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Effect of Paroxetine and Sertraline Treatment on Forced Swim Test-Induced Behavioral and Immune Changes in the Mouse (마우스 강제수영에 의한 행동 및 면역반응 변화에 대한 Paroxetine과 Sertraline의 효과)

  • Eum, Se-Yeun;Jeong, Min-Ho;Lim, Young-Jin;Kim, Bu-Kyung;Jeong, Soo-Jin;Hahn, Hong-Moo;Choe, Byeong-Moo
    • Korean Journal of Psychosomatic Medicine
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    • v.8 no.1
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    • pp.46-57
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    • 2000
  • Objectives : The purpose of the present study was to examine the effect of subacute treatment with the selective serotonin reuptake inhibitors(paroxetine and sertraline) on immobility in the forced swim test(FST) and on FST-induced changes in immune parameters of the mice. Methods : Authors applied a modified method of FST by Porsolt et al. Over 5 BALB/c mice were used for each group of experiments. To explore the changes in immune parameters by FST, authors investigated the production of anti-rat RBC antibody, concanavalin A(ConA)- or lipopolysaccharide(LPS)-stimulated splenocytes proliferation assay and cytokine gene expression. Results : Both paroxetine and sertraline decreased the duration of immobility in a dose-related manner. FST-performed mice showed a significant decrease in mitogenic responses of splenocytes and a slight increasing tendency in anti-rat RBC antibody response. All these responses were attenuated significantly by paroxetine and attenuated nearly nominal significance level by sertraline. The cytokine profiles of ConA-stimulated splenocytes from FST-performed mice showed stronger expression of IL-4 and weaker expression of IL-2 than control mice, and no changes in the expressions of IFN-$\gamma$ and lymphotoxin. IL-6 and IL-10 were not expressed in both group of mice. The pretreatment of paroxetine and sertraline attenuated the altered cytokine expressions in FST-performed mice to some extent. Some alterations of the expressions of IL-6 and IL-10 were observed in the mice which the selective serotonin reuptake inhibitors had been pretreated. Conclusion : The subacute treatment of paroxetine and sertraline attenuated the FST-induced behavioral and immune changes, and these serotonin reuptake inhibitors may exert some modulating effects on the immune system by the induction of cytokine gene expression, especially IL-6 and IL-10.

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Effects of Red-ginseng Extracts on the Activation of Dendritic Cells (고려홍삼의 수지상세포 활성화 효과)

  • Kim, Do-Soon;Park, Jueng-Eun;Seo, Kwon-Il;Ko, Sung-Ryong;Lee, Jong-Won;Do, Jae-Ho;Yee, Sung-Tae
    • Journal of Ginseng Research
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    • v.30 no.3
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    • pp.117-127
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    • 2006
  • Ginseng is a medicinal herb widely used in Asian countries. Dendritic cells(DCs) play a pivotal role in the initiation of T cell-mediated immune responses, making them an attractive cellular adjuvant for use in cancer vaccines. In this study, we examined the effects of Red-ginseng(water extract, edible and fermented ethyl alcohol extract, crude saponin) on the DCs phenotypic and functional maturation. Immature DCs were cultured in the presence of GM-CSF and IL-4, and the generated immature DCs were stimulated by water extract, edible and fermented ethyl alcohol extract, crude saponin and LPS, respectively, for 24hours. The expression of surface co-stimulatory molecules, including MHC(major histocompatibility complex) class II, CD40, CD80 and CD86, was increased on DCs that were stimulated with crude saponin, but antigen-uptake capacity was decreased. The antigen-presenting capacity of Red-ginseng extracts-treated DCs as analyzed by allogeneic T cells proliferation and IL-2, $IFN-{\gamma}$ production was increased. Furthermore, $CD4^+$ and $CD8^+$ syngeneic T cell(OVA-specific) proliferation and $IFN-{\gamma}$ production was significantly increased. However, $CD4^+$ syngeneic T cell secreted higher levels of IL-2 in responding but not $CD8^+$ syngeneic T cell. These results indicate the immunomodulatory properties of Red-ginseng extracts, which might be therapeutically useful in the control of cancers and immunodeficient diseases through the up-regulation of DCs maturation.

