• International Journal of Oral Biology
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• v.41 no.1
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• pp.1-8
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• 2016

OSCC is currently the most common malignancy of the head and neck, affecting tens of thousands of patients per year worldwide. Natural flavonoids from plants are potential sources for novel anti-cancer drugs. Icariin is the active ingredient of flavonol glycoside, which is derived from the medical plant Herba Epimedii. A metabolite of icariin, icariside II exhibits a variety of pharmacological actions, including anti-rheumatic, anti-depressant, cardiovascular protective, and immunomodulatory functions. However, the exact mechanism causing the apoptosis-inducing effect of icariside II in OSCC is still not fully understood. In the present study, we assessed the anti-cancer effect of icariside II in OSCC cell lines by measuring its effect on cell viability, cell proliferation, and mitochondria membrane potential (MMP). Icariside II treatment of OSCC cells resulted in a dose- and time-dependent decrease in cell viability. Hoechst staining indicated apoptosis in icariside II-treated HSC cells. Icariside II inhibited cell proliferation and induced apoptosis in HSC cells, with significant increases in all present parameters in HSC-4 cells. The results clearly suggested that icariside II induced apoptosis via activation of intrinsic pathways and caspase cascades in HSC-4 cell lines. The collective findings of the study suggested that Icariside II is a potential treatment for OSCC; in addition, the data could provide a basis for the development of a novel anti-cancer strategy.

• Korean Journal of Veterinary Research
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• v.49 no.1
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• pp.1-8
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• 2009

The ubiquitin-proteasome mediated protein degradation pathway plays an important role in regulating both cell proliferation and cell death. Proteasome inhibitors are well known to induce apoptosis in various human cancer cell lines. We investigated the effect of combined treatment with proteasome inhibitor and TRAIL, and a possible mechanism of the enhancing apoptosis by the both treatment, on TRAIL-resistant non-small cell lung cancer. A549 cells were exposed to the N-Acetyl-Leu-Leu-Norleu-al (ALLN) as a proteasome inhibitor and then treated with recombinant TRAIL protein. In A549 cells under proteasome inhibition conditions by pretreatment with ALLN, TRAIL treatment significantly decreased cell viability compared to that ALLN and TRAIL alone treatment. Also, the both treatment induced cell damage through DNA fragmentation and p53 expression. In addition, the combined treatment of both markedly increased caspase-8 activation, especially the exposure for 2 h, and Bax expression and induced the dissipation of mitochondrial transmembrane potential in A549 cells. Taken together, these findings showed that proteasome inhibition by ALLN enhanced TRAIL-induced apoptosis via DNA degradation by activated P53 and mitochondrial transmembrane potential loss by caspase-8 activation and bax expression. Therefore, our results suggest that proteasome inhibitor may be used a very effectively chemotherapeutic agent for the tumor treatment, especially TRAIL-resistant tumor cell.

• The Journal of Korean Medicine
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• v.23 no.1
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• pp.24-36
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• 2002

Objectives: The chemotherapeutic potential of Gagamgilgyung-tang for the treatment of human lung cancer, the antitumorigenic effects of Gagamgilgyung-tang on the proliferation and apoptosis of human lung cancer cell line A427 were investigated using molecular biological approaches, Methods: To determine Gagamgilgyung-tang concentrations which do not evoke cytotoxic damage to the cell line, cell viability was examined by MTT assay. To prove Gagamgilgyung-tang's antitumorigenic potential to human lung cancer, [3H]thymidine incorporation assay, trypan blue exclusion and Cpp32 protease activity assays and quantitative RT-PCR analysis were examined. Results: While A427 cells treated with $0.1-2.0{\mu\textrm{g}}/ml$ of Gagamgilgyung-tang showed no recognizable effect, marked reductions of cell viability were detected at concentrations over $5.0{\;}\mu\textrm{g}/ml$. DNA replication of A427 cells was inhibited by Gagamgilgyung-tang in a dose-dependent manner and Gagamgilgyung-tang induced the G1 cell cycle arrest through inhibition of DNA replication. Gagamgilgyung-tang triggered apoptotic cell death of A427 and enhanced the apoptotic sensitivity of the cells that were injured by a DNA damage-inducing chemotherapeutic drug etoposide. Gagamgilgyung-tang induces expression of growth-inhibiting genes such as p53 and p21/Wafl whereas it inhibited expression of growth-promoting genes such as c-Myc and Cyclin D1. Expression of a representative apoptosis-inducing gene Bax was also found to be induced by Gagamgilgyung-tang while apoptosis-suppressing Bcl-2 expression was not changed. Conclusions: Gagamgilgyung-tang could suppress the abnormal growth of tumor cells by suppressing the survival of genetically altered cells via induction of apoptosis. This study suggests that Gagamgilgyung-tang might have an antitumorigenic potential to human lung cancer cells, which might be associated with its growth-inhibiting and apoptosis-inducing properties.

