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OTUB1 knockdown promotes apoptosis in melanoma cells by upregulating TRAIL expression

  • Lee, Bok-Soon;Kang, Sung Un;Huang, Mei;Kim, Yeon Soo;Lee, Young-Sun;Park, Jae-Yong;Kim, Chul-Ho
    • BMB Reports
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    • v.54 no.12
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    • pp.608-613
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    • 2021
  • Melanoma, the most serious type of skin cancer, exhibits a high risk of metastasis. Although chemotherapeutic treatment for metastatic melanoma improves disease outcome and patient survival, some patients exhibit resistance or toxicity to the drug treatment regime. OTUB1 is a deubiquitinating enzyme overexpressed in several cancers. In this study, we investigated the effects of inhibiting OTUB1 expression on melanoma-cell proliferation and viability and identified the underlying molecular mechanism of action of OTUB1. We did endogenous OTUB1 knockdown in melanoma cells using short interfering RNA, and assessed the resulting phenotypes via MTT assays, Western blotting, and cell-cycle analysis. We identified differentially expressed genes between OTUB1-knockdown cells and control cells using RNA sequencing and confirmed them via Western blotting and reverse transcription polymerase chain reaction. Furthermore, we investigated the involvement of apoptotic and cell survival signaling pathways upon OTUB1 depletion. OTUB1 depletion in melanoma cells decreased cell viability and caused simultaneous accumulation of cells in the sub-G1 phase, indicating an increase in the apoptotic-cell population. RNA sequencing of OTUB1-knockdown cells revealed an increase in the levels of the apoptosis-inducing protein TRAIL. Additionally, OTUB1-knockdown cells exhibited increased sensitivity to PLX4032, a BRAF inhibitor, implying that OTUB1 and BRAF act collectively in regulating apoptosis. Taken together, our findings show that OTUB1 induces apoptosis of melanoma cells in vitro, likely by upregulating TRAIL, and suggest that approaches targeting OTUB1 can be developed to provide novel therapeutic strategies for treating melanoma.

Modeling of Precast Concrete Shear Walls BIM Program (BIM 프로그램을 이용한 프리캐스트 콘크리트 전단벽의 모델링)

  • Mun, Ju-Hyun;Yoon, Hyun-Sub;Kim, Jong-Won;Eom, Byung-Ho
    • Journal of the Korea Institute of Building Construction
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    • v.22 no.5
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    • pp.451-462
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    • 2022
  • The objective of the study is to establish a BIM modeling of precast concrete(PC) shear wall with various wall-to-base connections. The family library of PC shear wall was established in BIM program using component function in a IFC(Industry foundation classes) file format and SketchUp program. From the BIM program, the amounts of concrete, reinforcing bars and steel materials as well as the interference of arranged reinforcing bars can be accurately evaluated in the PC shear walls with spliced sleeves, bolt, or welding plate connection methods. Although the additional metallic materials such as steel plates, bolts, and nuts were used in the PC shear walls with welding plate connection method, their amounts of materials, economic efficiency, and environmental impact were similar to those with spliced sleeve connection. Consequently, the bolt or welding connection is a highly applicable method as wall-to-base connection of PC shear walls, and it was a more useful method than spliced sleeve method, particularly considering the constructability.

Apoptosis Induction of HCT-15 Cells by Extracts of Undaria pinnatifida with Fermented Micro-organism (미역 발효추출물의 HCT-15 대장암 세포 사멸 유도 효과)

  • Kim, Tae-Yun;Han, Hyo-Sang;Lee, Young-Jong
    • The Korea Journal of Herbology
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    • v.28 no.4
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    • pp.33-40
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    • 2013
  • Objectives : To study the apoptosis effects of fermented Undaria pinnatifida extracts(FUP) against HCT-15 colon cancer cells. Method : By measuring cell proliferation, DNA fragmentation, cell cycle, morphology, and western blot from FUP, the study investigated the effects of the extractions had upon the HCT-15 colon cancer cells, and concluded that the inhibiting effects upon cells were induced by apoptosis. Result : FUP effectively inhibited the growth of HCT-15 colon cancer cells. After analyzing the DNA fragmentation, the study observed a DNA ladder, while examining the cells, and found an increase of sub-G1 hypodiploid cells. On the changes regarding the nucleus of the cells, a condensation of cells and chromatin, as well as an apoptotic body was clearly observed. By observing through western blot from FUP, the study found a decreased level of Bcl-2 from HCT-15 colon cancer cells, but the increased level of Bax and cleaved caspase-3, which as a result induced apoptosis, inhibiting the growth of HCT-15 colon cancer cells. FUP increased the natural death of HCT-15 colon cancer cells by the induction of apoptosis. FUP seemed to have no suppressing effect upon HL-60/MX2 cells. However, compared to the fucoidan, the study was able to clearly observe morphological changes of HCT-15 cells apoptosis, in a 1/2 concentration. Conclusion : FUP had antiproliferative effects on different kinds of cancer cells, while proving especially efficacious against colon cancer cells.

