Aims
Multiple sclerosis (MS) still maintains increasing prevalence and poor prognosis, while glucagon‐like peptide‐1 receptor (GLP‐1R) agonists show excellent neuroprotective capacities recently. Thus, we aim to evaluate whether the GLP‐1R agonist liraglutide (Lira) could ameliorate central nervous system demyelination and inflammation.
Methods
The therapeutic effect of Lira was tested on experimental autoimmune encephalitis (EAE) in vivo and a microglia cell line BV2 in vitro.
Results
Lira administration could ameliorate the disease score of EAE mice, delay the disease onset, ameliorate pathological demyelination and inflammation score in lumbar spinal cord, reduce pathogenic T helper cell transcription in spleen, restore phosphorylated adenosine monophosphate‐activated protein kinase (pAMPK) level, autophagy level, and inhibit pyroptosis‐related NLR family, pyrin domain‐containing protein 3 (NLRP3) pathway in lumbar spinal cord. Additionally, cell viability test, lactate dehydrogenase release test, and dead/live cell staining test for BV2 cells showed Lira could not salvage BV2 from nigericin‐induced pyroptosis significantly.
Conclusion
Lira has anti‐inflammation and anti‐demyelination effect on EAE mice, and the protective effect of Lira in the EAE model may be related to regulation of pAMPK pathway, autophagy, and NLRP3 pathway. However, Lira treatment cannot significantly inhibit pyroptosis of BV2 cells in vitro. Our study provides Lira as a potential candidate for Multiple Sclerosis treatment.
Porous graphene oxide (GO) nanocomposite as scaffold has attracted increasing attention in bone tissue engineering recently. In this study, GO nanosheets was modified by 2,2′-(ethylenedioxy)-diethnethiol (EDDET), and dithiol-modified GO (DT-GO) nanosheets were obtained. The results confirmed that GO nanosheets were cross-linked by EDDET, meanwhile, the distance between GO layers reduced after modification. Next, DT-GO nanosheets were further incorporated into alginate hydrogels to fabricate DT-GO/alginate (DT-GA) nanocomposite as scaffold. The prepared DT-GA nanocomposite behaved the laminar network morphology with interconnected porous structure confirmed by SEM analysis. In addition, the DT-GA nanocomposite with the concentration of DT-GO nanosheets at 16.7% showed the highest porosity value and lowest compressive strength. Furthermore, the bone marrow derived mesenchymal stem cells (BMSCs) showed a good proliferation on DT-GA nanocomposite, demonstrated that prepared nanocomposite had a good cytocompatibility, which was identified by CCK-8 assay and fluorescent microscopy images. Lastly, ALP activity analysis certified that BMSCs seeded on DT-GA nanocomposite could differentiate into osteoblastic phenotype. Above results suggest that the dithiol-modified GO/alginate nanocomposite has the potential to be applied in bone tissue engineering.
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