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Effects of Flavonoids and Their Glycosides on Oxidative Stress in C6 Glial Cells (Flavonoids 및 그 배당체의 산화적 스트레스에 대한 신경교세포 보호 효과)

  • Kim, Ji Hyun;Kim, Hyun Young;Cho, Eun Ju
    • Journal of Life Science
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    • v.29 no.12
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    • pp.1371-1377
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    • 2019
  • Oxidative stress induced by the over-production of reactive oxygen species (ROS) in the brain is the most common cause of neurodegenerative diseases such as Alzheimer's. In the present study, we investigated the protective effects of flavonoids and their glycosides, namely kaempferol, kaempferol-3-O-glucoside, quercetin, and quercetin-3-β-D-glucoside, against H2O2-induced oxidative stress in the C6 glial cells. The H2O2-treated glial cells exhibited decreased cell viability and increased ROS production when compared with normal cells. However, cells treated with each of the four flavonoids/glycosides demonstrated significantly increased viability and suppressed ROS production when compared with the H2O2-treated control group. These results indicate that flavonoids/glycosides attenuate oxidative stress induced by H2O2 in C6 glial cells. To confirm the protective molecular mechanisms, we measured pro-inflammatory factors such as inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-1β. H2O2 treatment was seen to elevate these factors and decrease IκB-α in the C6 glial cells, while the flavonoids/glycosides induced a down-regulation of the pro-inflammatory factors and increased IκB-α, indicating a neuroprotective effects through attenuation of the inflammation. In particular, quercetin and its glycoside showed a higher neuroprotective effect than the kaempferol treatments. These results suggest that these flavonoids and their glycosides could be promising therapeutic agents for neurodegenerative diseases via the attenuation of oxidative stress.

Immunomodulatory Effects of β-sitosterol and Daucosterol Isolated from Dioscorea batatas on LPS-stimulated RAW 264.7 and TK-1 Cells (산약에서 분리한 β-sitosterol과 daucosterol의 RAW 264.7 세포와 TK-1 세포에서의 면역 활성 조절 효능)

  • Park, Min-Kyung;Cho, Sehee;Ahn, Tae-Kyu;Kim, Do-Hyun;Kim, So-Yeon;Lee, Jin-Wook;Kim, Jee-In;Seo, Eul-Won;Son, Kun-Ho;Lim, Jae-Hwan
    • Journal of Life Science
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    • v.30 no.4
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    • pp.359-369
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    • 2020
  • Although many studies on immune modulatory materials have used RAW 264.7 cells, few have used T cell-derived TK-1 cell lines. Moreover, although some studies have investigated the efficacy of plant-derived β-sitosterol, few have examined the immunomodulatory activity of its analogue, daucosterol. In this study, β-sitosterol and daucosterol were isolated from D. batatas and identified by nuclear magnetic resonance spectroscopy. To evaluate the immune-enhancing or inhibitory effects of the isolated phytosterols, the expression levels of the inflammatory response genes COX-2, TNF-α, IL-6, and iNOS were analyzed by RT-PCR. The relative expression levels of TNF-α and iNOS in RAW 264.7 cells were increased more than threefold with β-sitosterol treatment comparing to those of untreated control. In the case of TK-1 cells, the expression level of TNF-α was decreased and the expression level of iNOS was increased in a β-sitosterol concentration-dependent manner. The expression levels of COX-2, TNF-α, and IL-6 increased by approximately 0.7-1.2 times in RAW 264.7 cells treated with daucosterol compared to those of untreated control, but iNOS expression decreased by 0.8-0.18 times. In the case of daucosterol-treated TK-1 cells, the expression levels of TNF-α, IL-6, and iNOS were markedly reduced from those of TK-1 cells treated only with lipopolysaccaride. As a conclusion, β-sitosterol treatment increased TNF-α and iNOS expression levels in RAW 264.7 cells, thus exerting an immune- boosting effect. However, in TK-1 cells, iNOS expression increased while TNF-α expression decreased, indicating an immunosuppressive activity of β-sitosterol. Daucosterol appears to exert an immunosuppressive effect in both macrophages and T cell lines by inhibiting iNOS expression in RAW 264.7 cells and greatly inhibiting the expression of TNF-α, IL-6, and iNOS in TK-1 cells.

