• 제목/요약/키워드: Molecular screening

검색결과 822건 처리시간 0.027초

Genotoxicity on Structural Derivatives of Sophoricoside, a Component of Sophora Japonica, in Bacterial and Mammalian Cells

  • Ryu, Jae-Chun;Kim, Youn-Jung;Kim, Mi-Soon;Kim, Min-Ji;Sarma, Sailendra Nath;Jung, Sang-Hun
    • Molecular & Cellular Toxicology
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    • 제1권3호
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    • pp.179-188
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    • 2005
  • To develop the novel anti-allergic drug, many sophoricoside derivatives were synthesized. Among these derivatives, JSH-II-3, VI-3, VII-3, VIII-3, VII-20 and VII-20 (sodium salt) were selected and subjected to high throughput toxicity screening (HTTS) because they revealed strong IL-5 inhibitory activity and limitation of quantity. Single cell gel electrophoresis (Comet) assay, mouse lymphoma thymidine kinase ($tk^{+/-}$) gene assay (MOLY), chromosomal aberration assay in mammalian cells and Ames reverse mutation assay in bacterial system were used as simplified, inexpensive, short-term in vitro screening tests in our laboratory. Through the primary screening using the comet assay, we could choose the first candidates of sophoricoside derivatives with no genotoxic potentials as JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt). Also JSH-VII-3, VII-20 and VII-20 (sodium salt) are non-mutagenic in MOLY assay, while JSH-II-3 is mutagenic at high concentration with the presence of metabolic activation system in both comet assay and MOLY assay. The selected derivatives (JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt) are not mutagenic in S. typhimurium TA98 and TA100 strains both in the presence and absence of metabolic activation. From results of chromosomal aberration assay, 6 h treatment of JSH-VI-3, VII-3 and VII-20 (sodium salt) were not revealed clastogenicity both in the presence and absence of S-9 mixture. Therefore, we suggests that JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt), as the optimal candidates with both no genotoxic potential and IL-5 inhibitory effects must be chosen. To process the development into new anti-inflammatory drug of these derivatives, further investigation will need.

Noninvasive prenatal test for fetal chromosomal aneuploidies by massively parallel sequencing of cell-free fetal DNA in maternal plasma: The first clinical experience in Korea

  • Han, Sung-Hee;Yang, Young-Ho;Ryu, Jae-Song;Kang, Myung-Soo;Kim, Young-Jin;Lee, Kyoung-Ryul
    • Journal of Genetic Medicine
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    • 제12권2호
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    • pp.85-91
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    • 2015
  • Purpose: Noninvasive prenatal test (NIPT) by massively parallel sequencing (MPS) of cell-free fetal DNA in maternal plasma marks a significant advancement in prenatal screening, minimizing the need for invasive testing of fetal chromosomal aneuploidies. Here, we report the initial clinical performance of NIPT in Korean pregnant women. Materials and Methods: MPS-based NIPT was performed on 910 cases; 5 mL blood samples were collected and sequenced in the Shenzhen BGI Genomic Laboratory to identify aneuploidies. The risk of fetal aneuploidy was determined by L-score and t-score, and classified as high or low. The NIPT results were validated by karyotyping for the high-risk cases and neonatal follow-up for low-risk cases. Results: NIPT was mainly requested for two clinical indications: abnormal biochemical serum-screening result (54.3%) and advanced maternal age (31.4%). Among 494 cases with abnormal biochemical serum-screening results, NIPT detected only 9 (1.8%) high-risk cases. Sixteen cases (1.8%) of 910 had a high risk for aneuploidy: 8 for trisomy 21, 2 for trisomy 18, 1 for trisomy 13, and 5 for sex chromosome abnormalities. Amniocentesis was performed for 7 of these cases (43.8%). In the karyotyping and neonatal data, no false positive or negative results were observed in our study. Conclusion: MPS-based NIPT detects fetal chromosomal aneuploidies with high accuracy. Introduction of NIPT as into clinical settings could prevent about 98% of unnecessary invasive diagnostic procedures.

스틸벤유도체의 생물활성도를 예측하기 위한 QSAR 분자표현자의 검색방법에 관한 연구 (Primary Screening of QSAR Descriptors to Determine Biological Activities of Stilbene Derivatives)

  • 김재현;고동수;엄애선
    • Environmental Analysis Health and Toxicology
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    • 제16권3호
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    • pp.115-120
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    • 2001
  • The predictive screening of various molecular descriptors for predicting cyclooxygenase inhibitor, lipooxygenase inhibitor, leucotriene synthesis inhibitor, leucotriene antagonist activities of Stilbene moieties have been investigated for the application of quantitative structure-activity relationships (QSAR). The biological activities for 36 compounds were computed by the PASS program and molecular descriptors are cited from literatures or calculated, to investigate feasibility of screening relevant descriptors and of their applications among biological endpoints. Fairly good correlations varying from 0.7828 to 0.9032 were obtained using 12 descriptors with 29 Stilbene derivatives and 5 diazo-compounds. Our studies reveal that LogKow, electron density(X), electron density (Y),4th-order valence connectivity and water solubility can be usefully employed to predict biological activities of stilbene derivatives with simple regression models.

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An Antifungal Property of Burkholderia ambifaria Against Phytopathogenic Fungi

  • Lee Chul-Hoon;Kim Min-Woo;Kim Hye-Sook;Ahn Joong-Hoon;Yi Yong-Sub;Kang Kyung-Rae;Yoon Young-Dae;Choi Gyung-Ja;Cho Kwang-Yun;Lim Yoong-Ho
    • Journal of Microbiology and Biotechnology
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    • 제16권3호
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    • pp.465-468
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    • 2006
  • Even though many pesticides are known for barley powdery mildew and wheat leaf rust, alternative controls are necessary, because of consumer rejection of chemical pesticides and the appearance of fungi resistant to fungicides. To discover biopesticides, many broths of microorganisms were screened. Of those, a culture broth of Burkholderia ambifaria showed an excellent antifungal activity against both Erysiphe graminis and Puccinia recondita, which cause barley powdery mildew and wheat leaf rust, respectively.

