AXL-Induced Autophagy mitigates experimental autoimmune encephalomyelitis by suppressing microglial inflammation via the PI3K/AKT/mTOR signaling pathway.

Microglia, being the primary immune cells of the central nervous system (CNS), are responsible for pathological inflammatory demyelination in multiple sclerosis (MS). It has been demonstrated that AXL, one of the receptor tyrosine kinases, could alleviate the inflammatory response of microglia. However, the specific mechanism remains unclear. Herein, we explored the role of AXL in the autophagy of microglia and its effect on the experimental autoimmune encephalomyelitis (EAE) model. We revealed that knockout of AXL in BV2 microglia significantly promoted the expression of phosphorylated-PI3K/p-AKT/p-mTOR while significantly inhibiting LC3-Ⅱ/Beclin1. Similarly, autophagy was significantly inhibited in the AXL-/- mice. Knockout of AXL induced serious symptoms, infiltration of inflammatory cells, and demyelination changes, manifesting as the upregulation of pro-inflammatory factors TNF-α and IL-6 and downregulation of anti-inflammatory factors TGF-ß and IL-10. In conclusion, this study substantiated that autophagy induced by AXL inhibited the inflammatory response of microglia and alleviated symptoms of EAE. Autophagy activation was mediated by the PI3K/AKT/mTOR signaling pathway.

Prediction of active marker of seabuckthorn polysaccharides for prevention and treatment of cervical cancer and mechanism study.

Objective: To predict the target of Seabuckthorn polysaccharides in the prevention and treatment of cervical cancer, and to explore its multi-target and multi-pathway mechanism. Methods: Using the Swisstarget database, a total of 61 potential targets of polysaccharide active components were obtained. Cervical cancer related targets were obtained from the GeneCards database. The correlation score was greater than 5 targets for 2727; 15 intersection targets of active ingredients and disease were obtained by Venn diagram. Cytoscape3.6.0 software was used to construct the Polysaccharide composition-Target-Disease Network and Protein-Protein Interaction Networks (PPI). Cytoscape3.6.0 software was used for visualization and network topology analysis to obtain core targets. Kyoto encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were analyzed using Metascape database. SailVina and PyMOL software were used for molecular docking to verify binding strength. Results: A total of 15 core targets were obtained for cervical cancer. These targets are significantly enriched in HIF-1 signaling pathway, Galactose metabolism, EGFR tyrosine kinase inhibitor resistance, growth factor receptor binding, carbohydrate binding, protein homodimerization activity and other GO and KEGG entries; Molecular docking showed that ADA and GLB1 were well bound to Glucose, D-Mannose, and Galactose. Conclusion: The effect of seabuckthorn polysaccharides on the prevention and treatment of cervical cancer is characterized by multi-component, multi-target and multi-pathway, which provides scientific basis for further research on the activity of seabuckthorn polysaccharides.

Prognostic value of neurofilament light chain in natalizumab therapy for different phases of multiple sclerosis: A systematic review and meta-analysis.

A systematic review and meta-analysis of the prognostic value of neurofilament light chain levels in multiple sclerosis treatment with natalizumab Relevant studies published before January 2022 were retrieved from the PubMed, Web of Science, and clinicaltrials.gov databases. Qualitative analysis and meta-analysis were included in 7 of the 46 papers. Differences in the Neurofilament light chain levels were used as the main efficacy measures, and the meta-analysis was performed using Review Manager version 5.3 software. Seven clinical trials were selected. Neurofilament light chain levels were lower in the 947 patients on natalizumab treatment than the 959 patients before therapy, with a moderate effect size of 0.73 (p < 0.00001). Mean Neurofilament light chain levels showed no significant difference between the remitting and relapsing phase of MS before and after natalizumab treatment. The EDSS scores of 41 MS patients in the relapsing phase after natalizumab treatment were significantly lower than those in 102 MS patients without therapy (MD = -0.45;95% CI = -0.85 to -0.05;P < 0.001). However, the EDSS scores in the remitting phase demonstrated no difference. The comparison of Neurofilament light chain across multiple groups demonstrates the potential of Nfl as a noninvasive biomarker of neurodegeneration, evaluating the efficacy of natalizumab in MS patients. We also investigated the relationship between different phases of relapsing-remitting MS with Neurofilament light chain levels. However, the value of Neurofilament light chain as a biomarker was hard to assess due to the limited number of studies. For clinical application, a comprehensive understanding of Neurofilament light chain concentrations in disease subtypes is required, and disease stages should be defined to develop standardized criteria.

Dental Pulp Stem Cell Therapy in Ischemic Stroke: A Meta-Analysis of Preclinical Studies.

OBJECTIVE: More preclinical research evidence has shown that dental pulp stem cells (DPSCs) transplantation is expected to promote the recovery of ischemic stroke (IS), but it still lacks an evidence-based analysis. The purpose of this study was to investigate the effects of DPSCs on neurological function and infarct size in Sprague-Dawley (SD) rats with middle cerebral artery embolization (MCAO). METHODS: According to PRISMA guidelines, the preclinical study of DPSCs in the treatment of IS was screened according to the inclusion and exclusion criteria, and the relevant data and quality were evaluated by two independent researchers; A meta-analysis of histological and behavioral results was performed. RESULTS: Seven studies were finally included, with quality evaluation scores ranging from 8 to 9. Four articles reported modified Neurological Severity Scores (mNSS), three studies reported rotarod test, and six studies reported infarct volume. Meta-analysis showed that the mNSS score decreased by 1.17 times, the rotarod test increased by 1.11 times and the volume of cerebral infarction decreased by 1.91 times in the DPSC group compared with the blank control group. CONCLUSION: Transplantation of DPSCs can significantly improve the neurological function of ischemic stroke and reduce the infarct volume.