• Proceedings of the Korean Society of Applied Pharmacology
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• 2007.11a
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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.

• 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.

• Korean Journal of Crystallography
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• v.16 no.2
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• pp.66-74
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• 2005

Marine natural products with various bioactivities are featured with similar structure to the common secondary metabolites and generally modified by halogenides, such as chloride, bromide, and iodide ions. Vanadium haloperoxidase is a key enzyme for the production of marine natural products and a metalloenzyme which requires a cofactor of vanadate. This review will cover isolation of vanadium haloperoxidase and the protein structures, as well as reaction mechanism of the metalloenzyme. Finally, reactivity of vanadium haloperoxidase and the biosynthesis of the secondary metabolites of indole, terpenoids, and acetogenins will be described.

• Journal of The Korean Society of Clinical Toxicology
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• v.7 no.1
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• pp.32-37
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• 2009

Formic acid or formate is a common industrial compound used in the production of ensilage, disinfectants, decalcifying agents and mainly as a precursor in industrial chemical synthesis. It is also a well-known toxic metabolite produced in methanol poisoning. Thus, formate is a potential source of both accidental and deliberate poisoning. Very few reports have been published thus far, on the toxicology of direct formic acid poisoning. Here, we report a case of a 74-year-old man without a history of depression, who ingested about 30 gm of formic acid. The patient presented with profound high anion gap metabolic acidosis, acute renal failure and esophageal stricture. The patient was successfully treated with hemodialysis and supportive measures. But permanent esophageal stricture was complicated by formic acid burns in the gastrointestinal tract. We discuss the pathophysiology and treatment of this case.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.14 no.2
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• pp.1-8
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• 2001

We know paranasal sinusitis is one of the most common disease in the field of otolaryngology. Especially in the case of chronic paranasal sinusitis, patient is sufferred from recurrence. So we prescribed Bojungikgitang(補中益氣湯) to the patients who were suffered from chronic paranasal sinusitis, and we witness some noticeable improvement. Here are the findings of my experience 1. The addition and subtraction temperament drugs of Bojungikgitang(補中益氣湯加減方) are effective to the patient of chronic and feeble paranasal sinusitis by the effect of removing wind(祛風), unnecessary metabolite(祛痰), and draining pus(排膿) and strengthening digestive organs(健碑) and enriching the lung yin(益肺陰) and alleviation of pain(止痛). 2. In the symptom of chronic paranasal siunutitis, nasal obstruction, postnasal drip, sputum, headache were quick to disappear, and dysosmia, internasal polyp, etc got better slower. 3. The most quick improvement appeared within two weeks and most symptoms improved within one month, and disappeared within two months.

• Journal of Veterinary Clinics
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• v.34 no.4
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• pp.255-260
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• 2017

Ketosis has become a very common and important metabolic disorder that causes substantial economic loss in modern dairy herds. We determined the risk factors for ketosis and associations with some blood metabolite concentrations in dairy cows. Blood from 475 Holstein cows on four dairy farms was collected weekly until 4 weeks after calving to measure blood ${\beta}$-hydroxybutyrate (BHBA) concentrations using electronic handheld meters. Cows were grouped based on the BHBA concentration into two groups: a ketosis group (${\geq}1.2mmol/L$, n = 150) and a non-ketosis group (< 1.2 mmol/L, n = 325). Peripartum health status (dystocia, retained placenta, and metritis), cow parity, and calving season were recorded to identify the risk factors for ketosis. Serum albumin, total cholesterol (TCH), and haptoglobin concentrations were compared between sub-groups of cows selected from the ketosis (n = 92) and non-ketosis (n = 50) groups 1 week postpartum ($7.5{\pm}0.2days$). The farm influenced the incidence of ketosis (P < 0.05). Cows calved during summer tended to have a higher risk (odds ratio [OR]: 1.61, P < 0.1) of ketosis than cows calved during spring. Cows with parities of two (OR: 1.95, P < 0.05) and three or higher (OR: 2.55, P < 0.01) were at higher risk than primiparous cows. Cows with metritis had a higher risk (OR: 7.02, P < 0.0001) of ketosis than cows without metritis. Serum albumin and TCH concentrations were lower (P < 0.01) in the ketosis group than in the non-ketosis group, whereas haptoglobin concentration was higher (P < 0.05) in the ketosis group than in the non-ketosis group. In conclusion, our results indicate that farm, summer calving, parity greater than one, and postpartum disease (metritis) were risk factors for ketosis. In addition, lower serum albumin and TCH concentrations and higher haptoglobin concentration were also associated with the incidence of ketosis in dairy cows.

