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Cyclic AMP concentrations in dendritic cells induce and regulate Th2 immunity and allergic asthma
Lee, Jihyung,Kim, Tae Hoon,Murray, Fiona,Li, Xiangli,Choi, Sara S.,Broide, David H.,Corr, Maripat,Lee, Jongdae,Webster, Nicholas J. G.,Insel, Paul A.,Raz, Eyal National Academy of Sciences 2015 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.112 No.5
<P><B>Significance</B></P><P>Allergic asthma is characterized by Th2 type inflammation, leading to airway hyperresponsiveness and remodeling. However, the mechanisms by which DC promote Th2 differentiation remain unclear. Herein we demonstrate that low cAMP levels in DC induce Th2-biased responses in vitro and in vivo. Furthermore, mice with conditional deletion of <I>Gnas</I> in DC (<I>Gnas</I><SUP>ΔCD11c</SUP> mice) develop spontaneous bronchial asthma that shares multiple similarities with human asthma. In contrast, increasing cAMP levels inhibit these responses. Thus, regulators of cAMP levels in DC such as G-protein-coupled receptors are non-pattern recognition receptors that play a significant role in CD4 T cell differentiation.</P><P>The inductive role of dendritic cells (DC) in Th2 differentiation has not been fully defined. We addressed this gap in knowledge by focusing on signaling events mediated by the heterotrimeric GTP binding proteins Gαs, and Gαi, which respectively stimulate and inhibit the activation of adenylyl cyclases and the synthesis of cAMP. We show here that deletion of <I>Gnas</I>, the gene that encodes Gαs in mouse CD11c<SUP>+</SUP> cells (<I>Gnas</I><SUP>ΔCD11c</SUP> mice), and the accompanying decrease in cAMP provoke Th2 polarization and yields a prominent allergic phenotype, whereas increases in cAMP inhibit these responses. The effects of cAMP on DC can be demonstrated in vitro and in vivo and are mediated via PKA. Certain gene products made by <I>Gnas</I><SUP>ΔCD11c</SUP> DC affect the Th2 bias. These findings imply that G protein-coupled receptors, the physiological regulators of Gαs and Gαi activation and cAMP formation, act via PKA to regulate Th bias in DC and in turn, Th2-mediated immunopathologies.</P>
Park, Sang Mi,Lee, Tae Hoon,Zhao, Rongjie,Kim, Youn Sook,Jung, Ji Yun,Park, Chung A.,Jegal, Kyung Hwan,Ku, Sae Kwang,Kim, Jae Kwang,Lee, Chul Won,Kim, Young Woo,Cho, Il Je,An, Won G.,Kim, Sang Chan D.A. Spandidos 2018 International journal of molecular medicine Vol.41 No.5
<P>Socheongryong-Tang (SCRT) is a natural medicine prescription that has been mainly used in East Asia for the treatment of inflammatory disorders, including asthma and allergic rhinitis. The present study evaluated the anti-inflammatory effects of SCRT on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and in a rat model of carrageenan (CA)-induced paw edema. Levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>) in the culture supernatant were quantified and nitric oxide (NO) production was monitored. In addition, the effect of SCRT on the protein expression of nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was assessed by western blot analysis. Furthermore, the effects of SCRT on acute inflammation <I>in vivo</I> and changes in the histomorphometry and histopathology of paw skin were observed using CA-treated rats. SCRT (1 mg/ml) inhibited the LPS-induced changes in the protein expression of NF-κB, JNK, ERK1/2, iNOS and COX-2, as well as the production of NO, PGE<SUB>2</SUB> and cytokines. In the rat paw edema assay, administration of 1 g/kg of lyophilized powder obtained from the aqueous extracts of SCRT for 3 consecutive days inhibited the CA-induced increases in skin thickness, mast cell degranulation, and infiltration of inflammatory cells in the ventral and dorsal pedis skin within 4 h. These results demonstrated that SCRT exerts its anti-inflammatory activities in LPS-stimulated RAW 264.7 cells through decreasing the production of inflammatory mediators, including PGE<SUB>2</SUB>, NO and cytokines, via suppression of the NF-κB and JNK and ERK1/2 signaling pathways. In addition, the data of the CA-induced paw edema indicated an anti-edema effect of SCRT. SCRT (1 g/kg) reduced acute edematous inflammation through inhibition of mast cell degranulation and infiltration of inflammatory cells. Therefore, the present study provided scientific evidence for the anti-inflammatory activities of SCRT as well as the underlying mechanisms.</P>
Lee, Tae Hoon,Kim, Kwanpyo,Kim, Gwangwoo,Park, Hyo Ju,Scullion, Declan,Shaw, Leo,Kim, Myung-Gil,Gu, Xiaodan,Bae, Won-Gyu,Santos, Elton J. G.,Lee, Zonghoon,Shin, Hyeon Suk,Nishi, Yoshio,Bao, Zhenan American Chemical Society 2017 Chemistry of materials Vol.29 No.5
