ICAM-1在心血管疾病中的作用

细胞间黏附因子-1(intercellular adhesion molecule-1,ICAM-1)是免疫球蛋白超家族的成员之一,它可以通过识别其受体介导细胞间的黏附,参与多种炎症反应过程。近年来的研究结果显示,ICAM-1与心血管疾病的发生与发展有密切关系,本文对近年来国内外学者对ICAM-1与心血管疾病的关系做一综述。     

银杏达莫注射液联合地塞米松治疗突发性耳聋的疗效及对血清sVCAM-1、CGRP水平的影响

目的:探讨银杏达莫注射液联合地塞米松治疗突发性耳聋的的疗效及对血清可溶性血管细胞间黏附因子-1(sVCAM-1)、降钙素基因相关肽(CGRP)水平的影响。方法:选择2017年10月到2019年3月于我院进行治疗的突发性耳聋患者70例作为研究对象,根据随机数表法将其分为观察组(n=36)和对照组(n=34)。对照组使用地塞米松治疗,观察组在对照组的基础上加用银杏达莫进行治疗。比较两组的临床疗效、治疗前后血清s VCAM-1、CGRP水平、平均听阀比、耳鸣残疾量表(THI)评分的变化及并发症的发生情况。结果:治疗后,观察组总有效率为94.44%,显著高于对照组(73.53%,P0.05)。两组患者治疗后血清s VCAM-1、CGRP水平、平均听阀比、THI评分均较治疗前显著改善,且观察组患者血清s VCAM-1水平、平均听阀比、THI评分均显著低于对照组,血清CGRP水平显著高于对照组(P0.05)。治疗期间,观察组患者并发症总发生率为11.11%,显著低于对照组(32.35%,P0.05)。结论:银杏达莫联合地塞米松治疗突发性耳聋的效果显著优于单用地塞米松治疗,这可能与其显著改善患者血清s VCAM-1、CGRP水平有关。     

黄芪对急性白血病患者血清黏附分子水平影响的临床研究

目的:探讨黄芪对急性白血病病人可溶性细胞间黏附分子-1和可溶性血管细胞黏附分子-1水平的影响。方法:64例初治急性白血病患者随机分为化疗组32例和化疗加黄芪组32例,采用酶联免疫吸附测定方法(EuSA法),对治疗前后的血清可溶性细胞间黏附分子-1和可溶性血管细胞黏附分子-1水平进行检测。结果:①与正常组比较,急性白血病病人治疗前后可溶性细胞间黏附分子-1和可溶性血管细胞黏附分子-1水平升高(P<0 05)。②治疗后,化疗加黄芪组与化疗组血清可溶性细胞间黏附分子-1和可溶性血管细胞黏附分子-1水平均下降(P<0 05),化疗加黄芪组下降尤为明显(P<0 05)。结论黄芪可通过降低白血病血清sICAM-1和sVCAM-1水平的而发挥抗肿瘤作用。     

腰大池引流联合法舒地尔治疗动脉瘤性蛛网膜下腔出血的疗效及对血清sICAM-1、FABP、MCP-1水平和脑积水形成的影响

目的:分析腰大池引流联合法舒地尔治疗动脉瘤性蛛网膜下腔出血的疗效及对血清可溶性细胞间黏附分子-1(sICAM-1)、脂肪酸结合蛋白质(FABP)、核细胞趋化蛋白(MCP-1)水平和脑积水形成的影响。方法:选择我院2016年3月~2018年3月收治的112例动脉瘤性蛛网膜下腔出血患者,按随机数字表法分为对照组(n=48)和研究组(n=64)。对照组采用腰大池引流治疗,研究组基于对照组联合法舒地尔治疗。比较两组临床疗效,治疗前后血清sICAM-1、FABP、MCP-1水平、血压、大脑中动脉血流参数水平和神经功能的变化,脑积水发生率及不良反应发生情况。结果:治疗后,研究组总有效率显著高于对照组(89.02%vs.72.91%,P<0.05)。两组治疗后血清sICAM-1、FABP、MCP-1、血压、大脑中动脉血流参数水平和神经功能缺损评分量表(NIHSS)均较治疗前下降,格拉斯哥昏迷评分(GCS)均较治疗前上升,研究组以上指标较对照组改变更明显(均P<0.05)。两组不良反应发生情况比较差异无统计学意义(P>0.05)。结论:腰大池引流联合法舒地尔治疗动脉瘤性蛛网膜下腔出血的疗效明显优于单用腰大池引流治疗,其可显著降低血清sICAM-1、FABP、MCP-1水平,降低脑积水发生率,改善患者预后。     

