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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>
위상피세포에서 Helicobacter pylori 형태 변화가 Interleukin-8 분비에 미치는 영향
이학성,김혜원,홍원선,민영일,정훈용,김해련,양석균,이미화 대한소화기학회 1999 대한소화기학회지 Vol.33 No.6
Background/Aims: Interleukin-8 (IL-8) has been reported to play a critical role in Helicobacter pylori (H. pylori)-associated gastric mucosal damage. H. pylori exist in both bacillary and coccoid forms in the stomach. In contrast to bacillary forms, it is not clear whether coccoid forms stimulate gastric epithelial cells to produce IL-8. This study was conducted to investigate the effects of coccoid forms on IL-8 production. Methods: H. pylori strains of ATCC 43504, ATCC 43526 and three clinical isolates were used in the present study. Coccoid forms were induced by culturing bacillary forms of H. pylori for more than 84 hr. After co-culture of two human gastric adenocarcinoma cel lines (KATO III and AGS) with five strains of H. pylori, the levels of IL-8 were determined in th supernatants by enzyme linked immunosorbent assay. Results: The levels of IL-8 in KATO III and AGS cells were markedly elevated up to 6-9 hr after co-culture with the bacillary forms. The IL-8 levels produced in both cell lines by the coccoid forms were significantly lower than those by the bacillary forms in all strains. Conclusions: These results suggest that coccoid forms are much less implicated in IL-8- mediated gastric mucosal damage than bacillary forms.
The Anti -allergic Effects of Taraxaci Herba(蒲公英) on the RBL-2H3 Cells
조주흠,류지효,김철홍,강경화,윤화정,이승연,고우신,김원일,Jo, Ju-Heum,Lyu, Ji-Hyo,Kim, Cheol-Hong,Kang, Kyung-Hwa,Yoon, Hwa-Jung,Lee, Seung-Yeon,Ko, Woo-Shin,Kim, Won-Il The Society of Korean Medicine Ophthalmology 2007 한방안이비인후피부과학회지 Vol.20 No.1
청열해독(淸熱解毒) 작용을 하는 포공영의 항알러지 효과를 알아보기 위하여 RBL-2H3 cell line에 PMA와 A23187을 자극한 후 RBL-2H3 cell내 과립의 degranulation의 억제정도를 살펴보기 위하여 ${\beta}-Hexosaminidase$의 누출량의 억제 정도를 살펴본 결과 포공영은 농도 의존적으로 현저하게 degranulation을 억제하였다. 알러지 반응 시 세포내에서 분비되어 중요한 작용을 하는 것으로 알려진 사이토카인인 $TNF-{\alpha}$, IL-4의 합성조절 정+도를 살펴본 결과, $TNF-{\alpha}$, IL-4의 mRNA 수준에서의 발현의 조절을 통한 합성도 억제하였다. 이 결과로 보아 포공영은 알레르기와 관련된 질환에 치료약물로서 응용이 가능할 것으로 사료된다.
쾌속조형용 재료의 이방성과 강도에 대한 연구 - FDM
김승화,이홍경,이재일,안성훈 경상대학교 생산기술연구소 2001 工學硏究院論文集 Vol.1 No.-
Rapid Prototyping (RP) technology has been advanced to fabricate initial prototy various materials. Stratasys Fused Deposition Modeling (FDM) is one of the typical RP that provide functional prototypes of ABS plastic. In order to predict the behavior of parts, it is critical to understand the material properties of the raw FDM process mat the effect that FDM build parameters have on the FDM part. In this paper, we characterize the properties of ABS parts fabricated by the FDM 1650. Using the I Experiment (DOE) approach, the process parameters of FDM, such as raster orientatior bead width, color, and model temperature were examined. Tensile strengths of specimens, [45/-45], cross specimens, [0/90], and directionally fabricated tensile special and [90]) were measured and compared with the injection molded FDM-ABS P400 mat the FDM parts made with a 0.003 air gap, the typical tensile strength ranged be percent and 83 percent of the strength of injection molded ABS P4OO. From the expert couple of build rules for designing FDM parts were obtained.
