2025
Preclinical Activity of Datopotamab Deruxtecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2, in Uterine Serous Carcinoma.
Greenman M, Demirkiran C, Bellone S, Hartwich T, McNamara B, Ettorre V, Santin N, Sethi N, Yang-Hartwich Y, Papatla K, Ratner E, Santin A. Preclinical Activity of Datopotamab Deruxtecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2, in Uterine Serous Carcinoma. Cancer Research Communications 2025, 5: 774-782. PMID: 40299780, PMCID: PMC12062949, DOI: 10.1158/2767-9764.crc-25-0057.Peer-Reviewed Original ResearchConceptsTrophoblast cell surface antigen 2Uterine serous carcinomaAntibody-dependent cell-mediated cytotoxicityAntibody-drug conjugatesCell-mediated cytotoxicitySerous carcinomaPreclinical activityCell linesTargets trophoblast cell-surface antigen-2Presence of peripheral blood lymphocytesTreatment of uterine serous carcinomaInduce antibody-dependent cell-mediated cytotoxicityPrimary USC cell linesRecurrent uterine serous carcinomaUSC xenograftsUterine serous carcinoma cell linesAntigen 2In vivoPrimary tumor cell linesTROP2 overexpressionBiomarker-targeted therapiesControl ADCChromium release assayHigher recurrence rateTumor growth suppressionSimplified methods for SERT occupancy estimation measured with [11C]DASB PET bolus plus infusion
Ponce de León M, Murgaš M, Silberbauer L, Hacker M, Gryglewski G, Hahn A, Lanzenberger R. Simplified methods for SERT occupancy estimation measured with [11C]DASB PET bolus plus infusion. NeuroImage 2025, 311: 121208. PMID: 40221064, DOI: 10.1016/j.neuroimage.2025.121208.Peer-Reviewed Original ResearchSerotonin transporterBolus plus constant infusionSerotonin transporter occupancyDepressive disorderBinding potentialBolus plus infusionReference regionCitalopramHealthy controlsArterial blood samplesPET/MRI scansPET scansOccupational valuesIntravenous applicationConstant infusionBlood samplesIn vivoAntidepressantsInfusionSaline solutionSerotoninHighest agreementDisordersRadioligandPlaceboSuppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases
Rubinelli L, Manzo O, Sungho J, Del Gaudio I, Bareja R, Marino A, Palikhe S, Di Mauro V, Bucci M, Falcone D, Elemento O, Ersoy B, Diano S, Sasset L, Di Lorenzo A. Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases. Nature Communications 2025, 16: 1968. PMID: 40000621, PMCID: PMC11862206, DOI: 10.1038/s41467-025-56869-9.Peer-Reviewed Original ResearchConceptsNogo-BEndothelial dysfunctionHFD miceCardiometabolic diseasesSphingolipid signalingDevelopment of therapeutic strategiesBioactive sphingolipidsCeramide degradationSphingosine-1-phosphateHepatic glucose productionIn vivo evidenceEndothelial cellsEndothelial specific deletionCeramideBiosynthesisHigh-fat dietPathological implicationsSphingolipidsGlucose productionHFDIn vivoMale miceMetabolic dysfunctionTherapeutic strategiesMetabolic disorderstRNA m1A modification regulates cholesterol biosynthesis to promote antitumor immunity of CD8+ T cells
Miao S, Li H, Song X, Liu Y, Wang G, Kan C, Ye Y, Liu R, Li H. tRNA m1A modification regulates cholesterol biosynthesis to promote antitumor immunity of CD8+ T cells. Journal Of Experimental Medicine 2025, 222: e20240559. PMID: 39873720, PMCID: PMC11774205, DOI: 10.1084/jem.20240559.Peer-Reviewed Original ResearchConceptsCD8+ T cellsT cellsTumor-killing functionTransfer RNARegulating cholesterol biosynthesisAntitumor immunityCapacity of CD8+ T cellsActivation of CD8+ T cellsCholesterol biosynthesisM1A modificationTumor-killing capacityAntitumor responseATP citrate lyaseCancer immunotherapyCD8Effector functionsMetabolic reprogrammingProtein translationBiosynthetic demandsCitrate lyaseIn vitro assaysIn vivoPosttranscriptional mechanismsRegulatory checkpointsBiosynthesis
2024
Malate 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 reductionRole of Toll-like receptor 2 during infection of Leptospira spp: A systematic review
