Background And Objectives: The pathogen inactivation (PI) INTERCEPT Blood System for Red Blood Cells utilises amustaline (S-303) to inactivate a broad range of pathogens in red cell concentrates (RCC). The aim of this study was to investigate the effect on red cell quality of INTERCEPT treatment with and without prion reduction.
Methods/materials: Five pools of five RCC each were prepared. These were split and treated as follows: (i) stored at 2-6 °C for 18 h, (ii) stored at 18-24 °C for 18 h, (iii) PI-treated, (iv) PI-treated then prion reduced and (v) prion reduced then PI-treated. Prior to storage, PI-treated RCC underwent an exchange step to remove S-303 and other breakdown products. Components were tested throughout 35 days of storage for in vitro parameters of red cell quality.
Results: All RCC met specification for volume and haemoglobin content. Haemolysis, microvesicle formation, supernatant potassium and deformability were lower and ATP levels higher in PI-treated units when compared with control units. The effect of prion reduction in addition to PI treatment was minimal in all parameters tested except haemolysis, which was increased in units prion-reduced after being PI-treated.
Conclusion: The PI-treatment process did not increase red cell haemolysis or decrease ATP levels over storage. The lower haemolysis and supernatant potassium levels in treated RCC compared with control RCC were attributed to the exchange step. The effects of combining PI treatment and prion reduction were not more than additive when prion reduction precedes PI treatment.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1111/tme.12298 | DOI Listing |
Introduction: Age-associated depletion in nicotinamide adenine dinucleotide (NAD+) concentrations has been implicated in metabolic, cardiovascular, and neurodegenerative disorders. Supplementation with NAD+ precursors, such as nicotinamide riboside (NR), offers a potential therapeutic avenue against neurodegenerative pathologies in aging, Alzheimer's disease, and related dementias. A crossover, double-blind, randomized placebo (PBO) controlled trial was conducted to test the safety and efficacy of 8 weeks' active treatment with NR (1 g/day) on cognition and plasma AD biomarkers in older adults with subjective cognitive decline and mild cognitive impairment.
View Article and Find Full Text PDFNat Med
January 2025
Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Prion disease is a fatal neurodegenerative disease caused by the misfolding of prion protein (PrP) encoded by the PRNP gene. While there is currently no cure for the disease, depleting PrP in the brain is an established strategy to prevent or stall templated misfolding of PrP. Here we developed in vivo cytosine and adenine base strategies delivered by adeno-associated viruses to permanently modify the PRNP locus to achieve PrP knockdown in the mouse brain.
View Article and Find Full Text PDFBiochemistry
January 2025
Sunita Sanghi Centre of Aging and Neurodegenerative Diseases (SCAN), Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
Aggregation of α-synuclein (α-Syn) and Lewy body (LB) formation are the key pathological events implicated in Parkinson's disease (PD) that spread in a prion-like manner. However, biophysical and structural characteristics of toxic α-Syn species and molecular events that drive early events in the propagation of α-Syn amyloids in a prion-like manner remain elusive. We used a neuronal cell model to demonstrate the size-dependent native biological activities of α-Syn fibril seeds.
View Article and Find Full Text PDFCancer Cell Int
December 2024
Sezione di Farmacologia, Dipartimento di Medicina Interna, Università di Genova, Genova, Italy.
Background: Cellular prion protein (PrP) is a widely expressed membrane-anchored glycoprotein, which has been associated with the development and progression of several types of human malignancies, controlling cancer stem cell activity. However, the different molecular mechanisms regulated by PrP in normal and tumor cells have not been characterized yet.
Methods: To assess the role of PrP in patient-derived glioblastoma stem cell (GSC)-enriched cultures, we generated cell lines in which PrP was either overexpressed or down-regulated and investigated, in 2D and 3D cultures, its role in cell proliferation, migration, and invasion.
PLoS Pathog
September 2024
Department of Physics, Toronto Metropolitan University, Toronto, Canada.
Disease associated pathological aggregates of alpha-synuclein (αSynD) exhibit prion-like spreading in synucleinopathies such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Seed amplification assays (SAAs) such as real-time quaking-induced conversion (RT-QuIC) have shown high diagnostic sensitivity and specificity for detecting proteopathic αSynD seeds in a variety of biospecimens from PD and DLB patients. However, the extent to which relative proteopathic seed concentrations are useful as indices of a patient's disease stage or prognosis remains unresolved.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!