• Applied Chemistry for Engineering
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• v.28 no.4
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• pp.404-409
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• 2017

Natural polymer chitosan has been widely applied to medical fields due to its biochemical activities such as anticancer, antibacterial and lowering cholesterol in addition to biocompatibility and biodegradability. Currently, researches are being actively conducted to develop various drug-encapsulated chitosan nanoparticles for curing different diseases by applying chitosan to a drug delivery system. The free amine ($-NH_2$) group present in chitosan can bind to various hydrophobic groups by physical and chemical modification and the chitosan with hydrophobic groups can form shell-core nanoparticles by self-assembly when dispersed in water. In addition, an insoluble drug can increase the solubility against water when it was encapsulated in the core of chitosan nanoparticles. Also, the therapy effect can be maximized by minimizing side effects of drugs such as proteins, anticancer drugs and vaccines when they were encapsulated in the core of chitosan nanoparticles. Moreover, it is possible to control the particle size and release rate according to the hydrophobic group introduced to chitosan, so that it can be applied to a wide range of medical fields. The purpose of this review is to discuss the preparation and property of chitosan nanoparticles modified with various hydrophobic groups, and the application to drug delivery systems according to their property.

• Journal of Life Science
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• v.21 no.11
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• pp.1558-1564
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• 2011

Cytochrome P450 2J2 (CYP2J2) plays important roles in the metabolism of endogenous metabolites such as arachidonic acid as well as therapeutic drugs. CYP2J2 is overexpressed in human cancer tissues and cancer cell lines, as well as in epoxyeicosatrienoic acids (EETs) and CYP2J2-mediated metabolites, and prevent apoptosis of cancer cells. This study aimed to screen marketed drugs for inhibitory potential on CYP2J2 isoforms using human liver microsomes. The initial screen isolated 4 compounds, from 120 marketed drugs, that inhibited the CYP2J2-mediated astemizole O-demethylation more than 50% in the following the order: haloperidol (75%) > terfenadine (56%) > aripiprazole (55%) > miconazole (52%). Miconazole strongly inhibited CYP2J2-mediated ebastine hydroxylation ($IC_{50}$=11.2 ${\mu}M$) and terfenadine hydroxylation ($IC_{50}$=2.2 ${\mu}M$), and terfenadine also inhibited CYP2J2-mediated ebastine hydroxylation ($IC_{50}$=13.6 ${\mu}M$) in a dose dependent manner. The present data suggest that these drugs are potential candidates for further evaluation for their anti-cancer activities.

• Journal of Korean Traditional Oncology
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• v.15 no.1
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• pp.119-128
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• 2010

항암치료는 현재 암환자의 주요한 치료임에도 불구하고 항암제내성과 같은 문제점을 가지고 있다. 약물내성은 다양한 기전에 의해 발생하는데 수송단백질의 과발현, 비독성화발현, 손상유전자의 복구, 세포사멸신호의 변화, STAT-3와 NF-${\kappa}B$의 발현 등이 포함된다. 암세포는 저산소환경에서 발생하며 일반세포에 비해 무산소해당에 상대적 의존도가 높고 이는 암세포의 성장과 전이를 촉진하는 인자가 된다. 항암제가 효과를 내기 위해서는 산소가 필요한데 저산소환경은 이를 방해하며 또한 유전자의 불안정화로 인해 약물내성이 유도된다. NF-${\kappa}B$는 주요 전사인자 중 하나로서 각종 염증과 암에서 지속적으로 활성화되며 암세포의 변화, 증식, 침윤, 전이에 관여한다. 환경적 스트레스 등과 대부분의 항암약제들이 NF-${\kappa}B$를 활성화시키며 임상적으로도 암환자의 생존과 연관된 중요한 예후인자이다. NF-${\kappa}B$의 발현은 항암제로 인한 암세포의 자멸을 회피하게 만들고 수송단백질을 활성화시켜 항암제내성을 유도한다. 강황, 적포도, 고추, 건칠 등 다양한 천연물에서 NF-${\kappa}B$를 억제시키는 효능이 발견되었으며 이는 항암제내성을 억제시키고 항암제의 효과를 증대시킨다. 저산소환경의 개선과 NF-${\kappa}B$의 억제는 상호연관성을 가지고 있으며 항암제내성의 개선뿐만 아니라 암치료제 개발의 새로운 연구목표가 될 수 있다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.11a
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• pp.143-145
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• 1994

