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人类蛋白质N-糖基化的十二年全基因组关联研究 Review
Anna Timoshchuk, Sodbo Sharapov, Yurii S. Aulchenko
《工程（英文）》 2023年 第26卷 第7期 页码 17-31 doi: 10.1016/j.eng.2023.03.013
Most human-secreted and membrane-bound proteins have covalently attached oligosaccharide chains, or glycans. Glycosylation influences the physical and chemical properties of proteins, as well as their biological functions. Unsurprisingly, alterations in protein glycosylation have been implicated in a growing number of human diseases, and glycans are increasingly being considered as potential therapeutic targets, an essential part of therapeutics, and biomarkers. Although glycosylation pathways are biochemically well-studied, little is known about the networks of genes that guide the cell- and tissue-specific regulation of these biochemical reactions in humans in vivo. The lack of a detailed understanding of the mechanisms regulating glycome variation and linking the glycome to human health and disease is slowing progress in clinical applications of human glycobiology. Two of the tools that can provide much sought-after knowledge of human in vivo glycobiology are human genetics and genomics, which offer a powerful data-driven agnostic approach for dissecting the biology of complex traits. This review summarizes the current state of human populational glycogenomics. In Section 1, we provide a brief overview of the N-glycan's structural organization, and in Section 2, we give a description of the major blood plasma glycoproteins. Next, in Section 3, we summarize, systemize, and generalize the results from current N-glycosylation genome-wide association studies (GWASs) that provide novel knowledge of the genetic regulation of the populational variation of glycosylation. Until now, such studies have been limited to an analysis of the human blood plasma N-glycome and the N-glycosylation of immunoglobulin G and transferrin. While these three glycomes make up a rather limited set compared with the enormous multitude of glycomes of different tissues and glycoproteins, the study of these three does allow for powerful analysis and generalization. Finally, in Section 4, we turn to genes in the established loci, paying particular attention to genes with strong support in Section 5. At the end of the review, in Sections 6 and 7, we describe special cases of interest in light of new discoveries, focusing on possible mechanisms of action and biological targets of genetic variation that have been implicated in human protein N-glycosylation.
免疫球蛋白G N-糖基化与代谢特征之间的双向因果关联——一项孟德尔随机化研究 Article
孟晓妮, 曹维杰, 刘迪, Isinta Elijah Maranga, 邢薇佳, 侯海峰, 徐希柱, 宋曼殳, 王友信
《工程（英文）》 2023年 第26卷 第7期 页码 74-88 doi: 10.1016/j.eng.2022.11.004
既往研究已发现免疫球蛋白 G（immunoglobulin G, IgG）N-糖基化与代谢特征之间存在关联，但它们之间是否存在因果关联尚有待研究糖基化与代谢特征之间的双向因果关联。在正向MR分析中，通过整合IgG N-糖基-QTL遗传变异与GWAS 数据和代谢特征进行分析，分别发现59个包括影响体质指数（body mass index, BMI）的9个IgG N-糖基（glycan-糖基（GP2 和 GP11 等）和影响FPG的 4个IgG N-糖基（GP1和GP10等）]由遗传决定的 IgG N-糖基在单样本和两样本MR研究中与代谢特征存在因果关联（全部 P综上所述，本研究全面的双向MR分析提供了IgG N-糖基化与代谢特征之间双向因果关联的证据，在一定程度上揭示了 IgG N-糖基化与代谢特征之间的生物学机制。
月经周期中免疫球蛋白G N-糖基化的周期性变化 Article
Julija Jurić, Hongli Peng, Manshu Song, Frano Vučković, Jelena Šimunović, Irena Trbojević-Akmačić, Youxin Wang, Jiaonan Liu, Qing Gao, Hao Wang, Qiaoyun Chu, Marija Pezer, Wei Wang, Gordan Lauc
《工程（英文）》 2023年 第26卷 第7期 页码 108-118 doi: 10.1016/j.eng.2022.10.020
Immunoglobulin G (IgG) is the most abundant plasma glycoprotein and a prominent humoral immune mediator. Glycan composition affects the affinity of IgG to ligands and consequent immune responses. The modification of IgG N-glycosylation is considered to be one of the various mechanisms by which sex hormones modulate the immune system. Although the menstrual cycle is the central sex hormone-related physiological process in most women of reproductive age, IgG N-glycosylation dynamics during the menstrual cycle have not yet been investigated. To fill this gap, we profiled the plasma IgG N-glycans of 70 healthy premenopausal women at 12 time points during their menstrual cycles (every 7 days for 3 months) using hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC). We observed cyclic periodic changes in the N-glycosylation of IgG in association with the menstrual cycle phase and sex hormone concentration in plasma. On the integrated cohort level, the modeled average menstrual cycle effect on the abundance of IgG N-glycosylation traits was low for each trait, with the highest being 1.1% for agalactosylated N-glycans. However, intrapersonal changes were relatively high in some cases; for example, the largest difference between theminimum and maximum values during themenstrual cycle was up to 21% for sialylated N-glycans. Across all measurements, the menstrual cycle phase could explain up to 0.72% of the variation in the abundance of a single IgG glycosylation trait of monogalactosylation. In contrast, up to 99% of the variation in the abundance of digalactosylation could be attributed to interpersonal differences in IgG N-glycosylation. In conclusion, the average extent of changes in the IgG N-glycopattern that occur during the menstrual cycle is small; thus, the IgG N-glycoprofiling of women in large sample-size studies can be performed regardless of menstrual cycle phase.
