2025
A Comparison of Novel Serum Markers of Liver Health in Adolescents With Metabolic Dysfunction‐Associated Steatotic Liver Disease
Bade N, Hellman D, Matye D, Jiang S, Tryggestad J, Yu Z, Short K, Palle S. A Comparison of Novel Serum Markers of Liver Health in Adolescents With Metabolic Dysfunction‐Associated Steatotic Liver Disease. Journal Of Cellular And Molecular Medicine 2025, 29: e70817. PMID: 40874510, PMCID: PMC12392135, DOI: 10.1111/jcmm.70817.Peer-Reviewed Original ResearchConceptsMiR-192MiR-122Markers of liver healthCK-18 fragmentsCK-18N-terminal propeptideNormal weightLiver diseaseN-terminal propeptide of type III procollagenSteatotic liver diseaseMiRNA candidatesPropeptide of type III procollagenNon-invasive biomarkersLiver fibrosis stageMiRNAsArea under the receiver operating curveType III procollagenReceiver operating curveLiver histopathological featuresSerum markersFibrosis stageHistopathological featuresLiver healthYKL-40Cytokeratin 18Biliary pseudo tumor associated with hepatic atrophy
Joldoshova A, Khandakar B, Lee H, Lam R, Jain D. Biliary pseudo tumor associated with hepatic atrophy. Human Pathology 2025, 163: 105879. PMID: 40714130, DOI: 10.1016/j.humpath.2025.105879.Peer-Reviewed Original ResearchConceptsTrans-arterial chemoembolizationDuctular proliferationClinicopathological featuresPortal veinNon-infiltrative growth patternCaudate lobe hypertrophyMetastatic colon cancerRight portal veinRight lobe atrophyWild-type staining patternPseudo-tumoral lesionWedge resectionCytologic atypiaClinical presentationMetastatic fociSegmental hepatectomyPortal hypertensionTumor glandsAtrophic lobeParenchymal injurySegmental atrophyIntrahepatic cholangiocarcinomaVascular abnormalitiesRight lobeNuclear expressionExpression of DNAJB1-PRKACA oncogene suppresses the differentiation potential of liver progenitor organoids towards a hepatocyte lineage
DiPietro E, Bharath N, Karski M, Durfee O, Sherman M, Ma Q, Sun L, Farghli A, Smith C, Kycia I, Sethupathy P, Goessling W, Rogers M, Vakili K. Expression of DNAJB1-PRKACA oncogene suppresses the differentiation potential of liver progenitor organoids towards a hepatocyte lineage. Scientific Reports 2025, 15: 25796. PMID: 40670531, PMCID: PMC12267505, DOI: 10.1038/s41598-025-11028-4.Peer-Reviewed Original ResearchConceptsDNAJB1-PRKACA fusion geneFibrolamellar carcinomaDNAJB1-PRKACAFusion geneEpithelial cellsDifferentiation potentialPrimary liver cancerLiver progenitor cellsMature epithelial cellsFLC tumorsNormal differentiation processOncogenic driversProgenitor cellsHealthy adolescentsSingle-nucleus RNA sequencingHepatocyte lineageDownregulation of genesOncogenic mechanismsLiver cancerUpregulation of genesHepatocyte differentiationOrganoidsHepatocytesYoung adultsCellsModerate- to High-grade Blunt Liver and Spleen Injuries Warrant Repeat Imaging to Identify Treatable Complications
Perea L, Fletcher K, Morgan M, McNickle A, Fraser D, Rosenthal M, Wang E, Goldenberg A, Hancin E, Smith A, Leoni J, Meizoso J, O’Neil C, Noorbakhsh M, Almahmoud K, Lapham D, Sais E, Cullinane D, Falank C, Maung A, Bhattacharya B, Bjordahl P, Guido J, Dixon A, Carlson A, Udekwu P, Shell C, Bilaniuk J, Nemeth Z, Butts C, Zorn J, Ahmeti M, Briggs S, Haan J, Lightwine K, Oh J, Marshall G, Collom M, Lewis R, Davis G, Ratnasekera A, Okorafor O, Broderick M, Kundi R, Muse T, Mehta C, Collins M, Lawrence J, Jacobson L, Williams J, Ewing K, Narveson J, Lieser M, Streams J, Gadomski S, Berne J, Mederos D, Teichman A, Choron R, Grant J, Frederick N, Evans D, Doris S, Scantling D, Laudon A, Craft P, Kirsch J, Brigode W, Stecher J, Nahmias J, Alvarez C, Mousafeiris V, Mulita F, Turcotte M, Holliday T, Michetti C, Glass N, Jackovich A, Bankhead B, Thompson B, Chowdhury S, Thurston B, Bailey C, Bresz K, Horst M, Bernard