2025
Design of sensitive monospecific and bispecific synthetic chimeric T cell receptors for cancer therapy
Simon S, Bugos G, Prins R, Rajan A, Palani A, Heyer K, Stevens A, Zeng L, Thompson K, Atilla P, Price J, Kluesner M, Jaeger-Ruckstuhl C, Shabaneh T, Olson J, Su X, Riddell S. Design of sensitive monospecific and bispecific synthetic chimeric T cell receptors for cancer therapy. Nature Cancer 2025, 1-19. PMID: 40097658, DOI: 10.1038/s43018-025-00927-0.Peer-Reviewed Original ResearchChimeric antigen receptorChimeric T cell receptorT cell receptorT cellsAdoptive transfer of T cells expressing chimeric antigen receptorsT cells expressing chimeric antigen receptorsChimeric antigen receptor T cellsBispecific CAR-T cellsPersistence of cancer cellsTCR-like signalsCAR-T cellsAntigen expression in vivoB-cell malignanciesMyeloma antigensExpression in vivoAdoptive transferEradicate tumorsAntigen sensitizationAntigen receptorFemale miceB cellsTumor heterogeneityPrevent relapseBispecific targetingImmune synapsesOrexin/hypocretin receptor 2 signaling in MCH neurons regulates REM sleep and insulin sensitivity
Izawa S, Fusca D, Jiang H, Heilinger C, Hausen A, Wunderlich F, Steuernagel L, Kloppenburg P, Brüning J. Orexin/hypocretin receptor 2 signaling in MCH neurons regulates REM sleep and insulin sensitivity. Cell Reports 2025, 44: 115277. PMID: 39946231, DOI: 10.1016/j.celrep.2025.115277.Peer-Reviewed Original ResearchConceptsMelanin-concentrating hormoneNon-rapid eye movementFemale miceInhibitory responsesREM sleepMelanin-concentrating hormone neuronsInsulin sensitivityReceptor type 2Melanin-concentrating hormone neuron populationImpaired insulin sensitivityNeuronal sub-populationsOX2R expressionOrexin neuronsOrexin signalingSelective agonistsModulate sleepBrain slicesClinical trialsOX2RRegulate sleepNarcolepsy treatmentOrexinNeuronal populationsRNA expressionType 2Classification of psychedelics and psychoactive drugs based on brain-wide imaging of cellular c-Fos expression
Aboharb F, Davoudian P, Shao L, Liao C, Rzepka G, Wojtasiewicz C, Indajang J, Dibbs M, Rondeau J, Sherwood A, Kaye A, Kwan A. Classification of psychedelics and psychoactive drugs based on brain-wide imaging of cellular c-Fos expression. Nature Communications 2025, 16: 1590. PMID: 39939591, PMCID: PMC11822132, DOI: 10.1038/s41467-025-56850-6.Peer-Reviewed Original ResearchConceptsAcute fluoxetinePsychoactive drugsMarkers of neural plasticityImmediate early gene expressionC-fos expressionChronic fluoxetineNative brain tissueBehavioral effectsPsychedelic propertiesBrain regionsChance levelEarly gene expressionPsychoactive compoundsNeural plasticityFluoxetinePsilocybinMDMAMeasuring drug actionTested malesPsychedelicsPreclinical assaysDrug actionKetamineFemale miceDrug classificationMicroglia modulate the cerebrovascular reactivity through ectonucleotidase CD39
Fu Z, Ganesana M, Hwang P, Tan X, Kinkaid M, Sun Y, Bian E, Weybright A, Chen H, Sol-Church K, Eyo U, Pridans C, Quintana F, Robson S, Kumar P, Venton B, Schaefer A, Kuan C. Microglia modulate the cerebrovascular reactivity through ectonucleotidase CD39. Nature Communications 2025, 16: 956. PMID: 39843911, PMCID: PMC11754601, DOI: 10.1038/s41467-025-56093-5.Peer-Reviewed Original ResearchConceptsCerebral blood flowEctonucleotidases CD39Whisker stimulationResponse to whisker stimulationCerebrovascular reactivityDeletion of CD39Blood flowInjection of adenosine triphosphateModulation of cerebral blood flowRegulation of cerebral blood flowExtracellular adenosine triphosphateInjection of adenosineBorder-associated macrophagesMicroglia repopulationExtracellular adenosineAdenosine triphosphateFemale miceBlood flow anomaliesP2RY12 receptorCo-transmitterMouse modelPharmacological inhibitionCD39MicrogliaMiceOlanzapine Induces Adipogenesis and Glucose Uptake by Activating Glycolysis and Synergizing with the PI3K-AKT Pathway
