A5025902035- Ion Transport and Channel Regulation
- ATP Synthase and ATPases Research
- MicroRNA in disease regulation
- Mitochondrial Function and Pathology
- Ion channel regulation and function
- Advanced Electron Microscopy Techniques and Applications
- Barrier Structure and Function Studies
- RNA Research and Splicing
- Neurogenesis and neuroplasticity mechanisms
- Advanced Fluorescence Microscopy Techniques
- Extracellular vesicles in disease
- Cell Image Analysis Techniques
- Synthesis of β-Lactam Compounds
- Pancreatic function and diabetes
- Cardiac Ischemia and Reperfusion
- Anesthesia and Neurotoxicity Research
- 14-3-3 protein interactions
- Inflammatory mediators and NSAID effects
- Neuroscience and Neural Engineering
- Glycosylation and Glycoproteins Research
- Photoreceptor and optogenetics research
- Neonatal Respiratory Health Research
- Thermal properties of materials
- Nicotinic Acetylcholine Receptors Study
- Escherichia coli research studies
University of Bari Aldo Moro
2007-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2016-2024
Casa Sollievo della Sofferenza
2016-2024
University of Verona
2024
Weatherford College
2024
3-(5-Chlorofuran-2-yl)-5-methyl-4-phenylisoxazole (P6), a known selective cyclooxygenase-1 (COX-1) inhibitor, was used to design new series of 3,4-diarylisoxazoles in order improve its biochemical COX-1 selectivity and antiplatelet efficacy. Structure-activity relationships were studied using human whole blood assays for COX-2 inhibition vitro, results showed that the simultaneous presence 5-methyl (or -CF3), 4-phenyl, 5-chloro(-bromo or -methyl)furan-2-yl groups on isoxazole core essential...
Regulation of water homeostasis is a central feature nervous system pathophysiology. In this context, several lines evidence suggest crucial role for the channel aquaporin-4 (AQP4) and its plasma membrane supramolecular organization as key element. Here, we demonstrate expression in tissues additional isoforms AQP4 characterized by C-terminal extension generated programmed translational readthrough. These extended (AQP4ex) display perivascular polarization dystrophin-dependent pools. AQP4ex...
Abstract Crosstalk mechanisms between pericytes, endothelial cells, and astrocytes preserve integrity function of the blood-brain-barrier (BBB) under physiological conditions. Long intercellular channels allowing transfer small molecules organelles distant cells called tunneling nanotubes (TNT) represent a potential substrate for energy matter exchanges tripartite cellular compartments BBB. However, role TNT across BBB conditions in course dysfunction is unknown. In this work, we analyzed...
Abstract The glial water channel protein aquaporin-4 (AQP4) forms heterotetramers in the plasma membrane made of M23-AQP4 and M1-AQP4 isoforms. isoform ratio controls AQP4 aggregation into supramolecular structures called orthogonal arrays particles (AQP4-OAP). role OAP malignant gliomas is still unclear. In this study, we demonstrate that aggregation/disaggregation influences biology glioma cells. Selective expression OAP-forming (AQP4-OAP) triggered cell shape changes cells associated with...
Abstract Pre-clinical trials have demonstrated the neuroprotective effects of transplanted human neural stem cells (hNSCs) during post-ischemic phase. However, exact mechanism remains unclear. Tunneling nanotubes (TNTs) are long plasma membrane bridges that physically connect distant cells, enabling intercellular transfer mitochondria and contributing to repair processes. Whether hNSCs communicate through TNTs their role in neuroprotection unknown. In this study, non-immortalized hNSC lines...
Abstract Aquaporin‐1 ( AQP 1) is a proangiogenic water channel protein promoting endothelial cell migration. We previously reported that 1 silencing by RNA interference reduces angiogenesis‐dependent primary tumour growth in mouse model of melanoma. In this study, we tested the hypothesis inhibition also affects animal survival and lung nodule formation. Melanoma was induced injecting B16F10 cells into back C57 BL 6J mice. Intratumoural injection si CTRL performed 10 days after implantation....
Neuromyelitis optica (NMO) is characterized by the presence of pathogenic autoantibodies (NMO-IgGs) against supra-molecular assemblies aquaporin-4 (AQP4), known as orthogonal array particles (OAPs). NMO-IgGs have a polyclonal origin and recognize different conformational epitopes involving extracellular AQP4 loops A, C, E. Here we hypothesize pivotal role for transmembrane regions (TMs) in epitope assembly. On basis multialignment analysis, mutagenesis, NMO-IgG binding, cytotoxicity assay,...
Tunneling nanotubes (TNTs) are long F-actin-positive plasma membrane bridges connecting distant cells, allowing the intercellular transfer of cellular cargoes, and found to be involved in glioblastoma (GBM) crosstalk. Glial fibrillary acid protein (GFAP) is a key intermediate filament glial cells cytoskeleton remodeling linked GBM progression. Whether GFAP plays role TNT structure function unknown. Here, analyzing F-actin localization by laser-scan confocal microscopy followed 3D...
