• Title/Summary/Keyword: Double Mediating Effects

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Neuroprotective Effect of Chebulagic Acid via Autophagy Induction in SH-SY5Y Cells

  • Kim, Hee Ju;Kim, Joonki;Kang, Ki Sung;Lee, Keun Taik;Yang, Hyun Ok
    • Biomolecules & Therapeutics
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    • v.22 no.4
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    • pp.275-281
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    • 2014
  • Autophagy is a series of catabolic process mediating the bulk degradation of intracellular proteins and organelles through formation of a double-membrane vesicle, known as an autophagosome, and fusing with lysosome. Autophagy plays an important role of death-survival decisions in neuronal cells, which may influence to several neurodegenerative disorders including Parkinson's disease. Chebulagic acid, the major constituent of Terminalia chebula and Phyllanthus emblica, is a benzopyran tannin compound with various kinds of beneficial effects. This study was performed to investigate the autophagy enhancing effect of chebulagic acid on human neuroblastoma SH-SY5Y cell lines. We determined the effect of chebulagic acid on expression levels of autophagosome marker proteins such as, DOR/TP53INP2, Golgi-associated ATPase Enhancer of 16 kDa (GATE 16) and Light chain 3 II (LC3 II), as well as those of its upstream pathway proteins, AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and Beclin-1. All of those proteins were modulated by chebulagic acid treatment in a way of enhancing the autophagy. Additionally in our study, chebulagic acid also showed a protective effect against 1-methyl-4-phenylpyridinium ($MPP^+$) - induced cytotoxicity which mimics the pathological symptom of Parkinson's disease. This effect seems partially mediated by enhanced autophagy which increased the degradation of aggregated or misfolded proteins from cells. This study suggests that chebulagic acid is an attractive candidate as an autophagy-enhancing agent and therefore, it may provide a promising strategy to prevent or cure the diseases caused by accumulation of abnormal proteins including Parkinson's disease.

Early Activation of Apoptosis and Caspase-independent Cell Death Plays an Important Role in Mediating the Cytotoxic and Genotoxic Effects of WP 631 in Ovarian Cancer Cells

  • Gajek, Arkadiusz;Denel-Bobrowska, Marta;Rogalska, Aneta;Bukowska, Barbara;Maszewski, Janusz;Marczak, Agnieszka
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8503-8512
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    • 2016
  • The purpose of this study was to provide a detailed explanation of the mechanism of bisanthracycline, WP 631 in comparison to doxorubicin (DOX), a first generation anthracycline, currently the most widely used pharmaceutical in clinical oncology. Experiments were performed in SKOV-3 ovarian cancer cells which are otherwise resistant to standard drugs such as cis-platinum and adriamycin. As attention was focused on the ability of WP 631 to induce apoptosis, this was examined using a double staining method with Annexin V and propidium iodide probes, with measurement of the level of intracellular calcium ions and cytosolic cytochrome c. The western blotting technique was performed to confirm PARP cleavage. We also investigated the involvement of caspase activation and DNA degradation (comet assay and immunocytochemical detection of phosphorylated H2AX histones) in the development of apoptotic events. WP 631 demonstrated significantly higher effectiveness as a pro-apoptotic drug than DOX. This was evident in the higher levels of markers of apoptosis, such as the externalization of phosphatidylserine and the elevated level of cytochrome c. An extension of incubation time led to an increase in intracellular calcium levels after treatment with DOX. Lower changes in the calcium content were associated with the influence of WP 631. DOX led to the activation of all tested caspases, 8, 9 and 3, whereas WP 631 only induced an increase in caspase 8 activity after 24h of treatment and consequently led to the cleavage of PARP. The lack of active caspase 3 had no outcome on the single and double-stranded DNA breaks. The obtained results show that WP 631 was considerably more genotoxic towards the investigated cell line than DOX. This effect was especially visible after longer times of incubation. The above detailed studies indicate that WP 631 generates early apoptosis and cell death independent of caspase-3, detected at relatively late time points. The observed differences in the mechanisms of the action of WP631 and DOX suggest that this bisanthracycline can be an effective alternative in ovarian cancer treatment.

