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Improvement Effect of Non-alcoholic Fatty Liver Disease by Curcuma longa L. Extract (강황 추출물의 비알코올성 지방간 질환 개선 효과)

  • Lee, Young Seob;Lee, Dae Young;Kwon, Dong Yeul;Kang, Ok Hwa
    • Korean Journal of Medicinal Crop Science
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    • v.28 no.4
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    • pp.276-286
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    • 2020
  • Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with multiple metabolic disorders. The medicinal plant Curcuma longa L. is widely distributed in Asia and has been used to treat a spectrum diseases in clinical practice. To date, there are inadequate reports of the effects of C. longa 50% EtOH extract (CE) on NAFLD. Therefore, in this study, we evaluate the CE on an NAFLD animal and elucidate the mechanism of action. Methods and Results: C57BL/6J mice fed a methionine-choline deficient diet (MCD) were treated with CE or milk thistle, and changes in inflammation and stetosis were assessed. Experimental animals were divided into six group (n = 10); Normal, MCD, MCD + CE 50 mg/kg/day (CE 50), MCD + CE 100 mg/kg/day (CE 100), MCD + CE 150 mg/kg/day (CE 150), and the Control, MCD + Milk thistle 150 mg/kg/day (MT 150). Body weight, liver weight, liver function, and histological changes were assessed in experimental animals. Quantitative real-time polymerase chain reaction and western blot analyses were performed on samples collected after 4 weeks of treatment. We observed that CE administration improved MCD-diet-induced lipid accumulation, and triglyceride (TG) and total cholesterol (TC) levels in serum. Treatment with CE also decreased hepatic lipogenesis through modulation of the sterol regulatory element binding protein-1 (SREBP-1), CCAAT-enhancer binding protein α (C/EBPα), fatty acid synthase (FAS), and peroxisome proliferator-activated receptor γ (PPARγ) expresion. In addition, the use of CE increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and inhibited the up-regulation of toll-like receptor (TLR)-2 and TLR-4 signaling and the production of inflammatory mediators. Conclusions: In this report, we observed that CE regulated lipid accumulation in an MCD dietinduced NAFLD model by decreasing lipogenesis. These data suggeste that CE could effectively protect mice against MCD-induced NAFLD, by inhibiting the TLR-2 and TLR-4 signaling cascades.

Screeening of Natural Plant Resources with Acetylcholine esterase inhibitory activity and Effect on Scopolamine-induced Memory Impairment (천연식물자원으로부터 Acetylcholine esterase 저해 활성 탐색 및 인지기능에 미치는 영향)

  • Choi, Jang Won;Won, Mu-Ho;Joo, Han-Seung
    • Journal of agriculture & life science
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    • v.45 no.6
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    • pp.213-226
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    • 2011
  • This study was performed to investigate the effect of essential oils and ethanolic extracts of approximately 650 plant species on acetylcholine esterase (AChE) enzyme activity using Ellman's colorimetric method in 96-well microplates. The results showed that the ethanolic extracts from twig of Sophora subprostrata, twig of Phellodendron amurense, seed of Corylopsis coreana, and essential oil (EO) from Citrus paradisi, Cupressus sempervirens, Ocimum basilicum, Pinus sylvestris and Rosmarinus officinalis inhibited more than 80% of AChE activity. Among these, EO from Pinus sylvestris, C. sempervirens and C paradisi exhibited higher values of AChE inhibitory activity, which were 75, 84 and 99% at a concentration of 50 ug/ml, respectively. Finally, EO from C paradisi (grapefruit, GEO) showed the highest inhibitory activity towards AChE, which showed 91% of inhibition at a concentration of 20 ug/ml. We also examined the anti-dementia effects of GEO in mouse by passive avoidance test and Morris water maze test. The model mouse (male, ICR) of dementia (negative control) was induced by administration of scopolamine (1 mg/kg body weight). The latency time of sample group administrated with GEO (100 mg/kg, p.o.) increased significantly as compared with negative control on passive avoidance test. There were significant recovery from the scopolamine-induced deficits on learning and memory in water maze test through daily administrations with GEO (100 mg/kg, p.o.). From these results, we conclude that GEO treatment might enhance the cognitive function, suggesting that the EO of C. paradis may be a potential candidate for improvement of perceptive ability and dementia.

