• Asian-Australasian Journal of Animal Sciences
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• 제21권7호
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• pp.1003-1010
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• 2008

The objective of the present study was to identify differences in the expression levels of liver proteins between healthy and ketotic cows, establish a liver metabolic interrelationship of ketosis and elucidate the metabolic characteristics of the liver during ketosis. Liver samples from 8 healthy multiparous Hostein cows and 8 ketotic cows were pooled by health status and the proteins were separated by two-dimensional-electrophoresis (2D-E). Statistical analysis of gels was performed using PDQuest software 8.0. The differences in the expression levels of liver proteins (p<0.05) between ketotic and healthy cows were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF-TOF) tandem mass spectrometry. Five enzymes/proteins were identified as being differentially expressed in the livers of ketotic cows: expression of 3-hydroxyacyl-CoA dehydrogenase type-2 (HCDH), acetyl-coenzyme A acetyltransferase 2 (ACAT) and elongation factor Tu (EF-Tu) were down-regulated, whereas that of alpha-enolase and creatine kinase were up-regulated. On the basis of this evidence, it could be presumed that the decreased expression of HCDH, which is caused by high concentrations of acetyl-CoA in hepatic cells, in the livers of ketotic cows, implies reduced fatty acid ??oxidation. The resultant high concentrations of acetyl-CoA and acetoacetyl CoA would depress the level of ACAT and generate more ??hydroxybutyric acid; high concentrations of acetyl-CoA would also accelerate the Krebs Cycle and produce more ATP, which is stored as phosphocreatine, as a consequence of increased expression of creatine kinase. The low expression level of elongation factor Tu in the livers of ketotic cows indicates decreased levels of protein synthesis due to the limited availability of amino acids, because the most glucogenic amino acids sustain the glyconeogenesis pathway; thus increasing the level of alpha-enolase. Decreased protein synthesis also promotes the conversion of amino acids to oxaloacetate, which drives the Krebs Cycle under conditions of high levels of acetyl-CoA. It is concluded that the livers of ketotic cows possess high concentrations of acetyl-CoA, which through negative feedback inhibited fatty acid oxidation; show decreased fatty acid oxidation, ketogenesis and protein synthesis; and increased gluconeogenesis and energy production.

• BMB Reports
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• 제56권4호
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• pp.225-233
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• 2023

Hepatocellular carcinoma (HCC) is a very common form of cancer worldwide and is often fatal. Although the histopathology of HCC is characterized by metabolic pathophysiology, fibrosis, and cirrhosis, the focus of treatment has been on eliminating HCC. Recently, three-dimensional (3D) multicellular hepatic spheroid (MCHS) models have provided a) new therapeutic strategies for progressive fibrotic liver diseases, such as antifibrotic and anti-inflammatory drugs, b) molecular targets, and c) treatments for metabolic dysregulation. MCHS models provide a potent anti-cancer tool because they can mimic a) tumor complexity and heterogeneity, b) the 3D context of tumor cells, and c) the gradients of physiological parameters that are characteristic of tumors in vivo. However, the information provided by an multicelluar tumor spheroid (MCTS) model must always be considered in the context of tumors in vivo. This mini-review summarizes what is known about tumor HCC heterogeneity and complexity and the advances provided by MCHS models for innovations in drug development to combat liver diseases.

• Safety and Health at Work
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• 제3권4호
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• pp.287-293
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• 2012

Objectives: Metabolic syndrome has received attention as a risk factor for cardiovascular disease, with particular importance attached to visceral fat accumulation, which is associated with lifestyle-related diseases and is strongly correlated with waist circumference. In this study, our aim is to propose waist circumference cut-off values that can be used as a marker for fatty liver based on a sample of workers receiving health checkups in Japan. Methods: This study was conducted in a total of 21,866 workers who underwent periodic health checkups between January 2007 and December 2007. The mean age of the subjects was 47.4 years for men (standard deviation [SD]: 8.0) and 44.7 years for women (SD: 6.9). Evaluation included abdominal ultrasound and measurement of waist circumference, body mass index, fasting blood glucose, triglycerides, high-density lipoprotein cholesterol, and blood pressure. Results: Based on receiver operating characteristic curve analysis, the optimal waist circumference cut-off values were shown as 85.0 cm (sensitivity 0.72, specificity 0.69) for men and 80.0 cm (sensitivity 0.75, specificity 0.78) for women. Conclusion: Abdominal ultrasound is the most efficient means of diagnosing fatty liver, but this examination seldom occurs because the test is not routinely performed at workers' health checkups. In people found to have a high risk of fatty liver, recommendations can be made for abdominal ultrasound based on the waist circumference cut-off values obtained in this study. That is, waist circumference can be used in high risk individuals as an effective marker for early detection of fatty liver.

