2022
Association of renalase with clinical outcomes in hospitalized patients with COVID-19
Safdar B, Wang M, Guo X, Cha C, Chun HJ, Deng Y, Dziura J, El-Khoury JM, Gorelick F, Ko AI, Lee AI, Safirstein R, Simonov M, Zhou B, Desir GV. Association of renalase with clinical outcomes in hospitalized patients with COVID-19. PLOS ONE 2022, 17: e0264178. PMID: 35259186, PMCID: PMC8903289, DOI: 10.1371/journal.pone.0264178.Peer-Reviewed Original ResearchConceptsCOVID-19 patientsRenalase levelsIntensive care unit admissionHospitalized COVID-19 patientsMean age 64 yearsCOVID-19Cox proportional hazards modelCare unit admissionPrimary composite outcomeRetrospective cohort studyUse of vasopressorsSevere COVID-19IL-6 levelsAge 64 yearsRisk of deathCOVID-19 subjectsInitial disease severityProportional hazards modelCOVID-19 diseasePlasma renalaseUnit admissionICU admissionCohort studyComposite outcomeCytokine levels
2021
Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma
Gao Y, Wang M, Guo X, Hu J, Chen TM, Finn S, Lacy J, Kunstman JW, H. C, Bellin MD, Robert ME, Desir GV, Gorelick FS. Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma. PLOS ONE 2021, 16: e0250539. PMID: 34587190, PMCID: PMC8480607, DOI: 10.1371/journal.pone.0250539.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorCarcinoma, Pancreatic DuctalCase-Control StudiesFemaleGene Expression Regulation, NeoplasticHumansMaleMiddle AgedMonoamine OxidaseNeoplasm GradingPancreatic NeoplasmsPrognosisProspective StudiesRetrospective StudiesSurvival AnalysisUp-RegulationYoung AdultConceptsPlasma renalase levelsBorderline resectable PDACRenalase levelsPDAC precursor lesionsOverall survivalPDAC tissuesTumor characteristicsResectable PDACChronic pancreatitisPrecursor lesionsNormal pancreasPancreatic ductal adenocarcinoma growthAdvanced tumor characteristicsVaried clinical stagesWorse tumor characteristicsNode-positive diseasePancreatic ductal adenocarcinomaNormal pancreatic headSpindle-shaped cellsPlasma renalaseRenalase expressionUnderwent resectionAbdominal traumaPancreatic headPositive diseaseSex Differences in the Exocrine Pancreas and Associated Diseases
Wang M, Gorelick F, Bhargava A. Sex Differences in the Exocrine Pancreas and Associated Diseases. Cellular And Molecular Gastroenterology And Hepatology 2021, 12: 427-441. PMID: 33895424, PMCID: PMC8255941, DOI: 10.1016/j.jcmgh.2021.04.005.Peer-Reviewed Original ResearchConceptsPancreatic diseaseSex differencesExocrine pancreasLevels of estrogenAcute pancreatitis modelOverall health outcomesSex-specific mechanismsNormal exocrine pancreasG protein-coupled receptorsSex-specific changesMajor sex differencesObstructive etiologyPremenopausal womenProtein-coupled receptorsPancreatic surgeryAdrenal glandPancreatic histopathologyPancreatic secretionProtective effectLow prevalenceGranule numberDiagnostic criteriaPancreatitis modelPancreatic anatomyAssociated diseaseKetamine and xylazine effects in murine model of acute pancreatitis
Wang M, Gorelick FS. Ketamine and xylazine effects in murine model of acute pancreatitis. AJP Gastrointestinal And Liver Physiology 2021, 320: g1111-g1122. PMID: 33881355, PMCID: PMC8285583, DOI: 10.1152/ajpgi.00023.2021.Peer-Reviewed Original ResearchConceptsKet/XylAcute pancreatitis inductionPancreatitis inductionNeural pathwaysAcute pancreatitisPancreatitis severityAnesthetic agent administrationPancreatitis responsesMild acute pancreatitisExperimental animal modelsAcute pancreatitis severityAcute pancreatitis outcomesMarkers of autophagyXylazine effectsHourly injectionsC57BL/6 miceFuture studiesAnesthetic agentsAnesthetic combinationMurine modelVivo effectsAnesthesia administrationDisease processAnimal modelsAgent administration
