Renpeng Zhou
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2024
NS8593 inhibits sodium nitroprusside-induced chondrocyte apoptosis by mediating the STING signaling pathway
Zhu R, Hao W, Li S, Chen Y, Zhou F, Zhou R, Hu W. NS8593 inhibits sodium nitroprusside-induced chondrocyte apoptosis by mediating the STING signaling pathway. Heliyon 2024, 10: e31375. PMID: 38831839, PMCID: PMC11145487, DOI: 10.1016/j.heliyon.2024.e31375.Peer-Reviewed Original ResearchTransient receptor potential cation channel subfamily M member 7STING signaling pathwayCyclic GMP-AMP synthase (cGAS)-stimulatorSNP-induced decreaseAtrial fibrillation therapyPhosphorylation levelsSignaling pathwayApoptosis in vitroCell viabilityNS8593Atrial fibrillationDose-dependentlyImprove atrial fibrillationInterferon genesSNP-induced chondrocyte apoptosisArticular cartilage damageApoptosisChondrocyte apoptosisFeatures of osteoarthritisChondrocyte apoptosis in vitroArticular cartilage destructionCartilage destructionCartilage damageStingsTreatmentSafety, tolerability, and pharmacokinetics of the novel RdRp inhibitor SHEN26 against SARS-CoV-2: a randomized, placebo-controlled, double-blind Phase I study in healthy subjects
Sun C, Liu H, Ouyang Z, Ding J, Zhang Q, Ma H, Xu D, Zhang Q, Zhou R, Yang M, Hu W. Safety, tolerability, and pharmacokinetics of the novel RdRp inhibitor SHEN26 against SARS-CoV-2: a randomized, placebo-controlled, double-blind Phase I study in healthy subjects. Expert Opinion On Investigational Drugs 2024, 33: 533-542. PMID: 38662639, DOI: 10.1080/13543784.2024.2347302.Peer-Reviewed Original ResearchArea under the curveAscending-dose studyFood effect studyHealthy subjectsPlacebo-controlled phase I studySARS-CoV-2Increased approximately dose-proportionallyPlasma concentrationsTreatment-related adverse eventsApproximately dose-proportionallyPhase I studyHigh-fat mealBroad-spectrum antiviral drugsPreclinical activityDose proportionalityDouble-blindPlacebo-controlledReport safetyDose groupSafety profileStandard mealAdverse eventsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2TRPM7 facilitates fibroblast-like synoviocyte proliferation, metastasis and inflammation through increasing IL-6 stability via the PKCα-HuR axis in rheumatoid arthritis
Lin Y, Chen Y, Hu W, Liu X, Hao W, Xing J, Ding J, Xu Y, Yao F, Zhao Y, Wang K, Li S, Yu Q, Hu W, Zhou R. TRPM7 facilitates fibroblast-like synoviocyte proliferation, metastasis and inflammation through increasing IL-6 stability via the PKCα-HuR axis in rheumatoid arthritis. International Immunopharmacology 2024, 132: 111933. PMID: 38581988, DOI: 10.1016/j.intimp.2024.111933.Peer-Reviewed Original ResearchConceptsTransient receptor potential melastatin 7Rheumatoid arthritisInhibition of transient receptor potential melastatin 7Human RA patientsSynovial hyperplasiaAdjuvant-induced arthritis ratsIncreased TRPM7 expressionIL-6 mRNATreatment of RAPathogenesis of RAFibroblast-like synoviocytesTRPM7 silencingProgression of rheumatoid arthritisTRPM7 expressionChannel inhibitionCation channelsRA patientsMetastasisPharmacological inhibitionArthritis ratsInflammationNuclear translocationSynoviocyte proliferationHyperplasiaProliferationExtracellular CIRP induces abnormal activation of fibroblast-like synoviocytes from patients with RA via the TLR4-mediated HDAC3 pathways
