• Asian-Australasian Journal of Animal Sciences
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• v.33 no.4
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• pp.670-677
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• 2020

Objective: Interleukin-6 (IL-6) is a T cell-derived B cell stimulating factor which plays an important role in inflammatory diseases. In this study, the pharmacokinetic properties of LMT-28 including physicochemical property, in vitro liver microsomal stability and an in vivo pharmacokinetic study using BALB/c mice were characterized. Methods: LMT-28 has been synthesized and is being developed as a novel therapeutic IL-6 inhibitor. The physicochemical properties and in vitro pharmacokinetic profiles such as liver microsomal stability and Madin-Darby canine kidney (MDCK) cell permeability assay were examined. For in vivo pharmacokinetic studies, pharmacokinetic parameters using BALB/c mice were calculated. Results: The logarithm of the partition coefficient value (LogP; 3.65) and the apparent permeability coefficient values (P_app; 9.7×10^-6 cm/s) showed that LMT-28 possesses a moderate-high cell permeability property across MDCK cell monolayers. The plasma protein binding rate of LMT-28 was 92.4% and mostly bound to serum albumin. The metabolic half-life (t_1/2) values of LMT-28 were 15.3 min for rat and 21.9 min for human at the concentration 1 μM. The area under the plasma drug concentration-time curve and C_max after oral administration (5 mg/kg) of LMT-28 were 302±209 h·ng/mL and 137±100 ng/mL, respectively. Conclusion: These data suggest that LMT-28 may have good physicochemical and pharmacokinetic properties and may be a novel oral drug candidate as the first synthetic IL-6 inhibitor to ameliorate mammalian inflammation.

• Transactions of the Korean Society of Mechanical Engineers B
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• v.25 no.5
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• pp.722-730
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• 2001

The local heat transfer of an axisymmetric submerged air jet impinging on a heated flat plate is investigated experimentally with the variation of mesh-screen solidity. The screen installed in front of the nozzle exit modifies the flow structure and local heat transfer characteristics. The mean velocity and turbulence intensity profiles of streamwise velocity component are measured using a hot-wire anemometry. The temperature distribution on the heated flat surface is measured with thermocouples. The smoke-wire flow visualization technique was employed to understand the near-field flow structure qualitatively for different mesh screens. Large-scale toroidal vortices and high turbulence intensity enhance the heat transfer rate in the stagnation region. For a higher solidity, turbulence intensity become higher which increases the local heat transfer at small nozzle-to-plate spacings such as L/D<6. The local and average Nusselt numbers of impinging jet from the $\sigma$(sub)s=0.83 screen at L/D=2 are about 5.6∼7.5% and 7.1% larger than those for the case of no screen, respectively. For the nozzle-to-plate spacings larger than 6, however, the turbulence intensities for all tested screens approach to an asymptotic curve and the mean velocity along the jet centerline decreases monotonically. As the nozzle-to-plat spacing increases for high solidity screens, the heat transfer rate decreases due to the reduction in turbulence intensity and jet momentum.

• Korean Journal of Microbiology
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• v.50 no.1
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• pp.84-86
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• 2014

Mass production of biocontrol agent is an essential step for its commercial use. Media composition and culture conditions for production of Bacillus amyloliquefaciens SKU-78, a potential biocontrol agent against bacterial wilts, were optimized by a flask culture. Low cost media combining nitrogen and carbon sources were tested. Maximum cell growth (> $2{\times}10^9$ CFU/ml) was obtained in a medium of 5% soy flour combined with 3% corn starch after 24 h cultivation. The optimum initial pH, temperature and shaking speed was 5.5, $30^{\circ}C$ and 150-250 rpm, respectively. Fermentation of SKU-78 was scaled up in 30 L fermenter and the profiles of cell density, pH, dissolved oxygen and spore formation were recorded. After 8 h lag phase, exponential growth occurred and reached at maximum viable cell number ($1.2{\times}10^{11}$ CFU/ml) after 20 h. The SKU-78 strain grown in a low cost medium exhibited the high suppression of bacterial wilts. The results indicate that SKU-78 strain can be produced in a low cost medium and provide a basis for scaling up to industrial level.