2019
Early trypsin activation develops independently of autophagy in caerulein-induced pancreatitis in mice
Malla SR, Krueger B, Wartmann T, Sendler M, Mahajan UM, Weiss FU, Thiel FG, De Boni C, Gorelick FS, Halangk W, Aghdassi AA, Reinheckel T, Gukovskaya AS, Lerch MM, Mayerle J. Early trypsin activation develops independently of autophagy in caerulein-induced pancreatitis in mice. Cellular And Molecular Life Sciences 2019, 77: 1811-1825. PMID: 31363815, PMCID: PMC8221268, DOI: 10.1007/s00018-019-03254-7.Peer-Reviewed Original ResearchCELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation
Esteghamat F, Broughton JS, Smith E, Cardone R, Tyagi T, Guerra M, Szabó A, Ugwu N, Mani MV, Azari B, Kayingo G, Chung S, Fathzadeh M, Weiss E, Bender J, Mane S, Lifton RP, Adeniran A, Nathanson MH, Gorelick FS, Hwa J, Sahin-Tóth M, Belfort-DeAguiar R, Kibbey RG, Mani A. CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation. Nature Genetics 2019, 51: 1233-1243. PMID: 31358993, PMCID: PMC6675645, DOI: 10.1038/s41588-019-0470-3.Peer-Reviewed Original ResearchConceptsEarly-onset atherosclerosisMetabolic syndromeMetabolic syndrome traitsWhole-exome sequence analysisAttractive therapeutic targetPlatelet hyperactivationInsulin levelsPlasma insulinPlasma levelsInsulin sensitivityInsulin secretionTherapeutic targetPlatelet activationDisease mechanismsSyndrome traitsAtherosclerosisFunction mutationsSyndromeNovel lossInsulinMutationsSecretion
2017
Bidirectional regulation of Aβ levels by Presenilin 1
Bustos V, Pulina MV, Kelahmetoglu Y, Sinha SC, Gorelick FS, Flajolet M, Greengard P. Bidirectional regulation of Aβ levels by Presenilin 1. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 7142-7147. PMID: 28533411, PMCID: PMC5502639, DOI: 10.1073/pnas.1705235114.Peer-Reviewed Original ResearchConceptsAmyloid precursor proteinAβ levelsΓ-secretase complexAlzheimer's diseasePresenilin 1Pathogenesis of ADAβ peptidesEndogenous kinaseΒ-amyloid peptidePS1 functionIntramembranous proteinsCatalytic subunitΓ-secretase activityPlaque loadC-terminal fragmentAutophagic degradationPotential therapySer367Selective phosphorylationSequential proteolysisTransgenic micePhosphorylationCultured cellsΒ-secretaseDiseasePhosphorylated Presenilin 1 decreases β-amyloid by facilitating autophagosome–lysosome fusion
Bustos V, Pulina MV, Bispo A, Lam A, Flajolet M, Gorelick FS, Greengard P. Phosphorylated Presenilin 1 decreases β-amyloid by facilitating autophagosome–lysosome fusion. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 7148-7153. PMID: 28533369, PMCID: PMC5502640, DOI: 10.1073/pnas.1705240114.Peer-Reviewed Original Research
2016
Inhibition of renalase expression and signaling has antitumor activity in pancreatic cancer
Guo X, Hollander L, MacPherson D, Wang L, Velazquez H, Chang J, Safirstein R, Cha C, Gorelick F, Desir GV. Inhibition of renalase expression and signaling has antitumor activity in pancreatic cancer. Scientific Reports 2016, 6: 22996. PMID: 26972355, PMCID: PMC4789641, DOI: 10.1038/srep22996.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsAntibodiesApoptosisCarcinoma, Pancreatic DuctalCell Cycle CheckpointsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansImmunohistochemistryKaplan-Meier EstimateMaleMice, NudeMiddle AgedMonoamine OxidasePancreatic NeoplasmsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReverse Transcriptase Polymerase Chain ReactionRNA InterferenceSignal TransductionXenograft Model Antitumor AssaysConceptsRenalase expressionPancreatic cancerPancreatic ductal adenocarcinoma growthCohort of patientsPancreatic cancer tissuesPancreatic ductal adenocarcinomaPancreatic ductal adenocarcinoma cellsXenograft mouse modelAttractive therapeutic targetDuctal adenocarcinoma cellsTumor cell apoptosisOverall survivalPathogenic roleCell cycle arrestDuctal adenocarcinomaPrognostic makerTumor massMouse modelTherapeutic targetCellular injuryCancer tissuesRenalaseCancerAdenocarcinoma cellsGrowth factor