• Journal of Periodontal and Implant Science
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• v.52 no.6
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• pp.437-454
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• 2022

Embryonic stem cells have been a popular research topic in regenerative medicine owing to their pluripotency and applicability. However, due to the difficulty in harvesting them and their low yield efficiency, advanced cell reprogramming technology has been introduced as an alternative. Dental stem cells have entered the spotlight due to their regenerative potential and their ability to be obtained from biological waste generated after dental treatment. Cell reprogramming, a process of reverting mature somatic cells into stem cells, and transdifferentiation, a direct conversion between different cell types without induction of a pluripotent state, have helped overcome the shortcomings of stem cells and raised interest in their regenerative potential. Furthermore, the potential of these cells to return to their original cell types due to their epigenetic memory has reinforced the need to control the epigenetic background for successful management of cellular differentiation. Herein, we discuss all available sources of dental stem cells, the procedures used to obtain these cells, and their ability to differentiate into the desired cells. We also introduce the concepts of cell reprogramming and transdifferentiation in terms of genetics and epigenetics, including DNA methylation, histone modification, and non-coding RNA. Finally, we discuss a novel therapeutic avenue for using dental-derived cells as stem cells, and explain cell reprogramming and transdifferentiation, which are used in regenerative medicine and tissue engineering.

• BMB Reports
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• v.57 no.4
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• pp.188-193
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• 2024

Gastric cancer (GC), a leading cause of cancer-related mortality, remains a significant challenge despite recent therapeutic advancements. In this study, we explore the potential of targeting cell surface glucose-regulated protein 94 (GRP94) with antibodies as a novel therapeutic approach for GC. Our comprehensive analysis of GRP94 expression across various cancer types, with a specific focus on GC, revealed a substantial overexpression of GRP94, highlighting its potential as a promising target. Through in vitro and in vivo efficacy assessments, as well as toxicological analyses, we found that K101.1, a fully human monoclonal antibody designed to specifically target cell surface GRP94, effectively inhibits GC growth and angiogenesis without causing in vivo toxicity. Furthermore, our findings indicate that K101.1 promotes the internalization and concurrent downregulation of cell surface GRP94 on GC cells. In conclusion, our study suggests that cell surface GRP94 may be a potential therapeutic target in GC, and that antibody-based targeting of cell surface GRP94 may be an effective strategy for inhibiting GRP94-mediated GC growth and angiogenesis.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.2
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• pp.103-109
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• 2003

The cellular mechanisms that contribute to the acceleration of atherosclerosis in diabetes are poorly understood. Therefore, the potential mechanisms involved in the diabetes-dependent increase in vascular smooth muscle cell (VSMC) proliferation was investigated. Using primary culture of VSMC from streptozotocin-induced diabetic rat aorta, cell proliferation assay showed two-fold increase in cell number accompanied with enhanced superoxide generation compared to normal VSMC, 2 days after plating. Both the increased superoxide production and cell proliferation in diabetic VSMC were significantly attenuated by not only tiron (1 mM), a superoxide scavenger, but also by diphenyleneiodonium (DPI; $10{\mu}M$), an NAD(P)H oxidase inhibitor. NAD(P)H oxidase activity in diabetic VSMC was significantly higher than that in control cell, accompanied with increased mRNA expression of p22phox, a membrane subunit of oxidase. Furthermore, inhibition of p22phox expression by transfection of antisense p22phox oligonucleotides into diabetic VSMC resulted in a decrease in superoxide production, which was accompanied by a significant inhibition of cell proliferation. Based on these results, it is suggested that diabetes-associated increase in NAD(P)H oxidase activity via enhanced expression of p22phox contributes to augmented VSMC proliferation in diabetic rats.

