2025
Multicenter SPAN Trial of Fasudil in Ischemic Stroke.
Imai T, Morais A, Jin X, Qin T, Lamb J, Nagarkatti K, Chen M, Boisserand L, Patel R, Kumskova M, Chauhan A, Dhandapani K, Khan M, Kamat P, Shi Y, Cao S, Sanganahalli B, Mandeville J, Lyden P, Hess D, Leira E, Chauhan A, Aronowski J, McCullough L, Koehler R, Sansing L, Diniz M, Ayata C. Multicenter SPAN Trial of Fasudil in Ischemic Stroke. Stroke 2025 PMID: 40421536, DOI: 10.1161/strokeaha.125.050977.Peer-Reviewed Original ResearchSpontaneously Hypertensive RatsRho-associated kinase inhibitorHypertensive ratsAged miceActive treatment armsIschemic strokeModified intention-to-treat cohortKinase inhibitorsPrimary outcome end pointsIntention-to-treat cohortTest performanceEfficacy of fasudilPer-protocol populationOutcome end pointsMiddle cerebral artery occlusion modelHealthy young miceDiet-induced obese miceRodent modelsTrials NetworkTherapeutic profileFocal ischemic strokeTreatment armsYoung miceVehicle armSecondary outcomes
2024
Caloric restriction reduces trabecular bone loss during aging and improves bone marrow adipocyte endocrine function in male mice
Rinne C, Soultoukis G, Oveisi M, Leer M, Schmidt-Bleek O, Burkhardt L, Bucher C, Moussa E, Makhlouf M, Duda G, Saraiva L, Schmidt-Bleek K, Schulz T. Caloric restriction reduces trabecular bone loss during aging and improves bone marrow adipocyte endocrine function in male mice. Frontiers In Endocrinology 2024, 15: 1394263. PMID: 38904042, PMCID: PMC11188307, DOI: 10.3389/fendo.2024.1394263.Peer-Reviewed Original ResearchConceptsBone marrow adipose tissueTrabecular bone lossAged miceCaloric restrictionBone lossEndocrine profileMale C57BL6J miceCardio-metabolic diseasesTime of CRAge-matched littermatesBiochemical lipid profilesAssess bone microstructureFree food accessC57BL6J miceBone healthYoung miceContext of agingMale miceDietary interventionNutritional interventionAnatomical localizationLipid profileAdipogenic gene expressionBone dysfunctionTrabecular bone structure
2023
A multi-laboratory preclinical trial in rodents to assess treatment candidates for acute ischemic stroke
Lyden P, Diniz M, Bosetti F, Lamb J, Nagarkatti K, Rogatko A, Kim S, Cabeen R, Koenig J, Akhter K, Arbab A, Avery B, Beatty H, Bibic A, Cao S, Simoes Braga Boisserand L, Chamorro A, Chauhan A, Diaz-Perez S, Dhandapani K, Dhanesha N, Goh A, Herman A, Hyder F, Imai T, Johnson C, Khan M, Kamat P, Karuppagounder S, Kumskova M, Mihailovic J, Mandeville J, Morais A, Patel R, Sanganahalli B, Smith C, Shi Y, Sutariya B, Thedens D, Qin T, Velazquez S, Aronowski J, Ayata C, Chauhan A, Leira E, Hess D, Koehler R, McCullough L, Sansing L. A multi-laboratory preclinical trial in rodents to assess treatment candidates for acute ischemic stroke. Science Translational Medicine 2023, 15: eadg8656. PMID: 37729432, DOI: 10.1126/scitranslmed.adg8656.Peer-Reviewed Original ResearchConceptsPreclinical assessmentFocal cerebral ischemic insultAcute ischemic strokeCerebral ischemic insultLarge clinical trialsDiet-induced obesityNew clinical interventionsIntravascular thrombectomyIschemic strokeStroke treatmentHypertensive ratsIschemic insultBlinded assessmentClinical trialsYoung miceTreatment candidatesExclusion criteriaAnimal modelsYoung ratsFutile interventionsPreclinical trialsClinical interventionsFutility boundariesMiceDisease areasAge-associated disparity in phagocytic clearance affects the efficacy of cancer nanotherapeutics
