• Title/Summary/Keyword: Tolerance-Accumulation

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Efficacy of evogliptin and cenicriviroc against nonalcoholic steatohepatitis in mice: a comparative study

  • Wang, Zheng;Park, Hansu;Bae, Eun Ju
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.6
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    • pp.459-466
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    • 2019
  • Dipeptidyl peptidase (DPP)-4 inhibitors, or gliptins, are a class of oral hypoglycemic drugs that have been widely used as a second-line treatment for type 2 diabetes. Gliptins, which were introduced for clinical use a decade ago, have been shown to be beneficial against nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NASH) in animals and humans. Cenicriviroc (CVC), a dual antagonist of C-C chemokine receptor type 2 and 5, is currently under investigation against NASH and fibrosis. It was previously discovered that evogliptin (EVO) reduces hepatic steatosis in diet-induced obese animals but the effectiveness of EVO on NASH remains unexplored. Here, we compared the effectiveness of EVO and CVC against NASH and fibrosis in mice fed a high-fat and high-fructose diet (HFHF). Biochemical and histological analyses showed that mice fed a HFHF for 20 weeks developed severe hepatic steatosis and inflammation with mild fibrosis. Administration of EVO (0.2% wt/wt) for the last 8 weeks of HFHF feeding significantly reduced hepatic triglyceride accumulation, inflammation, and fibrosis as well as restored insulin sensitivity, as evidenced by lowered plasma insulin levels and the improvement in insulin tolerance test curves. Treatment of mice with CVC (0.1% wt/wt) inhibited hepatic inflammation and fibrogenesis with similar efficacy to that of EVO, without affecting hepatic steatosis. CVC treatment also reduced plasma insulin concentrations, despite no improvement in insulin tolerance. In conclusion, EVO administration efficiently ameliorated the development of NASH and fibrosis in HFHF-fed mice, corroborating its therapeutic potential.

Antioxidant Activity of Ethyl acetate Fraction of Oat in Caenorhabditis elegans (귀리 Ethyl acetate 분획물의 예쁜 꼬마선충 내의 항산화 효과)

  • Kwon, Kang Mu;Kim, Jun Hyeong;Yang, Jae Heon;Ki, Byeolhui;Hwang, In Hyun;Kim, Dae Keun
    • Korean Journal of Pharmacognosy
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    • v.52 no.4
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    • pp.251-256
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    • 2021
  • Oat, the seeds of Avena sativa L. (Gramineae), is an important dietary staple for people in many countries. Previous studies reported that A. sativa had various pharmacological effects such as anti-inflammatory, antitumor, neurotonic, and antispasmodic activities. In this study, Caenorhabditis elegans model system was used to investigate the antioxidant activity of methanol extract of oat. The ethyl acetate soluble fraction of the oat methanol extract showed the best DPPH radical scavenging activity. The ethyl acetate fraction was measured for the activity of superoxide dismutase (SOD), catalase, and oxidative stress tolerance by using C. elegans along with reactive oxygen species (ROS) level. In addition, to confirm that the regulation of the stress response gene is responsible for the increased stress tolerance of C. elegans treated by the ethyl acetate fraction, SOD-3 expression was measured using GFP-expressing transgenic worm. As a result, the ethyl acetate fraction increased SOD and catalase activities, and decreased ROS accumulation in a dose-dependent manner. In addition, the ethyl acetate fraction-treated CF1553 worm showed higher SOD-3::GFP intensity compared to the control.

Antioxidant Activities of n-Butanol Fraction of Pinus densiflora Siebold & Zucc. Needle in Caenorhabditis elegans. (솔잎 부탄올 분획의 예쁜꼬마선충 내의 항산화 효과)

  • Kim, Jun Hyeong;Kim, Na Yeong;Kwon, Kang Mu;Hwang, In Hyun;Kim, Dae Keun
    • Korean Journal of Pharmacognosy
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    • v.52 no.2
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    • pp.105-111
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    • 2021
  • To investigate the antioxidant activities of Pinus densiflora needle (Pinaceae), which is widely used as a traditional medicine in Korea, Caenorhabditis elegans model system was used. The n-butanol fraction of P. densiflora needle methanol extract showed the most potent DPPH radical scavenging and superoxide quenching activities in a dose-dependent manner. The n-butanol fraction was measured for the activities of superoxide dismutase (SOD), catalase, and oxidative stress tolerance by using C. elegans with reactive oxygen species (ROS) level. In addition, to see that the regulation of the stress response gene is responsible for the increased stress tolerance of C. elegans treated by the butanol extract, SOD-3 expression was measured using a transgenic strain. As a result, the P. densiflora needle n-butanol fraction increased SOD and catalase activities, and decreased ROS accumulation, dose-dependently. Furthermore, the n-butanol fraction-treated CF1553 worm showed higher SOD-3::GFP intensity than the control.

