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61.
Hiroshi Miyazaki Hiroshi Sai Hiroshi Ohmizu Jun Murakami Akio Ohtani Tsuyoshi Ogiku 《Bioorganic & medicinal chemistry》2010,18(5):1968-1979
Butadiene-imide 1 (T-686) derivatives were synthesized and evaluated for their inhibitory activity against PAI-1 production and their ADMET (DMPK and toxicology) profiles. Among these derivatives, compound 15k (T-2639) showed good antithrombotic activity in two rat thrombosis models without affecting bleeding time, indicating reduction of haemorrhagic risk. We also describe in this report a practical synthesis of 15k suitable for scale-up using Z,E-selective Stobbe condensation. 相似文献
62.
溶菌酶及其分子改造研究进展 总被引:1,自引:0,他引:1
溶菌酶是一种优异的天然抗菌蛋白,可以成为抗生素和化学防腐剂的有效替代物,解决日益严峻的细菌耐药性问题和抗生素残留、化学防腐剂超标等食品安全问题。因此,深入研究并构建具有新型广谱杀菌能力的溶菌酶,对食品、医药、畜牧等行业的发展有着重要意义。对溶菌酶的分类、胞壁质酶活性和非酶活性杀菌性质以及蛋白质改造方法,特别是利用现代生物技术对溶菌酶进行抗菌活性增强、抗菌谱拓展的研究进行了综述和展望。 相似文献
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64.
The development of novel targeted therapies holds promise for conquering chemotherapy resistance, which is one of the major hurdles in current breast cancer treatment. Previous studies indicate that mitochondria uncoupling protein 2 (UCP-2) is involved in the development of chemotherapy resistance in colon cancer and lung cancer cells. In the present study we found that lower level of miR133a is accompanied by increased expression of UCP-2 in Doxorubicin-resistant breast cancer cell cline MCF-7/Dox as compared with its parental cell line MCF-7. We postulated that miR133a might play a functional role in the development of Doxorubicin-resistant in breast cancer cells. In this study we showed that: 1) exogenous expression of miR133a in MCF-7/Dox cells can sensitize their reaction to the treatment of Doxorubicin, which is coincided with reduced expression of UCP-2; 2) knockdown of UCP-2 in MCF-7/Dox cells can also sensitize their reaction to the treatment of Doxorubicin; 3) intratumoral delivering of miR133a can restore Doxorubicin treatment response in Doxorubicin-resistant xenografts in vivo, which is concomitant with the decreased expression of UCP-2. These findings provided direct evidences that the miR133a/UCP-2 axis might play an essential role in the development of Doxorubicin-resistance in breast cancer cells, suggesting that the miR133a/UCP-2 signaling cohort could be served as a novel therapeutic target for the treatment of chemotherapy resistant in breast cancer. 相似文献
65.
Yoshihisa Hirota Kimie Nakagawa Natsumi Sawada Naoko Okuda Yoshitomo Suhara Yuri Uchino Takashi Kimoto Nobuaki Funahashi Maya Kamao Naoko Tsugawa Toshio Okano 《PloS one》2015,10(4)
UbiA prenyltransferase domain-containing protein 1 (UBIAD1) plays a significant role in vitamin K2 (MK-4) synthesis. We investigated the enzymological properties of UBIAD1 using microsomal fractions from Sf9 cells expressing UBIAD1 by analysing MK-4 biosynthetic activity. With regard to UBIAD1 enzyme reaction conditions, highest MK-4 synthetic activity was demonstrated under basic conditions at a pH between 8.5 and 9.0, with a DTT ≥0.1 mM. In addition, we found that geranyl pyrophosphate and farnesyl pyrophosphate were also recognized as a side-chain source and served as a substrate for prenylation. Furthermore, lipophilic statins were found to directly inhibit the enzymatic activity of UBIAD1. We analysed the aminoacid sequences homologies across the menA and UbiA families to identify conserved structural features of UBIAD1 proteins and focused on four highly conserved domains. We prepared protein mutants deficient in the four conserved domains to evaluate enzyme activity. Because no enzyme activity was detected in the mutants deficient in the UBIAD1 conserved domains, these four domains were considered to play an essential role in enzymatic activity. We also measured enzyme activities using point mutants of the highly conserved aminoacids in these domains to elucidate their respective functions. We found that the conserved domain I is a substrate recognition site that undergoes a structural change after substrate binding. The conserved domain II is a redox domain site containing a CxxC motif. The conserved domain III is a hinge region important as a catalytic site for the UBIAD1 enzyme. The conserved domain IV is a binding site for Mg2+/isoprenyl side-chain. In this study, we provide a molecular mapping of the enzymological properties of UBIAD1. 相似文献
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68.
