• 제목/요약/키워드: Promising target

검색결과 444건 처리시간 0.025초

Apios fortunei, Colubrina arborescens, Croton caudatus, Osmanthus matsumuranus, 그리고 Schima noronhae를 포함하는 5종 식물 추출물의 항산화 활성 (Anti-oxidative Activity of Five Plant Extracts including Apios fortune, Colubrina arborescens, Croton caudatus, Osmanthus matsumuranus and Schima noronhae)

  • 이수현;진경숙;권현주;김병우
    • 생명과학회지
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    • 제28권9호
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    • pp.1092-1099
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    • 2018
  • 본 연구에서는 식물자원으로부터 생리활성을 보유한 새로운 기능성 소재를 찾고자 하였다. 이를 위해 수종의 식물 추출물을 분석하여 강한 항산화능을 보유한 5종(Apios fortunei Maxim., Colubrina arborescens Sarg., Croton caudatus Geiseler, Osmanthus matsumuranus Hayata 그리고 Schima noronhae Reinw.)을 선별하고, 각 추출물의 항산화 활성을 시험관 분석법, 세포실험 모델계, 대상 단백질 발현 분석 등을 통해 평가하였다. 먼저 각 추출물의 항산화 활성을 DPPH 라디칼 소거능을 통해 분석한 결과 모두 양성 대조군으로 사용한 아스코르빈산과 유사한 정도의 높은 활성을 보여 각 소재가 매우 강한 항산화능을 보유함을 확인하였다. 또한 RAW 264.7 세포주에서 $H_2O_2$에 의해 유도된 ROS에 대한 각 추출물의 소거능을 분석한 결과에서도 농도의존적인 강한 소거능을 보였다. 뿐만 아니라 대표적인 항산화효소 중 하나로 항산화능 보유 천연물에 의해 발현이 유도되는 HO-1 및 그 전사인자인 Nrf2의 단백질 발현이 각 추출물의 처리에 의해 증가됨을 보였다. 이러한 결과를 통해 5종 식물 추출물의 강한 항산화 활성을 처음으로 확인하였으며 향후 기능성 소재로서 유용하게 활용될 수 있을 것으로 판단된다.

인체폐암세포 A549의 세포주기 조절인자에 미치는 histone deacetylase inhibitor trichostatin A의 영향 (Modulacon of Cell Cycle Control by Histone Deacetylase Inhibitor Trichostatin A in A549 Human Non-small Cell Lung Cancer Cells)

  • 황지원;김영민;홍수현;최병태;이원호;최영현
    • 생명과학회지
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    • 제15권5호
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    • pp.726-733
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    • 2005
  • Histone deacetylase (HDAC) 억제제가 새로운 항암치료제 후보물질로서 유용성이 높은 것으로 평가되지만, 아직까지 인체폐암세포에 관한 연구는 상대적으로 미미한 실정이다. 따라서 본 연구에서는 폐암세포에 미치는 HDAC 억제제의 항암작용 기전을 조사하기 위하여 A549 인체폐암세포주를 대상으로 암세포의 증식에 미치는 대표적인 HDAC 억제제인 tichostatin A (TSA)에 의한 영향을 세포주기 조절관련인자 중심으로 조사하였다. TSA의 처리에 의하여 A549 폐암세포의 증식은 처리 농도 의존적으로 억제되었으며, 심한 형태적 변형을 동반하였다. 저농도 처리군에서는 TSA 농도가 증가할수록 세포주기 G1기의 빈도가 증가하였으나, 고농도 처리군에서는 G2/M기에 속하는 세포의 빈도가 증가되었다. 또한 apoptosis 유발의 간접적인 지표가 되는 sub-G1기에 속하는 세포의 빈도 역시 TSA 처리 농도 의존적으로 매우 증가되었다. 이러한 TSA의 A549 폐암세포 증식억제 효과는 cyclins 및 CdkS의 발현 억제, 종양억제유전자인 p53 및 Cdks 억제제인 p21과 p27의 발현 증가와도 연관성이 있었다. TSA의 항암 기전을 규명하기 위해서는 더 많은 연구가 부가적으로 필요하겠지만, 본 연구의 결과들에 의하면 TSA는 강력한 인체폐암세포의 증식 억제 및 항암작용이 있음을 시사하여 준다고 할 수 있다.