Chimeric fusion proteins involving IgG have proven valuable in studying protein-protein interactions and may possess therapeutic applications as well. For example, three receptor subtypes for the natriuretic peptides, when fused to the Fc portion of human IgG ${\gamma}$ chain, were quantitatively and qualitatively indistinguishable from the native receptor, thus allowing detailed structure-function studies of the receptor. In an attempt to block human immunodeficiency virus infectivity with soluble derivatives of CD4, a CD4/IgG Fc chimeric molecule was shown to increase the plasma half life of soluble CD4 and possessed the added advantage of IgG Fc-mediated placental transfer. In the case of the KGFR, this approach provided a framework for dissection of its ligand binding domains and made it possible to demonstrate that high affinity binding sites for two ligands, aFGF and KGF, reside within different receptor Ig-like domains. Chimeric molecules fused to immunoglobulins would have the advantages of secretion from transfected cells as well as detection and purification from medium utilizing Staphylococcus aureus Protein A. In addition, where highly related receptors make their discrimination very hard due to the difficulties in generating specific immunochemical probes, IgG fusion protein with tailor-made specificities confers particular advantages to elucidate patterns of receptor distribution and expression. The approach described here may have general applications in defining ligand-receptor interactions as well as searching for specific agonists and antagonists of receptor function.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.144-144
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• 1993

한국에서 유행하는 페염균 type을 결정하기 위한 기초 실험을 수행하여 서울대병원과 서울중앙병원의 환자로부터 분리한 88개의 폐염균주를 담즙산에 의한 용해도 및 Optochin에 대한 민감성 등을 측정하고 폐염균의 type을 결정하기 위해서 Double diffusion, Countercurrent immunoelectrophoresis, Rocket immunoelectrophoresis 방법 등으로 폐염균 항혈청과 반응하였다. 또한 ATCC로부터 구입한 폐염균주를 이용하여 배지조성의 변화에 따른 폐염균 생장을 측정하기 위해 CAT broth, Brain Heart Infusion broth, Defined Media에서 3가지 type의 균주(Type I, III, IV)를 접종하고 37$^{\circ}C$에서 배양하면서 1시간마다 550nm에서 흡광도를 측정하였다. 3가지 type (Type I, III, IV)의 폐염균주로부터 협막다당류를 phenol Iysis 추출법으로 폐염균 Capsule 다당류의 분리하여 Total Sugar 함량, Uronic acid 함량, 0-Acetyl 함량, 단백질 함량, 핵산 함량, 분자량분포 Countr-current immunoelectrophoresis 등을 실시하여 폐염균 백신 규격에 부합되는지 확인하였다. 수집한 88개의 폐염균주가 모두 담즙산에 의해 용해되고 6mm Optochin disc를 사용하였을때 성장 저지원이 모두 14mm 이상으로 나타나 감수성이 있어서 폐염균임을 확인하였으며 폐염균의 type 결정에 필요한 방법을 설정하였다. 배지조성에 따른 폐염균의 생장을 측정한 결과 CAT broth 에서는 Type I만이 잘 배양되었고 Type III, IV는 늦게 배양되었으나, Brain Heart Infusion broth에서는 3가지 Type이 모두 잘 배양되었고, Defined Media 에서는 Type I만이 성장되었을 뿐 나머지 두 Type은 배양되지 않았다. 본 실험방법으로 분리된 폐염균 다당류는 폐염균 백신 규격중의 6가지 항목에서 적합하였으며 Statens(Denmark)로부터 구입한 항체와 뚜렷한 침강선을 나타내었다.

• Journal of Life Science
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• v.17 no.11
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• pp.1523-1532
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• 2007

In order to determine if the mRNA and protein expression levels of 3T3-L1 adipocytes are influenced by oriental medicines, adipocytes were treated with $100\;{\mu}g/ml$ of G-Re and aqueous extract of a Coix lachrymajobi var. mayuen (AEC) every other day for 12 days, respectively. The tumor necrosis factor alpha ($TNF-{\alpha}$). mRNA and protein expressions were suppressed markedly in treated mature adipocytes. Those of lipoprotein lipase (LPL) levels were found to increase gradually in preadipocytes differentiating into mature adipocytes. Those were higher than that of the untreated mature adipocytes. The treated adipocytes showed reduction of leptin expression levels, while in untreated mature adipocytes cell, those of levels were significantly higher after the conversion of preadipocytes into mature adipocytes. The resistin levels in the treated adipocytes were significantly decreased comparing to that of the untreated mature adipocytes. In conclusion, the expression levels of LPL, $TNF-{\alpha}$, leptin and resistin mRNA and proteins are shown to be regulated by G-Re and AEC, making them potential candidates for controlling fat mass related obesity.

