• Title/Summary/Keyword: 손상 메커니즘

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APEX-1 Regulates Cell Proliferation through GDNF/GFRα1 Signaling (APEX-1은 GDNF/GFRα1 시그널을 통해 세포증식을 조절한다)

  • Kim, Hong-Beum;Hariharasudhan, Gurusamy;Youn, Cha-Kyung
    • Journal of Life Science
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    • v.23 no.10
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    • pp.1183-1191
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    • 2013
  • Human apurinic/apyrimidinic endonuclease (APEX-1) is a multifunctional protein that is capable of repairing abasic sites and single-strand breaks in damaged DNA. In addition, it serves as a redox-modifying factor for a number of transcription factors. Identifying the transcriptional targets of APEX-1 is essential for understanding how it affects various cellular outcomes. Expression array analysis was used to identify glial cell-derived neurotropic factor receptor ${\alpha}1$ ($GFR{\alpha}1$), which is an encoding receptor for the glial cell-derived neurotropic factor (GDNF) family, the expression of which is induced by APEX-1. A target of GDNF/$GFR{\alpha}$ signaling, c-Src (Tyr418) was strongly phosphorylated by GNDF in the APEX-1 expressing cells. Moreover, GDNF initiated cell proliferation, measured by counting the number of cells, in the APEX-1 expressing cells. Importantly, the down-regulation of APEX-1 by siRNA caused a marked reduction in the $GFR{\alpha}1$ expression level, and it reduced the ability of GDNF to phosphorylate c-Src (Tyr418) and stimulate cell proliferation. These results demonstrate an association between APEX-1 and GDNF/$GFR{\alpha}$ signaling and suggest a potential molecular mechanism for the involvement of APEX-1 in cell survival and proliferation.

Overexpression of MicroRNA-31 as a Promising Biomarker for Prognosis and Metastasis in Human Colorectal Cancer (MicroRNA-31 과발현을 이용한 대장암의 예후예측 및 전이예측 바이오마커 발굴)

  • Hur, Keun
    • Journal of Life Science
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    • v.26 no.6
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    • pp.705-710
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    • 2016
  • Colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer-related death worldwide. Although several diagnostic and therapeutic tools have been available, CRC remains difficult to complete cure because of insufficient understanding of the molecular mechanisms underlying this disease progression. MicroRNAs (miRNAs) are small non-coding RNA molecules that strongly regulate gene expression via transcriptional and translational control mechanisms. Many crucial cellular pathways are frequently disrupted in cancer development process due to dysregulation of several miRNAs. Mir-31 functions as an oncogene that modulate expression of multiple cancer related genes. Thus, we aimed to demonstrate clinical relevance of miR-31 in human CRC. Quantitative RT-PCR analysis of miR-31 expression was performed in 175 CRC tissues and 16 normal colonic mucosa (NM). Next, we investigated clinical significances of miR-31 expression in various clinicopathologic features in CRC patients cohort. Mir-31 was significantly up-regulated in CRC tissues compared to NM. In CRC tissues, miR-31 expression level was significantly elevated in a stage-dependent manner, which was associated with poor survival in patients with CRC. High miR-31 levels in CRC tissues significantly correlated with poor prognosis (hazard ratio [HR]=2.4) as well as distant metastasis (odds ratio [OR]=2.3). In conclusion, we identified clinical significance of miR-31 expression in CRC. High miR-31 expression may be clinically able to use as a biomarker for CRC prognosis and predicting metastasis.

The Roles of Dietary Polyphenols in Brain Neuromodulation (뇌 신경조절에서의 식이 폴리페놀 화합물의 역할)

