2023
Effects of short‐term supervised exercise training on liver fat in adolescents with obesity: a randomized controlled trial
Tas E, Landes R, Diaz E, Bai S, Ou X, Buchmann R, Na X, Muzumdar R, Børsheim E, Dranoff J. Effects of short‐term supervised exercise training on liver fat in adolescents with obesity: a randomized controlled trial. Obesity 2023, 31: 2740-2749. PMID: 37731271, PMCID: PMC11519784, DOI: 10.1002/oby.23887.Peer-Reviewed Original ResearchConceptsHigh-intensity interval trainingCardiorespiratory fitnessOral glucose tolerance testDual-energy X-ray absorptiometryAttenuation parameter (CAP) scoreIntrahepatic triglyceride contentSerum alanine aminotransferaseGlucose tolerance testSteatotic liver diseaseX-ray absorptiometryLiver magnetic resonanceCardiometabolic markersCardiometabolic healthExercise trainingHIIT protocolsLiver diseaseLiver fatExercise protocolTolerance testCRF testAlanine aminotransferaseInterval trainingMRI-PDFFTriglyceride contentObesityCoffee as chemoprotectant in fatty liver disease: caffeine-dependent and caffeine-independent effects
Dranoff J. Coffee as chemoprotectant in fatty liver disease: caffeine-dependent and caffeine-independent effects. AJP Gastrointestinal And Liver Physiology 2023, 324: g419-g421. PMID: 36976807, DOI: 10.1152/ajpgi.00026.2023.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsLiver diseaseLiver-related mortalityChronic liver diseaseFatty liver diseasePositive health outcomesPrimary active ingredientCoffee consumptionEpidemiological studiesHealth outcomesAdenosine receptorsBiological plausibilityDiseaseActive ingredientsPatientsAntagonistMortalityRecent publicationsReceptors
2022
Obesity, but not glycemic control, predicts liver steatosis in children with type 1 diabetes
Tas E, Bai S, Mak D, Diaz E, Dranoff J. Obesity, but not glycemic control, predicts liver steatosis in children with type 1 diabetes. Journal Of Diabetes And Its Complications 2022, 36: 108341. PMID: 36345110, DOI: 10.1016/j.jdiacomp.2022.108341.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseBody mass indexMajor risk factorType 1 diabetesHDL ratioHDL cholesterolLiver diseaseClinical parametersRisk factorsCAP scoresDiagnostic performanceReceiver operator curve analysisCommon liver diseaseFatty liver diseaseNon-diabetic childrenNon-obese subjectsFindings of childrenCross-sectional studyNAFLD statusClinical characteristicsGlycemic controlObese groupObese subjectsFurther workupMass indexReview of existing evidence demonstrates that methotrexate does not cause liver fibrosis
Cheema HI, Haselow D, Dranoff JA. Review of existing evidence demonstrates that methotrexate does not cause liver fibrosis. Journal Of Investigative Medicine 2022, 70: 1452-1460. PMID: 36002175, DOI: 10.1136/jim-2021-002206.Peer-Reviewed Original ResearchConceptsChronic liver diseaseLiver diseaseLiver fibrosisLiver injuryPre-existing chronic liver diseaseNon-alcoholic fatty liver diseaseLong-term methotrexateMeta-analysis portionProgressive liver injurySerial liver biopsiesFatty liver diseaseAdvanced liver fibrosisCare of patientsMetabolic liver diseaseNon-invasive assessmentComprehensive literature searchAssessment of injuryMethotrexate doseAdvanced fibrosisCommon indicationDirect causeLiver biopsyTherapeutic dosesRisk factorsInclusion criteriaProteomics Indicates Lactate Dehydrogenase Is Prognostic in Acetaminophen-Induced Acute Liver Failure Patients and Reveals Altered Signaling Pathways
