• Title/Summary/Keyword: HDM

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HDM2-p53 상호작용 억제제 개발에서의 탄화수소체인의 역할과 중요성

  • Yeo, Jin-Hui;Im, Hae-Ri;Ham, Si-Hyeon
    • 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.

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Analyzing the Current Practice of the Home-Delivered Meal (HDM) Service Program for Homebound Elderly (재가노인을 위한 식사배달서비스 제공기관의 실태분석)

  • 양일선;정현영;이해영;채인숙
    • 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.

Structural and Thermodynamic Characteristics of cHLH Peptide and cHLH/HDM2 Complex

  • Im, Haeri;Cho, Sunhee;Ham, Sihyun
    • 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.

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Increased Allergen-specific IgE Values and Lymphocyte Proliferation Response to House Dust Mites in Dogs with Atopic Dermatitis (개의 아토피성 피부염에 대한 집먼지 진드기 항원 특이적 IgE와 림프구 증식 반응의 증가)

  • Park, Seong-jun
    • 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.

Effect of a Resident and Indoor Environmental Characteristics on the House Dust Mites Allergen (주거환경 특성에 따른 집먼지진드기 항원량에 관한 조사)

  • Kim, Yong-Soon;Park, Jee-Won;Song, Young-Shin
    • Research in Community and Public Health Nursing
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    • v.13 no.1
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    • pp.79-88
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    • 2002
  • Purpose: The purpose of this study was to identify the indoor environment i.e. house type and age, ventilation method, use of bed & sofa, cockroach, ants, etc. on HDM (House dust mites), especially Der fI allergen. Method: Samples of dust from mattresses, pillows and the floor were collected by using a vacuum cleaner from April. 2000. The amount of Group I allergen(Der. fI) of HDM (house dust mites) were measured by two-site ELISA. Indoor Environmental characteristics were accessed by using questionnaires on 178 house wives living in the Seoul area. Results: The amount of HDM allergen (Der fI) was higher in sofa using house. There were higher concentrations of HDM allergen (Der fI) in sofas made from quilt material than for those that were made from leather. Homes that had pets like dogs living in them had higher concentrations of HDM allergen (Der fI) than without dogs. Conclusion: The photophobic mites thrive in dark. warm and humid environments; Items such as pillows. mattresses, box springs, blankets. carpets. and upholstered furniture should be considered ideal environments for the mite. Therefore, an indoor environmental control program should be carried out to avoid the HDM allergen.

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House dust mite-specific immunoglobulin E and longitudinal exhaled nitric oxide measurements in children with atopic asthma

  • Lee, Youn Kyung;Yang, Sohyoung;Park, Joohyun;Kim, Heon;Hahn, Youn-Soo
    • 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.

Leukotriene B4 receptors contribute to house dust mite-induced eosinophilic airway inflammation via TH2 cytokine production

  • Park, Donghwan;Kwak, Dong-Wook;Kim, Jae-Hong
    • 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.

House Dust Mite Extract Induces $PLC/IP_3$-dependent $Ca^{2+}$ Signaling and IL-8 Expression in Human Gingival Epithelial Cells

  • Son, Ga-Yeon;Son, Aran;Park, Wonse;Shin, Dong Min
    • 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.

Comparison of the presentation of atopic dermatitis induced by trinitrochlorobenzene and house dust mite in NC/Nga mice

  • Kim, Yoon-Hwan;Kim, Tae Hyeong;Kang, Min Soo;Ahn, Jin-Ok;Choi, Jung Hoon;Chung, Jin-Young
    • 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.

A Proposal Of The Horizontality Development Method On The Spring MVC (스프링 MVC에서 수평 개발 방법의 제안)

  • Yang, Ill Deung;Kim, Seong Ryeol
    • Journal of the Korea Institute of Information and Communication Engineering
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    • v.19 no.10
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    • pp.2350-2358
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    • 2015
  • The Spring framework including the MVC design concept is the standard in web development in the JAVA environment. The programming style of the structure must be kept strictly, so every web program is able to employ the same structure. It is convenient to distribute jobs, but there are some side effects, like duplication of code, deterioration of professionalization, and deterioration of program performance. To ameliorate those problems, we propose the horizontality development method(HDM) on Spring MVC. We proved that the HDM can solve the problems through the experiment to keep the MVC structure.