• Proceeding of EDISON Challenge
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• 2017.03a
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• pp.158-164
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• 2017

암을 억제시키는 기능을 하는 단백질로 잘 알려진 p53은, 주로 종양세포에서 과도하게 발현되는 단백질인 HDM2와 복합체를 형성하여 비활성화되고 항암기능을 상실하게 됩니다. 때문에 종양세포에서의 p53-HDM2의 상호작용을 억제하기 위해 현재까지 많은 연구가 진행되어왔으며, 다양한 p53-HDM2 억제제가 개발된 바 있습니다. 최근 연구들에 따르면, HDM2와 결합친화도를 높이고 소수성 작용(hydrophobic interaction)에 기여하여 보다 안정한 구조를 만드는 탄화수소체인(staple)을 연결시킨 펩타이드 설계에 대한 관심이 높아지고 있는 추세입니다. 이에, 본 연구에서는 분자동역학 모의실험을 통해서 얻은 탄화수소체인-p53과 비탄화수소체인-p53 및 각각의 HDM2와 결합한 복합체를 기반으로 EDISON의 용매화 자유에너지(Solvation Free Energy) 프로그램을 이용하여 탄화수소체인의 특징 및 역할을 구조적인 측면과 열역학적인 측면으로 분석하여 비교하고자 합니다. 우리 연구에서 비탄화수소체인-p53의 구조는 분자동역학 시뮬레이션을 수행하는 동안 나선구조형태로 풀려 HDM2와 결합 유도 시에 주요결합 아미노산 잔기가 올바른 결합부위와 상호작용하지 못한 결과를 확인한 반면, 탄화수소체인이 형성된 구조는 시뮬레이션 동안에도 펩타이드의 나선구조를 유지시켜 HDM2와 주요 결합을 형성하는 아미노산 잔기들을 올바른 방향으로 배치시켜 HDM2와의 결합친화도를 높였습니다. 이 연구 결과는 탄화수소체인이 펩타이드의 나선성을 유지시키고, HDM2와의 상호작용을 통한 구조적인 안정성 유도 및 용매화 자유에너지에 큰 기여를 통해 p53-HDM2상호작용 억제제에서 긍정적인 역할을 할 가능성을 보여줍니다.

• Korean Journal of Community Nutrition
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• v.8 no.5
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• pp.736-743
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• 2003

The purpose of this study was to research the current home delivered meal (HDM) service programs for seniors living in the community. Fifty seven centers which operated a HDM service program were surveyed with respect to their administrative structure, menu management, food purchasing and production management, hygiene and equipment and facility. -Statistical data analyses were completed using the SAS 8.1 program for descriptive analysis and t-test. The results showed that 55 percent of the study group were from 70 to 79 years old. All of the participants received free HDM. As a result of the meal cost analysis, the meal cost at 56.1% of the HDM service centers was from ￦2,000 to ￦2,499 per meal. A total of 68.4% of the HDM service centers were operated without the services of a dietitian. According to the menu analysis, all nutrients except Vitamin B2 were at levels of more than 33% of the Recommended Dietary Allowances for Koreans. Although 96.6% of the HDM service centers required a therapeutic diet menu for the health of the elderly recipients, 68% of the directors responded that they could not afford to serve therapeutic meal. Food purchasing, menu planning and other foodservice management processes were handled by non-professionals, such as volunteers, cooks or social workers. Forty two percent of the HDM service centers never used standard recipes. For determining portion sizes, 75.4% of the HDM service centers depended on personal experience. Finally, the current HDM service programs for the homebound elderly were not operated systematically. It is suggested that professionally trained personnel should be included among the staff members to provide a more effective HDM service. The HDM service programs should be supported financially and systematically by the government.

• Proceeding of EDISON Challenge
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• 2016.03a
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• pp.62-66
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• 2016

Tumor suppressor protein p53 loses its function upon binding with the HDM2 protein, and inhibiting the p53-HDM2 interaction is critical to suppress tumor cell growth. Recently, the cyclized helix-loop-helix peptide (cHLH) mimicking the ${\alpha}-helix$ part of the p53 protein has been designed and found to exhibit high binding affinity with HDM2. Here, we report the structural and thermodynamic characteristics of the bound complex of the cHLH peptide with the HDM2 protein. We performed molecular dynamics simulations to investigate the structural features of the cHLH peptide as well as its complex with the HDM2. The binding free energy calculation based on the integral equation theory was also executed to quantify the binding affinity for the cHLH/HDM2 complex and to understand the factors contributing to the binding affinity. We found a variety of factors for the helix stability of the cHLH peptide as well as in the complexation with the HDM2, which may provide an insight into the development of anti-cancer drug designs.

