• Proceedings of the Korean Institute of Surface Engineering Conference
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• 2016.11a
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• pp.122.2-122.2
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• 2016

Surface topographical cues has been highlighted to control the fate of neural stem cells (NSCs). Herein we developed a hierarchically patterned substrate (HPS) platform for regulating NSC differentiation. The HPS induced cytoskeleton alignment and highly activated focal adhesion in hNSCs as indicated by enhanced expression of focal adhesion proteins such as focal adhesion kinase (FAK) and vinculin. hNSCs cultured on HPS exhibited enhanced neuronal differentiation compared to flat group. We also developed a graphene oxide (GO)-based hierarchically patterned substrates (GPS) that promote focal adhesion formation and neuronal differentiation of hNSCs. Enhanced focal adhesion and differentiation of hNSCs on the HPS was reversed by blocking the ${\beta}1$ integrin binding and mechanotransduction-associated signals including Rho-associated protein kinase (ROCK) and extracellular-regulated kinase (ERK) pathway, which may suggest a potential mechanism of beneficial effects of HPS. In addition, hNSCs on the HPS differentiated into functional neurons exhibiting sodium currents and action potentials as confirmed by whole cell patch-clamping analysis. The hierarchical topography can direct differentiation of NSCs towards functional neurons, and therefore would be an important element for the design of functional biomaterials for neural tissue regeneration applications.

• Journal of Ginseng Research
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• v.39 no.2
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• pp.105-115
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• 2015

Background: Alcoholic steatosis is the earliest and most common liver disease, and may precede the onset of more severe forms of liver injury. Methods: The effect of Korean Red Ginseng extract (RGE) was tested in two murine models of ethanol (EtOH)-feeding and EtOH-treated hepatocytes. Results: Blood biochemistry analysis demonstrated that RGE treatment improved liver function. Histopathology and measurement of hepatic triglyceride content verified the ability of RGE to inhibit fat accumulation. Consistent with this, RGE administration downregulated hepatic lipogenic gene induction and restored hepatic lipolytic gene repression by EtOH. The role of oxidative stress in the pathogenesis of alcoholic liver diseases is well established. Treatment with RGE attenuated EtOH-induced cytochrome P450 2E1, 4-hydroxynonenal, and nitrotyrosine levels. Alcohol consumption also decreased phosphorylation of adenosine monophosphate-activated protein kinase, which was restored by RGE. Moreover, RGE markedly inhibited fat accumulation in EtOH-treated hepatocytes, which correlated with a decrease in sterol regulatory element-binding protein-1 and a commensurate increase in sirtuin 1 and peroxisome proliferator-activated receptor-a expression. Interestingly, the ginsenosides Rb2 and Rd, but not Rb1, significantly inhibited fat accumulation in hepatocytes. Conclusion: These results demonstrate that RGE and its ginsenoside components inhibit alcoholic steatosis and liver injury by adenosine monophosphate-activated protein kinase/sirtuin 1 activation both in vivo and in vitro, suggesting that RGE may have a potential to treat alcoholic liver disease.

• Journal of Acupuncture Research
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• v.23 no.2
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• pp.113-123
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• 2006

Objectives : Deer antler Herbal-Acupuncture (DHA) solution represents one of the most commonly used medicine to treat rheumatoid arthritis. But, mechanisms of its antiarthritic activities are still poorly understood. Identification of common DHA aqua-acupuncture capable of affording protection or modulating the onset and severity of arthritis may have important human health implications. Results : We determined if DHA could prevent the binding of $IL-1{\beta}$ to its cellular receptors. DHA addition to rat chondrocytes treated with $IL-1{\beta}$ or with reactive oxygen species(ROS) prevents the activation of proteoglycan synthesis. After treatment with $IL-1{\beta}$, DHA increased the expression of mRNA encoding the type II $IL-1{\beta}$ receptor. These results emphasize the potential role of two regulating proteins of the $IL-1{\beta}$ signaling pathway that could account for the beneficial effect of DHA in osteRArthritis. The present study also identifies a novel mechanism of DHA-mediated anti-inflammatory activity. Conclusion : It is shown that DHA inhibits both $IL-1{\beta}-$ and $TNF-{\alpha}-induced$ NO production in normal human articular chondrocytes. The observed suppression of IL-1-induced NO production is associated with inhibition of inducible NO synthase(iNOS) mRNA and protein expression. In addition, DHA also suppresses the production of IL-1-induced cyclooxygenase-2 and IL-6. The constitutively expressed cyclooxygenase-1, however, was not affected by the sugar. These results demonstrate that DHA expresses a unique range of activities and identifies a novel mechanism for the inhibition of inflammatory processes.

