Recently, the productivity of drug discovery has gradually decreased as the limitations of single-target-based drugs for various and complex diseases become exposed. To overcome these limitations, drug combinations have been proposed, and great efforts have been made to predict efficacious drug combinations by statistical methods using drug databases. However, previous methods which did not take into account biological networks are insufficient for elaborate predictions. Also, increased evidences to support the fact that drug effects are closely related to metabolic enzymes suggested the possibility for a new approach to the study drug combinations. Therefore, in this paper we suggest a novel approach for analyzing drug combinations using a metabolic network in a systematic manner. The influence of a drug on the metabolic network is described using the distance between the drug target and an enzyme. Target-enzyme distances are converted into influence scores, and from these scores we calculated the correlations between drugs. The result shows that the influence score derived from the targetenzyme distance reflects the mechanism of drug action onto the metabolic network properly. In an analysis of the correlation score distribution, efficacious drug combinations tended to have low correlation scores, and this tendency corresponded to the known properties of the drug combinations. These facts suggest that our approach is useful for prediction drug combinations with an advanced understanding of drug mechanisms.
Sohn, Jee Hyung;Kim, Jong In;Jeon, Yong Geun;Park, Jeu;Kim, Jae Bum
Molecules and Cells
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v.41
no.10
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pp.900-908
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2018
Insulin resistance is closely associated with metabolic diseases such as type 2 diabetes, dyslipidemia, hypertension and atherosclerosis. Thiazolidinediones (TZDs) have been developed to ameliorate insulin resistance by activation of peroxisome proliferator-activated receptor (PPAR) ${\gamma}$. Although TZDs are synthetic ligands for $PPAR{\gamma}$, metabolic outcomes of each TZD are different. Moreover, there are lack of head-to-head comparative studies among TZDs in the aspect of metabolic outcomes. In this study, we analyzed the effects of three TZDs, including lobeglitazone (Lobe), rosiglitazone (Rosi), and pioglitazone (Pio) on metabolic and thermogenic regulation. In adipocytes, Lobe more potently stimulated adipogenesis and insulin-dependent glucose uptake than Rosi and Pio. In the presence of pro-inflammatory stimuli, Lobe efficiently suppressed expressions of pro-inflammatory genes in macrophages and adipocytes. In obese and diabetic db/db mice, Lobe effectively promoted insulin-stimulated glucose uptake and suppressed pro-inflammatory responses in epididymal white adipose tissue (EAT), leading to improve glucose intolerance. Compared to other two TZDs, Lobe enhanced beige adipocyte formation and thermogenic gene expression in inguinal white adipose tissue (IAT) of lean mice, which would be attributable to cold-induced thermogenesis. Collectively, these comparison data suggest that Lobe could relieve insulin resistance and enhance thermogenesis at low-concentration conditions where Rosi and Pio are less effective.
Kho, Min Chul;Lee, Yun Jung;Yoon, Jung Joo;Kang, Dae Gill;Lee, Ho Sub
Journal of Physiology & Pathology in Korean Medicine
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v.29
no.1
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pp.11-17
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2015
Overconsumption of fructose results in dyslipidemia, hypertension, which have documented as a risk of cardiovascular diseases. This experimental study was designed to investigate the beneficial effects of Rubus coreanus Miq.(RCM) in high-fructose diet-induced metabolic syndrome. Animals were divided into three groups; Control group fed regular diet and tap water, fructose groups were fed the 65% high-fructose (HF) diet with/without RCM 100 mg/kg/day for 8 weeks, respectively. Chronic treatment with RCM significantly decreased body weight, fat weight and adipocyte size. Moreover, RCM significantly prevented the development of the metabolic disturbances such as hyperlipidemia and hypertension. RCM also led to increase in high density lipoprotein level in the HF group. In addition, RCM suppressed vascular cell adhesion molecule-1 (VCAM-1) expression and significantly recovered the levels of endothelial nitric oxide synthase (eNOS) expression in aorta. These results demonstrates that RCM may be a beneficial therapeutic for metabolic syndrome through the improvement of hyperlipidemia, obesity, and hypertension.