Molecular and Biochemical Properties of a Cysteine Protease of Acanthamoeba castellanii

  • Hong, Yeonchul;Kang, Jung-Mi;Joo, So-Young;Song, Su-Min;Le, Huong Giang;Thai, Thl Lam;Lee, Jinyoung;Goo, Youn-Kyoung;Chung, Dong-Il;Sohn, Woon-Mok;Na, Byoung-Kuk
    • Parasites, Hosts and Diseases
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    • 제56권5호
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    • pp.409-418
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    • 2018
  • Acanthamoeba spp. are free-living protozoa that are opportunistic pathogens for humans. Cysteine proteases of Acanthamoeba have been partially characterized, but their biochemical and functional properties are not clearly understood yet. In this study, we isolated a gene encoding cysteine protease of A. castellanii (AcCP) and its biochemical and functional properties were analyzed. Sequence analysis of AcCP suggests that this enzyme is a typical cathepsin L family cysteine protease, which shares similar structural characteristics with other cathepsin L-like enzymes. The recombinant AcCP showed enzymatic activity in acidic conditions with an optimum at pH 4.0. The recombinant enzyme effectively hydrolyzed human proteins including hemoglobin, albumin, immunoglobuins A and G, and fibronectin at acidic pH. AcCP mainly localized in lysosomal compartment and its expression was observed in both trophozoites and cysts. AcCP was also identified in cultured medium of A. castellanii. Considering to lysosomal localization, secretion or release by trophozoites and continuous expression in trophozoites and cysts, the enzyme could be a multifunctional enzyme that plays important biological functions for nutrition, development and pathogenicity of A. castellanii. These results also imply that AcCP can be a promising target for development of chemotherapeutic drug for Acanthamoeba infections.

게임 맵 디자인을 위한 협업 가상 환경에서의 동시성 제어 및 공동 편집 방법 (A Concurrency Control and a Collaborative Editing Mechanism in a Collaborative Virtual Environment for Designing a Game Map)

  • 박성준;이준;임민규;김지인
    • 한국게임학회 논문지
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    • 제11권4호
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    • pp.15-26
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    • 2011
  • 게임 레벨 디자인은 재미있는 게임 플레이를 위하여 매우 중요한 게임 제작 요소 중의 하나이며, 게임의 플레이가 이루어지는 공간의 구성 및 해당 맵의 제작, 세부적인 장치, 객체와 물체의 설정 및 배치, 배경 설정 및 이벤트 연출 등을 설계하는 과정이다. 게임 맵 디자인 과정은 다수의 3D 객체를 공간 속에 배치하고, 지속적인 평가, 수정 및 보완 과정을 통하여 게임 공간의 성능을 개선하여야 하므로, 그 과정에서 비용과 시간을 많이 사용하게 된다. 하지만 기존의 게임 제작 환경에서는 여러 개발자들이 공동으로 작업을 하게 되므로, 게임 공간 속의 객체 및 작업들에 대한 동시성 제어가 어려워서, 전반적인 작업의 일관성이 유지가 되지 못하는 문제가 발생하고 있으며, 또한 공동 편집 과정이 복잡해지면 공동 작업의 품질이 하락하는 문제가 발생하고 있다. 본 논문에서는 이러한 문제를 해결하기 위해 게임 맵 디자인을 위한 협업 가상 환경에서의 동시성 제어 및 공동 편집 방법을 제안한다. 제안된 시스템은 계층 구조 기반의 객체들을 사용하고, 각 객체별 동시성 제어 기법을 제공한다. 또한 공동 편집 작업을 원활하게 수행하기에 필요한 소유권 관리 기반 Undo/Redo 메커니즘을 제공한다. 실험 결과 본 논문에서 제안한 시스템을 사용 하는 경우에 충돌의 횟수가 감소하며, 다른 개발자들이 작업을 취소하여 재수정을 하는 등의 불필요한 작업 횟수가 감소하는 결과를 가져 왔다.

