• Molecules and Cells
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• v.39 no.4
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• pp.286-291
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• 2016

Epstein-Barr virus (EBV) is the prototypical ${\gamma}$-herpesvirus and an obligate human pathogen that infects mainly epithelial cells and B cells, which can result in malignancies. EBV infects these target cells by fusing with the viral and cellular lipid bilayer membranes using multiple viral factors and host receptor(s) thus exhibiting a unique complexity in its entry machinery. To enter epithelial cells, EBV requires minimally the conserved core fusion machinery comprised of the glycoproteins gH/gL acting as the receptor-binding complex and gB as the fusogen. EBV can enter B cells using gp42, which binds tightly to gH/gL and interacts with host HLA class II, activating fusion. Previously, we published the individual crystal structures of EBV entry factors, such as gH/gL and gp42, the EBV/host receptor complex, gp42/HLA-DR1, and the fusion protein EBV gB in a postfusion conformation, which allowed us to identify structural determinants and regions critical for receptor-binding and membrane fusion. Recently, we reported different low resolution models of the EBV B cell entry triggering complex (gHgL/gp42/HLA class II) in "open" and "closed" states based on negative-stain single particle electron microscopy, which provide further mechanistic insights. This review summarizes the current knowledge of these key players in EBV entry and how their structures impact receptor-binding and the triggering of gB-mediated fusion.

• Journal of Preventive Medicine and Public Health
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• v.34 no.1
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• pp.41-46
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• 2001

Objectives : To investigate the effects of particulate matter (PM), a marker of environmental pollution derived from combustion sources, on lung epithelial cells (A549) and macrophage (RAW 264.7). Methods : The production of reactive radicals from lung cells, the lipid peroxidation of cell membrane, and the cytotoxicity of PM were measured using an in vitro model. The results were compared with a control group. Results : The presence of PM significantly increased the production of reactive oxygen species and reactive nitrogen species with time and in a dose dependent pattern and also increased the malondialdehyde concentration in lung epithelial cells. The cytotoxicity of PM was increased with increasing concentration of PM. Conclusions : It has been suggested that urban particulate matter causes an inflammatory reaction in lung tissue through the production of hydroxyl radicals, nitric oxides and numerous cytokines. The causal chemical determinant responsible for these biologic effects are not well understood, but the bioavailable metal in PM seems to determine the tonicity of inhaled PM.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.6
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• pp.1449-1459
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• 2009

Coptidis rhizoma (huanglian) is an herb that is widely used in traditional Chinese medicine that has recently been shown to possess anticancer activity. However, the molecular mechanism underlying the anticancer effects of this herb is poorly understood. In this study, we investigated the anticancer activity of a combination of CR extract and arsenic trioxide, as well as the apoptotic pathway associated with its mechanism of action in human lung cancer H157 cells. Combined treatment of H157 cells with CR extract and arsenic trioxide resulted in significant apoptotic death. In addition, combined treatment with CR extract and arsenic trioxide acted in concert to induce a loss of mitochondrial membrane potential (${\Delta}{\Psi}$), the release of cytochrome c from mitochondria, and an increase in the expression of pro-apoptotic p53 and Bax protein, which resulted in activation of caspases and apoptosis. CR extract combined with arsenic trioxide also increased the lipid peroxidation, mRNA expression of DR4 and DR5 and caspase-8 activity. These data indicate that combined treatment with CR extract and arsenic trioxide enhanced apoptotic cell death in H157 cells through diverse pathways, including mitochondrial dysfunction and death receptors, particularly DR4 and DR5. Thus, this treatment may be an effective from of chemotherapy.

• Journal of Pharmacopuncture
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• v.20 no.4
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• pp.235-242
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• 2017

Irisin is a novel hormone like polypeptide that is cleaved and secreted by an unknown protease from fibronectin type III domain-containing protein 5 (FNDC5), a membrane-spanning protein and which is highly expressed in skeletal muscle, heart, adipose tissue, and liver. Since its discovery in 2012, it has been the subject of many researches due to its potent physiological role. It is believed that understanding irisin's function may be the key to comprehend many diseases and their development. Irisin is a myokine that leads to increased energy expenditure by stimulating the 'browning' of white adipose tissue. In the first description of this hormone, increased levels of circulating irisin, which is cleaved from its precursor fibronectin type III domain-containing protein 5, were associated with improved glucose homeostasis by reducing insulin resistance. Irisin is a powerful messenger, sending the signal to determine the function of specific cells, like skeletal muscle, liver, pancreas, heart, fat and the brain. The action of irisin on different targeted tissues or organs in human being has revealed its physiological functions for promoting health or executing the regulation of variety of metabolic diseases. Numerous studies focus on the association of irisin with metabolic diseases which has gained great interest as a potential new target to combat type 2 diabetes mellitus and insulin resistance. Irisin is found to improve insulin resistance and type 2 diabetes by increasing sensitization of the insulin receptor in skeletal muscle and heart by improving hepatic glucose and lipid metabolism, promoting pancreatic ${\beta}$ cell functions, and transforming white adipose tissue to brown adipose tissue. This review is a thoughtful attempt to summarize the current knowledge of irisin and its effective role in mediating metabolic dysfunctions in insulin resistance and type 2 diabetes mellitus.

