• Biomolecules & Therapeutics
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• v.3 no.1
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• pp.21-27
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• 1995

The only compounds with antagonistic activity via AT$_1$receptor, one of two subtypes of angiotensin II (AII) receptor, have been demonstrated to block the vasoconstriction effects of AII and thereby provide therapeutic potential. This initiated the search for compounds with high specific affinity to AT$_1$receptor and their effective screening methods. The radioligand binding assay for the AII receptor is regarded as the primary method for the evaluation of AT$_1$receptor antagonists for their activity. In this paper, we characterized the liver AT$_1$receptor and describe the efficient method of the radioligand binding assay using rat liver as a source of AT$_1$receptor. Equilibrium binding studies with rat adrenal cortex, adrenal medulla, liver and bovine adrenal showed that the specific bindings of [$^3$H] AII were saturable in all tissues and the Scatchard plots of those data were linear, suggesting a single population of binding sites. Hill slopes were very near to the unity in all tissues. Kinetic studies of [$^3$H) AII binding in rat liver homogenates yielded two association rate constants, 4.10$\times$10$^{7}$ M$^{-1}$ min$^{-1}$ and 4.02$\times$10$^{9}$ M$^{-1}$ min$^{-1}$ , with a single dissociation rate constant, 7.07$\times$10$^{-3}$ min-$^{-1}$ , possibly due to the partial dissociation phenomenon. The rank order of inhibition potencies of [$^3$H] AII binding in rat liver was AII>Sarile>Losartan>PD 123177. Rat liver homogenates revealed to have very high density of homogeneous population of the AT$_1$receptor subtype, as the specifically bound [$^3$H] AII was not inhibited by PD 123177, the nonpeptide antagonist of AT$_2$. The results of this study demonstrated that the liver homogenates from rats could be the best receptor preparation for the AT$_1$receptor binding assay and provide an efficient system for the screening of newly synthesized candidate compounds of AT$_1$receptor antagonist.

• BMB Reports
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• v.48 no.5
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• pp.256-265
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• 2015

Cardiovascular and neurodegenerative diseases are major health threats in many developed countries. Recently, target tissues derived from human embryonic stem (hES) cells and induced pluripotent stem cells (iPSCs), such as cardiomyocytes (CMs) or neurons, have been actively mobilized for drug screening. Knowledge of drug toxicity and efficacy obtained using stem cell-derived tissues could parallel that obtained from human trials. Furthermore, iPSC disease models could be advantageous in the development of personalized medicine in various parts of disease sectors. To obtain the maximum benefit from iPSCs in disease modeling, researchers are now focusing on aging, maturation, and metabolism to recapitulate the pathological features seen in patients. Compared to pediatric disease modeling, adult-onset disease modeling with iPSCs requires proper maturation for full manifestation of pathological features. Herein, the success of iPSC technology, focusing on patient-specific drug treatment, maturation-based disease modeling, and alternative approaches to compensate for the current limitations of patient iPSC modeling, will be further discussed. [BMB Reports 2015; 48(5): 256-265]

• Korean Journal of Health Education and Promotion
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• v.23 no.2
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• pp.1-10
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• 2006

Purpose: This study was aimed to evaluate the effects of substance abuse prevention education for middle school students in Busan. Method: The data were collected by a self-administered questionnaire before education and one month later. The whole subjects were 458 students in first grade of middle school. The data were analyzed using frequencies and difference t-test after classifying the whole into potential drug abuse group and not potential group. Results: The substance abuse prevention education was ineffective in the whole group and the potential group. However, in the not potential group, the increasing rate of SPDA(Screening scale for Potential Drug-use Adolescents) score in experimental group was less than in control group. Conclusion: The substance abuse prevention education was effective for the not potential drug abuse group. On the other hand, intensive long-term drug abuse treatment program was needed for the potential group.