Kappagoda C, Senavirathna I, Agampodi T, Agampodi S. Role of Toll-like receptor 2 during infection of Leptospira spp: A systematic review. PLOS ONE 2024, 19: e0312466. PMID: 39729468, PMCID: PMC11676585, DOI: 10.1371/journal.pone.0312466.Peer-Reviewed Original ResearchConceptsToll-like receptor 2Toll-like receptor 2 expressionReceptor 2TLR2 responsesSystematic reviewIn vivoImmune effectorsIn vitroEx vivoHuman studiesInvolvement of Toll-like receptor 2Systematic Review Centre for Laboratory Animal Experimentation riskInvolvement of TLR4Increased TLR2 expressionNational Institutes of Health Quality Assessment ToolEffective immune responseIn vitro studiesHuman leptospirosisTLR2 involvementRisk of biasIn vivo studiesTLR2 expressionOffice of Health AssessmentWeb of ScienceImmune responseArtificial intelligence-guided design of lipid nanoparticles for pulmonary gene therapy
Witten J, Raji I, Manan R, Beyer E, Bartlett S, Tang Y, Ebadi M, Lei J, Nguyen D, Oladimeji F, Jiang A, MacDonald E, Hu Y, Mughal H, Self A, Collins E, Yan Z, Engelhardt J, Langer R, Anderson D. Artificial intelligence-guided design of lipid nanoparticles for pulmonary gene therapy. Nature Biotechnology 2024, 1-10. PMID: 39658727, DOI: 10.1038/s41587-024-02490-y.Peer-Reviewed Original ResearchLipid nanoparticlesMRNA deliveryIonizable lipidsImprove nanoparticle deliveryPulmonary gene therapyDelivery in vitroNucleic acid deliveryNeural networkGene therapyNasal mucosaNanoparticle deliveryMouse lungFerret lungsAcid deliveryMouse muscleMessage-passing neural networkDelivery technologiesIn vivoLipid designLungMiceDeliveryDeep learningMRNALipidTumor-Specific Antigen Delivery for T-cell Therapy via a pH-Sensitive Peptide Conjugate.
Yurkevicz A, Liu Y, Katz S, Glazer P. Tumor-Specific Antigen Delivery for T-cell Therapy via a pH-Sensitive Peptide Conjugate. Molecular Cancer Therapeutics 2024, 24: 105-117. PMID: 39382073, PMCID: PMC11695185, DOI: 10.1158/1535-7163.mct-23-0809.Peer-Reviewed Original ResearchMajor histocompatibility complexT cellsTumor cellsTreatment of tumor-bearing miceMajor histocompatibility complex class I pathwaySuppression of tumor growthTumor cells in vivoT-cell therapySyngeneic tumor modelsTumor-specific antigensTumor-bearing miceMelanoma tumor cellsT cell activationHealthy tissueTarget tumor cellsIn vivoIn vitroMicroenvironment of tumorsUnique delivery platformsClass I pathwayCell-based therapiesTargeted cancer therapyCells in vivoAntigen processing pathwayAcidic microenvironment of tumorsIdentification of FGFR4 as a regulator of myofibroblast differentiation in pulmonary fibrosis
Ghanem M, Justet A, Jaillet M, Vasarmidi E, Boghanim T, Hachem M, Vadel A, Joannes A, Mordant P, Balayev A, Adams T, Mal H, Cazes A, Poté N, Mailleux A, Crestani B. Identification of FGFR4 as a regulator of myofibroblast differentiation in pulmonary fibrosis. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2024, 327: l818-l830. PMID: 39350729, DOI: 10.1152/ajplung.00184.2023.Peer-Reviewed Original ResearchWild type littermatesFibroblast growth factorMurine embryonic fibroblastsEndothelin-1Pulmonary fibrosisFGFR4 inhibitionBleomycin-induced pulmonary fibrosisIn vitroMyofibroblast differentiationBleomycin-induced lung fibrosisPulmonary fibrosis in vivoTGF-bLung fibroblastsPro-fibrotic propertiesProtein levelsIn vivoAnti-fibrotic propertiesFibrosis in vivoRegulation of myofibroblast differentiationDevelopment of bleomycin-induced lung fibrosisWT miceTherapeutic optionsHuman lung fibroblastsIPF lungsLung fibrosisA Minimalist Pathogen‐Like Sugar Nanovaccine for Enhanced Cancer Immunotherapy
Miao Y, Niu L, Lv X, Zhang Q, Xiao Z, Ji Z, Chen L, Liu Y, Liu N, Zhu J, Yang Y, Chen Q. A Minimalist Pathogen‐Like Sugar Nanovaccine for Enhanced Cancer Immunotherapy. Advanced Materials 2024, 36: e2410715. PMID: 39210649, DOI: 10.1002/adma.202410715.Peer-Reviewed Original ResearchCancer immunotherapyMaturation of antigen-presenting cellsVaccine carriersImmune checkpoint blockade therapyAntigen-specific immune responsesInhibition of tumor growthCheckpoint blockade therapyEnhanced cancer immunotherapyAntigen-presenting cellsVaccine delivery technologiesB16-OVABlockade therapyImmune activationTumor modelTumor growthAntigen loadNanovaccineImmune responseMeticulous screeningAntigenic peptidesImmunostimulatory characteristicsChain ratioDelivery technologiesImmunotherapyIn vivoPhosphoglycerate kinase is a central leverage point in Parkinson’s disease–driven neuronal metabolic deficits
