2025
Design and rationale of the CORE-TIMI 72a and CORE2-TIMI 72b trials of olezarsen in patients with severe hypertriglyceridemia
Marston N, Bergmark B, Alexander V, Karwatowska-Prokopczuk E, Kang Y, Moura F, Prohaska T, Zimerman A, Zhang S, Murphy S, Tsimikas S, Giugliano R, Sabatine M. Design and rationale of the CORE-TIMI 72a and CORE2-TIMI 72b trials of olezarsen in patients with severe hypertriglyceridemia. American Heart Journal 2025, 286: 125-135. PMID: 40064331, PMCID: PMC12065585, DOI: 10.1016/j.ahj.2025.03.003.Peer-Reviewed Original ResearchConceptsSevere hypertriglyceridemiaAcute pancreatitis eventInvestigated antisense oligonucleotidesBaseline to 6 monthsPhase 3 trialTriglyceride-rich remnantsBaseline triglyceridesMatching placeboApolipoprotein C-IIIPancreatitis eventsMedian ageInhibit lipoprotein lipasePooled analysisClinical consequencesMRI substudyHypertriglyceridemiaSerum triglyceridesTG clearanceLife-threateningPatientsStudy populationApoC-IIIHepatic uptakeAntisense oligonucleotidesDedicated trials
2024
Nogo-B inhibition facilitates cholesterol metabolism to reduce hypercholesterolemia
Xue C, Zeng P, Gong K, Li Q, Feng Z, Wang M, Chen S, Yang Y, Li J, Zhang S, Yin Z, Liang Y, Yan T, Yu M, Feng K, Zhao D, Yang X, Zhang X, Ma L, Iwakiri Y, Chen L, Tang X, Chen Y, Chen H, Duan Y. Nogo-B inhibition facilitates cholesterol metabolism to reduce hypercholesterolemia. Cell Reports 2024, 43: 114691. PMID: 39235944, DOI: 10.1016/j.celrep.2024.114691.Peer-Reviewed Original ResearchLow-density lipoprotein receptorNogo-BCholesterol levelsCellular cholesterol levelsCholesterol excretionDecreased cellular cholesterol levelsATP-binding cassette transportersLiver x receptor-aHepatic uptakeLow-density lipoprotein receptor expressionCholesterol metabolic processHepatic cholesterol uptakeNogo-B expressionLowering cholesterol levelsMetabolic processesCassette transportersLipoprotein receptorApolipoprotein ELower cholesterol levelsCholesterol metabolismCholesterol uptakeDecreased cholesterol levelsReduce hypercholesterolemiaMolecular targetsExcretion
2023
Age-associated disparity in phagocytic clearance affects the efficacy of cancer nanotherapeutics
Wang Y, Deng W, Lee D, Yan L, Lu Y, Dong S, Huntoon K, Antony A, Li X, Ye R, Zhao Y, Zhao F, Schrank B, Ha J, Kang M, Yang M, Gong P, Lorenzi P, Tan L, Gallup T, Tang S, Yang Z, Li J, Sanford N, Wang H, Kim B, Jiang W. Age-associated disparity in phagocytic clearance affects the efficacy of cancer nanotherapeutics. Nature Nanotechnology 2023, 19: 255-263. PMID: 37723279, DOI: 10.1038/s41565-023-01502-3.Peer-Reviewed Original ResearchConceptsCancer nanotherapeuticsCancer nanomedicineScavenger receptor MARCOPhagocytic clearanceUptake of nanoparticlesAntitumour responseTumor deliveryTherapeutic blockadeAntitumour efficacyAge-Associated DecreaseHepatic phagocytesAntitumour effectsYoung miceHepatic macrophagesAged miceTreatment outcomesTreat multiple human diseasesProtein level analysisHepatic uptakeAge-related declineNon-human primatesNanotherapeuticsMiceNanomedicinePhagocytic uptakeOrganic Anion Transporting Polypeptide (OATP) 1B3 is a Significant Transporter for Hepatic Uptake of Conjugated Bile Acids in Humans
Pan Q, Zhu G, Xu Z, Zhu J, Ouyang J, Tong Y, Zhao N, Zhang X, Cheng Y, Zhang L, Tan Y, Li J, Zhang C, Chen W, Cai S, Boyer J, Chai J. Organic Anion Transporting Polypeptide (OATP) 1B3 is a Significant Transporter for Hepatic Uptake of Conjugated Bile Acids in Humans. Cellular And Molecular Gastroenterology And Hepatology 2023, 16: 223-242. PMID: 37146714, PMCID: PMC10394288, DOI: 10.1016/j.jcmgh.2023.04.007.Peer-Reviewed Original ResearchConceptsBA uptake transportersBile duct ligationHepatic neutrophil infiltrationCholestatic liver injuryProinflammatory cytokine productionCholic acid dietAdaptive protective responseLiver-specific overexpressionWild-type miceConjugated bile acidsUptake transportersPrimary hepatocytesUDCA feedingNeutrophil infiltrationBDL miceLiver injuryCytokine productionBile flowDuct ligationOrganic anion transporting polypeptide (OATP) 1B3Conjugated BAsTransgenic miceHepatic uptakeBile acidsProtective response
