Background Growing evidences have been revealing that long noncoding RNAs are vital factors in oncogenesis and tumor development. Among them, cancer susceptibility candidate 11 (CASC11) has displayed an impressively essential role in various kinds of cancers including hepatocellular carcinoma (HCC). Nevertheless, its role and potential mechanism in HCC still remain to be fully investigated. Methods CASC11 expression level was evaluated by real‐time polymerase chain reaction, western blotting, and in situ hybridization staining in HCC patients, and its prognostic effect was analyzed. The role of CASC11 in HCC tumorigenesis and progression was investigated by cell proliferation assay, transwell assay, extracellular acidification rate, western blotting, flow cytometry, and an in vivo xenograft model. The interactions among CASC11, E2F transcription factor 1 (E2F1), and eukaryotic translation initiation factor 4A3 (EIF4A3) were explored by using quantitative reverse transcriptase polymerase chain reaction, western blotting, RNA‐binding protein immunoprecipitation assay, and chromatin immunoprecipitation assays. Results Upregulation of CASC11 was confirmed in HCC tissues and associated with poor prognosis. Loss of function assays showed inhibition of CASC11 expression suppressed HCC cells proliferation, mobility, and glucose metabolism and promoted apoptosis. E2F1 expression significantly decreased after inhibition of CASC11. Rescue experiments illustrated that E2F1 overexpression alleviated the suppression of CASC11 inhibition on HCC progression in vitro and in vivo. Mechanistically, CASC11 recruited EIF4A3 to enhance the stability of E2F1 mRNA. CASC11 and E2F1 impacted the activation of the NF‐κB signaling and PI3K/AKT/mTOR pathway and further regulated the expression PD‐L1 that is an important target of immunotherapy. In addition, we identified YY1 could modulate CASC11 expression by binding to its promoter. Conclusions Our data revealed that CASC11 promoted the progression of HCC by means of EIF4A3‐mediated E2F1 upregulation, indicating CASC11 is a promising diagnostic biomarker and therapeutic target for HCC.

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Objectives Alzheimer's disease (AD) is a hidden neurological degenerative disease, which main clinical manifestations are cognitive dysfunction, memory impairment and mental disorders. Neuroinflammation is considered as a basic response of the central nervous system. NLRP3 (Nucleotide-binding domain leucine-rich repeat (NLR) and pyrin domain containing receptor 3) inflammasome is closely related to the occurrence of neuroinflammation. Activation of the NLRP3 inflammasome results in the release of cytokines, pore formation and ultimately pyroptosis, which has demonstrated one of the critical roles in AD pathogenesis. Inhibition of the activity of NLRP3 is one of the focuses of the research. Therefore, NLRP3 represents an attractive pharmacological target, and discovery compounds with good NLRP3 inhibitory activity are particularly important. Key findings Quinones have good neuroprotective effects and prevent AD, which may be related to their regulation of inflammatory response. The molecular docking was used to explore 12 quinones with AD prevention and treatment and NLRP3. Docking results showed that the combination of anthraquinones and NLRP3 were the best, and the top two chemical compounds were Purpurin and Rhein, which are the most promising NLRP3 inhibitors. Summary These quinones may provide the theoretical basis for finding lead compounds for novel neuroprotective agents. Quinones as NLRP3 inflammasomes inhibitors Da-bao Chen et al.

Objectives Chrysophanol (CHR), also well-known as Rhei radix et rhizome, is a crucial component in traditional Chinese medicine. It has been widely studied as a potential treatment for many diseases due to its anti-inflammatory effects. However, there are very few studies to establish the potential therapeutic effect of CHR in cell and animal models of Alzheimer’s disease (AD). Therefore, we aim to investigate whether CHR could be used as a potential therapeutic approach to patients with AD and further disclose the underlying mechanism. Increasing studies have shown that endoplasmic reticulum (ER) calcium (Ca2+) homeostasis emerges as a central player in AD pathogenesis. Moreover, augmentation of ER stress (ERS) promotes neuronal apoptosis, and excessive oxidative stress is an inducer of ERS. Therefore, we believe that ERS-mediated apoptosis may be one of the causes of AD. Methods This study examined the neuroprotective effects of CHR on AD rats and AD cell models and explored its potential mechanism. Key findings CHR could reduce the damage of neurons. In AD cell models, CHR significantly inhibited Aβ 25-35-induced neuronal damage, reduced the number of apoptotic cells and improved cell survival rate. Western blot showed that the expression of caspases 3, 9 and 12 was decreased after CHR treatment, and CHR also affected the ERS signalling pathway. In addition, the higher expression of pro-apoptotic proteins in the AD cell model was reduced after CHR treatment by inhibiting GRP78 signalling. Further studies have shown that overexpressed protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) inhibited the regulatory effect of CHR on PERK and weakened the neuroprotective effect of CHR on the AD cell model. Conclusions This study revealed a novel mechanism through which CHR plays a neuroprotective role by regulating ERS when it comes to the therapy of AD.

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