查看更多>>摘要：Intervertebral disc degeneration(IDD)is the cause of low back pain(LBP),and recent research has suggested that inflammatory cytokines play a significant role in this process.Maslinic acid(MA),a natural compound found in olive plants(Olea europaea),has anti-inflammatory properties,but its potential for treating IDD is unclear.The current study aims to investigate the effects of MA on TNFα-induced IDD in vitro and in other in vivo models.Our findings suggest that MA ameliorates the imbalance of the extracellular matrix(ECM)and mitigates senescence by upre-gulating aggrecan and collagen Ⅱ levels as well as downregulating MMP and ADAMTS levels in nucleus pulposus cells(NPCs).It can also impede the progression of IDD in rats.We further find that MA significantly affects the PI3K/AKT and NF-κB pathways in TNFα-induced NPCs determined by RNA-seq and experimental verification,while the AKT agonist Sc-79 eliminates these signaling cascades.Furthermore,molecular docking simulation shows that MA directly binds to PI3K.Dysfunction of the PI3K/AKT pathway and ECM metabolism has also been confirmed in clinical specimens of degenerated nucleus pulposus.This study demonstrates that MA may hold promise as a therapeutic agent for alleviating ECM metabolism disorders and senescence to treat IDD.
查看更多>>摘要：Acute lung injury(ALI)is a serious condition characterized by damage to the lungs.Recent research has revealed that activation of the NLRP3 inflammasome in alveolar macrophages,a type of immune cell in the lungs,plays a key role in the development of ALI.This process,known as pyroptosis,contributes significantly to ALI pathogenesis.Researchers have conducted comprehensive bioinformatics analyses and identified 15 key genes associated with alveolar macrophage pyroptosis in ALI.Among these,NLRP3 has emerged as a crucial regulator.This study further reveal that the ULK1 protein diminishes the expression of NLRP3,thereby reducing the immune response of alveolar macrophages and mitigating ALI.Conversely,TRAF3,another protein,is found to inhibit ULK1 through a process called ubiquitination,leading to increased activation of the NLRP3 inflammasome and exacerbation of ALI.This TRAF3-mediated suppression of ULK1 and subsequent activation of NLRP3 are confirmed through various in vitro and in vivo experiments.The presence of abundant M0 and M1 alveolar macrophages in the ALI tissue samples further support these findings.This research highlights the TRAF3-ULK1-NLRP3 regulatory axis as a pivotal pathway in ALI development and suggests that targeting this axis could be an effective therapeutic strategy for ALI treatment.
查看更多>>摘要：DPP3,a dipeptidyl peptidase,participates in a variety of pathophysiological processes.DPP3 is upregulated in cancer and might serve as a key factor in the tumorigenesis and progression of various malignancies.However,its specific role and molecular mechanism are still unknown.In this study,the expression of DPP3 in breast cancer tissues is analyzed using TCG A database.Kaplan-Meier survival analysis is performed to estimate the effect of DPP3 on the survival outcomes.To explore the biological function and mechanisms of DPP3 in breast cancer,biochemical and cell biology assays are conducted in vitro.DPP3 expresses at a higher level in breast cancer tissues than that in adjacent tissues in both TCGA database and clinical samples.Patients with high expression of DPP3 have poor survival outcomes.The proliferation and migration abilities of tumor cells with stable DPP3 knockout in breast cancer cell lines are significantly inhibited,and apoptosis is increased in vitro.GSEA analysis shows that DPP3 can affect lipid metabolism and fatty acid synthesis in tumors.Subsequent experiments show that DPP3 could stabilize FASN expression and thus promote fatty acid synthesis in tumor cells.The results of the metabolomic analysis also confirm that DPP3 can affect the content of free fatty acids.This study demonstrates that DPP3 plays a role in the reprogramming of fatty acid metabolism in tumors and is associated with poor prognosis in breast cancer patients.These findings will provide a new therapeutic target for the treatment of breast cancer.
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