2025
Mapping pesticide-induced metabolic alterations in human gut bacteria
Chen L, Yan H, Di S, Guo C, Zhang H, Zhang S, Gold A, Wang Y, Hu M, Wu D, Johnson C, Wang X, Zhu J. Mapping pesticide-induced metabolic alterations in human gut bacteria. Nature Communications 2025, 16: 4355. PMID: 40348778, PMCID: PMC12065874, DOI: 10.1038/s41467-025-59747-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacteriaFemaleGastrointestinal MicrobiomeHumansLipid MetabolismMaleMiceMice, Inbred C57BLPesticidesConceptsModulating gut microbiota compositionGut bacteria speciesGut microbial speciesHuman gut bacteriaGut microbiota compositionGut bacterial metabolismPesticide exposureHost healthGut bacteriaMicrobiota compositionMicrobial speciesBacterial metabolismBacteria speciesMolecular mechanismsComprehensive atlasLipid metabolismGutIn vivo mouse modelPesticidesHostMetabolismSpeciesInteractive atlasMouse modelMetabolic changesLiver lipid droplet cholesterol content is a key determinant of metabolic dysfunction–associated steatohepatitis
Sakuma I, Gaspar R, Nasiri A, Dufour S, Kahn M, Zheng J, LaMoia T, Guerra M, Taki Y, Kawashima Y, Yimlamai D, Perelis M, Vatner D, Petersen K, Huttasch M, Knebel B, Kahl S, Roden M, Samuel V, Tanaka T, Shulman G. Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction–associated steatohepatitis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2502978122. PMID: 40310463, DOI: 10.1073/pnas.2502978122.Peer-Reviewed Original ResearchConceptsCholine-deficient l-amino acid-defined high-fat dietBempedoic acidLiver fibrosisLiver diseaseL-amino acid-defined high-fat dietAdvanced liver diseaseCholesterol contentHSD17B13 variantsHigh-fat dietTotal liver cholesterol contentTreated miceActivate signaling pathwaysVariant rs738409Liver cholesterol contentLiver lipidsFibrotic responsePromote inflammationTherapeutic approachesSteatotic liver diseaseDietary cholesterol supplementationFibrosisHuman liver samplesI148MAntisense oligonucleotidesProgressive formNotch1 Signalling Is Downregulated by Aerobic Exercise, Leading to Improvement of Hepatic Metabolism in Obese Mice
Gaspar R, Macêdo A, Nakandakari S, Muñoz V, Abud G, Vieira R, de Sousa Neto I, Pavan I, da Silva L, Simabuco F, da Silva A, Salgado W, Marchini J, Nonino C, Cintra D, Ropelle E, Pajvani U, de Freitas E, Pauli J. Notch1 Signalling Is Downregulated by Aerobic Exercise, Leading to Improvement of Hepatic Metabolism in Obese Mice. Liver International 2025, 45: e70068. PMID: 40078075, DOI: 10.1111/liv.70068.Peer-Reviewed Original ResearchConceptsNotch1 signalingAerobic exerciseRegulation of hepatic glucoseObese miceImpact of aerobic exerciseEffects of Notch1 signalingAerobic exercise trainingMTORC1 pathway activationNotch1 pathwayObese individualsTissue of obese miceCross-sectional studyNotch1 mRNA levelsMitochondrial respirationExercise trainingLivers of obese individualsTreadmill runningGluconeogenic enzymesHepG2 cell lineLipid accumulationTraining groupHepatic glucoseHepatic metabolismNotch1 proteinPathway activationMAP Kinase Phosphatase-5 Deficiency Improves Endurance Exercise Capacity
