USP18 overexpression protects against spinal cord ischemia/reperfusion injury via regulating autophagy.

BACKGROUND: Spinal cord ischemia-reperfusion injury (SCII) is usually caused by spinal surgery, often leading to severe neurological deficits. The ubiquitin-specific protease 18 (USP18) plays a significant role in neurological diseases. OBJECTIVE: The present study was designed to assess the effects and mechanisms of USP18 on SCII. METHODS: By inducing transient aortic occlusion and subsequent reperfusion, a rat model of SCII was successfully established. The Basso-Beattie-Bresnahan scores, the inclined plane test, and hematoxylin and eosin (HE) were used to measure locomotor activity and histological changes in the injured spinal cords. Moreover, the SCII cell model was established using PC12 cells under oxygen-glucose deprivation and reoxygenation (OGD/R). Proinflammatory factors (TNF-α, IL-6, and INF-α) were examined using an ELISA kit. Cell apoptosis was assessed by Annexin V-FITC/PI double-staining and TUNEL assays. Western blot was used to detect the expression levels of proteins related to apoptosis and autophagy. RESULTS: USP18 expression was decreasedin vivo and in vitro SCII models. The upregulation of USP18 ameliorated hind limbs' motor function, inhibiting inflammation and apoptosis after SCII in rats. USP18 overexpression in vitro may protect PC12 cells from OGD/R-induced damage by modulating inflammatory responses and apoptosis. Moreover, Overexpression of USP18 enhanced autophagy to inhibit cell apoptosis induced by SCII in vivo and in vitro. CONCLUSIONS: In summary, USP18 overexpression protects against SCII via regulating autophagy.

Administration of combined spinal epidural anesthesia with ultrasound-assisted positioning in obese patients undergoing open hysterectomy: A randomized controlled trial.

BACKGROUND: Administration of combined spinal epidural anesthesia (CSEA) with traditional landmark-guided positioning can be challenging in patients with high body mass index (BMI). The popularization of ultrasound technology may effectively solve these problems. However, reports on the administration of CSEA ultrasound-assisted positioning in obese populations are relatively limited and have made inconsistent conclusions. We aimed to investigate the ability of ultrasound-assisted positioning to improve the success rate of CSEA in obese patients. METHODS: Overall, 118 adult women with a BMI ≥ 30 kg/m2 who scheduled to undergo open hysterectomy and received CSEA were recruited. Finally, 108 patients were enrolled and randomly assigned to 2 groups: the ultrasound-assisted positioning group (group A) and traditional landmark-guided positioning group (group B). Ultrasound-assisted or landmark-guided positioning was employed to locate the puncture interspace before anesthesia. The primary outcomes were the success rate of first attempt and number of attempts. The secondary outcomes were the patient positioning accuracy, positioning time, CSEA operation time, patient-satisfaction scores, anesthesia characteristics, and complications of CSEA. RESULTS: The success rate of patient first puncture attempt in group A was significantly higher than that in group B (78.4% vs 52.9%, P = .007). The total number of punctures was lower in group A than that in groups B (average rank 44.54 vs 58.46, P = .005). Using ultrasound positioning as the gold standard, the accuracy of landmark-guided location was only 67%. Positioning time in croup A was longer in group A than that in group B (P = .004), while CSEA operation time spent in Group A was less than that in Group B (P < .001). Patient satisfaction score in group A was significantly higher than that in group B (P = .002). The successful puncture interspace in group A were more likely at L3-4 than that in group B (P = .02). CONCLUSION: The success rate of first puncture attempt and positioning accuracy in CSEA with ultrasound-assisted is significantly higher than those based on landmark-guided location in obese patients.

Hypoxia Acclimation Protects against Heart Failure Postacute Myocardial Infarction via Fundc1-Mediated Mitophagy.

Mitochondrial dysfunction is the main cause of heart failure (HF) postacute myocardial infarction (AMI). Hypoxia acclimation (HA) reduces efficiently the area of AMI caused by ischemia and/or reperfusion and delays HF. Here, we examined whether HA improves mitochondrial structure and function through the hypoxic autophagy receptor FUNDC1 to prevent HF post-AMI. Male adult mice were acclimated in a low-pressure hypoxic animal chamber (11% oxygen (O2)) for 8 h/day for 28 days, and then, an induced HF post-AMI model via left anterior descending (LAD) artery ligation was structured to explore the efficacy and mechanism of HA. Our results showed that HA exposure can improve cardiac structure and function in mice with HF post-AMI and protected myocardial mitochondrial morphology and function. Further studies showed that HA increased the expression of Fundc1 protein and its associated mitophagy protein LC3 in myocardial tissue after infarction. We then established a cellular model of oxygen glucose deprivation (OGD) in vitro, and knockdown of FUNDC1 attenuated the protective effect of HA exposed on cardiomyocyte mitochondria and increased cardiomyocyte apoptosis. In conclusion, the protective effect of HA on HF post-AMI is achieved by regulating Fundc1-mediated mitophagy in myocardial tissue. FUNDC1-mediated mitophagy could be a promising strategy to treat cardiovascular diseases, including HF.