• BMB Reports
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• 제56권10호
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• pp.557-562
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• 2023

Dysregulation of the E3 ubiquitin ligase Parkin has been linked to various human cancers, indicating that Parkin is a tumor suppressor protein. However, the mechanisms of action of Parkin remain unclear to date. Thus, we aimed to elucidate the mechanisms of action of Parkin as a tumor suppressor in human lung and colorectal cancer cells. Results showed that Parkin overexpression reduced the viability of A549 human lung cancer cells by inducing G2/M cell cycle arrest. In addition, Parkin caused DNA damage and ATM (Ataxia telangiectasia mutated) activation, which subsequently led to p53 activation. It also induced the p53-mediated upregulation of p21 and downregulation of cyclin B1. Moreover, Parkin suppressed the proliferation of HCT-15 human colorectal cancer cells by a mechanism similar to that in A549 lung cancer cells. Taken together, our results suggest that the tumor-suppressive effects of Parkin on lung and colorectal cancer cells are mediated by DNA damage/p53 activation/cyclin B1 reduction/cell cycle arrest.

• 한국콘크리트학회:학술대회논문집
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• 한국콘크리트학회 1994년도 가을 학술발표회 논문집
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• pp.200-204
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• 1994

Low temperature associated damage mechanism is not well known for asphalt concrete. Many studies have related the thermal cracking of pavement in the roadway in cold region with overall shrinkage of the pavement surface under assumption of homogeneous material. This study, however, was intiated based on the assumption that thermal incompatibility of materials (heterogeneous) in asphalt concrete mixture would be the primary cause of the damages. Acoustic emission technique and microscopic obsevation were employed to evaluate damage mechanism of asphalt concrete due to low temperature. The first method showed the sufficient evidence that asphalt concrete could be damaged by lowered temperature only. The second method showed that the damage by temperature resulted in micro-cracks at the interface between asphalt matrix and aggregate particle. It was concluded that these damage mechanisms were the primary cause of major thermal cracking of asphalt pavement in cold region.

• Biomolecules & Therapeutics
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• 제32권1호
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• pp.84-93
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• 2024

Rosmarinic acid (RA) is a phenolic ester that protects human keratinocytes against oxidative damage induced by ultraviolet B (UVB) exposure, however, the mechanisms underlying its effects remain unclear. This study aimed to elucidate the cell signaling mechanisms that regulate the antioxidant activity of RA and confirm its cyto-protective role. To explore the signaling mechanisms, we used the human keratinocyte cell line HaCaT and SKH1 hairless mouse skin. RA enhanced glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione synthetase (GSS) expression in HaCaT cells in a dose- and time-dependent manner. Moreover, RA induced nuclear factor erythroid-2-related factor 2 (NRF2) nuclear translocation and activated the signaling kinases protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, the ERK inhibitor U0126, and small interfering RNA (siRNA) gene silencing suppressed RA-enhanced GCLC, GSS, and NRF2 expression, respectively. Cell viability tests showed that RA significantly prevented UVB-induced cell viability decrease, whereas the glutathione (GSH) inhibitors buthionine sulfoximine, LY294002, and U0126 significantly reduced this effect. Moreover, RA protected against DNA damage and protein carbonylation, lipid peroxidation, and apoptosis caused by UVB-induced oxidative stress in a concentration-dependent manner in SKH1 hairless mouse skin tissues. These results suggest that RA protects against UVB-induced oxidative damage by activating AKT and ERK signaling to regulate NRF2 signaling and enhance GSH biosynthesis. Thus, RA treatment may be a promising approach to protect the skin from UVB-induced oxidative damage.

