Sequential expression of miR-221-3p and miR-338-3p in Schwann cells as a therapeutic strategy to promote nerve regeneration and functional recovery

The functional properties of endogenous Schwann cells(SCs)during nerve repair are dynamic.Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the repair of damaged nerves.Previous studies showed that miR-221-3p promotes the proliferation and migration of SCs,and miR-338-3p promotes the myelination of SCs.In this study,we established rat models of sciatic nerve injury by bridging the transected sciatic nerve with a silicone tube.We injected a miR-221 lentiviral vector system together with a doxycycline-inducible Tet-On miR-338 lentiviral vector system into the cavity of nerve conduits of nerve stumps to sequentially regulate the biological function of endogenous SCs at different stages of nerve regeneration.We found that the biological function of SCs was sequentially regulated,the diameter and density of myelinated axons were increased,the expression levels of NF200 and myelin basic protein were increased,and the function of injured peripheral nerve was improved using this system.miRNA Target Prediction Database prediction,Nanopore whole transcriptome sequencing,quantitative PCR,and dual luciferase reporter gene assay results predicted and verified Cdkn1b and Nrp1 as target genes of miR-221-3p and miR-338-3p,respectively,and their regulatory effects on SCs were confirmed in vitro.In conclusion,here we established a new method to enhance nerve regeneration through sequential regulation of biological functions of endogenous SCs,which establishes a new concept and model for the treatment of peripheral nerve injury.The findings from this study will provide direct guiding significance for clinical treatment of sciatic nerve injury.

Evaluation of the malignant potential of gliomas using diffusion-weighted and gadolinium-enhanced magnetic resonance imaging

Objective:This study aimed to determine whether the apparent diffusion coefficients(ADCs)determined by diffusion-weighted imaging(DWI)of magnetic resonance imaging(MRI)could facilitate the malignancy grading of various gliomas.Methods:Sixty patients with a primary cerebral glioma underwent diffusion-weighted and gadolinium-enhanced(Gd)T1-weighted MRI using a 1.5-T MRI scanner.Scoring was performed based on signal intensities on DWI and Gd images.The mean and minimum ADC values were calculated,and Ki-67 staining was performed for each histological sample to evaluate their tumor proliferative potential.Then,the DWI,Gd,and combined scores were analyzed and compared with the Ki-67 staining index and malignant grade.The relationships among the mean and minimum ADC values,Ki-67staining index,and malignant grade were also evaluated.Results:The minimum ADC was inversely correlated with the Ki-67staining index,with a low minimum ADC suggestive of tumor malignancy.The qualitative evaluation of the D score of water molecule diffusion on DWI accurately reflected the pathological grades of gliomas,with an effectiveness that was at least as good as the quantitative analysis using the minimum ADC.The diagnostic value of Gd images in determining glioma malignancy grades was inferior to that of DWI.Conclusion:Both DWI and gadolinium-enhanced images of MRI should be considered essential for the diagnosis of tumor malignancy.