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The Endoplasmic Reticulum Stress Response Mediates Shikonin-Induced Apoptosis of 5-Fluorouracil-Resistant Colorectal Cancer Cells

  • Piao, Mei Jing;Han, Xia;Kang, Kyoung Ah;Fernando, Pincha Devage Sameera Madushan;Herath, Herath Mudiyanselage Udari Lakmini;Hyun, Jin Won
    • Biomolecules & Therapeutics
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    • v.30 no.3
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    • pp.265-273
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    • 2022
  • Resistance to chemotherapeutic drugs is a significant problem in the treatment of colorectal cancer, resulting in low response rates and decreased survival. Recent studies have shown that shikonin, a naphthoquinone derivative, promotes apoptosis in colon cancer cells and cisplatin-resistant ovarian cells, raising the possibility that this compound may be effective in drug-resistant colorectal cancer. The aim of this study was to characterize the molecular mechanisms underpinning shikonin-induced apoptosis, with a focus on endoplasmic reticulum (ER) stress, in a 5-fluorouracil-resistant colorectal cancer cell line, SNU-C5/5-FUR. Our results showed that shikonin significantly increased the proportion of sub-G1 cells and DNA fragmentation and that shikonin-induced apoptosis is mediated by mitochondrial Ca2+ accumulation. Shikonin treatment also increased the expression of ER-related proteins, such as glucose regulatory protein 78 (GRP78), phospho-protein kinase RNA-like ER kinase (PERK), phospho-eukaryotic initiation factor 2 (eIF2α), phospho-phosphoinositol-requiring protein-1 (IRE1), spliced X-box-binding protein-1 (XBP-1), cleaved caspase-12, and C/EBP-homologous protein (CHOP). In addition, siRNA-mediated knockdown of CHOP attenuated shikonin-induced apoptosis, as did the ER stress inhibitor TUDCA. These data suggest that ER stress is a key factor mediating the cytotoxic effect of shikonin in SNU-C5/5-FUR cells. Our findings provide an evidence for a mechanism in which ER stress leads to apoptosis in shikonin-treated SNU-C5/5-FUR cells. Our study provides evidence to support further investigations on shikonin as a therapeutic option for 5-fluorouracil-resistant colorectal cancer.

Contents of 'true education' in the Era of New Media and the Consciousness Structure of Modern People (뉴미디어 시대 속 '참교육' 콘텐츠와 현대인의 의식구조)

  • Kim, Se-Yeon
    • The Journal of the Korea Contents Association
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    • v.22 no.4
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    • pp.468-478
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    • 2022
  • 'True education', which was the core ideology of 'the Korean Teachers & Educational Workers Union', is re-appropriated in the new media era. This word, which is actively used by young people, means 'punishment against the object of social condemnation'. One of the characteristics of 'true education contents' commonly seen on the Internet is that it shows a tendency to 'fragmentation'. True educational contents are short in length, and the contents are very local. This reflects the characteristics of a postmodern society where totality disappears and small stories are consumed. Second, the standard for dividing good and evil is extremely 'arbitrary'. Whereas the existing stories of rewarding virtue and punishing vice had universal values such as love, consideration, and peace, the content of true education distinguishes good and evil with an extremely narrow perspective. The way to justify arbitrary standard is to incite public outrage. Third, 'humour' is added. Here, humor is combined with the emotion of hatred, causing the problem of weakening people's critical consciousness.

