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排序方式: 共有892条查询结果,搜索用时 46 毫秒
91.
Muraski JA Rota M Misao Y Fransioli J Cottage C Gude N Esposito G Delucchi F Arcarese M Alvarez R Siddiqi S Emmanuel GN Wu W Fischer K Martindale JJ Glembotski CC Leri A Kajstura J Magnuson N Berns A Beretta RM Houser SR Schaefer EM Anversa P Sussman MA 《Nature medicine》2007,13(12):1467-1475
The serine-threonine kinases Pim-1 and Akt regulate cellular proliferation and survival. Although Akt is known to be a crucial signaling protein in the myocardium, the role of Pim-1 has been overlooked. Pim-1 expression in the myocardium of mice decreased during postnatal development, re-emerged after acute pathological injury in mice and was increased in failing hearts of both mice and humans. Cardioprotective stimuli associated with Akt activation induced Pim-1 expression, but compensatory increases in Akt abundance and phosphorylation after pathological injury by infarction or pressure overload did not protect the myocardium in Pim-1-deficient mice. Transgenic expression of Pim-1 in the myocardium protected mice from infarction injury, and Pim-1 expression inhibited cardiomyocyte apoptosis with concomitant increases in Bcl-2 and Bcl-X(L) protein levels, as well as in Bad phosphorylation levels. Relative to nontransgenic controls, calcium dynamics were significantly enhanced in Pim-1-overexpressing transgenic hearts, associated with increased expression of SERCA2a, and were depressed in Pim-1-deficient hearts. Collectively, these data suggest that Pim-1 is a crucial facet of cardioprotection downstream of Akt. 相似文献
92.
Ichinohe T Kawaguchi A Tamura S Takahashi H Sawa H Ninomiya A Imai M Itamura S Odagiri T Tashiro M Chiba J Sata T Kurata T Hasegawa H 《Microbes and infection / Institut Pasteur》2007,9(11):1333-1340
The avian H5N1 influenza virus has the potential to cause a new pandemic. Since it is difficult to predict which strain of influenza will cause a pandemic, it is advantageous to produce vaccines that confer cross-protective immunity. Mucosal vaccine administration was reported to induce cross-protective immunity by inducing secretion of IgA at the mucosal surface. Adjuvants can also enhance the development of fully protective mucosal immunity. Here we show that a new mucosal adjuvant, poly I:poly C12U (Ampligen), a Toll-like receptor 3 agonist proven to be safe in a Phase III human trial, is an effective adjuvant for H5N1 influenza vaccination. Intranasal administration of a candidate influenza vaccine with Ampligen resulted in secretion of IgA, and protected mice that were subsequently challenged with homologous A/Vietnam/1194/2004 and heterologous A/HK/483/97 and A/Indonesia/6/2005 virus. 相似文献
93.
Hashimoto T Tashiro T Sasaki M Takikawa H 《Bioscience, biotechnology, and biochemistry》2007,71(8):2046-2051
A new and concise synthesis of (+/-)-sundiversifolide (1), an allelopathic bisnor-sesquiterpene lactone isolated from germinating sunflower (Helianthus annuus L.) seeds, was achieved by employing Lewis acid-mediated Claisen rearrangement as the key step. 相似文献
94.
Sasaki M Ohnishi M Tashiro F Niwa H Suzuki A Miyazaki J Kobayashi T Tamura S 《Mechanisms of development》2007,124(6):489-499
Protein phosphatase 2Cβ (PP2Cβ) is a member of a family of protein Ser/Thr phosphatases (PP2C) that is composed of at least twelve different gene products. Recent studies have revealed that PP2Cβ mRNA accumulates in mature sperm, unfertilized metaphase II-arrested oocytes and zygotes, but that the mRNA level then decreases sharply between the early two-cell and eight-cell stages, remaining at low levels during the 16-cell to blastocyst stages of mice. These observations raised the possibility that PP2Cβ plays a crucial role during gametogenesis, fertilization, and/or early stages of embryonic development. In this study, we employed a gene knockout technique in mice to test this possibility. We found that PP2CβΔ/wt mice generate normal mature gametes. However, PP2CβΔ/Δ embryos die between the two-cell and eight-cell stages. To our interest, PP2CβΔ/Δ ES cells which had been generated by transfecting PP2Cβ3lox/3lox ES cells with Cre-expressing plasmid were viable. In addition, knockdown of PP2Cβ using siRNA did not affect the proliferation of wild-type ES cells. These observations suggest that relatively high PP2Cβ expression is specifically required during the early stages of pre-implantation development. The possible mechanisms for the early pre-implantation lethality of PP2CβΔ/Δ mice are discussed. 相似文献
95.