Perales J, Lawan A, Bajpeyi S, Han S, Bennett A, Min K. MAP Kinase Phosphatase-5 Deficiency Improves Endurance Exercise Capacity. Cells 2025, 14: 410. PMID: 40136658, PMCID: PMC11941502, DOI: 10.3390/cells14060410.Peer-Reviewed Original ResearchConceptsResponse to aerobic exerciseEndurance exercise capacityAerobic exerciseExercise capacityProgressive exercise stress testExercise training programEnhance endurance performanceCardiac adaptationPhysiological cardiac adaptationExercise stress testExercise habituationEndurance performanceRunning distanceCardiovascular healthTreadmill exerciseTraining programExerciseImproving cardiovascular functionSedentary miceTreadmillCardiac muscleEnduranceMitogen-activated protein kinaseMuscleStress testAn atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis
El Bounkari O, Zan C, Yang B, Ebert S, Wagner J, Bugar E, Kramer N, Bourilhon P, Kontos C, Zarwel M, Sinitski D, Milic J, Jansen Y, Kempf W, Sachs N, Maegdefessel L, Ji H, Gokce O, Riols F, Haid M, Gerra S, Hoffmann A, Brandhofer M, Avdic M, Bucala R, Megens R, Willemsen N, Messerer D, Schulz C, Bartelt A, Harm T, Rath D, Döring Y, Gawaz M, Weber C, Kapurniotu A, Bernhagen J. An atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis. Nature Communications 2025, 16: 2297. PMID: 40055309, DOI: 10.1038/s41467-025-57540-z.Peer-Reviewed Original ResearchConceptsApoE-/- miceHyperlipidemic apoE-/- miceCoronary artery diseaseDecreased plasma lipid levelsPlasma lipid levelsHepatic lipid accumulationAtherogenic chemokinesFoam-cell formationFLIM-FRET microscopyArtery diseasePlasma concentrationsVascular inflammationInflammatory conditionsMetabolic dysfunctionAtherosclerotic patientsLipid accumulationAdvanced atherosclerosisMyocardial infarctionLipid levelsSuppressed hepatic lipid accumulationAdvanced atherogenesisCarotid plaquesDisease severityIschemic strokeChemokinesp53 enhances DNA repair and suppresses cytoplasmic chromatin fragments and inflammation in senescent cells
Miller K, Li B, Pierce-Hoffman H, Patel S, Lei X, Rajesh A, Teneche M, Havas A, Gandhi A, Macip C, Lyu J, Victorelli S, Woo S, Lagnado A, LaPorta M, Liu T, Dasgupta N, Li S, Davis A, Korotkov A, Hultenius E, Gao Z, Altman Y, Porritt R, Garcia G, Mogler C, Seluanov A, Gorbunova V, Kaech S, Tian X, Dou Z, Chen C, Passos J, Adams P. p53 enhances DNA repair and suppresses cytoplasmic chromatin fragments and inflammation in senescent cells. Nature Communications 2025, 16: 2229. PMID: 40044657, PMCID: PMC11882782, DOI: 10.1038/s41467-025-57229-3.Peer-Reviewed Original ResearchConceptsCytoplasmic chromatin fragmentsDNA repairGenome integrityChromatin fragmentsNuclear DNA damage signalsGenomic instabilitySenescent cellsActivation of p53Controlling DNA repairATM-dependent mannerDNA damage signalingSignatures of agingAge-associated accumulationActivate p53P53 activationHallmarks of agingDamage signalingAge-associated diseasesSignaling circuitsP53Molecular circuitsEnhanced DNA repairGenomePharmacological inhibitionAge-associated inflammationSex differences in the microglial response to stress and chronic alcohol exposure in mice
Soares A, Garcia-Rivas V, Fai C, Thomas M, Zheng X, Picciotto M, Mineur Y. Sex differences in the microglial response to stress and chronic alcohol exposure in mice. Biology Of Sex Differences 2025, 16: 19. PMID: 40038827, PMCID: PMC11881309, DOI: 10.1186/s13293-025-00701-y.Peer-Reviewed Original ResearchMeSH KeywordsAlcohol DrinkingAmygdalaAnimalsEthanolFemaleHippocampusMaleMiceMice, Inbred C57BLMicrogliaSex CharacteristicsStress, PsychologicalConceptsResponse to stressSex differencesAlcohol exposureStress-induced alcohol drinkingHeightened reactivity to stressInescapable footshock stressDevelopment of AUDReactivity to stressChronic alcohol exposureProminent sex differencesIncreased alcohol intakeCharacterize sex differencesFemale C57BL/6J miceDark paradigmComorbid moodFootshock stressStress disorderLimbic circuitsNeurobiological processesModify drinkingNeuroimmune signalingAdministered alcoholFemale rodentsMicroglial densityAlcohol drinkingHypercholesterolemia-induced LXR signaling in smooth muscle cells contributes to vascular lesion remodeling and visceral function