Wang Y, Deng W, Lee D, Yan L, Lu Y, Dong S, Huntoon K, Antony A, Li X, Ye R, Zhao Y, Zhao F, Schrank B, Ha J, Kang M, Yang M, Gong P, Lorenzi P, Tan L, Gallup T, Tang S, Yang Z, Li J, Sanford N, Wang H, Kim B, Jiang W. Age-associated disparity in phagocytic clearance affects the efficacy of cancer nanotherapeutics. Nature Nanotechnology 2023, 19: 255-263. PMID: 37723279, DOI: 10.1038/s41565-023-01502-3.Peer-Reviewed Original ResearchConceptsCancer nanotherapeuticsCancer nanomedicineScavenger receptor MARCOPhagocytic clearanceUptake of nanoparticlesAntitumour responseTumor deliveryTherapeutic blockadeAntitumour efficacyAge-Associated DecreaseHepatic phagocytesAntitumour effectsYoung miceHepatic macrophagesAged miceTreatment outcomesTreat multiple human diseasesProtein level analysisHepatic uptakeAge-related declineNon-human primatesNanotherapeuticsMiceNanomedicinePhagocytic uptakeA Treg-specific long noncoding RNA maintains immune-metabolic homeostasis in aging liver
Ding C, Yu Z, Sefik E, Zhou J, Kaffe E, Wang G, Li B, Flavell R, Hu W, Ye Y, Li H. A Treg-specific long noncoding RNA maintains immune-metabolic homeostasis in aging liver. Nature Aging 2023, 3: 813-828. PMID: 37277640, DOI: 10.1038/s43587-023-00428-8.Peer-Reviewed Original ResearchConceptsAged miceLiver diseaseLiver microenvironmentAge-related liver diseasesYin Yang 1Liver immune microenvironmentRegulatory T cellsTreg-specific deletionPotential therapeutic targetMitochondrial functionYang 1Treg apoptosisTreg homeostasisTreg cellsTreg functionImmune microenvironmentLiver fibrosisMetabolic dysfunctionOptimal mitochondrial functionYoung miceT cellsLiver cancerTherapeutic targetAged liverLong noncoding RNANav1.7 gain-of-function mutation I228M triggers age-dependent nociceptive insensitivity and C-LTMR dysregulation
Wimalasena N, Taub D, Shim J, Hakim S, Kawaguchi R, Chen L, El-Rifai M, Geschwind D, Dib-Hajj S, Waxman S, Woolf C. Nav1.7 gain-of-function mutation I228M triggers age-dependent nociceptive insensitivity and C-LTMR dysregulation. Experimental Neurology 2023, 364: 114393. PMID: 37003485, PMCID: PMC10171359, DOI: 10.1016/j.expneurol.2023.114393.Peer-Reviewed Original ResearchConceptsParoxysmal extreme pain disorderSmall fiber neuropathyFunction mutationsDRG neuron hyperexcitabilityYoung adult miceVoltage-gated sodium channel NaSodium conductanceAge-related changesNeuron hyperexcitabilityPain disordersCongenital insensitivitySodium channel NaExcitability changesFemale miceMouse DRGYoung miceNeuronal excitabilityNoxious heatSkin lesionsVoltage-gated channelsAdult miceNeuron subtypesNervous systemProfound insensitivityMiceChallenges and opportunities for modeling aging and cancer
Anczuków O, Airhart S, Chuang J, Coussens L, Kuchel G, Korstanje R, Li S, Lucido A, McAllister S, Politi K, Polyak K, Ratliff T, Ren G, Trowbridge J, Ucar D, Palucka K. Challenges and opportunities for modeling aging and cancer. Cancer Cell 2023, 41: 641-645. PMID: 37001528, PMCID: PMC10185379, DOI: 10.1016/j.ccell.2023.03.006.Peer-Reviewed Original ResearchMitochondrial stress response gene Clpp deficiency impairs oocyte competence and deteriorate cyclophosphamide-induced ovarian damage in young mice
Li G, Gu J, Zhou X, Wu T, Li X, Hua R, Hai Z, Xiao Y, Su J, Yeung W, Liu K, Guo C, Wang T. Mitochondrial stress response gene Clpp deficiency impairs oocyte competence and deteriorate cyclophosphamide-induced ovarian damage in young mice. Frontiers In Endocrinology 2023, 14: 1122012. PMID: 37033217, PMCID: PMC10081448, DOI: 10.3389/fendo.2023.1122012.Peer-Reviewed Original ResearchConceptsCyclophosphamide-induced ovarian damageOvarian damageOocyte-specific deletionOocyte competencePremature ovarian insufficiencyImpaired oocyte competenceChemotherapeutic drug cyclophosphamideCaseinolytic peptidase PDecreased mitochondrial membrane potentialAneuploidy rateMII oocytesCTX treatmentElevated ROS levelsOvarian insufficiencyEarly folliculogenesisKnockout miceYoung miceMitochondrial membrane potentialMouse modelDrug cyclophosphamideTreat cancerMiceOocytesSpindle rateMembrane potential
2022
CD38 Mediates Lung Fibrosis by Promoting Alveolar Epithelial Cell Aging.
