• Title/Summary/Keyword: new drugs

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The Anti-inflammatory Mechanism of the Peel of Zanthoxylum piperitum D.C. is by Suppressing NF-κB/Caspase-1 Activation in LPS-Induced RAW264.7 Cells

  • Choi, Yun-Hee;Myung, Noh-Yil
    • Korean Journal of Plant Resources
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    • v.32 no.6
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    • pp.669-676
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    • 2019
  • Zanthoxylum piperitum D.C. (ZP) peels has been used as a natural spice and herb medicine for hypertension reduction, for strokes, and for its anti-bacterial and anti-oxidant activity. However, the anti-inflammatory mechanisms employed by ZP have yet to be completely understood. In this study, we elucidate the anti-inflammatory mechanism of ZP in lipopolysaccharide (LPS)-induced RAW264.7 cells. We evaluated the effects of ZP in LPS-induced levels of inflammatory cytokines, prostaglandin E2 (PGE2), and caspase-1 using ELISA. The expression levels of inflammatory-related genes, including cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS), were assayed by Western blot analysis. We elucidated the effect of ZP on nuclear factor (NF)-κB activation by means of a luciferase activity assay. The findings of this study demonstrated that ZP inhibited the production of inflammatory cytokine and PGE2 and inhibited the increased levels of COX-2 and iNOS caused by LPS. Additionally, we showed that the anti-inflammatory effect of ZP arises by suppressing the activation of NF-κB and caspase-1 in LPS- induced RAW264.7 cells. These results provide novel insights into the pharmacological actions of ZP as a potential candidate for development of new drugs to treat inflammatory diseases.

Silibilin-Induces Apoptosis in Breast Cancer Cells by Modulating p53, p21, Bak and Bcl-xl Pathways

  • Pirouzpanah, Mohammad Bagher;Sabzichi, Mehdi;Pirouzpanah, Saeed;Chavoshi, Hadi;Samadi, Nasser
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.2087-2092
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    • 2015
  • Nowadays herbal-derived medicines are attracting attention as new sources of drugs with few side effects. Silibinin is a flavonoid compound with chemotheraputic effects on different cancers such as examples in the prostate, lung, colon and breast. In the present study, the cytotoxic effects of silibinin on MCF7 breast cancer cells were investigated. Apoptosis was determined by flow cytometry and the impact of silibinin on the expression of pivotal genes including Bak, P53, P21, BRCA1, BCL-X1 and ATM was analyzed. Treatment for 24h had a significant dose-dependent inhibitory effect on cell growth (p<0.05) with dose- and time- dependent induction of apoptosis (p<0.05). In addition, there were significant increases in BRCA1, ATM, Bak and Bcl-XL gene expression at the mRNA level with different concentrations of silibinin for 24 or 48 h (p<0.05). Taken together, the results suggest that silibinin inhibits the proliferation and induces apoptosis of MCF-7 cells by down-regulating Bak, P53, P21, BRCA1, BCL-Xl and thus may be considered as an effective adjuvant drug to produce a better chemopreventive response for the cancer therapy.

Cloning, Expression, and Characterization of a Cold-Adapted and Surfactant-Stable Alginate Lyase from Marine Bacterium Agarivorans sp. L11

  • Li, Shangyong;Yang, Xuemei;Zhang, Lan;Yu, Wengong;Han, Feng
    • Journal of Microbiology and Biotechnology
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    • v.25 no.5
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    • pp.681-686
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    • 2015
  • The purpose of this study was to find a cold-adapted and surfactant-stable alginate lyase as a candidate for biotechnological and industrial applications. The gene for a new alginate lyase, AlyL1, from Agarivorans sp. L11 was cloned and expressed in Escherichia coli. The recombinant AlyL1 was most active at 40℃ (1,370 U/mg). It was a cold-adapted alginate lyase, which showed 54.5% and 72.1% of maximum activity at 15℃ and 20℃, respectively. AlyL1 was an alkaliphilic enzyme and most active at pH 8.6. In addition, it showed high stability in the presence of various surfactants at a high concentration (from 0.1% to 1% (w/v)). AlyL1 was an endo-type alginate lyase that degraded both polyM and polyG blocks, yielding disaccharides and trisaccharides as the main products. This is the first report of the cloning and functional expression of a cold-adapted and surfactant-stable alginate lyase. AlyL1 might be an interesting candidate for biotechnological and industrial applications.