Yao F, Zhao Y, Yu Q, Hu W, Lin Y, Chen Y, Li L, Sun C, Li S, Wang K, Yang M, Zhou R, Hu W. Extracellular CIRP induces abnormal activation of fibroblast-like synoviocytes from patients with RA via the TLR4-mediated HDAC3 pathways. International Immunopharmacology 2024, 128: 111525. PMID: 38218010, DOI: 10.1016/j.intimp.2024.111525.Peer-Reviewed Original ResearchConceptsExtracellular cold-inducible RNA-binding proteinCold-inducible RNA-binding proteinToll-like receptor 4Histone deacetylase 3Endogenous proinflammatory moleculesRheumatoid arthritisActivity of RA-FLSAA ratsAbnormal activationProinflammatory moleculesEffect of cold-inducible RNA-binding proteinHistone deacetylase 3 knockdownRelease of IL-1bSeverity of arthritisFibroblast-like synoviocytesDevelopment of rheumatoid arthritisRA-FLSActivation of fibroblast-like synoviocytesIL-33Expression of N-cadherinProinflammatory effectsArthritis severityIL-1BInflammatory diseasesReceptor 4IUPHAR ECR review: The cGAS-STING pathway: Novel functions beyond innate immune and emerging therapeutic opportunities
He X, Wedn A, Wang J, Gu Y, Liu H, Zhang J, Lin Z, Zhou R, Pang X, Cui Y. IUPHAR ECR review: The cGAS-STING pathway: Novel functions beyond innate immune and emerging therapeutic opportunities. Pharmacological Research 2024, 201: 107063. PMID: 38216006, DOI: 10.1016/j.phrs.2024.107063.Peer-Reviewed Original ResearchStimulator of interferon genesAdaptor protein complex 1Function of STINGRegulation of cellular metabolismRegulatory functionsRegulation of stimulator of interferon genesInnate immune signaling pathwaysImmune signaling pathwaysInnate immune regulationInnate immune sensorsCellular physiologyCGAS-STING pathwayDNA repairNegative regulatorComplex regulationCellular metabolismCytosolic DNAStimulator of interferon genes agonistsCell deathAP-1Stimulators of interferon genes signallingSignaling pathwayMolecular mechanismsImmune regulatory drugImmune sensorsSafety and Pharmacokinetics of HRS-2261, a P2X3 Receptor Antagonist, in Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Study
Fan Y, Zhang X, Zhang Q, Zheng L, Zhou R, Sun C, Wang X, Song K, He Z, Wang H, Zhang Q, Hu W. Safety and Pharmacokinetics of HRS-2261, a P2X3 Receptor Antagonist, in Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Study. Clinical Pharmacokinetics 2024, 63: 293-302. PMID: 38198010, DOI: 10.1007/s40262-023-01330-7.Peer-Reviewed Original ResearchP2X3 receptor antagonistAdverse eventsReceptor antagonistHealthy subjectsChronic coughPlacebo-controlled phase 1 trialModerate adverse eventsMost adverse eventsTwice-daily dosingSelective P2X3 receptor antagonistPhase 1 studyPhase 1 trialUnexplained chronic coughSingle oral doseStudy phaseMedian tmaxPrimary endpointGood tolerabilityOral doseTherapeutic optionsResultsA totalDrug exposureMean t1/2Lower incidenceFood intake
2023
Safety, tolerability, pharmacokinetics and pharmacodynamics of a single intravenous dose of SHR‐1707 in healthy adult subjects: two randomized, double‐blind, phase 1 studies