Zhang H, de Urturi D, Fernández-Tussy P, Huang Y, Jovin D, Zhang X, Huang S, Lek M, da Silva Catarino J, Sternak M, Citrin K, Swirski F, Gustafsson J, Greif D, Esplugues E, Biwer L, Suárez Y, Fernández-Hernando C. Hypercholesterolemia-induced LXR signaling in smooth muscle cells contributes to vascular lesion remodeling and visceral function. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2417512122. PMID: 40035761, PMCID: PMC11912459, DOI: 10.1073/pnas.2417512122.Peer-Reviewed Original ResearchConceptsVascular smooth muscle cellsSmooth muscle cellsLiver X receptorLesion remodelingMuscle cellsVascular functionArterial media layerContribution of lipid metabolismPhenotypic switchingRegulate vascular toneMonocyte-derived macrophagesLipid metabolismPhenotypic switching of vascular smooth muscle cellsSwitching of vascular smooth muscle cellsNecrotic core areaRegulate vascular functionFoam cell populationVisceral myopathyBladder remodelingAortic atheromaFibrous cap thicknessRemodeling in vivoLipid malabsorptionVascular toneAbundant cell typeFGF21 Signaling Exerts Antifibrotic Properties during Pulmonary Fibrosis.
Ghanem M, Archer G, Justet A, Jaillet M, Vasarmidi E, Mordant P, Castier Y, Mal H, Cazes A, Poté N, Crestani B, Mailleux A. FGF21 Signaling Exerts Antifibrotic Properties during Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2025, 211: 486-498. PMID: 39637324, DOI: 10.1164/rccm.202311-2021oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisWild-type littermatesPlasma of patientsPulmonary fibrosisAntifibrotic propertiesIntratracheal injection of bleomycinDevelopment of pulmonary fibrosisDecreased fibrosis markersEffects of FGF21Increased sensitivity to bleomycinInjection of bleomycinPulmonary fibrosis developmentSensitivity to bleomycinDecrease of BaxConcentrations of FGF21Human lung fibroblastsTherapeutic optionsFibrosis markersAntifibrotic effectsControl subjectsInjury scoreIntratracheal injectionLiver fibrosisLung fibrogenesisFibroblast growth factorSuppression 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 disordersDevelopment of Syngeneic Murine Glioma Models with Somatic Mismatch Repair Deficiency to Study Therapeutic Responses to Alkylating Agents and Immunotherapy
Bhatt D, Sundaram R, López K, Lee T, Gueble S, Vasquez J. Development of Syngeneic Murine Glioma Models with Somatic Mismatch Repair Deficiency to Study Therapeutic Responses to Alkylating Agents and Immunotherapy. Current Protocols 2025, 5: e70097. PMID: 39995104, DOI: 10.1002/cpz1.70097.Peer-Reviewed Original ResearchConceptsImproved response to immune checkpoint blockadeGlioma modelResponse to immune checkpoint blockadeAlkylating agentsImmune checkpoint blockadeIncrease tumor immunogenicityMurine glioma modelMurine glioma cell lineResponse to alkylating agentsResistance to temozolomideDNA repair genotypesMMR deficiencyAntitumor immunityCheckpoint blockadeTumor immunogenicityMedian survivalImmunocompetent modelDismal prognosisMismatch repairMismatch repair deficiencyGlioma cell linesIntracranial tumorsAlkylating chemotherapySomatic lossSomatic acquisitionCD103+ dendritic cell — fibroblast crosstalk via TLR9, TDO2, and AHR signaling drives lung fibrogenesis
