• The Korean Journal of Physiology and Pharmacology
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• v.27 no.6
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• pp.521-531
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• 2023

Transmembrane protein TMEM16A, which encodes calcium-activated chloride channel has been implicated in tumorigenesis. Overexpression of TMEM16A is associated with poor prognosis and low overall survival in multiple cancers including lung adenocarcinoma, making it a promising biomarker and therapeutic target. In this study, three structure-related sesquiterpene lactones (mecheliolide, costunolide and dehydrocostus lactone) were extracted from the traditional Chinese medicine Aucklandiae Radix and identified as novel TMEM16A inhibitors with comparable inhibitory effects. Their effects on the proliferation and migration of lung adenocarcinoma cells were examined. Whole-cell patch clamp experiments showed that these sesquiterpene lactones potently inhibited recombinant TMEM16A currents in a concentration-dependent manner. The half-maximal concentration (IC50) values for three tested sesquiterpene lactones were 29.9 ± 1.1 µM, 19.7 ± 0.4 µM, and 24.5 ± 2.1 µM, while the maximal effect (E_max) values were 100.0% ± 2.8%, 85.8% ± 0.9%, and 88.3% ± 4.6%, respectively. These sesquiterpene lactones also significantly inhibited the endogenous TMEM16A currents and proliferation, and migration of LA795 lung cancer cells. These results demonstrate that mecheliolide, costunolide and dehydrocostus lactone are novel TMEM16A inhibitors and potential candidates for lung adenocarcinoma therapy.

• Journal of Service Research and Studies
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• v.13 no.4
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• pp.24-46
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• 2023

This study sought to examine how internal market orientation of service organizations affects the service providers' adaptive service behavior and to determine what psychological processes go through for this purpose. To achieve this purpose, based on previous research, a research model was set up to predict that internal market orientation of service organizations will increase service providers' adaptive service behavior by continuously mediating the psychological processes of person-environment fit and work engagement. To test the hypothesis, a survey was conducted and data were collected from nutritionists at consignment catering companies located in Busan and Gyeongnam. As a result of testing the hypotheses proposed in this study's research model, internal market orientation increased person-job fit and person-organization fit, which are key elements of person-environment fit. And, it was confirmed that person-job fit and person-organization fit have a positive effect on work engagement. Additionally, work engagement improved service providers' adaptive service behavior. Lastly, this study confirmed that the influence of internal market orientation on adaptive service behavior is continuously mediated by person-environment fit and job enthusiasm.

• Asia-Pacific Journal of Business Venturing and Entrepreneurship
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• v.17 no.6
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• pp.159-174
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• 2022

Entrepreneurs should continuously invest resource and capital for a long time to get tangible business results. In order to be successful, despite difficulties, it is essential for entrepreneurs to continue entrepreneurial businesses without giving up too early. Thus, it can be said that organizational commitment of entrepreneurs is essential for success. According to previous studies, the organizational commitment of entrepreneurs has a significant effect on organizing, establishments of new firms and new product developments. The purpose of this article is to examine the relationships among learning orientation, innovativeness and organizational commitment of entrepreneurs. Especially, we focus on the mediating effect of innovativeness in the relationship between learning orientation and organizational commitment and the moderating effect of career relevance among the relationships. Based on empirical analysis, we reported the following results. First, learning orientation, innovativeness and career relevance of entrepreneurs had significant positive effects on organizational commitment. Second, it was found that innovativeness of entrepreneurs has a partial mediating effect on the relationship between learning orientation and organizational commitment. Third, using Baron & Kenny's hierarchical multiple regression analysis, we examined the moderating effect of career relevance among the relationships of learning orientation, innovativeness and organizational commitment. Third, because the interaction term was found to be positively significant, it was concluded there is a moderating effect of career relevance between learning orientation and innovativeness. This means, when career relevance was higher than average, the influence of learning orientation on innovation increases even more. Fourth, it was also found there is a moderating effect of career relevance between learning orientation and organizational commitment. However, the results of the mediated moderating effect analysis showed the moderating effect of career relevance between learning orientation and organization commitment is an indirect effect of moderating effect of career relevance between learning orientation and innovativeness mediated by innovativeness.

• The Journal of the Korea Contents Association
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• v.21 no.5
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• pp.446-464
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• 2021

