Propofol Ameliorates Spinal Cord Injury Process by Mediating miR-672-3p/TNIP2 Axis.

Propofol has been found to have a protective effect against spinal cord injury (SCI). However, the underlying molecular mechanism of propofol regulating SCI process remains unclear. In this study, lipopolysaccharide (LPS)-induced PC12 cells were used to build SCI cell models. Cell viability and apoptosis were determined by cell counting kit 8 assay, flow cytometry, and caspase-3 activity detection. The protein levels of apoptosis-related markers and TNFAIP3 interacting protein 2 (TNIP2) were assessed using western blot analysis, and the levels of inflammatory factors were detected using ELISA. Cell oxidative stress was evaluated by measuring malondialdehyde (MDA) and reactive oxygen species (ROS) levels. The expression of microRNA (miR)-672-3p was examined by quantitative real-time PCR. SCI rat models were constructed to assess the effect of propofol in vivo. We found that propofol treatment promoted viability, while inhibited apoptosis, inflammation and oxidative stress of LPS-induced PC12 cells. Propofol decreased miR-672-3p expression, and miR-672-3p overexpression eliminated the inhibiting effect of propofol on LPS-induced PC12 cell injury. Besides, miR-672-3p targeted TNIP2, and TNIP2 knockdown reversed the protective effect of miR-672-3p inhibitor or propofol against LPS-induced PC12 cell injury. In vivo experiments, propofol treatment enhanced the motor function recovery and inhibited apoptosis of SCI rat models. In conclusion, propofol increased TNIP2 level by reducing miR-672-3p expression, thereby alleviating LPS-induced PC12 cell injury and improving the motor function of SCI rat models.

MicroRNA-424-5p Alleviates Isoflurane Anesthesia-Induced Neurotoxicity in Human Embryonic Stem Cell-Derived Neurons by Targeting FASN.

Isoflurane (ISO) is a type of anesthetic that might cause neurotoxicity in children. Although miR-424-5p is considerably downregulated in ISO-treated rat brain samples, its physiological role in ISO-induced neuronal injury in human embryonic stem cell-derived neurons remains unknown (hESC-derived neurons). miR-424-5p expression and fatty acid synthase (FASN) in ISO-treated hESC-derived neurons were tested via qRT-PCR. The amount of protein for Bax, Cleaved-caspase-8, Bcl-2, and FASN was investigated through western blot analysis. The viability and apoptosis of hESC-derived neurons were estimated through cell counting kit-8 assessment and TUNEL assay, accordingly. Superoxide dismutase, glutathione, and malondialdehyde levels were discovered via corresponding kits. The contents of inflammatory factors including interleukin-6 and tumor necrosis factor-α were examined by enzyme-linked immunosorbent assays. The combination between FASN and miR-424-5p was resolute via dual-luciferase reporter assessment. After exposure to ISO, induced neurotoxicity and a decreased miR-424-5p production were identified in hESC-derived neurons. Upregulation of miR-424-5p repressed ISO-induced apoptosis and mitigated ISO-induced inflammatory response and oxidative stress in vitro. FASN expression levels were reduced by elevation of miR-424-5p and upregulated after ISO treatment. Mechanically, FASN was directly targeted by miR-424-5p in hESC-derived neurons. Of note, the miR-424-5p elevation-suppressed neuronal apoptosis, inflammatory response, and oxidative stress were countered by upregulation of FASN.

MicroRNA-17-5p Protects against Propofol Anesthesia-Induced Neurotoxicity and Autophagy Impairment via Targeting BCL2L11.

Background: Propofol (PPF) has been shown in studies to cause cognitive impairment and neuronal cell death in developing animals. PPF has been demonstrated to decrease the expression of microRNA-17-5p (miR-17-5p) in a recent study. Nonetheless, the function of miR-17-5p in PPF-induced neurotoxicity and related mechanisms is uncharacterized. Methods: After the induction of neurotoxicity by treating the SH-SY5Y cells with PPF, qRT-PCR was conducted to evaluate the level of miR-17-5p. Using MTT and flow cytometry, cell viability and apoptosis rate were assessed, respectively. Interaction between miR-17-5p and BCL2 like 11 was (BCL2L11) studied using a Luciferase reporter assay. With the help of western blot analysis, we determined the level of proteins of apoptosis-related genes and autophagy-related markers. Results: In SH-SY5Y cells, PPF treatment induced neurotoxicity and downregulated miR-17-5p expression. In SH-SY5Y cells post-PPF exposure, overexpression of miR-17-5p increased cell viability and decreased apoptosis. Consistently, miR-17-5p mimics mitigated PPF-generated autophagy via inhibition of Atg5, Beclin1, and LC3II/I level and elevation of p62 protein expression. In addition, BCL2L11, which was highly expressed in PPF-treated SH-SY5Y cells, was directly targeted by miR-17-5p. Further, in PPF-treated SH-SY5Y cells, overexpressed BCL2L11 counteracted the suppressing behavior of miR-17-5p elevation on PPF-induced apoptosis. Conclusion: Overexpressed miR-17-5p alleviates PPF exposure-induced neurotoxicity and autophagy in SH-SY5Y cells via binding to BCL2L11, suggesting the possibility that miR-17-5p can serve as a candidate in the treatment of neurotoxicity (caused by PPF).