  • Lee, Hyeyoung;Lee, Heeseob
    • Journal of Life Science
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    • v.28 no.11
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    • pp.1386-1395
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    • 2018
  • Over recent years, it has become evident that the central nervous system bidirectionally interacts with the gastrointestinal tract along the gut-brain axis. A series of preclinical studies indicate that the gut microbiota can modulate central nervous system function through a multitude of physiological functions. Polyphenols are ubiquitous plant chemicals included in foods such as fruits, vegetables, tea, coffee and wine, and their consumption is directly responsible for beneficial health effects due to antioxidant, anti-inflammatory, antimicrobial, immunomodulatory, anticancer, vasodilating, and prebiotic-like effects. There is increasing evidence that dietary polyphenol can contribute to beneficial effects in neuronal protection acting against oxidative stress and inflammatory injury as well as in cognitive functions. In this paper, we overview the neuroprotective role of dietary polyphenols especially focusing on the neuroinflammation and neurovascular function by interaction with the gut microbiome. Polyphenol metabolites could directly act as neurotransmitters crossing the blood-brain barrier and modulating the cerebrovascular system or indirectly modulating gut microbiota. In addition, evidence suggests that dietary polyphenols are effective in preventing and managing neurological disorders, such as age-related cognitive decline and neurodegeneration, through a multitude of physiological functions. Dietary polyphenols are increasingly envisaged as a potential nutraceuticals in the prevention and treatment of neurological disorders, because they possess the ability to reduce neuroinflammation, to improve memory and cognitive function and to modulate the gut microbiota.

Structural Behavior Evaluation of a Cable-Stayed Bridge Subjected to Aircraft Impact: A Numerical Study (항공기 충돌에 대한 사장교의 구조거동 평가: 수치해석적 접근)

  • Choi, Keunki;Lee, Jungwhee;Chung, Chul-Hun;An, Dongwoo;Yoon, Jaeyong
    • Journal of the Computational Structural Engineering Institute of Korea
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    • v.34 no.3
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    • pp.137-149
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    • 2021
  • Cable-stayed bridges are infrastructure facilities of a highly public nature; therefore, it is essential to ensure operational safety and prompt response in the event of a collapse or damage caused by natural and social disasters. Among social disasters, impact accidents can occur in bridges when a vehicle collides with a pier or when crashes occur due to aircraft defects. In the case of offshore bridges, ship collisions will occur at the bottom of the pylon. In this research, a procedure to evaluate the structural behavior of a cable-stayed bridge for aircraft impact is suggested based on a numerical analysis approach, and the feasibility of the procedure is demonstrated by performing an example assessment. The suggested procedure includes 1) setting up suitable aircraft impact hazard scenarios, 2) structural modeling considering the complex behavior mechanisms of cable-stayed bridges, and 3) structural behavior evaluation of cable-stayed bridges using numerical impact simulation. It was observed that the scenario set in this study did not significantly affect the target bridge. However, if impact analysis is performed through various scenarios in the future, the load position and critical load level to cause serious damage to the bridge could be identified. The scenario-based assessment process employed in this study is expected to facilitate the evaluation of bridge structures under aircraft impact in both existing bridges and future designs.

Protective Effects of Traditional Korean Medicine Preparations, Herbs, and Active Compounds on the Blood-brain Barrier in Ischemic Stroke Models (허혈성 뇌졸중 모델에서 혈액-뇌 장벽에 보호효과를 나타내는 한약처방, 한약재 및 활성화합물)

  • Shin, Su Bin;Jang, Seok Ju;Lee, Na Gyeong;Choi, Byung Tae;Shin, Hwa Kyoung
    • Journal of Life Science
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    • v.32 no.7
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    • pp.550-566
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    • 2022
  • Stroke is among the leading causes of death and long-term physical and cognitive disabilities worldwide, affecting an estimated 15 million people annually. The pathophysiological process of stroke is complicated by multiple and coordinated events. The breakdown of the blood-brain barrier (BBB) in people with stroke can significantly contribute to the development of ischemic brain injury. Therefore, BBB disruption is recognized as a hallmark of stroke; thus, it is important to develop novel therapeutic strategies that can protect against BBB dysfunction in ischemic stroke. Traditional medicines are composed of natural products, which represent a promising source of new ingredients for the development of conventional medicines. Indeed, several studies have shown the effectiveness of Korean medicine on stroke, highlighting the value of Korean medicinal treatment for ischemic stroke. This review summarizes the current information and underlying mechanisms regarding the ameliorating effects of the formula, decoction, herbs, and active components of traditional Korean medicine on cerebral ischemia-induced BBB disruption. These traditional medicines were shown to have protective effects on the BBB in many cellular and animal ischemia models of stroke, and experiments in various animal species, such as mice and rats. In addition, they showed brain-protective effects by protecting the BBB through the regulation of tight junction proteins and matrix metalloproteinase-9, reducing edema, neuroinflammation, and neuronal cell death. We hope that this review will help promote further investigation into the neuroprotective effects of traditional Korean medicines and stimulate the performance of clinical trials on Korean herbal medicine-derived drugs in patients with stroke.