A, Hazelton J. Moderate- to High-grade Blunt Liver and Spleen Injuries Warrant Repeat Imaging to Identify Treatable Complications. Annals Of Surgery 2025, 282: 580-591. PMID: 40623163, DOI: 10.1097/sla.0000000000006831.Peer-Reviewed Original ResearchConceptsBlunt liverProspective observational studyBSI patientsNonoperative managementIdentification of complicationsProspective observational study of adult patientsClinical conditionsObservational study of adult patientsRepeated imagingStudy of adult patientsClinical changesInjury-related complicationsTime of diagnosisPatient's clinical conditionImages of patientsBlunt spleenAsymptomatic patientsGrade 4 to 5Adult patientsConsensus guidelinesTreatable complicationsOperative interventionComplicationsPatientsInjury patientsBinge drinking triggers VGLUT3-mediated glutamate secretion and subsequent hepatic inflammation by activating mGluR5/NOX2 in Kupffer cells
Yang K, Kim K, Ryu T, Shim Y, Kim H, Choi S, Kim M, Chung K, Lee E, Lee K, Jeon J, Kim P, Kim Y, Ku T, Jeong H, Nam K, Lim G, Choi D, Kim S, Eun H, Kim W, Jeong W. Binge drinking triggers VGLUT3-mediated glutamate secretion and subsequent hepatic inflammation by activating mGluR5/NOX2 in Kupffer cells. Nature Communications 2025, 16: 5546. PMID: 40595616, PMCID: PMC12216207, DOI: 10.1038/s41467-025-60820-3.Peer-Reviewed Original ResearchConceptsVesicular glutamate transporter 3Alcohol-related steatohepatitisKupffer cellsIntracellular Ca2+ levelsMetabotropic glutamate receptor 5Chronic alcohol intakeBinge drinkingImmune cell activationGlutamate receptor 5Analysis of patient samplesCa2+ levelsHepatic amino acid metabolismNADPH oxidase 2Plasma glutamate concentrationExocytosis of glutamateAlcohol intakeReceptor 5Male miceAryl hydrocarbon receptorAmino acid metabolismHepatic inflammationCell activationPerivenous hepatocytesGlutamate secretionPatient samplesA TMPRSS6-inhibiting mAb improves disease in a β-thalassemia mouse model and reduces iron in healthy humans
Lob H, Singh N, Mohammadi K, Ivanova L, Crowell B, Kim H, Kravets L, Das N, Ray Y, Kim J, Rottey S, Labriola-Tompkins E, Hassan H, Farrelly L, Chin H, Preda M, Noakes L, Saotome K, Franklin M, Retter M, Karayusuf E, Flanagan J, Olson W, Nannuru K, Idone V, Burczynski M, Harari O, Perlee L, Van Lancker G, Murphy A, Economides A, Hatsell S. A TMPRSS6-inhibiting mAb improves disease in a β-thalassemia mouse model and reduces iron in healthy humans. JCI Insight 2025, 10: e191813. PMID: 40548380, PMCID: PMC12220967, DOI: 10.1172/jci.insight.191813.Peer-Reviewed Original ResearchConceptsB-thalassemiaIneffective erythropoiesisIron overloadIron-refractory iron deficiency anemiaTransmembrane serine protease 6Placebo-controlled studyIron deficiency anemiaHealthy human volunteersNegative regulatorLoss-of-function mutationsHepatic hepcidin expressionTMPRSS6 geneTolerability profileSerum hepcidinHuman mAbsHepcidin levelsImpaired erythropoiesisSerum ironBone densityCardiac diseaseLiver fibrosisMouse modelB-globin geneHepcidin expressionHormone hepcidinTargeted inhibition of pathobiont virulence factor mitigates alcohol-associated liver disease
Yang Y, Duan Y, Lang S, Fondevila M, Schöler D, Harberts A, Cabré N, Chen S, Shao Y, Vervier K, Miyamoto Y, Zhang X, Chu H, Yang L, Tan C, Eckmann L, Bosques-Padilla F, Verna E, Abraldes J, Brown R, Vargas V, Altamirano J, Caballería J, Shawcross D, Louvet A, Lucey M, Mathurin P, Garcia-Tsao G, Bataller R, Stärkel P, Lawley T, Schnabl B. Targeted inhibition of pathobiont virulence factor mitigates alcohol-associated liver disease. Cell Host & Microbe 2025, 33: 957-972.e6. PMID: 40441146, PMCID: PMC12162233, DOI: 10.1016/j.chom.2025.05.003.Peer-Reviewed Original ResearchConceptsEthanol-induced liver diseaseAlcohol-associated liver diseaseAlcohol-associated hepatitisLiver diseaseGenome of Escherichia coliE. coliMetagenomic sequencing of fecal samplesInternational cohort of patientsGenetic manipulation of bacteriaGnotobiotic mouse modelOutcomes of patientsManipulation of bacteriaCohort of patientsScavenger receptor MARCOGlobal health burdenVirulence factorsMetagenomic sequencingGut microbiotaGenetic manipulationDisease progressionMouse modelKupffer cellsKpsMBacterial spreadInternational cohortGly-βMCA modulates bile acid metabolism to reduce hepatobiliary injury in Mdr2 KO mice