Cui H, Xie N, Banerjee S, Dey T, Liu RM, Antony VB, Sanders YY, Adams TS, Gomez JL, Thannickal VJ, Kaminski N, Liu G. CD38 Mediates Lung Fibrosis by Promoting Alveolar Epithelial Cell Aging. American Journal Of Respiratory And Critical Care Medicine 2022, 206: 459-475. PMID: 35687485, PMCID: PMC12039157, DOI: 10.1164/rccm.202109-2151oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisLung fibrosisCD38 expressionAlveolar epithelial cell injuryEpithelial cell injuryEffective therapeutic strategyHuman lung parenchymaIPF lungsLung functionPulmonary fibrosisDisease progressionFibrotic lungsReal-time PCRYoung miceLung parenchymaOld miceCell injuryTherapeutic strategiesFibrosisPharmacological inactivationCD38Single-cell RNA sequencingFlow cytometryWestern blottingOld animalsDeletion of matrix metalloproteinase-12 compromises mechanical homeostasis and leads to an aged aortic phenotype in young mice
Spronck B, Ramachandra AB, Moriyama L, Toczek J, Han J, Sadeghi MM, Humphrey JD. Deletion of matrix metalloproteinase-12 compromises mechanical homeostasis and leads to an aged aortic phenotype in young mice. Journal Of Biomechanics 2022, 141: 111179. PMID: 35759974, PMCID: PMC9585962, DOI: 10.1016/j.jbiomech.2022.111179.Peer-Reviewed Original ResearchConceptsPulse wave velocityAortic phenotypeYoung miceAortic agingMMP-12Matrix metalloproteinasesMMP-12-deficient miceOld adult miceMatrix metalloproteinase-12Biomechanical propertiesAbdominal aortaArterial agingDeficient miceEnd organsBlood flowAdult miceCentral arteriesPercent changeMetalloproteinase-12MiceArterial wallAortaYoung adultsMatrix turnoverStrong proteolytic activityDiurnal effects of polypharmacy with high drug burden index on physical activities over 23 h differ with age and sex
Tran T, Mach J, Gemikonakli G, Wu H, Allore H, Howlett SE, Little CB, Hilmer SN. Diurnal effects of polypharmacy with high drug burden index on physical activities over 23 h differ with age and sex. Scientific Reports 2022, 12: 2168. PMID: 35140291, PMCID: PMC8828819, DOI: 10.1038/s41598-022-06039-4.Peer-Reviewed Original ResearchConceptsHigher Drug Burden IndexDrug Burden IndexBurden indexYoung miceOld micePhysical activityDifferent drug regimensWeeks of treatmentDrug-induced deliriumDaily physical activityTreatment × sex interactionBehavioral changesConsideration of ageSex-specific effectsSimvastatin monotherapyDrug regimensGait speedFunctional impairmentGlobal healthcare challengePolypharmacyQuality useOlder ageBehavioral declineMiceOlder adults
2020
Aging exacerbates neutrophil pathogenicity in ischemic stroke
Roy-O'Reilly MA, Ahnstedt H, Spychala MS, Munshi Y, Aronowski J, Sansing LH, McCullough LD. Aging exacerbates neutrophil pathogenicity in ischemic stroke. Aging 2020, 12: 436-461. PMID: 31927534, PMCID: PMC6977697, DOI: 10.18632/aging.102632.Peer-Reviewed Original ResearchConceptsIschemic stroke patientsIschemic strokeNeutrophil-activating cytokineStroke patientsNeutrophil functionNeutrophil reactive oxygen speciesPoor post-stroke outcomesDepletion of neutrophilsPro-inflammatory functionsStrong risk factorExperimental mouse modelPost-stroke outcomesHigher stroke mortalityStroke outcomePoor outcomeFunctional outcomeStroke mortalityLong-term benefitsRisk factorsSpecific monoclonal antibodiesNeutrophil trafficTissue injuryYoung miceAged subjectsMouse model
2019
Hypervascularization in mTOR‐dependent focal and global cortical malformations displays differential rapamycin sensitivity
