• Journal of health informatics and statistics
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• v.41 no.1
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• pp.49-56
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• 2016

Objectives: Carotid intima-media thickness (CIMT) and the presence of carotid artery plaque are widely used as preclinical markers of atherosclerosis. Due to operator dependency in measuring CIMT, it is important to evaluate the reliability of measuring CIMT and plaque between centers in a multicenter study. The purpose of this study is to evaluate the inter-rater reliability of CIMT and plaque presence among three clinical centers of the Cardiovascular and Metabolic Disease Etiology Research Center (CMERC). Methods: Twenty people without known cardiovascular disease (age 37-64) were enrolled during 2014-2015, and their left and right carotid arteries were examined repeatedly with ultrasonography for CIMT measurements at three clinical centers according to a predetermined protocol. Maximum and mean values of CIMT at distal common carotid artery were recorded. Plaque presence at a carotid artery was checked by an operator. The reliability of CIMT and carotid plaque presence was assessed using an intraclass correlation coefficient (ICC) and kappa statistics, respectively. Results: Calculated ICC was 0.647 (95% CI: 0.487-0.779) for maximum CIMT, and 0.758 (95% CI: 0.632- 0.854) for mean CIMT. In Bland Altman plot, most observed values were distributed within mean difference ${\pm}1.96$ SD ranges. Kappa statistics of plaque presence between two centers were 0.304 (center 1 and 2), 0.507 (center 1 and 3), and 0.606 (center 2 and 3), respectively, while Fleiss kappa for overall agreement was 0.445. Conclusions: The inter-rater reliability of CIMT measurements among three clinical centers turned out to be high, and the agreement of measuring carotid plaque presence was fair.

• Journal of Ginseng Research
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• v.29 no.1
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• pp.1-18
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• 2005

Ginseng Radix, the root of Panax ginseng C. A. Meyer has been used in Eastern Asia for 2000 years as a tonic and restorative, promoting health and longevity. Two varieties are commercially available: white ginseng(Ginseng Radix Alba) is produced by air-drying the root, while red ginseng(Ginseng Radix Rubra) is produced by steaming the root followed by drying. These two varieties of different processing have somewhat differences by heat processing between them. During the heat processing for preparing red ginseng, it has been found to exhibit inactivation of catabolic enzymes, thereby preventing deterioration of ginseng quality and the increased antioxidant-like substances which inhibit lipid peroxide formation, and also good gastro-intestinal absorption by gelatinization of starch. Moreover, studies of changes in ginsenosides composition due to different processing of ginseng roots have been undertaken. The results obtained showed that red ginseng differ from white ginseng due to the lack of acidic malonyl-ginsenosides. The heating procedure in red ginseng was proved to degrade the thermally unstable malonyl-ginsenoside into corresponding netural ginsenosides. Also the steaming process of red ginseng causes degradation or transformation of neutral ginsenosides. Ginsenosides $Rh_2,\;Rh_4,\;Rs_3,\;Rs_4\;and\;Rg_5$, found only in red ginseng, have been known to be hydrolyzed products derived from original saponin by heat processing, responsible for inhibitory effects on the growth of cancer cells through the induction of apoptosis. 20(S)-ginsenoside $Rg_3$ was also formed in red ginseng and was shown to exhibit vasorelaxation properties, antimetastatic activities, and anti-platelet aggregation activity. Recently, steamed red ginseng at high temperature was shown to provide enhance the yield of ginsenosides $Rg_3\;and\;Rg_5$ characteristic of red ginseng Additionally, one of non-saponin constituents, panaxytriol, was found to be structually transformed from polyacetylenic alcohol(panaxydol) showing cytotoxicity during the preparation of red ginseng and also maltol, antioxidant maillard product, from maltose and arginyl-fructosyl-glucose, amino acid derivative, from arginine and maltose. In regard to the in vitro and in vivo comparative biological activities, red ginseng was reported to show more potent activities on the antioxidant effect, anticarcinogenic effect and ameliorative effect on blood circulation than those of white ginseng. In oriental medicine, the ability of red ginseng to supplement the vacancy(허) was known to be relatively stronger than that of white ginseng, but very few are known on its comparative clinical studies. Further investigation on the preclinical and clinical experiments are needed to show the differences of indications and efficacies between red and white ginsengs on the basis of oriental medicines.

