• 제목/요약/키워드: Down-Regulation

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Rosiglitazone Promotes Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL)-induced Apoptosis by Reactive Oxygen Species-mediated Up-regulation of Death Receptor 5 (DR5) and Down-regulation of c-FLIP

  • Kim, Yeon-Hee;Jung, Eun-Mi;Lee, Tae-Jin;Kim, Sang-Hyun;Choi, Yung-Hyun;Park, Jong-Wook;Choi, Kyeong-Sook;Kwon, Taeg-Kyu
    • 한국생명과학회:학술대회논문집
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    • 한국생명과학회 2007년도 제48회 학술심포지움 및 추계국제학술대회
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    • pp.84.2-84.2
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    • 2007
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Design of an Input-Parallel Output-Parallel Multi-Module DC-DC Converter Using a Ring Communication Structure

  • Hu, Tao;Khan, Muhammad Mansoor;Xu, Kai;Zhou, Lixin;Rana, Ahmad
    • Journal of Power Electronics
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    • 제15권4호
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    • pp.886-898
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    • 2015
  • The design feasibility of a micro unidirectional DC transmission system based on an input-parallel output-parallel (IPOP) converter is analyzed in this paper. The system consists of two subsystems: an input-parallel output-series (IPOS) subsystem to step up the DC link voltage, and an input-series output-parallel (ISOP) subsystem to step down the output voltage. The two systems are connected through a transmission line. The challenge of the delay caused by the communication in the control system is addressed by introducing a ring communication structure, and its influence on the control system is analyzed to ensure the feasibility and required performance of the converter system under practical circumstances. Simulation and experiment results are presented to verify the effectiveness of the proposed design.

Legal Regulation and Ways to Overcome Corruption in The Authorities of Public Administration

  • Puzyrnyi, Viacheslav;Liutikova, Margaryta;Butko, Mykola;Lashuk, Oksana;Olyfirenko, Yuliia
    • International Journal of Computer Science & Network Security
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    • 제21권12호
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    • pp.293-299
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    • 2021
  • This study is caused by the urgent need to constantly fight against such a shameful phenomenon of society as corruption, the flourishing of which cannot be overlooked. This phenomenon has many negative manifestations and consequences, undermines the national security of the state, slows down the development of democracy, worsens the state of all spheres of life (economic, political, administrative, etc.), worsens relations with foreign partners, forms tolerance for corruption in the public consciousness. Today, the process of fighting corruption is extremely important for our country, because it depends on the independence, democracy, sustainability of Ukraine. However, there is a complex and ambiguous situation regarding this process, as there is a clear coordination of state policy in the fight against corruption, insufficient and narrow understanding of ways to combat it. There is a lack of efforts by the authorities to overcome corruption challenges and use ineffective means of combating them. Instead, corruption causes great material and moral damage to states as a whole and many of its citizens.

The hypoxia regulation on CYP4501Al expression

  • Kim, Ji E.;Yhun Y. Sheen
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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    • pp.140-140
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    • 1998
  • The aim of this study was to find out the effect of hypoxic condition on the regulation of cyplal gene expression. pcyplal-Luc construct was cloned and transfected into Hepa I cells. When Hepa-I cells containing pcyplal-Luc were treated by DFO (desferrioxamine) which is iron-chelating agent, the stimulatory effect of luciferase by TCDD was decreased. This inhibitory effect of desferrioxamine on the luciferase activity was dose dependent and abolished by concomitant treatment with N$\^$G/-nitro-ι-arginine. And when cobalt chloride which is known as a hypoxia inducing chemical was administrated, the stimulatory effect of luciferase by TCDD was also decreased. This inhibitory effect of cobalt chloride on the luciferase activity was dose dependent and abolished by concomitant treatment with N$\^$G/-nitro-ι-arginine. These data showed that hypoxic condition down regulates cyplal gene expression and this might be through nitric oxide action.

