简介：

简介：AbstractObjective:The plant polyphenol resveratrol (3,4′,5-trihydroxystilbene) (RSV) has been proposed for use because of its protective effect on ultraviolet (UV)-induced skin disorders. In UVB-induced skin damage, cell autophagy and apoptosis have been approved to prevent the damage and to contribute to the cytoprotective role of RSV; however, the detailed mechanism remains unknown. So, we conducted this study to investigate the cytoprotective effects of RSV on UVB-irradiated human epidermal keratinocytes (HEKs) and its undergoing mechanisms.Methods:Secretion of thirty-six inflammatory cytokines of HEKs induced by 50 mJ/cm2 UVB at 0, 12, 24, and 48 hours were detected by a human cytokine assay and the interleukin (IL)-8 protein level in the culture media were determined by ELISA. Next, HEKs were treated with or without 100 μmol/L RSV in the presence or absence of 50 mJ/cm2 UVB, and activator protein 1 and NF-κB-related proteins were measured by Western blot. Furthermore, cells exposed to UVB radiation were treated with apoptosis activators procaspase-activating compound 1 (PAC-1), apoptosis activator 2 (AA2) or RSV to investigate the effect of RSV on the percentage of apoptotic cells by flow cytometry. Then cells were treated with autophagy inhibitors LY294002, 3-methyladenine (3-MA) or RSV in the presence of UVB and chloroquine (CQ) to investigate the effect of RSV on autophagy through detecting microtubule-associated protein 1 light chain 3 (LC3) expression by western blot. Finally, the effect of LY294002, 3-MA, ATG5 siRNA, PAC-1, and AA2 on RSV-mediated reduction of IL-8 expression was determined by ELISA assay.Results:RSV treatment decreased the secretion of IL-8 (UVB vs. UVB+ RSV: [1454.05 pg/mL ± 52.95 pg/mL] vs. [553.68 pg/mL ± 206.03 pg/mL], P < 0.001), and downregulated the protein level of c-Fos in UVB-irradiated HEKs (UVB vs. UVB+ RSV: [0.103 ± 0.009] vs. [0.048 ± 0.015], P < 0.01). In UVB-irradiated HEKs, the result of western blot showed that LY294002 and 3-MA inhibited RSV-induced LC3 II accumulation (UVB + CQ + RSV vs. UVB + CQ + 3-MA+ RSV vs. UVB + CQ + LY294002+ RSV: [1.15 ± 0.03] vs. [0.77 ± 0.13] vs. [0.67 ± 0.13], P < 0.01), and the result of flow cytometry showed that PAC-1 and AA2 prevented RSV from reducing cell apoptosis (UVB+ RSV vs. UVB+ PAC-1 + RSV vs. UVB+ AA2+ RSV: [19.56% ± 0.62%] vs. [94.33% ± 0.15%] vs. [94.97% ± 1.91%], P < 0.001). The data of ELSA assay showed that LY294002, 3-MA, and ATG5 siRNA reversed the RSV-mediated inhibition of IL-8 protein secretion by UVB-irradiated HEKs (UVB + LY294002 vs. UVB + LY294002 + RSV: [3283.00 pg/mL ± 444.05 pg/mL] vs. [1608.58 pg/mL ± 128.42 pg/mL], P < 0.05; UVB + 3-MA vs. UVB+ 3-MA+ RSV: [2941.88 pg/mL ± 103.80 pg/mL] vs. [1867.51 pg/mL ± 153.84 pg/mL], P < 0.01; UVB+ siATG5 vs. UVB+ siATG5+ RSV: [2530.11 pg/mL ± 685.34 pg/mL] vs. [3011.42 pg/mL ± 435.69 pg/mL], P > 0.05), whereas neither PAC-1 nor AA2 exerted similar effects.Conclusion:RSV may regulate autophagic flux to inhibit IL-8 expression in UVB-challenged keratinocytes.

简介：Objective:Tostudythecellularimmunitystatusofpatientswithrecurrentgenitalherpes.Methods:Serumlevelsofinterlukin-2anditssolublereceptorandinterlukin-6weremeasuredbyELISAin34patientswithrecurrentgenitalherpes.Results:SerumlevelsofIL-2andIL-6weresignificantlydecreasedinpatientscomparedtohealthycontrols(P<0.01),andthelevelofsIL-2Rwassignificantlyincreasedinpatientswithrecurrentgenitalherpes(P<0.01).Therewerenosignificantdifferencesinallvariablesamongstpatientsregardingrelapsestageandremissionstage(P>0.05).Conclusion:Therewasacellularimmunedeficiencyinpatientswithrecurrentgenitalherpes.

