Glioblastoma (GBM) has become the most aggressive primary brain tumor in the world. Patients with GBM usually have a poor prognosis. The median survival times of GBM patients retain less than 2 years. Thus, it is urgent to investigate the molecular mechanism of GBM. Recently, studies have demonstrated that transcription factors (TFs) participate in cancer pathology by regulating long noncoding RNAs (lncRNAs). However, the functional and regulatory roles of TF‐lncRNA crosstalks are still unclear. In this study, we constructed a global lncRNA‐TF network (GLTN) based on competing endogenous RNA. As a result, some topological features of GLTN were identified. A known GBM lncRNA MCM3AP‐AS1 showed multiple central topological features in GLTN. Furthermore, we identified hub genes and extracted the hub‐hub pairs from GLTN to form a hub associated lncRNA‐TF network (HALTN). Results showed that a risk model combined with multiple hubs had a significant effect on prognosis. Additionally, we performed module searching and two functional modules from HALTN were identified, which were confirmed as risk factors of GBM. More importantly, we also identified some core lncRNA‐TF crosstalks that might form feedback loops to control the biological processes in GBM. Our results demonstrated that the synergistic, competitive lncRNA‐TF crosstalks played an important role in pathological processes of GBM, and had strong effect on prognosis. All these results can help us to uncover the molecular mechanism and provide a new therapeutic target for GBM.

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Sepsis is a systemic inflammatory response syndrome with high mortality. Acute liver injury is an independent predictor for poor prognosis in septic patients. Polygonatum sibiricum polysaccharides (PSP) have been reported to possess anti-inflammatory and hepatoprotective activities. To evaluate the effects of PSP on septic liver injury and demonstrate the potential molecular mechanisms, the septic acute liver injury (SALI) model was established in BALB/c mice via intraperitoneal injection of lipopolysaccharide (LPS). We found that PSP treatment could remarkably reduce the 48 h mortality rate of septic mice; alleviate liver histopathologic damage; lower the activity of neutrophil infiltration marker MPO in liver tissue; and decrease the levels of liver function indexes AST, ALT, ALP, and TBIL, inflammatory cytokines TNFα and IL-6, and pyroptosis-related inflammatory cytokines IL-18 and IL-1β in serum. TUNEL staining and detecting GSDMD-NT protein expression level in liver tissue revealed that PSP could restrain excessive pyroptosis. In addition, PSP treatment reversed the upregulations of mRNA expression levels of the NLRP3/GSDMD signals in the liver. Our results indicated the potential protective role of PSP against SALI by inhibiting pyroptosis via NLRP3/GSDMD signals.

Senescence of activated hepatic stellate cells (aHSCs) is a stable growth arrest that is implicated in liver fibrosis regression. Senescent cells often accompanied by a multifaceted senescence-associated secretory phenotype (SASP). Induction of aHSCs senescence by inhibiting SASP may be a potential therapeutic model against hepatic fibrosis. To evaluate the role of atractylenolide III (ATR III) in the development of chemotherapeutic drug-induced SASPs in hepatic stellate cells. Etoposide-induced senescent HSC-LX2 model was established and treated with ATR III at different concentrations (20, 30 and 40 μM). We found that ATR III dose-dependently enhanced senescence in etoposideinduced LX2 cells. ATR III dose-dependently decreased the release and expression of SASP factors (interleukin [IL]-1α, IL-1β, IL6 and IL-8) in senescent cells. ATR III regulated cyclic GMP-AMP synthase (cGAS)/nuclear factor κ (NF-κB) signalling to affect SASP expression in senescent cells. The addition of 2'3 0 cGAMP counteracted the effect of ATR III. The release of SASP factors in the conditioned medium from senescent cells could affect cell migration, proliferation and contraction through paracrine manner. Our results indicated ATR III could still enter senescence and prevent the production of SASP and its paracrine effects in senescent cells, an effect that may be related to the possible inhibition of cGAS/NF-κB signalling by ATR III. Our study proves that ATR III may be an effective potential drug against liver fibrosis by promoting aHSC senescence, which can provide a new choice for the future clinical treatment of liver fibrosis.