2025
Evaluating pathogenicity of TPM1 variants of unknown significance using in-silico and in-vitro models
Halder S, Bellitto J, Rynkiewicz M, Cheung F, Liu D, Firlar I, Bongiorno A, Barry M, Sewanan L, Moore J, Lehman W, Campbell S. Evaluating pathogenicity of TPM1 variants of unknown significance using in-silico and in-vitro models. The Journal Of Precision Medicine Health And Disease 2025, 2: 100008. DOI: 10.1016/j.premed.2025.100008.Peer-Reviewed Original ResearchIn vitro motilityFilament motilityContext of cardiomyopathyVariant classificationGenetic screeningTwitch contraction forceComputational pipelineMyosin activityEvaluate pathogenicityDiversity changesFunctional studiesIn silicoTropomyosinTPM1VUSMotilityInherited cardiomyopathyCa2+ sensitivityVariantsIn vitro modelIn vitro dataReduced abilityIPSC-derived cardiomyocytesLow Ca2+Ca2+Prevalence and Phenotype of Food Allergy in Children with Cystic Fibrosis
Nguyen H, Shabanova V, McCollum S, Polk B, Lee T, Whittington K, Cunha P, Bruscia E, Egan M, Emmenegger M, Leeds S. Prevalence and Phenotype of Food Allergy in Children with Cystic Fibrosis. Annals Of Allergy Asthma & Immunology 2025 PMID: 40550267, DOI: 10.1016/j.anai.2025.06.024.Peer-Reviewed Original ResearchCystic fibrosisCF patientsFood allergyUS pediatric populationElectronic medical recordsPediatric populationPhenotypes of food allergyRetrospective pediatric cohort studyPrevalence of FAFA prevalenceCystic Fibrosis Foundation RegistryMale CF patientsUnited StatesPediatric CF patientsPancreatic enzyme replacementPediatric cohort studyIgE-mediated FACohort studyEstimated prevalenceInclusion criteriaMedical informationDevelopment of FAMedical recordsFA diagnosisPrevalence1647-P: Coenzyme A Synthase Knockdown Increases Hepatic Mitochondrial Fat Oxidation and Reduces Hepatic Steatosis and Hepatic Insulin Resistance
GASPAR R, SAKUMA I, HUBBARD B, LAMOIA T, ZHENG J, PARIKH S, KAHN M, SILVEIRA L, DUFOUR S, NASIRI A, PERELIS M, PETERSEN K, SAMUEL V, SHULMAN G. 1647-P: Coenzyme A Synthase Knockdown Increases Hepatic Mitochondrial Fat Oxidation and Reduces Hepatic Steatosis and Hepatic Insulin Resistance. Diabetes 2025, 74 DOI: 10.2337/db25-1647-p.Peer-Reviewed Original ResearchHFD-fed miceAcetyl-CoAHepatic insulin resistanceHFD-fedHepatic acetyl-CoA contentMalonyl-CoA levelsCoenzyme A synthaseFatty acid synthesisHepatic acetyl-CoAAcetyl-CoA contentSteatotic liver diseasePathogenesis of type 2 diabetesHigh-fat dietTCA cycleMitochondrial fat oxidationWhole-body energy expenditureCoA biosynthesisHepatic steatosisAcid synthesisMetabolic pathwaysInsulin resistanceReduced hepatic steatosisDecreased hepatic steatosisCOASYTriacylglycerol content1823-P: The Beta-Cell Secretagogue Glyceraldehyde Induces Mitochondrial Leak Respiration, Not OXPHOS
CARDONE R, KIBBEY R, ZHAO X. 1823-P: The Beta-Cell Secretagogue Glyceraldehyde Induces Mitochondrial Leak Respiration, Not OXPHOS. Diabetes 2025, 74 DOI: 10.2337/db25-1823-p.Peer-Reviewed Original ResearchIncreased respirationSn-glycerol-3-phosphateMitochondrial leak respirationPlasma membrane permeabilizationMitochondria in situOligomycin-sensitive respirationMembrane permeabilizationATP synthesisMitochondrial respirationIN cellsDLGALeak respirationOXPHOSNADH oxidationGlyceraldehydeG3PStimulated respirationRespirationMitochondriaNADHPre-incubationInsulin releaseCells pre-incubatedSuccinateRotenone1824-P: Bioenergetic Advantage of Pyruvate Kinase Overcomes Mitochondrial OXPHOS in Beta-Cells to Initiate Insulin Secretion
