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Enhanced antidiabetic efficacy and safety of compound K/β-cyclodextrin inclusion complex in zebrafish

  • Nam, Youn Hee;Le, Hoa Thi;Rodriguez, Isabel;Kim, Eun Young;Kim, Keonwoo;Jeong, Seo Yule;Woo, Sang Ho;Lee, Yeong Ro;Castaneda, Rodrigo;Hong, Jineui;Ji, Min Gun;Kim, Ung-Jin;Hong, Bin Na;Kim, Tae Woo;Kang, Tong Ho
    • Journal of Ginseng Research
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    • v.41 no.1
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    • pp.103-112
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    • 2017
  • Background: 20(S)-Protopanaxadiol 20-O-D-glucopyranoside, also called compound K (CK), exerts antidiabetic effects that are mediated by insulin secretion through adenosine triphosphate (ATP)-sensitive potassium ($K_{ATP}$) channels in pancreatic ${\beta}$-cells. However, the antidiabetic effects of CK may be limited because of its low bioavailability. Methods: In this study, we aimed to enhance the antidiabetic activity and lower the toxicity of CK by including it with ${\beta}$-cyclodextrin (CD) (CD-CK), and to determine whether the CD-CK compound enhanced pancreatic islet recovery, compared to CK alone, in an alloxan-induced diabetic zebrafish model. Furthermore, we confirmed the toxicity of CD-CK relative to CK alone by morphological changes, mitochondrial damage, and TdT-UTP nick end labeling (TUNEL) assays, and determined the ratio between the toxic and therapeutic dose for both compounds to verify the relative safety of CK and CD-CK. Results: The CD-CK conjugate ($EC_{50}=2.158{\mu}M$) enhanced the recovery of pancreatic islets, compared to CK alone ($EC_{50}=7.221{\mu}M$), as assessed in alloxan-induced diabetic zebrafish larvae. In addition, CD-CK ($LC_{50} =20.68{\mu}M$) was less toxic than CK alone ($LC_{50}=14.24{\mu}M$). The therapeutic index of CK and CD-CK was 1.98 and 9.58, respectively. Conclusion: The CD-CK inclusion complex enhanced the recovery of damaged pancreatic islets in diabetic zebrafish. The CD-CK inclusion complex has potential as an effective antidiabetic efficacy with lower toxicity.

Inhibitory Role of TRIP-Br1/XIAP in Necroptosis under Nutrient/Serum Starvation

  • Sandag, Zolzaya;Jung, Samil;Quynh, Nguyen Thi Ngoc;Myagmarjav, Davaajargal;Anh, Nguyen Hai;Le, Dan-Diem Thi;Lee, Beom Suk;Mongre, Raj Kumar;Jo, Taeyeon;Lee, MyeongSok
    • Molecules and Cells
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    • v.43 no.3
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    • pp.236-250
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    • 2020
  • Currently, many available anti-cancer therapies are targeting apoptosis. However, many cancer cells have acquired resistance to apoptosis. To overcome this problem, simultaneous induction of other types of programmed cell death in addition to apoptosis of cancer cells might be an attractive strategy. For this purpose, we initially investigated the inhibitory role of TRIP-Br1/XIAP in necroptosis, a regulated form of necrosis, under nutrient/serum starvation. Our data showed that necroptosis was significantly induced in all tested 9 different types of cancer cell lines in response to prolonged serum starvation. Among them, necroptosis was induced at a relatively lower level in MCF-7 breast cancer line that was highly resistant to apoptosis than that in other cancer cell lines. Interestingly, TRIP-Br1 oncogenic protein level was found to be very high in this cell line. Up-regulated TRIP-Br1 suppressed necroptosis by repressing reactive oxygen species generation. Such suppression of necroptosis was greatly enhanced by XIAP, a potent inhibitor of apoptosis. Our data also showed that TRIP-Br1 increased XIAP phosphorylation at serine87, an active form of XIAP. Our mitochondrial fractionation data revealed that TRIP-Br1 protein level was greatly increased in the mitochondria upon serum starvation. It suppressed the export of CypD, a vital regulator in mitochondria-mediated necroptosis, from mitochondria to cytosol. TRIP-Br1 also suppressed shikonin-mediated necroptosis, but not TNF-α-mediated necroptosis, implying possible presence of another signaling pathway in necroptosis. Taken together, our results suggest that TRIP-Br1/XIAP can function as onco-proteins by suppressing necroptosis of cancer cells under nutrient/serum starvation.

Transformation of Ginsenoside Rd to Ginsenoside F2 by Enzymes of Leuconostoc fallax LH3 (Leuconostoc fallax LH3이 생산하는 효소에 의한 Ginsenoside Rd의 Ginsenoside F2로의 전환)

  • Quan, Lin-Hu;Cheng, Le-Qin;Na, Ju-Ryun;Kim, Ho-Bin;Park, Min-Ju;Kim, Se-Hwa;Kim, Myung-Kyum;Yang, Deok-Chun
    • Korean Journal of Medicinal Crop Science
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    • v.16 no.3
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    • pp.155-160
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    • 2008
  • Ginsenosides have been regarded as the principal components, responsible for the pharmacological and biological activities of ginseng. Absorption of major ginsenosides at the gastrointestinal tract was extremely low, when ginseng taken orally. In order to improve the absorption and bioavailability, transformation of major ginsenosides into more active and valuable minor ginsenoside is much required. In this present study, We isolated a lactic acid bacteria Leuconostoc fallax LH3 from the Korean fermented food Kimchi, which have higher ${\beta}$-glucosidase activity. Using the ethanol precipitated curd enzyme of Leuconostoc fallax LH3, we investigated the biotransformation of ginsenoside Rd at different experimental condition to increase transformation. The maximum convertion was supported at 30 $^{\circ}C$ and decreased when temperatures increased. In order to optimize the effect of pH, the curd enzyme was mixed 20 mM sodium phosphate buffer (pH 3.5 to pH 8.0). Ginsenoside Rd was almost hydrolyzed between pH 7.0 and pH 9.0, but not hydrolyzed above pH 10.0. Ginsenoside Rd was hydrolyzed after 24 hrs incubation, but whereas the ginsenoside F2 was appeared from 36 hrs, and all ginsenoside Rd was transformed to F2 after the 60 hrs incubation. Based on this study, the curd enzyme of Leuconostoc fallax LH3 transformed the ginsenoside Rd at the 30$^{\circ}C$ and the pH optimum of 7.0 to 9.0 after the 60 hrs incubation time.

Expression of MEK1 Fusion Protein in Yeast for Developing Cell Based Assay System, a Major Substrate of LeTx (Yeast내에서 MEK1 융합 단백질 발현 및 Lethal Factor 활성 검증)

  • Hwang, Hye-Hyun;Kim, Joung-Mok;Choi, Kyoung-Jae;Park, Hae-Chul;Han, Sung-Hwan;Chung, Hoe-Il;Koo, Bon-Sung;Park, Joon-Shik;Yoon, Moon-Young
    • Korean Journal of Microbiology
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    • v.42 no.3
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    • pp.195-198
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    • 2006
  • Lethal toxin is a critical virulence factor of anthrax. It is composed two protein: protective antigen (PA) and lethal factor (LF). PA binds to specific cell surface receptors and, forms a membrane channel that mediates entry of LF into the cell. LF is a zinc-dependent metalloprotease, which cleaves MKKs [MAPK (mitogen-activated protein kinase) kinases] at peptide bonds very close to their N-termini. In this study, we suggest application of cell-based assays in the early phase of drug discovery, with a particular focus on the use of yeast cells. We constructed MEK1 expression system in yeast to determine LF activity and approached cell-based assay system to screen inhibitors, in which the results covering the construction of LF-substrate in yeast expression vector, expression, and LF-mediated proteolysis of substrate were described. These results could provided the basic steps in design of cell-based assay system with the high efficiency, rapidly and easy way to screening of inhibitors.