The Effects of Individuals' Perception toward Extramarital Affair on the Openness to Extramarital Sex : Focusing on Double Mediating Effects of the Acceptance toward Extramarital Relationship and Unacceptance of Spouse's Extramarital Relationship and Moderation Effect of Marital Status (불륜에 대한 인식이 혼외성관계 개방성에 미치는 영향 : 본인외도 용인과 배우자외도 불용인의 이중매개효과와 결혼상태의 조절효과분석을 중심으로)

  • Lee, Won-June;Lee, Hee-Jin
    • Journal of the Korea Convergence Society
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    • v.11 no.8
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    • pp.211-222
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    • 2020
  • This study is an empirical research based on data analysis obtained by surveying 655 adult men and women. The notable findings are as follow: First, overall, individuals' perception of extramarital affair is negative, but about 16.4% respondents have a positive perception of it. Second, the respondents have a more critical perception of their spouse's extramarital affairs compared to their own. Thirdly, the less critical perception of extramarital affair, the more acceptance of my extramarital relationship, the less tolerance of my spouse's extramarital relationship regardless marital status. Forth, while the less tolerance of spouse's extramarital relationship, the less openness to extramarital sex among unmarried group, the more acceptance of my own extramarital relationship, the more openness to extramarital sex among married group. Lastly, individuals' perception of extramarital relationship does not directly affect the openness to extramarital sex only among unmarried group, however, the correlation between the perception of extramarital affairs and the openness to extramarital sex is fully mediated by the effect of unacceptance of spouse's extramarital affairs. The moderating effect of marital status is proved.

The Effect of Job Stability on Senior Citizen's Quality of Life : Mediated Effect of Job Satisfaction (PR실무자의 직무특성이 번영에 미치는 영향 : 일의 의미와 직무열의의 이중매개효과 연구)

  • Rhee, Ji-young;Jung, Sung-cheol
    • Journal of Venture Innovation
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    • v.3 no.2
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    • pp.129-145
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    • 2020
  • The purpose of this study was to examine the effects of the job characteristics of the PR practitioner on flourishing and to identify the mediating effect of the meaning of work and job engagement. This study used a survey of 353 PR practitioners from PR firms and the hypothesis was verified by gathering the data of the job characteristics, the meaning of work, the job engagement and the flourishing by conducting hierarchical regression analysis and SPSS Process Macro bootstrapping analysis. The results showed that the job characteristics of the PR practitioner were found to influence the flourishing with the double-mediation effect, the meaning of the work and job engagement. The more PR practitioners regard their work affects their surroundings, the higher the degree of autonomy is, and the more they get feedbacks they engaged more, as they valued their job more thereby experience flourish more. Moreover, when PR practitioners valued their job more, they more engaged in their work and experience flourish. The meaning of work revealed to be the important factor to affect flourish regardless of the job characteristics and the job engagement so that gained the results that PR firms' effort to elevate the meaning of work of PR practitioners has is important. The study findings suggest that PR practitioners' flourishing is manageable in the organization by paying attention to oneself in the aspect of the organization, not leaving in individual areas. Limitaions and implications for future studies were discussed.

The Effect of Hospital Service Quality on Emotional Attachment, Perceived Value, and Customer Satisfaction (병원서비스품질이 감정적 애착과 지각된 가치 및 고객만족도에 미치는 영향)

  • Sin, Kyung-sook;An, Un-seok
    • Journal of Venture Innovation
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    • v.4 no.3
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    • pp.49-67
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    • 2021
  • This study analyzed the effects of hospital service quality, emotional attachment, and perceived value on customer satisfaction. In particular, the purpose of this study was to understand the role of emotional attachment and perceived value in the relationship between hospital service quality and customer satisfaction. For this purpose, the results of structural equation model analysis with the data collected by conducting a survey on customers visiting small and medium-sized hospitals were as follows. First, hospital service quality felt by hospital customers had a significant effect on emotional attachment and customer satisfaction, but had no significant effect on perceived value. Second, the emotional attachment felt by customers who visited the hospital had a significant effect on perceived value and customer satisfaction. Third, emotional attachment felt by customers in the relationship between hospital service quality and customer satisfaction had a significant mediating effect. Through the above results, it was confirmed that the service quality felt by customers visiting the hospital leads to attachment to the doctor's competence and medical technology competency, which leads to an increase in customer satisfaction through this attachment. The implications obtained based on these results are as follows. In order for the service quality felt by the customers who visit the hospital to lead to customer satisfaction, above all, it is important to focus on the emotional attachment they can have and find a strategy to improve the service quality. In other words, it is necessary to establish excellent medical staff and medical technology so that hospital customers can have high confidence in the competence of doctors and medical technology, and establish a public relations strategy that can effectively display these competences. Through these efforts, hospital customers will feel a strong attachment to doctors and medical technology, which will increase their satisfaction with the hospital.