• Title/Summary/Keyword: genetic toxicity

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Validation of Heterodimeric TAT-NLS Peptide as a Gene Delivery Enhancer

  • Doh, Kyung-Oh
    • Journal of Microbiology and Biotechnology
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    • v.25 no.6
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    • pp.788-794
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    • 2015
  • Cationic liposomes have been actively used as gene delivery vehicles despite their unsatisfactory efficiencies because of their relatively low toxicity. In this study, we designed novel heterodimeric peptides as nonviral gene delivery systems from TAT and NLS peptides using cysteine-to-cysteine disulfide bonds between the two. Mixing these heterodimeric peptides with DNA before mixing with lipofectamine resulted in higher transfection efficiencies in MCF-7 breast cancer cells than mixing unmodified TAT, NLS, and a simple mixture of TAT and NLS with DNA, but did not show an adverse effect on cell viability. In gel retardation assays, the DNA binding affinities of heterodimeric peptides were stronger than NLS but weaker than TAT. However, this enhancement was only observed when heterodimeric peptides were premixed with DNA before being mixed with lipofectamine. The described novel transfection-enhancing peptide system produced by the heterodimerization of TAT and NLS peptides followed by simple mixing with DNA, increased the gene transfer efficiency of cationic lipids without enhancing cytotoxicity.

Nephrotic syndrome: what's new, what's hot?

  • Kang, Hee Gyung;Cheong, Hae Il
    • Clinical and Experimental Pediatrics
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    • v.58 no.8
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    • pp.275-282
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    • 2015
  • While the incidence of nephrotic syndrome (NS) is decreasing in Korea, the morbidity of difficult-to-treat NS is significant. Efforts to minimize treatment toxicity showed that prolonged treatment after an initial treatment for 2-3 months with glucocorticosteroids was not effective in reducing frequent relapses. For steroid-dependent NS, rituximab, a monoclonal antibody against the CD20 antigen on B cells, was proven to be as effective, and short-term daily low-dose steroids during upper respiratory infections reduced relapses. Steroid resistance or congenital NS are indications for genetic study and renal biopsy, since the list of genes involved in NS is lengthening.

Toxicological Evaluation of Oriental Herbal Medicine Kamijadowhan Preparations

  • Park, Young-Jin;Ryu, Jae-Chun;Choi, Seung-Hun;Kwon, Oh-Seung
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.289.2-290
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    • 2002
  • Choi group reported that Kamijadowhan (KMD). an oriental herbal medicine, has anti-angiogenic effects and it may be a potential agent for clinical chemoprevention since it inhibits angiogenesis. Objectives of this experiment are to investigate acute, genetic and reproductive/developmental toxicities of KMD preparations. Acute toxicity was performed after single administration of KMO (200-500 mg/kg) to mice. Supravital staining micronucleus assay was conducted using peripheral reticulocytes in mice. (omitted)

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Evaluation of the Genetic Toxicity of Synthetic Chemicals (Ⅸ) a Synthetic Selective Herbicide, Pretilachlor- (합성화학물질들의 유전독성평가(Ⅸ) -합성 제초제 Pretilachlor -)

  • Ryu Jae-Chun;Kim Youn-Jung
    • Environmental Analysis Health and Toxicology
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    • v.19 no.1
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    • pp.93-100
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    • 2004
  • Pretilachlor [2-chloro-N -(2, 6-diethylphenyl)-N-(2-propoxyethyl) acetamide, $C_{17}$H$_{26}$ClNo$_2$, M.W.=311.9, CAS No.51218-49-6]는 제초제의 일종으로 본 연구에서는 박테리아 복귀 돌연변이 시험과 포유동물 세포를 이용한 염색체 이상 시험 및 마우스를 이용한 in vivo소핵 시험을 수행하여 pretilachlor의 유전독성을 평가하였다. 박테리아 복귀 돌연변이 시험에서 pretilachlor는 Salmonella typhimurium TA98, TA 100, TA1535, TA1537 균주의 대사 활성계 존재 및 부재시 313-5,000$\mu\textrm{g}$/plate의 범위에서 농도 의존적인 돌연변이 율의 증가를 관찰할 수 없었다. 또한 포유동물 세포인 Chinese hamster lung (CHL) fibroblast를 이용한 염색체 이상 시험에서 pretilachlor는 대사 활성계 존재 및 부재시 1.56-6.24$\mu\textrm{g}$/mL의 농도에서 clastogenicity를 보이지 않았고, 137.5-550.1 mg/kg의 pretilachlor를 복강 주사한 마우스의 골수세포를 이용한 in vivo소핵 시험의 결과에서도 통계적으로 유의한 소핵 유발능을 관찰할 수 없었다었다

