2024
MIF-Modulated Spinal Proteins Associated with Persistent Bladder Pain: A Proteomics Study
Ye S, Agalave N, Ma F, Mahmood D, Al-Grety A, Khoonsari P, Leng L, Svensson C, Bucala R, Kultima K, Vera P. MIF-Modulated Spinal Proteins Associated with Persistent Bladder Pain: A Proteomics Study. International Journal Of Molecular Sciences 2024, 25: 4484. PMID: 38674069, PMCID: PMC11050327, DOI: 10.3390/ijms25084484.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, Differentiation, B-LymphocyteCystitis, InterstitialDisease Models, AnimalFemaleHistocompatibility Antigens Class IIHyperalgesiaIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMiceProteomicsReceptors, CXCR4Receptors, ImmunologicSpinal CordUrinary BladderConceptsMacrophage migration inhibitory factorProtease activated receptor 4C-X-C chemokine receptor type 4Bladder hyperalgesiaBladder painSpinal proteinsMIF receptor CD74MIF antagonismL6-S1 spinal segmentsSpinal mechanismsInterstitial Cystitis/Bladder Pain SyndromeMIF receptorSeparate groups of miceChemokine receptor type 4Associated with reliefGroups of miceC-X-CMigration inhibitory factorChanges compared to controlsBladder inflammationPain syndromeFemale miceNo significant changesSham i.Receptor 4
2023
Fully automated radiosynthesis of [18F]mG4P027 for mGluR4 imaging
Moon S, Fakhri G, Zhang Z, Brownell A, Wang J. Fully automated radiosynthesis of [18F]mG4P027 for mGluR4 imaging. IRADIOLOGY 2023, 1: 120-127. PMID: 37496513, PMCID: PMC10371389, DOI: 10.1002/ird3.25.Peer-Reviewed Original ResearchUrothelial Oxidative Stress and ERK Activation Mediate HMGB1-Induced Bladder Pain
Ye S, Mahmood D, Ma F, Leng L, Bucala R, Vera P. Urothelial Oxidative Stress and ERK Activation Mediate HMGB1-Induced Bladder Pain. Cells 2023, 12: 1440. PMID: 37408274, PMCID: PMC10217556, DOI: 10.3390/cells12101440.Peer-Reviewed Original ResearchConceptsHigh mobility group box 1Macrophage migration inhibitory factorBladder painOxidative stressDisulfide HMGB1Mobility group box 1MIF-deficient miceNovel potential therapeutic strategyMigration inhibitory factorGroup box 1Potential therapeutic strategyOxidative stress productionN-acetylcysteine amideERK activationIntravesical treatmentMicturition volumeMicturition parametersReceptor 4Mechanical thresholdPainTherapeutic strategiesBox 1Bladder tissueInhibitory factorWestern blotDetailed radiosynthesis of [18F]mG4P027 as a positron emission tomography radiotracer for mGluR4
Wang J, Moon S, Cleary M, Shoup T, Fakhri G, Zhang Z, Brownell A. Detailed radiosynthesis of [18F]mG4P027 as a positron emission tomography radiotracer for mGluR4. Journal Of Labelled Compounds And Radiopharmaceuticals 2023, 66: 34-40. PMID: 36593743, PMCID: PMC9985952, DOI: 10.1002/jlcr.4011.Peer-Reviewed Original Research
2022
The relationship between TLR4/NF-κB/IL-1β signaling, cognitive impairment, and white-matter integrity in patients with stable chronic schizophrenia
Li H, Chen W, Gou M, Li W, Tong J, Zhou Y, Xie T, Yu T, Feng W, Li Y, Chen S, Tian B, Tan S, Wang Z, Pan S, Li N, Luo X, Zhang P, Huang J, Tian L, Li CR, Tan Y. The relationship between TLR4/NF-κB/IL-1β signaling, cognitive impairment, and white-matter integrity in patients with stable chronic schizophrenia. Frontiers In Psychiatry 2022, 13: 966657. PMID: 36051545, PMCID: PMC9424630, DOI: 10.3389/fpsyt.2022.966657.Peer-Reviewed Original ResearchStable chronic schizophreniaNF-κB/ILWhite matter integrityHealthy controlsMATRICS Consensus Cognitive BatteryFractional anisotropyChronic schizophreniaCortical thicknessCognitive impairmentInnate immunityCognitive functionToll-like receptor 4Higher TLR4 levelsLevels of TLR4Subcortical gray matter volumesWhite matter fractional anisotropyNegative Syndrome ScaleGray matter volumeTLR4 expressionTLR4 levelsWhite matter microstructureReceptor 4Cognitive deteriorationConsensus Cognitive BatteryLPS stimulationThe matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging
