• Title/Summary/Keyword: Mimetic

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Cobalt Chloride-Induced Down-Regulation of Puromycin-Sensitive Aminopeptidase Involved in Apoptosis of PC-3 Cells (PC-3 세포에서 cobalt chloride에 의해 down-regulation되는 puromycin-sensitive aminopeptidase의 apoptosis에 미치는 효과)

  • Lee, Suk-Hee;Kim, Hwan-Gyu
    • Journal of Life Science
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    • v.20 no.7
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    • pp.991-998
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    • 2010
  • Hypoxia is an indicative of pro-apoptotic and anti-apoptotic biphasic effects, which appear to be dependent upon the cell type and the condition of the cells. The hypoxia-mimetic agent, cobalt chloride ($CoCl_2$), has been shown to induce apoptosis in a variety of cell types, but the mechanism by which this occurs has yet to be thoroughly elucidated. Puromycin-sensitive aminopeptidase (PSA) gene was decreasingly expressed in response to $CoCl_2$. In this report, puromycin pretreatment applied to PC-3 cells resulted in apoptosis. To determine whether PSA is involved in apoptosis, we examined the apoptotic properties of the PC-3 cells after siRNA knockdown of PSA. PSA siRNA-induced PSA silencing revealed that endogenous PSA may be involved in apoptosis of the PC-3 cells. These results indicated that PSA may perform a vital function in cell survival of the PC-3 cells.

Design of a RANK-Mimetic Peptide Inhibitor of Osteoclastogenesis with Enhanced RANKL-Binding Affinity

  • Hur, Jeonghwan;Ghosh, Ambarnil;Kim, Kabsun;Ta, Hai Minh;Kim, Hyunju;Kim, Nacksung;Hwang, Hye-Yeon;Kim, Kyeong Kyu
    • Molecules and Cells
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    • v.39 no.4
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    • pp.316-321
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    • 2016
  • The receptor activator of nuclear factor ${\kappa}B$ (RANK) and its ligand RANKL are key regulators of osteoclastogenesis and well-recognized targets in developing treatments for bone disorders associated with excessive bone resorption, such as osteoporosis. Our previous work on the structure of the RANK-RANKL complex revealed that Loop3 of RANK, specifically the non-canonical disulfide bond at the tip, performs a crucial role in specific recognition of RANKL. It also demonstrated that peptide mimics of Loop3 were capable of interfering with the function of RANKL in osteoclastogenesis. Here, we reported the structure-based design of a smaller peptide with enhanced inhibitory efficiency. The kinetic analysis and osteoclast differentiation assay showed that in addition to the sharp turn induced by the disulfide bond, two consecutive arginine residues were also important for binding to RANKL and inhibiting osteoclastogenesis. Docking and molecular dynamics simulations proposed the binding mode of the peptide to the RANKL trimer, showing that the arginine residues provide electrostatic interactions with RANKL and contribute to stabilizing the complex. These findings provided useful information for the rational design of therapeutics for bone diseases associated with RANK/RANKL function.

Glycine- and GABA-mimetic Actions of Shilajit on the Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis in Mice

  • Yin, Hua;Yang, Eun-Ju;Park, Soo-Joung;Han, Seong-Kyu
    • The Korean Journal of Physiology and Pharmacology
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    • v.15 no.5
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    • pp.285-289
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    • 2011
  • Shilajit, a medicine herb commonly used in Ayurveda, has been reported to contain at least 85 minerals in ionic form that act on a variety of chemical, biological, and physical stressors. The substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc) are involved in orofacial nociceptive processing. Shilajit has been reported to be an injury and muscular pain reliever but there have been few functional studies of the effect of Shilajit on the SG neurons of the Vc. Therefore, whole cell and gramicidin-perfotrated patch clamp studies were performed to examine the action mechanism of Shilajit on the SG neurons of Vc from mouse brainstem slices. In the whole cell patch clamp mode, Shilajit induced short-lived and repeatable inward currents under the condition of a high chloride pipette solution on all the SG neurons tested. The Shilajit-induced inward currents were concentration dependent and maintained in the presence of tetrodotoxin (TTX), a voltage gated $Na^+$ channel blocker, CNQX, a non-NMDA glutamate receptor antagonist, and AP5, an NMDA receptor antagonist. The Shilajit-induced responses were partially suppressed by picrotoxin, a $GABA_A$ receptor antagonist, and totally blocked in the presence of strychnine, a glycine receptor antagonist, however not affected by mecamylamine hydrochloride (MCH), a nicotinic acetylcholine receptor antagonist. Under the potassium gluconate pipette solution at holding potential 0 mV, Shilajit induced repeatable outward current. These results show that Shilajit has inhibitory effects on the SG neurons of Vc through chloride ion channels by activation of the glycine receptor and $GABA_A$ receptor, indicating that Shilajit contains sedating ingredients for the central nervous system. These results also suggest that Shilajit may be a potential target for modulating orofacial pain processing.