2014
Lactate Reduces Liver and Pancreatic Injury in Toll-Like Receptor– and Inflammasome-Mediated Inflammation via GPR81-Mediated Suppression of Innate Immunity
Hoque R, Farooq A, Ghani A, Gorelick F, Mehal WZ. Lactate Reduces Liver and Pancreatic Injury in Toll-Like Receptor– and Inflammasome-Mediated Inflammation via GPR81-Mediated Suppression of Innate Immunity. Gastroenterology 2014, 146: 1763-1774. PMID: 24657625, PMCID: PMC4104305, DOI: 10.1053/j.gastro.2014.03.014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Inflammatory AgentsArrestinsBeta-Arrestin 2Beta-ArrestinsCarrier ProteinsCell LineCeruletideChemical and Drug Induced Liver InjuryCytoprotectionDisease Models, AnimalDose-Response Relationship, DrugDown-RegulationGalactosamineHumansImmunity, InnateInflammasomesInjections, IntraperitonealInterleukin-1betaLipopolysaccharidesLiverMacrophagesMaleMiceMice, Inbred C57BLMonocytesNF-kappa BNLR Family, Pyrin Domain-Containing 3 ProteinPancreasPancreatitisReceptors, G-Protein-CoupledRNA InterferenceRNA, Small InterferingSignal TransductionSodium LactateToll-Like Receptor 4Toll-Like ReceptorsTransfectionConceptsToll-like receptorsRelease of IL1βAdministration of lipopolysaccharideOrgan injuryNF-κBCaspase-1TLR inductionAcute pancreatitisPyrin domain-containing protein 3Administration of lactatePromising immunomodulatory therapyAcute liver injuryAcute organ injuryMacrophages of miceDomain-containing protein 3Production of IL1βRAW 264.7 cellsConcentration of lactateAcute hepatitisImmunomodulatory therapyImmune hepatitisPancreatic injuryLactate receptorLiver injuryNLRP3 inflammasome
2013
Calcium Ameliorates Diarrhea in Immunocompromised Children
Cheng SX, Bai HX, Gonzalez‐Peralta R, Mistry PK, Gorelick FS. Calcium Ameliorates Diarrhea in Immunocompromised Children. Journal Of Pediatric Gastroenterology And Nutrition 2013, 56: 641-644. PMID: 23343935, PMCID: PMC4448079, DOI: 10.1097/mpg.0b013e3182868946.Peer-Reviewed Original Research
2012
Tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone initiates and enhances pancreatitis responses
Alexandre M, Uduman AK, Minervini S, Raoof A, Shugrue CA, Akinbiyi EO, Patel V, Shitia M, Kolodecik TR, Patton R, Gorelick FS, Thrower EC. Tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone initiates and enhances pancreatitis responses. AJP Gastrointestinal And Liver Physiology 2012, 303: g696-g704. PMID: 22837343, PMCID: PMC3468532, DOI: 10.1152/ajpgi.00138.2012.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsAcetylcholine receptorsCigarette smoke toxinsParameters of pancreatitisPancreatitis responsesTobacco carcinogen 4Acinar cell responsesRat pancreatic aciniSmoke toxinsAcute pancreatitisCigarette smokingIntraperitoneal injectionAcinar cell preparationsClinical studiesLong-term effectsCarcinogen 4Pancreatitis modelAdrenergic receptorsReceptor typesCell responsesTobacco toxinsPyknotic nucleiNNKPancreatic aciniPancreatitisActivation of Soluble Adenylyl Cyclase Protects against Secretagogue Stimulated Zymogen Activation in Rat Pancreaic Acinar Cells
