简介:摘要目的研究痹祺胶囊水提取物对成骨细胞MC3T3-E1的作用及其机制。方法(1)体外培养成骨细胞MC3T3-E1,分为对照组及痹祺胶囊水提取物(0.125,0.25,0.5,1,2,4g·L-1)干预组,48h后,MTT法检测细胞增殖情况(2)培养MC3T3-E1细胞,分为对照组及痹祺胶囊水提取物(0.25,0.5,1g·L-1)干预组,48h后,用RT-PCR检测骨形成蛋白-2(BMP-2)mRNA,骨钙素(OC)mRNA以及碱性磷酸酶(ALP)mRNA表达。结果(1)痹祺胶囊水提取物各干预组MC3T3-E1细胞的OD值均明显升高,与对照组比较有统计学差异(P<0.01)。(2)痹祺胶囊水提取物0.5g·L-1组的BMP-2mRNA,ALPmRNA和OCmRNA表达均明显增强,痹祺胶囊水提取物0.25g·L-1组的ALPmRNA和痹祺胶囊水提取物1g·L-1组的OCmRNA表达也明显增强,与对照组比较均有统计学差异(P<0.05或P<0.01)。结论痹祺胶囊水提取物可促进成骨细胞MC3T3-E1增殖,通过上调BMP-2mRNA,ALPmRNA和OCmRNA的表达,也可促进成骨细胞的分化功能。
简介:摘要颅内黏液样间叶性肿瘤是一种罕见的肿瘤,分子遗传学伴EWSR1与CREB家族基因融合。本文报道1例9岁男性患儿,小脑占位性病变,肿瘤结节状生长,界限清楚,肿瘤细胞椭圆形、梭形或星芒状,疏密不等,大部分呈条索状或疏松网状分布于黏液性间质中,间质内可见“石棉样”纤维,局灶细胞较丰富,呈片状排列。免疫组织化学结果:波形蛋白阳性,结蛋白及CD68部分阳性,上皮细胞膜抗原及CD99弱阳性,胶质纤维酸性蛋白、Olig2、S-100蛋白、平滑肌肌动蛋白、p63、CD34等均阴性,p53野生型表达,热点区Ki-67阳性指数约20%。分子表型:荧光原位杂交检测到EWSR1基因分离,二代测序检测出EWSR1-CREB1及SELENOW-EWSR1融合基因。病理诊断为伴EWSR1-CREB1融合的颅内黏液样间叶性肿瘤。术后7个月,患者状态良好,无复发及转移。诊断时应与脑膜瘤、胶质瘤、伴EWSR1-CREB家族基因融合的其他肿瘤及骨外黏液样软骨肉瘤等形态相似的肿瘤鉴别。
简介:摘要:WNT1诱导信号通路蛋白1 (Wnt1 inducible signaling pathway protein 1,WISP1) 是一种富含半胱氨酸的蛋白质,属于CCN 蛋白家族。越来越多的研究表明WISP1在各种人类恶性肿瘤中发挥不同的生物学功能。新的研究证据显示WISP1蛋白与胃癌细胞增殖、凋亡、侵袭和转移密切相关。在这篇综述中,我们描述了WISP1蛋白在胃癌中的生理功能以及其如何参与胃癌发生进展过程。此外,我们讨论了WISP1有望成为胃癌的诊断标志物和/或治疗新靶点。
简介:摘要患儿 男,3岁9月龄,以“排稀便10个月、间断抽搐4个月”就诊,经乳糜泻抗体、人类白细胞抗原(HLA)-DQ基因检测、十二指肠病理活检明确诊断为乳糜泻,予去麦麸类饮食以及对症营养治疗后好转。随访过程中出现多饮多尿,查血糖明显升高,尿糖、尿酮体阳性,诊断为乳糜泻合并1型糖尿病,给予对症补充胰岛素治疗。随访6年患儿血糖控制平稳,生长发育正常。
简介:摘要目的了解新型狂犬疫苗“2-1-1”接种程序的临床应用效果,为新的接种方法积极推进进行前瞻性研究。方法对本社区2011年10月-2013年12月148例被被狗、猫、鼠等动物咬、抓伤人群进行按照就诊的先后顺序平均分为2组,观察组74例,实施“2-1-1”接种程序;对照组74例实施传统的“五针次法”接种程序。在接种程序中10d和接种程序结束后15d分别对患者进行血清抗狂犬病毒抗体水平进行统计比较,并进一步观察其影响因素。结果观察组与对照患者10d血清抗狂犬病毒抗体阳性率分别为56.76%、12.16%;接种程序完成后15d血清抗狂犬病毒抗体阳性率分别为97.30%、85.14%。抗体转阳率与年龄增长呈负相关。结论“2-1-1”狂犬疫苗接种程序完全符合药物动力学原理,它能迅速提高机体内血药浓度,并在短期内产生抗体,同时也减少患者就诊次数,更加方便患者。但疫苗的接种效果与患者各机体个体差异存在一定的联系,全程接种15d后应加强抗体水平的检测,如抗体阴性患者应积极寻找原因及加强接种。
简介:LFA-1andMac-1,twoβ2integrinmembersconstitutivelyexpressedonneutrophils,mediateleukocyterecruitmentcascadebybindingtothesameligandofICAM-1.TheslowrollingandfirmadhesionofleukocytesrelyonLFA-1whilethecellcrawlingisdependentonMac-1.Wehypothesizedthattheirdistinctroleswerelikelyattributedtothedifferencesinthebindingkineticsorinthediverseresponsesofoutside-inandinside-outsignaling.Inthisstudy,wecomparedtheICAM-1bindingfeaturesbetweensolubleormembrane-expressedLFA-1andMac-1withdifferentaffinityconformationsusingopticaltraptechnique.Ourdataindicatethattheaffinityup-regulationfromwidetype(WT)tohighaffinity(HA)isoff-ratedependentforLFA-1buton-ratedependentforMac-1.Thestructuralbasesofthisnewfindingwerefoundtobeconsistentwithourprevioussimulations.Theseresultsfurtheredourunderstandingontheirfunctiondifferencesundershearflow.
简介:AbstractBackground:Emerging evidence indicates that the sineoculis homeobox homolog 1-eyes absent homolog 1 (SIX1-EYA1) transcriptional complex significantly contributes to the pathogenesis of multiple cancers by mediating the expression of genes involved in different biological processes, such as cell-cycle progression and metastasis. However, the roles of the SIX1-EYA1 transcriptional complex and its targets in colorectal cancer (CRC) are still being investigated. This study aimed to investigate the roles of SIX1-EYA1 in the pathogenesis of CRC, to screen inhibitors disrupting the SIX1-EYA1 interaction and to evaluate the efficiency of small molecules in the inhibition of CRC cell growth.Methods:Real-time quantitative polymerase chain reaction and western blotting were performed to examine gene and protein levels in CRC cells and clinical tissues (collected from CRC patients who underwent surgery in the Department of Integrated Traditional and Western Medicine, West China Hospital of Sichuan University, between 2016 and 2018, n = 24). In vivo immunoprecipitation and in vitro pulldown assays were carried out to determine SIX1-EYA1 interaction. Cell proliferation, cell survival, and cell invasion were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, clonogenic assay, and Boyden chamber assay, respectively. The Amplified Luminescent Proximity Homogeneous Assay Screen (AlphaScreen) method was used to obtain small molecules that specifically disrupted SIX1-EYA1 interaction. CRC cells harboring different levels of SIX1/EYA1 were injected into nude mice to establish tumor xenografts, and small molecules were also injected into mice to evaluate their efficiency to inhibit tumor growth.Results:Both SIX1 and EYA1 were overexpressed in CRC cancerous tissues (for SIX1, 7.47 ± 3.54 