• Title/Summary/Keyword: new drugs

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Cloning and characterization of polyA- RNA transcripts encoded by activated B1-like retrotransposons in mouse erythroleukemia MEL cells exposed to methylation inhibitors

  • Tezias, Sotirios S.;Tsiftsoglou, Asterios S.;Amanatiadou, Elsa P.;Vizirianakis, Ioannis S.
    • BMB Reports
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    • v.45 no.2
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    • pp.126-131
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    • 2012
  • We have previously identified a DNA silent region located downstream of the 3'-end of the ${\beta}^{major}$ globin gene (designated B1-559) that contains a B1 retrotransposon, consensus binding sites for erythroid specific transcription factors and shares the capacity to act as promoter in hematopoietic cells interacting with ${\beta}$-globin gene LCR sequences in vitro. In this study, we have cloned four new non-polyA RNA transcripts being detected upon blockade of murine erythroleukemia (MEL) cell differentiation to erythroid maturation by methylation inhibitors and demonstrated that two of them share high structural homology with sequences of B1 element found within the B1-559 region. Although it is not clear yet whether and how these RNAs interfere with induction of erythroid maturation, these data provide evidence for the first time showing that methylation inhibitors can activate silent repetitive DNA sequences in MEL cells and may have implications in cancer chemotherapy using demethylating drugs as antineoplastic agents.

Biased G Protein-Coupled Receptor Signaling: New Player in Modulating Physiology and Pathology

  • Bologna, Zuzana;Teoh, Jian-peng;Bayoumi, Ahmed S.;Tang, Yaoliang;Kim, Il-man
    • Biomolecules & Therapeutics
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    • v.25 no.1
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    • pp.12-25
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    • 2017
  • G protein-coupled receptors (GPCRs) are a family of cell-surface proteins that play critical roles in regulating a variety of pathophysiological processes and thus are targeted by almost a third of currently available therapeutics. It was originally thought that GPCRs convert extracellular stimuli into intracellular signals through activating G proteins, whereas ${\beta}$-arrestins have important roles in internalization and desensitization of the receptor. Over the past decade, several novel functional aspects of ${\beta}$-arrestins in regulating GPCR signaling have been discovered. These previously unanticipated roles of ${\beta}$-arrestins to act as signal transducers and mediators of G protein-independent signaling have led to the concept of biased agonism. Biased GPCR ligands are able to engage with their target receptors in a manner that preferentially activates only G protein- or ${\beta}$-arrestin-mediated downstream signaling. This offers the potential for next generation drugs with high selectivity to therapeutically relevant GPCR signaling pathways. In this review, we provide a summary of the recent studies highlighting G protein- or ${\beta}$-arrestin-biased GPCR signaling and the effects of biased ligands on disease pathogenesis and regulation.

Treatment Rate-up Methods in the Oriental Medicine (한의학 치료율 제고 방안에 관한 연구)

  • Lee Sun-Dong
    • Journal of Society of Preventive Korean Medicine
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    • v.3 no.1
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    • pp.35-54
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    • 1999
  • This thesis shows about the meaning of treatment rate increasing, the current treated level and the reason of low treatment rate and increasing methods. 1. Treatment rate incresing means high treat level within short time, keeping treatment effect for a long time as well as raising treatment rate. 2. The current by diseases each others completed treatment rate of oriental medicine is 14.0% to 89.7%$(mean:\;{\pm}40.0%)$. Therefore the rate is show too low. 3. The reasons of low treatment rate; low academic level of oriental, academic limitation, clinic and prevention problem of oriental medicine, lack of medical approch suitable for current diseases and symptoms, mostly incurrable diseases using oriental medicine, lack of preventive education, disappropriate medical service and nonspecialty of the treatment, etc. 4. The next methods for incresing the treatment rate must be improved; such as accurate establishment of process that diagnosis symptoms and treats them, system research of microdiagnosis, positive treatment with medicine and nonmedicine method at the same time, appropriate subdivision and actualization of clinical basic research, research of dose and response, diversity of treatment methods and forms, development of treatment service and prevention based on health level, enormous change as cure medicine and opening-up of new disease field, specialization of medical examination, reinforcement of public medical part and herbal drugs use with same origin, mental and pysical stability of patients, accurate extract and oral drinking ways, etc.

