A Novel Small-Molecule Inhibitor Targeting the IL-6 Receptor β Subunit, Glycoprotein 130

Hong, Soon-Sun,Choi, Jung Ho,Lee, Sung Yoon,Park, Yeon-Hwa,Park, Kyung-Yeon,Lee, Joo Young,Kim, Juyoung,Gajulapati, Veeraswamy,Goo, Ja-Il,Singh, Sarbjit,Lee, Kyeong,Kim, Young-Kook,Im, So Hee,Ahn, Sun The American Association of Immunologists, Inc. 2015 JOURNAL OF IMMUNOLOGY Vol.195 No.1

<P>IL-6 is a major causative factor of inflammatory disease. Although IL-6 and its signaling pathways are promising targets, orally available small-molecule drugs specific for IL-6 have not been developed. To discover IL-6 antagonists, we screened our in-house chemical library and identified-LMT-28, a novel synthetic compound, as a candidate IL-6 blocker. The activity, mechanism of action, and direct molecular target of LMT-28 were investigated. A reporter gene assay showed that LMT-28 suppressed activation of STAT3 induced by IL-6, but not activation induced by leukemia inhibitory factor. In addition, LMT-28 downregulated IL-6-stimulated phosphorylation of STAT3, gp130, and JAK2 protein and substantially inhibited IL-6-dependent TF-1 cell proliferation. LMT-28 antagonized IL-6-induced TNF-alpha production in vivo. In pathologic models, oral administration of LMT-28 alleviated collagen-induced arthritis and acute pancreatitis in mice. Based on the observation of upstream IL-6 signal inhibition by LMT-28, we hypothesized IL-6, IL-6R alpha, or gp130 to be putative molecular targets. We subsequently demonstrated direct interaction of LMT-28 with gp130 and specific reduction of IL-6/IL-6R alpha complex binding to gp130 in the presence of LMT-28, which was measured by surface plasmon resonance analysis. Taken together, our data suggest that LMT-28 is a novel synthetic IL-6 inhibitor that functions through direct binding to gp130.</P>

Immuno-modulatory activity of hot water extracts isolated from Protaetia brevitarsis seulensis larvae following treatment with Bacillus velezensis TJS119

Kook-Il Han,Jeong Tae Kim,Young Ho Nam,Jum Oc Jung,Eunsun Kim,Mi-Hwa Lee 한국응용곤충학회 2023 한국응용곤충학회 학술대회논문집 Vol.2023 No.10

Protaetia brevitarsis seulensis larvae from industrial insects are traditionally recognized as functional health foods in South Korea. We evaluated the immuno-modulatory effects of feeding beneficial microorganism (Bacillus velezensis TJS119) to P. brevitarsis larvae as a dietary source. In this study, we investigated the immune-enhancing activities of P. brevitarsis larvae hot-water extract (PLW) and PLW after treatment with B. velezensis TJS119 (PLWB) using the RAW 264.7 macrophage cell line. We examined the effects of PLWB on cell proliferation, cytokine production, and nitric oxide production in RAW264.7 cells. PLWB showed no cytotoxicity at concentrations ranging from 7.8 to 1,000 μg/mL in RAW264.7 cells. Treatment with PLWB increased the production of nitric oxide and pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β)] at doses of 62.5 to 1,000 μ g/mL in RAW264.7 cells. As a result, PLWB exhibited a stronger immune-enhancing effect compared to PLW. In conclusion, the results of this study offer experimental evidence to support the potential utilization of PLWB as an immunity-enhancing nutraceutical ingredient.

Streptococcus dysgalactiae로부터 분리된 히알루론산과 황화된 유도체의 구조와 항염증 활성

홍창일(Chang-Il Hong),정의길(Eui-Gil Jung),한국일(Kook-Il Han),김용현(Yong Hyun Kim),이성희(Sung Hee Lee),이홍섭(Hong Sub Lee),한만덕(Man-Deuk Han) 한국생명과학회 2016 생명과학회지 Vol.26 No.5

