2025
MAP kinase phosphatases in metabolic diseases
Hota A, Bennett A. MAP kinase phosphatases in metabolic diseases. Trends In Endocrinology And Metabolism 2025 PMID: 40555575, DOI: 10.1016/j.tem.2025.05.002.Peer-Reviewed Original ResearchMitogen-activated protein kinaseInactivate mitogen-activated protein kinasesMAP kinase phosphatasesRegulation of MAPK signaling pathwaysMetabolic diseasesMAPK signaling pathwayRegulatory residuesInsulin signalingProtein kinaseSignaling pathwayCellular responsesKey pathwaysLipid metabolismGlucose homeostasisTherapeutic targetPathwayMetabolismKinaseResiduesHomeostasisMKPRegulationPhosphataseThe novel synbiotic (Lactiplantibacillus plantarum and galacto-oligosaccharides) ameliorates obesity-related metabolic dysfunction: Arginine as a key mediator signaling molecule
Shi R, Wei J, Ye J, Song X, Yang X, Zhang Y, Liu S, Ren J, Wang D, Zhao Z, Liu Z, Wang Y, Zhao B, Xiao C, Dai X, Ai L, Liu X. The novel synbiotic (Lactiplantibacillus plantarum and galacto-oligosaccharides) ameliorates obesity-related metabolic dysfunction: Arginine as a key mediator signaling molecule. Journal Of Advanced Research 2025 PMID: 40545235, DOI: 10.1016/j.jare.2025.06.041.Peer-Reviewed Original ResearchGalacto-oligosaccharidesGenome-wide analysisGut microbiota compositionAMPK Signaling PathwayLipid metabolismArginine productionCAZy databaseHigh-fat diet-induced obese miceMicrobiota compositionMicrobiota analysisAMPK pathwayDiet-induced obese miceSignaling moleculesASS1 geneSignaling pathwayGrowth substrateObesity-related metabolic dysfunctionImprove lipid metabolismAMPKAttenuate obesityArginineSynthesis inhibitionObese miceSerum arginine levelsPathwayDynamic decoding of VEGF signaling and coordinated control of multiple phenotypes by the Src-TEM4-YAP pathway
Lee S, Kang T, Shang X, Levchenko A. Dynamic decoding of VEGF signaling and coordinated control of multiple phenotypes by the Src-TEM4-YAP pathway. Cell Systems 2025, 101321. PMID: 40541183, DOI: 10.1016/j.cels.2025.101321.Peer-Reviewed Original ResearchSequential activation of SrcPaper's transparent peer review processTransparent peer review processActivation of SrcPathway levelMultiple phenotypesPhenotypic outcomesRearrangement of cellsPathway componentsPathway organizationNotch signalingPhysiological processesCell contactSequential activationPathwayVascular endothelial growth factor signalingSignal inputVascular endothelial growth factorDiverse time scalesDynamic decoderCoordinated controlVEGF signalingGrowth factorSignalElevated levelsHuman CCR4 deadenylase homolog Angel1 is a Non-Stop mRNA Decay factor.
