Urinary metabolomics of complete Freund's adjuvant‐induced hyperalgesia in rats

The aim of this study was to demonstrate the differences of metabolomics changes in a hyperalgesia model and find potent biomarkers of hyperalgesia. Seven rats were placed in metabolic cages. An emulsion containing 500 μg of Complete Freund's adjuvant (CFA) was used to induce hyperalgesia. Urine samples were collected prior to the injection of CFA and on post‐injection days 1, 3 and 7. Ultraperformance liquid chromatography, coupled with quadrupole‐time‐of‐flight mass spectrometry (UHPLC‐Q‐TOF/MS), was used for a quantitative analysis of urinary metabolic changes in the CFA‐induced hyperalgesia model. Differences between the metabolic profiles of the rats in the four groups were analyzed using partial least squares discriminant analysis. Thirty‐four potential urine metabolite biomarkers were identified, which changed in a trend similar to the pain threshold. These potential biomarkers were involved in 11 metabolic pathways, as follows: alanine, aspartate, and glutamate metabolism; ascorbate and aldarate metabolism; glycerolipid metabolism; glycerophospholipid metabolism; histidine metabolism; phenylalanine metabolism; sphingolipid metabolism; tryptophan metabolism; tyrosine metabolism; valine, leucine and isoleucine biosynthesis; and vitamin B6 metabolism. These results may improve our understanding of hyperalgesia and provide a basis for the clinical diagnosis of hyperalgesia.     

Effects of the ambient fine particulate matter (PM2.5) exposure on urinary metabolic profiles in rats using UPLC-Q-TOF-MS

The pathogenesis of PM2.5 was evaluated on rats in model groups using a metabonomic method by UPLC-Q-TOF-MS and 17 potential endogenous metablites were identified. The primary metabolism pathways involved pentose and glucuronate interconversions, starch and sucrose metabolism, tryptophan metabolism, tyrosine metabolism, phenylalanine metabolism, purine metabolism, acetaminophen metabolism pathway, retinol metabolism and valproic acid metabolism pathway.     

汞离子对细胞代谢通路影响的代谢组学

利用超高效液相色谱-四级杆飞行时间质谱（UPLC-Q-TOF-MS）技术对汞离子作用后细胞的代谢组学进行了研究,结合化学计量学方法,对代谢组学数据进行了多维统计分析.结果表明,与非汞离子作用组相比,汞离子作用组存在能量、磷脂、脂肪酸及氨基酸代谢异常,并发现16种有显著差异的生物标记物.进一步探讨了汞中毒的细胞代谢机理及细胞的应激保护.本研究建立的基于UPLC-Q-TOF-MS技术的细胞代谢组学快速分析方法可以对细胞在重金属作用后的代谢物变化进行轮廓分析.     

Serum metabolomic profiling in patients with Alzheimer disease and amnestic mild cognitive impairment by GC/MS

The aim of this study was to characterize the serum metabolic profiles of patients with Alzheimer’s disease (AD) and amnestic mild cognitive impairment (AMCI) using metabolomics based on gas chromatography–mass spectrometry (GC/MS). Serum samples were collected from patients with AD (n = 30) and AMCI (n = 32), and normal healthy controls (NOR, n = 40). Metabolite profiles were performed with GC/MS in conjunction with multivariate statistical analysis, and possible biomarker metabolites were identified. Thirty-one kinds of endogenous metabolites could be identified simultaneously. Eleven components were chosen as biomarker metabolites between AD and NOR groups, and these metabolites were closely related to seven biological pathways: arginine and proline metabolism, phenylalanine metabolism, β-alanine metabolism, primary bile acid synthesis, glutathione metabolism, starch and sucrose metabolism, and steroid hormone biosynthesis. Meanwhile, 10 components were chosen as biomarker metabolites between AMCI and NOR groups and seven biological pathways were closely related: arginine and proline metabolism, phenylalanine metabolism, citrate cycle, alanine, aspartate and glutamate metabolism, taurine and hypotaurine metabolism, starch and sucrose metabolism, and steroid hormone biosynthesis. Our study distinguished serum metabotypes between AD, AMCI and NOR patients successfully. The implementation of this metabolomic strategy may help to develop biochemical insight into the metabolic alterations in AD/AMCI and will be helpful for the further understanding of pathogenesis.     