IgG N-糖基心血管年龄独立于真实年龄精准表征心血管事件风险 Article
武志远, 郭政, 郑雨露, 王玉涛, 张海平, 潘慧颖, 李志伟, Lois Balmer, 李霞, 陶丽新, 郭秀花, 王嵬
《工程（英文）》 2023年 第26卷 第7期 页码 99-107 doi: 10.1016/j.eng.2022.12.004
转录因子HNF1A、HNF4A和FOXA2调节肝细胞蛋白质N-糖基化 Article
Vedrana Vičić Bočkor,Nika Foglar,Goran Josipović,Marija Klasić,Ana Vujić,Branimir Plavša,Toma Keser,Samira Smajlović,Aleksandar Vojta,Vlatka Zoldoš
《工程（英文）》 2024年 第32卷 第1期 页码 58-69 doi: 10.1016/j.eng.2023.09.019
Hepatocyte nuclear factor 1 alpha (HNF1A), hepatocyte nuclear factor 4 alpha (HNF4A), and forkhead box protein A2 (FOXA2) are key transcription factors that regulate a complex gene network in the liver, creating a regulatory transcriptional loop. The Encode and ChIP-Atlas databases identify the recognition sites of these transcription factors in many glycosyltransferase genes. Our in silico analysis of HNF1A, HNF4A, and FOXA2 binding to the 10 candidate glyco-genes studied in this work confirms a significant enrichment of these transcription factors specifically in the liver. Our previous studies identified HNF1A as a master regulator of fucosylation, glycan branching, and galactosylation of plasma glycoproteins. Here, we aimed to functionally validate the role of the three transcription factors on downstream glyco-gene transcriptional expression and the possible effect on glycan phenotype. We used the state-of-the-art clustered regularly interspaced short palindromic repeats/dead Cas9 (CRISPR/dCas9) molecular tool for the downregulation of the HNF1A, HNF4A, and FOXA2 genes in HepG2 cells—a human liver cancer cell line. The results show that the downregulation of all three genes individually and in pairs affects the transcriptional activity of many glyco-genes, although downregulation of glyco-genes was not always followed by an unambiguous change in the corresponding glycan structures. The effect is better seen as an overall change in the total HepG2 N-glycome, primarily due to the extension of biantennary glycans. We propose an alternative way to evaluate the N-glycome composition via estimating the overall complexity of the glycome by quantifying the number of monomers in each glycan structure. We also propose a model showing feedback loops with the mutual activation of HNF1A–FOXA2 and HNF4A–FOXA2 affecting glyco-genes and protein glycosylation in HepG2 cells.
关键词： Clustered regularly interspaced short palindromic repeats/dead Cas9 (CRISPR/dCas9) Epigenetics Hepatocyte nuclear factor 1 alpha (HNF1A) Hepatocyte nuclear factor 4 alpha (HNF4A) Forkhead box protein A2 (FOXA2) N-glycosylation HepG2 cells
基于正交质谱的N-糖组谱揭示哈夫病潜在病原学 Article
刘思, 刘圆圆, 林佳静, 刘笔锋, 何振宇, 吴晓旻, 刘欣
《工程（英文）》 2023年 第26卷 第7期 页码 63-73 doi: 10.1016/j.eng.2022.09.012
血清免疫球蛋白G N-糖基的高通量分析——一种消化道癌症的非侵入性生物标志物 Article
刘鹏程, 王小兵, 顿爱社, 李昱潼, 李厚强, 王璐, 张怡春, 李灿灿, 张金霞, 张晓雨, 马立兴, 侯海峰
《工程（英文）》 2023年 第26卷 第7期 页码 44-53 doi: 10.1016/j.eng.2023.02.008
免疫球蛋白G (Immunoglobulin G, IgG) 的 N-糖基化在炎症性疾病的发展中起着重要作用。本研究旨在评价IgG N-糖基在消化道癌症亚型中的诊断效能。/em>-糖基构成。与健康对照组相比，EC、GC、CRC和PC患者的唾液酸化和半乳糖基化水平降低，而二等分乙酰葡萄糖胺基化水平在消化道癌症患者中升高。 此外，只有胰腺癌患者具有低水平的岩藻糖基化。IgG N-糖基的组成与炎症因子相关 (r = 0.556)。这些研究结果表明，IgG N-糖基在调节消化道肿瘤的发病机制中发挥了重要作用。血清IgG N-糖基可以作为潜在的非侵入性辅助消化道癌症临床诊断的方法。
