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921.
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925.
A guide to naming sequenced plant genes 总被引:3,自引:0,他引:3
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David N. Deaton Young Do Jason Holt Michael R. Jeune H. Fritz Kramer Andrew L. Larkin Lisa A. Orband-Miller Gregory E. Peckham Chuck Poole Daniel J. Price Lee T. Schaller Ying Shen Lisa M. Shewchuk Eugene L. Stewart J. Darren Stuart Stephen A. Thomson Paris Ward Joseph W. Wilson Gordon Saxty 《Bioorganic & medicinal chemistry》2019,27(8):1456-1478
With the goal of discovering more selective anti-inflammatory drugs, than COX inhibitors, to attenuate prostaglandin signaling, a fragment-based screen of hematopoietic prostaglandin D synthase was performed. The 76 crystallographic hits were sorted into similar groups, with the 3-cyano-quinoline 1a (FP IC50?=?220,000?nM, LE?=?0.43) being a potent member of the 6,6-fused heterocyclic cluster. Employing SAR insights gained from structural comparisons of other H-PGDS fragment binding mode clusters, the initial hit 1a was converted into the 70-fold more potent quinoline 1d (IC50?=?3,100?nM, LE?=?0.49). A systematic substitution of the amine moiety of 1d, utilizing structural information and array chemistry, with modifications to improve inhibitor stability, resulted in the identification of the 300-fold more active H-PGDS inhibitor tool compound 1bv (IC50?=?9.9?nM, LE?=?0.42). This selective inhibitor exhibited good murine pharmacokinetics, dose-dependently attenuated PGD2 production in a mast cell degranulation assay and should be suitable to further explore H-PGDS biology. 相似文献
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YKL-40 protein expression in normal adult human tissues – an immunohistochemical study 总被引:1,自引:0,他引:1
Ringsholt M Høgdall EV Johansen JS Price PA Christensen LH 《Journal of molecular histology》2007,38(1):33-43
YKL-40, a 40 kDa plasma protein, is secreted by macrophages, neutrophils, chondrocytes, vascular smooth muscle cells and cancer
cells. High plasma YKL-40 is found in patients with inflammatory diseases and cancer, but it is not known how the protein
is expressed in tissues. This immunohistochemical study was carried out with the purpose of mapping and grading cytoplasmic
expression of YKL-40 in normal human tissue. Bovine serum albumin had to be used for pre-incubation in order to eliminate
background staining of YKL-40. The majority of cells were stained, but the intensity varied, not just among different cell
types but also within the same cell type. Cells known for exerting a high metabolic activity, i.e., high producing cells or
cells with high turn-over, tended to show the most intense cytoplasmic staining, which was weak or lacking in cells with no
or little activity. Many of these positive cells probably contribute to the YKL-40 found in plasma in healthy subjects in
accordance with previous findings on their in vitro production of the protein. In conclusion, all cells with a functioning
nucleus appeared to be capable of expressing YKL-40 in their cytoplasm, the intensity of which was dependent on cellular activity.
An erratum to this article can be found at 相似文献
930.
An ethnobotanical study was conducted from October 2005 to June 2006 to investigate the uses of medicinal plants by people in Zegie Peninsula, northwestern Ethiopia. Information was gathered from 200 people: 70 female and 130 males, using semistructured questionnaire. Of which, six were male local healers. The informants, except the healers, were selected randomly and no appointment was made prior to the visits. Informant consensus factor (ICF) for category of aliments and the fidelity level (FL) of the medicinal plants were determined. Sixty-seven medicinal plants used as a cure for 52 aliments were documented. They are distributed across 42 families and 64 genera. The most frequently utilized plant part was the underground part (root/rhizome/bulb) (42%). The largest number of remedies was used to treat gastrointestinal disorder and parasites infections (22.8%) followed by external injuries and parasites infections (22.1%). The administration routes are oral (51.4%), external (38.6%), nasal (7.9%), and ear (2.1%). The medicinal plants that were presumed to be effective in treating a certain category of disease, such as 'mich' and febrile diseases (0.80) had higher ICF values. This probably indicates a high incidence of these types of diseases in the region, possibly due to the poor socio-economic and sanitary conditions of this people. The medicinal plants that are widely used by the local people or used as a remedy for a specific aliment have higher FL values (Carissa spinarum, Clausena anisata, Acokanthera schimperi, Calpurnia aurea, Ficus thonningii, and Cyphostemma junceum) than those that are less popular or used to treat more than one type of aliments (Plumbago zeylanicum, Dorstenia barnimiana). 相似文献