Characterization of a Mucolipidosis Type II Mouse Model and Therapeutic Implication of Lysosomal Enzyme Enriched Fraction Derived from Placenta (뮤코지방증 2형 마우스 모델의 특징과 태반에서 추출한 리소좀 효소 투여의 결과)

  • Cho, Sung Yoon;Kim, Ki-Yong;Kim, Su Jin;Sohn, Young Bae;Maeng, Se Hyun;Kim, Chi Hwa;Ko, Ah-Ra;Song, Junghan;Yeau, Sung-Hee;Kim, Kyung-Hyo;Jin, Dong-Kyu
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.12 no.1
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    • pp.5-13
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    • 2012
  • I-cell disease (mucolipidosis type II; MIM 252500) and pseudo-Hurler polydystrophy (mucolipidosis type III; MIM 252600) are disorders caused by abnormal lysosomal transport in cells. The presence of numerous inclusion bodies in the cytoplasm of fibroblasts, a lack of mucopolysacchariduria, increased lysosomal enzyme activity in serum, and decreased GlcNAc-phosphotransferase activity are hallmark. Here, we attempted to investigate phenotypical and biochemical characteristics of the knockoutmouse of GlcNAc-phosphotransferase ${\alpha}/{\beta}$ subunits; in addition, we also attempted to determine whether the lysosome enriched fraction derived from placenta can be beneficial to phenotype and biochemistry of the knockout mouse.We found that the knockout mouse failed to thrive and had low bone density, as is the case in human. In addition, skin fibroblasts from the animal had the same biochemical characteristics, including increased lysosomal enzyme activity in the culture media, in contrast to the relatively low enzyme activity within the cells. Intravenous injection of the lysosome rich fraction derived from placenta into the tail vein of the animal resulted in a gain of weight, while saline injected animals didn't.In conclusion, our study demonstrated the phenotypical and biochemical similarities of the knockout mouse to a mucolipidosis type II patient and showed the therapeutic potential of the lysosome enriched fraction. We admit that a larger scale animal study will be needed; however, the disease model and the therapeutic potential of the lysosome enriched fraction will highlight the hope for a novel treatment approach to mucopolipidosis type II, for which no therapeutic modality is available.

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Physicochemical Properties of Several Korean Yam Starches (한국산 마전분의 이화학적 특성)

  • Kim, Wha-Sun;Kim, Sang-Soon;Park, Yong-Kon;Seog, Ho-Moon
    • Korean Journal of Food Science and Technology
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    • v.23 no.5
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    • pp.554-560
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    • 1991
  • The physicochemical properties of Korean yam starches (D. aimadoimo, D. batatas and D. japonica) were investigated. The mean granular size of starches were 23.5 μm for D. aimadoimo, 23.9 μm for D. batatas and 18.2 μm for D. japonica. Amylose content, blue value and water binding capacity was $29{\sim}33%,\;0.42{\sim}0.51%\;and\;109.9{\sim}118.3%$, respectively. The optical transmittance of 0.3% (dry basis) yam starch suspensions were increased at $70{\sim}75^{\circ}C$ and D. japonica showed typical two-step transmittance curve. The swelling power and solubility patterns increased over $60^{\circ}C$, and D. aimadoimo was the highest values. Amylogram patterns of 5% (dry basis) yam starch suspensions, determined by Brabender amylograph, were similar to that of yam flours and the viscosity of D. aimadoimo had 630 BU, which was about 5 times higher than 130 BU for D. batatas and D. japonica. Observation under scanning electron microscope lefted marks of resistance to glucoamylase because these surfaces were similar to the natural granules. In rates of solubiliazation by dimethyl sulfoxide, D. aimadoimo showed the highest value. (3-Amylolysis limits of yam starches and their amylose were $71.8%{\sim}75.5%\;and\;90.2{\sim}92.1%$, respectively. Gel filtration patterns of debranched amylopectin by pullulanase were divided into 3 peaks. The weight ratios of peak III to peak II in yam starches were $2.15%{\sim}2.42%$.

