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Frequency of fat mass and obesity-associated gene rs9939609 and peroxisome proliferator-activated receptor gamma 2 gene rs1801282 polymorphisms among Trinidadian neonates of different ethnicities and their relationship to anthropometry at birth. 特立尼达不同种族新生儿脂肪量与肥胖相关基因rs9939609和过氧化物酶体增殖物激活受体2基因rs1801282多态性频率及其与出生时人体测量的关系
Q Agricultural and Biological Sciences Pub Date : 2014-01-01 Epub Date: 2014-06-21 DOI: 10.1159/000363138
Candace E Cuthbert, D Dan Ramdath, Jerome E Foster

Background: The fat mass and obesity-associated gene (FTO) rs9939609 and peroxisome proliferator-activated receptor gamma 2 gene (PPARG2) rs1801282 polymorphisms are type 2 diabetes mellitus susceptibility gene variants associated with obesity. This study examined whether these variants are associated with anthropometry at birth among a representative multi-ethnic sample of Trinidadian neonates.

Methods: Cord blood was obtained from consecutive term live births and DNA was genotyped for FTO and PPARG2 variants using polymerase chain reaction. Associations between neonate anthropometry at birth and genotype frequency were assessed using the χ(2) test and linear regression.

Results: Significant associations were observed between neonate ethnicity and PPARG2 (p = 0.005) and FTO (p = 0.017) variants: high-risk alleles were more prevalent among African than South Asian neonates for both variants. The allelic and genotypic frequencies for mixed neonates were between those for the African and those for the South Asian neonates. No significant relationship was observed between rs9939609 and rs1801282 and anthropometric measures. For both variants, the allelic and genotypic frequencies among the African and South Asian neonates mirrored those found elsewhere for similar ethnic groups.

Conclusions: Neonates of African ethnicity possess the highest frequency of rs9939609 and rs1801282 alleles and genotypes; this may be associated with ethnic differences in the risk of lifestyle diseases.

背景:脂肪量和肥胖相关基因(FTO) rs9939609和过氧化物酶体增殖物激活受体2基因(PPARG2) rs1801282多态性是与肥胖相关的2型糖尿病易感基因变异。这项研究在特立尼达新生儿的代表性多种族样本中调查了这些变异是否与出生时的人体测量有关。方法:采集连续足月活产脐带血,采用聚合酶链反应对FTO和PPARG2基因型进行DNA分型。使用χ(2)检验和线性回归评估新生儿出生时人体测量与基因型频率之间的关系。结果:新生儿种族与PPARG2 (p = 0.005)和FTO (p = 0.017)变异之间存在显著关联:高危等位基因在非洲新生儿中比南亚新生儿中更普遍。混合新生儿的等位基因和基因型频率介于非洲和南亚新生儿之间。rs9939609和rs1801282与人体测量值无显著相关。对于这两种变异,非洲和南亚新生儿的等位基因和基因型频率反映了其他地方相似种族群体的发现。结论:非洲裔新生儿rs9939609和rs1801282等位基因和基因型频率最高;这可能与生活方式疾病风险的种族差异有关。
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引用次数: 0
DNA Methylation Changes Induced by a High-Fat Diet and Fish Oil Supplementation in the Skeletal Muscle of Mice. 高脂肪饮食和补充鱼油对小鼠骨骼肌DNA甲基化的影响。
Q Agricultural and Biological Sciences Pub Date : 2014-01-01 Epub Date: 2015-05-27 DOI: 10.1159/000381777
Catia L Amaral, Amanda R Crisma, Laureane N Masi, Amanda R Martins, Sandro M Hirabara, Rui Curi

Background/aims: To investigate the global changes in DNA methylation and methylation of the promoter region of the peroxisome proliferator-activated receptor gamma transcript variant 2 (Pparg2) gene resulting from a high-fat diet (HFD) and/or fish oil supplementation.

Methods: Fish oil, rich in omega-3 polyunsaturated fatty acids, or water was orally administered to male mice for 12 weeks. After the first 4 weeks, the animals were fed a control diet or an HFD until the end of the experimental protocol, when the epididymal fat, gastrocnemius muscle and liver were excised.

