TALANTA
·
2024
·
IF 5.6
Xiaoming Chen,Shuo Cao,Liye Tao,Runlan Yan,Sheng Cao,Jingwen Hao,Yuelin Yi,Chunyan Luan,Jianmin Wu,Yue Gao,Xiao Liang
Lipidomics has demonstrated significant potential for disease diagnosis and prediction. The development and optimization of a robust mass spectrometry (MS) platform for lipidome analysis is critically important, as it can facilitate biomarker discovery, cohort testing, and performance evaluation in clinical lipidomics studies. In this work, we developed a high-throughput and reliable platform, termed MS Lab on a Chip ( MS LOC ), which integrates the MetArray chip, an automated lipidomics pretreatment protocol, and the reflectron matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) instrument. The MetArray chip, produced through a mass production process, exhibited exceptional stability as an MS substrate. The integration of automated lipid pretreatment and MS detection processes ensures high throughput, stability and efficiency during sample preparation. The analysis of various lipid standards and different types of biological samples enabled comprehensive investigation of lipid features and annotation using the MS LOC . Furthermore, a small cohort study, consisting of hepatocellular carcinoma (HCC) and non-HCC groups, was conducted on this platform, providing preliminary validation of its performance and suggesting that this platform offers a comprehensive protocol for clinical lipidomics testing.
研究领域:
分析化学
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临床研究
·
质谱技术
·
组学技术
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2019
·
IF 3.571
Xuanming Zhang,Yongping Shi,Lizhen Wang,Xiaobin Li,Shanshan Zhang,Ximin Wang,Meng Jin,Chung-Der Hsiao,Houwen Lin,Liwen Han,Kechun Liu
Fermented black garlic has multiple beneficial biological activities, including cardiovascular protection, anticancer, hepatoprotective, and antibacterial properties. In this study, metabolic differences in the properties of black and fresh garlic were investigated via liquid chromatography quadrupole/time-of-flight-based metabolomics, leading to the identification of characteristic components. Fermented black garlic samples and their Amadori products (AC) promoted angiogenesis, prevented thrombus formation by rescuing chemical-induced vascular lesions in zebrafish, and inhibited H2O2-induced injury of endothelial cells, thus reducing the risk of cardiovascular disease. AC suppressed activation of the mitogen-activated protein kinase pathway through inhibition of p38 and ERK1/2 phosphorylation, in turn, increasing the availability of c-Fos/c-Jun or c-Jun/c-Jun complexes for apoptotic resistance. Clarification of the associated signaling pathways should therefore provide a solid foundation for optimization of black garlic-based therapies.
研究领域:
药理学
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代谢组学
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心脏病学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2023
·
IF 6.2
Jianan Wang,Wei Xie,Longqin Sun,Jingli Li,Songfeng Wu,Ruibing Li,Yan Zhao
Research on plasma proteomics has received extensive attention, because human plasma is an important sample for disease biomarker research due to its easy clinical accessibility and richness in biological information. Plasma samples contain a large number of leaked proteins from different tissues in the body, immune proteins and communication signal proteins. However, MS signal suppression from high-abundance proteins results in a large number of proteins that are present in low abundance in plasma not being detected by the LC-MS method. This situation makes it more difficult to study neurological diseases, where tissue sampling is difficult and body fluid samples such as plasma or cerebrospinal fluid are both affected by signal suppression. A large number of methods have been developed to deeply mine plasma proteomics information; however, their application limitations remain to some extent. Traditional immuno- or affinity-based depletion, fractionation and subproteome enrichment methods cannot meet the challenges of large clinical cohort applications due to limited time efficiency. In this study, a deep mining strategy of plasma proteomics was established by combing the protein corona formed by deep mining beads (DMB beads, hereafter referred to as magnetic covalent organic frameworks [email protected] ), DIA-MS detection and the DIA-NN library searching method. By optimizing the enrichment step, mass spectrometry acquisition and data processing, the evaluation results of the deep mining strategy showed the following: depth, the strategy identified and