Screening of the Antigen Epitopes of Basic Fibroblast Growth Factor by Phage Display

  • Xiang, Junjian;Zhong, Zhenyu;Deng, Ning;Zhong, Zhendong;Yang, Hongyu
    • BMB Reports
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    • 제38권3호
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    • pp.290-293
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    • 2005
  • In order to investigate the epitope of basic fibroblast growth factor (bFGF) and its immunogenicity, the epitopes of bFGF were screened from the phage display library with monoclonal antibody GF22, which can neutralize the bio-activity of bFGF. By three rounds of screening, the positive phage clones with bFGF epitopes were selected, which can effectively block the bFGF to bind with GF22. Sequence analysis showed that the epitopes shared a highly conservative sequence (Leu-Pro-Pro/Leu-Gly-His-Phe/Ile-Lys). The sequence of PPGHFK was located at 22-27 of the bFGF. The specific immuno-response of mouse could be highly induced by phage clones with the epitopes. And the anti-bFGF activity induced by LPGHFK was 3 times higher than the original sequence, which showed that the mimetic peptide LPLGHIK might be used as a tumor vaccine in the prevention and treatment of tumor.

Cell-Based Assay Design for High-Content Screening of Drug Candidates

  • Nierode, Gregory;Kwon, Paul S.;Dordick, Jonathan S.;Kwon, Seok-Joon
    • Journal of Microbiology and Biotechnology
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    • 제26권2호
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    • pp.213-225
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    • 2016
  • To reduce attrition in drug development, it is crucial to consider the development and implementation of translational phenotypic assays as well as decipher diverse molecular mechanisms of action for new molecular entities. High-throughput fluorescence and confocal microscopes with advanced analysis software have simplified the simultaneous identification and quantification of various cellular processes through what is now referred to as high-content screening (HCS). HCS permits automated identification of modifiers of accessible and biologically relevant targets and can thus be used to detect gene interactions or identify toxic pathways of drug candidates to improve drug discovery and development processes. In this review, we summarize several HCS-compatible, biochemical, and molecular biology-driven assays, including immunohistochemistry, RNAi, reporter gene assay, CRISPR-Cas9 system, and protein-protein interactions to assess a variety of cellular processes, including proliferation, morphological changes, protein expression, localization, post-translational modifications, and protein-protein interactions. These cell-based assay methods can be applied to not only 2D cell culture but also 3D cell culture systems in a high-throughput manner.

Noninvasive Testing for Colorectal Cancer Screening: Where Are We Now?

  • Jaeyoung Chun;Jie-Hyun Kim;Young Hoon Youn;Hyojin Park
    • Journal of Digestive Cancer Research
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    • 제11권2호
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    • pp.85-92
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    • 2023
  • Colorectal cancer (CRC) is one of the most prevalent cancers and is the leading cause of cancer-related mortality worldwide. Based on the current screening guidelines by the American Cancer Society and Korean multi-society expert committee, CRC screening is recommended in asymptomatic adults starting at the age of 45 years. Fecal immunochemical test-based screening programs reduce the development of CRC and related mortality in the general population. However, this most popular CRC screening strategy demonstrates a crucial limitation due to modest diagnostic accuracy. Colonoscopy may be considered as an alternative primary method for CRC screening; however, its implementation can still be challenging due to concerns regarding invasiveness, low adherence, cost-effectiveness, and quality assurance. To overcome the limitations of current screening tests, innovative noninvasive tests for CRC screening have been developed with advances in molecular biology, genetics, epigenetics, and microbiomics for detecting CRC, which may enhance the approach to CRC screening and diagnosis in clinical practice in the near future. This review explores the emerging screening methods and discusses their potential for integration into current practice.

두꺼운 박막 성장시 Steering 효과 연구 (The Study of Steering Effect in Multilayer Growth)

  • 서지근;김재성
    • 한국진공학회지
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    • 제15권4호
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    • pp.410-420
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    • 2006
  • Epitaxial 성장에서 screening 및 steering 효과 등과 같은 증착과정 중 나타나는 dynamic effects를 kinetic Monte Carlo 시뮬레이션으로 고찰하였다. 증착원자와 토대 원자와의 상호 작용을 엄밀하게 고려하기 위해 이 시뮬레이션 프로그램에 molecular dynamics 시뮬레이션을 결합시켰다. 기울어진 각도로 증착 시킬 경우 표면의 형상은 1) 증착 각도가 기울어짐에 따라 거칠기가 증가한다는 것, 2) 비대칭적인 언덕의 형성된다는 것, 그리고 3) 언덕의 면방향에 따라 비대칭적인 기울기를 갖는다는 세가지 특징을 보았다. 증착 각도나 온도 의존성에 대한 시뮬레이션 결과는 기존의 실험 결과와 잘 일치하는 것을 확인하였다. 기울어진 각도로 증착했을 때 나타나는 이러한 결과는 steering과 screening 효과에 따른 초기 증착 밀도의 불균일에 기인함을 알 수 있었고, 여기서 steering 효과가 screening 효과 보다 주요한 역할을 하는 것을 보았다. 시뮬레이션 계산에서 확인된 새로운 결과는 기울기 선택 (slope selection)이 이루어졌어도 언덕의 각 면이 단일한 기울기로 형성되어 있지 않고 여러 종류의 facet가 섞인 형태이며, 따라서 기울기 선택이 바로 facet 선택을 의미하지는 않는다는 것이다.