2024
Renalase peptides reduce pancreatitis severity in mice
Kolodecik T, Guo X, Shugrue C, Guo X, Desir G, Wen L, Gorelick F. Renalase peptides reduce pancreatitis severity in mice. AJP Gastrointestinal And Liver Physiology 2024, 327: g466-g480. PMID: 39010833, PMCID: PMC11427088, DOI: 10.1152/ajpgi.00143.2024.Peer-Reviewed Original ResearchAcute pancreatitisRecombinant renalaseProsurvival propertiesSeverity of acute pancreatitisModel of acute pancreatitisAcute inflammatory injuryClinically relevant modelAnti-inflammatoryHistological tissue injuryPost-ERCPCerulein modelCerulein-inducedInitial dosePancreatitis severityPreclinical modelsImmunohistochemical markersQuantify inflammationInflammatory changesMale micePancreatitisMacrophage populationsTissue injuryCerulein pancreatitisTherapeutic effectRenalaseEarly Hypophosphatemia as a Prognostic Marker in Acute Pancreatitis
Stewart C, Adeniran E, Yadav D, Gorelick F, Liddle R, Wu B, Pandol S, Jeon C. Early Hypophosphatemia as a Prognostic Marker in Acute Pancreatitis. Pancreas 2024, 53: e611-e616. PMID: 38696363, DOI: 10.1097/mpa.0000000000002344.Peer-Reviewed Original ResearchLength of stayAcute pancreatitisMultivariate log-linear modelElectronic health records of patientsGastrointestinal-related hospitalizationsRisk factorsHealth records of patientsMultivariate logistic regression modelAssociated with length of stayUnderstanding risk factorsPrognostic markerSerum phosphateLogistic regression modelsCedars-Sinai Medical CenterAssociated with lengthAssociated with ICU admissionHours of admissionOutcome of APRecords of patientsSerum phosphate levelsLonger hospital stayMedical CenterAP admissionsRegression modelsSevere APAcute pancreatitis: pathogenesis and emerging therapies
Zaman S, Gorelick F. Acute pancreatitis: pathogenesis and emerging therapies. Journal Of Pancreatology 2024, 7: 10-20. PMID: 38524855, PMCID: PMC10959536, DOI: 10.1097/jp9.0000000000000168.Peer-Reviewed Original ResearchAcute pancreatitisSevere inflammatory disordersLimited treatment optionsLong-term outcomesPotential treatment benefitsPromising new therapyDisease mechanismsPotential therapeutic targetEmerging TherapiesAcute injuryInflammatory disordersPharmacologic interventionsTreatment optionsTreatment benefitPotential therapyNew therapiesSpecific treatmentTherapeutic targetNew treatmentsTherapyPancreatitisTreatmentComplicationsPathogenesisInjury
2023
Plasma renalase levels are associated with the development of acute pancreatitis
Wang M, Weiss F, Guo X, Kolodecik T, Bewersdorf J, Laine L, Lerch M, Desir G, Gorelick F. Plasma renalase levels are associated with the development of acute pancreatitis. Pancreatology 2023, 23: 158-162. PMID: 36697349, DOI: 10.1016/j.pan.2023.01.001.Peer-Reviewed Original ResearchConceptsAcute pancreatitisSevere diseasePlasma renalase levelsAcute pancreatitis patientsSevere acute pancreatitisAcute pancreatitis modelPlasma renalaseRenalase levelsSignificant morbidityPancreatitis patientsPlasma levelsHealthy controlsPancreatitis modelPancreatitisPatientsPlasma samplesRenalaseDiseaseNonparametric statistical analysisSecretory proteinsMorbidityStatistical analysisMortalityLevels
2021
