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 cellsSepsisSystemic in utero gene editing as a treatment for cystic fibrosis
Ricciardi A, Barone C, Putman R, Quijano E, Gupta A, Nguyen R, Mandl H, Piotrowski-Daspit A, Lopez-Giraldez F, Luks V, Freedman-Weiss M, Farrelly J, Ahle S, Lynn A, Glazer P, Saltzman W, Stitelman D, Egan M. Systemic in utero gene editing as a treatment for cystic fibrosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2418731122. PMID: 40493185, PMCID: PMC12184489, DOI: 10.1073/pnas.2418731122.Peer-Reviewed Original ResearchConceptsUtero gene editingCystic fibrosisCF transmembrane conductance regulatorTreat CF patientsTransmembrane conductance regulatorWild-type miceIrreversible organ damageNormal organ developmentTreat monogenic diseasesCFTR activityCF patientsConductance regulatorDisease-causing genesMultiorgan diseaseDisease improvementOrgan damageGene editingMonogenic diseasesMutation correctionPolymeric nanoparticlesGastrointestinal tissuesDiseaseBirthFibrosisReproductive systemNeuronal ALKAL2 and its ALK receptor contribute to the development of colitis-associated colorectal cancer
Delanne-Cuménal M, Defaye M, Delanne-Cuménal A, Ahmed M, Ho V, Abdullah N, Alhassoun M, Svendsen K, Mager L, Schlessinger J, Hirota S, Altier C. Neuronal ALKAL2 and its ALK receptor contribute to the development of colitis-associated colorectal cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2500632122. PMID: 40493183, PMCID: PMC12184428, DOI: 10.1073/pnas.2500632122.Peer-Reviewed Original ResearchConceptsColitis-associated colorectal cancerAnaplastic lymphoma kinaseColorectal cancerAnaplastic lymphoma kinase activityColitis-associated colorectal cancer progressionAnaplastic lymphoma kinase receptorTRPV1+ nociceptorsDevelopment of colitis-associated colorectal cancerMouse colonic organoidsALK signalingInflammatory painTumor burdenTreatment resistanceSensory neuronsTumor growthColonic organoidsALKAL2Colonic mucosaOverall inflammationCancer progressionCancerIn vivoTRPV1NeuronsInflammationHeterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice
Ishchenko Y, Jeng A, Feng S, Nottoli T, Manriquez-Rodriguez C, Nguyen K, Carrizales M, Vitarelli M, Corcoran E, Greer C, Myers S, Koleske A. Heterozygosity for neurodevelopmental disorder-associated TRIO variants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice. ELife 2025, 13: rp103620. PMID: 40488445, PMCID: PMC12148328, DOI: 10.7554/elife.103620.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderGuanine nucleotide exchange factorNeurodevelopmental disordersPresynaptic glutamate releaseLayer 5 pyramidal neuronsAssociated with neurodevelopmental disordersIntellectual disabilitySpectrum disorderMouse behaviorCognitive behaviorNucleotide exchange factorNeuronal developmentBrain developmentGlutamate releaseIncreased Rac1 activityBrain sizeSynaptic functionControlling neuronal developmentSchizophreniaImpaired abilityAssociated with increased levelsNeurodevelopmental eventsActive GTPaseGEF Tiam1Exchange factorSeparation 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 ResearchMeSH KeywordsAnimalsDisease Models, AnimalGastritis, HypertrophicMetallothioneinMiceMice, TransgenicTransforming Growth Factor alphaConceptsSpasmolytic 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 optionsTargeted 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 cohortGly-βMCA modulates bile acid metabolism to reduce hepatobiliary injury in Mdr2 KO mice
Hasan M, Wang H, Luo W, Du Y, Li T. Gly-βMCA modulates bile acid metabolism to reduce hepatobiliary injury in Mdr2 KO mice. AJP Gastrointestinal And Liver Physiology 2025, 329: g45-g57. PMID: 40418643, PMCID: PMC12178242, DOI: 10.1152/ajpgi.00044.2025.Peer-Reviewed Original ResearchConceptsKO miceBile acid compositionBile acid pool sizeBile acid poolBile acid hydrophobicityHepatic bile acidsHepatobiliary toxicityBile acid metabolismMale miceTherapeutic benefitCholestasis modelMdr2-KO miceDecreased liver injuryBile acidsSerum alkaline phosphataseBile acid absorptionAlkaline phosphataseFecal bile acid excretionAcid compositionDiminished therapeutic efficacyImpaired bile flowAcid metabolismHepatobiliary injuryUnique pharmacokineticsBiliary injuryChanges in the FXR-cistrome and alterations in bile acid physiology in Wilson disease
