• Clean Technology
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• v.13 no.1 s.36
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• pp.34-45
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• 2007

Phase behavior of the ternary systems of water-insoluble simvastatin drug, which is well known to be effective drugs for hypercholesterolemia therapy, in solvent mixtures of dichloromethane and supercritical carbon dioxide was investigated to present a guideline of establishing operating conditions in the particle formation of the drugs by a supercritical anti-solvent recrystallization process utilizing dichloromethane as a solvent and carbon dioxide as an anti-solvent. The solubilities of simvastatin in the mixtures of dichloromethane and carbon dioxide were determined as functions of temperature, pressure and solvent composition by measuring the cloud points of the ternary mixtures at various conditions using a high-pressure phase equilibrium apparatus equipped with a variable-volume view cell. The solubility of the drug increased as the dichloromethane composition in solution and the system pressure increases at a fixed temperature. A lower solubility of the drug was obtained at a higher temperature. The second half of this work is focused on the particle formation of the simvastatin drug by a supercritical anti-solvent recrystallization process in a cylindrical high-pressure vessel equipped with an impeller. Microparticles of the simvastatin drug were prepared as functions of pressure (8 MPa to 12 MPa), temperature (303.15 K, 313,15 K), feed flow rate of carbon dioxide, and stirring speed (up to 3000 rpm), in order to observe the effect of those process parameters on the size and shape of the drug microparticles recrystallized.

• Journal of Nutrition and Health
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• v.47 no.4
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• pp.247-257
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• 2014

Purpose: It is reported that most senior people consume a high carbohydrate diet, while a high carbohydrate diet could contribute to the risk of chronic disease. The aim of this study is to determine whether a high carbohydrate diet can increase the risk of chronic disease in elderly Koreans. Methods: Using the 2007-2009 Korean National Health Nutrition Examination Survey data, out of a total of 3,917 individuals aged 65 and above, final 1,535 subjects were analyzed, divided by dietary carbohydrate energy ratio into two groups of moderate carbohydrate ratio (MCR, 55-70%) and excessive carbohydrate ratio (ECR, > 70%). All data were processed after the application of weighted value, using a general linear model or logistic regression. Results: Eighty one percent of elderly Koreans consumed diets with carbohydrate energy ratio above 70%. The ECR group included more female subjects, rural residents, lower income, and lower education level. The ECR group showed lower waist circumference, lower diastolic blood pressure, and lower frequency of consumption of meat and egg, milk, and alcohol. The intake of energy and most nutrients, with the exception of fiber, potassium, vitamin A, and carotene, was lower in the ECR group compared to the MCR group. When analyzed by gender, the ECR group showed lower risk of dyslipidemia in male and obesity in female subjects, even though the ECR group showed low intake of some nutrients. No difference in the risk of hypertension, diabetes, and anemia was observed between the two groups in male or female subjects. Conclusion: This result suggested that a high carbohydrate diet would not be a cause to increase the risk of chronic disease in the elderly. Further study is needed in order to determine an appropriate carbohydrate energy ratio for elderly Koreans to reduce the risk of chronic disease.

• Journal of Life Science
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• v.19 no.1
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• pp.15-20
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• 2009

Uncoupling protein 3 (UCP3) is a mitochondrial protein that is expressed predominantly in skeletal muscle. It may play a role in altering metabolic function. However, its major physiological roles are not fully understood. Recently de novo expression of UCP3 in rat liver by fenofibrate was reported. We also reported previously that fenofibrate-induced de novo expression of UCP3 contributes to reduction of adipose tissue in obese rats. In the present study, we investigated that ienofibrate-induced expression of UCP3 in rat liver is related with metabolic function such as body weight and hepatic lipid content by time-dependent manner in high-fat diet rats. Eight-week-old male Sprague-Dawley rats were randomly divided into two groups; the high fat diet group (HF, n=16) and fenofibrate-treated high fat diet group (HFF, n=16). The mRNA expression of hepatic UCP3 was detected as early as 1 week of fenofibrate treatment by quantitative real-time PCR and the amount of mRNA was increased time-dependently. The mean body weight of the HFF group was significantly less com. pared with the HF group after 6 weeks of fenofibrate treatment, even though there was no difference of food intake between the two groups. Rectal temperature was increased during 4 to 6 weeks of fenofibrate treatment and body weight was decreased after 6 weeks of treatment. These results were corresponded with the increased amount of the expression of UCP3 mRNA and protein. We suggest that de novo expression of hepatic UCP3 is increased time-dependently with fenofibrate treatment and that the amount of expression is correlated with metabolic function.