Ovariectomy Affects Acute Pancreatitis in Mice
Wang M, Gorelick F. Ovariectomy Affects Acute Pancreatitis in Mice. Digestive Diseases And Sciences 2021, 67: 2971-2980. PMID: 34169436, PMCID: PMC8702581, DOI: 10.1007/s10620-021-07116-w.Peer-Reviewed Original ResearchConceptsOvariectomized mouse modelEffects of estradiolOvariectomized miceAcute pancreatitisEstradiol levelsPancreatitis severityMouse modelPancreatic studiesSevere acute injurySerum estradiol levelsMild acute pancreatitisAcute pancreatitis severityEstradiol conditionsHospital mortalityHourly injectionsAcute injuryOvariectomized modelFemale hormonesEstradiol injectionPancreatitisEstradiol depletionCausative roleDisease severityConclusionsThese findingsMiceKetamine 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
2020
Zinc: Roles in pancreatic physiology and disease
Wang M, Phadke M, Packard D, Yadav D, Gorelick F. Zinc: Roles in pancreatic physiology and disease. Pancreatology 2020, 20: 1413-1420. PMID: 32917512, PMCID: PMC7572834, DOI: 10.1016/j.pan.2020.08.016.Peer-Reviewed Original ResearchConceptsZinc deficiencyReduced zinc levelsPancreatic injuryChronic pancreatitisAcute pancreatitisIL-1βInflammatory cytokinesGastrointestinal diseasesPancreatic diseaseIntestinal absorptionAnimal modelsMacrophage activationCalcium homeostasisNutritional deficienciesBiologic effectsPancreatic physiologyZinc levelsCellular changesDiseasePreliminary dataPancreatitisInflammationEssential trace elementDeficiencyCytokines
2019
Recent Insights Into the Pathogenic Mechanism of Pancreatitis: Role of Acinar Cell Organelle Disorders.
Gukovskaya AS, Gorelick FS, Groblewski GE, Mareninova OA, Lugea A, Antonucci L, Waldron RT, Habtezion A, Karin M, Pandol SJ, Gukovsky I. Recent Insights Into the Pathogenic Mechanism of Pancreatitis: Role of Acinar Cell Organelle Disorders. Pancreas 2019, 48: 459-470. PMID: 30973461, PMCID: PMC6461375, DOI: 10.1097/mpa.0000000000001298.Peer-Reviewed Original ResearchConceptsOrganelle dysfunctionCell death responseSecretion of proteinsAcinar cell homeostasisOrganelle disordersNascent proteinsDysfunctional organellesDeath responseAccessory proteinsVesicular compartmentsEndosomal pathwayCell homeostasisAcute pancreatitisEndoplasmic reticulumProtein synthesisCells triggersPancreatic acinar cellsLethal inflammatory diseaseDigestive enzymesCell constituentsRecent insightsDistinct mechanismsProteinOrganellesAcinar cell injury
2018
Cigarette toxin 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces experimental pancreatitis through α7 nicotinic acetylcholine receptors (nAChRs) in mice
Alahmari AA, Sreekumar B, Patel V, Ashat M, Alexandre M, Uduman AK, Akinbiyi EO, Ceplenski A, Shugrue CA, Kolodecik TR, Tashkandi N, Messenger SW, Groblewski GE, Gorelick FS, Thrower EC. Cigarette toxin 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces experimental pancreatitis through α7 nicotinic acetylcholine receptors (nAChRs) in mice. PLOS ONE 2018, 13: e0197362. PMID: 29870540, PMCID: PMC5988302, DOI: 10.1371/journal.pone.0197362.Peer-Reviewed Original ResearchConceptsNNK treatmentHuman acinar cellsNicotinic acetylcholine receptorsTrypsinogen activationAcetylcholine receptorsΑ7 nicotinic acetylcholine receptorIndependent risk factorMarkers of inflammationAcinar cellsΑ7nAChR knockout miceΑ7nAChR activationNeutrophil infiltrationWT miceAcute pancreatitisC57BL/6 miceCigarette smokingPancreatic edemaRisk factorsClinical studiesPancreatitisCigarette smokeKnockout miceExperimental pancreatitisΑ7 isoformPyknotic nuclei