Wooton-Kee C, Yalamanchili H, Mohamed I, Hassan M, Setchell K, Rivas M, Coskun A, Putluri V, Putluri N, Jalal P, Schilsky M, Moore D. Changes in the FXR-cistrome and alterations in bile acid physiology in Wilson disease. Hepatology Communications 2025, 9: e0707. PMID: 40408300, PMCID: PMC12106221, DOI: 10.1097/hc9.0000000000000707.Peer-Reviewed Original ResearchConceptsWild-type miceFarnesoid X receptorWilson's diseaseNon-parenchymal cellsDistal intergenic regionsLiver bile acid concentrationWD patientsHealthy controlsMetabolic target genesFarnesoid X Receptor RegulationBile salt export pumpIntergenic regionFXR activationAutosomal recessive disorderBile acid homeostasisBile acid physiologyFarnesoid X receptor activationPromoter regionHomeostasis pathwaysBile acid metabolismDecreasing FXR activityTarget genesBile acid profilesMarker genesStress pathwaysSecretory 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-6GALNT14 deficiency: connecting multiple links in the IgA nephropathy pathogenetic chain
Pell J, Menon M. GALNT14 deficiency: connecting multiple links in the IgA nephropathy pathogenetic chain. Journal Of Clinical Investigation 2025, 135: e192687. PMID: 40371648, PMCID: PMC12077885, DOI: 10.1172/jci192687.Peer-Reviewed Original ResearchCardiac macrophage: Insights from murine models to translational potential for human studies
Liu Y, Wang T, Lu Y, Riaz M, Qyang Y. Cardiac macrophage: Insights from murine models to translational potential for human studies. Journal Of Molecular And Cellular Cardiology 2025, 204: 17-31. PMID: 40354877, PMCID: PMC12162190, DOI: 10.1016/j.yjmcc.2025.05.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCardiovascular DiseasesDisease Models, AnimalHumansMacrophagesMiceMyocardiumTranslational Research, BiomedicalConceptsCardiovascular diseaseMurine studiesCardiac macrophagesImmune cellsDisease progressionCardiac homeostasisHuman studiesFunctional significanceCell typesTherapeutic targetCardiac microenvironmentTranslational potentialProgressive pathologyDevelopmental originsPhysiological maintenanceMacrophagesMicroenvironmentMechanical stimuliDiseaseFunctional responseCellsDynamic roleExperimental toolHuman modelLineagesSARM1 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 motifTyphoid toxin causes neuropathology by disrupting the blood–brain barrier
Zhao H, Catarino J, Stack G, Albizu A, Lara-Tejero M, Horvath T, Galán J. Typhoid toxin causes neuropathology by disrupting the blood–brain barrier. Nature Microbiology 2025, 10: 1340-1351. PMID: 40341334, DOI: 10.1038/s41564-025-02000-z.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ToxinsBlood-Brain BarrierDisease Models, AnimalHumansMiceNeuronsSalmonella typhiTyphoid FeverConceptsTyphoid toxinTyphoid feverBlood-brain barrierBlood brain barrier disruption in vivoDisruption in vivoManifestations of typhoid feverVirulence factorsSalmonella typhiCatalytic subunitBlood-brain barrier permeability changesToxin actionLife-threatening complicationsSevere neurological manifestationsTyphoidIn vitro modelToxinNeurological complicationsGlial cellsTherapeutic interventionsFeverToxin exposureVirulenceComplicationsNeuropathologyEncephalopathyCardiomyocyte-specific NHE1 overexpression confers protection against myocardial infarction during hyperglycemia
Jiang K, Su F, Deng R, Xu Y, Qin A, Yuan X, Xing D, Chen Y, Wang D, Shen L, Hwa J, Hou L, Xiang Y. Cardiomyocyte-specific NHE1 overexpression confers protection against myocardial infarction during hyperglycemia. Cardiovascular Diabetology 2025, 24: 184. PMID: 40287728, PMCID: PMC12034198, DOI: 10.1186/s12933-025-02743-3.Peer-Reviewed Original ResearchConceptsNa+/H+ exchanger 1Na+/H+ exchanger 1 activationAcute hyperglycemiaMyocardial infarctionNHE1 overexpressionNHE1 activityTherapeutic strategiesCardiomyocyte necroptosisHistory of diabetes mellitusReduced extracellular Na+Worsened cardiac dysfunctionRetrospective cohort studyDouble knockout miceIschemia-reperfusion modelNon-diabetic individualsPost-MI patientsReduced infarct sizePathophysiology of MIBackgroundAcute hyperglycemiaElevated BNPMLKL knockoutReduced cardiomyocyte deathAcute myocardial infarctionExtracellular Na+Intracellular Na+Sustained tenascin-C expression drives neointimal hyperplasia and promotes aortocaval fistula failure