Vazquez JH, Kennon-McGill S, Byrum SD, Mackintosh SG, Jaeschke H, Williams DK, Lee WM, Dranoff JA, McGill MR, Group A. Proteomics Indicates Lactate Dehydrogenase Is Prognostic in Acetaminophen-Induced Acute Liver Failure Patients and Reveals Altered Signaling Pathways. Toxicological Sciences 2022, 187: 25-34. PMID: 35172013, PMCID: PMC9216044, DOI: 10.1093/toxsci/kfac015.Peer-Reviewed Original ResearchConceptsAcute liver failureEnd-stage liver diseaseALF patientsLactate dehydrogenaseLiver diseaseDay 1Acute Liver Failure Study GroupAcute liver failure patientsTransplant-free survivorsKing's College criteriaLiver failure patientsMost clinical laboratoriesFailure patientsLiver failurePrognostic valueControl volunteersAlanine aminotransferaseStudy groupPrognostic potentialPeak injuryDay 3Good biomarkerDay 1 samplesNonsurvivorsPatientsShort‐Term Safety of Repeated Acetaminophen Use in Patients With Compensated Cirrhosis
McGill MR, James LP, McCullough SS, Moran JH, Mathews SE, Peterson EC, Fleming DP, Tripod ME, Vazquez JH, Kennon‐McGill S, Spencer HJ, Dranoff JA. Short‐Term Safety of Repeated Acetaminophen Use in Patients With Compensated Cirrhosis. Hepatology Communications 2022, 6: 361-373. PMID: 34558847, PMCID: PMC8793989, DOI: 10.1002/hep4.1810.Peer-Reviewed Original ResearchConceptsAPAP-protein adductsAcetaminophen useCirrhosis groupClinical outcomesDay 5Sensitive biomarkerAdverse clinical outcomesShort-term administrationCompensated cirrhosisLiver injuryAPAP administrationLiver damagePK analysisCurrent guidelinesStudy initiationCirrhosisTerm safetyDay 1Day 3APAP metabolitesHigh dosesPatientsPilot studyAPAPLonger treatment
2020
Fibroblast Growth Factor-21 to Adiponectin Ratio: A Potential Biomarker to Monitor Liver Fat in Children With Obesity
Tas E, Bai S, Ou X, Mercer K, Lin H, Mansfield K, Buchmann R, Diaz EC, Oden J, Børsheim E, Adams SH, Dranoff J. Fibroblast Growth Factor-21 to Adiponectin Ratio: A Potential Biomarker to Monitor Liver Fat in Children With Obesity. Frontiers In Endocrinology 2020, 11: 654. PMID: 33071964, PMCID: PMC7533567, DOI: 10.3389/fendo.2020.00654.Peer-Reviewed Original ResearchConceptsNon-alcoholic fatty liver diseaseMagnetic resonance imagingIntrahepatic triglyceridesPercent changePotential biomarkersClinical weight loss programSerum fibroblast growth factorFibroblast growth factor 21Liver fat percentFatty liver diseaseWeight loss programGrowth factor 21Non-invasive biomarkersFibroblast growth factorCourse diseaseSerum FGF21Adiponectin ratioFinal visitAdiponectin levelsLiver biopsyLiver diseaseObese childrenLoss programLiver fatFactor 21
2019
Reduction in SNAP-23 Alters Microfilament Organization in Myofibrobastic Hepatic Stellate Cells.