High Yield Bacterial Expression and Purification of Active Cytochrome P450 p-coumarate-3-hydroxylase (C3H), the Arabidopsis Membrane Protein (대장균 시스템을 이용한 Arabidopsis 막 단백질 cytochrome P450 p-coumarate-3hydroxylase (C3H) 활성형의 과발현 및 분리정제)

  • Yang, Hee-Jung;Kim, Wan-Yeon;Yun, Young-Ju;Yoon, Ji-Won;Kwon, Tae-Woo;Youn, Hye-Sook;Youn, Bu-Hyun
    • Journal of Life Science
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    • v.19 no.8
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    • pp.1039-1046
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    • 2009
  • The cytochrome P450s (P450s) metabolizing natural products are among the most versatile biological catalysts known in plants, but knowledge of the structural basis for their broad substrate specificity has been limited. The activity of p-coumarate 3-hydroxylase (C3H) is thought to be essential for the biosynthesis of lignin and many other phenylpropanoid pathway products in plants however, all attempts to express and purify the protein corresponding C3H gene have failed. As a result, no conditions suitable for the unambiguous assay of the enzyme are known. The detailed understanding of the mechanism and substrate-specificity of C3Hdemands a method for the production of active protein on the milligram scale. We have developed a bacterial expression and purification system for the plant C3H, which allows for the quick expression and purification of active wild-type C3H via introduction of combinational mutagenesis. The modified cytochrome P450 C3H ($C3H_{mod}$) could be purified in the absence of detergent using immobilized metal affinity chromatography and size exclusion chromatography following extraction from isolated membranes in a high salt buffer and catalytically activated. This method makes the use of isotopic labeling of C3H for NMRstudies and X-ray crystallography practical, and is also applicable to other plant cytochrome P450 proteins.

Anti-Inflammatory Effects of Picrasma Quassioides (D.DON) BENN Leaves Extracts (소태나무 잎 추출물의 항염증 효과)

  • Jung, Yeon Seop;Eun, Cheong Su;Jung, Young Tae;Kim, Hyun Jeong;Yu, Mi Hee
    • Journal of Life Science
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    • v.23 no.5
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    • pp.629-636
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    • 2013
  • This study was performed to evaluate the anti-inflammatory and antioxidant activities of methanol extract from the leaves of Picrasma quassioides BENNET (PLME). The antioxidant effects of PLME were measured based on polyphenol and flavonoid contents. PLME was found to have $367.52{\mu}g/mg$ and $46.61{\mu}g/mg$ high polyphenol and flavonoid contents. Cell viability was determined by MTT assay. The production of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) was measured by Griess assay and enzyme-linked immunosorbent assay (ELISA). In order to effectively anti-inflammatory agents, we examined the inhibitory effects on the production of lipopolysaccharide (LPS)-induced NO and $PGE_2$ in RAW 264.7 cells. PLME significantly decreased the production of NO and $PGE_2$ in a dose-dependent manner, and also reduced the expression of iNOS, a COX-2 protein. In addition, PLME reduced the NF-${\kappa}B$, $I{\kappa}B$ phosphorylation in RAW 264.7 cells upon stimulation with LPS (100 ng/ml) for 24 h. These results provide evidence for the anti-inflammatory and antioxidant effects of Picrasma quassioides leaves.

The Effect of Subject Well-being on the Consumer's Pricing of Alternatives (주관적 행복이 대안에 대한 소비자의 가격 책정에 미치는 영향)

