Inflammation plays a key role in the development of age-related diseases. In Alzheimer's disease, neuronal cell death is attributed to amyloidbeta oligomers that trigger microglial activation. Stem cells have shown promise as therapies for inflammatory diseases- because of their paracrine activity combined with their ability to respond to the inflammatory environment. However, the mechanisms underlying stem cell-promoted neurological recovery are poorly understood. To elucidate these mechanisms, we first primed stem cells with the secretome of lipopolysaccharide- or amyloidbeta-activated microglia. Then, we compared the immunomodulatory effects of extracellular vesicles (EVs) secreted from primed and non-primed stem cells. Our results demonstrate that EVs from primed cells are more effective in inhibiting microglia and astrocyte activation, amyloid deposition, demyelination, memory loss and motor and anxiety-like behavioral dysfunction, compared to EVs from non-primed cells. MicroRNA (miRNA) profiling revealed the upregulation of at least 19 miRNAs on primed-stem cell EVs. The miRNA targets were identified, and KEGG pathway analysis showed that the overexpressed miRNAs target key genes on the toll-like receptor-4 (TLR4) signaling pathway. Overall, our results demonstrate that priming mesenchymal stem cells (MSCs) with the secretome of activated microglia results in the release of miRNAs from EVs with enhanced immune regulatory potential able to fight neuroinflammation.
Emergent Coronaviridae viruses, such as SARS-CoV-1 in 2003, MERS-CoV in 2012, and SARS-CoV-2 (CoV-2) in 2019, have caused millions of deaths. These viruses have added to the existing respiratory infection burden along with respiratory syncytial virus (RSV) and influenza. There are limited therapies for respiratory viruses, with broad-spectrum treatment remaining an unmet need. Since gut fermentation of fiber produces short-chain fatty acids (SCFA) with antiviral potential, developing a fatty acid-based broad-spectrum antiviral was investigated. Molecular docking of fatty acids showed α-linolenic acid (ALA) is likely to interact with CoV-2-S, NL63-CoV-S, and RSV-F, and an ALA-containing liposome interacted with CoV-2 directly, degrading the particle. Furthermore, a combination of ALA and a SCFA-acetate synergistically inhibited CoV2-N expression and significantly reduced viral plaque formation and IL-6 and IL-1β transcript expression in Calu-3 cells, while increasing the expression of IFN-β. A similar effect was also observed in RSV-infected A549 cells. Moreover, mice infected with a murine-adapted SARS-CoV-2 (MA10) and treated with an ALA–liposome encapsulating acetate showed significant reductions in plaque-forming units present in lung tissue and in infection-associated lung inflammation and cytokines. Taken together, these results demonstrate that the ALA liposome-encapsulating acetate can be a promising broad antiviral therapy against respiratory infections.
The burgeoning field of nanotechnology aims to create and deploy nanoscale structures, devices, and systems with novel, size-dependent properties and functions. The nanotechnology revolution has sparked radically new technologies and strategies across all scientific disciplines, with nanotechnology now applied to virtually every area of research and development in the US and globally. NanoFlorida was founded to create a forum for scientific exchange, promote networking among nanoscientists, encourage collaborative research efforts across institutions, forge strong industry-academia partnerships in nanoscience, and showcase the contributions of students and trainees in nanotechnology fields. The 2019 NanoFlorida International Conference expanded this vision to emphasize national and international participation, with a focus on advances made in translating nanotechnology. This review highlights notable research in the areas of engineering especially in optics, photonics and plasmonics and electronics; biomedical devices, nano-biotechnology, nanotherapeutics including both experimental nanotherapies and nanovaccines; nano-diagnostics and -theranostics; nano-enabled drug discovery platforms; tissue engineering, bioprinting, and environmental nanotechnology, as well as challenges and directions for future research.