• Title/Summary/Keyword: $3{\beta}$

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FoxO3a mediates transforming growth factor-β1-induced apoptosis in FaO rat hepatoma cells

  • Kim, Byung-Chul
    • BMB Reports
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    • v.41 no.10
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    • pp.728-732
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    • 2008
  • FoxO3a is a member of the forkhead box class O (FoxO) transcription factor family and an important regulator of apoptosis. This work aimed to elucidate the involvement of FoxO3a in transforming growth factor-${\beta}1$(TGF-${\beta}1$)-induced apoptosis in FaO rat hepatoma cells. TGF-${\beta}1$ caused a time-dependent activation of FoxO3a and a subsequent increase in FoxO response-element-containing luciferase reporter activity, which was Akt-sensitive. The FaO cells stably transfected with a wild type FoxO3a were more susceptible to the formation of apoptotic bodies, populations of sub-G1 apoptotic cells, and collapse of the mitochondrial-membrane potential triggered by TGF-${\beta}1$. In contrast, transfection with small-interfering RNA (siRNA) oligonucleotide specific for FoxO3a significantly inhibited caspase activation in FaO cells treated with TGF-${\beta}1$. It thus appears that FoxO3a plays a crucial mediatory role in the TGF-${\beta}1$ signaling pathway leading to apoptosis.

In Vitro Anticomplementary Activity of Hederagenin Saponins Isolated from Roots of Dipsacus asper

  • Oh, Sei-Ryang;Jung, Keun-Young;Son, Kun-Ho;Park, Si-Hyung;Lee, Im-Seon;Ahn, Yung-Seop;Lee, Hyeong-Kyu
    • Archives of Pharmacal Research
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    • v.22 no.3
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    • pp.317-319
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    • 1999
  • Anticomplementary activity of hederagenin and related saponins isolated from Dipsacus asper was investigated in vitro. HN saponin F (3) was most potent with $IC_{50}$ value of$ 3.7{\times}10^{-5} M$ followed by 3-O-${\beta}-D-glucopyranosyl-(1{\rightarrow} 3)-{\alpha}-L-rhamnopyranosyl-(1{\rightarrow}2)-{\beta}-L-arabinopyranosyl$ hederagenin $28-O-{\beta}-D-glucopyranosyl-(1{\rightarrow}6)-beta$-D-glucopyrano side (8), $3-O-{\beta}-L-arabinopyranosyl$ hederagenin $28-O-{\beta}-D-glucopyranosyl-(1{\rightarrow}6)-{\beta}-D-glucopyranoside$ (5), dipsacus saponin A (4), and hederagenin (1) on the classical pathway (CP) of complement system, while the saponins 3-5 did not show the inhibition of hemolysis and rather increase the hemolysis on the alternative pathway (AP). However, all of C-3 monodesmosides [prosapogenin CP (2), dipsacus saponin B (6), and dipsacus saponin C (7)] evoked hemolysis directly on the erythrocytes.

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Properties of Beta-Ga2O3 Film from the Furnace Oxidation of Freestanding GaN (FS-GaN을 열산화하여 제작된 Beta-Ga2O3 박막의 특성)

  • Son, Hoki;Lee, YoungJin;Lee, Mijai;Kim, Jin-Ho;Jeon, Dae-Woo;Hwang, Jonghee;Lee, Hae-Yong
    • Journal of the Korean Institute of Electrical and Electronic Material Engineers
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    • v.30 no.7
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    • pp.427-431
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    • 2017
  • In this paper, we discuss ${\beta}-Ga_2O_3$ thin films that have been grown on freestanding GaN (FS-GaN) using furnace oxidation. A GaN template was grown by horizontalhydride vapor phase epitaxy (HVPE), and FS-GaN was fabricated using the laser lift off (LLO) system. To obtain ${\beta}-Ga_2O_3$ thin film, FS-GaN was oxidized at $900{\sim}1,100^{\circ}C$. Surface and cross-section of prepared ${\beta}-Ga_2O_3$ thin films were observed by field emission scanning electron microscopy (FE-SEM). The single crystal FS-GaNs were changed to poly-crystal ${\beta}-Ga_2O_3$. The oxidized ${\beta}-Ga_2O_3$ thin film at $1,100^{\circ}C$ was peel off from FS-GaN. Next, oxidation of FS-GaNwas investigated for 0.5~12 hours with variation of the oxidation time. The thicknesses of ${\beta}-Ga_2O_3$ thin films were measured from 100 nm to 1,200 nm. Moreover, the 2-theta XRD result indicated that (-201), (-402), and (-603) peaks were confirmed. The intensity of peaks was increased with increased oxidation time. The ${\beta}-Ga_2O_3$ thin film was generated to oxidize FS-GaN.