  • Kim, Moon-Seop;Choi, Jong-An
    • Journal of Distribution Science
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    • v.10 no.4
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    • pp.29-36
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    • 2012
  • Research on subjective well-being (SWB) has flourished in recent years. As SWB determines cognitive and motivational processes, including social comparison and cognitive dissonance, it determines how consumers make decisions, including the comparison and evaluation of alternatives. Considering that the comparison and evaluation of alternatives is related to social comparison and cognitive dissonance, the influence of SWB on the comparison and evaluation of alternatives needs to be investigated. This research aims to examine the effect of SWB on the comparison and evaluation of alternatives, especially when people acquire additional information about their chosen or non-chosen alternatives, leading to a change of absolute/relative value of alternatives. The reasonable price of an alternative as evaluated by individuals is used as a measure reflecting the perceived value of an alternative. Putting all of this together, the current study intended to investigate the influence of absolute and relative value on the reasonable price of an alternative depending on SWB. Participants were randomly assigned to one of two experiment groups (deterioration of non-chosen alternative vs. improvement of non-chosen alternative). After reading consumer report ratings of alternatives shown on monitor screens, participants chose one of the alternatives, followed by the change of the consumer report ratings (deterioration of non-chosen alternative vs. improvement of non-chosen alternative). Participants evaluated the reasonable price of their chosen alternative based on the provided price of the non-chosen alternative. Two weeks after the experiment, they were asked to answer survey questionnaire on SWB measures. A regression was performed on the reasonable price with experiment groups, mean-centered SWB, and their interaction. There was a significant simple effect of groups and SWB. More importantly, these effects were qualified by the predicted interaction of groups and SWB. To interpret this interaction further, simple slope tests were performed on the price when SWB was centered at one standard deviation above (i.e., happy people) and below (i.e., unhappy people) the mean. As predicted, happy people rated the reasonable price of the chosen alternative higher in the improvement of non-chosen alternative group than in the deterioration of non-chosen alternative group. Conversely, unhappy people showed no price difference between groups. These results show that happy people pay attention to the absolute value of the alternative, whereas unhappy people give more weight to the relative value as well as to the absolute value of a chosen alternative, indicating that unhappy people are more sensitive to the negative information of a non-chosen alternative compared to happy people. The present research expanded the existing research stream on SWB by showing the influence of SWB on the consumers' evaluation of alternatives. Furthermore, this study adds to previous research on SWB and social comparison by suggesting that unhappy people tend to be more sensitive to negative social comparison information of alternatives even when a target of social comparison is not explicitly present. Moreover, these results yield some managerial implications on how to provide product information based on SWB in order to make products more attractive among the alternatives available to consumers.

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Anti-Inflammatory Effect of Ethanol Extract from Onion (Allium cepa L.) Peel on Lipopolysaccharide-Induced Inflammatory Responses in RAW 264.7 Cells and Mice Ears (LPS로 유도된 RAW 264.7 세포와 마우스 귀 조직에 대한 양파(Allium cepa L.) 껍질 에탄올 추출물의 항염증 효과)

  • Ahn, Na-Kyung;Kang, Bo-Kyeong;Kim, Koth-Bong-Woo-Ri;Kim, Min-Ji;Bae, Nan-Young;Park, Ji-Hye;Park, Sun-Hee;Ahn, Dong-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.11
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    • pp.1612-1620
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    • 2015
  • Inflammation is a complex process involving a variety of immune cells, which defend the body from harmful stimuli. However, pro-inflammatory cytokines and inflammatory mediators can also exacerbate diseases such as cancer. Onion peel contains several phenolic compounds, including quercetin at an amount 20 times greater in peel than edible flesh. Therefore, in this study, the anti-inflammatory effects of onion peel ethanol extract (OPEE) were investigated lipopolysaccharide-induced inflammatory response. In our results, NO production decreased in a dose-dependent manner. Secretion of IL-6, $TNF-{\alpha}$, and $IL-1{\beta}$ was suppressed by 44%, 53%, and 60% respectively, at $100{\mu}g/mL$. Moreover, OPEE also suppressed expression of COX-2, iNOS, $NF-{\kappa}B$, and MAPKs in a dose-dependent manner. Formation of mice ear edema was reduced at the highest dose tested compared to the control, and reduction of ear thickness was observed in the histological analysis as well. In the acute toxicity test, no morality was observed in mice administered 5,000 mg/kg body weight of OPEE over a 2-week observation period. These results suggest that OPEE may have significant effects on inflammatory factors and be a potential anti-inflammatory material.

Effects Of Environmental Factors And Individual Traits On Work Stress And Ethical Decision Making (간호사의 환경적 요소와 개인적 특성이 직무스트레스와 윤리적 의사결정에 미치는 영향)