Ryu S, Sidorov S, Ravussin E, Artyomov M, Iwasaki A, Wang A, Dixit VD. The matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging. Immunity 2022, 55: 1609-1626.e7. PMID: 35963236, PMCID: PMC9474643, DOI: 10.1016/j.immuni.2022.07.007.Peer-Reviewed Original ResearchConceptsToll-like receptor 4ISG inductionMatricellular proteinPro-inflammatory phenotypeAnti-inflammatory macrophagesInterferon-stimulated gene expressionAdipocyte-specific deletionInhibition of glycolysisImmunometabolic adaptationsMyD88 pathwayReceptor 4Chronic diseasesFunctional declineCaloric restrictionInterferon responseHealth spanMacrophagesInflammationMitochondrial respirationSPARCInductionGene expressionAdipokinesObesityIFNGasdermin D-dependent platelet pyroptosis exacerbates NET formation and inflammation in severe sepsis
Su M, Chen C, Li S, Li M, Zeng Z, Zhang Y, Xia L, Li X, Zheng D, Lin Q, Fan X, Wen Y, Liu Y, Chen F, Luo W, Bu Y, Qin J, Guo M, Qiu M, Sun L, Liu R, Wang P, Hwa J, Tang WH. Gasdermin D-dependent platelet pyroptosis exacerbates NET formation and inflammation in severe sepsis. Nature Cardiovascular Research 2022, 1: 732-747. PMID: 35967457, PMCID: PMC9362711, DOI: 10.1038/s44161-022-00108-7.Peer-Reviewed Original ResearchToll-like receptor 4S100A8/A9Gasdermin DSevere sepsisNeutrophil extracellular trap formationPathology of sepsisRapid clinical deteriorationInflammatory cytokine releaseKey inflammatory cellsExtracellular trap formationGSDMD-deficient miceClinical deteriorationCecal ligationInflammatory cellsInflammatory cytokinesCytokine releaseReceptor 4SepsisExcessive releasePharmacological inhibitionGenetic ablationNET formationPyroptosisSignificant upregulationInflammationA Morphomolecular Approach to Alveolar Capillary Dysplasia
Kamp J, Neubert L, Ackermann M, Stark H, Plucinski E, Shah H, Janciauskiene S, Bergmann A, Schmidt G, Welte T, Haverich A, Werlein C, Braubach P, Laenger F, Schwerk N, Olsson K, Fuge J, Park D, Schupp J, Hoeper M, Kuehnel M, Jonigk D. A Morphomolecular Approach to Alveolar Capillary Dysplasia. American Journal Of Pathology 2022, 192: 1110-1121. PMID: 35649494, DOI: 10.1016/j.ajpath.2022.05.004.Peer-Reviewed Original ResearchConceptsAlveolar capillary dysplasiaHigh prevalencePersistent pulmonary arterial hypertensionPulmonary arterial hypertension groupC motif chemokine receptor 4CXCR4 ligand CXCL12Pulmonary arterial hypertensionEndothelial tyrosine kinase receptorHypoxia-inducible factor-1αChemokine receptor 4Anti-angiogenic agentsIntussusceptive angiogenesisArterial hypertensionHypertension groupTyrosine kinase receptorsFatal outcomeHealthy controlsReceptor 4Ligand CXCL12Vascular remodelingMicrovascular corrosion castsACD groupMicrovascular morphologyFactor-1αExome sequencingA hypothalamic pathway for Augmentor α–controlled body weight regulation
Ahmed M, Kaur N, Cheng Q, Shanabrough M, Tretiakov EO, Harkany T, Horvath TL, Schlessinger J. A hypothalamic pathway for Augmentor α–controlled body weight regulation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2200476119. PMID: 35412887, PMCID: PMC9169862, DOI: 10.1073/pnas.2200476119.Peer-Reviewed Original ResearchConceptsParaventricular nucleusBody weightDiet-induced obesityBody weight regulationDiscrete neuronal populationsMelanocortin receptor 4Whole-body energy homeostasisPhysiological rolePeptide neuronsHypothalamic pathwaysReceptor 4Neuronal pathwaysPhysical activityLittermate controlsWeight regulationNeuronal populationsMetabolic diseasesTherapeutic opportunitiesMutant miceEnergy homeostasisMiceALKCancerHuman cancersALK mutantsDysfunctional monocytic toll-like receptor 4 signaling pathway and cognitive deficits in chronic schizophrenia patients with tardive dyskinesia