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Down-regulation of Protease-activated Receptor 4 in Lung Adenocarcinoma is Associated with a More Aggressive Phenotype

  • Jiang, Ping;Yu, Guo-Yu;Zhang, Yong;Xiang, Yang;Hua, Hai-Rong;Bian, Li;Wang, Chun-Yan;Lee, Wen-Hui;Zhang, Yun
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권6호
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    • pp.3793-3798
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    • 2013
  • The role of protease-activated receptors (PARs) in lung tumors is controversial. Although PAR4 is preferentially expressed in human lung tissues, its possible significance in lung cancer has not been defined. The studies reported herein used a combination of clinical observations and molecular methods. Surgically resected lung adenocarcinomas and associated adjacent normal lung tissues were collected and BEAS-2B and NCI-H157 cell lines were grown in tissue culture. PAR4 expression was evaluated by RT-PCR, RT-qPCR, Western blotting and immunohistochemistry analysis. The results showed that PAR4 mRNA expression was generally decreased in lung adenocarcinoma tissues as compared with matched noncancerous tissues (67.7%) and was associated with poor differentiation (p=0.017) and metastasis (p=0.04). Western blotting and immunohistochemical analysis also showed that PAR4 protein levels were mostly decreased in lung adenocarcinoma tissues (61.3%), and were also associated with poor differentiation (p=0.035) and clinical stage (p=0.027). Moreover, PAR4 expression was decreased in NCI-H157 cells as compared with BEAS-2B cells. In conclusion, PAR4 expression is significantly decreased in lung adenocarcinoma, and down-regulation of PAR4 is associated with a more clinically aggressive phenotype. PAR4 may acts as a tumor suppressor in lung adenocarcinoma.

Post-cancer Treatment with Condurango 30C Shows Amelioration of Benzo[a]pyrene-induced Lung Cancer in Rats Through the Molecular Pathway of Caspase-3-mediated Apoptosis Induction -Anti-lung cancer potential of Condurango 30C in rats-

  • Sikdar, Sourav;Mukherjee, Avinaba;Bishayee, Kausik;Paul, Avijit;Saha, Santu Kumar;Ghosh, Samrat;Khuda-Bukhsh, Anisur Rahman
    • 대한약침학회지
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    • 제16권3호
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    • pp.11-22
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    • 2013
  • Objectives: The present investigation aimed at examining if post-cancer treatment with a potentized homeopathic drug, Condurango 30C, which is generally used to treat oesophageal cancer, could also show an ameliorating effect through apoptosis induction on lung cancer induced by benzo[a]pyrene (BaP) in white rats (Rattus norvegicus). Methods: Lung cancer was induced after four months by chronic feeding of BaP to rats through gavage at a dose of 50 mg/kg body weight for one month. After four months, the lung-cancer-bearing rats were treated with Condurango 30C for the next one ($5^{th}$), two ($5^{th}-6^{th}$) and three ($5^{th}-7^{th}$) months, respectively, and were sacrificed at the corresponding time-points. The ameliorating effect, if any, after Condurango 30C treatment for the various periods was evaluated by using protocols such as histology, scanning electron microscopy (SEM), annexinV-FITC/PI assay, flow cytometry of the apoptosis marker, DNA fragmentation, reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and western blot analyses of lung tissue samples. Results: Striking recovery of lung tissue to a near normal status was noticed after post-cancerous drug treatment, as evidenced by SEM and histology, especially after one and two months of drug treatment. Data from the annexinV-FITC/PI and DNA fragmentation assays revealed that Condurango 30C could induce apoptosis in cancer cells after post-cancer treatment. A critical analysis of signalling cascade, evidenced through a RT-PCR study, demonstrated up-regulation and down-regulation of different pro- and anti-apoptotic genes, respectively, related to a caspase-3-mediated apoptotic pathway, which was especially discernible after one-month and two-month drug treatments. Correspondingly, Western blot and immunohistochemistry studies confirmed the ameliorative potential of Condurango 30C by its ability to down-regulate the elevated epidermal growth factor receptor (EGFR) expression, a hallmark of lung cancer. Conclusion: The overall result validated a positive effect of Condurango 30C in ameliorating lung cancer through caspase-3-mediated apoptosis induction and EGFR down-regulation.

