Advanced Healthcare Materials
·
2024
·
IF 10
Weisin Chen,Hongwei Lu,Wenhao Yu,Lei Huang,Mengxuan Bian,Ning Wang,Xingdong Xiang,Guokang Mo,Cheng Zhang,Yulin Li,Libo Jiang,Jian Zhang
Autograft has long been the gold standard for various bone surgeries. Nevertheless, the increasing usage of synthetic implants is taking over the operation rooms due to biosafety and standardized protocols. To fulfill such tremendous needs, a magnesium-impregnated membrane is devised that steadily releases magnesium ions to stimulate osteogenesis. The compatibility of Magnesium oxide (MgO) particles is enhanced through hydration and grafting, characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). With detailed degradation profiles, an in-depth investigation of Magnesium transporter 1 (MagT1) for magnesium intake is carried out and engaging in the N-linked glycosylation by using RNAi and inhibitors. The glycosylation of secreted protein acidic and rich in cysteine (SPARC) affected extracellular secretion and mineral deposition, demonstrated by immunostaining and density-dependent color-SEM (DDC-SEM). Skull defects are treated by implanting magnesium-impregnated membranes in rats and evaluated them by micro-CT and histological exams. This study revealed the compatible integration of grafted magnesium hydroxide (g-MH) particles is the key to functional performance and critical to applicability in vivo; meanwhile, it opens the door to a biological rationale for designing biomimetic materials.
研究领域:
生物医学工程
·
分子生物学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2025
·Vol. 29
·期 7
·e70539
·
IF 4.2
Tianyi Ji,Xiangying Li,Jiachen Li,Guan Wang
Wnt signalling is a highly conserved signalling pathway that plays an important role in a variety of biological processes. Frizzled (Fzd) family proteins are receptors for Wnt ligands. The physiological processes involved in mature trafficking of Fzd proteins remain elusive. Here, we identified asparagine residues 59 and 144 as the N-glycosylation modification sites of Fzd4. Sequence analysis of Fzd4 in different species showed that the two asparagine residues were highly conserved. N-glycosylation modification of Fzd4 is indispensable for its maturation and transport to the plasma membrane. N-glycosylation modification enhances the stability of Fzd4 and is also necessary for Fzd4 activity, which promotes Fzd4 interaction with Wnt ligands and co-receptor Norrin. Knockout of Fzd4 in the non-small cell lung cancer (NSCLC) cell line A549 followed by replenishment of Fzd4 glycosylation site mutants inhibited the growth and migration ability of A549 cells in vitro and in vivo. In summary, we identified N-glycosylation modification sites of Fzd4. N-glycosylation modification of Fzd4 is necessary for its stability and activity. When N-glycosylation modification is absent, Fzd4 cannot mediate the Wnt/β-catenin signalling pathway, which can inhibit the proliferation and migration of NSCLC and provide new targets and strategies for the treatment of NSCLC.
研究领域:
细胞生物学
·
分子生物学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2021
·
IF 4.759
Canhong Zhu,Jiani Wu,Xueting Jin,Yinghua Yan,Chuan-Fan Ding,Keqi Tang,Qiaohong Zhang
Herein, a hydrophilic graphene composite functionalized with glutathione (GSH) and L(+)-Cysteine (Cys) was prepared via a simple and fast synthesis route, which was named G@S@Au@GC. The combination attack with two different zwitterionic polymers resulted in enhanced adsorption sites for glycopeptides. The obtained G@S@Au@GC exhibited excellent performance on a low limit of detection (0.2 fmol), a high selectivity (HRP: bovine serum albumin = 1:1500), a good load capacity (250 μg•mg −1 ) and recovery rate (93%), which was also evaluated with IgG. Subsequently, 60 glycopeptides from complex biological sample (human saliva) were identified by Nano-LC-MS/MS. The advantages of combination attack, low-cost, simple and fast synthesis, and superior enrichment performance make G@S@Au@GC composite a bright future on glycoproteomics analysis and related diseases.
