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BACKGROUND: Our previous research proved that vagus nerve stimulation (VNS) improved the neurological outcome after cardiopulmonary resuscitation (CPR) by activating α7 nicotinic acetylcholine receptor (α7nAChR) in a rat model, but the underlying mechanism of VNS in neuroprotection after CPR remains unclear. METHODS: In vivo, we established a mouse model of cardiac arrest (CA)/CPR to observe the survival rate, and the changes in inflammatory factors and brain tissue after VNS treatment. In vitro, we examined the effects of α7nAChR agonist on ischemia/reperfusion (I/R)-induced inflammation in BV2 cells under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions. We observed the changes in cell survival rate, the levels of inflammatory factors, and the expressions of α7nAChR/Janus kinase 2 (JAK2) and toll-like receptor 4 (TLR4) /nuclear factor-κB (NF-κB). RESULTS: In vivo, VNS preconditioning enhanced functional recovery, improved the survival rate, and reduced hippocampal CA1 cell damage, and the levels of inflammatory mediators after CA/CPR. The application of α7nAChR agonists provided similar effects against cerebral injury after the return of spontaneous circulation (ROSC), while α7nAChR antagonists reversed these neuroprotective impacts. The in vitro results mostly matched the findings in vivo. OGD/R increased the expression of tumor necrosis factor-alpha (TNF-α), TLR4 and NF-κB p65. When nicotine was added to the OGD/R model, the expression of TLR4, NF-κB p65, and TNF-α decreased, while the phosphorylation of JAK2 increased, which was prevented by preconditioning with α7nAChR or JAK2 antagonists. CONCLUSION: The neuroprotective effect of VNS correlated with the activation of α7nAChR. VNS may alleviate cerebral IR injury by inhibiting TLR4/NF-κB and activating the α7nAChR/JAK2 signaling pathway.
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BACKGROUND: Targeted temperature management (TTM), as a therapeutic temperature control strategy for cardiac arrest (CA), is recommended by guidelines. However, the relationship between post-rewarming fever (PRF) and the prognosis of CA patients is unclear. Therefore, we aim to summarize the studies regarding the influence of PRF on patients with CA. METHODS: EMBASE, PubMed, and Cochrane Central databases were searched from inception to March 13, 2022. Randomized clinical trials (RCTs) and cohort studies on PRF in CA patients were included. According to the heterogeneity, the meta-analysis was performed using a random effects model or fixed effects model to calculate the pooled odds ratios (ORs) and corresponding 95% confidence intervals (CI s). The outcome data were unfavorable neurological outcome and mortality. RESULTS: The meta-analysis included 11 observational studies involving 3,246 patients. The results of the meta-analysis show that PRF (body temperature >38.0 °C) has no effect on the neurological outcome of CA patients (OR 0.71, 95% CI 0.43-1.17, I 2 82%) and has a significant relationship with lower mortality (OR 0.63; 95% CI 0.49-0.80, I 2 39%). However, PRF with a stricter definition (body temperature >38.5 °C ) was associated with worse neurological outcome (OR 1.44, 95% CI 1.08-1.92, I 2 45%) and higher mortality (OR 1.71, 95% CI 1.25-2.35, I 2 47%). CONCLUSION: This study suggests that PRF >38.0 °C may not affect the neurological outcome and have a lower mortality in CA patients who completed TTM. However, PRF >38.5 °C is a potential prognostic factor for worse outcomes in CA patients.
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Despite the incidence rates of pancreatic cancer being low worldwide, the mortality rates remain high. To date, there is no effective drug treatment for pancreatic cancer. Numerous signalling pathways and cytokines regulate the occurrence and development of pancreatic cancer. Ferroptosis is a non-traditional form of cell death resulting from iron-dependent lipid peroxide accumulation. Studies have demonstrated that ferroptosis is associated with a variety of different types of cancer, such as breast cancer, hepatocellular carcinoma and pancreatic cancer. The present study demonstrated that ferroptosis controls the growth and proliferation of pancreatic cancer, providing a new approach for the treatment of pancreatic cancer. Iron metabolism and reactive oxygen species metabolism are the key pathways involved in ferroptosis in pancreatic cancer. In addition, a number of regulators of ferroptosis, such as glutathione peroxidase 4 and the cystine/glutamate antiporter system Xc-, also play pivotal roles in the regulation of ferroptosis. In the present review, the regulatory mechanisms associated with ferroptosis in pancreatic cancer are summarized, alongside other associated forms of digestive system cancer. The treatment of ferroptosis-based diseases is also addressed.