The molecular mechanism underlying the protective role of propofol against myocardial ischemia/reperfusion (I/R) injury remains poorly understood. Previous studies have shown that ferroptosis is an imperative pathological process in myocardial I/R injury. We hypothesized that propofol prevents myocardial I/R injury by inhibiting ferroptosis via the AKT/p53 signaling pathway. The ferroptosis-inducing agent erastin (E) and AKT inhibitor MK2206 (MK) were used to investigate the role of propofol in myocardial I/R injury. H9C2 cells treated without any reagents, erastin for 24 h, propofol for 1 h before adding erastin were assigned as the control (C), E, and E + P group, respectively. Cell viability, reactive oxygen species (ROS), and the expression of antioxidant enzymes, including ferritin heavy chain 1 (FTH1), cysteine/glutamate transporter (XCT), and glutathione peroxidase 4 (GPX4) in H9C2 cells. Rat hearts from the I/R + P or I/R groups were treated with or without propofol for 20 min before stopping perfusion for 30 min and reperfusion for 60 min. Rat hearts from the I/R + P + MK or I/R + MK groups were treated with or without propofol for 20 min, with a 10-min treatment of MK2206 before stopping perfusion. Myocardial histopathology, mitochondrial structure, iron levels, and antioxidant enzymes expression were assessed. Our results demonstrated that erastin increased H9C2 cell mortality and reduced the expression of antioxidant enzymes. I/R, which reduced the expression of antioxidant enzymes and increased iron or p53 (p < 0.05), boosted myocardium pathological and mitochondrion damage. Propofol inhibited these changes; however, the effects of propofol on I/R injury were antagonized by MK (p < 0.05). In addition, AKT siRNA inhibited the propofol-induced expression of antioxidant enzymes (p < 0.05). Our findings confirm that propofol protects myocardium from I/R injury by inhibiting ferroptosis via the AKT/p53 signal pathway.

Background: Remimazolam tosilate is a new ultra-short-acting benzodiazepine sedative medicine. In this study, we evaluated the effect of remimazolam tosilate on the incidence of hypoxemia during sedation in elderly patients undergoing gastrointestinal endoscopy.Methods: Patients in the remimazolam group received an initial dose of 0.1 mg/kg and a bolus dose of 2.5 mg of remimazolam tosilate, whereas patients in the propofol group received an initial dose of 1.5 mg/kg and a bolus dose of 0.5 mg/kg of propofol. Patients received ASA standard monitoring (heart-rate, non-invasive blood pressure, and pulse oxygen saturation) during the entire examination process. The primary outcome was the incidence of moderate hypoxemia (defined as 85%≤ SpO2< 90%, >15s) during the gastrointestinal endoscopy. The secondary outcomes included the incidence of mild hypoxemia (defined as SpO2 90%–94%) and severe hypoxemia (defined as SpO2< 85%, >15s), the lowest pulse oxygen saturation, airway maneuvers used to correct hypoxemia, patient’s hemodynamic as well as other adverse events.Results: 107 elderly patients (67.6 ± 5.7 years old) in the remimazolam group and 109 elderly patients (67.5 ± 4.9 years old) in the propofol group were analyzed. The incidence of moderate hypoxemia was 2.8% in the remimazolam group and 17.4% in the propofol group (relative risk [RR] = 0.161; 95% confidence interval [CI], 0.049 to 0.528; p < 0.001). The frequency of mild hypoxemia was less in the remimazolam group, but not statistically significant (9.3% vs. 14.7%; RR = 0.637; 95% CI, 0.303 to 1.339; p = 0.228). There was no significant difference in the incidence of severe hypoxemia between the two groups (4.7% vs. 5.5%; RR = 0.849; 95% CI, 0.267 to 2.698; p = 0.781). The median lowest SpO2 during the examination was 98% (IQR, 96.0%–99.0%) in patients in the remimazolam group, which was significantly higher than in patients in the propofol group (96%, IQR, 92.0%–99.0%, p < 0.001). Patients in the remimazolam group received more drug supplementation during endoscopy than patients in the propofol group (p = 0.014). There was a statistically significant difference in the incidence of hypotension between the two groups (2.8% vs. 12.8%; RR = 0.218; 95% CI, 0.065 to 0.738; p = 0.006). No significant differences were found in the incidence of adverse events such as nausea and vomiting, dizziness, and prolonged sedation.Conclusion: This study explored the safety of remimazolam compared with propofol during gastrointestinal endoscopy in elderly patients. Despite the increased supplemental doses during sedation, remimazolam improved risk of moderate hypoxemia (i.e., 85%≤ SpO2 < 90%) and hypotension in elderly patients.

Recently, the outbreak of coronavirus disease 2019 (COVID-19) is threatening human health globally. There is a dire need to find potential therapeutic agents. Angiotensin converting enzyme 2 (ACE2), as an entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is considered as potential therapeutic target in COVID-19 pandemic. Here, our bioinformatics analysis revealed that the biological function of ACE2 was correlated with regulation of blood pressure and mediation of SARS-CoV-2 entry into host cells. Ten ACE2 cooperative proteins were identified by using STRING with a high score. ACE2 expressed highly in the small intestine, testis, and kidney. The level of ACE2 expression in tumor tissues varies in different types of cancers compared with that in normal tissues. It was worth noting that the expression level of ACE2 in the tumor has no effect on patient survival. MiRNA hsa-miR-942-5p, and three transcription factors (TFs) including Signal transducer and activator of transcription 4 (STAT4), Estrogen related receptor α (ESRRA), and Signal transducer and activator of transcription 3 (STAT3) were selected as novel ACE2 regulators. Moreover, nine potential therapeutic drugs were predicted by two online databases. Thus, our research may expand the overall view of ACE2 in COVID-19 treatment.