简介：AIM:Tumorangiogenesishasbeenshowntobepromotedbyvascularendothelialgrowthfactor(VEGF)viastimulatingendothelialcellproliferation,migration,andsurvival.BlockadeofVEGFsignalingbydifferentmeanshasbeendemonstratedtoresultinreducedtumorgrowthandsuppressionoftumorangiogenesisindistincttumorentities.Here,wetestedarecombinantadenovirus,AdsFIt1-3,thatencodesanantagonisticallyactingfragmentoftheVEGFreceptor1(Flt-1),forsystemicantitumoreffectsinpre-establishedsubcutaneousCRCtumorsinmice.METHODS:Murinecolorectalcarcinomacells(CT26)wereinoculatedsubcutaneouslyintoBalb/cmiceforinvivostudies.Tumorsizeandsurvivalweredetermined.293celllinewasusedforpropagationoftheadenoviralvectors.HumanlungcancerlineA549andhumanumbilicalveinendothelialcellsweretransfectedforinvitroexperiments.RESULTS:InfectionoftumorcellswithAdsFlt1-3resultedinproteinsecretionintocellsupernatant,demonstratingcorrectvectorfunction.Asexpected,thesecretedsFlt1-3proteinhadnodirecteffectonCT26tumorcellproliferationinvitro,butendothelialcellfunctionwasinhibitedbyabout46%ascomparedtotheAdLacZcontrolinatubeformationassay.WhenAdsFlt1-3(5×109PFU/animal)wasappliedtotumorbearingmice,wefoundatumorinhibitionby72%atd12aftertreatmentinitiation.Inspiteoftheseantitumoraleffects,thesurvivaltimewasnotimproved.AccordingtoreducedintratumoralmicrovesseldensityinAdsFIt1-3-treatedmice,theantitumormechanismcanbeattributedtoangiostaticvectoreffects.WedidnotdetectincreasedsystemicVEGFlevelsafterAdsFlt1-3treatmentandlivertoxicitywaslowasjudgedbyserumalanineaminotransferasedetermination.CONCLUSION:InthisstudyweconfirmedthevalueofasystemicadministrationofAdsFIt1-3toblockVEGFsignalingasantitumortherapyinanexperimentalmetastaticcolorectalcarcinomamodelinmice.

简介：AIM:Toinvestigatewhethergenemethylationintheperitonealfluid(PF)predictsperitonealrecurrenceingastriccancerpatients.METHODS:ThegenemethylationofCHFR(checkpointwithforkheadandringfingerdomains),p16,RUNX3(runt-relatedtranscriptionfactor3),E-cadherin,hMLH1(mutLhomolog1),ABCG2(ATP-bindingcassette,sub-familyG,member2)andBNIP3(BCL2/adenovirusE1B19kDainteractingprotein3)wereanalyzedin80specimensofPFbyquantitativemethylation-specificpolymerasechainr...

简介：瞄准：为了为在肝炎B估计肝的纤维变性决定结缔组织生长因素(CCN2/CTGF)的用途，病毒(HBV)导致了长期的肝疾病(CLD-B)。方法：连接酶的immunosorbent试金被用来与导致HBV的活跃的肝肝硬化和30个健康个人与长期的肝炎B(CHB)和39个病人从107个病人在sera测量CCN2。从有CHB，有导致HBV的肝肝硬化的8个病人和有正常的肝组织学的8个HBV搬运人的31个病人的肝样品为转变生长因素-1(TGF-1)或CCN2mRNA层次由被检验在situ杂交，并且计算机图象分析被执行在肝纸巾测量CCN2mRNA积极的房间的综合最佳的密度(IOD)。组织学的发炎分级和纤维变性阶段被H并且E染色和凡·吉森斯方法评估。结果：分别地，浆液CCN2集中作为与健康个人相比在有CHB或活跃的肝肝硬化的病人更高是4.0褶层或4.9褶层(P<0.01)。在肝纸巾在在sera和CCN2mRNA表示的CCN2的层次之间有好一致性(r=0.87，P<0.01)。在sera的CCN2的层次与CLD-B在病人与组织学的纤维变性阶段的改进被增加(r=0.85，P<0.01)。浆液CCN2是为对肝纤维变性的评价的一个可靠标记，与在操作为从有F1阶段肝纤维变性的病人的分别地，区分的正常的肝控制的0.94或0.85的特征(巨鸟)曲线(AUC)或在温和、重要的纤维变性之间区别的接收装置下面的区域。结论：在有CLD-B的病人的浆液CCN2的察觉可以为对肝的纤维变性的严厉的评价有临床的意义。