Kolodecik TR, Shugrue CA, Thrower EC, Levin LR, Buck J, Gorelick FS. Activation of Soluble Adenylyl Cyclase Protects against Secretagogue Stimulated Zymogen Activation in Rat Pancreaic Acinar Cells. PLOS ONE 2012, 7: e41320. PMID: 22844459, PMCID: PMC3402497, DOI: 10.1371/journal.pone.0041320.Peer-Reviewed Original ResearchConceptsProtein kinase AActivation of SACZymogen activationPancreatic acinar cellsSpecific subcellular domainsAcinar cellsActivation of zymogensCerulein-treated cellsSubcellular domainsDownstream targetsKinase ASAC activitySAC inhibitorAdenylyl cyclaseDistinct mechanismsAdenylyl cyclase inhibitorElevates levelsApical regionAmylase secretionCellsActivationAcinar cell vacuolizationCAMPCAMP accumulationCell vacuolizationCerulein hyperstimulation decreases AMP-activated protein kinase levels at the site of maximal zymogen activation
Shugrue C, Alexandre M, de Villalvilla A, Kolodecik TR, Young LH, Gorelick FS, Thrower EC. Cerulein hyperstimulation decreases AMP-activated protein kinase levels at the site of maximal zymogen activation. AJP Gastrointestinal And Liver Physiology 2012, 303: g723-g732. PMID: 22821946, PMCID: PMC3468535, DOI: 10.1152/ajpgi.00082.2012.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAminoimidazole CarboxamideAMP-Activated Protein KinasesAnimalsCells, CulturedCeruletideCyclic AMP-Dependent Protein KinasesEnzyme PrecursorsGene Expression RegulationMaleMetforminOctoxynolPancreasPhosphorylationPyrazolesPyrimidinesRatsRats, Sprague-DawleyRibonucleotidesSodium Dodecyl SulfateConceptsAdenosine monophosphate-activated protein kinaseZymogen activationAMPK activityPancreatic acinar cellsMonophosphate-activated protein kinaseVacuolar ATPase activityAMPK levelsDigestive enzyme zymogensAMPK effectsProtein kinaseProtein kinase levelsE subunitAcinar cellsTime-dependent translocationCompound CCellular modelPancreatitis responsesATPase activityDifferential centrifugationPremature activationChymotrypsin activityActivationInitiating eventSoluble fractionCerulein hyperstimulation
2011
TLR9 and the NLRP3 Inflammasome Link Acinar Cell Death With Inflammation in Acute Pancreatitis
Hoque R, Sohail M, Malik A, Sarwar S, Luo Y, Shah A, Barrat F, Flavell R, Gorelick F, Husain S, Mehal W. TLR9 and the NLRP3 Inflammasome Link Acinar Cell Death With Inflammation in Acute Pancreatitis. Gastroenterology 2011, 141: 358-369. PMID: 21439959, PMCID: PMC3129497, DOI: 10.1053/j.gastro.2011.03.041.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsAnti-Inflammatory AgentsApoptosisApoptosis Regulatory ProteinsCARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1CeruletideCytoskeletal ProteinsDisease Models, AnimalDNAInflammasomesInterleukin-1MacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutNecrosisNeutrophil InfiltrationNLR Family, Pyrin Domain-Containing 3 ProteinPancreasPancreatitisPneumoniaProtein PrecursorsPurinergic P2X Receptor AntagonistsReceptors, Purinergic P2X7RNA, MessengerSeverity of Illness IndexSignal TransductionTaurolithocholic AcidToll-Like Receptor 9ConceptsToll-like receptor 9Acute pancreatitisWild-type miceAcinar cell deathPancreatic edemaTaurolithocholic acidDamage-associated molecular pattern receptorsResident immune cellsCell deathImmune cell populationsDevelopment of inflammationInitiation of inflammationCell populationsNew therapeutic strategiesMolecular pattern receptorsDAMP receptorsLung inflammationInflammatory infiltrateTLR9 expressionImmune cellsPancreatic necrosisReceptor 9TLR9 antagonistInflammasome activationPurinergic receptorsThe Emerging Role of Smoking in the Development of Pancreatitis
