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Correlative investigation of copper/low-density polyethylene nanocomposite on the endometrial angiogenesis

LI Jianxiong, LIU Zilong, DUAN Yonggang, YU Jing, ZHU Changhong, LI Shuang, XIE Changsheng

《医学前沿（英文）》 2007年 第1卷 第4期   页码 401-404 doi: 10.1007/s11684-007-0078-3

摘要： The purpose of this study was to investigate the effects of copper/low-density polyethylene nanocomposite (nano-Cu/LDPE) on the endometrial angiogenesis in rats, and 100 sexual mature female SD rats were randomly divided into five groups: sham-operation groups (SO group, = 20), bulk copper groups (Cu group, = 20), LDPE groups ( = 20), nano-Cu/LDPE groups I ( = 20) and II ( = 20). The levels of angiopoietin-2 (Ang-2), its receptor (Tie-2) and CD34 of the rats endometria in each group were examined by using the S-P method of the immunohistochemistry 30 and 180 days after insertion, respectively. Compared with those in the SO group, the expression of Ang-2 and Tie-2 in all the experimental groups was obviously increased 30 days after insertion, and these parameters in nano-Cu/LDPE groups, except for Ang-2 level in nano-Cu/LDPE group II, were significantly lower in comparison with those in Cu group (<0.05). On the 180th day after insertion, Ang-2 and Tie-2 levels were still higher in Cu group and LDPE group, but there was no difference of Ang-2 and Tie-2 levels between nano-Cu/LDPE groups and the SO group (>0.05). Compared with those in the SO group, the significant increases in microvessel density (MVD) were observed on the 30th and the 180th day after the insertion of the bulk copper (<0.05). There was no significant difference in MVD counts before and after the insertion of nano-Cu/LDPE (>0.05). The results show that Nano-Cu/LDPE have slighter influence on the endometrial angiogenesis than bulk copper.

关键词： significant difference     female     endometrial angiogenesis     nano-Cu/LDPE     CD34    

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Netrin-1 works with UNC5B to regulate angiogenesis in diabetic kidney disease

Xiaojing Jiao, Dong Zhang, Quan Hong, Lei Yan, Qiuxia Han, Fengmin Shao, Guangyan Cai, Xiangmei Chen, Hanyu Zhu

《医学前沿（英文）》 2020年 第14卷 第3期   页码 293-304 doi: 10.1007/s11684-019-0715-7

摘要： Netrin-1, an axon guidance factor, and its receptor UNC5B play important roles in axonal development and angiogenesis. This study examined netrin-1 and UNC5B expression in kidneys with diabetic kidney disease (DKD) and investigated their roles in angiogenesis. Netrin-1 and UNC5B were upregulated in streptozotocin-induced DKD Wistar rats, and their expression was compared with that in healthy controls. However, exogenous netrin-1 in UNC5B-depleted human renal glomerular endothelial cells (HRGECs) inhibited cell migration and tubulogenesis. This effect was likely associated with SRC pathway deactivation. Netrin-1 treatment also eliminated the pro-angiogenic effects of exogenous VEGF-165 on UNC5B-silenced HRGECs. These results indicate that UNC5B antagonizes netrin-1 and that UNC5B upregulation contributes partly to enhancing angiogenesis in DKD. Therefore, introducing exogenous netrin-1 and depleting endogenous UNC5B are potential strategies for reducing the incidence of early angiogenesis and mitigating kidney injury in DKD.

关键词： netrin-1     VEGF-165     UNC5B     angiogenesis     diabetic kidney disease    

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Effects of galectin-3 inhibition on endometrial cell cycle and adhesion