Prolonged Exposure to Lipopolysaccharide Induces NLRP3-Independent Maturation and Secretion of Interleukin (IL)-1β in Macrophages

  • Hong, Sujeong;Yu, Je-Wook
    • Journal of Microbiology and Biotechnology
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    • v.28 no.1
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    • pp.115-121
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    • 2018
  • Upon sensing of microbial infections or endogenous danger signals in macrophages, inflammasome signaling plays a significant role in triggering inflammatory responses via producing interleukin (IL)-$1{\beta}$. Recent studies revealed that active caspase-1, a product of the inflammasome complex, causes maturation of inactive pro-IL-$1{\beta}$ into the active form. However, the underlying mechanism by which this leaderless cytokine is secreted into the extracellular space remains to be elucidated. In this study, we demonstrated that prolonged lipopolysaccharide (LPS) treatment to macrophages could trigger the unexpected maturation and extracellular release of IL-$1{\beta}$ through a nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3)-independent manner. Short-term treatment (less than 6 h) of LPS induced robust production of the IL-$1{\beta}$ precursor form inside cells but did not promote the maturation and secretion of IL-$1{\beta}$ in bone marrow-derived macrophages or peritoneal macrophages. Instead, prolonged LPS treatment (more than 12 h) led to a significant release of matured IL-$1{\beta}$ with no robust indication of caspase-1 activation. Intriguingly, this LPS-triggered secretion of IL-$1{\beta}$ was also observed in NLRP3-deficient macrophages. In addition, this unexpected IL-$1{\beta}$ release was only partially impaired by a caspase-1 and NLRP3 inflammasome inhibitor. Collectively, our results propose that prolonged exposure to LPS is able to drive the maturation and secretion of IL-$1{\beta}$ in an NLRP3 inflammasome-independent manner.

Incremental Expression of 14-3-3 Protein Beta/Alpha in Urine Correlates with Advanced Stage and Poor Survival in Patients with Clear Cell Renal Cell Carcinoma

  • Kaneko, Shiho;Matsumoto, Kazumasa;Minamida, Satoru;Hirayama, Takahiro;Fujita, Tetsuo;Kodera, Yoshio;Iwamura, Masatsugu
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1399-1404
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    • 2016
  • We investigated the urinary levels of 14-3-3 protein beta/alpha to evaluate their diagnostic significance with regard to clear cell renal cell carcinoma (ccRCC) and angiomyolipoma (AML). Urine samples from 91 patients with ccRCC, 16 patients with AML and 24 healthy volunteers were assessed. We used an enzyme-linked immunosorbent assay (ELISA) to quantify 14-3-3 protein beta/alpha levels in urine. Values were higher in patients with ccRCC than in those with AML and in healthy volunteers. High levels were associated with pathologic stage, lymph node status, distant metastasis and poor survival. Urinary levels of 14-3-3 protein beta/alpha were significantly increased in patients with small-sized carcinoma, irrespective of being less than 4.0 cm and 2.0 cm, compared with levels in patients with AML. This study is the first to report that increased expression of 14-3-3 protein beta/alpha in urine is associated with advanced stage and poor survival in patients with ccRCC. In addition, urinary 14-3-3 protein beta/alpha may differentiate AML from RCC, even when small sized. These results suggest that examination of urinary 14-3-3 protein beta/alpha could serve as a diagnostic and prognostic marker in patients with ccRCC.