• BMB Reports
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• v.54 no.3
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• pp.182-187
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• 2021

Leukotriene B4 (LTB4) is a lipid mediator of inflammation that is generated from arachidonic acid via the 5-lipoxygenase pathway. Previous studies have reported that the receptors of LTB4, BLT1, and BLT2 play mediatory roles in the allergic airway inflammation induced by ovalbumin (OVA). However, considering that house dust mites (HDMs) are the most prevalent allergen and well-known risk factor for asthmatic allergies, we are interested in elucidating the contributory roles of BLT1/2 in HDM-induced allergic airway inflammation. Our aim in this study was to investigate whether BLT1/2 play any roles in HDM-induced allergic airway inflammation. In this study, we observed that the levels of ligands for BLT1/2 [LTB4 and 12(S)-HETE (12(S)-hydroxyeicosatetraenoic acid)] were significantly increased in bronchoalveolar lavage fluid (BALF) after HDM challenge. Blockade of BLT1 or BLT2 as well as of 5-lipoxygenase (5-LO) or 12-lipoxygenase (12-LO) markedly suppressed the production of TH2 cytokines (IL-4, IL-5, and IL-13) and alleviated lung inflammation and mucus secretion in an HDM-induced eosinophilic airway-inflammation mouse model. Together, these results indicate that the 5-/12-LO-BLT1/2 cascade plays a role in HDM-induced airway inflammation by mediating the production of TH2 cytokines. Our findings suggest that BLT1/2 may be a potential therapeutic target for patients with HDM-induced allergic asthma.

• Journal of Veterinary Clinics
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• v.21 no.2
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• pp.93-96
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• 2004

We examined the responses of PBMCs to house dust mite (HDM) allergen in atopic and healthy, non-atopic dogs to identify differences in lymphocyte reactivity that might reflect the immunologic status of atopic dermatitis. Thirteen of 20 (65%) atopic dogs showed a positive lymphocyte proliferative response to HDM allergen. The rate of response was significantly higher in the atopic dogs than that in healthy, non-atopic dogs insensitive to the allergen (P = 0.007). The proliferative responses were positively correlated with the level of HDM-specific IgE in serum (P = 0.035), and were thereby confirmed to reflect the activity of lymphocytes competent to promote IgE production. These results suggest that HDM-specific lymphocytes were present in peripheral blood and played a role in the pathogenesis of canine atopic dermatitis.

• International Journal of Oral Biology
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• v.40 no.1
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• pp.11-17
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• 2015

The gingival epithelium of the oral cavity is constantly exposed to exogenous stimuli such as bacterial toxins, allergens, and thermal changes. These exogenous stimuli are resisted by innate host defense in gingival epithelial cells. However, it is unclear exactly how the exogenous stimuli affect detrimentally on the human gingival epithelial cells. Here, we investigated whether the allergen, such as house dust mite (HDM) extract, is linked to $Ca^{2+}$ signaling and proinflammatory cytokine expression in primary cultured human gingival epithelial cells. HDM extract induced an increase in intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) in a dose-dependent manner. Extracellular $Ca^{2+}$ depletion did not affected on the HDM extract-induced increase in $[Ca^{2+}]_i$. The HDM extract-induced increase in $[Ca^{2+}]_i$ was abolished by the treatment with U73122 and 2-APB, which are inhibitors of phospholipase C (PLC) and inositol 1,4,5-trisphosphate ($IP_3$) receptor. Moreover, HDM extract induced the mRNA expression of pro-inflammatory cytokine, interleukin (IL)-8. These results suggest that HDM extract triggers $PLC/IP_3$-dependent $Ca^{2+}$ signaling and IL-8 mRNA expression in primary cultured human gingival epithelial cells.

• Clinical and Experimental Pediatrics
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• v.58 no.3
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• pp.89-95
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• 2015

Purpose: House dust mite (HDM) has been suggested to be the most important aeroallergen responsible for atopic asthma in Korea. We aimed to investigate that specific IgE antibodies to HDM and other common indoor aeroallergens contribute differently to total serum IgE and show different relationships with longitudinal fractional exhaled nitric oxide (FeNO) measurements in Korean atopic asthmatic patients. Methods: A total of 193 children aged 8 to 16 years with intermittent or mild persistent atopic asthma were recruited. Sera were assayed for total IgE and specific IgE antibodies to HDM and other common indoor allergens. FeNO was serially measured 10 times or more over 2 years when subjects were not receiving controller medications. Results: In 152 children who completed the study, IgE antibodies to specific HDM were more prevalent than those to other common indoor aeroallergens. In addition, IgE antibody titers to HDM were the strongest contributor to total IgE increases. Furthermore, only HDM-specific IgE antibody titer significantly correlated with maximum FeNO (r=0.21, P=0.029) and the rate of FeNO higher than 21 parts per billion (ppb) (r=0.30, P=0.002). Eight patients (5%) were found to have maximum FeNO of 21 ppb or less, suggesting the presence of a low FeNO phenotype among atopic asthmatic patients. Conclusion: The quantity of HDM-specific IgE antibody provides a possible explanation for increases of total IgE and significantly correlates with the amount and frequency of FeNO increases in Korean atopic asthmatic patients.