vs.1.88 ± 0.35, t = 4.92, P = 0.008; for EYA1, 7.61 ± 2.03 vs. 2.22 ± 0.45, t = 6.73, P = 0.005). The SIX1/EYA1 complex could mediate the expression of two important genes including cyclin A1 (CCNA1) and transforming growth factor beta 1 (TGFB1) by binding to the myocyte enhancer factor 3 consensus. Knockdown of both SIX1 and EYA1 could decrease cell proliferation, cell invasion, tumor growth, and in vivo tumor growth (all P < 0.01). Two small molecules, NSC0191 and NSC0933, were obtained using AlphaScreen and they could significantly inhibit the SIX1-EYA1 interaction with a half-maximal inhibitory concentration (IC50) of 12.60 ± 1.15 μmol/L and 83.43 ± 7.24 μmol/L, respectively. Administration of these two compounds could significantly repress the expression of CCNA1 and TGFB1 and inhibit the growth of CRC cells in vitro and in vivo.Conclusions:Overexpression of the SIX1/EYA1 complex transactivated the expression of CCNA1 and TGFB1, causing the pathogenesis of CRC. Pharmacological inhibition of the SIX1-EYA1 interaction with NSC0191 and NSC0933 significantly inhibited CRC cell growth by affecting cell-cycle progression and metastasis.
简介:摘要1例随访1年余的3-磷酸甘油脱氢酶(GPD1)基因突变致婴儿期短暂性高甘油三酯血症(HTGTI)患儿并复习文献,发现HTGTI婴儿期起病为主,临床以肝大、脂肪肝、高脂血症、轻度转氨酶异常为特征。且有长期甚至延续至成年的肝脏脂肪代谢异常、肝酶升高以及生长发育问题,故长期干预及远期预后值得临床医生关注。
简介:摘要目的研究蜕膜各淋巴细胞亚群中程序性细胞死亡蛋白1(programmed cell death protein 1,PD-1)、程序性细胞死亡蛋白配体1(programmed cell death ligand 1,PD-L1)和淋巴细胞活化基因3(lymphocyte-activation gene 3,LAG-3)的表达,及其与子痫前期免疫失衡的关系。方法纳入2019年5月至2020年1月于山东第一医科大学附属省立医院剖宫产分娩的单胎妊娠子痫前期患者25例为子痫前期组,按照1∶1的比例选取剖宫产日期和分娩孕周匹配的产前检查正常并择期剖宫产分娩的健康单胎妊娠孕妇25例为正常妊娠组。剖宫产胎盘娩出后收集蜕膜组织。采用流式细胞技术测定PD-1、PD-L1和LAG-3在蜕膜T细胞、自然杀伤(natural killer,NK)和自然杀伤T(natural killer T,NKT)细胞表面的表达水平。采用两独立样本t检验比较2组间PD-1、PD-L1和LAG-3的表达差异。结果子痫前期组蜕膜中PD-1在T细胞和NK细胞表面的表达水平低于正常妊娠组(37.84±3.82与57.02±3.89,t=3.529,P<0.001;3.28±0.48与5.69±0.99,t=2.184,P=0.034),而在NKT细胞表面的表达水平2组差异无统计学意义(P=0.461)。子痫前期组蜕膜中PD-L1在NK细胞表面的表达水平低于正常妊娠组(0.60±0.11与1.32±0.19,t=3.319,P=0.002),而在T细胞和NKT细胞表面的表达水平2组差异无统计学意义(P值均>0.05)。子痫前期组蜕膜中LAG-3在T细胞和NKT细胞表面的表达水平低于正常妊娠组(2.32±0.36与4.09±0.67,t=2.335,P=0.024;35.40±4.97与56.27±4.49,t=3.282,P=0.002),而在NK细胞表面的表达水平2组差异无统计学意义(P=0.112)。结论免疫检查点PD-1、PD-L1和LAG-3在子痫前期蜕膜淋巴细胞亚群中表达水平明显降低,可能通过母胎界面免疫细胞过度激活参与子痫前期的免疫失衡。