Eubanks HB, Lavoie EG, Goree J, Kamykowski JA, Gokden N, Fausther M, Dranoff JA. Reduction in SNAP-23 Alters Microfilament Organization in Myofibrobastic Hepatic Stellate Cells. Gene Expression 2019, 20: 25-37. PMID: 31757226, PMCID: PMC7284106, DOI: 10.3727/105221619x15742818049365.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActin Depolymerizing FactorsActinsAnimalsCarbon TetrachlorideCell LineCell MovementCell SeparationGene Knockdown TechniquesHepatic Stellate CellsHumansLiverLiver CirrhosisMiceMyofibroblastsQb-SNARE ProteinsQc-SNARE ProteinsRho-Associated KinasesRNA InterferenceRNA, Small InterferingSignal TransductionStress FibersWound HealingConceptsSNAP-23T-SNARE proteinsSpecific SNARE proteinsMyofibroblastic hepatic stellate cellsSNARE proteinsActin cytoskeletonActin dynamicsHepatic stellate cellsCytoskeletal reorganizationCell movementPlasma membraneHomologous proteinsExtracellular environmentMicrofilament organizationSNAP-25HSC phenotypeReceptor proteinProteinStellate cellsQuiescent hepatic stellate cellsPhenotypeCellsCritical effector cellsCytoskeletonVivo
2018
Junctional adhesion molecules JAM-B and JAM-C promote autoimmune-mediated liver fibrosis in mice
Hintermann E, Bayer M, Conti CB, Fuchs S, Fausther M, Leung PS, Aurrand-Lions M, Taubert R, Pfeilschifter JM, Friedrich-Rust M, Schuppan D, Dranoff JA, Gershwin ME, Manns MP, Imhof BA, Christen U. Junctional adhesion molecules JAM-B and JAM-C promote autoimmune-mediated liver fibrosis in mice. Journal Of Autoimmunity 2018, 91: 83-96. PMID: 29753567, DOI: 10.1016/j.jaut.2018.05.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell AdhesionCell Adhesion MoleculesCells, CulturedCholangitis, SclerosingDisease Models, AnimalEndothelial CellsFatty Acids, MonounsaturatedFemaleFibrosisHepatitis, AutoimmuneHumansImmunoglobulinsInflammationLiverLiver Cirrhosis, BiliaryMiceMice, Inbred C57BLMice, KnockoutMyocytes, Smooth MuscleMyofibroblastsVascular RemodelingVasoconstrictionConceptsPrimary sclerosing cholangitisHepatic stellate cellsPrimary biliary cholangitisPortal fibroblastsJunctional adhesion molecule JAMEndothelial cellsLiver fibrosisBile duct stricturesChronic liver diseaseAnti-fibrosis therapyBiopsies of patientsLoss of JAMRole of JAMSmooth muscle cellsEndothelial JAMIntrahepatic vasoconstrictionFunction of JAMSclerosing cholangitisDuct stricturesLiver inflammationBiliary cholangitisBiliary fibrosisChronic modelLeukocyte infiltrationLiver disease
2017
The Cholangiocyte Adenosine‐IL-6 Axis Regulates Survival During Biliary Cirrhosis
Lavoie EG, Fausther M, Goree JR, Dranoff JA. The Cholangiocyte Adenosine‐IL-6 Axis Regulates Survival During Biliary Cirrhosis. Gene Expression 2017, 17: 327-340. PMID: 28893353, PMCID: PMC5885153, DOI: 10.3727/105221617x15042723767876.Peer-Reviewed Original ResearchConceptsBile duct ligationIL-6 releaseExogenous IL-6Common bile duct ligationBiliary cirrhosisIL-6Duct ligationInjury responseIL-6 mRNA expressionIL-6 upregulationIL-6 secretionA2B adenosine receptorsLiver cell typesA2BAR activationBile infarctsInflammatory cellsCirrhosisEpithelial responseH69 cellsIntracellular Ca2Adenosine receptorsExtracellular adenosineInduces releaseMRNA expressionRegulates SurvivalCoffee Consumption and Prevention of Cirrhosis: In Support of the Caffeine Hypothesis
Dranoff JA. Coffee Consumption and Prevention of Cirrhosis: In Support of the Caffeine Hypothesis. Gene Expression 2017, 18: 1-3. PMID: 28893365, PMCID: PMC5885142, DOI: 10.3727/105221617x15046391179559.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsTransforming Growth Factors α and β Are Essential for Modeling Cholangiocarcinoma Desmoplasia and Progression in a Three-Dimensional Organotypic Culture Model
