RSC Advances
·
2025
·Vol. 15
·期 3
·1838-1845
·
IF 4.6
Yaqi Zhang,Qiangjun Chen,Lei Wang,Haoyuan Geng,Zihan Zhu,Cancan Lv,Yisheng Zhao,Xiao Wang,Chenglong Sun,Panpan Chen,Chao Zhang
Colorectal cancer is the second leading cause of cancer-related deaths worldwide, and its development typically involves complex metabolic reprogramming. By mapping the spatial distributions of metabolites and N-glycans in heterogeneous colorectal cancer tissues, we can elucidate cancer-associated metabolic and N-glycan changes. Herein, we combine mass spectrometry imaging-based metabolomics and N-glycomics to characterize the spatially resolved reprogramming of metabolites and N-glycans in colorectal cancer tissues. The metabolic characteristics of different regions of colorectal cancer were evaluated through the utilization of orthogonal partial least squares discriminant analysis. In combination with metabolic pathway enrichment analysis, significant alterations were identified in the fatty acid metabolism, arginine and proline metabolism of colorectal cancer. Cancer cell regions exhibited a marked upregulation of saturated fatty acids, monounsaturated fatty acids, polyamines, and histidine. Additionally, we discovered that the high-mannose N-glycans were predominantly distributed in tumor tissue regions, whereas complex N-glycans were more commonly found in the normal tissue regions adjacent to the tumor. Such findings provide new insights into the spatial signatures of metabolites and N-glycans in colorectal cancer, thereby offering a crucial basis for the diagnosis of colorectal cancer and potential vulnerabilities that might be targeted for cancer therapy.
研究领域:
肿瘤学
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代谢组学
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蛋白质组学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-12
·
IF 4.259
Wu Zhaoguan,Li Henghui,Zhang Qiwei,Liu Xin,Zheng Qi,Li Jianjun
O -Acetylation of sialic acid in protein N-glycans is an important modification and can occur at either 4-, 7-, 8- or 9-position in various combinations. This modification is usually labile under alkaline reaction conditions. Consequently, a permethylation-based analytical method, which has been widely used in glycomics studies, is not suitable for profiling O -acetylation of sialic acids due to the harsh reaction conditions. Alternatively, methylamidation can be used for N-glycan analysis without affecting the base-labile modification of sialic acid. In this report, we applied both permethylation and methylamidation approaches to the analysis of O -acetylation in sialic acids. It has been demonstrated that methylamidation not only stabilizes sialic acids during MALDI processing but also allow for characterization of their O -acetylation pattern. In addition, LC-MS/MS experiments were carried out to distinguish between the O -acetylated glycans with potential isomeric structures. The repeatability of methylamidation was examined to evaluate the applicability of the approach to profiling of O -acetylation in sialic acids. In conclusion, the combination of methylamidation and permethylation methodology is a powerful MALDI-TOF MS-based tool for profiling O -acetylation in sialic acids applicable to screening of N-glycans.
研究领域:
生物化学
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分析化学
·
糖组学
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产品关联
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
·
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
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2020
·
IF 4.192
Yu Lu,Wanjun Jin,Yuerong Yang,Yue Jia,Lujia Sun,Jie Liu,Langhong Wang,Fuxing Zhang,Wupeng Ge,Jiansheng Wang,Linjuan Huang,Zhongfu Wang
Goat milk oligosaccharides are complex carbohydrates with a variety of biological functions. Free oligosaccharides from goat milk show more similarity to human milk than cow milk. At present, changes in goat milk glycoconjugates at different parities remain poorly studied. Herein, we qualitatively and quantitatively compared the goat milk glycoprotein N/O-glycome at different parities using a stable isotope labeling followed by electrospray ionization mass spectrometry and online hydrophilic interaction chromatography. N-Glycans were mainly fucosylated and nonfucosylated nonsialylated, and both fucosylation and sialylation gradually increased with parity, amounting (at the third parity) to 1.25 times and 3.3 times those of the first parity, respectively. O-Glycans were mostly nonfucosylated and nonsialylated, and sialylation increased with increasing parity, and Neu5Ac-sialylated was up to 9 times higher in the third parity than in the first parity, whereas Neu5Gc-sialylated was 5.5 times higher. This study provides a reference for exploring an alternative milk source closest to human milk and for the development of humanized formula milk.