히알루론산(HA, Hyaluronic acid)은 β-1, 3-N-acetyl glucosamine과 β-1, 4-glucuronic acid가 반복된 선형 폴리머 고분자로서 생물학적 활성 및 생체친화성 특성 때문에 의약 및 약학분야에서 중요한 분자로 여겨지고 있다. 본 연구는 HA을 S. dysgalactiae으로 얻고, 화학적 방법을 통해 황화된 히알루론산(S-HA, Sulfated hyaluronic acid)유도체를 합성하여 그 구조와 항염증 활성을 비교하였다. HA의 생산은 S. dysgalactiae를 5 l 생물반응기를 이용하여 대량 배양하여 수용성 히알루론산(HA-WS, water soluble hyaluronic acid)과 비수용성 히알루론산(HA-WI, water insoluble hyaluronic acid)을 분리 정제하였다. 특히 HA-WI를 황화시켜 황화된 히알루론산(S-HA) 유도체를 합성하였으며, 그 수율은 90%로 나타났다. 합성된 S-HA의 구조를 FT-IR 및 ¹H/<SUP>13</SUP>C-NMR를 통해 S. dysgalactiae 로부터 생산된 표준 HA, HA-WS 및 HA-WI와 비교 분석한 결과, 황으로 치환된 양상을 확인하였다. 또한, S-HA의 항염증 활성을 RAW 264.7 대식세포를 통해 확인한 결과, S-HA는 천연 형태의 HA (HA, HA-WS)보다 nitric oxide (NO)와 COX-2 및 PGE₂ 유전자 발현이 유의하게 낮게 발현되었다. 염증 매개 cytokine인 TNF-α (<80 pg/ml) 및 IL-6 (<100 pg/ml)의 생성도 S-HA가 천연 HA보다 낮은 수준으로 정량되었다. 이 같은 결과에서 황화된 S-HA은 천연 히알루론산보다 용해성이 우수하고 염증관련 사이토카인의 생성 억제를 통해 항염증 효과를 나타내므로 염증치료제, 성형 및 생체 적용 약물전달 소재로 그 활용이 기대된다. Hyaluronic acid (HA) is an important macromolecule in medical and pharmaceutical fields. HA is a natural and linear polymer composed of repeating disaccharide units of β-1, 3-N-acetyl glucosamine and β-1, 4-glucuronic acid. This work aimed to confirm the structural characteristics and anti-inflammatory activities of HA and its chemically sulfated-HA. HA was produced from a fed-batch fermentation process using Streptococcus dysgalactiae in a 5 l bioreactor. HA was isolated water-soluble form (HA-WS) and water-insoluble form (HA-WI) from culture medium, and was obtained chemically sulfated-derivative (S-HA) that resulted in a 90% yield from HA-WI. The structural features of the sulfated- HA (S-HA) were investigated by FT-IR and ¹H-NMR spectroscopy. The FT-IR and NMR patterns revealed the similarity in both the FTIR spectrum as well as NMR spectrum of both reference standard and purified HA from S. dysgalactiae. The anti-inflammatory activities of HA and S-HA were examined on LPS-induced RAW 264.7 cells. S-HA was significantly inhibited production of pro-inflammatory mediators such as nitric oxide (NO) and PGE₂ and the gene levels of iNOS and COX-2, which are responsible for the production of NO and PGE₂, respectively. Furthermore, S-HA also suppressed the overproduction of pro-inflammatory cytokine TNF-α (<80 pg/ml) and IL-6 (<100 pg/ml) compared to that of HA-WI. The present study clearly demonstrates that HA-S exhibits anti-inflammatory activities in RAW 264.7 macrophage cells.

Interleukin-2와 결핵균 30 kDa 항원이 구개편도 및 말초혈액 T 세포 증식에 미치는 상승효과

박정규,박찬권,조은경,김화중,백태현,고필준,김병국,남부현,나기상,박찬일 충남대학교 의과대학 지역사회의학연구소 1995 충남의대잡지 Vol.22 No.1

Widespread use of BCG has not controlled tuberculosis, and more effective vaccines are clearly needed. Although chemotherapy will remain the mainstay of antituberculosis treatment, the use of adjunctive immunotherapeutic modalitites is attractive, particularly in persons with drug-resistant tuberculosis. Administration of IL-2 or IFN-γto tuberculosis patients enhance bacillary elimination. Cell-mediated immunity is the critical protective immune response in tuberculosis. Mycobacterial antigens are recognized by T cells and that elicit production of protective cytokines are potentially important vaccine antigens. The 30 kDa antigen is secreted in large quantities by growing mycobacteria. That antigen elicits greater proliferation in lymphocytes from healthy tuberculin reactors than healthy tuberculin nonreactors. In this study, the T lymphocyte proliferative responses to 30 kDa antigen from Mycobactrium tuberculosis H37Rv were examined by using tonsilar and peripheral blood lymphocytes from PPD(+) and PPD(-) tonsilectomized persons. When cultured with 30 kD antigen, tonsilar mononuclear leukocytes and T cells of PPD(+) demonstrated more ^3H-thymidine incorporation than PPD(-) persons (stimulation index was 2.5 and 1.9, 0.8 and 1.0, repectively). Peripheral blood mononuclear cells (PBMC) and peripheral blood T lymphocytes were shown the similar responses to this antigen. The combination of IL-2 and 30 kDa antigen elicited a significant proliferative responsiveness in tonsilar mononuclear leukocytes and T cells of PPD(+) persons (SI was 20 and 14.1). PBMC and peripheral blood T cells of PPD(+) persons were also shown a significant responsiveness, but PPD(-) persons did not show. These results demonstrate that the 30 kDa antigen and IL-2 have a synergistic stimulatory property in mycobacteria sensitizing lymphocytes.

