• Title/Summary/Keyword: Alternative activation

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An Anti-Cancer Drug Candidate CYC116 Suppresses Type I Hypersensitive Immune Responses through the Inhibition of Fyn Kinase in Mast Cells

  • Park, Young Hwan;Kim, Hyun Woo;Kim, Hyuk Soon;Nam, Seung Taek;Lee, Dajeong;Lee, Min Bum;Min, Keun Young;Koo, Jimo;Kim, Su Jeong;Kim, Young Mi;Kim, Hyung Sik;Choi, Wahn Soo
    • Biomolecules & Therapeutics
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    • v.27 no.3
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    • pp.311-317
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    • 2019
  • Mast cells are the most prominent effector cells of Type 1 hypersensitivity immune responses. CYC116 [4-(2-amino-4-methyl-1,3-thiazol-5-yl)-N-[4-(morpholin-4-yl)phenyl] pyrimidin-2-amine] is under development to be used as an anti-cancer drug, but the inhibitory effects of CYC116 on the activation of mast cells and related allergy diseases have not reported as of yet. In this study, we demonstrated, for the first time, that CYC116 inhibited the degranulation of mast cells by antigen stimulation ($IC_{50}$, ${\sim}1.42{\mu}M$). CYC116 also inhibited the secretion of pro-inflammatory cytokines including TNF-${\alpha}$ ($IC_{50}$, ${\sim}1.10{\mu}M$), and IL-6 ($IC_{50}$, ${\sim}1.24{\mu}M$). CYC116 inhibited the mast cell-mediated allergic responses, passive cutaneous anaphylaxis (ED50, ~22.5 mg/kg), and passive systemic anaphylaxis in a dose-dependent manner in laboratory experiments performed on mice. Specifically, CYC116 inhibited the activity of Fyn in mast cells and inhibited the activation of Syk and Syk-dependent signaling proteins including LAT, $PLC{\gamma}$, Akt, and MAP kinases. Our results suggest that CYC116 could be used as an alternative therapeutic medication for mast cell-mediated allergic disorders, such as atopic dermatitis and allergic rhinitis.

Exploring Factors That Inhibit and Activate Community-Based Child Care Community Activities -Focusing on Jeonbuk Area Cases- (지역기반 아동돌봄공동체 활동의 저해 및 활성화 요인 탐색 -전북지역 사례를 중심으로-)

  • Lee, Juyeon;Hwang, Mi-jin
    • Journal of Family Resource Management and Policy Review
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    • v.25 no.3
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    • pp.69-85
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    • 2021
  • The purpose of this study was to explore ways to revitalize the community-based child care community by identifying the factors that are hindering and activating the operation and use of this community by elementary school students. To this end, an in-depth interview survey was conducted of operators of child care communities in Jeollabuk-do and users of caring communities. Detailed themes, sub-ranges and upper ranges were determined through a qualitative research method. As a result of the study, it was determined that the basic environmental weakness of the caring community and its lack of power are the things hindering the operation and use of rhe communities the most. On the other hand, the main activation factors for community-based child care community activities were the stabilization of the environment and the strengthening of the internal capacity of the care community. This study is meaningful as basic data for the safe establishment and activation of a community-based child care community, which is emerging as an alternative to the child care gap due to the prolonged effects of COVID-19.

Effect of Wnt signaling pathway activation on the efficient generation of bovine intestinal organoids

  • Park, Kang Won;Yang, Hyeon;Wi, Hayeon;Ock, Sun A;Lee, Poongyeon;Hwang, In-Sul;Lee, Bo Ram
    • Journal of Animal Reproduction and Biotechnology
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    • v.37 no.2
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    • pp.136-143
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    • 2022
  • Recent progress has been made to establish intestinal organoids for an in vitro model as a potential alternative to an in vivo system in animals. We previously reported a reliable method for the isolation of intestinal crypts from the small intestine and robust three-dimensional (3D) expansion of intestinal organoids (basal-out) in adult bovines. The present study aimed to establish next-generation intestinal organoids for practical applications in disease modeling-based host-pathogen interactions and feed efficiency measurements. In this study, we developed a rapid and convenient method for the efficient generation of intestinal organoids through the modulation of the Wnt signaling pathway and continuous apical-out intestinal organoids. Remarkably, the intestinal epithelium only takes 3-4 days to undergo CHIR (1 µM) treatment as a Wnt activator, which is much shorter than that required for spontaneous differentiation (7 days). Subsequently, we successfully established an apical-out bovine intestinal organoid culture system through suspension culture without Matrigel matrix, indicating an apical-out membrane on the surface. Collectively, these results demonstrate the efficient generation and next-generation of bovine intestinal organoids and will facilitate their potential use for various purposes, such as disease modeling, in the field of animal biotechnology.