Estimation of Benzene Emissions from Mobile Sources in Korea (국내 이동오염원에서 발생되는 벤젠 배출량 산정)

  • Lee, Ju-Hyoung;Cha, Jun-Seok;Hong, Ji-Hyung;Jung, Dong-Il;Kim, Ji-Young
    • Journal of Korean Society for Atmospheric Environment
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    • v.24 no.1
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    • pp.72-82
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    • 2008
  • Benzene is a very harmful and toxic compound known as human carcinogen by all routes of exposure. Owing to the risky feature of benzene, several countries such as Japan, UK and EU have established the ambient air quality standard and protect from that risk of it. Korea also has designated it as one of the criteria air pollutants and established the concentration limit ($5\;{\mu}g/m^3$) in the air and is going to apply the standard from 2010. Benzene is emitted from various sources such as combustion plants, production processes, waste treatment facilities and also automobiles. Mobile source is known as one of the major emission sources of benzene. In this study, we estimated the domestic emissions of benzene from mobile source and compared the results with those of advanced countries. Mobile source was divided into 2 categories, Le., on-road source and non-road source. The total emissions of benzene from mobile source were estimated as 3,106 tons/yr and 1,612 tons/yr was emitted from on-road source and 1,494 tons/yr was from non-road source. Emission ratio of benzene from on-road source showed that 80.0% was from passenger cars, 10.1% was from taxis, 7.2% was from light-duty vehicles, 2.5% was from heavy-duty vehicles and 0.2% was from buses. In the case of non-road source, the distribution showed that 66.3% was from construction machineries, 14.5% was from locomotives, 11.7% was from ships, 7.1% was from agriculture equipments and 0.5% was from aircrafts. The cold-start emissions were estimated as 942 tons/yr and this value was almost 1.5 times greater than that for hot engine emissions (608 tons/yr). In addition, the fuel-based distribution was 65.9%, 31.1% and 2.8% from gasoline, LPG and diesel vehicles, respectively. The emission ratio from mobile source occupied 65% and 30% of total benzene emissions in USA and UK, respectively. In case of Korea, the emission ratio of benzene from mobile source occupied 29% (15% from on-road source, 14% from non-road source) which showed similar value with UK.

Numerical Analysis of the Hydraulic Characteristics of a Boundary Layer Streaming over Beach Cusps Surf-Zone Using LES and One Equation Dynamic Smagorinsky Turbulence Model (LES와 One Equation Dynamic Smagorinsky 난류모형을 이용한 Beach Cusps 쇄파역에서의 경계층 Streaming 수치해석)

  • Cho, Yong Jun
    • Journal of Korean Society of Coastal and Ocean Engineers
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    • v.32 no.1
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    • pp.55-68
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    • 2020
  • In order to investigate the hydraulic characteristics of a boundary layer streaming over the beach cusps appeared in swells prevailing mild seas, we numerically simulated the shoaling process of Edge waves over the beach cusp. Synchronous Edge waves known to sustain the beach cusps could successfully be duplicated by generating two obliquely colliding Edge waves in front of beach cusps. The amplitude AB and length LB of Beach Cusp were elected to be 1.25 m and 18 m, respectively based on the measured data along the Mang-Bang beach. Numerical results show that boundary layer streaming was formed at every phase of shoaling process without exception, and the maximum boundary layer streaming was observed to occur at the crest of sand bar. In RUN 1 where the shortest waves were deployed, the maximum boundary layer streaming was observed to be around 0.32 m/s, which far exceeds the amplitude of free stream by two times. It is also noted that the maximum boundary layer streaming mentioned above greatly differs from the analytical solution by Longuet-Higgins (1957) based on wave Reynolds stress. In doing so, we also identify the recovery procedure of natural beaches in swells prevailing mild seas, which can be summarized such as: as the infra-gravity waves formed in swells by the resonance wave-wave interaction arrives near the breaking line, the sediments ascending near the free surface by the Phase II waves orbital motion were carried toward the pinnacle of foreshore by the shoreward flow commenced at the steep front of breaking waves, and were deposited near the pinnacle of foreshore due to the infiltration.