The aim of this review was to understand the effects of ${\beta}$-adrenergic stimulation on oxidative stress, structural remodeling, and functional alterations in the heart and cerebral artery. Diverse stimuli activate the sympathetic nervous system, leading to increased levels of catecholamines. Long-term overstimulation of the ${\beta}$-adrenergic receptor (${\beta}AR$) in response to catecholamines causes cardiovascular diseases, including cardiac hypertrophy, stroke, coronary artery disease, and heartfailure. Although catecholamines have identical sites of action in the heart and cerebral artery, the structural and functional modifications differentially activate intracellular signaling cascades. ${\beta}AR$-stimulation can increase oxidative stress in the heart and cerebral artery, but has also been shown to induce different cytoskeletal and functional modifications by modulating various components of the ${\beta}AR$ signal transduction pathways. Stimulation of ${\beta}AR$ leads to cardiac dysfunction due to an overload of intracellular $Ca^{2+}$ in cardiomyocytes. However, this stimulation induces vascular dysfunction through disruption of actin cytoskeleton in vascular smooth muscle cells. Many studies have shown that excessive concentrations of catecholamines during stressful conditions can produce coronary spasms or arrhythmias by inducing $Ca^{2+}$-handling abnormalities and impairing energy production in mitochondria, In this article, we highlight the different fates caused by excessive oxidative stress and disruptions in the cytoskeletal proteome network in the heart and the cerebral artery in responsed to prolonged ${\beta}AR$-stimulation.
Journal of the Korea Society of Computer and Information
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v.27
no.4
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pp.193-203
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2022
The purpose of this study was to analyze the effect of home training with app on metabolic syndrome risk factors and atherogenic index in on obese middle aged women. It was carried out to present as an intervention method for improving obesity in the pandemic era of COVID-19. The subjects of this study were 33 obese middle aged women, AHTG(n=15) and CG(n=18). Home training using the app for 8 weeks was conducted 3 times a week. The results of this study as follow, metabolic syndrome risk factors was WC(p<.001) significantly decreased, HDL-C(p<.05) significantly increased and atherogenic index was LDL-C/HDL-C(p<.01) significantly increased in the AHTG. In the era of the COVID-19 pandemic, PA plays an important role in alleviating the severe COVID-19 pandemic, in addition to its ameliorating effects on several chronic diseases. The possibility of home training using an app is an effective intervention method for preventing obesity and metabolic syndrome.
Journal of The Korean Society of Integrative Medicine
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v.10
no.4
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pp.261-275
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2022
Purpose : According to the Korean Diabetes Association, the number of metabolic disease patients in Korea is approximately 14.97 million as of 2020;, the prevalence of diabetes among adults over 30 years old is 44.3 %, and the prevalence of diabetes in the elderly over 65 years old is 50.4%. These individuals exposed to the risk of complications. Therefore, the purpose of this study was to determine a distribution method for a customized fusion exercise marine healing program for metabolic disease patients. Methods : We have searched numerous papers concerning artificial intelligence (AI), virtual reality (VR), augmented reality (AR), and marine resources related to marine healing programs that can be introduced in marine healing centers for people with metabolic diseases Results : Through the production of various marine resources and evidence-based exercise programs, the provision of exercise programs using AI, and the development of exercise platforms using AR and VR, we were able to establish guidelines for how to operate marine healing programs at marine healing centers. Conclusion : Korea has much more diverse marine healing resources than other advanced countries in the marine healing industry. However, the development of these resources has only just begun. It is hoped that the studied marine healing program will be of great help to metabolic patients by creating contents that will be implemented in marine healing centers by using the cutting-edge technologies and various marine resources that Korea possesses.
Metabolic abnormalities in the liver are closely associated with diverse metabolic diseases such as non-alcoholic fatty liver disease, type 2 diabetes, and obesity. The aim of this study was to evaluate the ameliorating effect of robinetin (RBN) on the significant pathogenic features of metabolic failure in the liver and to identify the underlying molecular mechanism. RBN significantly decreased triglyceride (TG) accumulation by downregulating lipogenesis-related transcription factors in AML-12 murine hepatocyte cell line. In addition, mice fed with Western diet (WD) containing 0.025% or 0.05% RBN showed reduced liver mass and lipid droplet size, as well as improved plasma insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values. CD38 was identified as a target of RBN using the BioAssay database, and its expression was increased in OPA-treated AML-12 cells and liver tissues of WD-fed mice. Furthermore, RBN elicited these effects through its anti-histone acetyltransferase (HAT) activity. Computational simulation revealed that RBN can dock into the HAT domain pocket of p300, a histone acetyltransferase, which leads to the abrogation of its catalytic activity. Additionally, knock-down of p300 using siRNA reduced CD38 expression. The chromatin immunoprecipitation (ChIP) assay showed that p300 occupancy on the promoter region of CD38 was significantly decreased, and H3K9 acetylation levels were diminished in lipid-accumulated AML-12 cells treated with RBN. RBN improves the pathogenic features of metabolic failure by suppressing the p300-CD38 axis through its anti-HAT activity, which suggests that RBN can be used as a new phytoceutical candidate for preventing or improving this condition.
