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排序方式: 共有480条查询结果,搜索用时 15 毫秒
41.
42.
Kinzel O Alfieri A Altamura S Brunetti M Bufali S Colaceci F Ferrigno F Filocamo G Fonsi M Gallinari P Malancona S Hernando JI Monteagudo E Orsale MV Palumbi MC Pucci V Rowley M Sasso R Scarpelli R Steinkühler C Jones P 《Bioorganic & medicinal chemistry letters》2011,21(15):4429-4435
The Hedgehog (Hh-) signaling pathway is a key developmental pathway which gets reactivated in many human tumors, and smoothened (Smo) antagonists are emerging as novel agents for the treatment of malignancies dependent on the Hh-pathway, with the most advanced compounds demonstrating encouraging results in initial clinical trials. A novel series of potent bicyclic hydantoin Smo antagonists was reported in the preceding article, these have been resolved, and optimized to identify potent homochiral derivatives with clean off-target profiles and good pharmacokinetic properties in preclinical species. While showing in vivo efficacy in mouse allograft models, unsubstituted bicyclic tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-diones were shown to epimerize in plasma. Alkylation of the C-8 position blocks this epimerization, resulting in the identification of MK-5710 (47) which was selected for further development. 相似文献
43.
A synthetic process was developed to modify pectin samples under solvent free conditions, obtaining pectin at increasing concentration of palmitic, oleic, and linoleic acids. The weight loss of the modified powders showed a degradation path very similar to the pure pectin, indicating that the pristine structure was preserved after the chemical modification. A decreasing mass of evaporating water on increasing the fatty acid concentration, in particular for the palmitic acid modification, indicated a reduced water sorption by the modified powders. Differential scanning calorimetry confirmed the thermogravimetric results and in addition indicated the crystallization of the lateral chains in the case of palmitic-acid-modified pectins. This result was confirmed by X-ray diffractograms of the palmitic acid samples, indicating the main crystallization of the form C, although possible orientation phenomena can be inferred. The sorption curves of either the pristine pectin or the modified samples showed a dual sorption behavior. The sorption curves were interpreted by the BET and GAB equations, both giving very similar results. Palmitic acid modification was very effective in reducing all sorption parameters, whereas in the case of oleic and linoleic acids, only at high concentrations was the hydrophobic influence detected. 相似文献
44.
Bone regeneration and stem cells 总被引:1,自引:0,他引:1
Arvidson K Abdallah BM Applegate LA Baldini N Cenni E Gomez-Barrena E Granchi D Kassem M Konttinen YT Mustafa K Pioletti DP Sillat T Finne-Wistrand A 《Journal of cellular and molecular medicine》2011,15(4):718-746
This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed. 相似文献
45.
Mattioli E Columbaro M Capanni C Maraldi NM Cenni V Scotlandi K Marino MT Merlini L Squarzoni S Lattanzi G 《Cell death and differentiation》2011,18(8):1305-1315
Lamin A is a nuclear lamina constituent expressed in differentiated cells. Mutations in the LMNA gene cause several diseases, including muscular dystrophy and cardiomyopathy. Among the nuclear envelope partners of lamin A are Sad1 and UNC84 domain-containing protein 1 (SUN1) and Sad1 and UNC84 domain-containing protein 2 (SUN2), which mediate nucleo-cytoskeleton interactions critical to the anchorage of nuclei. In this study, we show that differentiating human myoblasts accumulate farnesylated prelamin A, which elicits upregulation and recruitment of SUN1 to the nuclear envelope and favors SUN2 enrichment at the nuclear poles. Indeed, impairment of prelamin A farnesylation alters SUN1 recruitment and SUN2 localization. Moreover, nuclear positioning in myotubes is severely affected in the absence of farnesylated prelamin A. Importantly, reduced prelamin A and SUN1 levels are observed in Emery-Dreifuss muscular dystrophy (EDMD) myoblasts, concomitant with altered myonuclear positioning. These results demonstrate that the interplay between SUN1 and farnesylated prelamin A contributes to nuclear positioning in human myofibers and may be implicated in pathogenetic mechanisms. 相似文献
46.
Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis 总被引:9,自引:0,他引:9
Camps M Rückle T Ji H Ardissone V Rintelen F Shaw J Ferrandi C Chabert C Gillieron C Françon B Martin T Gretener D Perrin D Leroy D Vitte PA Hirsch E Wymann MP Cirillo R Schwarz MK Rommel C 《Nature medicine》2005,11(9):936-943
Phosphoinositide 3-kinases (PI3K) have long been considered promising drug targets for the treatment of inflammatory and autoimmune disorders as well as cancer and cardiovascular diseases. But the lack of specificity, isoform selectivity and poor biopharmaceutical profile of PI3K inhibitors have so far hampered rigorous disease-relevant target validation. Here we describe the identification and development of specific, selective and orally active small-molecule inhibitors of PI3Kgamma (encoded by Pik3cg). We show that Pik3cg(-/-) mice are largely protected in mouse models of rheumatoid arthritis; this protection correlates with defective neutrophil migration, further validating PI3Kgamma as a therapeutic target. We also describe that oral treatment with a PI3Kgamma inhibitor suppresses the progression of joint inflammation and damage in two distinct mouse models of rheumatoid arthritis, reproducing the protective effects shown by Pik3cg(-/-) mice. Our results identify selective PI3Kgamma inhibitors as potential therapeutic molecules for the treatment of chronic inflammatory disorders such as rheumatoid arthritis. 相似文献
47.
Vania Patrone Raffaella Campana Emanuela Vittoria Wally Baffone 《Current microbiology》2010,60(4):237-241
The aim of this study is to evaluate possible synergistic antimicrobial interactions between common cosmetic preservatives
and selected essential oils or surfactants. The antimicrobial efficacy of six essential oils, three surfactants and five preservatives
against Pseudomonas aeruginosa ATCC 9027 and Staphylococcus aureus ATCC 43387 was assessed by a broth micro-dilution assay. MICs for individual and combined antimicrobials were determined
and then transformed to fractional inhibitory concentration (FIC) indexes. All essential oils exhibited antibacterial activity;
among surfactants, bacteria resulted most susceptible to the cationic agent. Synergy was observed when essential oils of eucalyptus
and mint were combined with methylparaben against P. aeruginosa, while essential oils of mint, oregano and sage combined with propylparaben and imidazolidinyl urea acted against S. aureus. Many binary mixtures of preservatives and surfactants produced synergistic activity with the most effective interactions
involving the cationic and amphoteric compounds under study. FIC indexes demonstrated synergistic effects when preservatives
were combined with either essential oils or surfactants against both bacterial strains. These results highlight the potential usefulness of essential oils and surfactants to enhance the activities of conventional
biocides. This kind of study should contribute to the selection and optimization of preservative systems for cosmetic preparations. 相似文献
48.
Coccetti P Zinzalla V Tedeschi G Russo GL Fantinato S Marin O Pinna LA Vanoni M Alberghina L 《Biochemical and biophysical research communications》2006,346(3):786-793
We have previously identified Ser201 of Sic1, a yeast cyclin-dependent kinase inhibitor, as an in vitro target of protein kinase CK2. Here we present new evidence, by using specific anti-P-Ser201 antibodies and 2-D gel electrophoresis coupled to MALDI mass spectrometry analysis, that Sic1 is phosphorylated in vivo on Ser201 shortly after its de novo synthesis, during late anaphase in glucose-grown cells. This phosphorylation is also detected in Sic1 immunopurified from G1 cells. In agreement with these data we also show that the catalytic alpha' subunit of CK2, whose function is required for cell cycle progression, is detected in Sic1 immunopurified complexes, and that phosphorylation on Ser201 is reduced after CK2 inactivation at the non-permissive temperature in a cka1delta cka2(ts) yeast strain. These data strongly support the notion that CK2 phosphorylates Sic1 in vivo. 相似文献
49.
50.
Xanthomonas axonopodis pv. citri (Xac) is the causal agent of citrus bacterial canker, an economically important disease to world citrus industry. To monitor the infection process of Xac in different citrus plants, the enhanced green florescent protein (EGFP) visualizing system was constructed to visualize the propagation and localization in planta. First, the wild-type Xac was isolated from the diseased leaves of susceptible 'Bingtang' sweet orange, and then the isolated Xac was labeled with EGFP by triparental mating. After PCR identification, the growth kinetics and pathogenicity of the transformants were analyzed in comparison with the wild-type Xac. The EGFP-labeled bacteria were inoculated by spraying on the surface and infiltration in the mesophyll of 'Bingtang' sweet orange leaves. The bacterial cell multiplication and diffusion processes were observed directly under confocal laser scanning microscope at different intervals after inoculation. The results indicated that the EGFP-labeled Xac releasing clear green fluorescence light under fluorescent microscope showed the infection process and had the same pathogenicity as the wild type to citrus. Consequently, the labeled Xac demonstrated the ability as an efficient tool to monitor the pathogen infection. 相似文献