• Title/Summary/Keyword: Pi-b

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The non-saponin fraction of Korean Red Ginseng (KGC05P0) decreases glucose uptake and transport in vitro and modulates glucose production via down-regulation of the PI3K/AKT pathway in vivo

  • Park, Soo-Jeung;Lee, Dasom;Kim, Dakyung;Lee, Minhee;In, Gyo;Han, Sung-Tai;Kim, Sung Won;Lee, Mi-Hyang;Kim, Ok-Kyung;Lee, Jeongmin
    • Journal of Ginseng Research
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    • v.44 no.2
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    • pp.362-372
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    • 2020
  • Background: The non-saponin fraction of Korean Red Ginseng has been reported to have many biological activities. However, the effect of this fraction on anti-diabetic activity has not been elucidated in detail. In this study, we investigated the effects of KGC05P0, a non-saponin fraction of Korean Red Ginseng, on anti-diabetic activity in vitro and in vivo. Methods: We measured the inhibition of commercially obtained α-glucosidase and α-amylase activities in vitro and measured the glucose uptake and transport rate in Caco-2 cells. C57BL/6J mice and C57BLKS/Jdb/db (diabetic) mice were fed diets with or without KGC05P0 for eight weeks. To perform the experiments, the groups were divided as follows: normal control (C57BL/6J mice), db/db control (C57BLKS/Jdb/db mice), positive control (inulin 400 mg/kg b.w.), low (KGC05P0 100 mg/kg b.w.), medium (KGC05P0 200 mg/kg b.w.), and high (KGC05P0 400 mg/kg b.w.). Results: KGC05P0 inhibited α-glucosidase and α-amylase activities in vitro, and decreased glucose uptake and transport rate in Caco-2 cells. In addition, KGC05P0 regulated fasting glucose level, glucose tolerance, insulin, HbA1c, carbonyl contents, and proinflammatory cytokines in blood from diabetic mice and significantly reduced urinary glucose excretion levels. Moreover, we found that KGC05P0 regulated glucose production by down-regulation of the PI3K/AKT pathway, which inhibited gluconeogenesis. Conclusion: Our study thereby demonstrated that KGC05P0 exerted anti-diabetic effects through inhibition of glucose absorption and the PI3K/AKT pathway in in vitro and in vivo models of diabetes. Our results suggest that KGC05P0 could be developed as a complementary food to help prevent T2DM and its complications.

Protective Effect of Niclosamide on Lipopolysaccharide-induced Sepsis in Mice by Modulating STAT3 Pathway (니클로사마이드를 이용한 STAT3 신호전달 조절을 통해 LPS로 유발된 패혈증 동물모델 보호 효과 검증 연구)

  • Se Gwang JANG
    • Korean Journal of Clinical Laboratory Science
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    • v.55 no.4
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    • pp.306-313
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    • 2023
  • Sepsis is a systemic inflammatory response, with manifestations in multiple organs by pathogenic infection. Currently, there are no promising therapeutic strategies. Signal transducer and activator of transcription 3 (STAT3) is a cell signaling transcription factor. Niclosamide is an anti-helminthic drug approved by the Food and Drug Administration (FDA) as a potential STAT3 inhibitor. C57BL/6 mice were treated with an intraperitoneal injection of lipopolysaccharide (LPS). Niclosamide was administered orally 2 hours after the LPS injection. This study found that Niclosamide improved the survival and lung injury of LPS-induced mice. Niclosamide decreased the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) in serum. The effects of Niclosamide on phosphoinositide 3-kinase (PI3K), AKT, nuclear factor-κB (NF-κB), and STAT3 signaling pathways were determined in the lung tissue by immunoblot analysis. Niclosamide reduced phosphorylation of PI3K, AKT, NF-κB, and STAT3 significantly. Furthermore, it reduced the phosphorylation of STAT3 by LPS stimulation in RAW 264.7 macrophages. Niclosamide also reduced the LPS-stimulated expression of proinflammatory mediators, including IL-6, TNF-α, and IL-1β. Niclosamide provides a new therapeutic strategy for murine sepsis models by suppressing the inflammatory response through STAT3 inhibition.

Knockdown of endogenous SKIP gene enhanced insulin-induced glycogen synthesis signaling in differentiating C2C12 myoblasts

  • Xiong, Qi;Deng, Chang-Yan;Chai, Jin;Jiang, Si-Wen;Xiong, Yuan-Zhu;Li, Feng-E;Zheng, Rong
    • BMB Reports
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    • v.42 no.2
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    • pp.119-124
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    • 2009
  • PI(3,4,5)$P_3$ produced by the activated PI3-kinase is a key lipid second messenger in cell signaling downstream of insulin. Skeletal muscle and kidney-enriched inositol phosphatase (SKIP) identified as a 5'-inositol phosphatase that hydrolyzes PI(3,4,5) $P_3$ to PI(3,4)$P_2$, negatively regulates the insulin-induced glycogen synthesis in skeletal muscle. However the mechanism by which this occurs remains unclear. To elucidate the function of SKIP in glycogen synthesis, we employed RNAi techniques to knockdown the SKIP gene in differentiating C2C12 myoblasts. Insulininduced phosphorylation of Akt (protein kinase B) and GSK-3$\beta$ (Glycogen synthase kinase), subsequent dephosphorylation of glycogen synthase and glycogen synthesis were increased by inhibiting the expression of SKIP, whereas the insulin-induced glycogen synthesis was decreased by overexpression of WT-SKIP. Our results suggest that SKIP plays a negative regulatory role in Akt/ GSK-3$\beta$/GS (glycogen synthase) pathway leading to glycogen synthesis in myocytes.