Differences in Panicle Structure and Spikelet Degeneration in Two Different Types of Rice Cultivars; Milyang 23 and Koshihikari (벼 품종 밀양 23호와 고시히카리의 수형태와 영화 퇴화 차이)

  • 강시용
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.42 no.6
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    • pp.833-840
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    • 1997
  • Differentiation and degeneration of spikelets in paddy rice has been studied in high yielding Indica$\times$Japonica hybrid cultivar, Milyang 23 and a Japonica type cultivar, Koshihikari. Germinated seeds planted in 5000$^{-1}$ a pots filled with submerged soil and cultured under natural conditions. The young panicles of main stem were continuously dissected and observered by Cryo-SEM from the panicle initiation stage, and investigated about formation position of the differentiation and degeneration spikelet within a panicle of 7 days after heading. The degeneration of spikelet appeared simultaneously throughout panicle just after closure of spikelet by the palea and lemma. Differentiated and degenerated spikelets per panicle were about 240, 80 for Milyang 23 and 87, 6 for Koshihikari, respectively. The spikelets degeneration in Milyang 23 was mainly on the secondary and tertiary branch which were developed from primary branch of middle-basal panicle node and hardly not the spikelets of primary branch, and degeneration rate of secondary and tertiary rachis branch and spikelets for Milyang 23 were 2.5 times greater than those of Koshihikari. The proper relation equation between total differentiation or normal spikelets number per panicle(Y) and each rachis branch number were different between cultivars, Le., Y=5.5X$_1$+3.0X$_2$ for Koshihikari as previously proposed, but those of Milyang 23, Y=5.7X$_1$+3.5X$_2$+2.8X$_3$ for total differentiation spikelets and Y=5.6X$_1$+3.2X$_2$+2.4X$_3$ for normally developed spikelets, where X$_1$, X$_2$, X$_3$ are number of primary, secondary, tertiary rachis branch, respectively.

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Occurrence, Geochemistry and Origin of $Co_2$-rich Water from the Chungcheong Area, Korea (충청지역 탄산수의 산출양상, 지화학적 특성 및 생성기원)

  • 정찬호;김종근;이재영
    • Economic and Environmental Geology
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    • v.34 no.2
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    • pp.227-241
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    • 2001
  • Several $Co_2$-rich springs in the Chungcheong area, Le., the Angsung spring, the Chojung spring, the Myungam spring, the Bukang spring and the Daepyung spring have been long known for their particular water chemistry. The occurrences of these springs are closely related to the geologic structure of Mesozoic granite such as dyke swarms, fault zones and the geologic boundary between granite and its adjacent gneiss. The $Co_2$-rich water samples show a high $Co_2$ concentration ($P_{CO2}$ 0.25 atm to 0.99 atm), weak acidic pHs and the electrical conductivity ranging from 101 to 2,950 ${\mu}$S/cm. The $Co_2$-rich water samples are classified into the Ca-$HC0_3$ type and the Ca(Na)-$HCO_3$) type in chemical composition. Environmental isotopic data $^{2}H/^{1}H, ^{18}O/^{16}O$) indicated that $Co_2$-rich water was meteoric origin. The ${\delta}^{13}C$ values of $Co_2$-rich water range from -3.1$\textperthousand$ to -6.8$\textperthousand$ PDB. The values indicate that $H_2CO_3^0$ and $HC0_3^-$ of the water samples are mainly originated from a deep-seated source and partly contributed from carbonatc minerals. The major minerals determining the chemistry of $Co_2$-rich watcr arc probably the carbonate minerals which are present as veins and secondary minerals, and the plagiocalse in granite and gneiss.