Antioxidant Activity of Helianthus tuberosus L. Flower in Caenorhabditis elegans (돼지감자꽃의 예쁜꼬마선충 내의 항산화 효과)

  • Kim, Jun Hyeong;Lee, Ye Bin;Han, Seon Yeo;Kim, Su Jin;Hwang, In Hyun;Kim, Dae Keun
    • Korean Journal of Pharmacognosy
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    • v.50 no.2
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    • pp.96-101
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    • 2019
  • Methanol extract of Helianthus tuberosus L. (Compositae) flower was investigated to research the anti-oxidative activity by using a Caenorhabditis elegans model system. Ethyl acetate soluble fraction of the methanol extract showed the most potent DPPH radical scavenging activity. The ethyl acetate fraction was measured on its activities of superoxide dismutase (SOD), catalase, and oxidative stress tolerance with reactive oxygen species (ROS) level in C. elegans. Furthermore, in order to verify if regulation of stress-response gene is responsible for the increased stress tolerance of C. elegans which treated by the ethyl acetate fraction, we checked SOD-3 expression using a transgenic strain. Consequently, the ethyl acetate fraction of H. tuberosus flower increased the catalase and SOD activities in a dose-dependent manner in C. elegans, reduced ROS accumulation dose-dependently. Besides, the ethyl acetate fraction-treated CF1553 worms showed higher SOD-3::GFP intensity than the control group.

Antioxidant Activity of Ethyl acetate Fraction of Ixeris dentata (Thunb.) Nakai in Caenorhabditis elegans (씀바귀 Ethyl acetate 분획물의 예쁜 꼬마선충 내의 항산화 효과)

  • Ji Woo, Choi;Jun Hyeong, Kim;Kang Mu, Kwon;In Hyun, Hwang;Nam Jin, Ju;Dae Keun, Kim
    • Korean Journal of Pharmacognosy
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    • v.53 no.4
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    • pp.207-212
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    • 2022
  • Through the Caenorhabditis elegans model system, the antioxidant activity of methanol extract of Ixeis dentata was investigated. The ethyl acetate soluble fraction of the I. dentata methanol extract showed the best DPPH radical scavenging activity. The ethyl acetate fraction was measured for the activity of superoxide dismutase (SOD), catalase, and oxidative stress tolerance by using C. elegans along with reactive oxygen species (ROS) level. In addition, to confirm that the regulation of the stress response gene is responsible for the increased stress tolerance of C. elegans treated by the ethyl acetate fraction, SOD-3 expression was measured using a transgenic strain (CF1553). As a result, the ethyl acetate fraction increased SOD and catalase activity, and decreased ROS accumulation in a dose-dependent manner. In addition, the ethyl acetate fraction-treated CF1553 worm showed higher SOD-3::GFP intensity than the control worm.

Antioxidant Activity of Ethyl acetate Fraction of Melampyrum roseum Maxim. in Caenorhabditis elegans (꽃며느리밥풀 Ethyl acetate 분획물의 예쁜 꼬마선충에 대한 항산화 효과)

  • Kim, Jun Hyeong;Park, Chang Bum;Park, Jong Hyun;Kwon, Kang Mu;Hwang, In Hyun;Ma, Sang Yong;Oh, Suk-Heung;Kim, Dae Keun
    • Korean Journal of Pharmacognosy
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    • v.53 no.2
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    • pp.96-101
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    • 2022
  • Caenorhabditis elegans model system was used to investigate the antioxidant activity of methanol extract of Melampyrum roseum (Scrophulariaceae). The ethyl acetate soluble fraction of the M. roseum methanol extract showed the best DPPH radical scavenging activity. The ethyl acetate fraction was measured for the activity of superoxide dismutase (SOD), catalase, and oxidative stress tolerance by using C. elegans along with reactive oxygen species (ROS) level. In addition, to confirm that the regulation of the stress response gene is responsible for the increased stress tolerance of C. elegans treated by the ethyl acetate fraction, SOD-3 expression was measured using a transgenic strain. As a result, the ethyl acetate fraction increased SOD and catalase activity, and decreased ROS accumulation in a dose-dependent manner. In addition, the ethyl acetate fraction-treated CF1553 worm showed higher SOD-3::GFP intensity than the control worm.

Overexpression of Ice Recrystallization Inhibition Protein (HvIRIP) from Barley Enhances Cold Tolerance in Transgenic rapeseed plants (HvIRIP 과발현 유채 형질전환체의 내한성 증진)

  • Roh, Kyung Hee;Park, Jong-Sug;Kang, Han-Chul;Kim, Jong-Bum;Jang, Young-Suk;Kim, Kwang-Soo;Yi, Hankuil
    • Journal of Applied Biological Chemistry
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    • v.58 no.4
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    • pp.325-332
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    • 2015
  • Rapeseed (Brassica napus) is now the second largest oilseed crop after soybean. Cold temperature tolerance is an important agronomic trait in winter rapeseed that determines the plant's ability to control below freezing temperatures. To improve cold tolerance of rapeseed plants, an expression vector containing an Barley Ice recrystallization inhibition protein (HvIRIP) cDNA driven by a cauliflower mosaic virus 35S promoter was transferred into rapeseed plants. Transgenic expression of HvIRIP was proved by southern- and northern-blot analyses. The level of freezing tolerance of transgenic $T_3$ plants was found to be significantly greater than that of wild-type rapeseed plants by freezing assay. Proline accumulation during cold stress was also highly induced in the transgenic rapeseed plants. The transgenic plants exhibited considerable tolerance against oxidative damage induced by cold stress. Our results indicated that heterologous HvIRIP expression in transgenic rapeseed plants may induce several oxidative-stress responsive genes to protect from cold stress.

