Decellularized extracellular matrix enriched with GDNF enhances neurogenesis and remyelination for improved motor recovery after spinal cord injury.

Motor functional improvement represents a paramount treatment objective in the post-spinal cord injury (SCI) recovery process. However, neuronal cell death and axonal degeneration following SCI disrupt neural signaling, impeding the motor functional recovery. In this study, we developed a multifunctional decellularized spinal cord-derived extracellular matrix (dSECM), crosslinked with glial cell-derived neurotrophic factor (GDNF), to promote differentiation of stem cells into neural-like cells and facilitate axonogenesis and remyelination. After decellularization, the immunogenic cellular components were effectively removed in dSECM, while the crucial protein components were retained which supports stem cells proliferation and differentiation. Furthermore, sustained release of GDNF from the dSECM facilitated axonogenesis and remyelination by activating the PI3K/Akt and MEK/Erk pathways. Our findings demonstrate that the dSECM-GDNF platform promotes neurogenesis, axonogenesis, and remyelination to enhance neural signaling, thereby yielding promising therapeutic effects for motor functional improvement after SCI. STATEMENT OF SIGNIFICANCE: The dSECM promotes the proliferation and differentiation of MSCs or NSCs by retaining proteins associated with positive regulation of neurogenesis and neuronal differentiation, while eliminating proteins related to negative regulation of neurogenesis. After crosslinking, GDNF can be gradually released from the platform, thereby promoting neural differentiation, axonogenesis, and remyelination to enhance neural signaling through activation of the PI3K/Akt and MEK/Erk pathways. In vivo experiments demonstrated that dSECM-GDNF/MSC@GelMA hydrogel exhibited the ability to facilitate neuronal regeneration at 4 weeks post-surgery, while promoting axonogenesis and remyelination at 8 weeks post-surgery, ultimately leading to enhanced motor functional recovery. This study elucidates the ability of neural regeneration strategy to promote motor functional recovery and provides a promising approach for designing multifunctional tissue for SCI treatment.

Association Between Aspirin Usage and Age-Related Macular Degeneration: An Updated Systematic Review and Meta-analysis.

Purpose: To investigate the association between long-term use of aspirin and age-related macular degeneration (AMD). Methods: An updated systematic literature search was conducted in PubMed, Medline, Cochrane Library, and embase from conception to February 26, 2021, without any language restriction. All studies that evaluated the relationship between long-term aspirin use and AMD were included. Results: In the current study, 16 articles were pooled. Overall, no significant association was observed (estimate ratio = 1.108, 95% confidence interval (CI): 0.886-1.385). When the subgroups were evaluated according to various standards, aspirin use was significantly correlated with AMD in studies with volunteer participants (estimate ratio = 0.899, 95% CI: 0.830-0.974, p < 0.01), studies followed up for >10 years (estimate ratio = 2.206, 95% CI: 2.124-2.292, p < 0.01), duration of aspirin use >10 years (estimate ratio = 2.323, 95% CI: 2.234-2.416, p < 0.01), and cohort studies (estimate ratio = 1.961, 95% CI: 1.893-2.032, p < 0.01). Conclusion: Therefore, the association of aspirin and AMD can be demonstrated with a long-term follow-up or aspirin use, appropriate study design and participant source. The findings in our study might provide practical information on intervention strategies.

Genetic variations in the SOCS3 gene in patients with Graves' ophthalmopathy.

AIMS: To explore the role of the suppressor of cytokine signalling 3 (SOCS3) gene in Graves' ophthalmopathy (GO) patients. METHODS: A case-control study was conducted in a Chinese Han population by recruiting 114 Graves' disease (GD) patients with GO and 156 GD patients without GO. We determined SOCS3 mRNA and protein levels in Epstein-Barr virus-transformed lymphoblastoid cell lines (EBV-LCLs) from peripheral blood mononuclear cells (PBMCs) by quantitative real-time (QRT)-PCR analysis and western blot analysis. We also genotyped five single nucleotide polymorphisms (SNPs) in the SOCS3 locus (SOCS3 rs12952093, rs4969170, rs4969168, rs4969169 and rs2280148) in all 270 GD patients using ligase detection reaction and multiplex PCR analyses. QRT-PCR and western blot assays were then performed to compare SOCS3 mRNA and protein levels between the rs4969170 AA and GG genotype groups from 20 GO patients. RESULTS: Basal SOCS3 mRNA and protein expression levels were significantly increased in patients with GO (p<0.05). The SOCS3 rs4969170 AA genotype was strongly associated with GO (OR=3.5, 95% CI 1.6 to 7.5, p=0.001). The AA genotype carriers had significantly higher SOCS3 mRNA and protein levels than those with the GG genotype (p<0.05). CONCLUSIONS: Patients with GD who carry the AA genotype of the rs4969170 SNP in SOCS3 are more susceptible to the development of GO.