• 제목/요약/키워드: $PI3K{\gamma}$

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PI3K, Akt, p38을 포함한 인산화단백질에 대한 Cordycepin의 억제효과 (The Inhibitory Effects of Cordycepin on Phosphoproteins including PI3K, Akt, and p38)

  • 권혁우;이동하
    • 대한임상검사과학회지
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    • 제49권2호
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    • pp.99-107
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    • 2017
  • 진균 속에 속하는 종인 Cordyceps는 중국의 전통약제로서, 그 유효성분인 cordycepin이 혈소판 응집에 관여한다는 보고가 있지만 phosphoprotein 조절에 관련된 연구는 미흡하다. 본 연구에서는, cordycepin이 fibrinogen binding에 관여한다고 알려진 PI3k/Akt와 $TXA_2$ 분비 및 과립방출에 관여한다고 알려진 p38와 같은 phosphoprotein의 인산화를 어떻게 조절하며 혈소판응집을 억제시키는지 규명하고자 하였다. 그 결과, cordycepin가 $261.1{\mu}M$$IC_{50}$으로 collagen이 유도한 혈소판 응집을 강력하게 억제하였고, PI3K와 Akt의 인산화를 감소시키며 ${\alpha}IIb/{\beta}_3$에 대한 fibrinogen 결합을 농도의존적으로 억제하였다. 또한, cordycepin은 collagen이 촉진시킨 p38의 인산화를 억제함으로써, 과립방출의 지표인 ATP 과 serotonin의 방출을 억제하였고 COX-1과 TXAS의 활성 및 $PLC-{\gamma}_2$ 인산화에 대한 영향없이 $TXA_2$ 생성량을 감소시켰다. 따라서, cordycepin은 PI3K/Akt, p38와 같은 phosphoprotein의 인산화를 억제함으로써 혈소판 응집억제를 나타내는 항혈전 치료 및 예방약물로서 유용한 가치가 있다고 여겨진다.

CAVITY OF CREATION FOR COLD FUSION AND GENERATION OF HEAT

  • Oh, Hung-Kuk
    • 한국에너지공학회:학술대회논문집
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    • 한국에너지공학회 1996년도 추계학술발표회 논문집
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    • pp.3-12
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    • 1996
  • Cold fusion technologies now are being developed very successfully. The $\pi$-far infrared rays are generated from three dimensional crystallizing $\pi$-bondings of oxygen atoms in water molecules. The growing cavity in water molecules make near resonance state and a vortex of infrared rays and attracts $\pi$-far infrared rays in the water. The cavity surrounded by a lot of $\pi$-far infrared rays has a very strong gravitational field. The $\pi$-far infrared rays are contracted into $\pi$-far infrared rays of half wave length and of one wave length. The $\pi$-far infrared rays of half wave length generate heat while $\pi$-far infrared rays of one wave length are contracted into $\pi$-gamma rays of one wave length. The contracted $\pi$-gamma rays of one wave length make nucleons and mesons, which is the creation and transmutation of matter by covalent bondings and three-dimensional crystallizing $\pi$-bondings into implosion bonding. Patterson power cell generates a very strong gravitational cavity because the electrolysized oxygen atoms make $\pi$-far infrared rays than in plain water.

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Cs-137 및 Co-60감마선 조사장치 설치 연구 (Installation Study of Gamma-ray Irradiation Systems Using Cs-137 and Co-60 Sources)

  • 김원식;하석호;황선태
    • Journal of Radiation Protection and Research
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    • 제11권2호
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    • pp.123-129
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    • 1986
  • Cs-137 및 Co-60감마선 조사장치를 사용하여 비임의 입체각이 $2.4{\pi}{\times}10^{-3}sr$에서 $17.3{\pi}{\times}10^{-3}sr$로 변함에 따른 공기의 산란인자와 두께 2.9cm 납 흡수체 사용에 따른 축적인자를 결정하였다. 그 결과 산란인자는 $1{\sim}1.064$, 축적인자는 $1.054{\sim}1.194$범위의 값을 갖는 것으로 각각 나타났다. 결정된 인자들의 검증을 위하여 계산값과 측정값을 비교한 결과 그 차이는 3.3%이하인 것으로 나타났다.

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ERROR BOUNDS FOR GAUSS-RADAU AND GAUSS-LOBATTO RULES OF ANALYTIC FUNCTIONS

  • Ko, Kwan-Pyo
    • 대한수학회논문집
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    • 제12권3호
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    • pp.797-812
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    • 1997
  • For analytic functions we give an expression for the kernel $K_n$ of the remainder terms for the Gauss-Radau and the Gauss-Lobatto rules with end points of multiplicity r and prove the convergence of the kernel we obtained. The error bound are obtained for the type $$\mid$R_n(f)$\mid$ \leq \frac{1}{\pi}l(\Gamma) max_{z \in \Gamma} $\mid$K_n(z)$\mid$ max_{z \in \Gamma} $\mid$f(z)$\mid$$, where $l(\Gamma)$ denotes the length of contour $\Gamma$.

