microRNA‐126 (miR‐126), an endothelial‐specific miRNA, is associated with vascular homeostasis and angiogenesis. However, the efficiency of miR‐126‐based treatment is partially compromised due to the low efficiency of miRNA delivery in vivo. Lately, exosomes have emerged as a natural tool for therapeutic molecule delivery. Herein, we investigated whether exosomes derived from bone marrow mesenchymal stem cells (BMMSCs) can be utilized to deliver miR‐126 to promote angiogenesis. Exosomes were isolated from BMMSCs overexpressed with miR‐126 (Exo‐miR‐126) by ultracentrifugation. In vitro study, Exo‐miR‐126 treatment promoted the proliferation, migration and angiogenesis of human umbilical vein endothelial cells (HUVECs). Furthermore, the gene/protein expression of angiogenesis‐related vascular endothelial growth factor (VEGF) and angiotensin‐1 (Ang‐1) were up‐regulated after incubation with Exo‐miR‐126. Additionally, the expression level of phosphoinositol‐3 kinase regulatory subunit 2 (PIK3R2) showed an inverse correlation with miR‐126 in HUVECs. Particularly, the Exo‐miR‐126 treatment contributed to enhanced angiogenesis of HUVECs by targeting PIK3R2 to activate the PI3K/Akt signalling pathway. Similarly, Exo‐miR‐126 administration profoundly increased the number of newly formed capillaries in wound sites and accelerated the wound healing in vivo. The results demonstrate that exosomes derived from BMMSCs combined with miR‐126 may be a promising strategy to promote angiogenesis.
Aims
General anesthesia has been widely applied in surgical or nonsurgical medical procedures, but the mechanism behind remains elusive. Because of shared neural circuits of sleep and anesthesia, whether serotonergic system, which is highly implicated in modulation of sleep and wakefulness, regulates general anesthesia as well is worth investigating.
Methods
Immunostaining and fiber photometry were used to assess the neuronal activities. Electroencephalography spectra and burst‐suppression ratio (BSR) were used to measure anesthetic depth and loss or recovery of righting reflex to indicate the induction or emergence time of general anesthesia. Regulation of serotonergic system was achieved through optogenetic, chemogenetic, or pharmacological methods.
Results
We found that both Fos expression and calcium activity were significantly decreased during general anesthesia. Activation of 5‐HT neurons in the dorsal raphe nucleus (DRN) decreased the depth of anesthesia and facilitated the emergence from anesthesia, and inhibition deepened the anesthesia and prolonged the emergence time. Furthermore, agonism or antagonism of 5‐HT 1A or 2C receptors mimicked the effect of manipulating DRN serotonergic neurons.
Conclusion
Our results demonstrate that 5‐HT neurons in the DRN play a regulative role of general anesthesia, and activation of serotonergic neurons could facilitate emergence from general anesthesia partly through 5‐HT 1A and 2C receptors.
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