• Journal of Audiology & Otology
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• v.23 no.2
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• pp.69-75
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• 2019

Background and Objectives: The antioxidant ebselen will be able to limit or prevent the ototoxicity arising from 2-hydroxypropyl-β-cyclodextrin (HPβCD). Niemann-Pick Type C (NPC) disease is a disorder of lysosomal storage manifested in sphingolipidosis. Recently, it was noted that experimental use of HPβCD could partially resolve the symptoms in both animals and human patients. Despite its desirable effect, HPβCD can induce hearing loss, which is the only major side effect noted to date. Understanding of the pathophysiology of hearing impairment after administration of HPβCD and further development of preventive methods are essential to reduce the ototoxic side effect. The mechanisms of HPβCD-induced ototoxicity remain unknown, but the resulting pathology bears some resemblance to other ototoxic agents, which involves oxidative stress pathways. To indirectly determine the involvement of oxidative stress in HPβCD-induced ototoxicity, we tested the efficacy of an antioxidant reagent, ebselen, on the extent of inner ear side effects caused by HPβCD. Materials and Methods: Ebselen was applied prior to administration of HPβCD in mice. Auditory brainstem response thresholds and otopathology were assessed one week later. Bilateral effects of the drug treatments also were examined. Results: HPβCD-alone resulted in bilateral, severe, and selective loss of outer hair cells from base to apex with an abrupt transition between lesions and intact areas. Ebselen co-treatment did not ameliorate HPβCD-induced hearing loss or alter the resulting histopathology. Conclusions: The results indirectly suggest that cochlear damage by HPβCD is unrelated to reactive oxygen species formation. However, further research into the mechanism(s) of HPβCD otopathology is necessary.

• Animal Bioscience
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• v.36 no.7
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• pp.1120-1129
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• 2023

Objective: This study aimed to determine the protective efficacy of Buddha's Temple (BT) extract against tert-butyl hydroperoxide (t-BHP)-induced oxidative stress in Gallus gallus chicken embryo fibroblast cell line (DF-1) and its effects on the cell lipid metabolism. Methods: In this experimental study, Gallus gallus DF-1 fibroblast cells were pretreated with BT 10^-7 for 24 hours, followed by their six-hour exposure to t-BHP (100 μM). Water-soluble tetrazolium salt-8 (WST-8) assays were performed, and the growth curve was computed. The intracellular gene expression changes caused by BT extract were confirmed through quantitative polymerase chain reaction (qPCR). Flow cytometry, oil red O staining experiment, and thin-layer chromatography were performed for the detection of intracellular metabolic mechanism changes. Results: The WST-8 assay results showed that the BT pretreatment of Gallus gallus DF-1 fibroblast cell increased their cell survival rate by 1.08%±0.04%, decreased the reactive oxygen species (ROS) level by 0.93%±0.12% even after exposure to oxidants, and stabilized mitochondrial activity by 1.37%±0.36%. In addition, qPCR results confirmed that the gene expression levels of tumor necrosis factor α (TNFα), TIR domain-containing adapter inducing IFN-beta (TICAM1), and glucose-regulated protein 78 (GRP78) were regulated, which contributed to cell stabilization. Thin-layer chromatography and oil red O analyses showed a clear decrease in the contents of lipid metabolites such as triacylglycerol and free fatty acids. Conclusion: In this study, we confirmed that the examined BT extract exerted selective protective effects on Gallus gallus DF-1 fibroblast cells against cell damage caused by t-BHP, which is a strong oxidative inducer. Furthermore, we established that this extract significantly reduced the intracellular ROS accumulation due to oxidative stress, which contributes to an increase in poultry production and higher incomes.

• Korean Journal of Audiology
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• v.23 no.2
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• pp.69-75
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• 2019