Choi, Eun Wha,Shin, Il Seob,Park, So Young,Park, Ji Hyun,Kim, Jong Sung,Yoon, Eun Ji,Kang, Sung Keun,Ra, Jeong Chan,Hong, Sung Hwa Wiley Subscription Services, Inc., A Wiley Company 2012 Vol.64 No.1
<P><B>Abstract</B></P><P><B>Objective</B></P><P>To investigate the efficacy of human adipose tissue–derived mesenchymal stem cell (AD‐MSC) transplantation in systemic lupus erythematosus (SLE) and to determine the optimal transplantation window for stem cells either before or after disease onset.</P><P><B>Methods</B></P><P>(NZB × NZW)F<SUB>1</SUB> mice with SLE were administered human AD‐MSCs (5 × 10<SUP>5</SUP>) intravenously every 2 weeks from age 6 weeks until age 60 weeks, while the control group received saline vehicle on the same schedule. Another experiment was carried out with a different initiation time point for serial transplantation (age 6 weeks or age 32 weeks).</P><P><B>Results</B></P><P>Long‐term serial administration (total of 28 times) of human AD‐MSCs ameliorated SLE without any adverse effects. Compared with the control group, the human AD‐MSC–treated group had a significantly higher survival rate with improvement of histologic and serologic abnormalities and immunologic function, and also had a decreased incidence of proteinuria. Anti–double‐stranded DNA antibodies and blood urea nitrogen levels decreased significantly with transplantation of human AD‐MSCs, and serum levels of granulocyte–macrophage colony‐stimulating factor, interleukin‐4 (IL‐4), and IL‐10 increased significantly. A significant increase in the proportion of CD4+FoxP3+ cells and a marked restoration of capacity for cytokine production were observed in spleens from the human AD‐MSC–treated group. In the second experiment, an early stage treatment group showed better results (higher survival rates and lower incidence of proteinuria) than an advanced stage treatment group.</P><P><B>Conclusion</B></P><P>Serial human AD‐MSC transplantation had beneficial effects in the treatment of SLE, without adverse effects. Transplantation of human AD‐MSCs before disease onset was preferable for amelioration of SLE and restoration of immune homeostasis.</P>
거대 점오염원이 주변 대기질에 미치는 영향에 관한 연구
김유근,이화운,전병일,장은숙,홍정혜,문윤섭,원경미,송정희 부산대학교 환경문제연구소 1996 環境硏究報 Vol.14 No.1
In order to show the effect of a vast point pollutant source on air quality of Pusan Thermoeletric Power Plant and its surrounding area, air quality around Pusan Thermoeletric Power Plant was simulated by ISCLT-2 which was supplied by EPA. For this purpose the emission amount of SO_2, NO_2 and TSP was calculated and atmospheric stability was classified for a recent decade(1985~1994) in Pusan. A result of the emission amount showed that much amount of NO_2, NO_2 and TSP are emitted from industrial area. It was clear that NO_2 is much emitted from line source and industrial area. And as a result of classification of atmospheric stability, neutral, stable and unstable state were 58%, 24.1% and 17.9%, respectivly. The result of ai quality simulation by ISCLT-2 showed that Pusan Thermoeletric Power Plant is affecting on the increse of 2.0ppb, 3.0ppb and 5.0㎍/㎥, SO_2, NO_2, and TSP respectively at its surrounding area, site A-3 which was located westward 2.2㎞ distance from Plant
신승수,신동화,지홍일,최승권,조용환 충북대학교 산업과학기술연구소 2002 산업과학기술연구 논문집 Vol.16 No.1
The Binary Scheduling Wheel(BSW) algorithm was proposed to carry on manage buffer efficiently at implementing of WRR scheduler. But, BSW algorithm cause serous performance degradation of cell delay and maximum queue length because it allocates more weight than the weight allocated actually in VC and could not serve cell if the VC queue is empty. In this paper, we propose new BSW of the old BSW structure. Also, we develop a cell scheduling algorithm which is suitable for the new BSW structure. The proposed BSW structure and the developed algorithm are capable of maintaining the allocated weight of each VC correctly, and decrease average cell delay and average buffer length by serving other VC cell when the selected VC queue is empty, and increase cell service ratio as a whole. The evaluation results show that the proposed structure can implement WRR algorithm more efficiently than the old BSW.