Introduction of Two-region Model for Simulating Long-Term Erosion of Bentonite Buffer (벤토나이트 완충재 장기 침식을 모사하기 위한 Two-region 모델 소개)

  • Jaewon Lee;Jung-Woo Kim
    • Tunnel and Underground Space
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    • v.33 no.4
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    • pp.228-243
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    • 2023
  • Bentonite is widely recognized and utilized as a buffer material in high-level radioactive waste repositories, mainly due to its favorable characteristics such as swelling capability and low permeability. Bentonite buffers play an important role in ensuring the safe disposal of radioactive waste by providing a low permeability barrier and effectively preventing the migration of radionuclides into the surrounding rock. However, the long-term performance of bentonite buffers still remains a subject of ongoing research, and one of the main concerns is the erosion of the buffer induced by swelling and groundwater flow. The erosion of the bentonite buffer can significantly impact repository safety by compromising the integrity of buffer and leading to the formation of colloids that may facilitate the transport of radionuclides through groundwater, consequently elevating the risk of radionuclide migration. Therefore, it is very important to numerically quantify the erosion of bentonite buffer to evaluate the long-term performance of bentonite buffer, which is crucial for the safety assessment of high-level radioactive waste disposal. In this technical note, Two-region model is introduced, a proposed model to simulate the erosion behavior of bentonite based on a dynamic bentonite diffusion model, and quantitative evaluation is conducted for the bentonite buffer erosion with this model.

Evaluation of Bonding Performance of Hybrid Materials According to Laser and Plasma Surface Treatment (레이저 및 플라즈마 표면처리에 따른 이종소재 접합특성평가)

  • Minha Shin;Eun Sung Kim;Seong-Jong Kim
    • Composites Research
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    • v.36 no.6
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    • pp.441-447
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    • 2023
  • Recently, as demand for high-strength, lightweight materials has increased, there has been great interest in joining with metals. In the case of mechanical bonding, such as bolting and riveting, chemical bonding using adhesives is attracting attention as stress concentration, cracks, and peeling occur. In this paper, surface treatment was performed to improve the adhesive strength, and the change in adhesive strength was analyzed. For the adhesive strength test were conducted with Carbon Fiber Reinforced Plastic(CFRP), CR340(Steel), and Al6061(Aluminum), and laser and plasma surface treatment were used. After plasma surface treatment, the adhesive strength improved by 7.3% and 39.2% in CFRP-CR340 and CFRP-Al6061, respectively. CR340-Al6061 was improved by 56.2% in laser surface treatment. Surface free energy(SFE) was measured by contact angle after plasma treatment, and it is thought that the adhesion strength was improved by minimizing damage through a chemical reaction mechanism. For laser surface treatment, it is thought that creates a rough bonding surface and improves adhesive strength due to the mechanical interlocking effect. Therefore, surface treatment is effect to improve adhesive strength, and based on this paper, the long-term fatigue test will be conducted to prevent fatigue failure, which is a representative cause of actual structural damage.

Effects of sucralose on memory and cognitive function relief in a scopolamine-induced amnesia model (Scopolamine으로 인한 건망증 모델에서 sucralose의 기억력 및 인지기능 완화 효과)

  • Eun-mi Jung;Eunhong Lee;Hyun-Ji Kwon;Jihye Lee;Hye-jeong Kim;Jinhan Park;Jongwon Lee;Ji Wook Jung
    • Journal of the Korean Applied Science and Technology
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    • v.40 no.6
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    • pp.1567-1579
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    • 2023
  • Sucralose is used as a sucrose alternative in the food sector and is a globally approved pyrogenic, high-intensity artificial sweetener. However, due to the lack of studies on the effects of sweeteners on the brain, this study confirmed whether short-term consumption of sucralose has cognitive and memory protective effects in scopolamine-induced memory-injured animal models. After oral administration of sucralose 2, 5, and 10 mg/kg, scopolamine (1 mg/kg) was administered to the control group and the drug group 30 minutes later, and saline was administered intraperitoneally to the normal group, followed by behavioral experiments As a result of the experiment, Y-Maze, passive avoidance, and Morris WaterMaze recovered more than 10% of cognitive function compared to the control group. In addition, as a result of measuring proinflammatory cytokines, sucralose was found to inhibit IL-6 and TNF-α by more than 30%, and we observed that the expression level of ERK-CREB with intracellular signaling mechanisms increased in a concentration-dependent manner. Therefore, it suggests that sucralose is associated with functional foods for the prevention of functional food patients.