Background and Objectives: The antioxidant ebselen will be able to limit or prevent the ototoxicity arising from 2-hydroxypropyl-β-cyclodextrin (HPβCD). Niemann-Pick Type C (NPC) disease is a disorder of lysosomal storage manifested in sphingolipidosis. Recently, it was noted that experimental use of HPβCD could partially resolve the symptoms in both animals and human patients. Despite its desirable effect, HPβCD can induce hearing loss, which is the only major side effect noted to date. Understanding of the pathophysiology of hearing impairment after administration of HPβCD and further development of preventive methods are essential to reduce the ototoxic side effect. The mechanisms of HPβCD-induced ototoxicity remain unknown, but the resulting pathology bears some resemblance to other ototoxic agents, which involves oxidative stress pathways. To indirectly determine the involvement of oxidative stress in HPβCD-induced ototoxicity, we tested the efficacy of an antioxidant reagent, ebselen, on the extent of inner ear side effects caused by HPβCD. Materials and Methods: Ebselen was applied prior to administration of HPβCD in mice. Auditory brainstem response thresholds and otopathology were assessed one week later. Bilateral effects of the drug treatments also were examined. Results: HPβCD-alone resulted in bilateral, severe, and selective loss of outer hair cells from base to apex with an abrupt transition between lesions and intact areas. Ebselen co-treatment did not ameliorate HPβCD-induced hearing loss or alter the resulting histopathology. Conclusions: The results indirectly suggest that cochlear damage by HPβCD is unrelated to reactive oxygen species formation. However, further research into the mechanism(s) of HPβCD otopathology is necessary.

• Korean Journal of Exercise Nutrition
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• v.23 no.3
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• pp.13-21
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• 2019

[Purpose] Chronic stress is a precipitating factor for depression, whereas exercise is beneficial for both the mood and cognitive process. The current study demonstrates the anti-depressive effects of regular exercise and the mechanisms linked to hippocampal neurogenesis. [Methods] Mice were subjected to 14 consecutive days of restraint, followed by 3 weeks of treadmill running, and were then subjected to behavioral tests that included the forced swimming and Y-maze tests. Protein levels were assessed using western blot analysis and newborn cells were detected using 5-bromo-2'-deoxyuridine (BrdU). [Results] Three weeks of treadmill running ameliorated the behavioral depression caused by 14 days of continuous restraint stress. The exercise regimen enhanced BrdU-labeled cells and class III β-tubulin levels in the hippocampal dentate gyrus, as well as those of thioredoxin-1 (TRX-1) and synaptosomal β2-adrenergic receptors (β2-AR) under stress. In vitro experiments involving treatment with recombinant human TRX-1 (rhTRX-1) augmented the levels of phospho-extracellular signal-regulated kinases 1 and 2 (ERK1/2), nuclear β-catenin, and proliferating cell nuclear antigens, which were previously inhibited by U0216 and FH535 (inhibitors of ERK1/2 and β-catenin/T cell factor-mediated transcription, respectively). The hippocampal neurogenesis elicited by a 7-day exercise regimen was abolished by a selective inhibitor of β2-AR, butoxamine. [Conclusion] These results suggest that TRX-1-mediated hippocampal neurogenesis by β2-AR function is a potential mechanism underlying the psychotropic effect of exercise.

• Journal of Microbiology and Biotechnology
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• v.34 no.4
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• pp.812-827
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• 2024

Phloroglucinol (PG) is one of the abundant isomeric benzenetriols in brown algae. Due to its polyphenolic structure, PG exhibits various biological activities. However, the impact of PG on anagen signaling and oxidative stress in human dermal papilla cells (HDPCs) is unknown. In this study, we investigated the therapeutic potential of PG for improving hair loss. A non-cytotoxic concentration of PG increased anagen-inductive genes and transcriptional activities of β-Catenin. Since several anagen-inductive genes are regulated by β-Catenin, further experiments were performed to elucidate the molecular mechanism by which PG upregulates anagen signaling. Various biochemical analyses revealed that PG upregulated β-Catenin signaling without affecting the expression of Wnt. In particular, PG elevated the phosphorylation of protein kinase B (AKT), leading to an increase in the inhibitory phosphorylation of glycogen synthase kinase 3 beta (GSK3β) at serine 9. Treatment with the selective phosphoinositide 3-kinase/AKT inhibitor, LY294002, restored the increased AKT/GSK3β/β-Catenin signaling and anagen-inductive proteins induced by PG. Moreover, conditioned medium from PG-treated HDPCs promoted the proliferation and migration of human epidermal keratinocytes via the AKT signaling pathway. Subsequently, we assessed the antioxidant activities of PG. PG ameliorated the elevated oxidative stress markers and improved the decreased anagen signaling in hydrogen peroxide (H₂O₂)-induced HDPCs. The senescence-associated β-galactosidase staining assay also demonstrated that the antioxidant abilities of PG effectively mitigated H₂O₂-induced senescence. Overall, these results indicate that PG potentially enhances anagen signaling and improves oxidative stress-induced cellular damage in HDPCs. Therefore, PG can be employed as a novel therapeutic component to ameliorate hair loss symptoms.