LEI Caixia, ZHANG Wei, SUN Xiaowei, DU Guoping, WANG Li, LIU Yinkun

《医学前沿（英文）》 2007年 第1卷 第4期   页码 390-397 doi: 10.1007/s11684-007-0076-5

摘要： Galectin-3 (gal-3) and its ligands have been implicated in cell transformation and cancer metastasis. Gal-3 protein has been found in uterine epithelial cells adjacent to implanting blastocysts in different cell types. In order to investigate the role of gal-3 in the establishment of human endometrial receptivity, the expression of gal-3 in human endometrial cell line RL95-2 was silenced by RNA interference technology using gal-3 specific small RNA. The expression of gal-3 was detected by the reverse transcriptase-polymerase chain reaction and Western blot analysis. After the suppression of gal-3, cell cycle changes and the expression of integrin 1 were detected by flow cytometry. The adhesive ability of RL95-2 cells was analyzed by the adhesion test. Gal-3 siRNA transfection efficiency reached 70%–90%. The expression of gal-3 mRNA and protein in RL95-2 cells was strongly inhibited by 70%–90% after RNA interference. Inhibition of gal-3 expression decreased S-phase but increased G1 phase cells. Integrin 1 expression was down-regulated, and the adhesive ability of RL95-2 cells to fibronectin (FN) was significantly reduced. Gal-3 may be involved in the establishment of endometrial receptivity by regulating the proliferation and adhesion of endometrial cells. The influence on adhesion may be related with the integrin modulation.
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tumor-targeted delivery of tumstatin (54-132) significantly suppresses tumor growth in mouse model by inhibiting angiogenesis

《医学前沿（英文）》 2022年 第16卷 第6期   页码 873-882 doi: 10.1007/s11684-022-0925-2

摘要： Tumor growth is an angiogenesis-dependent process and accompanied by the formation of hypoxic areas. Tumstatin is a tumor-specific angiogenesis inhibitor that suppresses the proliferation and induces the apoptosis of tumorous vascular endothelial cells. VNP20009, an attenuated Salmonella typhimurium strain, preferentially accumulates in the hypoxic areas of solid tumors. In this study, a novel Salmonella-mediated targeted expression system of tumstatin (VNP-Tum5) was developed under the control of the hypoxia-induced J23100 promoter to obtain anti-tumor efficacy in mice. Treatment with VNP-Tum5 effectively suppressed tumor growth and prolonged survival in the mouse model of B16F10 melanoma. VNP-Tum5 exhibited a higher efficacy in inhibiting the proliferation and inducing the necrosis and apoptosis of B16F10 cells in vitro and in vivo compared with VNP (control). VNP-Tum5 significantly inhibited the proliferation and migration of mouse umbilical vascular endothelial cells to impede angiogenesis. VNP-Tum5 downregulated the expression of anti-vascular endothelial growth factor A, platelet endothelial cell adhesion molecule-1, phosphorylated phosphoinositide 3 kinase, and phosphorylated protein kinase B and upregulated the expression of cleaved-caspase 3 in tumor tissues. This study is the first to use tumstatin-transformed VNP20009 as a tumor-targeted system for treatment of melanoma by combining anti-tumor and anti-angiogenic effects.

关键词： Salmonella VNP20009     tumstatin     B16F10     melanoma     apoptosis     angiogenesis    

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新型立式网状宫内节育器对动物子宫肌电和内膜容受性的影响

王磊光,郭成浩,邱毅

《中国工程科学》 2014年 第16卷 第5期   页码 47-51

摘要：

探讨新型立式网状宫内节育器（new three-dimensional and reticular intrauterine device，NTDR-IUD）对正常子宫肌电和内膜容受性的影响。制作3 种规格（短、中及长）的IUD，放置在成年雌性新西兰大白兔子宫内，按常规无菌手术在耻骨联合正中切口切开腹壁，应用电生理仪进行子宫肌电检测。放置NTDRIUD后，慢波频率加快，平均振幅增大，单波最大振幅增大，频率加快；短、中及长NTDR-IUD使兔子宫肌电爆发波的持续时间逐渐延长，最大振幅增大；10 只正常对照组合笼1 月后均妊娠，短NTDR-IUD组有5 只在未被IUD占据的部位发现兔胎，中NTDR-IUD组有2 只发现兔胎，长NTDR-IUD组未发现兔胎。妊娠只数长NTDR-IUD 组与对照组比较，差异有统计学意义（P=0.000）；短NTDR-IUD 组与对照组及长NTDR-IUD组比较，均有统计学意义（P=0.033），中等长度NTDR-IUD组与对照组比较，有统计学意义（P=0.001）。NTDR-IUD通过干扰子宫肌电参与避孕，其避孕效果与IUD大小有关。

