BIOMEDICAL CHROMATOGRAPHY
·
2016
·Vol. 30
·期 11
·1796-1806
·
IF 1.729
Junjun Ni,Li Xu,Wei Li,Lijun Wu
Easy-to-use early cancer detection methods based on metabolomics using serum samples have been developed recently. Among metabolites, amino acids and acylcarnitine are two of the most suitable candidates for diagnosing lung cancer. The purpose of the present study was to develop a novel, sensitive and specific liquid chromatography–tandem mass spectrometry (LC–MS/MS) method to simultaneously determine 13 amino acids and 8 acylcarnitines in lung cancer patients in serum. After derivatization, the 21 analytes were separated using a C 18 column with gradient elution program in 14 min, obtaining recovery within 90.4–113.8% and precision within 0.3–14.8%. The method was successfully applied in concentration determination of lung cancer patients and healthy controls. The results showed that the serum concentration of lung cancer patients were significant from those of healthy controls.
研究领域:
医学
·
分析化学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Chen Li,Zhu Ruiqin,Ma Yaxing,Huang Chuixiu,Shen Xiantao
Objective: LC-MS/MS-based metabolomics is an important tool for studying disease-related biomarkers. Conventionally, different strategies have been used to screen biomarkers. However, many studies for biomarker screening by different strategies have ignored the dose-response relationship between the biomarker level and exposure level, and no relevant studies have described and compared different strategies in detail. Phenobarbital (PHB) which belongs to the barbiturates, was selected as the typical representative of neurotoxins. Acylcarnitines have been promising candidates for diagnostic biomarkers for several neurological disorders and neurotoxicity. In this work, we aimed to use an acute PHB poisoning animal model to clarify PHB poisoning effects on plasma and brain acylcarnitine changes and how to rationally analyze data from LC-MS/MS.Methods: The acylcarnitine profiles in plasma and brain regions in an actuate PHB poisoning animal model were utilized. The dose-response relationship between plasma PHB and carnitine and acylcarnitines (CARs) in plasma and brain were assessed by the variance analysis trend test and Spearman’s rank correlation test. In different strategies, principal component analysis (PCA) and partial least squares discriminant analysis (OPLS-DA) screened the differential CARs, variable importance plots (VIPs) were utilized to select putative biomarkers for PHB-induced toxicity, and receiver operating characteristic (ROC) curve analysis then illustrated the reliability of biomarkers.Results: Under the first strategy, 14 potential toxicity biomarkers were obtained including eight downregulated CARs with AUC >0.8. Under the second strategy, 11 potential toxicity biomarkers were obtained containing five downregulated CARs with AUC >0.8. Only when the dose-response relationship was fully considered, different strategies screen for the same biomarkers (plasma acetyl-carnitine (C2) and plasma decanoyl-carnitine (C10)), which indicated plasma acylcarnitines might serve as toxicity biomarkers. In addition, the plasma CAR level changes showed differences from brain CAR level changes, and correlations between plasma CARs and their brain counterparts were weak.Conclusion: We found that plasma C2 and C10 might serve as toxicity biomarkers for PHB poisoning disorders, and PHB poisoning effects on changes in plasma CARs may not be fully representative of changes in brain CARs.
研究领域:
代谢组学
·
神经毒理学
·
医学
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Yali Yang,Jie Jiang,Jing He,Yun Ju,Yanxiao Jiang,Hong Zhang
Inherited metabolic diseases (IMDs) have drawn considerable attention due to their disruption of normal metabolic pathways. However, conventional extraction techniques are predominantly offline and time-consuming, making them inadequate for the rapid screening required in clinical settings. We developed a novel method involving the extraction of dried sample spots, which are subsequently mixed with charged water (H2O) before infusion electrospray ionization-mass spectrometry analysis. This method was successfully applied for the simultaneous determination of nine amino acid and seven acylcarnitine indicators in dried serum, blood, and urine spots, covering the majority of IMDs routinely screened in hospitals. Compared with conventional approaches, the sensitivity of the new technique improved by nearly threefold, and in some cases, by up to an order of magnitude. The method’s clinical applicability was further confirmed through comparison with the recommended liquid chromatography-tandem mass spectrometry platform and was evaluated using serum samples from three healthy individuals. Additionally, the effect of charged H2O was investigated in detail. A potential mechanism was proposed, suggesting that positively charged H2O enhances ionization by repelling inorganic salts and increasing the density of charges around the target analytes. Although the high surface tension of H2O can, to some extent, suppress ionization, the incorporation of charged H2O in this workflow boosted analytical sensitivity. Overall, this study introduces a simple, rapid, and highly efficient method for the clinical screening of amino acid and acylcarnitine-related IMDs, offering a promising alternative to conventional techniques.