Hasan M, Wang H, Luo W, Du Y, Li T. Gly-βMCA modulates bile acid metabolism to reduce hepatobiliary injury in Mdr2 KO mice. AJP Gastrointestinal And Liver Physiology 2025, 329: g45-g57. PMID: 40418643, PMCID: PMC12178242, DOI: 10.1152/ajpgi.00044.2025.Peer-Reviewed Original ResearchConceptsKO miceBile acid compositionBile acid pool sizeBile acid poolBile acid hydrophobicityHepatic bile acidsHepatobiliary toxicityBile acid metabolismMale miceTherapeutic benefitCholestasis modelMdr2-KO miceDecreased liver injuryBile acidsSerum alkaline phosphataseBile acid absorptionAlkaline phosphataseFecal bile acid excretionAcid compositionDiminished therapeutic efficacyImpaired bile flowAcid metabolismHepatobiliary injuryUnique pharmacokineticsBiliary injuryChanges in the FXR-cistrome and alterations in bile acid physiology in Wilson disease
Wooton-Kee C, Yalamanchili H, Mohamed I, Hassan M, Setchell K, Rivas M, Coskun A, Putluri V, Putluri N, Jalal P, Schilsky M, Moore D. Changes in the FXR-cistrome and alterations in bile acid physiology in Wilson disease. Hepatology Communications 2025, 9: e0707. PMID: 40408300, PMCID: PMC12106221, DOI: 10.1097/hc9.0000000000000707.Peer-Reviewed Original ResearchConceptsWild-type miceFarnesoid X receptorWilson's diseaseNon-parenchymal cellsDistal intergenic regionsLiver bile acid concentrationWD patientsHealthy controlsMetabolic target genesFarnesoid X Receptor RegulationBile salt export pumpIntergenic regionFXR activationAutosomal recessive disorderBile acid homeostasisBile acid physiologyFarnesoid X receptor activationPromoter regionHomeostasis pathwaysBile acid metabolismDecreasing FXR activityTarget genesBile acid profilesMarker genesStress pathwaysEmbryonic mast cells arise from the Cpa3-expressing precursors but not granulocyte-monocyte progenitors
Ma W, Chen H, Gao F, Zhao H, Wu N, Zhang S, Zhu Y, Xu Z, Lan Y, Liu B, Ye Y, Liu Z, Ginhoux F, Su B. Embryonic mast cells arise from the Cpa3-expressing precursors but not granulocyte-monocyte progenitors. Science China Life Sciences 2025, 68: 2363-2378. PMID: 40419842, DOI: 10.1007/s11427-024-2891-1.Peer-Reviewed Original ResearchConceptsGranulocyte-monocyte progenitorsMast cellsFetal liverMC precursorsEarly yolk sacIn vivo transplantation assaysSkin mast cellsDermal mast cellsIn vitro differentiationYolk sacImmune cellsTransplantation assaysSingle-cell RNA sequencingEmbryonic dayImmunological diseasesEmbryonic hematopoiesisPeripheral tissuesHost defenseEmbryonic originConnective tissueFate mappingFunctional studiesRNA sequencingDevelopmental programLiverMineralocorticoid receptor phase separation modulates cardiac preservation
Lei I, Sicim H, Gao W, Huang W, Noly P, Pergande M, Wilson M, Lee A, Liu L, Abou El Ela A, Jiang M, Saddoughi S, Pober J, Platt J, Cascalho M, Pagani F, Chen Y, Pitt B, Wang Z, Mortensen R, Ge Y, Tang P. Mineralocorticoid receptor phase separation modulates cardiac preservation. Nature Cardiovascular Research 2025, 4: 710-726. PMID: 40389663, PMCID: PMC12239668, DOI: 10.1038/s44161-025-00653-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Cycle ProteinsCold IschemiaHeart TransplantationHistone Deacetylase 1HumansKidneyLiverLungMaleMiceMice, Inbred C57BLMineralocorticoid Receptor AntagonistsMyocytes, CardiacNuclear ProteinsOrgan