• Title/Summary/Keyword: Th2 responses

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Effects of Indomethacin on the Production of Cytokines in Mice Exposed to Excessive Zinc (과량의 아연에 노출된 생쥐의 사이토카인 생산에 미치는 인도메타신의 영향)

  • 채병숙;신태용
    • YAKHAK HOEJI
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    • v.46 no.4
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    • pp.258-264
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    • 2002
  • Zinc plays an important role in immunobiological responses, while excessive zinc attenuates immune functions in a dose-dependent manner. Zinc excess has been reported to increase levels of plasma prostaglandin E$_2$ (PGE$_2$), which is known to inhibit production of Th (helper T) 1-associated cytokines and to induce inflammatory responses. Thus, this study was investigated the effects of indomethacin, a potent inhibitor of PGE$_2$ synthesis, on the proinflammatory cytokine and lymphokine production in ICR mice exposed to excessive zinc. Indomethacin at doses of 5 mg/kg was administered i.p. 30 minutes before zinc chloride (Zn) 30 mg/kg orally daily for 10 days. Excessive Zn remarkedly increased tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-1$\beta$ levels in both serum and splenic supernatants compared with those in controls, while indomethacin significantly reduced the excessive Zn-induced levels of IL-1$\beta$. In serum, excessive Zn significantly decreased the levels of IL-2 and interferon (IFN)-${\gamma}$ compared with those in controls, whereas indomethacin significantly enhanced the excessive Zn-decreased levels of IFN-${\gamma}$ but did not affect the Zn-decreased levels of serum IL-2. In splenic supernatants, All of excessive Zn, indomethacin, and combination of Zn and indomethacin significantly enhanced IL-2 levels compared with those in controls, but indomethacin didn't affect the Zn-induced production of IL-2. These data, therefore, suggest that indomethacin significantly attenuated the in vivo and ex vivo IL-1$\beta$ production increased by excessive zinc and remarkedly enhanced the in vivo excessive zinc-suppressed production of IFN-${\gamma}$ but not IL-2.

Deficiency of Sphingosine-1-Phosphate Receptor 2 (S1P2) Attenuates Bleomycin-Induced Pulmonary Fibrosis

  • Park, Soo-Jin;Im, Dong-Soon
    • Biomolecules & Therapeutics
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    • v.27 no.3
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    • pp.318-326
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    • 2019
  • Sphingosine 1-phosphate (S1P) levels are often found to be elevated in serum, bronchoalveolar lavage, and lung tissue of idiopathic pulmonary fibrosis patients and experimental mouse models. Although the roles of sphingosine kinase 1 and S1P receptors have been implicated in fibrosis, the underlying mechanism of fibrosis via Sphingosine 1-phosphate receptor 2 ($S1P_2$) has not been fully investigated. Therefore, in this study, the roles of $S1P_2$ in lung inflammation and fibrosis was investigated by means of a bleomycin-induced lung fibrosis model and lung epithelial cells. Bleomycin was found to induce lung inflammation on day 7 and fibrosis on day 28 of treatment. On the $7^{th}$ day after bleomycin administration, $S1P_2$ deficient mice exhibited significantly less pulmonary inflammation, including cell infiltration and pro-inflammatory cytokine induction, than the wild type mice. On the $28^{th}$ day after bleomycin treatment, severe inflammation and fibrosis were observed in lung tissues from wild type mice, while lung tissues from $S1P_2$ deficient mice showed less inflammation and fibrosis. Increase in TGF-${\beta}1$-induced extracellular matrix accumulation and epithelial-mesenchymal transition were inhibited by JTE-013, a $S1P_2$ antagonist, in A549 lung epithelial cells. Taken together, pro-inflammatory and pro-fibrotic functions of $S1P_2$ were elucidated using a bleomycin-induced fibrosis model. Notably, $S1P_2$ was found to mediate epithelial-mesenchymal transition in fibrotic responses. Therefore, the results of this study indicate that $S1P_2$ could be a promising therapeutic target for the treatment of pulmonary fibrosis.

Evaluation of Protective Immune Response Induced by a DNA Vaccine Encoding GRA8 against Acute Toxoplasmosis in a Murine Model