Long-Term Monitoring of the Barrier Effect of the Wild Boar Fence

  • Lim, Sang Jin;Kwon, Ji Hyun;Namgung, Hun;Park, Joong Yeol;Kim, Eui Kyeong;Park, Yung Chul
    • Journal of Forest and Environmental Science
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    • v.38 no.2
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    • pp.128-132
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    • 2022
  • Wild boars (Sus scrofa) not only cause crop damage and human casualties, but also facilitate the spread of many infectious diseases in domestic animals and humans. To determine the efficiency of a fencing system in blocking the movement of wild boars, long-term monitoring was performed in a fenced area in Bukhansan National Park using camera traps. Upon monitoring for a period of 46 months, there was a 72.6% reduction in the number of wild boar appearances in the fence-enclosed area, compared to that in the unenclosed area. For 20 months after the fence installation, the blocking effect of the fence was effective enough to reduce the appearance of wild boars by 92.6% in the fence-enclosed area, compared to that in the unenclosed area. The blocking effect of the fence remained effective for 20 months after its installation, after which its effectiveness decreased. Maintaining a fence for a long time is likely to lead to habitat fragmentation. It can also block the movement of other wild animals, including the endangered species - the long-tailed goral. This study suggests a 20-month retention period for the fences installed to inhibit the movement of wild boars in wide forests such as Gangwon-do in South Korea. To identify how long the blocking effect of the fences lasts, further studies are needed focusing on the length and height of the fence, and the conditions of the ground surface.

Algorithm for Block Packing of Main Memory Allocation Problem (주기억장치 할당 문제의 블록 채우기 알고리즘)

  • Lee, Sang-Un
    • The Journal of the Institute of Internet, Broadcasting and Communication
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    • v.22 no.6
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    • pp.99-105
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    • 2022
  • This paper deals with the problem of appropriately allocating multiple processors arriving at the ready queue to the block in the user space of the main memory is divided into blocks of variable size at compilation time. The existing allocation methods, first fit(FF), best fit(BF), worst fit(WF), and next fit(NF) methods, had the disadvantage of waiting for a specific processor because they failed to allocate all processors arriving at the ready queue. The proposed algorithm in this paper is a simple block packing algorithm that allocates as many processors as possible to the largest block by sorting the size of the partitioned blocks(holes) and the size of the processor in the ready queue in descending order. The application of the proposed algorithm to nine benchmarking experimental data showed the performance of allocating all processors while having minimal internal fragment(IF) for all eight data except one data in which the weiting processor occurs due to partition errors.

Actigraphy-Based Assessment of Sleep Parameters in Intensive Care Unit Patients Receiving Respiratory Support Therapy (호흡지지요법을 적용 중인 중환자실 입원환자의 액티그래피 측정 수면특성)

  • Kang, Jiyeon;Kwon, Yongbin
    • Journal of Korean Critical Care Nursing
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    • v.15 no.3
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    • pp.115-127
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    • 2022
  • Purpose : This study aimed to investigate sleep parameters and to identify differences according to respiratory support therapy, sedation, and pain medication in intensive care unit (ICU) patients. Methods : In this observational study, sleep parameters were measured using actigraphy. We observed 45 sleep events in 30 ICU patients receiving respiratory support therapy. We measured the sleep parameters, time, efficiency, and wakefulness after sleep onset (WASO). The differences in sleep parameters according to the respiratory support therapy were analyzed using the Mann-Whitney U test. Results : The average daily sleep time of the participants was 776.66±276.71 minutes, of which more than 60% accounted for daytime sleep. During night sleep, the duration of WASO was 156.93±107.91 minutes, and the frequency of WASO was 26.02±25.82 times. The high flow nasal cannula (HFNC) group had a significantly shorter night sleep time (𝑥2=7.86, p =.049), a greater number of WASO (𝑥2=5.69, p =.128), and a longer WASO duration (𝑥2=8.75, p =.033) than groups of other respiratory therapies. Conclusion : ICU patients on respiratory support therapy experienced sleep disturbances such as disrupted circadian rhythm and sleep fragmentation. Among respiratory support regimens, HFNC was associated with poor sleep parameters, which appears to be associated with the insufficient use of analgesics. The results of this study warrant the development of interventions that can improve sleep in ICU patients receiving respiratory support, including HFNC.