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Traditional medicines for common dermatological disorders in Mauritius

  • Mahomoodally, Mohamad Fawzi;Hossain, Ziad Dil
    • CELLMED
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    • v.3 no.4
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    • pp.31.1-31.8
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    • 2013
  • This study has been geared to document primary information on common complementary and alternative medicines (CAM) used to treat and/or manage common dermatological disorders in Mauritius, a tropical multicultural island in the Indian Ocean. Data from 355 key informants was collected via a semi-structured questionnaire. Pearson correlation and Chi-squared test were performed to delineate any association. Quantitative indexes including the Importance Value (IV) and fidelity value were calculated. Results tend to indicate that cultural reasons were behind the use of CAM among Mauritians and traditional knowledge was mainly acquired either from parents/relatives or from self-experience. Among the medicinal plants mentioned, Aziadiracta indica (IV = 0.78) and Paederia tomentosa (IV = 0.70) were found to be most used plants. Calendula officinalis (IV = 0.15), Centella asiatica (IV = 0.22) and Agauria salicifolia (IV = 0.11) were also recorded to be used for common dermatological disorders though greatly under-utilised. Animal products were mentioned by 38.0% respondents and cow ghee was found to be commonly used in the management of measles (IV = 0.88). Spiritual healing was found to be used mainly for measles and warts. Given the plethora of novel information documented from the present survey, it can be suggested that the Mauritian population still relies to a great extent on CAM which needs to be preserved and used sustainably. Nonetheless, further investigation is required to probe the possible active constituents that could be the basis of an evidence based investigation to discover new drugs.

Nanoparticle Induced Oxidative Stress in Cancer Cells: Adding New Pieces to an Incomplete Jigsaw Puzzle

  • Nogueira, Daniele Rubert;Rolim, Clarice M. Bueno;Farooqi, Ammad Ahmad
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4739-4743
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    • 2014
  • Nanotechnology is an emerging field with many promising applications in drug delivery systems. Because of outstanding developments in this field, rapidly increasing research is directed to the development of nanocarriers that may enhance the availability of drugs to the target sites. Substantial fraction of information has been added into the existing scientific literature focusing on the fact that nanoparticles usually generate reactive oxygen species to a greater extent than micro-sized particles. It is worth mentioning that oxidative stress regulates an array of cell signaling cascades that resulted in cancer cell damage. Accumulating experimental evidence over the years has shown that wide-ranging biological mechanisms are triggered by these NPs in cultured cells due to the unique properties of engineered nanoparticles. In this review, we have attempted to provide an overview of the signaling cascades that are activated by oxidative stress in cancer cells in response to different kinds of nanomaterials, including quantum dots, metallic and polymeric nanoparticles.

A New Rat Model of Cisplatin-induced Neuropathic Pain

  • Lin, Hai;Heo, Bong Ha;Yoon, Myung Ha
    • The Korean Journal of Pain
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    • v.28 no.4
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    • pp.236-243
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    • 2015
  • Background: Chemotherapy-induced peripheral neuropathy is a major side effect of anti-cancer drugs, and our knowledge of its mechanisms is lacking. Several models for chemotherapy-induced neuropathy have been introduced. However, the outcomes of these models differ significantly among laboratories. Our object was to create a model of chemotherapy-induced neuropathy in rats with cancer. Methods: Female Sprague-Dawley rats were used. Mammary rat metastasis tumor (MRMT-1) cells were implanted subcutaneously in rats. Chemotherapy-induced peripheral neuropathy was induced by injection of cisplatin once a day for four days. The responses to mechanical and thermal stimuli were examined using von Frey filaments, acetone, and radiant heat. Results: Cisplatin (2 mg/kg/day) produced mechanical allodynia, while it did not induce cold allodynia or thermal hyperalgesia. This dose of cisplatin could work successfully against cancer. Body weight loss was not observed in cisplatin-treated rats, nor were other abnormal behaviors noted in the same rats. Conclusions: Repeated injection of intraperitoneal cisplatin induced peripheral neuropathic pain in rats. Thus, this type of rat model has broad applicability in studies related to searching for the mechanism of cisplatin-induced mechanical allodynia and agents for the treatment of neuropathic pain.