Alexandre M, Pandol SJ, Gorelick FS, Thrower EC. The Emerging Role of Smoking in the Development of Pancreatitis. Pancreatology 2011, 11: 469-474. PMID: 21986098, PMCID: PMC3222114, DOI: 10.1159/000332196.Peer-Reviewed Original ResearchConceptsDevelopment of pancreatitisTobacco smokingChronic pancreatitisAcute pancreatitisCigarette smokingPancreatic cancerBACKGROUND/Cigarette smokeElectronic searchSmokingPancreatitisOnly articlesEmerging RolePancreasNicotineOriginal articlesRiskMetabolitesSpecific constituentsPubMedCancerDiseaseDoseProgression
2010
Adaptive Unfolded Protein Response Attenuates Alcohol-Induced Pancreatic Damage
Lugea A, Tischler D, Nguyen J, Gong J, Gukovsky I, French SW, Gorelick FS, Pandol SJ. Adaptive Unfolded Protein Response Attenuates Alcohol-Induced Pancreatic Damage. Gastroenterology 2010, 140: 987-997.e8. PMID: 21111739, PMCID: PMC3057335, DOI: 10.1053/j.gastro.2010.11.038.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAnimalsApoptosisApoptosis Regulatory ProteinsDisease Models, AnimalDNA-Binding ProteinsEndoplasmic ReticulumEthanolMaleMiceMice, Inbred BALB CMice, KnockoutPancreas, ExocrinePancreatitis, AlcoholicProtein Disulfide-IsomerasesRatsRats, WistarRegulatory Factor X Transcription FactorsStress, PhysiologicalTissue Culture TechniquesTranscription FactorsUnfolded Protein ResponseX-Box Binding Protein 1ConceptsProtein disulfide isomeraseX-box binding protein 1ER stressUPR regulatorOxidation of PDIER protein foldingDisulfide bond formationBinding protein 1Reticulum stress responseDisulfide isomeraseProtein foldingER functionProapoptotic signalsStress responseHuman disordersXBP1 deficiencyAcinar cell deathER dysfunctionCell deathXBP1 levelsAlcohol-induced ER stressPDI levelsProtein 1UPRWild-type mice
2009
Protein Kinase C &dgr;-Mediated Processes in Cholecystokinin-8-Stimulated Pancreatic Acini
Thrower EC, Wang J, Cheriyan S, Lugea A, Kolodecik TR, Yuan J, Reeve JR, Gorelick FS, Pandol SJ. Protein Kinase C &dgr;-Mediated Processes in Cholecystokinin-8-Stimulated Pancreatic Acini. Pancreas 2009, 38: 930-935. PMID: 19752773, PMCID: PMC2767410, DOI: 10.1097/mpa.0b013e3181b8476a.Peer-Reviewed Original ResearchMeSH KeywordsAcetophenonesAmylasesAnimalsBenzopyransCalcium-Calmodulin-Dependent Protein KinasesCells, CulturedCholecystokininDose-Response Relationship, DrugEnzyme InhibitorsImmunoblottingIndolesMaleMaleimidesMiceMice, Inbred C57BLMice, KnockoutNF-kappa BPancreasPeptide FragmentsProtein Kinase C-deltaRatsRats, Sprague-DawleyTrypsinogenImpaired autophagic flux mediates acinar cell vacuole formation and trypsinogen activation in rodent models of acute pancreatitis
Mareninova OA, Hermann K, French SW, O’Konski M, Pandol SJ, Webster P, Erickson AH, Katunuma N, Gorelick FS, Gukovsky I, Gukovskaya AS. Impaired autophagic flux mediates acinar cell vacuole formation and trypsinogen activation in rodent models of acute pancreatitis. Journal Of Clinical Investigation 2009, 119: 3340-3355. PMID: 19805911, PMCID: PMC2769194, DOI: 10.1172/jci38674.Peer-Reviewed Original ResearchReducing Extracellular pH Sensitizes the Acinar Cell to Secretagogue-Induced Pancreatitis Responses in Rats
Bhoomagoud M, Jung T, Atladottir J, Kolodecik TR, Shugrue C, Chaudhuri A, Thrower EC, Gorelick FS. Reducing Extracellular pH Sensitizes the Acinar Cell to Secretagogue-Induced Pancreatitis Responses in Rats. Gastroenterology 2009, 137: 1083-1092. PMID: 19454288, PMCID: PMC2736307, DOI: 10.1053/j.gastro.2009.05.041.Peer-Reviewed Original ResearchConceptsAcinar cellsAcute pancreatitisPancreatic acinar cellsSecretagogue-induced pancreatitisAcid loadAcid challengeAcute acid loadKey early eventPancreatic edemaClinical studiesCell injuryPancreatitisAmylase secretionIsolated aciniAbstractTextPhe effectTrypsinogen activationInjuryPancreatitis responsesZymogen activationAIMSEarly eventsRatsActivationRelevant concentrations