PCNA反义寡核苷酸对人不同恶性肿瘤细胞体外增殖活性的影响

目的 :探讨增殖细胞核抗原 (PCNA)反义寡核苷酸 (ASO)对人不同恶性肿瘤细胞体外生长的影响。方法 :PCNA ASO在脂质体 (lipofectin)介导下转染膀胱癌EJ细胞、结肠癌HCT 8细胞、肺癌GLC 82细胞及恶性胶质瘤BT 32 5细胞 ,运用细胞计数、MTT、流式细胞术、克隆形成及免疫组织化学方法分析其抗瘤活性及机制。结果 :PCNA ASO对上述 4种肿瘤细胞的体外生长均有明显抑制作用 ;不同细胞敏感性差异较大 ,其中以GLC 82细胞最敏感 ,HCT 8细胞最不敏感 ;4种细胞生长均受阻于G1期。结论 :PCNA在恶性肿瘤细胞的增殖中是必需的。PCNA

人PPARα受体cDNA全长序列的克隆及测序

目的对人过氧化物酶体增殖物激活受体α(hPPARα)全长cDNA序列进行克隆并测序,为构建含hPPARα基因真核表达载体奠定基础。方法通过逆转录-聚合酶链式反应(RT-PCR)从HepG2细胞总RNA克隆hPPARα全长cDNA序列,胶回收目的条带后与pMD19-T载体连接并转化DH5α感受态菌,用BamH I、Sal I双酶切及基因测序筛选鉴定阳性克隆pMD19-hPPARα-T载体中hPPARα基因的完整性和忠实性。结果经酶切和DNA测序证实pMD19-hPPARα-T载体中插入的hPPARα基因序列与GeneBank中提交的序列(NM001001928)一致。结论成功克隆了hPPARα基因,构建了pMD19-hPPARα-T中间载体,为含hPPARα基因真核表达载体的构建奠定了基础。

叉头转录因子3A和过氧化物酶体增殖物激活受体辅激活因子1A基因多态性协同增加中国南方汉族长寿人群2型糖尿病风险

目的 研究叉头转录因子3A（FOXO3A）基因rs2802288（G/A）和过氧化物酶体增殖物激活受体辅激活因子1A（PPARGC1A）基因rs8192678 （G/A）与广西汉族长寿及一般人群中2型糖尿病（T2DM）的相关性,并探讨基因间相互作用.方法 2008年7月至2010年8月随机分层选取中国长寿之乡广西永福长寿老人506名（＞ 90岁）和一般人群830名.T2DM诊断依照1999年WHO标准.采用高分辨率熔解曲线（HRM）和聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）技术检测rs2802288和rs8192678基因型,通过logistic回归进行关联分析,通过风险等位基因累积效应分析及非参数多因子降维法（MDR）评价基因间相互作用.结果 隐性遗传模型下,仅在长寿人群中发现FOXO3A基因rs2802288 （G）与T2DM的风险存在正关联（x2=10.933,P＜0.05）,并且同PPARGC1A基因rs8192678（A）存在协同作用（x2=9.617,P＜0.05）;发生T2DM的风险随风险等位基因数目增加,累积4个风险等位基因的携带者具有最高风险（OR=6.482,P＜0.001）.MDR分析提示最佳交互模型为rs2802288、rs8192678和增龄的联合作用模式,最终增加T2DM风险（交叉验证一致性=10/10,P＜0.05）.结论 FOXO3A基因rs2802288 （G）是南方汉族长寿人群T2DM的风险等位基因,PPARGC1A基因rs8192678 （A）与其存在协同作用.

