ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2022
·Vol. 414
·期 5
·1881-1890
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IF 4.478
Wu Yike,Liu Yuanyuan,Shang Zhengjun,Liu Xin,Xu Yong,Liu Wenlan
Aberrant protein N-glycosylation is one of the hallmarks of malignancy, while its role in oral cancer (OC) progression is still poorly understood making it a perfect biomarker for early-stage cancer. In this work, we describe a MALDI-MS-based N-glycomic analysis with multivariate data analysis approach for exploration and classification of the patients with OC. Various statistical analyses were used to determine differential N-glycome profiles. There were 8 glycan structures significantly increased ( p < 0.05) in all OC-derived microvesicles (MVs). Importantly, the increases in these glycans were significantly greater in the early stage of OC than those in the advanced stage of OC. Additionally, N-glycomic profiles from the serum were also performed, demonstrating a significant change of 11 glycan structures ( p < 0.05). Our data highlighted the effectiveness approach of MALDI-MS-based MV N-glycomic profiling on OC screening, and presented strong potential for further identifying targeted glycoproteomics signatures of the cancer.
研究领域:
生物化学
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肿瘤学
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分子生物学
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DOI
PubMed
高影响因子
Journal of Proteomics
·
2024
·
IF 2.8
Yan Cai,Weifu Ren,Siqian Li,Rijing Liao,Qi Bian
Idiopathic membranous nephropathy (IMN) is an antibody-mediated and kidney-specific autoimmune disease, with the antigen phospholipase A2 receptor 1 (PLA2R1) accounting for approximately 70% of IMN cases. Although a variety of new podocyte target antigens and their autoantibodies have been identified, they are still of limited diagnostic and therapeutic value due to lack of high specificity and sensitivity. N-glycans play vital roles in renal system and their pathobiological relevance has become increasingly recognized in many kidney diseases, but not fully explored in IMN. To find possible glyco-signatures for PLA2R1-related IMN diagnosis, we herein established a comprehensive workflow for total serum N-glycome analysis based on our recently developed mass spectrometry (MS)-based N-glycan purification method, named Ultrafast Glycoprotein Immobilization for Glycan extraction (UltraGIG). A total of 191 N-glycans were identified from IMN patients, representing the largest N-glycome dataset in IMN. Compared to healthy controls, up-regulation of sialylation and core-fucosylation as well as down-regulation of galactosylation were observed in PLA2R1-positive IMN patients, and up-regulation of hyper-galactosylation was specific for PLA2R1-negative IMN patients. A six-glycan marker panel consisting of H4N3S1, H4N3F1, H6N4S2, H6H5F1S2, H6N5 and H6N6F1S1, was proposed to aid in the accurate diagnosis of PLA2R1-related IMN, which provided new insights into IMN biomarker study . Significance PLA2R1-related IMN is a kidney-specific autoimmune disease with a high risk of developing end-stage renal disease (ESRD) and even kidney failure. Current biomarkers are still of limited diagnostic and therapeutic value due to lack of high specificity and sensitivity. An in-depth MS analysis of total serum N-glycome of PLA2R1-related IMN patients was conducted for the first time. We generated the largest dataset of serum N-glycome for IMN to date, and proposed a novel six-glycan marker panel that may help the accurate diagnosis of PLA2R1-related IMN.
研究领域:
医学
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肾脏病学
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蛋白质组学
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免疫学
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产品关联
DOI
PubMed
高影响因子
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
·
2025
·
IF 3.3
Zhao Shanshan,Du Shouwen,Guan Yudong,Schlüter Hartmut
The structural instability and electronegativity of sialic acids make N-sialoglycan profiling challenging. We compared commonly used preparation strategies, including native, acetohydrazide-based derivatization, and permethylation, in N-glycomics with nMatch, an R-based bioinformatics tool that ensures full coverage of the detected N-glycans using mass spectrometry. We demonstrated that permethylation leads to efficient detection of not only N-sialoglycans but also other N-glycans and, therefore, provides a valuable reference for the selection of the appropriate N-glycan preparation strategy in future studies.