• Journal of Pharmaceutical Investigation
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• v.22 no.3
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• pp.17-34
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• 1992

A novel drug delivery system, detergent-phospholipid mixed micelles as proliposomes, for water-insoluble compounds was developed by investigating (i) spontaneous formation of small unilamellar vesicles (SUV) from bile salt-egg phosphatidylcholine mixed micelles, (ii) the molecular mechanism of micelle-to-vesicle transition in aqueous mixtures of detergent-phospholipid, (iii) preparation and screening of a suitable liposomal formulation for a lipophilic drug: solubilization of the drug within the lipid bilayer, evaluation of the solubility limit, and characterization of the resulting product with respect to the physical properties and stability of the drug in the system, and (iv) testing antitumor activity in vitro. The results showed that the new carrier had a strong possibility to be a biocompatible universal formulation for water-insoluble drugs.

• Proceedings of the Korean Vacuum Society Conference
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• 2013.02a
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• pp.83-83
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• 2013

To date, various nanobiotechnologicalapproaches for biosensors and drug development have been explosively studied. Despite of successful demonstrations, the new technologies hardly enjoyed routine applications in practical nanobiomedicine. Here, researchers trained at the interface of basic sciences and engineering are expected to play critical roles. In this tutorial, I will introduce recent studies which harness graphene derivatives for developing bioanalytical platforms to quantitatively analyze various enzyme activities and biomarkers. The systems rely on attractive interaction between graphene oxide and nucleic acids or phospholipids. Recently, one of the graphene-based bioassay system was applied to anti-viral drug screening and potent hit compounds were identified to treat hepatitis C. This study clearly shows that a new nanobio-technology can be routinely implemented in drug discovery, providing many advantages over conventional methods.

• Journal of Korean Academy of Fundamentals of Nursing
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• v.14 no.4
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• pp.524-535
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• 2007

Purpose: The purpose was to identify the risk of drug use by adolescents. Method: The participants were 933 male students in the first grade of a high school in D city. The data were collected from Aug. 5th to Oct. 30th, 2004. The instrument was the High Risk Group Adolescent Drug User Screening Test(HIRIGADUST) developed by the Korea Adolescent Society(1996). The data were analyzed using SPSS. Results: For substance use, 64.5% of the students answered that they had drunk, 40.3% that they had smoked, and 2.0% that they had tried drug use. For scores on HIRIGADUST regarding socio-demographic characteristics, there were significant differences depending on school type, personality, academic performance, economic status, and ability to talk with parents. For scores on HIRIGADUST regarding drug using-related characteristics, there were significant differences depending on drinking experience, frequency of drinking, amount of alcohol intake, smoking experience and number of cigarettes smoked. Of the students 27.2% students were in the high risk group. Conclusion: In schools, systematic and intensive assessment of drug use should be done, and if needed, a service system connected to clinics specializing in drug addiction should be established. Prevention education should be carried out continuously.

• Genomics & Informatics
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• v.14 no.4
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• pp.241-254
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• 2016

Environmental microbes like Bordetella petrii has been established as a causative agent for various infectious diseases in human. Again, development of drug resistance in B. petrii challenged to combat against the infection. Identification of potential drug target and proposing a novel lead compound against the pathogen has a great aid and value. In this study, bioinformatics tools and technology have been applied to suggest a potential drug target by screening the proteome information of B. petrii DSM 12804 (accession No. PRJNA28135) from genome database of National Centre for Biotechnology information. In this regards, the inhibitory effect of nine natural compounds like ajoene (Allium sativum), allicin (A. sativum), cinnamaldehyde (Cinnamomum cassia), curcumin (Curcuma longa), gallotannin (active component of green tea and red wine), isoorientin (Anthopterus wardii), isovitexin (A. wardii), neral (Melissa officinalis), and vitexin (A. wardii) have been acknowledged with anti-bacterial properties and hence tested against identified drug target of B. petrii by implicating computational approach. The in silico studies revealed the hypothesis that lpxD could be a potential drug target and with recommendation of a strong inhibitory effect of selected natural compounds against infection caused due to B. petrii, would be further validated through in vitro experiments.