• Journal of the Korean Society of Radiology
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• v.13 no.1
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• pp.133-140
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• 2019

Triglycerides (TG) are one of the triggers of chronic inflammatory lesions in the blood vessels. In the key factors in the development of inflammatory diseases, Pro-inflammatory cytokines such as tumor necrosis factor-alpha $(TNF-){\alpha}$ and interleukin-1 beta ($IL-1{\beta}$) contribute to the development of inflammatory lesions by recruiting other immune cells in the inflamed area or causing cell necrotic death. In this study, I investigated the effect of Jurkat T lymphocytes and U937 monocytes involved in vascular inflammation development on the expression of $TNF-{\alpha}$ and $IL-1{\beta}$ on exposure to TGs. In Jurkat cells, mRNA expression of $TNF-{\alpha}$ is increased by exposure to TGs. However, the expression levels of $TNF-{\alpha}$ and $IL-1{\beta}$ were increased by TGs in U937 cells. To investigate whether inducible nitric oxide synthase (iNOS) is involved in the increase of expression of $TNF-{\alpha}$ and $IL-1{\beta}$ by TGs, treatment of W1400 (an iNOS inhibitor) resulted in recovery of expression level both $TNF-{\alpha}$ and $IL-1{\beta}$. Based on the present study, it was confirmed that the expression of $TNF-{\alpha}$ and $IL-1{\beta}$ in monocytes and T lymphocytes. This increased cytokines contribute to development of vascular inflammatory lesions. In addition, iNOS is involved in the increase of $TNF-{\alpha}$ and $IL-1{\beta}$ expression by TGs.

• Journal of Life Science
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• v.31 no.4
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• pp.418-424
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• 2021

Skin inflammation (dermatitis) is caused by varying skin damage due to ultraviolet radiation and microbial infection. Currently prescribed drugs for dermatitis include anti-histamine and steroid drug classes that soothe inflammation. However, incorrect or prolonged use of steroids can cause weakening of skin barriers as well as osteoporosis. Therefore, treating dermatitis with a drug that has minimal side effects is important. Statins, also known as 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are cholesterol-lowering drugs that have been widely treated for hyperlipidemia and cardiovascular diseases. Interestingly, recent studies have shown the anti-inflammatory effects of statins in both experimental and clinical models for of osteoarthritis. This study investigated the possible anti-inflammatory effects of atorvastatin and fluvastatin in human keratinocytes (HaCaT cells), which are crucial components of skin barriers. Stimulation of HaCaT cells with IL-1β increased the expression of the COX2 protein, a major player of inflammatory responses. However, this induction of the COX2 protein was downregulated by pretreatments with atorvastatin and fluvastatin. Treatment with IL-1ß-induced the upregulation of other inflammatory genes (such as iNOS and MMP-1) and these expressions were similarly lowered by these two statin drug treatments. Taken together, these results indicated that atorvastatin and fluvastatin can reduce IL-1β-induced inflammatory responses in HaCaT cells. In conclusion, the findings suggest that atorvastatin and fluvastatin can be potential modulators for ameliorating skin inflammation.