研究领域:
临床化学
·
质谱技术
·
代谢紊乱疾病
·
分析化学
·
医学诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LIPIDS
·
2025
·
IF 1.6
Xu Haixia,Chen Hui
Energy metabolism manipulation strategy, enhancing fat metabolism while reducing the dependence on glucose, is beneficial to improve exercise performance. The multi-ingredient supplements (MIS) mixed with valine, isoleucine, leucine, β-alanine, creatine, L-carnitine, quercetin, and betaine were found to be able to improve the endurance performance of mice, which was associated with a shift of energy substrates from glucose to fatty acids. Thus, we hypothesized that the MIS regulating lipid metabolism contributes to enhancing exercise endurance in mice. The present study aimed to explore the alterations in the biochemical composition of mice treated with the MIS using a metabolomics strategy after they were subjected to endurance exercise. The serum metabolite profile was investigated using ultrahigh performance liquid chromatography tandem mass spectrometry. Results showed that significant changes in lipid metabolism were observed in the MIS-treated mice during endurance exercise compared with the vehicle control. Specifically, the MIS treatment reduced glycerophospholipids, glycerolipids, long-chain fatty acids, and inflammatory signaling arachidonic acid derivatives, and increased medium-long-chain acylcarnitine levels relative to the exercised group. Furthermore, the levels of dimethylglycine (DMG), citrate (CA), glycerol, creatine, and corticosterone were also increased after the MIS supplementation, which was associated with the changes in the pathways of serotoninergic synapses, CA cycles, and amino acid metabolisms. In conclusion, the MIS tested in this study effectively alters serum metabolomics profiles, which provides further evidence to support a shift in energy substrate utilization contributing to the ability of the MIS to improve exercise performance.
研究领域:
代谢组学
·
营养补充剂
·
运动生理学
·
脂质代谢
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2024
·
IF 12.2
Mengqi Yan,Jintao Yang,Hongkai Zhu,Qiang Zou,Hongzhi Zhao,Hongwen Sun
Volatile organic compounds (VOCs) have proven to be hazardous to the human respiratory system. However, the underlying biological mechanisms remain poorly understood. Therefore, targeted determination of eleven VOC metabolites (mVOCs) along with the nontargeted metabolomic analysis was performed on urine samples collected from lung cancer patients and healthy individuals. Nine mVOCs mainly derived from aldehydes, alkenes, amides, and aromatics were detected in > 90 % of the urine samples, suggesting that the participants were ubiquitously exposed to these typical VOCs. A molecular gatekeeper discovery workflow was employed to link the exposure biomarkers with correlated clusters of endogenous metabolites. As a result, multiple metabolic pathways, including amino acid metabolism, steroid hormone biosynthesis and metabolism, and fatty acid β -oxidation were connected with VOC exposure. Furthermore, 16 of 73 molecular gatekeepers were associated with lung cancer and pointed to a few disrupted metabolic pathways related to hydroxysteroids and acylcarnitine. The shift in molecular profiles was validated in rat model post VOC administration. Thereinto, the up-regulation of enzymes involved in acylcarnitine synthesis and transport in rat lung tissues highlighted that the mitochondrial dysfunction may be a potential carcinogenic mechanism. Our findings provide new insights into the mechanisms underlying lung cancer induced by VOC exposure.
