• Journal of Marine Bioscience and Biotechnology
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• v.6 no.2
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• pp.102-109
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• 2014

Cetaceans (whales, dolphins, and porpoises) are aquatic mammals that experienced drastic changes during the transition from terrestrial to aquatic environment. Morphological changes include streamlined body, alterations in the face, transformation of the forelimbs into flippers, disappearance of the hindlimbs and the acquisition of flukes on the tail. For a prolonged diving, cetaceans acquired hypoxia-resistance by developing various anatomical and physiological changes. However, molecular mechanisms underlying these adaptations are still limited. CREB-binding protein (CREBBP) is a transcriptional co-activator critical for embryonic development, growth control, metabolic homeostasis and responses to hypoxia. Natural selection analysis of five cetacean CREBBPs compared with those from 15 terrestrial relatives revealed strong purifying selection, supporting the importance of its role in mammals. However, prediction for amino acid changes that elicit functional difference of CREBBP identified three cetacean specific changes localized within a region required for interaction with SRCAP and in proximal regions to KIX domain of CREBBP. Mutations in CREBBP or SRCAP are known to cause craniofacial and skeletal defects in human, and KIX domain of CREBBP serves as a docking site for transcription factors including c-Myb, an essential regulator of haematopoiesis. In these respects, our study provides interesting insights into the functional adaptation of cetacean CREBBP for aquatic lifestyle.

• Molecules and Cells
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• v.43 no.3
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• pp.222-227
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• 2020

Inositol polyphosphate multikinase (IPMK) is required for the biosynthesis of inositol phosphates (IPs) through the phosphorylation of multiple IP metabolites such as IP3 and IP4. The biological significance of IPMK's catalytic actions to regulate cellular signaling events such as growth and metabolism has been studied extensively. However, pharmacological reagents that inhibit IPMK have not yet been identified. We employed a structure-based virtual screening of publicly available U.S. Food and Drug Administration-approved drugs and chemicals that identified the antidepressant, vilazodone, as an IPMK inhibitor. Docking simulations and pharmacophore analyses showed that vilazodone has a higher affinity for the ATP-binding catalytic region of IPMK than ATP and we validated that vilazodone inhibits IPMK's IP kinase activities in vitro. The incubation of vilazodone with NIH3T3-L1 fibroblasts reduced cellular levels of IP5 and other highly phosphorylated IPs without influencing IP4 levels. We further found decreased Akt phosphorylation in vilazodone-treated HCT116 cancer cells. These data clearly indicate selective cellular actions of vilazodone against IPMK-dependent catalytic steps in IP metabolism and Akt activation. Collectively, our data demonstrate vilazodone as a method to inhibit cellular IPMK, providing a valuable pharmacological agent to study and target the biological and pathological processes governed by IPMK.

• Proceedings of the Korean Institute of Navigation and Port Research Conference
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• 2009.06a
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• pp.435-438
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• 2009

A navigation aid buoy is a kind of safety facility for maritime navigation with a purpose of leading the vessels for navigating, docking and sail off. An advanced rechargeable battery is required for stable power supply for navigation aid buoy as the high magnitude LED lamps, real time location/control for navigation aids and e-Navigation support systems with maritime climate observation equipments have recently been deployed. This study is focused on the lithium battery, especially lithium polymer battery which is believed to be safer than the other types of batteries. The lithium polymer battery reviewed in this study is designed with $LiFePO_4$-based cathode, which has superior safety features to the oxide-based cathodes. Besides, a 3.6kWh battery pack has been built with the above-mentioned unit cells for the purpose of comparative research with lead acid battery system.

• KIPS Transactions on Software and Data Engineering
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• v.8 no.10
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• pp.421-426
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• 2019

In this paper, we propose a method to visualize the geometric features of the contact region between proteins in a protein complex. When proteins or ligands are represented as curved surfaces with irregularities, the property that the two surfaces contact each other without intersections is called shape compatibility. Protein-Protein or Protein-Ligand docking researches have shown that shape complementarity, chemical properties, and entropy play an important role in finding contact regions. Usually, after finding a region with high shape complementarity, we can predict the contact region by using residual polarity and hydrophobicity of amino acids belonging to this region. In the research for predicting the contact region, it is necessary to investigate the geometrical features of the contact region in known protein complexes. For this purpose, it is essential to visualize the geometric features of the molecular surface. In this paper, we propose a method to find the contact region, and visualize the geometric features of it as normal vectors and mean curvatures of the protein complex.