시토신 탈메틸화 관련 NtROS2a 유전자 발현을 제어한 RNAi 식물의 DNA microarray 분석 (DNA microarray analysis of RNAi plant regulated expression of NtROS2a gene encoding cytosine DNA demethylation)

  • 최장선;이인혜;정유진;강권규
    • Journal of Plant Biotechnology
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    • 제43권2호
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    • pp.231-239
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    • 2016
  • 담배에서 후성유전관련 유전자의 발현연구를 위해 담배유래 시토신 DNA 탈메틸화 관련 NtROS2a 유전자를 과발현 및 RNAi 식물체를 육성하였다. 이들 형질전환체들은 고염 및 산화 스트레스하에서 내성이 증진되었으며, 다양한 표현형변이를 보였다(Lee et al. 2015). 본연구에서는 선발된 과발현 (OX1), RNAi 식물체(RNAi 13) 및 대조식물체(WT)를 이용하여 Agilent Tobacco 4 X 44K Oligo chip으로 microarray분석을 수행하였다. OX1과 RNAi13 계통을 이용하여 WT과 함께 비교 분석한 결과, 대부분 세포 내 이온 수송, 영양 공급 등과 같은 물질대사와 생물적 비생물적 스트레스 및 methylation과 관련되어 영향을 주는 유전자들에서 up-regulation 되었고, 물질대사관련 유전자와 세포 내 기능유전자의 역할을 담당하는 조효소, 그리고 다양한 스트레스 및 메틸레이션 관련 유전자군에서 또한 down-regulation되었다. 각각의 up-, down-regulation된 유전자들을 WT과 비교하여 qRT-PCR을 수행한 결과, KH domain-containing protein, MADS-box protein 및 Zinc phosphodiesterase ELAC protein 유전자들에서 발현이 높게 나타났으며, 반면에 pentatricopeptide (PPR) repeat-containing protein, histone deacetylase HDAC3 protein 및 protein kinase는 0.4 ~ 1.0-fold 발현양이 감소되었다. 따라서 DNA glycosylase를 암호화하는 NtROS2a 유전자는 demethylation과 관련되어 담배 식물체에서 다양한 전사레벨을 조절하는 것으로 판단된다.

Snail의 Akt/PKB의 활성화와 p53의 downregulation를 통한 5-FU-induced apoptosis의 necrosis로의 전환 (Snail Switches 5-FU-induced Apoptosis to Necrosis through Akt/PKB Activation and p53 Down-regulation)

  • 이수연;전현민;주민경;김초희;정의경;박혜경;강호성
    • 생명과학회지
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    • 제22권8호
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    • pp.1018-1023
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    • 2012
  • Snail은 E-cadherin 발현을 직접 억제하는 zinc finger transcription factor로서, 암세포의 invasion과 metastasis를 촉진시키는 epithelial-mesenchymal transition (EMT)를 유발한다. 또한 Snail은 세포사멸 자극과 세포 생존물질의 제거로 인한 세포사멸에 대해 저항성을 나타낸다. 그러나 이에 대한 분자기작은 잘 알려져 있지 않다. 본 연구에서는 가장 널리 사용되는 항암제 중의 하나인 5-fluorouracil (5-FU)에 의한 세포사멸에 대한 Snail의 저항성 기작에 대하여 조사하였다. MCF-7 #5 세포주에 doxycycline (DOX)을 처리하여 Snail을 과발현시킨 세포에서 5-FU에 의한 세포사멸이 억제되고 세포괴사가 일어남을 확인하였다. DOX 처리 및 Snail expression vectors인 pCR3.1-Snail-Flg와 phosphorylation-resistant mutant Snail vector인 pCR3.1-S104, 107A Snail-Flg을 이용하여 Snail을 과발현 시킨 경우 ERK1/2의 활성에는 영향을 주지 않는 반면 PTEN 발현억제 및 불활성화, 그리고 Akt/PKB 활성화가 유도됨을 관찰하였다. 또한, Snail은 5-FU에 의한 p53의 발현을 억제한다는 사실을 확인하였다. 따라서 Snail은 prosurvival kinase인 Akt/PKB의 활성화와 p53 억제를 통해 5-FU에 의한 세포사멸을 세포괴사로 전환하는 것으로 생각된다.

