• Title/Summary/Keyword: leading compound

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Compound K attenuates hyperglycemia by enhancing glucagon-like peptide-1 secretion through activating TGR5 via the remodeling of gut microbiota and bile acid metabolism

  • Tian, Fengyuan;Huang, Shuo;Xu, Wangda;Chen, Lan;Su, Jianming;Ni, Haixiang;Feng, Xiaohong;Chen, Jie;Wang, Xi;Huang, Qi
    • Journal of Ginseng Research
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    • v.46 no.6
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    • pp.780-789
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    • 2022
  • Background: Incretin impairment, characterized by insufficient secretion of L-cell-derived glucagon-like peptide-1 (GLP-1), is a defining step of type 2 diabetes mellitus (T2DM). Ginsenoside compound K (CK) can stimulate GLP-1 secretion; however, the potential mechanism underlying this effect has not been established. Methods: CK (40 mg/kg) was administered orally to male db/db mice for 4 weeks. The body weight, oral glucose tolerance, GLP-1 secretion, gut microbiota sequencing, bile acid (BA) profiles, and BA synthesis markers of each subject were then analyzed. Moreover, TGR5 expression was evaluated by immunoblotting and immunofluorescence, and L-cell lineage markers involved in L-cell abundance were analyzed. Results: CK ameliorated obesity and impaired glucose tolerance in db/db mice by altering the gut microbiota, especially Ruminococcaceae family, and this changed microbe was positively correlated with secondary BA synthesis. Additionally, CK treatment resulted in the up-regulation of CYP7B1 and CYP27A1 and the down-regulation of CYP8B1, thereby shifting BA biosynthesis from the classical pathway to the alternative pathway. CK altered the BA pool by mainly increasing LCA and DCA. Furthermore, CK induced L-cell number expansion leading to enhanced GLP-1 release through TGR5 activation. These increases were supported by the upregulation of genes governing GLP-1 secretion and L-cell differentiation. Conclusions: The results indicate that CK improves glucose homeostasis by increasing L-cell numbers, which enhances GLP-1 release through a mechanism partially mediated by the gut microbiota-BA-TGR5 pathway. Therefore, that therapeutic attempts with CK might be useful for patients with T2DM.

Combinatorial Synthesis of Organic Luminescent Materials (유기발광재료의 조합합성)

  • Kim, Chul-Bae;Jo, Hyun-Jong;Park, Kwang-Yong
    • Applied Chemistry for Engineering
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    • v.21 no.4
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    • pp.357-365
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    • 2010
  • Combinatorial synthesis, which has been adopted as an efficient method for deriving a leading compound in pharmaceutical chemistry, is recently being applied in various fields along with the rapid development of analysis and examination technology. It is especially attracting much attention as an efficient strategy to secure various potent compounds rapidly in the areas of developing new materials where the relationship between the chemical structure and the property is not revealed. Several reports and reviews have already been published for the combinatorial chemistry and combinatorial synthesis. This report briefly introduces trends in the combinatorial development of new materials and discusses the cases of developing organic luminescent materials.

Regulatory Effect of Atopic Allergic Reaction by Modified Gagam-danguieumja

  • Na, Ho-Jeong;Kwon, Dong-Yeul;Kim, Hyung-Min;Park, Eun-Jeong;Lee, Eun-Hee;Hong, Seung-Heon
    • Biomolecules & Therapeutics
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    • v.12 no.4
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    • pp.235-241
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    • 2004
  • Gagam-danguiemja (GDGJ), a traditional Korean prescription, has been used as therapeutics for atopic allergic diseases such as atopic dermatitis. To evaluate the atopic allergic effect of modified GDGJ, we investigated a possible effect of GDGJ on mast cell-mediated allergic reaction, cytokinases secretion and mRNA expression in vivo and in vitro. Mast cells are a potent source of mediators that regulate the inflammatory response in allergic reaction. In mice orally administered by GDGJ (0.01, 0.1 and 1.0 g/kg) for 1 h, compound 48/80-induced ear oedema was significantly reduced. TNF-${\alpha}$, IL-8, and IL-6 secretion were inhibited by GDGJ in the human mast cell line (HNC-1). But TNF-${\alpha}$, IL-8, and IL-6 mRNA expression were not inhibited by GDGJ at the dose of 0.01 mg/ml. These findings may help in understanding the mechanism of action of this herbal medication, leading to the control of mast cells in atopic allergic reaction like AD.

