代谢组学在乳腺癌生物标志物研究中的现状及展望

代谢组学是近年来系统生物学研究领域中最活跃的分支学科之一,通过研究生命体在不同生理病理状态下所产生的内源性代谢物变化规律来揭示疾病相关的代谢本质.作为系统生物学研究中的后起之秀,代谢组学以其特独的研究视角和技术优势迅速而广泛地应用于癌症研究领域,已初步展现出广阔的临床应用前景.乳腺癌是女性最常见的恶性肿瘤,严重威胁着女性健康且呈年轻化趋势.利用代谢组学技术平台对乳腺癌进行研究,寻找潜在的代谢性生物标志物,有助于乳腺癌的早期诊断、疗效评价、预后监控及制定合适的个体化治疗方案,对改善乳腺癌患者的存活率具有重要意义.本文将对代谢组学的概念、研究方法及其在乳腺癌生物标志物研究中的应用进行综述.     

脂质组学在医药研究中的应用

脂质组学是对整体脂质进行系统分析的一门新兴学科,通过比较不同生理状态下脂代谢网络的变化,进而识别代谢调控中关键的脂生物标志物,最终揭示脂质在各种生命活动中的作用机制。电喷雾电离-质谱技术是脂质组学领域中最核心的研究手段,目前已能对各种脂质尤其是磷脂进行高分辨率、高灵敏度、高通量的分析。随着质谱技术的进步,脂质组学在疾病脂生物标志物的识别、疾病诊断、药物靶点及先导化合物的发现和药物作用机制的研究等方面已展现出广泛的应用前景。     

脂质组学分析方法进展及其在癌症研究中的应用

脂质占人体内源性代谢物的一半以上,种类繁多,结构复杂,因而具有多种生物功能,与多种生命活动密切相关。脂质组学是代谢组学分支的新兴学科,它可以通过比较不同生理状态下脂质含量的变化,寻找代谢通路中关键的脂质生物标志物,最终揭示脂质在各种生命活动中的作用机制。随着质谱技术的进步,脂质组学在疾病脂类生物标志物的识别、疾病诊断、药物作用机制的研究等方面已展现出广泛的应用前景。本文主要就脂质组学近几年的分析方法进展及其在癌症中的最新应用进行了综述。     

代谢组学技术及其在毒理学研究领域中的应用

代谢组学是近几年发展起来的对某一生物或细胞所有低分子量代谢产物进行定性和定量分析的一门新学科,其研究对象主要是生物体液,研究手段主要是核磁共振和质谱。简要综述了代谢组学的概念、代谢组学在毒理学研究领域中的应用、当前代谢组学研究中存在的问题及今后的发展趋势,并探讨了代谢组学在研究毒物作用机制、药物的临床前安全性评价、确定毒物作用靶器官及器官特异性新的生物标志物中的实际应用。     

代谢组学技术及其在临床研究中的应用

在后基因组时代, 系统生物学研究成为人们关注的焦点。转录组学、蛋白质组学等功能基因组学研究方法可同时检测药物或其他因素影响下大量基因或蛋白质的表达变化情况, 但这些变化不能与生物学功能的变化建立直接联系。代谢组学方法则可为代谢物含量变化与生物表型变化建立直接相关性。代谢组学研究的目的是定量分析一个生物系统内所有代谢物的含量, 进行全面代谢物分析需要分析化学技术的支撑, 核磁共振和基于质谱的分析技术是代谢组学研究的两种主要技术手段。代谢组学研究可产生大量数据信息, 对这些数据进行分析离不开化学统计学的应用, 比如主成分分析、多维缩放、各种聚类分析技术以及功能差异分析等。文章综述了近年来代谢组学分析技术及数据分析技术的研究进展, 在此基础上, 对代谢组学在临床研究及临床前研究中的应用研究进展进行了综述。对疾病代谢表型图谱的研究有助于人们了解疾病发生、发展以及致死的机制; 在临床条件下, 这些代谢图谱可以作为疾病诊断、预后以及治疗的评判标准。代谢物组成的变化是毒物胁迫对机体造成的最终影响, 利用代谢组技术可以直接反映毒物对机体的影响。质谱技术、核磁共振技术的应用使得药物筛选过程可以快速完成, 并有助于实现个性化用药。此外, 利用代谢组学技术还可以进行已知酶的新活性研究, 也可以研究未知酶。     

