• Korean Journal of Plant Resources
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• v.32 no.5
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• pp.442-447
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• 2019

In this study, we evaluated the effect of Rodgersia podophylla leave extracts (RPL) on ${\beta}-catenin$ level in human cancer cells. RPL dose-dependently inhibited cell proliferation in SW480, A549, MDA-MB-231, PC-3 and AsPC-1 cells. RPL dramatically decreased ${\beta}-catenin$ protein level in all cancer cells. However, decreased level of ${\beta}-catenin$ mRNA expression was observed in A549 and AsPC-1 cells. In addition, RPL dramatically attenuated cyclin D1 mRNA expression in all cancer cells. MG132 decreased the downregulation of ${\beta}-catenin$ protein level induced by RPL in all cancer cells, while RPL-induced downregulation of ${\beta}-catenin$ was inhibited by the inhibition of $GSK-3{\beta}$ by LiCl in MDA-MB-231 cells. RPL phosphorylated ${\beta}-catenin$ and $GSK-3{\beta}$. In addition, the inhibition of $GSK-3{\beta}$ by LiCl attenuated RPL-induced ${\beta}-catenin$ phosphorylation. Based on these findings, RPL may be a potential candidate for the development of chemopreventive or therapeutic agents for human cancer.

• Korean Journal of Poultry Science
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• v.48 no.2
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• pp.81-90
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• 2021

Avian influenza viruses (AIVs) must utilize host cellular factors to complete their life cycle, and fragile X mental retardation protein (FMRP) has been reported to be a host factor promoting AIV ribonucleoprotein (vRNP) assembly and exports vRNP from the nucleus to the cytoplasm. The functional role of chicken FMRP translational regulator 1 (cFMR1) as a host factor of AIV is, however, poorly understood. In this study, we targeted the cFMR1 gene in DF1 cells using clustered regularly interspaced short palindromic repeats/Cas9-mediated genome editing to examine the functional role of cFMR1 as a host factor of AIV. We found that cFMR1 stimulated viral gene transcription during early stages of the viruses' life cycle and did not affect viral progeny production and viral polymerase activity in DF1 cells 24 hours post infection. cFMR1 overexpression did not exert significant effects on virus production, compared to the control. Therefore, unlike in mammalian systems (e.g., humans or mice), cFMR1 did not play a pivotal role in AIV but only seemed to stimulate viral proliferation during early stages of the viral life cycle. These results imply that the interplay between host factors and AIV differs between mammals and avian species, and such differences should be considered when developing anti-viral drugs for birds or establishing AIV-resistant bird models.

• Biomolecules & Therapeutics
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• v.27 no.5
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• pp.474-483
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• 2019

Vascular endothelial growth factor (VEGF) plays a pivotal role in pathologic ocular neovascularization and vascular leakage via activation of VEGF receptor 2 (VEGFR2). This study was undertaken to evaluate the therapeutic mechanisms and effects of the tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a VEGFR2 inhibitor, in the development of vascular permeability and choroidal neovascularization (CNV). In cultured human retinal microvascular endothelial cells (HRMECs), treatment with RLYE blocked VEGF-A-induced phosphorylation of VEGFR2, Akt, ERK, and endothelial nitric oxide synthase (eNOS), leading to suppression of VEGF-A-mediated hyper-production of NO. Treatment with RLYE also inhibited VEGF-A-stimulated angiogenic processes (migration, proliferation, and tube formation) and the hyperpermeability of HRMECs, in addition to attenuating VEGF-A-induced angiogenesis and vascular permeability in mice. The anti-vascular permeability activity of RLYE was correlated with enhanced stability and positioning of the junction proteins VE-cadherin, ${\beta}$-catenin, claudin-5, and ZO-1, critical components of the cortical actin ring structure and retinal endothelial barrier, at the boundary between HRMECs stimulated with VEGF-A. Furthermore, intravitreally injected RLYE bound to retinal microvascular endothelium and inhibited laser-induced CNV in mice. These findings suggest that RLYE has potential as a therapeutic drug for the treatment of CNV by preventing VEGFR2-mediated vascular leakage and angiogenesis.

• Convergence Security Journal
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• v.18 no.2
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• pp.167-177
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• 2018

Major countries, such as the U.S., UK and Germany have reformed their national intelligence systems in the face of transnational, asymmetric and comprehensive threats since September 11, 2001 and have strengthened the intelligence capacity involved in countering terrorism and WMD proliferation, right/left extremism threats. The Korean Moon Jae-in government is preparing a reform plan to eliminate illegal political intervention and abuse of power by the National Intelligence Service(NIS) and to rebuild it as an efficient national intelligence agency for national security. In discussing the reform direction of the NIS, it is necessary to discuss in detail whether adopting a separate model of intelligence agencies to restrict domestic intelligence activities of the NIS and concentrate on foreign intelligence activities or establish new domestic intelligence agencies. Second, as for the issue of transferring anti-Communism investigation authority of the NIS to the police, it needs to be carefully considered in terms of balancing the efficiency and professionalism of intelligence agency activity in the context of North Korea's continuous military provocation, covert operations and cyber threats. Third, it should strive to strengthen the control and supervision functions of the administration and the National Assembly to ensure the political neutrality of the NIS in accordance with the democratization era, to guarantee citizens' basic rights and to improve the transparency of budget execution.

