• Title/Summary/Keyword: production-inducing effect

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In vitro Activation of Procaspase-8 by Forming the Cytoplasmic Component of the Death-inducing Signaling Complex (cDISC)

  • Roy, Ankoor;Hong, Jong hui;Lee, Jin-Hee;Lee, Young-Tae;Lee, Bong-Jin;Kim, Key-Sun
    • Molecules and Cells
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    • v.26 no.2
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    • pp.165-170
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    • 2008
  • Procaspase-8 is activated by forming a death-inducing signaling complex (DISC) with the Fas-associated death domain (FADD) and the Fas receptor, but the mechanism of its activation is not well understood. Procaspase-8 devoid of the death effector domain at its N-terminus (${\Delta}nprocaspase-8$) was reported to be activated by kosmotropic salts, but it has not been induced to form a DISC in vitro because it cannot interact with FADD. Here, we report the production of full-length procaspase-8 and show that it is activated by adding the Fas death domain (Fas-DD) and the FADD forming the cytoplasmic part of the DISC (cDISC). Furthermore, mutations known to affect DISC formation in vivo were shown to have the same effect on procaspase-8 activation in vitro. An antibody that induces Fas-DD association enhanced procaspase-8 activation, suggesting that the Fas ligand is not required for low-level activation of procaspase-8, but that Fas receptor clustering is needed for high-level activation of procaspase-8 leading to cell death. In vitro activation of procaspase-8 by forming a cDISC will be invaluable for investigating activation of ligand-mediated apoptosis and the numerous interactions affecting procaspase-8 activation.

Immunomodulatory Activity of Ginsan, a Polysaccharide of Panax Ginseng, on Dendritic Cells

  • Kim, Mi-Hyoung;Byon, Yun-Young;Ko, Eun-Ju;Song, Jie-Young;Yun, Yeon-Sook;Shin, Taek-Yun;Joo, Hong-Gu
    • The Korean Journal of Physiology and Pharmacology
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    • v.13 no.3
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    • pp.169-173
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    • 2009
  • Ginsan, a Panax ginseng polysaccharide that contains glucopyranoside and fructofuranoside, has immunomodulatory effects. Although several biologic studies of ginsan have been performed, its effects on dendritic cells (DCs), which are antigen-presenting cells of the immune system, have not been studied. We investigated the immunomodulatory effects of ginsan on DCs. Ginsan had little effect on DC viability, even when used at high concentrations. Ginsan markedly increased the levels of production by DCs of IL-12 and TNF-${\alpha}$, as measured by ELISA. To examine the maturation-inducing activity of ginsan, we measured the surface expression levels of the maturation markers MHC class II and CD86 (B7.2) on DCs. It is interesting that ginsan profoundly enhanced the expression of CD86 on DC surfaces, whereas it increased that of MHC class II only marginally. In $^3H$-thymidine incorporation assays, ginsan-treated DCs stimulated significantly higher proliferation of allogeneic $CD4^+$ T lymphocytes than did medium-treated DCs. Taken together, our data demonstrate that ginsan stimulates DCs by inducing maturation. Because DCs are critical antigen-presenting cells in immune responses, this study provides valuable information on the activities of ginsan.

Oleanolic acid 3-acetate, a minor element of ginsenosides, induces apoptotic cell death in ovarian carcinoma and endometrial carcinoma cells via the involvement of a reactive oxygen species-independent mitochondrial pathway

