简介：摘要：

简介：TelomeraseisanenzymethatmaintainstelomeresindividingcellsusingatemplateonitsinherentRNAcomponent.Additionally,theproteinpartTERT(TelomeraseReverseTranscriptase)hasvariousnon-canonicalfunctions.Forexample,itcanlocalizetomitochondriaunderincreasedstressandprotectcellsinvitrofromoxidativestress,DNAdamageandapoptosis.RecentlyithasbeendemonstratedthatTERTproteinpersistsinadultneuronsinthebrainanddataemergesuggestingthatitmighthaveaprotectivefunctioninthesepost-mitoticcellsaswell.WehaverecentlypublishedthatTERTproteinaccumulatedinmitochondriafrombraintissueofmicethathaveundergoneshort-termdietaryrestriction(DR)andrapamycintreatment.Thislocalizationcorrelatedtolowerlevelsofoxidativestressinthesebrainmitochondria.SincerapamycintreatmentdecreasesmTORsignalingwhichisalsothoughttoplayanimportantroleforthebeneficialeffectsofDR,weconcludethatthemTORpathwaymightbeinvolvedintheTERTlocalizationanditseffectsinbrainmitochondriainvivo.ThesedataareinlinewithpreviousfindingsfromourgroupaboutincreasedmitochondriallocalizationofTERTinAlzheimer'sdisease(AD)brainsandaprotectivefunctionofTERTproteininneuronsinvitroagainstpathologicaltau.

简介：Dendritesareexquisitelyspecializedcellularcompartmentsthatcriticallyinfluencehowneuronsreceiveandprocessinformation.Mostsynapticinputsarereceivedontodendriticshafts,orsmallprotuberancesknownasdendriticspines,andarethenintegratedandtransmittedtothecellsoma.Duringnervoussystemdevelopment,

简介：摘要mTOR(mammalian/mechanistic targets of rapamycin）存在于两个功能性复合体mTORC1 和mTORC2中，通过对生长因子、营养物质、谷氨酸、神经递质等应答，调控细胞的重要生理过程。中枢神经系统mTOR通路异常活化可引起癫痫。文中通过回顾国内外研究报道，旨在分析和总结与mTOR通路相关的癫痫表型及可能的致痫机制，为相关癫痫的诊断和治疗新手段提供参考依据。

简介：无

简介：摘要目前，特异性的小分子抑制剂靶向杀伤肿瘤细胞已成为研究热点。PI3K/Akt/mTOR作为一个已被证实影响肿瘤发生、发展、迁移、侵袭的信号通路，mTOR是其中一个关键的靶点。本文探讨了近年来国内外对于PI3K/Akt/mTOR信号通路的机制和以及mTOR抑制剂对于肿瘤治疗的研究。

简介：AbstractObjectives:Mechanistic target of rapamycin (mTOR) activation has been identified in keloid. This study aimed to identify the role of mTOR-dependent autophagy activity in keloid.Methods:We detected the expression of specific proteins representing mTOR activity and baseline autophagy levels in keloid tissues (KTs) and primary keloid fibroblasts (KFs) using immunohistochemical staining and western blotting. Simultaneously, the formation of acid vesicles was assessed by acridine orange staining in KFs. To investigate whether mTOR-dependent pathway mediated the regulation of autophagy machinery in keloid, we first validated whether mTOR inhibitors, rapamycin (100 nmol/L) and KU-0063794 (5 μmol/L), could inhibit mTOR activity in KFs by western blotting. Then we explored the reverse effects on autophagy activity induced by mTOR inhibitors in the presence of lysosomal protease inhibitors by western blotting.Results:It demonstrated elevated expression of mTOR, S6, and their activated forms in KTs, and an elevated expression of p-S6 Ser235/236 in KFs, suggesting mTOR was activated in keloid. Less LC3 and Beclin1 were expressed in the cytoplasm of KFs, whereas Ubiquitin was abundantly expressed in KTs compared with extra-lesional tissues. In addition, at the cellular level, an impeded conversion of LC3-I to LC3-II was shown in KFs and the formation of acid vesicles were also decreased in KFs compared with normal fibroblasts (NFs), indicating that autophagy activity is defective in keloid. mTOR inhibitors, Rapamycin (E-64d + pepstatin vs. rapamycin + E-64d + pepstatin: [0.88 ± 0.35] vs. [1.56 ± 0.46], F= 5.56, P= 0.049) and KU-0063794 (E-64d + pepstatin vs. KU-0063794 + E-64d + pepstatin: [0.92 ± 0.22] vs. [1.51 ± 0.25], F= 25.88, P= 0.011) can reverse the inhibition effect on autophagy of KFs while inhibiting mTOR activity.Conclusion:Autophagy machinery is inhibited in keloid which is regulated by mTOR-dependent pathway.

