• IMMUNE NETWORK
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• v.14 no.2
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• pp.73-80
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• 2014

Because autoimmune diseases (AIDs) result from a complex combination of genetic and epigenetic factors, as well as an altered immune response to endogenous or exogenous antigens, systems biology approaches have been widely applied. The use of multi-omics approaches, including blood transcriptomics, genomics, epigenetics, proteomics, and metabolomics, not only allow for the discovery of a number of biomarkers but also will provide new directions for further translational AIDs applications. Systems biology approaches rely on high-throughput techniques with data analysis platforms that leverage the assessment of genes, proteins, metabolites, and network analysis of complex biologic or pathways implicated in specific AID conditions. To facilitate the discovery of validated and qualified biomarkers, better-coordinated multi-omics approaches and standardized translational research, in combination with the skills of biologists, clinicians, engineers, and bioinformaticians, are required.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.22 no.1
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• pp.21-27
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• 2022

Very long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency (VLCADD) leads to a defective 𝛽-oxidation, specifically during prolonged fasting, infection, or exercise. Patients with VLCADD usually suffer from cardiomyopathy, hypoketotic hypoglycemia, hepatic dysfunction, exercise intolerance, muscle pain, and rhabdomyolysis, and sometimes succumb to sudden death. VLCADD is generally classified into three phenotypes: severe early-onset cardiac and multiorgan failure, hypoketotic hypoglycemia, and later-onset episodic myopathy. Diagnostic evaluation comprises acylcarnitine analysis, genetic analysis, and VLCAD activity assay. In the acylcarnitine analysis, the key metabolites are C14:1, C14:2, C14, and C12:1. A C14:1 level >1 mmol/L strongly suggests VLCADD. Various treatment recommendations are available for this condition. Dietary management includes decreasing fat content, increasing medium-chain triglyceride levels, and decreasing fasting periods. Supplementation with L-carnitine is controversial. Triheptanoin (a seven-carbon fatty acid triglyceride) treatment demonstrates improvement of cardiac functions. Bezafibrate may improve the quality of life of patients with VLCAD.

• Mass Spectrometry Letters
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• v.14 no.4
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• pp.121-140
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• 2023

It is becoming more and more clear that each cell, even those of the same type, has a unique identity. This sophistication and the diversity of cell types in tissue are what are pushing the necessity for spatially distributed omics at the single-cell (SC) level. Single-cell chemical assessment, which also provides considerable insight into biological, clinical, pharmacodynamic, pathological, and toxicity studies, is crucial to the investigation of cellular omics (genomics, metabolomics, etc.). Mass spectrometry (MS) as a tool to image and profile single cells and subcellular organelles facilitates novel technical expertise for biochemical and biomedical research, such as assessing the intracellular distribution of drugs and the biochemical diversity of cellular populations. It has been illustrated that ambient mass spectrometry (AMS) is a valuable tool for the rapid, straightforward, and simple analysis of cellular and sub-cellular constituents and metabolites in their native state. This short review examines the advances in ambient mass spectrometry (AMS) and ambient mass spectrometry imaging (AMSI) on single-cell analysis that have been authored in recent years. The discussion also touches on typical single-cell AMS assessments and implementations.

• Journal of Ginseng Research
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• v.44 no.6
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• pp.770-774
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• 2020

Background: Fermentation has been shown to improve the biological properties of plants and herbs. Specifically, fermentation causes decomposition and/or biotransformation of active metabolites into high-value products. Polyacetylenes are a class of polyketides with a pleiotropic profile of bioactivity. Methods: Column chromatography was used to isolate compounds, and extensive NMR experiments were used to determine their structures. The transformation of polyacetylene in red ginseng (RG) and the production of cazaldehyde B induced by the extract of RG were identified by TLC and HPLC analyses. Results: A new metabolite was isolated from RG fermented by Chaetomium globosum, and this new metabolite can be obtained by the biotransformation of polyacetylene in RG. Panaxytriol was found to exhibit the highest antifungal activity against C. globosum compared with other major ingredients in RG. The fungus C. globosum cultured in RG extract can metabolize panaxytriol to Metabolite A to survive, with no antifungal activity against itself. Metabolites A and B showed obvious inhibition against NO production, with ratios of 42.75 ± 1.60 and 63.95 ± 1.45% at 50 µM, respectively. A higher inhibitory rate on NO production was observed for Metabolite B than for a positive drug. Conclusion: Metabolite A is a rare example of natural polyacetylene biotransformation by microbial fermentation. This biotransformation only occurred in fermented RG. The extract of RG also stimulated the production of a new natural product, cazaldehyde B, from C. globosum. The lactone in Metabolite A can decrease the cytotoxicity, which was deemed to be the intrinsic activity of polyacetylene in ginseng.