• The Plant Pathology Journal
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• v.15 no.1
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• pp.8-13
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• 1999

Hypersensitive cell death of plants during incompatible plant-pathogen interactions is one of the efficient defense mechanisms of plants against pathogen infections. For better understanding of the molecular mechanisms involved in the plant hypersensitive response (HR), TMV-induced biotic plant cell death and CuSO4-induced abiotic plant cell death were compared in terms of expression patterns of ten different defense-related genes as molecular markers. The genes include five pathogenesis-related protein genes, two plant secondary metabolite-associated genes, two oxidative stress-related genes and one wound-inducible gene isolated from tobacco. Northern blot analyses revealed that a same set of defense-related genes was induced during both biotic and abiotic cell death but with different time and magnitude. The expression of defense-related genes in tobacco plants was temporarily coincided with the time of cell death. However, when suspension cell cultures was used to monitor the expression of defense-related genes, different patterns of the gene expression were detected. This result implies that three are common and, in addition, also different branches of signaling pathways leading to the induced expression of defense-related genes in tobacco during the pathogen- and heavy metal-induced cell death.

• BMB Reports
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• v.43 no.10
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• pp.643-648
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• 2010

Sir William Osler (1849-1919) recognized that "variability is the law of life, and as no two faces are the same, so no two bodies are alike, and no two individuals react alike and behave alike under the abnormal conditions we know as disease". Accordingly, the traditional methods of medicine are not always best for all patients. Over the last decade, the study of genomes and their derivatives (RNA, protein and metabolite) has rapidly advanced to the point that genomic research now serves as the basis for many medical decisions and public health initiatives. Genomic tools such as sequence variation, transcription and, more recently, personal genome sequencing enable the precise prediction and treatment of disease. At present, DNA-based risk assessment for common complex diseases, application of molecular signatures for cancer diagnosis and prognosis, genome-guided therapy, and dose selection of therapeutic drugs are the important issues in personalized medicine. In order to make personalized medicine effective, these genomic techniques must be standardized and integrated into health systems and clinical workflow. In addition, full application of personalized or genomic medicine requires dramatic changes in regulatory and reimbursement policies as well as legislative protection related to privacy. This review aims to provide a general overview of these topics in the field of personalized medicine.

• Korean Journal of Pharmacognosy
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• v.46 no.1
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• pp.72-77
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• 2015

One of the most common forms of dementia, Alzheimer's disease (AD) is a progressive neurodegenerative disorder symptomatically characterized by impairment in memory and cognitive abilities. AD is characterized pathologically by the presence of intracellular neurofibrillary tangles and deposition of ${\beta}$-amyloid ($A{\beta}$) peptides, believed to be neurotoxic and now is also considered to have a role on the mechanism of memory dysfunction. In this study, we tested that MeOH extract of Impatiens balsamina L. (IBM) affects on the processing of APP from the APPswe over-expressing Neuro2a cell line. We found that IBM increased over 2 folds of the $sAPP{\alpha}$ secretion level, a main metabolite of ${\alpha}$-secretase. We shown that IBM reduced the secretion level of $A{\beta}42$ and $A{\beta}40$ without cytotoxicity. BACE (${\beta}$-site APP cleaving enzyme) FRET assay shown that BACE activity was specifically decreased in the presence of IBM. We suggest that Impatiens balsamina L. may be an useful source to develop a herbal medicine of BACE inhibitor for Alzheimer's disease.

• YAKHAK HOEJI
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• v.32 no.5
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• pp.343-350
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• 1988

Recent hypothesis suggested that intracellular accumulation of calcium is a common denominator of ischemic celullar damage. Flunarizine, a calcium entry blocker, posses vasodilating properties in cerebral vascular beds and clinically used in circulatory disorders. The present study was designed to evaluate the effect of flunarizine on ischemic and hypoxic brain damage. An ischemic model was made by bilateral carotid artery ligation (BCAL) in Wistar strain rat. Hypoxic model was made by intravenous injection(i.v.) of KCN to rats and mice. In mice, flunarizine not only reduced the mortality of KCN, but also delayed the onset time of convulsion. The contents of ATP, creatine phosphate and glucose, cerebral energy metabolite, decreased 30 minutes after BCAL and KCN i, v, while that of lactate increased. But these variations were suppressed by flunarizine. Furthermore, increase in the dosage of flunarizne generally promoted the recovery of cerebral energy metabolites in hypoxic animals. The results suggest that flunarizine had a protective effect against ischemic and hypoxic brain damage due to its ameliorating action on the cerebral energy metabolism.