2021
Hepatocyte-specific suppression of ANGPTL4 improves obesity-associated diabetes and mitigates atherosclerosis in mice
Singh AK, Chaube B, Zhang X, Sun J, Citrin KM, Canfrán-Duque A, Aryal B, Rotllan N, Varela L, Lee RG, Horvath TL, Price N, Suárez Y, Fernandez-Hernando C. Hepatocyte-specific suppression of ANGPTL4 improves obesity-associated diabetes and mitigates atherosclerosis in mice. Journal Of Clinical Investigation 2021, 131 PMID: 34255741, PMCID: PMC8409581, DOI: 10.1172/jci140989.Peer-Reviewed Original ResearchDiet-induced obesityGlucose intoleranceHigh-fat fed conditionsLipoprotein lipaseExcess hepatic lipid accumulationSystemic metabolic dysfunctionRole of ANGPTL4Liver lipid metabolismHepatic lipid accumulationTargeted pharmacologic therapyANGPTL4 gene expressionMetabolic turnover studiesHepatic lipase activityObesity-associated diabetesFatty acidsNovel inhibition strategiesPharmacologic therapyLiver steatosisLiver damageLipoprotein remnantsCholesterol levelsMetabolic dysfunctionHepatic uptakeANGPTL4 deficiencyHL activity
2015
Heat‐Induced Radiolabeling of Nanoparticles for Monocyte Tracking by PET
Normandin M, Yuan H, Wilks M, Chen H, Kinsella J, Cho H, Guehl N, Absi‐Halabi N, Hosseini S, Fakhri G, Sosnovik D, Josephson L. Heat‐Induced Radiolabeling of Nanoparticles for Monocyte Tracking by PET. Angewandte Chemie 2015, 127: 13194-13198. DOI: 10.1002/ange.201505525.Peer-Reviewed Original ResearchPositron emission tomographyRadiolabelling of nanoparticlesStandardized uptake valueMonocytes in vitroNP pharmacokineticsSlow uptake processUptake valueLymph nodesCirculating monocytesMonocyte traffickingIV injectionImmune responseBlood clearanceEmission tomographyHepatic uptakeMonocytesPharmacokineticsLymphUptake processHeat‐Induced Radiolabeling of Nanoparticles for Monocyte Tracking by PET
Normandin M, Yuan H, Wilks M, Chen H, Kinsella J, Cho H, Guehl N, Absi‐Halabi N, Hosseini S, Fakhri G, Sosnovik D, Josephson L. Heat‐Induced Radiolabeling of Nanoparticles for Monocyte Tracking by PET. Angewandte Chemie International Edition 2015, 54: 13002-13006. PMID: 26368132, PMCID: PMC4754124, DOI: 10.1002/anie.201505525.Peer-Reviewed Original ResearchConceptsPositron emission tomographyRadiolabelling of nanoparticlesStandardized uptake valueNP pharmacokineticsSlow uptake processUptake valueLymph nodesCirculating monocytesMonocyte traffickingIV injectionImmune responseBlood clearanceEmission tomographyHepatic uptakeMonocytesPharmacokineticsLymphUptake processCytometry
2002
Mechanisms of Hepatic Transport of Drugs: Implications for Cholestatic Drug Reactions
Bohan A, Boyer J. Mechanisms of Hepatic Transport of Drugs: Implications for Cholestatic Drug Reactions. Seminars In Liver Disease 2002, 22: 123-136. PMID: 12016544, DOI: 10.1055/s-2002-30099.Peer-Reviewed Original ResearchConceptsDrug-induced cholestasisCholestatic drug reactionDrug reactionsDrug transporter expressionNumber of drugsBiliary excretionCanalicular transport proteinsAnimal modelsHepatic uptakeHepatobiliary transportersCholestasisTransporter expressionHepatic transportGenetic polymorphismsNormal functionDrugsMajor determinantForeign compoundsStudy of mechanismsTransportersExcretion
1997
Enterohepatic circulation of scymnol sulfate in an elasmobranch, the little skate (Raja erinacea)
