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131.
132.
Manuj Tandon Joseph M. Salamoun Evan J. Carder Elisa Farber Shuping Xu Fan Deng Hua Tang Peter Wipf Q. Jane Wang 《PloS one》2015,10(3)
Protein kinase D (PKD) has been implicated in many aspects of tumorigenesis and progression, and is an emerging molecular target for the development of anticancer therapy. Despite recent advancement in the development of potent and selective PKD small molecule inhibitors, the availability of in vivo active PKD inhibitors remains sparse. In this study, we describe the discovery of a novel PKD small molecule inhibitor, SD-208, from a targeted kinase inhibitor library screen, and the synthesis of a series of analogs to probe the structure-activity relationship (SAR) vs. PKD1. SD-208 displayed a narrow SAR profile, was an ATP-competitive pan-PKD inhibitor with low nanomolar potency and was cell active. Targeted inhibition of PKD by SD-208 resulted in potent inhibition of cell proliferation, an effect that could be reversed by overexpressed PKD1 or PKD3. SD-208 also blocked prostate cancer cell survival and invasion, and arrested cells in the G2/M phase of the cell cycle. Mechanistically, SD-208-induced G2/M arrest was accompanied by an increase in levels of p21 in DU145 and PC3 cells as well as elevated phosphorylation of Cdc2 and Cdc25C in DU145 cells. Most importantly, SD-208 given orally for 24 days significantly abrogated the growth of PC3 subcutaneous tumor xenografts in nude mice, which was accompanied by reduced proliferation and increased apoptosis and decreased expression of PKD biomarkers including survivin and Bcl-xL. Our study has identified SD-208 as a novel efficacious PKD small molecule inhibitor, demonstrating the therapeutic potential of targeted inhibition of PKD for prostate cancer treatment. 相似文献
133.
叶绿体基因组进化的速率和方式 总被引:1,自引:0,他引:1
叶绿体是植物细胞重要的细胞器,叶绿体基因组被广泛用于系统进化的研究。对叶绿体基因组进化的速度和方式进行了介绍,并对造成其特异的点突变的原因进行了一定的分析。 相似文献
134.
设计合成了两个分别互补于乙肝病毒2.1kb mRNA起始区(片段A)和增强子区(片段B)的硫代磷酸的DNA片段,在经克隆HBV DNA转染HepG2细胞建立的HBV短暂表达系统及稳定产生HBV的2215细胞中研究二者对HBsAg及HBeAg表达的抑制作用。结果表明反义寡聚物能不同程序抑制乙肝抗原表达,并与剂量呈一定正相关。在HepG2细胞HBV短暂表达系统中,6μmol/L浓度时,片段A、B对HB 相似文献
135.
136.
Overexpression of Jatropha curcas Defensin (JcDef) Enhances Sheath Blight Disease Resistance in Tobacco 下载免费PDF全文
Qingwei Wang Shuhua Zhu Yao Liu Rui Li Shancai Tan Shenghua Wang Lin Tang Fang Chen 《Journal of Phytopathology》2017,165(1):15-21
Plant defensins are small, basic, cysteine‐rich peptides, belonging to the antimicrobial peptide superfamily, commonly found in the plant kingdom. In this study, we cloned and characterized a plant defensin gene from Jatropha curcas (JcDef). JcDef carried conserved receptor binding sites and a cysteine motif, and it was phylogenetically grouped together with defensin Ec‐AMP‐D2‐like in Elaeis guineensis. JcDef is localized to cytoplasm and highly expressed in young tissues with fast metabolism such as cotyledons and stem apexes. Transgenic expression of JcDef in tobacco showed enhanced resistance against sheath blight disease caused by R. solani, indicating the antibacterial function. 相似文献
137.
Wen-Xiang Cao Ting Li Zheng-Hai Tang Le-Le Zhang Zhao-Yu Wang Xia Guo Min-Xia Su Xiuping Chen Jin-Jian Lu 《Apoptosis : an international journal on programmed cell death》2018,23(9-10):521-531
The pseudokinase mixed lineage kinase domain-like protein (MLKL) is a core effector of necroptosis, and its function in necroptosis is widely studied. However, the function of MLKL in apoptosis remains unclear. In the present study, the role of MLKL in chelerythrine (CHE)-promoted apoptosis was studied. A special band of MLKL (i.e., *MLKL) was observed after treatment with CHE. MLKL and *MLKL were accumulated in the nucleus upon treatment with CHE and MLKL silencing reversed the CHE-induced apoptosis. Blockade of CHE-triggered reactive oxygen species (ROS) generation or inhibition of CHE-activated protein kinase-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2 α subunit (eIF2α) pathway reversed the apoptosis. A decreased ROS level inhibited CHE-mediated nuclear translocation of MLKL and *MLKL and the activation of eIF2α, whereas MLKL or eIF2α silencing did not affect the CHE-triggered ROS generation. Furthermore, MLKL silencing prevented the CHE-activated eIF2α signal, and eIF2α silencing blocked the CHE-induced nuclear translocation of MLKL and *MLKL. Our studies suggested that CHE possibly induces apoptosis through the nuclear translocation of MLKL and *MLKL, which is promoted by a mutual regulation between MLKL and PERK–eIF2α pathway in response to ROS formation. The present study clarified the new function of MLKL in apoptosis. 相似文献
138.
栀子(Gardenia jasminoides)为药用木本植物。以栀子果皮、种子团和种子为外植体,研究不同激素配比及不同培养方式对愈伤组织诱导和芽分化的影响。研究结果表明,培养基成分为MS+0.5 mg·L–12,4-D+0.25 mg·L–16-BA较适宜果皮和种子愈伤组织的诱导,诱导率分别为83.3%和88.5%;培养基成分为MS+1.0 mg·L–12,4-D+1.0 mg·L–16-BA较适宜种子团愈伤组织的诱导,诱导率为78.1%。3种外植体诱导的愈伤组织中,只有种子愈伤组织能通过液体培养分化出芽;TDZ对芽分化有明显的促进作用;最佳的芽分化培养基为MS+0.05 mg·L–1NAA+0.10 mg·L–1TDZ,其愈伤组织分化率为8.75%。该研究以栀子种子为外植体,并获得了再生植株,为药用植物栀子转基因体系的建立奠定了基础。 相似文献
139.
Some of the most successful gene therapy results have been obtained using recombinant viral vectors to treat animal models of inherited and acquired ocular diseases. Clinical trials using adenovirus vector systems have been initiated for two ocular diseases. Adeno-associated viruses (AAVs) represent an attractive alternative to adenoviral vector systems as they enable stable and long-term expression and can target a variety of different ocular cell types depending on the capsid serotype; recently clinical trails for congenital blindness was initiated with a vector-based AAV serotype 2. High levels of retinal gene transfer have been achieved using vectors based on AAV serotypes 1, 2, 4 and 5. This report compares the gene transfer efficacy and stability of expression of vector systems based on three novel AAV serotypes: AAV7, 8, 9, with the established vectors AAV1, 2, 5. We show here that AAV7 and 8 enable superior long-term transduction of retinal and also anterior chamber structures. 相似文献
140.
Arriesgado Dan M. Kurokochi Hiroyuki Nakajima Yuichi Matsuki Yu Uy Wilfredo H. Fortes Miguel D. Campos Wilfredo L. Nadaoka Kazuo Lian Chunlan 《Aquatic Ecology》2015,49(3):357-372
Aquatic Ecology - Persistence of populations at their distributional ranges relies on local population dynamics and the fitness of species with low dispersal potential. We analyzed the population... 相似文献