Zhang L, Huang T, Teaw S, Bordey A. Hypervascularization in mTOR‐dependent focal and global cortical malformations displays differential rapamycin sensitivity. Epilepsia 2019, 60: 1255-1265. PMID: 31125447, PMCID: PMC6558978, DOI: 10.1111/epi.15969.Peer-Reviewed Original ResearchConceptsBlood vesselsRapamycin treatmentVessel densityVessel abnormalitiesPostnatal day 14 miceAbsence of seizuresWild-type miceConditional transgenic miceTuberous sclerosis complexTypes of MCDDay 14 miceMCD modelFocal MCDMTOR blockersDysplastic neuronsFunctional outcomeEpilepsy treatmentSomatosensory cortexYoung miceFocal malformationsCortical developmentJuvenile miceTotal vessel lengthAnimal modelsTransgenic miceSynaptic Connectivity and Cortical Maturation Are Promoted by the ω-3 Fatty Acid Docosahexaenoic Acid
Carbone BE, Abouleish M, Watters KE, Vogel S, Ribic A, Schroeder OH, Bader BM, Biederer T. Synaptic Connectivity and Cortical Maturation Are Promoted by the ω-3 Fatty Acid Docosahexaenoic Acid. Cerebral Cortex 2019, 30: 226-240. PMID: 31034037, DOI: 10.1093/cercor/bhz083.Peer-Reviewed Original ResearchConceptsVisual acuityDietary DHASynaptic connectivityFatty Acid Docosahexaenoic AcidVivo electrophysiological recordingsSize of synapsesEarly neuronal differentiationDose-dependent mannerFatty acid DHACortical maturationYoung miceAwake miceDendritic arborsCultured neuronsDHA's roleVisual cortexFunctional maturationPostsynaptic specializationsElectrophysiological recordingsCortical processingBrain developmentDocosahexaenoic acidAcid DHAPostnatal stagesNeuronal differentiationShort-term high-fat diet modulates several inflammatory, ER stress, and apoptosis markers in the hippocampus of young mice
Nakandakari S, Muñoz V, Kuga G, Gaspar R, Sant'Ana M, Pavan I, da Silva L, Morelli A, Simabuco F, da Silva A, de Moura L, Ropelle E, Cintra D, Pauli J. Short-term high-fat diet modulates several inflammatory, ER stress, and apoptosis markers in the hippocampus of young mice. Brain Behavior And Immunity 2019, 79: 284-293. PMID: 30797044, DOI: 10.1016/j.bbi.2019.02.016.Peer-Reviewed Original ResearchConceptsHigh-fat dietYoung miceShort-term HFD feedingMice fed high-fat dietFed high-fat dietHippocampus of miceER stressDisease developmentShort-term consumptionAlzheimer's disease developmentPotential molecular mechanismsHOMA-IRHFD feedingAD markersMicroglial cellsAD pathogenesisRisk factorsInflammatory signalsDiet modulatesΒ-amyloidCleaved caspase3HippocampusApoptosis markersHigh expressionMice
2018
Metabolic imaging with the use of fluorescence lifetime imaging microscopy (FLIM) accurately detects mitochondrial dysfunction in mouse oocytes
Sanchez T, Wang T, Pedro MV, Zhang M, Esencan E, Sakkas D, Needleman D, Seli E. Metabolic imaging with the use of fluorescence lifetime imaging microscopy (FLIM) accurately detects mitochondrial dysfunction in mouse oocytes. Fertility And Sterility 2018, 110: 1387-1397. PMID: 30446247, PMCID: PMC6289735, DOI: 10.1016/j.fertnstert.2018.07.022.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedComputer SystemsEmbryo Culture TechniquesEmbryo, MammalianEmbryonic DevelopmentEndopeptidase ClpFemaleFlavin-Adenine DinucleotideFluorescenceMaleMaternal AgeMiceMice, Inbred C57BLMice, KnockoutMicroscopy, FluorescenceMitochondriaMolecular ImagingNADOocytesReactive Oxygen SpeciesConceptsBlastocyst development rateOocyte dysfunctionReactive oxygen species levelsFlavin adenine dinucleotide (FAD) autofluorescenceMetabolic dysfunctionOxygen species levelsYoung miceMetabolic parametersOld miceMAIN OUTCOMEGlobal knockoutDysfunctionNoninvasive toolNormal oocytesMetabolic imagingMitochondrial dysfunctionMiceOld oocytesFLIM parametersROS levelsMetabolic differencesMitochondrial functionNicotinamide adenine dinucleotide dehydrogenaseIndividual oocytesWild-type oocytes