Nicholson-Shaw T, Dowdle M, Ajaj Y, Perelis M, Fulzele A, Yeo G, Bennett E, Lykke-Andersen J. Human CCR4 deadenylase homolog Angel1 is a Non-Stop mRNA Decay factor. RNA 2025, rna.080399.125. PMID: 40441874, DOI: 10.1261/rna.080399.125.Peer-Reviewed Original ResearchMRNA decayRibosome-associated quality controlAbsence of stop codonsQuality control pathwaysMRNA decay factorsMRNA coding regionNonsense-mediated decayTargets aberrant mRNAsNascent polypeptidesCatalytic residuesPremature polyadenylationReporter mRNAAberrant mRNAsCoding regionStabilization of reporter mRNAsStop codonAngel1Control pathwaysBiochemical activityHuman cellsCodonMRNAPathwayDecayPolyadenylationUnveiling the shared etiology between gastrointestinal disorders and valvular heart diseases through a genome-wide pleiotropy study
Xu J, Liu Z, Wu L, Pei F, Jiang H, Cheng C, Yang W, Yuan J, Polimanti R, Yang Y. Unveiling the shared etiology between gastrointestinal disorders and valvular heart diseases through a genome-wide pleiotropy study. Npj Cardiovascular Health 2025, 2: 17. DOI: 10.1038/s44325-025-00054-w.Peer-Reviewed Original ResearchLinkage disequilibrium score regressionGenetic correlationsPleiotropic analysisPleiotropy analysisGut microbiotaGenetic pathwaysMicrobial influenceScore regressionPleiotropic effectsGenetic linkPathwayHeart diseaseButyricicoccusMicrobiotaGenesGutComposite null hypothesisVariantsGastrointestinal disordersCausal effectsLinkageDiseaseIBDRottlerin inhibits macropinocytosis of Porcine Reproductive and Respiratory Syndrome Virus through the PKCδ-Cofilin signaling pathway
Kang Y, Choi J, Lee J, Park S, Oh C. Rottlerin inhibits macropinocytosis of Porcine Reproductive and Respiratory Syndrome Virus through the PKCδ-Cofilin signaling pathway. PLOS ONE 2025, 20: e0324500. PMID: 40392868, PMCID: PMC12091787, DOI: 10.1371/journal.pone.0324500.Peer-Reviewed Original ResearchConceptsRespiratory syndrome virusPorcine ReproductiveLIM domain kinase 1Actin dynamicsPRRSV replicationPRRSV entryPRRSVSignaling pathwayDecreased actin polymerizationActin polymerizationCofilin activityEffects of rottlerinHost cellsKinase 1Enveloped virusesRottlerin treatmentInhibit viral replicationAntiviral moleculesReplicationRottlerinVirusMacropinocytosisEntry pathwayViral replicationPathwayPancreatic β-cell apoptosis caused by apolipoprotein C3-rich low-density lipoprotein is attenuated by kansuinine A through oxidative stress inhibition
Lulji Taraqaz B, Hsu Y, Tsai P, Li Y, Chen F, Yang W, Shen M. Pancreatic β-cell apoptosis caused by apolipoprotein C3-rich low-density lipoprotein is attenuated by kansuinine A through oxidative stress inhibition. Biomedicine & Pharmacotherapy 2025, 187: 118066. PMID: 40262236, DOI: 10.1016/j.biopha.2025.118066.Peer-Reviewed Original ResearchConceptsB cell apoptosisRat pancreatic B-cellsLow-density lipoproteinPathway analysisSignaling pathwayOxidative stressApoptosisImproved cell viabilityRIN-m5FB cellsLectin-like oxidized low-density lipoprotein receptor-1Pancreatic B-cellsHigh-fat dietCell viabilityInsulin toleranceAntiapoptotic propertiesKansuinine AMitigated apoptosisMechanism of actionMolecular dockingStress inhibitionPathwayLow-density lipoprotein receptor-1Improved glucoseHigh-fatIdentification of post-translationally modified MHC class I-associated peptides as potential cancer immunotherapeutic targets
Mahoney K, Reser L, Ruiz Cuevas M, Abelin J, Shabanowitz J, Hunt D, Malaker S. Identification of post-translationally modified MHC class I-associated peptides as potential cancer immunotherapeutic targets. Molecular & Cellular Proteomics 2025, 100971. PMID: 40239839, DOI: 10.1016/j.mcpro.2025.100971.Peer-Reviewed Original ResearchCirculating cytotoxic T-cellsMHC class I processing pathwayClass I processing pathwayCancer immunotherapy targetCytotoxic T cellsCancer immunotherapeutic targetsVaccine development effortsModern immunotherapyImmunotherapy targetMHC-associated peptidesImmunotherapeutic targetT cellsMalignant cellsAntigen presentationAberrant signalingMHC-peptideMass spectrometry-based technologiesCancerMHCPost-translational modificationsDysregulationIdentification of post-translationallyPeptideImmunotherapyPathwayTSC-mTORC1 Pathway in Postnatal V-SVZ Neurodevelopment