• Biomolecules & Therapeutics
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• v.25 no.6
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• pp.648-658
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• 2017

7-O-Succinyl macrolactin A (SMA) exerts several pharmacological effects including anti-bacterial, anti-inflammation, and anti-cancer activities. Recently, SMA has been extensively evaluated as an anti-cancer drug. Thus, the objectives of the present study were to characterise the pharmacokinetics of SMA via both non-compartmental and compartmental analysis in mice, rats, and dogs, and to derive an appropriate first-in-man dose based on allometric scaling of the animal data. The time courses of plasma SMA concentrations after intravenous administration to rats and dogs were analysed retrospectively, as were data collected after intraperitoneal SMA injection in mice. Pharmacokinetic parameters were estimated via both noncompartmental and compartmental analysis, and were correlated with body weight and/or the potential maximum life-span. The clearance and distribution volume of SMA in humans were predicted, and a first-in-man dose proposed. A two-compartment model best described the time courses of SMA plasma concentrations after a saturation elimination process was applied to fit the dataset obtained from rats. Incorporation of the maximum potential life-span during allometric scaling was required to improve the estimation of human clearance. The SMA clearance and the distribution volume in the steady state, in a 70-kg adult male, were estimated to be 30.6 L/h and 19.5 L, respectively. To meet the area under the curve (AUC) required for anti-tumour activity, a dose of 100 mg (~1.5 mg/kg) was finally proposed as the first dose for a 70-kg human. Although toxicological profiles derived from non-clinical studies must be considered before any final decision is made, our work will facilitate clinical studies on SMA.

• Journal of Life Science
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• v.14 no.1
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• pp.110-114
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• 2004

The optimized RAPD-PCR conditions, that can be utilized as a basic information for analysis of the gelletic characteristics were developed for genetic analysis of four mulberry varieties, named Milsung, Chungil, Suil, and Hansung using a primer, OPY15 (5'-AGTCGCCCTT-3') from Operon company. We tested several different factors for best PCR condition including concentrations of DNA, primer, Mgclu annealing temperature, number of PCR cycle, and prosence/absence of pre-heating time at the begining of PCR reaction in the $25 \mul$volume. The best RAPD profiles were obtained using 50 ng of DNA, 1 $\mu$M of primer, $1 \mum$of $MgCl_2\;,45^{\circ}C$ of annealing temperature and an absence of pre-heating time. An establishment of the stable and reproducible RAPD-PCR conditions are expected to be useful for the subsequent RAPD-related investigation, such as genetic characterization of the mulberry varieties, re-establishment of phylogenetic relationships and development of new varieties.

• Molecular & Cellular Toxicology
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• v.2 no.3
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• pp.159-165
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• 2006

To determine the anticancer effect of D-amygdalin (D-mandelinitrole-${\beta}$-D-gentiobioside) in human chronic myeloid leukemia cells K562, we profiled the gene expression between amygdalin treatment and control groups. Through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, the cytotoxicity of D-amygdalin was $57.79{\pm}1.83%$ at the concentration of 5 mg/mL for 24 h. We performed cDNA microarray analysis and compared the gene expression profiles between D-amygdalin (5 mg/mL, 24 h) treatment and control groups. Among the genes changed by D-amygdalin, we paid attention to cell cycle-related genes, and particularly cell cycle regulator genes; because arrest of cell cycle processing was ideal tactic in remedy for cancer. In our data, expressions of cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B), ataxia telangiectasia mutated (includes complementation groups A, C, and D) (ATM), cyclin-dependent kinase inhibitor 1C (p57, Kip2) (CDKN1C), and CHK1 checkpoint homolog (CHEK1, formally known as CHK1) were increased, while expressions of cyclin-dependent kinase 2 (CDK2), cell division cycle 25A (CDC25A), and cyclin E1 (CCNE1) were decreased. The pattern of these gene expressions were confirmed through RT-PCR. Our results showed that D-amygdalin might control cell cycle regulator genes and arrest S phase of cell cycle in K562 cells as the useful anticancer drug.