Li N, Li Y, Huang J, Zhang P, Tong J, Chen S, Cui Y, Tan S, Wang Z, Yang F, Hong E, Li CR, Tian L, Tan Y. Dysfunctional monocytic toll-like receptor 4 signaling pathway and cognitive deficits in chronic schizophrenia patients with tardive dyskinesia. Neuroscience Letters 2022, 777: 136581. PMID: 35337952, DOI: 10.1016/j.neulet.2022.136581.Peer-Reviewed Original ResearchConceptsToll-like receptor 4Abnormal Involuntary Movement ScaleTardive dyskinesiaChronic schizophrenia patientsSchizophrenia patientsMATRICS Consensus Cognitive BatteryReceptor 4TD patientsHigher toll-like receptor 4Cognitive deficitsSeverity of TDNegative Syndrome ScaleInnate immune systemNTD patientsTLR4 levelsHealthy controlsAIMS scoresMovement ScalePatientsConsensus Cognitive BatteryLPS stimulationTLR4 signalsPathway disturbancesLipopolysaccharide (LPS) stimulationSyndrome ScaleChemokine C-X-C receptor 4 mediates recruitment of bone marrow-derived nonhematopoietic and immune cells to the pregnant uterus
Fang YY, Lyu F, Abuwala N, Tal A, Chen AY, Taylor HS, Tal R. Chemokine C-X-C receptor 4 mediates recruitment of bone marrow-derived nonhematopoietic and immune cells to the pregnant uterus. Biology Of Reproduction 2022, 106: 1083-1097. PMID: 35134114, PMCID: PMC9198949, DOI: 10.1093/biolre/ioac029.Peer-Reviewed Original ResearchConceptsBone marrow-derived progenitor cellsBM-derived cellsPregnant deciduaPregnant uterusMarrow-derived progenitor cellsC receptor 4Pregnancy-induced increaseRecruitment of boneProgenitor cellsWild-type C57BL/6CXCL12-CXCR4 axisStem/progenitor cellsTamoxifen-inducible CreNK cellsControl miceBM donorsCXCR4 expressionTransgenic GFP miceImmune cellsReceptor 4Nonpregnant uterusChemokine CCXCL12 ligandFemale recipientsSuccessful implantationIntrinsic cardiac adrenergic cells contribute to LPS-induced myocardial dysfunction
Yang D, Dai X, Xing Y, Tang X, Yang G, Harrison A, Cahoon J, Li H, Lv X, Yu X, Wang P, Wang H. Intrinsic cardiac adrenergic cells contribute to LPS-induced myocardial dysfunction. Communications Biology 2022, 5: 96. PMID: 35079095, PMCID: PMC8789803, DOI: 10.1038/s42003-022-03007-6.Peer-Reviewed Original ResearchConceptsIntrinsic cardiac adrenergic cellsToll-like receptor 4ICA cellsTNF-α productionMyocardial dysfunctionSeptic cardiomyopathyAdrenergic cellsMyocardial TNF-α productionSecretion of NEPotential therapeutic targetΒ1-adrenergic receptorNE biosynthesisTLR4-MyD88Receptor 4Norepinephrine secretionP65 translocationTyrosine hydroxylaseNF-κBTherapeutic targetMitogen-activated protein kinase pathwayDependent protein kinase IILipopolysaccharideDysfunctionProtein kinase IIPathological processes
2021
Intravesical CD74 and CXCR4, macrophage migration inhibitory factor (MIF) receptors, mediate bladder pain
Ye S, Ma F, Mahmood DFD, Meyer-Siegler KL, Menard RE, Hunt DE, Leng L, Bucala R, Vera PL. Intravesical CD74 and CXCR4, macrophage migration inhibitory factor (MIF) receptors, mediate bladder pain. PLOS ONE 2021, 16: e0255975. PMID: 34424927, PMCID: PMC8382170, DOI: 10.1371/journal.pone.0255975.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorHigh mobility group box 1Bladder painMIF receptorHMGB1 releaseBladder hyperalgesiaMobility group box 1MIF receptor CD74Migration inhibitory factorGroup box 1Primary urothelial cellsInhibitory factor receptorWarrants further investigationCD74 receptorReceptor CD74Micturition parametersReceptor antagonistReceptor 4Box 1PainInhibitory factorHyperalgesiaCD74Urothelial cellsNovel targetOral anaphylaxis to peanut in a mouse model is associated with gut permeability but not with Tlr4 or Dock8 mutations
