• BMB Reports
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• v.51 no.1
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• pp.14-20
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• 2018

Biomedical research involving nanoparticles has produced useful products with medical applications. However, the potential toxicity of nanoparticles in biofluids, cells, tissues, and organisms is a major challenge. The '-omics' analyses provide molecular profiles of multifactorial biological systems instead of focusing on a single molecule. The 'omics' approaches are necessary to evaluate nanotoxicity because classical methods for the detection of nanotoxicity have limited ability in detecting miniscule variations within a cell and do not accurately reflect the actual levels of nanotoxicity. In addition, the 'omics' approaches allow analyses of in-depth changes and compensate for the differences associated with high-throughput technologies between actual nanotoxicity and results from traditional cytotoxic evaluations. However, compared with a single omics approach, integrated omics provides precise and sensitive information by integrating complex biological conditions. Thus, these technologies contribute to extended safety evaluations of nanotoxicity and allow the accurate diagnoses of diseases far earlier than was once possible in the nanotechnology era. Here, we review a novel approach for evaluating nanotoxicity by integrating metabolomics with metabolomic profiling and transcriptomics, which is termed "metabotranscriptomics."

• Molecules and Cells
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• v.42 no.10
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• pp.702-710
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• 2019

Neuroinflammation is an important contributor to the pathogenesis of neurodegenerative disorders including Parkinson's disease (PD). We previously reported that our novel synthetic compound KMS99220 has a good pharmacokinetic profile, enters the brain, exerts neuroprotective effect, and inhibits $NF{\kappa}B$ activation. To further assess the utility of KMS99220 as a potential therapeutic agent for PD, we tested whether KMS99220 exerts an anti-inflammatory effect in vivo and examined the molecular mechanism mediating this phenomenon. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice, oral administration of KMS99220 attenuated microglial activation and decreased the levels of inducible nitric oxide synthase and interleukin 1 beta ($IL-1{\beta}$) in the nigrostriatal system. In lipopolysaccharide (LPS)-challenged BV-2 microglial cells, KMS99220 suppressed the production and expression of $IL-1{\beta}$. In the activated microglia, KMS99220 reduced the phosphorylation of $I{\kappa}B$ kinase, c-Jun N-terminal kinase, and p38 MAP kinase; this effect was mediated by heme oxygenase-1 (HO-1), as both gene silencing and pharmacological inhibition of HO-1 abolished the effect of KMS99220. KMS99220 induced nuclear translocation of the transcription factor Nrf2 and expression of the Nrf2 target genes including HO-1. Together with our earlier findings, our current results show that KMS99220 may be a potential therapeutic agent for neuroinflammation-related neurodegenerative diseases such as PD.

• Fisheries and Aquatic Sciences
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• v.25 no.3
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• pp.140-150
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• 2022

A method of ultrahigh performance liquid chromatography coupled to high resolution mass spectrometry (UPLC-HRMS) was established for characterization of the lipid profile of Skipjack tuna. Over 300 lipid molecular species were identified through cross-acquisition in both positive and negative ion mode. Phospholipids (PLs) were dominant in Skipjack tuna. Lysophosphatidylethanolamine (LPE), phosphatidylethanolamine (PE), lysophosphatidylcholine (LPC) and phosphatidylcholine (PC) were the main lipid molecular species in PLs, accounting for 89.24% of the total PLs. The ratio of sphingolipids (SLs) and glycerolipids (GLs) were considerable, accounting for 12.30% and 13.60% of the total lipids respectively. Ceramide (Cer) was the main lipid molecular species of SLs, accounting for 64.96% of total SLs, followed by sphingomyelin (SM), accounting for 25.45% of total SLs. Ether diglycerides (ether DG) were the main lipid molecular species of GLs (97.83%). The main fatty acids (FAs) are unsaturated fatty acids (UFAs) in Skipjack tuna. Besides, a new FAs class branched fatty acid esters of hydroxy fatty acids (FAHFA) was detected, together with the FA. The active lipids identified in this study can be used to evaluate the nutritional value of Skipjack tuna.

• Molecular & Cellular Toxicology
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• v.4 no.1
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• pp.31-44
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• 2008

The forced swim test (FST) is the most widely used model for assessing potential antidepressant activity. Although it has been shown that lateral septum is involved with the FST-related behavior, it is not clear whether antidepressant treatments could alter the FST-induced gene expression profile in the lateral septum. In the present study, the gene expression profiles in response to FST and reboxetine pretreatment were observed in the lateral septum of rats. Reboxetine is known as a most selective serotonin norepinephrine reuptake inhibitor. In addition, we compared the changes in gene expression profile between reboxetine response and nonresponse groups, which were determined by counting FST-related behavior. After FST, lateral septum from controls and reboxetine pretreated group were dissected and gene expression profiles were assessed using an Affymetrix microarray system containing 15,923 genes. Various genes with different functions were changed in reboxetine response group compared with reboxetine nonresponse group, In particular, pleiotrophin, orexin receptor 2, serotonin 2A receptor, neuropeptide Y5 receptor and thyroid hormone receptor $\beta$ were decreased in reboxetine response group, but Lim motif-containing protein kinase 1 (Limk1) and histone deacetylase 1 (HDAC1) were increased. Although further studies are required for direct roles of these genes in reboxetine response, the microarray may provide tools to find out potential target genes and signaling pathways in antidepressant response.

