• Title/Summary/Keyword: Down-regulated

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CLK3 is a Novel Negative Regulator of NF-κB Signaling (NF-κB 신호경로에서 CLK3의 새로운 음성 조절자로서의 기능)

  • Byeol-Eun, Jeon;Chan-Seong, Kwon;Ji-Eun, Lee;Ye-Lin, Woo;Sang-Woo, Kim
    • Journal of Life Science
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    • v.32 no.11
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    • pp.833-840
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    • 2022
  • Chronic inflammation has been shown to be closely associated with tumor development and progression. Nuclear factor kappa B (NF-κB) is composed of a family of five transcription factors. NF-κB signaling plays a crucial role in the inflammatory response and is often found to be dysregulated in various types of cancer, making it an attractive target in cancer therapeutics. In this study, CDC-like kinase 3 (CLK3) was identified as a novel kinase that regulates the NF-κB signaling pathway. Our data demonstrate that CLK3 inhibits the canonical and non-canonical NF-κB pathways. Luciferase assays following the transient or stable expression of CLK3 indicated that this kinase inhibited NF-κB activation mediated by Tumor necrosis factor-alpha (TNFα) and Phorbol 12-myristate 13-acetate (PMA), which are known to activate NF-κB signaling via the canonical pathway. Consistent with data on the ectopic expression of CLK3, CLK3 knockdown using shRNA constructs increased NF-κB activity 1.5-fold upon stimulation with TNFα in HEK293 cells compared with the control cells. Additionally, overexpression of CLK3 suppressed the activation of this signaling pathway induced by NF-κB-inducing kinase (NIK) or CD40, which are well-established activators of the non-canonical pathway. To further examine the negative impact of CLK3 on NF-κB signaling, we performed Western blotting following the TNFα treatment to directly identify the molecular components of the NF-κB pathway that are affected by this kinase. Our results revealed that CLK3 mitigated the phosphorylation/activation of transforming growth factor-α-activated kinase 1 (TAK1), inhibitor of NF-κB kinase alpha/beta (IKKα/α), NF-κB p65 (RelA), NF-κB inhibitor alpha (IκBα), and Extracellular signal-regulated kinase 1/2-Mitogen-activated protein kinase (ERK1/2-MAPK), suggesting that CLK3 inhibits both the NF-κB and MAPK signaling activated by TNFα exposure. Further studies are required to elucidate the mechanism by which CLK3 inhibits the canonical and non-canonical NF-κB pathways. Collectively, these findings reveal CLK3 as a novel negative regulator of NF-κB signaling.

Whitening activity of Ficus carica L. fruits extract through inhibition of tyrosinase and MITF expression (무화과(Ficus carica L.) 열매 추출물의 tyrosinase 및 MITF 발현 억제를 통한 미백 활성)

  • Min Ji Kim;Si Eun Park;Geun soo Lee;Jin Hwa Kim;Sunwoo Kwon;Hyung Seo Hwang
    • Journal of Applied Biological Chemistry
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    • v.66
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    • pp.204-212
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    • 2023
  • Whitening is inhibitory activity of the melanin synthesis of melanocytes. Recently, whitening materials have been developed on natural materials because of its side effects on skin. Figs (Ficus Carica L.) is a fruit belonging to the Moraceae family and whitening activity was reported in focusing on the fig's stem and leaf components, but whitening activity of the figs fruit was not known. Thus, in this study, we tried to observe its anti-melanogenesis as well as antioxidant and anti-inflammation. The radical scavenging activity of figs fruits extract (FFE) was observed as the level of 34.52±1.98%/60.71±1.26% compared to the control in the its maximum concentration in the DPPH/ABTS assay. Cytotoxicity of FFE was observed at 10% concentration by CCK8 assay, so the maximum concentration was set at 5% and applied to all experiments. FFE concentration dependently decreased NO production associated with inducible nitric oxide synthase, cyclooxygenase-2, interleukin-6 and tumor necrosis factor-α gene expression, these strongly suggesting anti-inflammatory activity. In melanin contents assay, FFE significantly down-regulated melanin production in α-MSH-stimulated B16F10 cell as well as tyrosinase inhibition in vitro. In addition, FFE decreased the Microphthalmia-associated transcription factor (MITF) mRNA expression about 94.34% compared to the α-MSH treatment group in RT-PCR. Finally, FFE significantly reduced the MITF, cAMP response element-binding protein and tyrosinase protein expression in the α-MSH stimulated B16F10 cell. Through these results, we found that FFE can not only directly inhibit tyrosinase enzyme activity but also suppress melanogenesis through regulation of MITF gene expression in α-MSH signal transduction.