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Effects of low salinity stresses on the physiology of disc abalone, Haliotis discus discus (저염분 자극에 의한 둥근전복, Haliotis discus discus의 생리학적 변화)

  • Jwa, Min-Seok;Kang, Kyung-pil;Choi, Mi-Kyung;Yeo, In-Kyu
    • Journal of fish pathology
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    • v.22 no.3
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    • pp.293-303
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    • 2009
  • Effects of stress on the low salinity stress were examined in the pacific abalone Haliotis discus discus. Changes in survival rate, hemolymph count, antioxidant enzyme activities (catalase: CAT and superoxide dismutase: SOD), respiratory burst activity, phenoloxidase activity, lysozyme activity and expression of heat shock protein 70 (HSP70) mRNA were measured 0, 3, 6, 12, 24 or 48hours after low salinity treatment with 25, 30, 33 and 35 psu. Survival rates of pacific abalone were 100% at 33 and 35 psu, but 93 and 97% at 25 and 30 psu for 48 hours, respectively. Hemolymph counts decreased in the time elapsed-dependent way at all of the experimental groups. At low salinity, 25 and 30 psu, SOD and CAT activity increased compared to the experimental group of 33 psu. Moreover, respiratory burst activities of the pacific abalone seemed to have no effect on low salinity stress at any experimental group. However, phenoloxidase activity is an important component of the defence against pathogen that was decreased in a reduction of salinity dependent way. Lysozyme activity also immediately reduced at 25 psu experimental group for 48 h. The HSP70 mRNA was weakly expressed at 33 psu, but strongly detectable at 25 psu experimental group. The HSP 70 mRNA expression in gill increased in the time elapsed-dependent way at 25 psu experimental group and then recovered at 48 h. These results suggest that low salinity stress give rise to inhibitory action of immune system as a result of the decrease of phenoloxidase and lysozyme activity in the pacific abalone, especially.

Correlation between Glycemic Index and in vitro Starch Hydrolysis of Cereals (곡류의 혈당지수와 전분 가수분해율과의 상관관계)

  • Lee, Jung-Sun;Shin, Hyun-Kyung
    • Korean Journal of Food Science and Technology
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    • v.30 no.5
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    • pp.1229-1235
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    • 1998
  • To see the correlation between the rate of in vitro starch hydrolysis and the glycemic index, an in vitro digestion was carried out by incubating the cereal samples for 2 hours with ${\alpha}-amylase$ in dialysis tubing. Also the levels of blood glucose were measured over 2 hours after feeding healthy volunteers with 50 g carbohydrate portions. Hydrolysis area, hydrolysis index (HI) and the dialysate content of carbohydrate throughout the digestion time for barley was significantly below those for other cereals (p<0.05), and unpolished glutinous rice was significantly above (p<0.05). The GI-glucose of barley $(57%{\pm}7)$ to glucose as standard was significantly (p<0.05) lower than those of other cereals whereas the GI-glucose of glutinous rice $(110%{\pm}8)$ was significantly higher (p<0.05) than other cereals. The GI-rice values to rice as standard were $122%{\pm}4$ for glutinous sorghum, $116%{\pm}13$ for job's tear, $115%{\pm}13$ for glutinous millet, $106%{\pm}6$ for unpolished glutinous rice, $102%{\pm}7$ for glutinous rice, $100%{\pm}0$ for rice, $90%{\pm}12$ for unpolished rice, $85%{\pm}6$ for foxtail millet, $79%{\pm}5$ for buckwheat and $63%{\pm}6$ for barley. The GI-rice was significantly correlated to hydrolysis area and HI (r=0.75, p<0.01). It suggests that the in vitro starch hydrolysis offers good potential to predict the in vivo glycemic response of starch foods.

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Development of Evaluation Model for ITS Project using the Probabilistic Risk Analysis (확률적 위험도분석을 이용한 ITS사업의 경제성평가모형)

