• Title/Summary/Keyword: RAF

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Docking and Quantum Mechanics-Guided CoMFA Analysis of b-RAF Inhibitors

  • Muddassar, M.;Pasha, F. A.;Yoo, Kyung-Ho;Lee, So-Ha;Cho, Seung-Joo
    • Bulletin of the Korean Chemical Society
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    • v.29 no.8
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    • pp.1499-1504
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    • 2008
  • Pyrazine derivatives bind to b-RAF receptor which is important in cancer therapy. The ligand-receptor interactions have been studied by comparative molecular field analysis (CoMFA) and molecular docking methods. Applying conventional ligand-based alignment schemes for the whole set was not successful. However, QM and DFT results suggested that some ligands have electrostatic interaction while others have steric interactions. On the basis of these results, we divided the dataset into two subsets. Electrostatic effect was found to be important in one set while steric effect for the other. Best docking modes were obtained for each subset based on the available crystal structure. These receptor-guided CoMFA models propose an interesting possibility which is difficult to obtain otherwise. i.e., in one binding mode the electrostatic interaction plays a key role for one subset ($q^2$ = 0.46, $r^2$ = 0.98), while in another binding mode steric effect is important with another subset ($q^2$ = 0.43, $r^2$ = 0.74).

Exergy Analysis of Gas Turbine System Depending on Steam Injection Method (증기 분사 방식에 따른 가스터빈 시스템의 엑서지 해석)

  • MIJIDDORJ, DASHTSEDEN;LIM, SOK KYU;JUNG, YOUNG GUAN;KIM, KYOUNG HOON
    • Transactions of the Korean hydrogen and new energy society
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    • v.28 no.5
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    • pp.570-576
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    • 2017
  • Gas turbine system with steam injection has shown outstanding advantages such as high specific power and NOx reduction. In the present work, a comparative exergetic analysis was carried out for Steam Injected Gas Turbine (STIG), Regenerative Steam Injected Gas Turbine (RSTIG), and Regenerative After Fogging Gas Turbine (RAF). Effects of pressure ratio, steam injection ratio and steam injection method on the system performance was theoretically investigated. The results showed that the order of the highest exergy efficiency is RSTIG, RAF, and STIG for low pressure ratios but STIG, RSTIG, and RAF for high pressure ratios. In each arrangement, the combustion chamber has the highest exergy destruction and the compressor has the second one.

Radical-Scavenging Activities of Fermented Cactus Cladodes (Opuntia humifusa Raf.) (천년초 발효물의 라디칼 소거능)

  • Kim, Joo-Sung
    • The Korean Journal of Food And Nutrition
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    • v.29 no.2
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    • pp.200-205
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    • 2016
  • The aim of this work was to select suitable fermentation treatments for the efficient bioconversion of cactus (Opuntia humifusa Raf.) bioactive components with an improved radical scavenging activity for use as a nutraceutical. To obtain microorganisms for the microbial conversion of cactus, Leuconostoc mesenteroides ATCC8294, Lactobacillus plantarum KCTC 3099, Lactobacillus plantarum KERI 236 and Monascus pilosus KCCM 60029 (ATCC 22080) were used for fermentation. Fermentation by Lac. plantarum KCTC 3099 was the most effective at scavenging 1,1-diphenyl-2-picrylhydrazyl hydrate (DPPH) and 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals and reducing iron (III). In particular, uronic acid levels showed a remarkable increase in fermentation. The polyphenol and quercetin content of the fermented cactus showed large increases from $108.65{\mu}g/mL$ and $2.71{\mu}g/mL$ to $227.83{\mu}g/mL$ and $9.73{\mu}g/mL$, respectively, showing a maximum level at 36 h of fermentation with Lac. plantarum KCTC 3099. Thus, cactus fermentation with Lac. plantarum is an useful process for the enhancement of antioxidant contents and activity of fresh cactus.

Differential Activation of Ras/Raf/MAPK Pathway between Heart and Cerebral Artery in Isoproterenol-induced Cardiac Hypertrophy

  • Kim, Hyun-Ju;Kim, Na-Ri;Joo, Hyun;Youm, Jae-Boum;Park, Won-Sun;Warda, Mohamed;Kang, Sung-Hyun;Thu, Vu-Thi;Khoa, Tran-Minh;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.9 no.5
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    • pp.299-304
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    • 2005
  • Cardiac hypertrophy contributes an increased risk to major cerebrovascular events. However, the molecular mechanisms underlying cerebrovascular dysfunction during cardiac hypertrophy have not yet been characterized. In the present study, we examined the molecular mechanism of isoproterenol (ISO)-evoked activation of Ras/Raf/MAPK pathways as well as PKA activity in cerebral artery of rabbits, and we also studied whether the activations of these signaling pathways were altered in cerebral artery, during ISO-induced cardiac hypertrophy compared to heart itself. The results show that the mRNA level of c-fos (not c-jun and c-myc) in heart and these genes in cerebral artery were considerably increased during cardiac hypertrophy. These results that the PKA activity and activations of Ras/Raf/ERK cascade as well as c-fos expression in rabbit heart during cardiac hypertrophy were consistent with previous reports. Interestingly, however, we also showed a novel finding that the decreased PKA activity might have differential effects on Ras and Raf expression in cerebral artery during cardiac hypertrophy. In conclusion, there are differences in molecular mechanisms between heart and cerebral artery during cardiac hypertrophy when stimulated with β2 adrenoreceptor (AR), suggesting a possible mechanism underlying cerebrovascular dysfunction during cardiac hypertrophy.

