Cancer cell migration and invasion are essential features of the metastatic process. Volatile anesthetic sevoflurane inhibits the migration and invasion of multiple cancer cell lines; however, its effects on glioma cells are unclear. Emerging evidence suggests that microRNA (miRNA)-637 regulates glioma cell migration and invasion through the Akt1 pathway. Sevoflurane has been shown to modulate a number of miRNAs. In the present study, we examined whether sevoflurane inhibits glioma cell migration and invasion and, if so, whether these beneficial effects are mediated by miRNA-637. U251 glioma cells were treated without (control) or with sevoflurane at low, moderate or high concentrations for 6 h. To explore the molecular mechanisms, an additional group of U251 cells was treated with a miRNA‑637 inhibitor prior to treatment with a high concentration of sevoflurane. Compared with the control group, sevoflurane inhibited the migration and invasion of U251 cells in a dose-dependent manner. Molecular analyses revealed that sevoflurane increased the expression of miRNA‑637 and decreased the expression of Akt1 and phosphorylated Akt1 in a dose-dependent manner. Moreover, the inhibitory effects of sevoflurane on U251 cell migration and invasion were completely abolished by pre-treatment with miRNA‑637 inhibitor, which reversed the sevoflurane-induced reduction in the expression of Akt1 and phosphorylated Akt1 in the U251 cells. These results demonstrate that sevoflurane inhibits glioma cell migration and invasion and that these beneficial effects are mediated by the upregulation of miRNA‑637, which suppresses Akt1 expression and activity. These findings may have significant clinical implications for anesthesiologists regarding the choice of volatile anesthetic agents for the surgical resection of gliomas to prevent metastases and improve patient outcomes.
Mechanical ventilation (MV) may lead to ventilator-induced lung injury (VILI). Previous research has shown that dexmedetomidine attenuates pulmonary inflammation caused by MV, but the underlying mechanisms remain unclear. Our study aims to test whether dexmedetomidine has a protective effect against VILI and to explore the possible molecular mechanisms using the rat model. Thirty adult male Wistar rats weighing 200-250 g were randomly assigned to 5 groups (n = 6): control, low tidal volume MV (LMV), high tidal volume (HVT) MV (HMV), HVT MV + dexmedetomidine (DEX), HVT MV + dexmedetomidine + yohimbine (DEX+Y). Rats were euthanized after being ventilated for 4 hours. Pathological changes, lung wet/dry (W/D) weight ratio, lung myeloperoxidase (MPO) activity, levels of inflammatory cytokines (i.e., interleukin [IL]-1β, tumor necrosis factor alpha [TNF-α], and IL-6) in the bronchoalveolar lavage fluid (BALF) and lung tissues, expression of Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB, and activation of NF-κB in lung tissues were measured. Compared with HMV, DEX group showed fewer pathological changes, lower W/D ratios and decreased MPO activity of the lung tissues and lower concentrations of the inflammatory cytokines in the BALF and lung tissues. Dexmedetomidine significantly inhibited the expression of TLR4 and NF-κB and activation of NF-κB. Yohimbine partly alleviated the effects of dexmedetomidine. Dexmedetomidine reduced the inflammatory response to HVT-MV and had a protective effect against VILI, with the inhibition of the TLR4/NF-κB signaling pathway, at least partly via α2-adrenoceptors.
Sevoflurane, one of the most commonly used volatile anesthetics in clinical treatment, has been shown to induce a widespread increase in brain apoptosis. However, the underlying mechanism is still unknown. Sestrin 2 has been recently shown to regulate intracellular reactive oxygen species (ROS) levels and play a crucial role in p53-dependent antioxidant defenses. In this study, our results indicated that administration of Sevoflurane elevated the gene and protein expression of Sestrin-2 in a dose dependent manner in human neuroblastoma M17 cells. It was shown that silence of Sestrin-2 by small RNA interference (siRNA) ominously exacerbated the increase in intracellular ROS and reduction of SOD activity induced by Sevoflurane treatment. Notably, knockdown of Sestrin-2 in M17 cells significantly increases the number of apoptotic cells after treatment with Sevoflurane. Mechanistically, we also found that Sevoflurane treatment resulted in a reduced amount of the cytosolic anti-apoptotic protein Bcl-2 but an increased amount of Bax, which was exacerbated by knockdown of Sestrin-2. In addition, knockdown of Sestrin-2 remarkably increased the elevated cleaved Caspase-3 expression. Finally, we showed that the induction of Sestrin-2 by Sevoflurane was mediated by p53. These results suggest that the suppressive effects of Sestrin-2 on neuroapoptosis against the Sevoflurane anesthesia in neuronal cells might be associated with modulation of mitochondrial pathway.