Ethanolic Extract of Marsdenia condurango Ameliorates Benzo[a]pyrene-induced Lung Cancer of Rats -Condurango Ameliorates BaP-induced Lung Cancer in Rats-

  • Sikdar, Sourav;Mukherjee, Avinaba;Khuda-Bukhsh, Anisur Rahman
    • Journal of Pharmacopuncture
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    • v.17 no.2
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    • pp.7-17
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    • 2014
  • Objectives: Condurango is widely used in various systems of complementary and alternative medicines (CAM) against oesophageal and stomach ailments including certain types of cancer. However, until now no systematic study has been conducted to verify its efficacy and dose with proper experimental support. Therefore, we examined if ethanolic extract of Condurango could ameliorate benzo[a]pyrene (BaP)-induced lung cancer in rats, in vivo to validate its use as traditional medicine. Methods: Fifteen male and 15 female Sprague-Dawley (SD) rats were treated with 0.28 mg/kg of Sweet Bee Venom (SBV) (high-dosage group) and the same numbers of male and female SD rats were treated with 0.2 mL/kg of normal saline (control group) for 13 weeks. We selected five male and five female SD rats from the high-dosage group and the same numbers of male and female SD rats from the control group, and we observed these rats for four weeks. We conducted body-weight measurements, ophthalmic examinations, urinalyses and hematology, biochemistry, histology tests. Results: A histological study revealed gradual progress in lung tissue-repair activity in Condurango-fed cancer-bearing rats, showing gradual tissue recovery after three months of drug administration. Condurango has the capacity to generate reactive oxygen species (ROS), which may contribute to a reduction in anti-oxidative activity and to an induction of oxidative stress-mediated cancer cell-death. Condurango-activated pro-apoptotic genes (Bax, caspase-3, caspase-9, p53, cytochrome-c, apaf-1, ICAD and PARP) and down-regulated antiapoptotic-Bcl-2 expression were noted both at mRNA and protein levels. Studies on caspase-3 activation and PARP cleavage by western blot analysis revealed that Condurango induced apoptosis through a caspase-3-dependent pathway. Conclusion: The anticancer efficacy of an ethanolic extract of Condurango for treating BaP-induced lung cancer in rats lends support for its use in various traditional systems of medicine.

Gut-residing Microbes Alter the Host Susceptibility to Autoantibody-mediated Arthritis

  • Lee, Hyerim;Jin, Bo-Eun;Jang, Eunkyeong;Lee, A Reum;Han, Dong Soo;Kim, Ho-Youn;Youn, Jeehee
    • IMMUNE NETWORK
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    • v.14 no.1
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    • pp.38-44
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    • 2014
  • K/BxN serum can transfer arthritis to normal mice owing to the abundant autoantibodies it contains, which trigger innate inflammatory cascades in joints. Little is known about whether gut-residing microbes affect host susceptibility to autoantibody-mediated arthritis. To address this, we fed C57BL/6 mice with water containing a mixture of antibiotics (ampicillin, vancomycin, neomycin, and metronidazol) for 2 weeks and then injected them with K/BxN serum. Antibiotic treatment significantly reduced the amount of bacterial genomic DNA isolated from fecal samples, in particular a gene encoding 16S ribosomal RNA derived from segmented filamentous bacteria. Arthritic signs, as indicated by the arthritic index and ankle thickness, were significantly attenuated in antibiotic-treated mice compared with untreated controls. Peyer's patches and mesenteric lymph nodes from antibiotic-treated mice contained fewer IL-17-expressing cells than those from untreated mice. Antibiotic treatment reduced serum C3 deposition in vitro via the alternative complement pathway. IL-$17^{-/-}$ congenic C57BL/6 mice were less susceptible to K/BxN serum-transferred arthritis than their wild-type littermates, but were still responsive to treatment with antibiotics. These results suggest that gut-residing microbes, including segmented filamentous bacteria, induce IL-17 production in GALT and complement activation via the alternative complement pathway, which cause the host to be more susceptible to autoantibody-mediated arthritis.

