• Journal of Nutrition and Health
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• 제28권2호
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• pp.115-126
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• 1995

The effects of energy-yielding substrates on coronary circulation, myocardial oxygen metabolism, and intramyocytic adenylates of perfused Wistar control rat(WC) and spontaneously hypertensive rat(SHR) hearts were examined under basal and $\beta$-adrenergic stimulation conditions. The perfusion medium (1.0mM Ca2+) contained 5mM glucose (+5U/l insulin) in combination with 5mM pyruvate, 5mM lacate, 5mM acetate, or 5mM octanoate as energy substrates. Hearts were perfused with each substrate buffer for 20min under basal conditions. Coronary functinal hyperemia was induced by infusing for 20min isoproterenol (ISO, 1uM), a $\beta$-receptor agonist. Cardiac adenylates, glycolytic intermediates, and coronary venous lactate were measured by using an enzymatic analysis technique. Under basal conditions, acetate and octanoate significantly increased coronary flow(CF) of WC in parallel with myocardial oxygen consumption. However, CF of SHR was partly attenuated by coronary vasoconstriction despite metabolic acidosis. In addition, pyruvate and lactate depressd ISO-induced coronary functional hyperemia in SHR. It should be noted that octanoate exhibited coronary dysfunction under ISO conditions. On the other hand, fat substrates depleted myocardial high energy phosphate pool and accumulated breakdown intermediates. In SHR with coronary vasoconstriction under basal conditions, and with depressed coronary functional hyperemia, high energy phosphates were greatly depleted. These results suggest that energy substrates in the myocardium and coronary smooth muscle alter remarkably coronary circulation, and that coronary circulatory function is associated with a reserve of high energy phosphates and a balance between breakdown and nono synthesis of energy phosphates. These findings could be explained by alterations in the cytosolic redox state manipulated by LDH and hence in the cytosolic phosphorylation potential, which might be involved in hypertension of SHR.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3963-3969
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• 2016

Purpose:To assess IGFBP-6 expression in relation with the presence of the metabolic syndrome, adiponectin receptors (AdipoR1 and AdipoR2) and IGF-IR levels in colorectal adenocarcinoma cases. Materials and Methods: IGFBP-6 mRNA and protein levels were analyzed using real-time quantitative PCR and Western blotting in 46 patients. ELISA and flow cytometry were used for evaluation of AdipoR1, AdipoR2 and IGF-IR. Results: The results showed that IGFBP-6 mRNA expression and the IGFBP-6 content were higher in tumor tissue samples of colorectal cancer patients with tahtn without metabolic syndrome. In addition, the IGFBP-6 mRNA expression was associated with tumor invasion (tumor size) and the IGFBP-6 protein level was associated with nodal status. Positive correlations and positive nonlinear relations were found between the IGFBP-6 level and the AdipoR1 and AdipoR2 contents in colorectal cancer patients. Conclusions: The IGFBP-6 mRNA level and protein level were found to be associated with presence of metabolic syndrome. Positive correlations indicated probable cross-talk between the IGF-IR-mediated and adiponectin-mediated signaling pathways in colorectal carcinomas. IGFBP-6 may be considered as a potential biomarker associated with lymphogenous metastasis and the metabolic syndrome in colorectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5137-5142
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• 2014

Adriamycin (ADR) is an important chemotherapeutic agent frequently used in treatment of breast cancer. However, resistance to ADR results in treatment failure in many patients. Recent studies have indicated that microRNAs (miRNAs) may play an important role in such drug-resistance. In the present study, microRNA-452 (miR-452) was found to be significantly down-regulated in adriamycin-resistant MCF-7 cells (MCF-7/ADR) compared with the parental MCF-7 cells by miRNA microarray and real-time quantitative PCR (RT-qPCR). MiR-452 mimics and inhibitors partially changed the adriamycin-resistance of breast cancer cells, as also confirmed by apoptosis assay. In exploring the potential mechanisms of miR-452 in the adriamycin-resistance of breast cancer cells, bioinformatics analysis, RT-qPCR and Western blotting showed that dysregulation of miR-452 played an important role in the acquired adriamycin-resistance of breast cancer, maybe at least in part via targeting insulin-like growth factor-1 receptor (IGF-1R).

• Journal of Dairy Science and Biotechnology
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• 제34권1호
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• pp.1-7
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• 2016

젖소 초유에는 성장인자가 풍부하게 함유되어 있는데, 상처 치유에 중요한 역할을 하고, 초유의 생리활성 기능을 담당하고 있다. Tyrosine kinase receptor의 활성을 유도하는 성장인자가 특이적으로 관여하여 세포의 분화, 면역기능, 신경기능 등 세포간 상호작용에 관여하는 EGFR(상피증식인자 수용체)와 FGFR(섬유아세포 증식인자)가 있다. 또한 VEGFR (혈관내피 증식인자)와 PDGF(혈소판유래 증식인자)도 존재한다. 조직회복을 위한 각질세포 분화와 세포의 이행에 성장인자가 상승효과를 나타내었고, 초유 또는 초유에 포함된 성장인자 peptide들은 장관질환 치료에 효과가 있으므로 치료제로 이용 가능성을 보여주었다.

