• Oncology Letters
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• v.41 no.6
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• pp.3305-3312
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• 2019

Histone H2B monoubiquitination has been shown to play critical roles in diverse cellular processes including DNA damage response. Although recent data indicate that H2B monoubiquitination is strongly connected with tumor progression and regulation, the implications of this modification in lung adenocarcinoma are relatively unknown. In the present study, we demonstrated the clinical implication of H2B monoubiquitination and the potential role of tumor necrosis factor receptor-associated factor-interacting protein (TRAIP) in regulating its modification in lung adenocarcinoma. Immunohistochemical analysis showed that H2B monoubiquitination was significantly downregulated in 68 human lung adenocarcinoma patient samples compared to their normal adjacent tissues. Depletion of TRAIP by specific siRNA treatment markedly decreased ionizing radiation (IR)-induced H2B monoubiquitination. In addition, deletion mutants without RING domain or C-terminus of TRAIP diminished the ability to induce H2B monoubiquitination at lysine 120. Notably, the nuclear expression of TRAIP was positively related with H2B monoubiquitination levels in patients with lung adenocarcinoma. Furthermore, statistical analysis indicated that low levels of both TRAIP and H2B monoubiquitination, not each alone, in patients with lung adenocarcinoma were strongly correlated with poor survival. Taken together, these results suggest that TRAIP is a novel regulator of H2B monoubiquitination in DNA damage response and cancer development in lung adenocarcinoma.

• Molecular & Cellular Toxicology
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• v.2 no.3
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• pp.151-158
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• 2006

Khal was a synthetic congener of halocidin, a heterodimeric peptide consisting of 19 and 15 amino acid residues detected in Halocynthia aurantium. This compound was considered a candidate for the development of a novel peptide antibiotic. The genotoxicity of Khal was subjected to high throughput toxicity screening (HTTS) because they revealed strong antibacterial effects. Mouse lymphoma thymidine kinase ($tk^{+/-}$) gene assay (MOLY), single cell gel electrophoresis (Comet) assay and chromosomal aberration assay in mammalian cells and Ames reverse mutation assay in bacterial system were used as simplified, inexpensive, short-term in vitro screening tests in our laboratory. These compounds are not mutagenic in S. typhimurium TA98 and TA100 strains both in the presence and absence of metabolic activation. Before performing the comet assay, $IC_{20}$ of Khal was determined the concentration of $25.51\;{\mu}/mL\;and\;21.99\;{\mu}g/mL$ with and without S-9, respectively. In the comet assay, Khal was not induced DNA damage in mouse lymphoma cell line. Also, the mutation frequencies in the Khal-treated cultures were similar to the vehicle controls. It is suggests that Khal is non-mutagenic in MOLY assay. And no clastogenicity was observed in Khal-treated Chinese hamster lung cells. The results of this battery of assays indicate that Khal has no genotoxic potential in bacterial or mammalian cell systems. Therefore, we suggest that Khal, as the optimal candidates with both no genotoxic potential and antibacterial effects must be chosen.

• Radiation Oncology Journal
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• v.12 no.2
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• pp.143-150
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• 1994

The damage which radiation produces in tissues such as the lungs can be discussed at the molecular, biophysical, cellular, and organ levels. The cellular effects of irradiating the lungs are related to the histologic and clinical sequelae. In the present study the right lung of rabbits were exposed to single dose of 20 Gy of X-irradiation. Animals from each group were sacrificed monthly for 6 months postexposure. Sections of lung were examined by light microscopy(LM) and by transmission electron microscopy(TEM). Multiple exudative lesions were seen at 2 months after the 20Gy irradiation,and they progressed to a proliferative and then reparative fibrotic lesion by 6 months. Changes in epithelial lining of lung components, particulary the presence of type II pneumocytes were found by both LM and TEM. Capillary endothelial damages were less pronounced. The possible implication of cellular components in radiation pneumonitis and fibrosis is discussed.