2017
Macrophage-released ADAMTS1 promotes muscle stem cell activation
Du H, Shih C, Wosczyna M, Mueller A, Cho J, Aggarwal A, Rando T, Feldman B. Macrophage-released ADAMTS1 promotes muscle stem cell activation. Nature Communications 2017, 8: 669. PMID: 28939843, PMCID: PMC5610267, DOI: 10.1038/s41467-017-00522-7.Peer-Reviewed Original ResearchConceptsSatellite cell activationRegulation of satellite cell activityIncreased satellite cell activityCell activationSatellite cellsMuscle stem cell nicheActivation of satellite cellsActivation of muscle stem cellsImprove muscle regenerationMuscle stem cellsMacrophages in vivoPostnatal muscle growthStem cell nicheExpression of ADAMTS1Young miceMuscle regenerationMuscle injuryOverexpression of ADAMTS1Cell nicheStem cellsMetalloproteinase activityNotch signalingADAMTS1MacrophagesMuscle growthMETHIONINE RESTRICTION ALTERS HEPATIC MIRNAS INVOLVED IN METABOLISM IN YOUNG, OBESE, AND AGED MICE
Park M, Cooke D, Plummer J, Ables G, Hens J. METHIONINE RESTRICTION ALTERS HEPATIC MIRNAS INVOLVED IN METABOLISM IN YOUNG, OBESE, AND AGED MICE. Innovation In Aging 2017, 1: 857-857. PMCID: PMC6184731, DOI: 10.1093/geroni/igx004.3084.Peer-Reviewed Original ResearchDIO miceAged miceMethionine restrictionYoung miceNonalcoholic fatty liver diseaseDiet-induced obese miceMiR-33-5pFatty liver conditionFatty liver diseaseDietary methionine restrictionType II diabetesExpression of mRNAAge-associated disordersBile acid transportLiver diseaseLiver functionObese miceLet-7gLiver conditionsMR dietOld miceHepatic expressionTransport of cholesterolBile acidsII diabetesHistone deacetylase inhibitors reverse age-related increases in side effects of haloperidol in mice
Montalvo-Ortiz JL, Fisher DW, Rodríguez G, Fang D, Csernansky JG, Dong H. Histone deacetylase inhibitors reverse age-related increases in side effects of haloperidol in mice. Psychopharmacology 2017, 234: 2385-2398. PMID: 28421257, PMCID: PMC5538925, DOI: 10.1007/s00213-017-4629-2.Peer-Reviewed Original ResearchConceptsMotor side effectsAged miceSide effectsValproic acidAge-related increaseHDAC inhibitorsAntipsychotic-induced side effectsDrd2 promoterAdjunct treatment strategyHistone deacetylase inhibitor valproic acidProtein levelsDopamine D2 receptorsInhibitor valproic acidHistone deacetylase inhibitorsDrug-dependent decreaseBackgroundOlder patientsMotor deficitsC57BL/6 miceAntagonist haloperidolTreatment strategiesYoung miceD2 receptorsPharmacodynamic mechanismsHaloperidolDeacetylase inhibitorsTAM Receptors Are Not Required for Zika Virus Infection in Mice
Hastings AK, Yockey LJ, Jagger BW, Hwang J, Uraki R, Gaitsch HF, Parnell LA, Cao B, Mysorekar IU, Rothlin CV, Fikrig E, Diamond MS, Iwasaki A. TAM Receptors Are Not Required for Zika Virus Infection in Mice. Cell Reports 2017, 19: 558-568. PMID: 28423319, PMCID: PMC5485843, DOI: 10.1016/j.celrep.2017.03.058.Peer-Reviewed Original ResearchConceptsTAM receptorsZika virusAbsence of IFNARGlobal public health concernNon-pregnant miceZika virus infectionAdult female micePublic health concernZIKV entryZIKV infectionFemale miceViral inoculationZIKV replicationMertk (TAM) receptorsYoung miceVirus infectionEntry receptorViral titersViral replicationCell tropismInfectionHealth concernMiceAxlReceptors
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