Dexmedetomidine attenuates the neuroinflammation and cognitive dysfunction in aged mice by targeting the SNHG14/miR­340/NF­κB axis.

Neuroinflammation plays a key role in the pathogenesis of postoperative cognitive dysfunction (POCD). Results of our previous study demonstrated that dexmedetomidine (Dex) attenuates neuroinflammation in BV2 cells treated with lipopolysaccharide (LPS) by targeting the microRNA (miR)-340/NF-κB axis. However, the molecular mechanisms by which Dex improves POCD remain unclear. In the present study, the association between long non-coding (lnc)RNA small nucleolar RNA host gene 14 (SNHG14) and miR-340 in BV2 microglial cells was determined using a dual-luciferase reporter assay. In addition, SNHG14, miR-340 and NF-κB expression levels were measured in LPS-treated BV-2 cells and hippocampal tissues of mice with POCD, and an enzyme-linked immunosorbent assay was used to determine the levels of proinflammatory mediators. Results of the present study demonstrated that SNHG14 exhibited potential as a target of miR-340. In addition, SNHG14 knockdown increased the levels of miR-340 and reduced the levels of NF-κB in LPS-treated BV2 cells. In addition, Dex treatment significantly reduced the levels of SNHG14 and NF-κB, and elevated the levels of miR-340 in the hippocampus of aged mice with POCD. Moreover, Dex treatment notably decreased the expression levels of TNF-α, IL-1ß, IL-2, IL-6, IL-8 and IL-12 in the hippocampus of aged mice with POCD by upregulating miR-340. The spatial memory impairments in aged mice with POCD were also notably increased following Dex treatment via upregulation of miR-340. Collectively, results of the present study demonstrated that Dex may protect microglia from LPS-induced neuroinflammation in vitro and attenuate hippocampal neuroinflammation in aged mice with POCD in vivo via the SNHG14/miR-340/NF-κB axis. The present study may provide further insights into the mechanisms underlying Dex in the treatment of POCD.

Dexmedetomidine attenuates neuroinflammation and microglia activation in LPS-stimulated BV2 microglia cells through targeting circ-Shank3/miR-140-3p/TLR4 axis.

It has been shown that dexmedetomidine (Dex) could attenuate postoperative cognitive dysfunction (POCD) via targeting circular RNAs (circRNAs). Circ-Shank3 has been found to be involved in the neuroprotective effects of Dex against POCD. However, the role of circ-Shank3 in POCD remains largely unknown. Reverse transcription quantitative PCR (RT-qPCR) was performed to detect circ-Shank3 and miR-140-3p levels in lipopolysaccharide (LPS)-treated microglia BV-2 cells in the absence or presence of Dex. The relationship among circ-Shank3, miR-140-3p and TLR4 was confirmed by dual-luciferase reporter assay. Additionally, Western blot and immunofluorescence (IF) assays were conducted to evaluate TLR4, p65 and Iba-1 or CD11b levels in cells. In this study, we found that Dex notably decreased circ-Shank3 and TLR4 levels and elevated miR-140-3p level in LPS-treated BV2 cells. Mechanistically, circ-Shank3 harbor miR-140-3p, functioning as a miRNA sponge, and then miR-140-3p targeted the 3'-UTR of TLR4. Additionally, Dex treatment significantly reduced TLR4 level and phosphorylation of p65, and decreased the expressions of microglia markers Iba-1 and CD11b in LPS-treated BV2 cells. As expected, silenced circ-Shank3 further reduced TLR4, p65 and Iba-1 and CD11b levels in LPS-treated BV2 cells in the presence of Dex, whereas these phenomena were reversed by miR-140-3p inhibitor. Collectively, our results found that Dex could attenuate the neuroinflammation and microglia activation in BV2 cells exposed to LPS via targeting circ-Shank3/miR-140-3p/TLR4 axis. Our results might shed a new light on the mechanism of Dex for the treatment of POCD.

Ultrasound measurement of laryngeal structures in the parasagittal plane for the prediction of difficult laryngoscopies in Chinese adults.

