• Title/Summary/Keyword: Mechanism synthesis

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Genistein-induced Growth Inhibition was Associated with Inhibition of Cyclooxygenase-2 and Telomerase Activity in Human Cancer Cells. (인체 암세포에서 genistein에 의한 cyclooxygenase-2 및 telomerase의 활성 저하)

  • Kim, Jung-Im;Kim, Seong-Yun;Seo, Min-Jeong;Lim, Hak-Seob;Lee, Young-Choon;Joo, Woo-Hong;Choi, Byung-Tae;Jeong, Yong-Kee;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.18 no.6
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    • pp.884-890
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    • 2008
  • Genistein, an isoflavone in soybean products, is a potential chemopreventive agent against various types of cancer. There are several studies documenting molecular alterations leading to cell cycle arrest at G2/M phase and induction of apoptosis; however, its mechanism of action and its molecular targets on the prostaglandin $E_2$ ($PGE_2$) production and telomere length regulation in human cancer remain unclear. In this study, we investigated the effect of genistein on the levels of cyclooxygenases (COXs) and telomere regulatory components of several human cancer cell lines (T24, human bladder carcinoma cells; U937, human leukemic cells; AGS, human stomach adenocarcinoma cells and SK-MEL-2, human skin melanoma cells). Genistein treatment resulted in the inhibition of cancer cell proliferation in a concentration-dependent manner. It was found that genistein treatment markedly decreased the levels of COX-2 mRNA and protein expression without significant changes in the expression of COX-1, which was correlated with a decrease in $PGE_2$ synthesis. Genistein treatment also partly inhibited the levels of human telomerase reverse transcriptase (hTERT) as well as human telomerase RNA (hTR) and telomerase-associated protein (TEP)-1, and the activity of telomerase. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of genistein.

Optimization of Catalytic Reaction for Synthesis of 2-Methyl-4-methoxydiphenylamine (2-Methyl-4-methoxydiphenylamine 합성을 위한 촉매반응의 최적화)

  • Cho, Jeong-Woo;Kim, Eun-Seok;Kim, Kiseok;Kim, Seong-Hoon
    • Applied Chemistry for Engineering
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    • v.10 no.2
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    • pp.293-298
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    • 1999
  • Reaction mechanism was elucidated and reaction condition were optimized for the catalytic reaction synthesizing 2-methyl-4-methoxy-diphenylamine (MMDPA) which is an intermediate of Fluoran heat-sensitive dyestuff. Reactants consisted of 2-methyl-4-methoxyaniline (MMA), 3-methyl-4-nitroanisole (MNA), and cyclohexanone, and 5 wt % Pd/C was used as a catalyst. Experiments were run in an open slurry reactor equipped with reflux condenser, and products were analyzed by means of GC/MS and NMR. MMDPA yield of 90 mole % could be obtained after reaction time of 8~10 hours under the optimal reaction conditions comprising the reaction mass composition of MMA : MNA : cyclohexanone = 1 : 2 : 150 based on MMA input of 0.01 gmoles in xylene solvent, reaction temperature of $160^{\circ}C$, and catalyst amount of 0.5 g. It was found that the rate-determining step of overall reaction was dehydrogenation of the intermediate product obtained from condensation of MMA and cyclohexanone. Overall reaction rate and MMDPA yield were enhanced owing to hydrogen transfer reaction by introducing MNA together with MMA in the reaction mass. Excess cyclohexanone in the reaction mass played an important role of promoting the condensation of MMA and cyclohexanone.

