Exosomes From Muscle-Derived Stem Cells Repair Peripheral Nerve Injury by Inhibiting Ferroptosis via the Keap1-Nrf2-Ho-1 Axis.

Currently, the clinical outcomes of peripheral nerve injuries are suboptimal, highlighting the urgent need to understand the mechanisms of nerve injury to enhance treatment strategies. Muscle-derived stem cells (MDSCs) are a diverse group of multipotent cells that hold promise for peripheral nerve regeneration due to their strong antioxidant and regenerative properties. Our research has revealed that severe ferroptosis occurs in the sciatic nerve and ipsilateral dorsal root ganglion following sciatic nerve injury. Interestingly, we have observed that MDSC-derived exosomes effectively suppress cell ferroptosis and enhance cell viability in Schwann cells and dorsal root ganglion cells. Treatment with exosomes led to increased expression of BDNF and P62 in Schwann cells, decreased expression of Keap1, Nrf2, and HO-1 in Schwann cells, and upregulated dorsal root ganglion cells. Rats treated with exosomes exhibited improvements in sciatic nerve function, sensitivity to stimuli, and reduced muscle atrophy, indicating a positive impact on post-injury recovery. In conclusion, our findings demonstrate the occurrence of ferroptosis in the sciatic nerve and dorsal root ganglion post-injury, with MDSC exosomes offering a potential therapeutic strategy by inhibiting ferroptosis, activating the Keap1-Nrf2-HO-1 pathway, and optimizing the post-injury repair environment.

Muscle-derived stem cell exosomes with overexpressed miR-214 promote the regeneration and repair of rat sciatic nerve after crush injury to activate the JAK2/STAT3 pathway by targeting PTEN.

Introduction: This study aimed to investigate the effect of muscle-derived stem cell (MDSC) exosomes with overexpressed miR-214 on the regeneration and repair of rat sciatic nerve after crush injury and its molecular mechanism. Methods: First, primary MDSCs, Schwann cells (SCs) and dorsal root ganglion (DRG) neurons were isolated and cultured, and the characteristics of MDSCs-derived exosomes were identified by molecular biology and immunohistochemistry. NC mimics and miR-214 mimics were transfected to obtain exo-NC and exo-miR-214. An in vitro co-culture system was established to determine the effect of exo-miR-214 on nerve regeneration. The restoration of sciatic nerve function of rats by exo-miR-214 was evaluated by walking track analysis. Immunofluorescence for NF and S100 was used to detect the regeneration of axon and myelin sheath in injured nerve. The Starbase database was used to analyze the downstream target genes of miR-214. QRT-PCR and dual luciferase reporter assays were used to validate the miR-214 and PTEN interaction relationship. And the expression of the JAK2/STAT3 pathway-related proteins in sciatic nerve tissues were detected by western blot. Results: The above experiments showed that MDSCs-derived exosomes with overexpressed miR-214 was found to promote the proliferation and migration of SCs, increase the expression of neurotrophic factors, promote axon extension of DRG neurons and positively affect the recovery of nerve structure and function. In addition, PTEN was a target gene of miR-214. Exo-miR-214 can significantly inhibit the expression level of PTEN, increase the protein expression levels of p-JAK2 and p-STAT3 and the ratio of p-JAK2/JAK2 and p-STAT3/STAT3, also MDSCs-derived exosomes with overexpressed miR-214 can reduce the occurrence of denervated muscle atrophy. Conclusion: In summary, the MDSCs-derived exosomes with overexpressed miR-214 is involved in peripheral nerve regeneration and repair in rats after sciatic nerve crush injury to activate the JAK2/ STAT3 pathway by targeting PTEN.