Trametes villosa Lignin Peroxidase (TvLiP): Genetic and Molecular Characterization

  • Carneiro, Rita Terezinha de Oliveira;Lopes, Maiza Alves;Silva, Marilia Lordelo Cardoso;Santos, Veronica da Silva;Souza, Volnei Brito de;Sousa, Aurizangela Oliveira de;Pirovani, Carlos Priminho;Koblitz, Maria Gabriela Bello;Benevides, Raquel Guimaraes;Goes-Neto, Aristoteles
    • Journal of Microbiology and Biotechnology
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    • 제27권1호
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    • pp.179-188
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    • 2017
  • White-rot basidiomycetes are the organisms that decompose lignin most efficiently, and Trametes villosa is a promising species for ligninolytic enzyme production. There are several publications on T. villosa applications for lignin degradation regarding the expression and secretion of laccase and manganese peroxidase (MnP) but no reports on the identification and characterization of lignin peroxidase (LiP), a relevant enzyme for the efficient breakdown of lignin. The object of this study was to identify and partially characterize, for the first time, gDNA, mRNA, and the corresponding lignin peroxidase (TvLiP) protein from T. villosa strain CCMB561 from the Brazilian semiarid region. The presence of ligninolytic enzymes produced by this strain grown in inducer media was qualitatively and quantitatively analyzed by spectrophotometry, qPCR, and dye fading using Remazol Brilliant Blue R. The spectrophotometric analysis showed that LiP activity was higher than that of MnP. The greatest LiP expression as measured by qPCR occurred on the $7^{th}$ day, and the ABSA medium (agar, sugarcane bagasse, and ammonium sulfate) was the best that favored LiP expression. The amplification of the TvLiP gene median region covering approximately 50% of the T. versicolor LPGIV gene (87% identity); the presence of Trp199, Leu115, Asp193, Trp199, and Ala203 in the translated amplicon of the T. villosa mRNA; and the close phylogenetic relationship between TvLiP and T. versicolor LiP all indicate that the target enzyme is a lignin peroxidase. Therefore, T. villosa CCMB561 has great potential for use as a LiP, MnP, and Lac producer for industrial applications.

RNAi and miRNA in Viral Infections and Cancers

  • Mollaie, Hamid Reza;Monavari, Seyed Hamid Reza;Arabzadeh, Seyed Ali Mohammad;Shamsi-Shahrabadi, Mahmoud;Fazlalipour, Mehdi;Afshar, Reza Malekpour
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권12호
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    • pp.7045-7056
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    • 2013
  • Since the first report of RNA interference (RNAi) less than a decade ago, this type of molecular intervention has been introduced to repress gene expression in vitro and also for in vivo studies in mammals. Understanding the mechanisms of action of synthetic small interfering RNAs (siRNAs) underlies use as therapeutic agents in the areas of cancer and viral infection. Recent studies have also promoted different theories about cell-specific targeting of siRNAs. Design and delivery strategies for successful treatment of human diseases are becomingmore established and relationships between miRNA and RNAi pathways have been revealed as virus-host cell interactions. Although both are well conserved in plants, invertebrates and mammals, there is also variabilityand a more complete understanding of differences will be needed for optimal application. RNA interference (RNAi) is rapid, cheap and selective in complex biological systems and has created new insight sin fields of cancer research, genetic disorders, virology and drug design. Our knowledge about the role of miRNAs and siRNAs pathways in virus-host cell interactions in virus infected cells is incomplete. There are different viral diseases but few antiviral drugs are available. For example, acyclovir for herpes viruses, alpha-interferon for hepatitis C and B viruses and anti-retroviral for HIV are accessible. Also cancer is obviously an important target for siRNA-based therapies, but the main problem in cancer therapy is targeting metastatic cells which spread from the original tumor. There are also other possible reservations and problems that might delay or even hinder siRNA-based therapies for the treatment of certain conditions; however, this remains the most promising approach for a wide range of diseases. Clearly, more studies must be done to allow efficient delivery and better understanding of unwanted side effects of siRNA-based therapies. In this review miRNA and RNAi biology, experimental design, anti-viral and anti-cancer effects are discussed.

