Frontiers in Oncology
·
2025
·
IF 3.3
Yu-jiao Hua,Ying Zhang,Rui-Rong Wu,Juan Lv,Yan Zhang,Yan-yan Chen,Yong-juan Ding,Jing-hua Chen
Background Oxaliplatin-induced peripheral neuropathy (OIPN) poses a significant challenge for patients with colorectal tumor, often resulting in treatment interruption or discontinuation and subsequent treatment failure. Herein, a longitudinal untargeted metabolomic study to reveal the metabolomic profiles and biomarkers associated with the progression of OIPN. Methods A prospective cohort of 129 colorectal cancer patients receiving oxaliplatin-based chemotherapy was stratified into four OIPN severity grades (Level 0-3). Serum samples underwent untargeted LC-MS/MS metabolomic analysis, detecting 521 metabolites. Multivariate statistical models and SHAP-guided random forest algorithms were employed to prioritize biomarkers. Machine learning validation included six classifiers assessed via ROC-AUC. Results The cumulative dose of Oxaliplatin chemotherapy plays an important role in OIPN. At the same time, our findings implied that the occurrence of OIPN may be associated with the progression of the disease and the patients’ tumor markers (CEA, CA19-9, CA72-4), as well as immune response and inflammation (ANC, PLT), and metabolic and liver function abnormalities (GGT and UA) (P<0.05).Multivariate statistical analysis combined with SHAP-guided machine learning identified six biomarkers, including thiabendazole, 1-methylxanthine, imidazol-5-yl-pyruvate, 5-hydroxypentanoic acid, spermidine, and 4’-oxolividamine that consistently distinguished OIPN patients (Level 1-3) from non-OIPN controls (Level 0). Machine learning models, validated across six classifiers, demonstrated near-perfect discrimination for early-stage OIPN (AUC nearly 1). However, differentiation between intermediate OIPN grades (Level 1 vs 2, Level 1 vs 3, Level 2 vs 3) yielded lower predictive accuracy (AUC: 0.549–0.843), likely due to cohort size limitations and reliance on subjective sensory-based grading. Pathway enrichment analysis highlighted dysregulation in ABC transporters, central carbon metabolism in cancer, amino acid metabolism, and linoleic acid metabolism, suggesting potential roles in OIPN pathogenesis. Conclusions These findings suggest that the selected biomarkers could serve as a foundation for the prediction and management of OIPN in colorectal cancer patients.
研究领域:
肿瘤学
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神经毒理学
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转化医学
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药物代谢
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代谢组学
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精准医学
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临床药理学
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PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 17
·5717
·
IF 4.927
Christiana Mantzourani,Maroula G. Kokotou
Fatty acids (FAs) play pleiotropic roles in living organisms, acting as signaling molecules and gene regulators. They are present in plants and foods and may affect human health by food ingestion. As a consequence, analytical methods for their determination in biological fluids, plants and foods have attracted high interest. Undoubtedly, mass spectrometry (MS) has become an indispensable technique for the analysis of FAs. Due to the inherent poor ionization efficiency of FAs, their chemical derivatization prior to analysis is often employed. Usually, the derivatization of the FA carboxyl group aims to charge reversal, allowing detection and quantification in positive ion mode, thus, resulting in an increase in sensitivity in determination. Another approach is the derivatization of the double bond of unsaturated FAs, which aims to identify the double bond location. The present review summarizes the various classes of reagents developed for FA derivatization and discusses their applications in the liquid chromatography-MS (LC-MS) analysis of FAs in various matrices, including plasma and feces. In addition, applications for the determination of eicosanoids and fatty acid esters of hydroxy fatty acids (FAHFAs) are discussed.Keywords:charge reversal;derivatization reagents;fatty acids;liquid chromatography;mass spectrometry
研究领域:
分析化学
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生物医学
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代谢组学
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Bioanalysis
·
2023
·Vol. 15
·期 6
·
IF 1.8
Juan Li,Yongjing Cao,Xiaojie Zhang,Min An,Juntao Zhang,Yanhua Liu
Background: Indocyanine2,3-dioxygenase (IDO) is an enzyme that can catalyze the metabolism of tryptophan (Trp) into kynurenine (Kyn), thus inhibiting the tumor immune microenvironment. Method: Based on its inhibitor, NLG919 (NLG), the authors developed a new immunomodulatory polymer micelle and established and verified an ultrahigh performance liquid chromatography–mass spectrometry method for the simultaneous determination of NLG, Trp and Kyn in mouse tumors through the ratio determination of Trp/Kyn tissue distribution and pharmacokinetics. The linear range of the method was 0.001–10 μg/ml. Results: Compared with NLG solution, the immunomodulatory polymeric drug-loaded micelles based on polystyrene-arginine showed higher Trp/Kyn ratio, more tumor aggregation and good pharmacokinetics. Conclusion: This method has been successfully applied to the simultaneous determination of Trp/Kyn and NLG in tumor tissues of mice.
