简介：胆汁的形成取决于胆汁能分泌的仪器的结构、功能的正直，处于不同状况，它的缺陷导致胆汁郁积的症候群。象与它的作文和流动联系的各种各样的方面一样允许胆汁分泌物的结构的底处于生理的条件评价将首先被考察。小管胆汁被极化的hepatocytes生产在他们的basolateral(正弦曲线)的那抓住运输ers并且顶端(小管)血浆膜。这评论在这主要胆汁形成的分子的决定因素上总结最近的数据。当胆汁通过胆汁管，胆汁的树的主要功能是由在胆汁管上皮细胞(cholangiocytes)的能分泌、吸收性的过程的小管胆汁的修正。在cholangiocytes的液体和溶质运输的机制将也被讨论。与分泌物不变、糟糕控制的hepatocytes相对照，cholangiocyte分泌物被荷尔蒙和神经调整。奉献给胆汁分泌物的这些规章的机制的短节被包括了。这修订的目的与胆汁的生理学和病理是在将被奉献给特定的问题的这个系列将底放为另外的评论相关的。

简介：Eachsecretion(Sec)machineryminimallyconsistsofthreeintegralinnermembranepro-teinsSecYEG.InordertoknowthedistributionpatternoftheSeccomplexinStreptococcusmutans,weexploredthesubcellularlocalizationofSecY.Theanti-secYantibodywasexaminedonWesternblotstoevaluatespecificity.Anindirectpost-embeddingimmunogoldmethodwasusedtodeterminethesubcel-lularlocalizationoftheSecYinthecytoplasmicmembraneoftheStreptococcusmutansGS-5.Immuno-blottingexperimentsshowedthattheanti-secYantibodyspecificallyrecognizedasinglebandofabout47.8kDa.Immunogoldelectronmicroscopyimageofsectionwithanti-secYantibodyrevealedasingleintensefocusofgoldparticlesatadiscretelocationonthecytoplasmicmembraneoftheStreptococcusmutansGS-5.SecYclusteredtoanasyrmnetricmicrodomain,whichindicatedforthefirsttimethatSeccomplexpresentedauni-siteonthecytoplasmicmembraneofStreptococcusmutans.

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：DistributionandaccumulationofNd,anditseffectonsecretionofprogesteroneinmicewerestudiedusingradioisotopetracer(147Nd)technique.Followingsingleintraperitonealadministrationofneodymiumtracedwith147Ndatadoseof200mg*kg-1,unevendistributionoftheradioactiveNdoccurredinvarioustissuesandorgans.Muchamountof147Ndaccumulatesinthebone,andtheresidueincreaseswiththelapseoftime.Someamountofradioactivitywasalsodetectedineyes,bloodandbrain,buttheaccumulationdecreasedwiththetimeduetoexcretionandre-distributioninmice.Incomparisonwithcontrols,concentrationofprogesteroneisfoundtobesignificantlylowerintheserumofadministeredmice,indicatingasignificantlyinhibitoryeffectofNdonsecretionofprogesterone.

简介：Aim:Tostudytheeffectofprothymosinα(ProTα)asafusionproteinonthesecetionofINF-γ,IFN-αandTNF-αinvitro.Methods:Theinvitrostudywascarriedoutontheculturedofsplenocytes,splenicandperitonealmacrophagesisolatedfromBalb/cmice.SplenocyteswereincubatedwithvariousconcentrationsofProTα(1×10^-7-1×10^-10mol·L^-1)withorwithoutConA(5μg·mL^-1)for72h.SplenicandperitoealmacrophageswererespectivelytreatedwithProTα(1×10^-7-1×10^-10mol.L^-1)inthepresenceofLPS(10μg·mL^-1)for24h.ThenINF-γ′s,INF-α′sandTNF-α′slevelsinthesupernatantweredetecedbyELISA,Results:ProTα(1×10^-7)mol.L^-1)wasfoundtoobviouslyincreaseINF-γlevel(P<0.05)inthesupernatantofsplenocytescomparedwiththecontrolgroup.Moreover,ProTα(1×10^-7mol.L^-1)significantlyinducedthesecretionofINF-α(P<0.01)andTNF-α(P<0.01)insplenicandperitonealmacrophages.Conchusion:Invitro,ProTαcouldincreasethesecretionofIFN-γ,IFN-αandTNF-α.

