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Bone marrow mesenchymal stem cells reduce ureteral stricture formation in a rat model via the paracrine effect of extracellular vesicles
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Jintai Luo Shankun Zhao Jiamin Wang Lianmin Luo Ermao Li Zhiguo Zhu Yangzhou Liu Ran Kang Zhigang Zhao 《Journal of cellular and molecular medicine》2018,22(9):4449-4459
With no effective therapy to prevent or treat ureteral stricture (US), a multifactorial fibrotic disease after iatrogenic injury of the ureter, the need for new therapies is urgent. Mesenchymal stem cells (MSCs) have been widely studied for treating tissue defects and excessive fibrosis, and recent studies established that one of the main therapeutic vectors of MSCs is comprised in their secretome and represented by extracellular vesicles (EVs). Thus, we have determined to explore the specific role of MSCs‐derived EVs (MSC‐EVs) treatment in a pre‐clinical model of US. The results firstly showed that either a bolus dose of MSCs or a bolus dose of MSC‐EVs (administration via renal‐arterial) significantly ameliorated ureteral fibrosis and recuperated ureter morphological development in a US rat model. We confirmed our observations through MSCs or MSC‐EVs treatment alleviated hydronephrosis, less renal dysfunction and blunted transforming growth factor‐β1 induced fibration. Due to MSC‐EVs are the equivalent dose of MSCs, and similar curative effects of transplantation of MSCs and MSC‐EVs were observed, we speculated the curative effect of MSCs in treating US might on account of the release of EVs through paracrine mechanisms. Our study demonstrated an innovative strategy to counteract ureteral stricture formation in a rat model of US. 相似文献
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Xiang Zhou Jiamin Liu Jiao Meng Yihong Fu Zhibin Wu Guiping Ouyang Zhenchao Wang 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):1996
Microtubule dynamics are crucial for multiple cell functions, and cancer cells are particularly sensitive to microtubule-modulating agents. Here, we describe the design and synthesis of a series of (Z)-2-(5-benzylidene-4-oxo-2-thioxothiazolidin-3-yl)-N-phenylacetamide derivatives and evaluation of their microtubule-modulating and anticancer activities in vitro. Proliferation assays identified I20 as the most potent of the antiproliferative compounds, with 50% inhibitory concentrations ranging from 7.0 to 20.3 µM with A549, PC-3, and HepG2 human cancer cell lines. Compound I20 also disrupted cancer A549 cell migration in a concentration-dependent manner. Immunofluorescence microscopy, transmission electron microscopy, and tubulin polymerisation assays suggested that compound I20 promoted protofilament assembly. In support of this possibility, computational docking studies revealed a strong interaction between compound I20 and tubulin Arg β369, which is also the binding site for the anticancer drug Taxol. Our results suggest that (Z)-2-(5-benzylidene-4-oxo-2-thioxothiazolidin-3-yl)-N-phenylacetamide derivatives could have utility for the development of microtubule-stabilising therapeutic agents. 相似文献
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多源空间数据整合视角下的城市开发强度研究 总被引:3,自引:0,他引:3
城市开发强度能直观表征人类活动强度,对指导城市规划与管理、促进城市可持续发展具有重要价值。采用社会-经济-生态系统耦合视角构建城市开发强度的多维测度体系,整合多源空间数据,测度了杭州市主城及3个副城的开发强度并揭示了其空间分布特征。结果表明,杭州城市开发强度由主城向副城呈波动降低,高强度开发过度集中于主城,主城的功能疏散有待加强;各副城开发强度不一,江南城与主城呈现跨江融合,临平城、下沙城空间上较为独立;各开发维度中,建筑强度、功能强度及效益强度热点区分布基本一致,环境响应高强度区则集聚于主副城交界处,表现出空间异质性。多维测度体系可较好表征城市开发强度,对城市规划及精细化管理具有一定的应用价值。 相似文献
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通过对文山松毛虫质型多角体病毒(Dendrolimus punctatus Wenshanensis cytoplasmic polyhedrosis virus, DpwCPV)的增殖、纯化,获得一株单一类型的质型多角体病毒。提纯的病毒粒子经SDS热酚法抽提得到基因组dSRNA,使用低熔点琼脂糖凝胶电泳分离并回收纯化第九片段S9。S9 RNA双链经高温变性,逆转录合成cDNA双链。根据DpwCPV与BmCPV1的同源性设计引物,将S9进行PCR扩增后,克隆到PMD18T载体上。最终获得一个977bp的序列,其中包含一个963bp的开放阅读框(ORF)。推测DpwCPV S9基因编码一个320个氨基酸的蛋白,分子量约为35560。 相似文献
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为提高番石榴(Psidium guajava)副产物的综合利用率,测定了‘珍珠’、‘水蜜’、‘红宝石’和‘西瓜’4个品种叶和幼果提取物中的酚类与黄酮含量,并分析了其与清除DPPH·、ABTS+、HO·自由基能力和α-葡萄糖苷酶抑制活性的相关性,并用超高效液相色谱-串联质谱法(UPLC-MS/MS)分析了提取物的酚类成分。结果表明,4个番石榴品种叶的酚类和黄酮含量、清除自由基能力、α-葡萄糖苷酶抑制活性均显著高于幼果,‘珍珠’叶的酚类含量最高,生物活性最强。酚类、黄酮含量与清除自由基能力呈极显著正相关(P<0.01),与α-葡萄糖苷酶抑制活性呈显著正相关(P<0.05)。UPLC-MS/MS鉴定结果表明,4个品种叶酚类含量较高的均为槲皮素-3-O-葡萄糖苷、金丝桃苷、鞣花酸和杨梅苷,除鞣花酸外大部分存在于叶的酚类成分也存在于幼果中,且含量显著高于幼果。因此,4个品种中,‘珍珠’叶是开发天然抗氧化剂和α-葡萄糖苷酶抑制剂的优良资源。 相似文献