The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most frequently studied in the central nervous system and has been linked to neuropathic pain. In this study, a post-translational mechanism of microRNA (miR)-186 via regulating the expression of NLRP3 in the complete Freund's adjuvant (CFA)-treated mice was investigated. The injection of CFA was used to induce trigeminal neuropathic pain in mice. miRs microarray chip assay was performed in trigeminal ganglions (TGs). CFA treatment significantly increased the mRNA expression of NLRP3, interleukin (IL)-1β, and IL-18 in TGs compared to the control group. Moreover, 26 miRs were differentially expressed in TGs from trigeminal neuropathic pain mice, and the expression of miR-186 showed the lowest level of all the miRs. Further examination revealed that NLRP3 was a candidate target gene of miR-186. We delivered miR-186 mimics to CFA-treated mice. The head withdrawal thresholds of the CFA-treated mice were significantly increased by miR-186 mimics injection compared with CFA single treatment. The mRNA and protein expression of NLRP3, IL-1β, and IL-18 in TGs from trigeminal neuropathic pain mice were significantly inhibited by miR-186 mimics treatment compared to the CFA group. miR-186 was able to suppress the neuropathic pain via regulating the NLRP3 inflammasome signaling.
To investigate the clinical effect of different doses of midazolam combined with fentanyl during painless bronchoscopy in adult patients.In this retrospective study, a total of 200 patients who underwent painless bronchoscopy in The First People's Hospital of Wenling from January 2018 to January 2021 were selected as research subjects. These patients were assigned into an experimental group and a control group with 100 patients in each group. Patients from the experimental group were sedated with an intravenous infusion of 0.05 mg/kg midazolam and 0.2 μg/kg fentanyl, while patients from the control group were sedated using 0.1 mg/kg midazolam and 0.2 μg/kg fentanyl. The changes in heart rate (HR), saturation of pulse oximetry (SpO2), systolic blood pressure (SBP), and diastolic blood pressure (DBP) before and at 10 minutes after administration were compared between the two groups. Ramsay sedation scale, RSS agitation scale, awaking time, incidence of adverse reactions, and anesthetic effects were also compared.After medication, there was no significant difference in terms of HR, SBP, or DBP values between the two groups. The SpO2 value in the experimental group was higher than that in the control group (96.93±1.10% vs. 94.78±0.83%, P<0.05). Ramsay sedation scale of patients from the experimental group after medication was (3.88±0.66), which was significantly higher than that of the control group (2.32±0.63), while RSS agitation score in the experimental group was (1.08±0.16), lower than that of the control group (2.32±0.63). The awaking time in the experimental group was shorter than that in control group (43.60±3.30 min vs. 50.19±4.45 min, P<0.05). Moreover, the incidence of mild cough or no cough in the experimental group was significantly better than in the control group (P<0.05). The overall incidence of adverse reactions in the experimental group was lower than that of the control group (5.00% vs. 13.00%, P<0.05). In addition, the anesthetic effect in the experimental group was better than that of the control group (90% vs. 80%, P<0.05).The use of 0.05 mg/kg midazolam combined with 0.2 μg/kg fentanyl in adult painless bronchoscopy has little effect on SpO2 levels, possesses a good sedative and anesthetic effect, and reduces the awaking time, restlessness response, and adverse reactions.
Background: Acyl-CoA synthetase long chain family member 4 (ACSL4) has been reported to serve as a major player in the progress of ferroptosis in various diseases. Nevertheless, the functional role and mechanism of ACSL4 in sevoflurane (sev)-induced neuronal death has never been elucidated. Methods: Cell viability was assessed using Cell Counting Kit-8 (CCK-8). Iron levels, reactive oxygen species (ROS) production, and malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and glutathione (GSH) content were determined to assess ferroptosis level. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot were undertaken for the measurement of gene expression. Results: Sev hindered the viability of SH-SY5Y cells and suppression of ferroptosis by ferrostatin-1 (Fer-1) mitigated sev-induced inhibition of SH-SY5Y cell viability. Sev treatment increases the Fe2+ level and decreases the mRNA levels of SLC7A11 and GPX4 in SH-SY5Y cells. Sev increased the expression of ACSL4. Moreover, silencing of ACSL4 could abrogate sev-induced cell damage, as evidenced by increases in cell viability, GPX4 protein levels, and decreases in iron levels, ROS production, and MDA and 4-HNE content. Remarkably, sev hindered the activation of the 5' AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling, which was diminished by knockdown of ACSL4. Moreover, inhibition of the AMPK/mTOR signaling by compound C could mitigate the protective effect of ACSL4 silencing against sev-induced ferroptotic cell death. Conclusions: Downregulation of ACSL4 restrained sev-induced ferroptotic cell death via AMPK/mTOR signaling, providing the basis for an approach to alleviate sev-induced postoperative cognitive dysfunction (POCD).
The axon guidance factors and Rho/ROCK pathway play crucial roles in axon protection and nerve repair and has been implicated in the development of diabetic peripheral neuropathy (DPN). This study investigates the protective effects of quercetin against DPN, focusing on axon guidance factors and Rho/ROCK pathway. DPN was induced by intraperitoneal injection of streptozotocin (STZ) to Sprague-Dawley rats. The DPN model rats were allocated into three groups and administered quercetin at two different doses (30 mg/kg/day and 60 mg/kg/day) or a placebo. Concurrently, healthy rats were divided into two groups and administered either a placebo or quercetin (60 mg/kg/day). Administration was initiated 8 weeks post-STZ injection and continued for a duration of six weeks. To assess quercetin's neuroprotective effects, biochemical analyses, neurological function tests (mechanical threshold, thermal response latency, motor nerve conduction velocity), and morphological assessments via transmission electron microscopy were conducted. Immunofluorescence and immunohistochemical assays were performed on sciatic nerve tissue and high glucose-induced RSC96 rat Schwann cells to explore quercetin's pharmacological effects on DPN. Quercetin exhibited neuroprotective effects on both DPN rats and RSC96 cells exposed to high-glucose. A six-week administration of quercetin at both doses significantly improved the peripheral neurological functions and alleviated the pathological changes in sciatic nerve of DPN rats (P<0.05). Mechanistically, quercetin markedly upregulated the expressions of axonal growth factors, Slit-2 and Netrin-1 in vivo and in vitro (P<0.05), while inhibiting the aberrant activation of Rho/ROCK signaling pathway in the sciatic nerve of DPN rats. Our findings suggest that quercetin improves DPN through a novel mechanism, indicating its potential as a therapeutic agent for DPN therapy.
This paper discusses the system structure, data organization and Web application development methodology used in the Chinese language distance learning system. An XML based random test generation algorithm is described in this paper. Some proposed future improvements to the system are also presented at the end of this paper.
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