RUZ-MALDONADO I, CARDONE R, MERRINS M, KIBBEY R. 1824-P: Bioenergetic Advantage of Pyruvate Kinase Overcomes Mitochondrial OXPHOS in Beta-Cells to Initiate Insulin Secretion. Diabetes 2025, 74 DOI: 10.2337/db25-1824-p.Peer-Reviewed Original ResearchPyruvate kinaseATP/ADP ratioMitochondrial OXPHOSHuman isletsBeta-cellsIntact miceOxygen consumption rateKATP channel closureInsulin secretionMitochondrial membrane potentialPlasma membrane depolarizationDose-dependent mannerIntramitochondrial ADPADP availabilityHyperpolarized mitochondriaInitial insulin secretionKATP channelsMitochondrial hyperpolarizationOXPHOS inhibitionINS-1Pyruvate metabolismETC complexesMembrane depolarizationATP synthesisOXPHOS1840-P: Pyruvate Kinase Bioenergetically Restricts OXPHOS in Beta Cells and Myotubules by Inducing Mitochondrial Membrane Hyperpolarization
DAVIDSON E, KIBBEY R. 1840-P: Pyruvate Kinase Bioenergetically Restricts OXPHOS in Beta Cells and Myotubules by Inducing Mitochondrial Membrane Hyperpolarization. Diabetes 2025, 74 DOI: 10.2337/db25-1840-p.Peer-Reviewed Original ResearchMitochondrial membrane potentialPyruvate kinaseHyperpolarization of mitochondrial membrane potentialRespiratory suppressionMitochondrial membrane potential differenceMitochondrial membrane hyperpolarizationCytosolic ATP/ADP ratioComplex V activityDigestive and Kidney DiseasesINS-1ATP hydrolysisATP synthesisPhosphoenolpyruvateMembrane hyperpolarizationPK substratesBlocking electron transportOXPHOSKidney diseaseATP/ADP ratioBeta cellsHyperpolarizationMembrane potentialPK activityState 3Oligos83-OR: GLP-1RA Efficacy Doubled with Small Molecule Modulators of Pyruvate Kinase for Obesity Treatment
KIBBEY R, CARDONE R, RUZ-MALDONADO I, ZHAO X, BROWN S, FOSTER H, MERRINS M. 83-OR: GLP-1RA Efficacy Doubled with Small Molecule Modulators of Pyruvate Kinase for Obesity Treatment. Diabetes 2025, 74 DOI: 10.2337/db25-83-or.Peer-Reviewed Original ResearchGLP-1 RAsLean massCombo groupInsulin secretionOptimal treatment of obesityPreservation of lean massObesity treatmentTreatment groupsIslet healthCa2+ oscillationsCa2+ imagingFasting glucose levelsC57BL/6J male miceTreatment of obesityImproved insulin sensitivityGLP-1RAAUC glucoseOptimal treatmentDIO miceMale miceStudy endPlaceboGLP-1Body compositionInsulin sensitivity1686-P: Novel Combination of a Mitochondrial Protonophore (MP) and an Acetyl-CoA Carboxylase 2 (ACC2) Inhibitor Causes Weight Loss and Preserves Lean Mass in Obese Mice
SRODA N, SHARMA M, MURAKAMI E, LOGAN C, WENG S, KIRBY B, MYERS R, SUBRAMANIAN M, SHULMAN G, VIJAYAKUMAR A. 1686-P: Novel Combination of a Mitochondrial Protonophore (MP) and an Acetyl-CoA Carboxylase 2 (ACC2) Inhibitor Causes Weight Loss and Preserves Lean Mass in Obese Mice. Diabetes 2025, 74 DOI: 10.2337/db25-1686-p.Peer-Reviewed Original ResearchLean massMitochondrial protonophoreDIO miceFood intakeFat mass lossReduced lean massWeight lossBody weightAcetyl-CoA carboxylase 2Obesity-associated disordersMale DIO miceFat massSemaglutideDiet-inducedNovel combinationObese miceMetabolic disordersEnhanced fatty acid oxidationMiceFatty acid oxidationEvaluation of combinationsObesityInhibitorsTreated withIntake1687-P: Sequential Combination of the Mitochondrial Protonophore (MP) TLC-6740 with Semaglutide Normalizes Body Weight and Preserves Lean Mass in DIO Mice