Synthesis and Antitumor Evaluation of N-Alkyl-N-Nitrosocarbamoyl-$\alpha$-Amino- and 3$\beta$-Amino-$\alpha$-Cholestane Derivatives (N-Alkyl-N-Nitrosocarbamoyl-3$\alpha$-Amino-와 3$\beta$-Amino-5$\alpha$-Cholestane 유도체들의 합성 및 항암작용 평가)

  • 김정균;최순규;조인섭;유동식;유성호;문경호
    • YAKHAK HOEJI
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    • v.29 no.2
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    • pp.62-69
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    • 1985
  • The isomeric intermediates, $3{\alpha}$and $3{\beta}-amino-5{\alpha}-cholestane required for the synthesis of N-nitrosoureas, N-(2-chloroethyl)-N-nitrosocarbamoyl-$3{\alpha}-amino-5{\alpha}$-cholestane (9), N-methyl-N-nitrosocarbamoyl-3${\alpha}-amino-5{\alpha}-cholestane$ (10), N-(2-chloroethyl)-N-nitrosocarbamoyl-$3{\beta}-amino-5{\alpha}-cholestane$: (7), and N-methyl-N-nitrosocarbamoyl-$3{\beta}-amino-5{\alpha}-cholestane$ (8) were obtained through the $LiAlH_{4}$ reduction of $5{\alpha}$-cholestan-3-one oxime, followed by the chromatographic separation: the assignment of the stereochemistry of both isomers were based on the shape and chemical shift of $C_{3}$-proton resonances on their NMR spectra and on the elution mobility on the TLC. The urea intermediates, N-(2-chloroethyl) carbamoyl-3.alpha.-amino-5.alpha.-cholestane (13), N-methylcarbamoyl-$3{\alpha}-amino-5{\alpha}-cholestane$ (14), N-(2-chloroethyl) carbamoyl-$3{\beta}-amino-5{\alpha}-cholestane (11) and N-methyl-$3{\beta}-amino-5{\alpha}$-cholestane (12) were prepared by the treatment of each isomers ($3{\alpha}$-amino-and $3{\beta}-amino-5{\alpha}$-cholestane) with alkyl isocyanates in anhydrous $CHCl_{3}$, and the corresponding nitrosoureas, 7-10 were obtained by the nitrosation of the ureas, 11-14, with AcOH (or HCOOH)/$NaNO_{2}$ in ice-cold condition. The inhibitory activity of the nitrosoureas, 7-10, and their intermediates, 12-14 towards the growth of L1210 murine leukemia cells, were examined. Among them, the compounds 9 and 10 exhibited high activity having $ED_{50}$ to be 5.5g/ml and 6.1g/ml, respectively.

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A Study on the Mechanical Properties and Contact Damage of Silicon Nitrides : 1. Effect of ${\alpha}/{\beta}$ Phase Fraction (질화규소의 기계적 성질 및 접촉 손상: I. ${\alpha}/{\beta}$ 상분율의 영향)

  • 이승건
    • Journal of Powder Materials
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    • v.5 no.1
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    • pp.15-21
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    • 1998
  • The effect of $\alpha$/$\beta$ phase on the mechanical properties and contact damage of silicon nitrides $Si_3N_4$) was investigated. Silicon nitride materials were prepared from two starting powders, at selective increasing hot-pressing temperatures to coarsen the microstructures: (i) from relatively coarse $\alpha$-phase powder, essentially equiaxed $\alpha$-$Si_3N_4$ grains, with limited, slow transformation to $\beta$-$Si_3N_4$ grain; (ii) from relatively fine $\alpha$-phase powder, a more rapid transformation to $\beta$-$Si_3N_4$, with attendant grain elongation. The resulting micro-structure thereby provided a spectrum of $\alpha$/$\beta$ phase ratios, grain sizes, and grain shapes. Fracture strength, hardness, and toughness were measured, and contact damage and strength degradation after indentation were investigated by Hertzian indentation using spherical indenter. A brittle to ductile transition in $Si_3N_4$ depended on $\alpha$/$\beta$ phase ratio as well as grain size. Silicon nitride with elongated $\beta$ grains showed a superior, contact damage resistance.