Fricker G, Wössner R, Drewe J, Fricker R, Boyer J. Enterohepatic circulation of scymnol sulfate in an elasmobranch, the little skate (Raja erinacea). American Journal Of Physiology 1997, 273: g1023-g1030. PMID: 9374698, DOI: 10.1152/ajpgi.1997.273.5.g1023.Peer-Reviewed Original ResearchConceptsEnterohepatic circulationScymnol sulfateBile alcohol sulfatesBile flowBiliary secretionCholeretic effectMajor bile saltsHepatic uptakeHepatic eliminationIntestinal epitheliumBileLiverSkate liverHepatic transportSpecific transport mechanismsBile alcoholsMajor metaboliteFirst direct demonstrationBile saltsCholyltaurinePerfusateLittle skatePolar metabolitesCompetitive mannerDirect demonstration
1994
Characteristics of bile salt uptake into skate hepatocytes
Fricker G, Dubost V, Finsterwald K, Boyer J. Characteristics of bile salt uptake into skate hepatocytes. Biochemical Journal 1994, 299: 665-670. PMID: 8192655, PMCID: PMC1138072, DOI: 10.1042/bj2990665.Peer-Reviewed Original ResearchConceptsOrganic anion transport systemBile salt uptakeBile alcoholsBile saltsBeta-cholestane-3 alphaBile salt transportUnconjugated bile saltsTaurine-conjugated bile saltsHepatic uptakeAlpha-triolSkate bileInhibitory effectLiver cellsSkate hepatocytesIndependent transport systemsCholyltaurine transportCholyltaurineHepatocytesInhibitionAlphaUptakeSpecificity
1988
Characteristics of L-alanine uptake in freshly isolated hepatocytes of elasmobranch Raja erinacea
Ballatori N, Boyer J. Characteristics of L-alanine uptake in freshly isolated hepatocytes of elasmobranch Raja erinacea. American Journal Of Physiology 1988, 254: r801-r808. PMID: 3364608, DOI: 10.1152/ajpregu.1988.254.5.r801.Peer-Reviewed Original ResearchConceptsNeutral amino acid transport systemElasmobranch Raja erinaceaMajor gluconeogenic precursorMM alanineSodium-dependent systemAmino acid transport systemsRaja erinaceaHepatic uptakeHepatic concentrationsAcid transport systemL-alanine uptakeAminotransferase activityTumor cellsSpecific transport mechanismsMeAIB transportGluconeogenic precursorsSaturable mechanismSkate hepatocytesHepatocytesAlanine metabolismGlucose releaseMeAIBHepatocyte suspensionsRat hepatocytesUptake
1987
Identification of a single sinusoidal bile salt uptake system in skate liver
Fricker G, Hugentobler G, Meier P, Kurz G, Boyer J. Identification of a single sinusoidal bile salt uptake system in skate liver. American Journal Of Physiology 1987, 253: g816-g822. PMID: 3425718, DOI: 10.1152/ajpgi.1987.253.6.g816.Peer-Reviewed Original ResearchConceptsBile salt uptakeSkate liverAlpha-dihydroxy-5 betaBile salt derivativesAzo-3 alphaBile acid uptakeConcentration-dependent mannerPredominant bile saltHepatic uptakePhotolabile bile salt derivativeIndependent transport mechanismsAcid uptakeLiverApparent molecular weightBile saltsRat liverTaurocholate uptakeSkate hepatocytesAnion transport inhibitorUptake systemHepatocytesPhotoaffinity labelingTaurocholateDisulfonic acidIrreversible inhibitionTaurocholate uptake by isolated skate hepatocytes: effect of albumin
Smith D, Grossbard M, Gordon E, Boyer J. Taurocholate uptake by isolated skate hepatocytes: effect of albumin. American Journal Of Physiology 1987, 252: g479-g484. PMID: 3565567, DOI: 10.1152/ajpgi.1987.252.4.g479.Peer-Reviewed Original Research
1970
The effect of sodium taurocholate on the hepatic metabolism of sulfobromophthalein sodium (BSP). The role of bile flow
Boyer J, Scheig R, Klatskin G. The effect of sodium taurocholate on the hepatic metabolism of sulfobromophthalein sodium (BSP). The role of bile flow. Journal Of Clinical Investigation 1970, 49: 206-215. PMID: 5411780, PMCID: PMC322462, DOI: 10.1172/jci106229.Peer-Reviewed Original ResearchConceptsBile salt excretionBSP TmBile flowBile productionBiliary concentrationHepatic metabolismBile saltsBiliary bile salt excretionSalt excretionSulfobromophthalein sodiumSodium taurocholateMug/minSodium taurocholate infusionBile salt infusionBSP transportCholeretic propertiesSaline infusionTaurocholate infusionIndependent factorsConstant infusionHepatic uptakeMumoles/hrInfusionMul/minPeak levels
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