Identification of New Potential APE1 Inhibitors by Pharmacophore Modeling and Molecular Docking

  • Lee, In Won;Yoon, Jonghwan;Lee, Gunhee;Lee, Minho
    • Genomics & Informatics
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    • v.15 no.4
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    • pp.147-155
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    • 2017
  • Apurinic/apyrimidinic endonuclease 1 (APE1) is an enzyme responsible for the initial step in the base excision repair pathway and is known to be a potential drug target for treating cancers, because its expression is associated with resistance to DNA-damaging anticancer agents. Although several inhibitors already have been identified, the identification of novel kinds of potential inhibitors of APE1 could provide a seed for the development of improved anticancer drugs. For this purpose, we first classified known inhibitors of APE1. According to the classification, we constructed two distinct pharmacophore models. We screened more than 3 million lead-like compounds using the pharmacophores. Hits that fulfilled the features of the pharmacophore models were identified. In addition to the pharmacophore screen, we carried out molecular docking to prioritize hits. Based on these processes, we ultimately identified 1,338 potential inhibitors of APE1 with predicted binding affinities to the enzyme.

The Use of Phenanthraquinone Monophenyl Thiosemicarbazone for Preconcentration, Ion Flotation and Spectrometric Determination of Zinc(II) in Human Biofluids and Pharmaceutical Samples

  • Akl, Magda Ali
    • Bulletin of the Korean Chemical Society
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    • v.27 no.5
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    • pp.725-732
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    • 2006
  • A rapid flotation methodology for zinc(II) separation and enrichment from human biofluids is established. At pH 6.0 and ambient temperature, using oleic acid (HOL) as a foaming reagent, zinc(II) was separated with phenanthraquinone monophenyl thiosemicarbazone (PPT) as a new flotation collector for Zn(II). The floated red colored 1 : 2 Zn(II)-PPT complex was measured spectrophotometrically at 526 nm with a molar absorptivity of $1.83 \;{\times}\; 10^5\; L$ mol $L ^{-1}\;cm ^{-1}$. Beer's law was obeyed over a concentration range 0.05-1.0 mg $L ^{-1}$ in the aqueous as well as in the scum layers. The proposed preconcentration flotation methodology was applied to determine Zn(II) in human biofluids. Application was, also, extended to determine Zn(II) in pharmaceutical samples and natural water samples spiked with known amounts of Zn(II) with a preconcentration factor of 100 and a detection limit of 10 ng m$L ^{-1}$. The method was verified by comparison of the spectrophotometric results with flame atomic absorption spectrometric (AAS) measurements. Moreover a postulation for the mechanism of flotation is proposed.

Estrogen Regulate Neuroprotection and PDI Gene Expression in Ischemic Rat Brain

  • Yu, Seong-Jin;Kim, Do-Rim;Kim, Jee-Yun;Youm, Mi-Young;Lee, Chae-Kwan;Kang, Sung-Goo
    • Proceedings of the Korean Society of Developmental Biology Conference
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    • 2003.10a
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    • pp.69-69
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    • 2003
  • Neuroprotective strategies have been appeared to be effective in a variety of stroke models. One of the major focuses has been related to the activities of estrogen. $17\beta$-estradiol valerate(EV) has been reported to exert neuroprotective effects when administered before an ischemic insult. The purpose of this study was to determine whether EV can protect against brain injury via estrogen receptor. Chronic and acute pretreatment can reduce the ischemic damage of focal cerebral ischemia in OVX rat, indicating that EV may be a new therapeutic class of drugs to prevent neuronal damage associated with cerebral ischemia. RNAs were extracted from the hippocampus of ovariectomized female rat with or without EV. Differential gene expression profiles were revealed(Bone morphogenetic protein type 1A receptor, Protein disulphide isomerase, cytochrome bc-1 complex core P, thiol-specific antioxidant protein). RT-PCR and in situ hybridization were used to validate the relative expression pattern obtained by the cDNA array. This Study was supported by the Korea Science and Engineering Foundation(KOSEF) through the Biohealth Products Research Center(BPRC), Inje University, Korea

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Critical Review of health care economic evaluation methodology : With a special reference to study design and cost estimation (보건의료 경제성 평가 방법론 고찰 -연구 설계와 비용 추정을 중심으로-)

