• Journal of Life Science
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• v.31 no.6
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• pp.550-558
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• 2021

Fructus Corni, the fruit of Cornus officinalis, has long been used for the prevention and treatment of various diseases. We recently suggested that it was effective against benign prostatic hyperplasia (BPH). In this study, we investigated the inhibitory effect of Corni Fructus (CF) water extract on BPH induced by testosterone propionate (TP) in noncastrated and castrated animal models. BPH was induced in Sprague Dawley rats by an intramuscular injection of TP in castrated or noncastrated rats. Finasteride (FINA) treatment was used as a positive control for inhibition of BPH. According to our results, CF administration inhibited excessive enlargement of development of the prostate in both the noncastrated and castrated groups compared to the control and FINA-treated groups. The inhibitory effect of CF on BPH was associated with inhibition of expression of hypoxia-inducible factor-1α, 5α-reductase type 2, steroid receptor coactivator-1, androgen receptor (AR), and prostate-specific antigen. Serum levels of the stress hormone cortisol increased during BPH induction by TP in both the noncastrated and castrated groups, but they were attenuated significantly by CF administration. However, insulin and IGF-1 levels were not increased in the BPH-induced groups and CF, and no effective results were found by CF administration. These results point to a beneficial effect of CF on BPH through inhibition of AR signaling pathway activity and imply that CF shows excellent potential as a therapeutic agent for the prevention and treatment of BPH.

• Journal of Life Science
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• v.34 no.7
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• pp.476-484
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• 2024

Although two-dimensional (2D) monolayer cell culture models are still widely used as the optimal models for anticancer activity research, three-dimensional (3D) multicellular tumor spheroid (3D MTS) models that can better approximate the tumor environment can offer an alternative to bridge the gap between in vitro and animal model studies. Isoalantolactone is among the sesquiterpene lactones found in medicinal plants, including the roots of Elecampane (Inula helenium L.), and is known to have various pharmacological activities, including anticancer activity. In this study, we investigated whether the anticancer activity of isoalantolactone observed in 2D models could be reproduced in a 3D MTS model derived from human hepatocellular carcinoma (HCC) Hep3B cells. According to our results, isoalantolactone inhibited the formation of MTSs in a manner dependent on the treatment concentration, which was accompanied by an increase in reactive oxygen species (ROS) generation. In particular, as isoalantolactone treatment and the culture time increased, the area of proliferating cells was replaced by cells in which apoptosis was induced. Additionally, in MTSs, isoalantolactone increased the expression of death-receptor-related proteins and the activity of caspase-3, and it decreased the expression of the Bax/Bcl-2 expression ratio and total poly(ADP-ribose) polymerase. However, when the production of ROS was artificially blocked, all these changes caused by isoalantolactone were attenuated and the cell survival rate of MTS cells was restored. Therefore, the results of this study suggest that the induction of apoptosis in Hep3B cell-derived MTSs by isoalantolactone is achieved through the activation of extrinsic and intrinsic pathways and is ROS-dependent.

• Journal of Radiation Protection and Research
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• v.33 no.1
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• pp.27-34
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• 2008

A Korean urban contamination model METRO-K (${\underline{M}}odel$ for ${\underline{E}}stimates$ the ${\underline{T}}ransient$ Behavior of ${\underline{R}}adi{\underline{O}}active$ Materials in the ${\underline{K}}orean$ Urban Environment, which is capable of calculating the exposure doses resulting from radioactive contamination in an urban environment, is taking part in a model testing program EMRAS (${\underline{E}}nvironmental$ ${\underline{M}}odelling$ for ${\underline{RA}}diation$ ${\underline{S}}afety$) oragnized by the IAEA (${\underline{I}}nternational$ ${\underline{A}}tomic$ ${\underline{E}}nergy$ ${\underline{A}}gency$). For radioactive contamination scenarios of Pripyat districts and a hypothetical RDD (${\underline{R}}adiological$ ${\underline{D}}ispersal$ ${\underline{D}}evice$), the predicted results using METRO-K were submitted to the EMRAS's Urban Contamination Working Group. In this paper, the predicted results for the contamination scenarios of a Pripyat district were shown in case of both without remediation measures and with ones. Comparing with the predictied results of the models that have taken part in EMRAS program, a feasibility for decision-making support of METRO-K was investigated. As a predicted result of METRO-K, to take immediately remediation measures following a radioactive contamination, if possible, might be one of the best ways to reduce exposure dose. It was found that the discrepancies of predicted results among the models are resulted from 1) modeling approaches and applied parameter values, 2) exposure pathways which are considered in models, 3) assumptions of assessor such as contamination surfaces which might affect to an exposure receptor and their sizes, 4) parameter values which are related with remediation measures applied through literature survey. It was indentified that a Korean urban contamination model METRO-K is a useful tool for dicision-making support through the participation of EMRAS program.