Ginsenoside Rg3 in combination with artesunate overcomes sorafenib resistance in hepatoma cell and mouse models

  • Chen, Ying-Jie;Wu, Jia-Ying;Deng, Yu-Yi;Wu, Ying;Wang, Xiao-Qi;Li, Amy Sze-man;Wong, Lut Yi;Fu, Xiu-Qiong;Yu, Zhi-Ling;Liang, Chun
    • Journal of Ginseng Research
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    • v.46 no.3
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    • pp.418-425
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    • 2022
  • Background: Sorafenib is effective in treating hepatoma, but most patients develop resistance to it. STAT3 signaling has been implicated in sorafenib resistance. Artesunate (ART) and 20(R)-ginsenoside Rg3 (Rg3) have anti-hepatoma effects and can inhibit STAT3 signaling in cancer cells. This study aimed to evaluate the effects of Rg3 in combination with ART (Rg3-plus-ART) in overcoming sorafenib resistance, and to examine the involvement of STAT3 signaling in these effects. Methods: Sorafenib-resistant HepG2 cells (HepG2-SR) were used to evaluate the in vitro anti-hepatoma effects of Rg3-plus-ART. A HepG2-SR hepatoma-bearing BALB/c-nu/nu mouse model was used to assess the in vivo anti-hepatoma effects of Rg3-plus-ART. CCK-8 assays and Annexin V-FITC/PI double staining were used to examine cell proliferation and apoptosis, respectively. Immunoblotting was employed to examine protein levels. ROS generation was examined by measuring DCF-DA fluorescence. Results: Rg3-plus-ART synergistically reduced viability of, and evoked apoptosis in HepG2-SR cells, and suppressed HepG2-SR tumor growth in mice. Mechanistic studies revealed that Rg3-plus-ART inhibited activation/phosphorylation of Src and STAT3 in HepG2-SR cultures and tumors. The combination also decreased the STAT3 nuclear level and induced ROS production in HepG2-SR cultures. Furthermore, overactivation of STAT3 or removal of ROS diminished the anti-proliferative effects of Rg3-plus-ART, and removal of ROS diminished Rg3-plus-ART's inhibitory effects on STAT3 activation in HepG2-SR cells. Conclusions: Rg3-plus-ART overcomes sorafenib resistance in experimental models, and inhibition of Src/STAT3 signaling and modulation of ROS/STAT3 signaling contribute to the underlying mechanisms. This study provides a pharmacological basis for developing Rg3-plus-ART into a novel modality for treating sorafenib-resistant hepatoma.

Ginsenoside Rg1 attenuates cerebral ischemia-reperfusion injury due to inhibition of NOX2-mediated calcium homeostasis dysregulation in mice

  • Han, Yuli;Li, Xuewang;Yang, Liu;Zhang, Duoduo;Li, Lan;Dong, Xianan;Li, Yan;Qun, Sen;Li, Weizu
    • Journal of Ginseng Research
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    • v.46 no.4
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    • pp.515-525
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    • 2022
  • Background: The incidence of ischemic cerebrovascular disease is increasing in recent years and has been one of the leading causes of neurological dysfunction and death. Ginsenoside Rg1 has been found to protect against neuronal damage in many neurodegenerative diseases. However, the effect and mechanism by which Rg1 protects against cerebral ischemia-reperfusion injury (CIRI) are not fully understood. Here, we report the neuroprotective effects of Rg1 treatment on CIRI and its possible mechanisms in mice. Methods: A bilateral common carotid artery ligation was used to establish a chronic CIRI model in mice. HT22 cells were treated with Rg1 after OGD/R to study its effect on [Ca2+]i. The open-field test and poleclimbing experiment were used to detect behavioral injury. The laser speckle blood flowmeter was used to measure brain blood flow. The Nissl and H&E staining were used to examine the neuronal damage. The Western blotting was used to examine MAP2, PSD95, Tau, p-Tau, NOX2, PLC, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging was used to test the level of [Ca2+]i. Results: Rg1 treatment significantly improved cerebral blood flow, locomotion, and limb coordination, reduced ROS production, increased MAP2 and PSD95 expression, and decreased p-Tau, NOX2, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging results showed that Rg1 could inhibit calcium overload and resist the imbalance of calcium homeostasis after OGD/R in HT22 cells. Conclusion: Rg1 plays a neuroprotective role in attenuating CIRI by inhibiting oxidative stress, calcium overload, and neuroinflammation.

