• Clinical and Experimental Pediatrics
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• v.52 no.9
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• pp.984-990
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• 2009

Purpose : Being small for gestational age (SGA) is a risk factor of short stature in children. Genetic background such as mid-parental height (MPH) is known to influence growth of children born SGA. We studied the relationship between growth of children born SGA and MPH and studied the effects of insulin-like growth factor (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3) on postnatal growth in children born SGA according to MPH. Methods : Forty-nine neonates born SGA were included in this study. We defined corrected height standard deviation score (cHtSDS) by modified height SDS (HtSDS) based on their MPH. We categorized subjects into group 1 consisting of children with cHtSDS ${\geq}0$ (n=35) and group 2 consisting of children with cHtSDS <0 (n=14), and compared IGF-I and IGFBP-3 between the two groups. Results : The HtSDSs and cHtSDSs in groups 1 and 2 were $0.06{\pm}1.05$ vs. $-0.95{\pm}0.85$ (P=0.000) and $0.78{\pm}0.93$ vs. $-0.46{\pm}0.67$ (P=0.000), respectively. IGF-I SDS was higher in group 1 than in group 2 ($2.82{\pm}3.69$ vs. $0.23{\pm}2.42$, P=0.012). Total cHtSDS ($0.42{\pm}1.03$) was significantly higher than HtSDS ($-0.22{\pm}1.10$) (P=0.000). Conclusion : Our results show that cHtSDS differs significantly from HtSDS. Growth assessment by standardized growth curve does not uniformly show effects of genetic factors. A more accurate assessment of growth uses a personalized corrected growth curve that considers the genetic factor measured by MPH.

• Journal of Animal Science and Technology
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• v.46 no.4
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• pp.563-570
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• 2004

The insulin-like growth factor(IGF) system, consisting of IGFs-I and -II ligands and their receptors and six IGF-binding proteins(IGFBPs), plays an important role in survival, proliferation and differentiation of a variety of cell types. Lithium is a known modulator of survival and proliferation of many cell types in vitro. The present study was undertaken to investigate the relationship between LiCI-induced changes in cell survival and growth and the expression of the IGF system components in C6 rat glioma cell line which, besides IGF-I and its receptor, is known to express IGFBP-3 as its major IGF carrier. When C6 cells were cultured for 24h in the absence or presence of 2mM or 5mM LiCl in a 10% serwn-containing medium, the viability and the number of cells were not affected by added lithium. In 72-h culture, however, C6 cells clearly exhibited a dose-dependent response to added LiCl. The cells cultured for 72h in the presence of 0, 2mM and 5mM LiCl exhibited a typical mitotic, a growth-arrested and an apoptotic appearances, respectively. Moreover, the apoptotic cells were accompanied by reduced expression of IGF-I, IGF-I receptor and IGFBP-3 as examined by semi-quantitative reverse transcription-polymerase chain reaction. Interestingly, blockade of IGFBP-3 mRNA translation by addition of 101${\mu}M$ IGFBP-3 anti-sense oligodeoxyribonucleotide in serum-free, 24-h culture resulted in a decrease in the number of cells as well as relative abundance of the target mRNA. In summary, results suggest that the cytotoxic effect of lithium in C6 cell is likely to be mediated, in part, by suppression by this agent of the expression of the IGF system components. In this regard, IGFBP-3 may play at least a 'permissive' role in normal proliferation of this cell.

• Journal of Life Science
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• v.22 no.6
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• pp.744-750
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• 2012

The aim of the present study is to investigate the effects of 12 weeks-moderate aerobic exercise training on body composition, adiponectin, retinol-binding protein-4 (RBP-4), and vascular inflammation factors in obese children. The subjects were classified into two groups, one of which was an exercise group (n=15) practicing moderate aerobic exercise training for 12 weeks, and the other group, the control group (n=13), was not in that program. The exercise group participants performed on the treadmill running at heart rate reserve (HRR) 50% of exercise intensity for 300 kcal of the consumed time. The results of all the studies and inspections are as follows: Weight, body mass index, body fat, and systolic and diastolic blood pressure were significantly lower, while $VO_2$ max was higher in the exercise group than in the control group (p<0.05, respectively). Fasting glucose, insulin, and HOMA-IR levels in the exercise group were significantly decreased (p<0.05), whereas adiponectin levels in the exercise group were significantly increased after 12 weeks' exercise training (p<0.05). In addition, our results showed that RBP4, C-reactive protein (CRP), and interleukin-6 (IL-6) concentrations in the exercise group were significantly lower than those of the control group (p<0.05). This investigation has shown that a 12 weeks-regular aerobic exercise program offers useful effects such as an amelioration of inflammation and body indices in obese children.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4607-4611
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• 2012

Objective: Endometrial cancer (EC) is the most common gynecologic malignancy. Identification of potential biomarkers of EC would be helpful for the detection and monitoring of malignancy, improving clinical outcomes. Methods: The Weighted Gene Co-expression Network Analysis method was used to identify prognostic markers for EC in this study. Moreover, underlying molecular mechanisms were characterized by KEGG pathway enrichment and transcriptional regulation analyses. Results: Seven gene co-expression modules were obtained, but only the turquoise module was positively related with EC stage. Among the genes in the turquoise module, COL5A2 (collagen, type V, alpha 2) could be regulated by PBX (pre-B-cell leukemia homeobox 1)1/2 and HOXB1(homeobox B1) transcription factors to be involved in the focal adhesion pathway; CENP-E (centromere protein E, 312kDa) by E2F4 (E2F transcription factor 4, p107/p130-binding); MYCN (v-myc myelocytomatosis viral related oncogene, neuroblastoma derived [avian]) by PAX5 (paired box 5); and BCL-2 (B-cell CLL/lymphoma 2) and IGFBP-6 (insulin-like growth factor binding protein 6) by GLI1. They were predicted to be associated with EC progression via Hedgehog signaling and other cancer related-pathways. Conclusions: These data on transcriptional regulation may provide a better understanding of molecular mechanisms and clues to potential therapeutic targets in the treatment of EC.