Evaluation of the Genetic Toxicity of Synthetic Chemicals(XIV) -In vivo Bone Marrow Micronucleus Assay of 11 Synthetic Chemicals in Mice- (합성화학물질들의 유전독성평가(XIV)-마우스의 골수세포를 이용한 11종 합성화학물질들의 생체내 소핵시험-)

  • Ryu Jae Chun;Kim Youn Jung
    • Environmental Analysis Health and Toxicology
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    • v.19 no.3
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    • pp.307-314
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    • 2004
  • 합성화학물질들이 환경으로의 유입은 인체에는 물론 환경생태계에 많은 영향을 미치므로 이들의 유해성 검증은 매우 중요한 일이라 할 수 있다. 실제 산업체에서 사용되는 수많은 화학물질들의 유전적 손상 유발유무는 유해성검증에서 무엇보다 중요한 일이라 할 수 있다. 이에 산업체 공정과정에서 널리 사용되는 것으로 알려진 11종의 합성화학물질에 대해 마우스의 골수 세포를 이용한 in vivo소핵시험을 수행하여, 소핵형성 유발유무를 관찰하였다. 양성대조군으로 사용된 mitomycin C는 음성대조군과 비교시 유의하게 소핵을 유발하는 반면, 비교적 마우스에서 높은 50%치사량을 보이는 thiourea, 2,4-dichlorophenol 및 2,4-toluene diisocyanate 등의 합성물질들을 비롯한 나머지 8종의 물질들은 본 실험결과 통계적으로 유의하게 소핵을 유발하지 않는 것을 관찰 할 수 있었다.

MicroSPECT and MicroPET Imaging of Small Animals for Drug Development

  • Jang, Beom-Su
    • Toxicological Research
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    • v.29 no.1
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    • pp.1-6
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    • 2013
  • The process of drug discovery and development requires substantial resources and time. The drug industry has tried to reduce costs by conducting appropriate animal studies together with molecular biological and genetic analyses. Basic science research has been limited to in vitro studies of cellular processes and ex vivo tissue examination using suitable animal models of disease. However, in the past two decades new technologies have been developed that permit the imaging of live animals using radiotracer emission, X-rays, magnetic resonance signals, fluorescence, and bioluminescence. The main objective of this review is to provide an overview of small animal molecular imaging, with a focus on nuclear imaging (single photon emission computed tomography and positron emission tomography). These technologies permit visualization of toxicodynamics as well as toxicity to specific organs by directly monitoring drug accumulation and assessing physiological and/or molecular alterations. Nuclear imaging technology has great potential for improving the efficiency of the drug development process.

Review for Herbal Drug and Drug-Induced Liver Injury

  • Park, Bong-Ky;Son, Chang-Gue
    • The Journal of Korean Medicine
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    • v.31 no.3
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    • pp.128-132
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    • 2010
  • Objectives: This study aimed to review the general features of drug induced liver injury (DILI) and the important factors in consideration of herbal drugs and DILI. Methods: We reviewed general aspects of DILI such as classification, inducible factors, diagnosis methods, prevention, and the status of herbal drug-associated DILI via literature. Results: Besides the drug itself, genetic and environmental factors affect hepatic toxicity. There is a lack of definitive diagnoses of DILI by drugs, including herbal remedies. The possibility of herbal drug-associated DILI is exaggerated, and majority of herbal drug-derived hepatic injury could be easily prevented if Oriental doctors pay attention to this issue. Conclusion: This study can provide Oriental doctors an overview and be helpful in minimizing the episodes of hepatotoxicity in use of herbal drugs.