非布司他对痛风合并高尿酸血症患者血清sICAM-1, ET-1 及尿酸水平的影响

目的:探讨非布司他对痛风合并高尿酸血症患者血清内皮素-1(ET-1)、细胞间粘附分子-1(ICAM-1)及尿酸水平的影响。方法:收集在我院就诊或住院治疗的80例痛风合并高尿酸血症患者,随机分为实验组和对照组,每组40例。对照组患者给予别嘌呤醇片治疗;实验组患者给予非布司他片治疗。观察并比较两组患者治疗前后血尿酸、s ICAM-1、ET-1水平及临床疗效。结果:与治疗前相比,两组患者治疗后的血尿酸、s ICAM-1、ET-1水平均显著降低(P0.05);与对照组相比,实验组患者的血尿酸、s ICAM-1、ET-1水平较低(P0.05),临床治疗总有效率较高(P0.05)。结论:非布司他能够降低痛风合并高尿酸血症的s ICAM-1、ET-1及尿酸水平,且临床疗效较好。     

螺内酯治疗老年高血压的临床疗效及对血清炎性因子水平的影响

目的:探讨螺内酯治疗老年高血压的临床疗效及对血清炎性因子水平的影响。方法:选择2017年6月至2018年12月我院收治的144例老年高血压患者,根据治疗方法的不同将其分为观察组80例与对照组64例。对照组给予硝苯地平治疗,观察组给予螺内酯治疗,两组均治疗观察4周,对比两组治疗前后的血清内皮素(Endothelin,ET)-1和血栓素(Thromboxane,TX)-B2含量、白介素(Interleukin,IL)-6与可溶性细胞间粘附分子(Soluble intercellular adhesion molecule,s ICAM-1)水平的变化及临床疗效。结果:所有患者完成治疗,无严重不良反应发生。治疗后,观察组的总有效率为98.8%,显著高于对照组(85.9%,P0.05)。两组治疗后24 h收缩压(Systolic blood pressure,SBP)和舒张压(Diastolic bloodpressure,DBP)、血清ET-1、TX-B2、IL-6与s ICAM-1水平均显著低于治疗前(P0.05),且观察组以上指标均明显低于对照组(P0.05)。结论:螺内酯治疗老年高血压的临床疗效明显优于硝苯地平治疗,可能与其明显抑制血清与ET-1、TX-B2、IL-6与s ICAM-1水平有关。     

血管细胞黏附分子-1对卵巢癌细胞凋亡的影响及机制研究

目的:探讨过表达血管细胞黏附分子-1(vascular cell adhesion molecule-1,VCAM-1)对卵巢癌细胞凋亡的影响。方法:构建过表达VCAM-1的慢病毒载体GV358-VCAM1+,转染人类卵巢癌IGROV1细胞株,利用嘌呤霉素筛选稳定表达VCAM-1的IGROV1细胞,通过倒置荧光显微镜下观察绿色荧光,确定细胞转染效率,Western blot及RT-PCR法确定卵巢癌细胞VCAM-1蛋白和m RNA水平;采用流式细胞仪检测过表达VCAM-1的IGROV1的细胞凋亡变化,western blot法检测凋亡相关蛋白(Bcl-2、Bax、Casepase-3、Cleaved Casepase-3)以及STAT3、p-STAT3蛋白表达水平的变化。结果:成功构建的慢病毒载体GV358-VCAM1+在IGROV1细胞中的转染效率达到85%以上,转染细胞的VCAM-1蛋白及m RNA水平均呈稳定表达;VCAM-1过表达卵巢癌细胞的细胞凋亡显著高于空载体对照组(P=0.0149);Bax、Casepase-3、Cleaved Casepase-3表达水平均较对照组显著升高(P0.01),Bcl-2、p-STAT3表达水平明显低于对照组(P0.01),但STAT3表达水平无显著改变。结论:VCAM-1可能通过下调STAT3的磷酸化水平诱导卵巢癌细胞凋亡。     