• Journal of Veterinary Clinics
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• v.31 no.5
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• pp.394-402
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• 2014

The objective of this study was to investigate the effect of chronic unpredictable stress on the reproductive function and ovarian luteinizing hormone receptor (LHR) expression. 9-week-old C57BL/6 female mice were randomly divided into two groups: control group and stressed group. Mice have been stressed twice a day for 35 days with 12 different stressors which were randomly selected. The results demonstrate that there is significant increase in the anxiety-related behaviors (P < 0.05), decrease body weight gain rate (P < 0.01) and decrease in the average of litter size in stressed mice compared with control group (P < 0.01). Furthermore, the rate of primary, secondary and early antral follicles in stressed mice significantly decreased (P < 0.05), whereas that of atretic follicles significantly increased compared with control mice (P < 0.01). The immunohistochemical analysis revealed that reduced LHR expression in granulosa cells of follicle and luteal cells of corpus luteum in response to chronic unpredictable stress. The western blot analysis revealed significantly decrease in LHR expression in the stressed mice ovaries compared with the control (P < 0.05). These results suggest that ovarian LHR expression affected by chronic unpredictable stress and the modulated ovarian LHR is responsible for ovarian follicular maldevelopment and reproductive dysfunction.

• Neonatal Medicine
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• v.16 no.2
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• pp.221-233
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• 2009

Purpose: Erythropoietin (EPO) has neuroprotective effects in many animal models of brain injury, including hypoxic-ischemic (HI) encephalopathy, trauma, and excitotoxicity. Current studies have demonstrated the neuroprotective effects of EPO, but limited data are available for the neonatal periods. Here in we investigated whether recombinant human EPO (rHuEPO) can protect the developing rat brain from HI injury via modulation of NMDA receptors. Methods: In an in vitro model, embryonic cortical neuronal cell cultures from Sprague-Dawley (SD) rats at 19-days gestation were established. The cultured cells were divided into five groups: normoxia (N), hypoxia (H), and 1, 10, and 100 IU/mL rHuEPO-treated (H+E1, H+ E10, and H+E100) groups. To estimate cell viability and growth, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was done. In an in vivo model, left carotid artery ligation was performed on 7-day-old SD rat pups. The animals were divided into six groups; normoxia control (NC), normoxia Sham-operated (NS), hypoxia-ischemia only (H), hypoxia-ischemia+vehicle (HV), hypoxia-ischemia+rHuEPO before a HI injury (HE-B), and hypoxia-ischemia+rHuEPO after a HI injury (HE-A). The morphologic changes following brain injuries were noted using hematoxylin and eosin (H/E) staining. Real-time PCR using primers of subunits of NMDA receptors (NR1, NR2A, NR2B, NR2C and NR2D) mRNA were performed. Results: Cell viability in the H group was decreased to less than 60% of that in the N group. In the H+E1 and H+E10 groups, cell viability was increased to >80% of the N group, but cell viability in the H+E100 group did not recover. The percentage of the left hemisphere area compared the to the right hemisphere area were 98.9% in the NC group, 99.1% in the NS group, 57.1% in the H group, 57.0% in the HV group, 87.6% in the HE-B group, and 91.6% in the HE-A group. Real-time PCR analysis of the expressions of subunits of NMDA receptors mRNAs in the in vitro and in vivo neonatal HI brain injuries generally revealed that the expression in the H group was decreased compared to the N group and the expressions in the rHuEPO-treated groups was increased compared to the H group. Conclusion: rHuEPO has neuroprotective property in perinatal HI brain injury via modulation of N-methyl-D-aspartate receptors.