Manzanares MÁ, Usui A, Campbell DJ, Dumur CI, Maldonado GT, Fausther M, Dranoff JA, Sirica AE. Transforming Growth Factors α and β Are Essential for Modeling Cholangiocarcinoma Desmoplasia and Progression in a Three-Dimensional Organotypic Culture Model. American Journal Of Pathology 2017, 187: 1068-1092. PMID: 28315313, PMCID: PMC5417049, DOI: 10.1016/j.ajpath.2017.01.013.Peer-Reviewed Original ResearchConceptsIntrahepatic cholangiocarcinomaOrganotypic culture modelDesmoplastic reactionThree-dimensional organotypic culture modelsCulture modelMesenchymal cell originCholangiocarcinoma cell growthCancer-associated myofibroblastsGrowth factor αAggressive malignancyDense fibrocollagenous stromaMalignant gradingCell anaplasiaSitu tumorsExtracellular vesicles carry microRNA‐195 to intrahepatic cholangiocarcinoma and improve survival in a rat model
Li L, Piontek K, Ishida M, Fausther M, Dranoff JA, Fu R, Mezey E, Gould SJ, Fordjour FK, Meltzer SJ, Sirica AE, Selaru FM. Extracellular vesicles carry microRNA‐195 to intrahepatic cholangiocarcinoma and improve survival in a rat model. Hepatology 2017, 65: 501-514. PMID: 27474881, PMCID: PMC5258762, DOI: 10.1002/hep.28735.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBile Duct NeoplasmsCarcinogenesisCell MovementCholangiocarcinomaDisease Models, AnimalDown-RegulationExtracellular VesiclesFibroblastsHumansImmunohistochemistryMaleMicroRNAsRandom AllocationRatsRats, Inbred F344Real-Time Polymerase Chain ReactionSensitivity and SpecificitySurvival RateTransfectionTumor Cells, CulturedTumor MicroenvironmentConceptsExtracellular vesiclesMiR speciesCancer cellsCancer-associated fibroblastsFibroblasts-derived extracellular vesiclesMiR-195Rat modelMicroRNA speciesQuantitative reverse transcription polymerase chain reactionCCA cellsSpeciesCancer developmentCancer fibroblastsHuman cholangiocarcinomaMiR contentReverse transcription-polymerase chain reactionNovel therapeuticsFibroblastsCentral roleSize of cancerVesiclesCellsPolymerase chain reactionMicroRNA-195Cancer microenvironment
2015
Strategies and endpoints of antifibrotic drug trials: Summary and recommendations from the AASLD Emerging Trends Conference, Chicago, June 2014
Torok NJ, Dranoff JA, Schuppan D, Friedman SL. Strategies and endpoints of antifibrotic drug trials: Summary and recommendations from the AASLD Emerging Trends Conference, Chicago, June 2014. Hepatology 2015, 62: 627-634. PMID: 25626988, PMCID: PMC4515973, DOI: 10.1002/hep.27720.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsClinical trial designTrial designLiver diseaseLiver fibrosisClinical trialsFuture clinical trial designChronic liver diseaseOff-target toxicityKey unmetPotential off-target toxicityAntifibrotic agentsNoninvasive markerAntifibrotic therapyAntifibrotic drugsPreclinical proofDrug trialsStudy groupRisk populationsPharmacological targetsTrialsExpert overviewFibrosisDiseaseEndpointAmerican AssociationBeyond scar formation: Portal myofibroblast‐mediated angiogenesis in the fibrotic liver
Fausther M, Dranoff JA. Beyond scar formation: Portal myofibroblast‐mediated angiogenesis in the fibrotic liver. Hepatology 2015, 61: 766-768. PMID: 25502320, PMCID: PMC5115210, DOI: 10.1002/hep.27653.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2014
Expression of mediators of purinergic signaling in human liver cell lines