The purpose of this study is to verify the multi-mediated effects of human rights sensitivity and peer-coordination in the relationship between teenagers' school violence experience and cyberbullying in order to find alternatives to prevent cyberbullying as teenagers increase their use of smartphones. In order to achieve this research goal, four middle schools were selected by the education office located in downtown Busan and analyzed on 908 middle school students. The results of the study are as follows. First, school violence experiences have been shown to affect cyberbullying. Second, the experience of abuse and neglect during school violence affected human rights sensitivity, but the experience of damage did not affect human rights sensitivity. Third, among school violence experiences, the experience of damage and abuse influenced peer co-operation, but the experience of sitting on the sidelines did not affect peer co-operation. Fourth, human rights sensitivity affected cyberbullying. Fifth, peer groupings affected cyberbullying. Sixth, human rights sensitivity influenced peer-reaction. Seventh, among human rights sensitivities, bystander experience and cyberbullying were found to be mediating bystander experience and cyberbullying, but the damage experience and abuse experience did not have a mediating effect in human rights sensitization and cyberbullying. Eighth, peer cooperation was found to be mediating cyberbullying, but there was no mediating effect between on-the- sidelines experience and cyberbullying. Ninth, human rights sensitivity and peer creation are shown to mediate the relationship between on-the- sidelines experience and cyberbullying sequentially. However, human rights sensitivity and peer creation did not mediate cyberbullying sequentially between the experience of damage and the experience of perpetration. The implications of this study were to verify the effects of teenagers' school violence damage experience, abuse experience, and bystander experience on cyberbullying, and multiple interventions of human rights sensitivity and peer group.

• Journal of Ginseng Research
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• v.32 no.1
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• pp.39-47
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• 2008

UV irradiation causes skin-aging involving coarse wrinkles, thickening, dyspigmentation, and rough skin surface. These phenomena in complex skin tissue is controlled with receptor of cell surface growth factor and cytokine receptors. The activation of receptors induces multiple downstream signaling pathways including expression of MMPs (matrix metalloproteinases). This study was aimed to elucidate the mechanism for anti-wrinkle activity of Korean red ginseng, Torilis fructus and Corni fructus mixture (KTNG0345). In this animal study, we have investigated decreasing effects of Korean red ginseng mixture on MMP-3 synthesis through diminishing $TNF-{\alpha}$ signaling that express MMP-1, -3, and -9. c-Jun and c-fos as a component of transcription factor AP-1 (activator protein-1) were analyzed the expression level using real time PCR and western blotting. c-Jun was decreased dose dependent manner both gene and protein level where as cfos was not changed. In upstream, JNK and PAK was not changed, but p38 was decreased in down stream. MMP-3, final product in this pathway was significantly decreased in dose dependent manner. These results suggest that Korean red ginseng mixture have a anti-wrinkle activity through $TNF-{\alpha}$ mediated MMPs expression pathway.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.4
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• pp.231-238
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• 2005

Neuronal apoptotic events, which result in cell death, are occurred in hypoxic/ischemic conditions. Estradiol is a female sex hormone with steroid structure known to provide neuroprotection through multiple mechanisms in the central nervous system. This study was aimed to investigate the signal transduction pathway of $CoCl_2$-induced neuronal cell death and the inhibitory effects of estradiol. Administration of $CoCl_2$ decreased cell viability in both a dose- and time-dependent manner in PC12 cells. $CoCl_2$-induced cell death produced genomic DNA fragmentation and morphologic changes such as cell shrinkage and condensed nuclei. It was found that $CoCl_2$-treated cells increased the reactive oxygen species (ROS) as well as caspase-8, -9 and -3 activities. However, pretreatment with estradiol before exposure to $CoCl_2$ prevented the reduction in cell viability reduction and attenuated DNA fragmentation and morphologic changes caused by $CoCl_2$. Furthermore, the $CoCl_2$-induced increases of ROS levels and caspases activities were attenuated by estradiol. Gene expression analysis revealed that estradiol blocked the underexpression of the Bcl-2 and ameliorated the increase in the release of cytochrome c from mitochondria into cytoplasm and Fas-ligand (Fas-L) upregulated by $CoCl_2$. These results suggest that $CoCl_2$ induce apoptosis in PC12 cells through both mitochondria- and death receptor-mediated cell death pathway. Estradiol was found to have a neuroprotective effect against $CoCl_2$-induced apoptosis through the inhibition of ROS production and by modulating apoptotic effectors associated with the mitochondria- and death-dependent pathway in PC12 cells.

• Journal of Life Science
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• v.25 no.9
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• pp.984-992
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• 2015

Sanguinarine is a benzophenanthridine alkaloid originally isolated from the roots of Sanguinaria canadensis. It has multiple biological activities (e.g., antioxidant and antiproliferative) and immune-enhancing potential. In this study, we explored the proapoptotic properties and modes of action of sanguinarine in human hepatocellular carcinoma HepG2 cells. Our results revealed that sanguinarine inhibited HepG2 cell growth and induced apoptosis in a dose-dependent manner. The induction of apoptosis by sanguinarine was associated with the up-regulation of Fas and Bax, the release of cytochrome c from the mitochondria to the cytosol, and the loss of the mitochondrial membrane potential. In addition, sanguinarine activated caspase-9 and -8, initiator caspases of the intrinsic and death extrinsic pathways, respectively, and caspase-3, accompanied by proteolytic degradation of poly (ADP-ribose) polymerase. Sanguinarine also triggered the generation of reactive oxygen species (ROS). The elimination of ROS by N-acetylcysteine reversed sanguinarine-induced apoptosis. Furthermore, sanguinarine induced the dephosphorylation of Akt and the phosphorylation of mitogen-activated protein kinases, including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38. The growth inhibition was enhanced by the combined treatment of sanguinarine with a phosphatidylinositol 3'-kinase (PI3K) inhibitor and an ERK inhibitor but not JNK and p38 inhibitors. Overall, our data indicate that the proapoptotic effects of sanguinarine in HepG2 cells depend on ROS production and the activation of both intrinsic and extrinsic signaling pathways, which is mediated by blocking PI3K/Akt and activating the ERK pathway. Thus, our data suggest that sanguinarine may be a natural compound with potential for use as an antitumor agent in liver cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.1
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• pp.21-28
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• 2010