简介：AIMToinvestigatetherolesandinteractionsofmutThomolog（MTH）-1andhypoxia-induciblefactor（HIF）-1αinhumancolorectalcancer（CRC）.METHODS：TheexpressionanddistributionofHIF-1αandMTH-1proteinsweredetectedinhumanCRCtissuesbyimmunohistochemistryandquantitativerealtimepolymerasechainreaction（qRT-PCR）.SW480andHT-29cellswereexposedtonormoxiaorhypoxia.ProteinandmRNAlevelsofHIF-1αandMTH-1wereanalyzedbywesternblottingandqRT-PCR,respectively.InordertodeterminetheeffectofHIF-1αontheexpressionofMTH-1andtheamountof8-oxodeoxyguanosinetriphosphate（dGTP）inSW480andHT-29cells,HIF-1αwassilencedwithsmallinterferingRNA（siRNA）.GrowthstudieswereconductedoncellswithHIF-1αinhibitionusingaxenografttumormodel.Finally,MTH-1proteinwasdetectedbywesternblottinginvivo.RESULTS：HighMTH-1mRNAexpressionwasdetectedin64.2%ofcases（54/84）,andthiswassignificantlycorrelatedwithtumorstage（P=0.023）andsize（P=0.043）.HIF-1αproteinexpressionwascorrelatedsignificantlywithMTH-1expression（R=0.640;P〈0.01）inhumanCRCtissues.HypoxicstressinducedmRNAandproteinexpressionofMTH-1inSW480andHT-29cells.InhibitionofHIF-1αbysiRNAdecreasedtheexpressionofMTH-1andledtotheaccumulationof8-oxo-dGTPinSW480andHT-29cells.Intheinvivoxenografttumormodel,expressionofMTH-1wasdecreasedintheHIF-1αsiRNAgroup,andthetumorvolumewasmuchsmallerthanthatinthemocksiRNAgroup.CONCLUSION：MTH-1expressioninCRCcellswasupregulatedviaHIF-1αinresponsetohypoxicstress,emphasizingthecrucialroleofHIF-1α-inducedMTH-1intumorgrowth.

简介：AIMToexploretheprotectiveeffectsandunderlyingmechanismsoftotalpolysaccharidesoftheSijunzidecoction(TPSJ)ontheepithelialbarriersinvitro.METHODSCaco-2cellmonolayersweretreatedwithorwithoutTPSJinthepresenceorabsenceofTNF-α,andparacellularpermeabilityandtransepithelialelectricalresistance(TEER)weremeasuredtoevaluatetheepithelialbarrierfunction.Immunofluorescenceandwesternblottingwererespectivelyusedtoevaluatethedistributionandexpressionofthetightjunctionproteinsclaudin1,claudin2,zo3,andoccludininCaco-2cells.Westernblottingwasalsousedtoevaluatethecellularexpressionofmyosinlightchain(MLC),phosphorylatedMLC(pMLC),MLCkinase(MLCK),andnuclearfactor(NF)-κBp65.RESULTSTPSJpromotedtheproliferationofCaco-2cellsandinhibitedTNF-α-inducedsecretionofpro-inflammatorycytokines.Furthermore,TPSJsignificantlyamelioratedboththereductionofTEERandtheincreasedparacellularpermeabilityobservedintumornecrosisfactor(TNF)-α-damagedCaco-2monolayers.Furthermore,TPSJremarkablyattenuatedTNF-α-inducedmorphologicalchanges,downregulatedtheexpressionofclaudin1,claudin2,zo3,andoccludin,andmarkedlysuppressedTNF-α-mediatedupregulationofp-MLCandMLCKexpression.Finally,TPSJinhibitedtheactivationandexpressionofNF-κBp65.CONCLUSIONOurresultsdemonstratethatTPSJalleviatestheTNF-α-inducedimpairmentoftheintestinalepithelialcellbarrierfunctionbysuppressingNF-κBp65-mediatedphosphorylationofMLCKandMLC.

简介：AIM.Toinvestigatetheeffectofpyrrolidinedithiocarbamate(PDTC),anovelnuclearfactor-κB(NF-κB)inhibitor,onexpressionofmultipleinflammatorymediatorsandneutrophilicinflammationofcoldpreservedgraftsafterratlivertransplantationanditssignificance.METHODS:Orthotopiclivertransplantation(OLT)wasperformedafter24hofcoldstorageusingUniversityofWisconsinsolutionwithvariedconcentrationsofPDTC.WedeterminedthetimecourseofNF-κBactivationandexpressionofmultipleinflammatorysignals,suchastumornecrosisfactor-α(TNF-α),cytokine-inducibleneutrophilchemoattractant(CINC),andintercellularadhesionmolecule-1(ICAM-1)byELISAmethods.Serumalanineaminotransferase(ALT),intrahepaticmyeloperoxidase(MPO)/WBC(ameasureofneutrophilaccumulation)andMac-1expression(ameasureofcirculatingneutrophilactivity)werealsoevaluated.RESULTS:PDTCdecreasedNF-κBactivationinducedbyprolongedcoldpreservationinadosedependentmanner(from20mmol/Lto60mmol/L),diminishedTNF-α,CINC,ICAM-1proteinsinthegrafts,andreducedtheexpressionfincreasesinplasmaTNF-αlevelsinducedbyprolongedoldpreservation.NeutrophilicinflammationofthegraftwassignificantlysuppressedafterpreservationwithPDTC(P<0.05).ThetotalneutrophilaccumulationinPDTC(40mmol/L)group(7.04±0.97)wasmarkedlyreducedcomparedtocontrolgroup(14.07±1.31)(P<0.05).Mac-1expressionwassignificantlyreducedinPDTC(40retool/L)group(181±11.3%)comparedwiththecontrolgroup(281±13.2%)(P<0.05)at6hafterreperfusion.Furthermore,PDTCinhibitedtheincreasedserumALTlevelsafterlivertransplantation.CONCLUSION:PDTCcaninhibitBNF-κBactivationandexpressionoftheinflammatorymediators,whichareassociatedwithimprovedgraftviabilityviainhibitingintrahepaticneutrophilicinflammation.OurstudysuggeststhatatherapeuticstrategydirectedatinhibitionofNF-κBactivationinthetransplantedlivermightbeeffectiveinreducing

