• Genomics & Informatics
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• v.2 no.3
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• pp.134-141
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• 2004

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and a typical hypervascular tumor. Therefore, it is important to find factors related to angiogenesis in the process of HCC malignancy. In order to find angiogenesis-related factors in HCC, we used combined methods of in silico prediction and an experimental assay. We analyzed 1457 genes extracted from cDNA microarray of HCC patients by text-mining, sequence similarity search and domain analysis. As a result, we predicted that 16 genes were likely to be involved in angiogenesis and then the effects of these genes were confirmed by hypoxia response element(HRE)-luciferase assay. For instant, we classified osteopontin into a potent angiogenic factor and coagulation factor XII into a significant anti­angiogenic factor. Collectively, we suggest that using a combination of in silico prediction and experimental approaches, we can identify HCC-specific angiogenesis­related factors effectively and rapidly.

• Korean Journal of Biological Psychiatry
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• v.18 no.4
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• pp.181-188
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• 2011

Major depression is a devastating disorder of which lifetime prevalence rate is as high as up to 25% in general population. Although the etiology of the disorder is still poorly understood, it is generally accepted that both genetic and environmental factors are involved in the precipitation of depression. Stressful lifetime events are potent precipitating environmental factors for major depression and early-life stress is in particular an important element that predisposes individuals to major depression later in life. How environmental factors such as stress can make our neural networks susceptible to depression and how those factors leave long-lasting influences have been among the major questions in the field of depression research. Epigenetic regulations can provide a bridging mechanism between environmental factors and genetic factors so that these two factors can additively determine individual predispositions to major depression. Here we introduce epigenetic regulations as candidate mechanisms that mediate the integration of environmental adversaries with genetic predispositions, which may lead to the development of major depression, and summarize basic molecular events that underlie epigenetic regulations as well as experimental evidences that support the active role of epigenetic regulation in major depression.

• Journal of the Korean Society for Heat Treatment
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• v.1 no.1
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• pp.13-23
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• 1988

The hardenability of alloyed ductile cast irons was studied for 54 different alloy compositions obtained from eight commercial and laboratory foundries. The alloying elements investigated for their effects on hardenability were Si(2.0 to 3.0%), Mn(0.0 to 0.8%), Mo(0.0 to 0.6%), Cu(0.0 to 1.5%), and Ni(0.0 to 1.5%). Two hardenability criteria, a first-pearlite hardenability criterion and a half-hard hardenability criterion, were used to determine hardenability of ductile irons. Prediction models for each hardenability criterion were developed by multiple regression analysis and were well agreed with previous experimental results. Molybdenum was the most potent hardenability promoting element followed by manganese, copper and nickel ; silicon had little effect on hardenability and reduced the hardenability as silicon content increased. When alloying elements were presented in combination, strong synergistic effects on the hardenability were observed especially between molybdenum, copper and nickel. The hardenability of ductile iron was strongly influenced by austenitizing temperature. Increasing austenitizing temperature up to $955^{\circ}C$, hardenability increased gradually but decreasing rate and then decreased as temperature increased above $955^{\circ}C$. Unless reducing segregation by very long-time annealing treatment, the hardenability of ductile iron was not significantly influenced by segregation of alloying elements.

• Journal of Applied and Pure Mathematics
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• v.5 no.3_4
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• pp.187-196
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• 2023

This study is about spin half add operations in 𝓑₂ and 𝓑₃. The burden of technological structures has increased due to the increase in the use of today's technological applications or the processes in the digital systems used. This has increased the importance of fast transactions and storage areas. For this, less transactions, more gain and storage space are foreseen. We have handle tit (triple digit) system instead of bit (binary digit). 729 is reached in 3⁶ in 𝓑₃ while 256 is reached with 2⁸ in 𝓑₂. The volume and number of transactions are shortened in 𝓑₃. The limited storage space at the maximum level is storaged. The logic connectors and the complement of an element in 𝓑₂ and the course of the connectors and the complements of the elements in 𝓑₃ are examined. "Carry" calculations in calculating addition and "borrow" in calculating difference are given in 𝓑₃. The logic structure 𝓑₂ is seen to embedded in the logic structure 𝓑₃. This situation enriches the logic structure. Some theorems and lemmas and properties in logic structure 𝓑₂ are extended to logic structure 𝓑₃.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.3
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• pp.303-309
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• 2014