研究领域:
分析化学
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糖组学
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质谱技术
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生物信息学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2019
·
IF 6.35
Wanjun Jin,Chengjian Wang,Meifang Yang,Ming Wei,Linjuan Huang,Zhongfu Wang
Changes of α-2,3-/α-2,6-linked sialic acids (SAs) in sialylglycans have been found to be closely related with some diseases. However, accurate quantification of sialylglycans at the isomeric level remains challenging due to their instability, structural complexity, and low mass spectrometry (MS) detection sensitivity. Herein, we propose an analytical strategy named “glycoqueuing”, which allows sequential chromatographic elution and high-sensitivity MS quantification of various sialylglycan isomers based on isotopic labeling followed by analysis via online reversed-phase high performance liquid chromatography coupling with MS (RP-HPLC-MS). The new method was validated by detailed structural identification and quantification of fetal bovine serum (FBS) N-linked sialylglycan isomers, during which many branching isomers were successfully differentiated, and 28 sialylglycan compositions with Neu5Gc residues were analyzed. The method was successfully applied to isomer-specific, quantitative comparison of sialylated N-glycans between bovine and rabbit immunoglobulin G (IgG) and the search for serum sialylated N-glycan biomarker candidates of hepatocellular carcinoma, during which a 55% increase of α-2,6-sialylated fucosylated N-glycans was revealed, demonstrating the great applicability and potential clinical usage of the method.
研究领域:
生物化学
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医学诊断
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分析化学
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2022
·
IF 4.601
Chengjian Wang,Xi Gao,Guiping Gong,Lijuan Man,Qian Wei,Yao Lan,Meifang Yang,Jianli Han,Wanjun Jin,Ming Wei,Linjuan Huang,Zhongfu Wang
Glycomics analysis has been undermined by the lack of structurally defined individual glycans as model compounds. However, it is challenging to prepare individual glycans from natural resources, mainly due to separation difficulties caused by highly diverse structure, complicated mixture form and chromophore-free property of naturally-existing glycans. In this study, we report a simple, universal and low-cost glycan separation strategy, glycoselection, which allows preparation of individual reducing glycans from their mixtures through reversible chromogenic derivatization by hydrazide chemistry in combination with two-dimensional high-performance liquid chromatography (2D-HPLC). Investigations on reaction conditions using lactose and maltodextrin as model glycans showed the feasibility of reversible hydrazide labeling and one-pot hydrazone conversion under mild conditions, the good stability of hydrazone-form derivatives of glycans in solution and the difference among seven selected hydrazine-carrying chromogenic reagents in product yields during glycan labeling and post-column detagging. The 2D-HPLC separation conditions were established on maltodextrin, from which fourteen highly-purified individual reducing oligo-glucans were ultimately obtained. Using this strategy, we also successfully prepared and identified eleven individual neutral reducing N -glycans from chicken ovalbumin and thirteen individual neutral reducing oligosaccharides and eight individual sialylated ones from human milk, demonstrating its good applicability to different types of reducing glycans as well as biological samples. Given the compatibility of individual reducing glycans with almost all of glycan derivatization protocols and analytical techniques of glycans and the potential of the method for larger scale application, this work provides a universal approach to compound-specific analysis of natural glycans and has great significance for glycomics studies.
研究领域:
分析化学
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糖生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2020
·
IF 3.209
Fei Xu,Ming Kong,Jin-Di Xu,Jun Xu,Yan Jiang,Song-Lin Li
Sulfur fumigation and heating desulfurization are used together in the post-harvest processing of many medicinal herbs. However, little is known about the effects of sulfur fumigation on saccharide components, nor about the effects of heating desulfurization on all herbal constituents. In this study, metabolomics and glycomics were integrated to investigate the effects of these two processes on the chemistry of Codonopsis Radix (CR) as a pilot study. The results showed that both sulfur fumigation and heating desulfurization significantly changed the non-saccharide small-molecule metabolome and the glycome of CR in different ways. Chemical mechanisms, such as esterification, glycosidic hydrolysis, esterolysis, amide bond hydrolysis, oxidation and dehydration, are proposed to be involved. These facts strongly inspire that, in addition to investigations of how sulfur fumigation impacts non-saccharide small-molecule metabolites, researches on heating desulfurization and saccharides should be conducted so as to enable accurate, comprehensive evaluation of the quality of sulfur-fumigated herbs.