研究领域:
药理学
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肿瘤学
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分析化学
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生物技术
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JOURNAL OF CHROMATOGRAPHY A
·
2026
·
IF 4
Chenyue Zhu,Chuanxiang Yao,Huiting Qin,Wei Zhang,Xinyue Zheng,Siying Zheng,Xinyuan Ye,Ying Xiong,Lili Jiang,Sen Li,Meiqin Wang,Hongliang Jiang,Zhifeng Du
The presence of deamination impurities in phosphorothioate oligonucleotides (PS-ONs) presents a significant challenge to quality control, as their detection is complicated by minimal mass differences from the parent molecule and difficulties in chromatographic separation. Herein, a bottom-up strategy based on enzymatic digestion, chemical derivatization, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was proposed for the sensitive qualitative and quantitative analysis of trace cytosine deamination in PS-ONs. Fomivirsen (FMVS) and its deamination impurity were used as models. The method involved digestion with S1 nuclease, followed by derivatization of the 5’-phosphorothioate in digests with N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide (MTBSTFA) to enhance chromatographic retention and mass spectrometric response. This approach effectively eliminated the need for ion-pairing (IP) reagents. The mass shift upon deamination was amplified in the smaller digested fragments, and a unique isotopic pattern in the derivatized products, specifically, the decrease of the first isotopic peak and the increase of the second isotopic peak was exploited for quantification. The method demonstrated excellent linearity over a weight ratio of deamination product to prototype range from 0.05:1 to 0.9:1. Satisfactory accuracy (80–120%) and precision (RSD < 15%) were achieved. Furthermore, the precise deamination site (C8) within a sample containing 10% deamination impurities was successfully identified. Thus, this method provides a powerful tool for profiling deamination impurities in PS-ONs, with potential applications in quality control, stability studies, and the characterization of other nucleic acid modifications.
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EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY
·
2026
·Vol. 128
·期 9
·e70142
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IF 2.4
Yunping Yao,Zehui Zhang,Bingxin Li,Changmo Li
Accurate qualitative and quantitative determination of free radicals during lipid oxidation, which is the core process of edible oil quality deterioration and essentially a free radical chain reaction, is of crucial importance. To overcome this problem, we developed and validated an analytical method for the specific characterization of key radicals in lipid oxidation. These radicals (R•, RO•, and ROO•) were trapped using N-tert -butyl-α-phenylnitrone under iron-mediated conditions, leading to the formation of stable adducts that were subsequently analyzed by LC–MS/MS–IT–TOF. This method offers good sensitivity with low limits of detection (0.06–0.15 µM) and limits of quantification (0.20–0.50 µM). Density functional theory calculations further confirm that the reaction proceeds readily and yields thermodynamically stable products. When applied to the methyl linoleate oxidation system, the method demonstrated that methyl linoleate alkyl radical (L•) predominated during oxidation, with its concentration peaking at 3.74 × 10 −2 mM (accounting for up to 70% of radicals) at 4 h followed by a decline due to chain termination reactions, whereas methyl linoleate peroxyl radicals (LOO•) concentration stabilized as oxidation progressed (1.46 × 10 −2 mM, 27% of radicals), and methyl linoleate alkoxyl radicals (LO•) remained at a consistently low concentration (1.58 × 10 −3 mM) owing to its preferential conversion via the β-scission pathway. These results were consistent with electron spin resonance (ESR) data, thereby validating the method's reliability. Consequently, this method enables the precise monitoring of lipid oxidation processes, serving as a valuable tool for assessing antioxidant efficacy in lipid science. Practical Applications : We present an analytical method integrating N-tert -butyl-α-phenylnitrone (PBN)-based spin trapping with LC–MS/MS–IT–TOF for direct tracking of key lipid radicals (L•, LO•, and LOO•) throughout the lipid oxidation process. This method addresses a long-standing technical gap in lipid oxidation research, providing a robust, practical tool for both high-throughput screening of high-efficacy antioxidants and rational design of stable lipid-containing food formulations. By bridging fundamental analysis and product development, our technique has clear real-world implications for extending the shelf life of lipid-based foods, offering significant value to food chemistry research while delivering substantial economic and sustainability benefits to the global food industry.