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Formation of Methyl 2${\beta},\;3{\beta}$-Epoxy-23-hydroxyurs-12-en-28-oate from Asiaticoside and Its Reductive Epoxide Ring Opening Reaction (아시아티코사이드로부터 메칠 2${\beta},\;3{\beta}$-에폭시-23- 히드록시우르스-12-엔-28-오애이트의 합성 및 이의 환원적 에폭시환 개열반응)

  • Jew, Sang-Sup;Lim, Doo-Yeon;Seo, Sung-Ki;Nam, Tae-Gyu;Park, Hyeung-Geun;Kim, Hee-Doo;Kim, Chang-Min;Lee, Min-Hee;Paik, Hyeung-Geun;Lee, Min-Jung;Jung, Young-Hoon
    • YAKHAK HOEJI
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    • v.42 no.5
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    • pp.500-506
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    • 1998
  • Steroidal 2${\beta},\;3{\beta}$--epoxy compound was prepared from asiaticoside via six steps and reduced regioselectively with lithium aluminum hydride. Epoxide ring opening furnished 9 as a sole product at reflux condition through axial hydride attack at C-3.

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Saponins from the Roots of Pulsatilla koreana

  • Kang, Sam-Sik
    • Archives of Pharmacal Research
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    • v.12 no.1
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    • pp.42-47
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    • 1989
  • From the roots of Puisatiila koreana, three monodesmosides(pulsatilla saponins A, B and D) and two bisdesmosides(pulsatilla saponins F and H) were isolated. The structure of these saponins have been determined as hederagenin 3-O-${\beta}$-L-rhamnopyranosyl($1{\to}2$)- ${\alpha}$-L-arabinopyranoside(A), hederagenin 3-O-${\beta}$-D-glucopyrano syl($1{\to}4$) - ${\alpha}$-L-arabinopyranoside(B), hederagenin 3-O- ${\alpha}$-L-rhamnopyranosyl ($1{\to}2$)-[${\beta}$-D-glucopyranosyl($1{\to}4$]-${\alpha}$-L-arabinopyranoside(D), 3-O-${\alpha}$-L-rhamnopyranosyl($1{\to}2$)-{${\alpha}$-L-arabinopyranosyl hederagenin 28-O-${\alpha}$-L-rhamnopyrano syl($1{\to}4$)-${\beta}$-D-glucopyrano syl($1{\to}6$)-${\beta}$-D-glucopyranosyI ester (F) and 3-O-${\alpha}$-L-rhamnopyranosyl($1{\to}2$)-[${\beta}$-D-glucopyranosyl($1{\to}4$)]- ${\alpha}$-L-arabinopyranosyl hederagenin 28-O-${\alpha}$-L-lharnnopyranosyl($1{\to}4$)-${\beta}$-D-glucopyranosyl($1{\to}6$)-${\beta}$-D-glucop yranosyl ester(H) on the basis of chemical and spectral studies. Pulsatilla saponin B is the first report of its presence in plants but saponins A, D, F, and H have recently been isolated from the same genus p. cernua.

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GSK3β Inhibitor Peptide Protects Mice from LPS-induced Endotoxin Shock

  • Ko, Ryeojin;Jang, Hyun Duk;Lee, Soo Young
    • IMMUNE NETWORK
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    • v.10 no.3
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    • pp.99-103
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    • 2010
  • Background: Glycogen synthase kinase $3{\beta}$ ($GSK3{\beta}$) is a ubiquitous serine/threonine kinase that is regulated by serine phosphorylation at 9. Recent studies have reported the beneficial effects of a number of the pharmacological $GSK3{\beta}$ inhibitors in rodent models of septic shock. Since most of the $GSK3{\beta}$ inhibitors are targeted at the ATP-binding site, which is highly conserved among diverse protein kinases, the development of novel non-ATP competitive $GSK3{\beta}$ inhibitors is needed. Methods: Based on the unique phosphorylation motif of $GSK3{\beta}$, we designed and generated a novel class of $GSK3{\beta}$ inhibitor (GSK3i) peptides. In addition, we investigated the effects of a GSK3i peptide on lipopolysaccharide (LPS)-stimulated cytokine production and septic shock. Mice were intraperitoneally injected with GSK3i peptide and monitored over a 7-day period for survival. Results: We first demonstrate its effects on LPS-stimulated pro-inflammatory cytokine production including interleukin (IL)-6 and IL-12p40. LPS-induced IL-6 and IL-12p40 production in macrophages was suppressed when macrophages were treated with the GSKi peptide. Administration of the GSK3i peptide potently suppressed LPS-mediated endotoxin shock. Conclusion: Collectively, we present a rational strategy for the development of a therapeutic GSK3i peptide. This peptide may serve as a novel template for the design of non-ATP competitive GSK3 inhibitors.