高脂高糖饮食对自发性高血压大鼠腹主动脉舒张功能及VCAM-1和ICAM-1mRNA表达的影响

目的:探讨高脂高糖饮食对自发性高血压大鼠(spontaneously hypertensive rats,SHR)腹主动脉血管舒张功能及血管间粘附分子-1 (vascular adhesion molecule-1,VCAM-1)和细胞间粘附分子-1(intercellular adhesion molecule-1,ICAM-1)mRNA表达的影响.方法:将24只6周龄雄性SHR大鼠随机分成高脂高糖饲料组(实验组,n=12)和普通饲料组(对照组,n=12).每3周测量其空腹体重,12周后处死大鼠,分别取两组动物的腹主动脉做离体血管环对乙酰胆碱(Acetylcholine,Ach)的舒张功能实验,并提取主动脉总RNA,通过实时定量RT-PCR实验检测其VCAM-1和ICAM-1 mRNA的表达.结果:从第6周开始,实验组SHR的体重较对照组明显增加(P＜0.01).12周时,实验组血管环对Ach的最大舒张率较对照组明显降低(69.20± 5.25 vs.79.10± 3.84,P＜0.01);实验组动脉VCAM-1 mRNA的相对表达量是对照组的1.97倍,差异有统计学意义(197.91±22.16 vs.100.33±11.44,P＜0.01),而两组ICAM-1mRNA表达的比较差异无统计学意义(97.75±8.05 vs.100.25±10.83,P＞0.05).结论:高脂高糖饮食能致SHR腹主动脉血管舒张功能明显降低,可能与其显著增加其主动脉VCAM-1 mRNA的表达有关.     

奥拉西坦联合脉血康胶囊治疗急性脑梗死的疗效评价及对血清VCAM-1、ICAM-1、MMP-9水平的影响

目的:研究奥拉西坦联合脉血康胶囊治疗急性脑梗死的疗效及对血清血管细胞间黏附分子-1(VCAM-1)、细胞间粘附分子-1(ICAM-1)、基质金属蛋白酶-9(MMP-9)水平的影响。方法:选择2014年3月~2015年3月于我院就诊的急性脑梗死患者90例,按抽签法分为实验组和对照组,每组45例。两组均配合调脂、抗血小板、活血化瘀、维持电解质平衡、神经保护、降颅内压等常规治疗,必要时进行氧疗。对照组在此基础上加用奥拉西坦注射液治疗,每次4 g,加入250 mL生理盐水进行静脉滴注,每天1次。实验组在对照组基础上加用脉血康胶囊治疗,每次3粒,每天3次。两组治疗疗程均为3周。观察和比较两组的临床疗效,治疗前后NIHSS评分、血清VCAM-1、ICAM-1、MMP-9水平、MMSE、ADL评分的变化及不良反应的发生情况。结果:治疗后,实验组总有效率显著高于对照组(P0.05);NIHSS评分显著低于对照组(P0.05);血清VCAM-1、ICAM-1、MMP-9水平显著低于对照组(P0.05);MMSE、ADL评分显著高于对照组(P0.05);不良反应总发生率显著低于对照组(P0.05)。结论:奥拉西坦联合脉血康胶囊治疗急性脑梗死能够有效提高其临床疗效,显著促进神经功能的恢复,可能与其有效降低血清VCAM-1、ICAM-1、MMP-9水平,改善血管内皮功能有关。     

可溶性细胞间粘附分子-1在新生儿缺氧缺血性脑病血清中的表达及临床意义

目的:探讨可溶性细胞间粘附分子-1(ICAM-1)在新生儿缺氧缺血性脑病(HIE)血清中的表达及其与病情严重程度的关系。方法:采用酶联免疫吸附双抗体夹心法(ELISA)检测45例HIE新生儿和50例健康新生儿血清中可溶性ICAM-1水平。结果:HIE组血清可溶性ICAM-1浓度为(159.25±25.62)ng/ml,对照组血清可溶性ICAM-1浓度为(53.35±12.42)ng/ml,两组相比较有显著性并差异(P<0.05);轻、中、重度HIE患儿血清可溶性ICAM-1浓度与对照组比较显著升高(P<0.05),在HIE各组中可溶性ICAM-1浓度为重度>中度>轻度,各组相比较有显著性差异(P<0.05);HIE患儿血清可溶性ICAM-1水平与临床分度呈正相关相关(r=0.652,P<0.01)。结论:可溶性ICAM-1在HIE新生儿血清中呈高表达,可溶性ICAM-1的水平与病情严重程度密切相关。可溶性ICAM-l在新生儿缺氧缺血性脑损伤中起着重要作用。     

