This study aimed to investigate the effects of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, on endoplasmic reticulum (ER) stress in rats with neuropathic pain (NP). NP was induced in rats through ligation and transection of the sciatic nerve. After confirmation of NP, the animals were randomly divided into ketamine and control groups. The ketamine group was administered 50 mg/kg of ketamine at 15, 18, and 21 days after surgery. The expression of NMDA receptor subtype 2B (NR2B) and ER stress markers in the spinal cord (L5) was evaluated. The ipsilateral side of the surgery in the ketamine group was less sensitive to mechanical and cold stimulations. The expression of NR2B on the ipsilateral side was significantly lower in the ketamine group than in the control group (18.93 ± 1.40% vs. 31.08 ± 0.74%, p < 0.05). All markers for ER stress on the ipsilateral side of the surgery in both groups had higher expression than those on the contralateral side. The expression of activating transcription factor-6 (ATF-6) on the ipsilateral side was significantly lower in the ketamine group than in the control group (p < 0.05). Systemic administration of ketamine inhibited the expression of NMDA receptors and improved NP symptoms. Among the markers of ER stress, the therapeutic effect of ketamine is associated with the inhibition of ATF-6 expression.

Background. Ischemia‐reperfusion injury and inflammation after tourniquet deflation in total knee arthroplasty are known to be associated with endothelial glycocalyx (EG) injury. This study is aimed at comparing EG injury between desflurane‐ and propofol‐based anesthesia in patients undergoing total knee arthroplasty. Materials and Methods. Patients were allocated to the desflurane group or propofol group. The opioid remifentanil was administered intraoperatively in both groups. Blood samples were obtained from the arterial line preoperatively, immediately before and 5 min after tourniquet deflation, and at 1, 6, and 24 h, postoperatively. Serum syndecan‐1, cytokines (interleukin‐1β, 6, 10, and tumour necrosis factor‐α), and other laboratory values were investigated. Results. Eighty patients were included in the final analysis. The change in syndecan‐1 did not significantly differ between the desflurane and propofol groups (peak median level of syndecan‐1; 754.5 pg/ml vs. 780.3 pg/ml, respectively, P = 0.512). Laboratory values (serum cytokines, creatinine phosphokinase, lactate dehydrogenase, and lactate levels) were also similar between the two groups. Pulmonary oxygenation was briefly improved after tourniquet deflation in the desflurane group but was similar between the two groups begging at 1 h, postoperatively. Conclusions. The effect of desflurane was not superior to that of propofol in protecting the EG from ischemia‐reperfusion injury during total knee arthroplasty. This trial is registered with Trial Registry Number NCT02756715 (http://clinicaltrials.gov).

Background: This study was designed to investigate the effect of cluster differentiation (CD)39 and CD73 inhibitors on the expresion of tumour-associated macrophages (TAMs), M1- versus M2-tumour phenotypes in mice with colon cancer. Methods: An in vivo study of co-culture with colon cancer cells and immune cells from the bone marrow (BM) of mice was performed. After the confirmation of the effect of polyoxotungstate (POM-1) as an inhibitor of CD39 on TAMs, the mice were randomly divided into a control group without POM-1 and a study group with POM-1, respectively, after subcutaneous injection of CT26 cells. On day 14 after the injection, the mice were sacrificed, and TAMs were evaluated using fluorescence-activated cell sorting. Results: In the in vivo study, the co-culture with POM-1 significantly increased the apoptosis of CT26 cells. The cell population from the co-culture with POM-1 showed significant increases in the expression of CD11b⁺ for myeloid cells, lymphocyte antigen 6 complex, locus C (Ly6C⁺) for monocytes, M1-tumour phenotypes from TAMs, and F4/80⁺ for macrophages. In the in vivo study, tumour growth in the study group with POM-1 was significantly limited, compared with the control group without POM-1. The expressions of Ly6C⁺ and major histocompatibility complex class II⁺ for M1-tumour phenotypes from TAMs on F4/80⁺ from the tumour tissue in the study group had significantly higher values compared with the control group. Conclusion: The inhibition of CD39 with POM-1 prevented the growth of colon cancer in mice, and it was associated with the increased expression of M1-tumour phenotypes from TAMs in the cancer tissue.

This study aimed to investigate the relationship between microglial activity and gut microbiota composition in a rat model of neuropathic pain (NP), and to evaluate how pregabalin treatment may influence these interrelated parameters. NP was simulated in rats via ligation and transection of the sciatic nerve. After confirming NP, the rats were randomly divided into treatment and control groups. Pregabalin (10 mg/kg) and the same dose of normal saline were administered to the treatment and control groups, respectively, on scheduled days. Microglial activity, cytokine levels, and the composition of the gut microbiota (assessed by the Firmicutes/Bacteroidetes (F/B) ratio) were evaluated. Pregabalin treatment significantly reduced microglial activity (which was notably lower in the treatment group than in the control group) and modulated pro-inflammatory and anti-inflammatory cytokine levels. While the F/B ratio in the control group significantly increased after NP surgery, the treatment group showed an initial increase followed by a notable decrease, approaching pre-surgery levels by day 28. This finding suggests that pregabalin treatment in rats with NP ameliorates microglial activity and is associated with a beneficial shift in the gut microbiota composition.

This study evaluated the effect of epigallocatechin-3-gallate (EGCG), a flavonoid, on postoperative cognitive dysfunction by modulating microglial phenotype expression in aged rats following general anesthesia with isoflurane. Eighteen-month-old male Sprague–Dawley rats were randomly assigned to the EGCG and control groups. EGCG in distilled water (DW) or DW alone was administered orally for 7 days before anesthesia. After anesthesia, cognitive function was assessed using the Y-maze test, and neuronal damage was evaluated histologically. Microglial activation and phenotype differentiation were also analyzed. At 24 h after anesthesia, the alternation ratio was significantly higher in the EGCG group than in the control group (70.00 ± 7.98% vs. 28.14 ± 11.52%, p < 0.001). The EGCG group exhibited reduced neuronal damage and microglial activation. Additionally, M1 phenotype activation was significantly lower (30.03 ± 7.73% vs. 51.00 ± 9.83%, p < 0.001), and M2 phenotype activation was significantly higher (17.61 ± 5.52% vs. 5.99 ± 2.46%, p < 0.001) in the EGCG group than in the control group. In summary, pre-anesthetic administration of EGCG modulated microglial phenotype differentiation, reduced neuronal damage, and improved postoperative cognitive function in aged rats following general anesthesia.