The corona virus (SARS-CoV-2) pandemic and the resulting long-term neurological complications in patients, known as long COVID, have renewed interest in the correlation between viral infections and neurodegenerative brain disorders. While many viruses can reach the central nervous system (CNS) causing acute or chronic infections (such as herpes simplex virus 1, HSV-1), the lack of a clear mechanistic link between viruses and protein aggregation into amyloids, a characteristic of several neurodegenerative diseases, has rendered such a connection elusive. Recently, we showed that viruses can induce aggregation of purified amyloidogenic proteins via the direct physicochemical mechanism of heterogeneous nucleation (HEN).
View Article and Find Full Text PDFLipid nanoparticles (LNPs) have successfully entered the clinic for the delivery of mRNA- and siRNA-based therapeutics, most recently as vaccines for COVID-19. Nevertheless, there is a lack of understanding regarding their in vivo behavior, in particular cell targeting. Part of this LNP tropism is based on the adherence of endogenous protein to the particle surface.
View Article and Find Full Text PDFAim: This prospective, randomized, double-blind clinical trial investigated the impact of diclofenac potassium, prednisolone, and placebo as oral premedication on postendodontic pain and pulpal interleukin (IL)-8 expression in patients with irreversible pulpitis.
Methods: Thirty-six patients undergoing conventional endodontic treatment were assigned into one of 3 groups (n = 12). Pulpal blood samples were taken after access cavity preparation and stored until they were analyzed using enzyme-linked immunosorbent asssay for quantification of IL-8.
We introduce a method, single-particle profiler, that provides single-particle information on the content and biophysical properties of thousands of particles in the size range 5-200 nm. We use our single-particle profiler to measure the messenger RNA encapsulation efficiency of lipid nanoparticles, the viral binding efficiencies of different nanobodies, and the biophysical heterogeneity of liposomes, lipoproteins, exosomes and viruses.
View Article and Find Full Text PDFThe toxic proteinopathy paradigm has defined neurodegenerative disorders for over a century. This gain-of-function (GOF) framework posited that proteins become toxic when turned into amyloids (pathology), predicting that lowering its levels would translate into clinical benefits. Genetic observations used to support a GOF framework are equally compatible with a loss-of-function (LOF) framework, as the soluble pool of proteins rendered unstable by these mutations (e.
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