简介：AbstractBackground:Pancreatic stellate cells (PSCs) activation plays a critical role in the development of chronic pancreatitis. Previous studies confirmed that thromboxane A2 receptor (TxA2r) was overexpressed in activated PSCs in rats. The purpose of this study was to investigate the role of TxA2r in the activation of PSCs induced by 8-epi-prostaglandin F2α (8-epi-PGF2α).Methods:TxA2r expression in both quiescent and activated PSCs was detected by immunocytochemistry and immunoblot assay. Isolated PSCs were treated with 8-epi-PGF2α (10-6, 10-7, 10-8 mol/L) for 48 h, and SQ29548 (10-4, 10-6, and 10-7 mol/L), a TxA2r-specific antagonist, for 48 h, respectively, to identify the drug concentration with the best biological effect and the least cytotoxicity. Then isolated PSCs were treated with SQ29548 (10-4 mol/L) for 2 h, followed by 10-7 mol/L 8-epi-PGF2α for 48 h. Real-time polymerase chain reaction was performed to detect the messenger RNA (mRNA) levels of α-smooth muscle actin (α-SMA) and collagen I. Comparisons between the groups were performed using Student’s t test.Results:TxA2r was up-regulated in activated PSCs in vitro compared with quiescent PSCs (all P < 0.001). Compared with the control group, different concentrations of 8-epi-PGF2a significantly increased mRNA levels of α-SMA (10-6 mol/L: 2.23 ± 0.18 vs. 1.00 ± 0.07, t= 10.70, P < 0.001; 10-7 mol/L: 2.91 ± 0.29 vs. 1.01 ± 0.08, t= 10.83, P <0.001; 10-8 mol/L, 1.67 ± 0.07 vs. 1.00 ± 0.08, t= 11.40, P < 0.001) and collagen I (10-6 mol/L: 2.68 ± 0.09 vs. 1.00 ± 0.07, t = 24.94, P < 0.001; 10-7 mol/L: 2.12 ± 0.29 vs. 1.01 ± 0.12, t = 6.08, P < 0.001; 10-8 mol/L: 1.46 ± 0.15 vs. 1.00 ± 0.05, t = 4.93, P = 0.008). However, different concentrations of SQ29548 all significantly reduced the expression of collagen I (10-4 mol/L: 0.55 ± 0.07 vs. 1.00 ± 0.07, t = 10.47, P < 0.001; 10-6 mol/L: 0.56 ± 0.10 vs. 1.00 ± 0.07, t = 6.185, P < 0.001; 10-7 mol/L: 0.27 ± 0.04 vs. 1.00 ± 0.07, t= 15.41, P < 0.001) and α-SMA (10-4 mol/L: 0.06 ± 0.01 vs. 1.00 ± 0.11, t= 15.17, P < 0.001; 10-6 mol/L: 0.28 ± 0.03 vs. 1.00 ± 0.11, t= 11.29, P < 0.001; 10-7 mol/L: 0.14 ± 0.04 vs. 1.00 ± 0.11, t= 12.86, P < 0.001). After being treated with SQ29548 (10-4 mol/L) and then 8-epi-PGF2α (10-7 mol/L), the mRNA levels of a-SMA (0.20 ± 0.08 vs. 1.00 ± 0.00, t= 17.46, P < 0.001) and collagen I (0.69 ± 0.13 vs. 1.00 ± 0.00, t = 4.20, P = 0.014) in PSCs were significantly lower than those of the control group.Conclusions:The results show that 8-epi-PGF2α promoted PSCs activation, while SQ29548 inhibited PSCs activation induced by 8-epi-PGF2α. The result indicated that TxA2r plays an important role during PSC activation and collagen synthesis induced by 8-epi-PGF2αin vitro. This receptor may provide a potential target for more effective antioxidant therapy for pancreatic fibrosis.

