2025
Liver 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 form
2019
Expression of the type 3 InsP3 receptor is a final common event in the development of hepatocellular carcinoma
Guerra MT, Florentino RM, Franca A, Lima Filho AC, Dos Santos ML, Fonseca RC, Lemos FO, Fonseca MC, Kruglov E, Mennone A, Njei B, Gibson J, Guan F, Cheng YC, Ananthanarayanan M, Gu J, Jiang J, Zhao H, Lima CX, Vidigal PT, Oliveira AG, Nathanson MH, Leite MF. Expression of the type 3 InsP3 receptor is a final common event in the development of hepatocellular carcinoma. Gut 2019, 68: 1676-1687. PMID: 31315892, PMCID: PMC7087395, DOI: 10.1136/gutjnl-2018-317811.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsApoptosisCalcium SignalingCarcinogenesisCarcinoma, HepatocellularCell ProliferationCells, CulturedDNA MethylationFemaleGene Expression Regulation, NeoplasticHepatocytesHumansInositol 1,4,5-Trisphosphate ReceptorsLiverLiver NeoplasmsLiver RegenerationMaleMice, KnockoutMiddle AgedSurvival AnalysisConceptsChronic liver diseaseITPR3 expressionLiver cancer cellsLiver diseaseMouse modelFinal common eventCancer cellsSpecimens of patientsIndependent patient cohortsControl liver specimensHuman HCC cellsType 3 InsP3 receptorHuman liver samplesIncreased expression levelCancer deathPatient cohortCommon molecular eventPoor survivalHepatocellular carcinomaLiver specimensNormal liverHCC cellsAbstractTextHCCType 3 isoformDevelopmental Expression of the Cytosolic Sulfotransferases in Human Liver
Dubaisi S, Caruso J, Gaedigk R, Vyhlidal C, Smith P, Hines R, Kocarek T, Runge-Morris M. Developmental Expression of the Cytosolic Sulfotransferases in Human Liver. Drug Metabolism And Disposition 2019, 47: 592-600. PMID: 30885913, PMCID: PMC6505379, DOI: 10.1124/dmd.119.086363.Peer-Reviewed Original ResearchConceptsMRNA levelsLiver specimensHuman liverReverse transcription-quantitative polymerase chain reactionTranscription-quantitative polymerase chain reactionProtein levelsRT-qPCR analysisHuman liver cytosolHuman liver samplesQuantitative polymerase chain reactionCytosolic sulfotransferasesRNA sequencingHepatic sulfotransferasesPolymerase chain reactionDrug eliminationPredominant organInfant liverLiverLiver samplesChain reactionLiver cytosolForeign chemicalsImportant metabolic roleInfantsAdditional findings
2011
Nuclear expression of S100A4 calcium‐binding protein increases cholangiocarcinoma invasiveness and metastasization
Fabris L, Cadamuro M, Moserle L, Dziura J, Cong X, Sambado L, Nardo G, Sonzogni A, Colledan M, Furlanetto A, Bassi N, Massani M, Cillo U, Mescoli C, Indraccolo S, Rugge M, Okolicsanyi L, Strazzabosco M. Nuclear expression of S100A4 calcium‐binding protein increases cholangiocarcinoma invasiveness and metastasization. Hepatology 2011, 54: 890-899. PMID: 21618579, PMCID: PMC3753582, DOI: 10.1002/hep.24466.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnimalsApoptosisBile Duct NeoplasmsBile Ducts, IntrahepaticCell MovementCell NucleusCell ProliferationCholangiocarcinomaFemaleHumansMaleMatrix Metalloproteinase 2Matrix Metalloproteinase 9MiceMiddle AgedNeoplasm InvasivenessNeoplasm MetastasisPrognosisS100 Calcium-Binding Protein A4S100 ProteinsConceptsSurgical resectionCCA cellsNuclear expressionCCA patientsMetastatic propertiesSevere combined immunodeficiency miceTFK-1Time of surgeryRole of S100A4Log-rank testCombined immunodeficiency miceExpression of S100A4EGI-1 cellsHuman CCA cell linesPotential therapeutic targetMMP-9 secretionCCA cell linesHuman liver samplesCholangiocarcinoma invasivenessNuclear S100A4Severe prognosisPatient survivalPoor prognosisNeoplastic ductsImmunodeficiency mice
2007
Ontogeny of human hepatic cytochromes P450
Hines R. Ontogeny of human hepatic cytochromes P450. Journal Of Biochemical And Molecular Toxicology 2007, 21: 169-175. PMID: 17936930, DOI: 10.1002/jbt.20179.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAryl Hydrocarbon HydroxylasesChildChild, PreschoolCytochrome P-450 CYP2C19Cytochrome P-450 CYP2C9Cytochrome P-450 CYP2E1Cytochrome P-450 CYP3ACytochrome P-450 Enzyme SystemGene Expression Regulation, DevelopmentalGene Expression Regulation, EnzymologicHumansInfantLiverMixed Function OxygenasesConceptsHuman hepatic cytochrome P450Adverse drug reactionsConsiderable interindividual variabilityHepatic cytochrome P450Cytochrome P450Human liver samplesImportant endogenous functionsWeeks' gestationThird trimesterFirst trimesterDrug reactionsKey cytochrome P450Postnatal onsetPostnatal increaseTherapeutic efficacyInterindividual variabilityQuantitative Western blottingWestern blottingGestationLow levelsLiver samplesProbe substratesOnset of expressionTrimesterThird group
2002
Human Hepatic Flavin-Containing Monooxygenases 1 (FMO1) and 3 (FMO3) Developmental Expression
Koukouritaki S, Simpson P, Yeung C, Rettie A, Hines R. Human Hepatic Flavin-Containing Monooxygenases 1 (FMO1) and 3 (FMO3) Developmental Expression. Pediatric Research 2002, 51: 236-243. PMID: 11809920, DOI: 10.1203/00006450-200202000-00018.Peer-Reviewed Original ResearchConceptsFlavin-containing monooxygenasesExpression patternsSpecies-specific expression patternsFMO3 expressionTemporal expression patternsMajor adult isoformFMO genesPotential control mechanismsDevelopmental expressionProtein levelsAdult isoformsWestern blottingExpressionEmbryosNumerous therapeuticsIsoformsMonooxygenases 1Most individualsFMO3Microsomal fractionHuman liver samplesIntermediate levelsControl mechanismsGenesPrecise timing
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