  • Lee, Yong-Taeck;Nam, Doo-Hee;Lim, Kang-Won
    • Journal of Korean Society of Transportation
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    • v.23 no.3 s.81
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    • pp.95-108
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    • 2005
  • The purpose of this study is to develop the ITS evaluation model using the Probabilistic Risk Analysis (PRA) methodology and to demonstrate the goodness-of-fit of the large ITS projects through the comparative analysis between DEA and PRA model. The results of this study are summarized below. First, the evaluation mode] using PRA with Monte-Carlo Simulation(MCS) and Latin-Hypercube Sampling(LHS) is developed and applied to one of ITS projects initiated by local government. The risk factors are categorized with cost, benefit and social-economic factors. Then, PDF(Probability Density Function) parameters of these factors are estimated. The log-normal distribution, beta distribution and triangular distribution are well fitted with the market and delivered price. The triangular and uniform distributions are valid in benefit data from the simulation analysis based on the several deployment scenarios. Second, the decision making rules for the risk analysis of projects for cost and economic feasibility study are suggested. The developed PRA model is applied for the Daejeon metropolitan ITS model deployment project to validate the model. The results of cost analysis shows that Deterministic Project Cost(DPC), Deterministic Total Project Cost(DTPC) is the biased percentile values of CDF produced by PRA model and this project need Contingency Budget(CB) because these values are turned out to be less than Target Value(TV;85% value), Also, this project has high risk of DTPC and DPC because the coefficient of variation(C.V) of DTPC and DPC are 4 and 15 which are less than that of DTPC(19-28) and DPC(22-107) in construction and transportation projects. The results of economic analysis shows that total system and subsystem of this project is in type II, which means the project is economically feasible with high risk. Third, the goodness-of-fit of PRA model is verified by comparing the differences of the results between PRA and DEA model. The difference of evaluation indices is up to 68% in maximum. Because of this, the deployment priority of ITS subsystems are changed in each mode1. In results. ITS evaluation model using PRA considering the project risk with the probability distribution is superior to DEA. It makes proper decision making and the risk factors estimated by PRA model can be controlled by risk management program suggested in this paper. Further research not only to build the database of deployment data but also to develop the methodologies estimating the ITS effects with PRA model is needed to broaden the usage of PRA model for the evaluation of ITS projects.

Results of Three-Dimensional Conformal Radiation Therapy for the Treatment of a Solitary Sternal Relapse of Breast Cancer (흉골에 단독 전이된 유방암의 삼차원 입체조형 방사선 치료 성적)

  • Kim, Hae-Young;Huh, Seung-Jae;Park, Won;Choi, Do-Ho;Kang, Min-Kyu;Yang, Jung-Hyun;Nam, Seok-Jin;Im, Young-Hyuck
    • Radiation Oncology Journal
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    • v.26 no.2
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    • pp.91-95
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    • 2008
  • Purpose: To evaluate the response and survival rate after three-dimensional conformal radiation therapy(3D-CRT) of patients with a solitary sternal relapse of breast cancer. Materials and Methods: Seventeen patients between May 1996 and June 2005 were evaluated with the salvage 3D-CRT treatment of a solitary sternal relapse of breast cancer. The treatment fields included the gross tumor volume with 2 cm margins. The total radiation dose was $35.0{\sim}61.5$ Gy(biologic effective dose of $43.7{\sim}76.9Gy_{10}$ using an $\alpha/\beta$ ratio of 10 Gy), with a daily dose of $1.8{\sim}3.0$ Gy. The tumor response was evaluated by the change in maximum tumor size via follow up CT scans $1{\sim}3$ months after the completion of treatment. Results: An objective tumor response was achieved in all patients, with a complete response in 5 patients and a partial response in 12 patients. The 5-year overall survival rate was 51.9%(median survival time: 27 months), and the most important factor affecting overall survival was the disease-free interval(interval from primary surgery of breast cancer to the development of sternal metastasis): The 5-year overall survival rate was 61.8% for patients with a disease-free interval ${\geq}12$ months and 0.0% for patients with disease-free interval <12 months(p=0.03). Conclusion: The response to 3D-CRT was good in patients with solitary sternal relapse of breast cancer. Particularly, patients with long disease-free interval from primary surgery survived significantly longer than patients with short disease-free interval from primary surgery.

