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To provide a basis for promising exosome-based therapies against intervertebral disc degeneration (IDD), our present research aimed to identify a mechanism underlying the vesicle release from nucleus pulposus cells (NPCs). Scutellarin (SC) is a natural chemotherapeutic agent isolated from Erigeron breviscapus with a variety of biological activities. Here, we observed the significantly elevated autophagy levels in rat NPCs under the stimulation of SC, leading to a concomitant enhancement of intracellular vesicle release, which could be attributed to the inactivation of the phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/protein kinase B (Akt) pathway. To ensure that exosome release was driven by SC via the autophagic pathway, we implemented gain-of-function and loss-of-function studies by additionally using insulin-like growth factor-1 (IGF-1) and small-interfering RNA of autophagy-related gene 5 (ATG5), and the exosome secretion decreased in the case of attenuated autophagy. Evidently, the treatment with SC exerted the remarkable upregulation of Rab8a through the overexpression of ATG5. After the respective knockdown of ATG5 and Rab8a, the increased release of exosomes induced by SC was reversed, whereas the number of intracellular vesicles was restored. Overall, it can be concluded that SC contributes to the autophagy activation in NPCs by acting on the PI3K/PTEN/Akt pathway, which upregulates the expression of Rab8a and promotes the release of exosomes, inspiring novel therapeutic strategies in preventing IDD that might be fruitfully investigated.

Oxidative stress can lead to nucleus pulposus cell (NPC) apoptosis, which is considered to be one of the main contributors to intervertebral disc degeneration (IVDD). Procyanidin B2 is a natural antioxidant that protects against oxidative stress. However, whether procyanidin B2 protects NPCs from oxidative stress remains unknown. In this study, we demonstrated that procyanidin B2 could reduce tert-butyl hydroperoxide-induced reactive oxygen species in rat NPCs and attenuate rat NPC apoptosis. Further experiments revealed that procyanidin B2 upregulated the expression of both nuclear factor erythroid 2-related factor 2 (Nrf2) and phosphorylation of protein kinase B (Akt). We then used silencing of Nrf2 and LY294002 to silence Nrf2 expression and block the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, respectively, and found that the protective roles of procyanidin B2 in NPCs were inhibited. Therefore, we demonstrated that procyanidin B2 alleviated rat NPC apoptosis induced by oxidative stress by upregulating Nrf2 via activation of the PI3K/Akt signaling pathway. This study provides a potential therapeutic approach for procyanidin B2 in IVDD, which might help in the development of new drugs for IVDD treatment.

Objective To study the therapeutic efficacy of the “sandwich” method (medical glue + gelatin sponge + medical glue) of spinal dural repair for preventing cerebrospinal fluid (CSF) leaks during treatment of subdural tumors. Methods Fifty-four patients with spinal subdural tumors treated between April 2007 and June 2011 were retrospectively investigated. The patients were divided into two groups: a conventional group (Group A) and a “sandwich” group (Group B). The Group A patients included 16 males and 7 females with an average tumor course of 11 months (range, 2–34 months). Four of their 23 tumors were in the cervical spine, eight thoracic, and eleven lumbar. The Group B patients included 19 males and 12 females with an average tumor course of 12 months (range, 3–36 months). Five of their 31 tumors were in the cervical spines, 10 thoracic, and 16 lumbar. In Group A, the dural repairs were performed with interlocking sutures and a gelatin sponge covering the dura; whereas in Group B, they were performed with interlocking sutures, painting of medical glue around the dural incision, covering this with a gelatin sponge, and finally covering of the gelatin sponge with medical glue. The total volume of drainage after operation, incidence of CSF leaks, healing of the incision, and recovery of clinical performance were recorded. Results Compared to Group A patients, Group B patients had a significantly smaller total volume of drainage (P < 0.05) on the day of surgery, and the first, second, and third postoperative days. The incidence of CSF leakage in Group B was also significantly less than in Group A (P < 0.05). Before discharge, three patients in Group A developd hydrops, which was successfully treated by aspiration, continuous pressure from sandbags, and the prone position. During the first 3 months of follow-up, five patients developed deep hydrops under their incisions but required no treatment. There were no obvious abnormalities in Group B. Conclusion After removal of subdural spinal tumors by incising the dura mater, or in related spinal surgery, application of the “sandwich” complex to the damaged spinal dura reduces the volume of drainage postoperatively and reduces the incidence of CSF leakage.