  • Kim, Sang Mi L.;Shake ketefian
    • Journal of Korean Academy of Nursing
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    • v.23 no.3
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    • pp.417-430
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    • 1993
  • 이 연구는 환경적 요소(간호사의 자율성, 조직의 표준화)와 개인의 특성(통제위, 나이, 경험. 간호역할개념, 도덕성), 직무 스트레스, 윤리적 의사결정 사이의 관계를 이론적 틀을 구성하여 테스트함으로써 그 인과관계를 탐구하였다. 본 연구를 위해 개발된 모형은 1) Katz와 Kahn의 조직에 대한 개방체계 이론(open systems theory of organization) ; 2) Kahn. Wolfe, Quinn, Snoek의 스트레스 이론 (theory of stress) : 3) Kohlberg의 도덕발달 이론(theory of moral develop-ment): 그리고 4) 여러 문헌고찰을 기초로 하였다. 본 연구의 모형은 2가지의 주요 종속변수(직무 스트레스, 윤리적 간호행위), 2가지 매개변수(간호 역할개념, 도덕성 발달정도) 그리고 여러 독립변수들(조직의 표준화, 자율성, 통제위, 교육, 나이, 경험 등)로 구성되었다. 간단히 말해, 간호사의 스트레스와 윤리적 간호행위 를 개인 자신과 환경이라는 두 요소의 결과로 간주한 것이다. 미국(2개주)의 여러 건강관리기관에 근무하는 224명의 정규 간호사를 대상으로 하였고. 가설 검증을 위하여 1) 변수간의 인과관계를 조사하기 위한 Linear Structural Relationships(LISREL)기법과 2) 나이, 경험, 교육이 변수간의 관계에 미치는 중간역할을 알아보기 위해 상관분석을 이용하였다. LISREL결과를 보면 제시된 모델이 각 내재 변수에 상당한 설명력을 가지면서 자료에 잘 맞는 것으로 나타났다. 이 연구에서 가장 뚜렷한 점으로 나타난 것은 개인의 특성보다 환경적 요소로서의 자율성이 직무스트레스와 윤리적 의사결정을 예견하는데 훨씬 중요한 변수로 부각되었다는 점이다. 또한 간호사의 전문적 역할개념과 봉사적 역할개념이 간호사의 윤리적 의사결정을 예견하는 가장 중요한 요소로 나타났다. 중간영향(moderation effect)을 보면, 젊고 경험이 적은 간호사일수록 나이가 많고 경험있는 간호사보다 환경적 요소(자율성)에 더 큰 영향을 받는다는 것을 암시하고 있다. 또한 4년제 대학 이상을 졸업한 간호사의 윤리 적 간호행 위 는 2, 3년제 를 졸업 한 간호사 보다 환경적 요소에 의해 덜 영향을 받는 것으로 나타났다. 한편 자율성의 부족은 2, 3년제 졸업 간호사보다 4년제 졸업 간호사에게 더 심한 스트레스가 되고 있음을 시사하였다. 이 연구의 결과로부터 적어도 다음과 같은 두 가지 실제적인 제언을 도출할 수 있다. 첫째, 이 연구는 환경적요소로서의 자율성이 다른 어떤 개인적인 요소보다 직무 스트레스를 예견하는 데 중요한 요소라는 것을 제시하였다. 이것은 간호행정가들에게, 간호사의 직무 스트레스를 감소시키기 위해선 “자율성”이 아주 중요히 다루어져야 한다는 것을 의미한다. 만일 간호사들의 직무스트레스가 그 개인의 복지에 큰 해가 되고 환자를 간호하는 데 직접적으로 관계된다면, 간호행정가는 그 조직의 직무체계를 다시 평가해서 일에 대한 새로운 설계가 필요한지를 파악해야 한다. 또한 이 연구는 직무를 다시 설계할 경우, 누구에게 먼저 촛점을 두고 시작해야 하는지를 밝혀주고 있다. 즉, 젊고 경험이 미숙한 간호사들에게 촛점을 두고 시작해야 하며, 작업환경의 가장 중요한 차원중의 하나인 사회적 지원(social support)을 조심스럽게 고려해 보아야 한다. 둘째, 간호사의 윤리적 간호행위를 높히기 위해 전문적 역할개념과 봉사적 역할개념이 재강조될 필요가 있다. 이 두 역할개념 들을 교육을 통하여 효과적으로 가르칠 필요가 있다고 본다. 이 두 개념들이 간호사의 바람직한 간호행 위에 영향을 미치는 가장 중요한 요소로 나타났기 때문이다. 또한, 본 연구결과에 따르면, 경험이 많을수록 일에 싫증을 느껴 바람직한 윤리적 간호행위가 감소되는 경향이 있었다. 따라서, 건강관리체제 (health care system) 안에서의 간호사의 역할이-전문직으로서의, 그리고 환자를 위한 옹호자로서의-학교와 임상에서 효과적으로 교육되어져야 한다고 본다. 간호사들의 역할에 대한 계속적인 교육이 학생은 물론 임상 간호사들에게도 실시되어져야 할 것이다. 미래연구의 방향을 제시해 보면 첫째로 연구의 일반화를 높히기 위해 더 많은 대상자를 포함시켜야 한다. 이는 여러 종류의 표본을 반드시 한번에 전부 포함시켜야 한다는 것을 의미하는 것이 아니고, 특정한 여러 표본들을 연속적으로 연구함으로서 이 목표를 성취할 수 있다고 생각한다. 둘째는 여러 construct들(윤리적 간호행위, 직무 스트레스, 간호 역할개념 등)에 대한 적절한 측정도구를 개발해야 한다. 측정도구를 개발하기 위해서는 풍부하고 세세한 통찰력을 제공하는 질적인 정보를 얻는 것이 선행되어야 한다. 셋째, 윤리적 간호행위와 직무 스트레스에 관한 연구를 증진시키기 위해 실험설계 및 종단적 연구(expel-imental, longitudinal design)가 시도될 필요가 있다. 마지막으로, 윤리적 간호행위와 직무 스트레스를 예견할 수 있는 이론적 탐구(theoretical exploration), 즉 이론정립을 위하여, 환경적 요소와 개인의 특성에 대한 자세한 정보를 제공해 줄 수 있는 질적 연구들이 요구된다.