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简介：Thermalmaturationandpetroleumgenerationmodelingofshalesisessentialforsuccessfulexplorationandexploitationofconventionalandunconventionaloilandgasplays.Forbasinwideunconventionalresourceplayssuchmodeling,whenwellcalibratedwithdirectmaturitymeasurementsfromwells,cancharacterizeandlocateproductionsweetspotsforoil,wetgasanddrygas.Thetransformationofkerogentopetroleumisassociatedwithmanychemicalreactions,butmodelstypicallyfocusonfirst-orderreactionswithratesdeterminedbytheArrheniusEquation.AmisconceptionhasbeenperpetuatedformanyyearsthataccuratethermalmaturitymodelingofvitrinitereflectanceusingtheArrheniusEquationandasingleactivationenergy,toderiveatime-temperatureindex(∑TTIARR),asproposedbyWood(1988),isflawed.ThisclaimwasinitiallymadebySweeneyandBurnham(1990)inpromotingtheir'EasyRo'method,andrepeatedbyothers.Thispaperdemonstratesthroughdetailedmulti-dimensionalburialandthermalmodelinganddirectcomparisonofthe∑TTIARRand'EasyRo'methodsthatthisisnotthecase.The∑TTIARRmethodnotonlyprovidesaveryusefulandsensitivematurityindex,itcanreproducethecalculatedvitrinitereflectancevaluesderivedfrommodelsbasedonmultipleactivationenergies(e.g.,'EasyRo').Throughsimpleexpressionsthe∑TTIARRmethodcanalsoprovideoilandgastransformationfactorsthatcanbeflexiblyscaledandcalibratedtomatchtheoil,wetgasanddrygasgenerationwindows.Thisisachievedinamore-computationally-efficient,flexibleandtransparentwaybythe∑TTIARRmethodthanthe'EasyRo'method.Analysisindicatesthatthe'EasyRo'method,usingtwentyactivationenergiesandaconstantfrequencyfactor,generatesreactionratesandtransformationfactorsthatdonotrealisticallymodelobservedkerogenbehaviourandtransformationfactorsovergeologictimescales.

简介：人工的介绍抗原的房间被期望在注入前刺激T房间的最佳的治疗学的特征的扩大和获得。这里，绑在IgGmonoclonal抗体的可结晶的碎片的CD32遗传上在人的K562白血病房间上被表示为T房间受体提供ligand。CD86和4-1BBL，它是分别地，CD28和4-1BB的受体是的共同刺激的ligands也在K562上表示了房间。然后，我们由对CD3与OKT3monoclonal抗体联合K32/CD86/4-1BBL房间完成了人工的介绍抗原的房间，命名K32/CD86/4-1BBL/OKT3房间。这些人工的修改细胞有导致CD8+T细胞激活的能力，支持CD8+T细胞增长，分割，和长期的生长，禁止CD8+T细胞apoptosis，并且提高IFN-和perforin的CD8+T细胞分泌物。而且，抗原特定的细胞毒素的T淋巴细胞能在至少在28天以内与K32/CD86/4-1BBL/OKT3房间刺激的文化被保留。这条途径为CD8+T房间的扩大和激活柔韧、简单、可再现、节俭并且可以为采纳免疫疗法有重要治疗学的含意。

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简介：我们以前报导在C3H/HeN(C3H)老鼠的neutrophils的巨大的渗入不能高效地控制感染和力量贡献的Chlamydiamuridarum(厘米)到肺感染的这些老鼠的高危险性。为了推进，在chlamydial感染期间在C3H鼠标定义嗜中性的回答的性质，分别地，我们检验与neutrophils渗入和激活有关的粘附分子和CD11b的表达式后面的intranasal厘米感染。结果证明selectins(E-selectin，P-selectin和L-selectin)的表示，和在C3H老鼠的肺的细胞间的房间粘附molecule-1(ICAM-1)比在C57BL/6(B6)更显著地增加了老鼠，更抵抗的紧张。这些结果在C3H老鼠与巨大的neutrophils渗入相关很好。相反，外部血上的CD11b表示和在C3H鼠标的肺neutrophils在感染(白天14)的迟了的噬菌体期间与B6鼠标相比展出了重要减小。这些调查结果建议在C3H鼠标的粘附分子的高级表达式可以提高neutrophils招募到肺，但是neutrophils上的CD11b表示的衰落可以稀释嗜中性的功能。因此，neutrophils上的CD11b下面规定可以贡献C3H老鼠的失败控制chlamydial肺感染。