mir-518d在妊娠期糖尿病患者胎盘中的表达及意义

目的探讨mir-518d在妊娠期糖尿病(gestational diabetes mellitus,GDM)患者胎盘中的表达及意义。方法选择山东省交通医院2013年1月~2013年12月间收治的行剖宫产分娩的GDM产妇30例作为GDM组,同期行剖宫产的正常产妇30例作为对照组。应用实时定量PCR检测胎盘和血清mir-518d的表达;应用ELISA法检测血清雌二醇水平;应用电化学发光法检测血清胰岛素水平。结果 GDM组孕妇血清及胎盘mir-518d表达水平均显著高于对照组(P<0.01)。应用Targetscan和miRanda基因预测软件发现过氧化物酶体增殖物活受体a(peroxisome proliferator activated receptor A,PPARa)基因存在1个mir-518d结合位点,推测PPARa是mir-518d的靶基因。GDM组孕妇血清雌二醇水平显著高于对照组(P<0.05),血清胰岛素水平显著低于对照组(P<0.01)。Pearson相关性分析显示,胎盘mir-518d的表达水平与血清雌二醇水平呈正相关(r=0.686,P=0.012),与血清胰岛素水平呈负相关(r=-0.554,P=0.020)。结论 mir-518d可能通过调控PPARa基因影响机体糖代谢过程,在GDM发生发展中起到重要作用。

Peroxisome proliferator-activated receptor-γ is essential in the pathogenesis of gastric carcinoma

AIM： To investigate whether peroxisome proliferatoractivated receptor γ （PPAR-γ） is expressed in human gastric carcinoma and whether PPAR-γ, is a potential target for gastric carcinoma therapy. METHODS： PPAR-γ protein in gastric carcinoma was examined by immunohistochemistry. In the gastric carcinoma cell line MGCS03, PPAR-7, survivin, Skp2 and p27 protein and mRNA were examined by Western blotting and real-time reverse transcription-polymerase chain reaction, respectively; proliferation was examined by MTT; apoptosis was examined by chromatin staining with Hoechst 33342 and fluorescence activated cell sorting （FACS）. and cell cycle was examined by FACS; the knockdown of PPAR-γ was done by RNA interference. RESULTS： A high level of expression of PPAR-γ was observed in human gastric carcinoma and in a human gastric carcinoma cell line MGCS03. The PPAR-γ agonist 15-deoxy-△12,14-prostaglandin J2 （15d-PGJ2）inhibited growth, and induced apoptosis and G1/G0 cell cycle arrest in MGC803 cells in a concentration-dependent and time-dependent manner. The effect of 15d-PGJ2 on MGC803 cells was not reversed by the selective and irreversible antagonist GW9662 for PPAR-γ. Furthermore, survivin and Skp2 expression were decreased, whereas p27 expression was enhanced following 15d-PGJ2 treatment in a dose-dependent manner in MGC803 cells. Interestingly, we also found that small interfering RNA for PPAR-γ inhibited growth and induced apoptosis in MGC803 cells. The inhibition of PPAR-γ function may be a potentially important and novel modality for treatment and prevention of gastric carcinoma. CONCLUSION： A PPAR-γ agonist inhibited growth of human gastric carcinoma MGC803 cells by inducing apoptosis and G1/G0 cell cycle arrest with the involvement of survivin, Skp2 and p27 and not via PPAR-γ.

Cellular and molecular mechanisms of intestinal fibrosis

Fibrosis is a chronic and progressive process characterized by an excessive accumulation of extracellular matrix (ECM) leading to stiffening and/or scarring of the involved tissue. Intestinal fibrosis may develop in several different enteropathies, including inflammatory bowel disease. It develops through complex cell, extracellular matrix, cytokine and growth factor interactions. Distinct cell types are involved in intestinal fibrosis, such as resident mesenchymal cells (fibroblasts, myofibroblasts and smooth muscle cells) but also ECM-producing cells derived from epithelial and endothelial cells (through a process termed epithelialand endothelial-mesenchymal transition), stellate cells, pericytes, local or bone marrow-derived stem cells. The most important soluble factors that regulate the activation of these cells include cytokines, chemokines, growth factors, components of the renin-angiotensin system, angiogenic factors, peroxisome proliferator-activated receptors, mammalian target of rapamycin, and products of oxidative stress. It soon becomes clear that although inflammation is responsible for triggering the onset of the fibrotic proc-ess, it only plays a minor role in the progression of this condition, as fibrosis may advance in a self-perpetuating fashion. Definition of the cellular and molecular mechanisms involved in intestinal fibrosis may provide the key to developing new therapeutic approaches.