Current and Long Wave Influenced Plume Rise and Initial Dilution Determination for Ocean Outfall (해양 배출구에서 해류와 장파에 의한 플룸 상승과 초기 희석도 결정)

  • Kwon, S.J.
    • Journal of Korean Port Research
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    • v.11 no.2
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    • pp.231-240
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    • 1997
  • In the United States, a number of ocean outfalls discharge primary treated effluent into deep sea water and contribute for more efficient wastewater treatment. The long multiport diffuser connected by long pipe from a treatment plant discharge wastewater into deep water due to the steep slope of the sea bed. However, Plume discharged from the diffuser can have significant impacts on coastal communities and possibly immediate consequence on public health. Therefore, there have been growing interests about the dynamics of plume in the vicinity of the ocean outfalls. It is expected that the ocean outfall should be considered for more efficient and reliable wastewater treatments as soon as possible around coastal area in South Korea. A number of studies of plume ynamics have used various models to predict plume behavior. However, in many cases, the calculated values of plume behavior are in significantly poor agreement with realistic values. Therefore, in this study, it is recommended that improvements should be made in the application of the plume model to more simulate the actual discharge characteristics and ocean conditions. It should be noted that input parameters in plume models reflect realistic ocean conditions like waves as well as currents. In this study, as one of the new parameters, current and long wave-influenced plume rise and initial dilution have been taken into account by using simple linear wave theory under some specific assumptions for more reliable plume behavior description. Among the improved plume models approved by EPA (Environmental Protection Agency), the RSB(Roberts-Snyder-Baurngartner) and UM(Updated Merge) models were chosen for the calculation of plume behavior, and the variation calculated by both models on the basis of long period wave was compared in terms of plume rise and initial dilution.

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Risk Factors Related to Uterine Leiomyoma in Korean Women - A Retrospective Study - (한국인 여성에서 자궁근종 발생에 관여하는 인자들에 대한 연구 - 후향적 연구 -)

  • Hong, D.G.;Chung, M.J.;Kim, B.S.;Lee, J.M.;Cho, Y.L.;Lee, T.H.;Chun, S.S.
    • Clinical and Experimental Reproductive Medicine
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    • v.33 no.3
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    • pp.159-170
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    • 2006
  • Objective: The purpose of this study is to find out risk factors related to uterine leiomyoma in Korean women and to compare with the results of previous western studies. Methods: A retrospective analysis was carried out. All the cases of uterine leiomyoma (n=244) were diagnosed surgically or sonographically between Jannuary 1998 and December 2004. Total of 269 controls not having uterine leiomyoma were collected from patients who visited Kyungpook national university hospital for routine gynecologic check-up or treatment of their gynecologic or obstetric diseases other than uterine leiomyoma. Data were collected through review of medical records and interviews and analyzed with $x^2$ and logistic regression model. Results: In multivariate analysis, patient's age (OR 1.070; 95% CI 1.041~1.099), number of artificial abortion (OR 1.182; 95% CI 1.018~1.374) and alcohol drinking (OR 1.865; 95% CI 1.231~2.824) had significantly positive correlation with uterine leiomyoma. The duration of lactation was the only factor which had negative correlation (OR 0.985; 95% CI 0.972~0.998). BMI, parity, age at menarche, the duration and interval of menstruation, caffeine consumption and marital status did not show any correlations. Conclusion: In this study, patient's age, number of artificial abortion, and alcohol drinking were the risk factors of uterine leiomyoma in Korean women and the result was similar to that of western studies. Though we couldn't find out the specific risk factors related to the development of uterine leiomyoma in this study, but it has a great meaning to be the first trial in Korean women. The role of information bias should be carefully evaluated and further multicentered, randomized, controlled prospective studies will be needed to know the possible risk factors among Korean women.

