• 제목/요약/키워드: Tolerance-Accumulation

검색결과 228건 처리시간 0.021초

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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    • 제23권6호
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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.

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

  • 권강무;김준형;양재헌;기별희;황인현;김대근
    • 생약학회지
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    • 제52권4호
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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.

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

  • 김준형;김나영;권강무;황인현;김대근
    • 생약학회지
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    • 제52권2호
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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.

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

  • 김준형;이예빈;한선여;김수진;황인현;김대근
    • 생약학회지
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    • 제50권2호
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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.

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

  • 최지우;김준형;권강무;황인현;주남진;김대근
    • 생약학회지
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    • 제53권4호
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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.

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

  • 김준형;박창범;박종현;권강무;황인현;마상용;오석흥;김대근
    • 생약학회지
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    • 제53권2호
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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.

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

  • 노경희;박종석;강한철;김종범;장영석;김광수;이한길
    • Journal of Applied Biological Chemistry
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    • 제58권4호
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    • pp.325-332
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    • 2015
  • 유채는 월동작물로 내한성이 약해 남부지역에서만 재배가 가능하다. 따라서 재배면적 확대 및 안정적 생산성 확보를 위해 내한성 증진 품종 육성이 절실하다. 본 연구에서는 유채의 내한성을 증진시키기 위해 보리에서 유래한 HvIRIP 유전자를 CaMV35S 프로모터 조절하에서 전신발현되도록 운반체를 제작하였고, 아그로박테리움을 이용하여 유채에 형질전환하였다. Southern 분석을 통해 HvIRIP 유전자가 유채 Genome 안으로 전이 되었음을 확인하였다. 또한 Northern 분석을 통해 $4^{\circ}C$에서 2주간 처리된 유묘에서 HvIRIP 유전자의 발현이 크게 증대되는 것을 알 수 있었다. 본엽 3-4매 전개 유채 형질전환체를 영하 $5^{\circ}C$에서 2일간 저온에 노출한 후 회복여부를 조사한 결과, 대조구는 회복하지 못하고 죽은 반면, 형질전환체는 회복이 정상적으로 이루어졌다. 또한 저온스트레스가 진행되는 동안에 스트레스를 극복하는데 필요한 Proline 함량이 형질전환체에서 크게 증대되는 것이 관찰되었다. 이 외에도 저온스트레스 과정 중에 생성되는 활성산소의 독성을 감소시키는 항산화제 효소인 CAT, SOD 그리고 ADH 활성을 측정한 결과, 대조구에 비해 형질전환체에서 그 함량이 현저히 증가됨을 알 수 있었다. 따라서 이러한 결과를 통해 HvIRIP 유전자가 함유된 유채 형질전환체의 내한성이 증진되었음을 확인하였다.

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

  • 국용인;윤영범
    • 한국잡초학회지
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    • 제30권2호
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    • pp.111-121
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    • 2010
  • Protoporphyrinogen oxidase(Protox) 저해형 제초제인 oxyfluorfen에 대한 내성차이는 동일 개체내의 호박 엽령에서 관찰되었다. 엽위별 oxyfluorfen에 내성기작을 구명하기 위해 잎의 피해정도, 세포내 구성물질의 누출, 포르피린 생합성 경로의 tetrapyrrole 중간물질 축적량 및 항산화효소 활성을 포함한 생리적 반응을 조사하였다. 중앙애호박의 1, 2 및 3엽에 대한 oxyfluorfen에 내성은 4엽에 비해 각각 >10,000, 1,286 및 1.6배 높았고, 신토좌의 1, 2 및 3엽에 대한 oxyfluorfen에 내성은 4엽에 비해 각각 725, 366, >0.6배 높았다. 그러나 oxyfluorfen과 작용기작이 다른 paraquat 처리에서는 oxyfluorfen 처리의 결과와 다르게 두 품종 모두 상위엽인 4엽이 하위엽인 1, 2 및 3엽에 비해 훨씬 피해가 적었다. Oxyfluorfen 처리에 따른 전해물질의 누출은 처리 후 광노출 기간이 경과할수록 상위엽(4엽)에서 하위엽(1, 2, 3엽) 보다 많았다. Oxyfluorfen 처리에 의한 tetrapyrrole 중간물질 protoporphyrin IX(Proto IX), Mg-Proto IX 및 Mg-Proto IX monomethyl ester의 축적량은 감수성인 4엽이 내성인 1엽에 비해 많았다. 따라서 oxyfluorfen 처리에 대한 호박 엽령별 반응 차이는 tetrapyrrole 중간물질의 과다한 축적에 의해 기인되는 것으로 생각된다. Tetrapyrrole 중간 물질 축적량의 결과와 다르게 항산화효소 superoxide dismutase, catalase, peroxidase, ascorbate peroxidase 및 glutathione reductase 활성은 무처리 및 oxyfluorfen 처리 후 4엽이 1엽에 비해 높았다. 그러나 4엽에서 항산화효소 활성 유도는 Protox 저해제 oxyfluorfen의 독성효과를 극복하는데 충분하지 않아 결국 4엽은 고사하게 되는 것으로 생각된다.

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

  • 국용인;구자옥
    • 한국환경농학회지
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    • 제15권3호
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    • pp.316-324
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    • 1996
  • 26종의 식물종을 공시하여 다양한 선발조건에 의해 oxyfluorfen에 내성 및 감수성식물을 선발하여 이들종에 대한 protox 활성 저해, PPIX 축적정도 및 항산화효소 활성을 체계적으로 연구하여 oxyfluorfen의 내성차이를 구명하고자 하였다. Oxyfluorfen 처리에 따른 protox 활성 저해는 내성식물들 보다 감수성 피에서 컸다. 특히, $10^{-6}\;M$ 이상의 농도에서 감수성 피는 완전히 억제되었으나, 내성식물들은 $25{\sim}45%$의 활성을 보였다. 광 ${\cdot}$ 암조건에서 감수성 피는 내성식물종들 비하여 PPIX 축적량이 훨씬 많았다. Oxyfluorfen 처리후 항산화효소인 MDAR, POX, GR 및 SOD의 활성은 내성식물종들이 감수성 피보다 높았다.

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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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    • 제15권3호
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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).