SRODA N, SHARMA M, MURAKAMI E, LOGAN C, WENG S, KIRBY B, MYERS R, SUBRAMANIAN M, SHULMAN G, VIJAYAKUMAR A. 1687-P: Sequential Combination of the Mitochondrial Protonophore (MP) TLC-6740 with Semaglutide Normalizes Body Weight and Preserves Lean Mass in DIO Mice. Diabetes 2025, 74 DOI: 10.2337/db25-1687-p.Peer-Reviewed Original ResearchLean massDIO miceFM lossBody weightMitochondrial protonophoreData support evaluationNormal body weightReduced food intakeRegulate body weightOral glucose toleranceEvaluate weight lossIncreased energy expenditureMale DIO miceSequential combinationDiet-inducedFood intakeGlucose toleranceMetabolic disordersSemaglutideMiceWeight lossEnergy expenditureOGTTOGTT AUCIncretin1694-P: De Novo or Sequential Combination of the Mitochondrial Protonophore TLC-1180 with Semaglutide Improves Weight Loss and Preserves Lean Mass in Dio Mice
SHARMA M, SRODA N, MURAKAMI E, LOGAN C, WENG S, KIRBY B, MYERS R, SUBRAMANIAN M, SHULMAN G, VIJAYAKUMAR A. 1694-P: De Novo or Sequential Combination of the Mitochondrial Protonophore TLC-1180 with Semaglutide Improves Weight Loss and Preserves Lean Mass in Dio Mice. Diabetes 2025, 74 DOI: 10.2337/db25-1694-p.Peer-Reviewed Original Research215-OR: Increased White Adipose Tissue Oxidative Capacity and Insulin Resistance Are Early Changes upon High-Fat Diet in Healthy Humans
XOURAFA G, GRANATA C, TRENKAMP S, KORZEKWA B, SCHRAUWEN-HINDERLING V, PETERSEN K, SHULMAN G, KAHL S, RODEN M. 215-OR: Increased White Adipose Tissue Oxidative Capacity and Insulin Resistance Are Early Changes upon High-Fat Diet in Healthy Humans. Diabetes 2025, 74 DOI: 10.2337/db25-215-or.Peer-Reviewed Original ResearchWhite adipose tissueFat mass indexInsulin resistanceHigh-fat dietLipid contentEuropean Association for the StudyNon-esterified fatty acidsInsulin sensitivityLiver lipid contentParallel-group studyEuropean Association for the Study of DiabetesNon-obese individualsAdipose tissue insulin resistanceWhole-body insulin sensitivityPromote insulin resistanceTissue insulin resistanceHepatic ATP levelsHigh-resolution respirometryHyperinsulinemic-euglycemic clampMitochondrial respirationStudy of DiabetesWhole-body insulin resistanceInsulin stimulationHepatic lipid contentHypercaloric high-fat dietRelative roles of HCN4 and synaptic excitation in pyramidal neuron firing rates in a hyperactive Rheb‐mTOR condition
Chatzikalymniou A, Getz S, Xu Y, Patel D, Soltesz I, Bordey A. Relative roles of HCN4 and synaptic excitation in pyramidal neuron firing rates in a hyperactive Rheb‐mTOR condition. Epilepsia 2025 PMID: 40512428, DOI: 10.1111/epi.18456.Peer-Reviewed Original ResearchFocal malformations of cortical developmentExcitatory postsynaptic currentsPyramidal neuronsExcitatory postsynaptic current amplitudeFiring rateMalformations of cortical developmentPyramidal cell excitabilityExcitatory synaptic inputsNeuronal firing rateAcute brain slicesSingle-cell computational modelingIncreased dendritic complexityCortical pyramidal neuronsConstitutively active RhebPostsynaptic currentsFocal malformationsSynaptic excitationNeuronal excitabilityMTOR pathway genesDe Novo somatic mutationsPostnatal dayCell excitabilityFetal developmentIncreased mTOR activitySynaptic inputsML-ROM wall shear stress prediction in patient-specific vascular pathologies under a limited clinical training data regime