안드로이드 미니PC를 이용한 Retail-Store형 디지털사이니지 솔루션 개발 및 사용성 테스트 (Retail-Store Type Digital Signage Solution Development And Usability Test Using Android Mini PC)

  • 임정택;신동희
    • 한국콘텐츠학회논문지
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    • 제15권4호
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    • pp.29-44
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    • 2015
  • 디스플레이를 활용해 사용자에게 광고 및 정보를 노출 할 수 있는 디지털사이니지는 공공장소에서 광고 채널로서의 역할에서 확장되었다. 최근에는 음식점 및 소매상점으로 널리 확장되어 이용되고 있다. 그러나, 특정 용도에만 맞게 개발되어 있어 확장이 어렵고 단말의 가격 또한 비싸다. 본 연구에서는 이러한 단점을 모두 보완할 수 있는 합리적인 가격과 안정적인 운영성, 높은 확장성을 가진 안드로이드 스틱형 디지털 사이니지 상품을 개발하였다. 안정성 및 사용성을 테스트 하기 위해 H/W 및 App의 Performace Test실시하였다. H/W성능, 시나리오별 최대성능을 Load Runnner로 측정한 결과 모두 목표지수에 도달하였다. 사용성 테스트를 진행한 결과, 피험자들은 비 디지털사이니지 시스템 사용자를 포함해 모두 기능을 쉽게 습득하였다. 설문지를 통해 만족도를 측정하였다. 그 결과 어플리케이션의 학습률 및 사용성(LEU), 유익함 및 문제해결능력(HPSC), 정감적요소와 멀티미디어특성 (AAMP), 제어력 및 단기기억부담의 최소화(CMML), 작동과 효율성(CE)에서 긍정적인 반응을 보였다.

Effect of Double Replacement of L-Pro, D-Pro, D-Leu or Nleu in Hydrophobic Face of Amphipathic α-Helical Model Antimicrobial Peptide on Structure, Cell Selectivity and Mechanism of Action

  • Shin, Song Yub
    • Bulletin of the Korean Chemical Society
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    • 제35권11호
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    • pp.3267-3274
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    • 2014
  • In order to investigate the effects of the double replacement of $\small{L}$-Pro, $\small{D}$-Pro, $\small{D}$-Leu or Nleu (the peptoid residue for Leu) in the hydrophobic face (positions 9 and 13) of amphipathic ${\alpha}$-helical non-cell-selective antimicrobial peptide $L_8K_9W_1$ on the structure, cell selectivity and mechanism of action, we synthesized a series of $L_8K_9W_1$ analogs with double replacement of $\small{L}$-Pro, $\small{D}$-Pro, $\small{D}$-Leu or Nleu in the hydrophobic face of $L_8K_9W_1$. In this study, we have confirmed that the double replacement of $\small{L}$-Pro, $\small{D}$-Pro, or Nleu in the hydrophobic face of $L_8K_9W_1$ let to a great increase in the selectivity toward bacterial cells and a complete destruction of ${\alpha}$-helical structure. Interestingly, $L_8K_9W_1$-$\small{L}$-Pro, $L_8K_9W_1$-$\small{D}$-Pro and $L_8K_9W_1$-Nleu preferentially interacted with negatively charged phospholipids, but unlike $L_8K_9W_1$ and $L_8K_9W_1$-$\small{D}$-Leu, they did not disrupt the integrity of lipid bilayers and depolarize the bacterial cytoplasmic membrane. These results suggested that the mode of action of $L_8K_9W_1$-$\small{L}$-Pro, $L_8K_9W_1$-$\small{D}$-Pro and $L_8K_9W_1$-Nleu involves the intracellular target other than the bacterial membrane. In particular, $L_8K_9W_1$-$\small{L}$-Pro, $L_8K_9W_1$-$\small{D}$-Pro and $L_8K_9W_1$-Nleu had powerful antimicrobial activity (MIC range, 1 to $4{\mu}M$) against methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Pseudomonas aeruginosa (MDRPA). Taken together, our results suggested that $L_8K_9W_1$-$\small{L}$-Pro, $L_8K_9W_1$-$\small{D}$-Pro and $L_8K_9W_1$-Nleu with great cell selectivity may be promising candidates for novel therapeutic agents, complementing conventional antibiotic therapies to combat pathogenic microorganisms.