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Dynamic Patterns of Systemic Innate Immunity and Inflammatory Associated Factors in Experimental Caprine Coccidiosis

  • Tadayon, Shabnam;Razavi, Seyed Mostafa;Nazifi, Saeed
    • Parasites, Hosts and Diseases
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    • 제54권6호
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    • pp.719-724
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    • 2016
  • The present study was designed to assess the dynamic patterns of pro-inflammatory cytokines, including $IFN-{\gamma}$, $TNF-{\alpha}$, IL-4, IL-6, acute phase protein (${\alpha}1$-acid-glycoprotein, AGP), and an inflammation associated factor (adenosine deaminase; ADA) following experimental caprine coccidiosis. Ten kids aging from 2 to 4 months were infected orally with $5{\times}10^4$ sporulated oocysts and 10 animals served as controls. Blood samples were collected in both groups before infection and at days 3, 7, 14, 21, 28, and 35 post-infection (PI), and the levels of above-mentioned factors were measured. $IFN-{\gamma}$, $TNF-{\alpha}$, IL-4, IL-6, AGP, and ADA activities were significantly higher in infected animals from day 7 PI (P<0.05). In conclusion, the circulatory levels of most systemic inflammatory markers, including pro-inflammatory cytokines ($IFN-{\gamma}$, $TNF-{\alpha}$, IL-4, IL-6), AGP, and ADA increased significantly starting from day 3 to day 7 PI in caprine coccidiosis.

Changing Patterns of Acute Phase Proteins and Inflammatory Mediators in Experimental Caprine Coccidiosis

  • Hashemnia, Mohammad;Khodakaram-Tafti, Azizollah;Razavi, Seyed Mostafa;Nazifi, Saeed
    • Parasites, Hosts and Diseases
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    • 제49권3호
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    • pp.213-219
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    • 2011
  • This experiment was conducted to assess the changing patterns and relative values of acute phase proteins and inflammatory cytokines in experimental caprine coccidiosis. Eighteen newborn kids were allocated to 3 equal groups. Two groups, A and B, were inoculated with a single dose of $1{\times}10^3$ and$1{\times}10^5$sporulated oocysts of Eimeria arloingi, respectively. The third group, C, received distilled water as the control. Blood samples were collected from the jugular vein of each kid in both groups before inoculation and at days 7, 14, 21, 28, 35, and 42 post-inoculation (PI), and the levels of haptoglobin (Hp), serum amyloid A (SAA), TNF-${\alpha}$, and IFN-${\gamma}$ were measured. For histopathological examinations, 2 kids were selected from each group, euthanized, and necropsied on day 42 PI. Mean Hp concentrations in groups A and B (0.34 and 0.68 g/L) at day 7 PI were 3.2 and 6.3 times higher than the levels before inoculation. The mean SAA concentrations in groups A and B (25.6 and 83.5 ${\mu}g$/ml) at day 7 PI were 4.2 and 13.7 times higher than the levels before inoculation. The magnitude and duration of the Hp and SAA responses correlated well with the inoculation doses and the severity of the clinical signs and diarrhea in kids. These results were consistent with the histopathological features, which showed advanced widespread lesions in group B. In both groups, significant correlations were observed for TNF-${\alpha}$ and IFN-${\gamma}$ with SAA and Hp, respectively. In conclusion, Hp and SAA can be useful non-specific diagnostic indicators in caprine coccidiosis.

CURVATURES ON THE ABBENA-THURSTON MANIFOLD

  • Han, Ju-Wan;Kim, Hyun Woong;Pyo, Yong-Soo
    • 호남수학학술지
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    • 제38권2호
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    • pp.359-366
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    • 2016
  • Let H be the 3-dimensional Heisenberg group, ($G=H{\times}S^1$, g) a product Riemannian manifold of Riemannian manifolds H and S with arbitrarily given left invariant Riemannian metrics respectively, and ${\Gamma}$ the discrete subgroup of G with integer entries. Then, on the Riemannian manifold ($M:=G/{\Gamma}$, ${\Pi}^*g=\bar{g}$), ${\Pi}:G{\rightarrow}G/{\Gamma}$, we evaluate the scalar curvature and the Ricci curvature.