Effects of 3-Steps Mind Map Activities on the System Thinking of Science Gifted Students: Focused on the Astronomy Contents (3단계 마인드맵 활동이 과학영재 학생들의 시스템 사고 향상에 미치는 효과 : 천문 내용을 중심으로)

  • Son, Jun Ho;Kim, Jonghee
    • Journal of Gifted/Talented Education
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    • v.26 no.2
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    • pp.257-280
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    • 2016
  • This study is focused on how the science gifted students can improve their system thinking by applying 3-steps mind map activities about astronomy contents. Through the pre-study two times, 9 students in 6th grade were participated in this study. It was analyzed the degree of improvement of systems thinking through the science gifted students' mind maps, causal maps and their interviews. The results of the study showed that the experimental group's system thinking who learned 3-steps mind map activities was more complex and diverse than the controlled group's. Therefore 3-steps mind map activities that have been developed in this study will be valuable as an alternative to improve their system thinking. Through this study, 3-steps mind map activities were confirmed that by inducing background knowledge activation and thinking systematization can be an alternative to improve the system thinking of science gifted students. So the 3-steps mind map activities can be helpful in cultivate human resources with creative problem solving ability based on their system thinking.

Genetic Association of the Porcine C9 Complement Component with Hemolytic Complement Activity

  • Khoa, D.V.A.;Wimmers, K.
    • Asian-Australasian Journal of Animal Sciences
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    • v.28 no.9
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    • pp.1354-1361
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    • 2015
  • The complement system is a part of the natural immune regulation mechanism against invading pathogens. Complement activation from three different pathways (classical, lectin, and alternative) leads to the formation of C5-convertase, an enzyme for cleavage of C5 into C5a and C5b, followed by C6, C7, C8, and C9 in membrane attack complex. The C9 is the last complement component of the terminal lytic pathway, which plays an important role in lysis of the target cells depending on its self-polymerization to form transmembrane channels. To address the association of C9 with traits related to disease resistance, the complete porcine C9 cDNA was comparatively sequenced to detect single nucleotide polymorphisms (SNPs) in pigs of the breeds Hampshire (HS), Duroc (DU), Berlin miniature pig (BMP), German Landrace (LR), Pietrain (PIE), and Muong Khuong (Vietnamese potbelly pig). Genotyping was performed in 417 $F_2$ animals of a resource population (DUMI: $DU{\times}BMP$) that were vaccinated with Mycoplasma hyopneumoniae, Aujeszky diseases virus and porcine respiratory and reproductive syndrome virus at 6, 14 and 16 weeks of age, respectively. Two SNPs were detected within the third exon. One of them has an amino acid substitution. The European porcine breeds (LR and PIE) show higher allele frequency of these SNPs than Vietnamese porcine breed (MK). Association of the substitution SNP with hemolytic complement activity indicated statistically significant differences between genotypes in the classical pathway but not in the alternative pathway. The interactions between eight time points of measurement of complement activity before and after vaccinations and genotypes were significantly different. The difference in hemolytic complement activity in the both pathways depends on genotype, kind of vaccine, age and the interaction to the other complement components. These results promote the porcine C9 (pC9) as a candidate gene to improve general animal health in the future.

