简介:AbstractPancreatic ductal adenocarcinoma (PDAC) is a lethal, aggressive, and incurable disease. The patients with PDAC are often diagnosed at the advanced stage, leading to poor overall survival because of no current effective treatment. Further exploration of the mechanism is needed urgently to provide insights on the prevention, detection, or intervention of pancreatic cancer. Oncogenic KRAS and mutated tumor suppressor genes serve essential roles in PDAC tumorigenesis. Different groups of scientists indicated that yes-associated protein and transcriptional coactivator with PDZ-binding motif, which are the main effectors of the Hippo pathway, are the center in the development of PDAC. Here, we will focus on the recent advances of the molecular mechanisms of core components in the Hippo kinases cascade and discuss their clinical implications.
简介:类固醇作为在动物和植物表明分子工作。当动物类固醇荷尔蒙被抄写因素的原子受体家庭察觉时,在植物的brassinosteroids(BR)被房间表面受体kinase察觉,BRI1。最近的研究证明了到BRI1的细胞外的域的那BR绑定与另一受体kinase导致kinase激活和dimerization,BAK1。激活的BRI1或BAK1然后调整,可能间接地,BIN2kinase的活动或BSU1磷酸酶,它直接调整phosphorylation地位和二个相应抄写因素,BZR1和BES1的原子累积。BZR1和BES1直接绑在BR应答的基因的倡导者调整他们的表示。表明小径的BR为在一般来说由房间表面受体发信号的植物和类固醇发信号的两受体kinase成为了一个范例。
简介:Neurodegenerationischaracterizedbytheprogressiveandpermanentlossofneurons.Degenerationtypicallyresultsinadebilitatinglossoffunctioninanotherwisehealthyperson.Neurodegenerativediseaseshaveenormousdirecthealthcarecosts,withsomeestimatesfordiseases,suchasAlzheimer’sdiseaseexceeding$36,000
简介:摘要骨折发生后断端间组织修复程序的启动和运行对于骨折愈合至关重要,该过程经历血肿炎症机化期、原始骨痂期形成期和骨痂改造塑形期等三个相互交织和逐渐演进阶段,并由骨髓腔内多种组织、细胞、细胞因子等参与完成。在研究骨折愈合的机制中发现有许多信号通路及分子调控骨修复,包括骨形成、骨重建以及新生血管形成,而在细胞层面上则是对成骨细胞、软骨细胞、破骨细胞以及内皮细胞的调控。Hippo信号通路是一条维持器官体积大小和细胞增殖与凋亡平衡的信号通路,而在维持骨稳态以及骨代谢中也有着重要作用,在其调控骨发育和修复过程中,通过蛋白激酶级联反应和转录辅助激活因子作用下调控微环境下细胞的生理活动。Hippo信号通路上下游效应分子直接或间接调控骨代谢细胞增殖、分化和凋亡等多个过程,且与Wnt信号通路、Notch信号通路等相关骨修复过程重要通路的交互均表明,Hippo信号通路在调控骨折愈合中发挥着重要的作用,可能成为促进骨折愈合的治疗的新靶点。故综述Hippo信号通路的调节机制以及在骨折愈合过程中发挥调控作用的研究进展,并展望了以其为靶点促进骨愈合的研究前景。
简介:Irradiationfromdiversesourcesisubiquitousandcloselyassociatedwithhumanactivities.Radiationtherapy(RT),animportantcomponentofmultipleradiationorigins,isacommontherapeuticmodalityforcancer.Moreimportantly,RTprovidessignificantcontributiontooncotherapybykillingtumorcells.However,duringthecourseoftherapy,irradiationofnormaltissuescanresultinawiderangeofsideeffects,includingself-limitedacutetoxicities,mildchronicsymptoms,orsevereorgandysfunction.Althoughnumerouspromisingradioprotectiveagentshaveemerged,onlyafewhavesuccessfullyenteredthemarketbecauseofvariouslimitations.Atpresent,thewidelyacceptedhypothesisforprotectionagainstradiation-causedinjuryinvolvestheWntcanonicalpathway.ActivatingtheWnt/β-cateninsignalingpathwaymayprotectthesalivarygland,oralmucosa,andgastrointestinalepitheliumfromradiationdamage.Theunderlyingmechanismsincludeinhibitingapoptosisandpreservingnormaltissuefunctions.However,aberrantWntsignalingunderliesawiderangeofpathologiesinhumans,anditsvariouscomponentscontributetocancer.Moreover,studieshavesuggestedthatWnt/β-cateninsignalingmayleadtoradioresistanceofcancerstemcell.ThesefactsmarkedlycomplicateanydefinitionoftheexactfunctionoftheWntpathway.