关键词： 立式网状宫内节育器     子宫肌电     内膜容受性    

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The relationship between platelet-derived growth factor expression and angiogenesis/lymphangiogenesis

Guocheng LIU MD, Shouhua YANG MD, Zehua WANG MD,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 447-451 doi: 10.1007/s11684-009-0082-x

摘要： This paper is aimed to examine if changes in platelet-derived growth factor (PDGF) expression at different stages of cervical cancer are related to the variation in blood vessel density (BVD) and lymphatic vessel density (LVD) to evaluate the relationship between PDGF expression and stages and metastasis of cervical cancer. Polymerase chain reaction (PCR) and RT-PCR were used to detect the expression levels of PDGF in 45 cervical cancer tissue samples (the experimental group). The samples were immunohistochemically stained with monoclonal antibodies D2-40 and CD34, and BVD and LVD were measured. The expressions of PDGF-A, -B, and- D were all higher in the experimental group than in the control group (<0.05); no significant difference was found in the expression of PDGF-C between the experimental group and the control group (>0.05). PDGF-A and -B expression was positively related with BVD and LVD (<0.01, R= 0.49, 0.527, 0.327, 0.68). The expression levels of PDGF-C and -D were not significantly related with BVD and LVD. At the early stage of cervical cancer, BVD and LVD were significantly higher than in the controls (<0.01). The BVD and LVD in tissues in the surrounding areas of cervical cancer were significantly higher than in tissues at cancer center, and LVD was related to lymph node metastasis (<0.001). BVD and LVD were not associated with the differentiation and pathological stages of cervical cancer. The expressions of PDGF-A, -B, and -D in cervical cancer were closely related with the clinical stages of cervical cancer. PDGF-A and -B were intimately associated with the lymph node metastasis and prognosis of cervical cancer.

关键词： cervical cancer     lymphatic vessel density     blood vessel density     platelet-derived growth factor    

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Progress in tumor vascular normalization for anticancer therapy: challenges and perspectives

null

《医学前沿（英文）》 2012年 第6卷 第1期   页码 67-78 doi: 10.1007/s11684-012-0176-8

摘要：

Antitumor angiogenic therapy has been shown promising in the treatment of several advanced cancers since the approval of the first antiangiogenic drug Avastin in 2004. Although the current antiangiogenic drugs reduce the density of tumor blood vessels and result in tumor shrinkage at the early stage of treatment, recent studies have shown that antiangiogenic therapy has transient and insufficient efficacy, resulting in tumor recurrence in patients after several months of treatment. Blockage of blood and oxygen supplies creates a hypoxic and acidic microenvironment in the tumor tissues, which fosters tumor cells to become more aggressive and metastatic. In 2001, Jain proposed tumor vascular normalization as an alternative approach to treating cancers based on the pioneering work on tumor blood vessels by several other researchers. At present, normalizing the disorganized tumor vasculature, rather than disrupting or blocking them, has emerged as a new option for anticancer therapy. Preclinical and clinical data have shown that tumor vascular normalization using monoclonal antibodies, proteins, peptides, small molecules, and pericytes resulted in decreased tumor size and reduced metastasis. However, current tumor vascular normalizing drugs display moderate anticancer efficacy. Accumulated data have shown that a variety of vasculogenic/angiogenic tumor cells and genes play important roles in tumor neovascularization, growth, and metastasis. Therefore, multiple-targeting of vasculogenic tumor cells and genes may improve the efficacy of tumor vascular normalization. To this end, the combination of antiangiogenic drugs with tumor vascular normalizing therapeutics, as well as the integration of Western medicine with traditional Chinese medicine, may provide a good opportunity for discovering novel tumor vascular normalizing drugs for an effective anticancer therapy.