The Effects of Internet Addiction on Self-Esteem of the 2030 Generation -The Moderating effects of Stress Coping Styles- (인터넷 중독이 2030세대의 자아존중감에 미치는 영향 - 스트레스 대처 방식의 조절효과-)

  • Kang, Sun-Kyung;Cha, You-Jeong
    • Journal of the Korea Convergence Society
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    • v.12 no.11
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    • pp.391-401
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    • 2021
  • The purpose of this study was to verify the moderating effects of the stress coping styles on the effects of internet addiction on the self-esteem of the 2030 generation during the Covid19 period. The 762 samples were selected through an online survey, and the collected data were conducted using the SPSS WIN26.0 program for frequency analysis, correlation analysis, and hierarchical regression analysis. As a result of the analysis, Internet addiction had a negative effect on self-esteem, and only seeking social support among the four sub-factors of stress response served as a moderator variable in the relationship between Internet addiction and self-esteem. Based on the results, the followings were suggested: expansion of research subjects regarding Internet addiction and interdisciplinary convergence study, providing universal provision of stress coping management programs, building a community at the local level, and discovery and reinforcing variables that offset the negative role of self-esteem of 2030 generations.

Picropodophyllotoxin Inhibits Cell Growth and Induces Apoptosis in Gefitinib-Resistant Non-Small Lung Cancer Cells by Dual-Targeting EGFR and MET

  • Jin-Young, Lee;Bok Yun, Kang;Sang-Jin, Jung;Ah-Won, Kwak;Seung-On, Lee;Jin Woo, Park;Sang Hoon, Joo;Goo, Yoon;Mee-Hyun, Lee;Jung-Hyun, Shim
    • Biomolecules & Therapeutics
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    • v.31 no.2
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    • pp.200-209
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    • 2023
  • Patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) amplification or sensitive mutations initially respond to the tyrosine kinase inhibitor gefitinib, however, the treatment becomes less effective over time by resistance mechanism including mesenchymal-epithelial transition (MET) overexpression. A therapeutic strategy targeting MET and EGFR may be a means to overcoming resistance to gefitinib. In the present study, we found that picropodophyllotoxin (PPT), derived from the roots of Podophyllum hexandrum, inhibited both EGFR and MET in NSCLC cells. The antitumor efficacy of PPT in gefitinib-resistant NSCLC cells (HCC827GR), was confirmed by suppression of cell proliferation and anchorage-independent colony growth. In the targeting of EGFR and MET, PPT bound with EGFR and MET, ex vivo, and blocked both kinases activity. The binding sites between PPT and EGFR or MET in the computational docking model were predicted at Gly772/Met769 and Arg1086/Tyr1230 of each ATP-binding pocket, respectively. PPT treatment of HCC827GR cells increased the number of annexin V-positive and subG1 cells. PPT also caused G2/M cell-cycle arrest together with related protein regulation. The inhibition of EGFR and MET by PPT treatment led to decreases in the phosphorylation of the downstream-proteins, AKT and ERK. In addition, PPT induced reactive oxygen species (ROS) production and GRP78, CHOP, DR5, and DR4 expression, mitochondrial dysfunction, and regulated involving signal-proteins. Taken together, PPT alleviated gefitinib-resistant NSCLC cell growth and induced apoptosis by reducing EGFR and MET activity. Therefore, our results suggest that PPT can be a promising therapeutic agent for gefitinib-resistant NSCLC.