Li S, Fu Y, Wang W, Qiu J, Huang Y, Li X, Yang K, Yu X, Ma Y, Zhang Y, Zhang M, Li J, Li W. Olanzapine Induces Adipogenesis and Glucose Uptake by Activating Glycolysis and Synergizing with the PI3K-AKT Pathway. Current Neuropharmacology 2025, 23: 412-425. PMID: 39150031, DOI: 10.2174/1570159x22666240815120547.Peer-Reviewed Original ResearchAdministration of olanzapineTreated with olanzapineReactive oxygen speciesDownstream PI3K-Akt signal pathwayAssociated with obesityActive glycolysisAssessed body weightWeight gainDifferentiated 3T3-L1 preadipocytesLiver fat levelsPI3K-Akt pathwayOlanzapineDrug doseFemale miceDietary patternsMetabolic markersPI3K-AktFood intakeGlucose uptakeMouse modelGlycolipid abnormalitiesRodent modelsBody weightGAPDH expressionSignaling pathway
2024
Alcohol drinking is attenuated by PDE4 inhibition but partial microglia depletion is not sufficient to block stress-induced escalation of alcohol intake in female mice
Garcia-Rivas V, Soares A, Thomas M, Na J, Smith A, Picciotto M, Mineur Y. Alcohol drinking is attenuated by PDE4 inhibition but partial microglia depletion is not sufficient to block stress-induced escalation of alcohol intake in female mice. Alcohol 2024, 122: 31-42. PMID: 39725336, DOI: 10.1016/j.alcohol.2024.12.004.Peer-Reviewed Original ResearchConceptsAlcohol use disorderEthanol drinkingStress exposureEthanol intakeExposure to foot-shock stressDevelopment of alcohol use disordersTreatment of alcohol use disordersEscalation of alcohol intakeFemale miceReduced ethanol intakeFoot-shock stressIdentified sex differencesInhibitor of phosphodiesterase type 4Alcohol intakeEthanol reinforcementPharmacological depletion of microgliaLimbic circuitsUse disorderChronic ethanolNeuroinflammatory triggerDecreased preferenceC57BL/6J malesPhosphodiesterase type 4Sex differencesBinge drinkingSex-specific and developmental effects of early life adversity on stress reactivity are rescued by postnatal knockdown of 5-HT1A autoreceptors
Dixon R, Malave L, Thompson R, Wu S, Li Y, Sadik N, Anacker C. Sex-specific and developmental effects of early life adversity on stress reactivity are rescued by postnatal knockdown of 5-HT1A autoreceptors. Neuropsychopharmacology 2024, 50: 507-518. PMID: 39396089, PMCID: PMC11736140, DOI: 10.1038/s41386-024-01999-9.Peer-Reviewed Original ResearchEffects of early life adversityEarly life adversityVentral dentate gyrusAcute swim stressCorticotropin-releasing factorStress reactivityParaventricular nucleusSwim stressLife adversityNeuronal activityModel of early life adversityEarly life adversity effectsIn adulthoodIncreased passive copingSex-specific impairmentsFemale miceSerotonin-1ASerotonin systemNeurobiological mechanismsStress vulnerabilityIncreased microglia activationLimited beddingPassive copingAutoreceptorsCorticosterone levelsThe homeodomain transcription factor Six3 regulates hypothalamic Pomc expression and its absence from POMC neurons induces hyperphagia and mild obesity in male mice