Analysis and Quantitative Distribution of Glycosided Flavonoids in Citruses and Korean Chung-pi (감귤류와 한국산 청피에 함유된 Glycosided Flavonoids의 분석과 정량적 분포)

  • Baik, S.O.;Bock, J.Y.;Chun, H.J.;Jeong, S.I.;Baek, S.H.;Oh, H.B.;Kim, I.K.
    • Analytical Science and Technology
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    • v.14 no.4
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    • pp.340-348
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    • 2001
  • Glycosided flabonoids (naringenin, naringin, narirutin, hesperidin, and hesperetin) in Citrus and Korea Chung-pi were isolated and analyzed with HPLC, GC-mass, UV and high resolution NMR. Contents of glycosided flavonoids were compared according to kinds of Citrus and fruit ripening periods. Major compound of Korean Chung-pi was hesperidin and minors were narirutin and hesperetin. Major compounds of Gisil were naringin, narirutin, naringenin and were narirutin, hesperidin in Gigak. Major compounds of milgam and orange were narirutin, hesperidin, and the contents of glycoside flavonoids decreased according to the age of maturity.

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Comparative Effects of $PKB-{\alpha}$ and $PKC-{\zeta}$ on the Phosphorylation of GLUT4-Containing Vesicles in Rat Adipocytes

  • Hah, Jong-Sik
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.6
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    • pp.487-496
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    • 2000
  • Insulin stimulates glucose transport in muscle and fat cells by promoting the translocation of glucose transporter (GLUT4) to the cell surface. Phosphatidylinositide 3-kinase (PI3-kinase) has been implicated in this process. However, the involvement of protein kinase B (PKB)/Akt and $PKC-{\zeta}$, those are known as the downstream target of PI3-kinase in regulation of GLUT4 translocation, is not known yet. An interesting possibility is that these protein kinases phosphorylate GLUT4 directly in this process. In the present study, $PKB-{\alpha}$ and $PKC-{\zeta}$ were added exogenously to GLUT4-containing vesicles purified from low density microsome (LDM) of the rat adipocytes by immunoadsorption and immunoprecipitation for direct phosphorylation of GLUT4. Interestingly GLUT4 was phosphorylated by $PKC-{\zeta}$ and its phosphorylation was increased in insulin stimulated state but GLUT4 was not phosphorylated by $PKB-{\alpha}.$ However, the GST-fusion proteins, GLUT4 C-terminal cytoplasmic domain (GLUT4C) and the entire major GLUT4 cytoplasmic domain corresponding to N-terminus, central loop and C-terminus in tandem (GLUT4NLC) were phosphorylated by both $PKB-{\alpha}$ and $PKC-{\zeta}.$ The immunoblots of $PKC-{\zeta}$ and $PKB-{\alpha}$ antibodies with GLUT4-containing vesicles preparation showed that $PKC-{\zeta}$ was co-localized with the vesicles but not $PKB-{\alpha}.$ From the above results, it is clear that $PKC-{\zeta}$ interacts with GLUT4-containing vesicles and it phosphorylates GLUT4 protein directly but $PKB-{\alpha}$ does not interact with GLUT4, suggesting that insulin-elicited signals that pass through PI3-kinase subsequently diverge into two independent pathways, an Akt pathway and a $PKC-{\zeta}$ pathway, and that later pathway contributes, at least in part, insulin stimulation of GLUT4 translocation in adipocytes via a direct GLUT4 phosphorylation.

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STM Study of Low Dimensional Nanostructures Formed by Adsorption of Dipyrromethane-trimer Molecules on Graphite Surface (흑연 표면에 형성된 dipyrromethene-trimer 분자의 저차원 나노구조의 주사 터널링 현미경 연구)

  • Son, S.B.;Lee, S.J.;Hahn, J.R.;Shin, J.Y.;Dolphin, D.
    • Journal of the Korean Vacuum Society
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    • v.17 no.5
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    • pp.375-380
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    • 2008
  • We have investigated the low-dimensional nanostructures produced by adsorption of triangular Co coplexed dipyrromethane(DPM-trimer, Fig. 1) on graphite surface by using scanning tunneling microscope. DPM-trimer deposition on the graphite surface leads to the formation of long 1-D molecular wires and 2-D hexagonal patterns. We analyzed the heights and structures of 1-D molecular wires and 2-D hexagonal patterns. The 1-D molecular wires were formed 'edge-on' alignments on graphite surface result of continuos $\pi-\pi$ stacking interactions. The other case of 2-D hexagonal patterns were formed 'face-on' alignments on graphite surface.