研究领域:
食品科学
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生物化学
·
营养学
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DOI
高影响因子
ANALYTICA CHIMICA ACTA
·
2020
·
IF 5.977
Chang Wang,Yike Wu,Sheng Liu,Liang Zhang,Bi-Feng Liu,Xin Liu
N-glycans that are fluorescently tagged by glycosylamine acylation have become a promising way for glycan biomarker discovery . Here, we describe a simple and rapid method using Fmoc N-hydroxysuccinimide ester (Fmoc-OSu) to label N-glycans by reacting with their corresponding intermediate glycosylamines produced by microwave-assisted deglycosylation . After optimizing reaction conditions, this derivatization reaction can be effectively achieved under 40 °C for 1 h. Moreover, the comparison of fluorescent intensities for Fmoc-OSu, Fmoc-Cl and 2-AA labeling strategies were also performed. Among which, the fluorescent intensities of Fmoc-OSu labeled glycan derivatives were approximately 5 and 13 times higher than that labeled by Fmoc-Cl and 2-AA respectively. Furthermore, the developed derivatization strategy has also been applied for analyzing serum N-glycans, aiming to screen specific biomarkers for early diagnosis of lung squamous cell cancer. More interestingly, the preparation of free reducing N-glycan standards have been achieved by the combination of HPLC fraction of Fmoc labeled glycan derivatives and Fmoc releasing chemistry . Overall, this proposed method has the potential to be used in functional glycomic study.
研究领域:
生物化学
·
医学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Xiaoqin Wang,Wenqing Li,Zhenhua Li,Tianjiao Han,Jinqiao Rong,Jiangbo Fan,Linjuan Huang,Yu Lu,Zhongfu Wang
Human milk glycans are complex carbohydrates , which play a pivotal role in infant health and neonatal development . Maternal secretor status is known to affect free oligosaccharides in milk. Here, the milk N -glycome of secretor (Se+) and nonsecretor (Se−) individuals was qualitatively and quantitatively analyzed by hydrophilic interaction chromatography-electrospray ionization-tandem mass spectrometry. The total glycosylation , fucosylation , and sialylation of N -glycans was three times higher in the Se+ group compared to the Se− group ( p < 0.001) per equal volume of milk. Importantly, 52 out of 63 N -glycans—including the eight most abundant ones—differed greatly between Se+ and Se− individuals ( p < 0.05). Moreover, nine N -glycans (H5N3F1, H6N3, H3N5F1, H5N5F1, H5N5F1S1, H5N4F3S1, H6N4F2S1, H6N5F4S1, and H8N7S1) were >10 times more abundant in Se+ milk than in Se− milk. These findings lay a glycomics-basis for designing personalized nutrition supplements for infants.
研究领域:
生物化学
·
儿科医学
·
营养学
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产品关联
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2021
·
IF 4.952
Yue Jia,Yu Lu,Xue Wang,Yuerong Yang,Meiyi Zou,Jie Liu,Wanjun Jin,Xiaoqin Wang,Guoliang Pang,Linjuan Huang,Zhongfu Wang
Bovine lactoferrin is a functional N-glycoprotein whose glycan moieties play an important role in its biological activities. Although bovine lactoferrin is rich in sialylated N -glycans, there are no reports on the differentiation between α2,3-linked and α2,6-linked sialylated N- glycan isomers. In this study, bovine lactoferrin was separated and purified by cation exchange chromatography, and >95% pure protein was obtained. Following this, N- glycan derivatives of lactoferrin at different stages of lactation were qualitatively and quantitatively analyzed by MALDI-TOF-MS and HILIC-MS/MS. With prolonged lactation, the relative content of the sialylated and fucosylated bi-antenna complex N -glycan (Hex1Man3GlcNAc4GalNAc1Fuc1Neu5Ac1) changed the maximum, with 14.5%, 1.3%, and 0.9% contents in transitional milk, colostrum, and mature milk, respectively. Meanwhile, the contents of sialylated and fucosylated N -glycans in transitional milk were the hi ghest . More importantly, the sialylated N- glycans-linked isomers could be distinguished by linkage-specific derivatization of sialic acid . There were 11 α2,3- and 13 α2,6-linked sialyation N- glycans isomers in the colostrum, which transformed to 4 and 3 N- glycan isomers, respectively, in the mature milk. These findings provide a foundation for an in-depth research on the structure–function relationship of bovine lactoferrin.
研究领域:
生物化学
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营养学
·
分子生物学
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产品关联
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2019
·
IF 6.393
Zewei Luo,Yimin Wang,Ya Xu,Xu Wang,Zhijun Huang,Junman Chen,Yongxin Li,Yixiang Duan
Label-free and in situ detection of N -glycan expression on surface of cells is vital for understanding the progression of cancer. Herein, cytosensing based on U-shaped fiber optic local surface plasmon resonance (LSPR) was developed for cancer cell detection and N -glycan evaluation on cell surface. The U-shaped fiber optic LSPR has high refractive index sensitivity (RIS). Therefore, U-shaped fiber optic LSPR cytosensing afforded ultrasensitivity for cancer cell detection with the limit of detection (LOD) of 30 cells/mL and good linearity in a wide range of 1×10 2 -1×10 6 cells/mL under the optimal conditions of modified AuNPs size and Con A concentration. The U-shaped fiber optic LSPR cytosensing shows more than 29 times lower limit of detection than the straight ones. More importantly, the prepared U-shaped cytosensing was applied to evaluate the N -glycan expression level on the surface of cancer cells under different concentration external stimuli of inhibitor tunicamycin (TM). Noticeably, U-shaped fiber optic LSPR cytosensing showed an acceptable reproducibility, satisfactory anti-interference and good selectivity, and was also applied in the assessment of N -glycan expression on surface of six kinds of cell lines. Therefore, the U-shaped fiber optic LSPR offers a feasible tool in biophysical research and clinical diagnosis for cancer.