2017
Mitochondrial Dysfunction, Through Impaired Autophagy, Leads to Endoplasmic Reticulum Stress, Deregulated Lipid Metabolism, and Pancreatitis in Animal Models
Biczo G, Vegh ET, Shalbueva N, Mareninova OA, Elperin J, Lotshaw E, Gretler S, Lugea A, Malla SR, Dawson D, Ruchala P, Whitelegge J, French SW, Wen L, Husain SZ, Gorelick FS, Hegyi P, Rakonczay Z, Gukovsky I, Gukovskaya AS. Mitochondrial Dysfunction, Through Impaired Autophagy, Leads to Endoplasmic Reticulum Stress, Deregulated Lipid Metabolism, and Pancreatitis in Animal Models. Gastroenterology 2017, 154: 689-703. PMID: 29074451, PMCID: PMC6369139, DOI: 10.1053/j.gastro.2017.10.012.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsArginineAutophagyBile Acids and SaltsCalcium SignalingCeruletideCholine DeficiencyCyclophilin DCyclophilinsDisease Models, AnimalEndoplasmic Reticulum StressEthionineGenetic Predisposition to DiseaseHumansLipid MetabolismMembrane Potential, MitochondrialMice, Inbred C57BLMice, KnockoutMitochondriaMitochondrial Proton-Translocating ATPasesPancreasPancreatitisPhenotypeRatsTime FactorsTrehaloseConceptsDevelopment of APAcute pancreatitisEndoplasmic reticulum stressLipid metabolismImpaired autophagyMitochondrial dysfunctionAnimal modelsL-arginine-induced pancreatitisTreatment of APCyclophilin D knockout micePathogenesis of APAdministration of trehalosePancreatic ER stressParameters of pancreatitisReticulum stressSevere acute pancreatitisPancreas of miceDifferent animal modelsER stressPrincipal downstream effectorPancreatic injuryPathologic responsePancreatitis tissuesCyclophilin DNormal pancreasThe serum protein renalase reduces injury in experimental pancreatitis
Kolodecik TR, Reed AM, Date K, Shugrue C, Patel V, Chung SL, Desir GV, Gorelick FS. The serum protein renalase reduces injury in experimental pancreatitis. Journal Of Biological Chemistry 2017, 292: 21047-21059. PMID: 29042438, PMCID: PMC5743078, DOI: 10.1074/jbc.m117.789776.Peer-Reviewed Original ResearchMeSH KeywordsAcinar CellsAnimalsAnti-Inflammatory Agents, Non-SteroidalBiomarkersCalcium SignalingCarbacholCell LineCeruletideEnzyme ActivationFluorescent Antibody Technique, IndirectGene Expression Regulation, EnzymologicHumansHypertensionLigandsMembrane Transport ModulatorsMiceMice, KnockoutMonoamine OxidasePancreasPancreatitisPlasma Membrane Calcium-Transporting ATPasesRecombinant Fusion ProteinsTaurolithocholic AcidConceptsRecombinant human renalaseAcute pancreatitisAcute injuryCell injuryAcinar cell injuryHuman acinar cellsCytosolic calcium levelsPlasma membrane calcium ATPasePancreatitis onsetIschemic injuryWT micePathological increaseHistological changesProtective effectSevere diseaseMurine modelMembrane calcium ATPasePancreatitisCalcium levelsExperimental pancreatitisBile acidsTissue damageRenalaseInjuryCerulein modelDo Animal Models of Acute Pancreatitis Reproduce Human Disease?
