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20(S)-ginsenoside Rh2 induces caspase-dependent promyelocytic leukemia-retinoic acid receptor A degradation in NB4 cells via Akt/Bax/caspase9 and TNF-α/caspase8 signaling cascades

  • Zhu, Sirui;Liu, Xiaoli;Xue, Mei;Li, Yu;Cai, Danhong;Wang, Shijun;Zhang, Liang
    • Journal of Ginseng Research
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    • v.45 no.2
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    • pp.295-304
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    • 2021
  • Background: Acute promyelocytic leukemia (APL) is a hematopoietic malignancy driven by promyelocytic leukemia-retinoic acid receptor A (PML-RARA) fusion gene. The therapeutic drugs currently used to treat APL have adverse effects. 20(S)-ginsenoside Rh2 (GRh2) is an anticancer medicine with high effectiveness and low toxicity. However, the underlying anticancer mechanisms of GRh2-induced PML-RARA degradation and apoptosis in human APL cell line (NB4 cells) remain unclear. Methods: Apoptosis-related indicators and PML-RARA expression were determined to investigate the effect of GRh2 on NB4 cells. Z-VAD-FMK, LY294002, and C 87, as inhibitors of caspase, and the phosphatidylinositol 3-kinase (PI3K) and tumor necrosis factor-α (TNF-α) pathways were used to clarify the relationship between GRh2-induced apoptosis and PML-RARA degradation. Results: GRh2 dose- and time-dependently decreased NB4 cell viability. GRh2-induced apoptosis, cell cycle arrest, and caspase3, caspase8, and caspase9 activation in NB4 cells after a 12-hour treatment. GRh2-induced apoptosis in NB4 cells was accompanied by massive production of reactive oxygen species, mitochondrial damage and upregulated Bax/Bcl-2 expression. GRh2 also induced PML/PML-RARA degradation, PML nuclear bodies formation, and activation of the downstream p53 pathway in NB4 cells. Z-VAD-FMK inhibited caspase activation and significantly reversed GRh2-induced apoptosis and PML-RARA degradation. GRh2 also upregulated TNF-α expression and inhibited Akt phosphorylation. LY294002, an inhibitor of the PI3K pathway, enhanced the antitumor effects of GRh2, and C 87, an inhibitor of the TNF-α pathway, reversed NB4 cell viability, and GRh2-mediated apoptosis in a caspase-8-dependent manner. Conclusion: GRh2 induced caspase-dependent PML-RARA degradation and apoptosis in NB4 cells via the Akt/Bax/caspase9 and TNF-α/caspase8 pathways.

Environmental Effect of the Reduced Slag in the Electric Furnace (전기로 제강 환원슬래그 혼합토의 환경적 영향)

  • Na, Hyunsu;Yoon, Yeowon;Yoon, Gillim
    • Journal of the Korean GEO-environmental Society
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    • v.12 no.7
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    • pp.23-29
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    • 2011
  • The oxidation slag has been widely used in civil engineering project, whereas the reduced slag from electric furnace has yet to be applied. Consequently in order to find out the recycling method in civil engineering field, the mineral compositions of the reduced slag were analyzed and some tests on water quality were performed to estimate the potential release of toxic compounds. Slag-soil mixtures of 0, 10, 20 and 30%(dry weight) soil were prepared in lysimeter columns and the effluents were collected with the period of one, two and four week options in closed system, respectively. The result from qualitative and quantitative analysis using X-ray Diffraction(XRD) and X-ray Fluorescence(XRF) indicates that the main mineral of the reduced slag is $Ca_2(SiO_4)$, a kind of calcium silicate. Also, the leaching medium analyzed by Inductively Coupled Plasma Optical Emission Spectroscopy(ICP-OES) showed that main heavy metals such as Al, Fe and Mn are included in the reduced slag due to the effect of steel production process. It can be seen that the leachate does not violate the regulation guide line of waste material of heavy metal. Also the pH levels were increased from pH 6.9 for 0% soil to pH 10 for 30% soil. However the influence on leachate circulation period of one through four weeks was negligible.

Role of stearyl-coenzyme A desaturase 1 in mediating the effects of palmitic acid on endoplasmic reticulum stress, inflammation, and apoptosis in goose primary hepatocytes

