseFibrosis modelTherapeutic approachesMapping pesticide-induced metabolic alterations in human gut bacteria
Chen L, Yan H, Di S, Guo C, Zhang H, Zhang S, Gold A, Wang Y, Hu M, Wu D, Johnson C, Wang X, Zhu J. Mapping pesticide-induced metabolic alterations in human gut bacteria. Nature Communications 2025, 16: 4355. PMID: 40348778, PMCID: PMC12065874, DOI: 10.1038/s41467-025-59747-6.Peer-Reviewed Original ResearchConceptsModulating gut microbiota compositionGut bacteria speciesGut microbial speciesHuman gut bacteriaGut microbiota compositionGut bacterial metabolismPesticide exposureHost healthGut bacteriaMicrobiota compositionMicrobial speciesBacterial metabolismBacteria speciesMolecular mechanismsComprehensive atlasLipid metabolismGutIn vivo mouse modelPesticidesHostMetabolismSpeciesInteractive atlasMouse modelMetabolic changesSARM1 loss protects retinal ganglion cells in a mouse model of Autosomal Dominant Optic Atrophy
Ding C, Ndiaye P, Campbell S, Fry M, Gong J, Wienbar S, Gibbs W, Morquette P, Chao L, H. M, Schwarz T. SARM1 loss protects retinal ganglion cells in a mouse model of Autosomal Dominant Optic Atrophy. Journal Of Clinical Investigation 2025, 135: e191315. PMID: 40344041, PMCID: PMC12165793, DOI: 10.1172/jci191315.Peer-Reviewed Original ResearchConceptsAutosomal dominant optic atrophyRetinal ganglion cellsOptic atrophy type 1Dominant optic atrophyOptic atrophyMouse modelRGC degenerationGanglion cellsOptic nerve degenerationHereditary optic neuropathyMitochondrial intermembrane spaceRGC lossOptic neuropathyRGC functionVision lossNerve degenerationIntermembrane spaceType 1Mitochondrial fragmentationDegeneration phenotypeMitochondrial defectsTherapeutic targetMembrane dynamicsMiceTIR motifPantothenate kinase is an effective target for antifungal therapy
Regan J, DeJarnette C, Reitler P, Gihaz S, Srivastava A, Ge W, Tucker K, Peters T, Meibohm B, Ben Mamoun C, Fortwendel J, Hevener K, Palmer G. Pantothenate kinase is an effective target for antifungal therapy. Cell Chemical Biology 2025, 32: 710-721.e6. PMID: 40378822, DOI: 10.1016/j.chembiol.2025.04.007.Peer-Reviewed Original ResearchConceptsPantothenate kinasePathogenic yeast Candida albicansDisseminated C. albicans infectionYeast Candida albicansIn vivo antifungal efficacyChemical-genetic approachBroad-spectrum antifungalAntifungal therapeuticsCoA productionCandida albicansMammalian hostsAntifungal therapyCoenzyme ASmall molecule inhibitorsAntifungal efficacyPanKEssential cofactorChemical probesMolecule inhibitorsKinaseLiving organismsPantothenateMouse modelEffective targetVirulenceThe retrotransposon-derived capsid genes PNMA1 and PNMA4 maintain reproductive capacity
Wood T, Henriques W, Cullen H, Romero M, Blengini C, Sarathy S, Sorkin J, Bekele H, Jin C, Kim S, Wang X, Laureau R, Chemiakine A, Khondker R, Isola J, Stout M, Gennarino V, Mogessie B, Jain D, Schindler K, Suh Y, Wiedenheft B, Berchowitz L. The retrotransposon-derived capsid genes PNMA1 and PNMA4 maintain reproductive capacity. Nature Aging 2025, 5: 765-779. PMID: 40263616, PMCID: PMC12180178, DOI: 10.1038/s43587-025-00852-y.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesTranscription factor MYBL1Gonadal tissueMale gonadal tissueRNA intermediateEvolutionary innovationHuman genomeAssociation studiesHost genomeProtein self-assemblyDevelopmental regulationCapsid geneCapsid-like structuresHuman cellsCapsid formationYears ago4,5RetrotransposonsGenomeSequenceGenesRNAReproductive capacityPNMA1Reproductive functionMouse modelPreclinical Models of Solid Cancers for Testing Cancer Immunotherapies
Exposito F, Connolly K, Tang T, Chiorazzi M, Hunt B, Cardenas J, Nguyen D, Joshi N, Politi K. Preclinical Models of Solid Cancers for Testing Cancer Immunotherapies. Annual Review Of Cancer Biology 2025, 9: 285-305. DOI: 10.1146/annurev-cancerbio-062822-024810.Peer-Reviewed Original ResearchResponse to immunotherapyDevelopment of immunotherapyStandard treatment optionCancer immunotherapy drugsCancer-immune interactionsNumerous cancer typesImmunotherapy resistanceImmunotherapy drugsCancer immunologyPreclinical modelsTreatment optionsMouse modelImmunotherapyCancer typesAdvanced in vitro systemsHuman modelTherapyCancerMiceImmunologyDrugDecreased locus coeruleus multiunit activity in a mouse model of temporal lobe seizures with impaired consciousness