简介：Interleukin(IL)-15在生来的杀手(NK)和CD8+T房间增长和功能起一个重要作用并且是比为肿瘤免疫疗法的IL-2更有效的。由附近的房间的IL-15的trans演讲比它的可溶的IL-15为NK房间激活是更有效的。在这研究，熔化蛋白质dsNKG2D-IL-15，由经由一个连接器联合到人的IL-15的人的NKG2D的二相同的细胞外的域组成了，在Escherichiacoli被设计。DsNKG2D-IL-15能高效地与二个NKG2D领域和trans礼品IL-15把人的肿瘤房间的链相关的蛋白质A(云母)绑在主要histocompatibility建筑群一级到NK或CD8+T房间。我们移植了人的胃的癌症(SGC-7901)房间进裸体老鼠和有进C57BL/6老鼠的云母(B16BL6云母)的宫外的表示的老鼠黑瘤房间。然后，我们学习了反肿瘤效果在二个xenografted肿瘤模特儿由dsNKG2D-IL-15调停了。人的dsNKG2D-IL-15在压制胃的癌症生长比IL-15展出了更高的效率。外长的人的dsNKG2D-IL-15集中地在老鼠肿瘤纸巾被散布基于在vivo实时成像。房间渗入了进跟随外部血mononuclear房间的注射进忍受人的胃的癌症的裸体老鼠的肿瘤纸巾的人的CD56+的频率被人的dsNKG2D-IL-15治疗显著地增加。人的dsNKG2D-IL-15也由激活和招募的老鼠NK和CD8+T房间推迟了移植黑瘤(B16BL6云母)的生长。在C57BL/6老鼠的人的dsNKG2D-IL-15的反黑瘤效果主要被减少由在里面老鼠NK房间的vivo弄空。这些数据热点为肿瘤的人的dsNKG2D-IL-15的潜在的使用治疗。

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简介：AbstractObjective:This study was performed to investigate the relationship between the human melanogenesis and antioxidant systems and to further confirm the synergistic effect of oxyresveratrol (OXYR) and resveratrol (RES) in human epidermal melanocyte cell line.Methods:The human epidermal melanocyte line PIG1 cells were divided into the UV groups and control group, treated with different doses of UVB and without UVB, respectively. MTT assay and flow cytometry were used to detect cell viability and apoptosis. The expression of Nrf2/HO-1 and melanogenesis-associated proteins/genes was measured by Western blotting and real-time qPCR (RT-qPCR). pCMV6-XL5-Nrf2 was used to upregulate the expression of Nrf2. Subsequently, the proteins/genes levels of Nrf2/HO-1 and tyrosinase (TYR), melanin/eumelanin content, and reactive oxygen species (ROS) were analyzed. Isobologram analysis and cell experiment were used to analyze whether OXYR and RES inhibit TYR synergistically. Western blotting, RT-qPCR, and NaOH splitting method were used to determine the Nrf2/HO-1 and melanogenesis-associated proteins/genes expression and melanin content to evaluate the efficacy of OXYR and RES.Results:The activated Nrf2 and HO-1 eliminated ROS produced by UVB irradiation. The melanogenesis-associated proteins/genes of melanocyte-inducing transcription factor (MITF, P < 0.01 on protein expression), TYR (both P < 0.01), TYR-related protein (TRP)-1 (both P < 0.05), and TRP2 (P < 0.05 on mRNA expression) were activated in PIG1 cells by UVB irradiation. Simultaneously, the upregulation of Nrf2 significantly reduced melanogenesis formation (P < 0.001) and TYR level (P < 0.01 on protein expression). Moreover, OXYR and RES synergistically inhibited TYR activity (P < 0.001) and reduced melanin content (P < 0.001).Conclusions:A microbalance exists between Nrf2/HO-1 signaling and melanogenesis production in the UVB-induced responses of melanocytes. Simultaneously, OXYR enhances the ability of RES to inhibit melanin production.

