ObjectiveWe previously confirmed that propofol directly inhibited the viability, proliferation, and invasiveness of hepatocellular carcinoma cells in vitro. In this study, we investigated the mechanism underlying the anti-HCC effects of propofol.MethodsIn vivo antitumor activity was investigated in tumor-bearing mice following an intraperitoneal injection of propofol, with or without clodrolip. The co-culture system was used to verify that miR-142-3p was transported from macrophages to HCC cells. A miR-142-3p inhibitor was used to down-regulate the expression of miR-142-3p.ResultsPropofol drastically inhibited tumor growth in tomor-bearing mice through macrophage activation, and stimulated tumor-associated macrophages (TAMs) to secrete microvesicles (MVs), which delivered miR-142-3p to HCC cells, resulting in the inhibition of HCC cell invasion. In addition, MVs collected from the plasma of the tumor-bearing mice injected with propofol suppressed tumor growth. More importantly, down-regulation of the expression miR-142-3p reversed the effect of propofol on HCC cell migration.ConclusionsThis study reveals a novel role for propofol in the inhibition of HCC through MV-mediated transfer of miR-142-3p from macrophages to cancer cells in vivo.

Emerging studies have shown that long noncoding RNA (lncRNA) TUG1 (taurine‐up‐regulated gene 1) plays critical roles in multiple biological processes. However, the expression and function of lncRNA TUG1 in cerebral ischaemia/reperfusion injury have not been reported yet. In this study, we found that LncRNA TUG1 expression was significantly up‐regulated in cultured MA‐C cells exposed to OGD/R injury, while similar results were also observed in MCAO model. Mechanistically, knockdown of TUG1 decreased lactate dehydrogenase levels and the ratio of apoptotic cells and promoted cell survival in vitro. Moreover, knockdown of TUG1 decreased AQP4 (encoding aquaporin 4) expression to attenuate OGD/R injury. TUG1 could interact directly with miR‐145, and down‐regulation of miR‐145 could efficiently reverse the function of TUG1 siRNA on AQP4 expression. Finally, the TUG1 shRNA reduced the infarction area and cell apoptosis in I/R mouse brains in vivo. In summary, our results suggested that lncRNA TUG1 may function as a competing endogenous RNA (ceRNA) for miR‐145 to induce cell damage, possibly providing a new therapeutic target in cerebral ischaemia/reperfusion injury.

Abstract:Decreased glucose tolerance and diabetes are frequently observed in advanced liver cirrhosis patients and may be related to insulin resistance. Glucose transporter-4 (GLUT4), one of the most important glucose transporters, plays a key role in the development of type 2 diabetes. In order to study the mechanism of insulin resistance in liver cirrhosis patients, we measured the insulin sensitivity index and determined the GLUT4 protein and mRNA contents of skeletal muscle by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR), respectively, in normal people and liver cirrhosis patients. The results showed that the levels of glucose, insulin, and C-peptide in two liver cirrhosis groups were higher and the insulin sensitivity index lower than those of the normal control group. The sensitivity of insulin may decrease with the decline of liver function. However, the contents of GLUT4 protein and mRNA in patients with advanced liver cirrhosis were similar to those of normal controls. In conclusion, insulin resistance is observed in patients with advanced liver cirrhosis but may not be correlated with the skeletal contents of GLUT4 protein and mRNA.

To compare the efficacy and safety of ciprofol and propofol for sedation during hysteroscopy. Methods: A total of 149 patients undergoing hysteroscopy were randomly assigned to a ciprofol (Group C) or propofol group (Group P). All cases received intravenous sufentanil 0.1 µg/kg for analgesic preconditioning. Group C received an induction dose of ciprofol 0.4 mg/kg and a maintenance dosage of 0.6-1.2 mg/kg/h to maintain BIS value between 40-60. In Group P, propofol was started at 2.0 mg/kg and then maintained at 3.0-6.0 mg/kg/h. The primary outcome was the successful rate of hysteroscopy. Secondary outcomes included the change of hemodynamic, respiratory adverse events, injection pain, body movement, recovery time, anesthetist's satisfaction, time of disappearance of the eyelash reflex and the incidence of nausea and vomiting. Results: The success rate of hysteroscopy in each group was 100%. After drug administration, the incidence of hypotension in Group C was much lower than that in Group P (P< 0.05). The incidence of respiratory adverse events in Group C (4.0%) was much lower than that in Group P (31.1%) (P< 0.05). The incidence of injection pain and body movement in Group C was significantly lower than that in Group P (P< 0.05). The mean eyelash reflex disappearance time was less than 3 minutes in both groups. There was no statistically significant difference between the two groups in awakening times, anesthetist's satisfaction and the incidence of nausea and vomiting. No serious adverse events occurred in any patients. Conclusion: Ciprofol proved to be a safer alternative to propofol for anesthesia during hysteroscopy. In comparison to propofol, ciprofol does not cause injection pain, exerts less impact on hemodynamics, and results in less respiratory depression.

MiR-499a-5p was signi cantly down-regulated in degenerative tissues and correlated with apoptosis.Nonetheless, the biological function of miR-499a-5p in acute ischemic stroke has been still unclear. In this study, we found the plasma levels of miR-499a-5p were signi cantly down-regulated in 64 ischemic stroke patients and negatively correlated with the National Institutes of Health Stroke Scale score. Then, we constructed cerebral ischemia/reperfusion (I/R) injury in rats after middle cerebral artery occlusion and subsequent reperfusion and oxygen-glucose deprivation and reoxygenation (OGD/R) treated SH-SY5Y cell model. Transfection with miR-499a-5p mimic was accomplished by intracerebroventricular injection in the in vivo I/R injury model. We further found miR-499a-5p overexpression decreased infarct volumes and cell apoptosis in the in vivo I/R stroke model using TTC and TUNEL staining. PDCD4 was a direct target of miR-499a-5p by luciferase report assay and western blotting. Knockdown of PDCD4 reduced the infarct damage and cortical neuron apoptosis caused by I/R injury. MiR-499a-5p exerted neuroprotective roles mainly through inhibiting PDCD4-mediated apoptosis by CCK-8 assay, LDH release assay and ow cytometry analysis. These ndings suggest that miR-499a-5p might represent a novel target that regulates brain injury by inhibiting PDCD4-mediating apoptosis.