  • Tang, Bincheng;Qiu, Jiamin;Hu, Shenqiang;Li, Liang;Wang, Jiwen
    • Animal Bioscience
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    • v.34 no.7
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    • pp.1210-1220
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    • 2021
  • Objective: Unlike mammals, goose fatty liver shows a strong tolerance to fatty acids without obvious injury. Stearyl-coenzyme A desaturase 1 (SCD1) serves crucial role in desaturation of saturated fatty acids (SAFs), but its role in the SAFs tolerance of goose hepatocytes has not been reported. This study was conducted to explore the role of SCD1 in regulating palmitic acid (PA) tolerance of goose primary hepatocytes. Methods: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide was examined to reflect the effect of PA on hepatocytes viability, and quantitative polymerase chain reaction was used to detect the mRNA levels of several genes related to endoplasmic reticulum (ER) stress, inflammation, and apoptosis, and the role of SCD1 in PA tolerance of goose hepatocytes was explored using RNA interfere. Results: Our results indicated that goose hepatocytes exhibited a higher tolerant capacity to PA than human hepatic cell line (LO2 cells). In goose primary hepatocytes, the mRNA levels of fatty acid desaturation-related genes (SCD1 and fatty acid desaturase 2) and fatty acid elongate enzyme-related gene (elongase of very long chain fatty acids 6) were significantly upregulated with 0.6 mM PA treatment. However, in LO2 cells, expression of ER stress-related genes (x box-binding protein, binding immunoglobulin protein, and activating transcription factor 6), inflammatory response-related genes (interleukin-6 [IL-6], interleukin-1β [IL-1β], and interferon-γ) and apoptosis-related genes (bcl-2-associated X protein, b-cell lymphoma 2, Caspase-3, and Caspase-9) was significantly enhanced with 0.6 mM PA treatment. Additionally, small interfering RNA (siRNA) mediated downregulation of SCD1 significantly reduced the PA tolerance of goose primary hepatocytes under the treatment of 0.6 mM PA; meanwhile, the mRNA levels of inflammatory-related genes (IL-6 and IL-1β) and several key genes involved in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), forkhead box O1 (FoxO1), mammalian target of rapamycin and AMPK pathways (AKT1, AKT2, FoxO1, and sirtuin 1), as well as the protein expression of cytochrome C and the apoptosis rate were upregulated. Conclusion: In conclusion, our data suggested that SCD1 was involved in enhancing the PA tolerance of goose primary hepatocytes by regulating inflammation- and apoptosis-related genes expression.

Butyrate Ameliorates Lipopolysaccharide-induced Myopathy through Inhibition of JNK Pathway and Improvement of Mitochondrial Function in C2C12 Cells (C2C12 세포에서 lipopolysaccharide에 의해 유도된 근육위축증에 대한 butyrate의 개선효과: JNK 신호전달 억제와 미토콘드리아의 기능 개선)

  • Pramod, Bahadur KC;Kang, Bong Seok;Jeoung, Nam Ho
    • Journal of Life Science
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    • v.31 no.5
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    • pp.464-474
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    • 2021
  • Inflammation induced by metabolic syndromes, cancers, injuries, and sepsis can alter cellular metabolism by reducing mitochondrial function via oxidative stress, thereby resulting in neuropathy and muscle atrophy. In this study, we investigated whether butyrate, a short chain fatty acid produced by gut microbiota, could prevent mitochondrial dysfunction and muscle atrophy induced by lipopolysaccharide (LPS) in the C2C12 cell line. LPS-activated MAPK signaling pathways increased the levels of the mitochondrial fission signal, p-DRP1 (Ser616), and the muscle atrophy marker, atrogin 1. Interestingly, butyrate significantly inhibited the phosphorylation of JNK and p38 and reduced the atrogin 1 level in LPS-treated C2C12 cells while increasing the phosphorylation of DRP1 (Ser637) and levels of mitofusin2, which are both mitochondrial fusion markers. Next, we investigated the effect of MAPK inhibitors, finding that butyrate had the same effect as JNK inhibition in C2C12 cells. Also, butyrate inhibited the LPS-induced expression of pyruvate dehydrogenase kinase 4 (PDK4), resulting in decreased PDHE1α phosphorylation and lactate production, suggesting that butyrate shifted glucose metabolism from aerobic glycolysis to oxidative phosphorylation. Finally, we found that these effects of butyrate on LPS-induced mitochondrial dysfunction were caused by its antioxidant effects. Thus, our findings demonstrate that butyrate prevents LPS-induced muscle atrophy by improving mitochondrial dynamics and metabolic stress via the inhibition of JNK phosphorylation. Consequently, butyrate could be used to improve LPS-induced mitochondrial dysfunction and myopathy in sepsis.