• Bulletin of the Korean Chemical Society
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• v.33 no.11
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• pp.3671-3675
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• 2012

${\beta}$-Amyloid accumulation in the brain is a pathological hallmark of Alzheimer's disease (AD). Since early detection of ${\beta}$-amyloid may facilitate more successful and timely therapeutic interventions, many investigators have focused on developing AD diagnostic reagents that can penetrate the blood-brain barrier (BBB). Oleanolic acid (OA) is a substance found in a variety of plants that has been reported to prevent the progression of AD in mice. In this study, we synthesized and evaluated a new radioligand in which OA was conjugated to lactoferrin (Lf, an iron-binding glycoprotein that crosses the BBB) for the diagnosis of AD. In an in vitro study in which OA-Lf was incubated with ${\beta}$-amyloid (1-42) aggregates for 24 h, we found that OA-Lf effectively inhibited ${\beta}$-amyloid aggregation and fibril formation. In vivo studies demonstrated that $^{123}I$-OA-Lf brain uptake was higher than$^{123}I$-Lf uptake. Therefore, radiolabeled OA-Lf may have diagnostic potential for ${\beta}$-amyloid imaging.

• Transactions of the Korean hydrogen and new energy society
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• v.29 no.3
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• pp.260-266
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• 2018

To enhance catalyst activity of the palladium (Pd) towards oxygen reduction reaction (ORR), iridium (Ir) and yttrium (Y) were alloyed by polyol method. Due to the low reduction potential of Y, it is hard to reduce Y ion completely by polyol method. In XPS spectra, the binding energy of the Pd is shifted to a lower value, which indicates the d-electron of Pd is filled by the electron from the Y. And other phases of Y are observed by the XPS. Among the catalysts, the $Pd_4IrY_{0.1}/C$ showed the best activity towards ORR, which indicates the metallic Y is effective for improving the catalytic activity. Thus, for further enhancing ORR activity, the novel method for complete reduction of Y is needed.

• Genomics & Informatics
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• v.3 no.2
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• pp.61-65
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• 2005

Comparing 231 genes on chimpanzee chromosome 22 with their orthologous on human chromosome 21, we have found that 15 orthologs have indels within their coding sequences. It was rather surprising that significant number of genes have changed by indel, despite the shorter time since their divergence and led us hypothesize that indels and structural changes may represent one of the major mechanism of proteome evolution in the higher primates. Human T-complex protein 10 like (TCP 10L) is a representative having indel within its coding sequence. Gene structure of human TCP10L compared with chimpanzee TCP10L gene showed 16 base pair difference in genomic DNA. As a result of the indel, frame shift mutation occurs in coding sequence (CDS) and human TCP10L express longer polypeptide of 21 amino acid residues than that of chimpanzee. Our prediction found that the indel may affect to dramatic change of secondary protein structure between human and chimpanzee TCP10L. Especially, the structural changes in the C-terminal region of TCP10L protein may affect on the interacting potential to other proteins rather than DNA binding function of the protein. Through these changes, TCP10L might influence gene expression profiles in liver and testis and subsequently influence the physiological changes required in primate evolution.

• Genomics & Informatics
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• v.12 no.4
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• pp.268-275
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• 2014

The harshness of legionellosis differs from mild Pontiac fever to potentially fatal Legionnaire's disease. The increasing development of drug resistance against legionellosis has led to explore new novel drug targets. It has been found that phosphoglucosamine mutase, phosphomannomutase, and phosphoglyceromutase enzymes can be used as the most probable therapeutic drug targets through extensive data mining. Phosphoglucosamine mutase is involved in amino sugar and nucleotide sugar metabolism. The purpose of this study was to predict the potential target of that specific drug. For this, the 3D structure of phosphoglucosamine mutase of Legionella pneumophila (strain Paris) was determined by means of homology modeling through Phyre2 and refined by ModRefiner. Then, the designed model was evaluated with a structure validation program, for instance, PROCHECK, ERRAT, Verify3D, and QMEAN, for further structural analysis. Secondary structural features were determined through self-optimized prediction method with alignment (SOPMA) and interacting networks by STRING. Consequently, we performed molecular docking studies. The analytical result of PROCHECK showed that 95.0% of the residues are in the most favored region, 4.50% are in the additional allowed region and 0.50% are in the generously allowed region of the Ramachandran plot. Verify3D graph value indicates a score of 0.71 and 89.791, 1.11 for ERRAT and QMEAN respectively. Arg419, Thr414, Ser412, and Thr9 were found to dock the substrate for the most favorable binding of S-mercaptocysteine. However, these findings from this current study will pave the way for further extensive investigation of this enzyme in wet lab experiments and in that way assist drug design against legionellosis.

