2023
Analysis of the human kidney transcriptome and plasma proteome identifies markers of proximal tubule maladaptation to injury
Wen Y, Su E, Xu L, Menez S, Moledina D, Obeid W, Palevsky P, Mansour S, Devarajan P, Cantley L, Cahan P, Parikh C, Project K, Injury T. Analysis of the human kidney transcriptome and plasma proteome identifies markers of proximal tubule maladaptation to injury. Science Translational Medicine 2023, 15: eade7287. PMID: 38091407, PMCID: PMC11405121, DOI: 10.1126/scitranslmed.ade7287.Peer-Reviewed Original ResearchThe ASSESS-AKI Study found urinary epidermal growth factor is associated with reduced risk of major adverse kidney events
Menez S, Wen Y, Xu L, Moledina D, Thiessen-Philbrook H, Hu D, Obeid W, Bhatraju P, Ikizler T, Siew E, Chinchilli V, Garg A, Go A, Liu K, Kaufman J, Kimmel P, Himmelfarb J, Coca S, Cantley L, Parikh C. The ASSESS-AKI Study found urinary epidermal growth factor is associated with reduced risk of major adverse kidney events. Kidney International 2023, 104: 1194-1205. PMID: 37652206, PMCID: PMC10840723, DOI: 10.1016/j.kint.2023.08.007.Peer-Reviewed Original ResearchConceptsMajor adverse kidney eventsUEGF/CrUrinary epidermal growth factorAdverse kidney eventsChronic kidney diseaseEpidermal growth factorKidney eventsKidney failureEGF expressionUrinary EGF/CrAcute Kidney Injury studyGrowth factorIschemia-reperfusion injuryProportional hazards regressionTubular healthKidney atrophyObservational cohortHospitalized participantsTubular functionClinical findingsHazards regressionKidney diseaseClinical variablesProgressive atrophyUrinary EGF
2022
Urine Uromodulin as a Biomarker of Kidney Tubulointerstitial Fibrosis
Melchinger H, Calderon-Gutierrez F, Obeid W, Xu L, Shaw MM, Luciano RL, Kuperman M, Moeckel GW, Kashgarian M, Wilson FP, Parikh CR, Moledina DG. Urine Uromodulin as a Biomarker of Kidney Tubulointerstitial Fibrosis. Clinical Journal Of The American Society Of Nephrology 2022, 17: 1284-1292. PMID: 35948365, PMCID: PMC9625093, DOI: 10.2215/cjn.04360422.Peer-Reviewed Original ResearchConceptsInterstitial fibrosis/tubular atrophyUrine uromodulinTubular atrophyThick ascending limbUrine albuminSerum creatinineKidney biopsyTubulointerstitial fibrosisMultivariable linear regression modelsTime of biopsyKidney's thick ascending limbAcademic medical centerHuman kidney biopsiesKidney tubulointerstitial fibrosisTubular healthMultivariable analysisHistologic featuresHistologic findingsHistologic changesKidney fibrosisIndependent associationFibrotic modelMultivariable modelMedical CenterMurine modelKidney-Targeted Renalase Agonist Prevents Cisplatin-Induced Chronic Kidney Disease by Inhibiting Regulated Necrosis and Inflammation
Guo X, Xu L, Velazquez H, Chen TM, Williams RM, Heller DA, Burtness B, Safirstein R, Desir GV. Kidney-Targeted Renalase Agonist Prevents Cisplatin-Induced Chronic Kidney Disease by Inhibiting Regulated Necrosis and Inflammation. Journal Of The American Society Of Nephrology 2022, 33: 342-356. PMID: 34921111, PMCID: PMC8819981, DOI: 10.1681/asn.2021040439.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntineoplastic AgentsCell LineCisplatinCreatinineDisease Models, AnimalGene ExpressionGlomerular Filtration RateHepatitis A Virus Cellular Receptor 1HumansKidneyMiceMice, Inbred C57BLMice, KnockoutMonoamine OxidaseNanocapsulesPeptidesRenal Insufficiency, ChronicConceptsRenal proximal tubulesSingle-cell RNA sequencing analysisMesoscale nanoparticlesFirst doseCisplatin chemotherapyProximal tubulesAgonist peptideInduced Chronic Kidney DiseaseGenetic deletionNeck squamous cell carcinomaRNA sequencing analysisCisplatin-induced AKIKidney-targeted deliveryChronic kidney diseaseDevelopment of CKDSquamous cell carcinomaAdministration of cisplatinPlasma renalaseAdvanced headCell carcinomaInflammatory cytokinesKidney diseasePlasma creatinineSystemic administrationRegulated necrosisCharacterization of temporospatial distribution of renal tubular casts by nephron tracking after ischemia-reperfusion injury