Yu H, Chiang A, Rubinstein M, Low M. The homeodomain transcription factor Six3 regulates hypothalamic Pomc expression and its absence from POMC neurons induces hyperphagia and mild obesity in male mice. Molecular Metabolism 2024, 87: 101993. PMID: 39025297, PMCID: PMC11327434, DOI: 10.1016/j.molmet.2024.101993.Peer-Reviewed Original ResearchHypothalamic POMC expressionPOMC neuronsPOMC expressionFood intakeMild obesityDaily food intakeFemale micePOMC immunoreactivityAdult micePOMC-expressing neuronsSuppress food intakeMaintenance of physiological levelsPOMC mRNA levelsReduced POMC expressionBody weightKnockout mouse modelMouse hypothalamic neuronsIncreased daily food intakeCentral melanocortinEnhanced energy expenditureExpression of Six3Functional significanceMelanocortin neuronsHypothalamic neuronsAnorexigenic neuropeptidesSex differences in the distribution and density of regulatory interneurons in the striatum
Van Zandt M, Flanagan D, Pittenger C. Sex differences in the distribution and density of regulatory interneurons in the striatum. Frontiers In Cellular Neuroscience 2024, 18: 1415015. PMID: 39045533, PMCID: PMC11264243, DOI: 10.3389/fncel.2024.1415015.Peer-Reviewed Original ResearchFast spiking interneuronsCholinergic interneuronsDorsal striatumSex differencesTourette syndromeVentral striatumNeuropsychiatric disordersSomatostatin expressionContext of psychopathologyHuman neuropsychiatric disordersBasal ganglia functionInvestigate sex differencesNucleus accumbensCaudate-putamenBehavioral pathologyStriatumSomatostatin-expressing interneuronsStriatal interneuronsGABAergic interneuronsMale miceStereological quantificationFemale miceInterneuronsDisordersAccumbensO-077 Depletion of MFF from oocytes impairs mitochondrial dynamics, leading to inhibited oocyte maturation and early embryonic development in mice
Hua R, Hai Z, Gu J, Yeung W, Wang T. O-077 Depletion of MFF from oocytes impairs mitochondrial dynamics, leading to inhibited oocyte maturation and early embryonic development in mice. Human Reproduction 2024, 39: deae108.083. DOI: 10.1093/humrep/deae108.083.Peer-Reviewed Original ResearchMitochondrial fission factorEarly embryonic developmentMitochondrial dynamicsGV oocytesOocyte competenceKnockout mouse modelOvulated oocytesOocyte maturationCultured in vitroFemale miceEmbryonic developmentCre-loxP conditional knockout systemMouse modelGerminal vesicleRegulation of mitochondrial dynamicsMethods Female miceIn vitro maturationEmbryo development ratesRegulating mitochondrial dynamicsInhibited oocyte maturationMorphology of mitochondriaEarly embryo developmentPolar body extrusionAbnormal mitochondrial distributionConditional knockout systemP-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 supplementationAging is associated with sex-specific alteration in the expression of genes encoding for neuroestradiol synthesis and signaling proteins in the mouse trigeminal somatosensory input
Bautista-Abad Á, García-Magro N, Pinto-Benito D, Cáceres-Pajuelo J, Alises C, Ganchala D, Lagunas N, Negredo P, García-Segura L, Arevalo M, Grassi D. Aging is associated with sex-specific alteration in the expression of genes encoding for neuroestradiol synthesis and signaling proteins in the mouse trigeminal somatosensory input. GeroScience 2024, 46: 6459-6472. PMID: 38954130, PMCID: PMC11493896, DOI: 10.1007/s11357-024-01268-z.Peer-Reviewed Original ResearchExpression of aromataseTrigeminal ganglionPain perceptionAndrogen receptorEstrogen receptorSensory neuronsDorsal root ganglia sensory neuronsIncreased expression of aromataseIncidence of trigeminal neuralgiaAged female animalsAssociated with sex-specific alterationsPresence of aromataseModulate pain perceptionRegulating pain perceptionSex-specific alterationsInvolvement of aromataseSex-specific mannerTrigeminal neuralgiaGene expressionFemale miceAromatase immunoreactivitySomatosensory inputEstrogen synthesisAR geneSex differencesGrowth characteristics of HCT116 xenografts lacking asparagine synthetase vary according to sex