• Journal of Life Science
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• v.29 no.6
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• pp.653-661
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• 2019

The first small interfering RNA (siRNA) therapeutics have recently been approved by the Food and Drug Administration in the U.S., and the demand for a new RNA therapeutics bioanalysis method-which is essential for pharmacokinetics, including the absorption, distribution, metabolism, and excretion of siRNA therapeutics-is rapidly increasing. The stem-loop real-time qPCR (RT-qPCR) assay is a useful molecular technique for the identification and quantification of small RNA (e.g., micro RNA and siRNA) and can be applied for the bioanalysis of siRNA therapeutics. When the anti-HPV E6/E7 siRNA therapeutic was used in preclinical trials, the established stem-loop RT-qPCR assay was validated. The limit of detection was sensitive up to 10 fM and the lower limit of quantification up to 100 fM. In fact, the reliability of the established test method was further validated in three intra assays. Here, the correlation coefficient of $R^2$>0.99, the slope of -3.10 ~ -3.40, and the recovery rate within ${\pm}20%$ of the siRNA standard curve confirm its excellent robustness. Finally, the circulation profiles of siRNAs were demonstrated in rat serum, and the pharmacokinetic properties of the anti-HPV E6/E7 siRNA therapeutic were characterized using a stem-loop RT-qPCR assay. Therefore, the stemloop RT-qPCR assay enables accurate, precise, and sensitive siRNA duplex quantification and is suitable for the quantification of small RNA therapeutics using small volumes of biological samples.

• Journal of Life Science
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• v.31 no.11
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• pp.1028-1036
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• 2021

Firefly luciferase (FLuc) can function as an efficient marker in the gene and viral therapies. Nonetheless, its clinical translation has been unaccomplished with the concerns on its exogenous nature and the similarity with human fatty acyl-CoA synthetase. In this study, we aimed to show safety of FLuc by conducting a set of preclinical experiments and a human use. Initially, FLuc permeability across the plasma membrane was investigated by delivering the FLuc-carrying viral vector, OTS-412, or the FLuc recombinant protein. After in vitro infection of OTS-412 into different cancer cell lines, FLuc activity was detected only in the cell lysates, but not in culture media. In addition, recombinant FLuc protein further showed the impermeability against the plasma membrane. Similar result was also observed in the in vivo experiment. After being injected into the VX2 tumor-bearing rabbit, the FLuc exclusively resided within the tumor tissue without being detected in the blood plasma or other organs. Human cancer cell lines originated from various organs were lysed and treated to the FLuc, and none of the human substrates was reactive against the FLuc. As a final step, FLuc recombinant protein was intravenously injected into a human. The luciferase was degraded with the half-life of 20 to 30 minutes in blood, and was untraceable from 1.5 hr after the injection. In addition, the blood plasma was nonresponsive against the fatty acids. Hematological analysis was also comparable between the pre- and post-injection. Altogether, our study collectively demonstrates the safety of the firefly luciferase.

• Journal of Food Hygiene and Safety
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• v.38 no.2
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• pp.69-78
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• 2023

This study aimed to investigate the protective effect of enzymatically modified stevia (EMS) on C2C12 cell-based model of dexamethasone (DEX)-induced muscle atrophy to provide baseline data for utilizing EMS in functional health products. C2C12 cells with DEX-induced muscle atrophy were treated with EMS (10, 50, and 100 ㎍/mL) for 24 h. C2C12 cells were treated with EMS and DEX to test their effects on cell viability and myotube formation (myotube diameter and fusion index), and analyze the expression of muscle strengthening or degrading protein markers. Schisandra chinensis Extract, a common functional ingredient, was used as a positive control. EMS did not show any cytotoxic effect at all treatment concentrations. Moreover, it exerted protective effects on C2C12 cell-based model of DEX-induced muscle atrophy at all concentrations. In addition, the positive effect of EMS on myotube formation was confirmed based on the measurement and comparison of the fusion index and myotube diameter when compared with myotubes treated with DEX alone. EMS treatment reduced the expression of muscle cell degradation-related proteins Fbx32 and MuRF1, and increased the expression of muscle strengthening and synthesis related proteins SIRT1 and pAkt/Akt. Thus, EMS is a potential ingredient for developing functional health foods and should be further evaluated in preclinical models.

• Journal of the Korean Society of Radiology
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• v.81 no.4
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• pp.899-911
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• 2020

Purpose To evaluate the safety and efficacy of the newly designed open-cell type self-expandable nitinol stent (NiTi-stent) for peripheral arteries. Materials and Methods Twenty-eight limbs of 14 minipigs were randomly assigned to the NiTistent group or conventional nitinol stent group. Stents were symmetrically implanted into the iliac arteries of each animal using carotid artery approach and were observed for 1 month (n = 5) and 6 months (n = 9). The angiographic lumen diameter (ALD), late lumen loss, angiographic stenosis, histomorphometric lumen area, neointimal area, and area stenosis were analyzed and compared between the groups. Results Stent migration, stent fracture, or thrombus formation were not observed in either group. At the 1-month follow-up, the neointimal area (p = 0.008) and area stenosis (p = 0.016) were significantly smaller in the NiTi-stent group than in the control group. At the 6-months followup, the NiTi-stent group showed significantly larger ALD (p = 0.014), less late lumen loss (p = 0.019), less angiographic stenosis (p = 0.014), larger lumen area (p = 0.040), and smaller neointimal area and area stenosis (p = 0.004 and p = 0.014, respectively) compared with the control group. Conclusion The NiTi-stent is as safe and effective as the conventional nitinol stent and induces less neointimal hyperplasia in a minipig iliac artery model.