关键词： angiogenesis     vasculogenesis     neovascularization     tumor     vasculature     normalization     traditional Chinese medicine    

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Overexpression of netrin-1 improves neurological outcomes in mice following transient middle cerebral artery occlusion

null

《医学前沿（英文）》 2011年 第5卷 第1期   页码 86-93 doi: 10.1007/s11684-011-0118-x

摘要：

Netrin-1 (NT-1) is one of the axon-guiding molecules that are critical for neuronal development. Because of its structural homology to the endothelial mitogens, NT-1 may have similar effects on vascular network formation. NT-1 was shown to be able to stimulate the proliferation and migration of human cerebral endothelial cells in vitro and also promote focal neovascularization in adult brain in vivo. In the present study, we reported the delivery of NT-1 using an adeno-associated virus (AAV) vector (AAV-NT-1) into mouse brain followed by transient middle cerebral artery occlusion (tMCAO). We found that AAV vectors did not elicit a detectable inflammatory response, cell loss or neuronal damage after brain transduction. The level of NT-1 was increased in the AAV-NT-1-transduced tMCAO mice compared with the control mice. Furthermore, the neurobehavioral outcomes were significantly improved in AAV-NT-1-transduced mice compared with the control animals (P<0.05) 7 days after tMCAO. Our data suggests that NT-1 plays a neuronal function recovery role in ischemic brain and that NT-1 gene transfer might present a valuable approach to treat brain ischemic disorders.

关键词： adeno-associated virus     angiogenesis     gene transfer     ischemia     middle cerebral artery occlusion     netrin-1    

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Medical oncology management of advanced hepatocellular carcinoma 2019: a reality check

Amy Lee, Fa-Chyi Lee

《医学前沿（英文）》 2020年 第14卷 第3期   页码 273-283 doi: 10.1007/s11684-019-0728-2

摘要： In terms of global cancer-related deaths, hepatocellular carcinoma (HCC) has the fourth highest mortality rate. Up until 2017, treatment of advanced HCC was largely limited to sorafenib, an oral tyrosine kinase inhibitor, with little to no success in the development of alternative treatment options. However, in the past two years, there has been an unprecedented increase in both the number and type of treatment options available for HCC. As of 2019, the US FDA has approved four oral tyrosine kinase inhibitors, two immune checkpoint inhibitors, and one anti-angiogenesis antibody for the treatment of HCC. Even with this new variety, systemic treatment of advanced HCC remains largely unsatisfactory, and the median survival rate stands at approximately one year. The expected breakthrough of using immune checkpoint inhibitors in advanced HCC did not materialize in 2019. The use of immune checkpoint inhibitors in conjunction with oral tyrosine kinase inhibitors or anti-angiogenesis medications is the current clinical research trend, the results of which are eagerly anticipated. Despite limited progress in survival, HCC research is currently experiencing a period of growth and innovation, and there is hope for significant advances in the treatment of advanced HCC as the field continues to develop.

关键词： hepatocellular carcinoma     tyrosine kinase inhibitor     check point inhibitor     anti-angiogenesis    

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peritoneal fibrosis in peritoneal dialysis patients: new insights based on peritoneal inflammation and angiogenesis

null

《医学前沿（英文）》 2017年 第11卷 第3期   页码 349-358 doi: 10.1007/s11684-017-0571-2

摘要：

Peritoneal dialysis (PD) is an established form of renal replacement therapy. Long-term PD leads to morphologic and functional changes to the peritoneal membrane (PM), which is defined as peritoneal fibrosis, a known cause of loss of peritoneal ultrafiltration capacity. Inflammation and angiogenesis are key events during the pathogenesis of peritoneal fibrosis. This review discusses the pathophysiology of peritoneal fibrosis and recent research progress on key fibrogenic molecular mechanisms in peritoneal inflammation and angiogenesis, including Toll-like receptor ligand-mediated, NOD-like receptor protein 3/interleukin-1β, vascular endothelial growth factor, and angiopoietin-2/Tie2 signaling pathways. Furthermore, novel strategies targeting peritoneal inflammation and angiogenesis to preserve the PM are discussed in depth.