Heme oxygenase-1 prevents liver fibrosis in rats by regulating the expression of PPAR_γ and NF-_κB

AIM:To investigate the effects of heme oxygenase(HO)-1 on liver fibrosis and the expression of peroxisome proliferator-activated receptor gamma(PPARγ) and nuclear factor-kappa B(NF-κB) in rats.METHODS:Sixty Wistar rats were used to construct liver fibrosis models and were randomly divided into 5 groups:group A(normal,untreated),group B(model for 4 wk,untreated),group C(model for 6 wk,untreated),group D [model for 6 wk,treated with zinc protoporphyrin Ⅸ(ZnPP-Ⅸ) from week 4 to week 6],group E(model for 6 wk,treated with hemin from week 4 to week 6).Next,liver injury was assessed by measuring serum alanine aminotransferase(ALT),aspartate aminotransferase(AST) and albumin levels.The degree of hepatic fibrosis was evaluated by measuring serum hyaluronate acid(HA),type Ⅳ collagen(Ⅳ-C) and by histological examination.Hydroxyproline(Hyp) content in the liver homogenate was determined.The expres-sion levels of alpha-smooth muscle actin(α-SMA) in liver tissue were measured by real-time quantitative polymerase chain reaction(RT-PCR).The expression levels of PPARγ and NF-κB were determined by RT-PCR and Western blotting.RESULTS:The expression of HO-1 increased with the development of fibrosis.Induction of HO-1 by hemin significantly attenuated the severity of liver injury and the levels of liver fibrosis as compared with inhibition of HO-1 by ZnPP-Ⅸ.The concentrations of serum ALT,AST,HA and Ⅳ-C in group E decreased compared with group C and group D(P < 0.01).Amount of Hyp and α-SMA in the liver tissues in group E decreased compared with group C(0.62 ± 0.14 vs 0.84 ± 0.07,1.42 ± 0.17 vs 1.84 ± 0.17,respectively,P < 0.01) and group D(0.62 ± 0.14 vs 1.11 ± 0.16,1.42 ± 0.17 vs 2.56 ± 0.37,respectively,P < 0.01).The expression of PPARγ at levels of transcription and translation decreased with the development of fibrosis especially in group D;and it increased in group E compared with groups C and D(0.88 ± 0.15 vs 0.56 ± 0.19,0.88 ± 0.15 vs 0.41 ± 0.11,respectively,P < 0.01).The expression of NF-κB increased with the development of fibrosis especially in group D;and it decreased in group E compared with groups C and D(1.43 ± 0.31 vs 1.89 ± 0.29,1.43 ± 0.31 vs 2.53 ± 0.54,respectively,P < 0.01).CONCLUSION:Our data demonstrate a potential mechanism that HO-1 can prevent liver fibrosis by enhancing the expression of PPARγ and decreasing the expression of NF-κB in liver tissues.

Potential efficacy of ginger as a natural supplement for nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is one of the most common liver diseases and its prevalence is likely to reach epidemic proportions.According to the"two-stage hypothesis"proposed for the pathophysiology of NAFLD,insulin resistance,oxidative stress and pro-inflammatory cytokines are among the key promoters of the disease. Here,ginger has been hypothesized to prevent NAFLD or blunt its progression via several mechanisms,such as sensitizing insulin effects,activating peroxisome proliferator-activated receptorγwhich induces adiponectin and down-regulates pro-inflammatory cytokines,changing the balance between adiponectin and tumor necrosis factor-αin favor of adiponectin,promoting considerable antioxidant effects and antidyslipidemic properties,and reducing hepatic triglyceride content which can prevent steatosis.The aforementioned mechanisms imply that ginger possesses interesting potentials for serving as a natural supplement for the prevention and treatment of NAFLD.Therefore,conducting trials to explore its benefits in clinical practice is greatly recommended.