  • ;Brouwer WBF
    • Health Policy and Management
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    • v.14 no.2
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    • pp.58-77
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    • 2004
  • Cost containment has become high political issues since financial crisis of the Korean Health Insurance fund in 2000. Korean Government has developed and implemented several measures to reduce the pharmaceutical expenditures. Pharmaceutical economic evaluation can be a tool in decision to allocate scare resource efficiently. In order to increase the quality of economic evaluation for pharmaceuticals, the Korean Health Insurance Review Agency(HIRA) is considering the development of a guideline for economic evaluation. It mandates that pharmaceutical companies could submit the result of an economic evaluation when demanding reimbursement of new pharmaceutical drugs. The purpose of this study is to provide a critical review of the economic evaluations of health care technologies published in the Korean context whether they have been performed according to current guidelines and therefore whether their results are directly useful for decision making. We found there exist important problems and deviation from, good practice' both in the general features of the studies, like the study design and perspective, and in terms of cost measurement and valuation. There are needs to develop clear guidelines and to educate and train researchers in performing economic evaluations.

Natural Product Research in Dental Caries Prevention (임상가를 위한 특집 1 - 충치예방과 관련된 천연물(natural products) 연구의 현황)

  • Jeon, Jae-Gyu
    • The Journal of the Korean dental association
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    • v.50 no.9
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    • pp.544-551
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    • 2012
  • Dental caries is a biofilm-related oral disease, and continues to afflict the majority of the world's population. Although fluoride, delivered in various modalities, remains the mainstay for the prevention of caries, additional approaches are required to enhance its effectiveness. Natural products have been used as a major source of innovative and effective therapeutic agents throughout human history, and have shown promise as a source of components for the development of new drugs. In addition. studies using natural products to prevent or treat oral diseases such as dental caries have received a great deal of attention. A number of compounds, such as epicatechin, allicin and sanguinarine, isolated from natural products, have also been investigated for their efficacy against oral microbial pathogens. However, the use of natural products as an anti-caries agent in clinical practice was controversial because of inadequate knowledge concerning their mechanisms of action and chemical characterization. This study focuses on the current knowledge of natural products in dental caries prevention and suggests natural products are importance sources for the prevention of dental caries.

A Case of Thrombocytopenia and Purpura Induced by Rifampin, Pyrazinamide, and Ciprofloxacin (Rifampin, Pyrazinamide and Ciprofloxacin에 의한 혈소판 감소증, 자반증 1예)

  • Son, Hyung-Dae;Kim, Chang-Sun;Park, Mi-Ran;Seo, Ji-Yung;Rheu, Nam-Soo;Cho, Dong-Il
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.4
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    • pp.930-934
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    • 1997
  • Drug-induced thrombocytopenia and purpura have been developed by many various agents. Rifampin and Pyrazinamide have been known as bactericidal antituberculous drugs, but, the above side effects have been a problem. Especially, hematologic side effects are fatal to patients occasionally. Rifampin-induced thrombocytopenia and purpura have been well known, also, pyrazinamide-induced thrombocytopenia have been reported. A new quilonone agent, Ciprofloxacin, has been commonly used in clinics now, but it's side effects are not known well. So, we report a case of a 23-year-old female with thrombocytopenia and purpura after taking Rifampin, Pyrazinamide, and Ciprofloxacin as antituberculous agents.

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Gene-Editing: Interpretation of Current Law and Legal Policy

  • Kim, Na-Kyoung
    • Development and Reproduction
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    • v.21 no.3
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    • pp.343-349
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    • 2017
  • tWith the development of the third-generation gene scissors, CRISPR-Cas9, concerns are being raised about ethical and social repercussions of the new gene-editing technology. In this situation, this article explores the legislation and interpretation of the positive laws in South Korea. The BioAct does not specify and regulate 'gene editing' itself. However, assuming that genetic editing is used in the process of research and treatment, we can look to the specific details of the regulations for research on humans as well as gene therapy research in order to see how genetic editing is regulated under the BioAct. BioAct differentiates the regulation between (born) humans and embryos etc. and the regulation differ entirely in the manner and scope. Moreover, due to the fact that gene therapy products are regarded as drugs, they fall under different regulations. The Korean Pharmacopoeia Act put stringent sanctions on clinical trials for gene therapy products and the official Notification "Approval and Examination Regulations for Biological Products, etc." by Food and Drug Safety Administration may be applied to gene editing for gene therapy purposes.