Effects of Thinning and Climate on Stem Radial Fluctuations of Pinus ponderosa and Pinus lambertiana in the Sierra Nevada

  • Andrew Hirsch;Sophan Chhin;Jianwei Zhang;Michael Premer
    • Journal of Forest and Environmental Science
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    • v.39 no.2
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    • pp.81-95
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    • 2023
  • Due to the multiple ecosystem benefits that iconic large, old growth trees provide, forest managers are applying thinning treatments around these legacy trees to improve their vigor and reduce mortality, especially in the face of climate change and other forest health threats. One objectives of this study was to analyze sub-hourly stem fluctuations of legacy ponderosa (Pinus ponderosa Dougl. Ex P. & C. Laws) and sugar pines (Pinus lambertiana Dougl.) in the mixed-conifer forests of the Sierra Nevada in multiple different radius thinning treatments to assess the short-term effects of these treatments. Thinning treatments applied were: R30C0 (9.1 m radius), R30C2 (9.1 m radius leaving 2 competitors), and RD1.2 (radius equaling DBH multiplied by 1 ft/in multiplied by 1.25). The other objective was to assess climatic drivers of hourly stem fluctuations. Using the dendrometeR package, we gathered daily statistics (i.e. daily amplitude) of the stem fluctuations, as well as stem cycle statistics such as duration and magnitude of contraction, expansion, and stem radial increment. We then performed correlation analyses to assess the climatic drivers of stem fluctuations and to determine which radial thinning treatment was most effective at improving growth. We found an important role that mean solar radiation, air temperature, and relative humidity play in stem variations of both species. One of the main findings from a management perspective was that the RD1.2 treatment group allowed both species to contract less on warmer and higher solar radiation days. Furthermore, sugar pine put on more stem radial increment on higher solar radiation days. These findings suggest that the extended radius RD1.2 thinning treatment may be the most effective at releasing legacy sugar and ponderosa pine trees compared to the other forest management treatments applied.

Study on the Improvement of the Radiation Work Field Classification System in Republic of Korea (국내 방사선종사자 피폭 분류체계 개선에 관한 연구)

  • Su-Hui Park;Ji-Young Han;Yong-Min Kim
    • Journal of the Korean Society of Radiology
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    • v.17 no.2
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    • pp.267-275
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    • 2023
  • Occupational exposure records are subject of global interest, and analysis of radiation workers in work categories is being conducted. In Rep. of Korea, according to relevant ministries, the MOHW(Ministry of Health and Welfare), the MAFRA(Ministry of Agriculture, Food and Rural Affairs), and the NSSC(Nuclear Safety and Security Commission) collect and analyze records of occupational exposure by dividing them into 11 work categories. However, this classification system lacks consistency with the systems of major countries, including the UNSCEAR(United Nations Scientific Committee on the Effects of Atomic Radiation). The domestic radiation work field classification system does not have clear classification criteria and does not reflect the characteristics of the radiation work field. Through the analysis of the classification system of the UNSCEAR, we suggested the five main categories(nuclear cycle, medical, industrial, others(education/research, military/public) field and several sub-categories according to each radiation work field.

Licochalcone H Targets EGFR and AKT to Suppress the Growth of Oxaliplatin -Sensitive and -Resistant Colorectal Cancer Cells

  • Seung-On Lee;Mee-Hyun Lee;Ah-Won Kwak;Jin-Young Lee;Goo Yoon;Sang Hoon Joo;Yung Hyun Choi;Jin Woo Park;Jung-Hyun Shim
    • Biomolecules & Therapeutics
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    • v.31 no.6
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    • pp.661-673
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    • 2023
  • Treatment of colorectal cancer (CRC) has always been challenged by the development of resistance. We investigated the antiproliferative activity of licochalcone H (LCH), a regioisomer of licochalcone C derived from the root of Glycyrrhiza inflata, in oxaliplatin (Ox)-sensitive and -resistant CRC cells. LCH significantly inhibited cell viability and colony growth in both Ox-sensitive and Ox-resistant CRC cells. We found that LCH decreased epidermal growth factor receptor (EGFR) and AKT kinase activities and related activating signaling proteins including pEGFR and pAKT. A computational docking model indicated that LCH may interact with EGFR, AKT1, and AKT2 at the ATP-binding sites. LCH induced ROS generation and increased the expression of the ER stress markers. LCH treatment of CRC cells induced depolarization of MMP. Multi-caspase activity was induced by LCH treatment and confirmed by Z-VAD-FMK treatment. LCH increased the number of sub-G1 cells and arrested the cell cycle at the G1 phase. Taken together LCH inhibits the growth of Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, and inducing ROS generation and ER stress-mediated apoptosis. Therefore, LCH could be a potential therapeutic agent for improving not only Ox-sensitive but also Ox-resistant CRC treatment.