한국인 직무 스트레스 측정도구의 개발 및 표준화

장세진,고상백,강동묵,김성아,강명근,이철갑,정진주,조정진,손미아,채창호,김정원,김정일,김형수,노상철,박재범,우종민,김수영,김정연,하미나,박정선,이경용,김형렬,공정옥,김인아,김정수,박준호,현숙정,손동국 大韓産業醫學會 2005 대한직업환경의학회지 Vol.17 No.4

Background and Purposes: Over the past three decades, numerous studies performed in Korea have reported that job stress is a determinant risk factor for chronic diseases and work disability. Every society has its own culture and occupational climate particular to their organizations, and hence experiences different occupational stress. An occupational stress measurement tool therefore needs to be developed to estimate it objectively. The purpose of this study is to develop and standardize the Korean Occupational Stress Scale (KOSS) which is considered to be unique and specific occupational stressors in Korean employees. Subjects and Methods: Data were obtained from the National Study for Development and Standardization of Occupational Stress (NSDSOS Project: 2002-2004). A total of 12,631 employees from a nationwide sample proportional to the Korean Standard Industrial Classification and the Korean Standard Occupational Classification were administered. The KOSS was developed for 2 years (2002-2004). In the first year, we collected 255 items from the most popular job stress measurement tools such as JCQ, ERI, NIOSH and OSI, and 44 items derived from the a qualitative study (depth interview). Forty-three items of KOSS, in the second year, were retained for use in the final version of the KOSS by using Delphi and factor analysis. Items were scored using conventional 1-2-3-4 Likert scores for the response categories. Results: We developed eight subscales by using factor analysis and validation process: physical environment (3 items), job demand (8 items), insufficient job control (5 items), interpersonal conflict (4 items), job insecurity (6 items), organizational system (7 items), lack of reward (6 items), and occupational climate (4 items). Together they explained 50.0% of total variance. Internal consistency alpha scores were ranged from 0.51 to 0.82. Twenty-four items of the short form of the KOSS (KOSS-SF) were also developed to estimate job stress in the work setting. Because the levels of the subscales of occupational stress were gender dependent, gender-specific standard norms for both the 43-item full version and the 24-item short form using a quartile for the subscales of KOSS were presented. Conclusion: The results of this study suggest that KOSS might be an appropriate measurement scale to estimate occupational stress of Korean employees. Further and more detailed study needs to be conducted to improve the validity of this scale.

SS400강 용접부의 파괴인성치에 관한 연구

국정한,송일규,김봉중,오세용,성호현 한국기술교육대학교 1999 論文集 Vol.6 No.1

In this work, we studied the mechanical properties, structure and the stress intensity factor of the welded areas which were annealed from 500。C to 900。C with an interval of 100。C. The main results are as follow. 1. The as-welded specimen showed the highest tensile strength and yield point. The tensile strength and the yield point decrease as the annealing temperature increased from 500。C to 900。C, and they became smaller in the order of deposited metal, heat affected zone and base metal. 2. The hardness was maximum at about 9 mm from the welding center line, and it decreased drastically in the heat affected zone located between 9∼15mm from the center line. 3. The elongation decreased in the order of base metal, the fusion zone and heat affected zone while it increased as annealing temperature increased. 4. The stress intensity factor(S. I. F.) declined as the length of notch increased and it became smaller in the order of fusion zone, base metal and heat affected zone. This is because fracture toughness is affected by brittlization at heat affected zone as well as the initiation and propagation of cracks.

글쓰기 교육과 한문 교육의 앞으로의 방향

손병국,오정란,조규일,최기용,한지현 광운대학교 인문사회과학연구소 2000 인문사회과학논문집 Vol.29 No.-

분석결과 검증 및 신뢰성 확보를 위한 실험실간 협력 실험

박혜진,고광용,한국탁,김일중,이용재,김성헌,이규승 충남대학교 농업과학연구소 2005 농업과학연구 Vol.32 No.2

The residual study of pesticide has been used in various areas, such as food safety, environmental protection, establishment of tolerance, and explaining the pathway and reaction mode of pesticides, and its importance was expected to increase further more. The aspect of food safety, the pesticide residue survey have been practiced at many organizations, but there were no verification of analytical results at present. In this experiment, we focused on instrumental stability, including response of each instrument and the recovery ratio of each organization's method. As samples for this experiment, we prepared cucumber and sesame, and chose 4 pesticides (bifenthrin, chlorpyrifos, diazinon, and ethoprophos), which were mostly detected from pesticide residue survey and widely used for each crop. The standard deviation of peak areas in the chromatogram of each pesticide were under 1.212 %, so it showed that most instruments were stable. The relationship of recovery ratio of each organization were over 0.996 for every pesticide and each organization. Finally, the analytical results for pesticide residue from each participated organization were not statically significant and we could put confidence in the result from each organization.