Kokotos A, Antoniazzi A, Unda S, Ko M, Park D, Eliezer D, Kaplitt M, De Camilli P, Ryan T. Phosphoglycerate kinase is a central leverage point in Parkinson’s disease–driven neuronal metabolic deficits. Science Advances 2024, 10: eadn6016. PMID: 39167658, PMCID: PMC11338267, DOI: 10.1126/sciadv.adn6016.Peer-Reviewed Original ResearchConceptsPhosphoglycerate kinase 1Metabolic deficitsExpressions of Phosphoglycerate Kinase 1Dopamine axonsParkinson's diseasePD-associated pathologyViral expressionLoss of functionNeuronal glycolysisSusceptibility lociIn vivoFamilial Parkinson's diseasePD therapeuticsMetabolic lesionsProduction kineticsKinase 1Mitochondrial integrityPhosphoglycerate kinaseBioenergetic deficitsSynaptic dysfunctionGenetic originDeficitsPARK7/DJ-1PhosphoglycerateHebbian instruction of axonal connectivity by endogenous correlated spontaneous activity
Matsumoto N, Barson D, Liang L, Crair M. Hebbian instruction of axonal connectivity by endogenous correlated spontaneous activity. Science 2024, 385: eadh7814. PMID: 39146415, DOI: 10.1126/science.adh7814.Peer-Reviewed Original ResearchConceptsSpontaneous activitySpontaneous retinal wavesAxonal connectionsPatterns of correlated activityNeonatal miceEvidence in vivoRetinal wavesPostsynaptic neuronsNeuronal activityIn vivoAxonal arborsAxonal processesAxonsRetinocollicular axonsNeural connectionsIndividual axonsMorphological changesSubcellular precisionEndogenous patternTitration of RAS alters senescent state and influences tumour initiation
Chan A, Zhu H, Narita M, Cassidy L, Young A, Bermejo-Rodriguez C, Janowska A, Chen H, Gough S, Oshimori N, Zender L, Aitken S, Hoare M, Narita M. Titration of RAS alters senescent state and influences tumour initiation. Nature 2024, 633: 678-685. PMID: 39112713, PMCID: PMC11410659, DOI: 10.1038/s41586-024-07797-z.Peer-Reviewed Original ResearchConceptsTumor typesOncogenic RAS-induced senescenceInfluence tumor initiationProgenitor-like featuresTumor-initiating phenotypeSingle-cell RNA sequencing analysisModel in vivoHCC subclassesModel in vitroHepatocellular carcinomaTumor suppressor mechanismEarly tumorigenesisTumor initiationEarly-onsetProgenitor featuresInduce tumorsSuppressor mechanismTumorLate-onsetRNA sequencing analysisOncogenic stressRas-induced senescenceIn vivoMolecular signaturesOncogene dosageBACH2 regulates diversification of regulatory and proinflammatory chromatin states in TH17 cells
Thakore P, Schnell A, Huang L, Zhao M, Hou Y, Christian E, Zaghouani S, Wang C, Singh V, Singaraju A, Krishnan R, Kozoriz D, Ma S, Sankar V, Notarbartolo S, Buenrostro J, Sallusto F, Patsopoulos N, Rozenblatt-Rosen O, Kuchroo V, Regev A. BACH2 regulates diversification of regulatory and proinflammatory chromatin states in TH17 cells. Nature Immunology 2024, 25: 1395-1410. PMID: 39009838, DOI: 10.1038/s41590-024-01901-1.Peer-Reviewed Original ResearchConceptsTransposase-accessible chromatin sequencingSingle-cell RNA sequencingTh17 heterogeneitySingle-cell assaysScATAC-seqChromatin landscapeChromatin stateChromatin sequencingRegulatory networksScRNA-seqTh17 cell pathogenicityHuman geneticsIn vivoRNA sequencingChromatin configurationRegulatory pathwaysTissue homeostasisCell statesCells in vitroBach2ChromatinSequenceCellsType 1 helper T (Th1) cellsCD4+ T cell subsetsP-587 Salidroside improves the reproductive capacity of aged mice via improving oocyte mitochondrial function
Gu J, Hua R, Guo C, Hai Z, Xiao Y, Zhao P, Li Y, Su J, Wang T. P-587 Salidroside improves the reproductive capacity of aged mice via improving oocyte mitochondrial function. Human Reproduction 2024, 39: deae108.919. DOI: 10.1093/humrep/deae108.919.Peer-Reviewed Original ResearchOvarian agingIVM treatment groupsGV oocytesFemale miceTreatment groupsAged miceDays of in vivo treatmentOocyte mitochondrial functionIn vivoOvarian reserve functionIn vitroTreatment of ovarian agingFunction of miceMitochondrial functionFollicle reserveMII oocytesTherapeutic effect of salidrosideAged oocytesParthenogenetic activationC57/B6 miceOocyte qualityMaternal ageParthenogenetic embryosWIDER IMPLICATIONSSalidroside supplementationDisordered but effective: short linear motifs as gene therapy targets for hyperexcitability disorders