简介：瞄准：调查在肝的卵形的房间在试管内的增长和区别上表明小径的正规Wnt的激活的效果。方法：WB-F344房间与recombinantWnt3a被对待(20，40，80，160，200ng/mL)在24h的没有浆液的媒介。房间增长被Brdu加入分析测量；未经治疗的WB-F344房间作为控制被拿。有为24h的Wnt3a(160ng/mL)的术后疗法，在对待的WB-F344房间代替细胞的本地化和beta-catenin的蛋白质表示并且与Wnt3a未经治疗被免疫荧光染色和西方的污点分析检验。CyclinD1mRNA表示被半量的反向抄本的聚合酶链反应(RT-PCR)决定。一些表型的标记的mRNA层次(法新社，CK-19，白长袍的)并且二个肝的原子因素(HNF-4，HNF-6)被RT-PCR测量。CK-19和法新社蛋白质的表情被西方的污点分析检测。结果：Wnt3a支持了WB-F344房间的增长。有recombinantWnt3a的WB-F344房间的刺激导致了transcriptional使活跃之物beta-catenin的累积，和它进原子核，和起来调整的典型Wnt目标基因CyclinD1的易位。在当浆液不在时的Wnt3a处理的3d以后，WB-F344房间保留了他们的双性人潜力表示hepatocytes和cholangiocytes的几个特定的表型的标记，例如法新社和CK-19，跟随表明小径的正规Wnt的激活。结论：表明小径的正规Wnt支持老鼠的增长和自强肝的卵形的房间。

简介：Moststudiesaddressingthespecificityofmeridiansandacupuncturepointshavefocusedmainlyonthedifferentneuraleffectsofacupunctureatdifferentpointsinhealthyindividuals.Thisstudyexaminedtheeffectsofacupunctureonbrainfunctioninapathologicalcontext.Sixteenpatientswithischemicstrokewererandomlyassignedtotruepointgroup(trueacupunctureatrightWaiguan(SJ5))andshampointgroup(shamacupuncture).Resultsoffunctionalmagneticresonanceimagingrevealedactivationinrightparietallobe(Brodmannareas7and19),therighttemporallobe(Brodmannarea39),therightlimbiclobe(Brodmannarea23)andbilateraloccipitallobes(Brodmannarea18).Furthermore,inhibitionofbilateralfrontallobes(Brodmannarea4,6,and45),rightparietallobe(Brodmannareas1and5)andlefttemporallobe(Brodmannarea21)wereobservedinthetruepointgroup.Activationintheprecuneusofrightparietallobe(Brodmannarea7)andinhibitionoftheleftsuperiorfrontalgyrus(Brodmannarea10)wasobservedintheshamgroup.Comparedwithshamacupuncture,acupunctureatWaiguaninstrokepatientsinhibitedBrodmannarea5onthehealthyside.Resultsindicatedthatthealteredspecificityofsensation-associatedcortex(Brodmannarea5)ispossiblyassociatedwithacentralmechanismofacupunctureatWaiguanforstrokepatients.