• Journal of Ginseng Research
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• v.43 no.4
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• pp.550-561
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• 2019

Background: Gastric ulcer (GU) is a common gastrointestinal disease that can be induced by many factors. Finding an effective treatment method that contains fewer side effects is important. 20 (S)-ginsenoside Rg3 is a kind of protopanaxadiol and has shown superior antiinflammatory and antioxidant effects in many studies, especially cancer studies. In this study, we examined the treatment efficacy of 20 (S)-ginsenoside Rg3 on GU. Methods: Three kinds of GU models, including an alcohol GU model, a pylorus-ligated GU model, and an acetic acid GU model, were used. Mouse endothelin-1 (ET-1) and nitric oxide (NO) levels in blood and epidermal growth factor (EGF), superoxide dismutase, and NO levels in gastric mucosa were evaluated. Hematoxylin and eosin staining of gastric mucosa and immunohistochemical staining of ET-1, inducible nitric oxide synthase (NOS2), and epidermal growth factor receptors were studied. Ulcer index (UI) scores and UI ratios were also analyzed to demonstrate the GU conditions in different groups. Furthermore, Glide XP from $Schr{\ddot{o}}dinger$ was used for molecular docking to clarify the interactions between 20 (S)-ginsenoside Rg3 and EGF and NOS2. Results: 20 (S)-ginsenoside Rg3 significantly decreased the UI scores and UI ratios in all the three GU models, and it demonstrated antiulcer effects by decreasing the ET-1 and NOS2 levels and increasing the NO, superoxide dismutase, EGF, and epidermal growth factor receptor levels. In addition, high-dose 20 (S)-ginsenoside Rg3 showed satisfactory gastric mucosa protection effects. Conclusion: 20 (S)-ginsenoside Rg3 can inhibit the formation of GU and may be a potential therapeutic agent for GU.

• Biomolecules & Therapeutics
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• v.29 no.6
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• pp.630-636
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• 2021

Eupafolin, a constituent of the aerial parts of Phyla nodiflora, has neuroprotective property. Because reducing the synaptic release of glutamate is crucial to achieving pharmacotherapeutic effects of neuroprotectants, we investigated the effect of eupafolin on glutamate release in rat cerebrocortical synaptosomes and explored the possible mechanism. We discovered that eupafolin depressed 4-aminopyridine (4-AP)-induced glutamate release, and this phenomenon was prevented in the absence of extracellular calcium. Eupafolin inhibition of glutamate release from synaptic vesicles was confirmed through measurement of the release of the fluorescent dye FM 1-43. Eupafolin decreased 4-AP-induced [Ca²⁺]_i elevation and had no effect on synaptosomal membrane potential. The inhibition of P/Q-type Ca²⁺ channels reduced the decrease in glutamate release that was caused by eupafolin, and docking data revealed that eupafolin interacted with P/Q-type Ca²⁺ channels. Additionally, the inhibition of calcium/calmodulin-dependent protein kinase II (CaMKII) prevented the effect of eupafolin on evoked glutamate release. Eupafolin also reduced the 4-AP-induced activation of CaMK II and the subsequent phosphorylation of synapsin I, which is the main presynaptic target of CaMKII. Therefore, eupafolin suppresses P/Q-type Ca²⁺ channels and thereby inhibits CaMKII/synapsin I pathways and the release of glutamate from rat cerebrocortical synaptosomes.

