Purpose. Our study is aimed at investigating the mechanism by which electroacupuncture (EA) promoted nerve regeneration by regulating the release of exosomes and exosome‐mediated miRNA‐21 (miR‐21) transmission. Furthermore, the effects of Schwann cells‐ (SC‐) derived exosomes on the overexpression of miR‐21 for the treatment of PNI were investigated. Methods. A sciatic nerve injury model of rat was constructed, and the expression of miR‐21 in serum exosomes and damaged local nerves was detected using RT‐qPCR after EA treatment. The exosomes were identified under a transmission electron microscope and using western blotting analysis. Then, the exosome release inhibitor, GW4869, and the miR‐21‐5p‐sponge used for the knockdown of miR‐21 were used to clarify the effects of exosomal miR‐21 on nerve regeneration promoted by EA. The nerve conduction velocity recovery rate, sciatic nerve function index, and wet weight ratio of gastrocnemius muscle were determined to evaluate sciatic nerve function recovery. SC proliferation and the level of neurotrophic factors were assessed using immunofluorescence staining, and the expression levels of SPRY2 and miR‐21 were detected using RT‐qPCR analysis. Subsequently, the transmission of exosomal miR‐21 from SC to the axon was verified in vitro. Finally, the exosomes derived from the SC infected with the miR‐21 overexpression lentivirus were collected and used to treat the rat SNI model to explore the therapeutic role of SC‐derived exosomes overexpressing miR‐21. Results. We found that EA inhibited the release of serum exosomal miR‐21 in a PNI model of rats during the early stage of PNI, while it promoted its release during later stages. EA enhanced the accumulation of miR‐21 in the injured nerve and effectively promoted the recovery of nerve function after PNI. The treatment effect of EA was attenuated when the release of circulating exosomes was inhibited or when miR‐21 was downregulated in local injury tissue via the miR‐21‐5p‐sponge. Normal exosomes secreted by SC exhibited the ability to promote the recovery of nerve function, while the overexpression of miR‐21 enhanced the effects of the exosomes. In addition, exosomal miR‐21 secreted by SC could promote neurite outgrowth in vitro. Conclusion. Our results demonstrated the mechanism of EA on PNI from the perspective of exosome‐mediated miR‐21 transport and provided a theoretical basis for the use of exosomal miR‐21 as a novel strategy for the treatment of PNI.

Although the benefits of electroacupuncture (EA) for peripheral nerve injury (PNI) are well accepted in clinical practice, the underlying mechanism remains incompletely elucidated. In our study, we observed that EA intervention led to a reduction in the expression of the long non-coding RNA growth-arrest-specific transcript 5 (GAS5) and an increased in miR-21 levels within the injured nerve, effectively promoting functional recovery and nerve regeneration following sciatic nerve injury (SNI). In contrast, administration of adeno-associated virus expressing GAS5 (AAV-GAS5) weakened the therapeutic effect of EA. On the other hand, both silencing GAS5 and introducing a miR-21 mimic prominently enhanced the proliferation activity and migration ability of Schwann cells (SCs), while also inhibiting SCs apoptosis. On the contrary, inhibition of SCs apoptosis was found to be mediated by miR-21. Additionally, overexpression of GAS5 counteracted the effects of the miR-21 mimic on SCs. Moreover, SCs that transfected with the miR-21 mimic promoted neurite growth in hypoxia/reoxygenation-induced neurons, which might be prevented by overexpressing GAS5. Furthermore, GAS5 was found to be widely distributed in the cytoplasm and was negatively regulated by miR-21. Consequently, the targeting of GAS5 by miR-21 represents a potential mechanism through which EA enhances reinnervation and functional restoration following SNI. Mechanistically, the GAS5/miR-21 axis can modulate the proliferation, migration, and apoptosis of SCs while potentially influencing the neurite growth of neurons.

Stem cell‐based therapeutic strategies have obtained a significant breakthrough in the treatment of cardiovascular diseases, particularly in myocardial infarction (MI). Nevertheless, limited retention and poor migration of stem cells are still problems for stem cell therapeutic development. Hence, there is an urgent need to develop new strategies that can mobilize stem cells to infarcted myocardial tissues effectively. Electroacupuncture (EA) intervention can improve cardiac function and alleviate myocardial injury after MI, but its molecular mechanism is still unclear. This study is aimed at observing the effects of EA treatment on the stem cell mobilization and revealing possible mechanisms in the MI model of mice. EA treatment at Neiguan (PC6) and Xinshu (BL15) acupoints was conducted on the second day after the ligation surgery. Then, the number of stem cells in peripheral blood after EA in MI mice and their cardiac function, infarct size, and collagen deposition was observed. We found that the number of CD34‐, CD117‐, Sca‐1‐, and CD90‐positive cells increased at 6 h and declined at 24 h after EA intervention in the blood of MI mice. The expression of CXC chemokine receptor‐4 (CXCR4) protein was upregulated at 6 h after EA treatment, while the ratio of LC3B II/I or p‐ERK/ERK showed a reverse trend. In addition, there was obvious difference in EF and FS between wild‐type mice and CXCR4^+/− mice. The infarct size, collagen deposition, and apoptosis of the injured myocardium in CXCR4^+/− mice increased but could be ameliorated by EA. In a word, our study demonstrates that EA alleviates myocardial injury via stem cell mobilization which may be regulated by the SDF‐1/CXCR4 axis.

To investigate the expression and role of nicotinic acetylcholine α7 subunit (nAChRα7) in the hippocampus of rats with Parkinson's disease (PD) and Parkinson's disease dementia (PDD). PD model was established with 6-hydroxydopa. Then, methyllycaconitine was further used to prepare a PDD model. The behavioral indexes and malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured. The mRNA level and protein level of nAChRα7 in hippocampus was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western-blot, respectively. The α7nAchR and NeuN protein was detected by immunofluorescence. Compared with the PD model group, the escape latency of the PDD model group was significantly prolonged while the times of crossing platforms was significantly reduced (p < 0.05). The SOD level in the PDD and PD group decreased as compared with the control group (p < 0.05), while the MDA content increased (p < 0.05). The mRNA level and protein expression of nAChRα7 in the PDD and PD model group was significantly lower than that in the control group (p < 0.05). There was a significant difference in the nAChRα7 protein level between the PDD and PD model group (p < 0.05). Together, the nAChRα7 receptor level was significantly decreased in the PDD model group, indicating that the decrease in the nAChRα7 receptor levels is a possible mechanism of the pathogenesis of PDD.