简介：Inflammasomes是由响应病原体暴露或细胞的损坏便于煽动性的cytokines的版本调整天生的有免疫力的反应的多蛋白质建筑群。支持inflammatoryinflammasome发信号是重要的招待防卫，帮助开始跟随侮辱到主机，而是罐头的织物修理的进程有害，当过多或长期时。因此，inflammasome活动紧被调整。这里，我们讨论inflammasome规定的一批评机制，ubiquitination，那作为蛋白质稳定性和trafficking的一个通用调节的人工作。最近的研究由蛋白质ubiquitination提供了重要卓见进inflammasome激活的规定。明确地，当它联系到ubiquitination，我们考察inflammasome功能的分子的规定，并且讨论含意让治疗学的发展明确地指向异常inflammasome发信号。

简介：幼芽的中心kinases(GCK)参予需要包括apoptosis，房间增长，极性和移植调整细胞的函数的许多发信号的小径。最近的研究证明了GCK是在适应、天生的有免疫力的规定的参加者。然而，微分激活和GCK的规章的机制，以及在上游、下游的发信号的分子，尚待充分被定义。它仍然保持未解决是否并且怎么GCK可以有存在的串音表明小径。这评论在与免疫系统相关的GCK的研究强调进步。

简介：MicroRNAs(miRNAs)aresmall,non-codingsingle-strandedRNAsthatcanmodulatetargetgeneexpressionatposttranscriptionallevelandparticipateincellproliferation,differentiation,andapoptosis.Tcellshaveimportantfunctionsinacquiredimmuneresponse;miRNAsregulatethisimmuneresponsebytargetingthemRNAsofgenesinvolvedinTcelldevelopment,proliferation,differentiation,andfunction.Forinstance,miR-181familymembersfunctioninprogressionbytargetingBcl2andCD69,amongothers.MiR-17tomiR-92clustersfunctionbybindingtoCREB1,PTEN,andBim.ConsideringthatthesuppressionofTcell-mediatedimmuneresponsesagainsttumorcellsisinvolvedincancerprogression,weshouldinvestigatethemechanismbywhichmiRNAregulatesTcellstodevelopnewapproachesforcancertreatment.

简介：由模式识别受体(PRR)的病原体的天生的察觉到在在自我和非自我部件之间的天生的辨别起必要作用，导致天生的有免疫力的防卫和煽动性的回答的产生。天生的煽动性的反应的开始，激活和分辨率被相互作用的一个复杂网络在有免疫力、非有免疫力的系统的众多的细胞、分子的部件之中调停。当时一控制并且有益的天生的煽动性的反应是批评的因为病原体的消除和织物动态平衡，dysregulated或持续发炎的维护导致象长期的感染那样的病理学的条件，煽动性的自体免疫的疾病。在这评论，我们为天生的免疫和煽动性的回答的建立和规定在我们细胞、分子的机制的理解讨论一些最近的进展。

简介：Oxidativestressplaysanessentialroleinregulatinggrowthanddeathofcardiacmyocytes.ClassⅡhistonedeacetylases（cⅡ-HDACs）arelocalizedprimarilyinthenucleusinunstimulatedcardiacmyocytesandnegativelyregulatecardiachypertrophybyinteractingwithpro-hypertrophictranscriptionfactors,includingmyocyteenhancerfactor2（MEF2）,calmodulin-bindingtranscriptionactivator（CAMTA）,andnuclearfactoractivatedTcells（NFATs）.NuclearlocalizationofcII-HDACsisregulatednotonlybyphosphorylationbutalsothroughoxidationofconservedcysteineresidues（Agoetal2007）,suggestingthatposttranslationalmodulationplaysanimportantroleinmediatingpathologicalcardiachypertrophyandheartfailure.Inthispresentation,Iwilldiscusshowreactiveoxygenspecies（ROS）areproducedintheheartunderstressandhowROSregulatethesubcellularlocalizationofcII-HDACs,therebycausingpathologicalhypertrophy.TheNADPHoxidasefamilyisagroupoftransmembraneproteinsproducingsuperoxideandhydrogenperoxide.Nox4islocalizedprimarilyinmitochondria,endoplasmicreticulum,andnucleus,whoseexpressionisupregulatedbypressureoverloadandheartfailure.Nox4playsanessentialroleinmediatingincreasesinROSinthefailingheart.IncreasedoxidativestressinducesoxidationofcysteineresidesincⅡ-HDACs,suchasC667andC669inHDAC4,whichinturncausesnuclearexitofcⅡ-HDACs.ThecⅡ-HDACsarefurtherphospho-rylatedbytheHDACkinases,includingCa2+calmodulinkinaseandPKD,leadingtoprolongedcytoplasmiclocalizationofcⅡ-HDACsandconsequentcardiachypertrophy.Thioredoxin1（Trx1）,ananti-oxidant,reducesthecriticalcysteineresiduesincⅡ-HDACs,therebyrestoringthenuclearlocalizationofcⅡ-HDACsandinhibitingpathologicalhypertrophy.DownregulationofNox4enhancesnuclearlocalizationofHDAC4,therebyinhibitingcardiachypertrophy,suggestingthatendogenousNox4mediatesoxidationofHDAC4.Insummary,oxidatives

