• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2007년도 Proceedings of The Convention
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• pp.19-27
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• 2007

An important potential of metabolomics-based approach is the possibility to develop fingerprints of diseases or cellular responses to classes of compounds with known common biological effect. Such fingerprints have the potential to allow classification of disease states or compounds, to provide mechanistic information on cellular perturbations and pathways and to identify biomarkers specific for disease severity and drug efficacy. Metabolic profiles of biological fluids contain a vast array of endogenous metabolites. Changes in those profiles resulting from perturbations of the system can be observed using analytical techniques, such as NMR and MS. $^1H$ NMR was used to generate a molecular fingerprint of serum or urinary sample, and then pattern recognition technique was applied to identity molecular signatures associated with the specific diseases or drug efficiency. Several metabolites that differentiate disease samples from the control were thoroughly characterized by NMR spectroscopy. We investigated the metabolic changes in human normal and clinical samples using $^1H$ NMR. Spectral data were applied to targeted profiling and spectral binning method, and then multivariate statistical data analysis (MVDA) was used to examine in detail the modulation of small molecule candidate biomarkers. We show that targeted profiling produces robust models, generates accurate metabolite concentration data, and provides data that can be used to help understand metabolic differences between healthy and disease population. Such metabolic signatures could provide diagnostic markers for a disease state or biomarkers for drug response phenotypes.

• 대한지역사회영양학회지
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• 제29권3호
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• pp.212-221
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• 2024

Objectives: Metabolic disease is strongly associated with future insulin resistance, and its prevalence is increasing worldwide. Thus, identifying early biomarkers of metabolic-related disease based on serum profiling is useful to control future metabolic disease. Our study aimed to assess the association of serum branched chain amino acids (BCAAs) and aromatic amino acids (AAAs) ratio and metabolic disease according to body mass index (BMI) status among Korean adults. Methods: This cross-sectional study included 78 adults aged 20-59 years in Korea. We compared serum amino acid (AA) levels between adults with normal-weight and adults with obesity and investigated biomarkers of metabolic disease. We examined serum AA levels, blood profile, and body composition. We also evaluated the association between serum AAs and metabolic-related disease. Results: The height, weight, BMI, waist circumference, hip circumference, waist-hip-ratio, body fat mass, body fat percent, skeletal muscle mass, systolic blood pressure, and diastolic blood pressure were higher in the group with obesity compared to normal weight group. The group with obesity showed significantly higher levels of BCAA, AAA, and BCAA and AAA ratio. Further, BCAA and AAA ratio were significantly positively correlated with triglyceride, body weight, and skeletal muscle mass. The evaluation of metabolic disease risks revealed an association between the ratios of BCAAs and AAAs, hypertension, and metabolic syndrome. Conclusions: Our study is showed the associations between BCAA and AAA ratio, obesity, and obesity-related diseases using various analytical approaches. The elevated BCAA and AAA ratio could be early biomarkers for predicting future metabolic diseases in Korean population.

• Mass Spectrometry Letters
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• 제4권4호
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• pp.59-66
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• 2013

A metabolomics study was conducted to identify urinary biomarkers for breast cancer, using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), analyzed by principal components analysis (PCA) as well as a partial least squares-discriminant analysis (PLS-DA) for a metabolic pattern analysis. To find potential biomarkers, urine samples were collected from before- and after-mastectomy of breast cancer patients and healthy controls. Androgens, corticoids, estrogens, nucleosides, and polyols were quantitatively measured and urinary metabolic profiles were constructed through PCA and PLS-DA. The possible biomarkers were discriminated from quantified targeted metabolites with a metabolic pattern analysis and subsequent screening. We identified two biomarkers for breast cancer in urine, ${\beta}$-cortol and 5-methyl-2-deoxycytidine, which were categorized at significant levels in a student t-test (p-value < 0.05). The concentrations of these metabolites in breast cancer patients significantly increased relative to those of controls and patients after mastectomy. Biomarkers identified in this study were highly related to metabolites causing oxidative DNA damage in the endogenous metabolism. These biomarkers are not only useful for diagnostics and patient stratification but can be mapped on a biochemical chart to identify the corresponding enzyme for target identification via metabolomics.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5417-5421
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• 2014

Objectives: The identification of cutaneous T cell lymphoma (CTCL) biomarkers may serve as a predictor of disease progression and treatment response. The aim of this study was to map potential biomarkers in CTCL plasma. Design and Methods: Plasma metabolic perturbations between CTCL cases and healthy individuals were investigated using metabolomics and ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Results: Principal component analysis (PCA) of the spectra showed clear metabolic changes between the two groups. Thirty six potential biomarkers associated with CTCL were found. Conclusions: Based on PCA, several biomarkers were determined and further identified by LC/MS/MS analysis. All of these could be potential early markers of CTCL. In addition, we established that heparin as a nticoagulant has better pre-treatment results than EDTA with the UHPLC-QTOF/MS appraoch.