• Journal of Periodontal and Implant Science
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• 제38권sup2호
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• pp.299-308
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• 2008

Purpose: The aim of this study was to evaluate adhesion and gene expression of the MC3T3-E1 cells cultured on machined titanium surface (MS) and anodized titanium surface (AS) using MTT test, Scanning electron micrograph and cDNA microarray. Materials and Methods: The MTT test assay was used for examining the proliferation of MC3T3-E1 cells, osteoblast like cells from Rat calvaria, on MS and AS for 24 hours and 48 hours. Cell cultures were incubated for 24 hours to evaluate the influence of the substrate geometry on both surfaces using a Scanning Electron Micrograph (SEM). The cDNA microarray Agilent Rat 22K chip was used to monitor expressions of genes. Results: After 24 hours of adhesion, the cell density on AS was higher than MS (p < 0.05). After 48 hours the cell density on both titanium surfaces were similar (p > 0.05). AS had the irregular, rough and porous surface texture. After 48 hours incubation of the MC3T3-E1 cells, connective tissue growth factor (CTGF) was up-regulated on AS than MS (more than 2 fold) and the insulin-like growth factor 1 receptor was down-regulated (more than 2 fold) on AS than MS. Conclusion: Microarray assay at 48 hours after culturing the cells on both surfaces revealed that osteoinductive molecules appeared more prominent on AS, whereas the adhesion molecules on the biomaterial were higher on MS than AS, which will affect the phenotype of the plated cells depending on the surface morphology.

• Journal of Ginseng Research
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• 제34권4호
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• pp.369-375
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• 2010

This study evaluated the protective effects of ginseng leaf extract (GLE) against high fat-diet-induced hyperglycemia and hyperlipidemia, and explored the potential mechanism underlying these effects in C57BL/6J mice. The mice were randomly divided into four groups: normal control, high fat diet control (HFD), GLE-treated at 250 mg/kg, and GLE-treated at 500 mg/kg. To induce hyperglycemic and hyperlipidemic states, mice were fed a high fat diet for 6 weeks and then administered GLE once daily for 8 weeks. At the end of the treatment, we examined the effects of GLE on plasma glucose, lipid levels, and the expression of genes related to lipogenesis, lipolysis, and gluconeogenesis. Both GLE groups lowered levels of plasma glucose, insulin, triglycerides, total cholesterol, and non-esterified fatty acids when compared to those in HFD group. Histological analysis revealed significantly fewer lipid droplets in the livers of GLE-treated mice compared with HFD mice. To elucidate the mechanism, Western blots and RT-PCR were performed using liver tissue. Compared with HFD mice, GLE-treated mice showed higher levels of phosphorylation of AMP-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase, but no differences in the expression of lipogenic genes such as sterol regulatory element-binding protein 1a, fatty acid synthase, sterol-CoA desaturase 1 and glycerol-3-phosphate acyltransferase. However, the expression levels of lipolysis and fatty acid uptake genes such as peroxisome proliferator-activated receptor-$\alpha$ and CD36 were increased. In addition, phosphoenolpyruvate carboxykinase gene expression was decreased. These results suggest that GLE ameliorates hyperglycemia and hyperlipidemia by inhibiting gluconeogenesis and stimulating lipolysis, respectively, via AMPK activation.

• Genomics & Informatics
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• 제12권4호
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• pp.195-202
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• 2014

Metabolic syndrome (MetS) is a complex disorder related to insulin resistance, obesity, and inflammation. Genetic and environmental factors also contribute to the development of MetS, and through genome-wide association studies (GWASs), important susceptibility loci have been identified. However, GWASs focus more on individual single-nucleotide polymorphisms (SNPs), explaining only a small portion of genetic heritability. To overcome this limitation, pathway analyses are being applied to GWAS datasets. The aim of this study is to elucidate the biological pathways involved in the pathogenesis of MetS through pathway analysis. Cohort data from the Korea Associated Resource (KARE) was used for analysis, which include 8,842 individuals (age, $52.2{\pm}8.9years$ ; body mass index, $24.6{\pm}3.2kg/m^2$). A total of 312,121 autosomal SNPs were obtained after quality control. Pathway analysis was conducted using Meta-analysis Gene-Set Enrichment of Variant Associations (MAGENTA) to discover the biological pathways associated with MetS. In the discovery phase, SNPs from chromosome 12, including rs11066280, rs2074356, and rs12229654, were associated with MetS (p < $5{\times}10^{-6}$), and rs11066280 satisfied the Bonferroni-corrected cutoff (unadjusted p < $1.38{\times}10^{-7}$, Bonferroni-adjusted p < 0.05). Through pathway analysis, biological pathways, including electron carrier activity, signaling by platelet-derived growth factor (PDGF), the mitogen-activated protein kinase kinase kinase cascade, PDGF binding, peroxisome proliferator-activated receptor (PPAR) signaling, and DNA repair, were associated with MetS. Through pathway analysis of MetS, pathways related with PDGF, mitogen-activated protein kinase, and PPAR signaling, as well as nucleic acid binding, protein secretion, and DNA repair, were identified. Further studies will be needed to clarify the genetic pathogenesis leading to MetS.