• Childhood Kidney Diseases
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• v.2 no.1
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• pp.77-81
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• 1998

The author exprienced a case of glycogen storage disease type Ia(GSD-I) in an 18-year-old male patient who was admitted to our hospital due to proteinuria and hypertension. he was suspected to have GSD when 12 years old because of his family history of short stature and hepatomegaly. On admission, physical examination revealed short stature, heparomegaly, and The diagnosis of GSD-I was confirmed by compatible liver biopsy finding and enzyme assay which erealeddeficiency of glcose-6-phosphatase if hepatocyte. Sympromatic treatment was done using antihypertensive drugs and allopurinol with diet control. The authors report a case of glycogen storage disease type Ia completely confirmed by typical clinical manifestation, pathologic findings of the liver and the kidney, and the result of enzyme assay which revealed deficiency of glucose-6-phosphatase in hepatocytes with brief review fo related literatures.

• Microbiology and Biotechnology Letters
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• v.37 no.2
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• pp.118-124
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• 2009

Esterase EM2L8 gene isolated from deep sea sediment was expressed in Escherichia coli BL21 (DE3) and the esterase activity of the cell-free extract was assayed using p-nitrophenyl butyrate-spectrophotometric method. Its optimum temperature was $40-45^{\circ}C$ and 45% activity of the maximum activity was retained at $15^{\circ}C$. The activation energy at $15-45^{\circ}C$ was calculated to be 4.9 kcal/mol showing that esterase EM2L8 was a typical cold-adapted enzyme. Enzyme activity was maintained for 6 h and 4 weeks at $30^{\circ}C$ and $4^{\circ}C$, respectively. When each ethanol, methanol, and acetone was added to the reaction mixture to 15% concentration, enzyme activity was maintained. In the case of DMSO, enzyme activity was kept up to 40% concentration. (S)-4-Chloro-3-hydroxy butyric acid is a chiral intermediate for the synthesis of Atorvastatin, a hyperlipemia drug. When esterase EM2L8 (40 U) was added to buffer solution (1.2 mL, pH 9.0) containing ethyl-(R,S)-4-chloro-3-hydroxybutyrate (38 mM), it was hydrolyzed into 4-chloro-3-hydroxy butyric acid with a rate of $6.8\;{\mu}mole/h$. The enzyme hydrolyzed (S)-substrate more rapidly than (R)-substrate. When conversion yield was 80%, e.e.s value was 40%. When DMSO was added, hydrolysis rate increased to $10.4\;{\mu}mole/h$. The plots of conversion yield vs e.e.s in the presence or absence of DMSO were almost same, implying that the reaction enantioselectivity was not changed by the addition of DMSO. Taken together, esterase EM2L8 had high activity and stability at low temperatures as well as in various organic solvents/aqueous solutions. These properties suggested that it could be used as a biocatalyst in the synthesis of useful pharmaceuticals.

• KSBB Journal
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• v.22 no.5
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• pp.297-304
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• 2007

For large and rapid screening of high-yielding mutants of lovastatin produced by filamentous fungal cells of Aspergillus terreus, one of the most important stage is to test as large amounts of mutated strains as possible. For this purpose, we intended to develop a miniaturized cultivation method using $7m{\ell}$ culture tube instead of traditional $250m{\ell}$ flask (working volume $50m{\ell}$). For obtaining large amounts of conidiospores to be used as inoculums for miniaturized cultures, 4 components i.e., glucose, sucrose, yeast extract and $KH_2PO_4$ were intensively investigated, which had been observed to show positive effect on enhancement of spore production through Plackett-Burman design experimet. When optimum concentrations of these components that were determined through application of response surface method (RSM) based on central composite design (CCD) were used, maximum spore numbers amounting to $1.9\times10^{10}$ spores/plate were obtained, resulting in approximately 190 fold increase as compared to the commonly used PDA sporulation medium. Using the miniaturized cultures, intensive strain development programs were carried out for screening of lovastatin high-yielding as well as highly reproducible mutants. It was observed that, for maximum production of lovastatin, the producers should be activated through 'PaB' adaptation process during the early solid culture stage. In addition, they should be proliferated in condensed filamentous forms in miniaturized growth cultures, so that optimum amounts of highly active cells could be transferred to the production culture-tube as reproducible inoculums. Under these highly controlled fermentation conditions, compact-pelleted morphology of optimum size (less than 1 mm in diameter) was successfully induced in the miniaturized production cultures, which proved essential for maximal utilization of the producers' physiology leading to significantly enhanced production of lovastatin. As a result of continuous screening in the miniaturized cultures, lovastatin production levels of the 81% of the daughter cells derived from the high-yielding producers turned out to be in the range of 80%$\sim$120% of the lovastatin production level of the parallel flask cultures. These results demonstrate that the miniaturized cultivation method developed in this study is efficient high throughput system for large and rapid screening of highly stable and productive strains.