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Inhibitory Effect of Camp Antagonist and Pka Inhibitors, and Stimulatory Effect of Adenylate Cyclase Agonist on Cathepsin K Processing in Cultured Mouse Osteoclasts (cAMP 길항제와 PKA 억제제 및 Adenylate Cyclase 촉진제의 백서 파골세포에서 Cathepsin K 생성에 대한 효과)

  • Shim, Youn-Soo
    • Journal of dental hygiene science
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    • v.6 no.1
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    • pp.1-9
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    • 2006
  • Cathepsin K (cat K) is the major cysteine protease expressed in osteoclasts and was thought to play a key role in matrix degradation during bone resorption. It was shown that the intracellular maturation of cat K was prevented by the cAMP antagonist, Rp-cAMP, and the protein kinase A (PKA) inhibitors of KT5720 and H89. In contrast, forskolin, a adenylate cyclase agonist, rather induced Cat K processing and maturation in osteoclasts. Furthermore, to determine whether cat K processing and maturation signaling involves protein kinase C (PKC), mouse total bone cells were treated with calphostin C, a specific inhibitor of PKC, however, no effect was observed, indicating that calphostin C did not affect to osteoclast-mediated cat K processing and maturation. Thus, it is indicated that the cAMP-PKA signaling pathway regulates cat K maturation in osteoclasts. Since secreted proenzymes have the potential to reenter the cell via M6P receptor, to prevent this possibility, it was tested cAMP antagonist Rp-cAMP and the PKA inhibitors KT5720 and H89 in the absence or presence of M6P. Inhibition of cat K processing by Rp-cAMP, KT5720, or H89 was observed in a dose-dependent manner. Furthermore, the addition of M6P resulted in enhanced potency of Rp-cAMP, KT5720 and H89. These dose-dependently inhibited in vitro bone resorption with a potency similar to that observed for inhibition of cat K processing.

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Trans-10, cis-12 Conjugated Linoleic Acid Modulates Tumor Necrosis Factor-${\alpha}$ Production and Nuclear Factor-${\kappa}B$ Activation in RAW 264.7 Macrophages Through Formation of Reactive Oxygen Species (RAW 264.7 세포에 있어 t10c12-CLA의 ROS를 통한 TNF-${\alpha}$ 생산 및 NF-${\kappa}B$ 활성 조절)

