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Toll-like receptor 4 deficiency ameliorates experimental ileitis and enteric neuropathy: Involvement of nitrergic and 5-hydroxytryptaminergic neurotransmission.
Br J Pharmacol
January 2025
Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy.
Background And Purpose: Inflammatory bowel disease (IBD) patients display genetic polymorphisms in toll-like receptor 4 (TLR4) genes, contributing to dysregulate enteric nervous system (ENS) circuits with increased levels of 5-HT and alteration of the neuroimmune crosstalk. In this study, we investigated the impact of TLR4 signalling on mouse ENS dysfunction caused by dextran sulphate sodium (DSS)-induced ileitis.
Experimental Approach: Male C57BL/6J (wild-type [WT]) and TLR4 mice (10 ± 2 weeks old) received 2% DSS in drinking water for 5 days and then were switched to 3-day regular drinking water.
Competitive displacement of lipoprotein lipase from heparan sulfate is orchestrated by a disordered acidic cluster in GPIHBP1.
J Lipid Res
January 2025
Finsen Laboratory, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark. Electronic address:
Movement of lipoprotein lipase (LPL) from myocytes or adipocytes to the capillary lumen is essential for intravascular lipolysis and plasma triglyceride homeostasis-low LPL activity in the capillary lumen causes hypertriglyceridemia. The trans-endothelial transport of LPL depends on ionic interactions with GPIHBP1's intrinsically disordered N-terminal tail, which harbors two acidic clusters at positions 5-12 and 19-30. This polyanionic tail provides a molecular switch that controls LPL detachment from heparan sulfate proteoglycans (HSPGs) by competitive displacement.
View Article and Find Full Text PDFTherapies against hematological malignancies using chimeric antigen receptors (CAR)-T cells have shown great potential; however, therapeutic success in solid tumors has been constrained due to limited tumor trafficking and infiltration, as well as the scarcity of cancer-specific solid tumor antigens. Therefore, the enrichment of tumor-antigen specific CAR-T cells in the desired region is critical for improving therapy efficacy and reducing systemic on-target/off-tumor side effects. Here, we functionalized human CAR-T cells with superparamagnetic iron oxide nanoparticles (SPIONs), making them magnetically controllable for site-directed targeting.
View Article and Find Full Text PDFOptical Detection of Proteins Using Microgel-Stabilized Pickering Liquid Crystal-in-Water Emulsions.
Langmuir
January 2025
Department of Chemistry and Centre for Advanced Studies in Chemistry, Panjab University, Chandigarh 160014, India.
Herein, we present a novel liquid crystal (LC)-based sensing platform utilizing microgel-stabilized Pickering LC droplets dispersed in water for simple and label-free detection of proteins in an aqueous environment. This could be achieved by tailoring the surface of 4-cyano-4'-pentylbiphenyl (5CB) LC droplets dispersed in aqueous medium through the interfacial adsorption of poly(-isopropylacrylamide) (PNIPAM) microgel particles, followed by the introduction of model surfactants, such as anionic sodium dodecyl sulfate and cationic dodecyltrimethylammonium bromide. These surfactant/microgel complex-coated LC droplets underwent a configurational transition from radial-to-bipolar under a polarized optical microscope, upon exposure to model proteins, namely bovine serum albumin and lysozyme.
View Article and Find Full Text PDFEvolution of SARS-CoV-2 spike trimers towards optimized heparan sulfate cross-linking and inter-chain mobility.
Sci Rep
December 2024
Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Waldeyerstrasse 15, D-48149, Münster, Germany.
The heparan sulfate (HS)-rich extracellular matrix (ECM) serves as an initial interaction site for the homotrimeric spike (S) protein of SARS-CoV-2 to facilitate subsequent docking to angiotensin-converting enzyme 2 (ACE2) receptors and cellular infection. More recent variants, notably Omicron, have evolved by swapping several amino acids to positively charged residues to enhance the interaction of the S-protein trimer with the negatively charged HS. However, these enhanced interactions may reduce Omicron's ability to move through the HS-rich ECM to effectively find ACE2 receptors and infect cells, raising the question of how to mechanistically explain HS-associated viral movement.
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