• Investigative Magnetic Resonance Imaging
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• v.12 no.1
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• pp.8-19
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• 2008

Purpose : To investigate the 3-bond and spatial connectivity of human brain metabolites by scalar coupling and dipolar nuclear Overhauser effect/enhancement (NOE) interaction through 2D- correlation spectroscopy (COSY) and 2D- NOE spectroscopy (NOESY) techniques. Materials and Methods : All 2D experiments were performed on Bruker Avance 500 (11.8 T) with the zshield gradient triple resonance cryoprobe at 298 K. Human brain metabolites were prepared with 10% $D_2O$. Two-dimensional spectra with 2048 data points contains 320 free induction decay (FID) averaging. Repetition delay was 2 sec. The Top Spin 2.0 software was used for post-processing. Total 7 metabolites such as N-acetyl aspartate (NAA), creatine (Cr), choline (Cho), lutamine (Gln), glutamate (Glu), myo-inositol (Ins), and lactate (Lac) were included for major target metabolites. Results : Symmetrical 2D-COSY and 2D-NOESY pectra were successfully acquired: COSY cross peaks were observed in the only 1.0-4.5 ppm, however, NOESY cross peaks were observed in the 1.0-4.5 ppm and 7.9 ppm. From the result of the 2-D COSY data, cross peaks between the methyl protons ($CH_3$(3)) at 1.33 ppm and methine proton (CH(2)) at 4.11 ppm were observed in Lac. Cross peaks between the methylene protons (CH2(3,$H{\alpha}$)) at 2.50ppm and methylene protons ($CH_2$,(3,$H_B$)) at 2.70 ppm were observed in NAA. Cross peaks between the methine proton (CH(5)) at 3.27 ppm and the methine proton (CH(4,6)) at 3.59 ppm, between the methine proton (CH(1,3)) at 3.53 ppm and methine proton (CH(4,6)) at 3.59 ppm, and between the methine proton (CH(1,3)) at 3.53 ppm and methine proton (CH(2)) at 4.05 ppm were observed in Ins. From the result of 2-D NOESY data, cross peaks between the NH proton at 8.00 ppm and methyl protons ($CH_3$) were observed in NAA. Cross peaks between the methyl protons ($CH_3$(3)) at 1.33 ppm and methine proton (CH(2)) at 4.11 ppm were observed in Lac. Cross peaks between the methyl protons (CH3) at 3.03 ppm and methylene protons (CH2) at 3.93 ppm were observed in Cr. Cross peaks between the methylene protons ($CH_2$(3)) at 2.11 ppm and methylene protons ($CH_2$(4)) at 2.35 ppm, and between the methylene protons($CH_2$ (3)) at 2.11 ppm and methine proton (CH(2)) at 3.76 ppm were observed in Glu. Cross peaks between the methylene protons (CH2 (3)) at 2.14 ppm and methine proton (CH(2)) at 3.79 ppm were observed in Gln. Cross peaks between the methine proton (CH(5)) at 3.27 ppm and the methine proton (CH(4,6)) at 3.59 ppm, and between the methine proton (CH(1,3)) at 3.53 ppm and methine proton (CH(2)) at 4.05 ppm were observed in Ins. Conclusion : The present study demonstrated that in vitro 2D-COSY and NOESY represented the 3-bond and spatial connectivity of human brain metabolites by scalar coupling and dipolar NOE interaction. This study could aid in better understanding the interactions between human brain metabolites in vivo 2DCOSY study.