The fruit of Gleditsia sinensis has been extensively used as a key ingredient of an herbal remedy for the treatment of various inflammatory diseases in traditional Korean Medicine. However, the reason of using the fruit of G. sinensis for the remedy is unclear. Since Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key anti-inflammatory transcription factor, which is activated by the fruit of G. sinesis, we examined whether other plant parts of G. sinensis are also capable of suppressing inflammatory responses by activating Nrf2. Water extracts of various parts of G. sinensis were prepared and tested for Nrf2 activation by reporter assay and western blot analysis. Our results show that the hull of G. sinensis is the most potent in activating Nrf2. Sequential organic solvent extraction of the hull show that all the fractions had a higher potency in activating Nrf2 than the water extract, albeit differential degrees. The hull originated from Korea in general activated Nrf2 strongly compared to that of China. Chloroform fraction of the hull was further examined, showing that the fraction induced nuclear localization of Nrf2, indicative of activated Nrf2, and Nrf2-dependent gene expression including NAD(P)H dehydrogenase quinone 1 (NQO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and heme oxygenase - 1 (HO-1). Therefore, our results show that, among other plant parts examined in this study, the hull of G. sinensis is the most potent, providing the experimental basis for the use of the hull of G. sinensis as an active ingredient for an anti-inflammatory remedy.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.6
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• pp.822-828
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• 2014

Allium sacculiferum Max. (ASM) is a perennial plant of the Liliaceae family and grows over the entire regions of Korea. Obesity is a serious health problem worldwide and has currently become a prevalent chronic disease. Adipocytes produced by preadipocyte differentiation during adipogenesis and adipocytes combined with abnormal accumulation cause obesity. Recently, intracellular reactive oxygen species (ROS) were shown to accelerate lipid accumulation in 3T3-L1 cells. In this study, we investigated the effects of ASM methanol extracts on ROS production and lipid accumulation in 3T3-L1 adipocytes. Our results indicate that the 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity of ASM methanol extracts increased in a dose-dependent manner. ASM methanol extracts suppressed ROS production and lipid accumulation during adipogenesis. In addition, ASM methanol extracts inhibited the mRNA expression of both pro-oxidant enzymes such as glucose-6-phosphate dehydrogenase as well as the transcription factors, including sterol regulatory element-binding proteins 1c, peroxisome proliferator-activated receptor ${\gamma}$, and CCAAT/enhancer-binding protein ${\alpha}$. Our results suggest that ASM methanol extracts inhibit ROS production and lipid accumulation by controlling ROS regulatory genes and adipogenic transcription factors. Thus, ASM has potent natural antioxidant, anti-adipogenic properties and have potential in the development of a potent anti-obesity agent.

• Molecules and Cells
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• v.23 no.1
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• pp.23-29
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• 2007

Cyclic AMP-responsive element binding protein (CREB) is known to be associated with angiogenesis. In the present study we investigated the possible role of CREB in the expression of vascular endothelial growth factor (VEGF) by mouse macrophages. Over-expression of CREB increased VEGF secretion by cells of the RAW264.7 mouse macrophage cell line. It also increased the promoter activity of a mouse reporter driven by the VEGF promoter, while a dominant negative CREB (DN-CREB) abrogated the activity, suggesting that CREB mediates VEGF transcription. Forskolin, an adenylyl cyclase activator, stimulated VEGF transcription, and the PKA inhibitor H89 abolished this effect. IFN-${\gamma}$, a potent cytokine, stimulated VEGF expression only in part through the PKA-CREB pathway. These results indicate that PKA phosphorylates CREB and so induces VEGF gene expression. An analysis of mutant promoters revealed that one of the putative CREB responsive elements (CREs), at -399 ~ -388 in the promoter, is critical for CREB-mediated VEGF promoter activity, and the significance of this CRE was confirmed by chromatin immunoprecipitation assays.