THE INCREASE IN PLASMINOGEN ACTIVATOR INHIBITOR TYPE-1 EXPRESSION BY STIMULATION OF ACTIVATORS FOR PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS IN HUMAN ENDOTHELIAL CELLS

Objective.To investigate the effect of peroxis ome proliferator-activated recept ors(PPARs )activators on plasminogen activator inhibitor ty pe-1(PAI-1)expression in human umbilical vein e ndothelial cells and the possi-ble mechanism.Methods.Human umbilical vein endothelial ce lls(HUVECs )were obtained from normal fetus,and cul-tured conventionally.Then the HUVECs were exposed to test agents(linolenic acid,linoleic acid,oleic acid,stearic acid and prostaglandin J 2 respectively)in varying concentrations with fresh media.RT -PCR and ELISA were applied to determine the expression of PPARs and PAI-1in HUVECs.Results.PPARα,PPARδand PPARγmRNA were detected by using RT-PCR in HUVECs.Treatment of HUVECs with PPARαand PPARγactivators---linolenic acid,linoleic acid,oleic acid and prostaglandin J 2 respectively,but not with stearic a cid could augment PAI-I mRNA expression and protein secretion in a concentration-dependent manner.However,the mRNA expressions of 3subclasses of PPAR with their activators in HUVECs were not changed compared w ith controls.Conclusion.HUVECs express PPARs.PPARs activators may increase PAI-1expression in ECs,but the underlying mechanism remains uncle ar.Although PPARs expression was not enhanced after stimulated by their activators in ECs,the role of functionally active PPARs in regulating PA I-1expression in ECs needs to be further investigated by using transient gen e transfection assay.

Gut bacteria alteration in obese people and its relationshipwith gene polymorphism

AIM:To investigate the differences in cultivable gut bacteria and peroxisome proliferator-activated receptor γ2(PPAR-γ2) gene Pro12Ala variation in obese and normal-weight Chinese people.METHODS:Using culture methods,the amounts of Escherichia coli,Enterococci,Bacteroides,Lactobacilli,Bif idobacteria and Clostridium perfringens(C.perfringens) in the feces of 52 obese participants [body mass index(BMI):≥ 28 kg/m2] and 52 participants of normalweight(BMI:18.5-24 kg/m2) were obtained.Study participants completed comprehensive questionnaires and underwent clinical laboratory tests.The polymerase chain reaction-restriction fragment length polymorphism(PCR-PFLP) assay was used to analyze PPAR-γ2 gene Pro12Ala variation.RESULTS:The obese group exhibited a lower amount of C.perfringens(6.54 ± 0.65 vs 6.94 ± 0.57,P = 0.001)and Bacteroides(9.81 ± 0.58 vs 10.06 ± 0.39,P = 0.012) than their normal-weight counterparts.No major differences were observed in Pro12Ala genotype distribution between the two groups;however,obese individuals with a Pro/Ala genotype had a signif icantly lower level of Bacteroides(9.45 ± 0.62 vs 9.93 ± 0.51,P = 0.027) than those with a Pro/Pro genotype.In addition,the obese group demonstrated a higher stool frequency(U = 975,P < 0.001) and a looser stool(U = 1062,P = 0.015) than the normal-weight group.CONCLUSION:Our results indicated interactions among cultivable gut flora,host genetic factors and obese phenotype and this might be helpful for obesity prevention.