• Preventive Nutrition and Food Science
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• v.21 no.3
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• pp.208-220
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• 2016

The aim of this study was to investigate the protective effects of juice powders from sweet orange [Citrus sinensis (L.) Osbeck], unshiu mikan (Citrus unshiu Marcow), and mini tomato (Solanum lycopersicum L.), and their major flavonoids, hesperidin, narirutin, and rutin in tert-butyl hydroperoxide (t-BHP)-induced oxidative stress in HepG2 cells. The increased reactive oxygen species and decreased glutathione levels observed in t-BHP-treated HepG2 cells were ameliorated by pretreatment with juice powders, indicating that the hepatoprotective effects of juice powders and their major flavonoids are mediated by induction of cellular defense against oxidative stress. Moreover, pretreatment with juice powders up-regulated phase-II genes such as heme oxygenase-1 (HO-1), thereby preventing cellular damage and the resultant increase in HO-1 expression. The high-performance liquid chromatography profiles of the juice powders confirmed that hesperidin, narirutin, and rutin were the key flavonoids present. Our results suggest that these fruit juice powders and their major flavonoids provide a significant cytoprotective effect against oxidative stress, which is most likely due to the flavonoid-related bioactive compounds present, leading to the normal redox status of cells. Therefore, these fruit juice powders could be advantageous as bioactive sources for the prevention of oxidative injury in hepatoma cells.

• Animal cells and systems
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• v.10 no.1
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• pp.15-20
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• 2006

Allergic inflammation is thought to be a Th2 cell-dominant immune response during which tissue-resident fibroblasts produce chemokines which contribute to the recruitment of migratory leukocytes to sites of tissue injury. Thymus and activation-regulated chemokine (TARC; CCL17) is a potent member of the CC chemokine family and a selective chemoattractant for Th2 cells. In order to study the regulatory profiles of TARC production by $TNF-{\alpha}$, $IFN-{\gamma}$, and Il-4 in human normal skin fibroblast, CCD-986sk cell line was used. The expression of TARC protein was measured using ELISA, and mRNA level was detected by RT-PCR. The combination of $TNF-{\alpha}$ and IL-4 induced a time-and dose-dependent synergistic increase in the expression of TARC at both protein and mRNA levels in the cultured human skin fibroblasts. Exposure of the cells to single cytokine had no effect on TARC expression. The high concentration (100 ng/ml) and long incubation time (72 h) of $IFN-{\gamma}$ further enhanced the TARC production induced by $TNF-{\alpha}$/lL-4 in the skin fibroblast. This synergistic effect of Th1 and Th2 type cytokines on TARC production by skin fibroblasts may contribute to the inflammatory cell infiltration and tissue damage with allergic inflammation.

• Transactions of the Korean Society of Mechanical Engineers
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• v.14 no.3
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• pp.694-701
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• 1990

The cycle of heat engine which produces the maximum power output is constructed when heat sources are finitely constant, and the maximum power as a thermodynamic limit of the engine, is obtained. The characteristics of the maximum power cycle are as follows, which represent the operation conditions and design conditions of the heat engine to produce the maximum power output. In heat exchangers, the temperature profiles of the heat source and the working fluid have the same functional formula and the ratio of the working fluid temperature to the heat source temperature is constant. When heat capacity flow rates(product of the specific heat and the mass flow rate) of the working fluid as well as the heat source are constant, the values of those of working fluid exist between those of two heat sources. The relation of the temperature and the heat capacity flow rate is established without the states of the heat sources and the capacities of heat exchangers, which is ( $T_{h}$/ $T_{H}$)( $C_{h}$/ $C_{H}$)=( $T_{1}$/ $T_{L}$)( $c_{1}$/ $c_{L}$)=1. The capacity of the heat exchanger of hot side is equal to that of cold side regardless of the states of the heat sources and the total capacities of heat exchangers.hangers.ers.

• Applied Biological Chemistry
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• v.41 no.5
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• pp.355-362
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• 1998

The minor form of phosphofructokinase (EC 2.7.1.11; PFK), which was suggested to be of plastid origin from the host fraction of chickpea nodules, was isolated as a small protein with apparent molecular mass near 220 kDa and purified to a high degree. SDS-PAGE and western blot indicated that the enzyme was made up of a homotetrameric structure (55 kDa). The enzyme had sharp pH profiles with maximal activities at pH 8 and displayed Michaelis-Menten kinetics with respect to Fru-6-P and nucleoside triphosphate substrate at the pH optimum (pH 8) and at pH 7. MgATP was the most effective phosphoryl donor. Phosphoenolpyruvate was a potent inhibitor of minor PFK activity, and the enzyme was also strongly inhibited by 3-phosphoglycerate, 2-phosphoglycerate, and to a lesser extent, PPi. Minor PFK was weakly activated by KCl, NaCl and Pi, and was inhibitory at high concentration of KCl and Pi.