• Information Systems Review
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• v.13 no.3
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• pp.141-163
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• 2011

The advancement of information technologies including the Internet has affected the way of social information processing as well as brought about the paradigm shift to the information society. Accordingly, it is very important to study the process of social information processing over the digital media through which social information is generated, distributed, and led to social consensus. In this study, we analyze the mechanism of social information processing, identify a process model of social consensus and institutionalization of the results, and finally propose a set of information processing characteristics on the internet media. We deploy the ethnographic approach to analyze the meaning of group behavior in the context of society to analyze two major events which happened in Korean society. The formation process of social consensus is found to consist of 5 steps: suggestion of social issues, selective reflection on public opinion, acceptance of the issues and diffusion, social consensus, and institutionalization and feedback. The key characteristics of information processing in the Internet is grouped into proactive response to an event, the changes in the role of opinion leader, the flexibility of proposal and analysis, greater scalability, relevance to consensus making, institutionalization and interaction. This study contributes to the literature by proposing a process model of social information processing which can be used as the basis for analyzing the social consensus making process from the social network perspective. In addition, this study suggests a new perspective where the utility of the Internet media can be understood from the social information processing so that other disciplines including politics, communications, and management can improve the decision making performance in utilizing the Internet media.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.2
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• pp.389-396
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• 2002

In the present work, we examined the mechanism of vasorelaxant effect of scopoletin, an active constituent of Artemisia capillaris on rat thoracic descending aortic rings. Scopoletin induced a concentration-dependent relaxation in rat thoracic descending aortic rings pre-contracted with phenylephrine (EC/sub 50/ = 238.94±37.4 μM), while it was less effective in rat thoracic descending aortic rings precontracted with high potassium solution (KCI 30 mM). Vasorelaxation by scopoletin was significantly inhibited after endothelial removal, but recovered at high concentration. Pretreatment of rat thoracic descending aortic rings with N/sup G/-nitro-L-arginine (100 μM), a nitric oxide synthase inhibitor, and atropine (1 μM), a muscarinic receptor antagonist, significantly inhibited scopoletin-induced relaxation of rat thoracic descending aortic rings. Neither indomethacin (3 μM), an inhibitor of cydooxygenase, nor propranolol (1 μM), a β -adrenoceptor antagonist, modified the effect of scopoletin. The combination of N/sup G/ -nitro-L-arginine (100 μ M) and miconazole (10 μ M), an inhibitor of cytochrome P 450, did not modify the effect of scopoletin, when compared with pretreatment with N/sup G/-nitro-L-arginine(100 μM) alone. Vasorelaxant effect of scopoletin was inverted by pretreatment with diltiazem (10 μM), a Ca/sup 2+/-channel blocker, at low concentration, while restored at high concentration. Apamin (K/sub ca/-channel blocker, 1 μM), 4-aminopyridine (4-AP, K/sub v/-channel blocker, 1 mM), and tetrodotoxin (TTX, Na/sup +/-channel blocker 1 μM) potentiated the vasorelaxant effect of scopoledn, but glibendamide (K/sub ATP/-channel blocker, 10 μM), tetraetylammonium(TEA, non-selective K-channel blocker, 10 mM) did not affect the relaxation of scopoletin. Free radical scavengers (TEMPO, catalase, mannitol) did not modify vascular tone. These results suggest that nitric oxide, Ca/sup 2+/ -channels play a role in endothelium-dependent relaxations to scopoletin in rat aortas, that apamin, 4-AP, TTX but not glibenclamide, TEA potentiated relaxation to scopoletin mediated by these channels, and that free radicals do not concern to the vasorelaxant effect of scopoletin.

