简介：Nitricoxide(NO)isapleiotropicregulator,criticaltonumerousbiologicalprocesses,includingva-sodilatation,neurotransmissionandmacrophage-mediatedimmunity.Thefamilyofnitricoxidesynthases(NOS)comprisesinducibleNOS(iNOS),endothelialNOS(eNOS),andneuronalNOS(nNOS).Interest-ingly,variousstudieshaveshownthatallthreeisoformscanbeinvolvedinpromotingorinhibitingtheetiologyofcancer.NOSactivityhasbeendetectedintumourcellsofvarioushistogeneticoriginsandhasbeenassociatedwithtumourgrade,proliferationrateandexpressionofimportantsignalingcomponentsassociatedwithcancerdevelopmentsuchastheoestrogenreceptor.ItappearsthathighlevelsofNOSexpression(forexample,generatedbyactivatedmacrophages)maybecytostaticorcytotoxicfortumorcells,whereaslowlevelactivitycanhavetheoppositeeffectandpromotetumourgrowth.Paradoxicallytherefore,NO(andrelatedreactivenitrogenspecies)mayhavebothgenotoxicandangiogenicproperties.IncreasedNO-generationinacellmayselectmutantp53cellsandcontributetotumourangiogenesisbyupregulatingVEGF.Inaddition,NOmaymodulatetumourDNArepairmechanismsbyupregulatingp53,poly(ADP-ribose)polymerase(PARP)andtheDNA-dependentproteinkinase(DNA-PK).Anunderstand-ingatthemolecularleveloftheroleofNOincancerwillhaveprofoundtherapeuticimplicationsforthediagnosisandtreatmentofdisease.

简介：Matrixmetalloproteinases(MMPs)andtissueinhibitorsofmetalloproteinases(TIMPs)playasignificantroleinregulatingangiogenesis,theprocessofnewbloodvesselformation.Interstitialcollagenase(MMP-1),72kDagelatinaseA/typeIVcollagenase(MMP-2),and92kDAgelatinaseB/typeIVcollagenase(MMP-9)dissolveextracellularmatrix(ECM)andmayinitiateandpromoteangiogenesis.TIMP-1,TIMP-2,TIMP-3,andpossibly,TIMP-4inhibitneovascularization.Anewparadignisemergingthatmatrilysin(MMP-7),MMP-9,andmetalloelastase(MMP-12)mayblockangiogenesisbyconvertingplasminogentoangiostatin,whichisoneofthemostpotentangiogenesisantagonists.MMPsandTIMPsplayacomplexroleinregulatingangiogenesis.Anunderstandingofthebiochemicalandcellularpathwaysandmechanismsofangiogenesiswillprovideimportantinformationtoallowthecontrolofangiogenesis,e.g.thestimulationofangiogenesisforcoronarycollateralcirculationformation;whiletheinhibitionfortreatingarthritisandcancer.

简介：ApoptosisplaysanessentialroleinTcellbiology.ThymocytesexpressingnonfunctionalorautoreactiveTCRsareeliminatedbyapoptosisduringdevelopment.ApoptosisalsoleadstothedeletionofexpandedeffectorTcellsduringimmuneresponses.Thedysregulationofapoptosisintheimmunesystemresultsinautoimmunity,tumorogenesisandimmunodeficiency.Twomajorpathwaysleadtoapoptosis:theintrinsiccelldeathpathwaycontrolledbyBcl-2familymembersandtheextrinsiccelldeathpathwaycontrolledbydeathreceptorsignaling.Thesetwopathwaysworktogethertoregu

简介：PML基因涉及t(15；17)尖锐promyelocytic白血球过多症(APL)的translocation，它产生oncogenic熔化蛋白质PML(promyelocytic白血球过多症蛋白质)-retinoic酸受体高山哈。PML蛋白质本地化称为PML原子领域(PML-ND)的原子结构到一个代用品，哪个PML是必要结构的部件。在APL，PML-NDs被破坏，因此含有在这白血球过多症的致病的这些结构。出人意料地，最近的研究显示PML和PML-ND玩一个瘤在除了APL的人的瘤的几种不同类型的镇压角色。因为PML在多重细胞的小径的极端通用性和参与，理解位于它的功能下面的机制，并且因此在瘤抑制的角色，是一项挑战性的任务。在这评论，我们试图非常在这个领域里估价更最近的进展并且建议调查的新大街。