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简介：TheaimofthisstudyistoelucidatethemolecularandcellularmechanismsunderlyingtheimmunosuppressiveeffectofSanchiextract(SE)viainvestigatingtheeffectsofSEontheactivationandproliferationofmurinelymphocytesandNOsecretionbyperitonealmacrophagesinvitro.ConAwasusedtoactivatelymphocytes,andexpressionofCD69onTcellsandCFSElabeledcelldivisionweredetectedbyflowcytometry.MurineperitonealmacrophageswerestimulatedwithLPSorlymphocytesculturesupemate(LCS)andtheconcentrationofNOwasdeterminedbyGriessreagentassay.After6hofculture,SErangingfrom50to100μg/mldownregulatedCD69expressiononConA-activatedTcells,whileSErangingfrom12.5to100μg/mlinhibitedtheproliferativeresponseoflymphocytestoConA.Additionally,SE(12.5-100μg/ml)inhibitedsecretionofNObyperitonealmacrophagesstimu-latedbyLPSorLCS.ThisstudyrevealsthatSEinhibitstheactivationandproliferationofmurinelym-phocytesandNOsecretionbyperitonealmacrophages.

简介：Gastrodin,anactivecomponentoftallgastrodiatuber,iswidelyusedinthetreatmentofdizziness,paralysis,epilepsy,strokeanddementia,andexhibitsaneuroprotectiveeffect.AratmodelofspinalcordinjurywasestablishedusingAllen’smethod,andgastrodinwasadministeredviathesubarachnoidcavityandbyintraperitonealinjectionfor7days.Resultsshowthatgastrodinpromotedthesecretionofbrain-derivedneurotrophicfactorinratswithspinalcordinjury.Aftergastrodintreatment,themaximumangleoftheinclinedplanetest,andtheBasso,BeattieandBresnahanscoresincreased.Moreover,gastrodinimprovedneuraltissuerecoveryintheinjuredspinalcord.Theseresultsdemonstratethatgastrodinpromotesthesecretionofbrain-derivedneurotrophicfactor,contributestotherecoveryofneurologicalfunction,andprotectsneuralcellsagainstinjury.

简介：AIM:ToelucidatethemolecularmechanismsunderlyinghepatitisBvirus(HBV)occultinfectionofgenotypeC.METHODS:Atotalof10typesofhepatitisBsurfaceantigen(HBsAg)variantsfromaKoreanoccultcohortwereused.AfteracompleteHBVgenomeplasmidmutatedsuchthatitdoesnotexpressHBsAgandplasmidencoding,eachHBsAgvariantwastransientlyco-transfectedintoHuH-7cells.ThesecretioncapacityandintracellularexpressionoftheHBVvirionsandHBsAgsintheirrespectivevariantswereanalyzedusingreal-timequantitativepolymerasechainreactionassaysandcommercialHBsAgenzyme-linkedimmunosorbentassays,respectively.RESULTS:AllvariantsexhibitedlowerlevelsofHBsAgsecretionintothemediumcomparedwiththewildtype.Inparticular,ineightofthetenvariants,verylowlevelsofHBsAgsecretionthatweresimilartothenegativecontrolweredetected.Incontrast,mostvariants(9/10)exhibitednormalvirionsecretioncapacitiescomparablewith,orevenhigherthan,thewildtype.ThisprovidednewinsightintotheintrinsicnatureofoccultHBVinfection,whichleadstoHBsAgsero-negativenessbuthashorizontalinfectivity.Furthermore,mostvariantsgeneratedhigherreactiveoxidativespeciesproductionthanthewildtype.ThisfindingprovidespotentiallinksbetweenoccultHBVinfectionandliverdiseaseprogression.CONCLUSION:ThepresentlyobtaineddataindicatethatdeficiencyinthesecretioncapacityofHBsAgvariantsmayhaveapivotalfunctionintheoccultinfectionsofHBVgenotypeC.