PreservationPhase SeparationReceptors, MineralocorticoidTissue DonorsTranscription FactorsConceptsMineralocorticoid receptorDonor heartsHistone deacetylase 1Bromodomain-containing 4Gold standard treatmentEnd-stage heart failureCold ischemic timeShortage of donor heartsExpressed MRDonor cardiomyocytesHuman donor heartsHeart transplantationStandard treatmentIschemic timeHeart failureCardiac preservationSolid organsPharmacological inhibitionCold preservationPreserving biologyHeartLiver 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, PMCID: PMC12067271, 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 formMetabolomic and Proteomic Signatures of Ultra-processed Foods Are Positively Associated with Adverse Liver Outcomes
Zhao L, Chen Y, Clay-Gilmour A, Zhang J, Zhang X, Steck S. Metabolomic and Proteomic Signatures of Ultra-processed Foods Are Positively Associated with Adverse Liver Outcomes. Journal Of Nutrition 2025, 155: 1851-1858. PMID: 40334783, DOI: 10.1016/j.tjnut.2025.04.034.Peer-Reviewed Original ResearchConceptsUltra-processed food intakeUltra-processed foodsAssociated with increased riskAdverse liver outcomesAssociated with riskHigher consumption of ultra-processed foodsConsumption of ultra-processed foodsMultiple 24-h dietary recallsAssociated with increased risk of obesityHazard ratioLiver outcomesConfidence intervalsFood intakeEstimate hazard ratiosRisk of obesityIn-hospital recordsData of participantsCox proportional hazards modelsProteomic signatureLiver diseaseDeath RegistryProportional hazards modelUK BiobankDietary recallsMedian Follow-UpAcute Response of Hepatocyte MRP2 Internalization as an Indicator of Ischemia-reperfusion Injury in Liver Transplantation
Monti C, Hong S, Lee A, Hong J, Eriksen C, Joshi A, Dash R, Audi S, Lee W, Kumar S, Kim J. Acute Response of Hepatocyte MRP2 Internalization as an Indicator of Ischemia-reperfusion Injury in Liver Transplantation. Transplantation 2025, 109: 1495-1505. PMID: 40320583, DOI: 10.1097/tp.0000000000005418.Peer-Reviewed Original ResearchConceptsMultidrug resistance-associated protein 2Ischemia-reperfusion injuryNormothermic machine perfusionLiver transplantationIschemia timeGraft viabilityPerfusion levelsHepatic ischemia-reperfusion injurySerum aminotransferase levelsInverse correlationAcute responseLevels of liver injury markersLiver injury markersLiver graft viabilityImmunofluorescence colocalization analysisMrp2 internalizationAminotransferase levelsMRP2-mediated transport activityInjury markersRat modelHuman LTArginase 1Loss of functionBiliary excretionSodium fluoresceinTranscriptomic and epigenomic signatures of liver metabolism and insulin sensitivity in aging mice
González J, Scharfman O, Zhu W, Kasamoto J, Gould V, Perry R, Higgins-Chen A. Transcriptomic and epigenomic signatures of liver metabolism and insulin sensitivity in aging mice. Mechanisms Of Ageing And Development 2025, 225: 112068. PMID: 40324540, PMCID: PMC12151592, DOI: 10.1016/j.mad.2025.112068.Peer-Reviewed Original ResearchConceptsDNA methylation modulesHepatic insulin resistanceRNA modulesProtein-protein interaction network analysisMetabolic pathwaysMethylation modulatorsPyruvate carboxylase fluxInteraction network analysisCitrate synthase fluxDNA methylation analysisCanonical metabolic pathwaysLipid metabolic pathwaysDecreased fatty acid oxidationComprehensive phenotypic characterizationMZF-1Fatty acid oxidationEpigenomic signaturesInsulin-stimulated conditionsModule genesNetwork analysisPhenotypic characterizationMitochondrial metabolic defectsInsulin resistanceLiver insulin resistanceMethylation analysisClinical utility of intraoperative wedge biopsies after preoperative core needle biopsies in biliary atresia