  • Chu, Jia-Qi;Huang, Shuai;Ye, Wei;Fan, Xuan-Yan;Huang, Rui;Ye, Shi-Cai;Yu, Cai-Yuan;Wu, Wei-Yun;Zhou, Yu;Zhou, Wei;Lee, Young-Ha;Quan, Juan-Hua
    • Parasites, Hosts and Diseases
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    • v.56 no.4
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    • pp.325-334
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    • 2018
  • Toxoplasma gondii is an apicomplexan zoonotic protozoan parasite that infects most species of warm-blooded animals, including humans. The heavy incidence and severe or lethal damage caused by T. gondii infection clearly indicate a need for the development of an effective vaccine. T. gondii GRA8 is a member of the dense granules protein family and is used as a marker of acute infection. In the present study, we evaluated the protective immunity induced by DNA vaccination based on a recombinant eukaryotic plasmid, pDsRed2-GRA8, against acute toxoplasmosis in mice. BALB/c mice were intramuscularly immunized with the pDsRed2-GRA8 plasmid and then challenged by infection with the highly virulent GFP-RH strain of T. gondii. The specific immune responses and protective efficacy against T. gondii of this vaccine were analyzed by measuring cytokine and serum antibody titers, splenocyte proliferation assays, and the survival times of mice after challenge. Our results showed that mice immunized with pDsRed2-GRA8 demonstrated specific humoral and cellular responses, induced higher IgG antibody titers with predominant IgG2a production; increased levels of IL-10, IL-12 (p70), $IFN-{\gamma}$, $TNF-{\alpha}$, and splenocyte proliferation; and prolonged survival times compared to those of control mice. The present study showed that DNA immunization with pDsRed2-GRA8 induced humoral and cellular immune responses, and all immunized mice showed greater Th1-type immune responses and longer survival times than those of control mice. These results indicated that T. gondii GRA8 DNA immunization induces a partial protective effect against acute toxoplasmosis.

Exploring Learning Styles and Task Preferences of Disadvantaged Gifted Students (학년과 성에 따른 소외 영재의 학습 스타일과 과제선호도 탐색)

  • Lee, Mi-Soon
    • Journal of Fisheries and Marine Sciences Education
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    • v.26 no.2
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    • pp.296-307
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    • 2014
  • As an educational trial for pursuit of educational excellence in the disadvantaged gifted, this study was to explore learning styles and task preferences by student's grade and gender. Furthermore, this study sought to present the practical basis to develop programs for disadvantaged gifted students. Total 153 disadvantage gifted students responded items of the Learning Styles Inventory-III and the Task Preferences Scale, which responses were analyzed by student's grade and gender in using MANOVA. As the results, the 1st grade disadvantaged gifted students preferred Direct instruction, Technology, and Learning games to the higher grade level students. There were significant differences in task preferences by students' grade level. The 4th grade disadvantaged gifted students preferred Creative tasks and Difficult tasks more than other grade level students.

Current progress on development of respiratory syncytial virus vaccine

  • Chang, Jun
    • BMB Reports
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    • v.44 no.4
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    • pp.232-237
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    • 2011
  • Human respiratory syncytial virus (HRSV) is a major cause of upper and lower respiratory tract illness in infants and young children worldwide. Despite its importance as a respiratory pathogen, there is currently no licensed vaccine for prophylaxis of HRSV infection. There are several hurdles complicating the development of a RSV vaccine: 1) incomplete immunity to natural RSV infection leading to frequent re-infection, 2) immature immune system and maternal antibodies of newborn infants who are the primary subject population, and 3) imbalanced Th2-biased immune responses to certain vaccine candidates leading to exacerbated pulmonary disease. After the failure of an initial trial featuring formalin-inactivated virus as a RSV vaccine, more careful and deliberate efforts have been made towards the development of safe and effective RSV vaccines without vaccine-enhanced disease. A wide array of RSV vaccine strategies is being developed, including live-attenuated viruses, protein subunit-based, and vector-based candidates. Though licensed vaccines remain to be developed, our great efforts will lead us to reach the goal of attaining safe and effective RSV vaccines in the near future.

Comparative Analysis of BESS and Governor Responses for Maximum Load Variations in Korea Power System (국내 계통 최대부하변동에 대한 BESS 및 조속기 특성 비교 분석)

  • Kang, Han-Gu;Chun, Yeong-Han
    • The Transactions of The Korean Institute of Electrical Engineers
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    • v.67 no.2
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    • pp.194-198
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    • 2018
  • The government established the 8th national energy plan that electricity energy from renewables in 2030 will be 20%. The frequency stability problem is one of the key issues to overcome for accomplishing the energy plan. Frequency quality deteriorates due to short term variations of renewables output. Battery energy storage system(BESS) is considered as a good alternative to improve the frequency quality due to its quick response. In this paper, we examined the effectiveness of BESS against the conventional governor properties.

Modeling of Turbulent Ventilation through an Opening due to Outdoor Pressure Fluctuations (개구부를 통한 외부압력 변동에 의한 난류환기 모델링)

  • Han, Hwa-Taik;Yom, Chol-Min
    • Korean Journal of Air-Conditioning and Refrigeration Engineering
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    • v.20 no.2
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    • pp.121-127
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    • 2008
  • This paper investigates the effects of outdoor pressure fluctuations on natural ventilation through an opening on a building envelope. The ventilation airflow rate depends on the magnitude and the period of the pressure fluctuations, the size of the opening relative to the space volume, and the resistance characteristics of the opening. Non-dimensional parameters have been derived, which determine indoor pressure responses due to outdoor pressure fluctuations. The flow regions are categorized into (1) synchronized region, (2) opening resistance region, and (3) transition region depending on the non-dimensional parameter derived. Pressure fluctuations and flow characteristics are investigated numerically using the 4th order Runge-Kutta method.