Computational Tridimensional Protein Modeling of Cry1Ab19 Toxin from Bacillus thuringiensis BtX-2

  • Kashyap, S.;Singh, B.D.;Amla, D.V.
    • Journal of Microbiology and Biotechnology
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    • v.22 no.6
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    • pp.788-792
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    • 2012
  • We report the computational structural simulation of the Cry1Ab19 toxin molecule from B. thuringiensis BtX-2 based on the structure of Cry1Aa1 deduced by x-ray diffraction. Validation results showed that 93.5% of modeled residues are folded in a favorable orientation with a total energy Z-score of -8.32, and the constructed model has an RMSD of only $1.13{\AA}$. The major differences in the presented model are longer loop lengths and shortened sheet components. The overall result supports the hierarchical three-domain structural hypothesis of Cry toxins and will help in better understanding the structural variation within the Cry toxin family along with facilitating the design of domain-swapping experiments aimed at improving the toxicity of native toxins.

Biopsy and Mutation Detection Strategies in Non-Small Cell Lung Cancer

  • Jung, Chi Young
    • Tuberculosis and Respiratory Diseases
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    • v.75 no.5
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    • pp.181-187
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    • 2013
  • The emergence of new therapeutic agents for non-small cell lung cancer (NSCLC) implies that histologic subtyping and molecular predictive testing are now essential for therapeutic decisions. Histologic subtype predicts the efficacy and toxicity of some treatment agents, as do genetic alterations, which can be important predictive factors in treatment selection. Molecular markers, such as epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement, are the best predictors of response to specific tyrosine kinase inhibitor treatment agents. As the majority of patients with NSCLC present with unresectable disease, it is therefore crucial to optimize the use of tissue samples for diagnostic and predictive examinations, particularly for small biopsy and cytology specimens. Therefore, each institution needs to develop a diagnostic approach requiring close communication between the pulmonologist, radiologist, pathologist, and oncologist in order to preserve sufficient biopsy materials for molecular analysis as well as to ensure rapid diagnosis. Currently, personalized medicine in NSCLC is based on the histologic subtype and molecular status. This review summarizes strategies for tissue acquisition, histologic subtyping and molecular analysis for predictive testing in NSCLC.

The analysis of present condition and the method of medical treatment studies on Scolopendrid Herbal Acupuncture (오공약침(蜈蚣藥鍼)에 대한 연구현황분석(硏究現況分析)과 치료법(治療法)에 관한 연구(硏究))

  • Kim, Sung-Chul
    • Journal of Pharmacopuncture
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    • v.9 no.2
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    • pp.113-127
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    • 2006
  • Objectives : We review a result of studies until the present and suggest the method of medical treatment for the clinical treatment of Scolopendrid Herbalacupuncture. Methods : We analysis the paper of the bibliographic studies, the experiment studies and the clinical studies from 2001 developed Scolopendrid Herbalacupuncture and grope for the course of studies. Results : 1. Scolopendrid Herbalacupuncture is proved the clinical safety by the aninmal and human tests. 2. The pharmacological action of Scolopendra subspinipes mutilans L. Koch is anti-convulsive action, analgesic action, lowering blood pressure, anti-inflammatory action, anti-tumor action and microbe inhibition 3. Scolopendrid Herbalacupuncture has been a fine effect to the entrapment neuropathy and inflammatory. 4. Scolopendrid Herbalacupuncture was thought effective on a acute phase and to the excessive symptoms. The Sub-chronic toxicity experiment observing the response after hypodermic medication over 90 days, The Genetic-mutagenic toxity experiment and the clinical effect studies are necessary.