Feliciano D, Bordey A. TSC-mTORC1 Pathway in Postnatal V-SVZ Neurodevelopment. Biomolecules 2025, 15: 573. PMID: 40305300, PMCID: PMC12024678, DOI: 10.3390/biom15040573.Peer-Reviewed Original ResearchConceptsMTOR pathwayNeural stem cellsVentricular-subventricular zoneTranscriptional programsMTOR pathway signalingPathway signalingSignaling pathwayNutrient sufficiencyPathwayOlfactory bulb circuitryMTORNeurodevelopmental disordersFunctional cellsGrowth factorNeurogenesisCellsRodent brainStem cellsNarrative reviewTranslational genomics of osteoarthritis in 1,962,069 individuals
Hatzikotoulas K, Southam L, Stefansdottir L, Boer C, McDonald M, Pett J, Park Y, Tuerlings M, Mulders R, Barysenka A, Arruda A, Tragante V, Rocco A, Bittner N, Chen S, Horn S, Srinivasasainagendra V, To K, Katsoula G, Kreitmaier P, Tenghe A, Gilly A, Arbeeva L, Chen L, de Pins A, Dochtermann D, Henkel C, Höijer J, Ito S, Lind P, Lukusa-Sawalena B, Minn A, Mola-Caminal M, Narita A, Nguyen C, Reimann E, Silberstein M, Skogholt A, Tiwari H, Yau M, Yue M, Zhao W, Zhou J, Alexiadis G, Banasik K, Brunak S, Campbell A, Cheung J, Dowsett J, Faquih T, Faul J, Fei L, Fenstad A, Funayama T, Gabrielsen M, Gocho C, Gromov K, Hansen T, Hudjashov G, Ingvarsson T, Johnson J, Jonsson H, Kakehi S, Karjalainen J, Kasbohm E, Lemmelä S, Lin K, Liu X, Loef M, Mangino M, McCartney D, Millwood I, Richman J, Roberts M, Ryan K, Samartzis D, Shivakumar M, Skou S, Sugimoto S, Suzuki K, Takuwa H, Teder-Laving M, Thomas L, Tomizuka K, Turman C, Weiss S, Wu T, Zengini E, Zhang Y, Ferreira M, Babis G, Baras A, Barker T, Carey D, Cheah K, Chen Z, Cheung J, Daly M, de Mutsert R, Eaton C, Erikstrup C, Furnes O, Golightly Y, Gudbjartsson D, Hailer N, Hayward C, Hochberg M, Homuth G, Huckins L, Hveem K, Ikegawa S, Ishijima M, Isomura M, Jones M, Kang J, Kardia S, Kloppenburg M, Kraft P, Kumahashi N, Kuwata S, Lee M, Lee P, Lerner R, Li L, Lietman S, Lotta L, Lupton M, Mägi R, Martin N, McAlindon T, Medland S, Michaëlsson K, Mitchell B, Mook-Kanamori D, Morris A, Nabika T, Nagami F, Nelson A, Ostrowski S, Palotie A, Pedersen O, Rosendaal F, Sakurai-Yageta M, Schmidt C, Sham P, Singh J, Smelser D, Smith J, Song Y, Sørensen E, Tamiya G, Tamura Y, Terao C, Thorleifsson G, Troelsen A, Tsezou A, Uchio Y, Uitterlinden A, Ullum H, Valdes A, van Heel D, Walters R, Weir D, Wilkinson J, Winsvold B, Yamamoto M, Zwart J, Stefansson K, Meulenbelt I, Teichmann S, van Meurs J, Styrkarsdottir U, Zeggini E. Translational genomics of osteoarthritis in 1,962,069 individuals. Nature 2025, 641: 1217-1224. PMID: 40205036, PMCID: PMC12119359, DOI: 10.1038/s41586-025-08771-z.Peer-Reviewed Original ResearchConceptsEffector genesGenome-wide association study meta-analysesTargets of approved drugsVariant associationsTranslational genomicsEpigenomic profilingStudy meta-analysesCircadian clockBiological processesLines of evidenceConditions associated with disabilityRepurposing opportunitiesSignal enrichmentGenesEffectorPathwayIndependent associationsMeta-analysesEffect sizeAccelerated translationEpigenomeTranscriptomeProteomicsDisease-modifying treatmentsOsteoarthritisImmune inhibitory receptor agonist therapeutics
Lovewell R, Langermann S, Flies D. Immune inhibitory receptor agonist therapeutics. Frontiers In Immunology 2025, 16: 1566869. PMID: 40207220, DOI: 10.3389/fimmu.2025.1566869.Peer-Reviewed Original ResearchConceptsAgonist suppressionSurface of immune cellsCheckpoint inhibitorsStimulatory cellsStimulatory receptorsSuppressive cellsDysregulated inflammationImmune cellsPre-clinicalTreat diseasesDisease settingsAgonistsImmune systemImmune pathwaysClinical therapeuticsTherapeutic interventionsDiseaseReceptorsCellular levelTherapeuticsCellsPathwayInduced signalsAutoimmunityInflammationFibronectin matrix assembly at a glance.