代谢组学技术发展及其在农业动植物研究中的应用

代谢组学是依赖灵敏、稳定的分析流程和数据库,利用色谱–质谱联用、核磁共振技术对生物体内以及生物样品所有的小分子代谢物进行鉴定和定量分析的学科,在医学、食品科学、畜牧学、植物学等领域得到广泛应用。代谢组学方法可将代谢物种类和含量的变化与生物表型变化建立更直接的联系,因此代谢组学逐渐成为继基因组学、转录组学、蛋白组学后对复杂性状系统解析的新的研究手段。本文介绍了代谢组学常用分析策略、检测平台和常用数据库。在此基础上,综述了代谢组学在农业动物重要经济性状代谢分子鉴定、疾病诊断、肉品质及动物制品安全检测等领域取得的进展,并总结了利用代谢组学、转录组学和基因组学等多组学研究在动植物重要性状的发育、形成和解析等领域取得的最新成果。代谢组学与其他多组学方法整合分析,可以更全面地阐述各类复杂性状的遗传机制,有助于完善"突变–基因–表达–代谢–表型"的完整生物学过程,为复杂性状的机理解析提供新方法,为新型农业育种提供新思路。     

植物响应病原真菌的代谢组学研究进展

代谢组学是对特定条件下的生物体内代谢物进行定性或定量分析,从而得到与特定生理或病理反应相关的代谢物变化的一门新学科,并因此被广泛应用于植物学、微生物学、毒理学及疾病诊断等领域。近年来,代谢组学开始应用到植物–微生物互作研究领域,尤其是在植物响应病原菌胁迫的研究中。该文综述了代谢组学的定义、研究方法及其在植物–病原真菌互作领域中的应用,并讨论了其研究前景和所面临的挑战。     

基于稳定同位素的代谢组学临床研究进展

基于稳定同位素示踪的代谢组学不仅能检测疾病发生发展及治疗过程中相关代谢物的变化,还可以对生物体系的代谢物进行定量分析并描述代谢特性。目前,稳定同位素示踪的代谢组学技术可在受试者体内直接追踪到代谢网络的单个原子,更有利于发现与疾病病因和诊断及药物疗效评估相关的生物标志物。现就稳定同位素示踪代谢组学在临床研究中的应用做简要概述,以期为将来更好地开展代谢组学在临床方面的研究提供重要依据。     

代谢组学及其应用

对代谢组学的概念、特性、发展历史做了简要介绍,综述了当前代谢组学研究中的数据采集、数据分析中采用的技术,及代谢组学在疾病诊断、药物毒性研究、植物和微生物等邻域的应用,并对代谢组学的发展作了展望。     

代谢组学研究进展及其应用

代谢组学是系统生物学的重要组成部分,其通过研究生物体代谢物的变化来认识生命体的生理与生化状态,从而找出其中隐藏的规律。对代谢组学的含义,研究任务进行介绍;综述代谢组学的产生和技术平台及其在植物、微生物、疾病诊断及毒物学等领域的应用,并对代谢组学的发展趋势以及面临的挑战等问题进行评述。     

Role for dopamine in malonate-induced damage in vivo in striatum and in vitro in mesencephalic cultures