• Korean Journal of Veterinary Research
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• v.23 no.1
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• pp.45-56
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• 1983

In order to prepare an experimental model on the basis of morphological changes of liver, 90 rabbits were allocated into four groups and 5, 15, 30 and 50% of ethanol (5ml/day) were dosed to each group for 5, 10, 20, 30, 60 and 90 days, and observed the livers with light and electron microscope. The results obtained are summarized as follows: 1. Light microscopically, the hydropic changes were found in the liver from 10th day after 5% and 15% ethanol ingestion, and these findings were remarkable as time goes by. Necrosis of hepatocytes, however, was most remarkable on 60th and 90th day after ingestion. The proliferation of interlobular connective tissue was found from 30th day in this group. 2. The hydropic necrosis of liver cells was found from 5th day in 30% and 50% ethanol dosing groups. The proliferation of interlobular connective tissues and infiltration of the lymphocytes were observed from 30th day in 30% ethanol ingestion group, however, it was found from 20th day in 50% ethanol ingestion group. 3. Electron microscopically, the appearance of various lipid droplets and dilated rER, slightly increased sER and glycogen field, dense mitochondria with scanty cristae and hydropic change were observed on 5th day after 5% ethanol ingestion. These findings were more remarkable on 30th and 90th day. Especially, disorganized outer and inner membrane of mitochondria and autophagic vacuoles were appeared on 90th day. The similar findings were also found in 15%, 30% and 50% ethanol ingestion groups, however, the appearance of fibrillar and myelin-like structures were observed from 30th day after 15% ethanol ingestion. The severe hydropic change and increased sER were observed on 90th day after 15% ethanol ingestion. From 5th day after 30% and 50% ethanol ingestion these findings were more remarkable.

• Journal of the Korean Society of Food Science and Nutrition
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• v.26 no.6
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• pp.1173-1180
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• 1997

Hepatotoxicity of caffeine and acetaminophen was investigated in this study. Special attention was paid to the effect of vitamins on the reduction of hepatotoxicity caused by the chemicals. Rat hepaocytes isolated by two-step perfusion method were cultured in two differents methods-suspension, monolayer cultures-, and exposed to caffeine and/or acetaminophen for 24hrs. Caffeine or acetaminophen exhibited no significant hepatotoxicity in terms of intracellular glutathione(GSH) level and lipid peroxidation(MDA), but GSH level was significantly decreased after administrated acetaminophen, and the toxicity caused by the chemicals showed a dose-dependent manner. The synergistic effect of caffeine and acetaminophen was observed when both caffeine and acetaminophen were supplemented to culture medium. At the concentration 1mM, caffeine enhanced the intracellular GSH depletion and MDA formation by 63% and 64%, respectively, compared to single supplementation of 10mM acetaminophen in culture medium. This hepatotoxicity induced membrane integrity loss was observed by lightmicroscope on the simultaneous administration of caffeine and acetaminophen in monolayer cultured hepatocytes. Co-supplementation of vitamins with caffeine/acetaminophen to culture medium results in the protection of hepatocytes from hepatotoxic attach by caffeine/acetaminophen. Especially, vitamin E was superior to vitamin C and $\beta$-carotene from the standpoints of GSH depletion and MDA formation. From this results, it has been speculated that vitamin E may play a role of antioxidant scavenging radicals produced from acetaminophen. Taken all together, in vitro culture system like monolayer culture of hepatocytes may be a useful tool for the evaluation of hepatotoxicity or protection ability of food ingredients.

• Bulletin of the Korean Chemical Society
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• v.20 no.9
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• pp.1078-1084
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• 1999

A synthetic cecropin A(1-13)-melittin(1-13) [CA-ME] hybrid peptide was known to be an antimicrobial peptide having strong antibacterial, antifungal and antitumor activity with minimal cytotoxic effect against human erythrocyte. Analogues were synthesized to investigate the influences of the flexible hinge region of CA-ME on the antibiotic activity. Antibiotic activity of the peptides was measured by the growth inhibition against bac-terial, fungal and tumor cells and vesicle-aggregating or disrupting activity. The deletion of Gln-Gly-Ile (P1) or Gly-Gln-Gly-Ile-Gly (P3) from CA-ME brought about a significant decrease on the antibiotic activities. In contrast, Gly-Ile-Gly deletion (P2) from CA-ME or Pro insertion (P5) instead of Gly-Gln-Gly-Ile-Gly of CA-ME retained antibiotic activity. This result indicated that the flexible hinge or β-bend structure provided by Gly-Gln-Gly-Ile-Gly, Gln-Gly, or Pro in the central region of the peptides is requisite for its effective antibiotic activity and may facilitate easily the hydrophobic C-terminal region of the peptide to penetrate the lipid bilayers of the target cell membrane. In contrast, P4 and P6 with Gly-Gln-Gly-Pro-Gly or Gly-Gln-Pro in the central region of the peptide caused a drastic reduction on the antibiotic activities. This result suggested that the con-secutive β-bend structure provided by Gly-Gln-Gly-Pro-Gly or Gly-Gln-Pro in the central hinge region of the peptide seems to interrupt the ion channel/pore formation on the target cell membranes.