研究领域:
分析化学
·
蛋白质组学
·
生物医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Science and Human Wellness
·
2023
·
IF 7
Linglin Fu,Rongrong Wang,Jinru Zhou,Chong Wang,Yanbo Wang
N -glycans in many proteins are of great concern because of their strong association with food allergies. Triticum aestivum (bread wheat), a major food crop, is known as one of the “Big Eight” allergenic groups. However, little research has been done about N -glycans in wheat glycoproteins. In this study, a soluble wheat glycoprotein was purified from wheat and further identified as globulin-1 S allele (GSA). The wheat GSA displayed significant IgE-binding activity. Moreover, one N -glycosylation site and 6 kinds of N -glycans were identified by mass spectrometry, including 3 high mannose types and 3 complex types. Furthermore, the IgE-binding activity of wheat GSA is proved to be reduced by the removal of N -glycan, thermal treatment (temperatures > 80 °C), and strong acidic treatment (pH 3.0). These findings would provide a better understanding of the effects of N -glycosylation, thermal treatment, and acidic treatment on the molecular characteristics of GSA, and further provide new insights into the development of hypoallergenic wheat products.
研究领域:
食品科学
·
植物生物学
·
免疫学
✓ 已验证
DOI
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
·
分析化学
·
机器学习
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Ruobin Sun,Qipeng Yan,Wenhao Deng,Pengcheng Chen,Dan Wu,Pu Zheng
Achieving enzyme catalysis at high substrate concentrations is a substantial challenge in industrial biocatalysis, and the role of glycosylation in post-translational modifications that modulate enzyme substrate inhibition remains poorly understood. This study provides insights into the role of N -glycosylation in substrate inhibition by comparing the catalytic properties of d -lactonohydrolase ( d -Lac) derived from Fusarium moniliforme expressed in prokaryotic and eukaryotic hosts. Experimental evidence indicates that recombinant d -Lac expressed in Pichia pastoris ( Pp Lac-WT) exhibits higher hydrolysis rates at a substrate concentration of 400 g/L, with reduced substrate inhibition and enhanced stability compared to the recombinant d -Lac expressed in Escherichia coli ( Ec Lac-WT). Mutant Pp Lac-M1 achieves a conversion rate of 40 % at a substrate concentration of 400 g/L, with a space–time yield of d -pantoic acid reaching 91.1 g/L/h. Proteomics analysis reveals that residues N29 and N278, located approximately 10–20 Å from the active site undergo N -glycosylation in Pp Lac-WT. Using microsecond-scale molecular dynamics simulations and Markov state models, we elucidate the effects of glycosylation on the conformational flexibility of two key loops at the entrance of the binding pocket. Specifically, the loops in Pp Lac-WT can transition between open and closed states, whereas those in Ec Lac-WT tend to remain open. In high substrate concentration conditions, the open state causes congestion, leading to substrate inhibition. Shortest-path map analysis confirms that substrate entry is dynamically controlled by residue N29 on the loops surrounding the active site. Our findings enhance the understanding of the effects of glycosylation on enzyme conformational dynamics and provide insights into mitigating inhibition at high substrate concentrations.
研究领域:
生物化学
·
酶工程
·
结构生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PROTEOME RESEARCH
·
2024
·
IF 3.8
Huohuan Tian,Ze Tao,Wanli Zhang,Yuzhe Chen,Tao Su,Xinyuan Wang,Hao Yang,Hao Cai,Shuyun Liu,Yi Zhang,Yong Zhang
Human plasma proteomic and glycoproteomic analyses have emerged as an alternate avenue to identify disease biomarkers and therapeutic approaches. However, the vast number of high-abundance proteins in plasma can cause mass spectrometry (MS) suppression, which makes it challenging to detect low-abundance proteins (LAP). Currently, immunoaffinity-based depletion methods and strategies involving nanomaterial protein coronas have been developed to remove high-abundance proteins (HAP) and enhance the depth of plasma protein identification. Despite these advancements, there is a lack of systematic comparison and evaluation of the qualitative and quantitative effects of different strategies on the human plasma proteome and glycoproteome. In this study, we evaluated the performance of four depletion methods including combinatorial peptide ligand libraries (CPLL), Top 2, Top 14, and the nanomaterial protein corona formed by magnetic nanoparticles (MN) in both plasma proteomics and N-glycoproteomics. Compared to the CPLL, Top 2, and Top 14 strategies, the MN approach significantly increased the number of identified peptides and proteins. However, it demonstrated a relatively lower efficacy in identifying intact N-glycopeptides and N-glycoproteins. In contrast, the immunoaffinity-based depletion methods are better suited to glycoproteomics due to higher identification numbers. We believe that this work provides valuable insights and options for various research objectives, as well as clinical applications.
研究领域:
生物化学
·
医学
·
蛋白质组学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Zhejiang University-SCIENCE B
·
2024
·Vol. 25
·期 1
·51-64
·
IF 4.7
Xu Mingming,Liu Zhaoliang,Hu Wenhua,Han Ying,Wu Zhen,Chen Sufeng,Xia Peng,Du Jing,Zhang Xumin,Hao Piliang,Xia Jun,Yang Shuang
Pancreatic cancer is among the most malignant cancers, and thus early intervention is the key to better survival outcomes. However, no methods have been derived that can reliably identify early precursors of development into malignancy. Therefore, it is urgent to discover early molecular changes during pancreatic tumorigenesis. As aberrant glycosylation is closely associated with cancer progression, numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis; however, detailed glycoproteomic information, especially site-specific N -glycosylation changes in pancreatic cancer with and without drug treatment, needs to be further explored. Herein, we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans, glycosites, and intact glycopeptides in pancreatic cancer cells and patient sera. The profiling of N -glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells, whereas human sera, which contain many secreted glycoproteins, had significant changes of glycans at their specific glycosites. These results indicated the potential role for tumor-specific glycosylation as disease biomarkers. We also found that AMG-510, a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog ( KRAS ) G12C mutation, profoundly reduced the glycosylation level in MIA PaCa-2 cells, suggesting that KRAS plays a role in the cellular glycosylation process, and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.
研究领域:
肿瘤学
·
蛋白质组学
·
分子生物学
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2022
·
IF 6.556
Jingjing Shu,Wenli Xiong,Ran Zhang,Shanyun Ma,Kaiqiang Zhou,Xuwei Wang,Fen Yan,Da Huang,Jianhua Li,Yuanzi Wu,Jian'an He
In view of the biological significance and micro-heterogeneity of protein glycosylation for human health, specific enrichment of N -glycosylated proteins/peptides from complex biological samples is a prerequisite for the discovery of disease biomarkers and clinical diagnosis. In this work, we propose a “grafting-from” N-glycoprotein enriching method based on the in-situ growth of thermoresponsive polymer brushes from the N -glycosylated site of proteins. The initiator was first attached to the pre-oxidized glycan moieties by hydrazide chemistry , from which the thermoresponsive polymers can be grown to form giant protein-polymer conjugates (PPC). The thermosensitive PPC can be precipitated and separated by raising the temperature to above its lower critical solubility temperature (LCST). Mass spectrometry verified 210 N -glycopeptides corresponding to 136 N-glycoproteins in the rabbit serum. These results demonstrate the capability of the tandem thermoprecipitation strategy to enrich and separate N-glycoprotein/glycopeptide. Due to its simplicity and efficiency specifically, this method holds the potential for identifying biomarkers from biological samples in N -glycoproteome analysis.
研究领域:
生物化学
·
分析化学
·
蛋白质组学
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Wenyuan Zhang,Jing Lu,Baorong Chen,Peng Gao,Bo Song,Shuwen Zhang,Xiaoyang Pang,Kasper Hettinga,Jiaping Lyu
Milk samples were collected from 10 cows, in the colostrum (3–4 days) and mature (90 days) lactation stage, to assess the differential expression of all whey proteins and N-glycoproteins. In total, 240 whey proteins and 315 N-glycosylation sites on 214 glycoproteins were quantified. GO annotations, KEGG pathway analysis, and protein classification were performed to understand the similarities and differences of the biological functions of whey proteins and N-glycoproteins among different lactation stages in bovine milk. Furthermore, differential expression of whey proteins and whey N-glycosylated proteins was found between different lactation stages. The related changes of biological functions in differentially expressed proteins were discussed. For example, the increased frequency of glycosylation on lactoferrin and folate receptor alpha occurring in bovine colostrum may provide protection and stimulate development of the newborn calf. Our study thereby improves understanding of variations of glycosylation sites on milk glycoproteins among lactation stages.
