• Korean Journal of Veterinary Pathology
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• v.1 no.2
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• pp.91-96
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• 1997

General steps in the discovery and development of novel drugs in the United States are presented. The first step is the discovery of novel drugs. Brief histories and mechanisms of a few novel drugs in the American market are outlined. In this presentation preclinical animal toxicologic studies (drug safety evaluateion) are emphasized in regard to drug development. When preclinical animal studies have defined the toxicity and the doses at which it occurs an Investigational new Drug Application (IND) is submitted to the Food and Drug Administration (FDA) An IND notifies the FDA the intention to begin testing a novel drug in human subjects.

• Molecules and Cells
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• v.21 no.2
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• pp.174-185
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• 2006

Toll-like receptors (TLRs) were evolved to detect invading pathogens and to induce innate immune responses in order to mount host defense mechanisms. It becomes apparent that the activation of certain TLRs is also modulated by endogenous molecules including lipid components, fatty acids. Results from epidemiological and animal studies demonstrated that saturated and polyunsaturated dietary fatty acids can differentially modify the risk of development of many chronic diseases. Inflammation is now recognized as an important underlying etiologic condition for the pathogenesis of many chronic diseases. Therefore, if the activation of TLRs and consequent inflammatory and immune responses are differentially modulated by types of lipids in vivo, this would suggest that the risk of the development of chronic inflammatory diseases and the host defense against microbial infection may be modified by the types of dietary fat consumed.

• Preventive Nutrition and Food Science
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• v.6 no.4
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• pp.253-256
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• 2001

Irradiation of food is not only used for sanitation purposes but can be used for processing techniques to reduce or eliminate toxic or undesirable compounds on food. Irradiation wag effective to reduce the allergenicity of food by modification of the structure of proteins causing allergy reactions. Volatile N-nitrosmaine was reduced or eliminated by irradiation in the model system study and the breakdown products by irradiation did not recombine under human stomach conditions (pH 2,3, and 4,37$^{\circ}C$). The possibility of residual chlorophyll b reduction by irradiation was also found, and the model study indicated that irradiation be used to destroy chlorophyll b, resulting in protection from photooxidation in oil without acceleration of lipid oxidation during irradiation. In this paper, several on-going research projects for the application of food irradiation as a new processing technique are introduced, including reduction of food allergens, breakdown of volatile N-nitrosamine and residual chlorophyll b.

• Electronics and Telecommunications Trends
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• v.38 no.4
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• pp.70-80
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• 2023

In recent years, our society has shifted from an information society to an intelligent information society, in which computing has become a key factor in shaping and driving social development. In this new era of digital civilization powered by the Internet of Things, traditional data-based computing is no longer sufficient to meet the growing demand for higher levels of intelligence. Therefore, intelligent computing has emerged, reshaping traditional computing and forming new computing paradigms to promote the digital revolution in the era of the Internet of Things, big data, and artificial intelligence. Intelligent computing has greatly expanded the scope of computing through new computing theories, architectures, methodologies, systems, and applications, and it is expanding into diverse computing paradigms such as perceptual intelligence, cognitive intelligence, autonomous intelligence, and human-computer fusion intelligence. This paper introduces the concept and main features of intelligent computing and describes trends in standardization for intelligent computing within the ISO/IEC JTC 1, focusing on the technical trend report on intelligent computing that is currently under development within ISO/ IEC JTC 1/AG 2.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3213-3222
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• 2015

Background: Cancer metastasis depends on cell motility which is driven by cycles of actin polymerization and depolymerization. Reactive oxygen species (ROS) and metabolic oxidative stress have long been associated with cancer. ROS play a vital role in regulating actin dynamics that are sensitive to oxidative modification. The current work aimed at studying the effects of sub-lethal metabolic oxidative stress on actin cytoskeleton, focal adhesion and cell migration. Materials and Methods: T47D human breast cancer cells were treated with 2-deoxy-D-glucose (2DG), L-buthionine sulfoximine (BSO), or doxorubicin (DOX), individually or in combination, and changes in intracellular total glutathione and malondialdehyde (MDA) levels were measured. The expression of three major antioxidant enzymes was studied by immunoblotting, and cells were stained with fluorescent-phalloidin to evaluate changes in F-actin organization. In addition, cell adhesion and degradation ability were measured. Cell migration was studied using wound healing and transwell migration assays. Results: Our results show that treating T47D human breast cancer cells with drug combinations (2DG/BSO, 2DG/DOX, or BSO/DOX) decreased intracellular total glutathione and increased oxidized glutathione, lipid peroxidation, and cytotoxicity. In addition, the drug combinations caused a reduction in cell area and mitotic index, prophase arrest and a decreased ability to form invadopodia. The formation of F-actin aggregates was increased in treated T47D cells. Moreover, combination therapy reduced cell adhesion and the rate of cell migration. Conclusions: Our results suggest that exposure of T47D breast cancer cells to combination therapy reduces cell migration via effects on metabolic oxidative stress.