导电聚合物喷雾电离质谱法对微量全血代谢轮廓即时监测

血液代谢物水平可用于术后生理代谢状况的个体化精准评估,这对体液整体代谢轮廓的即时检验提出了迫切的技术需求。该文介绍了导电聚合物喷雾电离质谱(CPSI-MS)在体液代谢物多重监测中的应用价值。该技术采用由碳纳米管(CNT)和聚甲基丙烯酸甲酯(PMMA)组成的导电聚合物作为血液加载与原位电离喷头。当对该聚合物施加4.5 kV的直流电压后,喷头尖端的萃取溶剂液滴(甲醇-水,体积比1∶1,5μL)在高压驱动下形成带电荷喷雾,将从1μL稀释干血点中萃取解吸的内源性成分进行直接质谱检测。该方法覆盖了600多种内源性代谢物和脂质,涉及20多条代谢通路,包括能量代谢、氨基酸代谢、核苷酸代谢和脂质代谢等。该研究还将经肝大部切除手术的代谢C57BL/6小鼠选为模型对象,采集术后不同时间点的微量血液样本加载于导电聚合物喷头形成干血点样本,监测了数百种代谢物变化来精确表征个体的生理恢复差异。最终发现了分布于三羧酸循环、精氨酸代谢、甘油脂代谢、甘油磷酸胆碱代谢的一组代谢标志物群,从而为肝切除术后生理代谢功能恢复的分子评价提供了依据。     

一种新型希夫碱及其3d,4f配合物的抗菌活性

用微量热法研究一种新型希夫碱及其3d,4f配合物(2L, 2LZnYb)对大肠杆菌和金黄色葡萄球菌的抗菌活性, 得到了在它们作用下大肠杆菌和金黄色葡萄球菌生长代谢的产热曲线, 并且基于分析生长代谢和非生长代谢的产热曲线建立的热动力学方程, 获得了它们的抗菌活性. 结果表明, 两种化合物(ZL, 2LZnYb)对大肠杆菌的生长代谢有强的活性(IC50分别为6.1 和5.1 mg·L-1), 但对金黄色葡萄球菌的生长代谢的活性弱得多(IC50分别为310.1 和595.5 mg·L-1). Zn 和Yb的导入使化合物对大肠杆菌生长代谢的抑制作用稍微增加, 但大大降低了对金黄色葡萄球菌的抑制作用. 对于非生长代谢, 两种化合物的活性有很大的差别. 无论对大肠杆菌还是金黄色葡萄球菌, 由于配体2L的导入, 表现出显著的抑制作用, 2L的MSC50为6.4和209.7 mg·L-1. 配体2L可能成为新的抗菌先导化合物.     

微量元素铁代谢的研究进展

综述了微量元素铁在人体内的代谢,包括膳食结构及膳食中蛋白质、热 能、锌、钙营养水平对铁代谢的影响,妊娠期间和热环境下的铁代谢以及遗传缺陷疾病与铁代谢的关系研究成果,以期对预防缺物性疾病有进一步的认识。     

Glutamine reliance in cell metabolism

As knowledge of cell metabolism has advanced, glutamine has been considered an important amino acid that supplies carbon and nitrogen to fuel biosynthesis. A recent study provided a new perspective on mitochondrial glutamine metabolism, offering mechanistic insights into metabolic adaptation during tumor hypoxia, the emergence of drug resistance, and glutaminolysis-induced metabolic reprogramming and presenting metabolic strategies to target glutamine metabolism in cancer cells. In this review, we introduce the various biosynthetic and bioenergetic roles of glutamine based on the compartmentalization of glutamine metabolism to explain why cells exhibit metabolic reliance on glutamine. Additionally, we examined whether glutamine derivatives contribute to epigenetic regulation associated with tumorigenesis. In addition, in discussing glutamine transporters, we propose a metabolic target for therapeutic intervention in cancer.Subject terms: Cancer metabolism, Metabolomics, Cancer metabolism, Metabolomics     

Metabolomic profiles delineate the effect of Sanmiao wan on hyperuricemia in rats

A serum metabolomic method based on ultra‐high‐performance liquid chromatography coupled with mass spectrometry was developed to characterize hyperuricemia‐related metabolic profiles and delineate the mechanism of Sanmiao wan (SMW), a traditional Chinese medicine (TCM), in treating hyperuricemic rats. With partial least‐squares discriminant analysis for classification and selection of biomarkers, 13 potential biomarkers in mouse serum were identified in the screen, primarily involved in purine metabolism, arginine and proline metabolism, citrate cycle, phenylalanine metabolism, tryptophan metabolism and glycerophospholipid metabolism. Taking these potential biomarkers as screening indexes, SMW could reverse the pathological process of hyperuricemia through partially regulating the perturbed metabolic pathway except for glycerophospholipid metabolism. Our results showed that a metabolomic approach offers a useful tool to identify hyperuricemia‐related biomarkers and provides a new methodological cue for systematically dissecting the underlying efficacies and mechanisms of TCM in treating hyperuricemia.     