quantified results of 2000+ proteins per plasma sample; stability, more than 87% of the enriched low-abundance proteins had CV < 20%; accuracy, good agreement between measured and theoretical values (1.81/2, 8.68/10, 38.36/50) for the gradient addition of E. coli proteins to a plasma sample; time efficiency, the processing time was reduced from >12h in the traditional method to <5h (incubation 30 min, washing 15 min, reductive/alkylation/digestion/desalting 4 h), and more importantly, 96 samples can be processed simultaneously in combination with the magnetic module of the automated device. The optimal strategy enables greater enrichment of neurological disease-related proteins, including SNCA and BDNF. Finally, the deep mining strategy was applied in a pilot study of multiple system atrophy (MSA) for biomarker discovery . The results showed that a total of 215 proteins were upregulated and 184 proteins were downregulated (p < 0.05) in the MSA group compared with the healthy control group. Eighteen proteins of these differentially expressed proteins were reported to be associated with neurological diseases or expressed specifically in brain tissue, 8 and 4 of which have reference concentrations of μg/L and ng/L, respectively. The alterations of ENPP2 and SLC2A1/Glut1 were reanalyzed by ELISA , further supporting the results of mass spectrometry. In conclusion, the results of the evaluation and application of the deep mining strategy showed promise for clinical research applications.
研究领域:
蛋白质组学
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神经学
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临床研究
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质谱技术
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2024
·
IF 2.7
Dongping Rao,Luyan Meng,Xiuqin Sheng,Wenying Yu,Chuan-Fan Ding,Yinghua Yan
A hybrid material, M@C-Br@GMA@Glu, consisting of a porphyrin-based metal–organic framework-covalent organic framework (MOF@COF), has been meticulously synthesized using a post-synthetic modification approach. This advanced material has demonstrated exceptional effectiveness in glycopeptide enrichment, characterized by an impressively low detection limit (0.2 fmol μL−1), high selectivity (1 : 2000), and loading capacity for glycopeptides (100 mg g−1). In practical applications with complex biological samples, 210 glycopeptides associated with 87 glycoproteins from the serum of the healthy group, and 156 glycopeptides related to 85 glycoproteins from the serum of cervical cancer were identified after enrichment with M@C-Br@GMA@Glu. Subsequent genetic ontology analysis has elucidated the relationship between cervical cancer and glycosylation, focusing on biological processes such as complement activation, innate immune response mechanisms, and the structural dynamics of the extracellular matrix. The collective findings not only validate the material's proficiency in the sensitive and selective enrichment of glycopeptides, but also underscore its potential in biomarker discovery applications.
研究领域:
材料科学
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分析化学
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生物化学
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2016
·
IF 4.712
Henghui Li,Wenjie Gao,Xiaojun Feng,Bi-Feng Liu,Xin Liu
Sialic acids usually locate at the terminal of many glycan structures in either α(2,3) or α(2,6) linkage, playing different roles in various biological and pathological processes. Several linkage specific carboxyl derivatization methods have been reported to discriminate between α(2,3) and α(2,6)-linked sialic acids by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Among them, ethyl esterification was recently reported to achieve linkage specific derivatization between α(2,3) and α(2,6)-linked sialic acids with good selectivity . However, the method suffered from the instability of the generated lactones and byproducts of the derivatives. To overcome these shortcomings, a solid-phase two step derivatization method was introduced to convert the α(2,6)-linked sialic acid into ethyl esters and the α(2,3)-inked counterparts into N-methyl amides, respectively. Under the optimized derivatization conditions, our method was able to achieve accurate relative quantification of N-glycan as well as their corresponding sialylated linkage types, superior to the ethyl esterification method. The solid phase derivatization strategy was further applied to investigate N-glycans from biosimilar antibody drug and human serum from patients and healthy volunteers. This method has the potential to be used in the biomarker discovery and pharmaceutical industry .