Study into prosodic morphological analysis in Korean and Standard Chinese partial reduplication and contrastive analysis using optimality theory (한국어와 표준 중국어 부분 중첩 의성·의태어에 대한 운율 형태론적 분석의 문제와 최적성 이론적 분석을 통한 대조 분석)

  • Chang, Jae-Woong
    • Cross-Cultural Studies
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    • v.49
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    • pp.275-301
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    • 2017
  • Based on the previous analysis by Wanghongjun(2008), this paper applies Optimality Theory (OT) to the field of partial reduplication in Korea to increase its scientific validity. Toward this end, I propose an alternative analysis of Korean partial reduplication, applied as a single process of prefixation. Reduplicated words by prefixation are divided into two types: with a heavy syllable of the stem, and another with the stem. The two types of partial reduplication are closely related by the sound features. In addition, I discussed Chinese partial reduplication from a prefixation perspective within the framework of OT and performed contrastive analysis of Korean and Standard Chinese processes of reduplication by focusing on constrained rankings. As a result, the alternative analysis showed a systematic relationship among the reduplicated words in Korean and Standard Chinese. Lastly, I explained that the coronal /t/ and liquid /l/ have a special functional hierarchy in both languages. This study can be re-explained based on the framework of OT according to a few major constraints, involving MAX-BR, MAX-IO. Their rankings show the adequacy of analysis.

The Literary World of T. Tolstaya (따지야나 똘스따야의 문학세계 - '잃어버린 낙원', 유년으로의 회귀)

  • Lee, Soo Yeon
    • Cross-Cultural Studies
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    • v.23
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    • pp.265-293
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    • 2011
  • This study focused on the literary world of T. Tolstaya, a Russian writer who takes a crucial position in contemporary Russian literature, drawing upon the wrier's a couple of short stories. 'Youth' is a key motive encompassing all works of Tolstaya, so that it becomes the poetic keynote among her literary works. In order to examine such distinctions of the main characters' world awareness in their youth as shown in Tolstaya's literary works, Chapter 2 of this paper paid a special attention to the analyse of her representative works such as "Sitting on a Golden Terracing Stone" and "Meeting with a Bird", and expressed potential implications of youth with mimetic imagination for her. For Tolstaya, youth is perceived as a paradise but original imagination of youth gradually fades away in adult and ends up with a lost paradise. This is why Tolstaya uses poetic means based on nostalgia for youth like paradise and literary motto for recovery of imagination in youth. In this regard, this study particularly examined the retrospective prologue resisting the power of time as well as different fictional characters living in her own fantastic world. As a result, this study draws a conclusion that such longing and nostalgia for youth and lost paradise as delineated by Tolstaya through retrospective prologue and characters speak for an existential speculation that explores any profound implication of afflictions in reality of human life, rather than focusing on the painful reality of human life which consists of honest dialogues with realities like 'darkness' and 'pain.' In addition, this study, complying with Zolotonosov's ideas which deal with and define Tolstaya's literary works as a shabby and humble box invisibly containing a full wealth of precious jewels inside, sheds a new light on the writer's literary world.