• Journal of Microbiology and Biotechnology
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• v.14 no.6
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• pp.1286-1294
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• 2004

In a previous study by the current authors, hepatocellular carcinoma (HCC) was determined to be epidemiologically sex-dependent, and the incidence and multiplicity of HCC found to decrease in estradiol-3 benzoate (EB)-treated F344 rats. Therefore, to ascertain the anticancer mechanism of EB, a commercially available cDNA microarray, with a total of 14,815 cDNA rat gene clones, was used to determine the differentially expressed genes in nontreated livers, EB-treated livers, and diethynitrosolamine (DEN)-induced HCC. In the sequenced experiment, a total of 85 genes were differentially expressed at either two or more times the rate of the normal expression, where 33 genes were downregulated by EB, and 52 genes upregulated. Candidate genes were selected according to significant changes observed in the mRNA expression in the EB-treated livers compared with the nontreated livers, then these genes were filtered according to their different expression patterns in the DEN-induced tumors compared to the estrogen-treated livers. To confirm the microarray data, a real-time PCR analysis was performed for ten selected genes: the H-ras revertant protein 107 (H­rev107), insulin-like growth factor binding protein (lOFBP), parathyroid hormone receptor (PI'HR), SH3 domain binding protein (SH3BP), metallothionein, src-suppressed C-kinase substrate (SSeCK) gene, phosphodiesterase I, CD44, epithelial membrane protein 3 (EMP3), and estrogen receptor a (ERa). The SSeCK and phosphodiesterase I genes were both upregulated in the DEN-induced hepatocarcinomas, yet their possible carcinogenic functions remain unknown. Meanwhile, the other genes were downregulated, including the genes related to growth regulation (IOFBP, H-revI07, ER$\alpha$), adipogenesis inhibition (PTHR), and tumor suppression (metallothionein).

• Genomics & Informatics
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• v.12 no.4
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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.

• Korean Journal of Medicinal Crop Science
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• v.25 no.6
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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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• v.7 no.4
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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.

• Journal of Veterinary Science
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• v.23 no.1
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• pp.4.1-4.15
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• 2022

Background: Flavonoids are natural polyphenols found widely in citrus fruit and peel that possess anti-adipogenic effects. On the other hand, the detailed mechanisms for the antiadipogenic effects of flavonoids are unclear. Objectives: The present study observed the anti-adipogenic effects of five major citrus flavonoids, including hesperidin (HES), narirutin (NAR), nobiletin (NOB), sinensetin (SIN), and tangeretin (TAN), on AMP-activated protein kinase (AMPK) activation in palmitate (PA)-treated HepG2 cells. Methods: The intracellular lipid accumulation and triglyceride (TG) contents were quantified by Oil-red O staining and TG assay, respectively. The glucose uptake was assessed using 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose (2-NBDG) assay. The levels of AMPK, acetyl-CoA carboxylase (ACC), and glycogen synthase kinase 3 beta (GSK3β) phosphorylation, and levels of sterol regulatory element-binding protein 2 (SREBP-2) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) expression were analyzed by Western blot analysis. The potential interaction between the flavonoids and the γ-subunit of AMPK was investigated by molecular docking analysis. Results: The flavonoid treatment reduced both intracellular lipid accumulation and TG content in PA-treated HepG2 cells significantly. In addition, the flavonoids showed increased 2-NBDG uptake in an insulin-independent manner in PA-treated HepG2 cells. The flavonoids increased the AMPK, ACC, and GSK3β phosphorylation levels and decreased the SREBP-2 and HMGCR expression levels in PA-treated HepG2 cells. Molecular docking analysis showed that the flavonoids bind to the CBS domains in the regulatory γ-subunit of AMPK with high binding affinities and could serve as potential AMPK activators. Conclusion: The overall results suggest that the anti-adipogenic effect of flavonoids on PA-treated HepG2 cells results from the activation of AMPK by flavonoids.

• ALGAE
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• v.38 no.1
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• pp.81-92
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• 2023

Obesity-induced inflammation is crucial in the pathogenesis of insulin resistance and type 2 diabetes. In this study, we investigated the effects of the Gracilaria chorda (GC) on lipid accumulation and obesity-induced inflammatory changes or glucose homeostasis in cell models (3T3-L1 adipocytes and RAW 264.7 macrophages). Samples of GC were extracted using solvents (water, methanol, and ethanol) and subcritical water (SW) at different temperatures (90, 150, and 210℃). The total phenolic content of GCSW extract at 210℃ (GCSW210) showed the highest content compared to others, and GCSW210 highly inhibited lipid accumulation and significantly reduced gene expressions of peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding protein-α, sterol regulatory element-binding protein-1c, and fatty acid synthase in 3T3-L1 adipocytes. In addition, GCSW210 effectively downregulated the pro-inflammatory cytokine regulator pathways in RAW 264.7 macrophages, including mitogen-activated protein kinase, signal transducers and activators of transcription and nuclear factor-κB. In co-culture of 3T3-L1 adipocytes and RAW 264.7 macrophages, GCSW210 significantly reduced nitric oxide production and interleukin-6 levels, and improved glucose uptake with dose-dependent manner. These findings suggest that GCSW210 improves glucose metabolism by attenuating obesity-induced inflammation in adipocytes, which may be used as a possible treatment option for managing obesity and associated metabolic disorders.