An alternative method to reduce anaphylaxis by moxibustion

  • Jeong, Hyun-Ja;Nam, Sun-Young;Lee, Byong-Joo;Kim, Min-Gi;Kim, Jeong-Hwa;Kim, Hyung-Min
    • CELLMED
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    • v.4 no.2
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    • pp.12.1-12.12
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    • 2014
  • Epinephrine is a critical drug for patients at risk for anaphylaxis. Here, we suggest moxibustion as an alternative method to reduce anaphylaxis. Moxibustion was applied to the Shimen (CV5) acupoint and found to attenuate compound 48/80-induced mortality. Capsazepine, a transient receptor potential vanilloid (TRPV) 1 antagonist, significantly improved overall survival rates compared to groups treated with moxibustion or 2-aminoethoxydiphenyl borate (an activator of TRPV1, 2, and 3). Probenecid (a TRPV2 agonist) also increased survival rate and reduced histamine levels. Survival rates increased by moxibustion and probenecid were completely inhibited by ruthenium red (a TRPV2 and 3 antagonist) and gadolinium chloride (general TRPV antagonist), respectively. Passive cutaneous anaphylaxis and ear swelling were significantly reduced by moxibustion and probenecid (p < 0.05). In cardiomyocytes, TRPV2 was over-expressed by compound 48/80 and histamine but this increased TRPV2 expression decreased to baseline with moxibustion and probenecid treatment. In addition, intracellular calcium levels increased by compound 48/80 were reduced by probenecid. Overall, these findings suggest that the reduction of anaphylaxis caused by moxibustion could represent a new mechanism of moxibustion related to the regulation of TRPV2 activation and promotion of epinephrine secretion.

학술정보 커뮤니케이션 시스팀으로서의 대학출판부

  • 이영자
    • Journal of Korean Library and Information Science Society
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    • v.8
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    • pp.155-184
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    • 1981
  • The publication of the result of scholarly research is an integral part of the process by which learning is advanced. The university presses, as one of the major scholarly publishers are now confronted with many critical problems, such as the declining unit sales, the explosion of manuscripts, the challenge of new publishing technologies, etc., in performing the role of the scholarly communication system. The purpose of this study is to identify the problems imposed on the university presses and alternative strategies for them. For the study, the related literature to the subject were read, analyzed and synthesized, from which the overall prospect of the problems and alternative strategies are derived. The conclusion of the study can be summarized as follows: (1) The faith of the university should lie in its role to advance scholarly learning through production and dissemination of high-quality knowledge, and the university press should materialize such a faith. (2) The scholarly books, though not the best media of scholarly communication taking a side view of its timeliness and brevity, can perform the function of the best media for the specific subject and readers. (3) The scholarly books as national resource must be published for the scholars demanding them even though the publication can't help depending on the subsidiary fund. (4) For the survival and activation of the university presses, the following strategies should be examined, and put in force if necessary. (a) The role of the foundation su n.0, pporting the university presses should be expanded (b) The Co-operative system among the operations of the presses should be established. (c) It is desirable that the university without the press should participate in the university with the press for both the financial su n.0, pporting and the publicizing its faculty's manuscripts. (d) The positive efforts should be made for the increase of sales copies by implementing the dual-system of publication. (e) It is desirable that 'recording system' should be incorporated in the traditional publication system both for the lightening of financial problems and the explosion of publications. (f) It is necessary that the effective methods of the bibliographical control should be developed for the improvement of the scholarly communication. (g) Any kind of the permanent organization composed of the representatives from all the infrastructures of information industry should be established to study the character and direction of technological changes and to discern the better choice of specific, technologies in the scholarly communication system.

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A Study on the Activation of Dual Use Technology Program (민.군겸용기술사업 활성화 방안 연구)

  • Kim, Chul-Whan;Choi, Eun-Ho;Heo, Whan
    • Journal of the military operations research society of Korea
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    • v.32 no.1
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    • pp.13-35
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    • 2006
  • This study aims to propose alternative suggestions for practical and efficient implementation of Dual Use Technology Programs(CUTP) in Korea which can strengthen both national security and industrial competitiveness. DUTP of Korea has suffered from inefficiency and inactivity. This study analyzes the Inefficiency and negative factors of DUTP of Korea by examining the previous cases of the advanced countries. It also examines individual problems of DUTP carefully and attempts to derive alternative solutions to improve the current situation. First, a global government plan should be made considering Korea's weapon system and Korea's industrial characteristics. Second, DUTP should begin to develop core technology in connection with technology level evaluation and technology exchange project should establish a comprehensive information network system which links any civilian and military technology data. Third, technology transfer project should be promoted by utilizing cyber technology exchange market and military defense venture center. Fourth, standardization project should be expanded by establishing a national standard information system.