Propofol suppresses proliferation, invasion, and migration of human melanoma cells via regulating microRNA-137 and fibroblast growth factor 9.

Propofol is an intravenous anesthetic widely used in clinical surgeries, such as tumor resection. Propofol affects the growth of many cancers, though its effect on melanoma is unknown. Our study aimed to explore how propofol affects melanoma cells. Melanoma cells A2058 and WM793B were cultured with propofol for 24 hr. Propofol significantly suppressed proliferation, migration, and invasion of A2058 and WM793B cells. Lower miR-137 level was observed in A2058 and WM793B cells, compared with normal human epidermal melanocyte HEMa-LP cells. Propofol-induced miR-137 upregulation and decreased proliferation, invasive ability, and migrated ability of A2058 and WM793B cells. Transfection with the miR-137 inhibitor reversed these effects. Additionally, miR-137 was verified to target and negatively regulate fibroblast growth factor 9 (FGF9) expression. Propofol efficiently downregulated FGF9 protein expression by upregulating miR-137. Furthermore, FGF9 overexpression abrogated propofol's repressive effects on the malignant potential of A2058 and WM793B cells. These findings indicate that propofol suppressed melanoma cell proliferation, invasion, and migration by regulating miR-137 and FGF9.

Dexmedetomidine enables copper homeostasis in cerebral ischemia/reperfusion via ferredoxin 1.

Excessive oxygen free radicals and toxic substances are generated in cerebral ischemia-reperfusion (I/R) process. Dexmedetomidine (DEX), a common anesthetic and sedative drug, can considerably boost glutathione (GSH), which has anti-copper influx effects. Focusing on cuproptosis, the mechanism of DEX in the I/R was revealed. Using the I/R rat model, the effects of DEX and the copper chelator D-penicillamine on cerebral infarct volume, copper levels, mitochondrial respiration and membrane potential, GSH content, and enrichment of cuproptosis functional proteins were examined. The involvement of ferredoxin 1 (FDX1) in the DEX regulatory pathway was verified by overexpressing FDX1 in vitro. DEX could significantly reduce cerebral infarction in rats, reduce copper levels, maintain mitochondrial functions, increase GSH, and reduce the content of key proteins related to cuproptosis. These aspects were replicated in vitro and revealed that FDX1 overexpression partially reversed the impacts of DEX. Together, cuproptosis occurs in the brain I/R process and DEX can enhance cell survival by blocking the primary pathway mediated by FDX1.KEY MESSAGESDexmedetomidine reduces cerebral infarction in the I/R rat models.Dexmedetomidine reduces cuproptosis in the I/R rat models.FDX1, an upstream of protein fatty acylation, mediates regulation of Dexmedetomidine.

Effects of different sedatives/analgesics on stress responses in patients undergoing craniotomy and bone flap decompression.

OBJECTIVE: To explore the effects of sedation and analgesia with dexmedetomidine and other drugs on the stress response in patients with cerebral hemorrhage after craniotomy hematoma removal and bone flap decompression and insertion of an indwelling endotracheal catheter. METHODS: A total of 180 patients with cerebral hemorrhage with consciousness disturbance who underwent emergency surgery were included in this study. They were divided into six groups treated with propofol, dexmedetomidine, lidocaine, sufentanil, dezocine, and remifentanil, respectively. Intravenous medication was given after recovery of spontaneous respiration, and stress responses were compared among the group. RESULTS: Serum concentrations of norepinephrine, epinephrine, and cortisol and systolic blood pressure were significantly correlated with drug treatment. Serum norepinephrine concentrations differed significantly among the groups, except between the sufentanil and propofol groups. There were significant differences in serum epinephrine concentrations among all groups, and significant differences in serum cortisol concentrations among all groups, except the propofol, dexmedetomidine, and lidocaine groups. CONCLUSION: Dexmedetomidine can reduce the stress response in patients with intracerebral hemorrhage undergoing emergency craniotomy and bone flap decompression, and can reduce adverse events from an indwelling endotracheal catheter 3 hours post-operation.

Silencing of IRF3 alleviates chronic neuropathic pain following chronic constriction injury.

Interferon regulatory factor 3 (IRF3) is a member of IRF family which plays an important role in neuronal survival and neuroprotection. However, the role of IRF3 in neuropathic pain remains unclear. Thus, in this study, we investigated the effect of IRF3 on neuropathic pain in a rat chronic constriction injury (CCI) model. Our results showed that IRF3 was up-regulated in the dorsal root ganglion (DRG) in CCI rats. Intrathecal short-hairpin RNA (shRNA)-IRF3 attenuated mechanical allodynia and thermal hyperalgesia in CCI rats, as well as inhibited the production of TNF-α and IL-1ß in the DRG of CCI rats. Furthermore, we revealed that sh-IRF3 greatly suppressed the expression of p-NF-κB p65 and IκBα degradation in the DRG of CCI rats. In conclusion, our data suggest that knockdown of IRF3 may alleviate neuropathic pain by inhibiting the activation of NF-κB signaling pathway. Therefore, IRF3 may provide an important target for the treatment of neuropathic pain.

Transversus abdominis plane block versus local anaesthetic wound infiltration for postoperative analgesia: A systematic review and meta-analysis.

BACKGROUND: Transversus abdominis plane (TAP) block and local anaesthetic wound infiltration can provide effective pain relief at the wound site after surgery. However, the relative efficacy of two techniques for postoperative analgesia remains controversial. METHODS: We searched PUBMED, EMBASE and CENTRAL databases for randomized controlled trials (RCTs) comparing TAP block with wound infiltration for pain relief after surgery. The primary outcomes were pain scores at rest and on movement at 1, 8 and 24 hours postoperatively and cumulative morphine consumption over 24 hours. The secondary outcomes were time to first rescue analgesic, number of rescue analgesic use and opioids-related side-effects. RESULTS: Nine RCTs with a total of 500 participants were included. TAP block was associated with significant lower rest and dynamic pain scores at 8 hour [MD = -1.08, 95% CI (-1.89-0.26), P = 0.009] and 24 hour [MD = -0.83, 95% CI (-1.60, -0.06), P = 0.03] postoperatively than wound infiltration, but no significant difference was found at 1 hour [MD = -0.94, 95% CI (-1.97, 0.09), P = 0.08] postoperatively. In adults, TAP block significantly reduced 24-hour overall morphine consumption by 3.85 mg [MD = -3.85, 95% CI (-7.47, -0.22), P = 0.04] compared with wound infiltration. Subgroup analysis showed that adults received TAP block appeared to have lower rest pain scores at 24 hour than children (P = 0.008). CONCLUSION: TAP block provides superior analgesia compared with wound infiltration in the setting of a multimodal analgesic regimen. Subgroup analysis indicated that adults may have benefits additional to the analgesic effect than children.