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：在最后十年期间是的胆汁分泌物的概念仅仅把净化的部件加到肠的混合便于胖消化/吸收并且消除方面产品的一个方法他我新陈代谢更加演变。在肠胃病学的世界杂志是在它“热点话题”的节出版的微型评论的系列，我们将打算在这块地里给我们的知识的简短却更新的概述。这封介绍的信被打算谢谢在肠胃病学贡献了知识的这个区域的发展的所有科学家。

简介：Objective:Todetectthemodulationofcytokinesproductionbyacutepromyelocyticleukemia(APL)cellsbeforeorafterexposuretoall-transretinoicacid(ATRA).Methods:DiagnoseswereperformedaccordingtotheFABcytologicalclassificationcriteriaandcytogeneticcriteria.BonemarroworbloodsamplesfromAPLpatientswerecollectedinheparinizedmicrofugetube.PrimaryAPLcellswereseparatedandpurifiedbytraditionalFicoll-Hypaquedensitycentrifugationandenrichedafteradherencetoplasticsurfaces.IL-1(,IL-6,IL-8,TNF(andG-CSFlevelsinthesupernatantsofculturedleukemiacellswereestimatedbyELISAmethod.NBTmethodwasusedtodetectthedifferentiationofAPLcellsatthesametime.Results:96hafterexposuretoATRAat10-6Minvitroor60mg/dayinvivo,APLcellsshowedasignificantincreaseofIL-1((P<0.05)andG-CSF(P<0.05)production,andasignificantdecreaseofIL-6(P<0.05)andIL-8(P<0.05),however,therewasnoobviousvariationofTNF(.Ontheotherhand,theproliferationofAPLcellsinvitrowasstatisticallycorrelatedtotheIL-1(secretionorG-CSFsecretion.AndthecellnumberratioinpatientswithdetectableIL-1(orG-CSFwashigherthanthatwithoutdetectableIL-1(orG-CSF.Conclusion:IL-1(andG-CSFsecretionmayplayanimportantroleintheproliferationofAPLcellsafterexposuretoATRA.

简介：Salmeterol是长行动的β；激活adenylatecyclase的2收缩筋，引起长持续的bronchodilation并且被用于许多年到控制气喘。然而，很少信息都不关于salmeterol的immunoregulatory效果是可得到的。我们发现salmeterol减少在表示了肿瘤坏死factor-alpha，interleukin-1和interleukin-6的质问变应原的老鼠的一个模型的支持inflammatorycytokines的生产。树枝状的房间(DC)是介绍抗原的房间并且在航线充当哨兵。我们发现了那salmeterol(10−5mol/l)减少了lipopolysaccharide引起的发炎(0.1µ；g/ml)在激活的鼠科的骨头导出髓的DC。而且，西方的污点证明这保护的效果被禁止通过原子factor-kappaB发信号部分调停(NF-κ；B)，激活mitogen的蛋白质kinase(MAPK)小径和津贴的戏剧性地减少的层次。我们建议salmeterol由modulatingDC调整导致变应原的气喘的发炎。在结论，我们提供DC是为对气喘的salmeterol的行动负责的目标免疫者房间的证据。

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简介：AbstractBackground:There is growing evidence that 5-fluorouracil (5-FU) combined with therapeutic trauma can effectively induce skin repigmentation in vitiligo patients who are unresponsive to conventional treatments. Previous studies have mainly focused on identifying the antimitotic activity of 5-FU for the treatment of skin cancer, but few studies have investigated its extra-genotoxic actions favoring melanocyte recruitment.Methods:We utilized the full thickness excisional skin wound model in Dct-LacZ transgenic mice to dynamically assess the migration of melanocytes in the margins of wounds treated with or without 5-FU. The in-situ expression of CXCL12 was examined in the wound beds using immunofluorescence staining. Quantitative real-time polymerase chain reaction and Western blotting analyses were performed to detect the expression levels of CXCL12 mRNA and protein in primary mouse dermal fibroblasts treated with or without 5-FU. Transwell assays and fluorescein isothiocyanate (FITC)-phalloidin staining were used to observe cell migration and filamentous actin (F-actin) changes of melan-a murine melanocytes.Results:Whole mount and cryosection X-gal staining showed that the cell numbers of LacZ-positive melanocytes were much higher in the margins of dorsal and tail skin wounds treated with 5-FU compared with the controls. Meanwhile, CXCL12 immunostaining was significantly increased in the dermal compartment of wounds treated with 5-FU (control vs. 5-FU, 22.47 ± 8.85 vs. 44.69 ± 5.97, P < 0.05). Moreover, 5-FU significantly upregulated the expression levels of CXCL12 mRNA (control vs. 5-FU, 1.00 ± 0.08 vs. 1.54 ± 0.06, P < 0.05) and protein (control vs. 5-FU, 1.00 ± 0.06 vs. 2.93 ± 0.10, P < 0.05) in cultured fibroblasts. Inhibition of the CXCL12/CXCR4 axis suppressed melanocyte migration in vitro using a CXCL12 small interfering RNA (siRNA) or a CXCR4 antagonist (AMD3100).Conclusion:5-FU possesses a pro-pigmentary activity through activation of the CXCL12/CXCR4 axis to drive the chemotactic migration of melanocytes.