Bmi1 cooperates with Dnmt1-associated protein 1 in gene silencing

Polycomb group (PcG) proteins are involved in gene silencing through chromatin modifications. Among polycomb repressive complexes (PRCs), PRC1 exhibits H2A-K119 ubiquitin E3 ligase activity. However, the molecular mechanisms underlying PRC1-mediated gene silencing remain largely obscure. In this study, we found that Bmi1 directly interacts with Dnmt-associated protein 1 (Dmap1), which has been characterized to associate with the maintenance DNA methyltransferase, Dnmt1. Bmi1 was demonstrated to form a ternary complex with Dmap1 and Dnmt1 with Dmap1 in the central position. Chromatin immunoprecipitations confirmed the ternary complex formation within the context of the PRC1 at the Bmi1 target loci. Loss of Dmap1 binding to the Bmi1 target loci was tightly associated with derepressed gene expression in Bmi1-/- cells. Dmap1 knockdown exhibited the same impact as Bmi1 knockout did on the expression of Bmi1 targets, including Hox genes. Collectively, our findings suggest that Bmi1 incorporates Dmap1 in polycomb gene silencing.     

Association of SULT1A1 and UGT1A1 polymorphisms with breast cancer risk and phenotypes in Russian women

Estrogens are critical for breast cancer initiation and development. Sulfotransferase 1A1 (SULT1A1) and UDP-glucuronosyltransferase 1A1 (UGT1A1) conjugate and inactivate both estrogens and their metabolites, thus preventing estrogen-mediated mitosis and mutagenesis. SULT1A1 and UGT1A1 are both polymorphic, and different alleles encode functionally different allozymes. We hypothesize that low-activity alleles SULT1A1*2 and UGT1A1*28 are associated with higher risk for breast cancer and more severe breast tumor phenotypes. We performed a case-control study, which included 119 women of Russian ancestry with breast cancer and 121 age-matched Russian female controls. We used PCR followed by pyrosequencing to determine the SULT1A1 and UGT1A1 genotypes. Allele UGT1A1*28 was present at a higher frequency than the wild-type UGT1A1*1 allele in breast cancer patients as compared to controls (P = 0.002, OR = 1.79, CI 1.23–2.63). Consistently, the frequency of genotypes that contain allele UGT1A1*28 in the homozygous or the heterozygous state was greater in breast cancer patients as compared with the frequency of the wild-type UGT1A1*1/*1 genotype (P = 0.003, OR = 4.00, CI 1.49–11.11 and P = 0.014, OR = 2.04, CI 1.14–3.57, respectively). Individuals carrying allele UGT1A1*28 in the homo-or heterozygous state had larger breast tumors (>2 cm) as compared to the group with high-activity genotypes (P = 0.011, IR = 3.44, CI 1.42–8.36). No association was observed between any of the SULT1A1 genotypes and breast cancer risk or phenotypes. Our data suggest that UGT1A1, but not SULT1A1, genotypes are important for breast cancer risk and phenotype in Russian women. Published in Russian in Molekulyarnaya Biologiya, 2006, Vol. 40, No. 2, pp. 263–270. The article was translated by the authors.     

应用寡核苷酸芯片并行检测CYP1A1和 GSTM1基因多态性

利用寡核苷酸芯片检测方法分析CYP1A1单核苷酸多态性 (SNP)和GSTM1缺失与否 ,实验结果证明了寡核苷酸芯片技术可并行、准确、高效地检测基因的单核苷酸多态性和其他类型的基因多态型 ,可为疾病遗传易感性及单体型的研究提供强有力的研究工具。采用该寡核苷酸芯片 ,检测了 84份正常人的血液DNA样本 ,其中GSTM1基因缺失率达到 4 7 6 % ,接近报道数值。统计分析发现 ,CYP1A1m1 m2的 3种基因型组合TT AG、TT GG和TC GG的发生频率都为 0 ,而根据实验得到的m1和m2各自基因型数据计算 ,它们的发生频率应是11 4 %、2 6 %和 3 1% ,所以推测在所检测的样本中没有T(m1位点 )和G(m2位点 )的连锁组合 ,即m1和m2位点的组合只有 3种单体型 :T A、C A和C G ,其发生频率分别是 6 9 6 %、7 7%和 2 2 6 %。     

Galectin-1 interacts with beta-1 subunit of integrin

Galectin-1, a beta-galactoside-binding dimeric lectin, is involved in adhesion, migration, and proliferation of vascular smooth muscle cells (SMC), the key steps in the development of atherosclerosis and restenosis. Here we investigated the molecular basis of the interactions between galectin-1 and SMCs. Galectin-1 modulated SMC attachment in a dose- and beta-galactoside-dependent manner. Direct binding of galectin-1 to beta1 integrin was detected by the immune precipitation of beta1 integrin after chemical cross-linking of 125I-labelled galectin-1 to the cell surface proteins. Galectin-1 transiently increased availability of beta1 integrins on the cell surface to antibodies against beta1 integrin. Incubation of SMCs with galectin-1 transiently increased the amount of the active form of beta1 integrin and tyrosine phosphorylation of two cytoskeleton-associated proteins; one of them coincided with focal adhesion kinase (FAK). Galectin-1 is likely to affect SMC adhesion by interacting with beta1 integrin on the cell surface of SMCs and inducing outside-in signalling.     