• 약학회지
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• 제52권5호
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• pp.331-344
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• 2008

Recently, the FDA (Food and Drug Administration) of the United States and many advanced countries remark biomarkers and surrogate endpoints as a critical path tool on model based drug development. Economic, technical and social profit on model based drug development like a reduction of the length of research and development have been achieved. Therefore we summarize previous studies about biomarkers and surrogate endpoints and suggest a development direction of therapeutic agents. In diabetes mellitus (DM) and osteoporosis, there are remarkable increases in number of patients and most of patients take medicine during their whole lifetime. For this reason, many patients with DM and osteoporosis have a tolerance on their medicine. We expect that research and development on biomarkers and surrogate endpoints will contribute to new drug development on DM and osteoporosis. Biomarkers for DM are blood levels of glucose, insulin, ${HbA}_{1c}$, CRP, alpha-glucosidase, adiponectin and DPP-4. Among these, validated surrogate endpoints for DM are blood levels of glucose, insulin and ${HbA}_{1c}$ Biomarkers for osteoporosis are BMD, BMC, trabecular volume, ICTP, DPD, osteocalcin, the activity of osteoclast and production of osteoblast. The validated surrogate endpoints for osteoporosis are BMD only. This review summarizes all suggested biomarkers and surrogate endpoints in DM and osteoporosis. The biomarkers are classified by drugs, and the method of validation for surrogate endpoints is suggested. This information would contribute to suggest a direction of DM and osteoporosis therapeutic agent development.

• Asian-Australasian Journal of Animal Sciences
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• 제31권8호
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• pp.1244-1251
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• 2018

Objective: The objective of the present study was to elucidate the mechanism underlying liver metabolic perturbations in dairy cows exposed to heat stress (HS). Methods: Liquid chromatography massabl spectrometry was used to analyze metabolic differences in livers of 20 dairy cows, with and without exposure to HS. Results: The results revealed 33 potential metabolite candidate biomarkers for the detection of HS in dairy cows. Fifteen of these metabolites (glucose, lactate, pyruvate, acetoacetate, ${\beta}$-hydroxybutyrate, fumaric acid, citric acid, choline, glycine, proline, isoleucine, leucine, urea, creatinine, and orotic acid) were previously found to be potential biomarkers of HS in plasma or milk, discriminating dairy cows with and without HS. Conclusion: All the potential diagnostic biomarkers were involved in glycolysis, amino acid, ketone, tricarboxylic acid, or nucleotide metabolism, indicating that HS mainly affected energy and nucleotide metabolism in lactating dairy cows.

• Nutrition Research and Practice
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• 제9권2호
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• pp.165-173
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• 2015

BACKGROUND/OBJECTIVES: This study addressed the question whether the composition of supposedly 'healthy' or 'unhealthy' dietary regimes has a calorie-independent short-term effect on biomarkers of metabolic stress and vascular risk in healthy individuals. SUBJECTS/METHODS: Healthy male volunteers (age $29.5{\pm}5.9years$, n = 39) were given a standardized baseline diet for two weeks before randomization into three groups of different dietary regimes: fast food, Mediterranean and German cooking style. Importantly, the amount of calories consumed per day was identical in all three groups. Blood samples were analyzed for biomarkers of cardiovascular risk and metabolic stress after two weeks of the baseline diet and after two weeks of the assigned dietary regime. RESULTS: No dietary intervention affected the metabolic or cardiovascular risk profile when compared in-between groups or compared to baseline. Subjects applied to the Mediterranean diet showed a statistically significant increase of uric acid compared to baseline and compared to the German diet group. Plasma concentrations of urea were significantly higher in both the fast food group and the Mediterranean group, when compared to baseline and compared to the German diet group. No significant differences were detected for the levels of vitamins, trace elements or metabolic stress markers (8-hydroxy-2-deoxyguanosine, malondialdehyde and methylglyoxal, a potent glycating agent). Established parameters of vascular risk (e.g. LDL-cholesterol, lipoprotein(a), homocysteine) were not significantly changed in-between groups or compared to baseline during the intervention period. CONCLUSIONS: The calorie-controlled dietary intervention caused neither protective nor harmful short-term effects regarding established biomarkers of vascular or metabolic risk. When avoiding the noxious effects of overfeeding, healthy individuals can possess the metabolic capacity to compensate for a potentially disadvantageous composition of a certain diet.