Results: Pparg2 mRNA expression was upregulated by obesity and downregulated by fish oil supplementation in the liver. In the gastrocnemius muscle, diet-induced obesity increased global DNA methylation. Fish oil prevented the decrease in Pparg2 promoter methylation induced by obesity in the gastrocnemius muscle. Regardless of the diet given, fish oil supplementation increased Pparg2 promoter methylation at CpG-263 in muscle and adipose tissue.

Conclusion: HFD and fish oil modified global and Pparg2 promoter DNA methylation in a tissue-specific manner. Fish oil supplementation attenuated body weight gain, abolished the increase in Pparg2 expression in the liver and prevented the decrease in Pparg2 promoter methylation in the muscle induced by the HFD.

背景/目的:研究高脂肪饮食(HFD)和/或鱼油补充对DNA甲基化和过氧化物酶体增殖物激活受体γ转录变异体2 (Pparg2)基因启动子区域甲基化的影响。方法:雄性小鼠口服富含omega-3多不饱和脂肪酸的鱼油或水12周。4周后,分别饲喂对照饲粮或高脂饲料,直至实验结束,切除附睾脂肪、腓肠肌和肝脏。结果:肝脏中Pparg2 mRNA的表达在肥胖的作用下上调,在鱼油的作用下下调。在腓肠肌中,饮食引起的肥胖增加了整体DNA甲基化。鱼油可以防止腓肠肌肥胖引起的Pparg2启动子甲基化的减少。无论给予何种饮食,补充鱼油都增加了肌肉和脂肪组织中Pparg2启动子CpG-263的甲基化。结论:HFD和鱼油以组织特异性的方式改变了global和Pparg2启动子DNA甲基化。补充鱼油可以减轻体重增加,消除肝脏中Pparg2表达的增加,并阻止HFD引起的肌肉中Pparg2启动子甲基化的下降。
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引用次数: 23
The impact of the Bellagio Report on healthy agriculture, healthy nutrition, healthy people: scientific and policy aspects and the International Network of Centers for Genetics, Nutrition and Fitness for Health. 《贝拉吉奥报告》对健康农业、健康营养、健康人的影响:科学和政策方面以及遗传学、营养和健身促进健康中心国际网络。
Q Agricultural and Biological Sciences Pub Date : 2014-01-01 Epub Date: 2015-03-04 DOI: 10.1159/000375495
Artemis P Simopoulos

The Bellagio Report on Healthy Agriculture, Healthy Nutrition, Healthy People was the result of a meeting held at the Rockefeller Foundation Bellagio Center in the fall of 2012. The meeting was science based but policy oriented. The Bellagio Report concluded that: (1) sugar consumption, especially in the form of high-energy fructose in soft drinks, poses a major and insidious health threat, particularly for children; (2) current diets in most populations, albeit with regional differences, are deficient in omega-3 fatty acids but too high in omega-6 fatty acid intake, and (3) not all calories are the same since calories from different sources (i.e. glucose or fructose or omega-6 or omega-3 fatty acids) have different metabolic and neurohormonal effects. This paper summarizes the scientific progress and policy actions that have occurred in these three areas. Genetic variation in populations and gene-nutrient interactions are fundamental concepts that need to be taken into consideration in growth and development and in the prevention and management of chronic noncommunicable diseases since there is enormous variation in both the frequency of genetic variants and dietary composition worldwide. Furthermore, this paper updates the Bellagio Report in terms of the scientific and policy aspects, both of which have expanded over the past 2 years, and describes the progress made in establishing an International Network of Centers for Genetics, Nutrition and Fitness for Health.