Aladelokun O, Lu L, Zheng J, Yan H, Jain A, Gibson J, Khan S, Johnson C. Growth characteristics of HCT116 xenografts lacking asparagine synthetase vary according to sex. Human Genomics 2024, 18: 67. PMID: 38886847, PMCID: PMC11184737, DOI: 10.1186/s40246-024-00635-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAspartate-Ammonia LigaseCarbon-Nitrogen Ligases with Glutamine as Amide-N-DonorCell ProliferationColorectal NeoplasmsFemaleGene Expression Regulation, NeoplasticHCT116 CellsHeterograftsHumansMaleMiceReceptors, EstrogenReceptors, G-Protein-CoupledSex FactorsXenograft Model Antitumor AssaysConceptsFemale tumor-bearing miceFemale CRC patientsTumor-bearing miceCRC patientsTumor growthInferior survivalAssociated with inferior survivalMetabolic reprogrammingG protein-coupled estrogen receptorTriggering metabolic reprogrammingSustained tumor growthSuppressed tumor growthExpression of asparagine synthetaseCancer cell linesBackgroundSex-related differencesSurvival improvementImpact of sexFemale miceEstrogen receptorCancer growthTranslational relevanceRewiring of metabolic pathwaysCancer burdenMetabolic pathwaysAsparagine synthetaseRevisiting the Potency of Tbx2 Expression in Transforming Outer Hair Cells into Inner Hair Cells at Multiple Ages In Vivo
Bi Z, Ren M, Zhang Y, He S, Song L, Li X, Liu Z. Revisiting the Potency of Tbx2 Expression in Transforming Outer Hair Cells into Inner Hair Cells at Multiple Ages In Vivo. Journal Of Neuroscience 2024, 44: e1751232024. PMID: 38688721, PMCID: PMC11154855, DOI: 10.1523/jneurosci.1751-23.2024.Peer-Reviewed Original ResearchA mammalian tripartite enhancer cluster controls hypothalamic Pomc expression, food intake, and body weight
Rojo D, Hael C, Soria A, de Souza F, Low M, Franchini L, Rubinstein M. A mammalian tripartite enhancer cluster controls hypothalamic Pomc expression, food intake, and body weight. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2322692121. PMID: 38652744, PMCID: PMC11067048, DOI: 10.1073/pnas.2322692121.Peer-Reviewed Original ResearchConceptsFood intakeControl of food intakeHypothalamic POMC expressionBody weight homeostasisHypothalamic arcuate neuronsConvergent evolutionary processesReporter gene expressionPurifying selectionArcuate neuronsDeletion eventsMouse genomeMolecular evolutionWeight homeostasisFemale miceAdult micePOMC expressionTranscriptional enhancersMutant miceEnhancer mutantsTranscription factorsPlacental mammalsMammalian ordersGene expressionMiceEvolutionary processMIF-Modulated Spinal Proteins Associated with Persistent Bladder Pain: A Proteomics Study
Ye S, Agalave N, Ma F, Mahmood D, Al-Grety A, Khoonsari P, Leng L, Svensson C, Bucala R, Kultima K, Vera P. MIF-Modulated Spinal Proteins Associated with Persistent Bladder Pain: A Proteomics Study. International Journal Of Molecular Sciences 2024, 25: 4484. PMID: 38674069, PMCID: PMC11050327, DOI: 10.3390/ijms25084484.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, Differentiation, B-LymphocyteCystitis, InterstitialDisease Models, AnimalFemaleHistocompatibility Antigens Class IIHyperalgesiaIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMiceProteomicsReceptors, CXCR4Receptors, ImmunologicSpinal CordUrinary BladderConceptsMacrophage migration inhibitory factorProtease activated receptor 4C-X-C chemokine receptor type 4Bladder hyperalgesiaBladder painSpinal proteinsMIF receptor CD74MIF antagonismL6-S1 spinal segmentsSpinal mechanismsInterstitial cystitis/bladder pain syndromeMIF receptorSeparate groups of miceChemokine receptor type 4Associated with reliefGroups of miceC-X-CMigration inhibitory factorChanges compared to controlsBladder inflammationPain syndromeFemale miceNo significant changesSham i.Receptor 4Developmental changes in lung function of mice are independent of sex as a biological variable
