小肠Crohn's病患者肠黏膜中DLG1和DLG5表达的临床观察

目的探讨小肠型克罗恩病(CD)肠黏膜中DLG1和DLG5的表达以及与临床关联分析。方法收集CD患者小肠手术切除标本45例,另收集15例小肠肿瘤以及右半结肠肿瘤手术标本中正常小肠组织作为对照组,采用免疫组织化学方法研究DLG1和DLG5在CD组患者和对照组小肠黏膜上皮组织中的表达,并进行临床观察分析。结果与对照组比较,CD患者小肠黏膜上皮细胞DLG1主要表达在细胞质中,两组患者DLG1表达部位有明显差别(P<0.01),表达量无明显差别。与对照组比较,CD组患者小肠黏膜上皮细胞DLG5均表达在细胞质中,CD组患者DLG5的表达量明显降低(P<0.01)。DLG1表达部位和DLG5表达量与CD患者临床特征无明显关联。结论 DLG5表达降低可能参与CD的发病过程。

产肠毒素性大肠杆菌侵染猪肠上皮细胞后DLG5基因的表达变化分析

为了揭示DLG5基因在机体抵抗大肠杆菌刺激过程中发挥的功能,本试验利用产肠毒素性大肠杆菌(F18ab、F18ac和K88ac)侵染猪肠上皮细胞系(IPEC-J2)模拟个体的致病过程,用实时荧光定量检测DLG5基因在感染前后的表达变化情况,在细胞水平上探讨DLG5基因表达水平与产肠毒素性大肠杆菌抗性的关系。结果表明,3种大肠杆菌的菌清和菌体刺激IPEC-J2后,DLG5基因表达水平均发生显著或极显著上调;并且由F18ab和K88ac这2种菌体刺激后DLG5基因表达水平上调的程度要极显著高于F18ac菌体刺激后的表达水平。本研究结果提示,猪DLG5基因表达和大肠杆菌的抗性具有密切关系,可能与其在一定程度上能够促进肠道屏障的结构稳定和功能发挥有关。

DLG5与克罗恩病相关性的研究进展

炎症性肠病(IBD)包括Crohn′s病(CD)和溃疡性结肠炎(UC),是一组胃肠道慢性反复发作的非特异性炎性疾病。CD的发病机制尚不明确,但近来一系列研究表明遗传因素在其发病中具有重要的作用。DLG5是一个引人注意的CD候选易感基因,此文就DLG5基因与CD的相关性研究进展作一综述。

Single nucleotide polymorphisms of OCTN1, OCTN2, and DLG5 genes in Greek patients with Crohn's disease

AIM: To validate novel single nucleotide polymorphisms (SNPs) in Greek patients with Crohn's disease (CD).METHODS: A total of 120 patients with CD, 85 patients with UC, and 100 unrelated healthy controls were genotyped. Genotyping was performed by allele-specific PCR or by PCR-RFLP analysis.RESULTS: Our results showed that the 1672T and -207C alleles were obviously over-represented in CD patients only (P＜0.01 and P＜0.05, respectively) compared to the control population. The G113A polymorphism was completely absent in our studied population. The odds ratio for the carriage of the TC haplotype was 2.21 for CD patients as compared with controls. Additionally, the frequency of the TC haplotype was increased in patients with ileocolitis or colitis, and was mainly associated with the fibrostenotic phenotype of the disease. Furthermore, when the TC haplotype was compared jointly with the carriage of at least one mutation of the NOD2/CARD15 gene, there was an increased risk for CD, but not for UC, compared to controls. Regarding the location of the disease, the concomitant presence of the TC haplotype and NOD2/CARD15 mutations was mainly associated with ileocolitis or ileitis. CONCLUSION: Collectively, our results suggest that the 1672T variant of the OCTN1 gene and the -207C variant of the OCTN2 gene represent risk factors for CD in the Greek population.

Role of CARD15,DLG5 and OCTN genes polymorphisms in children with inflammatory bowel diseases

AIM: To investigate the contribution of variants of CARD15, OCTN1/2 and DLG5 genes in disease predispo- sition and phenotypes in a large Italian cohort of pediatric patients with inflammatory bowel diseases (IBD). METHODS: Two hundred patients with Crohn’s disease (CD), 186 ulcerative colitis (UC) patients, 434 par- ents (217 trios), and 347 healthy controls (HC) were studied. Polymorphisms of the three major variants of CARD15, 1672C/T and -207G/C SNPs for OCTN genes, IGR2096a_1 and IGR2198a_1 SNPs for the IBD5 locus, and 113G/A variant of the DLG5 gene were evaluated. Potential correlations with clinical sub-phenotypes were investigated. RESULTS: Polymorphisms of CARD15 were significantly associated with CD, and at least one variant was found in 38% of patients (15% in HC, OR = 2.7, P < 0.001). Homozygosis for both OCTN1/2 variants was more com- mon in CD patients (1672TT 24%, -207CC 29%) than in HC (16% and 21%, respectively; P = 0.03), with an in- creased frequency of the TC haplotype (44.8% vs 38.3% in HC, P = 0.04). No association with the DLG5 variant was found. CD carriers of OCTN1/2 and DLG5 variants more frequently had penetrating disease (P = 0.04 and P = 0.01), while carriers of CARD15 more frequently had ileal localization (P = 0.03). No gene-gene interaction was found. In UC patients, the TC haplotype was morefrequent (45.4%, P = 0.03), but no genotype/phenotype correlation was observed. CONCLUSION: Polymorphisms of CARD15 and OCTN genes, but not DLG5 are associated with pediatric on- set of CD. Polymorphisms of CARD15, OCTN, and DLG5 genes exert a weak influence on CD phenotype.

