简介：AsanewlydiscoveredtypeofRNA,circularRNAs(circRNAs)arewidespreadthroughouttheeukaryoticgenome.TheexpressionofcircRNAsisregulatedbybothcis-elementsandtrans-factors,andtheexpressionpatternofcircRNAsiscelltype-anddiseasespecific.Similartoothertypesofnon-codingRNAs,functionsofcircRNAsarealsoversatile.CircRNAshavebeenreportedpreviouslytofunctionasmicroRNA(miRNA)sponges,proteinsponges,codingRNAsorscaffoldsforproteincomplexes.Recently,severalcircRNAshavebeenreportedtoplayimportantrolesinhumanmalignancies,includingglioma.Here,wereviewedseveralreportsrelatedtocircRNAsandglioma,aswellasthepotentialdiagnosticandtherapeuticapplicationsofcircRNAsinbraincancer.Ingeneral,somecircRNAs,suchascircSMARCA5andcircCFH,arefoundtobeexpressedinagliomaspecificpattern,thesecircRNAsmaybeusedastumorbiomarkers.Inaddition,somecircRNAshavebeenfoundtoplayoncogenicrolesinglioma(e.g.,circNFIXandcircNT5E),whereasothershavebeenreportedtofunctionastumorsuppressors(e.g.,circFBXW7andcircSHPRH).Furthermore,circRNAisagoodtoolforproteinexpressionbecauseofitshigherstabilitycomparedtolinearRNAs.Thus,circRNAsmayalsobeanidealchoiceforgene/proteindeliveryinfuturebraincancertherapies.TherearesomechallengesincircRNAresearchingliomaandotherdiseases.ResearchrelatedtocircRNAsingliomaiscomparativelynewandmanymysteriesremaintobesolved.

简介：IntroductionAsoneofthemostfrequentlydiagnoseddevastatingdiseases,liverfailureisresponsibleforapproximatelytwomilliondeathsannuallyworldwidewithpoorprognosis1.Althoughlivertransplantationhasbeendevelopedforthemosteffectivetreatmentforliverfailure,itisfarfromdemandsforpatientsduetotheshortageofhigh-qualitydonorliversandexpensivetreatmentcosts.Currently,withthedevelopmentofcelltherapy,celltransplantationsincludingprimaryhumanhepatocytes(PHHs),humanhepatocyte-likecells(HLCs)andliverorganoidsareemergingasgreatpotentialtoolstoalleviatethisgrowingburden.

简介：AIM:Toconstructfunctionalhumanfull-thicknesscornealreplacements.METHODS:Acellularporcinecornealmatrix(APCM)wasdevelopedfromporcinecorneabydecellulariztion.Thebiomechanicalpropertiesofanterior-APCM(AAPCM)andposterior-APCM(PAPCM)werecheckedusinguniaxialtensiletesting.Humancornealcellswereobtainedbycellculture.Suspendingringwasdesignedbydeformationofanacupunctureneedle.MTTcytotoxicityassaywasusedtocheckthecytotoxicityofsuspendingringsoakingsolutions.Anewthree-dimensionalorganculturesystemwasestablishedbycombinationofsuspendingring,48-wellplateandmediumtogether.Ahumanfull-thicknesscornealsubstitutewasconstructedfromhumancornealcellswithAAPCMinanorgancoculturesystem.Biochemicalmarkerexpressionoftheconstructwasmeasuredbyimmunofluorescentstainingandmorphologicalstructureswereobservedusingscanningelectronmicroscopy.Pumpfunctionandbiophysicalpropertieswereexaminedbypenetratingkeratoplastyandfollow-upclinicalobservations.RESULTS:TherewerenocellsintheAAPCMorPAPCM,whereascollagenfibers,Bowman’smembrane,andDescemet’smembranewereretained.ThebiomechanicalpropertyofAAPCMwasbetterthanPAPCM.HumancornealcellsgrewbetterontheAAPCMthanonthePAPCM.Therewasnocytotoxicityforthesuspendingringsoakingsolutions.Fortheconstructedfull-depthhumancornealreplacementskeratocytesscattereduniformlythroughouttheAAPCMandexpressedvimentin.TheepitheliallayerwaslocatedonthesurfaceofBowman’smembraneandcomposedofthreeorfourlayersofepithelialcellsexpressingcytokeratin3.OnelayerofendothelialcellscoveredthestromalsurfaceofAAPCM,expressedNa+/K+ATPaseandformedtheendotheliallayer.Theconstructwassimilartonormalhumancorneas,withmanymicrovilliontheepithelialcellsurface,stromalcellswithalongshuttleshape,andzonulaoccludensontheinterfaceofendothelialcells.Theconstructwithstoodsurgicalprocedu

简介：Deareditors,Neurodegenerativediseasesarenowassociatedwiththeglobalobesityanddiabetesepidemicinthedevelopinganddevelopedworld.Neurodegenerativediseasesareaheterogeneousgroupofdisorderswithcomplexfactorssuchasneurohumoral,endocrineandenvironmentalfactorsinvolvedininductionoftheseneurodegenerativediseases.Thefutureofscienceandmedicineinneurodegenerativediseasesisnowdependentonnutritionalgenomicswithinsulinresistanceamajorfactorintheinductionofneurodegenerativediseases.Nutritionalgenomicsnowinvolvestheanti-aginggeneSirtuin1(Sirt1)thatisimportanttothepreventionofinsulinresistancewithitscriticalinvolvementintheimmunesystem(Martins,2018a,b).Sirt1inactivationleadstotoxicimmunereactionsconnectedtotheaccelerationofneurondeathinvariouscommunities.Appetitecontrolwithrelevancetoimmunometabolismhasbecomeofcriticalimportancetothetreatmentofneurodegeneration(Figure1).NutritionaldietsactivatetheheatshockgeneSirt1topreventtheincreaseinheatshockproteinsconnectedtoautoimmunedisease,mitophagy(Martins,2018a,b)andirreversibleprogrammedcelldeathinglobalpopulations(Figure1).