《关于健康农业、健康营养、健康人群的贝拉吉奥报告》是2012年秋天在洛克菲勒基金会贝拉吉奥中心举行的一次会议的结果。这次会议以科学为基础,但以政策为导向。Bellagio报告的结论是:(1)糖的消耗,特别是软饮料中的高能量果糖,对健康构成了重大和潜在的威胁,特别是对儿童;(2)尽管存在地区差异,但大多数人群目前的饮食缺乏omega-3脂肪酸,而omega-6脂肪酸摄入量过高;(3)并非所有卡路里都是相同的,因为来自不同来源的卡路里(即葡萄糖或果糖或omega-6或omega-3脂肪酸)具有不同的代谢和神经激素作用。本文总结了这三个领域的科学进展和政策行动。种群遗传变异和基因-营养相互作用是生长发育和慢性非传染性疾病预防和管理中需要考虑的基本概念,因为世界范围内遗传变异的频率和饮食组成都存在巨大差异。此外,本文在科学和政策方面更新了Bellagio报告,这两个方面在过去两年中都有所扩展,并描述了在建立遗传学、营养和健康健身中心国际网络方面取得的进展。
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引用次数: 15
Perspectives on personalized nutrition for obesity. 肥胖症个性化营养的观点。
Q Agricultural and Biological Sciences Pub Date : 2014-01-01 DOI: 10.1159/000365158
J Alfredo Martínez
Obesity can result from the disequilibrium between energy intake and expenditure associated with alterations of many metabolic pathways [1] . As many cellular functions related to energy homeostasis are regulated by gene expression and gene-environment interactions, individual variation in body weight/composition and adipose metabolism could be influenced by genetic makeup and nutrient intake. Nutritional outcomes can also be determined by gene-mediated biochemical pathways that regulate nutrient absorption, distribution, metabolism, and excretion as well as other cellular energy processes [2] . Indeed, the interplay between nutrients and genetic variation could be a key factor influencing obesity risk and development as well as associated conditions. About 25–70% of body weight variability is thought to be controlled by genes that affect energy homeostasis through the modulation of nuclear transcription factors, signalling molecules and receptors, adipogenesis and fat deposition, thermogenesis, hypothalamic networks, and other cellular functions related to energy efficiency [3, 4] . More than 50 genes have been implicated in obesity phenotypes, and adiposity traits have been identified in both animal and human studies [5] . For example, monogenic obesity is attributed to the mutation of specific alleles with profound effects, namely in the leptin, leptin receptor, pro-opiomelanocortin, proprotein convertase/kexin type 1, melanocortin-4 receptor, and single-minded homolog 1 genes. However, monogenic obesity is relatively uncommon, and studies on polygenic obesity support the notion that the modern prevalence of obesity has resulted from the interactions of unfavourable lifestyles with specific gene variants or single-nucleotide polymorphisms (SNPs) with less profound but converging effects [6] . Individuals susceptible to excessive fat gain may therefore carry gene variants that influence appetite control (CNR1, NPY, POMC, MC4R, etc.), nuclear and cytoplasm regulatory machinery (FTO, TFAPB2, TCF7L2, SCAP, DRD2, etc.), adipogenesis and lipid metabolism (ADRB3, PPAR, APOs, PLIN, etc.), energy expenditure (UCPs), insulin signalling (ISR-2, INSIG2, GIPR), and inflammation (ADIPOQ, IL-6, RESISTIN, etc.) [6] . Over 500 SNPs or chromosomal regions have been directly or indirectly associated with obesity [7] . Published online: July 24, 2014
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引用次数: 20
Association of genetic polymorphisms for glutathione peroxidase genes with obesity in Spanish children. 西班牙儿童谷胱甘肽过氧化物酶基因遗传多态性与肥胖的关系
Q Agricultural and Biological Sciences Pub Date : 2014-01-01 Epub Date: 2014-12-02 DOI: 10.1159/000368833
Azahara I Rupérez, Josune Olza, Mercedes Gil-Campos, Rosaura Leis, María Dolores Mesa, Rafael Tojo, Ramón Cañete, Ángel Gil, Concepción M Aguilera

Background/aims: Altered expression and activity of the antioxidant enzymes glutathione peroxidases (GPXs) have been observed in obesity in human and animal studies. We aimed to study 59 single nucleotide polymorphisms (SNPs) for GPX1-7 genes and to characterize their association with prepubertal childhood obesity and its associated biomarkers.

Methods: This case-control study included 193 obese and 191 normal-weight prepubertal Spanish children, in whom anthropometry, biochemical parameters, adipokines, antioxidant enzyme erythrocyte activities and biomarkers of oxidative stress, inflammation and cardiovascular risk were measured. The genotype analysis was performed in the Illumina platform. PLINK and SPSS were used for statistical analyses.