N-苄基十六碳酰胺促小鼠Leydig细胞增殖和分泌睾酮的1H NMR代谢组学研究

采用基于核磁共振氢谱(¹H NMR)的细胞代谢组学技术探讨了玛咖有效成分N-苄基十六碳酰胺(NBH)促进小鼠Leydig细胞增殖和分泌睾酮的作用机制. 测定了小鼠Leydig细胞在给药前后的细胞增殖率和细胞培养液中的睾酮含量, 采用主成分分析和正交偏最小二乘判别分析, 研究了小鼠Leydig细胞在给药前后细胞破碎液中的代谢物差异, 并进行了代谢通路分析. 实验结果表明, NBH能提高小鼠Leydig细胞增殖率和睾酮分泌量, 给药后小鼠Leydig细胞破碎液中的代谢轮廓明显改变, 共鉴定亮氨酸、 赖氨酸、 鲨肌醇、 缬氨酸和丙氨酸等24种差异代谢物. 经Metaboanalyst分析发现, 差异代谢物主要涉及丙氨酸/天冬氨酸/谷氨酸代谢、 甘氨酸/丝氨酸/苏氨酸代谢、 谷胱甘肽代谢及丙酮酸代谢等10条新陈代谢和遗传信息处理代谢通路, 初步阐明了NBH通过调节上述代谢通路的相关节点发挥促进小鼠Leydig细胞增殖和分泌睾酮作用.     

线粒体和亚线粒体体外代谢及漆酶影响的微量热研究

首次将微量热用于亚细胞层次的研究，测定了鲤鱼肝脏线粒体和亚线粒体代谢的热谱及其漆树漆酶的影响，并用ＭＴＤ方程和演化计算技术对它们的代谢热动力学参数进行了全局优化。     

Analysis of enzymopathies in the human red blood cells by constraint-based stoichiometric modeling approaches

The human red blood cell (RBC) metabolism is investigated by calculating steady state fluxes using constraint-based stoichiometric modeling approaches. For the normal RBC metabolism, flux balance analysis (FBA) is performed via optimization of various alternative objective functions, and the maximization of production of ATP and NADPH is found to be the primary objective of the RBC metabolism. FBA and two novel approaches, minimization of metabolic adjustment (MOMA) and regulatory on-off minimization (ROOM), which can describe the behavior of the metabolic networks in case of enzymopathies, are applied to observe the relative changes in the flux distribution of the deficient network. The deficiencies in several enzymes in RBC metabolism are investigated and the flux distributions are compared with the non-deficient FBA distribution to elucidate the metabolic changes in response to enzymopathies. It is found that the metabolism is mostly affected by the glucose-6-phosphate dehydrogenase (G6PDH) and phosphoglycerate kinase (PGK) enzymopathies, whereas the effects of the deficiency in DPGM on the metabolism are negligible. These stoichiometric modeling results are found to be in accordance with the experimental findings in the literature related to metabolic behavior of the human red blood cells, showing that human RBC metabolism can be modeled stoichiometrically.     

色谱指纹谱用于中药大黄抗肿瘤活性成分的筛选

采用液相色谱-质谱联用方法分析了中药大黄经过SD大鼠肝匀浆体外代谢前后的指纹谱中色谱峰面积、保留值的差异。指出5种游离型蒽醌化合物在SD大鼠肝匀浆体外代谢体系中只有大黄酚发生代谢反应转化为芦荟大黄素。考察了体外代谢条件下,肝匀浆浓度与代谢时间对大黄酚转化及其代谢产物的影响。SD大鼠体外抗肿瘤试验表明,大黄代谢物对于人宫颈癌(HeLa)细胞的抑制活性略高于其提取物。通过比较芦荟大黄素、大黄酸、大黄素、大黄酚、大黄素甲醚的活性,并结合大黄酚的体外代谢反应的考察,解释了大黄代谢物对肿瘤细胞活性的抑制率的提高是由大黄酚的代谢产物芦荟大黄素浓度的增加引起的。     

中药通心络对抑郁-动脉粥样硬化大鼠干预作用的血浆代谢组学研究

采用快速液相色谱串联离子阱飞行时间质谱(UFLC/MS-IT-TOF)技术对通心络干预下的抑郁-动脉粥样硬化大鼠的血浆代谢谱进行研究.结果表明,抑郁-动脉粥样硬化模型大鼠体内的氨基酸代谢、脂肪酸的β-氧化、胆固醇代谢及磷脂代谢发生了异常.中药通心络通过调节模型大鼠体内的色氨酸、苯丙氨酸代谢及某些胆汁酸的代谢,抑制大鼠抑郁-动脉粥样硬化的形成.该研究结果表明代谢组学在中药整体性药效评价、作用机理的阐明等方面具有很好的应用前景.     