研究领域:
生物物理学
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临床诊断
·
癌症研究
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产品关联
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Yuerong Yang,Yu Lu,Yinchuan Liu,Yu Pan,Hongjuan Ma,Linjuan Huang,Zhongfu Wang
Yak milk (YM) has higher protein content than other bovine milk (BM) varieties. The bioactivity of milk glycoproteins is related to N / O -glycans. We qualitatively and quantitatively compared the N / O -glycome of YM and BM glycoproteins using stable isotope labeling combined with hydrophilic interaction chromatography and electrospray ionization mass spectrometry. We identified 79 and 78 N -glycans in YM and BM, respectively. Two N -glycans (H4N5F1A1; H5N4F1) were exclusive to YM. The content ratios of different types of N -glycans differed significantly between YM and BM, with sialylated N -glycans 2.33 times more abundant in YM. Five and seven O -glycans were detected in YM and BM, respectively. Two O -glycans (H1N2; H1N2A1) were exclusive to BM. The bi-sialylated O -glycan, H1N1A2, accounted for 56.1% of O -glycans in YM; it was 5.97 times more abundant in YM than in BM (equal volume basis). This study provides a theoretical basis for the future utilization of YM as a functional food.
研究领域:
食品科学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD SCIENCE
·
2025
·Vol. 90
·期 1
·e70010
·
IF 3.4
Wanyi Zhang,Qiuqi Peng,Linhan Yuan,Caiwen Wu,Mengqi Wang,Hongbo Li,Hongjuan Li,Jinghua Yu
Infant formulas are constantly being updated and upgraded, and N-glycans are functional glycans that have not been fully exploited to date. Commercial whey protein materials are often used as basic ingredients in infant formulas. Therefore, it is important to study N-glycans in commercial whey protein materials. We used matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) and ion chromatography to analyze N-glycans in bovine lactoferrin (Lf), whey protein isolate (WPI), whey protein concentrate 70 (WPC 70), goat whey protein powder 50, demineralized whey powder 90 (D90), and desalted goat whey powder. The results showed that 30, 6, 28, 16, 8, and 9 N-glycans were found in Lf, D90, desalted goat whey powder, WPI, WPC 70, and goat whey protein powder 50, respectively. A total of four structures of N-glycans were detected in this study. Only bovine Lf and WPC 70 contained fucosylated and sialylated binding (SFN-type) glycan structures. Regarding content, WPC 70 showed the highest yield of 14.5 mg/g, and the degree of sialylation was higher than fucosylation. This study provides a potential basis for the future use of commercial whey protein materials in dairy products such as infant formula.
研究领域:
营养学
·
生物化学
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DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2020
·
IF 6.306
Wanjun Jin,Cheng Li,Meiyi Zou,Yu Lu,Ming Wei,Lijing Nan,Yue Jia,Chengjian Wang,Linjuan Huang,Zhongfu Wang
Sialylated N-glycans are an integral component of whey proteins in human milk and play an irreplaceable role in infant growth and development. Currently, there are few studies on quantitative comparison of sialylated N -glycans in milk obtained at different lactation stages. Here, a preliminary isomer-specific quantification of whey sialylated N -glycans of human colostrum milk (CM) and mature milk (MM) was performed by using our recently developed glycoqueuing strategy. Such a preliminary comparison revealed that the whey sialylated N -glycan content was 86.4% lower in MM than in CM. Twenty-three α2,6-linked sialylated N -glycan isomers were detected with no α2,3-linked isomer observed. For the first time, three mono-sialylated and four bi-sialylated glycan isomers were reported. With the prolongation of lactation, the relative abundance of mono-sialylated glycans increased, whilst the relative abundance of bi-sialylated glycans decreased significantly. These findings contribute to the understanding of the structure–function relationship of sialylated N -glycans in the human whey fraction.
研究领域:
营养学
·
生物化学
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2019
·
IF 3.858
Yike Wu,Qiuyue Sha,Chang Wang,Bi-Feng Liu,Song Wang,Xin Liu
Efficient sample pretreatment of N-glycans from glycoproteins is essential but challenging due to the limitations of existing tedious and laborious methods in N-glycomics. This study aimed to establish a filter-aided extraction method coupled with glycosylamine AQC labeling for a simple and rapid direct HPLC-FLD-based analysis of N-glycans. The developed method was demonstrated to be simpler and more sensitive compared to previous HILIC SPE purification method coupled with glycosylamine labeling. It has been validated with wild-type N-glycans from human transferrin and RNase B and then was successfully applied to investigate N-glycan profiles of the transferrin in human serum and a monoclonal antibody (mAb). Results showed good applicability of the method for complex samples. Additionally, this method is compatible with the replicate determination of N-glycan samples to assess the high-throughput analysis of glycan variability in mAb sample.
研究领域:
生物化学
·
分析化学
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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）