The novel peptide F29 facilitates the DNA-binding ability of hypoxia-inducible factor-1α

  • Choi, Su-Mi;Park, Hyun-Sung
    • BMB Reports
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    • v.42 no.11
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    • pp.737-742
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    • 2009
  • Hypoxia-inducible factor-$1{\alpha}/{\beta}$ (HIF-$1{\alpha}/{\beta}$) is a heterodimeric transcriptional activator that mediates gene expression in response to hypoxia. HIF-$1{\alpha}$ has been noted as an effective therapeutic target for ischemic diseases such as myocardiac infarction, stroke and cancer. By using a yeast two-hybrid system and a random peptide library, we found a 16-mer peptide named F29 that directly interacts with the bHLH-PAS domain of HIF-$1{\alpha}$. We found that F29 facilitates the interaction of the HIF-$1{\alpha/\beta}$ heterodimer with its target DNA sequence, hypoxia-responsive element (HRE). The transient transfection of an F29-expressing plasmid increases the expression of both an HRE-driven luciferase gene and the endogenous HIF-1 target gene, vascular endothelial growth factor (VEGF). Taken together, we conclude that F29 increases the DNA-binding ability of HIF-$1{\alpha}$, leading to increased expression of its target gene VEGF. Our results suggest that F29 can be a lead compound that directly targets HIF-$1{\alpha}$ and increases its activity.

A study on Chinese medicines of "Dongeuibogam" used for the face skin ailments (동의보감(東醫寶鑑)" 면문(面門) 중(中) 피부질환(皮膚疾患)에 사용된 한약제 연구(硏究))

  • Cheon, Hyun-Jung;Chang, Kyung-Eun;Moon, Young-Ok;Keum, Kyung-Soo
    • Journal of the Korean Institute of Oriental Medical Informatics
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    • v.16 no.1
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    • pp.105-133
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    • 2010
  • Koreans has regarded a fair skin as the supreme beauty emphasizing the white beauty so long, and mugwort and garlic were used as whitening materials. Also, it was recorded that the people of Eub-Rue (挹婁) applied some lard to protect their skin from cold and prevent frostbite, and this must be a great way of beauty care in the light of modern sense. The basic beauty care materials currently used as skin care materials, include natural minerals like loess or mud, and the ones composed of a highly polymerized compound. However, by reason that they are produced without consideration of an individual skin condition, and rather bring about a number of problems leading to skin diseases. To complement this issue, using natural resources would have priority to make up for the weak points. For this, we decided to select and study "Dongeuibogam".

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Effect of Depletion and Oxidation of Cellular GSH on Cytotoxicity of Mitomycin Small Cell Lung Cancer Cells

  • Lee, Chung-Soo
    • Biomolecules & Therapeutics
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    • v.12 no.2
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    • pp.92-100
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    • 2004
  • Effect of the depletion or oxidation of GSH on mitomycin c (MMC)-induced mitochondrial damage and cell death was assessed in small cell lung cancer (SCLC) cells. MMC induced cell death and the decrease in the GSH contents in SCLC cells, which were inhibited by z-LEHD.fmk (a cell permeable inhibitor of caspase-9), z-DQMD.fmk (a cell permeable inhibitor of caspase-3) and thiol compound, N-acetylcysteine. MMC caused nuclear damage, release of cytochrome c and activation of caspase-3, which were reduced by N-acetylcysteine. The depletion of GSH due to L-butionine-sulfoximine enhanced the MMC-induced cell death and formation of reactive oxygen species in SCLC cells, whereas the oxidation of GSH due to diamide or $NH_2Cl$ did not affect cytotoxicity of MMC. The results show that MMC may cause cell death in SCLC cells by inducing mitochondrial dysfunction, leading to activation of caspase-9 and -3. The MMC-induced change in the mitochondrial membrane permeability, followed by cell death, in SCLC cells may be significantly enhanced by the depletion of GSH. In contrast, the oxidation of GSH may not affect cytotoxicity of MMC.

Necessity of step-stress accelerated life testing experiment at higher steps

  • Chandra, N.;Khan, Mashroor Ahmad;Pandey, M.
    • International Journal of Reliability and Applications
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    • v.15 no.2
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    • pp.85-98
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    • 2014
  • Accelerated life testing (ALT) is a well famous technique in life testing and reliability studies, this is particularly used to induce so high stress leading to failure of the highly reliable units quickly under stipulated duration of time. The step-stress ALT is one of the systematic experimental strategy of ALT applied to fail the units in steps. In this article we focus on two important issues (i) necessity of life tests at higher steps with relevant causes (ii) to develop a new optimum test plan for 3-step SSALT under the modified cumulative exposure model proposed by Khamis and Higgins (1998). It is assumed that the lifetime of test units follows Rayleigh distribution and its scale parameter at constant stress level is assumed to be a log-linear function of the stress. The maximum likelihood estimates of the parameters involved in the step-stress ALT model are obtained. A simulation study is performed for numerical investigation of the proposed new optimum plan 3-step, step-stress ALT. The necessity of the life test units at 3-step step-stress is also numerically examined in comparison to simple step-stress setup.