Obesity and overweight pose a significant public health problem, as they are associated with an elevated risk of metabolic syndrome (MetS). Several studies have shown that diet quality is associated with the development of MetS risk factors. Analyzing dietary patterns may be more helpful in determining the relationship between eating habits and chronic diseases compared to focusing on single foods or nutrients. In this study, our objective was to evaluate the association of food quality score (FQS) with risk factors for MetS in individuals with obesity and overweight. The participants in this cross-sectional study were 340 adults with overweight and obesity. Participants' food intake was measured using a Food Frequency Questionnaire, then the FQS was calculated. A fasting blood sample assessed serum glucose, triglycerides, total cholesterol (TC), high-density lipoprotein cholesterol, and serum insulin levels. Fat-free mass, height, basal metabolic rate, socio-economic score, and waist-to-hip ratio significantly differed among FQS tertiles. TC, systolic and diastolic blood pressure, and fasting blood glucose were significantly lower in the highest tertile of FQS. After multivariable adjustment, our results showed that individuals in the third tertile of FQS had reduced risk of higher levels of TC (odds ratio [OR], 0.982; 95% confidence interval [CI], 0.970-0.984) and higher levels of low-density lipoprotein cholesterol (OR, 0.974; 95% CI, 0.974-0.999). Our findings demonstrate an inverse relationship between diet quality, as measured by FQS, and MetS risk factors. However, further experimental and longitudinal investigations are warranted to elucidate the causal nature of this association.
Taurine is an abundant, ${\beta}-amino$ acid with diverse cytoprotective activity. In some species, taurine is an essential nutrient but in man it is considered a semi-essential nutrient, although cells lacking taurine show major pathology. These findings have spurred interest in the potential use of taurine as a therapeutic agent. The discovery that taurine is an effective therapy against congestive heart failure led to the study of taurine as a therapeutic agent against other disease conditions. Today, taurine has been approved for the treatment of congestive heart failure in Japan and shows promise in the treatment of several other diseases. The present review summarizes studies supporting a role of taurine in the treatment of diseases of muscle, the central nervous system, and the cardiovascular system. In addition, taurine is extremely effective in the treatment of the mitochondrial disease, mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and offers a new approach for the treatment of metabolic diseases, such as diabetes, and inflammatory diseases, such as arthritis. The review also addresses the functions of taurine (regulation of antioxidation, energy metabolism, gene expression, ER stress, neuromodulation, quality control and calcium homeostasis) underlying these therapeutic actions.
The Journal of the Korea institute of electronic communication sciences
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v.8
no.4
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pp.639-648
/
2013
Metabolic syndrome is the most important risk factors of cardiovascular diseases So, it is judged that Quality of life of persons with metabolic syndrome inevitably deteriorate. For the purpose, the study aims to analyse the number of risk factors, and the relationship between abnormality of each risk factor and Quality of life, targeting adult women aged more than 19. For this study, data from the National Health and Nutrition Behavior Survey in 2007 and 2008 were incorporated and 4,365 subjects were collected for the study. Version 17.0 SPSS was used for data analysis. Statistical significance was defined as p<0.05. As a result of the study, the prevalence rate of metabolic syndrome was 24.2%. According to the number of risk factors of metabolic syndrome the regression coefficient of Quality of life was -0.024 when the number of risk factor was one, -0.048 when there were two risk factors, -0.090 when there were three risk factors, -0.117 when there were four risk factors, and -0.168 when there were five risk factors. The regression coefficient(abnormal/normal)of risk factors of metabolic syndrome were as follows; Waist circumference -0.035, Blood pressure was -0.064, Fasting glucose was -0,026 and HDL cholesterol was -0.012. In conclusion, as it was discovered that risk factors of metabolic syndrome had significant relations with Quality of life, it is suggested that the relations between some significant variables and Quality of life should be actively considered so that adult women can perceive metabolic syndrome properly and endeavor to improve their Quality of life.
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