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NLRC4 Inflammasome-Mediated Regulation of Eosinophilic Functions

  • Ilgin Akkaya;Ece Oylumlu;Irem Ozel;Goksu Uzel;Lubeyne Durmus;Ceren Ciraci
    • IMMUNE NETWORK
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    • v.21 no.6
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    • pp.42.1-42.20
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    • 2021
  • Eosinophils play critical roles in the maintenance of homeostasis in innate and adaptive immunity. Although primarily known for their roles in parasitic infections and the development of Th2 cell responses, eosinophils also play complex roles in other immune responses ranging from anti-inflammation to defense against viral and bacterial infections. However, the contributions of pattern recognition receptors in general, and NOD-like receptors (NLRs) in particular, to eosinophil involvement in these immune responses remain relatively underappreciated. Our in vivo studies demonstrated that NLRC4 deficient mice had a decreased number of eosinophils and impaired Th2 responses after induction of an allergic airway disease model. Our in vitro data, utilizing human eosinophilic EoL-1 cells, suggested that TLR2 induction markedly induced pro-inflammatory responses and inflammasome forming NLRC4 and NLRP3. Moreover, activation by their specific ligands resulted in caspase-1 cleavage and mature IL-1β secretion. Interestingly, Th2 responses such as secretion of IL-5 and IL-13 decreased after transfection of EoL-1 cells with short interfering RNAs targeting human NLRC4. Specific induction of NLRC4 with PAM3CSK4 and flagellin upregulated the expression of IL-5 receptor and expression of Fc epsilon receptors (FcεR1α, FcεR2). Strikingly, activation of the NLRC4 inflammasome also promoted expression of the costimulatory receptor CD80 as well as expression of immunoregulatory receptors PD-L1 and Siglec-8. Concomitant with NLRC4 upregulation, we found an increase in expression and activation of matrix metalloproteinase (MMP)-9, but not MMP-2. Collectively, our results present new potential roles of NLRC4 in mediating a variety of eosinopilic functions.

Research Joint Ventures and Cartels in International Product R&D

  • Yang, Il-Seok
    • Journal of Korea Trade
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    • v.23 no.2
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    • pp.46-58
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    • 2019
  • Purpose - This paper analyzes how Research and Development (R&D) cartelization and Research Joint Ventures (RJV) affect firms that engage in Cournot competition in their product market using a model in which the Home and Foreign firm produce differentiated products and export their total output to a third country's market. Design/Methodology - In a two-stage game, research expenditures incurred in the first stage improve product quality and are subject to various degrees of spillovers. We consider four different scenarios. Findings - In a symmetric equilibrium we observe the following: (i) an RJV that cooperates in R&D decision yields the highest R&D expenditure. However, the scenario which yields the lowest expenditure depends on the extent of differentiation between the goods and the degree of spillovers; (ii) RJV cartelization yields the highest product quality, output, and consumer surplus in the third country; however, the lowest is produced by R&D competition if spillovers are strong and by R&D cartelization if spillovers are weak; and (iii) each firm's profit is at its minimum in R&D competition and its maximum in RJV cartelization. Furthermore, if spillovers are strong, the profit of each firm in R&D cartelization is greater than that in RJV competition, and vice versa. Originality/value - By analyzing product innovation in international markets, we can find similarities and differences between process R&D and product R&D in international markets.

Increased Cytokine and Nitric Oxide Levels in Serum of Dogs Experimentally Infected with Rangelia vitalii

  • Paim, Francine C.;Da Silvaz, Aleksandro S.;Paim, Carlos Breno V.;Franca, Raqueli T.;Costa, Marcio M.;Duarte, Marta M.M.F.;Sangoi, Manuela B.;Moresco, Rafael N.;Monteiro, Silvia G.;Lopes, Sonia Terezinha A.
    • Parasites, Hosts and Diseases
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    • v.51 no.1
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    • pp.133-137
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    • 2013
  • This study aimed to measure the levels of interferon-gamma (IFN-${\gamma}$), tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin 1 (IL-1), interleukin 6 (IL-6), and nitrite/nitrate ($NO_x$) in serum of dogs experimentally infected with Rangelia vitalii. Twelve female mongrel dogs were divided into 2 groups; group A (uninfected controls) composed by healthy dogs (n=5) and group B consisting of dogs inoculated with R. vitalii (n=7). Animals were monitored by blood smear examinations, which showed intraerythrocytic forms of the parasite on day 5 post-infection (PI). Blood samples were collected through the jugular vein on days 0, 10, and 20 PI to determine the serum levels of IFN-${\gamma}$, TNF-${\alpha}$, IL-1, IL-6, and $NO_x$. Cytokines were assessed by ELISA quantitative sandwich technique, and $NO_x$ was measured by the modified Griess method. Cytokine levels (IFN-${\gamma}$, TNF-${\alpha}$, IL-1, and IL-6) were increased (P<0.01) in serum of infected animals. Serum levels of $NO_x$ were also increased on days 10 PI (P<0.01) and 20 PI (P<0.05) in infected animals. Therefore, the infection with R. vitalii causes an increase in proinflammatory cytokines and nitric oxide content. These alterations may be associated with host immune protection against the parasite.