Chatpattanasiri C, Ninno F, Stokes C, Dardik A, Strosberg D, Aboian E, von Tengg-Kobligk H, Díaz-Zuccarini V, Balabani S. ML-ROM wall shear stress prediction in patient-specific vascular pathologies under a limited clinical training data regime. PLOS ONE 2025, 20: e0325644. PMID: 40504795, PMCID: PMC12161591, DOI: 10.1371/journal.pone.0325644.Peer-Reviewed Original ResearchConceptsReduced order modelComputational fluid dynamicsWall shear stressWall shear stress dataWall shear stress predictionsShear stress predictionsStress predictionShear stressFluid dynamicsLong processing timeFlowrate waveformsComputational cost analysisML-ROMOrder modelNumerical simulationsSpeed-up ratioProcessing timeMapping modelComputational costComputational demandsComplex case studyCase studyData-driven approachCost analysisFlowEndothelial 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 cellsSepsisImprovements 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 PR, Busse B, Weise K, Oheim R, Rolvien T*, Braddock DT*. 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. J Bone Miner Res 2025 PMID: 40495691, DOI: 10.1093/jbmr/zjaf082.Peer-Reviewed Original ResearchSystemic 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 systemSensory Neurons that Detect Stretch and Nutrients in the Digestive System
Williams E, Chang R, Strochlic D, Umans B, Lowell B, Liberles S. Sensory Neurons that Detect Stretch and Nutrients in the Digestive System. Cell 2025, 188: 3623-3624. PMID: 40485186, DOI: 10.1016/j.cell.2025.05.043.Peer-Reviewed Original ResearchFertile Ground for Mathematical Modeling: Therapeutic and Diagnostic Nanoparticle Transport in the Glomerulus
Richfield O, Cortez R, Navar L, Pober J, Zheng J, Saltzman W. Fertile Ground for Mathematical Modeling: Therapeutic and Diagnostic Nanoparticle Transport in the Glomerulus. Regenerative Engineering And Translational Medicine 2025, 1-17. DOI: 10.1007/s40883-025-00424-x.Peer-Reviewed Original ResearchChronic kidney diseaseGlomerular diseaseTreat glomerular diseasesKidney diseaseMaintenance of fluid balanceGlomerular filtration barrierTherapeutic optionsGlomerular hemodynamicsGlomerular pathologyFluid balanceGlomerular cellsGlomerular dysfunctionKidney failureRenal glomeruliGlomeruliHuman kidneyGlomerular capillariesNanoparticle transportUrine formationDiseaseFiltration barrierNP transportKidneyNP interactionsPhysiological maintenanceApplication of instant assembly of collagen to bioprint cardiac tissues
Xiao H, Liang Z, Gong X, Jordan S, Rossello-Martinez A, Gokhan I, Li X, Wen Z, Lee S, Campbell S, Qyang Y, Mak M. Application of instant assembly of collagen to bioprint cardiac tissues. APL Bioengineering 2025, 9: 026124. PMID: 40520649, PMCID: PMC12165719, DOI: 10.1063/5.0252746.Peer-Reviewed Original ResearchPreoperative Smoking Cessation Impacts Presentation and Long-term Neurologic Outcomes of Carotid Endarterectomy
Schwartz A, Carter W, Tonnessen B, Arhuidese I, Cardella J, Dardik A, Guzman R, Chaar C. Preoperative Smoking Cessation Impacts Presentation and Long-term Neurologic Outcomes of Carotid Endarterectomy. Journal Of Vascular Surgery 2025, 81: e185-e186. DOI: 10.1016/j.jvs.2025.03.331.Peer-Reviewed Original Research
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