Bärnthaler T, Ramachandra A, Ebanks S, Guerrera N, Sharma L, Dela Cruz C, Humphrey J, Manning E. Developmental changes in lung function of mice are independent of sex as a biological variable. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2024, 326: l627-l637. PMID: 38375577, PMCID: PMC11380952, DOI: 10.1152/ajplung.00120.2023.Peer-Reviewed Original ResearchPulmonary function testsWeeks of ageStatic complianceMale miceInspiratory capacityLung functionBody weight-basedHuman lung pathologiesLung function of miceFemale C57BL/6J miceLung function parametersSex-dependent changesFunction of miceMeasures of lung functionIndependent of sexPreclinical modelsFemale miceC57BL/6J miceLung pathologyFunction testsMiceWeight-basedLungLung disease researchWeeksReciprocal activity of AgRP and POMC neurons governs coordinated control of feeding and metabolism
De Solis A, Del Río-Martín A, Radermacher J, Chen W, Steuernagel L, Bauder C, Eggersmann F, Morgan D, Cremer A, Sué M, Germer M, Kukat C, Vollmar S, Backes H, Rahmouni K, Kloppenburg P, Brüning J. Reciprocal activity of AgRP and POMC neurons governs coordinated control of feeding and metabolism. Nature Metabolism 2024, 6: 473-493. PMID: 38378998, PMCID: PMC10963273, DOI: 10.1038/s42255-024-00987-z.Peer-Reviewed Original ResearchInhibition of POMC neuronsPOMC neuronsFood intakeAgRP neuronsEffects of Agrp neuron activationActivation of AgRP neuronsActivating AgRP neuronsActivation of AgRPInhibit POMC neuronsProopiomelanocortin (POMC)-expressing neuronsAgRP neuron activityNucleus tractus solitariiRegulate food intakePromote food consumptionSystemic insulin sensitivityControl of feedingParaventricular nucleusTractus solitariiNeuronal inhibitionTH+ neuronsFemale miceChemogenetic receptorsNeuronal activityAgRPInsulin sensitivityIntermittent Methionine Restriction Reduces Marrow Fat Accumulation and Preserves More Bone Mass than Continuous Methionine Restriction
Plummer J, Horowitz M, Johnson J. Intermittent Methionine Restriction Reduces Marrow Fat Accumulation and Preserves More Bone Mass than Continuous Methionine Restriction. Aging Biology 2024, 2: 20230019. PMID: 38550776, PMCID: PMC10977905, DOI: 10.59368/agingbio.20230019.Peer-Reviewed Original ResearchMetabolic health benefitsBone massMethionine restrictionContinuous MRStatic histomorphometric analysisAccumulation of marrow fatMarrow fat accumulationLean body massMethionine-restricted dietLong-term adherenceCortical boneFemale miceMale miceDietary interventionHistomorphometric analysisDeleterious effectsContinuous interventionMarrow fatMiceAge-related pathologiesIntermittent formMammalian healthspanBoneConsistent with such findingsStrength of boneDynamic effects of ventral hippocampal NRG3/ERBB4 signaling on nicotine withdrawal-induced responses
Fisher M, Prantzalos E, O'Donovan B, Anderson T, Sahoo P, Twiss J, Ortinski P, Turner J. Dynamic effects of ventral hippocampal NRG3/ERBB4 signaling on nicotine withdrawal-induced responses. Neuropharmacology 2024, 247: 109846. PMID: 38211698, PMCID: PMC10923109, DOI: 10.1016/j.neuropharm.2024.109846.Peer-Reviewed Original ResearchConceptsAnxiety-like behaviorNeuregulin 3Ventral hippocampusAnxiety-related behaviorDrugs of abuseSmoking cessation therapySingle nucleotide polymorphismsNicotine withdrawalAnxiety-relatedErbB-4Nicotine addictionKnock-down miceGABAergic transmissionNeuronal mechanismsCA1 areaCessation therapyNicotineSynaptic expressionWithdrawalRelapse rateFemale miceNetwork activityGenetic factorsNucleotide polymorphismsGenetic disruption
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