• Journal of Korean Society for Atmospheric Environment
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• v.31 no.3
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• pp.223-238
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• 2015

The $PM_{2.1}$ was collected by LVCI (low volume cascade impactor) during Group-A Period (September 1990 to December 2012) and the $PM_{2.5}$ was collected by HVAS (high volume air sampler) during Group-B Period (September 2009 to April 2012) at Kyung Hee University, Global Campus located on the boarder of Yongin and Suwon. The 8 water-soluble ions ($Na^+$, $NH_4{^+}$, $K^+$, $Mg^{2+}$, $Ca^{2+}$, $Cl^-$, $ NO_3{^-}$, and $SO_4{^{2-}}$) were analyzed by IC, and the 14 inorganic elements (Al, Mn, Si, Fe, Cu, Pb, Cr, Ni, V, Cd, Ba, Zn, Ti, Ag) were analyzed by XRF and ICP-AES after performing proper pre-treatments of each sample filter. The average total mass fractions of $SO_4{^{2-}}$, $NO_3{^-}$, and $NH_4{^+}$+ to $PM_{2.5}$ samples during Group-B Period were 0.39 in normal days, 0.44 in haze days, and 0.27 in Asian dust days, respectively; however, the average total mass fractions of Al, Fe, and Si to $PM_{2.5}$ mass were 0.043 in normal days, 0.021 in haze days, and 0.036 in Asian dust days, respectively. Especially the concentration of Pb was significantly decreased during Group-B Period rather than during Group-A Period, while Cr and Ni was increased during Group-B Period. In this study, we intensively compared the annual and seasonal patterns of major chemical species among normal days, haze days, and Asian dust days. Further we developed mass fraction profiles by collecting episode cases of haze days and Asian dust days, which were consisting of 22 chemical species. Those profiles are considered to be useful when applying various receptor models and establishing air quality management plans near future.

• IMMUNE NETWORK
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• v.11 no.5
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• pp.258-267
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• 2011

Background: Current management strategies attempt to diagnose rheumatoid arthritis (RA) at an early stage. Transcription profiling is applied in the search for biomarkers for detecting early-stage disease. Even though gene profiling has been reported using several animal models of RA, most studies were performed after the development of active arthritis, and conducted only on the peripheral blood and joint. Therefore, we investigated gene expression during the initial phase of collagen-induced arthritis (CIA) before the arthritic features developed in the thymus in addition to the peripheral blood and synovium. Methods: For gene expression analysis using cDNA microarray technology, samples of thymus, blood, and synovium were collected from CIA, rats immunized only with type II collagen (Cll), rats immunized only with adjuvant, and unimmunized rats on days 4 and 9 after the first immunization. Arrays were scanned with an Illumina bead array. Results: Of the 21,910 genes in the array, 1,243 genes were differentially expressed at least 2-fold change in various organs of CIA compared to controls. Among the 1,243 genes, 8 encode T-cell receptors (TCRs), including CD3${\zeta}$, CD3${\delta}$, CD3${\varepsilon}$, CD8${\alpha}$, and CD8${\beta}$ genes, which were down-regulated in CIA. The synovium was the organ in which the genes were differentially expressed between CIA and control group, and no difference were found in the thymus and blood. Further, we determined that the differential expression was affected by adjuvant more than Cll. The differential expression of genes as revealed by real-time RT-PCR, was in agreement with the microarray data. Conclusion: This study provides evidence that the genes encoding TCRs including CD3${\zeta}$, CD3${\delta}$, CD3${\varepsilon}$, CD8${\alpha}$, and CD8${\beta}$ genes were down-regulated during the initial phase of CIA in the synovium of CIA. In addition, adjuvant played a greater role in the down-regulation of the CD3 complex compared to CII. Therefore, the down-regulation of TCR gene expression occurred dominantly by adjuvant could be involved in the pathogenesis of the early stage at CIA.