DLG5与炎症性肠病的研究进展

炎症性肠病(IBD)是一种多基因疾病,具有遗传易感性,主要表现为家族聚集倾向和单卵双生共患率显著增高[1]。近年来,随着人类基因组和多基因疾病研究方法的进展,相继发现多个IBD的基因易感位点。其中DLG5是近年来研究热点之一的易感基因,争议也颇多。

Macrophage-secreted exosomes inhibit breast cancer cell migration via the miR-101-3p/DLG5 axis

Objective:To investigate the role of macrophages in regulating breast cancer cell migration and its related mechanisms.Methods:Human leukemia monocytic cell line THP-1-secreted exosomes were isolated using multi-step ultracentrifugation and verified using nanoparticle tracking analysis.Differentially expressed miRNAs were identified using RNA sequencing.Overexpression of inhibitors of hsa-miR-101-3p in breast cancer MDA-MB-231 cells was performed by infecting their lentiviral constructs.The luciferase reporter assay was used to evaluate the interaction of DLG5 and miR-101.DGL5 expression was detected using qRT-PCR and Western blot analyses.Results:The migration of breast cancer cells was significantly inhibited after addition of exosomes.RNA sequencing results showed that miR-101-3p expression was significantly upregulated.Targetscan analysis predicted that miR-101-3p could target DLG5,and this prediction was verified using the luciferase assay.The addition of the miR-101-3p precursor significantly increased the expression of miR-101-3p,and the mRNA and protein levels of DLG5 were suppressed.In contrast,inhibiting the expression of miR-101-3p increased the mRNA and protein levels of DLG5.Furthermore,the scratch assay showed that inhibiting miR-101-3p could promote the migration of MDA-MB-231 cells.Conclusions:Macrophage exosomes can inhibit the migration of breast cancer cells,and increasing the expression of miR-101-3p to inhibit DLG5 expression may play an important role in this process,which needs further investigation.

DLG5与34βE12在乳腺癌中表达的相关性及临床意义

目的:探讨细胞极性蛋白DLG5与高分子量角蛋白(34βE12)在乳腺癌中表达的相关性,阐明其在乳腺癌临床诊断中的作用。方法:收集乳腺癌组织,通过免疫组织化学(immunohistochemistry,IHC)分析DLG5的表达情况,以及其与34βE12表达的相关性。利用慢病毒技术敲低DLG5的表达后,Western blot检测DLG5与34βE12的表达。结果:DLG5的表达随乳腺癌恶性程度增加而降低,与雌激素受体/孕激素受体(ER/PR)、34βE12的表达呈现正相关性。在乳腺上皮细胞MCF10A中,敲低DLG5表达后,34βE12的表达显著降低。结论:在乳腺癌中,DLG5可以用于早期诊断、恶性程度判定,并且可以作为ER/PR阳性乳腺癌治疗及预测预后的潜在生物标志物。

三阴性乳腺癌的耐药机制及与DLG5的研究进展

三阴性乳腺癌(Triple Negative Breast Cancer, TNBC)是乳腺癌的一种特定亚型,因其不表达雌激素受体 (Estrogen Receptor, ER)、孕酮受体(Progesterone Receptor, PR)或人表皮生长因子受体-2 (Epi-dermal Growth Factor Receptor, HER-2)具有高侵袭能力,预后较其他类型乳腺癌差,在治疗上往往因为出现耐药性导致癌症进展和复发。早期应用化疗药物对三阴性乳腺癌有明显治疗效果,但随着化疗药物的应用,患者可逐渐出现耐药,导致总体生存率低下。因此,研究三阴性乳腺癌的化疗耐药性是目前乳腺癌的关注热点。本文回顾了三阴性乳腺癌耐药的研究进展,特别是极性蛋白DLG5在三阴性乳腺癌耐药中的作用以及影响,以期为临床治疗提供参考。