• Journal of Veterinary Clinics
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• v.21 no.2
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• pp.219-228
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• 2004

Heart diseases related to conduction system can be occurred by primary defects in conduction system and by secondary to morphological heart diseases or drug toxicities. Multiple molecular defects responsible for arrhythmogenesis, including mutations in ion channels, cytoplasmic ion-channel-interacting proteins, gap-junction proteins, transcription factors and a kinase subunit, were found to be associated with the aetiology of primary cardiac conduction defects, especially inherited form. Despite a big progress in unveiling human arrhythmogenesis, conduction defects in dog has not been well studied except sudden death syndrome in German shepherd. In this review, molecular genetics in cardiac arrhythmogenesis, inherited human diseases associated with conduction defects and similar diseases in dogs will be discussed.

• Polymer(Korea)
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• v.32 no.3
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• pp.199-205
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• 2008

In this study, we fabricated poly (lactide-co-glycolide) (PLGA) scaffold modified with small intestinal submucosa (SIS) as a drug delivery matrix of bioactive molecules. SIS derived from the submucosa layer of porcine intestine has been widely used as biomaterial because of low immune response. PLGA scaffold was prepared by the method of solvent casting/salt leaching. Novel composite scaffolds of SIS/PLGA were manufactured by simple immersion method of PLGA scaffold in SIS solution under vacuum. SEM observation shows that PLGA and SIS/PLGA scaffolds have interconnective and open pores. Especially, SIS/PLGA scaffold showed that micro-sponge of SIS with interconnected pore structures were formed in the pores of PLGA scaffold. In order to assay release profile of proteins, we manufactured FITC conjugated BSA loaded PLGA and SIS/PLGA scaffold. And the release amount was identified by fluorescence intensity using the fluorescence spectrophotometer. The initial burst of BSA containing SIS/PLGA scaffolds was lower than that of PLGA scaffolds resulting in constant release. And release of BSA in SIS/PLGA scaffold was fast and incremental because of the increased content of BSA. In conclusion, we confirmed that penetrated SIS solution prevented the initial burst of BSA and PLGA modified with SIS scaffold is useful as protein carriers with controlled release pattern.

• KIPS Transactions on Software and Data Engineering
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• v.11 no.1
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• pp.11-18
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• 2022

De novo drug design is the process of developing new drugs that can interact with biological targets such as protein receptors. Traditional process of de novo drug design consists of drug candidate discovery and drug development, but it requires a long time of more than 10 years to develop a new drug. Deep learning-based methods are being studied to shorten this period and efficiently find chemical compounds for new drug candidates. Many existing deep learning-based drug design models utilize recurrent neural networks to generate a chemical entity represented by SMILES strings, but due to the disadvantages of the recurrent networks, such as slow training speed and poor understanding of complex molecular formula rules, there is room for improvement. To overcome these shortcomings, we propose a deep learning model for SMILES string generation using variational autoencoders with self-attention mechanism. Our proposed model decreased the training time by 1/26 compared to the latest drug design model, as well as generated valid SMILES more effectively.

• Childhood Kidney Diseases
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• v.13 no.2
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• pp.170-175
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• 2009

Purpose : FSGS do not respond well to any kind of therapy and gradually progress to end-stage renal disease. This study was conducted to investigate the difference of protein expression between MCNS and FSGS as a preliminary study for understanding the pathophysiology of FSGS. Methods : Renal biopsy samples of MCNS and FSGS were obtained, which was diagnosed by one pathologist. They were solubilized with a conventional extraction buffer for protein extraction. The solution was applied on immobilized linear gradient strip gel (pH 4-7) using IPGphor system. Silver staining was carried out according to standard method. Protein identification was done by searching NCBI database using MASCOT Peptide Mass Fingerprint software. Results : The differences in protein expressions between MCNS and FSGS were shown by increased or decreased protein spots. Most prominently expressed spot among several spots in FSGS was isolated and analyzed, one of which was glutathione S-transferase (GST) P1-1, whereas it was not found in MCNS. So GSTP1-1 was considered as the one of the key biomarkers in pathogenesis of FSGS. Conclusion : This result would be helpful in diagnosing FSGS and researching FSGS. Further studies for glutathione S-transferase P1-1 might be necessary to elucidate the mechanisms regarding FSGS.