Abstract In astrocytes, unknown mechanisms regulate the expression of M1 and M23 isoforms water channel aquaporin‐4 (M1‐AQP4 M23‐AQP4). The ratio between these two controls AQP4 assembly state in plasma membrane known as orthogonal arrays particles (OAPs). To give new insights into mechanisms, here, we explore regulation spinal cord a CRISPR/Cas9 M23‐null mouse model (M23‐null). OAP assembly, perivascular localization M1‐AQP4 protein were drastically reduced. heterozygous, was proportionally...
Extracellular vesicles (EVs) are membrane-enclosed particles released systemically by all cells, including tumours. Tumour EVs have been shown to manipulate their local environments as well distal targets sustain the tumour in a variety of tumours, glioblastoma (GBM). We previously demonstrated dual role glial water channel aquaporin-4 (AQP4) protein glioma progression or suppression depending on its aggregation state. However, possible communication mechanisms microenvironment malignant...
K+ channels do play a role in cell shape changes observed during proliferation and apoptosis. Research suggested that the dynamics of aggregation Aquaporin-4 (AQP4) into AQP4-OAPs isoforms can trigger malignant glioma cells. Here, we investigated relationship between AQP4 some U87 line. The cells transfected with human M1-AQP4 M23-AQP4 were for morphology, gene expression KCNJ8, KCNJ11, ABCC8, ABCC9, KCNMA1, Cyclin genes by RT-PCR, recording whole-cell ions currents patch-clamp experiments....
<title>Abstract</title> Pre-clinical trials have demonstrated the neuroprotective effects of transplanted human neural stem cells (hNSCs) during post-ischemic phase. However, exact mechanism remains unclear. Tunneling nanotubes (TNTs) are long plasma membrane bridges that physically connect distant cells, enabling intercellular transfer mitochondria, contributing to repair processes. Whether hNSCs communicate through TNTs and their role in neuroprotection remain unknown. In this study,...
Abstract The small Rho GTP‐binding proteins are important cell morphology, function, and apoptosis regulators. Unlike other proteins, RhoB can be subjected to either geranylgeranylation (RhoB‐GG) or farnesylation (RhoB‐F), making that the only target of farnesyltransferase inhibitor (FTI). Fluorescence resonance energy transfer experiments revealed is activated by hyperosmolarity. By contrast, hyposmolarity did not affect activity. Interestingly, treatment with inhibitor‐277 (FTI‐277)...
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<title>Abstract</title> Dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene, is rate-limiting enzyme governing fluoropyrimidines (FPs) catabolism. Impaired or abrogated DPD activity often caused genetic polymorphisms in gene that are well-validated predictors of FP-associated toxicity. Presently, four variants included FP genetic-based dosing guidelines. Patient safety treatment has been significantly improved pre-emptive screening for genotype and dose adjustments individuals...
The CNS plasma-membrane water channel aquaporin-4 (AQP4) is expressed as two major isoforms able to aggregate into supramolecular assemblies known 'orthogonal arrays of particles' (OAPs). OAP subnanometric features are largely unknown mainly because a method for the expression, isolation, and crystallization integral human OAPs has not been developed. Here, OAP-forming isoform M23-AQP4 was in insect mammalian cell lines AQP4 evaluated. Native size exclusion chromatography employed isolate...
ABSTRACT Crosstalk mechanisms between pericytes, endothelial cells, and astrocytes preserve integrity function of the blood-brain-barrier (BBB) under physiological conditions. Long intercellular channels allowing transfer small molecules organelles distant cells called tunneling nanotubes (TNT) represent a potential substrate for energy matter exchanges tripartite cellular compartments BBB. However, role TNT across BBB conditions in course dysfunction is unknown. In this work, we analyzed...
<div>Abstract<p>The glial water channel protein aquaporin-4 (AQP4) forms heterotetramers in the plasma membrane made of M23-AQP4 and M1-AQP4 isoforms. The isoform ratio controls AQP4 aggregation into supramolecular structures called orthogonal arrays particles (AQP4-OAP). role OAP malignant gliomas is still unclear. In this study, we demonstrate that aggregation/disaggregation influences biology glioma cells. Selective expression OAP-forming (AQP4-OAP) triggered cell shape...
<p>Supplementary Figure s1. M23-AQP4 C-terminus analysis for the ability to induce morphological changes in glioma cells. a) Schematic representation of untagged and mCherry-tagged isoforms used (b). b) Immuno fluorescence U87 U251 cells transfected with tagged isoforms. AQP4 (red) Phallodin (green) visualize F-actin. No were induced by when mCherry was used. Scale bar 50 µm. c) Quantification alterations observed experiments described (a). The histobar shows percentage altered...