Chondroitin sulfate proteoglycans (CSPGs) have been proven to inhibit morphological maturation of oligodendrocytes as well as their myelination capabilities. Yet, it remained unclear, whether CSPGs and/or their respective chondroitin sulfate glycosaminoglycan (CS-GAG) side chains also regulate the oligodendrocyte lineage progression. Here, we initially show that CS-GAGs detected by the monoclonal antibody 473HD are expressed by primary rat NG2-positive oligodendrocyte precursor cells (OPCs) and O4-positive immature oligodendrocytes. CS-GAGs become down-regulated with ongoing oligodendrocyte differentiation. Enzymatic removal of the CS-GAG chains by the bacterial enzyme Chondroitinase ABC (ChABC) promoted spontaneous differentiation of proliferating rat OPCs toward O4-positive immature oligodendrocytes. Upon forced differentiation, the enzymatic removal of the CS-GAGs accelerated oligodendrocyte differentiation toward both MBP-positive and membrane forming oligodendrocytes. These processes were attenuated on enriched CSPG fractions, mainly consisting of Phosphacan/RPTPβ/ζ and to less extent of Brevican and NG2. To qualify CS-GAGs as universal regulators of oligodendrocyte biology, we finally tested the effect of CS-GAG removal on OPCs from different sources such as mouse cortical oligospheres, mouse spinal cord neurospheres, and most importantly human-induced pluripotent stem cell-derived radial glia-like neural precursor cells. For all culture systems used, we observed a similar inhibitory effect of CS-GAGs on oligodendrocyte differentiation. In conclusion, this study clearly suggests an important fundamental principle for complex CS-GAGs to regulate the oligodendrocyte lineage progression. Moreover, the use of ChABC in order to promote oligodendrocyte differentiation toward myelin gene expressing cells might be an applicable therapeutic option to enhance white matter repair.
RA is a multifactorial autoimmune inflammatory disease characterized by synovitis, bone destruction and joint dysfunction that leads to shortening of lifespan and increased mortality rates. Currently available treatments of RA, by controlling various symptoms, only delay disease progression and have their own side effects. Consequently, there is the need for a novel therapeutic strategy that offers a more sustainable and biocompatible solution. Nanomedicine is a modern branch of nanobiotechnology that provides targeted therapy to inflamed rheumatic joints and thus prevents unwanted off-target side effects. This review highlights various nanotheranostic and nanotherapeutic strategies that are currently being used for the treatment of RA.
An era of SARS‐COVID‐19 outbreak with a high contagious percentage around the globe has been the subject of multi‐agency research aimed at generating vaccines for active immunization. Scientists across the world are joining hands for advanced tie‐ups between medical start‐ups and pharmaceutical industries for devices and vaccines development to hinder the progress of this outbreak. Moreover, the questions that need to be answered are how to improve the effectiveness and efficacy of vaccines with reduced side effects and the required doses of vaccines for enhanced surveillance. In this review article, we have discussed the effectiveness and efficacy of different Covid‐19 vaccines.
Purpose: The existing treatment modalities for rheumatoid arthritis are less effective and safe, therefore it is essential to develop new treatments that particularly target the inflamed joints with decreased off-target side-effects. The current study proposes a nanoparticle-based therapeutic approach to target the anti-oxidant defense system of arthritic Balb/c mice. Methods: Biogenic selenium nanoparticles (SeNPs) were synthesized by using Trachyspermum ammi seed extract and were evaluated for their toxicological, as well as their therapeutic potential in collagen-induced arthritic mice. Results: The tested doses of SeNPs had no significant toxic effects on liver, kidney, spleen, and serum biochemical parameters in comparison to healthy mice. The SeNPs treatment reduced the disease severity, as demonstrated by decreased paw edema along with reduced lymphocytic cellular infiltration in the histopathological findings. SeNPs also revealed doseindependent improvement in the redox state of inflamed synovium by significantly improving the activity of antioxidant enzymes in comparison to the arthritic controls. Conclusion: It is therefore concluded that nano-selenium in combination with TAE extract showed enhanced therapeutic efficacy as compared to their individual effects.
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.