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Chitosan is a natural copolymer derived from the deacetylation of chitin. Because of its specific physicochemical properties, chitosan is a perfect material to be used in bioengineering and biomedicine. In this study, we demonstrated how chitosan is able to affect the lipid order and organisation in biomimetic membranes. We formed large unilamellar vesicles (LUVs) composed of different lipids and their mixtures mimicking the lipid architecture of mammalian plasma membranes. Lipid order was probed by Laurdan spectroscopy measurements at physiological temperature. We studied LUVs composed of egg phosphatidylcholine (ePC) exhibiting lipid bilayer in liquid-disordered phase (Ld), egg sphingomyelin (eSM)/cholesterol (Chol) in liquid-ordered phase (Lo), and ePC/eSM/Chol mixtures representing Ld/Lo phase coexistence. The ternary mixture compositions mimic the plasma membrane organisation and formation of raft-like domains with different sizes. Membrane rafts are known to be involved in crucial cellular physiological events in health and disease. LUVs were treated by increasing chitosan concentration and lipid order was assessed by Laurdan fluorescence spectroscopy. The interaction of chitosan with lipid membranes induces an increase in the lipid order independently of the lipid phase state. The highest increase in the lipid order was observed for the Ld phases, whereas, the lowest one was detected for the Lo phase. We suggested molecular mechanisms of interaction of chitosan with the main lipid classes and their phase state. [ABSTRACT FROM AUTHOR]

Zic family member ZIC4 is a transcription factor that has been shown to be silenced in several cancers. However, understanding the regulation and function of ZIC4 in pediatric choroid plexus tumors (CPTs) remained limited. This study employed data mining and bioinformatics analysis to investigate the DNA methylation status of ZIC4 in CPTs and its correlation with patient survival. Our results unveiled ZIC4 methylation as a segregating factor, dividing CPT cohorts into two clusters, with hyper-methylation linked to adverse prognosis. Hyper-methylation of ZIC4 was confirmed in a choroid plexus carcinoma-derived cell line (CCHE-45) by bisulfite sequencing. Furthermore, our study demonstrated that demethylating agent and a histone methyltransferase inhibitor could reverse ZIC4 silencing. RNA sequencing and proteomic analysis showed that ZIC4 over-expression influenced genes and proteins involved in immune response, antigen processing and presentation, endoplasmic reticulum stress, and metabolism. Functionally, re-expressing ZIC4 negatively impacted cell proliferation and migration. Ultimately, these findings underscore ZIC4 hyper-methylation as a prognostic marker in CPTs and shed light on potential mechanisms underlying its tumor suppressor role in CPC. This insight paves the way for novel therapeutic targets in treating aggressive CPTs., (© 2024. The Author(s).)