• Korean Journal of Food Science and Technology
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• v.37 no.1
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• pp.84-89
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• 2005

Mongolian dandelion (Taraxacum mongolicum H.) extracted with solvents having different polarities were prepared to investigate protection activity of gastric mucosa. Ethanol extracts were successively reextracted with methylene chloride, and n-butanol. Concentrations of total flavonoids and luteolin in n-butanol extracts were 27.75 and 1.14%, respectively, much higher than those of other solvent extracts. Results of anti-microbial acitivity test against Helicobacter pylori and urease inhibition test revealed n-butanol extract exerted higher inhibition (13.16%) than other solvent extracts. Based on 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, n-butanol extract showed the highest efficiency of free radical-scavenger activity among the extracts ($SC_{50}\;47{\mu}g/mL$). Erythrocytic photohemolysis tests, for the protection of cell membrane showed that half-life of human erythrocytes was increased by the addition of n-butanol extract $({\tau}_{50}=172min;C=5.0{\mu}g/mL)$. These results indicate n-butanol extract of Mongolian dandelion may be useful as a adjuvant for gastric diseases.

• Archives of Pharmacal Research
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• v.20 no.3
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• pp.259-263
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• 1997

In the preparation of acyclic thymidine nucleoside analogues, $K_2CO_3$(or NaH) treated thymine in DMSO was alkylated with .omega.-chloroalkyl nitrite (Cl-(CH_2)n-CN; n=1, 2, 3, 4) to provide an isomeric mixture of 1-(${\omega}$-cyanoalkyl)thymine (2a-d) and 1,3-bis(${\omega}$-cyanoalkyl)thymine in approximately 5:1 ratios. Reduction of the cyano function 2a-d with $NaBH_{4}/CoCl_{2}$ center dot$ 6H_{2}O$gave the corresponding 1-(${\omega}$aminoalkyl)thymine (3a-d). The newly formed primary amino function in 3a-d was directly reacted with 2-chloroethylisocyanate to afford the 1-[.omega.($N^{I}$-2-chloroethylureido) alkyl]thymine (4a-d) in good yields. Nitrosation of 1-[5-($ N^{I}-2$-chloroethylureido)pentyl] thymine (4d) with glacial acetic acid and dry $NaNO_{2}$-powder in anhydrous $CH_{2}Cl_{2}$gave two types of regioisomeric nitrosoureas, 1-[5-($N^{I}$--chloroethyl-$N^{I}$--nitrosoureido)pentylithymine (5d) and 1-[5-($N^{I}-2$-chloroethyl-N-nitrosoureido)pentyllthymine in approximately 5 :1 ratios. The in vitro cytotoxicity of the synthesized compounds (2a-d, 3a-d, 4a-d and 5a-d) against three cell lines (K-562, P-388 and FM-3A) are measured as $IC^{50}$ values. Compounds 3b and 4c showed moderate activities against all three cell lines, and all other compounds were found to be not active.

• Tuberculosis and Respiratory Diseases
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• v.77 no.6
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• pp.243-250
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• 2014