SEINA: A two-dimensional steam explosion integrated analysis code

  • Wu, Liangpeng;Sun, Ruiyu;Chen, Ronghua;Tian, Wenxi;Qiu, Suizheng;Su, G.H.
    • Nuclear Engineering and Technology
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    • v.54 no.10
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    • pp.3909-3918
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    • 2022
  • In the event of a severe accident, the reactor core may melt due to insufficient cooling. the high-temperature core melt will have a strong interaction (FCI) with the coolant, which may lead to steam explosion. Steam explosion would pose a serious threat to the safety of the reactors. Therefore, the study of steam explosion is of great significance to the assessment of severe accidents in nuclear reactors. This research focuses on the development of a two-dimensional steam explosion integrated analysis code called SEINA. Based on the semi-implicit Euler scheme, the three-phase field was considered in this code. Besides, the influence of evaporation drag of melt and the influence of solidified shell during the process of melt droplet fragmentation were also considered. The code was simulated and validated by FARO L-14 and KROTOS KS-2 experiments. The calculation results of SEINA code are in good agreement with the experimental results, and the results show that if the effects of evaporation drag and melt solidification shell are considered, the FCI process can be described more accurately. Therefore, it is proved that SEINA has the potential to be a powerful and effective tool for the analysis of steam explosions in nuclear reactors.

Arctigenin induces caspase-dependent apoptosis in FaDu human pharyngeal carcinoma cells

  • Kang, Kyeong-Rok;Kim, Jae-Sung;Lim, HyangI;Seo, Jeong-Yeon;Park, Jong-Hyun;Chun, Hong Sung;Yu, Sun-Kyoung;Kim, Heung-Joong;Kim, Chun Sung;Kim, Do Kyung
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.6
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    • pp.447-456
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    • 2022
  • The present study was carried out to investigate the effect of Arctigenin on cell growth and the mechanism of cell death elicited by Arctigenin were examined in FaDu human pharyngeal carcinoma cells. To determine the apoptotic activity of Arctigenin in FaDu human pharyngeal carcinoma cells, cell viability assay, DAPI staining, caspase activation analysis, and immunoblotting were performed. Arctigenin inhibited the growth of cells in a dose-dependent manner and induced nuclear condensation and fragmentation. Arctigenin-treated cells showed caspase-3/7 activation and increased apoptosis versus control cells. FasL, a death ligand associated with extrinsic apoptotic signaling pathways, was up-regulated by Arctigenin treatment. Moreover, caspase-8, a part of the extrinsic apoptotic pathway, was activated by Arctigenin treatments. Expressions of anti-apoptotic factors such as Bcl-2 and Bcl-xL, components of the mitochondria-dependent intrinsic apoptosis pathway, significantly decreased following Arctigenin treatment. The expressions of pro-apoptotic factors such as BAX, BAD and caspase-9, and tumor suppressor -53 increased by Arctigenin treatments. In addition, Arctigenin activated caspase-3 and poly (ADP-ribose) polymerase (PARP) induced cell death. Arctigenin also inhibited the proliferation of FaDu cells by the suppression of p38, NF-κB, and Akt signaling pathways. These results suggest that Arctigenin may inhibit cell proliferation and induce apoptotic cell death in FaDu human pharyngeal carcinoma cells through both the mitochondria-mediated intrinsic pathway and the death receptor-mediated extrinsic pathway.

Discussing Metaverse Ethics with a Movie on Metaverse, 'Ready Player One' (메타버스를 영화 '레디 플레이어 원(Ready Player One)'을 통해 살펴본 메타버스 윤리)

  • Kim, Seong-Hee;Yi, Sang-Wook
    • Journal of Broadcast Engineering
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    • v.27 no.5
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    • pp.665-675
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    • 2022
  • After the COVID-19 pandemic, there has been growing interests in metaverse technology and social use of virtual reality platforms in non-face-to-face environments, but social issues and ethical concerns raised by metaverse have not been sufficiently discussed. In this paper, we discuss the social functions of the metaverse by examining the movie 'Ready Player One', and investigate the ethical problems that may arise in various implementation of metaverse. We identify the potential ethical problems that could occur in the context of metaverse including identity fragmentation, metaverse violence and crime, and mismanagement of personal information. We also propose some promising approaches to tackle these ethical problems ranging over descriptive ethics, normative ethics, and analytical (meta) ethics.