Potentiation of Antitumor Effect of Radiotherapy by Recombinant Tumor Necrosis Factor-$\alpha$ (방사선의 항암작용에 대한 재조합 TNF-$\alpha$의 효과)

  • Seong Jinsil;Shin Hang Chul;Kim Gwi Eon;Suh Chang Ok
    • Radiation Oncology Journal
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    • v.16 no.3
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    • pp.225-231
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    • 1998
  • Purpose : To determine whether TNF-$\alpha$ increases the antitumor effect of radiotherapy in murine syngeneic tumor system. Materials and Methods : Syngeneic murine tumors of MCa-K or MCa-4 (mammary carcinoma), OCa-I (ovarian carcinoma), or HCa-I(hepatocarcinoma were grown in hind legs of C3Hf/HeJ mice. When tumors were grown to 6 mm in mean diameter mice were treated with TNF-$\alpha$, radiation, or combination of the both. Gamma-radiation was given as a single dose of 30 Gy for HCa-I and 15 Gy for other tumors using Cobalt-60 teletherapy unit. A novel TNF-$\alpha$ mutein developed in Korea, was intraperitoneally administered daily at a dose of 10 ug per mouse for 7 days. In combination of radiation and TNF-$\alpha$, the drug was started 1 hour after radiation. Tumor growth delay assay was used to measure the tumor response to the treatment. Results : Among 4 tested tumors, TNF-$\alpha$ alone showed significant antitumor activity in MCa-K and OCa-I tumors, which showed absolute growth delay (AGD) of 5.0 days and 6.5 days, respectively. In combination with radiation, TNF-$\alpha$ showed significant delay of AGD (41.1 days) in OCA-I compared to AGDs of TNF-$\alpha$ alone and radiation, i.e., 6.5 days and 26.9 days, respectively(p<0.05). Enhancement factor was 1.29 in OCa-I, which showed supraadditive effect. TNF-$\alpha$ did not show significant delay of AGDs in the remaining 3 tumors compared to AGDs of TNF-$\alpha$ alone and radiation. Conclusions: TNF-$\alpha$ alone showed antitumor effects in MCa-K and OCa-I. In combination with radiation, TNF-$\alpha$ acted in supraadditive way in OCa-I only. The results of this study imply that the combination of TNF-$\alpha$ and radiation has different therapeutic potential depending on tumor model and further study is advocated.

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Contribution of Oswald Veblen to AMS and its meaning in Korea (Oswald Veblen이 미국수학계에 미친 영향과 한국에서의 의미)

  • Lee, Sang-Gu;Ham, Yoon-Mee
    • Journal for History of Mathematics
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    • v.22 no.2
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    • pp.27-52
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    • 2009
  • This article discusses the contributions of the leader Oswald Veblen, who was the president of AMS during 1923-1924. In 2006, Korea ranked 12th in SCIE publications in mathematics, more than doubling its publications in less than 10 years, a successful model for a country with relatively short history of modern mathematical research. Now there are 192 four-year universities in Korea. Some 42 of these universities have Ph.D. granting graduate programs in mathematics and/or mathematical education in Korea. Rapid growth is observed over a broad spectrum including a phenomenal performance surge in International Mathematical Olympiad. Western mathematics was first introduced in Korea in the 17th century, but real significant mathematical contributions by Korean mathematicians in modern mathematics were not much known yet to the world. Surprisingly there is no Korean mathematician who could be found in MaC Tutor History Birthplace Map. We are at the time, to have a clear vision and leadership for the 21st century. Even with the above achievement, Korean mathematical community has had obstacles in funding. Many people thinks that mathematical research can be done without funding rather unlike other science subjects, even though they agree fundamental mathematical research is very important. We found that the experience of early American mathematical community can help us to give a vision and role model for Korean mathematical community. When we read the AMS Notice article 'The Vision, Insight, and Influence of Oswald Veblen' by Steve Batterson, it answers many of our questions on the development of American mathematics in early 20th century. We would like to share the story and analyze its meaning for the development of Korean Mathematics of 21st century.