Anticancer Activity of Bispidinone Derivative by Induction of Apoptosis

  • Lee, Man Gi;Kwon, Ryong
    • Biomedical Science Letters
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    • v.26 no.4
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    • pp.336-343
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    • 2020
  • The present study was carried out to investigate the possibility that bispidinone derivative makes anticancer drug availability to human cervical carcinoma cell. The B8 has the lowest IC50 value among B8, B9 and B10 which are bispidinone analogue with bromide. According to cytotoxic test through WST-8 assay, B8 shows the most magnificent cytotoxicity effectiveness with 76 μM of IC50 value. In human cervical carcinoma cell treated with B8, it noticeably controlled cellular multiplication by increase of concentration and time. Furthermore, morphological changes like cellular shrink, disruption and nuclear condensation, feature of apoptosis, are observed. Annexin V-FITC/PI double staining assay test proved that B8 can cause apoptosis. Moreover, after treatment with 76 μM of B8, flow cytometry analysis shows that increase of active oxygen species are induced and membrane potential in mitochondria is decreased. Manifestation of Bcl-2 family and caspase cascades protein provides evidence that B8 induces apoptosis through mitochondria and caspase-related pathway. Taken together, we suggested that B8 reduced membrane potential in mitochondria and induce apoptosis through the pathway depended on mitochondria and caspase.

Synthesis of Tetracyclic Pyrido[2,3-b]azepine Derivatives as Analogues of Mirtazapine via N-Acyliminium Ion Cyclization

  • Lee, Jae-Yeol;Bang, Sung-Hun;Lee, Sook-Ja;Song, Yun-Seon;Jin, Chang-Bae;Park, Ho-Koon;Lee, Yong-Sup
    • Bulletin of the Korean Chemical Society
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    • v.23 no.11
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    • pp.1623-1628
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    • 2002
  • Tetracyclic pyrido[2,3-b]azepine derivatives 4a-d and 4f as analogues of mirtazapine were synthesized via N-acyliminium ion cyclization by using aromatic rings such as benzene and thiophene ring as a ${\pi}-nucleophile$, and evaluated for the binding affinity for ${\alpha}2-adrenoceptor$. Among tested compounds, 2,3,9,13b-tetrahydro-1H-benzo[f]pyrrolo[2,1-a]pyrido[2,3-c]azepine (4a) was the most potent (Ki = 0.26 ${\mu}M)$ but showed about 3-fold less binding affinity than mirtazapine (Ki = 0.08 ${\mu}M)$ for a2-adrenoceptor.

ON THE UNIFORM CONVERGENCE OF SPECTRAL EXPANSIONS FOR A SPECTRAL PROBLEM WITH A BOUNDARY CONDITION RATIONALLY DEPENDING ON THE EIGENPARAMETER

  • Goktas, Sertac;Kerimov, Nazim B.;Maris, Emir A.
    • Journal of the Korean Mathematical Society
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    • v.54 no.4
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    • pp.1175-1187
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    • 2017
  • The spectral problem $$-y^{{\prime}{\prime}}+q(x)y={\lambda}y,\;0 < x < 1, \atop y(0)cos{\beta}=y^{\prime}(0)sin{\beta},\;0{\leq}{\beta}<{\pi};\;{\frac{y^{\prime}(1)}{y(1)}}=h({\lambda})$$ is considered, where ${\lambda}$ is a spectral parameter, q(x) is real-valued continuous function on [0, 1] and $$h({\lambda})=a{\lambda}+b-\sum\limits_{k=1}^{N}{\frac{b_k}{{\lambda}-c_k}},$$ with the real coefficients and $a{\geq}0$, $b_k$ > 0, $c_1$ < $c_2$ < ${\cdots}$ < $c_N$, $N{\geq}0$. The sharpened asymptotic formulae for eigenvalues and eigenfunctions of above-mentioned spectral problem are obtained and the uniform convergence of the spectral expansions of the continuous functions in terms of eigenfunctions are presented.

ON THE SEVERAL DIFFERENCES BETWEEN PRIMES

  • Park, Yeonyong;Lee, Heonsoo
    • Journal of applied mathematics & informatics
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    • v.13 no.1_2
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    • pp.37-51
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    • 2003
  • Enumeration of the primes with difference 4 between consecutive primes, is counted up to 5${\times}$10$\^$10/, yielding the counting function ,r2,4(5${\times}$10$\^$10/) = l18905303. The sum of reciprocals of primes with gap 4 between consecutive primes is computed B$_4$(5 ${\times}$ 10$\^$10/) = 1.1970s4473029 and B$_4$ = 1.197054 ${\pm}$ 7 ${\times}$ 10$\^$-6/. And Enumeration of the primes with difference 6 between consecutive primes, is counted up to 5${\times}$10$\^$10/, yielding the counting function $\pi$$\_$2.6/(5${\times}$10$\^$10/) = 215868063. The sum of reciprocals of primes with gap 6 between consecutive primes is computed B$\_$6/(5${\times}$10$\^$10/) = 0.93087506039231 and B$\_$6/ = 1.135835 ${\pm}$ 1.2${\times}$10$\^$-6/.