Results: We found SNPs rs757228 and rs8103188 (GPX4) to be negatively associated and rs445870 (GPX5) and rs406113 (GPX6) to be positively associated with obesity in children. The variant rs2074451 (GPX4) increased GPX activity in erythrocytes. Although we did not find significant differences in erythrocyte GPX activity between obese and normal-weight children, GPX activity was found to be positively and significantly correlated with blood pressure, adipocyte fatty acid-binding protein and high-sensitivity C-reactive protein.

Conclusions: The GPX variants rs757228, rs8103188, rs445870 and rs406113 were associated with prepubertal childhood obesity. However, erythrocyte GPX activity was not altered in obese prepubertal Spanish children.

背景/目的:在人类和动物研究中发现,抗氧化酶谷胱甘肽过氧化物酶(gpx)的表达和活性在肥胖中发生改变。我们旨在研究GPX1-7基因的59个单核苷酸多态性(snp),并表征它们与青春期前儿童肥胖及其相关生物标志物的关系。方法:本病例对照研究纳入193例肥胖和191例正常体重的西班牙青春期前儿童,测量其人体测量、生化参数、脂肪因子、红细胞抗氧化酶活性以及氧化应激、炎症和心血管风险的生物标志物。在Illumina平台上进行基因型分析。采用PLINK和SPSS进行统计分析。结果:我们发现snp rs757228和rs8103188 (GPX4)与儿童肥胖呈负相关,rs445870 (GPX5)和rs406113 (GPX6)与儿童肥胖呈正相关。变体rs2074451 (GPX4)增加了红细胞中GPX的活性。虽然我们没有发现肥胖儿童与正常体重儿童红细胞GPX活性有显著差异,但我们发现GPX活性与血压、脂肪细胞脂肪酸结合蛋白和高敏c反应蛋白呈正相关。结论:GPX变异rs757228、rs8103188、rs445870和rs406113与青春期前儿童肥胖相关。然而,红细胞GPX活性在肥胖的青春期前西班牙儿童中没有改变。
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引用次数: 26
Solexa sequencing of microRNAs on chromium metabolism in broiler chicks. 肉仔鸡铬代谢microrna的Solexa测序。
Q Agricultural and Biological Sciences Pub Date : 2013-01-01 Epub Date: 2013-08-15 DOI: 10.1159/000353703
Y Z Pan, S G Wu, H C Dai, H J Zhang, H Y Yue, G H Qi

Aim: The aim of this study was to determine the effect of chromium picolinate (CrPic) on the differential expression of the known microRNAs (miRNAs) in broiler skeletal muscle.

Methods and results: A total of 288 1-day-old male Arbor Acres broilers were randomly assigned to one of four dietary treatments supplemented with 0, 0.4, 2.0, or 10.0 mg·kg(-1) CrPic, respectively. Dietary CrPic supplementation at 10.0 mg·kg(-1) increased the average daily feed intake in broilers (p < 0.05). On day 42, the serum total protein level was highest in animals treated with 2.0 mg·kg(-1) (p < 0.05) and 10.0 mg·kg(-1) CrPic (p < 0.05). Dietary supplementation with 10.0 mg·kg(-1) CrPic decreased the levels of serum glucose (p < 0.05) on day 42 and of serum triglyceride (p < 0.05) on days 21 and 42. To further identify miRNAs from broiler skeletal muscles, we sequenced two small RNA libraries using the Solexa sequencing approach, and 57 miRNAs were found to be significantly differentially expressed (p < 0.05). Among them, 6 upregulated and 2 downregulated miRNAs were validated by real-time qPCR (p < 0.05).

Conclusions: The results of the present study provide a valuable clue regarding the role of miRNA target genes in the mechanism of the dietary CrPic effect on protein synthesis in skeletal muscles of broilers.