研究领域:
分析化学
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药学
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生物化学
·
临床化学
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产品关联
DOI
PubMed
高影响因子
ANALYST
·
2023
·Vol. 148
·期 19
·4738-4745
·
IF 4.2
Luyan Meng,Bing Wang,Baichun Wang,Quanshou Feng,Sijia Zhang,Zi Xiong,Shun Zhang,Ting Cai,Chuan-Fan Ding,Yinghua Yan
A Ti4+-functionalized magnetic covalent organic framework material with flexible branched polymers (mCOF@ε-PL@THBA-Ti4+) built via an immobilized metal ion affinity chromatography (IMAC) enrichment strategy was proposed through post-synthesis modification. Hydrophilic ε-poly-L-lysine (ε-PL) rich in amino active groups was first introduced in the fabrication of the phosphopeptide enrichment material to increase the hydrophilicity while providing more functional modification pathways of the material. 2,3,4-Trihydroxy-benzaldehyde (THBA) provides abundant binding sites for the immobilization of numerous Ti4+, which is advantageous for the subsequent efficient phosphopeptide enrichment. The magnetic nanocomposite exhibited outstanding performance of phosphopeptide enrichment with good selectivity (1 : 5000), a low detection limit (2 fmol), and relatively high loading capacity (66.7 mg g−1). What's more, after treatment with mCOF@ε-PL@THBA-Ti4+, 16 endogenous phosphopeptides from fresh saliva of healthy people were recognized by MALDI-TOF MS, and 50 phosphopeptides belonging to 35 phosphoproteins from the serum of uremia patients were detected by nano-LC-MS/MS. Proteomics data analysis for the differential protein selection between uremia and normal controls was conducted using R software, and four down-regulated and three up-regulated proteins were obtained. The results suggested that the prepared material has potential applications in biomarker discovery.
研究领域:
材料科学
·
分析化学
·
生物医学工程
·
蛋白质组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Extracellular Vesicles
·
2024
·Vol. 13
·期 6
·e12467
·
IF 15.5
Danyu Li,Siyi Zou,Ziyang Huang,Congcong Sun,Guozhen Liu
Extracellular vesicles (EVs) carry disease-specific molecular profiles, demonstrating massive potential in biomarker discovery. In this study, we developed an integrated biochip platform, termed EVID-biochip (EVs identification and detection biochip), which integrates in situ electrochemical protein detection with on-chip antifouling-immunomagnetic beads modified with CD81 antibodies and zwitterion molecules, enabling efficient isolation and detection of neuronal EVs. The capability of the EVID-biochip to isolate common EVs and detect neuronal EVs associated with Parkinson's disease in human serum is successfully demonstrated, using the transmembrane protein L1-cell adhesion molecule (L1CAM) as a target biomarker. The EVID-biochip exhibited high efficiency and specificity for the detection of L1CAM with a sensitivity of 1 pg/mL. Based on the validation of 76 human serum samples, for the first time, this study discovered that the level of L1CAM/neuronal EV particles in serum could serve as a reliable indicator to distinguish Parkinson's disease from control groups with AUC = 0.973. EVID-biochip represents a reliable and rapid liquid biopsy platform for the analysis of complex biofluids offering EVs isolation and detection in a single chip, requiring a small sample volume (300 µL) and an assay time of 1.5 h. This approach has the potential to advance the diagnosis and biomarker discovery of various neurological disorders and other diseases.