Radiolabeling of antibody-mimetic scaffold protein with 99mTc tricarbonyl precursor via hexahistidine (His6)-tag

  • Shim, Ha Eun;Kim, Do Hee;Lee, Chang Heon;Choi, Dae seong;Lee, Dong-Eun
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.5 no.1
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    • pp.11-17
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    • 2019
  • Recently, antibody-like scaffold proteins have received a great deal of interest in diagnosis and therapy applications because of their intrinsic features that are often required for tumor imaging and therapy. Intrinsic issues that are associated with therapeutic application of antibody-like scaffold proteins, particularly in cancer treatment, include an efficient and straightforward radiolabeling for understanding in vivo biodistribution and excretion route, and monitoring therapeutic responses. Herein, we report an efficient and straightforward method for radiolabeling of antibody-like scaffold proteins with the $[^{99m}Tc(OH_2)_3(CO)_3]^+$ ($^{99m}Tc$-tricarbonyl) by using a site-specific direct labeling method via hexahistidine-tag, which is a widely used for general purification of recombinant proteins with His-affinity chromatography. Repebody is a new class of antibody-like scaffold protein that consists of highly diverse leucine-rich repeat (LRR) modules. Although all possible biomedical applications with repebody are ongoing, it's in vivo biodistribution and excretion pathway has not yet been explored. In this study, hexahistidine ($His_6$)-tag bearing repebody (rEgH9) was labeled with [$^{99m}Tc$]-tricarbonyl. Repebody protein was radiolabeled with high radiolabeling efficiency (>90%) and radiolabeled compound was more than 99% pure after purification. These results clearly demonstrate that the present radiolabeling method will be useful molecular imaging study.

Keratinocyte Migration in a Three-Dimensional In Vitro Wound Healing Model Co-Cultured with Fibroblasts

  • Iyer, Kritika;Chen, Zhuo;Ganapa, Teja;Wu, Benjamin M.;Tawil, Bill;Linsley, Chase S.
    • Tissue Engineering and Regenerative Medicine
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    • v.15 no.6
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    • pp.721-733
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    • 2018
  • BACKGROUND: Because three-dimensional (3D) models more closely mimic native tissues, one of the goals of 3D in vitro tissue models is to aid in the development and toxicity screening of new drug therapies. In this study, a 3D skin wound healing model comprising of a collagen type I construct with fibrin-filled defects was developed. METHODS: Optical imaging was used to measure keratinocyte migration in the presence of fibroblasts over 7 days onto the fibrin-filled defects. Additionally, cell viability and growth of fibroblasts and keratinocytes was measured using the $alamarBlue^{(R)}$ assay and changes in the mechanical stiffness of the 3D construct was monitored using compressive indentation testing. RESULTS: Keratinocyte migration rate was significantly increased in the presence of fibroblasts with the cells reaching the center of the defect as early as day 3 in the co-culture constructs compared to day 7 for the control keratinocyte monoculture constructs. Additionally, constructs with the greatest rate of keratinocyte migration had reduced cell growth. When fibroblasts were cultured alone in the wound healing construct, there was a 1.3 to 3.4-fold increase in cell growth and a 1.2 to 1.4-fold increase in cell growth for keratinocyte monocultures. However, co-culture constructs exhibited no significant growth over 7 days. Finally, mechanical testing showed that fibroblasts and keratinocytes had varying effects on matrix stiffness with fibroblasts degrading the constructs while keratinocytes increased the construct's stiffness. CONCLUSION: This 3D in vitro wound healing model is a step towards developing a mimetic construct that recapitulates the complex microenvironment of healing wounds and could aid in the early studies of novel therapeutics that promote migration and proliferation of epithelial cells.

Effects of Liriope muscari Water Extracts on the Cell Death and Inflammatory Cytokine Expression of Poly I:C-treated Lung Carcinoma Cells (맥문동 열수 추출물이 Poly I:C를 처리한 폐암세포주의 사멸 및 염증성 사이토카인 발현에 미치는 영향)