  • Jo, Hantae;Oh, Jeong-Hyun;Park, Dong-Wook;Lee, Changho;Min, Churl K.
    • Journal of Ginseng Research
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    • v.44 no.1
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    • pp.96-104
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    • 2020
  • Objectives: Oleanolic acid, a minor element of ginsenosides, and its derivatives have been shown to have cytotoxicity against some tumor cells. The impact of cytotoxic effect of oleanolic acid 3-acetate on ovarian cancer SKOV3 cells and endometrial cancer HEC-1A cells were examined both in vivo and in vitro to explore the underlying mechanisms. Methods: Cytotoxic effects of oleanolic acid 3-acetate were assessed by cell viability, phosphatidylserine exposure on the cell surface, mitochondrial release of cytochrome C, nuclear translocation of apoptosis-inducing factor, depolarization of mitochondrial transmembrane potential (∆Ψm), and generation of reactive oxygen species (ROS). In vivo inhibition of tumor growth was also assessed with xenografts in immunocompromised mice. Results: Oleanolic acid 3-acetate exhibited potent cytotoxicity toward SKOV3 and HEC-1A cells by decreasing cell viability in a concentration-dependent manner. Importantly, oleanolic acid 3-acetate effectively suppressed the growth of SKOV3 cell tumor xenografts in immunocompromised mice. Furthermore, oleanolic acid 3-acetate induced apoptotic cell death as revealed by loss of ∆Ψm, release of cytochrome c, and nuclear translocation of apoptosis-inducing factor with a concomitant activation of many proapoptotic cellular components including poly(ADP-ribose) polymerase, Bcl-2, and caspases-8, caspase-3, and caspase-7. Oleanolic acid 3-acetate, however, caused a decrease in ROS production, suggesting the involvement of an ROS-independent pathway in oleanolic acid 3-acetate-induced apoptosis in SKOV3 and HEC-1A cells. Conclusion: These findings support the notion that oleanolic acid 3-acetate could be used as a potent anticancer supplementary agent against ovarian and endometrial cancer. Oleanolic acid 3-acetate exerts its proapoptotic effects through a rather unique molecular mechanism that involves an unconventional ROS-independent but mitochondria-mediated pathway.

The Review on the Study related to Anti-inflammatory Mechanism of Bee Venom Therapy (봉독요법(蜂毒療法)의 항염증(抗炎症) 기전(機轉) 연구(硏究)에 관(關)한 고찰(考察))

  • Choi, Jung-Sik;Park, Jang-Woo;Oh, Min-Seok
    • Journal of Haehwa Medicine
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    • v.15 no.1
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    • pp.141-160
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    • 2006
  • The obtained results are summarized as follows 1. New findings are reporting year by year as for the study related to Anti-inflammatory mechanism of Bee Venom therapy. 2. The Anti-inflammatory effect of Bee Venom therapy is achieved through counterirritation, stimulations to adrenal cortex, immuno-regulation, antioxidation, removal of free radicals, modulation of AGP gene induction. 3. The chief components of Bee Venom related to Anti-inflammatory effect are Melittin, MCD peptide, Apamin, Adolapin etc. 4. Melittin binds to secretory phospholipase A2 and inhibits its enzymatic activity. 5. Melittin blocks neutophil O2-production. 6. MCD peptide(Peptide 401) stimulates the mast cell secrets histamine, Anti-inflammatory effect caused by this is 'conterirritation'. 7. Melittin & Apamin have an anti-inflammatory effect by inducing cortisone secretion. 8. MCD peptide & Apamin increase immunologic fuction by stimulating hypophysis & adrenal cortex and have an anti-inflammatory effect by inhibiting synthesis of prostaglandin from arachidonic acid. 9. Adolapin have an anti-inflammatory effect by inhibiting COX. 10. Bee Venom have an anti-inflammatory effect by suppressing AGP($\alpha$-acid glycoprotein). 11. Bee Venom have an anti-inflammatory effect by inhibiting NO, iNOS, PLA2, COX-2, TNF-$\alpha$, IL-1, NF-${\kappa}B$, MAP kinase.

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A Study on the Ripple Effect Economy of Busan Ubiquitous-Safety Realization on Using an Input-Output Model (I-O모형을 이용한 부산 U-방재 실현의 경제적 파급 효과 분석에 관한 연구)

  • Ryu, Tae-Chang;Kim, Tae-Min;Kim, Gyeong-Su
    • Journal of the Korean Society of Hazard Mitigation
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    • v.8 no.6
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    • pp.93-100
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    • 2008
  • Dense of population construction and high density of skyscraper, and geological characteristics caused natural disasters(e.g. typhoon, tsunami, flood, storm, earthquake, etc.) and manmade disasters(e.g. fire, collapse, explosion, traffic accident, etc.). the extent and scale of the disaster are getting larger. To cope with such problems, Busan City has established the basic plan to secure the life and property of the citizens through model strategy and design of Ubiquitous-Safety Busan. This study quantitatively analyzed the ripple effect on local economy through the fulfillment of Ubiquitous-Safety. The production inducing effect of 250 billion won directly and indirectly can be estimated due to the realization of Ubiquitous-Safety. The value added effect of 115 billion won can be estimated. the employment effect of 5,580 persons can be generated with income effect of 51 billion won.

