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.