Carter H, Costa R, Adams T, Gilchrist T, Emch C, Bame M, Oldham J, Huang S, Linderholm A, Noth I, Kaminski N, Moore B, Gurczynski S. CD103+ dendritic cell — fibroblast crosstalk via TLR9, TDO2, and AHR signaling drives lung fibrogenesis. JCI Insight 2025, 10 PMID: 39964756, PMCID: PMC11949071, DOI: 10.1172/jci.insight.177072.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDBasic Helix-Loop-Helix Transcription FactorsBleomycinDendritic CellsDisease Models, AnimalFibroblastsHumansIdiopathic Pulmonary FibrosisIntegrin alpha ChainsInterleukin-6LungMaleMiceMice, Inbred C57BLReceptors, Aryl HydrocarbonSignal TransductionToll-Like Receptor 9Tryptophan OxygenaseConceptsIdiopathic pulmonary fibrosisAhR signalingMice treated with BLMIL-17+ cellsCD103+ DCLoss of lung functionStudies of human samplesLimited treatment optionsTreated ex vivoProduction of IL-6Inflammatory cytokine productionExon 2 deletionExpression of TDO2IL-6 productionAdoptive transferCD11c-CreCD11c+ cellsImmunological changesPulmonary fibrosisTLR agonistsProgressive scarringTreatment optionsCytokine productionLung fibrogenesisAryl hydrocarbon receptorCold and hot fibrosis define clinically distinct cardiac pathologies
Miyara S, Adler M, Umansky K, Häußler D, Bassat E, Divinsky Y, Elkahal J, Kain D, Lendengolts D, Flores R, Bueno-Levy H, Golani O, Shalit T, Gershovits M, Weizman E, Genzelinakh A, Kimchi D, Shakked A, Zhang L, Wang J, Baehr A, Petrover Z, Sarig R, Dorn T, Moretti A, Saez-Rodriguez J, Kupatt C, Tanaka E, Medzhitov R, Krüger A, Mayo A, Alon U, Tzahor E. Cold and hot fibrosis define clinically distinct cardiac pathologies. Cell Systems 2025, 16: 101198. PMID: 39970910, PMCID: PMC11922821, DOI: 10.1016/j.cels.2025.101198.Peer-Reviewed Original ResearchConceptsHeart failureMyocardial infarctionAutocrine growth factor loopsUnmet medical needCardiac fibrosisNeutralizing antibodiesReduced fibrosisTreatment strategiesMyofibroblast proliferationAcute MIFibrosis post-MICardiac pathologyFibrosisTherapeutic approachesPost-MIChronic injuryMyofibroblastsMedical needFactor loopsDendritic cell phagosomes recruit GRASP55 for export of antigen-loaded MHC molecules
Cebrian I, Dinamarca S, Rodríguez M, Priego E, Brouwers N, Barends M, Brunnberg J, Tampé R, Blanchard N, Sancho D, Malhotra V. Dendritic cell phagosomes recruit GRASP55 for export of antigen-loaded MHC molecules. Cell Reports 2025, 44: 115333. PMID: 39955774, PMCID: PMC11861518, DOI: 10.1016/j.celrep.2025.115333.Peer-Reviewed Original ResearchConceptsExogenous antigen presentationDendritic cellsAntigen presentationMHC moleculesBone marrow-derived dendritic cellsBone marrow-derived DCCD4<sup>+</sup> T cellsMHC-IActivated CD8<sup>+</sup>MHC class IIDendritic cell phagosomesMHC II moleculesCD8<sup>+</sup>Peptide-loaded MHC moleculesT cellsExogenous antigensMHC-IIClass IIAntigenEndocytic systemGRASP55Cell surfaceIntracellular transportPlasma membranePresentationKLF2 maintains lineage fidelity and suppresses CD8 T cell exhaustion during acute LCMV infection