Topical Anti-inflammatory Activity of Dianemycin Isolated from Streptomyces sp. MT 2705-4

  • Lee, Song-Jin;Kim, Hyun-Pyo;Park, Byung-Keun;Ahn, Soon-Cheol;Lee, Hyun-Sun;Ahn, Jong-Seog
    • Archives of Pharmacal Research
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    • v.20 no.4
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    • pp.372-374
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    • 1997
  • In order to develop new anti-inflammatory agents having different action mechanisms compared with nonsteroidal and steroidal anti-inflammatory drugs, the culture broths of various actinomycetes isolated from soil were screened using an in vivo mouse ear edma assay and one strain (Streptomyces sp. MT 2705-4: KCTC 8651 P) was selected. Activity-guided purification led to the isolation of a polyether compound, dianemycin. Topically, dianemycin showed a potent anti-inflammatory activity in mouse ear edema induced by croton-oil or arachidonic acid.$ED_{50}$value of dianemycin was found to be 0.8 mg,/ear compared to 0.4 mg/ear of prednisolone in croton-oil ear edema. However, dianemycin did not show the inhibitory activity in UV-erythema and delayed hypersensitivity reaction. These results indicate that dianemycin is a potential topical anti-inflammatory agent.

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A Comparison between C4 and Cation-exchange Columns as a Pre-separation Method for Mass Spectrometric Analysis to Characterize a Global Identification of Phosphopeptides and Phosphorylation Sites (세포내 총체적인 인산화 펩타이드 및 인산화 위치 규명을 위해 질량분석기 전 단계의 C4 및 양이온 교환수지 칼럼 이용 방법의 비교)

  • Kim, Hye-Jeong;Baek, Moon-Chang
    • YAKHAK HOEJI
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    • v.59 no.3
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    • pp.113-119
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    • 2015
  • Protein phosphorylation is one of most important post-translational modifications (PTMs) and plays an important role in regulation of protein function. Here we develop a method for a global identification of phosphopeptides and phosphorylation sites using nano-LC MS/MS. We compared two separation methods, C4 and strong cation ion exchange (SCX). Before phosphopeptides enrichment with $TiO_2$, total proteins from Rat 1 cells have been separated using C4 column or tryptic peptides of proteins from the cells have been separated using SCX column. Finally, we have detected 52 phosphorylation sites on 41 proteins from SCX method and 375 phosphorylation sites on 252 proteins from C4 method, and determined the function and localization of identified phosphoproteins using DAVID software. In particular, we showed new phosphorylation sites from membrane proteins related to various cell signaling mechanisms. This method may contribute to study global signal networks induced by various signals including ligands and drugs.

Poly(vinyl pyrrolidone) Conjugated Lipid System for the Hydrophobic Drug Delivery

  • Lee, Hye-Yun;Yu, Seol-A;Jeong, Kwan-Ho;Kim, Young-Jin
    • Macromolecular Research
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    • v.15 no.6
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    • pp.547-552
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    • 2007
  • Water soluble polymer, poly(vinyl pyrrolidone) was chosen to conjugate with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(succinyl) (N-succinyl DPPE) to make a new drug delivery system. PVP with an amine group (amino-PVP) was polymerized by free radical polymerization. The amine group of amino-PVP was conjugated with the carboxylic group of N-succinyl DPPE. The resultant conjugate could form nanoparticles in the aqueous solution; these nanoparticles were termed a lipid-polymer system. The critical aggregation concentration was measured with pyrene to give a value of $1{\times}10^{-3}g/L$. The particle size of the lipid-polymer system, as measured by DLS, AFM and TEM, was about 70 nm. Lipophilic component in the inner part of the lipid-polymer system could derive the physical interaction with hydrophobic drugs. Griseofulvin was used as a model drug in this study. The loading efficiency and release profile of the drug were measured by HPLC. The loading efficiency was about 54%. The release behavior was sustained for a prolonged time of 12 days. The proposed lipid-polymer system with biodegradable and biocompatible properties has promising potential as a passive-targeting drug delivery carrier because of its small particle size.

C-PInvestigation on the technology trend by the intellectual property in Schizandra chinensis

  • Kim, Chang-Kug;Kim, Do-Wan;Lee, Dong-Jun;Oh, Jae-Hyeon;Lee, Tae-Ho
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2018.10a
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    • pp.39-39
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    • 2018
  • The Schizandra chinensis (Korean name : omija) is a fruit native to northeast Asia that is cultivated in South Korea and China. Using 1,938 valid patents of 6 group countries, we analyzed the patent trend based on year, countries, applicants, and technology. The technologies are categorized the 10 sub-technologies such as medicine, quasi-drugs, food, feed, cosmetics, cultivation, genome, manufacture, preprocessing, and etc. The technology level and competitiveness are analyzed using patent index such as cites per patent, patent impact index, patent family size and technology strength. In Korea, patent number rapidly increasing and individual technical level is lower than other countries. However, overall technical competitiveness is estimated high due to multiple patents. We suggest that cosmetics and cultivation fields are most likely to be developed in future omiza technology development in Korea. Our study will provides to the information of technical trend to support performing of new projects for omija plant.

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