Gonzalez L, Zhang W, Bai H, Taniguchi R, Ramachandra A, Jovin D, Ohashi Y, Nguyen M, Thaxton C, Yatsula B, Vazquez-Padron R, Humphrey J, Martin K, Kyriakides T, Dardik A. Sustained tenascin-C expression drives neointimal hyperplasia and promotes aortocaval fistula failure. AJP Heart And Circulatory Physiology 2025, 328: h1147-h1167. PMID: 40247455, PMCID: PMC12150301, DOI: 10.1152/ajpheart.00661.2024.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArteriovenous Shunt, SurgicalDisease Models, AnimalGraft Occlusion, VascularHuman Umbilical Vein Endothelial CellsHumansHyperplasiaMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutMyocytes, Smooth MuscleNeointimaNF-kappa BTenascinThrombomodulinVascular PatencyVascular RemodelingVena Cava, InferiorConceptsArteriovenous fistula patencyTenascin-C expressionArteriovenous fistulaTissue factor expressionEnd-stage kidney diseaseAnti-inflammatory macrophage polarizationNeointimal hyperplasiaWT miceTenascin-CInflammatory microenvironmentWild-typeFactor expressionMacrophage polarizationArteriovenous fistula outcomesArteriovenous fistula failurePatent arteriovenous fistulaVein smooth muscle cellsArteriovenous fistula maturationSmooth muscle cellsOccluded arteriovenous fistulaHuman umbilical vein smooth muscle cellsImprove dialysis outcomesHuman umbilical vein endothelial cellsRegulation of inflammationNF-kB activationDecreased 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 epilepsyDesign, Production and Study of Flexible Acrylic Keratoprosthesis
Fan V, Sun M, Al-Qahtani A, Vieira I, Yu C. Design, Production and Study of Flexible Acrylic Keratoprosthesis. Current Eye Research 2025, 50: 677-683. PMID: 40177932, PMCID: PMC12187538, DOI: 10.1080/02713683.2025.2485186.Peer-Reviewed Original ResearchConceptsTreatment of corneal blindnessCorneal blindnessMTT assayKeratoprosthesesHistological analysisComplex shapesImplantationSurgical implantationInjection molding techniquePilot studyBlindnessTreatmentFree radical polymerizationToxicityMaterial formulationMechanical propertiesMechanical characteristicsMolding techniqueAssayKeratoprosthesisCopolymer sheetsRadical polymerizationAcrylic sheetRefractive indexMonthsAutism-like atypical face processing in Shank3 mutant dogs
Yuan S, Pang C, Wu L, Yi L, Guo K, Jiang Y, Zhang Y, Han S. Autism-like atypical face processing in Shank3 mutant dogs. Science Advances 2025, 11: eadu3793. PMID: 40173245, PMCID: PMC11963970, DOI: 10.1126/sciadv.adu3793.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutism Spectrum DisorderAutistic DisorderBehavior, AnimalDisease Models, AnimalDogsFaceFemaleMaleMutationNerve Tissue ProteinsConceptsAtypical face processingAutism spectrum disorderFace processingCategorization of facesFace processing abilitiesWild-type controlsAttentional avoidanceNeurocognitive basisSocial deficitsCognitive markersTemporal cortexASD mechanismsSpectrum disorderNeural responsesFrontal/parietal regionsProcessing abilityAnimal modelsEffective animal modelRisk genesCortical responsesGenetic associationAutismFaceCortexSHANK3A mechanically resilient soft hydrogel improves drug delivery for treating post-traumatic osteoarthritis in physically active joints
Joshi N, Yan J, Dang M, Slaughter K, Wang Y, Wu D, Ung T, Bhingaradiya N, Pandya V, Chen M, Kaur S, Bhagchandani S, Alfassam H, Joseph J, Gao J, Dewani M, Chu R, Yip R, Weldon E, Shah P, Pisal N, Shukla C, Sherman N, Luo J, Conway T, Eickhoff J, Botelho L, Alhasan A, Karp J, Ermann J. A mechanically resilient soft hydrogel improves drug delivery for treating post-traumatic osteoarthritis in physically active joints. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2409729122. PMID: 40163719, PMCID: PMC12002200, DOI: 10.1073/pnas.2409729122.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDisease Models, AnimalDrug Delivery SystemsDrug LiberationHumansHydrogelsInjections, Intra-ArticularMaleMiceOsteoarthritisConceptsTreat post-traumatic osteoarthritisMechanical loadingSoft hydrogelsDrug releaseKinetics of drug releaseIntra-articular drug deliveryPost-traumatic osteoarthritisHydrogel potentialIntra-articular deliverySoft materialsHydrogelsDrug deliveryReduced cartilage degenerationSelf-healingMouse knee jointsRelease kineticsCartilage degenerationActive jointsLoadSuperior performanceStructural integrityEncapsulated drugJointsDisease-modifying osteoarthritis drugsKnee joint
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