简介：<正>常染色体显性多囊肾病(autosomaldominantpolycystickidneydisease,ADPKD)是人类最常见的遗传性肾病,其发病率为0.1%～2.5%,就诊多见于成人,其临床表现主要有肾脏体积增大、血尿、蛋白尿、高血压。其致病基因有3个,分别为PKD1、PKD2和PKD3,前两者均已被成功定位和克隆,而对PKD3的报道则较少。PKD1约占致病基因的85%,定位于16p13-3,编码分布于细胞膜的一种糖蛋白——多囊蛋白-1(polycystin-1,PC1)。PKD2约占致病基因的15%,定位于4q22～23,编码钙离子通道——多囊蛋白-2(polycystin-2,PC2)。PKD3约占致病基因的1%,由Daoust和deAlmeida分别于1994年和

简介：摘要脑胶质瘤恶性程度高，易复发。临床和基础研究证实，多种信号传导通路与脑胶质瘤的恶性进展相关。哺乳动物雷帕霉素靶蛋白(mTOR)信号通路是调控细胞生长与增殖的一个关键通路，近年来，有关mTOR信号通道对脑胶质瘤发生机制的研究日益增多。在脑胶质瘤的治疗中，以mTOR为靶点的抗肿瘤靶向治疗可以通过控制mTOR的表达来抑制肿瘤生长，具有重要的临床意义。本文对mTOR和脑胶质瘤的研究进展进行综述。

简介：Activationofthephosphoinositide3kinase(PI3K)/Akt/mammaliantargetofrapamycin(mTOR)pathwayiscommoninbreastcancer.Thereispreclinicaldatatosupportinhibitionofthepathway,andphaseⅠtoⅢtrialsinvolvinginhibitorsofthepathwayhavebeenorarebeingconductedinsolidtumorsandbreastcancer.Everolimus,anmTORinhibitor,iscurrentlyapprovedforthetreatmentofhormonereceptor(HR)-positive,humanepidermalgrowthfactorreceptor2(HER2)-negativebreastcancer.Inthisreview,wesummarisetheefficacyandtoxicityfindingsfromtherandomisedclinicaltrials,withsimplifiedguidelinesonthemanagementofpotentialadverseeffects.Educationofhealthcareprofessionalsandpatientsiscriticalforsafetyandcompliance.WhilethereissomeclinicalevidenceofactivityofmTORinhibitioninHR-positiveandHER2-positivebreastcancers,thebenefitsmaybemorepronouncedinselectedsubsetsratherthanintheoverallpopulation.FurtherdevelopmentofpredictivebiomarkerswillbeusefulintheselectionofpatientswhowillbenefitfrominhibitionofthePI3K/Akt/mTOR(PAM)pathway.

简介：哺乳动物雷帕霉素靶蛋白基因位于1p36．2上，其inRNA翻译后的蛋白质有2549个氨基酸残基，其分子结构复杂，分子质量为289kDa.mTOR是一种丝／苏氨酸蛋白激酶，通过调节细胞周期、蛋白质合成、细胞能量代谢等多种通路发挥重要的生理功能，在细胞增殖、生长、分化过程中起着中心调控点的作用。此外，mTOR在肿瘤的形成、发展、转移过程中也起着重要作用。在一些肿瘤中可见mTOR通路的持续活动的现象。到目前为止，mTOR抑制药作为靶向性抗肿瘤药物被有效地应用于肾癌及肝癌等治疗。因此，mTOR信号通路的深入研究对肿瘤的靶向治疗具有重要意义。