부산연안역에서의 대기오염기상 예보시스템 개발에 관한 연구 : 고농도 오존일의 예측을 중심으로 Centering around Forecast of Ozone Episode Day
김유근,이화운,전병일,홍정혜,문윤섭 한국환경과학회 1996 한국환경과학회지 Vol.5 No.4
Pusan is the largest coastal city with a population of about four million in Korea. Because of increased and confused traffic, photochemical air pollution become a major urban environmental problem recently. The photo-chemical air pollution weather forecasting method preciser than existing air pollution forecast method has been developed to forecast ozone episode days with meteorological conditions using the data measured at 7 air quality continuous monitoring stations from June to September using 2 years (1994, 1995). The method developed in present study showed higher percentage correct and skill score than existing air pollution forecasting in KMA (Korea Meteorological Administration).
Inhibitory Effect of Chan-Su on the Secretion of PGE2 and NO in LPS-stimulated BV2 Microglial Cells
Kim, Min-Hee,Lyu, Ji-Hyo,Lyu, Sun-Ae,Hong, Sang-Hoon,Kim, Won-Il,Yoon, Hwa-Jung,Ko, Woo-Shin The Physiological Society of Korean Medicine and T 2008 동의생리병리학회지 Vol.22 No.5
본 논문은 오랫동안 민간요법으로 염증치료에 사용되어오던 섬수가 lipopolysaccharide(LPS)-자극된 BV2 소교 세포의 nitric oxide(NO) 분비에 미치는 효과에 대해 연구한 내용이다. 실험 결과 섬수는 세포 생존력에 대한 영향 없이 BV2 소교 세포에서 NO 분비를 억제시켰고, nitric oxide synthase (iNOS) 단백질도 감소시켰다. 또한 섬수는 prostaglandin E2 (PGE2) 생산 및 cyclooxygenase (COX)-2 발현을 저지하였고, proinflammatory cytokines과 ${IkB-\alpha}$감소를 억제시켰다. 따라서 섬수가 $I{\kappa}B-{\alpha}$감소를 억제함으로써 NO 합성을 저해하여 항염증작용을 할 수 있다는 내용이다. Chan-Su (Venenum bufonis) has long been for a variety of other purposes including treatment of inflammation in the folk medicine recipe. Since nitric oxide (NO) is one of the major inflammatory parameters, we first studied the effects of Chan-Su on NO production in lipopolysaccharide (LPS)-stimulated BV2 microglial cells, Chan-Su inhibited the secretion of NO in BV2 microglial cells, without affecting cell viability, The protein level of inducible nitric oxide synthase (iNOS) was decreased by Chan-Su, And Chan-Su also inhibited production of prostaglandin E2 (PGE2) and expression of cyclooxygenase (COX)-2. Proinflammatory cytokines, such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$ and IL-12, were inhibited by Chan-Su in a dose-dependent manner. And Chan-Su inhibited the degradation of ${IkB-\alpha}$, which was considered to be inhibitor of nuclear factor $(NF)-{\kappa}B$, one of a potential transcription factor for the expression of iNOS, COX-2 and proinflammatory cytokines. These results suggest that Chan-Su could exert its anti-inflammatory actions by suppressing the synthesis of NO through inhibition of $I{\kappa}B-{\alpha}$ degradation.