• KSBB Journal
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• v.29 no.6
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• pp.432-436
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• 2014

We investigated antioxidative activity of the ethanol extracts of leaves of Cornus walteri Wanger (CWE) by treated enzyme in human dermal fibroblast (HDFs) irradiated by UVB. We examined the in vitro chemical and cellular antioxidant activities of CWE in HDFs. We employed scavenging assay for the 1,1-diphenyl-2,5-picrylhydrazyl (DPPH) radicals and cellular antioxidative activity of CWE, and we was investigated in $H_2O_2$-treated or UVB-irradiated HDFs. The CWE effectively scavenged DPPH radicals ($IC_{50}$ $7.03{\pm}0.4{\mu}g/mL$) when compared to the scavenging activities of L-ascorbic acid ($IC_{50}$ $4.69{\pm}0.3{\mu}g/mL$). CWE reduced UVB-induced cellular damage in HS68 cells by MTT assay and inhibited intracellular ROS generation in dose-dependent manner. In addition, CWE also attenuated the elevated levels of 8-isoprostane resulting from UVB-mediated oxidative stress. Collectively, these results suggest that CWE could be a new potential candidate as antioxidant against UVB-induced oxidative stress in HDFs.

• Molecules and Cells
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• v.40 no.9
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• pp.613-620
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• 2017

The most common form of senile dementia is Alzheimer's disease (AD), which is characterized by the extracellular deposition of amyloid ${\beta}-peptide$ ($A{\beta}$) plaques and the intracellular formation of neurofibrillary tangles (NFTs) in the cerebral cortex. Tau abnormalities are commonly observed in many neurodegenerative diseases including AD, Parkinson's disease, and Pick's disease. Interestingly, tau-mediated formation of NFTs in AD brains shows better correlation with cognitive impairment than $A{\beta}$ plaque accumulation; pathological tau alone is sufficient to elicit frontotemporal dementia, but it does not cause AD. A growing amount of evidence suggests that soluble $A{\beta}$ oligomers in concert with hyperphosphorylated tau (pTau) serve as the major pathogenic drivers of neurodegeneration in AD. Increased $A{\beta}$ oligomers trigger neuronal dysfunction and network alternations in learning and memory circuitry prior to clinical onset of AD, leading to cognitive decline. Furthermore, accumulated damage to mitochondria in the course of aging, which is the best-known nongenetic risk factor for AD, may collaborate with soluble $A{\beta}$ and pTau to induce synapse loss and cognitive impairment in AD. In this review, I summarize and discuss the current knowledge of the molecular and cellular biology of AD and also the mechanisms that underlie $A{\beta}-mediated$ neurodegeneration.

• Molecular & Cellular Toxicology
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• v.1 no.2
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• pp.78-86
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• 2005

Dioxins, especially 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin), are ubiquitous environmental contaminants. TCDD is known that it has toxic effects in animals and humans, including chloracne, immune, reproductive and developmental toxicities, carcinogenicity, wasting syndrome and death. TCDD induces a broad spectrum of biological responses, including disruption of normal hormone signaling pathways, reproductive and developmental defects, immunotoxicity, liver damage, wasting syndrome and cancer. Many researches showed that TCDD induces gene expression of transcriptional factors related cell proliferation, signal transduction, immune system and cell cycle arrest at molecular and cellular levels. These toxic actions of TCDD are usually mediated with AhR (receptor, resulted from cell culture, animal and clinical studies). cDNA microarray can be used as a highly sensitive and informative marker for toxicity. Additionally, microarray analysis of dioxin-toxicity is able to provide an opportunity for the development of candidate bridging biomarkers of dioxin-toxicity. Through microarray technology, it is possible to understand the therapeutic effects of agonists within the context of toxic effects, classify new chemicals as to their complete effects on biological systems, and identify environmental factors that may influence safety.

• Korean Journal of Agricultural Science
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• v.38 no.4
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• pp.625-629
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• 2011

To investigate the protective effect of eggplant (Solanum melongena L.) and its active compound, delphinidin, we used in vitro and cellular system. The active fraction from eggplant, BuOH fraction, showed protective effect from hydrogen peroxide-induced oxidative stress in WI-38 fibroblast cells. It suggests that eggplant would have the protective activity from radical-induced oxidative damage and its BuOH fraction would play the crucial role with antioxidative activity. In addition, delphinidin, the active compound from eggplant, exerted the strong 1,1-diphenyl-2-picrylhydrazyl scavenging effect with $IC_{50}$ value of 6.59 ${\mu}g/mL$. Furthermore, the cellular oxidative stress was induced by 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) in LLC-$PK_1$ cells, while treatment of delphinidin atteunated AAPH-induced oxidative stress as dose-dependent manner. The present study suggests the antioxidative activity of eggplant and delphinidin against free radical-induced oxidative stress.