Goree JR, Lavoie EG, Fausther M, Dranoff JA. Expression of mediators of purinergic signaling in human liver cell lines. Purinergic Signalling 2014, 10: 631-638. PMID: 25194703, PMCID: PMC4272373, DOI: 10.1007/s11302-014-9425-4.Peer-Reviewed Original ResearchConceptsLiver cell subpopulationsPurinergic signalingPurinergic signalsCell subpopulationsCell linesExpression of mediatorsLiver disease pathogenesisHuman liver cell lineHuman cell line modelsCell line modelsLiver cell lineHepatic functionP2Y receptorsP2X receptorsLX-2Disease pathogenesisAdenosine receptorsLiver physiologyRT-PCRReceptorsHuman cell linesPurinergicLiverSubpopulationsSignalingNT5E Mutations That Cause Human Disease Are Associated with Intracellular Mistrafficking of NT5E Protein
Fausther M, Lavoie EG, Goree JR, Baldini G, Dranoff JA. NT5E Mutations That Cause Human Disease Are Associated with Intracellular Mistrafficking of NT5E Protein. PLOS ONE 2014, 9: e98568. PMID: 24887587, PMCID: PMC4041762, DOI: 10.1371/journal.pone.0098568.Peer-Reviewed Original ResearchConceptsHuman diseasesWild typeCOS-7 kidney cellsWild-type proteinNovel genetic causesSubcellular traffickingER retentionMalachite green assayHeterologous expressionType proteinDefective proteinMutant fusionTrafficking defectsPlasma membraneExtracellular environmentGene mutationsDegradation of AMPBiochemical activityConfocal immunofluorescenceDistinct familiesWestern blot analysisCatalytic functionSynthetic apparatusMutant humanCell surfaceHow does coffee prevent liver fibrosis? biological plausibility for recent epidemiological observations
Dranoff JA, Feld JJ, Lavoie É, Fausther M. How does coffee prevent liver fibrosis? biological plausibility for recent epidemiological observations. Hepatology 2014, 60: 464-467. PMID: 24464631, PMCID: PMC4110162, DOI: 10.1002/hep.27032.Peer-Reviewed Original Research
2013
CXCL12 induces hepatic stellate cell contraction through a calcium-independent pathway
Saiman Y, Agarwal R, Hickman DA, Fausther M, El-Shamy A, Dranoff JA, Friedman SL, Bansal MB. CXCL12 induces hepatic stellate cell contraction through a calcium-independent pathway. AJP Gastrointestinal And Liver Physiology 2013, 305: g375-g382. PMID: 23812037, PMCID: PMC3761245, DOI: 10.1152/ajpgi.00185.2012.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCalciumCell LineCell ShapeChelating AgentsChemokine CXCL12CollagenDose-Response Relationship, DrugGelsHepatic Stellate CellsHumansMiceMyosin Light ChainsPhenotypePhosphorylationProtein Kinase InhibitorsReceptors, CXCR4Recombinant ProteinsRho-Associated KinasesRNA InterferenceSignal TransductionTransfectionConceptsHepatic stellate cellsChronic liver diseaseStellate cell contractionPortal hypertensionLiver diseaseLiver fibrosisSmall molecule inhibitorsStimulation of HSCsHepatic stellate cell contractionEnd-stage liver diseaseGel contractionActivated hepatic stellate cellsAddition of AMD3100Functional chemokine receptorsIntrahepatic blood flowCXCR4-dependent mannerCell contractionDeath of patientsRho-kinase pathwayMolecule inhibitorsCollagen gel latticeRho-kinase inhibitorCalcium-independent fashionCalcium-independent pathwayMyosin light chain phosphorylation
2012
Advances in cholangiocyte immunobiology
Syal G, Fausther M, Dranoff JA. Advances in cholangiocyte immunobiology. AJP Gastrointestinal And Liver Physiology 2012, 303: g1077-g1086. PMID: 22961800, PMCID: PMC3517647, DOI: 10.1152/ajpgi.00227.2012.Peer-Reviewed Original ResearchConceptsImmune responseMajor histocompatibility complex antigensExtrahepatic bile ductAdaptive immune responsesHistocompatibility complex antigensHepatic stellate cellsBiliary infectionBiliary cirrhosisInflammatory mediatorsBiliary tractPortal fibroblastsBile ductProfessional APCsBiliary systemInflammatory modulatorsImmune cellsComplex antigensStellate cellsDuct epitheliumMyofibroblastic differentiationIntracellular signaling cascadesCholangiocytesFirst lineAdhesion moleculesCytokines