• Molecules and Cells
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• v.44 no.9
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• pp.637-646
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• 2021

Free fatty acids are converted to acyl-CoA by long-chain acyl-CoA synthetases (ACSLs) before entering into metabolic pathways for lipid biosynthesis or degradation. ACSL family members have highly conserved amino acid sequences except for their N-terminal regions. Several reports have shown that ACSL1, among the ACSLs, is located in mitochondria and mainly leads fatty acids to the β-oxidation pathway in various cell types. In this study, we investigated how ACSL1 was localized in mitochondria and whether ACSL1 overexpression affected fatty acid oxidation (FAO) rates in C2C12 myotubes. We generated an ACSL1 mutant in which the N-terminal 100 amino acids were deleted and compared its localization and function with those of the ACSL1 wild type. We found that ACSL1 adjoined the outer membrane of mitochondria through interaction of its N-terminal region with carnitine palmitoyltransferase-1b (CPT1b) in C2C12 myotubes. In addition, overexpressed ACSL1, but not the ACSL1 mutant, increased FAO, and ameliorated palmitate-induced insulin resistance in C2C12 myotubes. These results suggested that targeting of ACSL1 to mitochondria is essential in increasing FAO in myotubes, which can reduce insulin resistance in obesity and related metabolic disorders.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.2
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• pp.113-120
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• 2019

Mannosylerythritol lipids (MELs) are glycolipids and have several pharmacological efficacies. MELs also show skin-moisturizing efficacy through a yet-unknown underlying mechanism. Aquaporin-3 (AQP3) is a membrane protein that contributes to the water homeostasis of the epidermis, and decreased AQP3 expression following ultraviolet (UV)-irradiation of the skin is associated with reduced skin moisture. No previous study has examined whether the skin-moisturizing effect of MELs might act through the modulation of AQP3 expression. Here, we report for the first time that MELs ameliorate the UVA-induced downregulation of AQP3 in cultured human epidermal keratinocytes (HaCaT keratinocytes). Our results revealed that UVA irradiation decreases AQP3 expression at the protein and messenger RNA (mRNA) levels, but that MEL treatment significantly ameliorated these effects. Our mitogen-activated protein kinase inhibitor analysis revealed that phosphorylation of c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase or p38, mediates UVA-induced AQP3 downregulation, and that MEL treatment significantly suppressed the UVA-induced phosphorylation of JNK. To explore a possible mechanism, we tested whether MELs could regulate the expression of peroxidase proliferator-activated receptor gamma ($PPAR-{\gamma}$), which acts as a potent transcription factor for AQP3 expression. Interestingly, UVA irradiation significantly inhibited the mRNA expression of $PPAR-{\gamma}$ in HaCaT keratinocytes, whereas a JNK inhibitor and MELs significantly rescued this effect. Taken together, these findings suggest that MELs ameliorate UVA-induced AQP3 downregulation in HaCaT keratinocytes by suppressing JNK activation to block the decrease of $PPAR-{\gamma}$. Collectively, our findings suggest that MELs can be used as a potential ingredient that modulates AQP3 expression to improve skin moisturization following UVA irradiation-induced damage.

• The Plant Pathology Journal
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• v.35 no.5
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• pp.445-458
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• 2019

The lipopolysaccharide (LPS) composed of lipid A, core, and O-antigen is the fundamental constituent of the outer membrane in gram-negative bacteria. This study was conducted to investigate the roles of LPS in Burkholderia glumae, the phytopathogen causing bacterial panicle blight and seedling rot in rice. To study the roles of the core oligosaccharide (OS) and the O-antigen region, mutant strains targeting the waaC and the wbiFGHI genes were generated. The LPS profile was greatly affected by disruption of the waaC gene and slight reductions were observed in the O-antigen region following wbiFGHI deletions. The results indicated that disruption in the core OS biosynthesis-related gene, waaC, was associated with increased sensitivity to environmental stress conditions including acidic, osmotic, saline, and detergent stress, and to polymyxin B. Moreover, significant impairment in the swimming and swarming motility and attenuation of bacterial virulence to rice were also observed in the waaC-defective mutant. The motility and virulence of O-antigen mutants defective in any gene of the wbiFGHI operon, were not significantly different from the wild-type except in slight decrease in swimming and swarming motility with wbiH deletion. Altogether, the results of present study indicated that the LPS, particularly the core OS region, is required for tolerance to environmental stress and full virulence in B. glumae. To our knowledge, this is the first functional study of LPS in a plant pathogenic Burkholderia sp. and presents a step forward toward full understanding of B. glumae pathogenesis.