简介:Purpose:Proctalgiafugax(PF)isabenignanorectalconditionwhichhasbeendescribedintheliteraturesincethenineteenthcenturycommonlypresentingtogeneralsurgeons.Thereislittlehighlevelevidenceonthesubjectanditstherapeuticmodalities.Weaimedthroughthissystematicliteraturereviewtooutlinethe
简介:Apoptosisorprogrammedcelldeath(PCD)isanevolutionarilyconservedcellularprocessthatisessentialfornormaldevelopmentandhomeostasisofmulticellularorganisms.Defectsintheapoptosissignalingresultinmanydiseasesincludingautoimmunediseasesandcancer.TheapoptosissignalingpathwaywasfirstdescribedgeneticallyinthenematodeCaenorhabditiseleganswhichservesasaframeworkforthemorecomplexapoptoticpathwaysthatexistinmammals.Inthisreview,wewilldiscusstheapoptoticpathwaysthatareemerginginmammalsaselucidatedbystudiesofgene-targetedmutantmice.
简介:摘要目的探讨Hippo信号传导通路对胃癌细胞黏附、侵袭、转移的影响。方法选取我院2010年10月至2013年5月接收的胃癌患者28例,对所有患者采取免疫组织化学检测、原位杂交检测和显微图像分析系统检查及实验分析。结果通过对胃癌患者癌变细胞的检查及分析发现,Hippo信号通路中的各类原癌基因和抑癌基因发生异常时会对胃癌细胞黏附、侵袭及转移造成影响。结论通过对Hippo信号传导通路进行探讨,良好的了解了Hippo信号通路的各类因子的构成及其相互作用,对日后临床肿瘤的应用提供了有效的使用价值。
简介:AbstractBone morphogenetic protein belongs to transcription growth factor superfamily β; bone morphogenetic protein signal pathway regulates cell proliferation, differentiation, and apoptosis among different tissues. Cerebrovascular system supplies sufficient oxygen and blood into brain to maintain its normal function. The disorder of cerebrovascular system will result into serious cerebrovascular diseases, which is gradually becoming a major threat to human health in modern society. In recent decades, many studies have revealed the underlying biology and mechanism of bone morphogenetic protein signal pathway played in cerebrovascular system. This review will discuss the relationship between the two aspects, aiming to provide new perspective for non-invasive treatment and basic research of cerebrovascular diseases.
简介:Thefibroblastgrowthfactorreceptor(FGFR)familyplaysimportantrolesinregulatingcellgrowth,proliferation,survival,differentiationandangiogenesis.DeregulationoftheFGF/FGFRsignalingpathwayhasbeenassociatedwithmultipledevelopmentsyndromesandcancers,andthustherapeuticstrategiestargetingFGFsandFGFRinhumancancerarecurrentlybeingexplored.However,fewstudiesontheFGF/FGFRpathwayhavebeenconductedinsarcoma,whichhasapooroutcomewithtraditionaltreatmentssuchassurgery,chemotherapy,andradiotherapy.Hence,inthepresentreview,weprovideanoverviewoftheroleoftheFGF/FGFRpathwaysignalinsarcomaandFGFRinhibitors,whichmightbenewtargetsforthetreatmentofsarcomasaccordingtorecentresearch.