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The Evidence for Pepsin-Catalyzed Transpeptidation (펩신촉매에 의한 Transpeptide의 생성)

  • 조용권
    • Journal of Life Science
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    • v.8 no.4
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    • pp.410-415
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    • 1998
  • Procine pepsin hydrolysis of hexapeptide L-S-pNF-Nle-A-OMe in the presence of dipeptide L-L generates a new peak on HPLC analysis of reaction mixtures that is not seen when enzyme is incubated with either peptide alone. The peaks can be detected spectroscopically at either 214 or 254 nm, the latter consistent with a new peptide containing the p-nitro-F residue. The data suggest acyl transpeptidation between E(L-S-pNF) and L-L to form L-S-pNF-L-L. Consistent with this inference are (1) the ability of L-L-NH$_{2}$ and inability of Boc-L-L to undergo a similar transpeptidation reaction, and (2) the data from electrospray mass spectrum. This synthesis requires that Nle-A-L-OMe be released before L-S-pNF, an order opposite to that proposed on the basis of product inhibition kinetics. Consistent with this inference are reciprocal solvent isotope effects ; normal isotope effects of 1.736$\pm$0.121 on the formation of Nle-A-L-OMe and 2.281$\pm$0.184 in the formation of L-S-pNF, coupled to an inverse isotope effects of 0.576$\pm$0.045 on the formation of L-S-pNF-L-L. Because transpeptidation precedes faster in D$_{2}$O, the isotopically-sensitive step must occur after release of Nle-A-L-OMe. Isotopically-enhanced transpeptidation is consistent with the Uni-Bi iso memchanism postulated on the basis of an isotope effects on Vmax but not on Vmax/Km$^{1)}$ and confirmed by isotope effects on the onset of inhibition by pepstatin$^{2)}$.

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Biodegradation of Recalcitrant Chlorinated Aromatic Compounds via Microbial Dechlorination (미생물의 탈염소화 작용에 의한 난분해성 염화방향족 오염물질의 분해)

  • 채종찬;김치경
    • Korean Journal of Environmental Biology
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    • v.17 no.2
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    • pp.129-138
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    • 1999
  • Chlorinated aromatic compounds are one of the largest groups of environmental pollutants as a result of world-wide distribution by using them as herbicides, insecticides, fungicides, solvents, hydraulic and heat transfer fluids, plasticizers, and intermediates for chemical synthesis. Because of their toxicity, persistence, and bioaccumulation, the compounds contaminated ubiquitously in the biosphere has attracted public concerns in terms of serious influences to wild lives and a human being, such as carcinogenicity, mutagenicity, and disturbance in endocrine systems. The biological recalcitrance of the compounds is caused by the number, type, and position of the chlorine substituents as well as by their aromatic structures. In general, the carbon-halogen bonds increase the recalcitrance by increasing electronegativity of the substituent, so that the dechlorination of the compounds is focused as an important mechanism for biodegradation of chlorinated aromatics, along with the cleavage of aromatic rings. The removal of the chlorine substituents has been known as a key step for degradation of chlorinated aromatic compounds under aerobic condition. This can occur as an initial step via oxygenolytic, reductive, and hydrolytic mechanisms. The studies on the biochemistry and genetics about microbial dechlorination give us the potential informations for microbial degradation of xenobiotics contaminated in natural microcosms. Such investigations might provide biotechnological approaches to solve the environmental contamination, such as designing effective bioremediation systems using genetically engineered microorganisms.

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The Metabolic Effects of FGF21: From Physiology to Pharmacology (생리, 약학적 관점에서 fibroblast growth factor 21 (FGF21)의 대사 효과 고찰)

  • Song, Parkyong
    • Journal of Life Science
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    • v.30 no.7
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    • pp.640-650
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    • 2020
  • Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF protein family which is highly synthesized in the liver, pancreas, and adipose tissue. Depending on the expression tissue, FGF21 uses endo- or paracrine features to regulate several metabolic pathways including glucose metabolism and energy homeostasis. Different physiologically stressful conditions such as starvation, a ketogenic diet, extreme cold, and mitochondrial dysfunction are known to induce FGF21 synthesis in various tissues to exert either adaptive or defensive mechanisms. More specifically, peroxisome proliferator-activated receptor gamma and peroxisome proliferator-activated receptor alpha control FGF21 expression in adipose tissue and liver, respectively. In addition, the pharmacologic administration of FGF21 has been reported to decrease the body weight and improve the insulin sensitivity and lipoprotein profiles of obese mice and type 2 diabetes patients meaning that FGF21 has attracted huge interest as a therapeutic agent for type 2 diabetes, obesity, and non-alcoholic fatty liver disease. However, understanding FGF21 remains complicated due to the paradoxical condition of its tissue-dependent expression. For example, nutrient deprivation largely increases hepatic FGF21 levels whereas adipose tissue-derived FGF21 is increased under feeding condition. This review discusses the issues of interest that have arisen from existing publications, including the tissue-specific function of FGF21 and its action mechanism. We also summarize the current stage of a clinical trial using several FGF21 analogs.

