The functionalization of chitosans is an emerging research area in the design of solutions for a wide range of biomedical applications. In particular, the modification of chitosans to incorporate sulfate groups has generated great interest since they show structural similarity to heparin and heparan sulfates. Most of the biomedical applications of heparan sulfates are derived from their ability to bind different growth factors and other proteins, as through these interactions they can modulate the cellular response. This review aims to summarize the most recent advances in the synthesis, and structural and physicochemical characterization of heparanized chitosan, a remarkably interesting family of polysaccharides that have demonstrated the ability to mimic heparan sulfates as ligands for different proteins, thereby exerting their biological activity by mimicking the function of these glycosaminoglycans.
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http://dx.doi.org/10.1039/d1mh00728a | DOI Listing |
Elife
December 2024
Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland.
Because of high mutation rates, viruses constantly adapt to new environments. When propagated in cell lines, certain viruses acquire positively charged amino acids on their surface proteins, enabling them to utilize negatively charged heparan sulfate (HS) as an attachment receptor. In this study, we used enterovirus A71 (EV-A71) as model and demonstrated that unlike the parental MP4 variant, the cell-adapted strong HS-binder MP4-97R/167G does not require acidification for uncoating and releases its genome in the neutral or weakly acidic environment of early endosomes.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Science Center San Antonio, San Antonio, Texas, USA.
Introduction: Alzheimer's disease (AD) and other tauopathies are characterized by intracellular aggregates of microtubule-associated protein tau that are actively released and promote proteopathic spread. Microglia engulf pathological proteins, but how they endocytose tau is unknown.
Methods: We measured endocytosis of different tau species by microglia after pharmacological modulation of macropinocytosis or clathrin-mediated endocytosis (CME) or antagonism/genetic depletion of known tau receptors heparan-sulfate proteoglycans (HSPGs) and low-density lipoprotein receptor-related protein 1 (LRP1).
Front Immunol
December 2024
Department of Critical Care Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
Sepsis is a clinical syndrome resulting from the interaction between coagulation, inflammation, immunity and other systems. Coagulation activation is an initial factor for sepsis to develop into multiple organ dysfunction. Therefore, anticoagulant therapy may be beneficial for sepsis patients.
View Article and Find Full Text PDFCell Death Dis
December 2024
Technion Integrated Cancer Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Little attention was given to heparanase 2 (Hpa2) over the last two decades, possibly because it lacks a heparan sulfate (HS)-degrading activity typical of heparanase. Emerging results suggest, nonetheless, that Hpa2 plays a role in human pathologies, including cancer progression where it functions as a tumor suppressor. Here, we examined the role of Hpa2 in cervical carcinoma.
View Article and Find Full Text PDFSci Adv
December 2024
Eye Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Laboratory of Ophthalmology, Zhejiang Provincial Clinical Research Center for Eye Diseases, Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou 310009, P. R. China.
Corneal injury-induced fibrosis occurs because of corneal epithelial basement membrane (EBM) injury and defective regeneration. Corneal fibrosis inhibition and transparency restoration depend on reestablished EBM, where the collagen network provides structural stability and heparan sulfate binds corneal epithelium-derived cytokines to regulate homeostasis. Inspired by this, bioactive hydrogels (Hep@Gel) composed of collagen-derived gelatins and highly anionic heparin were constructed for scarless corneal repair.
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