Background: Depression is a neurological disorder characterized by persistent low mood. A number of studies have suggested that the use of type 1 cannabinoid receptor (CB1R) agonists can reduce depressive behavior, but its effect on the depressive behavior and nerve damage of rats exposed to chronic unpredictable mild stress (CUMS) has not been reported.Methods: Rats were exposed to CUMS for 4 weeks to induce depressive behavior. Male Sprague-Dawley (SD) rats aged 6-8 weeks were randomly divided into six groups: control group (control), depression group (CUMS), depression + fluoxetine group (Flu), depression + WIN55212-2 group (WIN), depression + NF-κB inhibitor group (PDTC), and depression + WIN + PDTC group (WIN + PDTC). We performed four behavioral experiments test to evaluate the depressive behaviors of rats. Hematoxylin and eosin (HE) and Nissl staining were performed to observe the neuron structures of the hippocampus. Enzymelinked immunosorbent assay (ELISA) was used to measure the concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2). Biochemical experiments were performed to evaluate the concentrations of nitric oxide (NO), malondialdehyde (MDA), reactive oxygen species (ROS), and superoxide dismutase (SOD). Fluorescence quantitative PCR was used to detect the mRNA expression of brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), and inducible nitric oxide synthase (iNOS) in the hippocampus, and western blot was performed to detect protein expression levels related to the NF-κB signaling pathway in the hippocampus.Results: Compared with the normal control group, CUMS significantly induced abnormal behaviors in stressed rats. The concentrations of pro-inflammatory factors and oxidative stress injury factors in the hippocampus of the CUMS group increased significantly. The interventions of Flu, WIN, and PDTC significantly reduced neuroinflammation and oxidative stress injury. Compared with the WIN group, the WIN + PDTC intervention group had better results. In addition, WIN could significantly inhibit the activation of the NF-κB signaling pathway.Conclusions: This study showed that cannabinoid receptor agonists can reduce the CUMS-induced depressive behaviors of rats by blocking the NF-κB signaling pathway to alleviate neuroinflammation and oxidative stress injury.
Background Propofol is used to induce sadation or general anesthesia for procedures. Adjuvants, such as remifentanil characterized by a rapid onset of analgesia and a very short duration of action, which was proved to be an effective opioid receptor agonist considering its effective inhibition of autonomic nervous reflex during endoscopy. Meanwhile, it brings respiratory depression and hypoxia in particular, but there is few reports to explore the optimal dose of remifentanil during gastroscopy so far. So we design this randomized controlled trial (RCT) to identify an optimal remifentanil dosage in patients receiving gastroscopy. Methods A total of 200 patients were recruited and randomly assigned to receive one of four doses of remifentanil: 0 (control group), 1.25μg/ml (PR1 group), 2.5μg/ml (PR2 group), 5μg/ml (PR3 group) combined with propofol anesthesia. The primary outcome is the incidence of hypoxia. The secondary outcomes are the dosage of propofol, patients’ awakening time, and perioperative adverse reactions such as hypotension, hypertension, bradycardia, tachycardia, body movements, nausea and vomiting.Results The onset time of PR2 (19 ± 2 s) and PR3(18 ± 4 s) group were shorter than control group (21 ± 3 s). Awaking time in PR2 (1.6 ± 0.4 min) and PR3 (1.7 ± 0.6 min) groups were significantly less than control group (4.1± 1.1min). The dose of propofol in PR2(90 ± 11 mg) and PR3(87±12 mg) groups were also significantly less than control group( 180 ± 20 mg)。The incidence of hypoxia and increase the flow of oxygen and jaw lift in PR2 group were significantly decreased from 38% to 14% and 32% to 10% compared with the control group, respectively (p<0.01).While the incidence of hypoxia in PR3 group was increased to 46%, higher than other groups (p<0.01). Total number of Sedation-related adverse events in PR2 was significantly decreased from 32% to 8% (p=0.03).Conclusions Both 2.5μg/ml (PR2) and 5μg/ml (PR3) remifentanil combined with propofol used in gastroscopy can reduce the onset time、awaking time and the amount of propofol. But the incidence of hypoxia and total number of sedation-related adverse events in PR2 group were significantly decreased compared with other groups. In our study, 2.5μg/ml remifentanil combined with propofol in gastroscopy is an optimal remifentanil dosage.Trial registration: ClinicalTrials.gov, ChiCTR2000029216.