Sun Y, Hamlin A, Schwarzbauer J. Fibronectin matrix assembly at a glance. Journal Of Cell Science 2025, 138 PMID: 40130407, PMCID: PMC12050093, DOI: 10.1242/jcs.263834.Peer-Reviewed Original ResearchConceptsAbundant ECM proteinFibronectin matrix assemblyOrganization of FNExtracellular matrixMechanisms of extracellular matrixSecrete ECM componentsFN assemblyDomain organizationFN fibrilsFN matrixGlance articleECM proteinsMatrix assemblyECM componentsIntracellular pathwaysFibrillar matrixReceptor-mediated processFibronectinCell scienceProteinAssemblyCellsCell-mediated processPathwayMechanismMolecular mechanism of Arp2/3 complex activation by nucleation-promoting factors and an actin monomer
Iyer S, Wu J, Pollard T, Voth G. Molecular mechanism of Arp2/3 complex activation by nucleation-promoting factors and an actin monomer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2421467122. PMID: 40048273, PMCID: PMC11912402, DOI: 10.1073/pnas.2421467122.Peer-Reviewed Original ResearchConceptsArp2/3 complexActin monomersNeuronal Wiskott-Aldrich syndrome proteinWiskott-Aldrich syndrome proteinActin filament branchingMammalian Arp2/3 complexArp2/3 complex activationNucleation-promoting factorsActin-related proteinsCA motifsD-loopActin filamentsFilament branchingOrganelle movementBranch formationActive conformationActinMolecular mechanismsArp2/3Binding sitesArp3ProteinPathwayAtomistic molecular dynamics simulationsComplex activitySynthetic Genetic Elements Enable Rapid Characterization of Inorganic Carbon Uptake Systems in Cupriavidus necator H16
Nakamura A, Fulk E, Johnson C, Isaacs F. Synthetic Genetic Elements Enable Rapid Characterization of Inorganic Carbon Uptake Systems in Cupriavidus necator H16. ACS Synthetic Biology 2025, 14: 943-953. PMID: 40048245, PMCID: PMC11934965, DOI: 10.1021/acssynbio.4c00869.Peer-Reviewed Original ResearchConceptsSynthetic genetic elementsExpression of heterologous pathwaysUptake systemCupriavidus necator H16Genome engineering technologiesHeterologous pathwaysHeterotrophic conditionsGenetic elementsChromosomal expressionTunable expressionInducible promoterGenetic engineering technologyModel microbesCarbon sourceGene expressionFacultative chemolithotrophsUptake pathwayH16PathwayLanding padExpressionGenomeGenesMicrobesChemolithotrophsStructure of mitochondrial pyruvate carrier and its inhibition mechanism
He Z, Zhang J, Xu Y, Fine E, Suomivuori C, Dror R, Feng L. Structure of mitochondrial pyruvate carrier and its inhibition mechanism. Nature 2025, 641: 250-257. PMID: 40044865, PMCID: PMC12043432, DOI: 10.1038/s41586-025-08667-y.Peer-Reviewed Original ResearchConceptsMitochondrial pyruvate carrierPyruvate carrierMPC functionSubstrate-binding siteCytosolic glycolysisCentral metaboliteTranslocation pathwayCellular metabolismMolecular basisMetabolic gatekeeperMolecular mechanismsConformational statesInhibition mechanismTherapeutic reagentsTransport functionCritical roleStructural findingsNon-alcoholic steatohepatitisInhibitionTranslocationGlycolysisPathwayBindingMetabolismPhysiologySugar unmasking for trafficking
Calderwood D, Toomre D. Sugar unmasking for trafficking. Nature Cell Biology 2025, 27: 375-376. PMID: 40038537, DOI: 10.1038/s41556-025-01615-y.Peer-Reviewed Original ResearchThe pathways of secretory cargo export at the endoplasmic reticulum