简介：Interleukin-12(IL-12)isacriticalcytokinerepresentingthelinkbetweenthecellularandhumoralbranchesofhostimmunedefenseapparatus.IL-12-inducedcytotoxiclymphocyte(CTL)developmentisacentralmechanisminimmuneresponsesagainstintracellularinfectiousagentsaswellasmalignantgrowth.However,themolecularbasisoftumor-specificCTLresponsesmediatedbyIL-12remainspoorlydefined.Inthisstudy,weaddressedthisissueinacomprehensivemannertoprobeintoIL-12-inducedanti-tumorresponsesbyglobalgeneexpressionprofilingofmRNAexpressioninCD8+TcellsinatransplantablesyngeneicmousemammarycarcinomamodeltreatedornotwithrecombinantIL-12.AstrongtumorregressionwasinducedbytheIL-12treatment.AnintrospectionofdifferentialgeneexpressionatanearlystageoftheIL-12-initiatedCTLactivationrevealsinterestinggenesandmolecularpathwaysthatmayaccountforthemarkedtumorregression,andislikelytoprovidearichsourceofpotentialtargetsforfurtherresearchanddevelopmentofeffectivetherapeuticmodalities.Cellular&MolecularImmunology.2004;1(5):357-366.

简介：Objective:　Tocomparethedynamicchangesofinterleukin-1(IL-1),interleukin-6(IL-6),andtumornecrosisfactor(TNF)inintermingledskingraftwiththoseinothertypesofskingraftsinrats.　　Methods:　A10%-15%third-degreeburnwascreatedin180Spregue-Dawley(SD)rats.Afterremovingthescar,skingraftswereperformedontheopenwoundsimmediatelywithautoskin(aus,n=54),alloskin(als,n=54)andintermingledskin(n=36).Thatistosay,intheintermingledskingraft,abigpieceofalloskin(mals)wasgraftedfirst,and3dayslater,smallpiecesofautoskin(maus)wereembeddedinthealloskin.Therest36ratsweretakenasthecontrols.AndthebiologicalactivitiesofIL-1,IL-6andTNFingraftsheetsineachgroupweredetectedafterskingraft.　　Results:　ThelevelsofIL-1,IL-6andTNFintheausgroupdecreasedsteadilyaftertheirinitialelevations,whereasinthealsgrouptheyincreasedsignificantlyandkeptonthepeaklevelinthelaterphases.Intheintermingledgroup,thereappearedalowestIL-1levelinthemalsandahighestoneinthemaussimultaneouslyat7(4)days(Thenumberoutofparenthesisisthedaysaftertransplantingwithalloskinsheets,andthenumberinparenthesisisthedaysafterembeddingautoskinsheetsintheintermingledskingraft.Similarlyhereinafter.)afterskingraft(P<0.01),andthehighlevelinthemausabruptlydecreasedat14(11)daysafterskingraft.Atexactlythesamephaseonday7(4),aprominentpeakedIL-6inthemalsoccurred.Inthelaterphases,thelevelsofTNFremainedrelativelylowbothinthemalsandinthemaus.Fromday7(4)on,eachcytokinefluctuationinthemalssynchronizedwiththatinthemaus.Thelongertheposttransplantationperiodlasted,themorethepositivecytokinecorrelatedbetweenthemalsandthemaus.　　Conclusions:　ThelowlevelsofIL-1andTNFmaybeimportantfactorstolightentheintensityoflocalrejectionintheintermingledskingraft.Thetempo

简介：Interleukin-18(IL-18)wasdiscoveredasaninterferon-γ-inducingfactorandhadacriticalroleininflammatoryandimmuneresponse.Itstimulatesnaturalkiller(NK)andTcellsandenhancesTh1immuneresponse.Theseactivatedimmunecellseliminatecancercellsandvirus-infectedcellseffectively.However,IL-18hasalsobeenfoundtopromotetumorprogression.HigherexpressionorsecretionlevelofIL-18isdetectedinvariouscancercellsincomparisonwithnormalcontrol,andIL-18isabletoinduceangiogenesis,migration/metastasis,proliferationandimmuneescape.ThesedualeffectsandthemechanismofIL-18needtobeinvestigatedfurtherasitrelatestocancer.