研究领域:
神经学
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生物医学工程
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生物标志物发现
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诊断学
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生物化学
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DOI
PubMed
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
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临床诊断
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代谢组学
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生物标志物发现
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新生儿筛查
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2025
·
IF 4
Yehai Li,Shixin Liu,Yunsha Zhang,BoYa Guan,Chaojun Zhu,Hongbin Liu,Liang Xu
Conventional metabolomics and lipidomics typically require separate sample preparations, which can introduce systematic bias and reduce throughput, thereby hindering comprehensive elucidation of diabetic metabolic networks. In this study, we exploited the pH-responsive behavior of ZrO₂–SiO₂ composite microspheres to establish the first single-sample, dual-channel solid-phase extraction (SPE) pretreatment method: under acidic conditions, Zr⁴⁺–PO₄³⁻ coordination selectively adsorbs phospholipids, whereas under basic conditions, NH₄⁺ competes to gently elute them. The flow-through and elution fractions are used for metabolomic and lipidomic analyses, respectively. We integrated the entire workflow into an automated pretreatment platform and coupled it with high-resolution LC–IMS–QTOF detection to enable high-throughput processing. Method validation demonstrated high phospholipid recovery and excellent preservation of polar metabolites (representative results: LPC 18:0 elution recovery 100.1 % ± 3.0 %; DPPC elution recovery 94.0 % ± 2.0 %; 25-OH-VD₃ flow-through retention 99.0 % ± 2.0 %). In serum from diabetic patients and healthy controls, 390 differential metabolites were identified in the metabolome, significantly enriched in energy metabolism pathways such as galactose metabolism; lipidomics revealed disturbances in glycerophospholipid metabolism, indicating membrane signaling remodeling. Importantly, the dual-channel approach captured for the first time the coordinated disruption of the galactose–ether-lipid metabolic axis—a sequential reduction in UDP-galactose levels leading to diminished plasmalogen biosynthesis—providing direct molecular evidence for the pathogenic sequence in which disrupted glycolytic energy metabolism precipitates membrane structural dysfunction. This method not only markedly improves the consistency and throughput of omics data but also lays a technical foundation for advancing precision diagnostics and treatment of diabetes from “blood glucose management” to “metabolic network regulation.”
研究领域:
代谢组学
·
脂质组学
·
糖尿病研究
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分析化学
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生物标志物发现
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系统生物学
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临床诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2020
·
IF 4.848
Chen Zhongjian,Dai Yalan,Huang Xiancong,Chen Keke,Gao Yun,Li Na,Wang Ding,Chen Aiping,Yang Qingxia,Hong Yanjun,Zeng Su,Mao Weimin
Background: Esophageal squamous cell carcinoma (ESCC) is a gastrointestinal malignancy with a poor prognosis. Although studies have shown metabolic reprogramming to be linked to ESCC development, no prognostic metabolic biomarkers or potential therapeutic metabolic targets have been identified.Method: The present study investigated some circulating metabolites associated with overall survival in 276 curatively resected ESCC patients using liquid chromatography/mass spectrometry metabolomics and Kaplan-Meier analysis. Tissue metabolomic analysis of 23-paired ESCC tissue samples was performed to discover metabolic dysregulation in ESCC cancerous tissue. A method consisting of support vector machine recursive feature elimination and LIMMA differential expression analysis was utilized to select promising feature genes within transcriptomic data from 179-paired ESCC tissue samples. Joint pathway analysis with genes and metabolites identified relevant metabolic pathways and targets for ESCC.Results: Four metabolites, kynurenine, 1-myristoyl-glycero-3-phosphocholine (LPC(14:0)sn-1), 2-piperidinone, and hippuric acid, were identified as prognostic factors in the preoperative plasma from ESCC patients. A risk score consisting of kynurenine and LPC(14:0)sn-1 significantly improved the prognostic performance of the tumor-node-metastasis staging system and was able to stratify risk for ESCC. Combined tissue metabolomic analysis and support vector machine recursive feature elimination gene selection revealed dysregulated kynurenine pathway as an important metabolic feature of ESCC, including accumulation of tryptophan, formylkynurenine, and kynurenine, as well as up-regulated indoleamine 2,3-dioxygenase 1 in ESCC cancerous tissue.Conclusions: This work identified for the first time four potential prognostic circulating metabolites. In addition, kynurenine pathway metabolism was shown to be up-regulated tryptophan-kynurenine metabolism in ESCC. Results not only provide a metabolite-based risk score system for prognosis, but also improve the understanding of the molecular basis of ESCC onset and progression, and as well as novel potential therapeutic targets for ESCC.