• BMB Reports
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• v.40 no.3
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• pp.315-324
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• 2007

The novel $\alpha$-amylase purified from locally isolated strain, Bacillus sp. KR-8104, (KRA) (Enzyme Microb Technol; 2005; 36: 666-671) is active in a wide range of pH. The enzyme maximum activity is at pH 4.0 and it retains 90% of activity at pH 3.5. The irreversible thermoinactivation patterns of KRA and the enzyme activity are not changed in the presence and absence of $Ca^{2+}$ and EDTA. Therefore, KRA acts as a $Ca^{2+}$-independent enzyme. Based on circular dichroism (CD) data from thermal unfolding of the enzyme recorded at 222 nm, addition of $Ca^{2+}$ and EDTA similar to its irreversible thermoinactivation, does not influence the thermal denaturation of the enzyme and its Tm. The amino acid sequence of KRA was obtained from the nucleotide sequencing of PCR products of encoding gene. The deduced amino acid sequence of the enzyme revealed a very high sequence homology to Bacillus amyloliquefaciens (BAA) (85% identity, 90% similarity) and Bacillus licheniformis $\alpha$-amylases (BLA) (81% identity, 88% similarity). To elucidate and understand these characteristics of the $\alpha$-amylase, a model of 3D structure of KRA was constructed using the crystal structure of the mutant of BLA as the platform and refined with a molecular dynamics (MD) simulation program. Interestingly enough, there is only one amino acid substitution for KRA in comparison with BLA and BAA in the region involved in the calcium-binding sites. On the other hand, there are many amino acid differences between BLA and KRA at the interface of A and B domains and around the metal triad and active site area. These alterations could have a role in stabilizing the native structure of the loop in the active site cleft and maintenance and stabilization of the putative metal triad-binding site. The amino acid differences at the active site cleft and around the catalytic residues might affect their pKa values and consequently shift its pH profile. In addition, the intrinsic fluorescence intensity of the enzyme at 350 nm does not show considerable change at pH 3.5-7.0.

• Horticultural Science & Technology
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• v.35 no.1
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• pp.98-107
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• 2017

A DNA profile database was constructed to investigate the genetic relatedness of 72 germplasm samples of Pyrus and related cultivars using microsatellite markers. Three P. pyrifolia, four P. commus, and one P. betulifolia cultivars with different morphological traits were screened using 387 pairs of microsatellite primers. A core set of 11 primer pairs was selected to obtain 133 polymorphic amplified fragments meeting three criteria: high polymorphism information contents (PIC), high repeatability, and distinct allele patterns. The number of alleles per locus ranged between 4 and 22. Average PIC was 0.743 (range: 0.557 - 0.879). Cluster analysis using the unweighted pair - group method with arithmetical average (UPGMA) separated the 72 pear cultivars and germplasm samples into four major groups: Chinese, European pears, and a cluster of 55 Asian pears that could be reclassify into two subcluster, I - $1^{st}$ and II - $2^{nd}$, according to pedigree information. Almost all of the cultivars were discriminated by 11 microsatellite marker genotypes. The microsatellite DNA profile database may be utilized as tool to verify distinctness, uniformity, and stability between candidate cultivar, and to verify in the distinctness of existing cultivars.

• Korean Chemical Engineering Research
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• v.48 no.2
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• pp.147-156
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• 2010

There are four key factors for gas-phase biofilters; biocatalysts(microorganisms), packing materials, design/operating techniques, and diagnosis/management techniques. Biofilter performance is significantly affected by microbial community structures as well as loading conditions. The microbial studies on biofilters are mostly performed on basis of culture-dependent methods. Recently, advanced methods have been proposed to characterize the microbial community structure in environmental samples. In this study, the physiological, biochemical and molecular methods for profiling microbial communities are reviewed, and their applicability to biofilters is discussed. Community-level physiological profile is based on the utilization capability of carbon substrate by heterotrophic community in environmental samples. Phospholipid fatty acid analysis method is based on the variability of fatty acids present in cell membranes of different microorganisms. Molecular methods using DNA directly extracted from environmental samples can be divided into "partial community DNA analysis" and "whole community DNA analysis" approaches. The former approaches consist in the analysis of PCR-amplified sequence, the genes of ribosomal operon are the most commonly used sequences. These methods include PCR fragment cloning and genetic fingerprinting such as denaturing gradient gel electrophoresis, terminal-restriction fragment length polymorphism, ribosomal intergenic spacer analysis, and random amplified polymorphic DNA. The whole community DNA analysis methods are total genomic cross-DNA hybridization, thermal denaturation and reassociation of whole extracted DNA and extracted whole DNA fractionation using density gradient.