简介：AIM:Toevaluatetheepidemiologyandoutcomesofculture-positivespontaneousbacterialperitonitis(SBP)andspontaneousbacteremia(SB)indecompensatedcirrhosis.METHODS:Weprospectivelycollectedclinical,laboratorycharacteristics,typeofadministeredantibiotic,susceptibilityandresistanceofbacteriatoantibioticsinonehundredthirtycases(68.5%males)withpositiveasciticfluidand/orbloodculturesduringtheperiodfromJanuary1,2012toMay30,2014.AllpatientswithSBPhadpolymorphonuclearcellcountinasciticfluid>250/mm3.InpatientswithSBathoroughstudydidnotrevealanyothercauseofbacteremia.Thepatientswerefollowed-upfora30-dperiodfollowingdiagnosisoftheinfection.Thefinaloutcomeofthepatientswasrecordedintheendoffollow-upandcomparisonamong3groupsofpatientsaccordingtothepatternofdrugresistancewasperformed.RESULTS:Gram-positive-cocci(GPC)werefoundinhalfofthecases.ThemostprevalentorganismsinadescendingorderwereEscherichiacoli(33),Enterococcusspp(30),Streptococcusspp(25),Klebsiellapneumonia(16),S.aureus(8),Pseudomanasaeruginosa(5),otherGram-negative-bacteria(GNB)(11)andanaerobes(2).Overall,20.8%ofisolatesweremultidrug-resistant(MDR)and10%extensivelydrugresistant(XDR).Health-care-associated(HCA)and/ornosocomialinfectionswerepresentin100%ofMDR/XDRandin65.5%ofnon-DRcases.MeropenemwastheempiricallyprescribedantibioticinHCA/nosocomialinfectionsshowingadrug-resistancerateof30.7%whilethirdgenerationcephalosporinsof43.8%.MeropenemwasineffectiveonbothXDRbacteriaandEnterococcusfaecium(E.faecium).AllbutoneXDRweresusceptibletocolistinwhileallGPC(includingE.faecium)andthe86%ofGNBtotigecycline.Overall30-dmortalitywas37.7%(69.2%forXDRand34.2%fortherestofthepatients)(logrank,P=0.015).Inmultivariateanalysis,factorsadverselyaffectingoutcomeincludedXDRinfection(HR=2.263,95%CI:1.005-5.095,P=0.049),creatinine(HR

简介：瞄准：在老鼠碳在Kupffer房间决定激活血小板的因素(PAF)合成和它的受体表示导致四氯化物的肝硬化。方法：Kupffer房间，从控制和导致CCl4的肝脏硬化症的老鼠的肝孤立，一夜间被放在没有浆液的媒介。PAF浸透绑定，ET-1浸透和比赛绑定是assayed。导致的PAF合成，PAF的mRNA表示，preproendothelin-1，endothelinA(希腊语字母的第七字)和endothelinB(ETB)受体也是的ET-1决定了。结果：PAF合成的双重的增加(1.42+/-0.14对0.66+/-0.04pg/mugDNA)并且膜界限PAF的1.48褶层增加(1.02+/-0.06对0.69+/-0.07pg/mugDNA)在肝脏硬化症的老鼠的激活的Kupffer房间被观察。到Kupffer房间的ET-1的申请在激活的Kupffer房间经由ETB受体，而是PAF合成在肝脏硬化症、正常的老鼠以一种集中依赖者方式导致了PAF合成在正常Kupffer房间是比那更有效的。在激活的Kupffer房间，PAF受体表示和PAF绑定能力显著地被提高。激活的Kupffer房间涨了[125I]-ET-1绑定能力，而是改变的两个都不受体的亲密关系，也不希腊语字母的第七字的表达式受体。结论：在导致CCl4的肝硬化期间的Kupffer房间是增加的PAF的主要来源。ET-1内长地涉及由paracrine经由ETB受体在激活的Kupffer房间刺激PAF合成。希腊语字母的第七字受体没出现在激活的Kupffer房间，它可以加重肝硬化的肝、额外的肝的复杂并发症。