• Biomolecules & Therapeutics
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• 제5권2호
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• pp.202-210
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• 1997

Protective effect of DA-9601, an extract of Artemisia Herb, against ethanol-induced gastric mucosal injury was evaluated in rats. In the prophylactic study, DA-9601 exhibited total protection (99.4%) against absolute ethanol-induced gastropathy, And the protective effect of DA-9601 lasted up to 2 hours, which was longer than those of other contemporary mucoprotectants. In the treatment study, DA-9601 significantly facilitated the healing of 70% ethanol-induced mucosal damage, which was superior to cetraxate, a commonly used anti-ulcer drug. The mechanisms of mucoprotection of DA-9601 were also assessed. DA-9601 increased the release of prostaglandin E$_2$ from murine neutrophils in a dose-dependent manner in vitro. The cytoprotective effect of DA-9601 against ethanol-induced mucosal damage was significantly diminished by the concommitant injection of N$\omega$-nitro-L-arginine methyl ester (L-NAME, 5 mg/kg, i.v.), a non-specific nitric oxide (NO) synthase inhibitor, while it was not affected by preinjection of indomethacin (5 mg/kg, s.c.), a prostaglandins-depletor. And it was found that DA-9601 significantly enhanced adaptive cytoprotective action of 10% ethanol against absolute ethanol (56.9$\pm$6.5 vs 23.0$\pm$3.3 mm$^2$, p<0.05, mean$\pm$SEM), though its exact underlying mechanism remains to be clarified. The present fin[lings demonstrate that DA-9601 exerts gastroprotecticv actions for the stomach against ethanol through several different underlying mechanisms, in which prostanglandins and NO are involved. In conclusion, the results obtained suggest that DA-9601 can be useful both in prevention and treatment of ethanol-induced gastric damage.

• 한국복합재료학회:학술대회논문집
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• 한국복합재료학회 2004년도 추계학술발표대회 논문집
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• pp.167-170
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• 2004

In order to investigate the impact behaviors of 3-D braided glass/epoxy composites, the energy profiles and damage area were compared to the laminates of similar volume fraction and composition. The energy profiles showed different characteristics from each other which indicates they have distict energy absorption mechanisms. The image analysis on the damage projections visualized the crack propagation paths along the fiber direction.

• Corrosion Science and Technology
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• 제12권4호
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• pp.179-184
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• 2013

Pipe wall thinning caused by erosion and corrosion can adversely affect the operation of aged nuclear power plants. Some injured workers owing to pipe rupture has been reported and power reduction caused by unexpected pipe damage has been occurred consistently. Therefore, it is important to develop erosion-corrosion damage prediction model and investigate its mechanisms. Especially, liquid droplet impingement erosion(LDIE) is regarded as the main issue of pipe wall thinning management. To investigate LDIE mechanism with corrosion environment, we developed erosion-corrosion damage simulation apparatus and its capability has been verified through the preliminary damage experiment of 6061-Al alloy. The apparatus design has been based on ASTM standard test method, G73-10, that use high-speed rotator and enable to simulate water hammering and droplet impingement. The preliminary test results showed mass loss of 3.2% in conditions of peripheral speed of 110m/s, droplet size of 1mm-diameter, and accumulated time of 3 hours. In this study, the apparatus design revealed feasibility of LDIE damage simulation and provided possibility of accelerated erosion-corrosion damage test by controlling water chemistry.

• BMB Reports
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• 제52권8호
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• pp.520-525
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• 2019

Dihydroartemisinin (DHA) has been reported to possess anti-cancer activity against many cancers. However, the pharmacologic effect of DHA on HBV-positive hepatocellular carcinoma (HCC) remains unknown. Thus, the objective of the present study was to determine whether DHA could inhibit the proliferation of HepG2.2.15 cells and uncover the underlying mechanisms involved in the effect of DHA on HepG2.2.15 cells. We found that DHA effectively inhibited HepG2.2.15 HCC cell proliferation both in vivo and in vitro. DHA also reduced the migration and tumorigenicity capacity of HepG2.2.15 cells. Regarding the underlying mechanisms, results showed that DHA induced cellular senescence by up-regulating expression levels of proteins such as p-ATM, p-ATR, ${\gamma}-H_2AX$, P53, and P21 involved in DNA damage response. DHA also induced autophagy (green LC3 puncta gathered together and LC3II/LC3I ratio increased through AKT-mTOR pathway suppression). Results also revealed that DHA-induced autophagy was not linked to senescence or cell death. TPP1 (telomere shelterin) overexpression could not rescue DHA-induced anticancer activity (cell proliferation). Moreover, DHA down-regulated TPP1 expression. Gene knockdown of TPP1 caused similar phenotypes and mechanisms as DHA induced phenotypes and mechanisms in HepG2.2.15 cells. These results demonstrate that DHA might inhibit HepG2.2.15 cells proliferation through inducing cellular senescence and autophagy.