基于数据库分析肾透明细胞癌中DLG5的表达及预后判定作用

目的通过研究DLG5(discs large homolog5)在肾透明细胞癌(ccRCC)临床组织中的表达,阐明其对ccRCC诊断与预后的作用。方法结合癌症基因组图谱(TCGA)数据库与基因表达综合(GEO)数据库、免疫组织化学法分析DLG5在ccRCC组织与正常肾组织中的表达差异,运用LinkedOmics、GEPIA、String-DB等分析DLG5表达与ccRCC临床病理指标、预后的关系及与其可能发生相互作用的蛋白网络。结果ccRCC中DLG5mRNA表达高于正常组织,LinkedOmics网站分析发现,其高表达患者总生存率低于低表达者(P=2.997×10-5);DLG5表达随TNM分期等级升高而增加;DLG5与增殖细胞核抗原(PCNA)表达的相关系数R=0.19(P=1.1×10-6),与RAD1表达的相关系数R=0.18(P=5.7×10-6),均呈正相关。结论DLG5高表达是ccRCC不良预后的指标,有望作为预测患者转移、复发、预后等的分子靶标。

盘状大同源物5在肺腺癌中的表达及其临床意义

目的:探讨盘状大同源物5(discs large homolog 5,DLG5)在肺腺癌中的表达及其临床意义。方法:采用免疫组化SP法检测122例Ⅰ期和ⅢA期肺腺癌组织中DLG5的表达情况,并采用Western blotting法检测20对肺腺癌组织癌组织和癌旁组织DLG5的表达情况。统计患者的临床资料,分析DLG5表达与临床特征的相关性,采用Kaplan-Meier曲线对随访数据进行预后分析。结果:Ⅰ期肺腺癌组织中DLG5的阳性表达率明显高于ⅢA期肺腺癌组织(P<0.01)。肺腺癌组织中DLG5的阳性表达率明显低于癌旁肺组织。DLG5表达阳性的患者,5年生存率(OS)明显高于表达阴性的患者(51.1%vs 28.1%,P<0.01)。肺腺癌组织中DLG5的阳性表达水平与淋巴结转移(P<0.01)、TNM分期(P<0.01)和肿瘤复发(P<0.01)呈负相关。生存分析显示DLG5和TNM分期是肺腺癌的独立预后影响因素。结论:DLG5在肺腺癌中表达下降,DLG5可能对肺腺癌患者的预后有一定的指导意义。

Current concept on the pathogenesis of inflammatory bowel disease-crosstalk between genetic and microbial factors:Pathogenic bacteria and altered bacterial sensing or changes in mucosal integrity take"toll"?

The pathogenesis of inflammatory bowel disease （IBD） is only partially understood. Various environmental and host （e.g. genetic-, epithelial-, immune and nonimmune） factors are involved. It is a multifactorial polygenic disease with probable genetic heterogeneity. Some genes are associated with IBD itself, while others increase the risk of ulcerative colitis （UC） or Crohn＇ s disease （CD） or are associated with disease location and/or behaviour. This review addresses recent advances in the genetics of IBD. The article discusses the current information on the crosstalk between microbial and genetic factors （e.g. NOD2/CARD15, SLC22A46A5 and DLG5）. The genetic data acquired in recent years help in understanding the pathogenesis of IBD and can identify a number of potential targets for therapeutic intervention. In the future, genetics may help more accurately diagnose and predict disease course in IBD.

Role of discs large homolog 5

In 2004, an association of genetic variation in the discs large homolog 5 （DLG5＇） gene with inflammatory bowel disease （IBD） was described in two large European study samples. The initial report of DLG5 as a novel IBD susceptibility gene sparked a multitude of studies investigating its effect on CD and IBD, respectively, leading to controversial findings and ongoing discussions concerning the validity of the initial association finding and its role in the aetiology of Crohn disease. This review aims to summarize the current state of knowledge and to place the reported findings in the context of current concepts of complex diseases. This includes aspects of statistical power, phenotype differences and genetic heterogeneity between different populations as well as gene-gene and gene-environment interactions.

1：5万DLG空间数据位置精度的分析与研究

本文介绍了GPS RTK技术在1：5万DLG缩编成图数学精度外业检测的应用，并对1：5万DLG位置精度进行分析研究，提出在1：5万DLG数据缩编过程中应注意的几个问题。

基于ArcMap实现1∶5万DLG数据库到传统地形图的转换

DLG是一种将地理要素分层存储的矢量数据集,其包含了空间信息和属性信息,利用其属性信息,将空间展布的各要素以符号化的形式表达出来,形成传统地形图以供使用者判读、应用,将会大大提升传统地形图的生产成本、成图周期,弥补传统地形图现势性差的弱点。笔者借助ArcMap平台,通过投影转换、样式符号制作及要素符号化、符号标注、制图综合及图面整饰一系列过程,详细介绍了从1∶5万DLG数据库至传统地形图的转换过程,并总结出了转换过程中的重点和难点工作,同时提出了利用mxd文件模板采用修改数据源的方法可实现同比例尺其他图幅的快速转换,提高工作效率。