The pandemic of novel coronavirus 2 (SARS-CoV-2) has made global chaos for normal human living. Despite common COVID-19 symptoms, variability in clinical phenotypes was reported worldwide. Reports on SARS-CoV-2 suggest causing neurological manifestation. In addition, the susceptibility of SARS-CoV-2 in patients with neurodegenerative diseases and its complexity are largely unclear. Here, we aimed to demonstrate the possible transport of exosome from SARS-CoV-2–infected lungs to the brain regions associated with neurodegenerative diseases using multiple transcriptome datasets of SARS-CoV-2–infected lungs, RNA profiles from lung exosome, and gene expression profiles of the human brain. Upon transport, the transcription factors localized in the exosome regulate genes at lateral substantia nigra, medial substantia nigra, and superior frontal gyrus regions of Parkinson’s disease (PD) and frontal cortex, hippocampus, and temporal cortex of Alzheimer’s disease (AD). On SARS-CoV-2 infection, BCL3, JUND, MXD1, IRF2, IRF9, and STAT1 transcription factors in the exosomes influence the neuronal gene regulatory network and accelerate neurodegeneration. STAT1 transcription factor regulates 64 PD genes at lateral substantia nigra, 65 at superior frontal gyrus, and 19 at medial substantia nigra. Similarly, in AD, STAT1 regulates 74 AD genes at the temporal cortex, 40 genes at the hippocampus, and 16 genes at the frontal cortex. We further demonstrate that dysregulated neuronal genes showed involvement in immune response, signal transduction, apoptosis, and stress response process. In conclusion, SARS-CoV-2 may dysregulate neuronal gene regulatory network through exosomes that attenuate disease severity of neurodegeneration. Supplementary Information The online version contains supplementary material available at 10.1007/s12035-021-02485-9.
Biomaterials-based three-dimensional scaffolds are being extensively investigated in bone tissue engineering. A potential scaffold should be osteoconductive, osteoinductive, and osteogenic for enhanced bone formation. In this study, a three-dimensional porous polycapro-lactone (PCL) scaffold was engineered for prolonged release of resveratrol. Resveratrol-loaded albumin nanoparticles (RNP) were synthesized and entrapped into a PCL scaffold to form PCL-RNP by a solvent casting and leaching method. An X-ray diffraction study of RNP and PCL-RNP showed that resveratrol underwent amorphization, which is highly desired in drug delivery. Furthermore, Fourier transform infrared spectroscopy indicates that resveratrol was not chemically modified during the entrapment process. Release of resveratrol from PCL-RNP was sustained, with a cumulative release of 64% at the end of day 12. The scaffold was evaluated for its bone-forming potential in vitro using human bone marrow-derived mesenchymal stem cells for 16 days. Alkaline phosphatase activity assayed on days 8 and 12 showed a significant increase in activity (1.6-fold and 1.4-fold, respectively) induced by PCL-RNP compared with the PCL scaffold (the positive control). Moreover, von Kossa staining for calcium deposits on day 16 showed increased mineralization in PCL-RNP. These results suggest PCL-RNP significantly improves mineralization due to its controlled and prolonged release of resveratrol, thereby increasing the therapeutic potential in bone tissue engineering.
The fused-deposition modeling (FDM) process is carried out at an elevated temperature, preventing the addition of biological factors, drugs, bioactive compounds, etc, during fabrication. To overcome this disadvantage, a 3D interlinked porous polylactic acid (PLA) scaffold was fabricated by FDM, followed by the embedding of a polycaprolactone (PCL) scaffold into the pores of the PLA at room temperature, yielding a PLA-PCL scaffold. In addition, PLA-PCL scaffolds with nanohydroxyapatite (PLA-PCL-nHAP) and multiwalled carbon nanotubes (PLA-PCL-MWCNT) were also fabricated. Here, the FDM-fabricated PLA scaffold functions as the structural component, whereas the embedded PCL scaffold acts as the functional component, which provides a the ability to functionalize the scaffolds with the desired chemical or biological materials. The embedding process is straightforward, cost effective, and does not require sophistication. A mechanical characterization of the scaffolds suggests that the Young’s modulus of the PLA-PCL scaffold (16.02 MPa) was higher than that of the FDM-fabricated PLA (9.98 MPa) scaffold, by virtue of embedded PCL matrix. In addition, finite element analysis showed that the von Mises stress on a mandible with scaffolds was 4.04 MPa, whereas for a mandible with a defect, it was 6.7 MPa, confirming the stress distribution efficiency and mechanical stability of these scaffolds. Furthermore, field emission-scanning electron microscope analysis implied the presence of interlinked porous structures with pore diameters of 50 µm to 300 µm. X-ray diffraction results revealed an increased crystallinity (%) in the embedded models (PLA-PCL, PLA-PCL-nHAP and PLA-PCL-MWCNT), compared to a PLA printed scaffold. Additionally, Raman analysis revealed that the embedding process did not cause chemical alterations in the polymeric chains. In vitro analysis with human osteoblasts demonstrated the osteoconductive nature of the scaffold, which supported mineralization. In brief, the advantage of our model is that it helps to overcome the difficulties of manufacturing a filament with the desired additives for FDM, and offers the ability to incorporate the desired concentrations of heat-labile bioactive molecules during the embedding process at ambient temperatures.
This study presents the design, development, and optimization of multifunctional Doxorubicin (Dox)-loaded Indocyanine Green (ICG) proniosomal gel-derived niosomes, using Design of Experiments (23 factorial model). Herein, the multifunctional proniosomal gel was prepared using the coacervation phase separation technique, which on hydration forms niosomes. The effect of formulation variables on various responses including Zeta potential, Vesicle size, entrapment efficiency of Dox, entrapment efficiency of ICG, Invitro drug release at 72nd hour, and NIR hyperthermia temperature were studied using statistical models. On the basis of the high desirability factor, optimized formulation variables were identified and validated with the experimental results. Further, the chemical nature, vesicle morphology, surface charge, and vesicle size of optimized proniosomal gel-derived niosomes were evaluated. In addition, the effect of free ICG and bound ICG on NIR hyperthermia efficiency has been investigated to demonstrate the heating rate and stability of ICG in the aqueous environment and increased temperature conditions. The drug release and kinetic studies revealed a controlled biphasic release profile with complex mechanisms of drug transport for optimized proniosomal gel-derived niosomes. The potential cytotoxic effect of the optimised formulation was also demonstrated invitro using HeLa cell lines.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.