  • Park, So-Young;Kang, Byeong-Teck;Kang, Ji-Houn;Yang, Mhan-Pyo
    • Journal of Veterinary Clinics
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    • v.31 no.6
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    • pp.469-476
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    • 2014
  • The aims of this study were to explore the effects of conjugated linoleic acid (CLA) on reactive oxygen species (ROS) production in lipopolysaccharide (LPS)-naïve and LPS-stimulated RAW 264.7 macrophages and to examine whether these effects affect the regulation of tumor necrosis factor-alpha (TNF-${\alpha}$) production, and nuclear factor-kappa B (NF-${\kappa}B$) and peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) activation. Trans-10, cis-12(t10c12)-CLA increased the production of ROS, as well as TNF-${\alpha}$ in LPS-naïve RAW 264.7 cells. The CLA-induced TNF-${\alpha}$ production was suppressed by treatment of diphenyleneiodonium chloride (DPI), a NADPH oxidase inhibitor. In addition, CLA enhanced the activities of NF-${\kappa}B$ and $PPAR{\gamma}$ in LPS-naïve RAW 264.7 cells, and this effect was abolished with DPI treatment. LPS treatment increased ROS production, whereas CLA reduced LPS-induced ROS production. LPS increased both TNF-${\alpha}$ production and NF-${\kappa}B$ activity, whereas t10c12-CLA reduced TNF-${\alpha}$ production and NF-${\kappa}B$ activity in LPS-stimulated RAW 264.7 cells. DPI treatment suppressed LPS-induced ROS production and NF-${\kappa}B$ activity. Moreover, DPI enhanced the inhibitory effects of t10c12-CLA on TNF-${\alpha}$ production and NF-${\kappa}B$ activation in LPS-stimulated RAW 264.7 cells. However, neither t10c12-CLA nor DPI affected $PPAR{\gamma}$ activity in LPS-stimulated RAW 264.7 cells. Taken together, these data indicate that t10c12-CLA induces TNF-${\alpha}$ production by increasing ROS production in LPS-naïve RAW 264.7 cells, which is mediated by the enhancement of NF-${\kappa}B$ activity via $PPAR{\gamma}$ activation. By contrast, t10c12-CLA suppresses TNF-${\alpha}$ production by inhibiting ROS production and NF-${\kappa}B$ activation via a $PPAR{\gamma}$-independent pathway in LPS-stimulated RAW 264.7 cells. These results suggest that t10c12-CLA can modulate TNF-${\alpha}$ production and NF-${\kappa}B$ activation through formation of ROS in RAW 264.7 macrophages.

Effects of Entrepreneurial Competencies on Entrepreneurial Satisfaction and Life Satisfaction: Moderator Effect of Person-Job Fit (창업가역량이 창업만족도와 삶의 만족도에 미치는 영향: 직무적합도의 조절효과 검증)

  • Lee, Sung Ho;Nam, Jung Min
    • Asia-Pacific Journal of Business Venturing and Entrepreneurship
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    • v.16 no.4
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    • pp.85-99
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    • 2021
  • Due to the continuous unemployment problem, the number of jobs is gradually decreasing, and entrepreneurship is emerging as an alternative. This is because, despite the government operating various start-up support programs to build a start-up-friendly culture, young entrepreneurs cannot endure the valley of death and disappear. Therefore, through this study, we intend to provide implications by analyzing the impact on Entrepreneurial satisfaction, which is essential for continuously running a business, and life satisfaction, which can act as a social awareness. This study was conducted with 573 non-wage workers who belonged to the founders among the participants of the 'College Graduation Occupational Migration Path Survey(GOMS)' survey provided by the Korea Employment Information Service. In order to analyze the relationship between entrepreneurial competency and job fit, Entrepreneurial satisfaction, and life satisfaction, the analysis was conducted using the SPSS 23.0 program. The main research results are summarized as follows. First, entrepreneurial competency has a positive effect on Entrepreneurial satisfaction and life satisfaction. Second, job fit indicates a moderating role in the relationship between entrepreneurial competency and Entrepreneurial satisfaction. Third, start-up satisfaction appears to have a partial mediating role in the relationship between entrepreneurial competency and life satisfaction. Fourth, as a result of analyzing the difference between groups according to the type of start-up(single/partnership), the group that worked together showed higher Entrepreneurial satisfaction and life satisfaction. The main implications of this study are: First, in order to increase the Entrepreneurial satisfaction and life satisfaction of university graduates who are the subject of the study, it will be necessary to design a program that can diagnose and enhance the entrepreneurial competency of students at the university level. Second, entrepreneurial competency is a basic intrinsic factor that founders must have, and it should act as an important evaluation factor when selecting founders for support programs from start-up support organizations as well as founders. Third, it is necessary to maintain mutual trust by documenting problems (positions, wages, management rights, distribution of profits, etc.) that may occur in joint ventures with objective data. Fourth, it is necessary to establish an environment in which the MZ generation, armed with the challenging spirit and creativity, can continue to take on challenges even if they fail.