Numerical Modeling of Hydrogen Embrittlement-induced Ductile Fracture Using a Gurson-Cohesive Model (GCM) and Hydrogen Diffusion (Gurson-Cohesive Model(GCM)과 수소 확산 모델을 결합한 수소 취화 파괴 해석 기법)

  • Jihyuk Park;Nam-Su Huh;Kyoungsoo Park
    • Journal of the Computational Structural Engineering Institute of Korea
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    • v.37 no.4
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    • pp.267-274
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    • 2024
  • Hydrogen embrittlement fracture poses a challenge in ensuring the structural integrity of materials exposed to hydrogen-rich environments. This study advances our comprehension of hydrogen-induced fracture through an integrated numerical modeling approach. In addition, it employs a ductile fracture model named the Gurson-cohesive model (GCM) and hydrogen diffusion analysis. GCM is employed as a fracture model that combines the Gurson model to illustrate the continuum damage evolution and the cohesive zone model to describe crack surface discontinuity and softening behavior. Moreover, porosity and stress triaxiality are considered as crack initiation criteria . A hydrogen diffusion analysis is also integrated with the GCM to account for hydrogen enhanced decohesion (HEDE) mechanisms and their subsequent impacts on crack initiation and propagation. This framework considers the influence of hydrogen on the softening behavior of the traction-separation relationship on the discontinuous crack surface. Parametric studies explore the sensitivity to diffusion properties and hydrogen-induced fracture properties. By combining numerical models of hydrogen diffusion and the ductile fracture model, this study provides an understanding of hydrogen-induced fracture and thereby contributes significantly to the ongoing efforts to design materials that are resilient to hydrogen embrittlement in practical engineering applications.

Cellular Localization and Translocation of Duplication and Alternative Splicing Variants of Olive Flounder Phospholipase C-δ1 (넙치 3가지 타입 인지질가수분해효소(PLC-δ1)의 세포 내 위치 및 이동)

  • Kim, Na Young;Kim, Moo-Sang;Jung, Sung Hee;Kim, Myoung Sug;Cho, Mi Young;Chung, oon Ki;Ahn, Sang Jung
    • Journal of Life Science
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    • v.27 no.11
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    • pp.1369-1375
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    • 2017
  • The purpose of this study was to investigate the cellular characterization of phospholipase C-${\delta}1$ in olive flounders (Paralichthys olivaceus). In general, phospholipase C signaling pathways are distributed in nuclei at plasma membranes and in cytoplasms, although the pathways' nuclear localization mechanisms are unclear. P. olivaceus duplicates type-A PoPLC-${\delta}1$ (PoPLC-${\delta}1A$), which has a high similarity to the human isoform PLC-${\delta}$; type-B PoPLC-${\delta}1$ (PoPLC-${\delta}1B$ [Sf]), which has a low similarity to the human isoform PLC-${\delta}$ and the alternative splice variant PoPLC-${\delta}1B$ (Lf), which has a nuclear localization signal (NLS) and a nuclear export signal (NES) for nuclear imports and exports, respectively. This study confirmed the effects of the cellular localization and translocation of GFP-tagged PoPLC-${\delta}1A$, PoPLC-${\delta}1B$ (Sf) and PoPLC-${\delta}1B$ (Lf). It administered treatments of $Ca^{2+}$ ionophore ionomycin and endoplasmic reticulum (ER)-$Ca^{2+}$ pump inhibitor thapsigargin to hirame natural-embryo (HINAE) cells. A laser-scanning confocal microscope was used. GFP-tagged PoPLC-${\delta}1A$ was distributed to the cellular organelles, rather than to the cytoplasms and cytomembranes, when PoPLC-${\delta}1B$ (Lf) and PoPLC-${\delta}1B$ (Sf) were localized at the plasma membranes. The treatments of ionomycin and thapsigargin showed the accumulation of PoPLC-${\delta}1A$ in the nuclei when PoPLC-${\delta}1B$ (Lf) nucleocytoplasmic shuttling and PoPLC-${\delta}1B$ (Sf) nucleocytoplasmic shuttling were not observed. The results were the first evidence that PoPLC-${\delta}1A$, which contains functional, intact NES sequences, has a main role in nucleocytoplasmic shuttling and translocation in fish.