BACKGROUND Patients with ankylosing spondylitis (AS) combined with severe cervical fusion deformity have difficult airways. Awake fiberoptic intubation is the standard treatment for such patients. Alleviating anxiety and discomfort during intubation while maintaining airway patency and adequate ventilation is a major challenge for anesthesiologists. Bronchial blockers (BBs) have significant advantages over double-lumen tubes in these patients requiring one-lung ventilation. AIM To evaluate effective drugs and their optimal dosage for awake fiberoptic nasotracheal intubation in patients with AS and to assess the pulmonary isolation effect of one-lung ventilation with a BB. METHODS We studied 12 AS patients (11 men and one woman) with lung or esophageal cancer who underwent thoracotomy with a BB. Preoperative airway evaluation found that all patients had a difficult airway. All patients received an intramuscular injection of penehyclidine hydrochloride (0.01 mg/kg) before anesthesia. In the operating room, dexmedetomidine(0.5 μg/kg) was infused intravenously for 10 min, with 2% lidocaine for airway surface anesthesia, and a 3% ephedrine cotton swab was used to contract the nasal mucosa vessels. Before tracheal intubation, fentanyl (1 μg/kg) and midazolam (0.02 mg/kg) were administered intravenously. Awake fiberoptic nasotracheal intubation was performed in the semi-reclining position. Intravenous anesthesia was administered immediately after successful intubation, and a BB was inserted laterally. The pre-intubation preparation time, intubation time, facial grimace score, airway responsiveness score during the fiberoptic introduction, time of end tracheal catheter entry into the nostril, and lung collapse and surgical field score were measured. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were recorded while entering the operation room (T1), before intubation (T2), immediately after intubation (T3), 2 min after intubation (T4), and 10 min after intubation (T5). After surgery, all patients were followed for adverse reactions such as epistaxis, sore throat, hoarseness, and dysphagia . RESULTS All patients had a history of AS (20.4 ± 9.6 years). They had a Willson's score of 5 or above, grade III or IV Mallampati tests, an inter-incisor distance of 2.9 ± 0.3 cm, and a thyromental (T-M) distance of 4.8 ± 0.7 cm. The average pre-intubation preparation time was 20.4 ± 3.4 min, intubation time was 2.6 ± 0.4 min, facial grimace score was 1.7 ± 0.7, airway responsiveness score was 1.1 ± 0.7, and pulmonary collapse and surgical exposure score was 1.2 ± 0.4. The SBP, DBP, and HR at T5 were significantly lower than those at T1-T4 ( P < 0.05). While the values at T1 were not significantly different from those at T2-T4 ( P > 0.05), they were significantly different from those at T5 ( P < 0.05)....
Objective: To improve skills of tracheal intubation and tracheotomy on medical corpsmen using SimMan simulation and experiments on living goats. Methods: A total of 90 medical corpsmen from one certain group army were trained for the skills of tracheal intubation and tracheotomy using medical simulator and experiments on living goats. Both theoretical tests and practical examinations were performed on all medics to evaluate the efficacy of such training program. Results: Only 25.6% and 15.6% of all medics have previously received trainings related to tracheal intubation and tracheotomy, respectively. Before training, these medics got an average score of 35.3 marks in the theoretical test, and the successful rate of tracheal intubation was only 18.9%. Their performances in both tests, however, increased to 85.2% and 81.1% respectively after training. All these differences were of statistical significance compared to those before training (p<0.01). In a further practical test related to tracheotomy, 14 randomly selected medical corpsmen reached a 71.4% successful rate after training compared to only 14.3% before training (p<0.01). Conclusion:Training modules combined both simulator and goat experiments are effective in improving tracheal intubation techniques on medics especially those from primary units.
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