简介：

简介：摘要炎症性肠病（IBD）是一种慢性非特异性肠道炎症性疾病，发病机制不明。部分IBD患者对常规药物治疗反应不佳。目前认为哺乳动物雷帕霉素靶蛋白（mTOR）可通过PI3K/AKT/mTOR、TLR4/MAPK/mTOR和AMPK/mTOR等多种机制影响肠道自噬和炎症过程，从而影响疾病的发生发展过程。通过靶向mTOR信号通路可为IBD的治疗提供新的可能。本文就mTOR信号通路在IBD中的作用机制以及靶向mTOR信号通路治疗IBD进行总结。

简介：目的检测mTOR信号通路在胰腺癌组织中的表达，探讨其在胰腺癌发病中的作用。方法选择经手术、病理证实的6例胰腺癌及相应癌旁组织，抽提RNA，应用Agilent人全基因表达谱芯片进行检测，生物信息学分析mTOR信号通路在胰腺癌组织中的表达。结果总共筛选到1276个差异基因，其中癌组织上调的有691个，下调的有585个。KEGG通路的Enrichment和基因计数两项指标得分最高的是mTOR信号通路中的hsa04150，其Enrichment为4．5622519，基因计数为9，基因计数百分率为1．15％，EASEScoreP值为6．23E-04，最有生物学意义，其中ULK2、PIK3R3、PDPK1、EIF4EBP1、PGF、VEGFB、ULK3、RICTOR与PIK3R5等9个关键基因具有显著性差异（P值均〈0．05）。结论胰腺癌发病与mTOR信号通路激活密切相关。

简介：无

简介：探讨胃癌组织中p-mTOR的表达与患者临床病理参数及预后的相关性。2007年1月—2011年5月，214例胃癌患者采用免疫组化染色方法检测患者胃癌组织中的p-mTOR表达，并分析不同临床病理特征及生存率与p-mTOR表达的相关性。结果显示，214例患者中p-mTOR表达阳性者112例，占52.33％；不同年龄、性别、肿瘤大小、Borrmann分型组间的p-mTOR阳性率未见显著性差异（P>0.05）；不同TNM分期及淋巴结转移组间p-mTOR阳性表达存在显著性差异（P<0.05）；淋巴结转移阳性患者p-mTOR阳性表达率高于阴性患者（P<0.05）；TNM分期越高，p-mTOR阳性表达率越高（P<0.05）。p-mTOR表达阴性患者无病存活率（DFS）为51.0%，阳性患者为27.7%；5年总存活率（OS）p-mTOR表达阴性患者为55.9%，阳性患者为30.4%，均存在显著性差异（P<0.05）。结果表明，p-mTOR与胃癌的临床分期与淋巴结转移情况密切相关，因此可成为预测胃癌淋巴结转移和肿瘤进展的新型分子标志物，并作为临床靶向治疗的新靶点。

简介：AbstractBackground:Ubiquitin-conjugating enzyme E2C (UBE2C) has been shown to be associated with the occurrence of various cancers and involved in many tumorigenic processes. This study aimed to investigate the specific molecular mechanism through which UBE2C affects breast cancer (BC) proliferation.Methods:BC-related datasets were screened according to filter criteria in the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. Then differentially expressed genes (DEGs) were identified using Venn diagram analysis. By using DEGs, we conducted the following analyses including Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI), and survival analysis, and then validated the function of the hub gene UBE2C using quantitative reverse transcription-polymerase chain reaction (RT-qPCR), cell counting kit-8 (CCK-8) assay, transwell assay, and Western blot assay.Results:In total, 151 DEGs were identified from the GEO and TCGA databases. The results of GO analysis demonstrated that the DEGs were significantly enriched with mitotic nuclear division, lipid droplet, and organic acid-binding. KEGG analysis showed that the peroxisome proliferators-activated receptor (PPAR) signaling pathway, regulation of lipolysis in adipocytes, and proximal tubule bicarbonate reclamation were significantly enriched in the signal transduction pathway category. The top three hub genes that resulted from the PPI network were FOXM1, UBE2C, and CDKN3. The results of survival analysis showed a close relationship between UBE2C and BC. The results of CCK-8 and transwell assays suggested that the proliferation and invasion of UBE2C knockdown cells were significantly inhibited (P < 0.050). The results of Western blot assay showed that the level of phosphorylated phosphatase and tensin homology deleted on chromosome 10 (p-PTEN) was obviously increased (P < 0.050), whereas the levels of phosphorylated protein kinase B (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), and hypoxia-inducible factor-1 alpha (HIF-1α) were dramatically decreased (P < 0.050) in the UBE2C knockdown cell.Conclusion:UBE2C can promote BC proliferation by activating the AKT/mTOR signaling pathway.

