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631.
Moon MJ Lee SK Lee JW Song WK Kim SW Kim JI Cho C Choi SJ Kim YC 《Bioorganic & medicinal chemistry》2006,14(1):237-246
Indirubin, an active ingredient of a traditional Chinese recipe Danggui Longhui Wan, has been known as a CDK inhibitor competing with ATP for binding to the catalytic site of cyclin-dependent kinases (CDKs). Since CDKs, a group of serine/threonine kinases forming active heterodimeric complexes with cyclins, are key regulators of the cell cycle regulation, therapeutic interventions targeting CDKs have been stimulated for the treatment of proliferative diseases, such as cancer, psoriasis, and for the prevention of chemotherapy-associated side effects, such as alopecia. A series of novel indirubin analogs was synthesized and evaluated for anti-proliferative and CDK2 inhibitory activities. Among the indirubin derivatives tested in the growth inhibitions against several human cancer cell lines, 5-nitro, halide, and bulky group containing acylamino substituted analogs showed high anti-proliferative effects. Selected analogs showing potent anti-proliferative activities were evaluated further in the CDK2 enzyme assay, which resulted in the discovery of potent CDK2 inhibitors. 相似文献
632.
Thurmond J Yoon H Kuiken C Yusim K Perkins S Theiler J Bhattacharya T Korber B Fischer W 《Bioinformatics (Oxford, England)》2008,24(14):1639-1640
We present a suite of on-line tools to design candidate vaccine proteins, and to assess antigen potential, using coverage of k-mers (as proxies for potential T-cell epitopes) as a metric. The vaccine design tool uses the recently published 'mosaic' method to generate protein sequences optimized for coverage of high-frequency k-mers; the coverage-assessment tools facilitate coverage comparisons for any potential antigens. To demonstrate these tools, we designed mosaic protein sets for B-clade HIV-1 Gag, Pol and Nef, and compared them to antigens used in a recent human vaccine trial. AVAILABILITY: http://hiv.lanl.gov/content/sequence/MOSAIC/. 相似文献
633.
634.
Young-Ok Son Ki-Choon Choi Jeong-Chae Lee Sung-Ho Kook Suk-Kyeong Lee Kenzo Takada Yong-Suk Jang 《Biochimica et Biophysica Acta (BBA)/General Subjects》2006
Taxol (paclitaxel) is one of the most potent antimicrotubule agents currently used in cancer chemoprevention and treatment. However, the effects of taxol on the induction of apoptosis in Epstein–Barr virus (EBV)-infected cells are unknown. This study investigated the mechanisms of taxol on cell cycle arrest and apoptosis induction using the EBV-infected cell line, Akata. Taxol treatment sensitively and dose-independently induced growth inhibition, cytotoxicity, and apoptosis in the cells, which was demonstrated by the decreased level of tritium incorporation and cell viability, the increased number of positively stained cells in the trypan blue staining and TUNEL assay, the increased population of cells in the sub-G0/G1 phase in flow cytometric analysis, and ladder formation of the genomic DNA. Treatment with z-VAD-fmk almost completely protected the cells from taxol-induced apoptosis indicating that the taxol-induced apoptosis of Akata cells is caspase-dependent. In addition, taxol-induced apoptosis is proposed to be associated with a lower mitochondrial membrane potential and G2/M arrest. However, the tubulin expression level doses not appear to be a direct mediator of taxol-induced apoptosis in cells. The presence of EBV in these cells was not related to the sensitivity of the cells to the induction of apoptosis by taxol. Overall, these results demonstrate that taxol induces apoptosis in EBV-infected Akata cells in a dose-independent manner, and that caspase activation and mitochondrial stress are involved in the induction. 相似文献
635.
Park HS Lee JH Jeong EJ Kim JE Hong SJ Park TK Kim TY Jang WJ Park KH Kim BJ Kook YH Lee SH 《Microbiology and immunology》2005,49(6):545-549
In this study, two new duplex PCR methods based on the groEL gene were developed and investigated for the diagnosis of rickettsiae. The first duplex PCR assay amplified the 229-bp and the 366-bp DNAs of 6 strains including typhus group (TG) and spotted fever group (SFG) rickettsiae, and 5 scrub typhus group (STG) rickettsiae, respectively. The second duplex PCR assay amplified the 397-bp and the 213-bp DNAs of 6 Rickettsia strains and 5 STG strains. These duplex PCR methods could simultaneously perform the rapid identification of rickettsiae and the differential diagnosis of STG and other group rickettsiae in a single reaction. 相似文献
636.
Chung HJ Jung OJ Chae MJ Hong SY Chung KH Lee SK Ryu CK 《Bioorganic & medicinal chemistry letters》2005,15(14):3380-3384
A series of 6-arylamino-2,3-bis(pyridin-2-yl)-7-chloro-quinoxaline-5,8-diones were synthesized and evaluated for their inhibitory activity on the rat aortic smooth muscle cell (RAoSMC) proliferation. The quinoxaline-5,8-diones exhibited a potent antiproliferative activity. Further mechanistic study revealed that the inhibitory effect of one representative quinoxaline-5,8-dione on SMC proliferation was mediated by modulation of the extracellular signal-regulated kinase 1/2 signaling pathway in the RAoSMCs. 相似文献
637.