Effect of stroke volume variation-guided fluid therapy on perioperative haemodynamics and tissue perfusion in patients with end-stage renal disease undergoing parathyroidectomy / 中华麻醉学杂志

Objective:To evaluate the effect of stroke volume variation (SVV)-guided fluid therapy on perioperative haemodynamics and tissue perfusion in the patients with end-stage renal disease (ESRD) undergoing parathyroidectomy.Methods:One hundred and twenty-one patients of either sex, aged 18-64 yr, of American Society of Anesthesiologists Physical Status classification Ⅲ, with body mass index of 18-28 kg/m 2, with ESRD undergoing elective parathyroidectomy, who received haemodialysis treatment within 24 h before surgery, were enrolled in this study. The patients were divided into standard restrictive fluid therapy group (group SRT, n=61) and goal-directed fluid therapy group (group GDT, n=60) using a random number table method. Group SRT received restrictive fluid therapy, with a continuous infusion of 0.9% normal saline at a rate of 4 ml·kg -1·h -1. Group GDT received goal-directed fluid therapy guided by SVV, and when the SVV≥10% lasted for 5 min, the 0.9% normal saline 3 ml/kg was infused within 5 min until SVV<10%. Systolic blood pressure (SBP) was maintained at ≥90 mmHg or mean arterial pressure(MAP) at ≥65 mmHg throughout the perioperative period in both groups. The intraoperative volume of fluid infused, usage rate and consumption of intraoperative vasoactive drugs were recorded, and arterial blood lactate (Lac) level, MAP, heart rate, cardiac output, and inferior vena cava collapse index (IVC-CI) after removal of endotracheal tube at the end of surgery were measured. MAP was continuously recorded within 12 h after surgery, and MAP variability (CV MAP) was calculated. The occurrence of cardiovascular and cerebrovascular events within 30 days after operation was also recorded. Results:Compared with group SRT, the intraoperative volume of fluid infused was significantly increased, the usage rate of ephedrine and norepinephrine was decreased, the consumption of ephedrine was reduced, and the percentage of postoperative IVC-CI<50% and cardiac output were increased, the percentage of Lac≥2.0 mmol/L and CV MAP were decreased ( P<0.05), and no significant change was found in the incidence of cardiovascular and cerebrovascular events within 30 days after surgery in group GDT ( P>0.05). Conclusions:Compared with restrictive fluid therapy, SVV-guided fluid therapy can optimize the perioperative hemodynamics and tissue perfusion in the patients with ESRD undergoing parathyroidectomy.

Estabishment and application of modified lung reperfusion injury animal model / 中华胸心血管外科杂志

Objective:In this study, we established a reliable surgical procedure of lung ischaemia-reperfusion(IR) injury in rats. The research progress of different lung IR injury models and application value was also discussed.Methods:Twenty-eight adult SD rats were randomly divided into SHAM group and lung IR injury group(IR group), 14 rats in each group. In IR group, rats underwent tracheotomy under general anesthesia and received mechanical ventilation. Chest was opened in supine position, and pulmonary hilum was blocked for 30 minutes then the occlusion was removed. Samples were harvested after reperfusion for 45minutes. Rats in SHAM group received surgery and exposure of the right pulmonary artery, and experienced the same amount of time before the chest closed. Arterial blood gas was extracted postoperatively. Gross view of the lungs and pathological changes were observed, and the dry/wet ratio(W/D) was determined. Protein level of pro-inflammatory factors, markers in oxidative stress pathway, and endothelial functional markers in lung were tested by western blot analysis.Results:In IR group, there was pink foamy secretion in the airway, and the lungs exhibited signs of edema and congestion. In IR group, the alveolitis score was significantly increased, the W/D ratio was also increased, p38MAPK and NF-κB signaling pathways were activated, and the expression of TNF-α was significantly increased, while the expression of eNOS was significantly decreased.Conclusion:Left hilum clamping and bilateral reperfusion injury in lung is a practical animal model, it is a simple, low-cost and repeatable animal model for further studies. No microsurgical instruments were required during the procedure. Lung IR injury is characterized by oxidative stress response, inflammatory response and endothelial cell dysfunction.