简介：

简介：AbstractGlucagon is a potent glucose-elevating hormone that is secreted by pancreatic α- cells. While well-controlled glucagon secretion plays an important role in maintaining systemic glucose homeostasis and preventing hypoglycaemia, it is increasingly apparent that defects in the regulation of glucagon secretion contribute to impaired counter-regulation and hyperglycaemia in diabetes. It has therefore been proposed that pharmacological interventions targeting glucagon secretion/signalling can have great potential in improving glycaemic control of patients with diabetes. However, despite decades of research, a consensus on the precise mechanisms of glucose regulation of glucagon secretion is yet to be reached. Second messengers are a group of small intracellular molecules that relay extracellular signals to the intracellular signalling cascade, modulating cellular functions. There is a growing body of evidence that second messengers, such as cAMP and Ca2+, play critical roles in α-cell glucose-sensing and glucagon secretion. In this review, we discuss the impact of second messengers on α-cell electrical activity, intracellular Ca2+ dynamics and cell exocytosis. We highlight the possibility that the interaction between different second messengers may play a key role in the glucose-regulation of glucagon secretion.

简介：天生的免疫系统认识到通过编码germline的模式识别受体(PRR)入侵病原体，它得到天生的抗菌剂和煽动性的回答并且开始适应免疫控制或消除感染。像使用费的受体(TLR)和retinoic酸可诱导的基因(RIG-I)我是关键天生的有免疫力的PRR并且被精致的机制紧调整响应外国侵略者保证有益的结果。尽管许多在文学的焦点在发炎的蛋白质管理者的学习上，microRNAs(miRNAs)作为煽动性的过程的某些特征的重要控制器出现了。几miRNAs被TLR和RIG-I激活作为TLR并且RIG-I发信号的反馈管理者在myeloid房间和行为导致。在这评论，我们包括地讨论miRNA网络怎么对TLR并且RIG-I在煽动性的回答的开始和结束发信号和他们的角色作出回应的最近的理解。增加的证据也显示编码病毒的miRNAs和细胞的miRNAs在病毒的复制有重要功能并且招待抗病毒的豁免。

简介：NF-κBisatranscriptionfactorofeukaryote,fivemembersofwhosefamilyinmammalsandthreeindrosophila.TranscriptionfactorsoftheNF-κfamilyareactivatedinresponsetosignalsthatleadtocellgrowth,differentiation,apoptosisandotherevents.NF-κBtakespartinexpressionofnumerouscytokinesandadhesionmoleculeswhicharecriticalelementsinvolvedintheregulationofimmuneresponses.Inthisreview,wefocusonourcurrentunderstandingofNF-κBsignalpathwayanditsroleintheinnateandadaptiveimmuneresponsesinwhichthesetranscriptionfactorshaveakeyregulatoryfunction.Furthermorewereviewwhatiscurrentlyknownabouttheireffectsassociatedwithapoptosis.Cellular&MolecularImmunology.2004;1(5):343-350.

简介：Thecombinationofelectroencephalogram(EEG)andfunctionalmagneticresonanceimaging(fMRI)isaveryattractiveaiminneuroscienceinordertoachievebothhightemporalandspatialresolutionforthenon-invasivestudyofcognitivebrainfunction.Inthispaper,werecordsimultaneousEEG-fMRIofthesamesubjectinemotionalprocessingexperimentinordertoexplorethecharacteristicsofdifferentemotionalpictureprocessing,andtrytofindthedifferenceofthesubjects’brainhemispherewhileviewingdifferentvalenceemotionalpictures.Thelatepositivepotential(LPP)isareliableelectrophysiologicalindexofemotionalperceptioninhumans.Accordingtotheanalysisresults,theslow-waveLPPandvisualcorticalbloodoxygenlevel-dependent(BOLD)signalsarebothmodulatedbytheratedintensityofpicturearousal.TheamplitudeoftheLPPcorrelatesignificantlywithBOLDintensityinvisualcortex,amygdala,temporalarea,prefrontalandcentralareasacrosspicturecontents.