• KSII Transactions on Internet and Information Systems (TIIS)
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• v.10 no.5
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• pp.1976-1997
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• 2016

This paper investigates the problem of co-tier interference mitigation for dynamic small- cell networks, in which the load of each small-cell varies with the number of active associated small-cell users (SUs). Due to the fact that most small-cell base stations (SBSs) are deployed in an ad-hoc manner, the problem of reducing co-tier interference caused by dynamic loads in a distributed fashion is quite challenging. First, we propose a new distributed channel allocation method for small-cells with dynamic loads and define a dynamic interference graph. Based on this approach, we formulate the problem as a dynamic interference graph game and prove that the game is a potential game and has at least one pure strategy Nash equilibrium (NE) point. Moreover, we show that the best pure strategy NE point minimizes the expectation of the aggregate dynamic co-tier interference in the small-cell network. A distributed dynamic learning algorithm is then designed to achieve NE of the game, in which each SBS is unaware of the probability distributions of its own and other SBSs' dynamic loads. Simulation results show that the proposed approach can mitigate dynamic co-tier interference effectively and significantly outperform random channel selection.

• Journal of the Korean Ceramic Society
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• v.51 no.4
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• pp.289-294
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• 2014

The stability of a solid oxide fuel cell (SOFC) stack is strongly dependent on the magnitude and profile of the internal chemical potential of the solid electrolyte. If the internal partial pressure is too high, the electrolyte can be delaminated from the electrodes. The formation of high internal pressure is attributed to a negative cell voltage, and this phenomenon can occur in a bad cell (with higher resistance) in a stack. This fact implies that the internal chemical potential plays an important role in determining the lifetime of a stack. In the present work, we fabricate planar type anode-supported cells ($25cm^2$) with a bi-layer electrolyte (with locally increased electronic conduction at the anode side) to prevent high internal pressure, and we test the fabricated cells under a negative voltage condition. The results indicate that the addition of electronic conduction in the electrolyte can effectively depress internal pressure and improve the cell stability.

• Journal of Periodontal and Implant Science
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• v.26 no.3
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• pp.681-688
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• 1996

Periodontal regeneration requires the migration and proliferation of gingival fibroblasts and periodontal ligament cells. These cellular events are influenced and regulated by growth factors and some drugs. The purpose of this study is to examine the effect of Rhizoma coptidis and Centella asiatica extracts on human gingival fibroblasts. Gingival fibroblasts were primarily cultured from extracted premolar with non-periodontal diseases. Cells were cultured with ${\alpha}-MEM$ at $37^{\circ}C$, 5% $CO_2$, 100% humidity incubator for 2 or 3 days, as a measure of cell proliferation potential, it was examined that the DNA synthesis using $[^3H]-thyrnidine$ incorporation, the cell numbers (with or without dye), and cell viabilities. Rhizoma coptidis is increased the proliferation of gingival fibroblasts at concentration of $10^{-9}g/ml$, but Centella asiatica is decreased the proliferation at all concentrations. This study demonstrated that Rhizoma coptidis is a potential mitogen for human gingival fibroblasts in vitro, and we can expect the usefulness of this drug in periodontal regeneration.

• Natural Product Sciences
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• v.10 no.2
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• pp.74-79
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• 2004

Dietary flavonoids are currently receiving considerable attention in developing novel cancer-preventive approaches because of their potential capacities to actively induce apoptosis of cancer cells. In our previous report, a flavonoid fraction, which consisted mainly of protocatechuic acid, fustin, fisetin, sulfuretin, and butein and named RCMF (RVS chloroform-methanol fraction), was prepared from a crude acetone extract of Rhus verniciflua Stokes (RVS) that is traditionally used as food additive and herbal medicine. In this study, we evaluated the effects of the RCMF on cell proliferation and apoptosis using SV40-transformed tumorigenic hepatocytes, BNL SV A.8. Tritium uptake assay showing the proliferative capacity of the cells was strongly suppressed in the presence of RCMF. This anti-proliferative effect was further confirmed through trypan blue exclusion. RCMF-mediated suppression of cell growth was verified to be apoptotic, based on the increase in DNA fragmentation, low fluorescence intensity in nuclei after propidium iodide staining, and the appearance of DNA laddering. Collectively, this study demonstrated that RCMF can be approached as a potential agent that is capable of significantly inhibiting cell growth of hepatic cancer cells.