<P>Organic field-effect transistors have attracted much attention because of their potential use in low-cost, large area, flexible electronics. High-performance organic transistors require a low density of grain boundaries in their organic films and a decrease in the charge trap density at the semiconductor dielectric interface for efficient charge transport. In this respect, the role of the dielectric material is crucial because it primarily determines the growth of the film and the interfacial trap density. Here, we demonstrate the use of chemical vapor-deposited hexagonal boron nitride (CVD hBN) as a scalable growth template/dielectric for highperformance organic field-effect transistors. The field-effect transistors based on C-60 films grown on single-layer CVD h-BN exhibit an average mobility of 1.7 cm(2) V-1 s(-1) and a maximal mobility of 2.9 cm(2) s(-1) with on/off ratios of 10(7). The structural and morphology analysis shows that the epitaxial, two-dimensional growth of C-60 on CVD h-BN is mainly responsible for the superior charge transport behavior. We believe that CVD h-BN can serve as a growth template for various organic semiconductors, allowing the development of large-area, high-performance flexible electronics.</P>
Fact 검증 기반 정답 재순위화를 이용한 다중추론 질의응답
이정두(Jeong-Doo Lee),나승훈(Seung-Hoon Na),김태형(Tae-Hyeong Kim),최윤수(Yun-Su Choi),장두성(Du-Seong Chang) 한국정보과학회 2021 한국정보과학회 학술발표논문집 Vol.2021 No.6
최근 딥러닝 기술의 발전에 따라 오픈 도메인 질의응답 시스템의 발전 또한 가속화 되고 있다. 오픈 도메인 질의응답의 최신 기계 독해 모델은 일반적으로 상위 K개의 예측에서 높은 재현율을 보이지만 전체 정확도가 낮아 답변 순위를 다시 매길 필요가 있다는 것을 기존 연구를 통해 알 수 있다. 본 논문에서는 자동 사실 검증 모듈을 활용해 예측된 상위 정답 후보들의 순위 재지정 방법을 제안한다. 결과적으로 다중추론 질의응답 모델의 성능을 개선시켰고 이 방법은 기존 모든 오픈 도메인질의응답 시스템에 적용할 수 있어 활용가치가 높다.
Clinical Practice Guidelines for Gastric Cancer in Korea: An Evidence-Based Approach
Lee, Jun Haeng,Kim, Jae G.,Jung, Hye-Kyung,Kim, Jung Hoon,Jeong, Woo Kyoung,Jeon, Tae Joo,Kim, Joon Mee,Kim, Young Il,Ryu, Keun Won,Kong, Seong-Ho,Kim, Hyoung-Il,Jung, Hwoon-Yong,Kim, Yong Sik,Zang, D The Korean Gastric Cancer Association 2014 Journal of gastric cancer Vol.14 No.2
Although gastric cancer is quite common in Korea, the treatment outcome is relatively favorable compared to those in western countries. However, there are currently no Korean multidisciplinary guidelines for gastric cancer. Experts from related societies developed guidelines de novo to meet Korean circumstances and requirements, including 23 recommendation statements for diagnosis (n=9) and treatment (n=14) based on relevant key questions. The quality of the evidence was rated according to the GRADE evidence evaluation framework: the evidence levels were based on a systematic review of the literature, and the recommendation grades were classified as either strong or weak. The applicability of the guidelines was considered to meet patients' view and preferences in the context of Korea. The topics of the guidelines cover diagnostic modalities (endoscopy, endoscopic ultrasound, and radiologic diagnosis), treatment modalities (surgery, therapeutic endoscopy, chemotherapy, and radiotherapy), and pathologic evaluation. An external review of the guidelines was conducted during the finalization phase.
Structural and Electrical Investigation of C<sub>60</sub>–Graphene Vertical Heterostructures
Kim, Kwanpyo,Lee, Tae Hoon,Santos, Elton J. G.,Jo, Pil Sung,Salleo, Alberto,Nishi, Yoshio,Bao, Zhenan American Chemical Society 2015 ACS NANO Vol.9 No.6
<P>Graphene, with its unique electronic and structural qualities, has become an important playground for studying adsorption and assembly of various materials including organic molecules. Moreover, organic/graphene vertical structures assembled by van der Waals interaction have potential for multifunctional device applications. Here, we investigate structural and electrical properties of vertical heterostructures composed of C<SUB>60</SUB> thin film on graphene. The assembled film structure of C<SUB>60</SUB> on graphene is investigated using transmission electron microscopy, which reveals a uniform morphology of C<SUB>60</SUB> film on graphene with a grain size as large as 500 nm. The strong epitaxial relations between C<SUB>60</SUB> crystal and graphene lattice directions are found, and van der Waals <I>ab initio</I> calculations support the observed phenomena. Moreover, using C<SUB>60</SUB>–graphene heterostructures, we fabricate vertical graphene transistors incorporating n-type organic semiconducting materials with an on/off ratio above 3 × 10<SUP>3</SUP>. Our work demonstrates that graphene can serve as an excellent substrate for assembly of molecules, and attained organic/graphene heterostructures have great potential for electronics applications.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2015/ancac3.2015.9.issue-6/acsnano.5b00581/production/images/medium/nn-2015-00581y_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn5b00581'>ACS Electronic Supporting Info</A></P>