• Title/Summary/Keyword: drug development

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Calcium Signaling of Dioleoyl Phosphatidic Acid via Endogenous LPA Receptors: A Study Using HCT116 and HT29 Human Colon Cancer Cell Lines

  • Chang, Young-Ja;Kim, Hyo-Lim;Sacket, Santosh J.;Kim, Kye-Ok;Han, Mi-Jin;Jo, Ji-Yeong;Im, Dong-Soon
    • Biomolecules & Therapeutics
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    • v.15 no.3
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    • pp.150-155
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    • 2007
  • In the present study, we have tested the effect of dioleoyl phosphatidic acid (PA) on intracellular $Ca_{2+}$ concentration ($[Ca^{2+}]_{i}$) in two human colon cancer cell lines (HCT116 and HT29). PA and lysophosphatidic acid (LPA), a bioactive lysolipid, increased $[Ca^{2+}]_{i}$ in both HCT116 and HT29 cell lines. Increases of $[Ca^{2+}]_{i}$ by PA and LPA were more robust in HCT116 cells than in HT29 cells. A specific inhibitor of phospholipase C (U73122), however, was not inhibitory to the cell responses. Pertussis toxin, a specific inhibitor of $G_{i/o}$ type G proteins, however, had an inhibitory effect on the responses except for an LPA-induced one in HT29 cells. Ruthenium red, an inhibitor of the ryanodine receptor, was not inhibitory on the responses, however, 2-APB, a specific inhibitor of inositol 1,4,5-trisphosphate receptor, completely inhibited both lipid-induced $Ca^{2+}$ increases in both cell types. Furthermore, by using Ki16425 and VPC32183, two structurally dissimilar specific antagonists for $LPA_{1}/LPA_{3}$ receptors, an involvement of endogenous LPA receptors in the $Ca^{2+}$ responses was observed. Ki16425 completely inhibited the responses but the susceptibility to VPC32183 was different to PA and LPA in the two cell types. Expression levels of five LPA receptors in the HCT116 and HT29 cells were also assessed. Our data support the notion that PA could increase $[Ca^{2+}]_{i}$ in human colon cancer cells, probably via endogenous LPA receptors, G proteins and $IP_{3}$ receptors, thereby suggesting a role of PA as an intercellular lipid mediator.

Development and validation of an analytical method for the quantification of 2,6-diisopropylnaphthalene in agricultural products using GC-MS/MS

  • Lee, Han Sol;Park, Ji-Su;Lee, Su Jung;Shin, Hye-Sun;Chung, Yun mi;Choi, Ha na;Yun, Sang Soon;Jung, Yong-hyun;Oh, Jae-Ho
    • Analytical Science and Technology
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    • v.34 no.1
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    • pp.1-8
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    • 2021
  • An analytical method was developed and optimized for the quantification of a plant growth regulator, 2,6-diisopropylnaphthalene (2,6-DIPN), in agricultural products using gas chromatography-tandem mass spectrometry. The samples were extracted, partitioned, and were purified using a Florisil® cartridge. To validate the analytical method, its specificity, linearity, limit of detection (LOD) and limit of quantification (LOQ) of the instrument, LOQ of the analytical method (MLOQ), accuracy, and repeatability were considered. The method displayed excellent results during validation, and is suitable for the determination and quantification of the low residual levels of the analyte in the agricultural samples. All of the results with the optimized method were satisfactory and within the criteria ranges requested in the Codex Alimentarius Commission guidelines and the Ministry of Food and Drug Safety guidelines for pesticide residue analysis. The developed method is simple and accurate and can be used as a basis for safety management of 2,6-DIPN.

New Drug Development using Korean Herbal Formulae: A model role study

  • Cho, Jung-Hyo;Wang, Jing-Hua;Son, Chang-Gue
    • The Journal of Korean Medicine
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    • v.30 no.6
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    • pp.96-102
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    • 2009
  • Objectives: Traditional Korean herbal formulae are composed of multiple medicinal plants. This situation of multiple-ingredient mixtures has been considered as a major obstacle to new drug development using herbal formulae in the world market, despite the effectiveness of such mixtures. This study reviewed Liv-52 as a representative model of successful drug development using a multiple-herb mixture. Methods: All articles for Liv-52 were collected from the PubMed database. The history, composition of Liv-52, its pharmaceutical efficacy and mechanisms, and data from clinical studies including its market size were analyzed. Results: Liv-52 is composed of seven herbal plants and it is the best known in Ayurvedic medicine for treating liver disorders. Since its 1955 introduction, forty four international papers have been published based on pre-clinical and clinical trials. The efficacy and mechanisms of Liv-52 were intensively studied. Currently, Liv-52 is one of the top-selling products, with over 10 million dollars sales annually, in the world market. Conclusions: These results indicate that Korean herbal formulae could be new global drugs if scientific evidence for efficacy and standardization are produced via literature researches.