• Allergy, Asthma & Immunology Research
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• v.10 no.6
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• pp.628-647
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• 2018

Purpose: Obesity is associated with metabolic dysregulation, but the underlying metabolic signatures involving clinical and inflammatory profiles of obese asthma are largely unexplored. We aimed at identifying the metabolic signatures of obese asthma. Methods: Eligible subjects with obese (n = 11) and lean (n = 22) asthma underwent body composition and clinical assessment, sputum induction, and blood sampling. Sputum supernatant was assessed for interleukin $(IL)-1{\beta}$, -4, -5, -6, -13, and tumor necrosis factor $(TNF)-{\alpha}$, and serum was detected for leptin, adiponectin and C-reactive protein. Untargeted gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)-based metabolic profiles in sputum, serum and peripheral blood monocular cells (PBMCs) were analyzed by orthogonal projections to latent structures-discriminate analysis (OPLS-DA) and pathway topology enrichment analysis. The differential metabolites were further validated by correlation analysis with body composition, and clinical and inflammatory profiles. Results: Body composition, asthma control, and the levels of $IL-1{\beta}$, -4, -13, leptin and adiponectin in obese asthmatics were significantly different from those in lean asthmatics. OPLS-DA analysis revealed 28 differential metabolites that distinguished obese from lean asthmatic subjects. The validation analysis identified 18 potential metabolic signatures (11 in sputum, 4 in serum and 2 in PBMCs) of obese asthmatics. Pathway topology enrichment analysis revealed that cyanoamino acid metabolism, caffeine metabolism, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, pentose phosphate pathway in sputum, and glyoxylate and dicarboxylate metabolism, glycerolipid metabolism and pentose phosphate pathway in serum are suggested to be significant pathways related to obese asthma. Conclusions: GC-TOF-MS-based metabolomics indicates obese asthma is characterized by a metabolic profile different from lean asthma. The potential metabolic signatures indicated novel immune-metabolic mechanisms in obese asthma with providing more phenotypic and therapeutic implications, which needs further replication and validation.

• Translational and Clinical Pharmacology
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• v.25 no.2
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• pp.67-73
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• 2017

Glimepiride, a third generation sulfonylurea, is an antihyperglycemic agent widely used to treat type 2 diabetes mellitus. In this study, an untargeted urinary metabolomic analysis was performed to identify endogenous metabolites affected by glimepiride administration. Urine samples of twelve healthy male volunteers were collected before and after administration of 2 mg glimepiride. These samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and then subjected to multivariate data analysis including principal component analysis and orthogonal partial least squares discriminant analysis. Through this metabolomic profiling, we identified several endogenous metabolites such as adenosine 3', 5'-cyclic monophosphate (cAMP), quercetin, tyramine, and urocanic acid, which exhibit significant metabolomic changes between pre- and posturine samples. Among these, cAMP, which is known to be related to insulin secretion, was the most significantly altered metabolite following glimepiride administration. In addition, the pathway analysis showed that purine, tyrosine, and histidine metabolism was affected by pharmacological responses to glimepiride. Together, the results suggest that the pharmacometabolomic approach, based on LC-MS/MS, is useful in understanding the alterations in biochemical pathways associated with glimepiride action.

• Journal of Animal Science and Technology
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• v.64 no.4
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• pp.800-811
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• 2022

