• IMMUNE NETWORK
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• v.22 no.1
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• pp.8.1-8.20
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• 2022

Rheumatoid arthritis (RA) is a representative autoimmune disease that is primarily characterized by persistent inflammation and progressive destruction of synovial joints. RA has a complex and heterogeneous pathophysiology, involving interactions among various immune and joint stromal cells and a diverse network of cytokines and intracellular signaling pathways. With improved understanding of RA, over the past decades, therapeutic strategies have become considerably advanced and now included targeted molecular therapies, such as tumor necrosis factor inhibitors, IL-6 blockers, B-cell depletion agents, as well as inhibitors of T-cell co-stimulation and Janus kinases. However, a considerable proportion of RA patients experience refractory disease and interrupted treatment owing to the associated risk of developing serious infections and cancers. In contrast, although IL-1β, IL-17A, and p38α play significant roles in RA pathogenesis, several drugs targeting these factors have not been approved because of their low efficacy and severe adverse effects. In this review, we provide an overview of the working mechanism, advantages, and limitations of the currently available targeted drugs for RA. Additionally, we suggest potential mechanistic causes for clinically approved and failed drugs. Thus, this review provides perspectives on approaches for basic and translational studies that hold promise for identifying future next-generation therapeutics for RA.

• Korea Journal of Hospital Management
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• v.10 no.1
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• pp.93-114
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• 2005

The prenatal care is the preventive medical service to help the pregnant mother deliver the healthy baby. It's regular examines give some chances to check-up the healthy conditions. This thesis concentrates on the CRM system to support an effective prenatal care system and prove the effectiveness of it. As CRM is the adapted management related to the customer's own information, it is important to develop the CRM model classified by the patients characteristics. A general hospital in Busan operated the CRM system to carry out the effective prenatal care and there is an analysis to ensure the effectiveness of CRM system for the pregnant women in our maternity ward. The results can be summarized as follows: 1) According to the comparisons with the CRM system, we can conclude the system is desirable. (1) Maternal Age : In the age distribution, the prenatal visit frequency, triple marker freqency, oral GTT and targeted ultrasonography in the experimental group in 30 to 34 years old is higher on the whole. For over 35 years old group, the higher frequency comes out in the oral GTT and targeted ultrasonography and for 25 to 29 years old group the different figure shows just in the targeted ultrasonography. (2) Area of residence: There is a clear difference in all the items in Busan and near area but no sign of difference in prenatal visits and oral GTT in other residencial area. Especially in the targeted ultrasonography the higher figure shows in the experimental group located in the both areas. The targeted ultrasonography is known as the specific examination which should be examined by the specialists, on the contrary the other examinations can be operated in the small clinic. So the public information and seminars related with ultrasonography increases the check-up frequency. The clinic requests some ultrasonographical examinations to the specialists in general hospital. (3) Parity: The clear difference shows that the CRM system causes the prenatal visit frequency to become higher in experimental group. The figure is 9.7 times and 8.6 times each. This is opposite that the past study said multiparity reduced the average prenatal visits. But the result of CRM is considered as the method to help the multiparity understand the importance of the prenatal care. (4) Obstetrical history: In the experimental group of the spontaneous delivery group, the figure is higher in the prenatal visit frequency, triple marker, oral GTT and targeted ultrasonography but the Caesarean section delivery group has higher figure in targeted ultrasonography. (5) In the first check-up, the rate of targeted ultrasonography in under 16 week pregnancy, in the 16 week pregnancy to 32 week pregnancy and the over 32 week pregnancy in the experimental group is upper than the compared one. For the oral GTT, there is a difference in under 16 week pregnancy but no difference in prenatal visits and triple marker. 2) The analysis of characteristics of prenatal care through the decision tree resulted in the fact that the most important variable is the residential area. After the delivery frequency is following, the obstetrical history and maternal age are in order. It is the same result in the triple marker and oral GTT. Consequently it is the same order of important variables in CRM system. The effectiveness of CRM system is proved in this study. The CRM system is a marketing method to control and lead the customers through the segmentation of customer data. It increases the new customer aquisition, maintenance of loyal customers, augmentation of customers value, activation of potential customers and creation of life time customers. So eventually it can enlarge the customers value. The medical institution should make efforts to establish the data base enforced by the customer's information on the underlying ordinary data system to carry out the CRM system effectively. In addition, it should develop the a variety of marketing strategy in order to set up one to one marketing satisfying the needs of individual patients.