• Journal of Life Science
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• v.29 no.3
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• pp.332-336
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• 2019

Obesity is associated with an increased risk of many diseases including type 2 diabetes mellitus, hypertension, and hyperlipidemia. The flowers of Chrysanthemum boreale have been used as traditional medicines for the treatment of diseases such as obesity and type 2 diabetes mellitus. This study aimed to evaluate the effect of C. boreale Makino flower essential oil (CFEO) on adipocyte differentiation using preadipocyte cell line 3T3-L1. CFEO at concentrations between 0.1 and $5{\mu}g/ml$ did not affect 3T3-L1 cell viability. A CFEO concentration of between 0.1 and $1{\mu}g/ml$ significantly inhibited lipid accumulation during MDI-induced differentiation in 3T3-L1 cells in a dose-dependent manner, reaching a maximal level at $1{\mu}g/ml$ ($28.94{\pm}2.01%$; approximately 30% of control treated with MDI alone). Western blot analysis revealed that CFEO concentrations between 0.1 and $1{\mu}g/ml$ suppressed the activations of three adipogenic transcription factors in the MDI-stimulated 3T3-L1 cells: peroxisome proliferator-activated receptor ${\gamma}$; CCATT/enhancer binding protein ${\alpha}$; and sterol regulatory element binding protein-1. Moreover, the expressions of lipogenic enzymes, acetyl-CoA carboxylase, and fatty acid synthase were also inhibited by treatment with CFEO between 0.1 and $1{\mu}g/ml$. CFEO may therefore be a promising functional material for obesity prevention.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.11
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• pp.1278-1285
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• 2017

Accumulation of excess low density lipoprotein (LDL) cholesterol in the blood can initiate and accelerate atherosclerosis. Statins mediate the transactivation of proprotein convertase subtilisin/kexin type 9 (PCSK9), which in turn limits their cholesterol-lowering effects via LDL receptor (LDLR) degradation. The objective of this study was to investigate whether or not Allium tuberosum (AT) regulates LDLR and PCSK9. Mice were fed a low fat control diet (LD) or Western diet (WD) supplemented with AT (1%, w/w). AT significantly attenuated total and LDL cholesterol levels in mice fed WD (P<0.05). AT also significantly inhibited hepatic PCSK9 gene expression (P<0.05) while AT maintained hepatic LDLR gene expression. To further investigate AT-mediated PCSK9 regulation, HepG2 cells were treated with 10% delipidated serum (DLPS) in the presence or absence of AT. Non-toxic level of AT dose-dependently increased the LDLR protein level, and AT at $400{\mu}g/mL$ markedly inhibited PCSK9 protein expression. Similarly, AT significantly increased LDLR gene expression, whereas it significantly down-regulated PCSK9 gene expression. AT-mediated reduction of PCSK9 gene expression is likely due to decreased hepatic nuclear factor $1{\alpha}$ ($HNF1{\alpha}$) expression, but not SREBP2 in HepG2 cells under lipid-depleted conditions. AT-mediated PCSK9 inhibition contributed to LDLR protein stabilization via protection against LDLR lysosomal degradation in HepG2 cells under lipid-depleted conditions. Further investigation is warranted to determine the active components of AT and whether or not these components are effective in reducing hypercholesterolemia.