Comparison Analysis of Environmental Performance between Reconstruction and Remodeling Alternatives for Aged - Focused on CO2 Emissions Analysis - (공동주택 재건축과 리모델링의 친환경성 비교분석 - CO2 배출량 분석을 중심으로 -)

  • Kim, Chibaek;Shin, Dongwoo;Han, Juyeon;Hwang, Youngkyu
    • Korean Journal of Construction Engineering and Management
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    • v.15 no.1
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    • pp.87-100
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    • 2014
  • Environmental problems and the shortage of natural resources are currently gathering more attention in Korea and international countries. With these problems, it is reported that most current domestic buildings are emitting approximately 138 million tons of greenhouse gas. According to a recent report from the investigation of Korean housing population, the total number of households is approximately 12.9 millions, and the apartments that were built more than 15 years ago amounted to 3.1 millions. This shows that the rates of old apartment housings are increasing. Therefore, it is necessary to consider the deteriorated facilities and environmental improvement. Also, the construction industry is benefited by improving these housings which may need either remodeling or reconstruction. Environmental friendly buildings are a rising consideration for remodeling and reconstruction projects; it helps to determine many business matters in construction. The main purpose of this research is to improve environmental condition in apartments with comparison analysis between remodeling and reconstruction alternatives. This research is focused on characteristics of remodeling and reconstruction and it sets up the same condition with each level in order to evaluate the value of environmental friendliness and analyze its definition. The result of this research provides a unique emitting rate at a novel framework and this will cause the reduction of $CO_2$. It is analyzed that the remodeling construction can reduce the great amount of $CO_2$. Therefore, it will be a good decision guideline in selecting the most eco-friendly alternative to improve environment for building construction. Although reconstruction is a popular alternative nowadays in Korea, this research can provide a reason why decision makers should put more emphasis on remodeling as an environment-friendly alternative.

Variations in Nutrients & CO2 Uptake Rates and Photosynthetic Characteristics of Saccharina japonica from the South Coast of Korea (다시마(Saccharina japonica)의 생장에 따른 영양염 및 CO2 흡수율과 광합성 특성 변화)

  • Hwang, Jae-Ran;Shim, Jeong-Hee;Kim, Jeong-Bae;Kim, Sook-Yang;Lee, Yong-Hwa
    • The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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    • v.16 no.4
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    • pp.196-205
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    • 2011
  • To investigate the contribution of macroalgae to biogeochemical nutrients and carbon cycles, we measured the uptake rates of nutrients and $CO_2$ and characteristics of fluorescence of Saccharina japonica (Laminaria japonica Areschoug) using an incubation method in an acrylic chamber. From January to May 2011, S.japonica was sampled at Ilkwang, one of well-known macroalgae culture sites around Korea and ranged 46~288 cm long and 4.8~22.0 cm wide of whole thallus. The production rate of dissolved oxygen by S. japonica (n=25) was about $6.9{\pm}5.8{\mu}mol\;g^{-1}$ fresh weight(FW) $h^{-1}$. The uptake rate of total dissolved inorganic carbon ($TCO_2$), calculated by total alkalinity and pH, was $8.9{\pm}7.9{\mu}mol\;g^{-1}\;FW\;h^{-1}$. Mean nutrients uptake were $175.6{\pm}161.1\;nmol\;N\;g^{-1}\;FW\;h^{-1}$ and $12.7{\pm}10.1\;nmol\;P\;g^{-1}\;FW\;h^{-1}$. There were logarithmic relationships between thallus length and uptake rates of nutrients and $CO_2$, which suggested that younger specimens (<100-150 cm) were much more efficient at nutrients and $CO_2$ uptake than old specimens > 150 cm. There was a positive linear correlation ($r^2$=9.4) existed between the dissolved oxygen production rate and the $TCO_2$ uptake rate, suggesting that these two factors may serve as good indicators of S. japonica photosynthesis. There was also positive linear relationship between maximal quantum yield ($F_v/F_m$) and production/uptake rates of dissolved oxygen, $TCO_2$ and phosphate, suggested that $F_v/F_m$ could be used as a good indicator of photosynthetic ability and $TCO_2$ consumption of macroalgae. Maximum relative electron transport rate ($rETR_{max}$) of S. japonica increased as thallus grew and was high in distal part of thallus which may be resulted from the increase of photosynthetic cell density per area. The annual $TCO_2$ uptake by S. japonica in Gijang area was estimated about $1.0\sim1.7{\times}10^3C$ ton, which was about 0.02-0.03% of carbon dioxide emission in Busan City. Thus, more research should be focused on macroalgae-based biogeochemical cycles to evaluate the roles and contributions of macroalgae to the global carbon cycle.