  • Kang, Dayeon;Cho, Namjoon;Renchinkhand, Gereltuya;Lee, Bo-Hee;Kim, Eun-Mi;Nam, Myoung Soo;Kim, Keekwang
    • The Korea Journal of Herbology
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    • v.36 no.1
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    • pp.97-102
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    • 2021
  • Objectives : Virus infection through the respiratory tract causes various inflammatory diseases such as pneumonia, cystic fibrosis, and obstructive pulmonary disease, causing enormous social damage. Therefore, it is very important to develop a treatment and prevention of infectious diseases. In this study, we investigated the effect of water extracts of Liriope muscari (WELM), known to improve lung function, on the inflammatory response of lung carcinoma cell line A549 cells induced by the viral double stranded RNA mimetic Polyinosinic:polycytidylic acid (Poly I:C). Methods : The cell viability by WELM treatment was analyzed using MTS assay in A549 cells. After inducing an inflammatory response to WELM-treated A549 cells with Poly I:C, the degree of apoptosis was confirmed through bright field microscopy. Interferon beta (IFN-β) mRNA expression level in A549 cells was analyzed by quantitative reverse transcription PCR (qRT-PCR). Results : WELM treatment has no significant effect on cell viability of A549 cells. We confirmed that pre-treatment of WELM effectively reduces the Poly I:C-induced apoptotic cell death in A549 cells. In addition, it was confirmed that the mRNA expression level of IFN-β, a pro-inflammatory cytokine increased by Poly I:C treatment, was significantly suppressed by WELM treatment in A549 cells. Conclusions : These results provide the evidence that WELM is effective at inhibiting inflammation on respiratory viral infections and suggest that Liriope muscari might be a valuable natural substance in the prevention and treatment of infectious diseases.

The Effect of Silymarin and Ethanol Intake on Vascular Contractility (엉겅퀴 유래 Silymarin의 단독 및 알코올 병용 시 혈압 조절 효과)

  • Je, Hyun Dong;Min, Young Sil
    • Journal of Industrial Convergence
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    • v.20 no.7
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    • pp.131-137
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    • 2022
  • In the study, we endeavored to assess the convergence effect of Silybum marianum-derived silymarin and epidemiologically-correlated alcohol intake on vascular contractility and to determine the mechanism involved. There were few reports addressing the question whether thin or thick filament modulation is included in ethanol and silymarin-induced regulation. We hypothesized that ethanol at a low concentration and silymarin play a role in agonist-dependent regulation of vascular contractility. Denuded arterial muscles of Sprague-Dawley male rats were suspended in organ baths and isometric tensions were transduced and recorded using isometric transducers and an automatic data acquisition system. Interestingly, both silymarin and ethanol didn't encourage silymarin alone-induced inhibition in agonists-induced contraction suggesting that endothelial nitric oxide synthesis might be involved in ethanol or silymarin-induced modulation of vascular contractility and additional pathways besides endothelial nitric oxide synthesis such as ROCK inactivation might be involved in the silymarin-induced modulation of vascular contractility.

A Study of K-Pop Girl Group's Graduation System through the Application of the Scapegoat Mechanism - Focusing on <9 Muses of Star Empire> - (희생양 메커니즘 적용을 통한 케이팝 걸그룹의 졸업제도 연구 - <9 Muses of Star Empire>를 중심으로 -)

  • Lee, Hark-Joon;Kim, Jeong-Hwan
    • Journal of Korea Entertainment Industry Association
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    • v.14 no.2
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    • pp.63-71
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    • 2020
  • K-Pop is powerful. Once considered to be at the periphery of global music scene, it is now reaching the whole world. Not surprisingly, the media, domestic and foreign, have scrambled to unlock the secrets of K-Pop's phenomenal growth. In doing so, they have not failed to highlight the underside of its success, such as cut-throat competition among idol-group members and the programmed member replacement by their agencies. One of the most notable characteristics in this process is called, in their business jargon, 'the graduation system'. This paper attempts to explicate this management practice unique to K-pop industry. To do so, this paper draws on Rene Girard's work on desires, particularly his notion of mimesis, violence and the scapegoat mechanism. Based on a documentary film, interactive online sites and a monograph that have chronicled how the K-pop girl group <9 Muses> have 'graduated' during their debut process, this paper applies, as its main analytical tool, the scapegoat mechanism and attempts to explore on its basis what 'the system' entails for the K-pop industry in general and the actors working within it in particular.