• Tuberculosis and Respiratory Diseases
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• v.42 no.3
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• pp.302-313
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• 1995

Background: Tumor necrosis factor(TNF) showed antitumor cytolytic effects on sensitive tumor cells in numerous in vivo and in vitro studies. But it could not be administered systemically to human because of severe systemic adverse effects at effective concentrations against tumor cells. Many studies showed that a high concentrations of TNF in the local milieu may evoke in vivo TNF-responsive mechanisms sufficient to suppress tumor growth. Recently developed technique of TNF gene transfer to tumor cells using retrovirus vector could be a good candidate for local TNF administration. TNF is also known to synergistically enhance in vitro cytotoxicity of chemotherapeutic drugs targeted to DNA topoisomerase II against TNF-sensitive tumor cell lines. In this study the in vitro chemosensitivity against DNA topoisomerase II targeted chemotherapeutic drugs was evaluated using some respiratory cancer cell lines to which TNF gene had been transferred. Method: NCI-H2058, a human mesothelioma cell line, A549, a human lung adenocarcinoma cell line and WEHI 164 cell line, a murine fibrosarcoma cell line were treated with etoposide and doxorubicin, which are typical topoisomerase II - targeted chemotherapeutic agents, at different concentration. The resultant cytotoxicity was measured by MIT assay. Then the cytotoxicity of the same chemotherapeutic agents was measured after TNF-$\alpha$ gene-transfer and the two results were compared. Results: The cytotoxicity was not increased significantly in WEHI164 cell line and A549 cell line but statistically significant increase was observed in H2058 cell line when TNF-$\alpha$ gene was transferred(p<0.05). Conclusion: These findings show that TNF-$\alpha$ gene transfer to respiratory cancer cell lines results in variable effects on chemosensitivity against topoisomerase II inhibitor among different cell lines in vitro and can be additively cytotoxic in certain selective tumor cell lines.

• Journal of Microbiology and Biotechnology
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• v.21 no.1
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• pp.14-19
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• 2011

A cyclic undecapeptide-family natural product, cyclosporin A (CyA), which is one of the most valuable immunosuppressive drugs, is produced nonribosomally by a multifunctional cyclosporin synthetase enzyme complex in a filamentous fungal strain named Tolypocladium niveum. Previously, structural modifications of cyclosporins such as a regionspecific hydroxylation at the $4^{th}$ N-methyl leucine in a rare actinomycetes called Sebekia benihana were reported to lead to dramatic changes in their bioactive spectra. However, the reason behind this change could not be determined since a system to genetically manipulate S. benihana has not yet been developed. To address this limitation, in this study, we utilized the most commonly practiced gene manipulation techniques including conjugation-based foreign gene transfer-and-expression as well as targeted gene disruption to genetically manipulate S. benihana. Using these optimized genetic manipulation systems, a putative cytochrome P450 hydroxylase (CYP) gene named CYP506, which is involved in CyA hydroxylation in S. benihana, was specifically disrupted and genetically complemented. The S. benihana${\Delta}$CYP506 exhibited a significantly reduced CyA hydroxylation yield as well as considerable yield restoration by functional complementation of the S. benihana CYP506 gene, suggesting that the genetically manipulated S. benihana CYP mutant strains may serve as a more efficient bioconversion host for various valuable metabolites including CyA.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.10
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• pp.1500-1507
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• 2016

Myostatin (MSTN) can negatively regulate the growth and development of skeletal muscle, and natural mutations can cause "double-muscling" trait in animals. In order to block the inhibiting effect of MSTN on muscle growth, we transferred zinc-finger nucleases (ZFN) which targeted sheep MSTN gene into cultured fibroblasts. Gene targeted colonies were isolated from transfected fibroblasts by serial dilution culture and screened by sequencing. Two colonies were identified with mono-allele mutation and one colony with bi-allelic deletion. Further, we introduced the MSTN-ZFN mRNA into sheep embryos by microinjection. Thirteen of thirty-seven parthenogenetic embryos were targeted by ZFN, with the efficiency of 35%. Our work established the technical foundation for generation of MSTN gene editing sheep by somatic cloning and microinjection ZFN into embryos.

• Journal of the Korean Society of Fisheries and Ocean Technology
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• v.35 no.3
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• pp.237-241
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• 1999

It was investigated that the condition of fishing ground gave what kind of effect school type in relation to the property for the target school after the vertical temperature profile and school type were observed when tuna purse seiner for tuna purse seine was operated in the western pacific Ocean around the equator between December 12, 1993 and January 26, 1994. The results are as follows;1. This study divided fish schools associated with drift objects, a one targeted-operation, and the pelagic migrating fish schools that are another one for the property. The total of 23 operations were complected including 6 that targeted fish schools associated with drift objects and 17 that targeted pelagic migrating fish schools. It was known that the main operation was conducted on pelagic migrating fish school.2. Average and standard deviation of the depth of the surface mixing layer was 86.0m and 13.8m for fish schools associated with drift objects. 61.6m and 13.0m for pelagic migrating fish schools, respectively. The average depth of the surface mixing layer of the pelagic migrating fish schools was lower when compared to the fish schools associated with drift objects however the concentration of standard deviation was higher than those fish schools associated with drifted objects. Accordingly, it was assumed that the effect of vertical temperature profile for pelagic migrating fish school was higher than the fish schools associated with drift objects.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2005.09a
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• pp.134-138
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• 2005