• Korean Journal of Plant Resources
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• v.32 no.2
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• pp.109-115
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• 2019

In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of branches from Taxillus yadoriki parasitic to Neolitsea sericea (TN-NS-B) against human lung cancer cells, A549. TY-NS-B dose-dependently suppressed the growth of A549 cells. TY-NS-B decreased ${\beta}$-catenin protein level, but not mRNA level in A549 cells. The downregulation of ${\beta}$-catenin protein level by TY-NS-B was attenuated in the presence of MG132. Although TY-NS-B phosphorylated ${\beta}$-catenin protein, the inhibition of $GSK3{\beta}$ by LiCl did not blocked the reduction of ${\beta}$-catenin by TY-NS-B. In addition, TY-NS-B decreased ${\beta}$-catenin protein in A549 cells transfected with Flag-tagged wild type ${\beta}$-catenin or Flag-tagged S33/S37/T41 mutant ${\beta}$-catenin construct. Our results suggested that TN-NS-B may downregulate ${\beta}$-catenin protein level independent on $GSK3{\beta}$-induced ${\beta}$-catenin phosphorylation. Based on these findings, TY-NS-B may be a potential candidate for the development of chemopreventive or therapeutic agents for human lung cancer.

• 한국사회정책
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• v.20 no.2
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• pp.233-260
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• 2013

Despite various policies have been implemented to curb shadow education in Korea, it has continued to grow in recent two decades. This study investigates the expansion mechanism of shadow education focused on mobilization capabilities and market strategies of the suppliers. The success and failure of policy toward shadow education depends on how effectively it could block off the way by which the suppliers as the most important actors in politics of shadow education market mobilize consumers' anxieties. But shadow education policies have failed in two points. First, they have lacked honest intention to stop its proliferation. The Constitutional Court Decision Against Anti-Out-Of-School Classes Legislation of 2000 widened the windows of opportunity for the suppliers, and 5.31 educational reform of 1995 was neutral to their mobilization capabilities, though seemingly designed to control shadow education. This policy orientation, which reflected neoliberal Gesinnungsethik defective of Verantwortungsethik, stimulated shadow education to expand in that suppliers' mobilization capabilities were reinforced or remained intact. Second, shadow education suppliers have succeeded in mobilizing the desire and anxiety of potential consumers. To cope with government's policy including improving the qualities of public education, realignment of college entrance systems, and meeting the shadow education needs, they have developed various market strategies such as management of existing demands, creation of responsive demands, and squeezing out new demands. They have succeeded in nullifying policies by employing or mixing strategies with effect. Policy decisions in the future need to be made with reference to Verantwortungsethik, and be more cautious to socio-political contexts of Korea, to mobilization capabilities and market strategies of the suppliers in particular.

• Journal of Microbiology and Biotechnology
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• v.32 no.4
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• pp.531-540
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• 2022

Due to the high incidence of malignant melanoma, the establishment of in vitro models that recapitulate the tumor microenvironment is of great biological and clinical importance for tumor treatment and drug research. In this study, 3D printing technology was used to prepare GelMA/PEGDA composite scaffolds that mimic the microenvironment of human malignant melanoma cell (A375) growth and construct in vitro melanoma micro-models. The GelMA/PEGDA hybrid scaffold was tested by the mechanical property, cell live/dead assay, cell proliferation assay, cytoskeleton staining and drug loading assay. The growth of tumor cells in two- and three-dimensional culture systems and the anti-cancer effect of luteolin were evaluated using the live/dead staining method and the Cell Counting Kit-8 (CCK-8) method. The results showed a high aggregation of tumor cells on the 3D scaffold, which was suitable for long-term culture. Cytoskeleton staining and immunofluorescent protein staining were used to evaluate the degree of differentiation of tumor cells under 2D and 3D culture systems. The results indicated that 3D bioprinted scaffolds were more suitable for tumor cell expansion and differentiation, and the tumor cells were more aggressive. In addition, luteolin was time- and dose-dependent on tumor cells, and tumor cells in the 3D culture system were more resistant to the drug.

