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51.
Ogino Hideki; Nakabayashi Kazuhiko; Michishita Eriko; Scherer Stephen W.; Fujii Michihiko; Suzuki Toshikazu; Ayusawa Dai 《DNA research》1998,5(4):247-250
Pieces of metaphase chromosomes prepared from mouse cells containingneo-tagged human chromosome 7 were transferred to mouse cellswith calcium phosphate to isolate G418-resistant clones. FISHanalysis revealed that the majority of them contained humanDNA at a single site on their genome. These transformants containedSTS markers mapped to various regions of chromosome 7. It isthus suggested that pieces of human chromosomes tend to assembleand integrate on the mouse genome. 相似文献
52.
Toshio Watanabe Toshihisa Takeuchi Osamu Handa Yasuhisa Sakata Tetsuya Tanigawa Masatsugu Shiba Yuji Naito Kazuhide Higuchi Kazuma Fujimoto Toshikazu Yoshikawa Tetsuo Arakawa 《PloS one》2015,10(4)
Background
Low-dose aspirin (LDA) frequently causes small bowel injury. While some drugs have been reported to be effective in treating LDA-induced small intestinal damage, most studies did not exclude patients with mild damage thought to be clinically insignificant.Aim
We conducted a multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy of a high dose of rebamipide, a gastroprotective drug, for LDA-induced moderate-to-severe enteropathy.Methods
We enrolled patients who received 100 mg of enteric-coated aspirin daily for more than 3 months and were found to have more than 3 mucosal breaks (i.e., erosions or ulcers) in the small intestine by capsule endoscopy. Eligible patients were assigned to receive either rebamipide 300 mg (triple dose) 3 times daily or placebo for 8 weeks in a 2:1 ratio. Capsule endoscopy was then repeated. The primary endpoint was the change in the number of mucosal breaks from baseline to 8 weeks. Secondary endpoints included the complete healing of mucosal breaks at 8 weeks and the change in Lewis score (an endoscopic score assessing damage severity) from baseline to 8 weeks.Results
The study was completed by 38 patients (rebamipide group: n = 25, placebo group: n = 13). After 8 weeks of treatment, rebamipide, but not placebo, significantly decreased the number of mucosal breaks (p = 0.046). While the difference was not significant (p = 0.13), the rate of complete mucosal break healing in the rebamipide group (32%, 8 of 25) tended to be higher than that in the placebo group (7.7%, 1 of 13). Rebamipide treatment significantly improved intestinal damage severity as assessed by the Lewis score (p = 0.02), whereas placebo did not. The triple dose of rebamipide was well tolerated.Conclusions
High-dose rebamipide is effective for the treatment of LDA-induced moderate-to-severe enteropathy.Trial Registration
UMIN Clinical Trials Registry UMIN000003463 相似文献53.
54.
Fu-Zheng Wei Ziyang Cao Xi Wang Hui Wang Mu-Yan Cai Tingting Li Naoko Hattori Donglai Wang Yipeng Du Boyan Song Lin-Lin Cao Changchun Shen Lina Wang Haiying Wang Yang Yang Dan Xie Fan Wang Toshikazu Ushijima Ying Zhao Wei-Guo Zhu 《Autophagy》2015,11(12):2309-2322
Macroautophagy is an evolutionarily conserved cellular process involved in the clearance of proteins and organelles. Although the autophagy regulation machinery has been widely studied, the key epigenetic control of autophagy process still remains unknown. Here we report that the methyltransferase EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) epigenetically represses several negative regulators of the MTOR (mechanistic target of rapamycin [serine/threonine kinase]) pathway, such as TSC2, RHOA, DEPTOR, FKBP11, RGS16 and GPI. EZH2 was recruited to these genes promoters via MTA2 (metastasis associated 1 family, member 2), a component of the nucleosome remodeling and histone deacetylase (NuRD) complex. MTA2 was identified as a new chromatin binding protein whose association with chromatin facilitated the subsequent recruitment of EZH2 to silenced targeted genes, especially TSC2. Downregulation of TSC2 (tuberous sclerosis 2) by EZH2 elicited MTOR activation, which in turn modulated subsequent MTOR pathway-related events, including inhibition of autophagy. In human colorectal carcinoma (CRC) tissues, the expression of MTA2 and EZH2 correlated negatively with expression of TSC2, which reveals a novel link among epigenetic regulation, the MTOR pathway, autophagy induction, and tumorigenesis. 相似文献
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57.
