• Molecules and Cells
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• v.37 no.12
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• pp.888-898
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• 2014

Pancreatic cancer is one of the most fatal cancers and is associated with limited diagnostic and therapeutic modalities. Currently, gemcitabine is the only effective drug and represents the preferred first-line treatment for chemotherapy. However, a high level of intrinsic or acquired resistance of pancreatic cancer to gemcitabine can contribute to the failure of gemcitabine treatment. To investigate the underlying molecular mechanisms for gemcitabine resistance in pancreatic cancer, we performed label-free quantification of protein expression in intrinsic gemcitabine-resistant and -sensitive human pancreatic adenocarcinoma cell lines using our improved proteomic strategy, combined with filter-aided sample preparation, single-shot liquid chromatography-mass spectrometry, enhanced spectral counting, and a statistical method based on a power law global error model. We identified 1931 proteins and quantified 787 differentially expressed proteins in the BxPC3, PANC-1, and HPDE cell lines. Bioinformatics analysis identified 15 epithelial to mesenchymal transition (EMT) markers and 13 EMT-related proteins that were closely associated with drug resistance were differentially expressed. Interestingly, 8 of these proteins were involved in glutathione and cysteine/methionine metabolism. These results suggest that proteins related to the EMT and glutathione metabolism play important roles in the development of intrinsic gemcitabine resistance by pancreatic cancer cell lines.

• Journal of Ginseng Research
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• v.42 no.1
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• pp.57-67
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• 2018

Background: Ginseng contains many small metabolites such as amino acids, fatty acids, carbohydrates, and ginsenosides. However, little is known about the relationships between microorganisms and metabolites during the entire ginseng fermentation process. We investigated metabolic changes during ginseng fermentation according to the inoculation of food-compatible microorganisms. Methods: Gas chromatography mass spectrometry (GC-MS) datasets coupled with the multivariate statistical method for the purpose of latent-information extraction and sample classification were used for the evaluation of ginseng fermentation. Four different starter cultures (Saccharomyces bayanus, Bacillus subtilis, Lactobacillus plantarum, and Leuconostoc mesenteroide) were used for the ginseng extract fermentation. Results: The principal component analysis score plot and heat map showed a clear separation between ginseng extracts fermented with S. bayanus and other strains. The highest levels of fructose, maltose, and galactose in the ginseng extracts were found in ginseng extracts fermented with B. subtilis. The levels of succinic acid and malic acid in the ginseng extract fermented with S. bayanus as well as the levels of lactic acid, malonic acid, and hydroxypruvic acid in the ginseng extract fermented with lactic acid bacteria (L. plantarum and L. mesenteroide) were the highest. In the results of taste features analysis using an electronic tongue, the ginseng extracts fermented with lactic acid bacteria were significantly distinguished from other groups by a high index of sour taste probably due to high lactic acid contents. Conclusion: These results suggest that a metabolomics approach based on GC-MS can be a useful tool to understand ginseng fermentation and evaluate the fermentative characteristics of starter cultures.

• Molecular & Cellular Toxicology
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• v.5 no.3
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• pp.250-256
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• 2009

Toxicogenomics using microarray technology offers the ability to conduct large-scale detections and quantifications of mRNA transcripts, particularly those associated with alterations in mRNA stability or gene regulation. In this study, we developed the HazChem Human Array V2 using the Agilent Sure-Print technology-based custom array, which is expected to facilitate the identification of environmental toxicants. The array was manufactured using 600 VOCs and PAHs-specific genes identified in previous studies. In order to evaluate the viability of the manufactured HazChem human array V2, we analyzed the gene expression profiles of 9 environmental toxicants (6 VOCs chemicals and 3 PAHs chemicals). As a result, nine toxicants were separated into two chemical types-VOCs and PAHs. After the chip validations with VOCs and PAHs, we conducted an expression profiling comparison of additional chemical groups (POPs and EDCs) using data analysis methods such as hierarchical clustering, 1-way ANOVA, SAM, and PCA. We selected 58 genes that could be classified into four chemical types via statistical methods. Additionally, we selected 63 genes that evidenced significant alterations in expression with all 13 environmental toxicants. These results suggest that the HazChem Human Array V2 will expedite the development of a screening system for environmentally hazardous materials at the level of toxicogenomics in the future.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.2
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• pp.179-186
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• 2014