简介：Theintrinsicgrowthabilityofalltheneuronsdeclinesduringdevelopmentalthoughsomemaygrowbetterthanothers.Numerousintracellularsignalingproteinsandtranscriptionfactorshavebeenshowntoregulatetheintrinsicgrowthcapacityinmatureneurons.Amongthem,PI3kinase/Aktpathwayisimportantforcontrollingaxonelongation.Asanegativeregulatorofthispathway,thetumorsuppressorphosphataseandtensinhomolog(PTEN)appearscriticaltocontroltheregenerativeabilityofyoungandadultneurons.ThisreviewwillfocusonrecentresearchprogressinaxonregenerationandneuralrepairbyPTENinhibitionandtherapeuticpotentialofblockingthisphosphataseforneurologicaldisorders.InhibitionofPTENbydeletioninconditionalknockoutmice,knockdownbyshort-hairpinRNA,orblockadebypharmacologicalapproaches,includingadministrationofselectivePTENantagonistpeptides,stimulatesvariousdegreesofaxonregrowthinjuvenileoradultrodentswithcentralnervoussysteminjuries.Importantly,post-injuryPTENsuppressioncouldenhanceaxonalgrowthandfunctionalrecoveryinadultcentralnervoussystemafterinjury.

简介：Apoptosisisprimarilyexecutedbyactivecaspases,whicharederivedfromtheinactiveprocaspasezymogensthroughproteolyticcleavage.Wedeterminedthecrystalstructuresofacaspasezymogen,procaspase-7,andanactivecaspase-7withoutanyboundinhibitors.Comparedtotheinhibitor-boundcaspase-7,procaspase-7zymogenexhibitssignificantstructuraldifferencessurroundingthecatalyticcleft,whichprecludestheformationofaproductiveconformation.Proteolyticcleavageinbetweenthelargeandsmallsubunitsallowsrearrangementofessentialloopsintheactivesite,primingactivecaspase-7forinhibitor/substratebinding.Strikingly,bindingbyinhibitorscausesa180-degree-flippingoftheN-terminusinthesmallsubunit,whichinteractswithandstabilizesthecatalyticcleft.Theseanalysesrevealthestructuralmechanismsofcaspaseactivationanddemonstratethattheinhibitor/substratebindingisaprocessof

简介：Demyelinationofthecentralnervoussystem(CNS)isahallmarkofmultiplesclerosis(MS),chronicinflammatoryandneurodegenerativedisease.Chronicdemyelinationfavorsneurodegenerationofdenudedaxons,whichisamajorcauseofirreversibleneuronaldeficitsanddisabilityinMSpatients(Lucchinettietal.,2000).MSremainsanincurabledisease,despiteformida-

简介：

简介：ToexplorethemechanismoftheinhibitionofHIV-1byMycoplasmafermerttans,culturesupernatantsandthallodicproteinsfromM.fermerttansPG18werepreparedandtheproteincomponentsofthesupernatantswerepurifiedwithhighperformanceliquidchromatography(HPLC).Theinhibitoryactivitiestoreversetranscriptase(RT)andthenucleaseactivitiesweredetected;theinfluenceofM.fermerttansonIL-10secretionbybothnormalandH1V-1infectedhumanPBMCweredetermined,andtheinhibitoryeffectofrhIL-10onH1V-1replicationwasdetectedwithEI,ISAmethod.Theresultsshowedthatthepurifiedproteinswithamolecularweightof67-100kDaor10-25kDashoweda36%or34%inhibitoryac-tivitytoRTandpartialnucleaseactivity.ThethallodicproteincouldinducebothnormalandH1V-1infectedPBMCtosecretIL-10remarkably,andtothelatter,thiseffectwasmoreapparent.WhilerhIL-10couldinhibitreplicationofH1V-1inPB-MCinvitroinadose-dependantmanner.ItconcludesthattheinhibitoryeffectoftheM.fermentansPG18culturesupernatantsonRTandthepromotingeffectofPG18thallodicproteinonIL-10secretioninPBMCexplainthemechanismsofinhibitiontoHIV-1byM.fermentansPG18.

简介：Objective:Toexploretheantitumormechanismsofbifidobacteriaadolescenceinvivo.Methods:Thecontentofextracellularsignalregulatedproteins(ERK)1/2,C-JunN-terminalkinase(JNK),p38,c-fosandc-juninnudemousetransplantedlargebowelcarcinomawasdetectedbyusinglaserconfocalmicroscopy.TheexpressionofNF-kBwasdeterminedbyimmunohistochemistry.Results:Afterthenudemousetransplantedtumorwastreatedwithbifidobacteria,theaveragefluorescentstrengthofERK1/2,JNK,c-fosandc-junwassignificantlylowerthanthatintumorcontrolgroup(P<0.01).Theaveragefluorescentstrengthofp38wasnotobviousdifferenceinthetwogroups(P>0.05).ThepositivecelldensityofNF-kBinlargebowelcarcinomatransplantationtumorsinBifidobacteriuminjectiongroupwasmarkedlylowerthanthatintumorgroup(P<0.01).Conclusion:bifidobacteriaadolescencecouldmarkedlydecreasetheactivityofERK1/2andJNK,theexpressionc-fosandc-jun,andtheactivityofNF-kB.