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ANALYTICA CHIMICA ACTA
·
2026
·
IF 6.1
Yanling Wang,Chi Zhang,Tong Liu,Qingsong Li,Xue Guan,Yutian Hu,Bo Cao,Xiaohong Wu,Qin Zhou,Feiyun Cui
Label-free surface-enhanced Raman spectroscopy (SERS) offers a promising avenue for rapid metabolic phenotyping in complex biofluids, yet its translational potential is hindered by the challenge of deconvoluting overlapping spectral contributions and identifying specific metabolite signatures. Herein, we report a liquid chromatography-mass spectrometry (LC-MS)–guided AI enabled serum molecule-interpretable SERS Platform, termed AMI-SERS, which integrates SERS, untargeted metabolomics and machine learning (ML) for Alzheimer's disease (AD) patient serum exploratory metabolic profiling. ML has achieved excellent classification performance with an accuracy of 96.67% under leave-one-out cross-validation. A novel multi-source matching algorithm was devised to trace dominant spectral features directly to specific metabolite changes, uncovering hypoxanthine as a key pre-analytical confounder and nominating adenine as a potential AD biomarker. However, due to the limited sample size, these results are only applicable to exploratory analysis. In conclusion, the AMI-SERS platform establishes a molecular-resolvable, LC-MS-interpretable AI methodological framework for exploratory serum metabolomics and its clinical applicability requires large-scale independent validation.
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MICROCHEMICAL JOURNAL
·
2026
·
IF 5.2
Xin Xin,Qi Zhang,Sujun Yan,Zilong Chen,Xinhai Zhu
Background Monosaccharides and disaccharides are central components of carbohydrate metabolism, and fluctuations in their abundances are closely associated with disease onset, progression, and diagnostic outcomes. However, accurate analysis of trace-level saccharides in complex biological matrices remains challenging due to their limited chromatographic retention, modest ionization efficiency, and limited MS/MS fragmentation. Derivatization has been widely explored to improve analytical performance in LC-MS-based saccharide analysis; nevertheless, further development of simple, sensitive, and broadly applicable strategies is desirable, particularly for small-volume and low-abundance biological samples. This work presents an efficient derivatization-LC-MS approach enabling ultrasensitive quantification of saccharides under microscale analytical conditions. Results A derivatization strategy based on 2-hydrazinyl-6-methoxy-1,3-benzothiazole (HMBT) was developed to enhance LC-MS analysis of monosaccharides and disaccharides. The mild reaction generated stable derivatives directly compatible with LC-MS. HMBT tagging significantly improved chromatographic retention and separation on conventional C18 columns and markedly enhanced ionization efficiency. The derivatives produced high-intensity precursor ions and a dominant, highly responsive product ion, enabling ultrasensitive MRM detection on a triple-quadrupole system. Using nine representative saccharides, the method achieved excellent quantitative linearity down to 10 pg·mL −1 . Application to mouse serum enabled the quantification of glucose at single-cell-equivalent levels, and spiked galactose showed a linear range of 0.05–100 ng·mL −1 . Importantly, the workflow enabled quantification of five endogenous saccharides in individual HeLa cells. Significance The HMBT derivatization workflow provides an ultrahigh-sensitivity LC-MS platform for saccharide analysis, enabling robust MRM-based quantification at pg·mL −1 levels. Its operational simplicity, minimal sample handling, and full compatibility with conventional LC-MS instrumentation facilitate practical implementation. The demonstrated applicability to true single-cell measurements highlights its potential for glycometabolic studies in microscale biological systems.