Establishment and Characterization of Carboplatin-Resistant Retinoblastoma Cell Line

  • Cho, Chang Sik;Jo, Dong Hyun;Kim, Jin Hyoung;Kim, Jeong Hun
    • Molecules and Cells
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    • v.45 no.10
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    • pp.729-737
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    • 2022
  • Carboplatin-based chemotherapy is the primary treatment option for the management of retinoblastoma, an intraocular malignant tumor observed in children. The aim of the present study was to establish carboplatin-resistant retinoblastoma cell lines to facilitate future research into the treatment of chemoresistant retinoblastoma. In total, two retinoblastoma cell lines, Y79 and SNUOT-Rb1, were treated with increasing concentrations of carboplatin to develop the carboplatin-resistant retinoblastoma cell lines (termed Y79/CBP and SNUOT-Rb1/CBP, respectively). To verify resistance to carboplatin, the degree of DNA fragmentation and the expression level of cleaved caspase-3 were evaluated in the cells, following carboplatin treatment. In addition, the newly developed carboplatin-resistant retinoblastoma cells formed in vivo intraocular tumors more effectively than their parental cells, even after the intravitreal injection of carboplatin. Interestingly, the proportion of cells in the G0/G1 phase was higher in Y79/CBP and SNUOT-Rb1/CBP cells than in their respective parental cells. In line with these data, the expression levels of cyclin D1 and cyclin D3 were decreased, whereas p18 and p27 expression was increased in the carboplatin-resistant cells. In addition, the expression levels of genes associated with multidrug resistance were increased. Thus, these carboplatin-resistant cell lines may serve as a useful tool in the study of chemoresistance in retinoblastoma and for the development potential therapeutics.

Effectiveness of the Pico-toning Technique for the Treatment of Melasma with a Low Fluence 1,064-nm Nd:YAG Laser in Asian Patients

  • Kim, Dong Gyu;Nam, Seung Min;Shin, Jin Soo;Park, Eun Soo
    • Medical Lasers
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    • v.9 no.2
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    • pp.166-171
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    • 2020
  • Background and Objectives Melasma is an acquired pigmentary disorder characterized by brown or dark brown colored macules and patches which mostly involve the face. Compared to nanosecond lasers, picosecond lasers have fewer adverse effects on surrounding tissues and give better results for melanin fragmentation. The purpose of this study was to evaluate the efficacy of the pico-toning technique using a low fluence 1,064-nm Nd:YAG laser on melasma patients. Materials and Methods This study is a retrospective analysis of melasma cases treated using the pico-toning technique from June 2017 to November 2020. Based on photographic images, the modified Melasma Area and Severity Index (mMASI) score was blind evaluated by two independent plastic surgeons. Patient satisfaction was assessed through a 5-point Likert scale questionnaire after treatment sessions. All adverse effects and complications were reviewed based on medical records. Results A total of 23 patients were included in the study. The mMASI scores for baseline and 2 months after the last procedure were 5.1 ± 1.4 and 2.6 ± 0.4, respectively. The mean mMASI score reduced significantly after the treatment session (p < 0.05). The patient satisfaction score with the procedure was 3.8 ± 1.0. The subject satisfaction score and difference in the mMASI score before the procedure and 2 months after the last procedure showed a significant correlation. Adverse effects observed in this study were erythema (n = 1) and edema (n = 1). Conclusion The results of the study show that the pico-toning technique is effective in Asian patients with melasma. We believe that safety was enhanced by using low fluence, and thus better results were achieved with fewer adverse effects.