Malhotra V. The pathways of secretory cargo export at the endoplasmic reticulum. Nature Communications 2025, 16: 2138. PMID: 40032897, PMCID: PMC11876584, DOI: 10.1038/s41467-025-57408-2.Peer-Reviewed Original ResearchIdentification of plasma proteomic markers underlying polygenic risk of type 2 diabetes and related comorbidities
Loesch D, Garg M, Matelska D, Vitsios D, Jiang X, Ritchie S, Sun B, Runz H, Whelan C, Holman R, Mentz R, Moura F, Wiviott S, Sabatine M, Udler M, Gause-Nilsson I, Petrovski S, Oscarsson J, Nag A, Paul D, Inouye M. Identification of plasma proteomic markers underlying polygenic risk of type 2 diabetes and related comorbidities. Nature Communications 2025, 16: 2124. PMID: 40032831, PMCID: PMC11876343, DOI: 10.1038/s41467-025-56695-z.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkersCardiovascular DiseasesComorbidityDiabetes Mellitus, Type 2Extracellular Matrix ProteinsFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInsulin-Like Growth Factor Binding Protein 2MaleMiddle AgedMultifactorial InheritanceProteomicsRisk FactorsUnited KingdomConceptsPolygenic scoresNon-coding variantsEtiology of type 2 diabetesMolecular dataVariant effectsPathway enrichmentPlasma proteomic markersPotential therapeutic targetType 2 diabetesProteinDisease biologyPolygenic riskUK BiobankProteomic markersTherapeutic targetPathwayCirculating proteinsGenomeRisk of type 2 diabetesCardiometabolic scoreBiologyInteractive portalVariantsEnrichmentDiabetes comorbiditiesdiAcCA, a Pro-Drug for Carnosic Acid That Activates the Nrf2 Transcriptional Pathway, Shows Efficacy in the 5xFAD Transgenic Mouse Model of Alzheimer’s Disease
Banerjee P, Wang Y, Carnevale L, Patel P, Raspur C, Tran N, Zhang X, Natarajan R, Roberts A, Baran P, Lipton S. diAcCA, a Pro-Drug for Carnosic Acid That Activates the Nrf2 Transcriptional Pathway, Shows Efficacy in the 5xFAD Transgenic Mouse Model of Alzheimer’s Disease. Antioxidants 2025, 14: 293. PMID: 40227330, PMCID: PMC11939361, DOI: 10.3390/antiox14030293.Peer-Reviewed Original ResearchAlzheimer's diseaseNrf2 transcriptional pathwayTranscriptional pathwaysAmyloid plaque formationMouse model of Alzheimer's diseaseTransgenic mouse model of Alzheimer's diseaseModel of Alzheimer's diseaseAD transgenic miceCorrelated to cognitive declineNeuritic aggregatesTau tanglesAmyloid plaquesPhospho-tauCarnosic acidSynapse lossHuman ADPurified CATransgenic mouse modelPhenolic diterpenesAmyloidMicroglial inflammationPathwayPlaque formationTransgenic miceNrf2Polyamine metabolism is dysregulated in COXFA4-related mitochondrial disease
Marquez J, Viviano S, Beckman E, Thies J, Friedland-Little J, Lam C, Deniz E, Shelkowitz E. Polyamine metabolism is dysregulated in COXFA4-related mitochondrial disease. Human Genetics And Genomics Advances 2025, 6: 100418. PMID: 39967265, PMCID: PMC11946867, DOI: 10.1016/j.xhgg.2025.100418.Peer-Reviewed Original ResearchOrnithine decarboxylase pathwayCytochrome c oxidaseMitochondrial diseaseCause of mitochondrial diseaseAnalysis of cellular gene expressionSubunits of cytochrome c oxidaseC oxidaseTissue-specific diseasesCellular gene expressionDeficiency of cytochrome c oxidaseLeigh-like diseaseElectron donor NADHDownstream deficienciesMitochondrial membraneProtein complexesCellular functionsOxidative phosphorylationProtein subunitsGene expressionMetabolic pathwaysPolyamine metabolismPathwayProteinPoor growthAdenosine triphosphate
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