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Characterization of Soldering Property on Heating Condition by Infrared Lamp Soldering Process for C-Si Photovoltaic Modules (적외선 램프 가열방식을 이용한 태양전지 셀의 솔더링 공정 및 열처리 조건 별 특성 평가)

  • Son, Hyoun Jin;Lee, Jung Jin;Kim, Sung Hyun
    • Current Photovoltaic Research
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    • v.4 no.2
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    • pp.59-63
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    • 2016
  • A key point of a soldering process for photovoltaic (PV) modules is to increase an adhesive strength leading a low resistivity between ribbon and cell. In this study, we intended to optimize a heating condition for the soldering process and characterize the soldered joint via physical and chemical analysis methods. For the purpose, the heating conditions were adjusted by IR lamp power, heating time and hot plate temperature for preheating a cell. Since then the peel test for the ribbon and cell was conducted, consequently the peel strength data shows that there is some optimum soldering condition. In here, we observed that the peel strength was modified by increasing the heating condition. Such a soldering property is affected by a various factors of which the soldered joint, flux and bus bar of the cell are changed on the heating condition. Therefore, we tried to reveal causes determining the soldering property through analyzing the soldered interface.

Effects of Co-Ti Addition on the Sintering Characteristics of (Ti1-xAlx)N Ntride Powder ((Ti1-xAlx)N계 질화물의 소결특성에 미치는 Co, Co-Ti 금속결합제의 영향)

  • Lee, Young-Ki;Sohn, Young-Un
    • Journal of the Korean Society for Heat Treatment
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    • v.11 no.3
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    • pp.177-185
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    • 1998
  • The purpose of this research is to investigate the effects of Co, Co-Ti addition on the sintering characteristic of $(Ti_{1-x}Alx)N$ material synthesized by the direct nitriding method for a application as a cermet material. The observed shrinkage rates of $(Ti_{1-x}Alx)N$ pellets increase with the additive (Co, Co-Ti) content, temperature and time, and also the pellets with the same additive content exhibit the shrinkage behavior that depends on the Ti/Al ratio. However, although the shrinkage rates in this study is the mast higher (36%), the density of the sintered $(Ti_{1-x}Alx)N$ pellet is below 80% density in theory because of the partial segregation and the dense band defect of AlCo compound. Consequentely, it is considered that Co was not effective as a binder material because the wettability of liquid Co metal on $(Ti_{1-x}Alx)N$ materials is poor, In $(Ti_{1-x}Alx)N$ with Ti-Co additive, the stoichiometric TiN is transformed by the under-stoichiometric TiNx(x<1.0) during sintering, leading to the good properties such as hardnees and hot oxidation.

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Expression of Indica rice OsBADH1 gene under salinity stress in transgenic tobacco

  • Hasthanasombut, Supaporn;Ntui, Valentine;Supaibulwatana, Kanyaratt;Mii, Masahiro;Nakamura, Ikuo
    • Plant Biotechnology Reports
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    • v.4 no.1
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    • pp.75-83
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    • 2010
  • Glycine betaine has been reported as an osmoprotectant compound conferring tolerance to salinity and osmotic stresses in plants. We previously found that the expression of betaine aldehyde dehydrogenase 1 gene (OsBADH1), encoding a key enzyme for glycine betaine biosynthesis pathway, showed close correlation with salt tolerance of rice. In this study, the expression of the OsBADH1 gene in transgenic tobacco was investigated in response to salt stress using a transgenic approach. Transgenic tobacco plants expressing the OsBADH1 gene were generated under the control of a promoter from the maize ubiquitin gene. Three homozygous lines of $T_2$ progenies with single transgene insert were chosen for gene expression analysis. RT-PCR and western blot analysis results indicated that the OsBADH1 gene was effectively expressed in transgenic tobacco leading to the accumulation of glycine betaine. Transgenic lines demonstrated normal seed germination and morphology, and normal growth rates of seedlings under salt stress conditions. These results suggest that the OsBADH1 gene could be an excellent candidate for producing plants with osmotic stress tolerance.