研究领域:
肿瘤学
·
代谢组学
·
生物标志物发现
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2024
·Vol. 22
·期 1
·1-17
·
IF 6.1
Gong Sisi,Huang Rongfu,Wang Meie,Lian Fen,Wang Qingshui,Liao Zhijun,Fan Chunmei
Triple-negative breast cancer (TNBC) is known for its aggressive nature, lack of effective diagnostic tools and treatments, and generally poor prognosis. The objective of this study was to investigate metabolic changes in TNBC using metabolomics approaches and explore the underlying mechanisms through integrated analysis with transcriptomics. In this study, serum untargeted metabolic profiles were first examined between 18 TNBC patients and 21 healthy control (HC) subjects using liquid chromatography-mass spectrometry (LC-MS), identifying a total of 22 significantly differential metabolites (DMs). Subsequently, receiver operating characteristic analysis revealed that 7-methylguanine could serve as a potential biomarker for TNBC in both the discovery and validation sets. Additionally, transcriptomic datasets were retrieved from the GEO database to identify differentially expressed genes (DEGs) between TNBC and normal tissues. An integrative analysis of the DMs and DEGs was conducted, uncovering potential molecular mechanisms underlying TNBC. Notably, three pathways—tyrosine metabolism, phenylalanine metabolism, and glycolysis/gluconeogenesis—were enriched, providing insight into the energy metabolism disorders in TNBC. Within these pathways, two DMs (4-hydroxyphenylacetaldehyde and oxaloacetic acid) and six DEGs (MAOA, ADH1B, ADH1C, AOC3, TAT, and PCK1) were identified as key components. In summary, this study highlights metabolic biomarkers that could potentially be used for the diagnosis and screening of TNBC. The comprehensive analysis of metabolomics and transcriptomics data offers a validated and in-depth understanding of TNBC metabolism.
研究领域:
肿瘤学
·
分子生物学
·
代谢组学
·
转录组学
·
生物标志物发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Qiang Li,Saisong Zhan,Xiaoqing Yang,Zhaowei Zhang,Ning Sun,Xiang Wang,Jingjing Kang,Rui Du,Xiaoqin Hong,Minghao Yue,Xiaomin Li,Yujing Tang,Guangming Liu,Yue Liu,Dingbin Liu
Urinary extracellular vesicles (uEVs) are regarded as highly promising liquid-biopsy biomarkers for the early diagnosis and prognosis of bladder cancer (BC). However, detection of uEVs remains technically challenging owing to their huge heterogeneity and ultralow abundance in real samples. We herein present a choline phosphate-grafted platinum nanozyme (Pt@CP) that acts as a universal EV probe for the construction of a high-throughput and high-sensitivity immunoassay, which allowed multiplex profiling of uEV protein markers for BC detection. With the Pt@CP-based immunoassays, three uEV protein markers (MUC-1, CCDC25, and GLUT1) were identified for BC, by which the BC cases (n = 48), cystitis patients (n = 27), and healthy donors (n = 24) were discriminated with high clinical sensitivity and specificity (area under curve = 98.3%). For the BC cases (n = 9) after surgery, the Pt@CP-based immunoassay could report the postoperative residual tumor that cannot be observed by cystoscopy, which is clinically significant for assessing BC recurrence. This work provides generally high sensitivity for EV detection, facilitating the discovery and clinical use of EV-based biomarkers.
研究领域:
癌症生物学
·
纳米技术
·
生物标志物发现
·
医学诊断
✓ 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）