研究领域:
中药学
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分析化学
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植物化学
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产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2018
·
IF 5.123
Ying Zhang,Bo Wang,Wanjun Jin,Yanan Wen,Lijing Nan,Mingming Yang,Rendan Liu,Yuyang Zhu,Chengjian Wang,Linjuan Huang,Xuezheng Song,Zhongfu Wang
Sensitive glycomics analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) is of great importance but significantly hampered by their low ionization efficiency and labile sialic acid moieties. Chemical derivatization offers a viable way to improve both the ionization efficiency and analytical sensitivity of the glycans in MS analysis by altering their hydrophobicity or charge property. Here we employed Girard's reagent T (GT) for on-target derivatization (GTOD) of reducing glycan under mild acid condition to form stable hydrazones at room temperature , allowing rapid and sensitive identification of neutral and sialylated glycans in positive-ion mode as only permanently positive charged molecular ions without multiple ion adducts by MALDI-TOF-MS. The MS signal intensities of lactose, sialylated N-glycans derived from bovine fetuin and neutral N-glycans derived from RNaseB and ovalbumin were boosted by 7.44, 9.13, 12.96 and 13.47 folds on average (n = 3), respectively. More importantly, after GTOD strategy, unwanted desialylation of sialylated glycans during MS was suppressed. The detection limit of the assay is desirable since the nanogram of N-glycans derived from 0.16 μg ovalbumin could be detected. The assay demonstrated good stability (RSD≤2.95%, within 10 days), reliable reproducibility (RSD = 2.96%, n = 7) and a desirable linear dynamic range from 78 nmol/mL to 10 μmol/mL. The strategy has been successfully applied to MS analysis of reducing glycans from human milks, neutral and sialylated O-, N-glycans from glycoproteins , and reducing glycans derived from glycosphingolipids , presenting neater [M] + signals which allow detection of more low-abundance glycans and assignation of Neu5Ac vs. Neu5Gc or fucose vs. hexose in glycans due to the absence of the ambiguous interpretation from multiple peaks (ion adducts [M+Na] + and [M+K] + ). Moreover, the GTOD assay prevents desialylation during MALDI-TOF-MS profiling and enables distinct linkage-specific characterization of terminal sialic acids of N-glycans derived from human serum protein when combines with an esterification .
研究领域:
生物化学
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分析化学
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医学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PROTEOME RESEARCH
·
2013
·
IF 5.056
Chengjian Wang,Zhiyu Wu,Jiangbei Yuan,Bo Wang,Ping Zhang,Ying Zhang,Zhongfu Wang,Linjuan Huang
Fast, sensitive, and simple methods for quantitative analysis of disparities in glycan expression between different biological samples are essential for studies of protein glycosylation patterns (glycomics) and the search for disease glycan biomarkers. Relative quantitation of glycans based on stable isotope labeling combined with mass spectrometric detection represents an emerging and promising technique. However, this technique is undermined by the complexity of mass spectra of isotope-labeled glycans caused by the presence of multiple metal ion adduct signals, which result in a decrease of detection sensitivity and an increase of difficulties in data interpretation. Herein we report a simplified quantitative glycomics strategy, which features nonreductive isotopic labeling of reducing glycans with either nondeuterated (d0-) or deuterated (d5-) Girard’s reagent P (GP) without salts introduced and simplified mass spectrometric profiles of d0- and d5-GP derivatives of neutral glycans as molecular ions without complex metal ion adducts, allowing rapid and sensitive quantitative comparison between different glycan samples. We have obtained optimized GP-labeling conditions and good quantitation linearity, reproducibility, and accuracy of data by the method. Its excellent applicability was validated by comparatively quantitative analysis of the neutral N-glycans released from bovine and porcine immunoglobulin G as well as of those from mouse and rat sera. Additionally, we have revealed the potential of this strategy for the high-sensitivity analysis of sialylated glycans as GP derivatives, which involves neutralization of the carboxyl group of sialic acid by chemical derivatization.