Lactic Acid Bacteria Improves Peyer's Patch Cell-Mediated Immunoglobulin A and Tight-Junction Expression in a Destructed Gut Microbial Environment

  • Kim, Sung Hwan;Jeung, Woonhee;Choi, Il-Dong;Jeong, Ji-Woong;Lee, Dong Eun;Huh, Chul-Sung;Kim, Geun-Bae;Hong, Seong Soo;Shim, Jae-Jung;Lee, Jung Lyoul;Sim, Jae-Hun;Ahn, Young-Tae
    • Journal of Microbiology and Biotechnology
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    • v.26 no.6
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    • pp.1035-1045
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    • 2016
  • To evaluate the effects of lactic acid bacteria (LAB) on Peyer's patch cells, mice were treated with a high dose of kanamycin to disturb the gut microbial environment. The overarching goal was to explore the potential of LAB for use as a dietary probiotic that buffers the negative consequences of antibiotic treatment. In vitro, LAB stimulated the production of immunoglobulin A (IgA) from isolated Peyer's patch cells. Inflammation-related genes (TNF-α, IL-1β, and IL-8) were up-regulated in Caco-2 cells stimulated with lipopolysaccharide (LPS), while tight-junction-related genes (ZO-1 and occludin) were down-regulated; the effects of LPS on inflammatory gene and tight-junction gene expression were reversed by treatment with LAB. Mice treated with a high dose of kanamycin showed increased serum IgE levels and decreases in serum IgA and fecal IgA levels; the number of Peyer's patch cells decreased with kanamycin treatment. However, subsequent LAB treatment was effective in reducing the serum IgE level and recovering the serum IgA and fecal IgA levels, as well as the number of Peyer's patch cells. In addition, ZO-1 and occludin mRNA levels were up-regulated in the ileum tissues of mice receiving LAB treatment. Lactic acid bacteria can enhance the intestinal immune system by improving the integrity of the intestinal barrier and increasing the production of IgA in Peyer's patches. Lactic acid bacteria should be considered a potential probiotic candidate for improving intestinal immunity, particularly in mitigating the negative consequences of antibiotic use.

Production of Flavonoid Compounds and Anti-inflammatory Property of Fermented Licorice Extract with the Basidiomycete Grifola frondosa HB0071 (잎새버섯 균사체를 이용한 감초추출발효물의 플라보노이드 생성과 항염 활성 연구)

  • Bae, Jun Tae;Song, Min Hyeon;Kim, Jin Hwa;Lee, Geun Soo;Pyo, Hyeong Bae
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.38 no.4
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    • pp.327-338
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    • 2012
  • Liquiritigenin and isoliquiritigenin are the major flavonoids present in licorice. These flavonoid compounds were prepared by submerged culture of Grifola frondosa (G. frondosa) HB0071 mycelia producing ${\beta}$-glucosidase in the aqueous extract of licorice. The contents of liquiritigenin and isoliquiritigenin were increased during the fermentation. This fungus produced a high ${\beta}$-glucosidase (activity of 91.5 mU/mL), thereby achieving high amounts of liquiritigenin and isoliquiritigenin ($568.5{\mu}g/mL$ and $89.6{\mu}g/mL$), respectively at 96 h. A reversed- phase high-performance liquid chromatography method was established for simultaneous determination of liquiritigenin and isoliquiritigenin in fermented licorice extract (FLEx). The anti-inflammatory activities were investigated by licorice extract (LEx) before and after fermentation with G. frondosa HB0071. The treatment of UVB-irradiated HaCaT keratinocytes with FLEx resulted in a dose-dependent decrease in the expression level of cyclooxygenase-2 (COX-2) mRNA. Furthermore, FLEx dose-dependently decreased mRNA of the pro-inflammatory cytokines of IL-$1{\beta}$ and IL-6 in UVB-irradiated HaCaT cells. These results suggest that FLEx may mitigate the effects of skin inflammation by reducing UVB-induced adverse skin reactions.

