MiR-615 Regulates NSC Differentiation In Vitro and Contributes to Spinal Cord Injury Repair by Targeting LINGO-1.

LINGO-1(LRR and Ig domain-containing NOGO receptor interacting protein 1) is a viable target for spinal cord injury (SCI) repair due to its potent negative regulation in neuron survival and axonal regeneration. Although promising, the intracellular mechanism underlying LINGO-1 regulation is unclear. Here, we identified miR-615 as a potential microRNA (miRNA) that directly targets LINGO-1 by binding its 3'-untranslated region (3'-UTR) and caused the translation inhibition of LINGO-1. MiR-615 negatively regulated LINGO-1 during neural stem cell (NSC) differentiation and facilitated its neuronal differentiation in vitro. Interestingly, compared to the control, neurons differentiated from miR-615-treated NSCs were immature with short processes. Further results showed LINGO-1/epidermal growth factor receptor (EGFR) signaling may be involved in this process, as blockade of EGFR using specific antagonist resulted in mature neurons with long processes. Furthermore, intrathecal administration of miR-615 agomir in SCI rats effectively knocked down LINGO-1, increased neuronal survival, enhanced axonal extension and myelination, and improved recovery of hindlimbs motor functions. This work thus uncovers miR-615 as an effective miRNA that regulates LINGO-1 in NSC and SCI animals, and suggests miR-615 as a potential therapeutic target for traumatic central nervous system (CNS) injury.

Effect of Gua Sha therapy on patients with diabetic peripheral neuropathy: A randomized controlled trial.

OBJECTIVE: To examine the effect of Gua Sha therapy in the treatment of diabetic peripheral neuropathy (DNP). DESIGN: An open-label randomized controlled study was conducted with usual care as the control (60 subjects in Gua Sha group and 59 subjects in usual care group). Outcome measures included Toronto Clinical Scoring System (TCSS), Vibration Perception Threshold (VPT), Ankle Brachial Index (ABI), and fasting plasma glucose (FPG). There were 12 consecutive sessions of Gua Sha, one session per week. RESULTS: After the first cycle of Gua Sha intervention, only performance of sensory function measured by the VPT, and peripheral artery disease symptoms by the ABI were statistically significant differences between the two groups (both P values < 0.01), and the total TCSS score and the FPG level were no group differences (P = 0.14, and 0.25, respectively). At the eight-week and 12-week post intervention assessment, Gua Sha therapy significantly reduced severity of neuropathy symptoms, improved performance of sensory function, reduced peripheral artery disease, and better controlled plasma glucose by comparing with the control group (all P values < 0.01). The changes of mean scores of TCSS, VPT, ABI and the plasma glucose levels in the Gua Sha group showed a significant change from baseline to week 12, indicating that Gua Sha therapy induced progressive improvement in the management of DPN symptoms, sensory function, peripheral artery disease and glucose levels. No serious adverse events were reported in either arm. Gua Sha therapy in this study was effective, safe and well tolerated by patients. CONCLUSION: Gua Sha therapy appears to be effective at reducing the severity of DPN in a clinically relevant dimension, and at improving other health outcomes in patients with DPN. While this study found that Gua Sha therapy is a promising treatment in reducing the symptoms of patients with DPN, further, larger sample studies are required to confirm the effects of Gua Sha therapy in patients with DPN.