Nemeh C, Schmoke N, Wu Y, Wang P, Lagana S, Remotti H, Martinez M, Spector P, Cowles R, Kadenhe-Chiweshe A, Kurlansky P, Duron V, Stylianos S. Clinical utility of intraoperative wedge biopsies after preoperative core needle biopsies in biliary atresia. The American Journal Of Surgery 2025, 245: 116367. PMID: 40319559, DOI: 10.1016/j.amjsurg.2025.116367.Peer-Reviewed Original ResearchConceptsIntraoperative wedge biopsyPreoperative core needle biopsyCore needle biopsyNative liver survivalWedge biopsyLiver survivalNeedle biopsyBiliary atresiaFibrosis stageSingle-institution retrospective reviewClinical utilityPreoperative core biopsyLiver wedge biopsyCore biopsyIntraoperative biopsyPreoperative factorsKasai portoenterostomyRetrospective reviewCore needlePediatric surgeonsNative liverBiopsyDiscordant resultsDiscordant samplesAlanine transferaseThe peptidoglycan of Borrelia burgdorferi can persist in discrete tissues and cause systemic responses consistent with chronic illness
McClune M, Ebohon O, Dressler J, Davis M, Tupik J, Lochhead R, Booth C, Steere A, Jutras B. The peptidoglycan of Borrelia burgdorferi can persist in discrete tissues and cause systemic responses consistent with chronic illness. Science Translational Medicine 2025, 17: eadr2955. PMID: 40267217, PMCID: PMC12207536, DOI: 10.1126/scitranslmed.adr2955.Peer-Reviewed Original ResearchConceptsAcute infectionPeripheral blood mononuclear cellsBlood mononuclear cellsMurine modelPostinfectious complicationsMononuclear cellsMinimal pathologyKupffer cellsPersistent symptomsLyme arthritisPublic health concernLiver occupationLiver accumulationInflamed jointsSecreted protein profileInfectionChronic illnessOrgan-specificPatientsSynovial fluidPathogenic moleculesIn vivo 2H‐MR spectroscopy and imaging of hepatic metabolic formation of trimethylamine‐N‐oxide
Dessau H, Harris T, de Graaf R, Montrazi E, Allouche‐Arnon H, Bar‐Shir A. In vivo 2H‐MR spectroscopy and imaging of hepatic metabolic formation of trimethylamine‐N‐oxide. Magnetic Resonance In Medicine 2025, 94: 521-529. PMID: 40228097, PMCID: PMC12137761, DOI: 10.1002/mrm.30531.Peer-Reviewed Original ResearchType I interferons induce guanylate-binding proteins and lysosomal defense in hepatocytes to control malaria
Marques-da-Silva C, Schmidt-Silva C, Bowers C, Charles-Chess N, Samuel C, Shiau J, Park E, Yuan Z, Kim B, Kyle D, Harty J, MacMicking J, Kurup S. Type I interferons induce guanylate-binding proteins and lysosomal defense in hepatocytes to control malaria. Cell Host & Microbe 2025, 33: 529-544.e9. PMID: 40168996, DOI: 10.1016/j.chom.2025.03.008.Peer-Reviewed Original ResearchConceptsGuanylate-binding proteinsType I interferonPlasmodium infectionI interferonParasitophorous vacuoleLiver-stage malariaNon-immune cellsInfected host cellsCaspase-1 inflammasomeNADPH oxidase 2Clinical malariaControl malariaLysosomal fusionAntimicrobial programPlasmodium parasitesHost cellsInfected erythrocytesProtective immunityMalariaPlasmodiumGenetic inhibitionCaspase-1Immunization programsImmune circuitsMouse hepatocytesTargeting Polymeric Nanoparticles to Specific Cell Populations in the Liver
Harkins L, Vilarinho S, Saltzman W. Targeting Polymeric Nanoparticles to Specific Cell Populations in the Liver. Biochemistry 2025, 64: 1685-1697. PMID: 40127248, DOI: 10.1021/acs.biochem.4c00712.Peer-Reviewed Original ResearchConceptsLiver-resident macrophagesCell-specific targetingCell-specific deliveryAccumulation of nanoparticlesSpecific cell populationsDelivery of drugsConjugation of targeting ligandsTreatment of liver diseasesResident macrophagesKupffer cellsLiver diseaseNP administrationCell populationsConjugated nanoparticlesNP designDiseased liverSpecific deliveryCellular distributionTherapeutic carriersLiverSustained releaseNP characteristicsPolymer nanoparticlesCellsDelivery
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