Gertie JA, Zhang B, Liu EG, Hoyt LR, Yin X, Xu L, Long LL, Soldatenko A, Gowthaman U, Williams A, Eisenbarth SC. Oral anaphylaxis to peanut in a mouse model is associated with gut permeability but not with Tlr4 or Dock8 mutations. Journal Of Allergy And Clinical Immunology 2021, 149: 262-274. PMID: 34051223, PMCID: PMC8626534, DOI: 10.1016/j.jaci.2021.05.015.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAnimalsArachisDisease Models, AnimalFemaleGastrointestinal MicrobiomeGenetic Predisposition to DiseaseGuanine Nucleotide Exchange FactorsIntestinal MucosaMaleMice, Inbred C3HMice, Inbred C57BLMutationPassive Cutaneous AnaphylaxisPeanut HypersensitivityPermeabilitySpecies SpecificityToll-Like Receptor 4ConceptsC3H/HeJ miceGut permeabilityHeJ miceOral anaphylaxisPeanut challengeFood allergyMouse modelToll-like receptor 4BALB/c miceCytokinesis 8 (DOCK8) mutationsEnhanced gut permeabilityOral peanut challengesDOCK8 functionIngested allergenImmunologic mechanismsAnaphylaxis responsesImmunologic pathwaysAllergic diseasesC57BL/6 micePeanut allergyAntibody responseC miceReceptor 4DOCK8 mutationsIntraperitoneal challenge
2020
Designed CXCR4 mimic acts as a soluble chemokine receptor that blocks atherogenic inflammation by agonist-specific targeting
Kontos C, El Bounkari O, Krammer C, Sinitski D, Hille K, Zan C, Yan G, Wang S, Gao Y, Brandhofer M, Megens RTA, Hoffmann A, Pauli J, Asare Y, Gerra S, Bourilhon P, Leng L, Eckstein HH, Kempf WE, Pelisek J, Gokce O, Maegdefessel L, Bucala R, Dichgans M, Weber C, Kapurniotu A, Bernhagen J. Designed CXCR4 mimic acts as a soluble chemokine receptor that blocks atherogenic inflammation by agonist-specific targeting. Nature Communications 2020, 11: 5981. PMID: 33239628, PMCID: PMC7689490, DOI: 10.1038/s41467-020-19764-z.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnimalsAntigens, CDAtherosclerosisBinding SitesCarotid Artery, CommonChemokine CXCL12Crystallography, X-RayDisease Models, AnimalDrug DesignDrug Evaluation, PreclinicalEndarterectomy, CarotidFemaleHumansIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMaleMiceMice, Knockout, ApoEMiddle AgedPeptide FragmentsReceptors, CXCR4SialyltransferasesSignal TransductionConceptsMacrophage migration inhibitory factorCXC motif chemokine receptor 4Chemokine receptorsChemokine/receptor axisCXCR4/CXCL12 interactionHuman carotid endarterectomy specimensMigration inhibitory factorChemokine receptor 4MIF/CD74Carotid endarterectomy specimensAtherogenic inflammationCXCL12 interactionReceptor axisReceptor 4MIF inhibitorsReceptor-based strategiesAtherosclerotic plaquesAtherosclerosisAtypical chemokineLeukocyte adhesionCell activityProtective pathwaysInflammationChemokinesPlaquesInflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets
Karimy JK, Reeves BC, Damisah E, Duy PQ, Antwi P, David W, Wang K, Schiff SJ, Limbrick DD, Alper SL, Warf BC, Nedergaard M, Simard JM, Kahle KT. Inflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets. Nature Reviews Neurology 2020, 16: 285-296. PMID: 32152460, PMCID: PMC7375440, DOI: 10.1038/s41582-020-0321-y.Peer-Reviewed Original ResearchConceptsPosthaemorrhagic hydrocephalusPostinfectious hydrocephalusNeurosurgical disordersPathogenic mechanismsToll-like receptor 4Pathogenesis of hydrocephalusImportant protective responseEpendymal denudationCommon neurosurgical disorderSustained inflammationInflammatory mediatorsNeuroinflammatory conditionsImmune cellsReceptor 4Therapeutic approachesReparative inflammationCerebrospinal fluidCSF pathwaysHydrocephalusTherapeutic targetInflammationTherapeutic interventionsBrain ventriclesProtective responsePhysical irritants