Analysis of Economic Value and Regional Economic Impact of Jeju Port Redevelopment Project (제주항 재개발사업의 경제적 가치 및 지역경제 파급효과 분석)

  • Sim, Ki-Sup
    • Journal of Korea Port Economic Association
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    • v.38 no.3
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    • pp.53-68
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    • 2022
  • In this study, the economic value and economic ripple effect of the Jeju Inland Port redevelopment project were estimated. The economic value was estimated from the viewpoint of amenity, the value of non-market goods such as landscape improvement, environmental improvement, and recreation effects. As a result of the estimation, the population was divided into Jeju Island and other regions and the individual's willingness to pay was estimated to be 2,952.9 won in Jeju Island and 4,722.8 won in other regions. On the other hand, the economic ripple effect of the Jeju Inland Port redevelopment project was estimated during the project period and after the completion of the economic ripple effect was estimated. As a result of the estimation, the production inducement value was KRW 84,387 million, the value-added inducement effect was KRW 37,292 million, and the employment inducement value was 5,846 employment when the (direct employment + indirect employment) effect was combined. After the end of the project period, as of 2022, there were 518,000 foreign tourists, and the value-added inducing effect was estimated to be about 149,885 million won.

Effects of Oral Administration of Phellinus linteus on the Productions of the Th1- and Th2-type Cytokines in Mice

  • Oh, Gi-Su;Pae, Hyun-Ock;Choi, Byung-Min;Kwon, Ji-Wung;Yun, Yeong-Ho;Choi, Jeong-Ho;Kwon, Tae-Oh;Park, Young-Chul;Chung, Hun-Teag
    • IMMUNE NETWORK
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    • v.3 no.3
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    • pp.182-187
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    • 2003
  • Background: The mushroom Phellinus linteus (PL) has been shown to have the anti-tumor and immunostimulatory effects. We hypothesized that the hot water extract of PL (WEPL) exerts its significant immunostimulatory effect by inducing production of the Th1-derived cytokine interferon-${\gamma}$ (IFN-${\gamma}$) by T lymphocytes. Methods: T lymphocytes were isolated from the mice fed with 200 mg/kg of WEPL once a day for 4 weeks, and then stimulated with the mitogen concanavaline A (Con A). IFN-${\gamma}$ gene and intracellular protein expressions were analyzed by RT-PCR and flow cytometry, respectively. The production of IFN-${\gamma}$ was measured by enzyme-linked immunosorbent assay. Results: WEPL significantly enhanced the transcription of IFN-${\gamma}$ mRNA. The effect of WEPL on IFN-${\gamma}$ expression was further supported by a concomitant increase in the number of cells with intracellular IFN-${\gamma}$ protein as well as the secretion of IFN-${\gamma}$. However, WEPL did not modulate either gene expression or protein secretion of interleukin-4, a Th2-associated cytokine, by Con A-stimulated T lymphocytes. Conclusion: Our results demonstrate that one of the potentially beneficial anti-tumor and immunostimulatory effects of WEPL may be mediated through the enhancement of IFN-${\gamma}$ secretion by T lymphocytes.

Prostaglandin Affects In Vitro Ovulation and 17α, 20β-Dihydroxy-4-pregnen-3-one Production in Longchin Goby, Chasmichthys dolichognathus Oocytes