Shin NS, Marlier A, Xu L, Lam T, Cantley LG, Guo JK. Characterization of temporospatial distribution of renal tubular casts by nephron tracking after ischemia-reperfusion injury. American Journal Of Physiology. Renal Physiology 2022, 322: f322-f334. PMID: 35100823, PMCID: PMC8897010, DOI: 10.1152/ajprenal.00284.2021.Peer-Reviewed Original ResearchConceptsIschemia-reperfusion injuryCast formationGlomerular filtration rateTubular cast formationUrine 24 hDetached epithelial cellsDead cell debrisRenal recoveryRenal functionFiltration rateS3 tubulesTubular castsTubular cellsTubular nucleiKidney sectionsOuter medullaTrypsin levelsEntire nephronRenal tubular castsFuture interventionsInjurySelective lossTubule segmentsEpithelial cellsKidney
2021
The Role of Myeloid Cells in Acute Kidney Injury and Kidney Repair
Xu L. The Role of Myeloid Cells in Acute Kidney Injury and Kidney Repair. Kidney360 2021, 2: 1852-1864. PMID: 35372990, PMCID: PMC8785849, DOI: 10.34067/kid.0000672021.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsBiomarkers of inflammation and repair in kidney disease progression
Puthumana J, Thiessen-Philbrook H, Xu L, Coca SG, Garg AX, Himmelfarb J, Bhatraju PK, Ikizler T, Siew E, Ware LB, Liu KD, Go AS, Kaufman JS, Kimmel PL, Chinchilli VM, Cantley L, Parikh CR. Biomarkers of inflammation and repair in kidney disease progression. Journal Of Clinical Investigation 2021, 131 PMID: 33290282, PMCID: PMC7843225, DOI: 10.1172/jci139927.Peer-Reviewed Original ResearchConceptsKidney disease progressionComposite kidney outcomeChronic kidney diseaseDisease progressionEGFR declineKidney outcomesRenal atrophyMouse modelMonocyte chemoattractant protein-1CHI3L1 mRNA expressionComposite renal outcomeGreater eGFR declineIntroductionAcute kidney injuryProspective cohort studyGlomerular filtration rateBiomarkers of inflammationProgressive renal fibrosisYKL-40 levelsChemoattractant protein-1Traditional clinical variablesLong-term progressionLoop of HenleMultimarker scoreRenal outcomesKidney injury
2019
Folate-Decorated Polyamidoamine Dendrimer Nanoparticles for Head and Neck Cancer Gene Therapy
Xu L, Yang H. Folate-Decorated Polyamidoamine Dendrimer Nanoparticles for Head and Neck Cancer Gene Therapy. Methods In Molecular Biology 2019, 1974: 393-408. PMID: 31099016, DOI: 10.1007/978-1-4939-9220-1_26.BooksConceptsGene therapyGene delivery systemsNeck cancer gene therapyCancer gene therapyDelivery systemNanoparticle carriersGene deliveryDendrimer nanoparticlesHigh biocompatibilityGene transfectionKnockdown efficiencyTumor targetingSuitable platformFolic acidIRDye 800CWSustained retentionGeneration 4DendrimersNanoparticlesBioimagingCarriersBiocompatibilityHereinPlatformPlasmid
2017
Folic acid-decorated polyamidoamine dendrimer exhibits high tumor uptake and sustained highly localized retention in solid tumors: Its utility for local siRNA delivery
Xu L, Yeudall WA, Yang H. Folic acid-decorated polyamidoamine dendrimer exhibits high tumor uptake and sustained highly localized retention in solid tumors: Its utility for local siRNA delivery. Acta Biomaterialia 2017, 57: 251-261. PMID: 28438704, PMCID: PMC5555737, DOI: 10.1016/j.actbio.2017.04.023.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinoma, Squamous CellCell Line, TumorDendrimersFemaleFolic AcidGene Transfer TechniquesHead and Neck NeoplasmsHumansMiceMice, NudeNeoplasm ProteinsNeovascularization, PathologicPolyaminesRNA, Small InterferingVascular Endothelial Growth Factor AXenograft Model Antitumor AssaysConceptsHigh tumor uptakeNeck squamous cell carcinomaSquamous cell carcinomaTumor uptakeCell carcinomaLocal deliveryRegimen studiesNeck squamous cancer cellsPronounced tumor suppressionTumor size reductionVascular endothelial growth factorSquamous cancer cellsTumor mouse modelEndothelial growth factorXenograft tumor modelEnhanced tumor uptakeTumor suppressionTumor inhibition effectCommon cancerMicrovessel countImaging assessmentTherapeutic modalitiesMouse modelCD31 stainingTreatment groupsFolate-mediated chemotherapy and diagnostics: An updated review and outlook