Leptin and peroxisome proliferator-activated receptor γ expression in colorectal adenoma

AIM： To investigate the expressions of leptin and per- oxisome proliferator-activated receptor y （PPARG） in relation to body mass index （BMI）. METHODS： We evaluated leptin and PPARG expres- sion in 30 adenomas over 1 cm in size by immunohisto- chemical staining. In addition, clinicopathologic features including BMI were assessed. RESULTS： PPARG and leptin expression showed a strong positive correlation （P = 0.035）. The average BMI of the leptin-positive group was higher than that of the leptin-negative group （25.4 ＋ 3.4 kg/m2 vs 22.6 ＋ 2.4 kg/m2, P = 0.018）, and leptin expression was sig- nificantly correlated with high BMI （P = 0.024）. Leptinexpression was more frequently observed in intermedi- ate/high grade dysplasia than in low grade dysplasia （P = 0.030）. However, PPARG expression was not cor- related with BMI and grade of dysplasia. CONCLUSION： BMI has influenced on the leptin ex- pression of colorectal adenoma. The exact mechanism underlies the strong correlation between leptin and PPARG expression needs further study.

Glucose Metabolic and Gluconeogenic Pathways Disturbance in the Intrauterine Growth Restricted Adult Male Rats

Objective To explore the molecular mechanism of type 2 diabetes in intrauterine growth restricted adult rats through determination of blood glucose and expression of gluconeogenic enzymes in liver.Methods Male intrauterine growth restriction(IUGR) offspring induced by maternal protein-malnutrition and normal controls were studied.The body weights of offspring rats were weighted from birth to 12 weeks of age.Fasting plasma glucose and insulin levels were determined by glucose oxidase method and enzyme-linked immunosorbent assay(ELISA) respectively at 1 week,8 weeks,and 12 weeks.Peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α),phosphoenolpyruvate carboxykinase(PEPCK),and glucose-6-phosphatase(G6Pase) mRNA and protein levels in liver were measured by real time RT-PCR and Western blot in newborn rats(Week 1) and adult rats(Week 12).Results Birth weights of IUGR rats were significantly lower than those of controls until 4 weeks later,when IUGR rats caught up to controls.Between 8 and 12 weeks,the growth of IUGR rats surpassed that of controls.No significant differences were observed in blood glucose and insulin levels at newborn rats between the two groups.However,by the end of 8 weeks IUGR rats developed hyperinsulinemia and high insulin resistance index.At the age of 12 weeks,IUGR rats had mild fasting hyperglycemia.In addition,hepatic PGC-1α mRNA and protein levels as well as hepatic mRNA levels of PEPCK and G6Pase at Week 1 and Week 12 in IUGR rats were all significantly higher than those of controls(P<0.05).Conclusions As a result of intrauterine malnutrition,the expression of gluconeogenic genes is exaggerated in offspring.This change stays through adulthood and may contribute to the pathogenesis of type 2 diabetes.

Curcumin suppresses PPARδ expression and related genes in HT-29 cells

AIM:To investigate the effects of curcumin on the expression of peroxisome proliferator-activated receptorδ(PPARδ)and related genes in HT-29 cells. METHODS:HT-29 cells were treated with curcumin (0-80μmol/L)for 24 h.The effects of curcumin on the morphology of HT-29 cells were studied by Hoechst 33342 staining.The activity of caspase-3 was determined using DEVD-p NA as substrate.The levels of peroxisome PPARδ,14-3-3εand vascular endothelial growth factor(VEGF)in HT-29 cells were determined by Western blotting analysis and their mRNA expression was determined by real-time quantitative RT-PCR. RESULTS:Treatment with 10-80μmol/L curcumin induced typical features of apoptosis and activated the caspase-3 in HT-29 cells.The expression of PPARδ, 14-3-3εand VEGF was reduced and the activity of β-catenin/Tcf-4 signaling was inhibited by curcumin treatment. CONCLUSION:Curcumin can induce apoptosis of HT-29 cells and down-regulate the expression of PPARδ,14-3-3εand VEGF in HT-29.