PBT-6, a Novel PI3KC2γ Inhibitor in Rheumatoid Arthritis

  • Kim, Juyoung;Jung, Kyung Hee;Yoo, Jaeho;Park, Jung Hee;Yan, Hong Hua;Fang, Zhenghuan;Lim, Joo Han;Kwon, Seong-Ryul;Kim, Myung Ku;Park, Hyun-Ju;Hong, Soon-Sun
    • Biomolecules & Therapeutics
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    • 제28권2호
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    • pp.172-183
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    • 2020
  • Phosphoinositide 3-kinase (PI3K) is considered as a promising therapeutic target for rheumatoid arthritis (RA) because of its involvement in inflammatory processes. However, limited studies have reported the involvement of PI3KC2γ in RA, and the underlying mechanism remains largely unknown. Therefore, we investigated the role of PI3KC2γ as a novel therapeutic target for RA and the effect of its selective inhibitor, PBT-6. In this study, we observed that PI3KC2γ was markedly increased in the synovial fluid and tissue as well as the PBMCs of patients with RA. PBT-6, a novel PI3KC2γ inhibitor, decreased the cell growth of TNF-mediated synovial fibroblasts and LPS-mediated macrophages. Furthermore, PBT-6 inhibited the PI3KC2γ expression and PI3K/AKT signaling pathway in both synovial fibroblasts and macrophages. In addition, PBT-6 suppressed macrophage migration via CCL2 and osteoclastogenesis. In CIA mice, it significantly inhibited the progression and development of RA by decreasing arthritis scores and paw swelling. Three-dimensional micro-computed tomography confirmed that PBT-6 enhanced the joint structures in CIA mice. Taken together, our findings suggest that PI3KC2γ is a therapeutic target for RA, and PBT-6 could be developed as a novel PI3KC2γ inhibitor to target inflammatory diseases including RA.

Peroxisome Proliferator-Activated Receptor-Gamma Agonist 4-O-Methylhonokiol Induces Apoptosis by Triggering the Intrinsic Apoptosis Pathway and Inhibiting the PI3K/Akt Survival Pathway in SiHa Human Cervical Cancer Cells

  • Hyun, Seungyeon;Kim, Man Sub;Song, Yong Seok;Bak, Yesol;Ham, Sun Young;Lee, Dong Hun;Hong, Jintae;Yoon, Do Young
    • Journal of Microbiology and Biotechnology
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    • 제25권3호
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    • pp.334-342
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    • 2015
  • 4-O-Methylhonokiol (MH), a bioactive compound derived from Magnolia officinalis, is known to exhibit antitumor effects in various cancer cells. However, the precise mechanism of its anticancer activity in cervical cancer cells has not yet been studied. In this study, we demonstrated that MH induces apoptosis in SiHa cervical cancer cells by enhancing peroxisome proliferator-activated receptor-gamma (PPARγ) activation, followed by inhibition of the PI3K/Akt pathway and intrinsic pathway induction. MH upregulated PPARγ and PTEN expression levels while it decreased p-Akt in the MH-induced apoptotic process, thereby supporting the fact that MH is a PPARγ activator. Additionally, MH decreased the expression of Bcl-2 and Bcl-XL, inducing the intrinsic pathway in MH-treated SiHa cells. Furthermore, MH treatment led to the activation of caspase-3/caspase-9 and proteolytic cleavage of polyADP ribose polymerase. The expression levels of Fas (CD95) and E6/E7 oncogenes were not altered by MH treatment. Taken together, MH activates PPARγ/PTEN expression and induces apoptosis via suppression of the PI3K/Akt pathway and mitochondria-dependent pathways in SiHa cells. These findings suggest that MH has potential for development as a therapeutic agent for human cervical cancer.

Galangin Suppresses Pro-Inflammatory Gene Expression in Polyinosinic-Polycytidylic Acid-Stimulated Microglial Cells

  • Choi, Min-Ji;Park, Jin-Sun;Park, Jung-Eun;Kim, Han Su;Kim, Hee-Sun
    • Biomolecules & Therapeutics
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    • 제25권6호
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    • pp.641-647
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    • 2017
  • Galangin (3,5,7-trihydroxyflavone) is a polyphenolic compound abundant in honey and medicinal herbs, such as Alpinia officinarum. In this study, we investigated the anti-inflammatory effects of galangin under in vitro and in vivo neuroinflammatory conditions caused by polyinosinic-polycytidylic acid (poly(I:C)), a viral mimic dsRNA analog. Galangin suppressed the production of nitric oxide, reactive oxygen species, and pro-inflammatory cytokines in poly(I:C)-stimulated BV2 microglia. On the other hand, galangin enhanced anti-inflammatory interleukin (IL)-10 production. Galangin also suppressed the expression of pro-inflammatory markers in poly(I:C)-injected mouse brains. Further mechanistic studies showed that galangin inhibited poly(I:C)-induced nuclear factor (NF)-${\kappa}B$ activity and phosphorylation of Akt without affecting MAP kinases. Interestingly, galangin increased the expression and transcriptional activity of peroxisome proliferator-activated receptor (PPAR)-${\gamma}$, known to play an anti-inflammatory role. To investigate whether PPAR-${\gamma}$ is involved in the anti-inflammatory function of galangin, BV2 cells were pre-treated with PPAR-${\gamma}$ antagonist before treatment of galangin. We found that PPAR-${\gamma}$ antagonist significantly blocked galangin-mediated upregulation of IL-10 and attenuated the inhibition of tumor necrosis factor (TNF)-${\alpha}$ and IL-6 in poly(I:C)-stimulated microglia. In conclusion, our data suggest that PI3K/Akt, NF-${\kappa}B$, and PPAR-${\gamma}$ play a pivotal role in mediating the anti-inflammatory effects of galangin in poly(I:C)-stimulated microglia.