Objective:To investigate the effects of bromodomain and extraterminal domain (BET) inhibitor JQ1 combined with siPD-L1 on the proliferation and apoptosis of oral squamous cell carcinoma (OSCC) Scc-25 cells and its mechanism.Methods:Scc-25 cells were cultured in vitro and treated with different concentrations of JQ1 (0, 0.2, 1, 5 μmol/L). Cell proliferation was detected by cell count kit-8 (CCK-8) assay; the expression levels of programmed cell death ligand 1(PD-L1) and forkhead box M1(FoxM1) protein were detected by Western blot. Appropriate concentration of JQ1 was selected for subsequent experiments. Scc-25 cells were divided into four groups: control group (without any treatment), siPD-L1 group (transfected with siPD-L1), JQ1 group (added JQ1 after transfected with non-specific siRNA), and combined treatment group (added JQ1 after transfected with siPD-L1). CCK-8 assay was used to detect the proliferation ability of Scc-25 cells in each group. Western blot was used to detect the expression levels of cleaved caspase-3, PD-L1 and FoxM1, and flow cytometry was used to detect the apoptosis rate of cells in each group. Results:With the increase of JQ1 concentration, the proliferation ability of SCC-25 cells and the expression levels of PD-L1 and FoxM1 decreased gradually (all P<0.01). JQ1 concentration of 1 μmol/L had obvious inhibitory effect on cell proliferation and the expression levels of PD-L1 and FoxM1, so JQ1 concentration of 1 μmol/L was selected for subsequent experiments. The proliferation ability of Scc-25 cells, the expression of PD-L1 and FoxM1 proteins in JQ1 group, siPD-L1 group and combination treatment group were significantly lower than those in the control group (all P<0.01), and the expression of cleaved caspase-3 protein and the rate of apoptosis were significantly higher than those in the control group (all P<0.01); Moreover, the effect of the combination treatment group was more significant than that of siPD-L1 group, JQ1 group (all P<0.01). Conclusions:The combination of JQ1 and siPD-L1 could effectively inhibit the proliferation and promotes the apoptosis of OSCC Scc-25 cells, and its mechanism may be related to the suppression of PD-L1 and FoxM1 signaling pathways.

Objective:To explore the effect of silent information regulator 1 (SIRT1) activator SRT1720 on inflammatory response in chronic periodontal disease mice and whether its mechanism is related to the toll like receptor 4 (TLR4)/nuclear factor κB (NF-κB) signaling pathway.Methods:Forty 8-week-old male C57BL/6 mice were selected and divided into a blank control group ( n=8) and an experimental group ( n=32). The experimental group mice were ligated with periodontal pockets and fed with high sugar drinking water. The experimental group was randomly divided into a model group ( n=8) and an SRT1720 group ( n=24). The blank control group and the model group were given physiological saline orally every day. The SRT1720 group was further divided into a low dose group [20 mg/(kg·d), n=8], a medium dose group [50 mg/(kg·d), n=8], and a high dose group [100 mg/(kg·d), n=8] based on the different doses of SRT1720. Four weeks later, the expression levels of interleukin-6 (IL-6), interleukin-1β (IL-1β) and monocyte chemoattractant protein-1 (MCP-1) in gingival crevicular fluid of mice in each group were detected by enzyme linked immunosorbent assay (ELISA); The real-time quantitative polymerase chain reaction (RT-qPCR) method was used to detect the mRNA expression levels of IL-6, IL-1β, MCP-1, SIRT1, TLR4, NF-kB p65 in the gingival tissue of mice in each group; Western blot was used to determine the expression levels of SIRT1, TLR4, and NF-κB p65 proteins in mouse gingival tissue. Results:Compared with the blank control group, the expression levels of IL-6, IL-1β, and MCP-1 inflammatory factors in the gingival crevicular fluid of experimental group mice increased, while the expression levels of IL-6, IL-1β, MCP-1, TLR4, NF-κB p65 mRNA in gingival tissue increased. The expression levels of TLR4, NF-κB p65 protein in gingival tissue increased, while the expression levels of SIRT1 mRNA and protein in gingival tissue decreased, with statistical significance (all P<0.05). Compared with the model group, the expression levels of IL-6, IL-1β, and MCP-1 inflammatory factors in the gingival crevicular fluid, IL-6, IL-1β, MCP-1, TLR4, NF-κB p65 mRNA expression levels in gingival tissue, and TLR4, NF-κB p65 protein expression levels in the gingival tissue of SRT1720 group mice showed a dose-dependent decrease. The expression levels of SIRT1 mRNA and protein in gingival tissue showed a dose-dependent increase, and the differences were statistically significant (all P<0.05). Conclusions:SIRT1 activator SRT1720 can improve the inflammatory response of chronic periodontal disease mice, which may be related to the inhibition of TLR4/NF-kB signaling pathway.

Objective To explore the prognostic value of serum gap connexin 43(Cx43)and galectin-9(Gal-9)levels in elderly patients with acute cerebral infarction(ACI)after ultra-early intravenous thrombo-lytic therapy.Methods A total of 106 elderly patients with ACI who received ultra-early intravenous throm-bolytic therapy in the hospital from September 2020 to September 2022 were selected as the study group,and 100 healthy subjects who came to the hospital for physical examination during the same period were selected as the health group.The levels of Cx43 and Gal-9 in serum of all subjects were detected by enzyme-linked im-munosorbent assay(ELISA).After 2 weeks of treatment,106 elderly ACI patients were divided into good prognosis group(81 cases)and poor prognosis group(25 cases)according to the National Institutes of Health Stroke Scale(NIHSS)score.Receiver operating characteristic(ROC)curve was used to analyze the evaluation value of serum Cx43 and Gal-9 in the prognosis of ultra-early intravenous thrombolytic therapy in elderly ACI patients.Multivariate Logistic regression analysis was used to explore the influencing factors of poor prognosis of ultra-early intravenous thrombolytic therapy in elderly ACI patients.Results The levels of Cx43 and Gal-9 in the study group were higher than those in the health group(P＜0.05).The levels of Cx43 and Gal-9 in the poor prognosis group were higher than those in the good prognosis group(P＜0.05).The area under the curve(AUC)of serum Cx43 and Gal-9 for predicting the poor prognosis in elderly ACI patients was 0.721(95％CI:0.673-0.758)and 0.837(95％CI:0.787-0.886),respectively,and the AUC of combined detection of CX43 and GAL-9 was 0.901(95％CI:0.857-0.946).The proportion of hypertension in the poor progno-sis group was higher than that in the good prognosis group(P＜0.05).Hypertension(OR=3.487,95％CI:1.564-7.773),serum Cx43≥106.53 pg/mL(OR=4.586,95％CI:1.982-10.611),serum Gal-9≥11.84 ng/mL(OR=4.345,95％CI:1.957-9.648)were risk factors for poor prognosis in elderly patients with ACI after ultra-early intravenous thrombolysis(P＜0.05).Conclusion Serum Cx43 and Gal-9 are highly expressed in elderly ACI patients,which could be used to evaluate the prognosis of elderly ACI patients after ultra-early intravenous thrombolysis therapy,and their combined detection has higher evaluation value.