Phenolic compounds affect intracellular free $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) signaling. The study examined whether the simple phenolic compound octyl gallate affects ATP-induced $Ca^{2+}$ signaling in PC12 cells using fura-2-based digital $Ca^{2+}$ imaging and whole-cell patch clamping. Treatment with ATP ($100\;{\mu}M$) for 90 s induced increases in $[Ca^{2+}]_i$ in PC12 cells. Pretreatment with octyl gallate (100 nM to $20\;{\mu}M$) for 10 min inhibited the ATP-induced $[Ca^{2+}]_i$ response in a concentration-dependent manner ($IC_{50}=2.84\;{\mu}M$). Treatment with octyl gallate ($3\;{\mu}M$) for 10 min significantly inhibited the ATP-induced response following the removal of extracellular $Ca^{2+}$ with nominally $Ca^{2+}$-free HEPES HBSS or depletion of intracellular $Ca^{2+}$ stores with thapsigargin ($1\;{\mu}M$). Treatment for 10 min with the L-type $Ca^{2+}$ channel antagonist nimodipine ($1\;{\mu}M$) significantly inhibited the ATP-induced $[Ca^{2+}]_i$ increase, and treatment with octyl gallate further inhibited the ATP-induced response. Treatment with octyl gallate significantly inhibited the $[Ca^{2+}]_i$ increase induced by 50 mM KCI. Pretreatment with protein kinase C inhibitors staurosporin (100 nM) and GF109203X (300 nM), or the tyrosine kinase inhibitor genistein ($50\;{\mu}M$) did not significantly affect the inhibitory effects of octyl gallate on the ATP-induced response. Treatment with octyl gallate markedly inhibited the ATP-induced currents. Therefore, we conclude that octyl gallate inhibits ATP-induced $[Ca^{2+}]_i$ increase in PC12 cells by inhibiting both non-selective P2X receptor-mediated influx of $Ca^{2+}$ from extracellular space and P2Y receptor-induced release of $Ca^{2+}$ from intracellular stores in protein kinase-independent manner. In addition, octyl gallate inhibits the ATP-induced $Ca^{2+}$ responses by inhibiting the secondary activation of voltage-gated $Ca^{2+}$ channels.

• Journal of Korea Multimedia Society
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• v.17 no.2
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• pp.180-190
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• 2014

Social network services are increasingly being used in organizational settings to improve relationships among employees and enhance prospects for information exchange and cooperative work. Social Networking Service(SNS) has deeply penetrated organizational job settings, influencing multiple aspects of employee's life. This study is designed to explore the impact of SNS engagement on the job performance mediated as team cooperation and decision making quality effects. Data were collected from 146 employees who use organizational SNS in there company. Factor analysis and structural equation method are employed. Results from a survey accompanied by the substantial impacts of organizational employee's social networking engagement on social learning processes and outcomes. SNS engagement not only directly influences organizational employee's job performance, but also helps their team cooperation and decision making quality from others and adapt to organizational culture, both of which play prominent roles in improving their job performance.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.19 no.4
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• pp.211-220
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• 2018

This study was conducted to identify the mediating effects of the therapeutic relationship with mental health professionals between empowerment and recovery in mental illness. The participants were 168 adults in two community mental health centers and three rehabilitation centers in Jeonbuk. The data were collected by structured questionnaires from April 15 to April 30, 2015 and analyzed using descriptive statistics, Pearson's correlation coefficient, and multiple regression analysis with the SPSS 19.0 statistical program. The mean score of empowerment for mental illness, recovery and therapeutic relationship were $60.4{\pm}10.85$, $101.8{\pm}20.70$ and $74.5{\pm}14.30$, respectively. There were significantly positive correlations between recovery in empowerment and therapeutic relationship (r=0.33, p<0.001), as well as empowerment and recovery (r=0.51, p<0.001), while there were significantly positive correlations between therapeutic relationship and recovery (r=0.55, p<0.001). Therapeutic relationship had a partial mediated effect between empowerment and recovery, which was found to be significant by the Sobel test (z=3.706, p<0.001). The results of this study can be used as basic data for development of a practical recovery-enhancing program to promote therapeutic relationships and improve empowerment in relation to therapist of the mentally disabled.