• Toxicological Research
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• v.34 no.1
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• pp.13-21
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• 2018

Anthocyanins are naturally occurring water-soluble polyphenolic pigments in plants that have been shown to protect against cardiovascular diseases, and certain cancers, as well as other chronic human disorders. However, the anti-obesity effects of anthocyanins are not fully understood. In this study, we investigated the effects of anthocyanins isolated from the fruit of Vitis coignetiae Pulliat on the adipogenesis of 3T3-L1 preadipocytes. Our data indicated that anthocyanins attenuated the terminal differentiation of 3T3-L1 preadipocytes, as confirmed by a decrease in the number of lipid droplets, lipid content, and triglyceride production. During this process, anthocyanins effectively enhanced the activation of the AMP-activated protein kinase (AMPK); however, this phenomenon was inhibited by the co-treatment of compound C, an inhibitor of AMPK. Anthocyanins also inhibited the expression of adipogenic transcription factors, including peroxisome proliferator-activated receptor-${\gamma}$, CCAAT/enhancer-binding protein a and b, and sterol regulatory element-binding protein-1c. In addition, anthocyanins were found to potently inhibit the expression of adipocyte-specific genes, including adipocyte fatty acid-binding protein, leptin, and fatty acid synthase. These results indicate that anthocyanins have potent anti-obesity effects due to the inhibition of adipocyte differentiation and adipogenesis, and thus may have applications as a potential source for an anti-obesity functional food agent.

• Toxicological Research
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• v.23 no.2
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• pp.135-142
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• 2007

Formononetin is an isoflavonoid phytoestrogen found in certain foodstuffs such as soy and red clover. In this study, we examined the action of formononetin with the carcinogen activation pathway mediated through the aryl hydrocarbon receptor (AhR) in MCF-7 breast carcinoma cells. Treating the cells with formononetin alone caused the accumulation of CYP1A1 mRNA as well as elevation in CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity in a dose dependent manner. However, a concomitant treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and formononetin markedly reduced both the DMBA-inducible EROD activity and CYP1A1 mRNA level. Under the same conditions, formononetin inhibited the DMBA-induced AhR transactivation, as shown by reporter gene analysis using a xenobiotic responsive element (XRE). Additionally, formononetin inhibited both DMBA-inducible nuclear localization of the aryl hydrocarbon receptor (AhR) and metabolic activation of DMBA, as measured by the formation of the DMBA-DNA adducts. Furthermore, formononetin competed with the prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), for binding to the AhR in an isolated rat cytosol. These results suggest that formononetin might be considered as a natural ligand to bind on AhR and consequently produces a potent protective effect against DMBA-induced genotoxicity. Therefore, that's the potential to act as a chemopreventive agent that is related to its effect on AhR pathway as antagonist/agonist.

• Molecules and Cells
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• v.27 no.3
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• pp.351-357
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• 2009

Phytoestrogens are the natural compounds isolated from plants, which are structurally similar to animal estrogen, $17{\beta}$-estradiol. Tectoridin, a major isoflavone isolated from the rhizome of Belamcanda chinensis. Tectoridin is known as a phytoestrogen, however, the molecular mechanisms underlying its estrogenic effect are remained unclear. In this study we investigated the estrogenic signaling triggered by tectoridin as compared to a famous phytoestrogen, genistein in MCF-7 human breast cancer cells. Tectoridin scarcely binds to ER ${\alpha}$ as compared to $17{\beta}$-estradiol and genistein. Despite poor binding to ER ${\alpha}$, tectoridin induced potent estrogenic effects, namely recovery of the population of cells in the S-phase after serum starvation, transactivation of the estrogen response element, and induction of MCF-7 cell proliferation. The tectoridin-induced estrogenic effect was severely abrogated by treatment with U0126, a specific MEK1/2 inhibitor. Tectoridin promoted phosphorylation of ERK1/2, but did not affect phosphorylation of ER ${\alpha}$ at $Ser^{118}$. It also increased cellular accumulation of cAMP, a hallmark of GPR30-mediated estrogen signaling. These data imply that tectoridin exerts its estrogenic effect mainly via the GPR30 and ERK-mediated rapid nongenomic estrogen signaling pathway. This property of tectoridin sets it aside from genistein where it exerts the estrogenic effects via both an ER-dependent genomic pathway and a GPR30-dependent nongenomic pathway.