Metabolomics is the study of changes in the metabolic status of an organism as a consequence of drug treatment, environmental influences, nutrition, lifestyle, genetic variations, toxic exposure, disease, stress, etc, through global or comprehensive identification and quantification of every single metabolite in a biological system. Since most chronic diseases have been demonstrated to be linked to nutrition, nutritional metabolomics has great potential for improving our understanding of the relationship between disease and nutritional status, nutrient, or diet intake by exploring the metabolic effects of a specific food challenge in a more global manner, and improving individual health. In particular, metabolite profiling of biofluids, such as blood, urine, or feces, together with multivariate statistical analysis provides an effective strategy for monitoring human metabolic responses to dietary interventions and lifestyle habits. Therefore, studies of nutritional metabolomics have recently been performed to investigate nutrition-related metabolic pathways and biomarkers, along with their interactions with several diseases, based on animal-, individual-, and population-based criteria with the goal of achieving personalized health care in the future. This article introduces analytical technologies and their application to determination of nutritional phenotypes and nutrition-related diseases in nutritional metabolomics.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5037-5041
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• 2013

Accumulated evidence has indicated that Ephrin A1 (EFNA1) is associated with angiogenesis and tumorigenesis in various types of malignancies, including colorectal cancer (CRC). In the current study, we performed an online search using the public microarray database to investigate whether EFNA1 expression might be altered in CRC tissues. We then conducted a case-control study including 306 subjects (102 cases and 204 well-matched controls) in Xiaoshan County to assess any association between genetic polymorphisms in EFNA1 and CRC susceptibility. Searches in the Oncomine expression profiling database revealed EFNA1 to be overexpressed in CRC tissue compared with adjacent normal tissue. The rs12904 G-A variant located in the 3' untranslated region (UTR) of EFNA1 was observed to be associated with CRC susceptibility. Compared with the AA homozygous genotype, those carrying GA genotype had a decreased risk of developing CRC (odds ratio (OR)=0.469, 95% confidence interval (CI): 0.225-0.977, and P=0.043). The association was stronger among smokers and tea drinkers, however, no statistical evidence of interaction between rs12904 polymorphism and smoking or tea drinking on CRC risk was found. Our results suggest that EFNA1 is involved in colorectal tumorigenesis, and rs12904 A>G polymorphism in the 3' UTR of EFNA1 is associated with CRC susceptibility. Larger studies and further mechanistic investigations are warranted to confirm our findings.

• Environmental Analysis Health and Toxicology
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• v.25 no.4
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• pp.295-306
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• 2010

Objectives : This study was undertaken to examine the metabolomic changes due to gender and diurnal variation at sampling time and to identify an appropriate time point for urine sampling in epidemiologic studies using metabolomic profiles. Methods : Urine samples were collected twice a day (morning and afternoon) from 20 healthy Korean adults after fasting for 8 hours. The metabolomic assay was investigated using $^1H$ NMR spectroscopy coupled with the principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA). The metabolites responsible for differentiation between groups were identified through the loading plot of PLS-DA and quantified using Chenomx NMR Suite with a 600 MHz library. Results : Metabolites responsible for differentiation in gender and sampling time were creatinine, trimethyl anine oxide (TMAO), hippurate, mannitol, citrate and acetoacetate. Dimethylamine showed difference only as a factor of diurnal time. The level of creatinine was higher in men compared to women, and the levels of citrate, TMAO, hippurate, mannitol, and acetoacetate were higher in women compared to men. The levels of creatinine, TMAO, hippurate, dimethylamine and mannitol were higher in the morning rather than the afternoon while those of citrate and acetoacetate were higher in the afternoon rather than the morning. Conclusions : Since urinary metabolomic profiles varied by gender and diurnal cycle, urine sampling should be performed at the same time point for all participants in epidemiologic studies using metabolomic profiles.

• Korean Journal of Agricultural and Forest Meteorology
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• v.12 no.1
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• pp.63-73
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• 2010

A comprehensive mapping project for agroclimatic zoning in South Korea will end by April 2010, which has required 4 years, a billion won (ca. 0.9 million US dollars) and 22 experts from 7 institutions to complete it. The map database from this project may be categorized into primary, secondary and analytical products. The primary products are called "high definition" digital climate maps (HD-DCMs) and available through the state of the art techniques in geospatial climatology. For example, daily minimum temperature surfaces were prepared by combining the climatic normals (1971-2000 and 1981-2008) of synoptic observations with the simulated thermodynamic nature of cold air by using the raster GIS and microwave temperature profiling which can quantify effects of cold air drainage on local temperature. The spatial resolution of the gridded climate data is 30m for temperature and solar irradiance, and 270m for precipitation. The secondary products are climatic indices produced by statistical analysis of the primary products and includes extremes, sums, and probabilities of climatic events relevant to farming activities at a given grid cell. The analytical products were prepared by driving agronomic models with the HD-DCMs and dates of full bloom, the risk of freezing damage, and the fruit quality are among the examples. Because the spatial resolution of local climate information for agronomic practices exceeds the current weather service scale, HD-DCMs and the value-added products are expected to supplement the insufficient spatial resolution of official climatology. In this lecture, state of the art techniques embedded in the products, how to combine the techniques with the existing geospatial information, and agroclimatic zoning for major crops and fruits in South Korea will be provided.

