High-mobility group box chromosomal protein (HMGB-1) contributes to osteoarthritis (OA) by modulating various oxidative, inflammatory and apoptotic signaling pathways. The effect of chrysin (CH), a natural plant flavonoid, and its functional interaction with HMGB-1, was investigated in a chondrocyte model of OA. Human chondrocytes were pre-treated with CH, and then subsequently treated with IL-1β to induce the formation of chondrocytes similar to those found in OA joints. Next, the expression level of HMGB-1 was determined by immunofluorescence and western blot analysis. Additionally, inflammatory factor expression was measured by ELISA, and cell apoptosis was analyzed with flow cytometry. To further explore the effects of CH, HMGB-1 expression was silenced following CH treatment with small interfering (si)RNA. The results demonstrated that CH inhibited cell apoptosis, dose-dependently reduced matrix metalloproteinase (MMP) 13, collagenase and IL-6 expression, and increased collagen α-1 (II) chain (COL2A1) expression in human osteoarthritis chondrocytes. These effects of CH were accompanied by decreased HMGB-1 expression. Additionally, the expression of MMP13, collagenase, IL-6 and COL2A1, as well as apoptosis, was significantly reduced by HMGB-1 siRNA. These results demonstrated that HMGB-1 is critical for the protective effect of CH on human osteoarthritis chondrocytes, including cell apoptosis and inflammatory factor inhibition, which suggests that CH may have potential therapeutic effect in treating OA by protecting human osteoarthritis chondrocytes via HMGB1 suppression.
Objective. Sufentanil is the most common drug in clinical practice for the treatment of ischemic heart disease. This study is to investigate the protective mechanism of sufentanil on rat myocardial ischemia-reperfusion (I/R) injury. Methods. A rat I/R model was established by ligating the left anterior descending coronary artery. A total of 24 SD male rats were enrolled and divided randomly into the control group, I/R group, sufentanil group (SUF; 3 μg/kg), and diltiazem group (DLZ; 20 mg/kg; positive control). The rat hearts were subjected to 30 min of ischemia followed by 120 min of reperfusion. Subsequently, hemodynamics, pathological changes of myocardial tissue, serum biochemical parameters, oxidative stress factors, the level of serum inducible nitric oxide synthases (iNOS), interleukin-6 (IL-6), and other bioactive factors were analyzed in the rats. Result. Compared with the I/R group, sufentanil significantly improved cardiac action, myocardial fiber, and cardiomyocyte morphology and reduced inflammatory cell infiltration in rats in the SUF group. And the level of creatine kinase isoenzyme (CK-MB), troponin (cTn), lactate dehydrogenase (LDH), malondialdehyde (MDA), iNOS, and IL-6 was significantly declined in the serum of SUF group, while the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were significantly activated in the myocardial tissues. In addition, sufentanil also significantly decreased the protein expression of GRP78, CHOP, Caspase 12, and ATF6 in the myocardial tissue of the SUF group. Conclusion. Sufentanil has a significant protective activity on myocardial I/R injury in rats, the mechanism of which may be associated with the inhibition of endoplasmic reticulum stress and oxidative stress.
Purpose: This study is aimed to investigate the analgesic effect of combined dexmedetomidine and thoracic paravertebral nerve block (TPVB) on gastric cancer (GC) patients undergoing open gastrectomy.Methods: From May 2019 to Nov 2020, a total of 80 GC patients preparing for open gastrectomy were enrolled in our hospital and were divided into the ropivacaine (RO) group and the ropivacaine + dexmedetomidine (RD) group ad libitum. All of the patients underwent TPVB. The characteristics, usage of patient-controlled analgesia (PCA), adverse events, visual analogue scale (VAS) scores, in ammatory cytokines, and T cell subgroups between the two groups were compared. Patients in the RD group showed the decreased occurrence rate of postoperative adverse events and VAS scores and improved anti-in ammation and immune function.Results: These ndings implied that the application of dexmedetomidine in combination with ropivacaine in TPVB has a good postoperative analgesic effect, as well as anti-in ammatory and immune-enhancing effects.Conclusion: Thus, dexmedetomidine as an adjunct analgesic may be potentially applied in clinical practice for GC patients undergoing open gastrectomy.
Objectives Anesthetic drugs had been reported may impact the bio-behavior of the tumor. Propofol and sevoflurane are common anesthetics in the operation for glioblastoma (GBM). This study aims to establish a co-expression prognostic-related genes signature base on propofol and sevoflurane anesthesia to predict prognosis and immunotherapy response in GBM. Method GPM tissues with different anesthetics gene expression profiles (GSE179004) were obtained from the Gene Expression Omnibus (GEO) database. Core modules and central genes associated with propofol and sevoflurane anesthesia were identified by weighted gene coexpression network analysis (WGCNA) and establish a risk score prognostic model. Immune cell signature analysis in TCGA datasets was predicted via CIBERSORT. At last, serum methylation level of O6-methylguanine-DNA methyltransferase (MGMT) promoter was detected in GPM patient in different time during perioperative period. Results The burlywood1 group screened was significantly associated with sevoflurane-treated GBM tissue. 22 independent prognostic differential genes were construct a prognostic-related genes risk score in GBM, and showed good predictive ability. The risk score was strongly correlated with the age of the patients, but not with the sex of the patients. In addition, the differential responses to immunotherapy in high and low risk groups were analyzed, indicating that sevoflurane signature genes were consistent in the classification of gliomas. High-risk patients have high T-cell damage score and are less sensitive to immunotherapy. At last, serum methylation level of MGMT promoter was decreased in GBM patients during propofol and sevoflurane anesthesia. Conclusions Propofol and sevoflurane anesthesia associated impact on the gene expression of GBM, included the methylation level of MGMT promoter. Propofol and sevoflurane anesthesia-based risk score prognostic model, which has good prognostic power and is an independent prognostic factor in GBM patients. Therefore, this model can be used as a new biomarker for judging the prognosis of GBM patients. KEY MESSAGES Propofol and sevoflurane anesthesia-based risk score prognostic model has good prognostic power and is an independent prognostic factor in GBM patients. High Propofol and sevoflurane anesthesia-based risk score GBM patients have high T-cell damage scores and are less sensitive to immunotherapy. Serum methylation level of MGMT promoter decrease during propofol and sevoflurane anesthesia in GBM patients.
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