简介：

简介：AbstractPeriodontitis is one of the most prevalent epidemics affecting human health and life recently, and exploration of the pathogenesis and treatment of periodontitis has been valued by scholars. In recent years, sclerostin, a new factor on bone resorption and reconstruction caused by inflammation and mechanical stimulation, has been a research hotspot. This article summarizes the researches on sclerostin in periodontitis development in recent years. Among them, sclerostin has been shown to be a critical negative regulator of bone formation, thereby inhibiting bone remodeling in periodontitis development, and is closely associated with tooth movement. Besides, evidence indicates that the removal of sclerostin seems to reasonably protect the alveolar bone from resorption. Regulation of sclerostin expression is a novel, promising treatment for periodontitis and addresses several complications seen with traditional therapies; accordingly, many drugs with similar mechanisms have emerged. Moreover, the application prospect of sclerostin in periodontal therapy combined with orthodontic treatment is another promising approach. There are also a lot of drugs that regulate sclerostin. Anti-sclerostin antibody (Scl-Ab) is the most direct one that inhibits bone resorption caused by sclerostin. At present, drugs that inhibit the expression of sclerostin have been applied to the treatment of diseases such as multiple myeloma and osteoporosis. Therefore, the application of sclerostin in the oral field is just around the corner, which provides a new therapeutic bone regulation strategy in oral and general health.

简介：AbstractAlternative splicing plays a pivotal role in the posttranscriptional regulation of gene expression, contributing to the generation of proteome diversity. Autophagy is a conserved cellular machinery governing degradation and recycling of long-lived or damaged proteins and organelles. However, there is limited knowledge of the roles of alternative splicing in autophagy, in particular mitochondrial selective autophagy, termed mitophagy. Emerging evidence suggests autophagy-related proteins (Atg), key molecules in autophagy process, are involved. This review highlights recent advances in the understanding of mechanisms by which alternative splicing affects the functions of ATG genes including BECN1, ATG5, ATG16L1, and Bim genes, and thus manipulates autophagy levels in various diseases. This review found that the effects of splicing of ATG genes generally result in inhibiting autophagy. However, very few of the many autophagy associated proteins have been studied. More research into the transcriptional and post-transcriptional regulation of splicing factors will be necessary to understand their roles in pathological conditions associated with autophagy and mitophagy.

简介：Receptortyrosinekinases(RTKs)suchastheepidermalgrowthfactorreceptor(EGFR)regulatecellularhomeostaticprocesses.EGFRactivatesdownstreamsignalingcascadesthatpromotetumorcellsurvival,proliferationandmigration.DysregulationofEGFRsignalingasaconsequenceofoverexpression,amplificationandmutationoftheEGFRgeneoccursfrequentlyinseveraltypesofcancersandmanybecomedependentonEGFRsignalingtomaintaintheirmalignantphenotypes.Consequently,concertedeffortshavebeenmountedtodeveloptherapeuticagentsandstrategiestoeffectivelyinhibitEGFR.However,limitedtherapeuticbenefitstocancerpatientshavebeenderivedfromEGFR-targetedtherapies.Awell-documentedobstacletoimprovedpatientsurvivalisthepresenceofEGFR-inhibitorresistanttumorcellvariantswithinheterogeneoustumorcellmasses.Here,wesummarizethemechanismsbywhichtumorsresistEGFR-targetedtherapiesandhighlighttheemergingroleofmicroRNAs(miRs)asdownstreameffectormoleculesutilizedbyEGFRtopromotetumorinitiation,progressionandthatplayaroleinresistancetoEGFRinhibitors.WealsoexamineevidencesupportingtheutilityofmiRsaspredictorsofresponsetotargetedtherapiesandnoveltherapeuticagentstocircumventEGFR-inhibitorresistancemechanisms.

简介：在抗原刺激之上，天真的T助手房间区分进不同的系达到专业化性质和受动器功能。TH17房间，CD4+受动器T房间的一个最近识别的系，对真菌和细胞外的细菌在有免疫力的防卫起一个关键作用，而且贡献许多自体免疫的条件的致病。TH17房间被在T房间表明小径和transcriptional管理者的一个复杂网络安排。当T房间内在的小径的参与广泛地被描述了时，我们开始就正在欣赏怎么TH17房间开发被外来的小径塑造，特别天生的有免疫力的信号。树枝状的房间(DC)，到天生的桥牌的最重要的房间类型和适应免疫，驱动器T由提供antigenic，costimulatory和cytokine的H17房间区别发信号。这被DC被天生、煽动性的信号的识别经由模式识别受体，cytokine受体和接着激活细胞内部的发信号网络的另外的immunomodulatory受体调停。特别地，p38α；地图kinase作为一条批评小径出现了编程序DC依赖的T由在DC集成多重有启发性的信号的H17房间区别。这里，我们在导出DC的天生的有免疫力的信号由驾驶TH17房间区别。