流感与COVID-19患者的免疫球蛋白G糖基化差异 Article
Marina Kljaković-Gašpić Batinjan, Tea Petrović, Frano Vučković, Irzal Hadžibegović, Barbara Radovani, Ivana Jurin, Lovorka Đerek, Eva Huljev, Alemka Markotić, Ivica Lukšić, Irena Trbojević-Akmačić, Gordan Lauc, Ivan Gudelj, Rok Čivljak
《工程（英文）》 2023年 第26卷 第7期 页码 54-62 doi: 10.1016/j.eng.2022.08.007
The essential role of immunoglobulin G (IgG) in immune system regulation and combatting infectious diseases cannot be fully recognized without an understanding of the changes in its N-glycans attached to the asparagine 297 of the Fc domain that occur under such circumstances. These glycans impact the antibody stability, half-life, secretion, immunogenicity, and effector functions. Therefore, in this study, we analyzed and compared the total IgG glycome—at the level of individual glycan structures and derived glycosylation traits (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc))—of 64 patients with influenza, 77 patients with coronavirus disease 2019 (COVID-19), and 56 healthy controls. Our study revealed a significant decrease in IgG galactosylation, sialylation, and bisecting GlcNAc (where the latter shows the most significant decrease) in deceased COVID-19 patients, whereas IgG fucosylation was increased. On the other hand, IgG galactosylation remained stable in influenza patients and COVID-19 survivors. IgG glycosylation in influenza patients was more time-dependent: In the first seven days of the disease, sialylation increased and fucosylation and bisecting GlcNAc decreased; in the next 21 days, sialylation decreased and fucosylation increased (while bisecting GlcNAc remained stable). The similarity of IgG glycosylation changes in COVID-19 survivors and influenza patients may be the consequence of an adequate immune response to enveloped viruses, while the observed changes in deceased COVID-19 patients may indicate its deviation.
人体前列腺特异性抗原携带含酮基-脱氧壬酮糖酸的N-聚糖 Article
Wei Wang, Tao Zhang, Jan Nouta, Peter A. van Veelen, Noortje de Haan, Theo M. de Reijke, Manfred Wuhrer, Guinevere S.M. Lageveen-Kammeijer
《工程（英文）》 2023年 第26卷 第7期 页码 119-131 doi: 10.1016/j.eng.2023.02.009
Ketodeoxynononic acid (Kdn) is a rather uncommon class of sialic acid in mammals. However, associations have been found between elevated concentrations of free or conjugated Kdn in relation to human cancer progression. Hitherto, there has been a lack of conclusive evidence that Kdn occurs on (specific) human glycoproteins (conjugated Kdn). Here, we report for the first time that Kdn is expressed on prostate-specific antigen (PSA) N-linked glycans derived from human seminal plasma and urine. Interestingly, Kdn was found only in an α2,3-linkage configuration on an antennary galactose, indicating a highly specific biosynthesis. This unusual glycosylation feature was also identified in a urinary PSA cohort in relation to prostate cancer (PCa), although no differences were found between PCa and non-PCa patients. Further research is needed to investigate the occurrence, biosynthesis, biological role, and biomarker potential of both free and conjugated Kdn in humans.