简介：全身的豺狼座erythematosus(SLE)是B房间hyperreactivity描绘的自体免疫的疾病。像使用费的受体7(TLR7)表明小径反常地在SLEB房间被激活。CyclinD3(CCND3)在B房间增长，开发，和区别起一个重要作用。尽管以前的研究为自发的幼芽的中心的发展集中了于TLR7的B房间内在的角色，在SLEB房间的CCND3上的TLR7的影响仍然不是清楚的。这里，我们使用了介绍薄片的B房间并且发现CCND3与SLE有关并且显著地在SLEB房间提高了。而且，我们决定CCND3的表示水平更高，当miR-15b与正常题目相比在从SLE病人和B6.MRL-Faslpr/J豺狼座老鼠的B房间是显著地更低的时。而且，我们证明TLR7的激活戏剧性地增加了CCND3表示，但是显著地减少了在在vitro的B房间的miR-15b并且我们鉴别CCND3是miR-15b的一个直接目标。为了推进，证实我们的结果，我们由谈论地对待C57BL/6(B6)建立了另一个豺狼座模型有为8个星期的TLR-7收缩筋imiquimod(IMQ)的老鼠根据以前描述的协议。Expectedly，有IMQ的热门治疗显著地也增加了CCND3并且减少在B6老鼠的B房间的miR-15b。一起拿，我们的结果鉴别TLR7的激活在Bcells;经由miR-15b的downregulation增加了CCND3表示；因此，这些调查结果建议那外来的导致因素的CCND3表情可以在SLE贡献B房间的反常。

简介：Anacardic酸(AA)是2-hydroxy-6-alkylbenzoic酸相当或相同的事物的混合物。它广泛地被认为是p300的一个非特定的histoneacetyltransferase禁止者。效果和在LNCaP房间(前列腺癌症房间)的AA的机制仍然保持未知。在LNCaP房间上调查AA的效果，我们执行了几个实验并且发现AA禁止LNCaP房间增长，导致G1/S房间周期拘捕和LNCaP的apoptosis房间。AA对LNCaP房间经由起作用的机制可能由于下列方面。首先，AA能除了它在LNCaP房间通过translational以后修正调整p300的功能的机制调整p300抄写和蛋白质水平。第二，AA能通过在LNCaP房间在Ser15上增加p53的phosphorylation激活p53。AA能有选择地激活p21(p53的目标基因)。第三，通过supressingp300的AA罐头下面调整雄激素受体(AR)。我们的学习建议AA在LNCaP房间举办多重反肿瘤活动并且保证进一步的调查。

简介：Thisexperimentusedwhole-cellpatch-clamptechniquetoinvestigatethecourseofrecoveryfromuse-dependentblockofNa+channels(Nav1.5)inhumanembryonickidney(HEK)cells,onwhichtoverifytheeffectsofvolatileoilofNardostachychinesisBatal(Gansong).MethodsTwopulsesgeneratedbycomputerfollowedbyarecoverypulseandatestpulse,theintervaldurationbetweenthetwopulsesvariedfrom16msto1s,andholdingpotentialis-80mVto-140mV.ThepeakNa+currentforagivenrecoverytimewasnormalizedtothefullyrecoveredpeakcurrent,andthenormalizedvaluewastheplotasafunctionoftherecoverytimetostudytheeffectsof3ppmconcentrationGansongvolatileoilonrecoveryfromuse-dependentblockofNav1.5inHEK.ResultsItshowedthatGansonggroup,comparingwithcontrolgroup,delayedthetimecoursesofrecoveryfromuse-dependentblock[(33.2±5.77)msforcontrolgroupand(52.5±6.08)msfor3ppmGansonggroup,P<0.05].InthepresenceofGansong,inhibitionoftheNa+currentwasenhancedbyincreasingfrequencyofdepolarizingpulsefrom56.5msto16ms.Inthecontrolgroup,thetimecourseofrecoveryshowedthatrecoverystartedat19.5msandfinishedby36.5ms.InthepresenceofGansong,thetimecourseofrecoveryshowedthatrecoverystartedat36.5msandfinishedby56.5ms.Na+currentsrecoveredfromtheuse-dependentblockvaryingwithholdingpotential(holdingpotential-dependent).ConclusionsTheresultssuggestedthatNa+currentsrecoveredfromtheuse-dependentblockcorrelatedwithpersistenttime,holdingpotential.TheGansongvolatileoilhasinhibitiveeffectontheNa+currentrecovery.