研究领域:
生物化学
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医学诊断
·
分析化学
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2020
·
IF 5.339
Yifang Zhang,Zhaoyu Hu,Chun Zhang,Bi-Feng Liu,Xin Liu
Chemical derivatization of glycans is a common strategy to increase the analytical performance of MALDI-MS-based glycan profiling techniques. Hydrazide , one of the most popular tags, offers important advantages including allowing purification-free procedures. Several hydrazides have thus been used for glycomics combined with an on-target strategy to further simplify the analytical procedures. Usually, gentle heating and mildly acidic conditions with somewhat long reaction times are needed for these hydrazide derivatizations to reach a high reaction efficiency, which makes the current hydrazide tags not yet perfectly conducive to high-throughput analysis. To further optimize these hydrazide tags for high-throughput analysis, based on the structure of a reported hydrazide and the theoretical calculations, a new cationic hydrazide tag, 4-(hydrazinecarbonyl)- N , N , N -trimethylbenzenaminium (HTMBA), was designed, synthesized and tested in this work. HTMBA could completely derivatize glycans at room temperature in several seconds under very mildly acidic conditions (<3% acetic acid). A 19-fold enhancement in the signal intensity was obtained without interference from alkali adduct ions in the MALDI-MS detection of HTMBA-labeled maltoheptaose . To broaden the applicability of HTMBA, an HTMBA on-target derivatization (HOD) strategy was developed and fully validated with maltoheptaose and RNase B, and the method showed a good repeatability and stability. Finally, the HOD strategy was successfully applied to serum samples, 44 glycans in human serum were detected, and the O-acetylation information of sialic acid in horse serum was preserved. These results showed that the HOD strategy was suitable for the MS-based rapid analysis of all glycoforms in complex biological samples.
研究领域:
生物化学
·
分析化学
·
医学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 46
·26116-26123
·
IF 2.936
Ran Wang,Yufei Liu,Chang Wang,Henghui Li,Xin Liu,Liming Cheng,Yanhong Zhou
Monitoring serum glycomics is one of the most important emerging approaches for diagnosis of various cancers, and the majority of previous studies were based on MALDI-MS or HPLC analysis. Considering the difference of these analytical methods employed for serum glycomics, it is necessary to compare the effectiveness of different analytical methods for monitoring the aberrant changes in serum glycomics. In this study, a strategy based on machine learning was firstly applied for comparing the analysis results of MALDI-MS and HPLC on the same serum glycomics of hepatocellular carcinoma (HCC) samples. The capability of these two analytical methods for identifying HCC is demonstrated by the classification results obtained from MALDI-MS and HPLC data. In addition, by comparing glycomics which were significantly correlated with HCC based on MALDI-MS and HPLC, some N-glycans which may be the potential biomarkers for HCC were identified, validating the capability of these two analytical methods for the differentiated identification in the analysis of glycomics. Meanwhile, it is noteworthy that various physiological and environmental factors may cause the aberrant changes in glycosylation, and all these interference factors may be minimized by analyzing the same sample sets of HCC. Overall, these results showed that MALDI-MS and HPLC are complementary in qualitative and quantitative analysis of serum glycomics.
