Sevoflurane inhibits oral squamous carcinoma progression by modulating the circ_0000857/miR-145-5p axis.

Oral squamous cell carcinoma (OSCC) is a kind of oral malignant tumor with the highest incidence. This study investigated whether sevoflurane (SEV) inhibited OSCC cell progression by regulating circular RNA_0000857 (circ_0000857). OSCC cells were anesthetized with SEV at different concentrations. The expression of circ_0000857 and microRNA-145-5p (miR-145-5p) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was assayed by the Cell Counting Kit-8 (CCK-8), and cell migration and invasion were examined by the wound-healing assay and transwell. Tube formation assay detected angiogenesis. Western blot was used to detect the expression of related proteins. Compared with the control group, SEV inhibited OSCC cell migration, invasion, and angiogenesis. SEV treatment significantly decreased circ_0000857 expression level, but increased miR-145-5p expression level in SCC4 and HSC3 cells. MiR-145-5p was a target of circ_0000857, and miR-145-5p inhibitor reversed the suppressing effects mediated by circ_0000857 silencing on OSCC cell migration, invasion, and angiogenesis. SEV inhibited the level of matrix metalloproteinases 2 (MMP2), MMP9, and vascular endothelial growth factor A (VEGFA) protein by regulating the circ_0000857/miR-145-5p axis. In all, SEV regulated the migration, invasion, and angiogenesis of OSCC cells through the circ_0000857/miR-145-5p axis, which provided a basis for the potential role of SEV in the treatment of OSCC.

The role of testosterone in mu-opioid receptor expression in the trigeminal ganglia of opioid-tolerant rats.

Although tolerance serves as a major limitation in the long-term clinical use of opioids in patients with chronic severe pain, mechanisms of opioid tolerance are poorly understood. In this study, a morphine tolerance model was established by subcutaneously injecting male rats with morphine (10 mg/kg) twice a day for 10 consecutive days. In addition, a subset of morphine-tolerant rats underwent testosterone replacement therapy. The levels of mu-opioid receptor (MOR) mRNA and protein in the trigeminal ganglia (TGs) of morphine-tolerant versus control rats and of morphine-tolerant rats with vs. without testosterone replacement therapy were measured. We found that testosterone levels were significantly lower in morphine-tolerant rats than in the controls (1.248 ± 0.231 ng/ml vs. 2.223 ± 0.153 ng/ ml, respectively; p = 0.008). Furthermore, chronic morphine exposure led to a downregulation in the levels of MOR mRNA to 79.3%, and of MOR protein to 68.9%. Testosterone replacement therapy restored MOR mRNA and protein levels specifically in rats who had developed a tolerance to morphine, thereby suggesting a potential role of testosterone in the opioid-receptor response to chronic morphine exposure. In summary, our study provides evidence for the involvement of testosterone in the proper regulation of the peripheral MOR system in rats following prolonged morphine exposure. We also suggest that analgesic therapeutic measures should take into account the testosterone levels of patients who have built up a tolerance to morphine.