  • Baek, Hea Ja;Lee, Da Som
    • Development and Reproduction
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    • v.23 no.2
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    • pp.111-117
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    • 2019
  • This study focused on the association of prostaglandins and a progestin, $17{\alpha}$, $20{\beta}P$-dihydroxy-4-pregnen-3-one ($17{\alpha}20{\beta}P$) during the ovulation process in longchin goby, Chasmichthys dolichognathus. We performed several in vitro experiments using $850-920{\mu}m$ diameter oocytes which were at the migratory nucleus stage. With the $890-920{\mu}m$ diameter oocytes, no significant difference in ovulation was observed in any of the prostaglandins (PGE1, PGE2, and $PGF2{\alpha}$) treated groups although PGE2 and $PGF2{\alpha}$ at concentrations of 50 ng/mL increased ovulation slightly compared with controls; however, $17{\alpha}20{\beta}P$ production was stimulated with PGE1 alone at low concentrations (5 ng/mL). In $850{\mu}m$ diameter oocytes, $PGF2{\alpha}$ at concentrations of 50 and 500 ng/mL resulted in a significant increase in ovulation. $17{\alpha}20{\beta}P$ (50 ng/mL) alone had no observable effect on ovulation, but in the combined of $PGF2{\alpha}$ 50 or 500 ng/mL it caused the greatest effect on ovulation. The sensitivity of oocytes to the induction of ovulation varies between 850 and $890-920{\mu}m$, it appeared to vary depending on the migration status of nucleus. These results suggest that $PGF2{\alpha}$ (or combined of $17{\alpha}20{\beta}P$) was more potent in inducing ovulation of the longchin goby.

Anti-oxidative Effect of Chungsimyeonja-um (CSYJE) via Nrf2/HO-1 Pathway Activity in Lipopolysaccharide (LPS) Induced RAW 264.7 Macrophages (대식세포에서 Nrf2/HO-1경로를 통한 청심연자음의 항산화효과)

  • Jeon, Seon Hong;Oh, Sol La;Kim, So Jeong;Jeon, Bo Hee;Sung, Jin Young;Kim, Yong Min
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.46 no.3
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    • pp.253-263
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    • 2020
  • Reactive oxygen species (ROS) plays an important role in maintaining homeostasis. However, excessive ROS production damages cellular components such as proteins, lipids, and nucleic acids and promotes skin aging. In this study, we confirmed the antioxidant effect of CSYJE to prevent excessive oxidative stress. First, DPPH and ABTS assays were performed to confirm the antioxidant effect of CSYJE and the radical scavenging activity was confirmed depending on the concentration. As a result of performing the MTT assay to confirm the cell viability, it was confirmed that there was no cytotoxicity at a concentration of 1,000 ㎍/mL. As a result of western blotting to confirm the expression levels of the antioxidant-related proteins nuclear-E2-related factor 2 (Nrf2) and Heme oxygenase-1 (HO-1), it was confirmed that the expression was increased in a concentration-dependent manner. After inducing ROS with lipopolysaccharide (LPS), an intracellular ROS-causing substance, DCF-DA was performed to confirm the inhibitory effect of ROS production, and the inhibition of ROS production was confirmed to concentration-dependent. Real-time RT-PCR was performed to confirm the mRNA expression level of inflammatory cytokines and inflammatory mediator caused by ROS generation, mRNA expression was reduced in a dose dependent manner. Therefore, this study confirmed the antioxidant effect of CSYJE through the Nrf2/HO-1 signaling pathway, which suggests that CSYJE can be used as an antioxidant cosmetic material by inhibiting free radicals.

Modulation of Aqueous Extracted Angelicae sinensis Radix on Nitric Oxide Production and Pro-inflammatory Cytokine Gene Expressions in RAW 264.7 Macrophage Cells

  • Lee Young Sun;Han Ok Kyung;Shin Sang Woo;Park Jong Hyun;Kwon Young Kyu
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.6
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    • pp.1514-1518
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    • 2003
  • Angelica sinensis radix, Danggui, is a traditional oriental medication, which has been used to modulate immune response. We report here that aqueous extract of Angelica sinensis radix (ASR) can induces NO production, and inhibit LPS-induced NO production in dose-dependent manner in RAW 264.7 macrophage cells. ASR also induces iNOS mRNA and iNOS protein expression, and exhibit inhibitory effect on iNOS mRNA and protein expression in a dose-dependent manner in LPS-stimulated RAW 264.7 macrophage cells. Cytokines involved in the regulation of inflammatory reaction and immune response may play a role in the pathogenesis. ASR induces. pro-inflammatory cytokine gene expression (IL-1α, IL-1β and IL-6 gene) in a dose-dependent manner, and inhibits the expressions of these cytokines in LPS-stimulated RAW 264.7 macrophage cells. These data indicate that (1) ASR may be a potential therapeutic modulator of NO synthesis in various pathological conditions, and (2) the immunomodulatory effects of ASR may be, in part, associated with the inducing or suppression of pro-inflammatory cytokine gene expressions.