简介:Houttuyniacordatapolysaccharide(HCP)isextractedfromHouttuyniacordata,akeytraditionalChinesemedicine.ThestudywastoinvestigatetheeffectsofHCPonintestinalbarrierandmicrobiotainH1N1virusinfectedmice.MicewereinfectedwithH1N1virusandorallyadministratedHCPatadosageof40mg(kg^-1(d^-1.H1N1infectioncausedpulmonaryandintestinalinjuryandgutmicrobiotaimbalance.HCPsignificantlysuppressedtheexpressionofhypoxiainduciblefactor-1αanddecreasedmucosubstancesingobletcells,butrestoredthelevelofzonulaoccludens-1inintestine.HCPalsoreversedthecompositionchangeofintestinalmicrobiotacausedbyH1N1infection,withsignificantlyreducedrelativeabundancesofVibrioandBacillus,thepathogenicbacterialgenera.Furthermore,HCPrebalancedthegutmicrobiotaandrestoredtheintestinalhomeostasistosomedegree.TheinhibitionofinflammationwasassociatedwiththereducedlevelofToll-likereceptorsandinterleukin-1βinintestine,aswellastheincreasedproductionofinterleukin-10.OraladministrationofHCPalleviatedlunginjuryandintestinaldysfunctioncausedbyH1N1infection.HCPmaygainsystemictreatmentbylocalactingonintestineandmicrobiota.Thisstudyprovedthehigh-valueapplicationofHCP.
简介:Antifungaldrugresistanceisasignificantclinicalproblem,andantifungalagentsthatcanevaderesistanceareurgentlyneeded.Ininfectiveniches,resistantorganismsoftenco-existedwithsensitiveones,orasubpopulationofantibiotic-susceptibleorganismsmayevolveintoresistantonesduringantibiotictreatmentandeventuallydominatethewholepopulation.Inthisstudy,weestablishedaco-cultureassayinwhichanazole-resistantCandidaalbicansstrainwasmixedwithasusceptiblestrainlabeledwithgreenfluorescentproteintomimicinvivoconditionsandscreenforantifungaldrugs.Fluconazolewasusedasapositivecontroltoverifythevalidityofthisco-cultureassay.FivenaturalmoleculesexhibitedantifungalactivityagainstbothsusceptibleandresistantC.albicans.Twoofthesecompounds,retigericacidB(RAB)andriccardinD(RD),preferentiallyinhibitedC.albicansstrainsinwhichtheeffluxpumpMDR1wasactivated.Thisselectivitywasattributedtogreaterintracellularaccumulationofthedrugsintheresistantstrains.Changesinsterolandlipidcompositionswereobservedintheresistantstrainscomparedtothesusceptiblestrain,andmightincreasecellpermeabilitytoRABandRD.Inaddition,RABandRDinterferedwiththesterolpathway,furtheraggregatingthedecreaseinergosterolinthesterolsynthesispathwayintheMDR1-activatedstrains.Ourfindingshereprovideanalternativeforcombatingresistantpathogenicfungi.
简介:Resistancetocisplatin(DDP)-basedchemotherapyisamajorcauseoftreatmentfailureinhumangastriccancer(GC).Itisnecessarytoidentifythedrugstore-sensitizeGCcellstoDDP.Inourpreviousresearch,ZuoJinWanFormula(ZJW)hasbeenprovedcouldincreasethemitochondrialapoptosisviacofilin-1inaimmortalizedcellline,SGC-7901/DDP.Duetotheimmortalizedcellsmaystilldifficulthighlyrecapitulatetheimportantmoleculareventsinvivo,primaryGCcellsmodelderivedfromclinicalpatientwasconstructedinthepresentstudytofurtherevaluatetheeffectofZJWandtheunderlyingmolecularmechanism.ImmunofluorescentstainingwasusedtoindentifyprimaryculturedhumanGCcells.Westernblottingwascarriedouttodetecttheproteinexpression.CellCountingKit-8(CCK-8)wasusedtoevaluatecellproliferation.Flowcytometryanalysiswasperformedtoassesscellapoptosis.ZJWinhibitedproliferationandinducedapoptosisinprimaryDDP-resistantGCcells.Notably,theapoptosisinGCcellswasmediatedbyinducingcofilin-1mitochondrialtranslocation,down-regulatingBcl-2andup-regulatingBaxexpression.Surprisingly,thelevelofp-AKTproteinwashigherinDDP-resistantGCcellsthanthatoftheDDP-sensitiveGCcells,andtheactivationofAKTcouldattenuateZJW-inducedsensitivitytoDDP.ThesedatarevealedthatZJWcanincreasethechemosensitivityinDDP-resistantprimaryGCcellsbyinducingmitochondrialapoptosisandAKTinactivation.ThecombiningchemotherapywithZJWmaybeaneffectivetherapeuticstrategyforGCchemoresistancepatients.
简介:目的:观察脑髓康对短暂性大脑中动脉阻断(tMCAo)小鼠学习记忆与运动能力的影响及机理。方法:采用tMCAo方法诱导血管性痴呆模型,并在手术后连续7天用脑髓康或对照药物进行干预。分别通过恐惧记忆的学习与精确区分、转棒实验评价小鼠学习记忆能力与活动能力;免疫荧光法染色小鼠CA1脑区小胶质细胞、肿瘤坏死因子,ELISA试剂盒检测血清中IL-6、IL-10表达水平,多通道在体电生理的方法记录小鼠大脑海马CA1脑区放电水平。结果:仅有脑髓康9g/kg组能对恐惧记忆进行精确区分;各给药组较模型组均显著提高小鼠的运动能力;脑髓康4.5、9g/kg组的海马肿瘤坏死因子、小胶质细胞水平明显低于模型对照组和尼莫地平组;9g/kg组脑髓康组IL-6含量显著低于模型组和尼莫地平组,IL-10含量显著高于模型组和尼莫地平组;海马CA1脑区神经元放电水平明显提高,与尼莫地平组水平相当。结论:脑髓康能更好地改善tMCAo小鼠对于精确信号的学习记忆能力,其神经保护机制与抑制炎症反应、调控免疫细胞表达、促进神经元放电有关。