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排序方式: 共有322条查询结果,搜索用时 15 毫秒
41.
Akira Kaieda Dr. Masashi Takahashi Hiromi Fukuda Dr. Rei Okamoto Dr. Shinji Morimoto Masayuki Gotoh Takahiro Miyazaki Yuri Hori Satoko Unno Dr. Tomohiro Kawamoto Dr. Toshimasa Tanaka Dr. Sachiko Itono Terufumi Takagi Dr. Hiroshi Sugimoto Dr. Kengo Okada Dr. Weston Lane Dr. Bi-Ching Sang Dr. Kumar Saikatendu Dr. Shinichiro Matsunaga Dr. Seiji Miwatashi 《ChemMedChem》2019,14(24):2093-2101
We identified novel potent inhibitors of p38 mitogen-activated protein (MAP) kinase using a structure-based design strategy, beginning with lead compound, 3-(butan-2-yl)-6-(2,4-difluoroanilino)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one ( 1 ). To enhance the inhibitory activity of 1 against production of tumor necrosis factor-α (TNF-α) in human whole blood (hWB) cell assays, we designed and synthesized hybrid compounds in which the imidazo[4,5-b]pyridin-2-one core was successfully linked with the p-methylbenzamide fragment. Among the compounds evaluated, 3-(3-tert-butyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-6-yl)-4-methyl-N-(1-methyl-1H-pyrazol-3-yl)benzamide ( 25 ) exhibited potent p38 inhibition, superior suppression of TNF-α production in hWB cells, and also significant in vivo efficacy in a rat model of collagen-induced arthritis (CIA). In this paper, we report the discovery of potent, selective, and orally bioavailable imidazo[4,5-b]pyridin-2-one-based p38 MAP kinase inhibitors. 相似文献
42.
Minami Sakamoto Tomomitsu Miyagaki Hiroaki Kamijo Tomonori Oka Hikari Boki Naomi Takahashi-Shishido Hiraku Suga Makoto Sugaya Shinichi Sato 《International journal of molecular sciences》2021,22(15)
CD147, a transmembrane glycoprotein that belongs to the immunoglobulin superfamily, and cyclophilin A (CypA), one of the binding partners of CD147, are overexpressed in tumor cells and associated with the progression of several malignancies, including both solid and hematological malignancies. However, CD147 and CypA involvement in cutaneous T-cell lymphoma (CTCL) has not been reported. In this study, we examined CD147 and CypA expression and function using clinical samples of mycosis fungoides (MF) and Sézary syndrome (SS) and CTCL cell lines. CD147 and CypA were overexpressed by tumor cells of MF/SS, and CypA was also expressed by epidermal keratinocytes in MF/SS lesional skin. Serum CypA levels were increased and correlated with disease severity markers in MF/SS patients. Anti-CD147 antibody and/or anti-CypA antibody suppressed the proliferation of CTCL cell lines, both in vitro and in vivo, via downregulation of phosphorylated extracellular-regulated kinase 1/2 and Akt. These results suggest that CD147-CypA interactions can contribute to the proliferation of MF/SS tumor cells in both a autocrine and paracrine manner, and that the disruption of CD147-CypA interactions could be a new therapeutic strategy for the treatment of MF/SS. 相似文献
43.
Solar Cells: Self‐Organized Superlattice and Phase Coexistence inside Thin Film Organometal Halide Perovskite (Adv. Mater. 8/2018) 下载免费PDF全文
44.
Energy value and digestibility of dietary oil containing mainly 1,3-diacylglycerol are similar to those of triacylglycerol 总被引:15,自引:7,他引:15
Diacylglycerol (DAG) is a component of various vegetable oils. Approximately 70% of the DAG in edible oils are in the configuration
of 1,3-DAG. We recently showed that long-term ingestion of dietary oil containing mainly 1,3-DAG reduces body fat accumulation
in humans as compared to triacylglycerol (TAG) oil with a similar fatty acid composition. As the first step to elucidate the
mechanism for this result, we examined the difference in the bioavailabilities of both oils by measuring food energy values
and digestibilities in rats. Energy values of the DAG oil and the TAG oil, measured by bomb calorimeter, were 38.9 and 39.6
kJ/g, respectively. Apparent digestibility expressed according to the formula: (absorbed) x (ingested)−1x100=(ingested—excreted in feces)x(ingested)−1x100 for the DAG oil and the TAG oil were 96.3±0.4 and 96.3±0.3% (mean±SEM), respectively. The similarity in the bioavailabilities
of both oils supports the hypothesis that the reduced fat accumulation by dietary DAG is caused by the different metabolic
fates after the absorption into the gastrointestinal epithelial cells. 相似文献
45.
The mouse gene Punc encodes a member of the immunoglobulin superfamily of cell surface proteins. It is highly expressed in the developing embryo in nervous system and limb buds. At mid-gestation, however, expression levels of Punc decrease sharply. To allow investigation of such a regulatory mechanism, the genomic locus encompassing the Punc gene was cloned, characterized, and mapped. Fluorescent in situ hybridization was used to determine the chromosomal location of the Punc gene of mouse and human. Mouse Punc maps to Chromosome (Chr) 9 in the region D-E1, whereas the human PUNC gene is localized to Chr 15 at 15q22.3-23, a region known to be syntenic to mouse 9D-E1. The human PUNC gene therefore maps close to a genetic locus that is linked to Bardet-Biedl Syndrome, an autosomal recessive human disorder. Confirmation for the location of human PUNC was obtained through sequence relationships between mouse Punc cDNA, human PUNC cDNA, genomic sequence upstream of the murine Punc gene, and human STS markers that had been previously mapped on Chr 15. The STS sequence WI-14920 is in fact derived from the 3'-untranslated region of the human PUNC gene. WI-14920 had been placed at 228cR from the top of the Chr 15 linkage group, which provided positional information for the human PUNC gene at high resolution. Thus, this study identifies PUNC as the gene corresponding to a previously anonymous marker and serves as a basis to investigate its role in genetic disorders. 相似文献
46.