• The Journal of Advanced Prosthodontics
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• v.8 no.1
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• pp.43-52
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• 2016

PURPOSE. This study was conducted to evaluate the effects of full-coverage all-ceramic zirconia, lithium disilicate glass-ceramic, leucite glass-ceramic, or stainless steel crowns on antagonistic primary tooth wear. MATERIALS AND METHODS. There were four study groups: the stainless steel (Steel) group, the leucite glass-ceramic (Leucite) group, the lithium disilicate glass-ceramic (Lithium) group, and the monolithic zirconia (Zirconia) group. Ten flat crown specimens were prepared per group; opposing teeth were prepared using primary canines. A wear test was conducted over 100,000 chewing cycles using a dual-axis chewing simulator and a 50 N masticating force, and wear losses of antagonistic teeth and restorative materials were calculated using a three-dimensional profiling system and an electronic scale, respectively. Statistical significance was determined using One-way ANOVA and Tukey's test (P<.05). RESULTS. The Leucite group ($2.670{\pm}1.471mm^3$) showed the greatest amount of antagonist tooth wear, followed by in decreasing order by the Lithium ($2.042{\pm}0.696mm^3$), Zirconia ($1.426{\pm}0.477mm^3$), and Steel groups ($0.397{\pm}0.192mm^3$). Mean volume losses in the Leucite and Lithium groups were significantly greater than in the Steel group (P<.05). No significant difference was observed between mean volume losses in the Zirconia and Steel groups (P>.05). CONCLUSION. Leucite glass-ceramic and lithium disilicate glass-ceramic cause more primary tooth wear than stainless steel or zirconia.

• Journal of the Korean Wood Science and Technology
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• v.48 no.5
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• pp.591-607
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• 2020

This study was aimed to investigate the changes of chemical composition of the volatile organic compounds (VOCs) emitted from red pine needles in the process of needle abscission or senescence. The VOCs in intact, senescent, and litter red pine needle samples were analyzed by headspace-solid phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC/MS). And then, multivariate statistical interpretation of the processed data sets was conducted to investigate similarities and dissimilarities of the needle samples. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to investigate the dataset structure and discrimination between samples, respectively. From the data preview, the levels of major components of VOCs from needles were not significantly different between needle samples. By PCA investigation, the data reduction according to classification based on the chlorophyll a / chlorophyll b (Ca/Cb) ratio were found to be ideal for differentiating intact, senescent, and litter needles. The following OPLS-DA taking Ca/Cb ratio as y-variables showed that needle samples were well grouped on score plot and had the significant discriminant compounds, respectively. Several compounds had significantly correlated with Ca/Cb ratio in a bivariate correlation analysis. Notably, the litter needles had a higher content of oxidized compounds than the intact needles. In summary, we found that chemical compositions of VOCs between intact, senescent, and litter needles are different each other and several compounds reflect characteristic of needle.

• Animal Bioscience
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• v.36 no.3
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• pp.506-520
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• 2023

Objective: Japanese Brown (JBR) cattle, especially the Kochi (Tosa) pedigree (JBRT), is a local breed of moderately marbled beef. Despite the increasing demand, the interbreed differences in muscle metabolites from the highly marbled Japanese Black (JBL) beef remain poorly understood. We aimed to determine flavor-related metabolites and postmortem metabolisms characteristic to JBRT beef in comparison with JBL beef. Methods: Lean portions of the longissimus thoracis (loin) muscle from four JBRT cattle were collected at 0, 1, and 14 d postmortem. The muscle metabolomic profiles were analyzed using capillary electrophoresis time-of-flight mass spectrometry. The difference in post-mortem metabolisms and aged muscle metabolites were analyzed by statistical and bioinformatic analyses between JBRT (n = 12) and JBL cattle (n = 6). Results: A total of 240 metabolite annotations were obtained from the detected signals of the JBRT muscle samples. Principal component analysis separated the beef samples into three different aging point groups. According to metabolite set enrichment analysis, post-mortem metabolic changes were associated with the metabolism of pyrimidine, nicotinate and nicotinamide, purine, pyruvate, thiamine, amino sugar, and fatty acid; citric acid cycle; and pentose phosphate pathway as well as various amino acids and mitochondrial fatty acid metabolism. The aged JBRT beef showed higher ultimate pH and lower lactate content than aged JBL beef, suggesting the lower glycolytic activity in postmortem JBRT muscle. JBRT beef was distinguished from JBL beef by significantly different compounds, including choline, amino acids, uridine monophosphate, inosine 5'-monophosphate, fructose 1,6-diphosphate, and betaine, suggesting interbreed differences in the accumulation of nucleotide monophosphate, glutathione metabolism, and phospholipid metabolism. Conclusion: Glycolysis, purine metabolism, fatty acid catabolism, and protein degradation were the most common pathways in beef during postmortem aging. The differentially expressed metabolites and the relevant metabolisms in JBRT beef may contribute to the development of a characteristic flavor.