• Genomics & Informatics
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• v.14 no.3
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• pp.125-135
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• 2016

Helicobacter pylori is a Gram-negative bacteria that is responsible for gastritis in human. Its spiral flagellated body helps in locomotion and colonization in the host environment. It is capable of living in the highly acidic environment of the stomach with the help of acid adaptive genes. The genome of H. pylori 26695 strain contains 1,555 coding genes that encode 1,445 proteins. Out of these, 340 proteins are characterized as hypothetical proteins (HP). This study involves extensive analysis of the HPs using an established pipeline which comprises various bioinformatics tools and databases to find out probable functions of the HPs and identification of virulence factors. After extensive analysis of all the 340 HPs, we found that 104 HPs are showing characteristic similarities with the proteins with known functions. Thus, on the basis of such similarities, we assigned probable functions to 104 HPs with high confidence and precision. All the predicted HPs contain representative members of diverse functional classes of proteins such as enzymes, transporters, binding proteins, regulatory proteins, proteins involved in cellular processes and other proteins with miscellaneous functions. Therefore, we classified 104 HPs into aforementioned functional groups. During the virulence factors analysis of the HPs, we found 11 HPs are showing significant virulence. The identification of virulence proteins with the help their predicted functions may pave the way for drug target estimation and development of effective drug to counter the activity of that protein.

• BMB Reports
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• v.41 no.11
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• pp.814-819
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• 2008

Interleukin-32 (IL-32) induces a variety of proinflammatory cytokines and chemokines. The IL-32 transcript was reported originally in activated T cells; subsequently, it was demonstrated to be abundantly expressed in epithelial and endothelial cells upon stimulation with inflammatory cytokines. IL-32 is regulated robustly by other major proinflammatory cytokines, thereby suggesting that IL-32 is crucial to inflammation and immune responses. Recently, an IL-32$\alpha$-affinity column was employed in order to isolate an IL-32 binding protein, neutrophil proteinase 3 (PR3). Proteinase 3 processes a variety of inflammatory cytokines, including TNF$\alpha$, IL-$1{\beta}$, IL-8, and IL-32, thereby enhancing their biological activities. In the current study, we designed four PR3-cleaved IL-32 separate domains, identified by potential PR3 cleavage sites in the IL-32$\alpha$ and $\gamma$ polypeptides. The separate domains of the IL-32 isoforms $\alpha$ and $\gamma$ were more active than the intrinsic $\alpha$ and $\gamma$ isoforms. Interestingly, the N-terminal IL-32 isoform $\gamma$ separate domain evidenced the highest levels of biological activity among the IL-32 separate domains.

• Archives of Pharmacal Research
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• v.29 no.5
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• pp.384-393
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• 2006

Protein carboxylmethylation methylates the free carboxyl groups in various substrate proteins by protein carboxyl O-methyltransferase (PCMT) and is one of the post-translational modifications. There have been many studies on protein carboxylmethylation. However, the precise functional role in mammalian systems is unclear. In this study, immunoglobulin, a specific form of $\gamma-globulin$, which is a well-known substrate for PCMT, was chosen to investigate the regulatory roles of protein carboxylmethylation in the immune system. It was found that the anti-BSA antibody could be carboxylmethylated via spleen PCMT to a level similar to $\gamma-globulin$. This carboxylmethylation increased the hydrophobicity of the anti-BSA antibody up to 11.4%, and enhanced the antigen-binding activity of this antibody up to 24.6%. In particular, the Fc region showed a higher methyl accepting capacity with 80% of the whole structure level. According to the amino acid sequence alignment, indeed, 7 aspartic acids and 5 glutamic acids, as potential carboxylmethylation sites, were found to be conserved in the Fc portion in the human, mouse and rabbit. The carboxylmethylation of the anti-BSA antibody was reversibly demethylated under a higher pH and long incubation time. Therefore, these results suggest that protein carboxylmethylation may reversibly regulate the antibody-mediated immunological events via the Fc region.