Complete Assignment of $^1H$- and $^{13}C-NMR$ in (20R)-panaxadiol and (20R)-panaxatriol ((20R)-파낙사디올과 (20R)-파낙사트리올에 대한 $^1H$- 및 $^{13}C-NMR$의 완전동정)

  • Kim, Dong-Seon;Baek, Nam-In;Park, Jong-Dae;Lee, You-Hui;Kim, Shin-Il
    • YAKHAK HOEJI
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    • v.40 no.3
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    • pp.293-299
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    • 1996
  • The $^1H$- and $^{13}C$-NMR signals of (20R)-panaxadiol and (20R)-panaxatriol were completely assigned by the extensive application of modern 2D-NMR techniques, $^1H-^1H$ COSY, HMQC and HMBC.

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In Vitro Anti-bacterial and Anti-inflammatory Effects of Six Types of Herb Aqueous Extracts (일부 살충해독유(殺蟲解毒類) 한약의 Staphylococcus aureus에 대한 시험관 내 항균 및 항염 효과)

  • Jang, Se-Ran;Kim, Dong-Chul
    • The Journal of Korean Obstetrics and Gynecology
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    • v.27 no.1
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    • pp.81-100
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    • 2014
  • Objectives: The object of this study was to observe the in vitro anti-bacterial and anti-inflammatory effects of six single aqueous herbal extracts-Quisqualis Fructus (QuF), Meliae Cortex (MeC), Arecae Semen (ArS), Crassirhizomae Rhizoma (CrR), Ulmi Pasta Semen(UlS), Torreyae Semen(ToS)- against Staphylococcus aureus (S. aureus) and Lipopolysaccharide(LPS)-activated Raw 264.7 cells. Methods: Anti-bacterial activities against S. aureus of aqueous extracts of QuF, MeC, ArS, CrR, UlS and ToS were detected using standard agar microdilution methods. In addition, the effects on the cell viability, prostaglandin $E_2$ ($PGE_2$), nitric oxide (NO), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$ and IL-6 productions of LPS activated Raw 264.7 cells were detected. The anti-bacterial and anti-inflammatory effects were respectively compared with lincomycin and piroxicam. Results: Minimal Inhibition Concentration (MIC) of aqueous extracts of QuF, MeC, ArS, CrR, UlS and ToS against S. aureus was respectively detected $5.625{\pm}4.075$ (3.125~12.500), $0.332{\pm}0.273$ (0.098~0.782), $1.094{\pm}0.428$ (0.782~1.563), $2.969{\pm}2.096$ (0.782~6.250), $9.375{\pm}4.419$ (3.125~12.500)>25 mg/ml. MIC of lincomycin was detected as $0.469{\pm}0.297$ (0.195~0.782) ${\mu}g/ml$ at same conditions. In addition, $ED_{50}$ against LPS-induced cell viabilities and cytokine releases of QuF, MeC, ArS, CrR, UlS and ToS was as follows - Cell viability: 66.370, 2.908, 1.747, 259.553, 18.150 and 34.160 mg/ml; NO production: 389.486, 0.294, 0.138, 523.060, 45.363 and 49.327 mg/ml; $PGE_2$ production: 114.271, 0.223, 0.046, 243.078, 8.829 and 28.947 mg/ml; TNF-${\alpha}$ production: 406.288, 0.343, 0.123, 9404.227, 125.406 and 140.775 mg/ml; IL-$1{\beta}$ production: 117.178, 0.135, 0.019, 237.451, 7.923 and 19.418 mg/ml; IL-6 production: 31.261, 0.105, 0.055, 128.434, 2.290 and 3.745 mg/ml. ED50 of piroxicam against LPS-induced cell viabilities, NO, $PGE_2$, TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 were detected as 35.179, 6.552, 1.162, 7.273, 7.101 and $5.044{\mu}g/ml$, respectively at same conditions. Conclusions: All six single aqueous herbal extracts showed anti-bacterial effects against S. aureus, in the order of MeC, ArS, CrR, QuF and UlS aqueous extracts except for ToS; they did not showed any anti-bacterial effects (MIC>25 mg/ml). They also showed anti-inflammatory effects against LPS-activated Raw 264.7 cells in the order of ArS, MeC, UlS, ToS, QuF and CrR aqueous extracts. It means that the ArS and MeC will be showed favorable potent anti-bacterial and related anti-inflammatory effects.