目的:研究吡啶甲酸铬(CrPic)对肉鸡骨骼肌中已知microRNAs (miRNAs)差异表达的影响。方法与结果:288只1日龄爱拔益加肉仔鸡,随机分为4组,分别添加0、0.4、2.0和10.0 mg·kg(-1) CrPic。饲粮中添加10.0 mg·kg(-1)的CrPic可提高肉仔鸡平均日采食量(p < 0.05)。第42天,2.0 mg·kg(-1)和10.0 mg·kg(-1) CrPic组血清总蛋白水平最高(p < 0.05)。饲粮中添加10.0 mg·kg(-1) CrPic降低了第42天的血清葡萄糖水平(p < 0.05)和第21天和第42天的血清甘油三酯水平(p < 0.05)。为了进一步鉴定肉鸡骨骼肌的mirna,我们使用Solexa测序方法对两个小RNA文库进行了测序,发现57个mirna表达有显著差异(p < 0.05)。其中6个上调mirna和2个下调mirna通过real-time qPCR验证(p < 0.05)。结论:本研究结果为miRNA靶基因在饲粮中添加CrPic对肉鸡骨骼肌蛋白质合成影响机制中的作用提供了有价值的线索。
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引用次数: 13
Gene expression changes in spleens and livers of tumour-bearing mice suggest delayed inflammation and attenuated cachexia in response to oil palm phenolics. 荷瘤小鼠脾脏和肝脏的基因表达变化表明,油棕酚类物质可延缓炎症和减轻恶病质。
Q Agricultural and Biological Sciences Pub Date : 2013-01-01 Epub Date: 2014-03-13 DOI: 10.1159/000357948
Soon-Sen Leow, Shamala Devi Sekaran, Kalyana Sundram, Yewai Tan, Ravigadevi Sambanthamurthi

Background/aim: Plant phenolics can inhibit, retard or reverse carcinogenesis, and may thus help prevent or treat cancer. Oil palm phenolics (OPP) previously showed anti-tumour activities in vivo via a cytostatic mechanism at 1,500 ppm gallic acid equivalent. Here, we report other possible molecular mechanisms by which this extract attenuates cancer, especially those concerning the immune response.

Methods: We subcutaneously injected J558 myeloma cells in BALB/c mice and supplemented OPP orally at 1,500 ppm gallic acid equivalent. We observed the physiology parameters of these animals and harvested their spleens and livers after 18 h, 1 week and 4 weeks for microarray gene expression analysis using Illumina MouseRef-8 BeadChips.

Results: Time course microarray analysis on spleens after injecting J558 myeloma cells in mice revealed that the immune response of tumour-bearing mice supplemented with OPP was lower compared to controls, thus suggesting delayed inflammation in response to OPP. In livers, cholesterol biosynthesis genes were upregulated while inflammatory genes were downregulated through time, further suggesting attenuation of systemic inflammation and cachexia. These effects correlated with the delayed in vivo development of syngeneic tumours in mice given OPP.

Conclusions: This study suggests the possible utilisation of OPP as an anti-tumour and anti-cachexia agent.

