• Title/Summary/Keyword: CK model

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Direct Intramuscular Gene Transfer of Naked DNA Expressing Human Vascular Endothelial Growth Factor (pCK-VEGF) Enhances Collateral Growth in a Rabbit Ischemic Hind Limb Model (토끼 허혈성 하지 모델에서 VEGF 발현 Naked DNA 벡터인 pCK-VEGF의 근육내 투여가 측부혈관형성에 미치는 영향)

  • 채제건;전현순;박은진;김종묵;김덕경;김선영
    • YAKHAK HOEJI
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    • v.45 no.1
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    • pp.108-115
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    • 2001
  • We have recently reported the development of a high efficiency expression vector, pCK, which can drive a high level of gene expression in mouse skeletal muscle. In this study, we tested the therapeutic potential of pCK expressing human VEGF165, pCK-VEGF in the rabbit ischemic hind limb model. To determine the optimal dose of plasmid DNA, various concentrations of pCK-CAT were injected into the muscle of a rabbit hind limb and the levels of CAT activity were determined. It was found that the expression level of the exogenously added gene became stable between 250 and 1,000 $\mu$g. Based on this result, we tested whether intramuscular transfer of 500$\mu$g of pCK-VEGF could actually modulate collateral vessel development in a rabbit ischemic hind limb model. It was found that relative to the control group injected with the pCK lacking the VEGF sequence, single intramuscular doses (500$\mu$g) of pCK-VEGF produced statistically significant augmentation of collateral vessels as determined by the angiographic vessel count, maximal blood flow by Doppler flowmeter and the number of capillaries by histology. These results suggest that a single 500$\mu$g-delivery of pCK-VEGF is potent enough to induce sufficient angiogenic activity and achieve therapeutic benefit on this rabbit model.

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An Estimation of an Old Age Mortality Rate Using CK Model and Relational Model

  • Jung, Kyunam;Kim, Donguk
    • Communications for Statistical Applications and Methods
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    • v.19 no.6
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    • pp.859-868
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    • 2012
  • Due to a rapidly aging society, the future Korea mortality rate is important for planning national financial strategies and social security policies. Old age mortality statistics are very limited in their ability to project a future mortality rate; therefore, it is essential to accurately estimate the old age mortality rate. In this paper, we show that the CK model with a Relational model as a base model provides accurate estimates of old age mortality rates.

An eCK-secure Authenticated Key Exchange Protocol without Random Oracles

  • Moriyama, Daisuke;Okamoto, Tatsuaki
    • KSII Transactions on Internet and Information Systems (TIIS)
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    • v.5 no.3
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    • pp.607-625
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    • 2011
  • Two-party key exchange protocol is a mechanism in which two parties communicate with each other over an insecure channel and output the same session key. A key exchange protocol that is secure against an active adversary who can control and modify the exchanged messages is called authenticated key exchange (AKE) protocol. LaMacchia, Lauter and Mityagin presented a strong security definition for public key infrastructure (PKI) based two-pass protocol, which we call the extended Canetti-Krawczyk (eCK) security model, and some researchers have provided eCK-secure AKE protocols in recent years. However, almost all protocols are provably secure in the random oracle model or rely on a special implementation technique so-called the NAXOS trick. In this paper, we present a PKI-based two-pass AKE protocol that is secure in the eCK security model. The security of the proposed protocol is proven without random oracles (under three assumptions), and does not rely on implementation techniques such as the NAXOS trick.

CK2 phosphorylates AP-2α and increases its transcriptional activity

  • Ren, Kaiqun;Xiang, Shuanglin;He, Fangli;Zhang, Wenfeng;Ding, Xiaofeng;Wu, Yanyang;Yang, Liping;Zhou, Jianlin;Gao, Xiang;Zhang, Jian
    • BMB Reports
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    • v.44 no.7
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    • pp.490-495
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    • 2011
  • Transcription factor AP-$2{\alpha}$ involves in the process of mammalian embryonic development and tumorigenesis. Many studies have shown that AP-$2{\alpha}$ functions in association with other interacting proteins. In a two-hybrid screening, the regulatory subunit ${\beta}$ of protein casein kinase 2 ($CK2{\beta}$) was identified as an interacting protein of AP-$2{\alpha}$; we confirmed this interaction using in-vitro GST pull-down and in-vivo co-immunoprecipitation assays; in an endogenous co-immunoprecipitation experiment, we further found the catalytic subunit ${\alpha}$ of protein casein kinase 2 ($CK2{\alpha}$) also exists in the complex. Phosphorylation analysis revealed that AP-$2{\alpha}$ was phosphorylated by CK2 kinase majorly at the site of Ser429, and such phosphorylation could be blocked by CK2 specific inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) in a dose-dependent manner. Luciferase assays demonstrated that both $CK2{\alpha}$ and $CK2{\beta}$ enhanced the transcription activity of AP-$2{\alpha}$; moreover, $CK2{\beta}$ increased the stability of AP-$2{\alpha}$. Our data suggest a novel cellular function of CK-2 as a transcriptional co-activator of AP-$2{\alpha}$.