Role of PGC-1αin muscle function and aging

This article focuses on the current underlying of molecular mechanisms of the peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α） mediated pathway and discuss possible therapeutic benefits of increased mitochondrial biogenesis in compensating for mitochondrial dysfunction and ameliorating aging and aging-related diseases. PGC-1α is the master transcription regulator that stimulates mitochondrial biogenesis, by upregulating nuclear respiratory factors and mitochondrial transcription factor A, leading to increased mitochondrial DNA replication and gene transcription. PGC-1α also regulates cellular oxidant-antioxidant homeostasis by stimulating the gene expression of superoxide dismutase-2, catalase, glutathione peroxidase 1, and uncoupling protein. Recent reports from muscle-specific PGC-1α overexpression underline the benefit of PGC-1α in muscle atrophy and sarcopenia, during which PGC-1α enhanced mitochondrial biogenic pathway and reduced oxidative damage. Thus, PGC-1α seems to have a protective role against aging associated skeletal muscle deterioration.

Omega-3 fatty acids for the treatment of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease （NAFLD） has been recognized as a major health burden. It is the most important cause of chronic liver disease and a major in- dependent cardiovascular risk factor. Lacking a definite treatment for NAFLD, a specific diet and an increase in physical activity represent the most commonly used therapeutic approaches. In this review, major literature data about the use of omega-3 polyunsaturated fatty ac- ids （n-3 PUFAs） as a potential treatment of NAFLD have been described, n-3 PUFAs, besides having a beneficial impact on most of the cardio-metabolic risk factors （hy- pertension, hyperlipidemia, endothelial dysfunction and atherosclerosis） by regulating gene transcription factors [i.e., peroxisome proliferator-activated receptor （PPAR） cz, PPARy, sterol regulatory element-binding protein-i, carbohydrate responsive element-binding protein], im- pacts both lipid metabolism and on insulin sensitivity. In addition to an enhancement of hepatic beta oxidation and a decrease of the endogenous lipid production, n-3 PUFAs are able to determine a significant reduction of the expression of pro-inflammatory molecules （tumor necrosis factor-~ and interleukin-6） and of oxygen reac- tive species. Further strengthening the results of the in vitro studies, both animal models and human interven- tion trials, showed a beneficial effect of n-3 PUFAs on the severity of NAFLD as expressed by laboratory pa- rameters and imaging measurements. Despite available results provided encouraging data about the efficacy of n-3 PUFAs as a treatment of NAFLD in humans, well- designed randomized controlled trials of adequate size and duration, with histological endpoints, are needed to assess the long-term safety and efficacy of PUFA, as well as other therapies, for the treatment of NAFLD and non-alcoholic steatohepatitis patients. It is worthwhile to consider that n-3 PUFAs cannot be synthesized by the human body and must be derived from exogenous sources （fish oil, flaxseeds, olive oil） which are typical foods of the Mediterranean diet, known for its beneficial effects in preventing obesity, diabetes and, in turn, cardiovascular events. According to these data, it is important to consider that most of the beneficial effects of n-3 PUFAs can also be obtained by an equilibrate nutrition program.

GCN5 Acetyltransferase Inhibits PGC1α-induced Hepatitis B Virus Biosynthesis

Hepatitis B virus （HBV） biosynthesis is primarily restricted to hepatocytes due to the governing of liver-enriched nuclear receptors （NRs） on viral RNA synthesis. The liver-enriched NR hepatocyte nuclear factor 4α （HNF4α, the key regulator of genes implicated in hepatic glucose metabolism, is also a primary determinant of HBV pregenomic RNA synthesis and HBV replication. Peroxisome proliferator-activated receptor-r coactivator la （PGCla） coactivates and further enhances the effect of HNF4α on HBV biosynthesis. Here, we showed that the acetyltransferase General Control Non-repressed Protein 5 （GCN5） acetylated PGC 1 α, leading to alteration of PGC 1 α from a transcriptionally active state into an inactive state. As a result, the coactivation activity of PGCla on HBV transcription and replication was suppressed. Apparently, an acetylation site mutant of PGC 1 α （PGC 1 αR13） still had coactivation activity as GCN5 could not suppress the coactivation activity of the mutant. Moreover, a catalytically inactive acetyltransferase mutant GCN5m, due to the loss of acetylation activity, failed to inhibit the coactivation function of PGClα in HBV biosynthesis. Our results demonstrate that GCN5, through its acetyltransferase activity, inhibits PGCla-induced enhancement of HBV transcription and replication both in vitro and in vivo.