A Case of Interstitial Pneumonitis Caused by Leflunomide (Leflunomide에 의한 약물유발 간질성 폐렴 1예)

  • Lee, Jung Hwa;Cheon, Won Seok;Seo, Young Il;Eom, Kwang-Seok;Jang, Seung Hun;Bahn, Joon-Woo;Kim, Dong-Gyu;Jung, Ki-Suck
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.1
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    • pp.83-88
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    • 2005
  • Leflunomide is a new disease modifying anti rheumatic drug (DMARD) for the treatment of active rheumatoid arthritis. Its mechanism of action differs from other DMARDs in that it inhibits the de novo pyrimidine synthesis by inhibiting dihydroorotate dehydrogenase and therefore prevents the proliferation of activated lymphocytes. As it has been prescribed worldwide, there is a great deal of much concerns regarding its potential adverse effects. Because leflunomide has an active metabolite with a long elimination half-life of approximately 2 weeks, serious adverse reactions may occur even after the leflunomide treatment has been stopped. The profile of serious reactions includes liver dysfunction, hematological disorders, severe skin reactions and respiratory dysfunction. Respiratory dysfunctions with leflunomide therapy are very rare and its incidence is lower than that of methotrexate therapy. However, there are reports in Japan showing that 5 patients died of interstitial pneumonitis and another 11 patients developed serious lung complications associated with leflunomide. This suggests the possibility of fatal respiratory toxicity of leflunomide. There are no reports of interstitial pneumonitis associated with leflunomide in Korea. We report a case of a 62-year old woman who developed interstitial pneumonitis, which might have been induced by leflunomide during the treatment of rheumatoid arthritis.

Histochemical Analysis of the Cutaneous Wound Healing in the Amphibian (양서류 피부 상처회복과정에 대한 조직화학적 분석)

  • Lim, Do-Sun;Jeong, Soon-Jeong;Jeong, Je-O;Park, Joo-Cheol;Kim, Heung-Joong;Moon, Myung-Jin;Jeong, Moon-Jin
    • Applied Microscopy
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    • v.34 no.1
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    • pp.1-11
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    • 2004
  • The wound healing is very complex biological processing including inflammatory, reepithelialization and matrix construction. According to the biological systematic category, the ability of the healing is very different. Generally healing ability of the lower animal group has been known more excellent compared to its higher group. Therefore, lower animals have been used as the experimental model to explore the mechanism of the wound healing or repair. To verify histochemical characteristics of the wound healing, we have used skin of the frog (Bombina orientalis) as known common amphibian. At day 1, 10, and 16, the mucous substance was very actively synthesized and strong positive by PAS and Alcian blue (pH 2.5). Day 10 after wounding, margin of the wound was gradually strong positive by PTAH staining for detection of collagen synthesis. At 3 to 6 hour and day 23 to 27, we have found the cell division was active through the MG-P staining, in which the concentration and division of DNA in nucleus was green to deep blue color.

Preparation of $BaTiO_3$ powder in solid reaction and basic study on dielectrics of $CeAIO_3-BaTiO_3$system ($BaTiO_3$ 분말합성조건 및 $CeAIO_3-BaTiO_3$계 유전체의 기초적 연구)

