Publications (23) View all
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Article: Pathways Involved in Sasang Constitution from Genome-Wide Analysis in a Korean Population.
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ABSTRACT: Abstract Objective: Sasang constitution (SC) medicine, a branch of Korean traditional medicine, classifies the individual into one of four constitutional types (Taeum, TE; Soeum, SE; Soyang, SY; and Taeyang, TY) based on physiologic characteristics. The authors of the current article recently reported individual genetic elements associated with SC types via genome-wide association (GWA) analysis. However, to understand the biologic mechanisms underlying constitution, a comprehensive approach that combines individual genetic effects was applied. Design: Genotypes of 1222 subjects of defined constitution types were measured for 341,998 genetic loci across the entire genome. The biologic pathways associated with SC types were identified via GWA analysis using three different algorithms-namely, the Z-static method, a restandardized gene set assay, and a gene set enrichment assay. Results: Distinct pathways were associated (p<0.05) with each constitution type. The TE type was significantly associated with cytoskeleton-related pathways. The SE type was significantly associated with cardio- and amino-acid metabolism-related pathways. The SY type was associated with enriched melanoma-related pathways. TY subjects were excluded because of the small size of that sample. Among these functionally related pathways, core-node genes regulating multiple pathways were identified. TJP1, PTK2, and SRC were selected as core-nodes for TE; RHOA, and MAOA/MAOB for SE; and GNAO1 for SY (p<0.05), respectively. Conclusions: The current authors systematically identified the biologic pathways and core-node genes associated with SC types from the GWA study; this information should provide insights regarding the molecular mechanisms inherent in constitutional pathophysiology.Journal of alternative and complementary medicine (New York, N.Y.) 08/2012; · 1.69 Impact Factor -
Article: Overexpression of romo1 promotes production of reactive oxygen species and invasiveness of hepatic tumor cells.
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ABSTRACT: Chronic oxidative stress from reactive oxygen species (ROS) produced by the mitochondria promotes hepatocarcinogenesis and tumor progression. However, the exact mechanism by which mitochondrial ROS contributes to tumor cell invasion is not known. We investigated the role of ROS modulator 1 (Romo1) in hepatocellular carcinoma (HCC) development and tumor cell invasiveness. We performed real-time, semi-quantitative, reverse transcriptase polymerase chain reaction; invasion and luciferase assays; and immunofluorescence and immunohistochemical analyses. The formation of pulmonary metastatic nodules after tumor cell injection was tested in severe combined immunodeficient mice. We analyzed Romo1 expression in HCC cell lines and tissues (n = 95). Expression of Romo1 was increased in HCC cells, compared with normal human lung fibroblast cells. Exogenous expression of Romo1 in HCC cells increased their invasive activity, compared with control cells. Knockdown of Romo1 in Hep3B and Huh-7 HCC cells reduced their invasive activity in response to stimulation with 12-O-tetradecanoylphorbol-13-acetate. Levels of Romo1 were increased compared with normal liver tissues in 63 of 95 HCC samples from patients. In HCC samples from patients, there was an inverse correlation between Romo1 overexpression and patient survival times. Increased levels of Romo1 also correlated with vascular invasion by the tumors, reduced differentiation, and larger tumor size. Romo1 is a biomarker of HCC progression that might be used in diagnosis. Reagents that inhibit activity of Romo1 and suppress mitochondrial ROS production, rather than eliminate up-regulated intracellular ROS, might be developed as cancer therapies.Gastroenterology 06/2012; 143(4):1084-1094.e7. · 11.68 Impact Factor -
Article: Comparison of pathways associated with hepatitis B- and C-infected hepatocellular carcinoma using pathway-based class discrimination method.
