• BMB Reports
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• 제56권11호
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• pp.600-605
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• 2023

Intrahepatic cholangiocarcinoma (ICC) is a bile duct cancer and a rare malignant tumor with a poor prognosis owing to the lack of an early diagnosis and resistance to conventional chemotherapy. A combination of gemcitabine and cisplatin is the typically attempted first-line treatment approach. However, the underlying mechanism of resistance to chemotherapy is poorly understood. We addressed this by studying dynamics in the human ICC SCK cell line. Here, we report that the regulation of glucose and glutamine metabolism was a key factor in overcoming cisplatin resistance in SCK cells. RNA sequencing analysis revealed a high enrichment cell cycle-related gene set score in cisplatin-resistant SCK (SCK-R) cells compared to parental SCK (SCK WT) cells. Cell cycle progression correlates with increased nutrient requirement and cancer proliferation or metastasis. Commonly, cancer cells are dependent upon glucose and glutamine availability for survival and proliferation. Indeed, we observed the increased expression of GLUT (glucose transporter), ASCT2 (glutamine transporter), and cancer progression markers in SCK-R cells. Thus, we inhibited enhanced metabolic reprogramming in SCK-R cells through nutrient starvation. SCK-R cells were sensitized to cisplatin, especially under glucose starvation. Glutaminase-1 (GLS1), which is a mitochondrial enzyme involved in tumorigenesis and progression in cancer cells, was upregulated in SCK-R cells. Targeting GLS1 with the GLS1 inhibitor CB-839 (telaglenastat) effectively reduced the expression of cancer progression markers. Taken together, our study results suggest that a combination of GLUT inhibition, which mimics glucose starvation, and GLS1 inhibition could be a therapeutic strategy to increase the chemosensitivity of ICC.

• IMMUNE NETWORK
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• 제24권3호
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• pp.21.1-21.16
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• 2024

IL-1, a pleiotropic cytokine with profound effects on various cell types, particularly immune cells, plays a pivotal role in immune responses. The proinflammatory nature of IL-1 necessitates stringent control mechanisms of IL-1-mediated signaling at multiple levels, encompassing transcriptional and translational regulation, precursor processing, as well as the involvement of a receptor accessory protein, a decoy receptor, and a receptor antagonist. In T-cell immunity, IL-1 signaling is crucial during both the priming and effector phases of immune reactions. The fine-tuning of IL-1 signaling hinges upon two distinct receptor types; the functional IL-1 receptor (IL-1R) 1 and the decoy IL-1R2, accompanied by ancillary molecules such as the IL-1R accessory protein (IL-1R3) and IL-1R antagonist. IL-1R1 signaling by IL-1β is critical for the differentiation, expansion, and survival of Th17 cells, essential for defense against extracellular bacteria or fungi, yet implicated in autoimmune disease pathogenesis. Recent investigations emphasize the physiological importance of IL-1R2 expression, particularly in its capacity to modulate IL-1-dependent responses within Tregs. The precise regulation of IL-1R signaling is indispensable for orchestrating appropriate immune responses, as unchecked IL-1 signaling has been implicated in inflammatory disorders, including Th17-mediated autoimmunity. This review provides a thorough exploration of the IL-1R signaling complex and its pivotal roles in immune regulation. Additionally, it highlights recent advancements elucidating the mechanisms governing the expression of IL-1R1 and IL-1R2, underscoring their contributions to fine-tuning IL-1 signaling. Finally, the review briefly touches upon therapeutic strategies targeting IL-1R signaling, with potential clinical applications.

• 복식
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• 제58권8호
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• pp.74-90
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• 2008

Since the late of 20th Century, philosophy, art, and aesthetics have attention to the movement of object that persue the dynamics and qualitative change, not existing fixed and quantitative object. Qualitative continuity, including discontinuity of specific spot and surface that occurs sudden change, is distinct characteristics considered in contemporary logo civilization, which combines and disperses according as various purpose among the different elements and objects. Therefore, I studied about the characteristics of qualitative continuity that creates the change and the differentiation continuously through the "formative characteristics of the continuity expressed in contemporary fashion" of my preceding paper. This paper is the following study of above mentioned paper, and Investigates about aesthetic consciousness leading to the various change. This is intends to consider the trans-aesthetic consciousness that accepts dynamic movement and change the different object and reforms new relationship continuously. This studies' conclusion is as follows; 1) sublimity-Infinity, de-constructive, excessive 2) jouissance - functional, structural 3) paradox-perceptual, spatial. A study about the trans-aesthetic consciousness would help to offer philosophical basis, and make a change building aesthetic foundation in explaining various relationship like as phenomenon of the retro, neo, post, fusion expressed since the late of 20th Century.