The integration of metabolomics and transcriptomics may elucidate the correlation between the genotypic and phenotypic patterns in organisms. In equine physiology, various metabolite levels vary during exercise, which may be correlated with a modified gene expression pattern of related genes. Integrated metabolomic and transcriptomic studies in horses have not been conducted to date. The objective of this study was to detect the effect of moderate exercise on the metabolomic and transcriptomic levels in horses. In this study, using nuclear magnetic resonance (NMR) spectroscopy, we analyzed the concentrations of metabolites in muscle and plasma; we also determined the gene expression patterns of branched chain (alpha) keto acid dehydrogenase kinase complex (BCKDK), which encodes the key regulatory enzymes in branched-chain amino acid (BCAA) catabolism, in two breeds of horses, Thoroughbred and Jeju, at different time intervals. The concentrations of metabolites in muscle and plasma were measured by ¹H NMR (nuclear magnetic resonance) spectroscopy, and the relative metabolite levels before and after exercise in the two samples were compared. Subsequently, multivariate data analysis based on the metabolic profiles was performed using orthogonal partial least square discriminant analysis (OPLS-DA), and variable important plots and t-test were used for basic statistical analysis. The stress-induced expression patterns of BCKDK genes in horse muscle-derived cells were examined using quantitative reverse transcription polymerase chain reaction (qPCR) to gain insight into the role of transcript in response to exercise stress. In this study, we found higher concentrations of aspartate, leucine, isoleucine, and lysine in the skeletal muscle of Jeju horses than in Thoroughbred horses. In plasma, compared with Jeju horses, Thoroughbred horses had higher levels of alanine and methionine before exercise; whereas post-exercise, lysine levels were increased. Gene expression analysis revealed a decreased expression level of BCKDK in the post-exercise period in Thoroughbred horses.

• Journal of The Korean Society of Grassland and Forage Science
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• v.31 no.2
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• pp.191-200
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• 2011

Four ruminally cannulated Hanwoo steers (BW 600 ${\pm}$ 48.4 kg) fed whole crop rice silage (WRS) as forage were used to investigate the effects of its dietary on rumen fermentation and blood metabolites at different harvesting time such as milk, dough, yellow ripe and mature stages of WRS, respectively. Mean ruminal pH sampled at 0, 1, 2, 4, 6 and 8 h after the morning feeding was not significantly (p>0.05) different between the WRS by the harvesting time. In diurnal pattern in ruminal pH, the lowest pH for the mature stage treatment (Mature) appeared at 6 h after the feeding while it appeared at 2-4 h for the other treatments. This may indicate that retention time in the rumen of Hanwoo fed WRS harvested at the Mature increased. Although feeding WRS harvested at different stages did not significantly (p>0.05) affect ruminal ammonia N concentration, the ammonia N for WRS harvested at the milk stage (Milk) tended (p=0.11) to decrease compared with that for the yellow stage treatment (Yellow). In the blood metabolites analysis, BUN concentration for Yellow numerically decreased compared with that for Milk. This, taking lower concentration of ruminal ammonia N for Milk than the other treatments into account, clearly indicates that the BUN concentrations may not increase in proportion to ruminal ammonia N concentration according to ammonia N concentration entering into the lower gastric tracts. Lower (p=0.03) concentration of blood albumin for the dough stage treatment than that for Mature may indicate high protein synthesis in Hanwoo fed WRS at the dough stage, but further studies in terms of mechanism of nutrients distribution should be required. Present results indicate that different harvesting time did not affect rumen fermentation and blood metabolites in Hanwoo. Thus, based on the results of the present and the previous studies, utilizing WRS harvested at yellow stage could be recommendable for Hanwoo steers.

• Biomolecules & Therapeutics
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• v.17 no.2
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• pp.133-137
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• 2009

The root of Astragalus membranaceus is a traditional folk medicine that has been used for many therapeutic purposes in Asia. It reportedly acts as an immunostimulant, tonic, hepatoprotective, diuretic, antidiabetic, analgesic, expectorant, sedative, and anticancer drug. In this study, metabolomic profiling was applied to the roots of A. membranaceus of different ages using NMR coupled with two multivariate statistical analysis methods: such as principal components analysis (PCA) and canonical discriminant analysis (CDA). This allowed various metabolites to be assigned in NMR spectra, including $\gamma$-aminobutyric acid (GABA), aspartic acid, succinic acid, glutamic acid, glutamine, N-acetyl aspartic acid, acetic acid, arginine, alanine, threonine, lactic acid, and valine. The score plot from PCA and also CDA allowed a clear separation between samples according to age.