简介：AbstractAnti-influenza drugs are one of the most critical pathways for control of influenza virus infection. Drugs that have been developed or are developing may function via different mechanisms, and so far, inhibitors of influenza virus polymerase are among the most promising types of drugs. Favipiravir and Baloxavir, also named T-705 and Xofluza respectively, have been approved for influenza treatment in Japan and the United States. Favipiravir effectively and selectively inhibits the RNA-dependent RNA polymerase (RdRp) of RNA viruses while Baloxavir specifically targets the cap-dependent endonuclease PA of influenza viruses. These two drugs have been suggested as the first candidate drugs for influenza infection treatment, especially for strains resistant to other anti-influenza drugs. This review will focus on the pharmaceutical mechanisms and anti-influenza activity of these two drugs.

简介：像成纤维细胞的synoviocytes(FLS)在风湿性关节炎(RA)贡献synovial增生。Smoothened(Smo)是发信号的声音的刺猬(嘘)的一个关键部件并且贡献肿瘤房间增长。这研究的目的是在RAsynoviocyte增长调查Smo的角色。FLS从RAsynovium被孤立。发信号的嘘用一个Smo对手(GDC-0449)和在FLS指向Smo基因的小介入RNA(siRNA)被学习。房间增长被使用kit-8试金和房间周期分发确定，apoptosis被流动cytometry评估。房间周期相关的基因和蛋白质被即时PCR和西方的污点检测。与GDC-0449或Smo-siRNA对待的FLS与控制相比显示出显著地减少的增长(P<；0.05)。有GDC-0449的孵化或有Smo-siRNA的transfection与控制相比导致了G1阶段房间的重要增加(P<；0.05)。房间周期拘捕被cyclinD1和E1mRNA表示的重要增加验证，在在Smo-siRNAtransfected房间的cyclin依赖的kinasep21mRNA表示的减少(P<；0.05)。cyclinD1的蛋白质表示也是在Smo基因以后的downregulated击倒(P<；0.05)。结果建议发信号的嘘以一种Smo依赖的方式在RA-FLSs增长起一个重要作用并且可以贡献synovial增生。指向嘘发信号可以帮助与RA在病人控制联合损坏。

简介：

简介：Anewthermokineticreducedextentmethodforstudyingofthereversiblecompetitiveinhibitionofsinglesubstrateenzyme-catalyzedreactionswasproposedinthispaper.Thereactionthatarginase-catalyzedhydrolysisofL-argininetoL-ornithineandureaandtheinhibitionofthisreactionbytheproduct,L-ornithine,andexogenousL-lysinewerestudiedat37℃in40mmol·L^-1sodiumbarbiturate-HC1buffersolution(pH=9.4).MichealisconstantKmforarginineandmaximumvelocityVmofthereactionweredeterminedtobe5.14mmol·L^-1and1.13×10^-2mmol·L^+1·s^-1,respectively.TheproductinhibitionconstantKpandinhibitoryconstantK1ofL-lysineweredeterminedtobe1.18and5.6mmol.L-l,respectively.Alltheresultshavebetterrepeatabilityandself-consistencyandareinagreementwithliteraturevalues.Thisnewmethodusingmoredirectthermalinformationfromtheprocesswouldgivemorereliablekineticinformationthanthetraditionalinitialratemethod.

简介：

简介：

简介：γ-Aminobutyricacid(GABA)isamajorneurotransmitterandplaysimportantrolesinboththedevelopingandmaturecentralnervoussystem(CNS).OnewaythatGABAcanactisbybindingtofast,ionotropicGABAAreceptorsinneurons.ThebindingofGABAtoGABAAreceptorscausesaconformationalchangethatopensionchannels,

简介：Objective:Toinvestigatetherolesofinterleukin-2(IL-2)andinterleukin-10(IL-10)inpathogenesisofearlysyphilis.Methods:TheserumlevelsofIL-2andIL-10in48patientswithearlysyphilisweredetectedbyABC-ELISA.Results:(1)ThelevelofIL-2inthepatientswithearlysyphiliswassignificantlyhigherthanthatinhealthycontrols,whilethatofIL-10waslower(P<0.001andP<0.001).(2)ThelevelsofIL-2andIL-10werealmostidenticalinpatientswithprimaryandsecondarysyphilis(P>0.05),aswellasbetweendif-ferentRPRtiters(P>0.05).(3)Aftertherapy,thelevelofIL-2decreasedmarkedly(P<0.05),whilethatofIL-10increase(p>0.05).(4)AsignificantcorrelationwasfoundbetweentheserumlevelsofIL-2andIL-10(r=0.5385P<0.05).Conclusions:Th1up-regulationoccursinpatientswithearlysyphilis,andplaysanactiveroleinfightingagainstTPinfection.