• BMB Reports
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• 제45권11호
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• pp.623-628
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• 2012

Tissue inhibitor of metalloproteinases (TIMPs; TIMP-1, -2, -3 and -4) are endogenous inhibitor for matrix metalloproteinases (MMPs) that are responsible for remodeling the extracellular matrix (ECM) and involved in migration, invasion and metastasis of tumor cells. Unlike under normal conditions, the imbalance between MMPs and TIMPs is associated with various diseased states. Among TIMPs, TIMP-1, a 184-residue protein, is the only N-linked glycoprotein with glycosylation sites at N30 and N78. The structural analysis of the catalytic domain of human stromelysin-1 (MMP-3) and human TIMP-1 suggests new possibilities of the role of TIMP-1 glycan moieties as a tuner for the proteolytic activities by MMPs. Because the TIMP-1 glycosylation participate in the interaction, aberrant glycosylation of TIMP-1 presumably affects the interaction, thereby leading to pathogenic dysfunction in cancer cells. TIMP-1 has not only the cell proliferation activities but also anti-oncogenic properties. Cancer cells appear to utilize these bilateral aspects of TIMP-1 for cancer progression; an elevated TIMP-1 level exerts to cancer development via MMP-independent pathway during the early phase of tumor formation, whereas it is the aberrant glycosylation of TIMP-1 that overcome the high anti-proteolytic burden. The aberrant glycosylation of TIMP-1 can thus be used as staging and/or prognostic biomarker in colon cancer.

• 한국실내디자인학회논문집
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• 제14권5호
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• pp.89-97
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• 2005

The purpose of this study is to analyze the interior characteristics of Philips Exeter Academy library by Louis I. Kahn. Kahn's main thoughts of 'what it wants to be ' and 'how it was done' play a important role in this research because these statements act as a clue to understand this library. 'What it wants to be' means the essence and existence of architecture and 'how it was done' shows the tectonic of architecture and construction process to enhance its presence. Most of his works inform that Kahn had consistently applied his thoughts into design process. The thoughts of the essence of library leads Kahn to configurate 3 layers of interior space. The emphasis of tectonic expression is also the characteristics of interior in that structure is the logical part of whole building system rather than concealing object for the exterior of buildings. In Exeter library, interior characteristics are summarized as 3 layers of interior configuration, the order in dynamics, the visualization of construction process, and the relationship between structure and space.

• The Korean Journal of Physiology and Pharmacology
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• 제16권1호
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• pp.71-77
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• 2012

Mitochondrial dynamics and distribution is critical for their role in bioenergetics and cell survival. We investigated the consequence of altered fission/fusion on mitochondrial function and motility in INS-1E rat clonal ${\beta}$-cells. Adenoviruses were used to induce doxycycline-dependent expression of wild type (WT-Mfn1) or a dominant negative mitofusin 1 mutant (DN-Mfn1). Mitochondrial morphology and motility were analyzed by monitoring mitochondrially-targeted red fluorescent protein. Adenovirus-driven overexpression of WT-Mfn1 elicited severe aggregation of mitochondria, preventing them from reaching peripheral near plasma membrane areas of the cell. Overexpression of DN-Mfn1 resulted in fragmented mitochondria with widespread cytosolic distribution. WT-Mfn1 overexpression impaired mitochondrial function as glucose- and oligomycin-induced mitochondrial hyperpolarization were markedly reduced. Viability of the INS-1E cells, however, was not affected. Mitochondrial motility was significantly reduced in WT-Mfn1 overexpressing cells. Conversely, fragmented mitochondria in DN-Mfn1 overexpressing cells showed more vigorous movement than mitochondria in control cells. Movement of these mitochondria was also less microtubule-dependent. These results suggest that Mfn1-induced hyperfusion leads to mitochondrial dysfunction and hypomotility, which may explain impaired metabolism-secretion coupling in insulin-releasing cells overexpressing Mfn1.

