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The interaction of tPA with NMDAR1 drives neuroinflammation and neurodegeneration in α-synuclein-mediated neurotoxicity.
J Neuroinflammation
January 2025
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
The thrombolytic protease tissue plasminogen activator (tPA) is expressed in the CNS, where it regulates diverse functions including neuronal plasticity, neuroinflammation, and blood-brain-barrier integrity. However, its role in different brain regions such as the substantia nigra (SN) is largely unexplored. In this study, we characterize tPA expression, activity, and localization in the SN using a combination of retrograde tracing and β-galactosidase tPA reporter mice.
View Article and Find Full Text PDFA synthetic cyclic peptide for promoting antigen presentation and immune activation.
NPJ Vaccines
January 2025
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Cyclic peptides are often used as scaffolds for the multivalent presentation of drug molecules due to their structural stability and constrained conformation. We identified a cyclic deca-peptide incorporating lipoamino acids for delivering T helper and B cell epitopes against group A Streptococcus (GAS), eliciting robust humoral immune responses. In this study, we assessed the function-immunogenicity relationship of the multi-component vaccine candidate (referred to as VC-13) to elucidate a mechanism of action.
View Article and Find Full Text PDFIntelligent in-cell electrophysiology: Reconstructing intracellular action potentials using a physics-informed deep learning model trained on nanoelectrode array recordings.
Nat Commun
January 2025
Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, CA, USA.
Intracellular electrophysiology is essential in neuroscience, cardiology, and pharmacology for studying cells' electrical properties. Traditional methods like patch-clamp are precise but low-throughput and invasive. Nanoelectrode Arrays (NEAs) offer a promising alternative by enabling simultaneous intracellular and extracellular action potential (iAP and eAP) recordings with high throughput.
View Article and Find Full Text PDFElevated phosphate levels in CKD - a direct threat for the heart.
Nephrol Dial Transplant
January 2025
Division of Nephrology and Section of Mineral Metabolism, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA.
Elevations in systemic phosphate levels, also called hyperphosphatemia, occur in chronic kidney disease (CKD) and during the normal aging process and are associated with various pathologies, such as cardiovascular injury. Experimental studies suggest that at high serum concentrations, phosphate can induce osteogenic differentiation of vascular smooth muscle cells and contribute to vascular calcification. However, the precise underlying mechanism leading to cardiovascular injury is not well understood.
View Article and Find Full Text PDFUnlocking the power of empagliflozin: Rescuing inflammation in hyperglycaemia- exposed human cardiomyocytes through comprehensive multi-level analysis.
Eur J Heart Fail
January 2025
Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
Aims: Hyperglycaemic conditions increase cardiac stress, a common phenomenon associated with inflammation, aging, and metabolic imbalance. Sodium-glucose cotransporter 2 inhibitors, a class of anti-diabetic drugs, showed to improve cardiovascular functions although their mechanism of action has not yet been fully established. This study investigated the effects of empagliflozin on cardiomyocytes following high glucose exposure, specifically focusing on inflammatory and metabolic responses.
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