Defects in mitochondrial energy metabolism have been implicated in the pathology of several neurodegenerative disorders. In addition, the reactive metabolites generated from the metabolism and oxidation of the neurotransmitter dopamine (DA) are thought to contribute to the damage to neurons of the basal ganglia. We have previously demonstrated that infusions of the metabolic inhibitor malonate into the striata of mice or rats produce degeneration of DA nerve terminals. In the present studies, we demonstrate that an intrastriatal infusion of malonate induces a substantial increase in DA efflux in awake, behaving mice as measured by in vivo microdialysis. Furthermore, pretreatment of mice with tetrabenazine (TBZ) or the TBZ analogue Ro 4-1284 (Ro-4), compounds that reversibly inhibit the vesicular storage of DA, attenuates the malonate-induced DA efflux as well as the damage to DA nerve terminals. Consistent with these findings, the damage to both DA and GABA neurons in mesencephalic cultures by malonate exposure was attenuated by pretreatment with TBZ or Ro-4. Treatment with these compounds did not affect the formation of free radicals or the inhibition of oxidative phosphorylation resulting from malonate exposure alone. Our data suggest that DA plays an important role in the neurotoxicity produced by malonate. These findings provide direct evidence that inhibition of succinate dehydrogenase causes an increase in extracellular DA levels and indicate that bioenergetic defects may contribute to the pathogenesis of chronic neurodegenerative diseases through a mechanism involving DA.     

Scurvy in capybaras bred in captivity in Argentine

In order to determine if the absence of vitamin C in the diet of capybaras (Hydrochoerus hydrochaeris) causes scurvy, a group of seven young individuals were fed food pellets without ascorbic acid, while another group of eight individuals received the same food with 1 g of ascorbic acid per animal per day. Animals in the first group developed signs of scurvy-like gingivitis, breaking of the incisors and death of one animal. Clinical signs appeared between 25 and 104 days from the beginning of the trial in all individuals. Growth rates of individuals deprived of vitamin C was considerably less than those observed in the control group. Deficiency of ascorbic acid had a severe effect on reproduction of another population of captive capybaras. We found that the decrease in ascorbic acid content in the diet affected pregnancy, especially during the first stages. The results obtained suggest that it is necessary to supply a suitable quantity of vitamin C in the diet of this species in captivity.     

Changes in lactate dehydrogenase activity in chicken tissues in hyperthyreosis in ontogenesis

The lactate dehydrogenase activity in reactions of lactate oxidation and synthesis was studied in subfractions of the chicken brain, heart and liver at the embryonal, early postembryonal and adult stages of development after thyroxine administration. It has been shown that during embryogenesis thyroxine predominantly enhanced the rate of lactate oxidation in the mitochondrial tissues. A marked increase in the lactate synthesis was found in cytoplasm of the adult chicken tissues. Specificity of enzyme activity alterations was detected in the chicken brain during ontogenesis after thyroxine administration.     

SSTR5 ablation in islet results in alterations in glucose homeostasis in mice

Somatostatin (SST) peptide is a potent inhibitor of insulin secretion and its effect is mediated via somatostatin receptor 5 (SSTR5) in the endocrine pancreas. To investigate the consequences of gene ablation of SSTR5 in the mouse pancreas, we have generated a mouse model in which the SSTR5 gene was specifically knocked down in the pancreatic beta cells (betaSSTR5Kd) using the Cre-lox system. Immunohistochemistry analysis showed that SSTR5 gene expression was absent in beta cells at three months of age. At the time of gene ablation, betaSSTR5Kd mice demonstrated glucose intolerance with lack of insulin response and significantly reduced serum insulin levels. Insulin tolerance test demonstrated a significant increase of insulin clearance in vivo at the same age. In vitro studies demonstrated an absence of response to SST-28 stimulation in the betaSSTR5Kd mouse islet, which was associated with a significantly reduced SST expression level in betaSSTR5Kd mice pancreata. In addition, betaSSTR5Kd mice had significantly reduced serum glucose levels and increased serum insulin levels at 12 months of age. Glucose tolerance test at an older age also indicated a persistently higher insulin level in betaSSTR5Kd mice. Further studies of betaSSTR5Kd mice had revealed elevated serum C-peptide levels at both 3 and 12 months of age, suggesting that these mice are capable of producing and releasing insulin to the periphery. These results support the hypothesis that SSTR5 plays a pivotal role in the regulation of insulin secretion in the mouse pancreas.