Valcarce-Aspegren M, Paszkowski P, Liu S, Wu Q, McGill S, Sieu L, Blumenfeld H. Decreased locus coeruleus multiunit activity in a mouse model of temporal lobe seizures with impaired consciousness. Experimental Neurology 2025, 389: 115233. PMID: 40189126, PMCID: PMC12083539, DOI: 10.1016/j.expneurol.2025.115233.Peer-Reviewed Original ResearchConceptsLocus coeruleusFocal limbic seizuresLimbic seizuresRight orbitofrontal cortexFiring of LC neuronsBasal forebrain cholinergic neuronsForebrain cholinergic neuronsAwake mouse modelHead-fixed miceOrbitofrontal cortexDorsal hippocampiImpaired consciousnessMouse modelTemporal lobe epilepsyCortical impairmentLC neuronsNoradrenergic pathwaysRecording multiunit activitySubcortical pathwaysMultiunit activityCholinergic neuronsTemporal lobe seizuresPeriod of impaired consciousnessRodent modelsLobe epilepsyIn 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 microscopyMIFInjuryDisease modification upon 2 weeks of tofacitinib treatment in a mouse model of chronic epilepsy
Hoffman O, Koehler J, Espina J, Patterson A, Gohar E, Coleman E, Schoenike B, Espinosa-Garcia C, Paredes F, Varvel N, Dingledine R, Maguire J, Roopra A. Disease modification upon 2 weeks of tofacitinib treatment in a mouse model of chronic epilepsy. Science Translational Medicine 2025, 17: eadt0527. PMID: 40106581, DOI: 10.1126/scitranslmed.adt0527.Peer-Reviewed Original ResearchConceptsTranscriptome dataJanus kinase/signal transducer and activatorKinase/signal transducer and activatorReverse cognitive deficitsJAK/STAT activationJAK/STAT3 signalingChronic epilepsyModel of temporal lobe epilepsySpontaneous seizuresMouse models of chronic epilepsyMouse modelCognitive deficitsSpatial memoryTransient inductionTemporal lobe epilepsyMouse model of temporal lobe epilepsyModel of chronic epilepsyLobectomy samplesDisease modificationTreat symptomsLobe epilepsyWhole tissueDrug treatmentEpileptogenic insultTofacitinib treatmentRecommendations for Design, Execution, and Reporting of Studies on Experimental Thoracic Aortopathy in Preclinical Models
Daugherty A, Milewicz D, Dichek D, Ghaghada K, Humphrey J, LeMaire S, Li Y, Mallat Z, Saeys Y, Sawada H, Shen Y, Suzuki T, Zhou Z, Dissections F. Recommendations for Design, Execution, and Reporting of Studies on Experimental Thoracic Aortopathy in Preclinical Models. Arteriosclerosis Thrombosis And Vascular Biology 2025, 45: 609-631. PMID: 40079138, PMCID: PMC12018150, DOI: 10.1161/atvbaha.124.320259.Peer-Reviewed Original ResearchEngineering Mice to Study Human Immunity
Sefik E, Xiao T, Chiorazzi M, Odell I, Zhang F, Agrawal K, Micevic G, Flavell R. Engineering Mice to Study Human Immunity. Annual Review Of Immunology 2025, 43: 451-487. PMID: 40020225, DOI: 10.1146/annurev-immunol-082523-124415.Peer-Reviewed Original ResearchHumanized miceHuman hematopoiesisImmune responseImmune systemHumanized mouse modelHuman hematopoietic stemImmunocompromised murine hostsResident immune cellsHuman immune responseStudy human immunityHuman immune systemIntegration of multi-omicsHematopoietic stemImmune cell growthImmune cellsEngineered miceProgenitor cellsMouse modelImmunological diseasesMurine hostCancer treatmentPreclinical drugsHuman immunityMiceModel diseaseFAK inhibition combined with the RAF-MEK clamp avutometinib overcomes resistance to targeted and immune therapies in BRAF V600E melanoma
Lubrano S, Cervantes-Villagrana R, Faraji F, Ramirez S, Sato K, Adame-Garcia S, Officer A, Arang N, Rigiracciolo D, Anguiano Quiroz P, Martini C, Wang Y, Ferguson F, Bacchiocchi A, Halaban R, Coma S, Holmen S, Pachter J, Aplin A, Gutkind J. FAK inhibition combined with the RAF-MEK clamp avutometinib overcomes resistance to targeted and immune therapies in BRAF V600E melanoma. Cancer Cell 2025, 43: 428-445.e6. PMID: 40020669, PMCID: PMC11903146, DOI: 10.1016/j.ccell.2025.02.001.Peer-Reviewed Original ResearchConceptsBRAF V600E melanomaFocal adhesion kinaseV600E melanomaFAK inhibitorActivated focal adhesion kinaseFocal adhesion kinase inhibitionRaf-MEKActivation of focal adhesion signalingFocal adhesion kinase inhibitorResistance to BRAFiSyngeneic mouse modelMAPK pathway inhibitionFocal adhesion signalingPro-apoptotic activityMelanoma patientsAdhesion signalingImmune therapyBRAF mutationsBRAFiTranscriptome analysisMelanomaMouse modelPathway inhibitionBRAFMelanoma cells
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