Both erythropoietin (EPO) and the short-form thrombopoietin (TPO) were expressed at low levels whereas the long-form TPO was expressed at high levels in transgenic animals. To elucidate the role of carboxy-terminal half of the long-form TPO which is absent in the short-form, we generated recombinant TPO or EPO expression vectors which contain or lack the carboxy-terminal half of TPO and examined their expression in the HC11 and 293 cells. The long-form TPO was expressed higher than the short-form regardless of the cell types, transfection modes, and promoters. When 3'-half of the long-form TPO cDNA was placed downstream of the EPO cDNA to act as a 3'-untranslated region, expression of EPO was moderately increased at the RNA level, however, no remarkable increase was observed at the protein level. These results suggest that the low expression of EPO, as like as the short-form TPO, is due to absence of the 3'-half in the full-length TPO that confers stability both at the RNA and protein levels. 相似文献
638.
Previous reports showed that human RAD50 (hRAD50) gene delivery induced regression of an experimental rat tumor and porcine neointimal hyperplasia. In this study, we examined the effects of hRAD50 on the morphological changes and migration of endothelial cells (EC) as possible mechanisms by which hRAD50 might block angiogenesis. Quantitative image analysis revealed significant inhibition of the number and total area of blood vessels in rat tumor tissues following hRAD50 gene delivery. hRAD50 distorted actin and tubulin arrangements, and significantly reduced the F/G-actin ratio and increased the nitric oxide (NO) production in the primary cultured human EC. These effects were blocked by pretreatment with L-NAME (N(G)-nitro-L-arginine-methyl ester), a NO synthase inhibitor. FACScan analysis showed that NO was involved in the necrosis and apoptosis of EC by hRAD50. hRAD50 also inhibited EC migration in an in vitro wound-healing model. These results indicate that NO-dependent cytoskeletal changes and inhibition of EC migration contribute to the suppression of angiogenesis by hRAD50 delivery in vivo. 相似文献
639.
The intracellular degradation of polyhydroxyalkanoic acid (PHA) in pseudomonads was investigated by first-order kinetics analysis using the initial rate method. One type of PHA was accumulated in five Pseudomonas spp., P. oleovorans, P. aeruginosa, P. fluorescens, P. citronellolis, and P. putida, by growing them on octanoic acid. The monomer compositions of the five PHA were not significantly different from one another: 85-90 mol % 3-hydroxyoctanoic acid (3HO), 7-12 mol % 3-hydorxycaproic acid (3HC), and 3-6 mol % 3-hydroxydecanoic acid (3HD). The first-order degradation rate constants (k(1)) for the octanoate-derived PHA (designated P(3HO)) in the five species were in a similar range between 0.060 and 0.088 h(-1). This may indicate the similar specificities of the five intracellular depolymerases. In addition, the similar k(1) among the different species may correlate with the high degree of amino acid sequence identities (over 85%) among the intracellular PHA depolymerase phaZ genes. Six other chemically different types of PHA were accumulated in P. putida from n-nonanoic acid, n-decanoic acid, 5-phenyvaleric acid, or 11-phenoxyundecanoic acid as a single or a mixed carbon source. The calculated k(1) values were characteristic to each PHA, reflecting their chemical structures. In comparison with P(3HO), an increase in the levels of the two minor monomers 3HC and 3HD as in P(21 mol % 3HC-co-56 mol % 3HO-co-23 mol % 3HD) significantly slowed the rate of intracellular degradation. From the comparison of k(1) values, it is suggested that the P. putida intracellular depolymerase is most active against P(3HO). 相似文献
640.
The injured brain interacts reciprocally with neural stem cells supported by scaffolds to reconstitute lost tissue 总被引:18,自引:0,他引:18
Hypoxic-ischemic injury is a prototype for insults characterized by extensive tissue loss. Seeding neural stem cells (NSCs) onto a polymer scaffold that was subsequently implanted into the infarction cavities of mouse brains injured by hypoxia-ischemia allowed us to observe the multiple reciprocal interactions that spontaneously ensue between NSCs and the extensively damaged brain: parenchymal loss was dramatically reduced, an intricate meshwork of many highly arborized neurites of both host- and donor-derived neurons emerged, and some anatomical connections appeared to be reconstituted. The NSC-scaffold complex altered the trajectory and complexity of host cortical neurites. Reciprocally, donor-derived neurons were seemingly capable of directed, target-appropriate neurite outgrowth (extending axons to the opposite hemisphere) without specific external instruction, induction, or genetic manipulation of host brain or donor cells. These "biobridges" appeared to unveil or augment a constitutive reparative response by facilitating a series of reciprocal interactions between NSC and host, including promoting neuronal differentiation, enhancing the elaboration of neural processes, fostering the re-formation of cortical tissue, and promoting connectivity. Inflammation and scarring were also reduced, facilitating reconstitution. 相似文献