Interleukin-8-like chemotactic factor from feline peripheral blood mononuclear cells cultured with egg white derivatives (계난백유래물질로 배양한 고양이 말초혈액 단핵구세포에서 분비되는 interleukin- 8 양(樣) 유주성인자)

  • Lee, Jae-kwon;Yang, Mhan-pyo
    • Korean Journal of Veterinary Research
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    • v.40 no.2
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    • pp.393-401
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    • 2000
  • The feline chemotactic factor(s) for polymorphonuclear cells (PMN) in culture supernatant from mononuclear cells (MNC) treated with egg white derivatives (EWD) were examined. Culture supernatant from MNC treated with EWD and human recombinant (hr) IL-8 remarkably enhanced chemo-taxis of feline PMN. To investigate feline chemotactic factor(s), gel electrophoresis was performed with culture supernatant from MNC treated with EWD under denaturing (18% loading gel/5% stacking gel) and nondenaturing (12.5% loading gel/5% stacking gel) condition. Hr IL-8 and culture supernatant from MNC treated with EWD yielded a distinct band in a molecular weight, 6 to 8 kDa. Eluted solution from gel slices of 6 to 8 kDa band in denaturing condition also enhanced feline PMN chemotaxis. These chemotactic activities of feline PMN induced by culture supernatant from MNC treated with EWD, hr IL-8 and eluted solution were inhibited in a dose-dependent manner by rabbit anti-feline polyclonal IgG (RAF pIgG) and monoclonal antibody (mAb) against hr IL-8. RAF pIgG also showed a binding activity with hr IL-8, suggesting that RAF pIgG against feline IL-8-like chemotactic factor(s) had cross-reactivity with human IL-8. These results suggested that feline MNC treated with EWD might release feline IL-8-like chemotactic factor(s) with a molecular weight, 6 to 8 kDa, which induces the chemotaxis of feline PMN.

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NDRG3-mediated lactate signaling in hypoxia

  • Park, Kyung Chan;Lee, Dong Chul;Yeom, Young Il
    • BMB Reports
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    • v.48 no.6
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    • pp.301-302
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    • 2015
  • Hypoxia is associated with many pathological conditions as well as the normal physiology of metazoans. We identified a lactate-dependent signaling pathway in hypoxia, mediated by the oxygen- and lactate-regulated protein NDRG family member 3 (NDRG3). Oxygen negatively regulates NDRG3 expression at the protein level via the PHD2/VHL system, whereas lactate, produced in excess under prolonged hypoxia, blocks its proteasomal degradation by binding to NDRG3. We also found that the stabilized NDRG3 protein promotes angiogenesis and cell growth under hypoxia by activating the Raf-ERK pathway. Inhibiting cellular lactate production abolishes NDRG3-mediated hypoxia responses. The NDRG3-Raf-ERK axis therefore provides the genetic basis for lactate-induced hypoxia signaling, which can be exploited for the development of therapies targeting hypoxia-induced diseases in addition to advancing our understanding of the normal physiology of hypoxia responses. [BMB Reports 2015; 48(6): 301-302]

Flavonoids from the Stems of Eastern Picklypear Opuntia humifusa, Cactaceae

  • Park, Si-Hyung;Kim, Hui;Rhyu, Dong-Young
    • Journal of Applied Biological Chemistry
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    • v.50 no.4
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    • pp.254-258
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    • 2007
  • Five flavonoids, isorhamnetin 3-O-${\beta}$-D-galactosyl-4'-O-${\beta}$-D-glucoside (1), isorhamnetin 3,4'-di-O-${\beta}$-D-glucoside (2), isorhamnetin 3-O-${\beta}$-D-(6-O-${\alpha}$-L-rhamnosyl)glucosyl-4'-O-${\beta}$-D-glucoside (3), isorhamnetin 3-O-${\beta}$-D-(6-O-${\alpha}$-L-rhamnosyl)glucoside (4), and isorhamnetin 3-O-${\beta}$-D-(6-O-${\alpha}$-L-rhamnosyl) galactoside (5) were isolated from the stems of Opuntia humifusa (Raf.) Raf. and their structures were identified based on LC-MS and NMR data.