Tissue-engineered nerve grafts (TENGs) are the most promising way for repairing long-distance peripheral nerve defects. Chitosan and poly (lactic-co-glycolic acid) (PLGA) scaffolds are considered as the promising materials in the pharmaceutical and biomedical fields especially in the field of tissue engineering. To further clarify the effects of a chitosan conduit inserted with various quantity of poly (lactic-co-glycolic acid) (PLGA) scaffolds, and their degrades on the peripheral nerve regeneration, the chitosan nerve conduit inserted with different amounts of PLGA scaffolds were used to repair rat sciatic nerve defects. The peripheral nerve regeneration at the different time points was dynamically and comprehensively evaluated. Moreover, the influence of different amounts of PLGA scaffolds on the regeneration microenvironment including inflammatory response and cell state were also revealed. The modest abundance of PLGA is more instrumental to the success of nerve regeneration, which is demonstrated in terms of the structure of the regenerated nerve, reinnervation of the target muscle, nerve impulse conduction, and overall function. The PLGA scaffolds aid the migration and maturation of Schwann cells. Furthermore, the PLGA and chitosan degradation products in a correct ratio neutralize, reducing the inflammatory response and enhancing the regeneration microenvironment. The balanced microenvironment regulated by the degradants of appropriate PLGA scaffolds and chitosan conduit promotes peripheral nerve regeneration. The findings represent a further step towards programming TENGs construction, applying polyester materials in regenerative medicine, and understanding the neural regeneration microenvironment.

Wallerian degeneration (WD) in injured peripheral nerves is associated with a large number of up- or down-regulated genes, but the effects of these changes are poorly understood. In our previous studies, we reported some key factors that are differentially expressed to activate nerve degeneration and regeneration during WD. Here, we determined the effects of secreted phosphoprotein 1 (Spp1) on WD after rat sciatic nerve injury. Spp1 was upregulated from 6 h to 14 days after sciatic nerve injury. Altered expression of Spp1 in Schwann cells (SC) resulted in altered mRNA and protein expression levels for cytokines, c-Fos, PKCα and phospho-ERK/ERK and affected SC apoptosis in vitro. Silencing of Spp1 expression in SCs using siRNA technology reduced proliferation and promoted migration of SCs in vitro. By contrast, overexpression of Spp1 promoted proliferation and reduced migration in SCs in vitro. Differential expression of Spp1 after sciatic nerve injury in vivo altered the expression of cytokines, c-Fos, PKCα, and the p-ERK/ERK pathway. Spp1 is a key regulatory factor that affects nerve degeneration and regeneration through c-Fos, PKCα and p-ERK/ERK pathways after rat sciatic nerve injury. These results shed new light on the role of Spp1 in nerve degeneration and regeneration during WD.

Decellularized extracellular matrix (dECM), with its distinct biological properties, has gained significant attention as a natural biomaterial. Leveraging its potentials, we successfully developed a three-dimensional matrix-based oriented nerve graft by encapsulating a fibrous scaffold with multilayered conformationally intact and biologically active human bone marrow mesenchymal stem cell-derived decellularized extracellular matrix (hBMSC-dECM). Convincingly, the hBMSC-dECM group exhibited comparable functional recoveries to the autograft group by postoperative week 12. In the comprehensive analysis, the molecular regulations in the hBMSC-dECM group were more intricate and nuanced compared to the autograft group. Nevertheless, both groups displayed similar molecular regulatory processes in terms of vascularization and extracellular matrix. Notably, the hBMSC-dECM group demonstrated sustained high levels of regulation in axon and myelin regeneration at week 12, while the immunomodulation returned to the normal levels after peaking at week 2. Collectively, our findings illustrated the satisfactory construction of a cell-matrixed nerve graft that established a microenvironment conducive to nerve regeneration, and elucidated the distinct molecular regulation patterns and characteristics associated with different repair modes.

