Objective:To evaluate the predictive value of secreted phosphoprotein 1(SPP1)gene expression for postoperative survival in patients with advanced liver cancer undergoing hepatic artery interventional chemoembolization...Objective:To evaluate the predictive value of secreted phosphoprotein 1(SPP1)gene expression for postoperative survival in patients with advanced liver cancer undergoing hepatic artery interventional chemoembolization treatment.Method:Bioinformatics methods,including gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,were used to identify genes related to survival prognosis in hepatocellular carcinoma(HCC)patients.A retrospective analysis of 115 advanced liver cancer patients treated between January 2016 and October 2017 was conducted.Patients were categorized into SPP1 high-expression(n=89)and low-expression groups(n=26).Additionally,115 healthy individuals served as the control group.The relationship between SPP1 expression and clinical pathological features was analyzed.A 60-month follow-up and logistic regression analysis identified risk factors affecting survival.Results:SPP1 mRNA expression was significantly higher in liver cancer patients compared to healthy controls(P<0.05).SPP1 expression levels were significantly associated with tumor size,Child-Pugh grading,lymph node metastasis,and BCLC staging(P<0.05).High SPP1 expression,along with tumor size,Child-Pugh grading,lymph node metastasis,and BCLC staging,were independent risk factors for survival(P<0.05).The 60-month survival rate was 17.39%,with a median survival of 40 months in the low-expression group versus 18 months in the high-expression group(P<0.05).Conclusion:SPP1 expression is significantly upregulated in advanced liver cancer patients and has predictive value for postoperative survival following hepatic artery chemoembolization treatment.SPP1,combined with clinical indicators such as tumor size,Child-Pugh grading,lymph node metastasis,and BCLC staging,may serve as a prognostic biomarker for interventional treatment outcomes.展开更多
BACKGROUND Neuropathic pain(NP)is the primary symptom of various neurological condi-tions.Patients with NP often experience mood disorders,particularly depression and anxiety,that can severely affect their normal live...BACKGROUND Neuropathic pain(NP)is the primary symptom of various neurological condi-tions.Patients with NP often experience mood disorders,particularly depression and anxiety,that can severely affect their normal lives.Microglial cells are as-sociated with NP.Excessive inflammatory responses,especially the secretion of large amounts of pro-inflammatory cytokines,ultimately lead to neuroinflam-mation.Microglial pyroptosis is a newly discovered form of inflammatory cell death associated with immune responses and inflammation-related diseases of the central nervous system.METHODS Two models,an in vitro lipopolysaccharide(LPS)-stimulated microglial cell model and a selective nerve injury model using BTX-A and SPP1 knockdown treatments,were used.Key proteins in the pyroptosis signaling pathway,NLRP3-GSDMD,were assessed using western blotting,real-time quantitative polymerase chain reaction,and immunofluorescence.Inflammatory factors[interleukin(IL)-6,IL-1β,and tumor necrosis factor(TNF)-α]were assessed using enzyme-linked immuno-sorbent assay.We also evaluated microglial cell proliferation and apoptosis.Furthermore,we measured pain sensation by assessing the delayed hind paw withdrawal latency using thermal stimulation.RESULTS The expression levels of ACS and GSDMD-N and the mRNA expression of TNF-α,IL-6,and IL-1βwere enhanced in LPS-treated microglia.Furthermore,SPP1 expression was also induced in LPS-treated microglia.Notably,BTX-A inhibited SPP1 mRNA and protein expression in the LPS-treated microglia.Additionally,depletion of SPP1 or BTX-A inhibited cell viability and induced apoptosis in LPS-treated microglia,whereas co-treatment with BTX-A enhanced the effect of SPP1 short hairpin(sh)RNA in LPS-treated microglia.Finally,SPP1 depletion or BTX-A treatment reduced the levels of GSDMD-N,NLPRP3,and ASC and suppressed the production of inflammatory factors.CONCLUSION Notably,BTX-A therapy and SPP1 shRNA enhance microglial proliferation and apoptosis and inhibit microglial death.It improves pain perception and inhibits microglial activation in rats with selective nerve pain.展开更多
