RNA interference technology's research progress in the treatment of retinal disease

RNA interference exists widely in animals, which can induce specific genetic sequence to silence by double-stranded RNA molecules at the mRNA level. As a kind of new methods of blocking gene expression, RNA interference technology has become increasingly mature and perfect, it has opened up a new approach of gene therapy. RNA interference can effectively prevent the formation of new vessels in retina, restrain the occurrence and development of the proliferative vitreous retinopathy, and induce apoptosis of retinoblastoma cells. The research progress of the RNA interference in the above retinopathy was summarized in this review

血管内皮细胞生长抑制因子的研究进展

血管内皮细胞生长抑制因子(vascularendothelialgrowthinhibitor,VEGI)是一种新型的血管内皮细胞生长抑制因子,属于TNF超家族,是Ⅱ型跨膜蛋白。重组VEGI不仅可以抑制内皮细胞增殖和诱导血管内皮细胞凋亡,而且可阻止新生血管生成,从而产生抗肿瘤生长的作用。VEGI作为一个内皮细胞产生的血管生成负调控因子可激活JNK、P38MAPA及胱冬肽,也可激活NF-κB,从而诱导内皮细胞的凋亡。VEGI的N段部分缺失可影响其生物活性,具有重要的病理生理意义,在肿瘤生物治疗方面有很大的应用前景

Characterization of Dll4 Monoclonal Antibody which can block the Dll4-Notch signaling pathway

1917年，ThomasHuntMorgan在果蝇中首次发现Notch基因，1980年Notch基因首次被克隆出来。Notch信号通路是一条保守而重要的信号转导通路，它对细胞命运的影响非常大，通过相邻细胞之间的相互作用调节细胞分化、增殖和凋亡，在许多至关重要的生理、病理过程中都起着重要作用。Notch信号通路由Notch受体、Notch配体（DSL蛋白）、CSL（CBF-1，Suppressorofhairless，Lag的合称）DNA结合蛋白、其他的效应物和Notch的调节分子等组成。哺乳动物有4种Notch受体（Notch1-4）和5种Notch配体（Delta-like1，3，4，Jag...In 1917,Notch gene was first found by Thomas Hunt Morgan in fruit flies, and in 1980, the gene was first cloned. Notch signaling pathway is conservative and important, it regulates cell differentiation, proliferation and apoptosis via the interaction between adjacent cells, and plays an important role in a series of physiological and pathological process. Notch signaling pathway is formed by Notch...学位：理学硕士院系专业：生命科学学院_细胞生物学学号：2162014115250

The role and mechanism of hnRNP A2/B1 in MCF-7 Cells

核不均一核糖核蛋白A2/B1（hnRNPA2/B1）在很多肿瘤中高表达，但其在 乳腺癌发生发展中的作用还不明确。为了探究其在乳腺癌中的具体作用与机制， 我们通过CRISPR-Cas9基因编辑技术构建敲除hnRNPA2/B1的MCF-7细胞系， 检测其对生物学功能的影响，并研究hnRNPA2/B1对部分基因的可变剪接的作用。 还通过亲和纯化技术结合液质联用质谱（HPLC-MS），构建与分析hnRNPA2/B1 相互作用蛋白网络，利用生物信息学方法对hnRNPB1相互作用蛋白进行KEGG 信号通路及功能分析，进一步来研究hnRNPA2/B1在乳腺癌细胞中的作用与机制。 MTT法检测发...An emerging body of data shows the overexpression of hnRNPA2/B1 in many cancers, but its specific molecular mechanism in tumors is still poorly understand. In order to explore the mechanism of hnRNPA2/B1 and find valid therapeutic target in breast cancer. We used CRISPR-Cas9 to construct the stable MCF-7 cells in which hnRNPA2/B1 were konck-out, and explored the change of proliferation, migrat...学位：理学硕士院系专业：医学院_微生物学学号：2452013115343

Sorafenib promotes Hepatocellular carcinoma cells apoptosis by downregulating AIB1 protein expression

Sorafenib是一种口服的多激酶抑制剂，它给临床上治疗晚期肝细胞癌领域带来了主要的突破性进展。然而在肝细胞癌中，Sorafenib发挥其抗肿瘤效应的分子机制并不是十分清楚。在肝细胞癌组织中AIB1被发现频繁的高表达，并且过表达的AIB1可以促进肝细胞癌的发展进程。在这里，我们研究调查了在肝细胞癌中Sorafenib对AIB1蛋白表达的影响以及调控的分子机制；与此同时我们也研究了AIB1在Sorafenib发挥抗肿瘤效应中所介导的作用。我们的研究表明在肝细胞癌细胞系中Sorafenib可以剂量和时间依赖式的抑制AIB1蛋白的表达。进一步研究结果显示，Sorafenib并不能减少AIB1mRN...Sorafenib is an oral multi-kinase inhibitor and represents a major breakthrough in the therapy of advanced hepatocellular carcinoma. However, the mechanisms of Sorafenib mediated-antitumor affects in HCC have not been fully elucidated. AIB1 is frequently overexpressed in human HCC tissues and promotes hepatocellular carcinoma progression. In our study, we investigate the effect of Sorafenib on exp...学位：理学博士院系专业：生命科学学院_细胞生物学学号：2162011015394