新型冠状病毒HCoV-19 S蛋白与人ACE2蛋白表面糖链和独特翻译后修饰的质谱分析 Article
孙泽宇, 任科燚, 张兴, 陈景华, 姜正一, 江静, 季飞洋, 欧阳晓希, 李兰娟
《工程（英文）》 2021年 第7卷 第10期 页码 1441-1451 doi: 10.1016/j.eng.2020.07.014
Estimating the effect of urease inhibitor on rice yield based on NDVI at key growth stages
Kailou LIU,Yazhen LI,Huiwen HU
《农业科学与工程前沿（英文）》 2014年 第1卷 第2期 页码 150-157 doi: 10.15302/J-FASE-2014028
关键词： normalized difference vegetation index (NDVI) N-(n-butyl) thiophosphoric triamide (NBPT) rice grain yield
用于提高叔胺的二氧化碳吸收能力的纳米多孔碳材料促进剂的制备 Review
Masood S. Alivand, Omid Mazaheri, Yue Wu, Geoffrey W. Stevens, Colin A. Scholes, Kathryn A. Mumford
《工程（英文）》 2020年 第6卷 第12期 页码 1381-1394 doi: 10.1016/j.eng.2020.05.004
Chengkun WANG, Xiaojian ZHANG, Jun WANG, Chao CHEN
《环境科学与工程前沿（英文）》 2012年 第6卷 第6期 页码 770-777 doi: 10.1007/s11783-012-0412-0
关键词：
可去除染料——N-聚糖多方法深入分析中的缺失环节 Article
Samanta Cajic, René Hennig, Valerian Grote, Udo Reichl, Erdmann Rapp
《工程（英文）》 2023年 第26卷 第7期 页码 132-150 doi: https://doi.org/10.1016/j.eng.2023.02.016
As the roles of glycans in health and disease continue to be unraveled, it is becoming apparent that glycans' immense complexity cannot be ignored. To fully delineate glycan structures, we developed an integrative approach combining a set of cost-effective, widespread, and easy-to-handle analytical methods. The key feature of our workflow is the exploitation of a removable fluorescent label—exemplified by 9-fluorenylmethyl chloroformate (Fmoc)—to bridge the gap between diverse glycoanalytical methods, especially multiplexed capillary gel electrophoresis with laser-induced fluorescence detection (xCGE-LIF) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Through the detailed structural analysis of selected, dauntingly complex N-glycans from chicken ovalbumin, horse serum, and bovine transferrin, we illustrate the capabilities of the presented strategy. Moreover, this approach "visualizes" N-glycans that have been difficult to identify thus far—such as the sulfated glycans on human immunoglobulin A—including minute changes in glycan structures, potentially providing useful new targets for biomarker discovery.
血清N-聚糖生物标志物诊断ALT水平正常慢性乙型肝炎患者显著肝纤维化和肝硬化的临床意义 Article
王林, 刘艺琪, 顾启馨, 张驰, 徐蕾, 王蕾, 陈翠英, 刘学恩, 赵鸿, 庄辉
《工程（英文）》 2023年 第26卷 第7期 页码 151-158 doi: 10.1016/j.eng.2023.03.008
标题 作者 时间 类型 操作
免疫球蛋白G N-糖基化与代谢特征之间的双向因果关联——一项孟德尔随机化研究
孟晓妮, 曹维杰, 刘迪, Isinta Elijah Maranga, 邢薇佳, 侯海峰, 徐希柱, 宋曼殳, 王友信
期刊论文
月经周期中免疫球蛋白G N-糖基化的周期性变化
Julija Jurić, Hongli Peng, Manshu Song, Frano Vučković, Jelena Šimunović, Irena Trbojević-Akmačić, Youxin Wang, Jiaonan Liu, Qing Gao, Hao Wang, Qiaoyun Chu, Marija Pezer, Wei Wang, Gordan Lauc
期刊论文
IgG N-糖基心血管年龄独立于真实年龄精准表征心血管事件风险
武志远, 郭政, 郑雨露, 王玉涛, 张海平, 潘慧颖, 李志伟, Lois Balmer, 李霞, 陶丽新, 郭秀花, 王嵬
期刊论文
转录因子HNF1A、HNF4A和FOXA2调节肝细胞蛋白质N-糖基化
Vedrana Vičić Bočkor,Nika Foglar,Goran Josipović,Marija Klasić,Ana Vujić,Branimir Plavša,Toma Keser,Samira Smajlović,Aleksandar Vojta,Vlatka Zoldoš
期刊论文
血清免疫球蛋白G N-糖基的高通量分析——一种消化道癌症的非侵入性生物标志物
刘鹏程, 王小兵, 顿爱社, 李昱潼, 李厚强, 王璐, 张怡春, 李灿灿, 张金霞, 张晓雨, 马立兴, 侯海峰
期刊论文
流感与COVID-19患者的免疫球蛋白G糖基化差异
Marina Kljaković-Gašpić Batinjan, Tea Petrović, Frano Vučković, Irzal Hadžibegović, Barbara Radovani, Ivana Jurin, Lovorka Đerek, Eva Huljev, Alemka Markotić, Ivica Lukšić, Irena Trbojević-Akmačić, Gordan Lauc, Ivan Gudelj, Rok Čivljak
期刊论文
人体前列腺特异性抗原携带含酮基-脱氧壬酮糖酸的N-聚糖
Wei Wang, Tao Zhang, Jan Nouta, Peter A. van Veelen, Noortje de Haan, Theo M. de Reijke, Manfred Wuhrer, Guinevere S.M. Lageveen-Kammeijer
期刊论文
Estimating the effect of urease inhibitor on rice yield based on NDVI at key growth stages
Kailou LIU,Yazhen LI,Huiwen HU
期刊论文
用于提高叔胺的二氧化碳吸收能力的纳米多孔碳材料促进剂的制备
Masood S. Alivand, Omid Mazaheri, Yue Wu, Geoffrey W. Stevens, Colin A. Scholes, Kathryn A. Mumford
期刊论文
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