研究领域:
环境健康
·
癌症生物学
·
代谢组学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PROTEOME RESEARCH
·
2024
·
IF 3.8
Jie Zhang,Xiaoling Zang,Peng Jiao,Jiangyu Wu,Wei Meng,Lizhen Zhao,Zhihua Lv
Abnormal lipid metabolism plays an important role in cancer development. In this study, nontargeted lipidomic study on 230 tissue specimens from 79 nonsmall cell lung cancer (NSCLC) patients was conducted using ultraperformance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). Downregulation of sphingosine and medium–long-chain ceramides and short–medium-chain acylcarnitine, upregulation of long-chain acylcarnitine C20:0, and enhanced histamine methylation were revealed in NSCLC tissues. Compared with paired noncancerous tissues, adenocarcinoma (AC) tissues had significantly decreased levels of sphingosine, medium–long-chain ceramides (Cer d18:1/12:0 and Cer d16:1/14:0, Cer d18:0/16:0, Cer d18:1/16:0, Cer d18:2/16:0, Cer d18:2/18:0), short–medium-chain (C2–C16) acylcarnitines, LPC 20:0 and LPC 22:1, and significantly increased levels of the long-chain acylcarnitine C20:0, LPC 16:0, LPC P-16:0, LPC 20:1, LPC 20:2, glyceroPC, LPE 16:0, and LPE 18:2. In squamous cell carcinoma (SCC) tissues, sphingosine, Cer d18:2/16:0 and Cer d18:2/18:0, and short–medium-chain acylcarnitines had significantly lower levels, while long-chain acylcarnitines (C20:0, and C22:0 or C22:0 M), LPC 20:1, LPC 20:2, and N1,N12-diacetylspermine had significantly higher levels compared to controls. In AC and SCC tissues, the levels of LPG 18:0, LPG 18:1, and LPS 18:1 were significantly decreased, while the levels of ceramide-1-phosphate (C1P) d18:0/3:0 or LPE P-16:0, N1-acetylspermidine, and 1-methylhistamine were significantly increased than controls. Furthermore, an orthogonal partial least-squares-discriminant analysis (OPLS-DA) model based on a 4-lipid panel was established, showing good discrimination ability between cancerous and noncancerous tissues.
研究领域:
癌症生物学
·
脂质组学
·
质谱分析
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2025
·
IF 8.9
Tian Tang,Ying Zhang,Xinrui Xing,Ruiqi Sun,Zhe Yu,Yuan Tian,Zunjian Zhang,Pei Zhang,Fengguo Xu
Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder with an increasing incidence worldwide. Due to the complex and unclear therapeutic targets, unmet UC therapeutic drugs still exist. Recently, acylcarnitine metabolism disorder has been linked to intestinal inflammation, but its role in UC remains elusive. According to our preliminary non-targeted metabolomics data, acylcarnitines (ACs) was screened as the disturbed metabolites in the different intestinal inflammation-related diseases. Here we quantified 26 ACs within liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the dextran sulfate sodium (DSS)-induced UC rat model, and found that long-chain acylcarnitines (LCACs) were increased to varying degrees. As the key metabolites of fatty acid β-oxidation (FAO), the upstream metabolites long-chain fatty acids (LCFAs) and the related metabolic enzymes were further characterized, the results showed that the rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A)-mediated LCFAs-LCACs metabolic axis was activated sharply. Next in vitro experiments exhibited that CPT1A was significantly upregulated in both inflammatory macrophages and colonic epithelial cells, and inhibition or knockdown of CPT1A could reduce the inflammation level remarkably. Thus, we screened the pharmacologic inhibitors of CPT1A from FDA approved drugs, within molecular docking, Western blot and cell membrane chromatography (CMC) technology, gliquidone was found to inhibit CPT1A in a dose-dependent manner and exert anti-inflammatory effects in vitro . Animal experiments also showed that gliquidone alleviated DSS-induced UC significantly. In summary, our study presents that within metabolomics analysis, inhibiting CPT1A is focused to be a potential therapeutic strategy against UC, and gliquidone represents an alternative treatment.
研究领域:
代谢组学
·
炎症性肠病
·
药理学
·
分子生物学
·
胃肠病学
·
药物研发
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
·
2025
·
IF 2.7
Shuo Cao,Xinrong Jiang,Xiaoming Chen,Xuetong Qu,Jianmin Wu
Acylcarnitines (ACs), essential intermediates in fatty acid β-oxidation, are increasingly recognized as biomarkers for inborn errors of metabolism (IEM), insulin resistance, heart failure, and neurodegenerative diseases. However, conventional liquid chromatography–mass spectrometry (LC-MS) and flow injection–mass spectrometry (FI-MS) methods are hindered by complex sample preparation, limited throughput, and matrix interferences. Meanwhile, matrix-assisted laser desorption/ionization–MS (MALDI-MS) suffers from low-mass background noise and poor reproducibility. Here, we present a dual-innovation mass spectrometry platform combining a substrate composed of sulfonic acid–gold nanoparticle-decorated silicon nanowires (Sulfo-Au-SiNWs) for electrostatic adsorption-laser desorption/ionization (EALDI) and a full-spectrum internal standard (FS IS) strategy based on d6-ethanol derivatization. The optimized Sulfo-Au-SiNWs offer uniform crystallinity, in situ electrostatic enrichment, efficient thermal desorption, and gold-mediated charge–hole separation, resulting in a ∼300% increase in AC signal intensity. This enabled the selective detection of over ten medium- and long-chain ACs that were previously undetectable using unmodified SiNWs. The FS IS method incorporates over 30 derivatized AC species, enabling simultaneous quantification with detection limits below 0.01 μmol/L, surpassing the sensitivity of traditional FI-MS. The platform delivers spike recovery rates of 96–112% and supports high-throughput analysis, processing each sample within seconds. Validation against FI-ESI-MS/MS in both urine and dried blood spot samples demonstrated excellent agreement (ρ > 0.95) and effectively identified IEM patient profiles via statistically significant AC elevations. With strong intra- and interbatch precision (median RSD < 12.5%) and substrate stability exceeding one month, this EALDI-MS/FS IS workflow provides a high-throughput, high-coverage, and quantitatively robust solution for clinical AC profiling and newborn screening.