Intersectin 1 forms complexes with SGIP1 and Reps1 in clathrin-coated pits

Intersectin 1 (ITSN1) is an evolutionarily conserved adaptor protein involved in clathrin-mediated endocytosis, cellular signaling and cytoskeleton rearrangement. ITSN1 gene is located on human chromosome 21 in Down syndrome critical region. Several studies confirmed role of ITSN1 in Down syndrome phenotype. Here we report the identification of novel interconnections in the interaction network of this endocytic adaptor. We show that the membrane-deforming protein SGIP1 (Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1) and the signaling adaptor Reps1 (RalBP associated Eps15-homology domain protein) interact with ITSN1 in vivo. Both interactions are mediated by the SH3 domains of ITSN1 and proline-rich motifs of protein partners. Moreover complexes comprising SGIP1, Reps1 and ITSN1 have been identified. We also identified new interactions between SGIP1, Reps1 and the BAR (Bin/amphiphysin/Rvs) domain-containing protein amphiphysin 1. Immunofluorescent data have demonstrated colocalization of ITSN1 with the newly identified protein partners in clathrin-coated pits. These findings expand the role of ITSN1 as a scaffolding molecule bringing together components of endocytic complexes.     

Molecular docking of selected phytocompounds with H1N1 Proteins

The H1N1 influenza virus is a serious threat to human population. Oseltamivir and Zanamivir are known antiviral drugs for swine flu with observed side effects. These drugs are viral neuraminidase and hemagglutinin inhibitor prevents early virus multiplication by blocking sialic acid cleavage on host cells. Therefore, it is of interest to identify naturally occurring novel compounds to control viral growth. Thus, H1N1 proteins (neuraminidase and hemagglutinin) were screened with phytocompounds isolated from Tulsi plant (Ocimum sanctum L.) using molecular docking tools. This identified Apigenin as an alternative to Oseltamivir and Zanamivir with improved predicted binding properties. Hence, it is of interest to consider this compound for further in vitro and in vivo evaluation.     

TopBP1 functions with 53BP1 in the G1 DNA damage checkpoint

TopBP1 is a checkpoint protein that colocalizes with ATR at sites of DNA replication stress. In this study, we show that TopBP1 also colocalizes with 53BP1 at sites of DNA double‐strand breaks (DSBs), but only in the G1‐phase of the cell cycle. Recruitment of TopBP1 to sites of DNA replication stress was dependent on BRCT domains 1–2 and 7–8, whereas recruitment to sites of DNA DSBs was dependent on BRCT domains 1–2 and 4–5. The BRCT domains 4–5 interacted with 53BP1 and recruitment of TopBP1 to sites of DNA DSBs in G1 was dependent on 53BP1. As TopBP1 contains a domain important for ATR activation, we examined whether it contributes to the G1 cell cycle checkpoint. By monitoring the entry of irradiated G1 cells into S‐phase, we observed a checkpoint defect after siRNA‐mediated depletion of TopBP1, 53BP1 or ATM. Thus, TopBP1 may mediate the checkpoint function of 53BP1 in G1.     

Euphorbia factor L1 reverses ABCB1-mediated multidrug resistance involving interaction with ABCB1 independent of ABCB1 downregualtion

Euphorbia factor L1 (EFL1) belongs to diterpenoids of genus Euphorbia. In this article, its reversal activity against ABCB1-mediated MDR in KBv200 and MCF-7/adr cells was reported. However, EFL1 did not alter the sensitivity of KB and MCF-7 cells to chemotherapeutic agents. Meanwhile, EFL1 significantly increased accumulation of doxorubicin and rhodamine 123 in KBv200 and MCF-7/adr cells, showing no significant influence on that of KB and MCF-7 cells. Furthermore, EFL1 could enhance the ATP hydrolysis activity of ABCB1 stimulated by verapamil. At the same time, EFL1 inhibited the efflux of ABCB1 in KBv200 and MCF-7/adr cells. In addition, EFL1 did not downregulate expression of ABCB1 in KBv200 and MCF-7/adr cells either in mRNA or protein level.