BACKGROUND: Abnormal laryngeal structures are likely to be associated with a difficult laryngoscopy procedure. Currently, laryngeal structures can be measured by ultrasonography, however, little research has been performed on the potential role of ultrasound on the evaluation of a difficult laryngoscopy. The present study investigated the value of laryngeal structure measurements for predicting a difficult laryngoscopy. OBJECTIVE: The main objective of this study was to explore the value of laryngeal structure measurements for predicting a difficult laryngoscopy. METHODS: Two hundred and eleven adult patients (over 18 years old) were recruited to undergo elective surgery under general anesthesia via endotracheal intubation. Ultrasound was utilized to measure the distance between the skin and thyroid cartilage (DST), the distance between the thyroid cartilage and epiglottis (DTE), and the distance between the skin and epiglottis (DSE) in the parasagittal plane. These metrics were then investigated as predictors for classifying a laryngoscopy as difficult vs easy, as defined by the Cormack and Lehane grading scale. RESULTS: Multivariate logistic regression showed that the DSE, but not DST or DTE, was significantly related to difficult laryngoscopies. Specifically, a DSE ≥ 2.36 cm predicted difficult laryngoscopies with a sensitivity and specificity of 0.818 (95% CI: 0.766-0.870) and 0.856 (95% CI: 0.809-0.904). Furthermore, when combining the best model constructed of other indicators (i.e. sex, body mass index, modified Mallampati test) to predict the difficult laryngoscopy, the AUC reached 93.28%. CONCLUSION: DSE is an independent predictor of a difficult laryngoscopy; a DSE cutoff value of 2.36 cm is a better predictor of a difficult laryngoscope than other ultrasound or physiological measurements for predicting a difficult laryngoscope. Nevertheless, it's more valuable to apply the best model of this study, composed of various physiological measurements, for this prediction purpose.

Dexmedetomidine Attenuates Neuroinflammation In LPS-Stimulated BV2 Microglia Cells Through Upregulation Of miR-340.

BACKGROUND: Dexmedetomidine (Dex) was reported to exhibit anti-inflammatory effect in the nervous system. However, the mechanism by which Dex exhibits anti-inflammation effects on LPS-stimulated BV2 microglia cells remains unclear. Thus, this study aimed to investigate the role of Dex in LPS-stimulated BV2 cells. METHODS: The BV2 cells were stimulated by lipopolysaccharides (LPS). BV2 cells were infected with short-hairpin RNAs targeting NF-κB (NF-κB-shRNAs) and NF-κB overexpression lentivirus, respectively. In addition, miR-340 mimics or miR-340 inhibitor was transfected into BV2 cells, respectively. Meanwhile, the dual-luciferase reporter system assay was used to explore the interaction of miR-340 and NF-κB in BV2 cells. CCK-8 was used to detect the viability of BV2 cells. In addition, Western blotting was used to detect the level of NF-κB in LPS-stimulated BV2 cells. The levels of TNF-α, IL-6, IL-1ß, IL-2, IL-12, IL-10 and MCP-1 in LPS-stimulated BV2 cells were measured with ELISA. RESULTS: The level of miR-340 was significantly upregulated in Dex-treated BV2 cells. Meanwhile, the level of NF-κB was significantly increased in BV2 cells following infection with lenti-NF-κB, which was markedly reversed by Dex. LPS markedly increased the expression of NF-κB and proinflammatory cytokines in BV2 cells, which were reversed in the presence of Dex. Moreover, miR-340 mimics enhanced the anti-inflammatory effects of Dex in LPS-stimulated BV2 cells via inhibiting NF-κB and proinflammatory cytokines. Furthermore, Dex obviously inhibited LPS-induced phagocytosis in BV2 cells. CONCLUSION: Taken together, our results suggested that Dex might exert anti-inflammatory effects in LPS-stimulated BV2 cells via upregulation of miR-340. Therefore, Dex might serve as a potential agent for the treatment of neuroinflammation.