Regeneration of Bovine Mammary Gland in Immunodeficient Mice by Transplantation of Bovine Mammary Epithelial Cells Mixed with Matrigel

  • Park, Hyun Jung;Lee, Won Young;Jeong, Ha Yeon;Song, Hyuk
    • International Journal of Stem Cells
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    • v.9 no.2
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    • pp.186-191
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    • 2016
  • Background and Objectives: With the global demand for dairy protein for consumption growing annually, there has been increasing activity in the research field of dairy protein synthesis and production. From a manipulation perspective, it is more difficult to use live cattle for laboratory studies on the production of milk as well as of dairy protein such as casein, as compared with using laboratory animals like rodents. Therefore, we aimed to develop a mouse model of bovine mammary alveolar ducts for laboratory-scale studies. We studied the formation of the bovine mammary gland ductal structure by transplanting the MAC-T bovine alveolar cell line into mice. Methods and Results: MAC-T cells ($1{\times}10^7$) were suspended in Matrigel and injected into the dorsal tissue of 8-week-old male BALB/C nude mice. Histological analysis of tissue dissected from the MAC-T cell-transplanted mice after 6 weeks showed the typical morphology of the tubuloalveolar female gland, as well as glands made up of branching ducts that were surrounded by smooth muscle with small alveoli budding off the ducts. In addition, the epithelial markers CK14 and CK18 were expressed within the duct-like structure. Prolactin was detected in the duct interior in these CK14+ and CK18+ cells but not in the non-transplanted MAC-T cells. Conclusions: These results showed that duct-like tissue had been successfully formed after 6 weeks of transplantation of the CK14+ and CK18+ MAC-T cells into mice dorsal tissue. This mouse model will be a useful tool for further research on the bovine mammary gland.

Myocardial Protection of Contractile Function After Global Ischemia by Compound K in the Isolated Heart

  • Kim, Jong-Hoon
    • Journal of Ginseng Research
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    • v.33 no.4
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    • pp.268-277
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    • 2009
  • Ginsenosides are among the most well-known traditional herbal medicines frequently used for the treatment of cardiovascular symptoms in South Korea. The anti-ischemic effects of compound K (CK), a metabolite of ginsenoside Rb1, on ischemia-induced isolated rat hearts were investigated through the analyses of the changes in the hemodynamics (blood pressure, aortic flow, coronary flow, and cardiac output) and the measurement of the infarct region. The subjects in this study were divided into four groups: the normal control, the CK-alone group, the ischemia-induced group without any treatment, and the ischemia-induced group treated with CK. No significant differences in perfusion pressure, aortic flow, coronary flow, and cardiac output were found between the groups before ischemia was induced. The oxygen and buffer supply was stopped for 30 min to induce ischemia 60 min after reperfusion in the isolated rat hearts, and the CK was administered 5 min before ischemia induction. The CK treatment significantly prevented decreases in perfusion pressure, aortic flow, coronary flow, and cardiac output under ischemic conditions. In addition, the hemodynamics (except for the heart rate) of the group treated with CK significantly recovered 60 min after reperfusion, unlike in the control group. CK significantly limited the infarct. These results suggest that CK treatment has distinct anti-ischemic effects in an exvivo model of an ischemia-reperfusion-induced rat heart.

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.

Compound K improves skin barrier function by increasing SPINK5 expression

  • Park, No-June;Bong, Sim-Kyu;Lee, Sullim;Jung, Yujung;Jegal, Hyun;Kim, Jinchul;Kim, Si-Kwan;Kim, Yong Kee;Kim, Su-Nam
    • Journal of Ginseng Research
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    • v.44 no.6
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    • pp.799-807
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    • 2020
  • Background: The skin acts as a barrier to protect organisms against harmful exogenous agents. Compound K (CK) is an active metabolite of ginsenoside Rb1, Rb2 and Rc, and researchers have focused on its skin protective efficacy. In this study, we hypothesized that increased expression of the serine protease inhibitor Kazal type-5 (SPINK5) may improve skin barrier function. Methods: We screened several ginsenosides to increase SPINK5 gene promoter activity using a transactivation assay and found that CK can increase SPINK5 expression. To investigate the protective effect of CK on the skin barrier, RT-PCR and Western blotting were performed to investigate the expression levels of SPINK5, kallikrein 5 (KLK5), KLK7 and PAR2 in UVB-irradiated HaCaT cells. Measurement of transepidermal water loss (TEWL) and histological changes associated with the skin barrier were performed in a UVB-irradiated mouse model and a 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis-like model. Results: CK treatment increased the expression of SPINK5 and decreased the expression of its downstream genes, such as KLKs and PAR2. In the UVB-irradiated mouse model and the DNCB-induced atopic dermatitis model, CK restored increased TEWL and decreased hydration and epidermal hyperplasia. In addition, CK normalized the reduced SPINK5 expression caused by UVB or DNCB, thereby restoring the expression of the proteins involved in desquamation to a level similar to normal. Conclusions: Our data showed that CK contributes to improving skin-barrier function in UVB-irradiated and DNCB-induced atopic dermatitis-like models through SPINK5. These results suggest that therapeutic attempts with CK might be useful in treating barrier-disrupted diseases.