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Characterization of Binding Mode for Human Coagulation Factor XI (FXI) Inhibitors

  • Cho, Jae Eun;Kim, Jun Tae;Jung, Seo Hee;Kang, Nam Sook
    • Bulletin of the Korean Chemical Society
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    • v.34 no.4
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    • pp.1212-1220
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    • 2013
  • The human coagulation factor XI (FXI) is a serine protease that plays a significant role in blocking of the blood coagulation cascade as an attractive antithrombotic target. Selective inhibition of FXIa (an activated form of factor XI) disrupts the intrinsic coagulation pathway without affecting the extrinsic pathway or other coagulation factors such as FXa, FIIa, FVIIa. Furthermore, targeting the FXIa might significantly reduce the bleeding side effects and improve the safety index. This paper reports on a docking-based three dimensional quantitative structure activity relationship (3D-QSAR) study of the potent FXIa inhibitors, the chloro-phenyl tetrazole scaffold series, using comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) methods. Due to the characterization of FXIa binding site, we classified the alignment of the known FXIa inhibitors into two groups according to the docked pose: S1-S2-S4 and S1-S1'-S2'. Consequently, highly predictive 3D-QSAR models of our result will provide insight for designing new potent FXIa inhibitors.

Pathophysiological Roles of ASK1-MAP Kinase Signaling Pathways

  • Nagai, Hiroaki;Noguchi, Takuya;Takeda, Kohsuke;Ichijo, Hidenori
    • BMB Reports
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    • v.40 no.1
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    • pp.1-6
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    • 2007
  • Apoptosis signal-regulating kinase 1 (ASK1) is a mitogenactivated protein kinase (MAPK) kinase kinase that activates JNK and p38 kinases. ASK1 is activated by various stresses, such as reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, lipopolysaccharide (LPS) and calcium influx which are thought to be responsible for the pathogenesis or exacerbations of various human diseases. Recent studies revealed the involvement of ASK1 in ROS- or ER stressrelated diseases, suggesting that ASK1 may be a potential therapeutic target of various human diseases. In this review, we focus on the current findings for the relationship between pathogenesis and ASK1-MAPK pathways.

Chlorella virus-mediated disruption of microalgal cell wall for biodiesel production (클로렐라 바이러스 매개 미세조류 세포벽 파쇄를 이용한 바이오 디젤 생산)

  • Kim, Soojin;Kim, Yeon-Soo
    • Korean Journal of Microbiology
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    • v.54 no.2
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    • pp.140-145
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    • 2018
  • The most energy-intensive processes in lipids extraction were the disruption of the cell wall of microalgae. Here, we tried to extract lipids through lysis using virus-infecting microalgae, to compare with those by the other two methods using microwave or ultrasonication. The lipids yield using viral infection was not significantly different from those using ultrasonication and microwave oven. This suggests that the same amount of lipids can be obtained with low energy and costs, as well as that microalgal lipids extraction by chlorella virus infection might provide the price competitiveness in biodiesel production even if it will be applied to mass production facilities.

Anti-inflammatory and Cytotoxic Activities of Phenolic Compounds from Broussonetia kazinoki

  • Vu, Ngoc Khanh;Le, Thi Thanh;Woo, Mi Hee;Min, Byung Sun
    • Natural Product Sciences
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    • v.27 no.3
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    • pp.176-182
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    • 2021
  • The phytochemical investigation of Broussonetia kazinoki roots led to the isolation of ten compounds, including six flavonoids (1-6), two lignans (7 and 8), and two coumarins (9 and 10) by comparing their 1H and 13C NMR spectra with reference values. To the best of our knowledge, compounds 9 and 10 were isolated from this plant for the first time. Among the ten isolates, compounds 2, 4, and 6 exhibited inhibitory effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW264.7 cells with IC50 values of 11.98, 10.16, and 24.06 μM, respectively. Furthermore, compounds 2, 4, and 6 reduced LPS-induced inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner. Pre-incubation of cells with these compounds also significantly suppressed LPS-induced COX-2 protein expression. Compounds 2, 4, and 6 also showed cytotoxic activity against HL-60 cells with IC50 values ranging between 46.43 and 94.06 μM.

NON-RADIO ISOTOPIC ENDPOINT FOR LOCAL LYMPH NODE ASSAY USING IMMUNOHISTOCHEMISTRY

  • Lee, Jong-Kwon;Park, Jae-Hyun;Kim, Hyung-Soo;Jang, Eun-Jung;Hwang, In-Chang;Jung, Seung-Tae;Jun H. Eum;Oh, Hye-Young
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.193-193
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    • 2001
  • A murine local lymph node assay (LLNA) has been developed as an alternative to guinea pig models for contact sensitization potential. However, a disadvantage of the LLNA is the need for the use of radioactive material. In this study, we aimed to investigate the development of non-radio isotopic endpoint for LLNA using immunohistochemistry.(omitted)

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