Xu L, Bai Q, Zhang X, Yang H. Folate-mediated chemotherapy and diagnostics: An updated review and outlook. Journal Of Controlled Release 2017, 252: 73-82. PMID: 28235591, PMCID: PMC5479736, DOI: 10.1016/j.jconrel.2017.02.023.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsFolate receptorCellular uptake mechanismVivo applicationsDiagnostic agentsNanomedicineNanoprobeTremendous effortsNanoparticlesMajor challengeClinical applicationAdministration routeDiagnosticsChemotherapyApplicationsHuman cancersLatest developmentsUptake mechanismPharmacokineticsConcise reviewRouteReview
2016
Folic acid-decorated polyamidoamine dendrimer mediates selective uptake and high expression of genes in head and neck cancer cells
Xu L, Kittrell S, Yeudall WA, Yang H. Folic acid-decorated polyamidoamine dendrimer mediates selective uptake and high expression of genes in head and neck cancer cells. Nanomedicine 2016, 11: 2959-2973. PMID: 27781559, PMCID: PMC5144492, DOI: 10.2217/nnm-2016-0244.Peer-Reviewed Original ResearchConceptsNeck cancer cellsCancer cellsFR-dependent mannerEnhanced gene expressionGene expressionSame binding siteCellular uptakeGenesDelivery of genesBinding sitesHigh expressionFree FASuitable vectorPlasmidDNA plasmidsCellsTransfection resultsExpressionTransfection efficiencySelective uptakeUptakeFolate receptorHigh levelsVectorFA
2014
Cholesterol Sulfate and Cholesterol Sulfotransferase Inhibit Gluconeogenesis by Targeting Hepatocyte Nuclear Factor 4α
Shi X, Cheng Q, Xu L, Yan J, Jiang M, He J, Xu M, Stefanovic-Racic M, Sipula I, O'Doherty RM, Ren S, Xie W. Cholesterol Sulfate and Cholesterol Sulfotransferase Inhibit Gluconeogenesis by Targeting Hepatocyte Nuclear Factor 4α. Molecular And Cellular Biology 2014, 34: 485-497. PMID: 24277929, PMCID: PMC3911511, DOI: 10.1128/mcb.01094-13.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAnimalsBlotting, WesternCarcinoma, HepatocellularCell Line, TumorCell NucleusCells, CulturedCholesterol EstersCoenzyme A LigasesColforsinDiet, High-FatGene ExpressionGluconeogenesisGlucoseHepatocyte Nuclear Factor 4HumansInsulin ResistanceMiceMice, Inbred C57BLMice, ObeseMice, TransgenicObesityReverse Transcriptase Polymerase Chain ReactionSulfotransferasesConceptsDiet-induced obesityHepatocyte nuclear factor 4αNuclear factor 4αCholesterol sulfateLeptin-deficient miceTreatment of micePotential therapeutic targetPotential therapeutic agentExpression of SULT2B1bMetabolic abnormalitiesObese miceMetabolic disordersImportant metabolic regulatorGlucose metabolismTherapeutic targetTransgenic miceFed stateHepatic gluconeogenesisTherapeutic agentsMiceTransgenic overexpressionSULT2B1bMetabolic regulatorFunctional homeostasisInhibits gluconeogenesis
2013
Dendrimer Advances for the Central Nervous System Delivery of Therapeutics
Xu L, Zhang H, Wu Y. Dendrimer Advances for the Central Nervous System Delivery of Therapeutics. ACS Chemical Neuroscience 2013, 5: 2-13. PMID: 24274162, PMCID: PMC3894720, DOI: 10.1021/cn400182z.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsBlood-brain barrierCNS therapeutic agentsDendrimer-mediated deliveryTherapeutic agentsCentral nervous system diseaseTreatment of CNSCentral nervous system deliveryNervous system diseasesMost CNS drugsBrain parenchymaSystem diseasesBrain tumorsCNS drugsNoninvasive treatmentCNS therapeuticsPoor accessDeliveryTreatmentTherapeuticsAgentsSystem deliveryTumorsCNSDiseaseDiagnosis
2012