关键词： peritoneal dialysis     peritoneal fibrosis     inflammation     angiogenesis    

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募集抗原特异性T细胞的3D打印支架促进血管化 Article

李翠笛, 马振江, 李文韬, 颉天阳, 钟丽萍, 陈宏方, 王文豪, 王金武, 崔文国, 赵永祥

《工程（英文）》 2022年 第17卷 第10期   页码 183-195 doi: 10.1016/j.eng.2021.05.018

摘要：

3D打印支架植入后激起的免疫反应是组织修复效果的主要决定性因素。因此，巧妙调控免疫反应的支架材料具有高效修复组织的潜能。本研究受抗原特异性免疫反应对血管新生促进作用的启发，通过动态共价键将介孔二氧化硅微棒（MSR）/聚乙烯亚胺（PEI）/卵清蛋白（OVA）自组装疫苗与3D打印自固化磷酸钙骨水泥（CPC）基支架结合，构建了一种具有调控局部体液免疫反应功能的组织修复支架。通过局部释放OVA激活体液免疫反应，支架可有效募集抗原特异性CD4+ 2 型辅助性T细胞（Th2 细胞），从而促进支架植入早期的血管新生；在提供充足和丰富的血供环境的同时，MSR微棒中释放的硅离子还能有效加速骨再生。在室温下稳定成型的自固化磷酸钙基打印浆料能够促进功能性氧化透明质酸在材料中的均匀分布和结构保持，并构建具有均匀连通孔道的支架。将MSR/PEI 作为抗原载体共价结合于富含醛基的支架，可实现OVA的稳定释放。在体外实验中，该疫苗负载支架有效募集并激活了树突细胞使树突细胞呈递抗原，还促进了骨髓间充质干细胞（BMSC）成骨分化。在皮下包埋实验中，疫苗负载支架增加了Th2 细胞在脾脏中的比例，局部募集了抗原特异性T细胞并促进了支架内的血管新生。此外，原位颅骨缺损修复模型结果表明，负载疫苗的支架可促进血管化骨组织再生。总之，该方法为具有促进血管新生功能个性化植入体的设计提供了一种新思路。

关键词： 3D打印     免疫微环境调控     血管新生     骨再生    

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Endostatin specifically targets both tumor blood vessels and lymphatic vessels

Wei Zhuo, Yang Chen, Xiaomin Song, Yongzhang Luo

《医学前沿（英文）》 2011年 第5卷 第4期   页码 336-340 doi: 10.1007/s11684-011-0163-5

摘要： Endostatin, a 20 kDa C-terminal fragment of collagen XVIII, was first identified as a potent angiogenic inhibitor. The anti-angiogenic function of endostatin has been well documented during the past decade. Recently, several studies demonstrated that endostatin also inhibits tumor lymphangiogenesis and lymphatic metastasis. However, the exact mechanism that endostatin executes its anti-angiogenic and anti-lymphangiogenic functions remains elusive. In the current mini-review, we briefly summarize recent novel findings, including the functions of endostatin targeting not only angiogenesis but also lymphangiogenesis, and the underlying mechanism by which endostatin internalization regulates its biological functions.

关键词： endostatin     angiogenesis     lymphangiogenesis     nystatin     internalization     tumor    

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Construction of eukaryotic expression vector of human arresten gene and its secreted expression in HEK 293 cells

Wei LI PhD , Siming GUAN MM , Zifang SONG PhD , Qichang ZHENG PhD , Jun XIONG PhD , Dan SHANG PhD , Xiaogang SHU PhD ,

《医学前沿（英文）》 2009年 第3卷 第3期   页码 297-302 doi: 10.1007/s11684-009-0058-x

摘要： The eukaryotic expression vector of human arresten gene was constructed and its secretive expression human embryonic kidney (HEK 293) cells was detected. Human arresten gene was amplified from recombinant plasmid pGEM-Arr by polymerase chain reaction (PCR), and then digested with restriction endonucleases I and I. The target fragment was inserted into the I and I restriction sites of eukaryotic expression vector pSecTag2 to construct pST-AT. Restriction analysis and DNA sequencing indicated that the arresten gene was successfully inserted into pSecTag2. The recombinant plasmid was subsequently transfected into HEK 293 cells with LipofectAMINETM2000 Reagent, and the expression of the target gene was detected. RT-PCR revealed that the mRNA of the target gene was transcribed in the transfected HEK 293 cells. Western Blot analysis verified that the recombinant protein in supernatants was correct. The supernatants of transfected cells were prepared, and 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay was carried out to assess their effect on the proliferation of human umbilical vein endothelial cells, which showed that the recombinant protein could significantly suppress the proliferation of human umbilical vein endothelial cells . These results provided a solid foundation to explore the usage of arresten in tumor anti-angiogenic gene therapy.