Hirokawa YS Takagi A Uchida K Kozuka Y Yoneda M Watanabe M Shiraishi T 《Cellular & molecular biology letters》2007,12(3):370-377
In this paper, we describe the isolation and characterization of two PC3 subclones. One subclone, mr, showed an epithelial
phenotype, the other, M1, showed a sarcomatous morphology. Transplanted into nude mice, mr developed tumors at a dramatically
faster rate than M1. Comparing the two subclones, differentially expressed genes were identified, including E-cadherin, IL-8
and STAG1/PMEPA1. These genes were expressed at higher levels in mr than in M1. 相似文献
96.
Ryu Tashiro Masahiro Iwamoto Hironobu Morinaga Tomoko Emura Kumi Hidaka Masayuki Endo Hiroshi Sugiyama 《Nucleic acids research》2015,43(14):6692-6700
DNA has recently emerged as a promising material for the construction of nanosized architectures. Chemically modified DNA has been suggested to be an important component of such architectural building blocks. We have designed and synthesized a novel H-shaped DNA oligonucleotide dimer that is cross-linked with a structurally rigid linker composed of phenylene and ethynylene groups. A rotatable DNA unit was constructed through the self-assembly of this H-shaped DNA component and two complementary DNA oligonucleotides. In addition to the rotatable unit, a locked DNA unit containing two H-shaped DNA components was also constructed. As an example of an extended locked structure, a hexagonal DNA origami dimer and oligomer were constructed by using H-shaped DNA as linkers. 相似文献
97.
98.
Fan S Li L Chen S Yu Y Qi M Tashiro S Onodera S Ikejima T 《Free radical research》2011,45(11-12):1307-1324
Silibinin, as the major active constituent of silymarin, has its various biological effects. Here, we investigated the inhibitory effects of silibinin on HeLa cell growth in relation to autophagy and apoptosis induced by reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation. Silibinin dose and time-dependently decreased cell growth cultured in medium containing 10% fetal bovine serum or in serum free media (SFM) with an IC(50) of approximately 80-100 and 40-60 μM at 24 h, respectively. Silibinin induced autophagy at 12 h, confirmed by monodansylcadervarine (MDC) staining and up-regulation of beclin-1, and induced apoptosis at 24 h, detected by observation of apoptotic bodies and activation of caspase-3. 3-methyladenine (3-MA) inhibited silibinin-induced autophagy and attenuated the silibinin's inhibitory effect on cell viability, suggesting that autophagy enhanced silibinin-induced cell death. Silibinin increased ROS levels at 12 h, and ROS scavenger, N-acetylcysteine (NAC), significantly reversed the cytotoxicity of silibinin through inhibiting both autophagy and apoptosis. Specific antioxidants were applied and results indicated that hydroxyl radical (·OH) was the major ROS induced by silibinin, and OH scavenger glutathione (GSH) inhibited apoptosis and autophagy. Silibinin also generated RNS production in the cells at 12 h. High concentration of N omega-nitro-l-arginine methyl ester (L-NAME) as nitric oxide synthase (NOS) inhibitor attenuated the cytotoxicity of silibinin by decreasing ROS levels, leading to down-regulation of apoptosis. Silibinin also could interrupt the respiring functions of mitochondria, leading to ROS production and oxidative damage. 相似文献
99.
Liu B Yang P Ye Y Zhou Y Li L Tashiro S Onodera S Ikejima T 《Free radical research》2011,45(7):835-847
Silibinin mostly has been used as hepatoprotectants, but it has other interesting activities, e.g. anti-cancer, cardial protective and brain-protective activities. A previous study demonstrated that silibinin protected amyloid β (Aβ)-induced mouse cognitive disorder by behavioural pharmacological observation. This study assessed the effect of silibinin on sodium nitroprusside (SNP)-treated rat pheochromocytoma PC12 cells. Subsequent morphologic observation, flow cytometric analysis and Western blot analysis indicated that treatment with SNP significantly induced apoptosis in PC12 cells. However, silibinin eliminated the apoptotic effect by reactive oxygen species (ROS) generation, especially hydroxyl free radical. Silibinin-induced autophagy through ROS generation when exerting a protective effect and silibinin-induced autophagy also enhanced the ROS generation since 3-methyladenine (3-MA), a specific autophagy inhibitor, decreased the ROS generation and rapamycin, an autophagy inducer, enhanced the ROS generation. Therefore, there exists a positive feedback loop between autophagy and ROS generation. Autophagy prevented SNP-induced apoptosis, since the addition of 3-MA significantly eliminated the protective effect of silibinin. This protective effect was attributed to the generation of ROS and its two downstream Ras/PI3K/NF-κB and Ras/Raf/MEK/ERK pathways. Both prevented PC12 cells from apoptosis. The PI3K/NF-κB pathway induced autophagy to protect PC12 cells, but the Raf/MEK/ERK pathway directly protected PC12 cells bypassing the autophagic effect. 相似文献
100.