• BMB Reports
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• 제53권11호
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• pp.551-564
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• 2020

Proper development of the nervous system is critical for its function, and deficits in neural development have been implicated in many brain disorders. A precise and predictable developmental schedule requires highly coordinated gene expression programs that orchestrate the dynamics of the developing brain. Especially, recent discoveries have been showing that various mRNA chemical modifications can affect RNA metabolism including decay, transport, splicing, and translation in cell type- and tissue-specific manner, leading to the emergence of the field of epitranscriptomics. Moreover, accumulating evidences showed that certain types of RNA modifications are predominantly found in the developing brain and their dysregulation disrupts not only the developmental processes, but also neuronal activities, suggesting that epitranscriptomic mechanisms play critical post-transcriptional regulatory roles in development of the brain and etiology of brain disorders. Here, we review recent advances in our understanding of molecular regulation on transcriptome plasticity by RNA modifications in neurodevelopment and how alterations in these RNA regulatory programs lead to human brain disorders.

• 복식
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• 제63권1호
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• pp.1-15
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• 2013

This study deals with the aesthetic characteristics in Gareth Pugh's fashion film. As fashion films are becoming a newly emerging communication tool in fashion, the aim of this study will be to build a database on these films. For the specific method in this work, literature reviews were performed along with the empirical study of seven pieces of fashion film. The results of the study showed that Gareth Pugh released the fashion films from 2008 to 2012, and he collaborated with SHOW Studio member and photographer Nick Knight and Ruth Hogben. Common themes in their films were fear, fantasy, dynamics, and going off-limits, and these can be summed up in the following ways. First, a sense of fear was expressed via black colors, bizarre mechanical sounds, decalcomania shape in abstract images, and transformed physical body images. Second, an image of fantasy was presented with diverse expression techniques including colorful light presentations and abstract image setups from repeatedly changed image reproduction. Third, dynamic feature was denoted with a combination of fast development of images and quick reproduced layouts, as well as quick beat sounds, and big and powerful action movements. Fourth, characteristic of going off-limits was reflected, by showing the collections with a communication tool called fashion film instead of existing collection concept.

• Molecules and Cells
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• 제37권12호
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• pp.851-856
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• 2014

ATAD2, a remarkably conserved, yet poorly characterized factor is found upregulated and associated with poor prognosis in a variety of independent cancers in human. Studies conducted on the yeast Saccharomyces cerevisiae ATAD2 homologue, Yta7, are now indicating that the members of this family may primarily be regulators of chromatin dynamics and that their action on gene expression could only be one facet of their general activity. In this review, we present an overview of the literature on Yta7 and discuss the possibility of translating these findings into other organisms to further define the involvement of ATAD2 and other members of its family in regulating chromatin structure and function both in normal and pathological situations.

• 한국작물학회:학술대회논문집
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• 한국작물학회 2017년도 9th Asian Crop Science Association conference
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• pp.87-87
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• 2017

Flowering time of either early or late is one of the crucial parameters that determine the crop productivity. Therefore, elucidation of regulatory mechanisms of flowering time should contribute to breeding for yield enhancement. However, comprehensive explanation on molecular mechanism of flowering has not yet been reported in hexaploidy common wheat (Triticum asetivum L.). The mechanism of flowering in wheat has been studied mostly using flag leaf or floral meristem. The exposed peduncle, which is a shoot part between bottom of the spike and flag leaf, could be an important tissue that is responsible for flowering through various molecules expressing. To clarify for transcriptomic dynamics in the wheat peduncle that was uncovered by leaf sheath of flag leaf, RNA sequencing and transcriptomic analysis were conducted. With this, we also analyzed other transcriptomic results deposited in the public DB to identify genes specially expressed in peduncle tissue at transition from vegetative to reproductive phase. The obtained results will provide valuable information to understand the role of peduncle for flowing regulation in wheat aimming for elucidation of the regulatory mechanism of wheat flowering.