• BMB Reports
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• v.55 no.11
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• pp.565-570
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• 2022

Pulmonary arterial hypertension (PAH) is a progressive and devastating disease whose pathogenesis is associated with a phenotypic switch of pulmonary arterial vascular smooth muscle cells (PASMCs). Bone morphogenetic protein (BMP) signaling and potassium two pore domain channel subfamily K member 3 (KCNK3) play crucial roles in PAH pathogenesis. However, the relationship between BMP signaling and KCNK3 expression in the PASMC phenotypic switching process has not been studied. In this study, we explored the effect of BMPs on KCNK3 expression and the role of KCNK3 in the BMP-mediated PASMC phenotypic switch. Expression levels of BMP receptor 2 (BMPR2) and KCNK3 were downregulated in PASMCs of rats with PAH compared to those in normal controls, implying a possible association between BMP/BMPR2 signaling and KCNK3 expression in the pulmonary vasculature. Treatment with BMP2, BMP4, and BMP7 significantly increased KCNK3 expression in primary human PASMCs (HPASMCs). BMPR2 knockdown and treatment with Smad1/5 signaling inhibitor substantially abrogated the BMP-induced increase in KCNK3 expression, suggesting that KCNK3 expression in HPASMCs is regulated by the canonical BMP-BMPR2-Smad1/5 signaling pathway. Furthermore, KCNK3 knockdown and treatment with a KCNK3 channel blocker completely blocked BMP-mediated anti-proliferation and expression of contractile marker genes in HPAMSCs, suggesting that the expression and functional activity of KCNK3 are required for BMP-mediated acquisition of the quiescent PASMC phenotype. Overall, our findings show a crosstalk between BMP signaling and KCNK3 in regulating the PASMC phenotype, wherein BMPs upregulate KCNK3 expression and KCNK3 then mediates BMP-induced phenotypic switching of PASMCs. Our results indicate that the dysfunction and/or downregulation of BMPR2 and KCNK3 observed in PAH work together to induce aberrant changes in the PASMC phenotype, providing insights into the complex molecular pathogenesis of PAH.

• Advances in nano research
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• v.12 no.6
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• pp.639-652
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• 2022

The prolyl 3-hydroxylase family member 4 (P3H4), is associated with post-translational modification of fibrillar collagens and aberrantly activated in cancer leading to tumor progression. However, its role in clear cell renal cell carcinoma (ccRCC) is still unknown. Here we reported that P3H4 was highly expressed in renal cancer tissues and significantly positive correlated with poor prognosis. Knockdown of P3H4 inhibited the proliferation, migration and metastasis of renal cancer cells in vitro and in vivo, and also, overexpression of it enhanced the oncogenic process. Mechanistically, P3H4 depletion decreased the levels of GDF15-MMP9 axis and repressed its downstream signaling. Further functional studies revealed that inhibition of GDF15 suppressed renal cancer cell growth and GDF15 recombinant human protein (rhGDF15) supplementation effectively rescued the inhibitory effect induced by P3H4 knockdown. Moreover, decreased levels of MMP9 caused by inhibition of P3H4-GDF15 signaling constrained the expression of PD-L1 and suppression of P3H4 accordingly promoted anti-tumor immunity via stimulating the infiltration of CD4+ and CD8+ T cells in syngeneic mice model. Taken together, our findings firstly demonstrated that P3H4 promotes ccRCC progression by activating GDF15-MMP9-PD-L1 axis and targeting P3H4-GDF15-MMP9 signaling pathway can be a novel strategy of controlling ccRCC malignancy.

• Journal of Ginseng Research
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• v.48 no.1
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• pp.77-88
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• 2024

Background: Lung inflammation occurs in many lung diseases, but has limited effective therapeutics. Ginseng and its derivatives have anti-inflammatory effects, but their unstable physicochemical and metabolic properties hinder their application in the treatment. Panaxadiol (PD) is a stable saponin among ginsenosides. Inhalation administration may solve these issues, and the specific mechanism of action needs to be studied. Methods: A mouse model of lung inflammation induced by lipopolysaccharide (LPS), an in vitro macrophage inflammation model, and a coculture model of epithelial cells and macrophages were used to study the effects and mechanisms of inhalation delivery of PD. Pathology and molecular assessments were used to evaluate efficacy. Transcriptome sequencing was used to screen the mechanism and target. Finally, the efficacy and mechanism were verified in a human BALF cell model. Results: Inhaled PD reduced LPS-induced lung inflammation in mice in a dose-dependent manner, including inflammatory cell infiltration, lung tissue pathology, and inflammatory factor expression. Meanwhile, the dose of inhalation was much lower than that of intragastric administration under the same therapeutic effect, which may be related to its higher bioavailability and superior pharmacokinetic parameters. Using transcriptome analysis and verification by a coculture model of macrophage and epithelial cells, we found that PD may act by inhibiting TNFA/TNFAR and IL7/IL7R signaling to reduce macrophage inflammatory factor-induced epithelial apoptosis and promote proliferation. Conclusion: PD inhalation alleviates lung inflammation and pathology by inhibiting TNFA/TNFAR and IL7/IL7R signaling between macrophages and epithelial cells. PD may be a novel drug for the clinical treatment of lung inflammation.