Background: Information regarding prognostic value of growth differentiation factor 15 (GDF-15) and heart-type fatty acid-binding protein (H-FABP) in patients with chronic obstructive pulmonary disease (COPD) exacerbation is limited. The aim of this study was to investigate whether serum levels of GDF-15 and H-FABP predict an adverse outcome for COPD exacerbation. Methods: Clinical variables, including serum GDF-15 and H-FABP levels were compared in prospectively enrolled patients with COPD exacerbation that did or did not experience an adverse outcome. An adverse outcome included 30-day mortality and need for endotracheal intubation or inotropic support. Results: Ninety-seven patients were included and allocated into an adverse outcome (n=10) or a control (n=87) group. Frequencies of mental change and $PaCO_2$>37 mm Hg were significantly higher in the adverse outcome group (mental change: 30% vs. 6%, p=0.034 and $PaCO_2$>37 mm Hg: 80% vs. 22%, p<0.001, respectively). Serum GDF-15 elevation (>1,600 pg/mL) was more common in the adverse outcome group (80% vs. 43%, p=0.041). However, serum H-FABP level and frequency of serum H-FABP elevation (>755 pg/mL) did not differ between the two groups. Multivariate analysis showed that an elevated serum GDF-15 and $PaCO_2$>37 mm Hg were significant predictors of an adverse outcome (odds ratio [OR], 25.8; 95% confidence interval [CI], 2.7-243.8; p=0.005 and OR, 11.8; 95% CI, 1.2-115.3; p=0.034, respectively). Conclusion: Elevated serum GDF-15 level and $PaCO_2$>37 mm Hg were found to predict an adverse outcome independently in patients with COPD exacerbation, suggesting the possibility that serum GDF-15 could be used as a prognostic biomarker of COPD exacerbation.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.6
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• pp.405-413
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• 2011

This study was designed to elucidate high-$K^+$ induced response of circular and longitudinal smooth muscle from human gastric corpus using isometric contraction. Contraction from circular and longitudinal muscle stripes of gastric corpus greater curvature and lesser curvature were compared. Circular smooth muscle from corpus greater curvature showed high $K^+$ (50 mM)-induced tonic contraction. On the contrary, however, longitudinal smooth muscle strips showed high $K^+$ (50 mM)-induced sustained relaxation. To find out the reason for the discrepancy we tested several relaxation mechanisms. Protein kinase blockers like KT5720, PKA inhibitor, and KT5823, PKG inhibitor, did not affect high $K^+$-induced relaxation. $K^+$ channel blockers like tetraethylammonium (TEA), apamin (APA), glibenclamide (Glib) and barium ($Ba^{2+}$) also had no effect. However, N(G)-nitro-L-arginine (L-NNA) and 1H-(1,2,4) oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC) and 4-AP (4-aminopyridine), voltage-dependent $K^+$ channel (KV) blocker, inhibited high $K^+$ -induced relaxation, hence reversing to tonic contraction. High $K^+$-induced relaxation was observed in gastric corpus of human stomach, but only in the longitudinal muscles from greater curvature not lesser curvature. L-NNA, ODQ and KV channel blocker sensitive high $K^+$-induced relaxation in longitudinal muscle of higher portion of corpus was also observed. These results suggest that longitudinal smooth muscle from greater curvature of gastric corpus produced high $K^+$-induced relaxation which was activated by NO/sGC pathway and by $K_V$ channel dependent mechanism.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7943-7957
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• 2015

Background and Aims: Colorectal cancer is one of the leading causes of death in the world. The aim of this study was to investigate the growth-suppression potentiality of a crude saponin extract (CSENS) prepared from medicinal herb, Nigella sativa, on human colon cancer cells, HCT116. Materials and Methods: HCT116 cells were subjected to increasing doses of CSENS for 24, 48 and 72 h, and then harvested and assayed for cell viability by WST-1. Flow cytometry analyses, cell death detection ELISA, fluorescent stains (Hoechst 33342 and acridine orange/ethidium bromide), DNA laddering and comet assays were carried out to confirm the apoptogenic effects of CSENS. Luciferase reporter gene assays, quantitative reverse transcription-polymerase chain reaction and Western blot analyses were performed to assess the impact of CAERS and CFEZO on the expression levels of key regulatory proteins in HCT116 cells. Results: The results demonstrated that CSENS inhibited proliferation and induced apoptosis. Apoptosis was confirmed by flow cytometry analyses, while CSENS-treated cells exhibited morphological hallmarks of apoptosis including cell shrinkage, irregularity in cellular shape, cellular detachment and chromatin condensation. Biochemical signs of apoptosis, such as DNA degradation, were observed by comet assay and gel electrophoresis. The pro-apoptotic effect of CSENS was caspase-3-independent and associated with increase of the Bax/Bcl-2 ratio. CSENS treatment down-regulated transcriptional and DNA-binding activities of NF-${\kappa}B$ and AP-1 proteins, associated with down-regulation of their target oncogenes, c-Myc, cyclin D1 and survivin. On the other hand, CSENS up-regulated transcriptional and DNA-binding activities of Nrf2 and expression of cytoprotective genes. In addition, CSENS modulated the expression levels of ERK1/2 MAPK, p53 and p21. Conclusions: These findings suggest that CSENS may be a valuable agent for treatment of colon cancer.