• Molecular & Cellular Toxicology
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• v.2 no.1
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• pp.60-66
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• 2006

Methylmercury (MeHg), one of the heavy metal compounds, can cause severe damage to the central nervous system in humans. Many reports have shown that MeHg is poisonous to human body through contaminated foods and has released into the environment. Despite many studies on the pathogenesis of MeHg-induced central neuropathy, no useful mechanism of toxicity has been established so far. This study, using of suppression subtractive hybridization (SSH) method, was peformed to identify differentially expressed genes by MeHg in SH-SY5Y human neuroblastoma cell line. We prepared to total RNA from SH-SY5Y cells treated with solvent (DMSO) and $6.25\;{\mu}M\;(IC_{50})$ MeHg and performed forward and reverse SSH. Differentially expressed cDNA clones were screened by dot blot, sequenced and confirmed that individual clones indeed represent differentially expressed genes with real time RT-PCR. These sequences were identified by BLAST homology search to known genes or expressed sequence tags (ESTs). Analysis of these sequences may provide an insight into the biological effects of MeHg in the pathogenesis of neurodegenerative disease and a possibility to develop more efficient and exact monitoring system of heavy metals as ubiquitous environmental pollutants.

• Structural Engineering and Mechanics
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• v.71 no.3
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• pp.283-290
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• 2019

In global competition manufacturing companies have to produce modern, new constructions from advanced materials in order to increase competitiveness. The aim of my research was to develop a new composite cellular plate structure, which can be primarily used for structural elements of road, rail, water and air transport vehicles (e.g. vehicle bodies, ship floors). The new structure is novel and innovative, because all materials of the components of the newly developed structure are composites (laminated Carbon Fiber Reinforced Plastic (CFRP) deck plates with pultruded Glass Fiber Reinforced Plastic (GFRP) stiffeners), furthermore combines the characteristics of sandwich and cellular plate structures. The material of the structure is much more advantageous than traditional steel materials, due mainly to its low density, resulting in weight savings, causing lower fuel consumption and less environmental damage. In the study the optimal construction of a given geometry of a structural element of a road truck trailer body was defined by single- and multi-objective optimization (minimal cost and weight). During the single-objective optimization the Flexible Tolerance Optimization method, while during the multi-objective optimization the Particle Swarm Optimization method were used. Seven design constraints were considered: maximum deflection of the structure, buckling of the composite plates, buckling of the stiffeners, stress in the composite plates, stress in the stiffeners, eigenfrequency of the structure, size constraint for design variables. It was confirmed that the developed structure can be used principally as structural elements of transport vehicles and unit load devices (containers) and can be applied also in building construction.

• BMB Reports
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• v.52 no.1
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• pp.13-23
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• 2019

Aging is accompanied by a time-dependent progressive deterioration of multiple factors of the cellular system. The past several decades have witnessed major leaps in our understanding of the biological mechanisms of aging using dietary, genetic, pharmacological, and physical interventions. Metabolic processes, including nutrient sensing pathways and mitochondrial function, have emerged as prominent regulators of aging. Mitochondria have been considered to play a key role largely due to their production of reactive oxygen species (ROS), resulting in DNA damage that accumulates over time and ultimately causes cellular failure. This theory, known as the mitochondrial free radical theory of aging (MFRTA), was favored by the aging field, but increasing inconsistent evidence has led to criticism and rejection of this idea. However, MFRTA should not be hastily rejected in its entirety because we now understand that ROS is not simply an undesired toxic metabolic byproduct, but also an important signaling molecule that is vital to cellular fitness. Notably, mitochondrial function, a term traditionally referred to bioenergetics and apoptosis, has since expanded considerably. It encompasses numerous other key biological processes, including the following: (i) complex metabolic processes, (ii) intracellular and endocrine signaling/communication, and (iii) immunity/inflammation. Here, we will discuss shortcomings of previous concepts regarding mitochondria in aging and their emerging roles based on recent advances. We will also discuss how the mitochondrial genome integrates with major theories on the evolution of aging.