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Prediction of present and future distribution of the Schlegel's Japanese gecko (Gekko japonicus) using MaxEnt modeling

  • Kim, Dae-In;Park, Il-Kook;Bae, So-Yeon;Fong, Jonathan J.;Zhang, Yong-Pu;Li, Shu-Ran;Ota, Hidetoshi;Kim, Jong-Sun;Park, Daesik
    • Journal of Ecology and Environment
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    • v.44 no.1
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    • pp.33-40
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    • 2020
  • Background: Understanding the geographical distribution of a species is a key component of studying its ecology, evolution, and conservation. Although Schlegel's Japanese gecko (Gekko japonicus) is widely distributed in Northeast Asia, its distribution has not been studied in detail. We predicted the present and future distribution of G. japonicus across China, Japan, and Korea based on 19 climatic and 5 environmental variables using the maximum entropy (MaxEnt) species distribution model. Results: Present time major suitable habitats for G. japonicus, having greater than 0.55 probability of presence (threshold based on the average predicted probability of the presence records), are located at coastal and inland cities of China; western, southern, and northern coasts of Kyushu and Honshu in Japan; and southern coastal cities of Korea. Japan contained 69.3% of the suitable habitats, followed by China (27.1%) and Korea (4.2%). Temperature seasonality (66.5% of permutation importance) was the most important predictor of the distribution. Future distributions according to two climate change scenarios predicted that by 2070, and overall suitable habitats would decrease compared to the present habitats by 18.4% (scenario RCP 4.5) and 10.4% (scenario RCP 8.5). In contrast to these overall trends, range expansions are expected in inland areas of China and southern parts of Korea. Conclusions: Suitable habitats predicted for G. japonicus are currently located in coastal cities of Japan, China, and Korea, as well as in isolated patches of inland China. Due to climate change, suitable habitats are expected to shrink along coastlines, particularly at the coastal-edge of climate change zones. Overall, our results provide essential distribution range information for future ecological studies of G. japonicus across its distribution range.

Korean Red Ginseng alleviates dehydroepiandrosterone-induced polycystic ovarian syndrome in rats via its antiinflammatory and antioxidant activities

  • Choi, Jong Hee;Jang, Minhee;Kim, Eun-Jeong;Lee, Min Jung;Park, Kyoung Sun;Kim, Seung-Hyun;In, Jun-Gyo;Kwak, Yi-Seong;Park, Dae-Hun;Cho, Seung-Sik;Nah, Seung-Yeol;Cho, Ik-Hyun;Bae, Chun-Sik
    • Journal of Ginseng Research
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    • v.44 no.6
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    • pp.790-798
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    • 2020
  • Background: Beneficial effects of Korean Red Ginseng (KRG) on polycystic ovarian syndrome (PCOS) remains unclear. Methods: We examined whether pretreatment (daily from 2 hours before PCOS induction) with KRG extract in water (KRGE; 75 and 150 mg/kg/day, p.o.) could exert a favorable effect in a dehydroepian-drosterone (DHEA)-induced PCOS rat model. Results: Pretreatment with KRGE significantly inhibited the elevation of body and ovary weights, the increase in number and size of ovarian cysts, and the elevation of serum testosterone and estradiol levels induced by DHEA. Pretreatment with KRGE also inhibited macrophage infiltration and enhanced mRNA expression levels of chemokines [interleukin (IL)-8, monocyte chemoattractant protein-1), proinflammatory cytokines (IL-1β, IL-6), and inducible nitric oxide synthase in ovaries induced by DHEA. It also prevented the reduction in mRNA expression of growth factors (epidermal growth factor, transforming growth factor-beta (EGF, TGF-β)) related to inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cell pathway and stimulation of the nuclear factor erythroid-derived 2-related factor 2 pathway. Interestingly, KRGE or representative ginsenosides (Rb1, Rg1, and Rg3(s)) inhibited the activity of inflammatory enzymes cyclooxygenase-2 and iNOS, cytosolic p-IκB, and nuclear p-nuclear factor kappa-light-chain-enhancer of activated B in lipopolysaccharide-induced RAW264.7 cells, whereas they increased nuclear factor erythroid-derived 2-related factor 2 nuclear translocation. Conclusion: These results provide that KRGE could prevent DHEA-induced PCOS via antiinflammatory and antioxidant activities. Thus, KRGE may be used in preventive and therapeutic strategies for PCOS-like symptoms.