Kazunori Wakasugi Akira Iida Tomonori Misaki Yoshinori Nishii Yoo Tanabe 《Advanced Synthesis \u0026amp; Catalysis》2003,345(11):1209-1214
We have developed an efficient method for the esterification or thioesterification of equimolar amounts of carboxylic acids and alcohols or thiols using a novel reagent, p‐toluenesulfonyl chloride (TsCl) together with N‐methylimidazole. The present method is simple, mild, and reactive, uses readily available and economical reagents. The choice of amine is critical for the present method. The amine, N‐methylimidazole, has two roles: (i) as an HCl scavenger for the initial smooth generation of mixed anhydrides between carboxylic acids and TsCl and (ii) successive formation of highly reactive ammonium intermediates from mixed anhydrides. This method could be applied to various types of carboxylic acids, alcohols, and thiols: a) several functionalities were tolerated; b) two N‐Cbz amino acids were smoothly esterified without racemization; and c) the labile 1β‐methylcarbapenem key intermediate and a pyrethroid insecticide, prallethrin, were successfully prepared. The related amide formation between carboxylic acids and primary or secondary amines was also performed. The proposed reaction mechanism involves a novel method for producing the reactive acylammonium intermediates. The production of these intermediates was rationally supported by a careful 1H NMR monitoring study. 相似文献
47.
Tomonori Unno Akio Sugimoto Takami Kakuda 《Journal of the science of food and agriculture》2000,80(5):601-606
Catechins are a major group of polyphenolic compounds contained in abundance in green tea. Using electron spin resonance spectroscopy along with a spin‐trapping agent, the scavenging effect of tea catechins and their corresponding epimers against superoxide anion radicals generated by a hypoxanthine and xanthine oxidase reaction system was evaluated. The presence of 3′,4′,5′‐trihydroxyl groups attached to the B‐ring of the flavan skeleton of tea catechins elevated their radical‐scavenging efficiency in comparison to those with 3′,4′‐dihydroxyl groups. There were no significant differences between the four dominant tea catechins and their corresponding epimers with regard to radical‐scavenging ability. Under the different spin‐trapping agent concentrations, the sigmoid curves of reducing spin‐trapping adducts produced by tea catechins were shifted leftward, suggesting that a likely possible action of tea catechins is to scavenge superoxide anion radicals directly, not to inhibit the function of xanthine oxidase. Although caffeine is also known as a major ingredient of tea, its superoxide anion radical‐scavenging effect was much weaker than that of the catechin family. It is concluded that tea catechins and their epimers serve as powerful antioxidants for directly eliminating superoxide anion radicals, and may be useful in the prevention of diseases relating to in vivo oxidative stress. © 2000 Society of Chemical Industry 相似文献
48.
49.
Takashi Maekawa Author Vitae Tetsuya Noda Author Vitae Author Vitae Tomonori Ozaki Author Vitae Author Vitae 《Computer aided design》2010,42(4):350-359
In this paper we introduce a roadmap algorithm for generating collision-free paths in terms of cubic B-spline curves for unmanned vehicles used in mining operations. The algorithm automatically generates collision-free paths that are curvature continuous with an upper bounded curvature and a small slope discontinuity of curvature at knots, when we are given the locations of the obstacles, the boundary geometry of the working area, positions and directions of the vehicle at the start, loading, and the goal points. Our algorithm also allows us to find a switch back point where the vehicle reverses its direction to enter the loading area. Examples are provided to demonstrate the effectiveness of the proposed algorithms. 相似文献
50.
Quantification of anaerobic ammonium-oxidizing bacteria in enrichment cultures by real-time PCR 总被引:7,自引:0,他引:7
The anaerobic ammonium-oxidizing (ANAMMOX) bacteria were enriched from a rotating disk reactor (RDR) biofilm in semi-batch cultures. Based on fluorescence in situ hybridization (FISH) analysis, this enrichment led to a relative population size of 36% ANAMMOX bacteria. Phylogenetic analysis revealed that all the detected clones were related to the previously reported ANAMMOX bacteria, Candidatus Brocadia anammoxidans (AF375994), with 92% sequence similarity. Furthermore, we successfully developed a real-time polymerase chain reaction (PCR) assay to quantify populations of ANAMMOX bacteria in the enrichment cultures. For this real-time PCR assay, PCR primer sets targeting 16S ribosomal RNA genes of ANAMMOX bacteria were designed and used. The quantification range of this assay was 6 orders of magnitude, from 8.9x10(1) to 8.9x10(6) copies per PCR, corresponding to the detection limit of 3.6x10(3) target copies mL(-1). A significant correlation was found between the increase in copy numbers of 16S rRNA gene of ANAMMOX bacteria and the increase in nitrogen removal rates in the enrichment cultures. Quantifying ANAMMOX bacterial populations in the enrichment culture made it possible to estimate the doubling time of the enriched ANAMMOX bacteria to be 3.6 to 5.4 days. The real-time PCR assay gave comparable population sizes in the enrichment cultures with the FISH results. These results suggest that the real-time PCR assay developed in this study is useful and reliable for quantifying the populations of ANAMMOX bacteria in environmental and engineering samples. 相似文献