研究领域:
分子生物学
·
蛋白质组学
·
动物科学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CLINICAL RHEUMATOLOGY
·
2025
·
IF 2.8
Yin Jia,Yin Xuan,Tao Lei,Peng Yuanzhi,Zhao Shuhan,Hou Haifeng,Yin Xinyue,Ran Zhangshen,Zhou Aihong,Ding Guoyong
Background Alterations in immunoglobulin G (IgG) N -glycosylation have been implicated in various diseases, potentially including ankylosing spondylitis (AS). However, empirical evidence regarding the associations IgG N -glycosylation, inflammatory factors, and AS is sparse. We aimed to investigate these associations and evaluate the diagnostic performance of IgG glycosylation traits as a biomarker for AS. Methods This case–control study recruited 142 AS patients and 142 controls. We used hydrophilic interaction liquid chromatography with ultra-performance liquid chromatography to detect the profiles of plasma IgG N -glycans. An enzyme-linked immunosorbent assay kit was used to measure the levels of serum inflammatory factors. We used multivariate logistic regression, canonical correlation analysis (CCA), and Lasso regression to analyze the data. Results Multivariate logistic analysis identified 14 IgG N -glycan-derived traits significantly associated with AS. The changes were primarily characterized by decreased galactosylation, sialylation, bisgalactosylated fucosylation and sialated fucosylation, alongside increased core fucosylation, agalactosylated fucosylation, neutral fucosylation and sialated bisecting N -acetylglucosamine. Significant differences were observed between cases and controls in levels of C-reactive protein (CRP), IL-17, IL-22, IL-6, and TNF-α. CCA demonstrated a moderate correlation between IgG N -glycan-derived traits and inflammatory factors ( r = 0.476). The combined diagnostic performance of derived traits and inflammatory factors yielded a higher area under the curve (AUC = 0.90) than either alone (AUC derived traits = 0.88, AUC inflammatory factors = 0.78). Conclusion The findings indicate that abnormal IgG N -glycosylation may play an important role in the development of AS through promoting the pro-inflammatory function. The derived traits combined with inflammatory factors may serve as potential biomarkers to distinguish AS.
Key Points • We comprehensively analyzed IgG N-glycan-derived traits in AS by an HILIC-UPLC-based high-throughput method. • Abnormal IgG N-glycosylation plays a role in the development of AS through promoting the proinflammatory. • IgG N-glycosylation combined with inflammatory factors demonstrated strong diagnostic performance for AS.
研究领域:
免疫学
·
风湿病学
·
糖生物学
·
分子医学
·
转化医学
·
炎症机制
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CLINICA CHIMICA ACTA
·
2022
·
IF 6.314
Jiyun Zhang,Zhizhen Lai,Rui Ding,Jinyu zhou,Zhonghao Yuan,Dan Li,Xuzhen Qin,Jiang Zhou,Zhili li
Background Altered glycosylation modulates the structure and function of disease-related proteins. The associations between serotransferrin (STF) N -glycosylation and liver diseases (LDs) have been revealed. However, how intact N -glycopeptides vary among different types of liver diseases remains unclear. Methods Intact STF N -glycopeptides from patients with chronic liver disease (CLD, n = 92), primary liver cancer (PLC, n = 123), metastatic liver cancer (MLC, n = 57), and healthy controls (HCs, n = 59) were determined using high-resolution mass spectrometry. Results Significant changes were displayed in STF glycosylation among 4 groups. The LD screening model, including Asn432 G1S/G2S, Asn432 G2S/G2S2, and Asn630 G2NS2/G2FNS2, was constructed to differentiate LDs from HCs, with a AUC of 0.92. The liver cancer (LC) diagnostic model, a combination of Asn432 G1-N/G1S-N, Asn432 G1/G2, Asn432 G2FS/G2FS2, and Asn630 G1S-N /G1S, showed good performance in discriminating LC from CLD (AUC = 0.93). Moreover, AFP-negative LC patients (93 %) were successfully predicted by the LC diagnostic model. Furthermore, the MLC triage model, composed of Asn432 G1/G2, Asn432 G3F/G3FS, Asn630 G2/G2S, Asn630 G2S2/G2NS2, and Asn630 G3FS/G3FS2, yielded an AUC of 0.98 between PLC and MLC. Conclusions STF N -glycosylation is a potential biomarker for the accurate classification of different LDs.
研究领域:
医学研究
·
分子生物学
·
临床诊断
✓ 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）