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Journal of Food Measurement and Characterization
·
2024
·
IF 2.9
Li Huanhuan,Zhao Ke,Chen Lihong,Huang Qicheng,Ma Xiaozhong,Ge Shengyuan,Su Mingwei,Tang Honggang
In the present study, we evaluated the physicochemical properties, free amino acids concentration, metabolomics, and the relationship between main metabolites and volatile compounds of Jinhua ham prepared using Taihu black pigs during a ripening period of 210 days to elucidate the distinguishing features and formation process of the quality of this ham. During the eight timepoints, the color parameters redness and yellowness exhibited significant changes. Water activity gradually decreased. The tastes of saltiness, sourness and umami were main taste characteristics of Jinhua ham. Carnosine and glutamic acid were the main umami taste compounds and their contents reached to 1785 ± 92.2 and 699 ± 65.1 mg/100 g respectively. Metabolomics-based analysis showed that the dominant biochemical reaction was the metabolism of carboxylic acids and their derivatives. Total 153 significantly differential metabolites were identified. The main metabolic pathways were different in the three different periods respectively. Lipid metabolism was the predominant pathway in low–temperature stage, while amino acid formation and protein metabolism were the predominant pathways in the moderate–temperature and high–temperature stage. The dominant flavor compounds were closely related to the key differential metabolites. Our study findings revealed the quality, significantly differential metabolites, and formation process of Jinhua ham prepared using Taihu black pigs.
研究领域:
食品科学
·
代谢组学
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农业
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生物化学
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高影响因子
SAUDI PHARMACEUTICAL JOURNAL
·
2025
·Vol. 33
·期 5
·1-17
·
IF 3.4
Wang Ziheng,Xu Yuchen,Liu Manting,Yang Yuchang,Shi Wenjuan,Zhu Qian,Liu Juan,Yi Lisha,Wu Huimin,Yin Xingbin,Dong Xiaoxv,Ni Jian,Qu Changhai
This study aimed to establish a method for quantifying baicalin (BC) in rabbit ocular tissues and plasma, and evaluate the pharmacological efficacy and pharmacokinetic properties of BC and BC@HS15/DSPE-PEG2000-L-Val, a novel ocular formulation for dry eye treatment. BC@HS15/DSPE-PEG2000-L-Val or free BC was administered via eye drops to benzalkonium chloride (BAC)-induced dry eye mice. Corneal and conjunctival tissues were assessed for anti-dry eye efficacy. BC concentrations in cornea, conjunctiva, aqueous humor, and ocular plasma were quantified using LC–MS/MS. Noncompartmental pharmacokinetic parameters (AUC, Tmax) were calculated using DAS 2.0 software. The method demonstrated excellent linearity (0.50–500.00 ng/mL, r > 0.9905), precision (RSD < 10%), and accuracy (± 13%). Compared to free BC, BC@HS15/DSPE-PEG2000-L-Val significantly increased tear secretion, reduced MMP-3/MMP-9 expression, and preserved corneal epithelium integrity. In the micelle group, corneal and conjunctival Cmax values were 2.7- and 3.6-fold higher than the solution group, respectively. A sensitive and validated liquid chromatography-tandem mass spectrometry (LC–MS/MS) method was developed to measure baicalin concentrations in ocular plasma and tissues of rabbits. BC@HS15/DSPE-PEG2000-L-Val for treating dry eye demonstrated significantly superior outcomes. The nano-micelle notably enhanced BC concentration on the ocular surface and effectively prolonged its retention time. Graphical abstract
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 26
·期 1
·77
·
IF 4.9
Zhiting Guo,Huiyan Yu,Kexin Yang,Wenjing Feng,Miao Liu,Tao Wang,Rong Xiao
Oxysterols, as metabolites of cholesterol, play a key role in cholesterol homeostasis, autophagosome formation, and regulation of immune responses. Disorders in oxysterol metabolism are closely related to the pathogenesis of neurodegenerative diseases. To systematically investigate the profound molecular regulatory mechanisms of neurodegenerative diseases, it is necessary to quantify oxysterols and their metabolites in central and peripheral biospecimens simultaneously and accurately. However, there are a lot of unsolved problems with the existing methods, such as the hindrance of applying a single method to different biological specimens or the challenge of simultaneous quantification due to differential groups on the ends of the oxysterol side chains. Herein, according to the physicochemical properties and structure of oxysterols, an optimized liquid chromatography-tandem mass spectrometry method for the quantification of oxysterols was established by optimizing the sample preparation process, chromatographic conditions, mobile phase pH, and solvent selection. Seven oxysterols were detected by this method, including 27-hydroxycholesterol, 7α-hydroxycholesterol, 7α,27-dihydroxycholesterol, 7-dehydrocholesterol, 7α-hydroxy-3-oxo-4-cholestenoic acid, 3-hydroxy-5-cholestenoic acid, and 24(S)-hydroxycholesterol. Non-derivatization extraction with methyl tert-butyl ether was used for different biospecimens, followed by simultaneous chromatographic separation of oxysterols on a phenyl hexyl column. By repeated validation, this method exhibited satisfactory linearity, precision, recovery, sensitivity, repeatability, and stability, and it was successfully applied to the detection of oxysterols in the plasma, cerebral cortex, and liver of mouse. In summary, our optimized method enables concurrent analysis and quantification of oxysterols and their metabolites in various biospecimens, presenting a broad range of applicability.
