Hyperbaric oxygen (HBO) treatment has been proven to be a promising candidate for protection of the nervous system after acute injury in animal models of neuropathic pain. The purposes of this study were to examine the antinociceptive response phase induced by HBO treatment in a model of neuropathic pain and to determine the dependence of the treatment's mechanism of alleviating neuropathic pain on the inhibition of spinal astrocyte activation. Neuropathic pain was induced in rats by chronic constriction injury of the sciatic nerve. Mechanical threshold and thermal latency were tested preoperatively and for 1 week postoperatively, four times daily at fixed time points. Methane dicarboxylic aldehyde (MDA) and superoxide dismutase (SOD) parameters were used as indices of oxidative stress response and tested before and after the treatment. The inflammatory cytokines interleukin (IL)-1β and IL-10 were assayed in the sciatic nerve were with enzyme-linked immunoassay. Glial fibrillary acidic protein activation in the spinal cord was evaluated immunohistochemically. The rats exhibited temporary allodynia immediately after HBO treatment completion. This transient allodynia was closely associated with changes in MDA and SOD levels. A single HBO treatment caused a short-acting antinociceptive response phase. Repetitive HBO treatment led to a long-acting antinociceptive response phase and inhibited astrocyte activation. These results indicated that HBO treatment played a dual role in the aggravation and alleviation of neuropathic pain, though the aggravated pain effect (transient allodynia) was far less pronounced than the antinociceptive phase. Astrocyte inhibition and anti-inflammation may contribute to the antinociceptive effect of HBO treatment after nerve injury.

BackgroundHyperbaric oxygen (HBO) therapy is proven to attenuate neuropathic pain in rodents. The goal of the present study was to determine the potential involvement of the Kindlin-1/Wnt-10a signaling pathway during astrocyte activation and inflammation in a rodent model of neuropathic pain.MethodsRats were assigned into sham operation, chronic constriction injury (CCI), and CCI + HBO treatment groups. Neuropathic pain developed in rats following CCI of the sciatic nerve. Rats in the CCI + HBO group received HBO treatment for five consecutive days beginning on postoperative day 1. The mechanical withdrawal threshold (MWT) and the thermal withdrawal latency (TWL) tests were performed to determine mechanical and heat hypersensitivity of animals, respectively. Kindlin-1, Wnt-10a and β-catenin protein expression was examined by immunohistochemistry and Western blot analysis. Expression of tumor necrosis factor (TNF)-α was also determined by ELISA.ResultsOur findings demonstrated that HBO treatment significantly suppressed mechanical and thermal hypersensitivity in the CCI neuropathic pain model in rats. HBO therapy significantly reversed the up-regulation of Kindlin-1 in dorsal root ganglia (DRG), spinal cord, and hippocampus of CCI rats. CCI-induced astrocyte activation and increased levels of TNF-α were efficiently reversed by HBO (P < 0.05 vs. CCI). HBO also reversed Wnt-10a up-regulation induced by CCI in the DRG, spinal cord, and hippocampus (P < 0.05 vs. CCI).ConclusionsOur findings demonstrate that HBO attenuated CCI-induced rat neuropathic pain and inflammatory responses, possibly through regulation of the Kindlin-1/Wnt-10a signaling pathway.

Fu (2020) Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway,

AimsThe prognostic significance of perineural invasion (PNI) for gastric cancer (GC) patients was under debate. This study aimed to review relevant studies and evaluate the impact of PNI on the survival outcome of GC patients.MethodsSystematic literature search was performed using PubMed and Embase databases. The relevant data were extracted, and the association between PNI and clinicopathological characteristics or survival outcome in GC patients were evaluated using a fixed-effect model or random-effect model.ResultsA total 13 studies involving 7004 GC patients were included in this meta-analysis. The positive rate of PNI was 35.9% (2512/7004) in GC patients, ranging from 6.9% to 75.6%. There were significant relationships between PNI and a series of unfavourable clinicopathological factors including undifferentiated histology type (OR: 1.78, 95% CI 1.37 to 2.33, p<0.001; I2=75.3%), diffuse type (OR: 1.96, 95% CI 1.07 to 3.60, p=0.029; I2=79.5%), lymphatic invasion (OR: 7.00, 95% CI 3.76 to 13.03, p<0.001; I2=83.6%), vascular invasion (OR: 5.79, 95% CI 1.59 to 21.13, p=0.008; I2=95.8%), deeper tumour invasion (OR: 4.79, 95% CI 3.65 to 6.28, p<0.001; I2=65.0%) and lymph node metastasis (OR: 3.60, 95% CI 2.37 to 5.47, p<0.001; I2=89.6%). In addition, PNI was significantly associated with worse survival outcome in GC patients (HR: 1.69, 95% CI 1.38 to 2.06, p<0.001; I2=71.0%).ConclusionPNI was frequently detected in surgically resected specimens of GC patients, and it was a predictive factor for survival outcomes in these patients.