简介：AbstractEndometriosis (EM) is a benign gynecological disease that affects the fertility and health of women of reproductive age; it is characterized by the presence of endometrial glands and stroma outside the uterine cavity. Although several hypotheses have been proposed to explain the underlying cause of EM, its pathogenesis remains obscure. Recently, non-coding RNAs were reported to be involved in the occurrence and development of EM. MicroRNAs and long non-coding RNAs are the main members of the non-coding RNA family that contribute to EM progression in various aspects, such as cell proliferation, apoptosis, invasion, and angiogenesis. Angiogenesis plays a pivotal role in the initiation and development of EM and provides a substantial background for the invasion, proliferation, and long-term growth of endometriotic implants. This review aimed to investigate the role of microRNAs and long non-coding RNAs in regulating angiogenesis in EM and discuss how this mechanism can be used for diagnostic and therapeutic purposes in EM.

简介：AbstractWith the deepening of research, proteomics has developed into a science covering the study of all the structural and functional characteristics of proteins and the dynamic change rules. The essence of various biological activities is revealed from the perspectives of the biological structure, functional activity and corresponding regulatory mechanism of proteins by proteomics. Among them, phospholipid-binding protein is one of the hotspots of proteomics, especially annexin A1, which is widely present in various tissues and cells of the body. It has the capability of binding to phospholipid membranes reversibly in a calcium ion dependent manner. In order to provide possible research ideas for researchers, who are interested in this protein, the biological effects of annexin A1, such as inflammatory regulation, cell signal transduction, cell proliferation, differentiation and apoptosis are described in this paper.

简介：Inthispresentstudy,theruodeloftherabbitwithacutemyocardialischemia（AMI）wasusedtoexploremechanismsofinterrelationhetweenNeiguanacupoint（PC6）ofthePeri-cardiumMeridianandthehearthyemployingphysiologicalandmorphologicaImethods.Itwasdemonstratedthatelectroacupuncture（EA）atNeiguan（PC6）couIdraisetheeIectricalexcitahilityofischemicmyocardium,lessenthedispersityofrecoveryexcitability,correctthedisorderofelectricalactivity;protectmyocardiacglycogenandphosphorylaseandalleviatetheirdepletion,increasecontentofribonucleiacid（RNA）,etc.,indicatingthatEAcouldhelpoxidativernetaholismcarryoutnormal-IyandirnProvenutritionalstateoftheischemicmyocardiurn.ThekeypointofEAactionisprobablyregulatesthecoronarymicroclrculationofheartandreclistributesmyocardialbloodflow.Studieswithalkalinephosphatase（ALP）,Mg2--ATPaseandABScastingoftheIeftcoronaryarteryshowedthatafterEAthenumberandtheIengthof

简介：AbstractSkeletal muscle plays an essential role in generating the mechanical force necessary to support the movement of our body and daily exercise. Compared with cardiac and smooth muscle, in mammals, skeletal muscle exhibits remarkable regenerative capacity in response to damage. Muscle stem cells, also known as satellite cells, directly contribute to regeneration. Here, we review primary and secondary myogenesis processes with a focus on muscle stem cells, as well as the function and regulation of muscle stem cells in adult muscle regeneration in mammals.

简介：Polyreactive天生类型的B房间说明在圆周表示自我反应的许多B房间。这些B房间的不适当的规定可以是位于自体免疫的疾病下面的一个重要因素。这里，我们在导致骨胶原的关节炎(中央情报局)的开发探索了自我反应的天生的B房间的影响，风湿性关节炎的一个鼠标模型。我们显示出那个脾的边缘的地区(MZ)，然而并非B-1B房间在naı展出自发的IgM反应到自体同源的骨胶原II；¨；ve老鼠。在有在完全的Freund’的heterologous骨胶原II的免疫之上；骨胶原反应的MZB房间很快扩展了的s助手，当B-1B房间显示出谦虚反骨胶原回答时。MZB房间被像使用费的受体(TLR)容易激活4并且在vitro，导致的增长和cytokine分泌物的9-ligands，暗示B房间受体和TLR的那个双约会可以把有免疫力的反应提升到自我抗原。而且，告知骨胶原的MZB房间显示出在vivo在IgG反骨胶原抗体的vitro和正式就职由血缘的T房间增长思考了的重要介绍抗原的能力。在1和2表明了的补充受体是缺乏的MZB房间增加了增长和cytokine生产，当时Fcγ；房间的受体IIb缺乏导致增加的cytokine生产和抗原表示。在结论，我们的数据在中央情报局作为自体免疫的反应的开始者加亮自我反应的MZB房间，在补充和Fc受体在在房间控制自我反应是相关的的地方。