Congenital myopathies (CMs) are a kind of non-progressive or slow-progressive muscle diseases caused by genetic mutations, which are currently defined and categorized mainly according to their clinicopathological features. CMs exhibit pleiotropy and genetic heterogeneity. Currently, supportive treatment and pharmacological remission are the mainstay of treatment, with no cure available. Some adeno-associated viruses show promising prospects in the treatment of MTM1 and BIN1-associated myopathies; however, such gene-level therapeutic interventions target only specific mutation types and are not generalizable. Thus, it is particularly crucial to identify the specific causative genes. Here, we outline the pathogenic mechanisms based on the classification of causative genes: excitation-contraction coupling and triadic assembly (RYR1, MTM1, DNM2, BIN1), actin-myosin interaction and production of myofibril forces (NEB, ACTA1, TNNT1, TPM2, TPM3), as well as other biological processes. Furthermore, we provide a comprehensive overview of recent therapeutic advancements and potential treatment modalities of CMs. Despite ongoing research endeavors, targeted strategies and collaboration are imperative to address diagnostic uncertainties and explore potential treatments.

Background: Salvia miltiorrhiza is a traditional Chinese medicine with remarkable antioxidant, antibacterial, and anticoagulant properties. In the present study, we investigated the effects of Salvia miltiorrhiza injection in protecting Schwann cells (SCs) from hydrogen peroxide (H₂O₂)-induced cell apoptosis. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and immunofluorescence staining were used to detect the establishment of the SC apoptosis model induced by H₂O₂. The effect of Salvia miltiorrhiza injection on injured cell morphology was observed, and the effect on cell apoptosis was determined by Annexin V-fluorescein isothiocyanate (FITC) apoptosis detection kit and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Western blotting analysis was used to detect the effect of Salvia miltiorrhiza injection on apoptosis-related protein expression. Results: The results of the MTT assay showed that cell activity significantly decreased after treatment with 1 mM H₂O₂, but different concentrations of Salvia miltiorrhiza injection could improve cell activity at different degrees. The number of cells increased significantly after treatment with Salvia miltiorrhiza injection. Annexin V-FITC/PI double staining and TUNEL results revealed that Salvia miltiorrhiza injection could significantly reduce apoptosis induced by H₂O₂. Western blotting analysis showed that the expression of Bcl-2 was significantly upregulated, while the expression level of Bax was significantly downregulated. Conclusions: Salvia miltiorrhiza injection can protect SCs from H₂O₂-induced cell apoptosis, and has potential therapeutic effects in neurological disease.

Background: Achyranthes bidentata polypeptide k (ABPPk) is an active ingredient separated from the Achyranthes bidentata polypeptides (ABPP) in traditional Chinese medicine. In the present study, we investigated the promoting effects and molecular mechanisms of ABPPk on the proliferation of Schwann cells (SCs). Methods: Primary SCs were cultured with ABPPk or nerve growth factor (NGF) in vitro, and cell viability, cell cycle, EdU assay, and the expressions of proliferating cell nuclear antigen (PCNA) and Ki67 were analyzed. In addition, RNA-seq was used for bioinformatics analysis at different time points. PCNA was detected at different time points in a rat sciatic nerve injury model to further determining the role of ABPPk in sciatic nerve injury repair. Results: We found that ABPPk could effectively promote the proliferation of SCs, while ABPPk and NGF had different molecular mechanisms for their proliferation at different time points. Weighted gene co-expression network analysis (WGCNA) showed that ABPPk was mainly involved in the positive regulation of cell proliferation and epigenetic regulation of cell proliferation, while the main cell proliferation-related modules that NGF participated in were attenuation of negative regulation of cell proliferation and positive regulation of cell cycle. There were significant differences in the genes involved in different modules between the two groups, and ABPPk differed from NGF in the biological process of SC migration, differentiation, movement, and development in terms of action time and key genes. Functional enrichment analysis revealed ABPPk had more advantages and participation in the axon extension and vascular system areas. Furthermore, ABPPk significantly promoted the proliferation of SCs in vivo. Conclusions: Through in vitro and in vivo studies, we identified the promoting effects of ABPPk on the proliferation of SCs. Using high-throughput sequencing technology, our work more comprehensively revealed the characteristics and mechanism of ABPPk on SCs. These results further enrich an understanding of the positive function and molecular mechanism of ABPPk in peripheral nerve regeneration and are conducive to the discovery of new therapeutic targets for peripheral nerve regeneration.