简介：Itiswellrecognizedthatcelldeathplaysanimportantroleduringthematurationofthenervoussystemaswellasinmanyneurologicaldiseases.Apoptosishasbeenshowntobeimportantparticularyduringembryogenesisasameanstoeliminatingunwantedneurons.SeveredaxonshavealsobeenshowntodegenerateinanorganizedfashiontermedWalleriandegeneration.Excitotoxicdeathisanotherformofcelldeathinthenervoussystemwhichisinducedbyhighconcentrationsofneurotransmitterssuchasglutamate.Itisnotknownwhetherthesamemolecularmechanismsunderliethesedifferentformsofcelldeathinthenervoussystem.TheBax-/-Bak-/-doubleknock-outmouseprovidesanidealsystemtostudy

简介：补充系统对普通病原体在天生的防卫起一个关键作用。补充的激活导致柔韧、有效的解朊的串联，它通过有势力proinflammatory分子的生产在病原体以及在古典煽动性的反应的产生的opsonization和细胞溶解终止。然而，更最近，在有免疫力的反应的补充的角色由于连接补充激活到适应有免疫力的回答的观察被扩展了。补充是在允许综合主人防卫到病原的挑战的天生、适应的有免疫力的回答之间的一座功能的桥，这现在被欣赏。因此，它的函数的研究象主机免疫者反应的组织和组织一样允许卓见进主人病原体相互作用的分子的underpinnings。这评论试图总结在主人防卫上在天生、适应的有免疫力的回答和这些相互作用的后果补充戏的角色。

简介：在病原体识别的像使用费的受体(TLR)的角色在最近的年里是快速地先进的。然而，进在非传染的织物损害的TLR的功能的调查刚开始了。以前，我们和其它表明了那碎裂的hyaluronan(哈)在织物损害期间积累。CD44被要求在织物损害期间清除HA，并且损害了清理哈在不停的发炎的结果。另外，碎裂哈在损害地点由煽动性的房间刺激煽动性的基因的表示。最近，我们识别了那哈碎片要求TLR2和TLR4刺激老鼠巨噬细胞生产煽动性的chemokines和cytokines。在一个非传染的肺损害模型，在TLR2和TLR4缺乏的老鼠显示出煽动性的房间的损害transepithelial迁居，增加的织物损害，提高的肺上皮的房间apoptosis，和减少的幸存。在高分子的质量的表示上的肺上皮的房间哈对尖锐的肺损害和apoptosis的保护的老鼠，部分地通过NF-kappaB的TLR依赖的基础激活。在TLR2和TLR4的夸大的损害缺乏的老鼠看起来由于上皮的房间上的损害HA-TLR相互作用。这些研究识别那个主机矩阵部件哈并且TLR相互作用提供开始煽动性的回答的信号，维持上皮的房间完整，并且支持从尖锐的肺损害的恢复。房间研究(2006)16：693-701。做i：10.1038/sj.cr.7310085；出版联机2006年8月8日。

简介：Thehedgehog-patched(hh-ptc)intercellularsignalingpathwayhasrecentlybeenshowntocontroltheproliferationofepithelialstemcellsinbothDrosophilaandVertebrated.MutantandectopicexpressionanalysesinDrosophilasuggestthattheHHproteindiffusesfromthesignalingcellstopromotetheproliferationofnearbyovariansomaticstemcellsbyantagonizingthesuppressionofitsreceptorPTCtowardstheCItranscriptionfactorinthestemcells.Consequently,thetranscriptionofCIdependentgenesleadstostemcellproliferation.Thisregulatorypathwayappearstofunctionalsoinvertebrates,wheredefectsinptccausebasalcellcarcinoma,tumorsofepidermalstemcellorigin.BasalcellcarcinomacanalsobeinducedbyectopicexpressionofSonichedgehog(shh)orGlil,thevertebratehomologofci.Thesestudiessuggesttheconservationofthehhsignalingpathwayincontrollingepithelialstemcelldivisionsamongdifferentorganisma.

简介：<正>Uponactivation,naiveT-helpercellscandifferentiateintotwomajordistinctsubsets,Thelper1(Th1)andThelper2(Th2),asdefinedbytheireffectorfunctionsandcytokinesecretionpatterns.CytokinemilieuandcostimulatorymoleculeshavebeenshowntoplayanessentialroleindeterminingThelperdifferentiation.However,itisstillunclearhowtheeffectsofsignalsofco-stimulatorymoleculesandcytokinesareexertedduringThelperdifferentiation.Weshowevidencesuggestingthatwhilecytokinesignalsinitiatedifferentiationprogram,theselectiveactionofdeatheffectorsdeterminestheendpointbalanceofdifferenti-