• Journal of Microbiology and Biotechnology
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• v.31 no.4
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• pp.621-629
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• 2021

Shigella flexneri is a facultative intracellular pathogen that causes bacillary dysentery in humans. Infection with S. flexneri can result in more than a million deaths yearly and most of the victims are children in developing countries. Therefore, identifying novel and unique drug targets against this pathogen is instrumental to overcome the problem of drug resistance to the antibiotics given to patients as the current therapy. In this study, a comparative analysis of the metabolic pathways of the host and pathogen was performed to identify this pathogen's essential enzymes for the survival and propose potential drug targets. First, we extracted the metabolic pathways of the host, Homo sapiens, and pathogen, S. flexneri, from the KEGG database. Next, we manually compared the pathways to categorize those that were exclusive to the pathogen. Further, all enzymes for the 26 unique pathways were extracted and submitted to the Geptop tool to identify essential enzymes for further screening in determining the feasibility of the therapeutic targets that were predicted and analyzed using PPI network analysis, subcellular localization, druggability testing, gene ontology and epitope mapping. Using these various criteria, we narrowed it down to prioritize 5 novel drug targets against S. flexneri and one vaccine drug targets against all strains of Shigella. Hence, we suggest the identified enzymes as the best putative drug targets for the effective treatment of S. flexneri.

• Mass Spectrometry Letters
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• v.12 no.2
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• pp.31-40
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• 2021

Probable human carcinogenic compounds nitrosamines, have been detected as by-product impurities in sartan pharmaceuticals in recent years which has drawn worries for medication safety. To provide a sensitive and effective method for the quality control of sartan pharmaceuticals, this study established a feasible gas chromatography-tandem mass spectrometry (GC-MS/MS) method for simultaneous determination of 13 nitrosamines. The target analytes were separated on a DB-WAX Ultra Inert column (30 m × 0.25 mm; i.d., 0.25 ㎛) and were then subjected to electron impact ionization in multiple reaction monitoring mode. The established method was validated and further employed to analyze authentic samples. Limits of detection (LODs) and limits of quantification (LOQs) of the 13 nitrosamines were 15-250 ng/g and 50-250 ng/g, respectively, which also exhibited intra-day and inter-day accuracies of 91.4-104.8%, thereby satisfying validation criteria. Five nitrosamines, viz., N-nitrosodiethylamine, N-nitrosodimethylamine, N-nitrosodiphenylamine, N-nitrosomorpholine, and N-nitrosopiperidine were detected at concentrations above their LODs in 68 positive samples out of 594 authentic samples from seven sartans.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3817-3825
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• 2015

Background: The human protein methyl-transferase DOT1L catalyzes the methylation of histone H3 on lysine 79 (H3K79) at homeobox genes and is also involved in a number of significant processes ranging from gene expression to DNA-damage response and cell cycle progression. Inhibition of DOT1L activity by shRNA or small-molecule inhibitors has been established to prevent proliferation of various MLL-rearranged leukemia cells in vitro, establishing DOT1L an attractive therapeutic target for mixed lineage leukemia (MLL). Most of the drugs currently in use for the MLL treatment are reported to have low efficacy, hence this study focused on various natural compounds which exhibit minimal toxic effects and high efficacy for the target receptor. Materials and Methods: Structures of human protein methyl-transferase DOT1L and natural compound databases were downloaded from various sources. Virtual screening, molecular docking, dynamics simulation and drug likeness studies were performed for those natural compounds to evaluate and analyze their anti-cancer activity. Results: The top five screened compounds possessing good binding affinity were identified as potential high affinity inhibitors against DOT1L's active site. The top ranking molecule amongst the screened ligands had a Glide g-score of -10.940 kcal/mol and Glide e-model score of -86.011 with 5 hydrogen bonds and 12 hydrophobic contacts. This ligand's behaviour also showed consistency during the simulation of protein-ligand complex for 20000 ps, which is indicative of its stability in the receptor pocket. Conclusions: The ligand obtained out of this screening study can be considered as a potential inhibitor for DOT1L and further can be treated as a lead for the drug designing pipeline.