Mechanism of Protoporphyrinogen Oxidase-inhibiting Herbicide, Oxyfluorfen Tolerance in Squash leaves of Various Ages (Protoporphyrinogen Oxidase 저해형 제초제 Oxyfluorfen에 대한 호박 엽령별 내성기작)

  • Kuk, Yong-In;Yun, Young-Beom
    • Korean Journal of Weed Science
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    • v.30 no.2
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    • pp.111-121
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    • 2010
  • Differential tolerance to protoporphyrinogen oxidase (Protox)-inhibiting herbicides, oxyfluorfen was observed between leaf ages in squash. Physiological responses to oxyfluorfen, including leaf injury, cellular leakage, accumulation of tetrapyrroles, and antioxidative enzymes activity, were investigated in leaf age classes of squash to identify mechanisms of oxyfluorfen tolerance. Leaf 1, 2, and 3 injuries for Joongangaehobak were >10,000, 1,286, and 1.6-fold higher than that of leaf 4, after treatment of oxyfluorfen. On the other hand, leaf 1, 2, and 3 injuries for Sintowjahobak were 725, 366, and >0.6-fold higher than that of leaf 4, after treatment of oxyfluorfen. However, in contrast to oxyfluorfen treatment results, leaf injury of squash leaf 4 treated with paraquat was much smaller than in leaves 1, 2 and 3. Electrolyte leakage from the tissues treated with oxyfluorfen was higher in the youngest leaf (Leaf 4) than in the older leaves 1, 2, and 3. Differential leaf response to oxyfluorfen of squash appears to be due in large part to differences in protoporphyrin IX (Proto IX), Mg-Proto IX, and Mg-Proto IX monomethyl ester accumulation in treated leaves. In contrast, leaf 4 had higher activities of superoxide dismutase, catalase, peroxidase, ascorbate peroxidase, and glutathione reductase than leaf 1 after treatment with oxyfluorfen. However, the induction in antioxidant activity in leaf 4 was not enough to overcome the toxic effects of a Protox inhibitor, oxyfluorfen, so the leaf eventually died.

Differential Tolerance of Plant Species to Protoporphyrinogen Oxidase-Inhibiting Oxyfluorfen (Protoporphyrinogen oxidase 저해형 Oxyfluorfen에 대한 식물종간 내성차이)

  • Kuk, Yong-In;Guh, Ja-Ock
    • Korean Journal of Environmental Agriculture
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    • v.15 no.3
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    • pp.316-324
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    • 1996
  • The four tolerant and one susceptible plant to oxyfluorfen were selected from 26 species and investigated for the inhibition of protox activity, the PPIX accumulation, and the activity of antioxidative enzymes by oxyfluorfen treatment. When treated, the oxyfluorfen-tolerant plant species showed a less decrease in fresh weight and height than the susceptible one. The susceptible barnyardgrass showed more inhibition of protox activity due to the treatment of oxyfluorfen than the tolerant species. Especially at the concentration of $10^{-6}M$, protox activity of the susceptible barnyardgrass was inhibited completely, but tolerant species maintained $25{\sim}45%$ of the activity. Under the light and dark condition, the susceptible barnyardgrass showed more PPIX accumulation than the tolerant.

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Approaching the assessment of ageing bridge infrastructure

  • Boller, Christian;Starke, Peter;Dobmann, Gerd;Kuo, Chen-Ming;Kuo, Chung-Hsin
    • Smart Structures and Systems
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    • v.15 no.3
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    • pp.593-608
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    • 2015
  • In many of the industrialized countries an increasing amount of infrastructure is ageing. This has become specifically critical to bridges which are a major asset with respect to keeping an economy alive. Life of this infrastructure is scattering but often little quantifiable information is known with respect to its damage condition. This article describes how a damage tolerance approach used in aviation today may even be applied to civil infrastructure in the sense that operational life can be applied in the context of modern life cycle management. This can be applied for steel structures as a complete process where much of the damage accumulation behavior is known and may even be adopted to concrete structures in principle, where much of the missing knowledge in damage accumulation has to be substituted by enhanced inspection. This enhanced and continuous inspection can be achieved through robotic systems in a first approach as well as built in sensors in the sense of structural health monitoring (SHM).