• Proceedings of the Korean Vacuum Society Conference
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• 2015.08a
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• pp.61.1-61.1
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• 2015

Nanoscale semiconductor plasma processing has become one of the most challenging issues due to the limits of physicochemical fabrication routes with its inherent complexity. The mission of future and emerging plasma processing for development of next generation semiconductor processing is to achieve the ideal nanostructures without abnormal profiles and damages, such as 3D NAND cell array with ultra-high aspect ratio, cylinder capacitors, shallow trench isolation, and 3D logic devices. In spite of significant contributions of research frontiers, these processes are still unveiled due to their inherent complexity of physicochemical behaviors, and gaps in academic research prevent their predictable simulation. To overcome these issues, a Korean plasma consortium began in 2009 with the principal aim to develop a realistic and ultrafast 3D topography simulator of semiconductor plasma processing coupled with zero-D bulk plasma models. In this work, aspects of this computational tool are introduced. The simulator was composed of a multiple 3D level-set based moving algorithm, zero-D bulk plasma module including pulsed plasma processing, a 3D ballistic transport module, and a surface reaction module. The main rate coefficients in bulk and surface reaction models were extracted by molecular simulations or fitting experimental data from several diagnostic tools in an inductively coupled fluorocarbon plasma system. Furthermore, it is well known that realistic ballistic transport is a simulation bottleneck due to the brute-force computation required. In this work, effective parallel computing using graphics processing units was applied to improve the computational performance drastically, so that computer-aided design of these processes is possible due to drastically reduced computational time. Finally, it is demonstrated that 3D feature profile simulations coupled with bulk plasma models can lead to better understanding of abnormal behaviors, such as necking, bowing, etch stops and twisting during high aspect ratio contact hole etch.

• Molecular & Cellular Toxicology
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• v.2 no.4
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• pp.273-278
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• 2006

95 squamous cell lung carcinoma samples (normal tissue: 40 samples, tumor: 55 samples) were analyzed with 8 K cDNA microarray. 1-way ANOVA test was employed to select differentially expressed genes in tumor with FDR<0.01. Among the selected 1,655 genes, final 212 genes were chosen according to the expression fold change and used for following analysis. The expression of up-regulated 64 genes was verified with Reverse Transcription PCR and 10 genes were identified as candidates for SCC markers. In our opinion, those candidates can be exploited as diagnostic or therapeutic purposes. Gene Ontology (GO) based analysis was performed using those 212 genes, and following categories were revealed as significant biological processes: Immune response (GO: 0006955), antigen processing (GO: 0030333), inflammatory response (GO: 0006954), Cell adhesion (GO: 0007155), and Epidermis differentiation (GO: 0008544). Gene set enrichment analysis (GSEA) also carried out on overall gene expression profile with 522 functional gene sets. Glycolysis, cell cycle, K-ras and amino acid biosynthesis related gene sets were most distinguished. These results are consistent with the known characteristics of SCC and may be interconnected to rapid cell proliferation. However, the unexpected results from ERK activation in squamous cell carcinoma gripped our attention, and further studies are under progress.

• Biomolecules & Therapeutics
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• v.20 no.2
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• pp.171-176
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• 2012

HaCaT cells are the immortalized human keratinocytes and have been extensively used to study the epidermal homeostasis and its pathophysiology. T helper cells play a role in various chronic dermatological conditions and they can affect skin barrier homeostasis. To evaluate whether HaCaT cells can be used as a model cell system to study abnormal skin barrier development in various dermatologic diseases, we analyzed the gene expression profile of epidermal differentiation markers of HaCaT cells in response to major T helper (Th) cell cytokines, such as $IFN{\gamma}$, IL-4, IL-17A and IL-22. The gene transcriptional profile of cornified envelope-associated proteins, such as filaggrin, loricrin, involucrin and keratin 10 (KRT10), in HaCaT cells was generally different from that in normal human keratinocytes (NHKs). This suggests that HaCaT cells have a limitation as a model system to study the pathophysiological mechanism associated with the Th cell cytokine-dependent changes in cornified envelope-associated proteins which are essential for normal skin barrier development. In contrast, the gene transcription profile change of human ${\beta}2$-defensin (HBD2) in response to $IFN{\gamma}$, IL-4 or IL-17A in HaCaT cells was consistent with the expression pattern of NHKs. $IFN{\gamma}$ also up-regulated transglutaminase 2 (TGM2) gene transcription in both HaCaT cells and NHKs. As an alternative cell culture system for NHKs, HaCaT cells can be used to study molecular mechanisms associated with abnormal HBD2 and TGM2 expression in response to $IFN{\gamma}$, IL-4 or IL-17A.