背景/目的:植物酚类物质可以抑制、延缓或逆转癌症的发生,从而有助于预防或治疗癌症。油棕酚类物质(OPP)先前在1500 ppm没食子酸当量下通过细胞抑制机制在体内显示出抗肿瘤活性。在这里,我们报告了其他可能的分子机制,通过这种提取物减轻癌症,特别是那些有关免疫反应。方法:在BALB/c小鼠皮下注射J558骨髓瘤细胞,并以1500 ppm没食子酸当量口服补充OPP。分别于18 h、1周和4周采集小鼠的脾脏和肝脏,使用Illumina MouseRef-8 BeadChips进行微阵列基因表达分析。结果:对小鼠注射J558骨髓瘤细胞后的脾脏进行时程微阵列分析发现,荷瘤小鼠补充OPP后的免疫应答较对照组降低,提示OPP对炎症反应的延迟,肝脏中胆固醇生物合成基因随着时间的推移而上调,炎症基因下调,进一步提示全身炎症和恶病质的减弱。结论:本研究提示了OPP作为一种抗肿瘤和抗恶病质药物的可能应用。
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引用次数: 10
Frontiers of nutritional intervention. 营养干预的前沿。
Q Agricultural and Biological Sciences Pub Date : 2013-01-01 Epub Date: 2014-04-04 DOI: 10.1159/000362481
Jing X Kang
It is increasingly recognized that nutritional intervention holds great potential for the management of modern chronic disease. Understanding the relationship between nutrient metabolism and disease development is an important foundation for nutritional intervention. To maximize the utility of nutritional intervention, it is critical that we identify the factors underlying chronic disease that can be modulated by nutrients. Based on recent research, I consider the following three areas to be among the frontiers of nutritional intervention: chronic low-grade inflammation, gut microbiota, and epigenetics. Chronic low-grade inflammation is known to be a common mechanism underlying the pathology of many chronic diseases, including obesity, diabetes, heart disease, cancer, and neurodegenerative diseases [1] . Interventions that suppress the development of chronic lowgrade inflammation could therefore be of great utility in addressing these diseases. In fact, much of the current research on the prevention and treatment of these diseases has targeted chronic inflammation. Inflammatory response involves multiple processes, including lipid mediator formation, cytokine expression, immune cell migration, etc., which can be modulated directly or indirectly by nutrients and/or their metabolites in differential manners. Certain nutrients exhibit opposing effects on inflammation. For example, omega-6 polyunsaturated fatty acids and their metabolites generally promote inflammatory processes, while omega-3 fatty acids and their metabolites largely suppress them [2] . Thus, a full understanding of the specific nutrients’ effect on chronic inflammation should be an important area of nutritional research. Given the complexity of the diet and the numerous interactions that occur between nutrients in different compositions, there remains much to be investigated about the overall effect of a diet on chronic low-grade inflammation. Future studies to elucidate how the steps of chronic low-grade inflammation are influenced by the type and quantity of nutrients and their metabolites will allow us to formulate effective interventions to modulate chronic low-grade inflammation. The gut microbiota, which is highly variable among individuals, has recently been shown to play a key role in human health and disease [3] . More and more studies have shown that alterations in the gut microbiota can influence many physiological and pathological processes, Published online: April 4, 2014
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引用次数: 1
Nutritional genetics: the case of alcohol and the MTHFR C677T polymorphism in relation to homocysteine in a black South African population. 营养遗传学:南非黑人人群中酒精和MTHFR C677T多态性与同型半胱氨酸的关系
Q Agricultural and Biological Sciences Pub Date : 2013-01-01 Epub Date: 2013-03-27 DOI: 10.1159/000348839
Cornelie Nienaber-Rousseau, Pedro T Pisa, Christine S Venter, Suria M Ellis, Annamarie Kruger, Sarah J Moss, Alida Melse-Boonstra, G Wayne Towers

Background/aims: It is unknown whether the effect of alcohol consumption on homocysteine (Hcy) is modulated by the methylenetetrahydrofolate reductase (MTHFR) C677T. We explored this hypothesized effect by analyzing cross-sectional data of 1,827 black South Africans.

Methods: Total Hcy concentrations were determined by fluorescence polarization immunoassay and the genotype through polymerase chain reaction-based RFLP analysis.

Results: Subjects harboring the 677 TT genotype had the highest Hcy. Among subjects harboring the 677 CC genotype, men had higher Hcy (p = 0.04). Age and gamma-glutamyltransferase (GGT) correlated best (r = 0.26 and r = 0.27; p < 0.05), while the percentage carbohydrate-deficient transferrin and the B vitamins correlated weakly (r < 0.1; p < 0.05) with Hcy. Hcy was positively associated with the reported alcohol intake (p ≤ 0.01). There was no interaction between alcohol consumption and the MTHFR 677 CC or CT genotypes (p > 0.05) for Hcy concentrations; however, an interaction was determined for GGT and the MTHFR genotype (p = 0.02). Age, GGT, gender, MTHFR and vitamin B6 explained 16.8% of the variation in Hcy (p < 0.01).

Conclusion: The determined interactions might result in differences in the risk conveyed through Hcy with regard to disease development in those with unfavorable GGT concentrations.