Acute Toxicity Evaluation to Daphnia magna of Disease Resistant(OsCK1) Rice (병저항성 GM(OsCK1)벼의 물벼룩(Daphnia magna)에 대한 급성독성 평가)

  • Oh, Sung-Dug;Lee, Kijong;Park, Soo-Yun;Ryu, Tae-Hun;Suh, Sang Jae
    • Korean Journal of Environmental Agriculture
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    • v.33 no.2
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    • pp.121-128
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    • 2014
  • BACKGROUND: The disease resistant (OsCK1) rice was generated by inserting choline kinase (CK1) and phosphinothricin acetyltransferase (PAT) genes isolated from Oryza sativa and Streptomyces hygroscopicus into the genome of the rice, Nakdongbyeo. With the potential problems of safeties, the evaluations on non-target organisms are essentially required for the environmental risk assessment of genetically modified (GM) crops. In the present study, we conducted the evaluation of acute toxicity on Daphnia magna that commonly used as a model organism in ecotoxicological studies for non-target organism evaluation. METHODS AND RESULTS: Effect of acute toxicity to Daphnia magna by each concentration were investigated in the disease resistant (OsCK1) rice and non-genetically modified (non-GM) rice, Nakdongbyeo, as concentration (0, 1,000, 1,800, 3,240, 5,830, 10,500 and 20,000 mg/L). The OsCK1 rice used for the test was confirmed to express the OsCK1/PAT gene by the PCR(Polymerase chain reaction) and western blot analysis. Feeding test showed that no significant differences in cumulative immobility and abnormal response of Daphnia magna fed on OsCK1 rice or non-GM rice. The 48hr-$EC_{50}$ values showed no difference between OsCK1 rice (3,147.18 mg/L) and non-GM rice (3,596.27 mg/L). CONCLUSION: This result suggested that there was no significant difference in toxicity to Daphnia magna between OsCK1 rice and non-GM counterpart.

Behaviors of Soft Bangkok Clay behind Diaphragm Wall Under Unloading Compression Triaxial Test (삼축압축 하에서 지중연속벽 주변 방콕 연약 점토의 거동)

  • Le, Nghia Trong;Teparaksa, Wanchai;Mitachi, Toshiyuki;Kawaguchi, Takayuki
    • Journal of the Korean Geotechnical Society
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    • v.23 no.9
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    • pp.5-16
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    • 2007
  • The simple linear elastic-perfectly plastic model with soil parameters $s_u,\;E_u$ and n of undrained condition is usually applied to predict the displacement of a constructed diaphragm wall(DW) on soft soils during excavation. However, the application of this soil model for finite element analysis could not interpret the continued increment of the lateral displacement of the DW for the large and deep excavation area both during the elapsed time without activity of excavation and after finishing excavation. To study the characteristic behaviors of soil behind the DW during the periods without excavation, a series of tests on soft Bangkok clay samples are simulated in the same manner as stress condition of soil elements happening behind diaphragm wall by triaxial tests. Three kinds of triaxial tests are carried out in this research: $K_0$ consolidated undrained compression($CK_0U_C$) and $K_0$ consolidated drained/undrained unloading compression with periodic decrement of horizontal pressure($CK_0DUC$ and $CK_0UUC$). The study shows that the shear strength of series $CK_0DUC$ tests is equal to the residual strength of $CK_0UC$ tests. The Young's modulus determined at each decrement step of the horizontal pressure of soil specimen on $CK_0DUC$ tests decreases with increase in the deviator stress. In addition, the slope of Critical State Line of both $CK_0UC$ and $CK_0DUC$ tests is equal. Moreover, the axial and radial strain rates of each decrement of horizontal pressure step of $CK_0DUC$ tests are established with the function of time, a slope of critical state line and a ratio of deviator and mean effective stress. This study shows that the results of the unloading compression triaxial tests can be used to predict the diaphragm wall deflection during excavation.