Growth factors improve the proliferation of Jeju black pig muscle cells by regulating myogenic differentiation 1 and growth-related genes

  • Park, Jinryong;Lee, Jeongeun;Song, Ki-Duk;Kim, Sung-Jo;Kim, Dae Cheol;Lee, Sang Cheol;Son, Young June;Choi, Hyun Woo;Shim, Kwanseob
    • Animal Bioscience
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    • v.34 no.8
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    • pp.1392-1402
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    • 2021
  • Objective: The growth rate of pigs is related to differentiation and proliferation of muscle cells, which are regulated by growth factors and expression of growth-related genes. Thus, the objective of this study was to establish optimal culture conditions for Jeju black pig (JBP) muscle cells and determine the relationship of various factors involved in muscle growth with the proliferation of JBP muscle cells. Methods: Muscles were taken from the femur skeletal muscle of JBP embryos. After isolation of the muscle cells, cells were cultured in a 6-well plate under four different culture conditions to optimize culture conditions for JBP muscle cells. To analyze proliferation rate of JBP muscle cells, these muscle cells were seeded into 6-well plates at a density of 1.5×105 cells per well and cultured for 3 days. Western blot and quantitative real-time polymerase chain reaction were applied to verify the myogenic differentiation 1 (MyoD) expression and growth-related gene expression in JBP muscle cells, respectively. Results: We established a muscle cell line from JBP embryos and optimized its culture conditions. These muscle cells were positive for MyoD, but not for paired box 7. The proliferation rate of these muscle cells was significantly higher in a culture medium containing bFGF and epidermal growth factor + basic fibroblast growth factor (EGF+bFGF) than that without a growth factor or containing EGF alone. Treatment with EGF and bFGF significantly induced the expression of MyoD protein, an important transcription factor in muscle cells. Moreover, we checked the changes of expression of growth-related genes in JBP muscle cells by presence or absence of growth factors. Expression level of collagen type XXI alpha 1 gene was changed only when EGF and bFGF were added together to culture media for JBP muscle cells. Conclusion: Concurrent use of EGF and bFGF increased the expression of MyoD protein, thus regulating the proliferation of JBP muscle cells and the expression of growth-related genes.

The impact of Covid-19 on the Performing Arts Sector and the responses needed (코로나19로 본 공연예술계 충격과 그 대응 방안)

  • Lee, Soo-Young
    • Journal of Digital Convergence
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    • v.19 no.3
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    • pp.453-463
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    • 2021
  • The purpose of this study is to establish the most severe impacts of Covid-19 in the field of the performing arts and to explore countermeasures taken both at home and abroad. This study has been conducted through literature surveys. The conclusion is as follows. First, since the outbreak of Covid-19, theater venues around the world have actively taken part in uploading recorded performances to streaming services. Secondly, these performance visualizings are generally considered as being complimentary goods rather than a substitute for live performance. Thirdly, although more audiences are tuning into watch on-line performances, consumption is concentrated on a few theaters which have a worldwide reputation and a broad range of content. Fourthly, to tackle the impact that Covid-19, the UK government announced a series of job protection schemes in the field of the Arts. In addition, Arts Council England prepared an emergency response package. In Korea, some countermeasures such as government support for artists and cultural establishments have also been implemented. Lastly, some suggestions for the sector. I conclude that there is an need for domestic companies to secure core contents of significant quality and to make strategic alliances with leading overseas performance companies so that they may cooperate together.

Analysis of the Fashion Customization Platform Design Cases (패션 커스터마이징 플랫폼 디자인 사례분석 연구)

  • Jeong, Je-Yoon;Lee, Saem;Nam, Won-Suk
    • Journal of the Korea Convergence Society
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    • v.12 no.8
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    • pp.23-30
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    • 2021
  • Various customizing services are also being introduced in the fashion industry in line with the diversification of consumer tastes and the demand for small production of multiple varieties. However, barriers to entry are high for consumers who are not customized, and various functions are rather complicated. This study selected the three platforms that provide the most similar services to Marple, the No. 1 fashion platform sales, as comparative models and used them as a basic study for web-based fashion customization platform design through case analysis. As a research method, theoretical examinations were conducted through literature surveys, followed by web analysis based on layout, menu, color, icon, and interaction. The study found that the placement of options, the composition of menu windows, the number of point colors, and the use of icons without functions of metaphores hindered the use of customizing platforms. This work proposes a solution, and aims to contribute to increasing the usability of future customizing web by comprehensively analyzing the visual shaping elements of web platform design.

A Study on the Flower Design Based on Storytelling : Focus on the Funeral Flower Design (스토리텔링을 적용한 화훼디자인에 관한 연구 -장례 화훼디자인을 중심으로-)

  • Lee, Seung Beom
    • Journal of the Korean Society of Floral Art and Design
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    • no.42
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    • pp.3-21
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    • 2020
  • In this paper, the funeral was defined as a culture of death and, on the most important ideological basis, the biological death was not recognized as the end of the world, but as a starting point for another life. Various funeral cultures were investigated and the funeral floral design was analyzed through the case. Based on this, it was concluded that Korea's funeral floral design was an impediment to the development of funeral floral design, similar to the use of limited materials. Storytelling, a communicative concept through the exchange of emotions and opinions, rather than unilaterally conveying a message as an answer, is one of the most effective marketing strategies in the emotional consumption era. Based on this, the target person was selected to analyze life and draw suggestions from his life. Accordingly, the production of the work was attempted by applying storytelling to the funeral floral design. The painting design applied to storytelling expressed the symbol and meaning of the painting design material, and the color and form of the floral design in various forms and colors of pastel line, which are based on peach color that symbolizes the deceased, in a departure from the traditional funeral painting design with the solemn atmosphere of the geometric design centered on the white chrysanthemum material.