Matrix Metalloproteinase-8 Inhibitor Ameliorates Inflammatory Responses and Behavioral Deficits in LRRK2 G2019S Parkinson's Disease Model Mice

  • Kim, Taewoo;Jeon, Jeha;Park, Jin-Sun;Park, Yeongwon;Kim, Jooeui;Noh, Haneul;Kim, Hee-Sun;Seo, Hyemyung
    • Biomolecules & Therapeutics
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    • v.29 no.5
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    • pp.483-491
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    • 2021
  • Parkinson's disease (PD) is a neurodegenerative disorder that involves the loss of dopaminergic neurons in the substantia nigra (SN). Matrix metalloproteinases-8 (MMP-8), neutrophil collagenase, is a functional player in the progressive pathology of various inflammatory disorders. In this study, we administered an MMP-8 inhibitor (MMP-8i) in Leucine-rich repeat kinase 2 (LRRK2) G2019S transgenic mice, to determine the effects of MMP-8i on PD pathology. We observed a significant increase of ionized calcium-binding adapter molecule 1 (Iba1)-positive activated microglia in the striatum of LRRK2 G2019S mice compared to normal control mice, indicating enhanced neuro-inflammatory responses. The increased number of Iba1-positive activated microglia in LRRK2 G2019S PD mice was down-regulated by systemic administration of MMP-8i. Interestingly, this LRRK2 G2019S PD mice showed significantly reduced size of cell body area of tyrosine hydroxylase (TH) positive neurons in SN region and MMP-8i significantly recovered cellular atrophy shown in PD model indicating distinct neuro-protective effects of MMP-8i. Furthermore, MMP-8i administration markedly improved behavioral abnormalities of motor balancing coordination in rota-rod test in LRRK2 G2019S mice. These data suggest that MMP-8i attenuates the pathological symptoms of PD through anti-inflammatory processes.

The Students' Causal Inference Modes on Experimental Evidence Evaluation for Optical Phenomena (광학 현상 증거 해석의 인과적 추론 방식)

  • Pak, Sung-Jae;Jang, Byung-Ghi
    • Journal of The Korean Association For Science Education
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    • v.14 no.2
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    • pp.123-132
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    • 1994
  • The experimental evidence evaluation of the 11th grade students(N:91) was investigated. Specially, the influence of students' ideas about optical phenomena and presented evidence types on their evidence evaluation, and the influence of students' ideas on their causal inference modes were investigated. After eliciting the students' ideas about shadow phenomena and conformity of their idea, the experimental results with a binary outcome were presented as the evidence. Then the students were asked to evaluate the evidence. Again students' ideas were elicited. Most of students had causal ideas such that the shape of object(96%) and the inclination of screen(75%) were causes of shadow shape, not the shape(70%) and color(92%) of light source. In the case of the shape of object and the color of light source, most students(70%) believed strongly their ideas. Most responses(80%) in the evidence were evidence-based, and 12% of them were theory-based. There was no significant difference of reponses types between students with causal ideas(81%) and students with non-causal ideas(78%), between covariable and non-covariable evidence. But in the case of non-causal ideas, covariable evidence was more likely to yield evidence-based reponses than non-covariable evidence. If students had preconcepts inconsistent(84%) with the evidence, they were more likely to make evidence-based responses than the students with consistent ideas (75%) with the evidence. Especially in the case perceptually biased evidence, this tendency was marked. In the case of covariable evidence, many students made inclusion inferences(40%) rather than uncertainty inferences(32%). In the case of uncertainty inferences(94%), students more likely to make evidence-based reponses than inclusion inferences(83%) and exclusion infernces(88%). In the case of inclusion inferences and exclusion infernces, students tended to make idea-based responses and distort the evidences. In conclusion, when the students evaluate the experimental evidences, their ideas influence the causal inference modes. Especially, according to the conformity of the preconcepts and logical relation of evidences, the inference modes are more strongly depended upon the preconcepts rather than evidences.

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Parametric Study on Earthquake Responses of Soil-structure Interaction System by Substructure Method (부분구조법에 의한 지반-구조물상호작용시스템의 지진응답 매개변수 연구)

  • 박형기;조양희
    • Journal of the Earthquake Engineering Society of Korea
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    • v.2 no.1
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    • pp.1-10
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    • 1998
  • In the dynamic soil-structure interaction(SSI) analysis, numerous uncertain parameters are involved. They include the uncertainties in the definition of input motions, modeling of soil-structure interaction systems. analysis techniques, etc. This paper presents the results of parametric studies of the seismic responses of a reactor containment structure built on the viscoelastic layered soil. Among the numerous parameter, this study concentrates on the effects of definition point of the input motion, embedment of structure to the base soil, thickness of the top soil layer, and rigidity of the base soil. The substructure method using frequency independent impedances is adopted. The method is based on the mode superposition method in time domain using the composite modal damping values of th SSI system computed from the ratio of dissipated energy to the strain energy for each model. From the study results, the sensitivity of each parameter on the earthquake responses has been suggested for the practical application of the substructure method of SSI analysis.

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