Inhibition of Wntless/GPR177 suppresses gastric tumorigenesis

  • Seo, Jaesung;Kee, Hyun Jung;Choi, Hye Ji;Lee, Jae Eun;Park, Soo-Yeon;Lee, Seung-Hyun;Jeong, Mi-Hyeon;Guk, Garam;Lee, SooYeon;Choi, Kyung-Chul;Choi, Yoon Young;Kim, Hyunki;Noh, Sung Hoon;Yoon, Ho-Geun;Cheong, Jae-Ho
    • BMB Reports
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    • 제51권5호
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    • pp.255-260
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    • 2018
  • Wntless/GPR177 functions as WNT ligand carrier protein and activator of $WNT/{\beta}$-catenin signaling, however, its molecular role in gastric cancer (GC) has remained elusive. We investigated the role of GPR177 in gastric tumorigenesis and provided the therapeutic potential of a clinical development of anti-GPR177 monoclonal antibodies. GPR177 mRNA expression was assessed in GC transcriptome data sets (GSE15459, n = 184; GSE66229, n = 300); protein expression was assessed in independent patient tumor tissues (Yonsei TMA, n = 909). GPR177 expression were associated with unfavorable prognosis [log-rank test, GSE15459 (P = 0.00736), GSE66229 (P = 0.0142), and Yonsei TMA (P = 0.0334)] and identified as an independent risk predictor of clinical outcomes: GSE15459 [hazard ratio (HR) 1.731 (95% confidence interval; CI; 1.103-2.715), P = 0.017], GSE66229 [HR 1.54 (95% CI, 1.10-2.151), P = 0.011], and Yonsei TMA [HR 1.254 (95% CI, 1.049-1.500), P = 0.013]. Either antibody treatment or GPR177 knockdown suppressed proliferation of GC cells and sensitized cells to apoptosis. And also inhibition of GPR177 suppresses in vitro and in vivo tumorogenesis in GC cells and inhibits $WNT/{\beta}$-catenin signaling. Finally, targeting and inhibition of GPR177 with antibody suppressed tumorigenesis in PDX model. Together, these results suggest GPR177 as a novel candidate for prognostic marker as well as a promising target for treatment of GC patients.

HOCl Oxidation-modified CT26 Cell Vaccine Inhibits Colon Tumor Growth in a Mouse Model

  • Zhou, Rui;Huang, Wen-Jun;Ma, Cong;Zhou, Yan;Yao, Yu-Qin;Wang, Yu-Xi;Gou, Lan-Tu;Yi, Chen;Yang, Jin-Liang
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권8호
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    • pp.4037-4043
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    • 2012
  • Despite progress in elucidating mechanisms associated with colorectal cancer and improvement of treatment methods, it remains a frequent cause of death worldwide. New and more effective therapies are therefore urgently needed. Recent studies have shown that immunogenicity of whole ovarian tumor cells and subsequent T cell response were potentiated by oxidation modification with hypochlorous acid (HOCl) in vitro and ex vivo. These results prompted us to investigate the protective antitumor response with an HOCl treated CT26 colorectal cancer cell vaccine in an in vivo mouse model. Administration of HOCl modified vaccine triggered robust antitumor immunity to autologous tumor cells in mice and prolonged survival period significantly. In addition, increased necrosis and apoptosis were found in tumor tissue from the oxidation group. Interestingly, ELISPOT assays showed that specific T cell responses were not elicited in response to the immunizing cellular antigen, in contrast to raising sera antibody titer and antibody binding activity shown by ELISA assay and flow cytometry. Further evaluation of the mechanisms underlying HOCl modified vaccine mediated humoral immunity highlighted the role of antibody-dependent cell-mediated cytotoxicity. These results combined with previous studies suggest that HOCl oxidation modified whole cell vaccine has wide applicability as a cancer vaccine because it can target both T cell- and B cell-specific responses. It may thus represent a promising approach for the immunotherapy of colorectal cancer.