2019
Tlr4 participates in the responses of markers of apoptosis, inflammation, and ER stress to different acute exercise intensities in mice hearts
de Vicente L, Pinto A, Muñoz V, Rovina R, da Rocha A, Gaspar R, da Silva L, Simabuco F, Frantz F, Pauli J, de Moura L, Cintra D, Ropelle E, da Silva A. Tlr4 participates in the responses of markers of apoptosis, inflammation, and ER stress to different acute exercise intensities in mice hearts. Life Sciences 2019, 240: 117107. PMID: 31785241, DOI: 10.1016/j.lfs.2019.117107.Peer-Reviewed Original ResearchConceptsAcute exercise intensityAcute physical exerciseLeft ventricleTLR4 deletionIL-17Serum levelsTNF-alphaPhysical exerciseExercise intensityER stressToll-like receptor 4Heart mRNA levelsSame exercise conditionTLR4 KO miceRole of TLR4Myocardium of miceExpression of inflammationResponse of markersEndoplasmic reticulum stressKO miceReceptor 4CK-MBImmune responseInflammationER stress genesPathobiology of inherited biliary diseases: a roadmap to understand acquired liver diseases
Fabris L, Fiorotto R, Spirli C, Cadamuro M, Mariotti V, Perugorria MJ, Banales JM, Strazzabosco M. Pathobiology of inherited biliary diseases: a roadmap to understand acquired liver diseases. Nature Reviews Gastroenterology & Hepatology 2019, 16: 497-511. PMID: 31165788, PMCID: PMC6661007, DOI: 10.1038/s41575-019-0156-4.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCystic fibrosis-related liver diseaseFibropolycystic liver diseaseLiver diseasePolycystic liver diseaseBiliary repairAlagille syndromeEpithelial toll-like receptor 4Toll-like receptor 4Acquired liver diseasesGut-derived productsPrimary sclerosing cholangitisDuct epithelial cellsSclerosing cholangitisΒ-catenin signalingPortal fibrosisBiliary diseaseIL-1βUnknown etiologyDependent cytokinesReceptor 4Peribiliary inflammationRole of NotchCholangiopathyNovel treatmentsCyst growthEndothelial toll‐like receptor 4 maintains lung integrity via epigenetic suppression of p16INK4a
Kim S, Shan P, Hwangbo C, Zhang Y, Min J, Zhang X, Ardito T, Li A, Peng T, Sauler M, Lee PJ. Endothelial toll‐like receptor 4 maintains lung integrity via epigenetic suppression of p16INK4a. Aging Cell 2019, 18: e12914. PMID: 30790400, PMCID: PMC6516428, DOI: 10.1111/acel.12914.Peer-Reviewed Original ResearchConceptsToll-like receptor 4Senescence-related gene expressionLung integritySenescence-associated genesReceptor 4New functional roleLung ECsInnate immune receptor toll-like receptor 4Immune receptor toll-like receptor 4Role of TLR4Endothelial Toll-like receptor 4Receptor Toll-like receptor 4Epigenetic regulationHistone H4Epigenetic suppressionTLR4-/- miceGene expressionEndogenous p16Molecular mechanismsWild-type miceNovel roleExpression of p16Lung endothelial cellsFunctional roleDistinct rolesEffects of Endotoxin on Type 3 Inositol 1,4,5‐Trisphosphate Receptor in Human Cholangiocytes
Franca A, Filho A, Guerra MT, Weerachayaphorn J, dos Santos M, Njei B, Robert M, Lima C, Vidigal P, Banales JM, Ananthanarayanan M, Leite MF, Nathanson MH. Effects of Endotoxin on Type 3 Inositol 1,4,5‐Trisphosphate Receptor in Human Cholangiocytes. Hepatology 2019, 69: 817-830. PMID: 30141207, PMCID: PMC6351171, DOI: 10.1002/hep.30228.Peer-Reviewed Original ResearchConceptsToll-like receptor 4Alcoholic hepatitisEffect of endotoxinBile duct cellsNF-κBInhibition of TLR4Human cholangiocytesStimulation of TLR4Duct cellsSevere alcoholic hepatitisCholestasis of sepsisForms of cholestasisNF-κB subunitsP65/p50Trisphosphate receptorReceptor 4Clinical conditionsBicarbonate secretionHepatocellular changesITPR3 expressionCholestasisType 3 inositolLPS receptorAgonist stimulusSepsis
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