• Molecules and Cells
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• 제38권7호
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• pp.587-596
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• 2015

Obesity and diabetes arise from an intricate interplay between both genetic and environmental factors. It is well recognized that obesity plays an important role in the development of insulin resistance and diabetes. Yet, the exact mechanism of the connection between obesity and diabetes is still not completely understood. Metabolomics is an analytical approach that aims to detect and quantify small metabolites. Recently, there has been an increased interest in the application of metabolomics to the identification of disease biomarkers, with a number of well-known biomarkers identified. Metabolomics is a potent approach to unravel the intricate relationships between metabolism, obesity and progression to diabetes and, at the same time, has potential as a clinical tool for risk evaluation and monitoring of disease. Moreover, metabolomics applications have revealed alterations in the levels of metabolites related to obesity-associated diabetes. This review focuses on the part that metabolomics has played in elucidating the roles of metabolites in the regulation of systemic metabolism relevant to obesity and diabetes. It also explains the possible metabolic relation and association between the two diseases. The metabolites with altered profiles in individual disorders and those that are specifically and similarly altered in both disorders are classified, categorized and summarized.

• 동아시아식생활학회지
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• 제23권3호
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• pp.282-296
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• 2013

The study classified 83 obese adults by constitution and had them follow a strict diet according to their constitution in order to see if the Yin-Yang method would be effective on the metabolic syndrome, which is one of the main causes of death in Korea. Overall, the application of both Yin and Yang methods improved the following factors: weight, body fat percentage, systolic blood pressure, diastolic pressure, neutral fats and total cholesterol. In particular, the Yin constitution group of men showed more improvements than the Yang constitution group. Furthermore, waist circumference and the prevalence rate of systolic blood pressure, diastolic pressure, total cholesterol and metabolic syndrome were decreased noticeably. Total energy intake was increased in both men and women after the constitutional diet, along with the increase of nutrient intake, such as dietary fiber, vitamins and minerals, among others. Among various nutrients, vitamin A, vitamin C, thiamine, vitamin B6, folic acid, calcium, phosphorus, potassium, magnesium and iron intake were increased noticeably after the constitutional diet. In addition, subjects' intake of all nutrients, except for magnesium, satisfied the nutrition intake standards. Further, the nutrients adequacy ratio (NAR) and the mean adequacy ratio (MAR) improved for both men and women. The intake of potatoes, starch, greens and mushrooms increased noticeably, whereas the intake of meat, dairy, drinks and alcohol decreased after the constitutional diet. For the Yin constitution, the intake of Yin foods noticeably decreased, where as the intake of Yang foods decreased for the Yang constitution. In conclusion, the constitutional diet effectively improves the metabolic syndrome. Among many nutrients, the intake of dietary fiber, vitamins A, C and E, potassium and magnesium is positively associated with the improvement of metabolic syndrome biomarkers.

• 한국환경보건학회지
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• 제36권5호
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• pp.418-434
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• 2010

As concerns regarding water pollution grow, the need increases for a fast and accurate assessment of ecological risk. In this context, many studies have been conducted to identify biomarkers which can sensitively indicate exposure to and effects of various contaminants in a water environment. However, the utility of most such biomarkers in the real water environment is not yet validated. In this paper, we conducted a thorough review of publications that were related to developing or evaluating molecular and biochemical biomarkers of freshwater fish in ecological risk assessment, and evaluated whether these biomarkers of interest could link to the effects on higher biological levels, such as histopathology and above. Biomarkers of interest included those associated with metabolism, oxidative stress, reproduction and endocrine disruption, genotoxicity, and defense against heavy metal exposure. We found that, when used alone, most molecular and biochemical biomarkers are not sufficient to understand the effects of toxic substances in higher biological levels, due to defense or acclimation mechanisms of organisms. Moreover, some biomarkers respond not only to hazardous substances but also to the changes in water quality and disease outbreak. Molecular and biochemical biomarkers may be most useful in understanding the potential biological effects of toxic compounds when used in parallel with relevant endpoints of higher biological levels.