Atsuzawa K Nakazawa A Mizutani K Fukasawa M Yamamoto N Hashimoto T Usuda N 《Histochemistry and cell biology》2010,134(6):565-579
The presence of a mitochondrial fatty acid β-oxidation system in the retina was shown by immunohistochemistry. Fatty acids
are considered to serve as a major energy source metabolized by fatty acid β-oxidation together with glucose metabolized by
glycolysis in the organs of the entire body, but almost nothing is known about this metabolic system in the retina. Adult
rat retinae were subjected to immunofluorescence and immuno-electron microscopy for the localization of fatty acid β-oxidation
enzymes, together with western blot analysis for quantitation of the amount of enzyme proteins and DNA microarray analysis
for gene expression. All the enzymes examined were shown to be present in the retina, but in small amounts, with the amount
of protein and gene expression in the retina being about 1/10 of those in the liver. Immunohistochemistry at light and electron
microscopic levels revealed the enzymes to be more preferentially localized to the mitochondria of Müller cells than the retinal
neurons. The Müller cells were isolated from the retina and confirmed for the presence of mitochondrial fatty acid β-oxidation
enzymes. A mitochondrial fatty acid β-oxidation system was thus shown to be present in the retina heterogeneously. 相似文献
69.
A new species of the genus Machilus Nees (Lauraceae) from China, M. parapauhoi F. N. Wei, S. C. Tang & W. B. Xu is described and illustrated. The new species is similar to M. pauhoi Kanehira, but differs in its densely appressed pubescent branchlets and petioles, shorter petiole, 0.8–1.2 cm long and an infructescence conspicuously shorter than the leaf. It is also similar to M. kwangtungensis Yang, but differs by its oblique leaves, with falcately curved apex and 14–18 lateral veins on both sides of the midrib. Based on a study of the type and isotype specimens of M. balansae (Airy Shaw) F. N. Wei & S. C. Tang and M. grandifolia S. Lee & F. N. Wei, M. grandifolia is regarded as a new synonym of M. balansae. 相似文献
70.
Ramadurai Gowrishankar Manish Kumar Vinay Menon Sai Mangala Divi M. Saravanan P. Magudapathy B. K. Panigrahi K. G. M. Nair K. Venkataramaniah 《Biological trace element research》2010,133(3):357-363
Traditionally, Tinospora cordifolia (Willd.) Hook. F. & Thomson (Menispermaceae), Ocimum sanctum L. (Lamiaceae), Moringa oleifera Lam. (Moringaceae), and Phyllanthus niruri L. (Euphorbiaceae) are some of the commonly used medicinal plants in India for curing ailments ranging from common cold,
skin diseases, and dental infections to major disorders like diabetes, hypertension, jaundice, rheumatism, etc. To understand
and correlate their medicinal use, trace element studies on the aqueous extract of these medicinal plants have been carried
out using particle-induced X-ray emission technique. A 2-MeV proton beam was used to identify and characterize major and minor
elements namely Cl, K, Ca, Ti, Cr, Mn, Fe, Co, Ni, Cu, Zn, Br, and Sr in them. Results have revealed that these elements are
present in varying concentrations in the selected plants. Notable results include very high concentrations of Cl, K, and Ca
in all the leaf samples, appreciable levels of Mn in all plants, high Zn content in T. cordifolia, and the aqueous extract of Moringa leaves compared to others and relative higher concentrations of Cr in all the plants. 相似文献