• The Journal of Internal Korean Medicine
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• v.30 no.2
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• pp.257-269
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• 2009

Objective : Obesity is an important cause of diabetes, and lipotoxicity causes insulin resistance. Recently a lot of research is being done on PPAR-${\alpha}$. TNF-${\alpha}$. adiponectin, and leptin, which are important obesity related factors. In this study, we investigated the effects of Supungsunki-hwan on high fat. high carbohydrate diet-induced obese type 2 diabetic mouse models. Methods: Diabetes was induced in ICR male mouse (30${\pm}$5g) with Surwit's high fat, high sucrose diet. Mice were divided into 4 groups(n=10) of Normal. Control. Supungsunkj-hwan group. and acarbose group. The Supungsunki-hwsn group was given 10% Supungsunkj-hwan in their diet. and the acarbose group was given 0.5% acarbose in their diet. After 6 weeks. body weight. food intake, FBS and OGTT. lipid profile and liver enzymes, epididymal fat weight, and gene expression of leptin, adiponectin, TNF-${\alpha}$ and PPAR-${\alpha}$ were measured. Leptin. adiponectin. tumor necrosis factor(TNF)-${\alpha}$ and peroxisome proliferator-activated receptor (PPAR)-${\alpha}$ were evaluated by reverse transcription-polymerase chain reaction. Results : Supungsunkj-hwan increased the gene expression of PPAR-${\alpha}$, which reduces lipotoxicity and insulin resistance. Supungsunkj-hwan also significantly reduced triglyceride. AST. ALT serum levels. and 1 hour oral glucose tolerance levels. Conclusion : These results show that Supungsunkj-hwan improves insulin resistance in the liver and muscles, by reducing triglyceride levels and lipotoxicity through increased PPAR-${\alpha}$ gene expression. This is supported by the fact that Supungsunkj-hwan significantly reduces 1 hour oral glucose tolerance levels. Therefore we suggest that Supungsunkj-hwan would be an effective treatment for obese type 2 diabetic patients.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.11
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• pp.1691-1694
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• 2010

In the present study, we assessed whether the extracts of Codonopsis lanceolata and fermented C. lanceolata posses the cognition-enhancing effect in rats with impaired learning and memory by scopolamine treatment (1 mg/kg, i.p.), an antagonist of muscarinic acetylcholine (ACh) receptor. The fermented C. lanceolata extract (333, 667 mg/kg) significantly reversed the scopolamine-induced cognitive impairments in the passive avoidance test (p<0.05). Moreover, fermented C. lanceolata extract (333 mg/kg) also improved escape latencies in training trials of Morris water maze test (p<0.05). The water extract of fermented C. lanceolata showed significant anti-amnestic and cognitive-enhancing activities related to the memory processes, and these activities were parallel to treatment duration and dependent of the learning models.

• Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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• v.7 no.1
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• pp.39-47
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• 2009

The METRO-K is a model for a radiological dose assessment due to a radioactive contamination in the Korean urban environment. The model has been taken part in the Urban Remediation Working Group within the IAEA's (International Atomic Energy Agency) EMRAS (${\mathbf{\underline{E}}}nvironmental$ ${\mathbf{\underline{M}}}odeling$ for ${\mathbf{\underline{RA}}}diation$ ${\mathbf{\underline{S}}}afety$) program. The Working Croup designed for the intercomparison of radioactive contamination to be resulted from the explosion of a radiological dispersal device in a hypothetical city. This paper dealt intensively with a part among a lot of predictive results which had been performed in the EMRAS program. The predictive results of three different models (METRO-K, RESRAD-RDD, CPHR) were submitted to the Working Group. The gap of predictive results was due to the difference of mathemathical modeling approaches, parameter values, understanding of assessors. Even if final results (for example, dose rates from contamintaed surfaces which might affect to a receptor) are similar, the understanding on the contribution of contaminated surfaces showed a great difference. Judging from the authors, it is due to the lack of understanding and information on radioactive terrors as well as the social and cultural gaps which assessors have been experienced. Therefore, it can be known that the experience of assessors and their subjective judgements might be important factors to get reliable results. If the acquisition of a little additional information is possible, it was identified that the METRO-K might be a useful tool for decision support against contamination resulting from radioactive terrors by improving the existing model.