• Journal of Microbiology and Biotechnology
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• v.31 no.3
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• pp.483-491
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• 2021

Two putative genes, lip29 and est29, encoding lipolytic enzymes from the thermophilic bacterium Geobacillus thermocatenulatus KCTC 3921 were cloned and overexpressed in Escherichia coli. The recombinant Lip29 and Est29 were purified 67.3-fold to homogeneity with specific activity of 2.27 U/mg and recovery of 5.8% and 14.4-fold with specific activity of 0.92 U/mg and recovery of 1.3%, respectively. The molecular mass of each purified enzyme was estimated to be 29 kDa by SDS-PAGE. The alignment analysis of amino acid sequences revealed that both enzymes belonged to GDSL lipase/esterase family including conserved blocks with SGNH catalytic residues which was mainly identified in plants before. While Est29 showed high specificity toward short-chain fatty acids (C4-C8), Lip29 showed strong lipolytic activity to long-chain fatty acids (C12-C16). The optimal activity of Lip29 toward p-nitrophenyl palmitate as a substrate was observed at 50℃ and pH 9.5, respectively, and its activity was maintained more than 24 h at optimal temperatures, indicating that Lip29 was thermostable. Lip29 exhibited high tolerance against detergents and metal ions. The homology modeling and substrate docking revealed that the long-chain substrates showed the greatest binding affinity toward enzyme. Based on the biochemical and insilico analyses, we present for the first time a GDSL-type lipase in the thermophilic bacteria group.

• Genomics & Informatics
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• v.19 no.1
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• pp.6.1-6.10
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• 2021

Vascular endothelial growth factor (VEGF) is expressed at elevated levels by most cancer cells, which can stimulate vascular endothelial cell growth, survival, proliferation as well as trigger angiogenesis modulated by VEGF and VEGFR (a tyrosine kinase receptor) signaling. The angiogenic effects of the VEGF family are thought to be primarily mediated through the interaction of VEGF with VEGFR-2. Targeting this signaling molecule and its receptor is a novel approach for blocking angiogenesis. In recent years virtual high throughput screening has emerged as a widely accepted powerful technique in the identification of novel and diverse leads. The high resolution X-ray structure of VEGF has paved the way to introduce new small molecular inhibitors by structure-based virtual screening. In this study using different alkaloid molecules as potential novel inhibitors of VEGF, we proposed three alkaloid candidates for inhibiting VEGF and VEGFR mediated angiogenesis. As these three alkaloid compounds exhibited high scoring functions, which also highlights their high binding ability, it is evident that these alkaloids can be taken to further drug development pipelines for use as novel lead compounds to design new and effective drugs against cancer.

• Journal of Ginseng Research
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• v.43 no.3
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• pp.442-451
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• 2019

Background: Ginseng has a wide range of beneficial effects on health, such as the mitigation of minor and major inflammatory diseases, cancer, and cardiovascular diseases. There are abundant data regarding the health-enhancing properties of whole ginseng extracts and single ginsenosides; however, no study to date has determined the receptors that mediate the effects of ginseng extracts. In this study, for the first time, we explored whether the antiinflammatory effects of Rg3-enriched red ginseng extract (Rg3-RGE) are mediated by retinoid X receptor ${\alpha}$-peroxisome-proliferating receptor ${\gamma}$ ($RXR{\alpha}-PPAR{\gamma}$) heterodimer nuclear receptors. Methods: Nitric oxide assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay, quantitative reverse transcription polymerase chain reaction, nuclear hormone receptor-binding assay, and molecular docking analyses were used for this study. Results: Rg3-RGE exerted antiinflammatory effects via nuclear receptor heterodimers between $RXR{\alpha}$ and $PPAR{\gamma}$ agonists and antagonists. Conclusion: These findings indicate that Rg3-RGE can be considered a potent antiinflammatory agent, and these effects are likely mediated by the nuclear receptor $RXR{\alpha}-PPAR{\gamma}$ heterodimer.

• Journal of the Korean Society of Marine Environment & Safety
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• v.25 no.1
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• pp.122-129
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• 2019

Due to its nature the manufacturing industry faces a cyclical economy, and therefore there is an urgent need for a companion industry to cope with this cyclic pattern in the long run. The sector suitable for meeting this demand is the repair and shipbuilding industry. In order to operate a shipbuilding repair business, a floating dock is indispensable, and most obsolete floating docks were imported from overseas and operated through repair/maintenance. However, there is no precise guideline for floating dock safety, and most models have been in use for at least 30 years without being required to enter classification at the time of operation. In this study, structural strength analysis was carried out using measured thickness information of aged floating docks, and the residual structural strength of floating docks in operation was analyzed. The main results derived from this study can be referred to as guidelines for the review of the structural safety of similar equipment, and it is expected that an optimal solution will be found within a short time using this method for repair/maintenance.