Functional Variant of C-689T in the Peroxisome Proliferator-Activated Receptor-γ2 Promoter is Associated with Coronary Heart Disease in Chinese Nondiabetic Han People

Objective To investigate the association between the polymorphism of C-689T in the peroxisome proliferator-activated receptor-γ2 （PPARγ2） promoter and coronary heart disease （CHD）. Methods This case-controlled study was conducted in nondiabetic Chinese Han people, which enrolled 455 patients with CHD （cases） and 693 subjects without CHD （controls）. Data of clinical indexes were collected, including height, body weight, waist circumstance, systolic blood pressure （SBP）, diastolic blood pressure （DBP）, smoking, drinking, physical activity, as well as body mass index （BMI）. Fasting blood glucose （FBG）, plasma total cholesterol （TC） and triglyceride （TG） levels were measured. Polymerase chain reaction-restricted fragments length polymorphism （PCR-RFLP） was used to determine the PPARγ2 promoter C-689→T substitution. The genotype distribution of PPARγ2 promoter C-689T, allelic frequency, clinical indexes, and laboratorial measurements were compared between the two groups. The effect of genotype on the risk of CHD was assessed using univariate and multivariate regression model. Results The genotype frequencies of CC, CT and TT in PPARγ2 promoter C-689T were 89.7%, 9.9% and 0.4% in the case group, and 93.1%, 6.6% and 0.3% in the control group, respectively （CC vs. CT＋TT, χ^2= 6.243, P=0.041）. Carriers of -689T allele （n=95） had significantly higher TC level than non-carriers （n=1053） （5.12±1.26 vs. 4.76±1.22 mmol/L, P=0.001）. Male carriers of -689T allele （n=51） were significantly higher in waist circumference, body weight, TC and TG than male non-carriers （n=656） （all P〈0.05）. In subjects whose BMI was over 25 kg/m2, carriers of -689T allele （n=82） had significantly higher levels of waist circumference, BMI, SBP and TC than non-carriers （n=231） （all p〈0.05）. The -689T allele was an independent risk factor for CHD （OR=1.668, 95%CI： 1.031-2.705, P=0.037） after adjusting for age, gender, waist circumference, body weight, BMI, smoking, physical activities, SBP, DBP, FBG, TC and TG level. Conclusion These data support the hypothesis that the -689T allele is associated with an increased risk of CHD, in Chinese Han people and correlates significantly with the profiles of CHD-related risk factors.

Moro orange juice prevents fatty liver in mice

AIM:To establish if the juice of Moro,an anthocyaninrich orange,may improve liver damage in mice with diet-induced obesity.METHODS:Eight-week-old mice were fed a high-fat diet(HFD) and were administrated water or Moro juice for 12 wk.Liver morphology,gene expression of lipid transcription factors,and metabolic enzymes were assessed.RESULTS:Mice fed HFD displayed increased body weight,insulin resistance and dyslipidemia.Moro juice administration limited body weight gain,enhanced insulin sensitivity,and decreased serum triglycerides and total cholesterol.Mice fed HFD showed liver steatosis associated with ballooning.Dietary Moro juice markedly improved liver steatosis by inducing the expression of peroxisome proliferator-activated receptor-α and its target gene acylCoA-oxidase,a key enzyme of lipid oxidation.Consistently,Moro juice consumption suppressed the expression of liver X receptor-α and its target gene fatty acid synthase,and restored liver glycerol-3-phosphate acyltransferase 1 activity.CONCLUSION:Moro juice counteracts liver steatogenesis in mice with diet-induced obesity and thus may represent a promising dietary option for the prevention of fatty liver.