• Clinical and Experimental Pediatrics
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• v.45 no.3
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• pp.354-361
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• 2002

Purpose : Selective introduction of genes conferring chemosensitivity into proliferating tumor cells may be used to treat cancer. We first investigated the bystander effect of retrovirus-mediated gene transfer of herpes simplex virus thymidine kinase(HSV-TK) gene to murine neuroblstoma cell line(neuro-2a) in vitro and in vivo. Second, we examined the mechanism and its enhancement of the bystander effect in murine neuroblastoma. Methods : To investigate the bystander effect, we studied tumor growth and survival time after HSV-TK/ganciclovir(GCV) treatment in a syngenic A/J mouse neuroblastoma model by mixing various ratios of HSV-TK-expressing neuro-2a cells with wild type neuro-2a cells followed by GCV treatment. To investigate the mechanism of the bystander effect in murine neuroblastoma, immunohistochemistry using connexin 43, CD4 and CD8-specific monoclonal antibodies was analyzed. We studied whether IL-2-secreting neuro-2a cells(neuro-2a/IL-2) would potentiate the bystander effect. Results : A strong bystander effect was observed in vitro and in vivo. The bystander effect in murine neuroblastoma was dependent on the immune response rather than connexin-mediated gap junction. Neuro-2a/IL-2 treatment enhanced the bystander effect in the HSV-TK/GCV system in murine neuroblastoma model. Conclusion : We conclude that the bystander effect in murine neuroblastoma depends on immune response and is enhanced by neuro-2a/IL-2.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.5
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• pp.555-560
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• 2008

Amino acid transporters are essential for the growth and proliferation in all living cells. Among the amino acid transporters, the system L amino acid transporters are the major nutrient transport system responsible for the $Na^+$-independent transport of neutral amino acids including several essential amino acids. The L-type amino acid transporter 1 (LAT1), an isoform of system L amino acid transporter, is highly expressed in cancer cells to support their continuous growth and proliferation. 2-Aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) is a model compound for the study of amino acid transporter as a system L selective inhibitor. We have examined the effect and mechanism of BCH on cell growth suppression in HEp2 human head and neck squamous cell carcinoma. The BCH inhibited the L-leucine transport in a concentration-dependent manner with a $IC_{50}$ value of $51.2{\pm}3.8{\mu}M$ in HEp2 cells. The growth of HEp2 cells was inhibited by BCH in the timeand concentration-dependent manners. The formation of DNA ladder was not observed with BCH treatment in the cells. Furthermore, the proteolytic processing of caspase-3 and caspase-7 in the cells were not detected by BCH treatment. These results suggest that the BCH inhibits the growth of HEp2 human head and neck squamous cell carcinoma through the intracellular depletion of neutral amino acids for cell growth without apoptotic processing.

• Proceedings of the Korean Society of Crop Science Conference
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• 2017.06a
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• pp.141-141
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• 2017

The ubiquitin-proteasome pathway is the major regulatory mechanism in a number of cellular processes for selective degradation of proteins and involves three steps: (1) ATP dependent activation of ubiquitin by E1 enzyme, (2) transfer of activated ubiquitin to E2 and (3) transfer of ubiquitin to the protein to be degraded by E3 complex. F-box proteins are subunit of SCF complex and involved in specificity for a target substrate to be degraded. F-box proteins regulate many important biological processes such as embryogenesis, floral development, plant growth and development, biotic and abiotic stress, hormonal responses and senescence. However, little is known about the F-box genes in wheat. The draft genome sequence of wheat (IWGSC Reference Sequence v1.0 assembly) used to analysis a genome-wide survey of the F-box gene family in wheat. The Hidden Markov Model (HMM) profiles of F-box (PF00646), F-box-like (PF12937), F-box-like 2 (PF13013), FBA (PF04300), FBA_1 (PF07734), FBA_2 (PF07735), FBA_3 (PF08268) and FBD (PF08387) domains were downloaded from Pfam database were searched against IWGSC Reference Sequence v1.0 assembly. RNA-seq paired-end libraries from different stages of wheat, such as stages of seedling, tillering, booting, day after flowering (DAF) 1, DAF 10, DAF 20, and DAF 30 were conducted and sequenced by Illumina HiSeq2000 for expression analysis of F-box protein genes. Basic analysis including Hisat, HTseq, DEseq, gene ontology analysis and KEGG mapping were conducted for differentially expressed gene analysis and their annotation mappings of DEGs from various stages. About 950 F-box domain proteins identified by Pfam were mapped to wheat reference genome sequence by blastX (e-value < 0.05). Among them, more than 140 putative F-box protein genes were selected by fold changes cut-offs of > 2, significance p-value < 0.01, and FDR<0.01. Expression profiling of selected F-box protein genes were shown by heatmap analysis, and average linkage and squared Euclidean distance of putative 144 F-box protein genes by expression patterns were calculated for clustering analysis. This work may provide valuable and basic information for further investigation of protein degradation mechanism by ubiquitin proteasome system using F-box proteins during wheat development stages.