Fagerberg E, Attanasio J, Dien C, Singh J, Kessler E, Abdullah L, Shen J, Hunt B, Connolly K, De Brouwer E, He J, Iyer N, Buck J, Borr E, Damo M, Foster G, Giles J, Huang Y, Tsang J, Krishnaswamy S, Cui W, Joshi N. KLF2 maintains lineage fidelity and suppresses CD8 T cell exhaustion during acute LCMV infection. Science 2025, 387: eadn2337. PMID: 39946463, DOI: 10.1126/science.adn2337.Peer-Reviewed Original ResearchConceptsCD8 T cellsT cellsCD8 T cell exhaustionNaive CD8 T cellsAcute LCMV infectionT cell exhaustionT cell fate decisionsLineage fidelityLCMV infectionEffector differentiationAcute infectionExhaustion programTranscription factorsImmune responseEpigenetic modulationSuppress differentiationProgenitor stateKLF2InfectionFunctional stateFate decisionsCD8Astrocyte Kir4.1 expression level territorially controls excitatory transmission in the brain
Tyurikova O, Kopach O, Zheng K, Rathore D, Codadu N, Wu S, Shen Y, Campbell R, Wykes R, Volynski K, Savtchenko L, Rusakov D. Astrocyte Kir4.1 expression level territorially controls excitatory transmission in the brain. Cell Reports 2025, 44: 115299. PMID: 39951378, DOI: 10.1016/j.celrep.2025.115299.Peer-Reviewed Original ResearchConceptsKir4.1 channelsExtracellular potassiumInducing long-term synaptic potentiationHigh-frequency afferent stimulationLong-term synaptic potentiationPresynaptic Ca<sup>2+</sup> entryCortical spreading depolarizationKir4.1 levelsExcitatory transmissionSynaptic potentialsAfferent stimulationExcitatory synapsesGlutamate uptakePotassium homeostasisSpreading depolarizationPotassium levelsRelease probabilityAstrocytic mechanismsAstrocytesHigh potassiumKir4.1Brain circuitsSynapsesBrainOrexin/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 classificationShort-term disruption of TGFβ signaling in adult mice renders the aorta vulnerable to hypertension-induced dissection
Jiang B, Ren P, He C, Wang M, Murtada S, Ruiz-Rodríguez M, Chen Y, Ramachandra A, Li G, Qin L, Assi R, Schwartz M, Humphrey J, Tellides G. Short-term disruption of TGFβ signaling in adult mice renders the aorta vulnerable to hypertension-induced dissection. JCI Insight 2025, 10 PMID: 39932797, PMCID: PMC11949005, DOI: 10.1172/jci.insight.182629.Peer-Reviewed Original ResearchConceptsSmooth muscle cellsBlood pressureAortic dissectionAdult miceInherited connective tissue disorderConnective tissue disordersTGF-b signalingAccumulation of bloodHigh blood pressureAortic phenotypeTissue disordersMolecule expressionTGFB signalingMuscle cellsRisk factorsSynthesis of extracellular matrixSustained increaseTransient increaseBlood extravasationDissectionMedial injuryExtracellular matrix productionVascular degenerationExperimental modelMiceHigher-order thalamic input to cortex selectively conveys state information
Neske G, Cardin J. Higher-order thalamic input to cortex selectively conveys state information. Cell Reports 2025, 44: 115292. PMID: 39937647, PMCID: PMC11920878, DOI: 10.1016/j.celrep.2025.115292.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCerebral CortexFemaleMaleMiceMice, Inbred C57BLNeuronsOptogeneticsThalamusVisual CortexConceptsHigher-order thalamic nucleiHigher-order visual thalamusHigher-order thalamusCortical sensory processingCorticocortical communicationVisual thalamusImaging of neuronsMedial visual cortexStrong synaptic inputVisual cortexContextual signalsVisual informationCortical areasThalamic inputRelay of informationSynaptic inputsCorticocortical projectionsSensory peripheryThalamic nucleiCortical neuronsThalamocortical projectionsAxon terminalsOptogenetic manipulationNeocortical areasInformation
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply