Emerging Roles for MFG‐E8 in Synapse Elimination

Journal of Neurochemistry, Journal Year: 2025, Volume and Issue: 169(2)

Published: Feb. 1, 2025

Synapse elimination is an essential process in the healthy nervous system and dysregulated many neuropathologies. Yet, underlying molecular mechanisms under what conditions they occur remain unclear. MFG-E8 a secreted glycoprotein well known to act as opsonin, tagging stressed dying cells for engulfment by phagocytes. Opsonization of debris microglial phagocytosis CNS established, its role astrocytic phagocytosis, trogocytosis-like synapses beginning be explored. However, MFG-E8's function other tissues highly diverse, evidence suggests that on synapse particular may more complex varied than opsonization. In this review, we outline documented direct indirect effects elimination, while also proposing potential roles explored further, particular, cytoskeletal reorganization neurites glia leading various mechanisms. Finally, demonstrate need several open questions answered-chiefly, might MFG-E8-mediated favor mechanisms, when activity dysregulated, increasing unwanted neurotoxicity?

Language: Английский

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Glycan‐Anchored Fluorescence Labeling of Milk‐Derived Extracellular Vesicles for Investigating Their Cellular Uptake and Intracellular Fate

Small Methods, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Abstract Milk‐derived extracellular vesicles (mEVs) are promising therapeutic delivery platforms due to their natural bioactivity, biocompatibility, and ability cross biological barriers. However, analyzing cellular uptake trafficking is limited by existing fluorescent labeling methods, which often cause dye leakage disrupt vesicle integrity. Here, a glycan‐anchored fluorescence strategy for mEVs developed, involving periodate oxidation of surface sialic acids followed aniline‐catalyzed ligation hydrazide‐functionalized fluorophores. Nano‐flow cytometry characterization confirmed ≈100% efficiency without compromising integrity or behavior. This approach enabled quantitative analysis internalization, identifying clathrin‐mediated endocytosis macropinocytosis as the primary pathways confirming mEVs’ capacity lysosomal escape. Comparative analyses showed that traditional lipophilic dyes induced aggregation, leakage, transfer, potentially misrepresenting Additionally, co‐labeling with fluorophores FITC‐conjugated paclitaxel real‐time tracking drug delivery, revealing burst release from lysosomes led significant cytotoxicity. Overall, allows precise intracellular fate, paving way further research application in targeted delivery.

Language: Английский

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Urinary extracellular vesicle N-glycomics identifies diagnostic glycosignatures for bladder cancer

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 7, 2025

Bladder cancer (BC) is the most common urologic malignancy, facing enormous diagnostic challenges. Urinary extracellular vesicles (EVs) are promising source for developing markers bladder because of direct contact between urine and bladder. This study pioneers urinary EV N-glycomics diagnosis. We have generated a comprehensive N-glycome landscape EVs through high-throughput analysis, identifying total 252 N-glycans from 333 individuals. In patients, exhibit decreased fucosylation increased sialylation level. An Eight N-glycan model demonstrates strong performance in both validation cohorts, achieving ROC AUC values 0.88 0.86, respectively. Furthermore, this successfully differentiates non-muscle invasive (NMIBC) muscle-invasive (MIBC) healthy individuals, underscoring model's superiority. Moreover, N-glycoproteomic analysis reveals that glycoproteins carrying cancer-associated signatures closely associated with immune activities. The comparative their cells indicate glycosylation profiles do not completely match backgrounds cells. summary, our establishes as non-invasive BC screening tool provide framework glycan biomarker discovery across cancers. diagnosis lacks biomarkers. Here, authors discover vesicle (EV) distinguish patients controls, paving way EV-based liquid biopsy.

Language: Английский

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Sialyl Lewis X decorated integrin α3 on small extracellular vesicles promotes metastasis of bladder cancer via enhancing vascular permeability

Angiogenesis, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 2, 2024

Language: Английский

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SLeX decorated integrin α3 on sEVs promotes metastasis of bladder cancer via enhancing vascular permeability

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: May 20, 2024

The permeability of blood vessels plays a crucial role in the spread cancer cells, leading to their metastasis at distant sites. Small extracellular vesicles (sEVs) contribute various cancers by crossing vessel wall. However, abnormal glycoconjugates on sEVs tumor is unknown. Our study found elevated levels fucosyltransferase VII and its product sialyl Lewis X (sLeX) muscle-invasive bladder (BLCA), high sLeX can promote growth invasion BLCA cells. Further revealed that was enriched originating from BLCA. sLeX-decorated increased disrupting tight junctions human umbilical vein endothelial cells (HUVECs). Using glycoproteomics approach, we identified integrin α3 (ITGA3) as sLeX-bearing glycoprotein sEVs. Mechanically, modification stabilized ITGA3 inhibiting degradation lysosomes. carrying sLeX-modified be effectively internalized HUVECs, decreased expression junction protein. In contrast, silencing restored protein reduced MAPK pathway. Moreover, sLeX-modification Asn 265 HUVECs promoted occludin dephosphorylation Ser/Thr residues, followed inducing importin α1-mediated nuclear translocation resulting destroyed junction. findings suggest potential strategy for formation metastatic microenvironment preventing malignant cancer.

Language: Английский

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Salivary adenoid cystic carcinoma-derived α2,6-sialylated extracellular vesicles increase vascular permeability by triggering ER-stress in endothelial cells and promote lung metastasis

Cancer Letters, Journal Year: 2024, Volume and Issue: unknown, P. 217407 - 217407

Published: Dec. 1, 2024

Language: Английский

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