关键词： angiogenesis inhibitor     arresten     eukaryotic expression     HEK 293 cells     endothelial cells    

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全氟化碳乳剂19F磁共振成像的最新进展 Review

Anne H. Schmieder,Shelton D. Caruthers,Jochen Keupp,Samuel A. Wickline,Gregory M. Lanza

《工程（英文）》 2015年 第1卷 第4期   页码 475-489 doi: 10.15302/J-ENG-2015103

摘要：

19F磁共振成像(MRI) 的研究可追溯到30多年前。在这30多年间，氢原子核(1H)成像技术迅速发展，并在全球得到广泛应用，使得磁共振成像成为生物医学诊断成像技术中不可缺少的支柱。多年来，由于各种原因，对19F成像技术的研究进展缓慢。但是在过去的十年间，尤其是最近几年，19F成像的研究和临床相关性呈爆发式发展。部分原因归结为MRI仪器、19F/1H线圈设计以及临床前和临床核磁共振仪的超高速脉冲序列的发展。这些成就再加上对解剖生理学分子成像技术的兴趣以及一批创新造影剂的出现使19F的概念进入了早期的临床评估中。本篇综述重点探讨以液态全氟化碳化合物为基础的造影剂，并试图呈现这段丰富的研究和发展历史。

关键词： 氟     磁共振成像(MRI)     双调线圈     全氟化碳     血管生成术     细胞标记    

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3D 打印细胞容器样支架在多细胞组织工程中的应用研究 Article

王晓亚, 张猛, 马景阁, 徐梦驰, 常江, Michael Gelinsky, 吴成铁

《工程（英文）》 2020年 第6卷 第11期   页码 1276-1284 doi: 10.1016/j.eng.2020.08.001

摘要：

人工设计的非接触式多细胞共培养模型可以模仿人体组织的细胞内微环境，但其发展始终面临各种挑战。本研究利用3D打印技术，成功制得了一种含β-磷酸三钙/羟基磷灰石（β-TCP/HA）的细胞容器样支架，该支架设计了四种不同形状的微孔结构：三角形、正方形、平行四边形和长方形微孔结构。这些支架可以在非接触的方式下同时培养四种细胞。本研究构建了一种由人骨髓间质干细胞（HBMSC）、人脐静脉内皮细胞（HUVEC）、人脐静脉平滑肌细胞（HUVSMC）、人真皮成纤维细胞（HDF）组成的3D共培养模型，用以研究这些细胞在促进骨生成和血管生成过程中细胞的个体效应与协同效应。结果表明，相较于在3D细胞容器中仅培养一种细胞，共培养三种或四种细胞展现出了更高的细胞增殖率。HBMSC与HUVEC的细胞间相互作用的研究表明，含有四种独立空间结构的3D细胞容器可以通过放大共培养细胞的旁分泌效应促进细胞的骨生成和血管生成能力。此外，在3D细胞容器中建立多细胞非接触体系，特别是含有三种或四种细胞的共培养体系，相对于单细胞培养模式与两种细胞共培养模式来说，在促进细胞成骨分化和成血管分化方面展现出明显的优势。本研究为基于支架的多细胞非接触式共培养体系的发展提供了新的研究方向。

关键词： 3D细胞容器     非接触式多细胞共培养     相互作用     血管生成     骨生成    

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标题 作者 时间 类型 操作

Correlative investigation of copper/low-density polyethylene nanocomposite on the endometrial angiogenesis

LI Jianxiong, LIU Zilong, DUAN Yonggang, YU Jing, ZHU Changhong, LI Shuang, XIE Changsheng

期刊论文

Netrin-1 works with UNC5B to regulate angiogenesis in diabetic kidney disease

Xiaojing Jiao, Dong Zhang, Quan Hong, Lei Yan, Qiuxia Han, Fengmin Shao, Guangyan Cai, Xiangmei Chen, Hanyu Zhu

期刊论文

Effects of galectin-3 inhibition on endometrial cell cycle and adhesion

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