简介:AIM:JS-38(mitothiolore),asyntheticversionofametaboliteisolatedfromXenorhabdussp.,wasevaluatedforitsanti-tumorandwhitebloodcell(WBC)elevatingactivities.METHOD:Theseanti-proliferativeactivitieswereassessedinvitrousingapaneloftencelllines.Theanti-tumoractivitiesweretestedinvivousingB16allograftmousemodelsandxenograftmodelsofA549humanlungcarcinomaandQGYhumanhepatomainnudemice.Theanti-tumorinteractionsofJS-38andcyclophosphamide(CTX)or5-fluorouracil(5-Fu)werestudiedinaS180sarcomamodelinICRmice.SpecificstimulatoryeffectsweredeterminedonperipheralneutrophilsinnormalandCTX-and5-Fu-inducedneutropenicmice.RESULTS:TheIC50valuesrangedfrom0.1to2.0μmol·L-1.JS-38(1μmol·L-1)causedanincreaseinA549tumorcellapoptosis.Multi-dailygavageofJS-38(15,30,and60mg?kg-1?d-1)inhibitedinvivotumorprogressionwithoutasignificanteffectonbodyweight.JS-38additivelyenhancedtheinvivoanti-tumoreffectsofCTXor5-Fu.JS-38increasedperipheralneutrophilcountsandneutrophilratesinnormalBALB/cmicealmostaseffectivelyasgranulocytecolony-stimulatingfactor(G-CSF).InmicewithneutropeniainducedbyCTXor5-Fu,JS-38rapidlyrestoredneutrophilcounts.CONCLUSION:TheseresultssuggestthatJS-38hasanti-tumoractivity,andalsohastheabilitytoincreaseperipheralbloodneutrophils.
简介:AIM:ToevaluatetheeffectofOcimumsanctumleafextractonthedietarysupplementationinthetransgenicDrosophilamodelofParkinson’sdisease.METHOD:TheeffectofOcimumsanctumleafextractwasstudiedonthetransgenicDrosophilamodeloffliesexpressingnormalhumanalphasynuclein(h-αs)intheneurons.O.sanctumextractatfinalconcentrationsof0.0428×10-4,0.87×10-4,and1.85×10-4g·mL-1ofdietwereestablishedandtheflieswereallowedtofeedfor21days.Theclimbingassayandlipidperoxidationweretakenasparametersforthestudy.RESULTS:ThesupplementationofO.sanctumextractshowedadose-dependentsignificantdelayinthelossofclimbingabilityandreductioninoxidativestressinthebrainofPDmodelflies.CONCLUSION:TheresultsofthepresentstudyshowedthattheO.sanctumextractispotentinreducingthePDsymptomsintransgenicDrosophilamodel.
简介:ThisstudydevelopedapopulationpharmacokineticmodelforsodiumtanshinoneIIAsulfonate(STS)inhealthyvolunteersandcoronaryheartdisease(CHD)patientsinordertoidentifysignificantcovariatesforthepharmacokineticsofSTS.Bloodsampleswereobtainedbyintensesamplingapproachfrom10healthyvolunteersandsparsesamplingfrom25CHDpatients,andapopulationpharmacokineticanalysiswasperformedbynonlinearmixed-effectmodeling.Thefinalmodelwasevaluatedbybootstrapandvisualpredictivecheck.Atotalof230plasmaconcentrationswereincluded,137fromhealthyvolunteersand93fromCHDpatients.Itwasatwo-compartmentmodelwithfirst-orderelimination.Thetypicalvalueoftheapparentclearance(CL)ofSTSinCHDpatientswithtotalbilirubin(TBIL)levelof10μmol(L?1was48.7L(h?1withinterindividualvariabilityof27.4%,whereasthatinhealthyvolunteerswiththesameTBILlevelwas63.1L(h?1.Residualvariabilitywasdescribedbyaproportionalerrormodelandestimatedat5.2%.TheCLofSTSinCHDpatientswaslowerthanthatinhealthyvolunteersanddecreasedwhenTBILlevelsincreased.Thebootstrapandvisualpredictivecheckconfirmedthestabilityandvalidityofthefinalmodel.TheseresultssuggestedthatSTSdosageadjustmentmightbeconsideredbasedonTBILlevelsinCHDpatients.