研究领域:
生物化学
·
癌症研究
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分析化学
·
机器学习
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产品关联
DOI
PubMed
高影响因子
ACS Chemical Neuroscience
·
2023
·
IF 5
Mingming Xu,Hong Jin,Wei Ge,Lingbo Zhao,Zhaoliang Liu,Zeyu Guo,Zhen Wu,Jing Chen,Chengjie Mao,Xumin Zhang,Chun-Feng Liu,Shuang Yang
Urine is thought to provide earlier and more sensitive molecular changes for biomarker discovery than blood. Numerous glycoproteins, peptides, and free glycans are present in urine through glomerular filtration of plasma, cell shedding, apoptosis, proteolytic cleavage, and exosome secretion. Urine biomarkers have enormous diagnostic potential, and the use of these biomarkers is a long-standing practice. The discovery of non-urological disease biomarkers from urine is also gaining attention due to its non-invasive sample collection and ease of analysis. Abnormal protein glycosylation in plasma or cerebrospinal fluid has been associated with Parkinson’s disease, however, whether urine with Parkinson’s disease has characteristic glycosylation remains to be explored. Here, we use mass spectrometry-based glycomics and glycoproteomics approaches to analyze urine samples for glycans, glycosites, and intact glycopeptides of urine samples. Reduced abundance of N-glycans was detected at the level of total glycans as well as specific glycosites of glycopeptides. The most abundant N-glycan in urine is S(6)1H5N4F1; S(6)2H5N4 and N4H4F1 are highly present in serum and urine, and 10 biantennary galactosylated N-glycans in the urine of PD patients were significantly decreased. The downregulation of sialylation may be due to the reduction of ST3GAL2. Site-specific N-glycosylation analysis revealed that AMBP, UMOD, and RNase1 have PD-specific N-glycosylation sites. GO and KEGG analysis revealed that N-glycosylation changes may provide clues to identify disease-specific glycosylation biomarkers in Parkinson’s disease.
研究领域:
神经病学
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生物化学
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分子生物学
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临床化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2022
·
IF 3.571
Hui Liu,Si-Yu Wang,Jin-Hao Zhu,Jin-Di Xu,Shan-Shan Zhou,Ming Kong,Qian Mao,Song-Lin Li,He Zhu
Si-Jun-Zi decoction (SJZD) with ginseng as the principal medicinal herb is a traditional Chinese Medicine multi-herb prescription that commonly employed to treat colorectal cancer etc. Previous studies showed that nearly half of the commercial ginseng was sulfur-fumigated, one of the postharvest processing methods that commonly causes sulfur-dioxide (SO 2 ) residue and chemical composition transformation in medical herbs. In this study, the effect of sulfur-fumigated ginseng on global quality of SJZD was evaluated by UPLC-QTOF-MS/MS based metabolomics and multiple chromatographic techniques based glycomics strategies. For non-saccharides components, sulfur-fumigated ginseng led to the emergence of sulfur-containing derivatives and alteration of saponins and flavonoids in SJZD. For saccharide components, sulfur-fumigated ginseng decreased the total contents and molecular weights of polysaccharides , changed the monosaccharide composition of polysaccharides, and increased the contents of oligosaccharides and free monosaccharides of SJZD. The alterations of SJZD were aggravated with the sulfur-fumigated content of ginseng. Those phenomena might be attributed to 1) sulfur-fumigation caused the generation of sulfur-containing derivatives in ginseng, which further transferred to SJZD, and 2) sulfur-fumigation caused the residue of SO 2 in ginseng, which reduced the pH value and further changed the dissolution of saponins and flavonoids and accelerated the degradation of the polysaccharides to oligosaccharides and/or monosaccharides in SJZD. Furthermore, although storage reduced the SO 2 residue in sulfur-fumigated ginseng, it couldn’t recover the alterations of chemical profiles in SJZD. In conclusion, sulfur-fumigated ginseng altered the global quality of SJZD, which promoted that extra attention must be paid during the application of herbal formulas that containing sulfur-fumigated herbs.
研究领域:
中医
·
药理学
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代谢组学
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糖组学
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草药
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产品关联
DOI
PubMed
高影响因子
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