研究领域:
生物化学
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医学分析
·
神经科学
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Frontiers in Immunology
·
2024
·
IF 5.7
Li Na,Wang Tianyi,Zhang Huiying,Li Xiao,Bai Haochen,Lu Ning,Lu Kaizhi
Objective: This investigation sought to delineate the causal nexus between plasma glutamine concentrations and leukemia susceptibility utilizing bidirectional Mendelian Randomization (MR) analysis and to elucidate the metabolic ramifications of asparaginase therapy on glutamine dynamics in leukemia patients.Methods: A bidirectional two-sample MR framework was implemented, leveraging genetic variants as instrumental variables from extensive genome-wide association studies (GWAS) tailored to populations of European descent. Glutamine quantification was executed through a rigorously validated Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) protocol. Comparative analyses of glutamine levels were conducted across leukemia patients versus healthy controls, pre- and post-asparaginase administration. Statistical evaluations employed inverse variance weighted (IVW) models, MR-Egger regression, and sensitivity tests addressing pleiotropy and heterogeneity.Results: The MR findings underscored a significant inverse association between glutamine levels and leukemia risk (IVW p = 0.03558833), positing lower glutamine levels as a contributory factor to heightened leukemia susceptibility. Conversely, the analysis disclosed no substantive causal impact of leukemia on glutamine modulation (IVW p = 0.9694758). Notably, post-asparaginase treatment, a marked decrement in plasma glutamine concentrations was observed in patients (p = 0.0068), underlining the profound metabolic influence of the therapeutic regimen.Conclusion: This study corroborates the hypothesized inverse relationship between plasma glutamine levels and leukemia risk, enhancing our understanding of glutamine’s role in leukemia pathophysiology. The pronounced reduction in glutamine levels following asparaginase intervention highlights the critical need for meticulous metabolic monitoring to refine therapeutic efficacy and optimize patient management in clinical oncology. These insights pave the way for more tailored and efficacious treatment modalities in the realm of personalized medicine.
研究领域:
医学
·
遗传学
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代谢组学
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高影响因子
MOLECULES
·
2024
·Vol. 29
·期 5
·1055
·
IF 4.2
Jing Xu,Xiu-Wei Yang
Berberine is a natural isoquinoline alkaloid with low toxicity, which exists in a wide variety of medicinal plants. Berberine has been demonstrated to exhibit potent prevention of indomethacin-induced gastric injury (GI) but the related mechanism remains unclear. In the present study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied for the first time to investigate the alteration of serum metabolites in the protection of berberine against indomethacin-induced gastric injury in rats. Subsequently, bioinformatics was utilized to analyze the potential metabolic pathway of the anti-GI effect of berberine. The pharmacodynamic data indicated that berberine could ameliorate gastric pathological damage, inhibit the level of proinflammatory factors in serum, and increase the level of antioxidant factors in serum. The LC-MS-based metabolomics analysis conducted in this study demonstrated the presence of 57 differential metabolites in the serum of rats with induced GI caused by indomethacin, which was associated with 29 metabolic pathways. Moreover, the study revealed that berberine showed a significant impact on the differential metabolites, with 45 differential metabolites being reported between the model group and the group treated with berberine. The differential metabolites were associated with 24 metabolic pathways, and berberine administration regulated 14 of the 57 differential metabolites, affecting 14 of the 29 metabolic pathways. The primary metabolic pathways affected were glutathione metabolism and arachidonic acid metabolism. Based on the results, it can be concluded that berberine has a gastroprotective effect on the GI. This study is particularly significant since it is the first to elucidate the mechanism of berberine’s action on GI. The results suggest that berberine’s action may be related to energy metabolism, oxidative stress, and inflammation regulation. These findings may pave the way for the development of new therapeutic interventions for the prevention and management of NSAID-induced GI disorders.
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