背景/目的:目前尚不清楚饮酒对同型半胱氨酸(Hcy)的影响是否受到亚甲基四氢叶酸还原酶(MTHFR) C677T的调节。我们通过分析1827名南非黑人的横断面数据来探索这种假设的影响。方法:采用荧光偏振免疫法测定总Hcy浓度,采用基于聚合酶链反应的RFLP分析测定基因型。结果:677 TT基因型人群Hcy最高。在携带677 CC基因型的受试者中,男性的Hcy较高(p = 0.04)。年龄与γ -谷氨酰转移酶(GGT)相关性最好(r = 0.26和r = 0.27;p < 0.05),而缺糖转铁蛋白百分比与B族维生素相关性较弱(r < 0.1;p < 0.05)。Hcy与报告的酒精摄入量呈正相关(p≤0.01)。在Hcy浓度方面,饮酒与MTHFR 677 CC或CT基因型之间无交互作用(p > 0.05);然而,确定GGT和MTHFR基因型存在相互作用(p = 0.02)。年龄、GGT、性别、MTHFR和维生素B6解释了16.8%的Hcy变异(p < 0.01)。结论:确定的相互作用可能导致在GGT浓度不利的人群中,通过Hcy传递的疾病发展风险存在差异。
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引用次数: 11
Epigallocatechin-3-gallate inhibits IGF-I-stimulated lung cancer angiogenesis through downregulation of HIF-1α and VEGF expression. 表没食子儿茶素-3-没食子酸酯通过下调HIF-1α和VEGF表达抑制igf - i刺激的肺癌血管生成。
Q Agricultural and Biological Sciences Pub Date : 2013-01-01 Epub Date: 2013-08-31 DOI: 10.1159/000354402
Xiangyong Li, Yun Feng, Jinhua Liu, Xiaowei Feng, Keyuan Zhou, Xudong Tang

Background/aims: Numerous studies have shown that epigallocatechin-3-gallate (EGCG), a polyphenol component extracted from green tea, can inhibit the growth and induce apoptosis of various types of human tumor cells. In this study, we evaluated the inhibitory effects of EGCG on the proangiogenic capabilities of A549 cells.

Methods: A549 cells starved in serum-free culture medium for 24 h were pretreated with EGCG at various concentrations (0, 10, 25, 50, and 100 μmol/l) for 1 h, followed by the addition of insulin-like growth factor-I (IGF-I) at the final concentration of 40 ng/ml and continued culturing for an additional 16 h. The in vitro angiogenesis analyzing test kit with ECMatrix™ gel was used to detect the formation of capillary tube-like structures. The mRNA expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) was determined by real-time PCR. The protein expression of HIF-1α and VEGF was detected by Western blotting and ELISA, respectively.

Results: EGCG significantly inhibited the formation of capillary tube-like structures on the surface of ECMatrix induced by IGF-I both in vitro and in vivo and reduced the level of hemoglobin in Matrigel plugs. In addition, EGCG was shown to significantly inhibit the IGF-I-induced upregulation of HIF-1α protein expression. Meanwhile, EGCG at the concentration of 25 and 100 μmol/l exhibited obvious inhibitory effects on IGF-I-induced VEGF expression (p < 0.01).

Conclusion: Our results suggest that EGCG has potent inhibitory effects on tumor angiogenesis induced by IGF-I in human non-small cell lung cancer cells, which may possibly contribute to the downregulation of HIF-1α and VEGF expression.

背景/目的:大量研究表明,从绿茶中提取的一种多酚成分表没食子儿茶素-3-没食子酸酯(EGCG)可以抑制人类多种类型肿瘤细胞的生长并诱导其凋亡。在本研究中,我们评估了EGCG对A549细胞促血管生成能力的抑制作用。方法:A549细胞在无血清培养基中培养24 h后,分别用不同浓度(0、10、25、50、100 μmol/l)的EGCG预处理1 h,然后添加最终浓度为40 ng/ml的胰岛素样生长因子- i (IGF-I),继续培养16 h。使用ECMatrix™凝胶体外血管生成分析试剂盒检测毛细血管样结构的形成。实时荧光定量PCR检测缺氧诱导因子-1α (HIF-1α)和血管内皮生长因子(VEGF) mRNA表达。采用Western blotting和ELISA分别检测HIF-1α和VEGF的蛋白表达。结果:EGCG在体外和体内均能显著抑制igf - 1诱导的ECMatrix表面毛细血管样结构的形成,降低基质塞血红蛋白水平。此外,EGCG可显著抑制igf -i诱导的HIF-1α蛋白表达上调。同时,25和100 μmol/l浓度的EGCG对igf -i诱导的VEGF表达有明显的抑制作用(p < 0.01)。结论:EGCG对人非小细胞肺癌细胞igf -1诱导的肿瘤血管生成具有明显的抑制作用,可能与下调HIF-1α和VEGF的表达有关。
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引用次数: 61
期刊
Journal of Nutrigenetics and Nutrigenomics
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