김치 발효 시 용기의 종류가 세균 생장에 미치는 영향

한국일 ( Kook Il Han ),김미정 ( Mi Jung Kim ),권현정 ( Hyun Jung Kwon ),김용현 ( Yong Hyun Kim ),김완종 ( Wan Jong Kim ),한만덕 ( Man Deuk Han ) 한국식품영양학회 2013 韓國食品營養學會誌 Vol.26 No.2

본 연구는 한국의 전통 김치 발효 용기인 옹기의 발효 효과를 알아보기 위해 다른 용기와 비교 실험하였다. 옹기, 밀폐 옹기, 플라스틱 용기, 밀폐 플라스틱 용기를 사용하여 15℃에서 10일간 김치 발효 중 미생물학적 변화 및 품질에 미치는 영향을 확인한 결과, 옹기는 발효 6일차부터 젖산균 수가 다른 용기에 비해 현저한 증가를 보였으며, 발효 10일차에는 1.42× 1010 CFU/㎖로 가장 많은 균수를 나타내었다. 젖산균의 증가가 우수한 발효 용기 순서는 옹기, 밀폐 옹기, 밀폐 플라스틱 용기, 플라스틱 용기 순으로 높았다. 옹기에서 발효된 김치로부터 분리한 우점종은 5균주로 B. subtilis, B. licheniformis, B. safensis, L. brevis, B. pumilus 모두 발효식품에서 분리되어지는 균들로 확인되었다. 이 같은 결과로 볼 때 옹기는 김치 발효 시 젖산균을 증가시키는데 우수한 용기이며, 특히 L. brevis 같은 probiotics의 생육을 촉진하여 김치 내 유해 세균의 억제, 섭취 시 정장 효과를 얻을 수 있는 용기인 것으로 확인되었다. This study is being performed to confirm the container effects during the fermentation processes of kimchi. Kimchi fermentation was prepared in the laboratory with four different types of containers; namely, a traditional Onggi vessel (Korean traditional clay pot, TOV), plastic airtight covered Onggi vessel (PAOV), plastic covered vessel (PCV) and plastic airtight covered vessel (PACV). The kimchi fermentation in the different containers was followed by taking samples at 48 hour intervals for 10 days. In all fermentation containers, the pH changes of kimchi were decreased with fermentation days, while salt content was the same for all types of containers. The number of lactic acid bacteria in kimchi were 1.09×108 CFU/㎖ at first. But the TOV, PAOV, PCV, and PACV after fermentation for 10 days were 1.42×1010, 9.13×109, 4.93×109 and 7.46×109 CFU/㎖, respectively. The kimchi fermented in the TOV with the most dominant bacterial species were the following 5 strains: Bacillus subtilis, B. licheniformis, B. safensis, Lactobacillus brevis and B. pumilus. The use of different types of containers therefore influenced the number of L. brevis and the four Bacillus species. in kimchi, and may influence the characteristics of the fermented kimchi products. The TOV offered the greatest L. brevis numbers and suggested that it could be the best suited for preparing traditional kimchi fermentation.

Effects of patch size and forest type on ground beetles in Korea

Jong-Kook Jung,Sun Kyung Lee,Seung-Il Lee,Joon-Ho Lee 한국응용곤충학회 2015 한국응용곤충학회 학술대회논문집 Vol.2015 No.04

To identify the key effects of human disturbance on terrestrial ecosystems is a major issue in the contemporary conservation. We compared the community structure of ground beetles among different forest patch sizes according to the different forest types. In addition, we examined how different functional groups and species responded to patch size, and habitat and geographical variables. We sampled ground beetles in 9 continuous forests and 18 patches including 6 deciduous, 6 Korean pine, and 6 Japanese red pine. Ground beetles were collected using 5 pitfall traps in each site, and replaced every month during May to October in 2013. Individual-based rarefaction curves indicated that higher species richness was found in continuous forests than forest patches irrespective of the forest types. Positive relationships were found between forest patch size and species richness of each functional group associated with forest habitat. When all patch size, geographical, and habitat variables were considered simultaneously for multiple regressions, patch size, longitude, latitude, elevation, organic matter, and litter depth were generally selected as significant predictor variables of the abundance and species richness of forest specialists, brachypterous, dimorphic, and large-bodied species, although longitude was only selected as a best predictor for 27 study sites in MRT. In conclusion, decreasing patch size is a major factor to the loss of biodiversity for ground beetles. To reduce biodiversity loss caused by habitat fragmentation, therefore, protecting as large as old-growth forests and improving habitat quality are critical for the biodiversity conservation and enhancement.