Effect of dexmedetomidine added to ropivicaine for caudal anesthesia in patients undergoing hemorrhoidectomy: A prospective randomized controlled trial.

BACKGROUND: To assess the effect of dexmedetomidine added to ropivaccaine on the onset and duration of sensory block, as well as postoperative analgesia during caudal anesthesia in patients undergoing hemorrhoidectomy. METHODS: Fifty adult patients scheduled for hemorrhoidectomy were divided into 2 groups. The group R received caudal anesthesia using 18 mL 0.3% ropivacaine plus 2 mL normal saline. The group RD received 18 mL 0.3% ropivacaine plus 2 mL 1 µg/kg dexmedetomidine. Heart rate, mean blood pressure, onset time and duration of sensory block, and duration of analgesia were observed. RESULTS: The onset time of sensory block was shortened (9.2 ±â€Š1.3 vs 7.2 ±â€Š1.2), and the duration of sensory block (3.0 ±â€Š0.7 vs 3.8 ±â€Š0.8) and duration of analgesia (3.9 ±â€Š0.7 vs 5.3 ±â€Š0.8) were prolonged in group RD compared with group R (P < .05). The heart rate and the mean blood pressure were also lower in the group RD compared with group R at each observation time points, except the baseline (P < .05). No bradycardia or hypotension was reported. CONCLUSION: Dexmedetomidine as an adjuvant to ropivacaine prolonged the duration of caudal block and improved postoperative analgesia without significant side effects in adult patients undergoing hemorrhoidectomy.

Hydrogen sulfide postconditioning protects isolated rat hearts against ischemia and reperfusion injury mediated by the JAK2/STAT3 survival pathway

The JAK2/STAT3 signal pathway is an important component of survivor activating factor enhancement (SAFE) pathway. The objective of the present study was to determine whether the JAK2/STAT3 signaling pathway participates in hydrogen sulfide (H2S) postconditioning, protecting isolated rat hearts from ischemic-reperfusion injury. Male Sprague-Dawley rats (230-270 g) were divided into 6 groups (N = 14 per group): time-matched perfusion (Sham) group, ischemia/reperfusion (I/R) group, NaHS postconditioning group, NaHS with AG-490 group, AG-490 (5 µM) group, and dimethyl sulfoxide (DMSO; <0.2%) group. Langendorff-perfused rat hearts, with the exception of the Sham group, were subjected to 30 min of ischemia followed by 90 min of reperfusion after 20 min of equilibrium. Heart rate, left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and the maximum rate of increase or decrease of left ventricular pressure (± dp/dt max) were recorded. Infarct size was determined using triphenyltetrazolium chloride (TTC) staining. Myocardial TUNEL staining was used as the in situ cell death detection method and the percentage of TUNEL-positive nuclei to all nuclei counted was used as the apoptotic index. The expression of STAT3, bcl-2 and bax was determined by Western blotting. After reperfusion, compared to the I/R group, H2S significantly improved functional recovery and decreased infarct size (23.3 ± 3.8 vs 41.2 ± 4.7%, P < 0.05) and apoptotic index (22.1 ± 3.6 vs 43.0 ± 4.8%, P < 0.05). However, H2S-mediated protection was abolished by AG-490, the JAK2 inhibitor. In conclusion, H2S postconditioning effectively protects isolated I/R rat hearts via activation of the JAK2/STAT3 signaling pathway.

Hydrogen sulfide postconditioning protects isolated rat hearts against ischemia and reperfusion injury mediated by the JAK2/STAT3 survival pathway.

The JAK2/STAT3 signal pathway is an important component of survivor activating factor enhancement (SAFE) pathway. The objective of the present study was to determine whether the JAK2/STAT3 signaling pathway participates in hydrogen sulfide (H2S) postconditioning, protecting isolated rat hearts from ischemic-reperfusion injury. Male Sprague-Dawley rats (230-270 g) were divided into 6 groups (N = 14 per group): time-matched perfusion (Sham) group, ischemia/reperfusion (I/R) group, NaHS postconditioning group, NaHS with AG-490 group, AG-490 (5 µM) group, and dimethyl sulfoxide (DMSO; <0.2%) group. Langendorff-perfused rat hearts, with the exception of the Sham group, were subjected to 30 min of ischemia followed by 90 min of reperfusion after 20 min of equilibrium. Heart rate, left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and the maximum rate of increase or decrease of left ventricular pressure (± dp/dt(max)) were recorded. Infarct size was determined using triphenyltetrazolium chloride (TTC) staining. Myocardial TUNEL staining was used as the in situ cell death detection method and the percentage of TUNEL-positive nuclei to all nuclei counted was used as the apoptotic index. The expression of STAT3, bcl-2 and bax was determined by Western blotting. After reperfusion, compared to the I/R group, H2S significantly improved functional recovery and decreased infarct size (23.3 ± 3.8 vs 41.2 ± 4.7%, P < 0.05) and apoptotic index (22.1 ± 3.6 vs 43.0 ± 4.8%, P < 0.05). However, H2S-mediated protection was abolished by AG-490, the JAK2 inhibitor. In conclusion, H2S postconditioning effectively protects isolated I/R rat hearts via activation of the JAK2/STAT3 signaling pathway.