SIRT1 inhibitor에 의한 Hsp90 inhibitor의 Hsp90 샤페론 기능 억제 및 항암제 내성세포의 Hsp90 inhibitor에 대한 세포독성 증강 (SIRT1 Inhibitor Enhances Hsp90 Inhibitor-mediated Abrogation of Hsp90 Chaperone Function and Potentiates the Cytotoxicity of Hsp90 Inhibitor in Chemo-resistant Human Cancer Cells)

  • 문현정;이수훈;김학봉;이경아;강치덕;김선희
    • 생명과학회지
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    • 제26권7호
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    • pp.826-834
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    • 2016
  • 본 연구는 Hsp90 inhibitor 및 SIRT1 inhibitor의 병용처리가 항암제 다제내성(MDR) 인간 암세포의 증식 억제에 효과적임을 밝혔다. SIRT1 활성 억제가 Hsp90 inhibitor인 17-AAG의 세포 독성의 효과를 증강시켰으며, 이로 인해 Hsp90 inhibitors에 대한 내성을 극복시킬 수 있음을 인간 자궁암세포인 HeyA8의 MDR 변이주인 HeyA8- MDR 세포에서 확인하였다. SIRT1 inhibitor는 Hsp90 inhibitor에 의한 Hsp90 샤페론 기능 억제를 증강시키며, ubiquitin ligase CHIP의 발현 증강을 유발하여, Hsp90 client protein 인 mutant p53 (mut p53)의 분해를 촉진시킨다. Mut p53 의 발현 감소는 암세포의 Hsp90 inhibitor 내성 획득의 가장 중요한 원인으로 지적되는 heat shock factor 1 (HSF1)/heat shock proteins (Hsps)의 발현 억제와 관련됨을 알 수 있었으며, 이는 항암제 다제내성 세포에서 SIRT1 inhibitor에 의하여 Hsp90 inhibitor에 대한 감수성이 증강되는 분자적 기전임을 밝혔다. 그러므로, SIRT1 억제에 의한 mut p53/HSF1 발현 감소가 MDR 암세포의 Hsp90 inhibitors 내성 극복에 매우 유효함을 시사하는 결과를 얻었다.

Artesunate와 비스테로이드소염제 NSAID의 병용 처리에 의한 항암 활성 증강 (Potentiation of Anticancer Effect of Artesunate by Combination with Nonsteroidal Anti-inflammatory Drugs on Human Cancer Cells)

  • 문현정;강치덕;김선희
    • 생명과학회지
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    • 제31권10호
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    • pp.873-884
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    • 2021
  • 본 연구에서는 다양한 인체 암포주를 대상으로 NSAID의 항암 효과를 증강시키는 artesunate (ART)의 역할과 이에 대한 분자적 기전을 연구하였다. 다양한 타입의 암세포주를 대상으로 암세포 성장 억제 활성을 조사한 결과, ART는 NSAID인 celecoxib (CCB) 또는 dimethyl-CCB (DMC)와의 병용 효과를 나타내었다. ART 처리로 ATF4/CHOP의 발현 증강과 함께 오토파지 유도 표식인 p62 감소의 결과로서, ATF4/CHOP 경로가 ART의 오토파지 유도 활성에 관여할 것으로 예상되었으며, ART의 오토파지 활성과 관련하여 NRF2 및 암 줄기 세포 관련 단백질인 CD44, CD133, ALDH1, Oct4, mutated p53 (mutp53) 및 c-Myc의 발현이 감소되었다. 또한 DMC 단독처리 보다 ART와 DMC의 병용으로 ATF4/CHOP의 발현 증강과 p62의 감소가 더욱 촉진되고, NRF2 및 암 줄기 세포 관련 단백질 발현 감소도 현저히 촉진되면서 궁극적으로 PARP 활성화에 의해 apoptosis가 유도됨을 알 수 있었다. 이러한 결과는 ART/DMC 병용 처리가 각 물질 단독 처리보다 암세포의 성장 억제 및 apoptosis 유도에 더욱 효과적이고, ART 및 DMC 의 오토파지 유도 활성은 암 줄기 세포 관련 단백질의 분해를 촉진함으로써, 암 줄기 세포가 제거될 수 있음을 시사하였다. 이와 같이 ART는 NSAID 뿐만 아니라 imatinib의 항암 효과를 증강시키는 활성으로, chemosensitizer로서 중요한 후보 물질이 될 수 있음을 밝혔다.