Physical Dosimetry in Radioactive Iodine Treatment in the Patients with Thyroid Cancer (갑상선암 환자에 대한 방사성옥소 치료시 물리적 선량 측정)

  • Kim, Myung-Seon;Jeong, Nae-In;Lee, Jai-Yong;Kim, Chong-Soon;Kim, Chong-Ho;Lee, Myung-Chul;Koh, Channg-Soon;Kim, Hee-Geun;Kang, Duck-Won;Song, Myung-Jae
    • The Korean Journal of Nuclear Medicine
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    • v.28 no.1
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    • pp.124-132
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    • 1994
  • Radioactive iodine has been widely used in patients with thyroid cancer combined with surgical treatment. However, due to individual variations in absorption and excretion and uptake by tumor tissue of radioactive iodine, there are differences in therapeutic effect and adverse effects even if the same doses are administrated. So this study compared the therapeutic effect and radiation hazard by measuring internal radiation dose. Of total 27 patients with well differentiated thyroid cancer who had been thyroidectomized, we administered radioactive iodine 100 mCi, 150 mCi, 200 mCi. According to BEL DOSIMETRY PROTO-COL, beta and gamma ray dose were estimated from a pelt of the logarithm of the percent of dose per liter of whole blood versus day, and percent dose retained versus day using somilogarithmic paper, respectively. 1) Physical dose to whole blood averaged $56.54{\pm}13.02$ rad in 100 mCi administered group, $76.83{\pm}19.97$ rad in 150 mCi administered group, $95.08{\pm}25.51$ rad in 200 mCi administered group and there has been a significant correlation among the groups. 2) Mean percent dose retained 48 hours later was 26.34%. 3) There was no significant correlation of physical dose between absence and presence of metastasis. 4) 17 of 19 patients who has been followed up with TSH and serum throglobulin, Thallium scan were successfully ablated by radioactive iodine. 5) Leukocyte, lymphocyte, neutrophil, platelet counts all deelined in 4.6 weeks and most of all were restored 3 months later. 6) There was no significant correlation between physical dosimetry and biologic dosimetry. Generally administered doses of radioactive iodine (100-200 mCi) to patients with thyroid cancer postoperatively had developed transient bone marrow suppression and minimal chromosomal aberration, but they were within safety dose to blood (200 rad). And there has been no significant differences in residual dose 48 hours later between Korean and western people.

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Biodistribution and Scintigraphy of Iodine-131-Iododeoxyadenosine in Rats Bearing Breast Cancer (흰쥐에서 Iodine-131-Iododeoxyadenosine의 생체분포 및 유방암 영상화에 관한 연구)

  • Kim, Seon-Gu;Kim, Chang-Guhn;Lee, Kang-Mo;Kim, Hye-Won;Min Byung-Cheol;Choi, See-Sung;Lee, Jong-Deuk;Yang, David J.;Kim, E. Edmund;Lee, Hyun-Chul;Won Jong-Jin
    • The Korean Journal of Nuclear Medicine
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    • v.32 no.4
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    • pp.374-381
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    • 1998
  • Purpose: I-131 labeled (2'-deoxy-2'-iodo-${\beta}$-D-arabinofuranosyl) adenine (IAD) may be involved in DNA synthesis during active proliferation of tumor cells. We conducted this study to find out the biodistribution of IAD and it's feasibility for scintigraphic tumor imaging. Materials and Methods: Tosyl acetyl-adenosine was dissolved in acetonitrile, and I-131-NaI was added and heated to synthesize IAD. Female Fisher 344 rats innoculated with breast tumor cells were injected with 0.27 MBq of IAD. Rats were sacrificed at 0.5, 1, 2, 4, 24h and the % of injected dose per gram of tissue (%ID/g) was determined. For scintigraphy, rats bearing breast cancer were administered with 1.11 MBq of IAD and imaging was performed after 2 and 24h. Then, rat body was fixed and microtomized slice was placed on radiographic film for autoradiography. Results: %ID/g of tumor was 0.74 (0.5h),0.73 (1h), 0.55 (2h), 0.38 (4h), and 0.05 (24h), respectively. At 1h after injection, %ID/g of tumor was higher than that of heart (0.34), liver (0.42), spleen (0.47), kidney (0.69), muscle (0.14), bone (0.33) and intestine (0.51). However, %ID/g of tumor was lower than blood (1.06), lung (0.77), and thyroid (177.71). At 4h, %ID/g of tumor in comparison with other tissue did not change. Tumor contrast expressed by tumor to blood ratio was 0.69 and tumor to muscle ratio was 5.11 at 1h. However, these ratios did not improve through 24h. On autoradiogram and scintigraphy at 2 and 24 hour, the tumor was well visualized. Conclusion: This results suggest that IAD may have a potential for tumor scintigraphy. However, further work is needed to improve localization in tumor tissue.

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