Characteristics of Spatio-temporal Variation of the Water Quality in the Lower Keum River (금강 하류역에서 수질의 시공간적 변화특성)

  • YANG Han-Soeb;KIM Seong-Soo
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.23 no.3
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    • pp.225-237
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    • 1990
  • Various chemical constituents were measured from April to August 1988 at the down-ward 20 stations of Keum River, which is located in the Midwest of Korea, to understand the characteristics of water quality with respect to spatio-temporal variations of each constituent. The 24-hrs continuous measurements with 2-hrs interval were made simultaneously at station 2 near the estuary weir and station 9(Ganggyeong) of 35 km upstream from the weir in April. By the results observed for one day in April at station 2, salinity has a range of $7.88\~22.14\%_{\circ}$ and its temporal variability is identical to the pattern of tidal cycle in the neigh-bouring Kunsan Harbor. However, turbidity shows relatively high values only at an interval of 4~5 hours after the lowest salinity time, though hourly fluctuation of pH is very small. Silicate and dissolved inorganic nitrogen have inversively linear correlationships with salinity, implying the concentration of the two nutrients strongly regulated by estuarine mixing of sea and river waters. In contrast, phosphate sustains roughly a constant level over a wide salinity range and distinctly lower values than those corresponding to nitrate in the oceans. Such distributions of phosphate have been observed in some estuaries, and interpreted as driven by removal of dissolved phosphate into bottom sediments and the bufforing of phosphate by particulate matter. COD values at station 2 are relatively high in day-time(particularly afternoon) and in high-salinity periods. At station 9, saltwater intrusion was never found but water level changed to the extent of 2.5 m for one day. Although each parameter at this station exhibits very slight variations in their abundance for 24 hours compared with station 2, the contents of COD, silicate and ammonia are significantly higher than at station 2. Concentration of suspended matter is relatively high in the brackish water region up to $\~20$ km above the river mouth, probably due to strong tidal stirring of the bottom de-posits. Also, relatively high pH, COD and $O_2$ saturation at the upward stations of $40\~50$ km from the weir are presumably attributable to active photosynthesis of plants in the region. In general, COD and nutrients except phosphate are higher values at the upper stations than in the estuary zone, and show the highest abundances in July nearly at all stations. Finally, in the estuarine region tidal mixing of sea-river waters seems to be an important factor controlling the distributions of turbidity, COD, silicate and nitrate as well as salinity. However, water quality in the upward fresh-water zone is remarkably variable according to months or seasons.

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The Melodic Structure of the Bulmosan Youngsanjae, Ongho-ge (불모산 영산재 범패 옹호게의 선율구조)

  • Choi, Heon
    • (The) Research of the performance art and culture
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    • no.34
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    • pp.383-421
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    • 2017
  • Because the Jitsori and the Hotsori of the Beompae(the Korean Budhhist chant) has no meter and no Jangdan(a Rhythmic cycle of the Korean Music), so it is hard to analyze the melody of the Beompae. Also the melody of the Beompae is different from that of the other Korean traditional music, so studying of the Beompae has been out of the limelight of many scholars, studying the Korean music. But the melody of Beompae had been handed down for thousands of years in Korea, it and other Korean trditional music, had exchanged the impacts each other for a longtime. So I thinks that the Korean Beomapae have shared the similarity of the musical features with the other Korean traditional music. Because the Beompae of the Bulmosan Yeongsanjae on the Geongsangnamdo province has also no meters and no Jangdan, it is difficult to understand, too. But because the Onghoge of Bulmosan Yeongsanjae have a well-regulated melodic structure in comparison with the Beompae of the Seoul province, so called Geongjae Beompae, it seem to be easy to analyze its melody. So I will analyze the melody of Bulmosan Yeongsanjae Onghoge. This analyze should be contribute to investigate the rule of the melodic progress method on the convoluted Beompae melody. Onghoge has been sung on the procedure for Siryeon, Samsiniun(Goebuliun), Jojeonjeoman, Sinjungjakbeop. And the monk for the ritual has sung the chant first to purify the ritual place and to protect the soul. They has called the song, Onghoge a Jitsori at the Bulmosan Yeongsanjae preservation society of the Gyeongnam province. Commonly, there were Jitsori and Hotsori in the Beompae melody, and the melody of Jitsori is longer than that of the Hotsori. So, the melody of Onghoge is lengthened. In other word, the melody of the Onghoge show the lengthened and curved melodic feture of the Beompae very well. Hahn Manyeong, who had studied on the Beompae, Budhhist chant, said that the Hotsori has five letters in a phrase, and there were 4 phrases in a song. And he had insisted that the form of the song, Hotsori, is ABAB. I analyze the melody of the Onghoge by the Hahn's method. I will extract the Wonjeom(a primary tone of a skeletal melodic structure) from the melody of Onghoge, and in the progress of the Wonjeom of Onghoge melodies, I will arrange the repeat of the Wonjeom melody. It is a structural melody of Onghoge. The first phrase of Bulmosan Yeongsanjae Onghoge, 'Pal bu geum gang ho do ryang(八部金剛護道場)' have 4 structural melodies, the second phrase 'Gong sin sog bu bo cheon wang(空神速赴報天王)', the third phrase 'Sam gye je cheon ham le jip(三界諸天咸來集)', the firth phrase 'Yeo geum bul chal bo jeong sang(如今佛刹補禎祥)' have 2 structural melodies each. The structural melodies of Onghoge are 10 in total. And the structural melody of the Onghoge is formed the shape of 'Mi - La - do - La - Mi'. All of the Onghoge melodies is repeated 10 times by the melodic shape. The form of the Onghoge is not ABAB by Hahn, but is 10 times repeat of the shape.