Dib-Hajj S, Waxman S. Disordered but effective: short linear motifs as gene therapy targets for hyperexcitability disorders. Journal Of Clinical Investigation 2024, 134: e182198. PMID: 38949022, PMCID: PMC11213459, DOI: 10.1172/jci182198.Peer-Reviewed Original ResearchConceptsTetrodotoxin-sensitiveHyperexcitability disordersSensory neuronsExcitability of sensory neuronsGene therapy modalitiesPeripheral sensory neuronsVoltage-gated sodiumMinimal side effectsGene therapyInduce analgesiaTherapy modalitiesSide effectsTherapeutic strategiesNav channelsAttenuating excitationIn vivoHyperexcitabilityAnalgesiaNeuronsDisordersPainTherapyGenesBiodistributionRats1583-P: Measuring Mitochondrial Metabolism In Vivo with [1,2-13C2]-L-Glutamine Mass Isotopomers
SIEBEL S, CARDONE R, MASON G, KIBBEY R. 1583-P: Measuring Mitochondrial Metabolism In Vivo with [1,2-13C2]-L-Glutamine Mass Isotopomers. Diabetes 2024, 73 DOI: 10.2337/db24-1583-p.Peer-Reviewed Original ResearchAbstract 2121: SUV39H1 Mediated Regulation Of KLF4 And KDM4a Coordinate Smooth Muscle Cell Phenotypic Plasticity
Chatterjee P, Chakraborty R, Sizer A, Xie Y, Hwa J, Martin K. Abstract 2121: SUV39H1 Mediated Regulation Of KLF4 And KDM4a Coordinate Smooth Muscle Cell Phenotypic Plasticity. Arteriosclerosis Thrombosis And Vascular Biology 2024, 44: a2121-a2121. DOI: 10.1161/atvb.44.suppl_1.2121.Peer-Reviewed Original ResearchRNA-seqPhenotypic plasticityEpigenetic regulationH3K9me3 repressive marksRNA-seq transcriptomicsContractile genesEpigenetic transcriptional repressionCell phenotypic plasticityH3K9me3 markExpression of SUV39H1Repressive marksTranscriptional repressionChromatin immunoprecipitationHistone methyltransferaseDedifferentiation in vitroIn vivoSUV39H1 knockdownH3K9me3MRNA stabilitySUV39H1Gene expressionPlasticity of vascular smooth muscle cellsRegulation of Klf4GenesH3K9me3 expressionMacrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT): Pathways to Tumorigenesis and Therapeutic Opportunities
Valdez C, Sánchez-Zuno G, Bucala R, Tran T. Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT): Pathways to Tumorigenesis and Therapeutic Opportunities. International Journal Of Molecular Sciences 2024, 25: 4849. PMID: 38732068, PMCID: PMC11084905, DOI: 10.3390/ijms25094849.Peer-Reviewed Original ResearchConceptsInhibition of MIFResponse to infectionNon-canonical signaling pathwaysClinical studiesCancer patientsClinical trialsInflammatory cytokinesDriving tumorigenesisClinical explorationCancer typesCancerDual inhibitionTherapeutic targetIn vivoIn vitroSignaling pathwayMIFAntitumor candidateBinding partnersFood perception promotes phosphorylation of MFFS131 and mitochondrial fragmentation in liver
Henschke S, Nolte H, Magoley J, Kleele T, Brandt C, Hausen A, Wunderlich C, Bauder C, Aschauer P, Manley S, Langer T, Wunderlich F, Brüning J. Food perception promotes phosphorylation of MFFS131 and mitochondrial fragmentation in liver. Science 2024, 384: 438-446. PMID: 38662831, DOI: 10.1126/science.adk1005.Peer-Reviewed Original ResearchConceptsMitochondrial fragmentationInsulin-stimulated suppression of hepatic glucose productionInduced mitochondrial fragmentationMitochondrial fission factorPro-opiomelanocortin (POMC)-expressing neuronsControl of hepatic glucose metabolismKnock-in mutationHepatic glucose metabolismFission factorMitochondrial dynamicsSerine 131Fragments in vitroNutrient availabilityKnock-in miceMitochondrial functionDynamic regulationHepatic glucose productionLiver mitochondriaSuppression of hepatic glucose productionMetabolic adaptationPhosphorylationNutritional stateGlucose productionIn vivoGlucose metabolism
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