基金Medical Research Project of Xi’an Science and Technology Bureau“Molecular Mechanism of miR-1305 Competitive Endogenous circRNA in the Development of Liver Cancer”(Project No.22YXYJ0134)General Project of Key Research and Development Program of Shaanxi Provincial Department of Science and Technology“Mechanism Study on the Inhibition of Liver Cancer Invasion and Metastasis by Downregulating METTL3 and Reducing the m6A Modification Level of MMP3 with Honokiol”(Project No.2023-YBSF-631)。
文摘Objective:To evaluate the predictive value of secreted phosphoprotein 1(SPP1)gene expression for postoperative survival in patients with advanced liver cancer undergoing hepatic artery interventional chemoembolization treatment.Method:Bioinformatics methods,including gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,were used to identify genes related to survival prognosis in hepatocellular carcinoma(HCC)patients.A retrospective analysis of 115 advanced liver cancer patients treated between January 2016 and October 2017 was conducted.Patients were categorized into SPP1 high-expression(n=89)and low-expression groups(n=26).Additionally,115 healthy individuals served as the control group.The relationship between SPP1 expression and clinical pathological features was analyzed.A 60-month follow-up and logistic regression analysis identified risk factors affecting survival.Results:SPP1 mRNA expression was significantly higher in liver cancer patients compared to healthy controls(P<0.05).SPP1 expression levels were significantly associated with tumor size,Child-Pugh grading,lymph node metastasis,and BCLC staging(P<0.05).High SPP1 expression,along with tumor size,Child-Pugh grading,lymph node metastasis,and BCLC staging,were independent risk factors for survival(P<0.05).The 60-month survival rate was 17.39%,with a median survival of 40 months in the low-expression group versus 18 months in the high-expression group(P<0.05).Conclusion:SPP1 expression is significantly upregulated in advanced liver cancer patients and has predictive value for postoperative survival following hepatic artery chemoembolization treatment.SPP1,combined with clinical indicators such as tumor size,Child-Pugh grading,lymph node metastasis,and BCLC staging,may serve as a prognostic biomarker for interventional treatment outcomes.
文摘BACKGROUND Neuropathic pain(NP)is the primary symptom of various neurological condi-tions.Patients with NP often experience mood disorders,particularly depression and anxiety,that can severely affect their normal lives.Microglial cells are as-sociated with NP.Excessive inflammatory responses,especially the secretion of large amounts of pro-inflammatory cytokines,ultimately lead to neuroinflam-mation.Microglial pyroptosis is a newly discovered form of inflammatory cell death associated with immune responses and inflammation-related diseases of the central nervous system.METHODS Two models,an in vitro lipopolysaccharide(LPS)-stimulated microglial cell model and a selective nerve injury model using BTX-A and SPP1 knockdown treatments,were used.Key proteins in the pyroptosis signaling pathway,NLRP3-GSDMD,were assessed using western blotting,real-time quantitative polymerase chain reaction,and immunofluorescence.Inflammatory factors[interleukin(IL)-6,IL-1β,and tumor necrosis factor(TNF)-α]were assessed using enzyme-linked immuno-sorbent assay.We also evaluated microglial cell proliferation and apoptosis.Furthermore,we measured pain sensation by assessing the delayed hind paw withdrawal latency using thermal stimulation.RESULTS The expression levels of ACS and GSDMD-N and the mRNA expression of TNF-α,IL-6,and IL-1βwere enhanced in LPS-treated microglia.Furthermore,SPP1 expression was also induced in LPS-treated microglia.Notably,BTX-A inhibited SPP1 mRNA and protein expression in the LPS-treated microglia.Additionally,depletion of SPP1 or BTX-A inhibited cell viability and induced apoptosis in LPS-treated microglia,whereas co-treatment with BTX-A enhanced the effect of SPP1 short hairpin(sh)RNA in LPS-treated microglia.Finally,SPP1 depletion or BTX-A treatment reduced the levels of GSDMD-N,NLPRP3,and ASC and suppressed the production of inflammatory factors.CONCLUSION Notably,BTX-A therapy and SPP1 shRNA enhance microglial proliferation and apoptosis and inhibit microglial death.It improves pain perception and inhibits microglial activation in rats with selective nerve pain.