Li Z Mizuno S Nakamura T 《American journal of physiology. Gastrointestinal and liver physiology》2007,292(2):G639-G646
Cholestasis, an impairment of bile outflux, frequently occurs in liver diseases. In this process, an overaccumulation of bile acids causes hepatocyte necrosis and apoptosis, leading to advanced hepatitis. Hepatocyte growth factor (HGF) is mitogenic toward hepatocytes, but it is still unclear whether HGF has physiological and therapeutic functions during the progression of cholestasis. Using anti-HGF IgG or recombinant HGF in mice that had undergone bile duct ligation (BDL), we investigated the involvement of HGF in cholestasis-induced hepatitis. After the BDL surgery, HGF and c-Met mRNA levels transiently increased in livers during the progression of cholestatic hepatitis. When c-Met tyrosine phosphorylation was blocked in the livers of BDL-treated mice by anti-HGF IgG, hepatic dysfunction became evident, associated with the acceleration of hepatocyte necrosis and apoptosis. Inversely, administration of recombinant HGF into the mice led to the prevention of cholestasis-induced inflammation: HGF suppressed the hepatic expression of intracellular adhesion molecule-1 and neutrophil infiltration in BDL-treated mice. As a result, parenchymal necrosis was suppressed in the HGF-injected BDL mice. In addition, HGF supplement therapy reduced the number of apoptotic hepatocytes in cholestatic mice, associated with the early induction of Bcl-xL. The administration of HGF enhanced hepatic repair, via accelerating G1/S progression in hepatocytes. Our study showed that 1) upregulation of HGF production is required for protective mechanisms against cholestatic hepatitis and 2) enhancement of the intrinsic defense system by adding HGF may be a reasonable strategy to attenuate hepatic inflammation, necrosis, and apoptosis under bile-congestive conditions. 相似文献
58.
Shiina I Sano Y Nakata K Suzuki M Yokoyama T Sasaki A Orikasa T Miyamoto T Ikekita M Nagahara Y Hasome Y 《Bioorganic & medicinal chemistry》2007,15(24):7599-7617
Two new synthetic pathways to the anti-cancer agent tamoxifen and its derivatives were developed. The first route involved the aldol reaction of benzyl phenyl ketone with acetaldehyde followed by Friedel–Crafts substitution with anisole in the presence of Cl2Si(OTf)2 to produce 1,1,2-triaryl-3-acetoxybutane, a precursor of the tamoxifen derivatives. The second one utilized the novel three-component coupling reaction among aromatic aldehydes, cinnamyltrimethylsilane, and aromatic nucleophiles using HfCl4 as a Lewis acid catalyst to produce 3,4,4-triarylbutene, that is also a valuable intermediate of the tamoxifen derivatives. The former strategy requires a total of 10 steps from the aldol formation to the final conversion to tamoxifen, whereas the latter needs only three or four steps to produce tamoxifen and droloxifene including the installation of the side-chain moiety and the base-induced double-bond migration to form the tetra-substituted olefin structure. This synthetic strategy seems to serve as a new and practical pathway to prepare not only the tamoxifen derivatives but also the other SERMs (selective estrogen receptor modulators) including estrogen-dependent breast cancer and osteoporosis agents. 相似文献
59.
Aoi W Naito Y Nakamura T Akagiri S Masuyama A Takano T Mizushima K Yoshikawa T 《The Journal of nutritional biochemistry》2007,18(2):140-145
Milk fermented with a starter containing Lactobacillus helveticus and Saccharomyces cerevisiae is drunk on a daily basis by many people in Japan and has several beneficial effects. We studied the influence of this fermented milk product on muscle damage after prolonged exercise in rats. Wistar rats were divided into four groups: rested controls, rested rats given fermented milk diet, exercised rats and exercised rats given fermented milk diet. After 3 weeks of acclimatization, both exercise groups were made to run on a treadmill at 26 m/min for 60 min. Exercise increased the serum creatine kinase level, as well as myeloperoxidase activity and the level of thiobarbituric-acid-reactive substances in the gastrocnemius muscle after 24 h. These changes were ameliorated by intake of fermented milk. An increase of CINC-1 was also ameliorated by fermented milk. Furthermore, milk diet increased the mRNA and protein levels of protective proteins such as antioxidants and chaperone proteins. These results indicate that fermented milk can ameliorate delayed-onset muscle damage after prolonged exercise, which is associated with an increased antioxidant capacity of muscles. 相似文献
60.
Epigenetic field for cancerization 总被引:2,自引:0,他引:2
Ushijima T 《Journal of biochemistry and molecular biology》2007,40(2):142-150