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911.
Limnology - The objective of this study was to develop a hydro-chemical model using the Soil and Water Assessment Tool (SWAT) and to evaluate the climate change impacts on discharge and... 相似文献
912.
Nobuhiko Fushimi Hideki Fujikura Hiroaki Shiohara Hirotaka Teranishi Kazuo Shimizu Shigeru Yonekubo Kohsuke Ohno Takashi Miyagi Fumiaki Itoh Toshihide Shibazaki Masaki Tomae Yukiko Ishikawa-Takemura Takeshi Nakabayashi Noboru Kamada Tomonaga Ozawa Susumu Kobayashi Masayuki Isaji 《Bioorganic & medicinal chemistry》2012,20(22):6598-6612
Sodium glucose co-transporter 1 (SGLT1) plays a dominant role in the absorption of glucose in the gut and is considered a promising target in the development of treatments for postprandial hyperglycemia. A series of 4-benzyl-1H-pyrazol-3-yl β-d-glucopyranoside derivatives have been synthesized, and its inhibitory activity toward SGLTs has been evaluated. By altering the substitution groups at the 5-position of the pyrazole ring, and every position of the phenyl ring, we studied the structure–activity relationship (SAR) profiles and identified a series of potent and selective SGLT1 inhibitors. Representative derivatives showed a dose-dependent suppressing effect on the escalation of blood glucose levels in oral mixed carbohydrate tolerance tests (OCTT) in streptozotocin–nicotinamide-induced diabetic rats (NA-STZ rats). 相似文献
913.
Yoshitomo Nagata Satoru Kanuka Takatoshi Kinoshita Akira Takizawa Yoshiharu Tsujita Hiroaki Yoshimizu 《Biopolymers》1994,34(6):701-707
The complex formation behaviors of an α-helical polypeptide containing pyridyl ligands in the side chains, poly (Nω-2-pyridylmethyl L -glutamine) (P2PG), were investigated by absorption and CD spectroscopy using Cu2+ ion as a guest molecule in 2,2,2-trifiuoroethanol solution. In the low Cu2+ ion concentration, P2PG exhibited the predominant formation of Cu2+ and two pyridyl side-chain complexes, involving a regular arrangement of the pyridyl side chains. On the other hand, the complexes were converted to Cu2+ and one pyridyl side-chain species with increasing Cu2+ ion concentration. The conversion was accompanied by the disappearance of the side-chain ordered structure without any changes in the backbone conformation. Moreover, the still remaining coordination sites of Cu2+ were capable of complexing monomer pyridine (Py) added as a second guest to form ternary complexes, P2PG-Cu2+-Py, following the reconstitution of the ordered structure on the periphery of the α-helix backbone. The unique characteristics of P2PG can be explained in terms of the restriction of the pyridyl side chains to form intramolecular chelate complexes, depending on the rigid α-helix conformation. © 1994 John Wiley & Sons, Inc. 相似文献
914.
Protein Tyrosine Kinase 6 (PTK6) is a non-receptor type tyrosine kinase that may be involved in some cancers. However, the biological role and expression status of PTK6 in pancreatic cancer is unknown. Therefore in this study, we evaluated the functional role of PTK6 on pancreatic cancer invasion. Five pancreatic cancer cell lines expressed PTK6 at varying levels. PTK6 expression was also observed in human pancreatic adenocarcinomas. PTK6 suppression by siRNA significantly reduced both cellular migration and invasion (0.59/0.49 fold for BxPC3, 0.61/0.62 for Panc1, 0.42/0.39 for MIAPaCa2, respectively, p<0.05 for each). In contrast, forced overexpression of PTK6 by transfection of a PTK6 expression vector in Panc1 and MIAPaCa2 cells increased cellular migration and invasion (1.57/1.67 fold for Panc1, 1.44/1.57 for MIAPaCa2, respectively, p<0.05). Silencing PTK6 reduced ERK1/2 activation, but not AKT or STAT3 activation, while PTK6 overexpression increased ERK1/2 activation. U0126, a specific inhibitor of ERK1/2, completely abolished the effect of PTK6 overexpression on cellular migration and invasion. These results suggest that PTK6 regulates cellular migration and invasion in pancreatic cancer via ERK signaling. PTK6 may be a novel therapeutic target for pancreatic cancer. 相似文献
915.
H Okazaki H Tokuda K Ishii S Ishibashi 《Biochemical and biophysical research communications》1992,184(2):673-679
Exposure to the pentobarbital potently inhibited the 2-deoxy glucose uptake in cultured neuroblastoma cells. The inhibition was assumed to be due to saturation of the uptake in the early stage where the incorporation was linear in the nontreated cells. On the contrary, the incorporation of 3-O-methyl glucose, another glucose analog which is not phosphorylated by hexokinase, was not altered by the treatment with pentobarbital. These results suggest that the suppression of hexokinase is involved in the above-mentioned effect of pentobarbital. 相似文献
916.
917.