Reduction of Inflammation and Enhancement of Motility after Pancreatic Islet Derived Stem Cell Transplantation Following Spinal Cord Injury

  • Karaoz, Erdal;Tepekoy, Filiz;Yilmaz, Irem;Subasi, Cansu;Kabatas, Serdar
    • Journal of Korean Neurosurgical Society
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    • v.62 no.2
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    • pp.153-165
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    • 2019
  • Objective : Spinal cord injury (SCI) is a very serious health problem, usually caused by a trauma and accompanied by elevated levels of inflammation indicators. Stem cell-based therapy is promising some valuable strategies for its functional recovery. Nestin-positive progenitor and/or stem cells (SC) isolated from pancreatic islets (PI) show mesenchymal stem cell (MSC) characteristics. For this reason, we aimed to analyze the effects of rat pancreatic islet derived stem cell (rPI-SC) delivery on functional recovery, as well as the levels of inflammation factors following SCI. Methods : rPI-SCs were isolated, cultured and their MSC characteristics were determined through flow cytometry and immunofluorescence analysis. The experimental rat population was divided into three groups : 1) laminectomy & trauma, 2) laminectomy & trauma & phosphate-buffered saline (PBS), and 3) laminectomy+trauma+SCs. Green fluorescent protein (GFP) labelled rPI-SCs were transplanted into the injured rat spinal cord. Their motilities were evaluated with Basso, Beattie and Bresnahan (BBB) Score. After 4-weeks, spinal cord sections were analyzed for GFP labeled SCs and stained for vimentin, $S100{\beta}$, brain derived neurotrophic factor (BDNF), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase), vascular endothelial growth factor (VEGF) and proinflammatory (interleukin [IL]-6, transforming growth factor $[TGF]-{\beta}$, macrophage inflammatory protein [MIP]-2, myeloperoxidase [MPO]) and anti-inflammatory (IL-1 receptor antagonis) factors. Results : rPI-SCs were revealed to display MSC characteristics and express neural and glial cell markers including BDNF, glial fibrillary acidic protein (GFAP), fibronectin, microtubule associated protein-2a,b (MAP2a,b), ${\beta}3$-tubulin and nestin as well as anti-inflammatory prostaglandin E2 receptor, EP3. The BBB scores showed significant motor recovery in group 3. GFP-labelled cells were localized on the injury site. In addition, decreased proinflammatory factor levels and increased intensity of anti-inflammatory factors were determined. Conclusion : Transplantation of PI-SCs might be an effective strategy to improve functional recovery following spinal cord trauma.

A Study on R&D Critical Factors Affecting R&D Performance in Aviation and Aerospace Industries (항공·우주분야 연구개발사업(R&D) 성과영향요인이 R&D 성과에 미치는 영향에 관한 연구)

  • So, Eun Jung;Kim, Ki-Woong;Kim, Kwang-Il
    • Journal of the Korean Society for Aviation and Aeronautics
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    • v.27 no.2
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    • pp.26-36
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    • 2019
  • Although the investment size of R&D in Aviation and Aerospace Industries is increasing, R&D performance has not been quite good considering resources invested in it. This study is to find which R&D critical factors affect R&D Performance in aviation and aerospace industries. According to the result of research, a technology provider factor, an organization factor, a system factor and a market environment factor influence positively on financial performance, and a policy factor influences negatively on financial performance. Otherwise, a technology provider factor and an organization factor influence positively on non financial performance, and technology factor influences negatively on non financial performance. Thus, personnel involved in R&D of Aviation and Aerospace Industries should develop policy and system taking positive and negative factors to improve R&D performance. It could lead to take the better performance from R&D in Aviation and Aerospace Industires.

An Electrical Effect Analysis of Asynchronous Phenomena in Parallel Operation of Synchronous Generator (동기발전기(同期發電機)의 병열혼전(竝列渾轉)시 비동기현상(非同期現象)에서 발생(發生)하는 전기현상해석(電氣現象解析))

  • Lee, Eun-Woong;Lim, Jae-Il;Lee, Dong-Ju;Kim, Jong-Gyeum;Jo, Sung-Bae
    • Proceedings of the KIEE Conference
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    • 1997.07a
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    • pp.234-237
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    • 1997
  • In the Closing time in order to operate synchronous generators parallely, it is generated the asynchronous phenomena. These asynchronous phenomena give rise of the eddy current on the rotor. These eddy current are solved analytically for the Laplace' Equ. ${\nabla}^2{\widetilde{H}}=0$ in free space and for the Bullard's Equ. ${\nabla}^2{\widetilde{H}}$+${\sigma}_r{\mu}_r{\nabla}$${\times}$${\widetilde{\nu}}_r$${\times}$${\widetilde{H}}^{III}$=${\sigma}_r{\mu}_r{\frac{{\partial}H}{{\partial}t}}$ for the rotor by using each double Fourier series component of the 3D H-field

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