研究领域:
质谱分析
·
临床诊断
·
代谢组学
·
生物标志物发现
·
新生儿筛查
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2023
·
IF 6.1
Qinsheng Chen,Qinwei Lu,Lianglong Zhang,Chenhan Zhang,Jingxian Zhang,Yu Gu,Qingxia Huang,Huiru Tang
Consistent retention time ( t R ) of metabolites is vital for identification in metabolomic analysis with ultrahigh-performance liquid-chromatography (UPLC). To minimize inter-experimental t R variations from the reversed-phase UPLC-MS, we developed an endo genous r etention- i ndex (endoRI) using in-sample straight-chain acylcarnitines with different chain-length ( L C , C0–C26) without additives. The endoRI-corrections reduced the t R variations caused by the combined changes of mobile phases , gradients, flow-rates, elution time, columns and temperature from up to 5.1 min–0.2 min for most metabolites in a model metabolome consisting of 91 metabolites and multiple biological matrices including human serum, plasma, fecal, urine, A549 cells and rabbit liver extracts. The endoRI-corrections also reduced the inter-batch and inter-platform t R variations from 1.5 min to 0.15 min for 95 % of detected features in the above biological samples. We further established a quantitative model between t R and L C for predicting t R values of acylcarnitines when absent in samples. This makes it possible to compare metabolites’ t R from different t R databases and the UPLC-based metabolomic data from different batches.
研究领域:
分析化学
·
代谢组学
·
生物化学
✓ 已验证
DOI
高影响因子
Frontiers in Microbiology
·
2022
·
IF 6.064
Xu Jue,Lan Yue,Wang Xinqi,Shang Ke,Liu Xu,Wang Jiao,Li Jing,Yue Bisong,Shao Meiying,Fan Zhenxin
Aging is a complex multifactorial process that greatly affects animal health. Multi-omics analysis is widely applied in evolutionary biology and biomedical research. However, whether multi-omics can provide sufficient information to reveal comprehensive changes in aged non-human primates remains unclear. Here, we explored changes in host–microbe interactions with aging in Chinese rhesus macaques (Macaca mulatta lasiota, CRs) using multi-omics analysis. Results showed marked changes in the oral and gut microbiomes between young and aged CRs, including significantly reduced probiotic abundance and increased pathogenic bacterial abundance in aged CRs. Notably, the abundance of Lactobacillus, which can metabolize tryptophan to produce aryl hydrocarbon receptor (AhR) ligands, was decreased in aged CRs. Consistently, metabolomics detected a decrease in the plasma levels of AhR ligands. In addition, free fatty acid, acyl carnitine, heparin, 2-(4-hydroxyphenyl) propionic acid, and docosahexaenoic acid ethyl ester levels were increased in aged CRs, which may contribute to abnormal fatty acid metabolism and cardiovascular disease. Transcriptome analysis identified changes in the expression of genes associated with tryptophan metabolism and inflammation. In conclusion, many potential links among different omics were found, suggesting that aged CRs face multiple metabolic problems, immunological disorders, and oral and gut diseases. We determined that tryptophan metabolism is critical for the physiological health of aged CRs. Our findings demonstrate the value of multi-omics analyses in revealing host–microbe interactions in non-human primates and suggest that similar approaches could be applied in evolutionary and ecological research of other species.
研究领域:
衰老生物学
·
微生物组研究
·
代谢组学
·
转录组学
·
免疫学
·
非人灵长类动物
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）