25-Hydroxycholesterol-3-sulfate attenuates inflammatory response via PPARγ signaling in human THP-1 macrophages
Xu L, Shen S, Ma Y, Kim JK, Rodriguez-Agudo D, Heuman DM, Hylemon PB, Pandak WM, Ren S. 25-Hydroxycholesterol-3-sulfate attenuates inflammatory response via PPARγ signaling in human THP-1 macrophages. AJP Endocrinology And Metabolism 2012, 302: e788-e799. PMID: 22275753, PMCID: PMC3330710, DOI: 10.1152/ajpendo.00337.2011.Peer-Reviewed Original ResearchMeSH KeywordsAnti-Inflammatory AgentsBlotting, WesternCell NucleusCholesterol EstersCytokinesCytosolEnzyme-Linked Immunosorbent AssayHumansHydroxycholesterolsHypoglycemic AgentsI-kappa B ProteinsLipopolysaccharidesMacrophagesNF-kappa BPPAR gammaProtein TransportReal-Time Polymerase Chain ReactionRNA, MessengerRNA, Small InterferingRosiglitazoneSignal TransductionThiazolidinedionesConceptsNF-κB protein levelsPeroxisome proliferator-activated receptorInflammatory responseNuclear PPARγReporter gene assayLipid metabolismNuclear receptor peroxisome proliferator-activated receptorIL-1β expressionLiver X receptor ligandsProtein levelsActivation of PPARγHuman THP-1 macrophagesProliferator-activated receptorGene assayLuciferase activityTHP-1 macrophagesPPARγ-specific antagonistIκB/NF-κBX receptor ligandsIL-1βPromoter reporter gene assaysCholesterol metabolitesPPARγ activityPotent regulatory moleculesNF-κB
2010
Sulfation of 25-hydroxycholesterol by SULT2B1b decreases cellular lipids via the LXR/SREBP-1c signaling pathway in human aortic endothelial cells
Bai Q, Xu L, Kakiyama G, Runge-Morris MA, Hylemon PB, Yin L, Pandak WM, Ren S. Sulfation of 25-hydroxycholesterol by SULT2B1b decreases cellular lipids via the LXR/SREBP-1c signaling pathway in human aortic endothelial cells. Atherosclerosis 2010, 214: 350-356. PMID: 21146170, PMCID: PMC3031658, DOI: 10.1016/j.atherosclerosis.2010.11.021.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedCholesterol EstersChromatography, High Pressure LiquidEndothelial CellsFatty Acids, NonesterifiedGene Expression RegulationHumansHydrocarbons, FluorinatedHydroxycholesterolsLiver X ReceptorsOrphan Nuclear ReceptorsRNA, MessengerSignal TransductionSterol Regulatory Element Binding Protein 1SulfonamidesSulfotransferasesTime FactorsTransfectionTriglyceridesConceptsHuman aortic endothelial cellsLipid metabolismAortic endothelial cellsSULT2B1b overexpressionSREBP-1cEndothelial cellsIntracellular lipid homeostasisOxysterol sulfotransferaseReceptor agonistLipid levelsPresence of T0901317Cellular lipid levelsLipid homeostasisRecombinant adenovirusACC-1Protein levelsSULT2B1bSulfated metabolitesMetabolismCellular lipidsOverexpressionKey regulatorSimilar resultsCells
2008
25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-1 signaling pathway
Ma Y, Xu L, Rodriguez-Agudo D, Li X, Heuman DM, Hylemon PB, Pandak WM, Ren S. 25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-1 signaling pathway. AJP Endocrinology And Metabolism 2008, 295: e1369-e1379. PMID: 18854425, PMCID: PMC2603552, DOI: 10.1152/ajpendo.90555.2008.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisCell ProliferationCells, CulturedCholesterol EstersDNA-Binding ProteinsDose-Response Relationship, DrugGene Expression RegulationHumansHydroxycholesterolsLipid MetabolismLipidsLiver X ReceptorsMacrophagesModels, BiologicalOrphan Nuclear ReceptorsReceptors, Cytoplasmic and NuclearSignal TransductionSterol Regulatory Element Binding Protein 1SulfatesConceptsLXR/SREBPFatty acid synthaseSREBP-1Lipid metabolismFatty acid synthetic pathwayKey transcriptional regulatorMacrophage lipid metabolismImportant regulatory moleculesTHP-1-derived macrophagesMature proteinTranscriptional regulatorsAcetyl-CoA carboxylase 1MRNA levelsFAS mRNA levelsKey proteinsGene expressionRegulatory moleculesHuman THP-1-derived macrophagesAcid synthaseSREBPLipid synthesisOxysterol sulfationLXR ligandsCarboxylase 1Cell proliferation