CARBOHYDRATE POLYMERS
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2023
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IF 11.2
Zhenhua Li,Xiaoqin Wang,Xiaoli Deng,Jiansen Song,Tong Yang,Yujie Liao,Guiping Gong,Linjuan Huang,Yu Lu,Zhongfu Wang
Glycosphingolipids (GSLs) in human milk regulate the immune system, support intestinal maturation, and prevent gut pathogens. The structural complexity and low abundance of GSLs limits their systematic analysis. Here, we coupled the use of monosialoganglioside 1–2-amino-N-(2-aminoethyl) benzamide (GM1-AEAB) derivatives as internal standards with HILIC-MS/MS to qualitatively and quantitatively compare GSLs in human, bovine, and goat milk. One neutral glycosphingolipid (GB) and 33 gangliosides were found in human milk, of which 22 were newly detected and three were fucosylated. Five GB and 26 gangliosides were identified in bovine milk , of which 21 were newly discovered. Four GB and 33 gangliosides were detected in goat milk, 23 of them newly reported. GM1 was the main GSL in human milk; whereas disialoganglioside 3 (GD3) and monosialogangloside 3 (GM3) were dominant in bovine and goat milk, respectively; N -acetylneuraminic acid (Neu5Ac) was detected in >88 % of GSLs in bovine and goat milk. N -hydroxyacetylneuraminic acid (Neu5Gc)-modified GSLs were 3.5 times more abundant in goat than in bovine milk; whereas GSLs modified with both Neu5Ac and Neu5Gc were 3 times more abundant in bovine than in goat milk. Given the health benefits of different GSLs, these results will facilitate the development of custom-designed human milk-based infant formula.
研究领域:
营养学
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生物化学
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代谢组学
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DOI
PubMed
高影响因子
TALANTA
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2023
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IF 6.1
Qi Zhang,Yan Li,Ping Sui,Xue-Heng Sun,Yufei Gao,Chun-Yan Wang
Aging and neurodegenerative disease are accompanied by lipid perturbations in the brain. Understanding the changes in the contents and functional activity of lipids remains a challenge not only because of the many areas in which lipids perform bioactivities but also because of the technical limitations in identifying lipids and their metabolites. In the present study, we aimed to evaluate how brain lipids are altered in Alzheimer's disease (AD)-like pathology by using mass spectrometry imaging (MSI). The spatial distributions and relative abundances of lipids in the brains were compared between APP/PS1 mice and their age-matched wild-type (WT) mice by matrix-assisted laser desorption ionization (MALDI) MSI assays. The comparisons were correlated with the analysis using a spectrophotometric method to determine the relative contents of sulfatides in different brain regions. Significant changes of brain lipids between APP/PS1 and WT mice were identified: eight sulfoglycosphingolipid species, namely, sulfatides/sulfated hexosyl ceramides (ShexCer) and two glycerophosphoinositol (GroPIn) species, PI 36:4 and PI 38:4. The declines in the spatial distributions of these ShexCer and GroPIn species in the APP/PS1 mice brains were associated with learning- and memory-related brain regions. Compared with young WT mice, aged WT mice showed significant decreases in the levels of these ShexCer and GroPIn species. Our results provide technical clues for assessing the impact of brain lipid metabolism on the senescent and neurodegenerative brain. The decline in sulfatides and GroPIns may be crucial markers during brain senescence and AD pathology. Appropriate lipid complementation might be important potentials as a therapeutic strategy for AD.
研究领域:
神经科学
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分子生物学
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医学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2025
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IF 12.5
Qingchi Wang,Yuhang Luo,Yi Xin,Yuanxiang Jin,Guiling Yang,Quanbin Zhang,Zhengshun Wen
Marine polysaccharides have emerged as promising immunomodulators. However, conventional analytical approaches have failed to elucidate their activation mechanisms from a global perspective. In this study, we isolated a highly branched glycogen (GCEP2a) from eggs of the sea urchin Glyptocidaris crenularis . Structural characterization revealed that GCEP2a possesses a backbone composed of →4)-α-D-Glc p -(1 → residues, with one C6-branch per five residues, and a molecular weight of 8.06 × 10 3 kDa. Employing nascent-proteome bioorthogonal non-canonical amino acid tagging (BONCAT) enrichment followed by DIA-FAIMS, we unraveled the global immunostimulatory mechanisms of GCEP2a in RAW264.7 macrophages. This advanced approach enabled dynamic profiling of nascent protein synthesis, uncovering a multi-receptor and multi-pathway regulatory network. Specifically, GCEP2a activates signaling consistent with engagement of the toll-like receptors (TLRs), C-type lectin receptors (CLRs), and RIG-I-like receptors (RLRs), thereby triggering downstream signaling cascades including the NF-κB, MAPK, and PI3K-AKT pathways. Additionally, GCEP2a downregulates the biosynthesis of lacto- and neolacto-series glycosphingolipids, indicating metabolic reprogramming associated with M1 polarization. These findings not only suggest that GCEP2a exhibits potential as an immune adjuvant, but also provide initial insights into the application of BONCAT-based nascent proteomics for investigating the multi-modal immunostimulatory mechanisms of marine polysaccharides.
研究领域:
免疫学
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海洋生物化学
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糖生物学
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蛋白质组学
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分子免疫学
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细胞信号转导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROBIOLOGY OF DISEASE
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2023
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IF 6.1
Qiaoying Huang,Congmin Chen,Weizhao Chen,Chaoyu Cai,Hailin Xing,Junyu Li,Mingtao Li,Shanshan Ma
Parkinson's disease (PD) is the most common neurodegenerative movement disorder, characterized by the progressive loss of nigrostriatal dopaminergic neurons (DANs), involving the dysregulation of both neurons and glial cells. Cell type- and region-specific gene expression profiles can provide an effective source for revealing the mechanisms of PD. In this study, we adopted the RiboTag approach to obtain cell type (DAN, microglia, astrocytes)- and brain region (substantia nigra, caudate-putamen)-specific translatomes at an early stage in an MPTP-induced mouse model of PD. Through DAN-specific translatome analysis, the glycosphingolipid biosynthetic process was identified as a significantly downregulated pathway in the MPTP-treated mice. ST8Sia6, a key downregulated gene related to glycosphingolipid biosynthesis, was confirmed to be downregulated in nigral DANs from postmortem brains of patients with PD. Specific expression of ST8Sia6 in DANs exerts anti-inflammatory and neuroprotective effects in MPTP-treated mice. Through cell type (microglia vs. astrocyte) and brain region (substantia nigra vs. caudate-putamen) comparisons, nigral microglia showed the most intense immune responses. Microglia and astrocytes in the substantia nigra showed similar levels of activation in interferon-related pathways and interferon gamma (IFNG) was identified as the top upstream regulator in both cell types. This work highlights that the glycosphingolipid metabolism pathway in the DAN is involved in neuroinflammation and neurodegeneration in an MPTP mouse model of PD and provides a new data source for elucidating the pathogenesis of PD.
研究领域:
神经科学
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分子生物学
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神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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