Background Ropivacaine is widely used for clinical anesthesia and postoperative analgesia. However, the neurotoxicity induced by ropivacaine in a concentration- and duration-dependent manner, and it is difficult to prevent neurotoxicity. Osthole inhibits phosphodiesterase-4 activity by binding to its catalytic site to prevent cAMP hydrolysis. The aim of this present study is to explore the precise molecular mechanism of osthole-mediated inhibition of neurotoxicity induced by ropivacaine. Methods: SH-SY5Y cell viability and apoptosis were measured in different concentration and duration. Protein concentration was determined in each signaling pathway. The molecular mechanism of osthole-mediated inhibition of ropivacaine-caused neurotoxicity was evaluated. Results The study demonstrated that osthole inhibits SH-SY5Y cells neurotoxicity in a duration- and concentration-dependent manner. Moreover, ropivacaine significantly increased the expression of caspase-3 by promoting the phosphorylation of p38. Osthole-induced upregulation of cAMP activated cAMP-dependent signaling pathway, sequentially leading to elevated cyclic nucleotide response element-binding protein levels, which inhibits P38-dependent signaling and decreases apoptosis of SH-SY5Y. Conclusions This study display the evidence confirmed the molecular mechanism by which osthole amplification of cAMP-dependent signaling pathway, and overexpression of cyclic nucleotide response element-binding protein inhibits P38-dependent signaling and decreases ropivacaine-induced SH-SY5Y apoptosis.

Background Borojó (Borojoa patinoi Cuatrec) fruit has recently been shown to have a variety of health benefit, but the mechanisms have been little studied. The aim of this study was to investigate the effect of 4,8-dicarboxyl-8,9-iridoid-1-glycoside (388) on proliferation and differentiation of embryonic neural stem cells (NSCs). Methods NSCs were treated with 388 and stem cell differentiation was determined by western blotting and immunofluorescence staining. The role of MeCP2 in 388-mediated embryonic NSCs differentiation was examined. Results The results showed that in the presence of mitogen when NSCs proliferated and maintained their multipotency, treatment with 388 did not affect the viability of NSCs. Following mitogen withdrawal to initiate NSC differentiation, treatment with 388 at the doses of 10 and 50 μg/mL significantly increased neural differentiation in both cortex and spinal cord-derived culture. 388 also significantly up-regulated MeCP2 expression. The expression of the neuronal and oligodendrocytic markers was enhanced after addition of 388 in the differentiation culture. However, knockdown of MeCP2 results in inhibition of NSC differentiation, and the pro-differentiation effect of 388 was mostly abolished. Conclusions This study confirmed that 388 stimulates differentiation of NSCs and identifies its mechanism of action by upregulating MeCP2.

BackgroundDexmedetomidine can effectively decrease the incidences of emergence agitation (EA) in adult patients, but there are major side effects related to increased dose of dexmedetomidine. The purpose of this study was to determine of the median effective dose of dexmedetomidine in the prevention of EA among geriatric patients undergoing major open surgery with general anesthesia.MethodsA total of 50 geriatric patients were enrolled in this study. Dexmedetomidine 0.5µg·kg-1·h-1 continuous intravenous infusion was administered to the first patient. The next dose was increased or decreased by 0.05 depending on the response of the previous patient, according to the Dixon up-and-down method. An “effective” or “ineffective” response was determined based on the Riker sedation-agitation score(RSAS), we defined “effective” as RSAS < 5, and “ineffective” as RSAS ≥ 5.ResultsThe ED50 of dexmedetomidine in prevention of EA was 0.30µg·kg-1·h-1 (95% CI, 0.27–0.33) and the predicted ED95 was 0.42µg·kg-1·h-1(95% CI, 0.38–0.51). The incidence of bradycardia was significant increased in group without EA compared to the group with EA (57.1% vs 13.6%, P = 0.002).ConclusionsThe ED50 of dexmedetomidine in prevention of EA was 0.30µg·kg-1·h-1 (95% CI, 0.27–0.33) and the predicted ED95 was 0.42µg·kg-1·h-1 (95% CI, 0.38–0.51). Bradycardia was the main complication.Trial registrationThis study was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR1900023769) on June 11th, 2019.