• Proceedings of the Korea Water Resources Association Conference
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• 2021.06a
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• pp.248-248
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• 2021

본 연구에서 개발한 하천흐름해석모형 HDM-2Di는 2차원 추적모형에 필요한 격자생성기(RAMS-G) 및 GUI (RAMS+)와 연계하여 요소망 생성기능 및 요소망 처리기능을 통해 실제 지형을 반영할 수 있는 전처리 과정을 수행할 수 있다. 장구간 하천에서 신속하고 정확하게 모의결과를 도출할 수 있도록 입출력 체계를 구조화하다. 또한 하천의 복잡한 지형과 자연 하천구조의 동역학적인 흐름환경을 효과적으로 재현할 수 있으며 흐름해석모의 결과인 2차원 평면상의 유속과 수심을 2차원 유해화학물질 추적모형(CTM-2D-TX)의 입력자료로 활용할 수 있도록 개발하였다. HDM-2Di 모형의 성능 검증을 위하여 정상류 및 준부정류, 부정류 조건 흐름해석 성능 테스트를 진행하였으며, 실제 자연하천의 물리적 구조를 재현한 사행수로 추적자 실험 결과와 모형 결과를 비교분석하였다. 또한 자연하천 적용을 위하여 구미보와 칠곡보 구간을 대상으로 ADCP 실측 결과와 상용모형인 Nays-2DH 모의 결과와의 비교를 통해 HDM-2Di 흐름해석모형의 정확성 및 적용성을 평가하였다.

• Journal of Veterinary Science
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• v.21 no.4
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• pp.59.1-59.12
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• 2020

Background: Atopic dermatitis (AD) is a common chronic inflammatory skin disease. To understand AD, there have been many trials establishing AD animal models. Although various trials to establish AD animal models have been existed, even the mechanisms of AD in animal models are not enough clarified. Objectives: This study assessed AD characteristics induced in Nishiki-nezumi Cinnamon/Nagoya (Nc/Nga) mice following trinitrochlorobenzene (TNCB) treatment for different periods and house dust mite (HDM) treatment to compare each model's immunological patterns, especially with cytokine antibody array tool. Methods: In this study, we exposed Nc/Nga mice to TNCB or HDM extract to induce AD. Nc/Nga mice were divided into 4 groups: control, TNCB 2 weeks-treated, TNCB 8 weeks-treated, and HDM-treated groups. After AD induction, all mice were evaluated by serum immunoglobulin E (IgE) concentration and serum cytokine antibody assays, scoring of skin lesions, scoring of scratching frequency, and histological analysis. Results: The results showed significant differences between groups in serum IgE concentration, skin lesion scores, and scratching frequency. The analysis results for serum cytokine antibody arrays showed that in the TNCB 8 weeks- and HDM-treated groups, but not in the TNCB 2 weeks-treated group, expressions of genes related to the immune response were enriched. Among the histological results, the skin lesions in the HDM-treated group were most similar to those of AD. Conclusions: We confirmed that immunological pattern of AD mice was markedly different between HDM and TNCB treated groups. In addition, the immunological pattern was quietly different dependent on TNCB treated duration.

• Proceedings of the Korea Water Resources Association Conference
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• 2018.05a
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• pp.140-140
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• 2018

다수의 자연 하천은 사행의 형태를 가지고 있으며 자연 상태에서의 직선 하천 형태는 비율이 20% 이하이다. 이러한 하천의 사행 형상으로 인하여 편수위 발달, 횡방향 압력의 불균형, 그리고 수심차에 의한 원심력이 발생하여 이차류 흐름이 발생된다. 정확한 이차류 구현을 위해서는 3차원 모형을 사용하는 것이 바람직하나, 3차원 모형의 격자 구성과 사용에서는 상당한 시간 및 노력이 요구되기 때문에 수심적분 2차원 모형을 사용하면서도 이차류의 영향을 구현하기 위한 연구들이 이루어졌다. 본 연구에서는 이러한 이차류의 영향을 2차원 모형으로 구현하고자 하였으며 이를 위해 이차류 연직 분포에 대한 기존 연구를 검토하여 새로운 이차류 공식을 개발하였다. 그리고 한국건설기술연구원 하천실험센터의 실규모 실험을 통해서 이차류 공식에 사용되는 계수를 보정하였다. 이처럼 개발된 식은 이차원 수리해석 모형인 HDM-2D에 적용되었다. HDM-2D는 수심 적분된 2차원 운동량 방정식을 지배방정식으로 사용하는 수리해석모형으로서, 이차류의 영향을 반영하기 위하여 개발한 황방향 유속의 연직분포식을 분산 응력항에 대입하여 이차류에 의한 전단 효과를 구현하였다. HDM-2D 흐름 모의 수행 결과와 하천실험센터 실험결과와 비교하여 이차류 효과가 주 흐름 유속의 분포에 미치는 영향을 확인하였다. 분석 결과, 모의 결과는 실험에서 발생하는 유속의 주 흐름 분포가 바깥쪽으로 편중되는 현상을 적절하게 재현함을 알 수 있었다. 모의 결과를 통해 HDM-2D 모형이 이러한 이차류 영향을 구현할 수 있음을 확인하였으며, 사행수로에서 주 흐름분포의 재분배는 하천 환경에서 유사 이동 및 오염물 이동에 큰 영향을 미칠 것으로 판단된다.