Background. Epidural morphine has an effective analgesic effect in cesarean section patients; however, a very common adverse effect caused by epidural morphine is pruritus, which is difficult to treat or prevent. Here, we aimed to investigate whether a μ-opioid antagonist with central and peripheral effects reduces morphine-induced pruritus. Methods. In this prospective randomized trial, eighty patients scheduled for an elective cesarean section under spinal aesthesia with 3 mg of epidural morphine were assigned into the nalmefene group (n=40) or placebo group (n=40). After delivery, either 50 μg of intravenous nalmefene hydrochloride (Nalmefene group) or an equivalent amount of normal saline (Placebo group) was administered to the patients. In the meantime, an assessment of a series of side effects such as pruritus, nausea, and pain was conducted at 2, 4, 8, 12, and 24h after epidural morphine administration. Results. All eighty participants completed this trial. The total incidence of pruritus in the first 24 hours following the section was reduced in IV nalmefene group compared with the placebo group (37.5% vs 65%, P=0.003). Moreover, IV nalmefene administration relieved the pruritus intensity, whereas the difference in the incidence of nausea and vomiting between the two groups was not significant. Besides, the nalmefene group displayed significantly higher pain scores at 8, 12 and 24h than the placebo group (all P<0.05). However, no significant difference in the percentage of patients with an analgesic treatment was found between the two groups (P=0.37). Conclusion. In this study, a single dose of 50 μg of IV nalmefene was found to decrease the overall severity and incidence of epidural morphine-induced pruritus, but cause no adverse effect on postoperative analgesia.
To explore the influence and mechanism of lncRNA SNHG14 on oxidized low-density lipoprotein (oxLDL)-induced vascular endothelial cell injury, cellular levels of SNHG14 and miRNA-93-5p were detected in oxLDL-induced vascular endothelial cells by RT-qPCR, and the levels of MDA, SOD and GSH-Px were detected by ELISA. Flow cytometry was used to detect cellular apoptosis, and western blot analysis was used to determine the abundance of Bcl-2 and Bax proteins. SNHG14 small interfering RNA or miRNA-93-5p mimics were transfected into vascular endothelial cells to interfere with SNHG14 expression or overexpress miRNA-93-5p. To study the effects of interfering with SNHG14 expression or overexpression of miRNA-93-5p, the levels of MDA, SOD and GSH-Px, apoptosis and the levels of Bcl-2 and Bax protein were studied in oxLDL-induced endothelial cells with either altered SNHG14 expression or overexpressed miRNA-93-5p. A dual-luciferase reporter gene experiment verified the regulatory connection between SNHG14 and miRNA-93-5p. After oxLDL acted on vascular endothelial cells, the expression levels of SNHG14 were significantly increased, while the expression levels of miRNA-93-5p were significantly reduced, MDA levels were increased, and SOD and GSH-Px activities were reduced. Both the apoptosis rate and Bax protein levels were significantly increased, and Bcl-2 expression was reduced. Interference with SNHG14 expression or overexpression of miRNA-93-5p can reduce the MDA content in oxLDL-induced vascular endothelial cells, increase the activity of SOD and GSH-Px, and reduce the apoptosis rate and Bax protein levels, and promote Bcl-2 expression. SNHG14 targeted to negatively regulate miRNA-93-5p expression, inhibited miRNA-93-5p expression and reversed the interference of SNHG14 expression with oxLDL-induced variation in MDA, SOD and GSH-Px levels, apoptosis rate, and Bax and Bcl-2 protein levels. Interference of SNHG14 expression may reduce oxidative stress and apoptosis of vascular endothelial cells induced by oxLDL by negatively regulating the expression of miRNA-93-5p.
Background. Epidural morphine provides an effective analgesic effect on cesarean section patients, while epidural morphine-induced pruritus is a very common side-effect that is difficult to prevent or treat. The aim of this study was to determine whether a μ-opioid antagonist with central and peripheral effects could reduce morphine-induced pruritus. Methods. Eighty patients who underwent elective cesarean delivery under spinal aesthesia with epidural morphine 3mg were divided into two groups of 40 each in this prospective, randomized study. After delivery, participants received either intravenous nalmefene hydrochloride 50μg( Nalmefene group, n=40) or saline(Placebo group, n=40). Pruritus, nausea, pain, and side-effects were assessed at 2, 4, 8, 12, 24h after epidural morphine administration. Results. Eighty women completed the study. Compared to IV saline , the total incidence of pruritus within the first 24 hours was reduced in IV nalmefene group (37.5% vs 65%, P=0.003). IV nalmefene also reduced the severity of pruritus. There was no significant difference in the incidence of nausea and vomiting. Remarkably, although the pain scores were significantly higher at 8, 12 and 24h(all P<0.05) in the nalmefene groups, but there was no difference between two groups in the number of patients who needed analgesic treatment(P=0.37). Conclusions. A single dose of IV nalmefene 50μg can reduce the overall severity and incidence of epidural morphine-related pruritus without adversely affecting the quality of postoperative analgesia. TRIAL REGISTRY: ChiCTR1900022268. Registered on 2 April 2019
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