Gorelick FS, Lerch MM. Do Animal Models of Acute Pancreatitis Reproduce Human Disease? Cellular And Molecular Gastroenterology And Hepatology 2017, 4: 251-262. PMID: 28752114, PMCID: PMC5518169, DOI: 10.1016/j.jcmgh.2017.05.007.Peer-Reviewed Original ResearchAcute pancreatitisBiological disease mechanismsNonmalignant gastrointestinal diseasesPathophysiological disease mechanismsDisease mechanismsPotential therapeutic targetPaucity of dataHospital admissionCommon causeExperimental pancreatitis modelGastrointestinal diseasesPancreatitis modelTherapeutic targetAnimal modelsNatural historySpecific causesDiseaseDisease modelsPancreatitisDisease developmentUnderlying cellMolecular mechanismsHuman diseasesCauseLimited information
2014
Low pH enhances connexin32 degradation in the pancreatic acinar cell
Reed AM, Kolodecik T, Husain SZ, Gorelick FS. Low pH enhances connexin32 degradation in the pancreatic acinar cell. AJP Gastrointestinal And Liver Physiology 2014, 307: g24-g32. PMID: 24812055, PMCID: PMC4080162, DOI: 10.1152/ajpgi.00010.2014.Peer-Reviewed Original ResearchConceptsPancreatic acinar cellsAcinar cellsGap junctionsGap junctional intercellular communicationIntercellular communicationRat pancreatic acinar cellsPredominant gap junction proteinExtracellular pHAcute pancreatitisJunctional intercellular communicationClinical conditionsGap junction proteinJunction proteinsGap junctional intracellular communicationAutophagic pathwayFirst evidenceCellsIntracellular communicationConnexin32PancreatitisLactate 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
Impaired autophagic flux mediates acinar cell vacuole formation and trypsinogen activation in rodent models of acute pancreatitis
Mareninova O, Hermann K, French S, O’Konski M, Pandol S, Webster P, Erickson A, Katunuma N, Gorelick F, Gukovsky I, Gukovskaya A. Impaired autophagic flux mediates acinar cell vacuole formation and trypsinogen activation in rodent models of acute pancreatitis. Journal Of Clinical Investigation 2013, 123: 1844-1844. PMCID: PMC3613939, DOI: 10.1172/jci69660.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 aciniPancreatitisSterile Inflammatory Response in Acute Pancreatitis
Hoque R, Malik AF, Gorelick F, Mehal WZ. Sterile Inflammatory Response in Acute Pancreatitis. Pancreas 2012, 41: 353-357. PMID: 22415665, PMCID: PMC3306133, DOI: 10.1097/mpa.0b013e3182321500.Peer-Reviewed Original ResearchConceptsDamage-associated molecular patternsSterile inflammatory responseAcute pancreatitisInterleukin-1βInflammatory responseExperimental pancreatitisNOD-like receptor protein 3High mobility group box protein 1Toll-like receptor 4Remote organ injuryReceptor protein 3Acinar cellsExperimental acute pancreatitisIL-1 receptorNovel therapeutic targetBox protein 1Necrotic acinar cellsDAMP receptorsShock protein 70Disease resolutionPancreatic injuryOrgan injuryInitial injuryIL-18Pharmacologic antagonism
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
2009
Genetic and pharmacologic manipulation of vacuolar ATPase: Effects on zymogen activation in pancreatic acini
Kolodecik T, Gorelick F, Thrower E. Genetic and pharmacologic manipulation of vacuolar ATPase: Effects on zymogen activation in pancreatic acini. Open Access Animal Physiology 2009, Volume 1: 1-11. PMID: 21572923, PMCID: PMC3092382, DOI: 10.2147/oaap.s7252.Peer-Reviewed Original ResearchZymogen activationVacuolar ATPaseATP-dependent proton pumpTreatment of cellsGenetic approachesE subunitAcinar cellsProton pumpPancreatic acinar cellsPancreatitis responsesDigestive enzymesAcute pancreatitisPremature activationVATPaseSiRNAATPaseActivationSalicylihalamideCellsRecent studiesOrthologuesBaseline levelsHigh dosesPharmacologic manipulationAmylase secretion