The design of ion channel targeted library is a valuable methodology that can aid in the selection and prioritization of potential ion channel-likeness for ion-channel-targeted bio-screening from large commercial available chemical pool. The differences of property profiling between the 93 ion-channel active compounds from MDDR and CMC database and the ACDSC compounds were classified by suitable descriptors calculated with preADME software. Through the PCA, clustering, and similarity analysis, the compounds capable of ion channel activity were defined in ACDSC compounds pool. The designed library showed a tendency to follow the property profile of ion-channel active compounds and can be implemented with great time and economical efficiencies of ligand-based drug design or virtual high throughput screening from an enormous small molecule space.

• Biomolecules & Therapeutics
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• v.24 no.3
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• pp.305-311
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• 2016

Mitochondria-targeted vitamin E (MVE) is designed to accumulate within mitochondria and is applied to decrease mitochondrial oxidative damage. However, the protective effects of MVE in skin cells have not been identified. We investigated the protective effect of MVE against UVB in dermal fibroblasts and immortalized human keratinocyte cell line (HaCaT). In addition, we studied the wound-healing effect of MVE in animal models. We found that MVE increased the proliferation and survival of fibroblasts at low concentration (i.e., nM ranges). In addition, MVE increased collagen production and downregulated matrix metalloproteinase1. MVE also increased the proliferation and survival of HaCaT cells. UVB increased reactive oxygen species (ROS) production in fibroblasts and HaCaT cells, while MVE decreased ROS production at low concentration. In an animal experiment, MVE accelerated wound healing from laser-induced skin damage. These results collectively suggest that low dose MVE protects skin from UVB irradiation. Therefore, MVE can be developed as a cosmetic raw material.

• Journal of Environmental Health Sciences
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• v.35 no.5
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• pp.365-375
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• 2009

Agriculture reservoirs need a systematic approach that can control water purity and water improvement. The area under study, Bunam Lake exceeds the agricultural water standard level due to contamination from the upper stream. When the Taean Enterprise City was planned, the water quality improvement plan was applied to minimize the environmental change. However, in order to continuously maintain the water quality in the Bunam Lake, it was essential to apply the Total Pollution Load Management System (TPLMs). In order to achieve the targeted water quality in the Bunam Lake, standard flow rates and targeted water quality levels were applied to obtain the loading capacity which is as follows : BOD 1,891.2 kg/d, T-N 1,945.7 kg/d, T-P 131.7 kg/d. Also, the regional development load was calculated as, BOD 1,083.6 kg/d, T-N 942.2 kg/d, T-P 61.8 kg/d, which is required to be deceased :- by BOD 378.4 kg/d, T-N 198.9 kg/d, T-P 31.6 kg/d in order to safely achieve the targeted water quality in the Bunam Lake.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.5
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• pp.411-422
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• 2020

With the increasing number of children with inflammatory bowel disease (IBD), very early-onset IBD (VEO-IBD), defined as IBD that is diagnosed or that develops before 6 years of age, has become a field of innovation among pediatric gastroenterologists. Advances in genetic testing have enabled the diagnosis of IBD caused by gene mutations, also known as monogenic or Mendelian disorder-associated IBD (MD-IBD), with approximately 60 causative genes reported to date. The diagnosis of VEO-IBD requires endoscopic and histological evaluations. However, satisfactory small bowel imaging studies may not be feasible in this small population. Both genetic and immunological approaches are necessary for the diagnosis of MD-IBD, which can differ among countries according to the available resources. As a result of the use of targeted gene panels covered by the national health insurance and the nationwide research project investigating inborn errors of immunity, an efficient approach for the diagnosis of MD-IBD has been developed in Japan. Proper management of VEO-IBD by pediatric gastroenterologists constitutes a challenge. Some MD-IBDs can be curable by allogenic hematopoietic stem cell transplantation. With an understanding of the affected gene functions, targeted therapies are being developed. Social and psychological support systems for both children and their families should also be provided to improve their quality of life. Multidisciplinary team care would contribute to early diagnosis, proper therapeutic interventions, and improved quality of life in patients and their families.