Anti-oxidant and anti-inflammatory activities of the various kinds of herbal tea

  • Lee, Jin Wook;Eo, Hyun Ji;Park, Gwang Hun;Song, Hun Min;Woo, So Hee;Kim, Mi Kyoung;Eom, Jung Hye;Lee, Man Hyo;Lee, Jeong Rak;Koo, Jin Suk;Jeong, Jin Boo
    • The Korea Journal of Herbology
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    • v.29 no.2
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    • pp.1-6
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    • 2014
  • Objectives : Reactive oxygen species (ROS) are involved in a wide spectrum of diseases including chronic inflammation and cancer. In this study, we investigated the antioxidant activities and anti-inflammatory effects of the extracts from the herbal teas such as Lonicera japonica Thunberg (L. japonica), Chrysanthemum morifolium Ramat (C. morifolium), Mentha arvensis L. (M. arvensis), and P.rhizoma. Methods : Anti-oxidant activity was evaluated using DPPH radical scavenging assay and $Fe^{2+}$ chelating assay. And DNA cleavage assay was performed to evaluate an anti-oxidative effect. Anti-inflammatory effect was performed using NO generation assay and western blot in LPS-stimulated RAW264.7 cell line. Results : L. japonica scavenged DPPH radical by 9.8% at 12.5 ${\mu}g/ml$, 24.8% at 25 ${\mu}g/ml$, 34.3% at 50 ${\mu}g/ml$, 61.1% at 100 ${\mu}g/ml$ and 75.8% at 200 ${\mu}g/ml$, respectively. In addition, C. morifolium and M. arvensis removed DPPH radical by 15.6% and 10.4% at 12.5 ${\mu}g/ml$, 34.8% and 22.8% at 25 ${\mu}g/ml$, 66.9% and 43.3% at 50 ${\mu}g/ml$, 87.4% and 69.1% at 100 ${\mu}g/ml$, and 92.1% and 73.2% at 200 ${\mu}g/ml$, respectively. However, P. rhizoma did not affect on DPPH radical scavenging. The $Fe^{2+}$ chelating activity was highest in L. japonica, but lowest in P. rhizoma among the herbal teas. In addition, the extracts from L. japonica, C. morifolium and M. arvensis inhibited oxidative DNA damage via its anti-oxidant activity. In anti-inflammatory effect, the extracts from C. morifolium inhibited NO production. In addition, it suppressed the $NF-{\kappa}B$ signaling pathway in LPS-stimulated RAW 264.7 cells. Conclusions : Together, this study indicates that L. japonica, M. arvensis and C. morifolium possess the protective effect against the oxidative DNA damage. Furthermore, C. morifolium exerts an anti-inflammatory effect.

Application of Primary Rat Corneal Epithelial Cells to Evaluate Toxicity of Particulate Matter 2.5 to the Eyes (눈에 대한 미세먼지의 독성 평가를 위한 쥐 각막 상피 세포의 적용)

  • Kim, Da Hye;Hwangbo, Hyun;Lee, Hyesook;Cheong, Jaehun;Choi, Yung Hyun
    • Journal of Life Science
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    • v.32 no.9
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    • pp.712-720
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    • 2022
  • The purpose of this study was to investigate the efficacy of rat corneal-derived epithelial cells as an in vitro model to evaluate the harmfulness of the cornea caused by particulate matter 2.5 (PM2.5). To establish an experimental model for the effect of PM2.5 on corneal epithelial cells, it was confirmed that primary cultured cells isolated from rat eyes were corneal epithelial cells through pan-cytokeratin staining. Our results showed that PM2.5 treatment reduced cell viability of primary rat corneal epithelial (RCE) cells, which was associated with the induction of apoptosis. PM2.5 treatment also increased the generation of reactive oxygen species due to mitochondrial dysfunction. In addition, the production of nitric oxide and inflammatory cytokines was increased in PM2.5-treated RCE cells. Furthermore, through heatmap analysis showing various expression profiling between PM2.5-exposed and unexposed RCE cells, we proposed five genes, including BLNK, IL-1RA, Itga2b, ABCb1a and Ptgs2, as potential targets for clinical treatment of PM-related ocular diseases. These findings indicate that the primary RCE cell line is a useful in vitro model system for the study of PM2.5-mediated pathological mechanisms and that PM2.5-induced oxidative and inflammatory responses are key factors in PM2.5-induced ocular surface disorders.