微量元素与脂代谢

铬是人体内必需的微量元素．综述了缺铬对脂代谢的影响、补铬对脂代谢的效应和铬对脂代谢作用的机制．根据动物实验和人群研究调查，阐述了铬与脂代谢有关，且补充铬对胆固醇和某些脂蛋白含量都有良好的作用．指出了铬可能与胰岛素及铬对脂代谢中关键酶的作用密切相关．但是,有关的作用机制仍未充分阐明。有必要进一步研究。     

Simulation of chemical metabolism for fate and hazard assessment. I. Approach for simulating metabolism

Information regarding the metabolism of xenobiotic chemicals plays a central role in regulatory risk assessments. In regulatory programmes where metabolism studies are required, the studies of metabolic pathways are often incomplete and the identification of activated metabolites and important degradation products are limited by analytical methods. Because so many more new chemicals are being produced than can be assessed for potential hazards, setting assessment priorities among the thousands of untested chemicals requires methods for predictive hazard identification which can be derived directly from chemical structure and their likely metabolites. In a series of papers we are sharing our experience in the computerized management of metabolic data and the development of simulators of metabolism for predicting the environmental fate and (eco)toxicity of chemicals. The first paper of the series presents a knowledge-based formalism for the computer simulation of non-intermediary metabolism for untested chemicals, with an emphasis on qualitative and quantitative aspects of modelling metabolism.     

Serum metabolomics using ultra-high performance liquid chromatography–Q-Exactive tandem mass spectrometry reveals the mechanism of action of exercise training on chronic obstructive pulmonary disease rats

Exercise training is the cornerstone component of pulmonary rehabilitation, which results in symptom-reducing, psychosocial, and health economic benefits for chronic obstructive pulmonary disease (COPD) patients. However, the potential mechanisms of its action are poorly understood. This study conducted serum metabolomics using ultra-high performance liquid chromatography–Q-Exactive tandem mass spectrometry to determine the metabolic changes in COPD rats, and the effects of exercise training on improvement in COPD were further investigated. Twelve differential metabolites—which are primarily related to tryptophan metabolism, sphingolipid metabolism, glycerophospholipid metabolism, riboflavin metabolism, pantothenate and CoA biosynthesis, and lysine degradation—were identified in relation to COPD. After the intervention of exercise training, the levels of most metabolites were restored, and the changes in five metabolites were statistically significant, which suggested that exercise training provided effective protection against COPD and might play its role by rebalancing disordered metabolism pathways. This work enhanced our comprehension of the protective mechanism of exercise training on COPD.     

不同条件下离体大鼠肝脏线粒体能量代谢微量热分析

为了探究线粒体的能量代谢过程,本文以离体大鼠肝脏线粒体为模型,利用多通道、高灵敏度的热活性检测仪TAM Ⅲ,实时监测了不同线粒体浓度、不同底物、不同缓冲液、几种呼吸抑制剂以及Ca²⁺和线粒体渗透转换孔抑制剂CsA存在时线粒体的能量代谢,获得了完整的热功率―时间曲线,并通过计算得到了线粒体能量代谢的热动力学参数。通过分析发现：（1）线粒体浓度越大,代谢越快;（2）直接底物琥珀酸钠使线粒体代谢更快;（3）高浓度Ca²⁺能够刺激线粒体快速产热,且在长期代谢进程中,线粒体渗透转换孔抑制剂CsA并不能改变Ca²⁺造成的影响;（4）不同缓冲液对线粒体代谢的影响基于其组分的不同,缓冲液中含有呼吸底物;（5）呼吸抑制剂都能抑制线粒体的能量代谢,尤其是复合物IV的抑制剂NaN₃,高浓度下使代谢停止。     

细胞不同代谢类型的热化学研究Ⅰ.生长、非生长及内源代谢水平的量热测定

细胞是生命的基本单位．对其代谢过程能量输出水平的直接测定，对细胞生理学来说是重要的实验基础数据，对于生物生理和研究能量代谢方面也有一定的理论意义．当然细胞的多样性及其代谢过程的复杂性使这一研究工作相当困难·作为开展研究的第一步我们选择便于培养处理的单细胞生物大肠杆菌作为研究对象，并对其所进行时三种基本代谢类型29Llxi：L谢；非生长依队和内派代谢分别进行研究，本文分别测定了＊烟三种不同类型代谢的热功率输出水平，得到了单个细胞在上述代谢过程热功率输出的定量数据．实验结果表明，不同类型代谢的能量输出水平…