• 한국약용작물학회지
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• 제25권6호
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• pp.367-374
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• 2017

Background: An imbalance in energy intake and expenditure can cause obesity, which is a major risk factor for chronic diseases such as heart disease, type 2 diabetes, insulin resistance, cancers and hyperlipidemia. Methods and Results: In this study, we evaluated the anti-obesity effects of a water extract from the young leaves of barley sprout (BS) in 3T3-L1 cells and in high-fat diet (HFD)-induced obese mice (HF). Lipid accumulation measurement indicates that BS markedly inhibited adipogenesis by reducing lipid droplet production in a dose-dependent manner. Furthermore, the mRNA expression of adipogenic transcription factors peroxisome proliferator-activated receptor-${\gamma}$ and fatty acid synthetase, CCAAT/enhancer binding protein-${\alpha}$ and fatty acid binding protein 4 in 3T3-L1 cells was significantly inhibited by BS treatment. In an in vivo test, the BS-administered group of HFD-induced mice showed less body weight gain, and lower liver and epididymal white adipose tissue weights. The BS-treated mice showed decreased serum levels of leptin and lipids compared to untreated HFD mice and the levels of adiponectin and the HDL-cholesterol/total cholesterol ratio increased. These results indicate that BS inhibits body fat accumulation by reducing the mRNA expression of lipogenesis transcription factors and increasing serum adipokine concentration in in vitro and in vivo tests. Conclusions: BS reduced high fat diet-induced weight gain and had a positive effect on dyslipidemia.

• Nutrition Research and Practice
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• 제7권4호
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• pp.294-301
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• 2013

In this study, we examined the hepatic anti-steatosis activity of carnosic acid (CA), a phenolic compound of rosemary (Rosmarinus officinalis) leaves, as well as its possible mechanism of action, in a high-fat diet (HFD)-fed mice model. Mice were fed a HFD, or a HFD supplemented with 0.01% (w/w) CA or 0.02% (w/w) CA, for a period of 12 weeks, after which changes in body weight, blood lipid profiles, and fatty acid mechanism markers were evaluated. The 0.02% (w/w) CA diet resulted in a marked decline in steatosis grade, as well as in homeostasis model assessment of insulin resistance (HOMA-IR) index values, intraperitoneal glucose tolerance test (IGTT) results, body weight gain, liver weight, and blood lipid levels (P < 0.05). The expression level of hepatic lipogenic genes, such as sterol regulating element binding protein-1c (SREBP-1c), liver-fatty acid binding protein (L-FABP), stearoyl-CoA desaturase 1 (SCD1), and fatty acid synthase (FAS), was significantly lower in mice fed 0.01% (w/w) CA and 0.02% (w/w) CA diets than that in the HFD group; on the other hand, the expression level of ${\beta}$-oxidation-related genes, such as peroxisome proliferator-activated receptor ${\alpha}$ (PPAR-${\alpha}$), carnitine palmitoyltransferase 1 (CPT-1), and acyl-CoA oxidase (ACO), was higher in mice fed a 0.02% (w/w) CA diet, than that in the HFD group (P < 0.05). In addition, the hepatic content of palmitic acid (C16:0), palmitoleic acid (C16:1), and oleic acid (C18:1) was significantly lower in mice fed the 0.02% (w/w) CA diet than that in the HFD group (P < 0.05). These results suggest that orally administered CA suppressed HFD-induced hepatic steatosis and fatty liver-related metabolic disorders through decrease of de novo lipogenesis and fatty acid elongation and increase of fatty acid ${\beta}$-oxidation in mice.

• BMB Reports
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• 제54권6호
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• pp.323-328
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• 2021

Periodontal diseases have been reported to have a multidirectional association with metabolic disorders. We sought to investigate the correlation between periodontitis and diabetes or fatty liver disease using HFD-fed obese mice inoculated with P. gingivalis. Body weight, alveolar bone loss, serological biochemistry, and glucose level were determined to evaluate the pathophysiology of periodontitis and diabetes. For the evaluation of fatty liver disease, hepatic nonalcoholic steatohepatitis (NASH) was assessed by scoring steatosis, inflammation, hepatocyte ballooning and the crucial signaling pathways involved in liver metabolism were analyzed. The C-reactive protein (CRP) level and NASH score in P. gingivalis-infected obese mice were significantly elevated. Particularly, the extensive lobular inflammation was observed in the liver of obese mice infected with P. gingivalis. Moreover, the expression of metabolic regulatory factors, including peroxisome proliferator-activated receptor γ (Pparγ) and the fatty acid transporter Cd36, was up-regulated in the liver of P. gingivalis-infected obese mice. However, inoculation of P. gingivalis had no significant influence on glucose homeostasis, insulin resistance, and hepatic mTOR/AMPK signaling. In conclusion, our results indicate that P. gingivalis can induce the progression of fatty liver disease in HFD-fed mice through the upregulation of CD36-PPARγ axis.