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简介：免疫疗法和化疗的联合为癌症的某些类型的治疗被认为是一条有希望的途径。然而，内在的机制需要充分被调查为癌症chemoimmunotherapy指导更有效的协议的设计。联系危险的分子的模式(阻尼)能激活有免疫力的房间，是众所周知的，包括树枝状的房间(DC)，经由像使用费的受体(TLR)；然而，在有免疫力的反应的激活免除化学对待药的肿瘤房间的阻尼的角色需要进一步被阐明。这里，我们发现那colorectal与oxaliplatin(OXA)对待的癌症(CRC)房间或5氟尿嘧啶(5-Fu)释放了高活动性的组盒子1的高水平(HMGB1)和热吃惊蛋白质70(HSP70)。在OXA/5-Fu治疗以后，也展出的CRC病人的sera增加了HMGB1和HSP70的层次，哪个是著名阻尼。与OXA/5-Fu对待的垂死的CRC房间的上层清液支持了老鼠和人的DC成熟，与HLA医生，CD80和CD86表示和IL-1β的改进的upregulation；，TNF-α；，MIP-1α；，MIP-1β；，RANTES和IP-10生产。由DC组成的疫苗与导致的化学上强调的CRC房间的上层清液搏动了更重要的IFN-γ；在vitro并且在vivo生产Th1反应。然而，化学上强调的CRC房间的上层清液没能在TLR4缺乏的DC导致phenotypic成熟和cytokine生产，显示在导致阻尼的DC成熟和激活的TLR4的一个必要角色。而且，有化学上强调的CRC房间的上层清液的pulsing高效地没导致IFN-γ；在TLR4缺乏的DC生产Th1反应。一起，这些结果证明免除化学上强调的癌症房间的阻尼能经由TLR4激活DC并且提高反肿瘤T房间有免疫力的回答的正式就职，描出一条临床上相关的免疫助手小径由阻尼被触发。

简介：1-methyl-4-phenylpyridiniumion(MPP+)inducesendoplasmicreticulumstressandactivatescaspase-12inPC12cells,leadingtoneuronalapoptosis.However,theunderlyingmolecularmechanismremainsunknown.Thepresentstudyinvestigatedtheregulatoryeffectsofnervegrowthfactor(Aktactivator)andlithiumchloride(glycogensynthasekinase-3βinhibitor)ontheendoplasmicreticulumstresssignalingpathway.TheresultsrevealedthatMPP+inducedexpressionofBipandC/EBPhomologousprotein.TheupregulationofBipandC/EBPhomologousprotein,aswellasthedecreasedpro-caspase-12levelinducedbyMPP+wereinhibitedbypretreatmentofthenervegrowthfactororlithiumchloride.Theseresultssuggestthatthephosphatidylinositol3kinase-Akt-glycogensynthasekinase-3βpathwayisinvolvedinMPP+-inducedendoplasmicreticulumstress.

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简介：WehavedevelopedandtestedchimericT-cellreceptors(TCR)specificforp185HER2.Intheseexperiments,retroviralvectorsexpressingtheN297orN29ξreceptorswereconstructedinpRET6.AmphotropicviralproducercellswereestablishedintheGALV-basedPG13packagingcellline.Ficollpurifiedhumanperipheralbloodlymphocytes(PBL)werevitallytransducedusinganoptimizedprotocolincorporatingactivationwithimmobilizedanti-CD3/anti-CD28monoclonalantibodies,followedbyviralinfectioninthepresenceoffibronectinfragmentCH296.Transducedcellswereco-culturedwithhumantumorcelllinesthatoverexpress(SK-OV-3)orunderexpress(MCF7)p185HER2toassayforantigenspecificimmuneresponses.BothCD4^+andCD8^+T-cellstransducedwiththeN297orN29ξchTCRdemonstratedHER2-specificantigenresponses,asdeterminedbyreleaseofTh1likecytokines,andcellularcytotoxicityassays.OurresultssupportthefeasibilityofadoptiveimmunothempywithgeneticallymodifiedT-cellsexpressingachTCRspecificforp185HER2.