• 융합정보논문지
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• 제10권12호
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• pp.146-155
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• 2020

본 연구는 대사증후군을 예측하는 대리 표지자로서 감마 글루타밀 전이효소(gamma glutamyl transferase, GGT)의 유용성을 평가하고자 하였다. 20세 이상의 비만하지 않은 남성 7,155명을 연구대상자로 하였다. 대사증후군 진단기준은 NCEP-ATP III (National Cholesterol Education Program - Third Adult Treatment Panel) 기준을 적용하였다. GGT에 따른 대사증후군 발병 위험도는 로지스틱 회귀분석을 적용하였으며, GGT의 대사증후군 위험 예측능력을 확인하기 위해 ROC (receiver operating characteristic) 곡선을 구하였다. 연령과 체질량지수와 무관하게 GGT 1사분위수보다 4사분위수에서 대사증후군 발병위험이 7.09배 높게 나타났다(p<0.001). 대사증후군 진단을 위한 GGT의 곡선아래면적(area under the curve)은 0.715였으며, GGT의 절단값(cut-off value)은 40.0 U/L, 민감도는 65.0%, 특이도 70.2%로 나타났다. 따라서 GGT는 대사증후군을 진단하기 위한 유용한 진단 지표로 판단된다.

• Biomolecules & Therapeutics
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• 제12권4호
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• pp.202-208
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• 2004

Diabetes mellitus is a complex metabolic derangement with hyperglycaemia being the most characteristic symptom of diabetes. Hyperglycaemia can be caused by an increase in the rate of glucose production by the liver or by a decrease in the rate of glucose use by peripheral tissues. Impaired glucose transport is one of the major factors contributing to insulin resistance in type 2 diabetic patients. The ability of insulin to mediate tissue glucose uptake is a critical step in maintaining glucose homeostasis and in clearing the post-prandial glucose load. Glucose transport is mediated by specific carriers called glucose transporters (GLUTs). In this article, the functional importance and molecular mechanisms of insulin-induced glucose transport and development of hypoglycaemic agents which increase glucose transport are reviewed.

• Laboraroty Animal Research
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• 제34권4호
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• pp.232-238
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• 2018

Animal models have been used to elucidate the pathophysiology of varying diseases and to provide insight into potential targets for therapeutic intervention. Although alternatives to animal testing have been proposed to help overcome potential drawbacks related to animal experiments and avoid ethical issues, their use remains vital for the testing of new drug candidates and to identify the most effective strategies for therapeutic intervention. Particularly, the study of metabolic diseases requires the use of animal models to monitor whole-body physiology. In line with this, the National Institute of Food and Drug Safety Evaluation (NIFDS) in Korea has established their own animal strains to help evaluate both efficacy and safety during new drug development. The objective of this study was to characterize the response of C57BL/6NKorl mice from the NIFDS compared with that of other mice originating from the USA and Japan in a chemical-induced diabetic condition. Multiple low-dose treatments with streptozotocin were used to generate a type-1 diabetic animal model which is closely linked to the known clinical pathology of this disease. There were no significantly different responses observed between the varying streptozotocin-induced type-1 diabetic models tested in this study. When comparing control and diabetic mice, increases in liver weight and disturbances in serum amino acids levels of diabetic mice were most remarkable. Although the relationship between type-1 diabetes and BCAA has not been elucidated in this study, the results, which reveal a characteristic increase in diabetic mice of all origins are considered worthy of further study.

• 대한유전성대사질환학회지
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• 제18권1호
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• pp.30-34
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• 2018

C형 Niemann-Pick 병은 NPC1 및 NPC2 유전자의 돌연변이로 인해 발생하며 상염색체 열성으로 유전된다. 신생아 간염 및 간비비대로 발현하며 안구의 수직운동 마비, 조화운동불능, 근육긴장이상, 경련 등의 신경학적 증상이 서서히 발현 하는 것을 특징으로 한다. 저자들은 복부 팽만 및 심한 비장비대로 입원한 3세 남아에서 간 조직 검사 및 유전자 검사, 섬유모세포의 Filipin 염색으로 확진 된 C형 Niemann-Pick 병 1례를 보고하는 바이다.