简介：ThisstudywasaimedtoobservetheexpressionofP70S6kinase(P70S6K)inoralaciniccellcarcinoma.PT0S6kinaseexpressionwasexaminedbymeansofWestern-blottestandActivityas-say.Specimenswerefrom30casesoforalaciniccellcarcinomaand15casesofnormaloraltissuewereusedascontrols.StatisticalanalysissoftwareSPSS10.0wasusedforttesttodeterminetherelationshipbetweengeneexpressionandclinicalfeatures.TheexpressionlevelofP70S6Kincreasedobviouslyinoralaciniccellcarcinomatissue(P<0.01).ActivityassaywasthesameastheWestemblottest(P<0.01).P70S6Kexpressionlevelandactivityplayedanimportantroleinthedevelopmentoforalaciniccellcarcinoma.Inconclusion,P70S6Kisamplifiedandoverexpressedinoralaciniccellcarci-nomatissue,whichsuggestsapotentialoncogenicfunction.P70S6KandotherpossibletargetsofmTORcontributesignificantlytotumordevelopmentandthatinhibitionoftheseproteinsmaybethera-peuticforcancerpatients.OverexpressionofP70S6Kmaybeinvolvedinthepathogenesisoforalacin-iccellcarcinoma.

简介：前列腺癌症(PCa)是在在世界上的人之中的第二很普通的恶意。阉割抵抗的前列腺癌症(CRPC)是疾病的致命的形式，它在抵抗之上发展首先衬里雄激素剥夺治疗(ADT)。新兴的证据为在CRPC的发展和维护表明轴的PI3K-AKT-mTOR表明一个关键角色。这条小径，是在先进PCas的多数的deregulated，与象蛋白质合成，增长，幸存，新陈代谢和区别那样的下游地细胞的过程为生长信号的集成用作批评连结，因此提供机制让癌症细胞克服压力与雄激素剥夺联系了。而且，现出症状之前的潜的研究阐明了在发信号的PI3K-AKT-mTOR和雄激素受体(AR)之间的一个直接连接削减，在ADT抵抗的发展期间揭示在这些小径之间的动态相互影响。因此，为PI3K小径的很多个新奇禁止者的继续的临床的发展有一个清楚的基本原理，它提供堵住CRPC生长和幸存的潜力。在这评论，我们将在PCa前进和阉割抵抗探索PI3K-AKT-mTOR小径的关联以便在先进PCa通知临床的发展特定的小径禁止者。另外，我们将在我们的临床的知识加亮当前的缺乏，最尤其是对能精确地为对PI3K小径禁止者的反应预言的biomarkers的需要。

简介：摘要脓毒症的发生、发展及预后与机体免疫调控密切相关，免疫代谢是近年来脓毒症免疫干预的研究热点。AMP活化蛋白激酶(AMP-activated protein kinase，AMPK)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin，mTOR)是机体代谢调控的经典信号通路，参与中性粒细胞趋化性、巨噬细胞极化、自然杀伤性细胞和树突状细胞的发育分化、T细胞发育及功能调节，是脓毒症免疫代谢调控的重要途径。本文就AMPK-mTOR信号通路调节免疫细胞代谢重编程参与脓毒症免疫调节的研究进展做一综述。