Sakai Kanae Hara Yasumasa Ishibashi Masami Sakai Mai Kawahara Seiya Imanishi Susumu Harada Kenichi Hoshino Yasutaka Komaki Hisayuki Mukai Akira Gonoi Tohru 《International journal of peptide research and therapeutics》2020,26(1):281-290
International Journal of Peptide Research and Therapeutics - Nocardithiocin is a thiopeptide compound produced by the pathogenic actinomycete Nocardia pseudobrasiliensis that displays activity... 相似文献
918.
Diverse involvements of Ni protein in superoxide anion production in polymorphonuclear leukocytes depending on the type of membrane stimulants 总被引:1,自引:0,他引:1
N Okamura M Uchida T Ohtsuka M Kawanishi S Ishibashi 《Biochemical and biophysical research communications》1985,130(3):939-944
Effects of islet-activating protein (IAP) were examined to assess the involvement of the guanine nucleotide-binding regulatory protein responsible for inhibition of adenylate cyclase system (Ni protein) in the superoxide anion (O-2) production in polymorphonuclear leukocytes (PMNL) stimulated with various agents. N-Formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated O-2 production was inhibited by the pretreatment with IAP. O-2 production induced by each of phorbol myristate acetate, concanavalin A, and A23187, however, was rather resistant to the pretreatment with IAP. This observation indicates that the Ni protein does not involve in the common pathway for the O-2 production. in PMNL, and the involvement is rather specific for the FMLP-induced production. O-2 production in PMNL stimulated with various membrane perturbing agents was also diverse in the requirement of extracellular Ca2+. 相似文献
919.
Apolipoprotein E and lipoprotein lipase secreted from human monocyte-derived macrophages modulate very low density lipoprotein uptake 总被引:10,自引:0,他引:10
S Ishibashi N Yamada H Shimano N Mori H Mokuno T Gotohda M Kawakami T Murase F Takaku 《The Journal of biological chemistry》1990,265(6):3040-3047
We investigated the roles of lipoprotein lipase and apolipoprotein E (apoE) secreted from human monocyte-derived macrophages in the uptake of very low density lipoproteins (VLDL). ApoCII-deficient VLDL were isolated from a patient with apoCII deficiency. The lipolytic conversion to higher density and the degradation of the apoCII-deficient VLDL by macrophages were very slight, whereas the addition of apoCII enhanced both their conversion and degradation. This suggests that the lipolysis and subsequent conversion of VLDL to lipoproteins of higher density are essential for the VLDL uptake by macrophages. VLDL incubated with macrophages obtained from subjects with E3/3 phenotype (E3/3-macrophages) showed a 17-fold greater affinity in inhibiting the binding of 2 micrograms/ml 125I-low density lipoprotein (LDL) to fibroblasts than native VLDL, whereas the incubation of VLDL with macrophages obtained from a subject with E2/2 phenotype (E2/2-macrophages) did not cause any increase in their affinity. Furthermore, 3 micrograms/ml 125I-VLDL obtained from a subject with E3/3 phenotype were degraded by E3/3-macrophages to a greater extent than by E2/2-macrophages (2-fold), indicating that VLDL uptake is influenced by the phenotype of apoE secreted by macrophages. From these results, we conclude that both lipolysis by lipoprotein lipase and incorporation of apoE secreted from macrophages alter the affinity of VLDL for the LDL receptors on the cells, resulting in facilitation of their receptor-mediated endocytosis. 相似文献
920.
H Shimano N Yamada S Ishibashi K Harada A Matsumoto N Mori T Inaba K Motoyoshi H Itakura F Takaku 《The Journal of biological chemistry》1990,265(22):12869-12875
To investigate the effects of recombinant human monocyte colony-stimulating factor (M-CSF) on plasma cholesterol metabolism, we injected M-CSF intravenously into New Zealand White rabbits (n = 13) at a dose of 100 micrograms/day for 7 days. After the treatment, the plasma cholesterol levels fell by 33.2% from 61.4 +/- 25.9 to 41.0 +/- 10.2 mg/dl (mean +/- S.D.). We also injected a large dose of M-CSF (500 micrograms/day) for 6 days into Watanabe Heritable Hyperlipidemic rabbits, which are deficient in low density lipoprotein (LDL) receptors. Again, there was a significant reduction in plasma cholesterol levels by 36.2% from 730.5 +/- 176.4 to 466.0 +/- 104.9 mg/dl (n = 4). In the kinetic studies in New Zealand White rabbits with very low density lipoprotein, LDL, and methylated LDL, the removal rates of those lipoproteins were increased 1.9-, 1.7-, and 2.0-fold, respectively, after the treatment. Immunoblot analysis of LDL receptors in the treated rabbits showed no significant changes in LDL receptor proteins in livers but a great increase in spleens and bone marrows compared with the controls. Messenger RNA was also estimated by Northern blotting in both groups, and the results were compatible with those from the immunoblot. The data suggest that M-CSF stimulates the clearance of lipoproteins containing apolipoprotein B-100 via both LDL receptor-dependent and -independent pathways in target cells of M-CSF and reduces plasma cholesterol. 相似文献