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ABSTRACT: Molecular signatures causing hepatocellular carcinoma (HCC) from chronic infection of hepatitis B virus (HBV) or hepatitis C virus (HCV) are not clearly known. Using microarray datasets composed of HCV-positive HCC or HBV-positive HCC, pathways that could discriminate tumor tissue from adjacent non-tumor liver tissue were selected by implementing nearest shrunken centroid algorithm. Cancer-related signaling pathways and lipid metabolism-related pathways were predominantly enriched in HCV-positive HCC, whereas functionally diverse pathways including immune-related pathways, cell cycle pathways, and RNA metabolism pathways were mainly enriched in HBV-positive HCC. In addition to differentially involved pathways, signaling pathways such as TGF-β, MAPK, and p53 pathways were commonly significant in both HCCs, suggesting the presence of common hepatocarcinogenesis process. The pathway clustering also verified segregation of pathways into the functional subgroups in both HCCs. This study indicates the functional distinction and similarity on the pathways implicated in the development of HCV- and/or HBV-positive HCC.Genomics 04/2012; 99(6):347-54. · 3.02 Impact Factor -
Article: Extracts of Scutellaria baicalensis Reduced Body Weight and Blood Triglyceride in db/db Mice.
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ABSTRACT: Scutellaria baicalensis has been extensively employed for the clinical treatment of hyperlipidemia, atherosclerosis, hypertension, dysentery, inflammatory diseases, and the common cold. The present study was performed to investigate the anti-obesity and anti-dyslipidemia effect of Scutellaria baicalensis extracts (SBE) in type 2 diabetic db/db mice. Male db/db mice were divided into three groups (n = 5) and orally administrated vehicle (control), SBE 10, and 100 mg/kg body weight/day for 4 weeks everyday. Administration of SBE improves weight gain, hypertriglyceridemia, and hyperinsulinemia in db/db mice. In obese db/db mice, SBE treatment also reduced plasma alanine aminotransferase levels. In the livers of db/db mice, SBE promoted 5' AMP-activated protein kinase activity and restored metabolic process and insulin signaling pathways. Our data demonstrate that SBE exerts potent anti-obesity and anti-hypertriglyceride effects suggesting its useful potential function as adjuvant therapeutic agent for the treatment of weight gain and hypertriglyceridemia. Copyright © 2012 John Wiley & Sons, Ltd.Phytotherapy Research 04/2012; · 2.09 Impact Factor -
Article: Genome-wide association analysis of Sasang constitution in the Korean population.
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ABSTRACT: Sasang constitutional medicine is a traditional Korean medicine in which an individual is classified into one of four types of constitution: Taeum (TE), Soeum (SE) Soyang (SY), and Taeyang (TY). These constitution types are determined with biologic and physiologic characteristics, so it has been assumed that genetic factors are associated with each constitution type. Identifying the genetic elements underlying each constitution is necessary for the elucidation of the molecular mechanism of Sasang constitutional medicine. A total of 341,998 genetic loci across the whole genome were genotyped for 1222 subjects of defined constitution type. The genetic loci associated with each constitution type were identified and the functional connectivity of genes within these loci was analyzed using statistical text mining. From the difference in allele frequencies between constitution types, significant genetic loci associated with each type were identified. Chromosomes 3q27.3 (rs10937331, p=2.71×10(-6)), 15q22.2 (rs7180547, p=1.58×10(-6)), and 14q22.3 (rs12431592, p=1.31×10(-6)) were most significantly associated with TE, SE, and SY constitution types, respectively. From the functional relationship analysis using all loci with a p-value≤10(-4), genes associated with each constitution type were identified. Fifteen (15) genes, including GPM6A, SYT4, and GRIK1, were significantly associated with the TE constitution type (p<0.05); 12 genes, including DRGX and AKAP11, were significantly associated with the SE constitution type (p<0.05); and 17 genes, including ZFP42, CDH22, ALDH1A2, OTX2, and EN2, were significantly associated with the SY constitution type (p<0.05). Genetic loci and genes associated with Sasang constitution types were systematically identified from a genome-wide association study using a large number of subjects.Journal of alternative and complementary medicine (New York, N.Y.) 03/2012; 18(3):262-9. · 1.69 Impact Factor