Clinical Significance of Circulating Dickkopf-1 Levels in Patients with Intraocular Neovascularization

研究背景及目的 渗出性年龄相关性黄斑变性(AMD)与糖尿病视网膜病变(DR)等眼内新生血管性疾病是常见的致盲性眼病。实验研究证实Wnt/β-catenin信号通路的异常激活在这些疾病的发生中起着重要的作用，但缺乏临床依据。Wnt/β-catenin信号通路异常激活受胞外抑制剂DKK-1的调节。本研究以渗出性AMD及DR分别作为CNV和RNV性疾病的代表，研究循环血中DKK-1水平与这些眼内新生血管性疾病发生发展的关系，并对其临床意义进行探讨，可为Wnt/β-catenin信号通路异常参与眼内新生血管的发生提供临床依据，还可为这些疾病防治方法的研究提供思路；可以认识这些疾病新的危险因素，为这些...Background and Purpose Blindness caused by the intra-ocular neovascularization including choroidal neovascularization (CNV) and retinal neovascularization (RNV) in diabetic retinopathy (DR) and in exudative age-related macular degeneration (AMD) remains one of the most urgent medical problems of our times. The Wnt/β-catenin signaling pathway has been shown to involve in the pathogenesis of CNV and...学位：理学博士院系专业：医学院_生理学学号：2452009015372

The molecular biological expression of SDF-1 and VEGF in rat diabetic retinopathy and the intervention effect of AMD3100

AIM: To measure the expression of stromal cell derived factor-1(SDF-1)and vascular endothelial growth factor(VEGF)in retina of diabetic rats model at the different stage and explore the inhibitory effect of AMD3100 on the expression of SDF-1 and VEGF mRNA by RT-PCR and Western-Blot test.<p>METHODS: RT-PCR and Western-Blot tests were carried out. In RT-PCR test, 60 adult SD rats were divided into normal group, antagonist group, and diabetes group. After diabetic rat model was induced using streptozotocin and antagonist group and diabetic group were injected intravitreously and postocularly with AMD3100 and PBS respectively. All rats were killed and the retina was extracted. after 1,3,5 months and the HE stain of paraffin sections was used and the expression of SDF-1 and VEGF mRNA were measured with RT-PCR. In Western-Blot test, 18 rats were divided into normal group, diabetes group and four antagonist groups which were using different concentration of AMD3100, and killed after 3 months.<p>RESULTS: SDF-1 and VEGF mRNA were expressed in normal group, antagonist group and diabetes group. At the same age group(1, 3 and 5 months)and among the normal group, antagonist group and diabetes group, the difference of expression of SDF-1 and VEGF mRNA were significant. The expressions in diabetic group were always highest and antagonist group lower than diabetic group. The expression of SDF-1 and VEGF mRNA was increased significantly with the extension of disease. The HE Stain of paraffin sections showed DM group had more cell nucleus which protruded internal limited membranes than normal control group and antagonist group. The Western-Blot test showed in 4 antagonist groups the SDF -1 and VEGF protein expression levels gradually decreased with the increases of SDF-1 antagonist AMD3100 concentration, the difference was significant. When intravitreous injected concentration of AMD3100 increased over 10μg/μL, the expression of SDF-1 and VEGF protein did not change, the difference was not statistically significant<p>CONCLUSION: With the progression of diabetic retinopathy, the expression of VEGF and SDF-1 mRNA in the retinal tissue of diabetic rats increased. The antagonist AMD3100 could reduce the expression of SDF-l, VEGF and inhibit the development of new blood vessels. In a certain concentration range, this inhibitory effect of AMD3100 was dose-dependent

靶向Neuropilin-1的抗肿瘤研究进展

Neuropilin-1(NRP-1)又称神经鞭毛素蛋白,是一个大小为130～140 kD的非酪氨酸激酶跨膜蛋白,参与脊椎动物胚胎的神经和心血管系统发育。它作为一个多功能受体调节VEGF(血管内皮生长因子),PDGF(血小板衍生生长因子),bFGF(成纤维生长因子)等细胞因子的信号通路,与肿瘤血管新生和肿瘤转移密切相关。NRP-1被认为是一个新的肿瘤治疗靶点,近年来针对NRP-1为靶点的药物研究有不少新进展。本文主要介绍NRP-1的生物学特征,对肿瘤作用以及相关药物研究