简介：AccordingtotheearliesthistoricalbookinChina(Shangshu),duringthereignofEmperorYaomorethan4,000yearsago,peopleincentralplainssufferedfromdiseasessuchasjointpainduetothebadweather.

简介：Objective:MemorystemTcells(Tscm)haveattractedattentionbecauseoftheirenhancedself-renewal,multipotentcapacity,andanti-tumorcapacities.However,littleisknownaboutTscminpatientswithrenalclearcellcarcinoma(RCC)andtheroleofWntsignalinginthesecells.WeevaluatedTscmfromRCCpatientsconcerningtheiractivationofWntsignalinginvitroandexploredthemechanismofpreferentialsurvival.Methods:FlowcytometryidentifiedsurfacemarkersandcytokinesproducedfromaccumulatedTscminthepresenceoftheglycogensynthasekinasebetainhibitorTWS119.Apoptosiswasevaluatedafterinductionusingtumornecrosisfactor-alpha.ImmunofluorescenceandWesternblotanalyseswereusedtoinvestigatetheactivationofthenuclearfactor-kappaB(NF-КB)pathway.Results:RCCpatientshadasimilarpercentageofCD4~+andCD8~+Tscmashealthydonors.ActivationofWntsignalingbyTWS119resultedintheaccumulationofTscminactivatedTcells,butreversalofdifferentiatedTcellstoTscmwasnotachieved.PreferentialsurvivalofTscmwasassociatedwithincreasedanti-apoptoticabilitymediateddownstreamoftheNF-КBactivationpathway.Conclusions:ThefindingthatTscmcanaccumulatebyWntsignalinginvitroinbloodfromRCCpatientswillhelpindevisingnewcancertherapystrategiesofTscm-basedadoptiveimmunotherapy,suchasdendriticcell-stimulatedTscm,andTcellreceptororchimericantigenreceptor-engineeredTscm.

简介：Recently,thehumancochleahasbeenshowntocontainnumerousresidentmacrophagesundersteady-state.Themacrophagesaccumulateinthestriavascularis,amongtheauditorynerves,andarealsospottedinthehumanorganofCorti.ThesemacrophagesmayprocessantigensreachingthecochleabyinvasionofpathogensandinsertionofCIelectrode.Thus,macrophagesexecuteaninnate,andpossiblyanadaptiveimmunity.Here,wedescribethemolecularmarkersCD4andCD8ofTcells,macrophagemarkersMHCⅡandCD11b,aswellasthemicroglialmarkersTEME119andP2Y12,inthehumancochlea.Immunohistochemistryandtheadvantageoussuper-resolutionstructuredilluminationmicroscopy(SR-SIM)wereusedinthestudy.CD4~+andCD8~+cellswerefoundinthehumancochleae.Theywereseeninthemodiolusinasubstantialnumberadjacenttothevessels,intheperipheralregionoftheRosenthal’scanal,andoccasionallyinthespiralligament.Whilethereareasurprisinglylargenumberofmacrophagesinthestriavascularisaswellasbetweentheauditoryneurons,CD4~+andCD8~+cellsarehardlyseenintheseareas,andneitherareseenintheorganofCorti.Inthemodiolus,macrophages,CD4~+andCD8~+cellsappearedofteninclusters.InteractionbetweenthesedifferentcellswaseasilyobservedwithSR-SIM,showingcloselyplacedcellbodies,andtheprocessesfrommacrophagesreachingoutandtouchingthelymphocytes.OtherwisetheCD4~+andCD8~+cellsinhumancochleartissuearediscretelyscattered.Thepossiblerolesoftheseimmunecellsarespeculated.

简介：Resistancetocisplatin(DDP)-basedchemotherapyisamajorcauseoftreatmentfailureinhumangastriccancer(GC).Itisnecessarytoidentifythedrugstore-sensitizeGCcellstoDDP.Inourpreviousresearch,ZuoJinWanFormula(ZJW)hasbeenprovedcouldincreasethemitochondrialapoptosisviacofilin-1inaimmortalizedcellline,SGC-7901/DDP.Duetotheimmortalizedcellsmaystilldifficulthighlyrecapitulatetheimportantmoleculareventsinvivo,primaryGCcellsmodelderivedfromclinicalpatientwasconstructedinthepresentstudytofurtherevaluatetheeffectofZJWandtheunderlyingmolecularmechanism.ImmunofluorescentstainingwasusedtoindentifyprimaryculturedhumanGCcells.Westernblottingwascarriedouttodetecttheproteinexpression.CellCountingKit-8(CCK-8)wasusedtoevaluatecellproliferation.Flowcytometryanalysiswasperformedtoassesscellapoptosis.ZJWinhibitedproliferationandinducedapoptosisinprimaryDDP-resistantGCcells.Notably,theapoptosisinGCcellswasmediatedbyinducingcofilin-1mitochondrialtranslocation,down-regulatingBcl-2andup-regulatingBaxexpression.Surprisingly,thelevelofp-AKTproteinwashigherinDDP-resistantGCcellsthanthatoftheDDP-sensitiveGCcells,andtheactivationofAKTcouldattenuateZJW-inducedsensitivitytoDDP.ThesedatarevealedthatZJWcanincreasethechemosensitivityinDDP-resistantprimaryGCcellsbyinducingmitochondrialapoptosisandAKTinactivation.ThecombiningchemotherapywithZJWmaybeaneffectivetherapeuticstrategyforGCchemoresistancepatients.