简介：AbstractBackground:Tourette syndrome (TS) is a neuropsychiatric disorder with onset in childhood that warrants effective therapies. Gut microbiota can affect central physiology and function via the microbiota-gut-brain axis. Therefore, the gut microbiota plays an important role in some mental illnesses. A small clinical trial showed that fecal microbiota transplantation (FMT) may alleviate TS symptoms in children. Herein, FMT effects and mechanisms were explored in a TS mouse model.Methods:TS mice model (TSMO) (n = 80) were established with 3,3＇-iminodipropionitrile, and 80 mice were used as controls. Mice were grouped into eight groups and were subjected to FMT with feces from children or mice with or without TS, or were given probiotics. Fecal specimens were collected 3 weeks after FMT. 16S rRNA sequencing, behavioral observation, and serum serotonin (5-HT) assay were performed. Differences between groups were analyzed using Mann-Whitney U test and Kolmogorov-Smirnov (KS) tests.Results:A total of 18 discriminative microbial signatures (linear discriminant analysis score > 3) that varied significantly between TS and healthy mice (CONH) were identified. A significant increase in Turicibacteraceae and Ruminococcaceae in TSMO after FMT was observed (P < 0.05). Compared with non-transplanted TSMO, the symptoms of those transplanted with feces from CONH were alleviated (W = 336, P = 0.046). In the probiotic and FMT experiments, the serum 5-HT levels significantly increased in TSMO that received probiotics (KS = 1.423, P = 0.035) and in those transplanted with feces from CONH (W= 336.5, P = 0.046) compared with TSMO without transplantation.Conclusions:This study suggests that FMT may ameliorate TS by promoting 5-HT secretion, and it provides new insights into the underlying mechanisms of FMT as a treatment for TS.

简介：AbstractObjective:This study was performed to investigate the effects of honokiol on the activation of transient receptor potential channel V1 (TRPV1) and the secretion of thymic stromal lymphopoietin (TSLP) in a human benign epidermal keratinocyte line (HaCaT).Methods:HaCaT keratinocytes were cultivated and divided into six groups: capsaicin-induced model control group, capsazepine control group, solvent control group, and three honokiol treatment groups (7.81, 15.63, and 31.25 mg/L of honokiol). The effect of honokiol on calcium (Ca2+) influx was measured by a Ca2+ fluorescence imaging system. The fluorescence intensity (F) of cells was measured. The rate of change in F (ΔF/F0) was calculated, and the ΔF/F0-time curve was constructed. HaCaT keratinocytes were stimulated with polyinosinic:polycytidylic acid, recombinant human tumor necrosis factor α, and recombinant human interleukin 4. Different concentrations of honokiol (15.63, 7.81, and 3.91 mg/L) were added to the cells in the respective honokiol groups; 20 mg/L of dexamethasone or 0.5% dimethyl sulfoxide was added to the cells in the positive control group or solvent control group. The TSLP concentration in the HaCaT keratinocytes of each group was detected by enzyme-linked immunosorbent assay. Statistical analysis was performed by one-way analysis of variance and Dunnett t test.Results:The capsaicin-induced Ca2+ fluorescence intensity in HaCaT keratinocytes was significantly inhibited in the 31.25 mg/L honokiol group; ΔF/F0 at 45 second was 0.76 in the model control group and 0 in the 31.25 mg/L honokiol group. The TSLP level in the 15.63 and 7.81 mg/L honokiol groups was lower than that in the solvent control group (t= 7.382, P= 0.003, and t= 2.766, P= 0.023, respectively), while the TSLP level in the 3.91 mg/L honokiol group was not significantly different from that in the solvent control group (t= 1.872, P= 0.124).Conclusions:Honokiol inhibited the Ca2+ influx induced by capsaicin (TRPV1 agonist) in HaCaT keratinocytes. Honokiol has an inhibitory effect on TSLP secretion in HaCaT keratinocytes.

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