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On the Evaluation of Physical Distribution Service in Ports (항만물류서비스의 평가에 관하여)

    • Journal of Korean Port Research
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    • v.10 no.2
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    • pp.17-29
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    • 1996
  • It is required to consider pricing and non-pricing factors and external economy in order to achieve the objects of physical distribution system in a port. Recently, among the three factors, much attention has been paid to non-pricing factor in the system. Although physical distribution service in a port(PDSP)has been frequently mentioned in documents and literature related to port and shipping studies, few study on it has not been systematically and scientifically made due to the following problems; $\circ$ there are not proper criteria to evaluate level and quality of PDSP and as a result it is difficult to set up a unified standard for doing so. $\circ$ algorithms to evaluate problems with complex and ambiguous attributes and multiple levels in PDSP are not available. This thesis aims to establish a paradigm to evaluate PDSP and to abvance existing decision making methods to deal with complex and ambiguous problems in PDSP. To tackle the first purpose, extensive and thorough literature survey was carried out on general physical distribution service, which is a corner stone to handle PDSp. In addition, through interviews and questionnaire to the expert, it have extracted 82 factors of physical distribution service in a port. They have been classified into 6 groups by KJ method and each group defined by the expert's advice as follows; a. Potentiality b. Exactness c. safety d. Speediness e. Convenience f. Linkage Prior to the service evaluation, many kinds of its attributes must be identified on the basis of rational decision owing to complexity and ambiguity inherent in PDSP. An analytical hierarchy process (AHP) is a method to evaluate them but it is not applicable to PDSP that have property of non-additivity and overlapped attributes. Therefore, probablility measure can not be used to evaluate PDSP but fuzzy measure is required. Hierarchical fuzzy integral method, which is merged AHP with fuzzy measure, is also not effective method to evaluate attributes because it has vary complicated way to calculate fuzzy measure identification coefficient of attributes. A new evaluation algorithm has been introduced to solve problems with multi-attribute and multi-level hierarchy, which is called hierarchy fuzzy process(HFP).Analysis on ambiguous aspects of PDSP under study which is not easy to be defined is prerequisite to evaluate it. HFP is different from algorithm existed in that it clarified the relationship between fuzzy measure and probability measure adopted in AHP and that it directly calculates the family of fuzzy measure from overlapping coefficient and probability measure to treat and evaluate ambiguous and complex aspects of PDSP. A new evaluation algorithm HFP was applied to evaluate level of physical distribution service in the biggest twenty container port in the world. The ranks of the ports are as follows; 1. Rotterdam Port, 2. Hamburg Port, 3. Singapore Port, 4. Seattle Port, 5. Yokohama Port, 6. Long beach Port, 7. Oakland Port, 8. Tokyo Port, 9. Hongkong Port, 10. Kobe Port, 11. Los Angeles Port, 12. New york Port, 13. Antwerp Port, 14. Felixstowe Port, 15. Bremerhaven Port, 16. Le'Havre Port, 17. Kaoshung Port, 18. Killung Port, 19. Bangkok Port, 20. Pusan Port

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Characteristics of Submarine's Turbulent Wake using Analytical Solution of B(ξ) for the given λ (임의 λ에 대한 근사해 B(ξ)를 이용한 잠수함 난류항적 특성 연구)

  • Lee, Yong-Chol
    • Journal of the Korea Institute of Information and Communication Engineering
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    • v.21 no.8
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    • pp.1604-1610
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    • 2017
  • Using analytical solution of $B({\xi})$, I could find out the characteristics of Submarine's turbulent wake for the given various ${\lambda}$, which were unknown facts before. As the results, $B({\xi}){\approx}{\frac{B({\xi})_{max}}{2}}$ and ${{\int}_{0}^{{\approx}0.6}}B({\xi})d{\xi}{\approx}0.85{{\int}_{0}^{1}}B({\xi})d{\xi}$ in the vicinity ${\xi}{\approx}0.6$, there was some dependencies on the given ${\lambda}$ though. The values of ${\lambda}$, in the range of $4{\leq}{\lambda}{\leq}8$, are more suitable to describe submarine's turbulent wake realistically, due to the bases on the quasi equilibrium state of turbulent wake. ${\lambda}$ mainly affects on the radius and detection range of the submarine's turbulent wake on the surface, however, the speed of submarine mainly affect on the duration of the wake rather than shape. If $7{\leq}{\lambda}{\leq}8$, it can be expected that the turbulent wake can be seen on the surface in the West sea, however, snorkeling(or snorkeled) submarine's wake can be found easily in the East sea.