  • Lim, Dae-Young;Kim, Jong-Ock;Lee, Chae-hyun;Park, Won-Kyu
    • The Journal of Natural Sciences
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    • v.8 no.1
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    • pp.61-69
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    • 1995
  • It is hard to synthesize pure $BaTiO_3$ from $BaCO_3$ and $TiO_2$ in solid reaction for the activity of BaO and secondary phase. For this reason, the wet chemical techniques have been studied. Starting material which was used in these methods were expensive and the properties of powder which was synthesized in same defined. So, some process have been studying again to improve soild reaction method. This study which was one of those was to defin the forming mechanism of $Ba_2TiO_4$ and to control some condition of $Ba_2TiO_4$. The synthesis temperature of $BaTiO_3$ in solid reaction was near $1120^{\circ}C$. The quantity and forming temperature of $Ba_2TiO_4$ could be controlled by atmosphere heat treatment. $Ba_2TiO_4$ was related to expansion in Ba-rich region of $BaTiO_3$. $BaTiO_2O_5$ and $BaTiO_3O_7$ was reason to expand in Ti-rich region. The dielectrics of $CeAIO_3$ which was synthesized and sintered in reduction atmosphere and $BaTiO_3$ system were affected by $CeO_2$ which was formed for the decomposition of $CeAIO_3$ heat treatment in air.

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Synthesis and Anaiysis of Photohnninescence Properties of $^5D_1$$^7F_1$ Transition in $LaGaO_3$:$Eu^{3+}$ Red Phosphor ($LaGaO_3$:$Eu^{3+}$형광체의 합성 및 발광 특성)

  • Kim, Kyoung Hwa;Choi, Yoon Young;Sohn, Kee Sun;Kim, Chang Hae;Park, Hee Dong;Choe, Se Young
    • Journal of the Korean Chemical Society
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    • v.44 no.5
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    • pp.453-459
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    • 2000
  • FED has deserved an intensive attentioD as a new flat panel display. The present investigationaims at undemtanding the photoluminescence and cathodoluminescent properties of hGaO$_3$: $Eu^{3+}$ phosphor bytaking into account the possibility that this phosphor could be applied for FED. In onler to investigate on.sucha detailed behavior; 8everM experimental skil18 Je conducted to the LaGaO$_3$:$Eu^{3+}$ phosphoL The excimtion srectrum artd emission spectmn were rnezsured in the UV range and then decay curve of $^5D_0$+$^7F_j$transitions\vas examined. The decay behavior of $^5D_0$ emission was anMyzed by a newly Iuoposed cross-relaxation mech-ani8In in asswiation with inteFwnter di1ffision (or migration). The cross-mlaxation from $^5D_0$ to CTB (Cha'geTransfer Band) wuld be a quite retsonable by considering the excitation spectrum. It could be also found thatthe quenching type was changed from ditfrsion controlled process to the direct quenching process -s inJeasing $Eu^{3+}$ oncntration.

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SREBP as a Global Regulator for Lipid Metabolism (지질대사 조절에서 SREBP의 역할)

  • Lee, Wonhwa;Seo, Young-kyo
    • Journal of Life Science
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    • v.28 no.10
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    • pp.1233-1243
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    • 2018
  • Sterol regulatory-element binding proteins (SREBPs) are a family of transcription factors that regulate lipid homeostasis and metabolism by controlling the expression of enzymes required for endogenous cholesterol, fatty acid (FA), triacylglycerol, and phospholipid synthesis. The three SREBPs are encoded by two different genes. The SREBP1 gene gives rise to SREBP-1a and SREBP-1c, which are derived from utilization of alternate promoters that yield transcripts in which distinct first exons are spliced to a common second exon. SREBP-2 is derived from a separate gene. Additionally, SREBPs are implicated in numerous pathogenic processes, such as endoplasmic reticulum stress, inflammation, autophagy, and apoptosis. They also contribute to obesity, dyslipidemia, diabetes mellitus, and nonalcoholic fatty liver diseases. Genome-wide analyses have revealed that these versatile transcription factors act as important nodes of biological signaling networks. Changes in cell metabolism and growth are reciprocally linked through SREBPs. Anabolic and growth signaling pathways branch off and connect to multiple steps of SREBP activation and form complex regulatory networks. SREBPs are activated through the PI3K-Akt-mTOR pathway in these processes, but the molecular mechanism remains to be understood. This review aims to provide a comprehensive understanding of the role of SREBPs in physiology and pathophysiology at the cell, organ, and organism levels.