Hu W, Shakib S, Williams J, Fan Y, Zhang Q, Qin H, Wu J, Zhang X, Liu Y, Zhou R, Yang Y, Zhang Q, Ye Z, Qiu H, Ma J, Zhu M, Feng S, Fei Y, Li N, Cui X, Dong F, Wang T. Safety, tolerability, pharmacokinetics and pharmacodynamics of a single intravenous dose of SHR‐1707 in healthy adult subjects: two randomized, double‐blind, phase 1 studies. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.074758.Peer-Reviewed Original ResearchPhase 1 studySingle intravenous doseHealthy young adultsPK/PD profilesHealthy adult subjectsIntravenous doseElderly subjectsYoung adultsDose levelsPD profilesAdult subjectsDose-proportional mannerPK/pharmacodynamicsFurther clinical developmentDose-dependent increaseSame dose levelIgG1 monoclonal antibodyPlacebo groupLaboratory abnormalitiesMicroglial phagocytosisAβ plaquesPreclinical studiesSHRClinical developmentAβ42 concentrationsSafety, pharmacokinetics and pharmacodynamics of HRS‐7535, a novel oral small molecule glucagon‐like peptide‐1 receptor agonist, in healthy participants: A phase 1, randomized, double‐blind, placebo‐controlled, single‐ and multiple‐ascending dose, and food effect trial
Wu J, Zhou R, Zhang Q, Zhang Q, Qin H, Ye Z, Xu Y, Feng S, Shu C, Shen Y, Fan Y, Wang Q, Du Y, Hu W. Safety, pharmacokinetics and pharmacodynamics of HRS‐7535, a novel oral small molecule glucagon‐like peptide‐1 receptor agonist, in healthy participants: A phase 1, randomized, double‐blind, placebo‐controlled, single‐ and multiple‐ascending dose, and food effect trial. Diabetes Obesity And Metabolism 2023, 26: 901-910. PMID: 38100147, DOI: 10.1111/dom.15383.Peer-Reviewed Original ResearchGlucagon-like peptide-1 receptor agonistsPeptide-1 receptor agonistsSingle ascending doseMAD partsReceptor agonistGeometric mean tNovel glucagon-like peptide-1 receptor agonistFood effectHealthy participantsMultiple ascending dosePhase 1 trialType 2 diabetesGLP-1RAsPrimary endpointSingle doseDay 29Day 28Mean reductionClinical developmentMean TBody weightPharmacokineticsPlaceboTolerabilityEffect trialASIC1a-CMPK2-mediated M1 macrophage polarization exacerbates chondrocyte senescence in osteoarthritis through IL-18
Dong L, Zhao Y, Sun C, Ou Yang Z, Chen F, Hu W, Zhang H, Wang Y, Zhu R, Cheng Y, Chen Y, Li S, Wang K, Ding C, Zhou R, Hu W. ASIC1a-CMPK2-mediated M1 macrophage polarization exacerbates chondrocyte senescence in osteoarthritis through IL-18. International Immunopharmacology 2023, 124: 110878. PMID: 37660594, DOI: 10.1016/j.intimp.2023.110878.Peer-Reviewed Original ResearchAcid-sensing ion channel 1aM1 macrophage polarizationM1 macrophagesChondrocyte senescenceMacrophage polarizationIL-18OA patientsPcTX-1IL-18 stimulationOA cartilage damageArticular cartilage destructionMouse OA modelIntra-articular administrationPromising treatment targetIon channel 1aMacrophage-associated genesMacrophage-mediated diseasesMechanism of actionASIC1a expressionOA miceCartilage destructionM1 polarizationCartilage damageOA modelSynovial fluidTargeting regulated chondrocyte death in osteoarthritis therapy
Zhu R, Wang Y, Ouyang Z, Hao W, Zhou F, Lin Y, Cheng Y, Zhou R, Hu W. Targeting regulated chondrocyte death in osteoarthritis therapy. Biochemical Pharmacology 2023, 215: 115707. PMID: 37506921, DOI: 10.1016/j.bcp.2023.115707.Peer-Reviewed Original ResearchConceptsChondrocyte deathCartilage degenerationArticular cartilage degenerationBone erosionExtracellular matrix degradationOA preventionOA pathogenesisChondrocyte senescenceCartilage lossOsteoarthritis therapyOA treatmentOsteoarthritisCell death modeDeathMatrix degradationEssential hallmarkTreatment methodsDegenerationForm of deathDeath modeTreatmentPathogenesisTherapyProgressionPrevention