• Journal of Radiation Protection and Research
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• 제36권4호
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• pp.190-194
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• 2011

After the first report that electrons with sub-ionization energy of DNA could cause single strand breaks or double strand breaks to DNA, there have been various studies to investigate the mechanisms of DNA damage by low-energy electrons. In this paper, we examined the possibility of using X-ray photoelectron spectroscopy (XPS) to analyze the dissociation patterns of the molecular bonds by electron irradiation on DNA thin films and tried to establish the method as a general tool for studying the radiation damage of biomolecules by low energ yelectrons. For the experiment, pBR322 plasmid DNA solution was formed into the films on tantalum plates by lyophilization and was irradiated by 5-eV electrons. Un-irradiated and irradiated DNA films were compared and analyzed using the XPS technique.

• 약학회지
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• 제55권3호
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• pp.251-259
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• 2011

Cigarette smoke condensate (CSC) is known to be carcinogenic compound. CSC contains many organic compounds such as polycyclic aromatic hydrocarbons (PAHs), and heterocyclic amine compounds (HCAs). Reactive oxygen species (ROS) are also generated and induce oxidative DNA damage during the metabolism of CSC. The rat microsome mediated and DNA repair enzyme treated comet assays together with conventional comet assay were performed to evaluate the mechanisms of CSC genotoxicity. The organic extract of CSC induced oxidative and microsome mediated DNA damage. Vitamin C as a model antioxidant reduced DNA damage in endonuclease III treated comet assay. One of flavonoid, galangin as a CYP1A1 inhibitor, reduced DNA damage in the presence of S-9 mixture. The ethanol extracts of the mixed vegetables (BV) or the mixed fruits (BF) showed potent inhibitory effects against CSC induced DNA damage with oxidative DNA lesions and in the prescence of S-9 mixture. These results indicate that BV and BF could prevent CSC-induced cellular DNA damage by inhibiting oxidative stress and suppressing cytochrome P450 in mammalian cells.

• Computers and Concrete
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• 제27권2호
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• pp.153-162
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• 2021

This paper aims to simulate the isotropic elastic damage theory of Liu Jun (2012) using the self-programmed UMAT subroutine in the interface of ABAQUS. Liu Jun (2012)'s method based on the mechanic theory can not be used interactively with the currently commonly used finite element software ABAQUS. The advantage of this method in the paper is that it can interact with ABAQUS and provide a constitutive program framework that can be modified according to user need. The model retains the two scalar damage variables and the corresponding two energy dissipation mechanisms and damage criteria for considering the tensile and compressive asymmetry of concrete. Taking C45 concrete as an example, the relevant damage evolution parameters of its tensile and compressive constitutive model are given. The study demonstrates that the uniaxial tensile stress calculated by the subroutine is almost the same as the Chinese Concrete Design Specification (GB50010) before the peak stress, but ends soon after the peak stress. The stress-strain curve of uniaxial compression calculated by the subroutine is in good agreement with the peak stress in Chinese Concrete Design Specification (GB50010), but there is a certain deviation in the descending stage. In addition, this paper uses the newly compiled subroutine to simulate the shear bearing capacity of the shear key in a new structural system, namely the open-web sandwich slab. The results show that the damage constitutive subroutine has certain reliability.