Neuroinflammation and neuro-oxidative damage are now considered to be key factors in the neurological diseases. Therefore, it is important to study anti-inflammatory and neuroprotective agents. The present study investigated the anti-inflammatory and neuroprotective effects of catalpol (CAT), and the potential molecular mechanisms involved. The findings revealed that CAT markedly downregulated pro-inflammatory mediator nitric oxide (NO) and cytokines, including interleukin (IL)-6 and tumor necrosis factor (TNF)-a in lipopolysaccharide (LPS)-treated BV2 microglial cells. Moreover, CAT significantly decreased the levels of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA), increased superoxide dismutase (SOD) activity and glutathione (GSH) level, reversed apoptosis, and restored mitochondrial membrane potential (MMP) in primary cortical neurons stimulated with hydrogen peroxide (H 2 O 2 ). Furthermore, mechanistic studies showed that CAT inhibited nuclear factor-kB (NF-kB) pathway and p53-mediated Bcl-2/Bax/casaspe-3 apoptotic pathway. Moreover, it targeted the Kelchlike ECH-associated protein 1(Keap1)/Nuclear factor E2-related factor 2 (Nrf2) pathway. In summary, CAT may exert neuroprotective potential by attenuating microglial-mediated neuroinflammatory response through inhibition of the NF-kB signaling pathway. It blocked cortical neuronal oxidative damage by inhibiting p53-mediated Bcl-2/Bax/casaspe-3 apoptosis pathway and regulating Keap1/Nrf2 pathway. These results collectively indicate the potential of CAT as a highly effective therapeutic agent for neuroinflammatory and neuro-oxidative disorders.

Background Glioma is a heterogeneous aggressive tumor. Ropivacaine, a widely used anesthetic, has been shown to repress the progression of multiple cancers, including glioma. In this study, the effects of ropivacaine on cell proliferation, migration, invasion and apoptosis in glioma were revealed. Methods The expression levels of circSCAF11 and miR-145-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in glioma tissues and cells. The expression levels of epithelial–mesenchymal transition (EMT)-related proteins were determined by Western blot. Oxidative stress was evaluated by the measurement of reactive oxygen species (ROS) and determination of mitochondrial 8-hydroxy-2-deoxyguanosine (8-OHdG) assay in glioma cells. Cell proliferation was determined by cell counting kit-8 (CCK-8) assay and cell colony formation assay. Cell apoptosis and metastasis were detected by flow cytometry analysis and transwell assay, respectively. The binding relationship between circSCAF11 and miR-145-5p was predicted by circular RNA Interactome and identified by dual-luciferase reporter assay and RNA immunoprecipitation assay. In vivo tumor formation assay was performed to reveal the effects between ropivacaine and circSCAF11 overexpression on tumorigenesis in vivo. Results CircSCAF11 expression was obviously upregulated and miR-145-5p was significantly downregulated in glioma tissues and cells compared with control groups. Ropivacaine treatment upregulated E-cadherin protein expression and repressed the protein expression of Vimentin. Functionally, ropivacaine exposure promoted ROS and 8-OHdG production and cell apoptosis, whereas inhibited cell proliferation, migration and invasion; however, these effects were hindered by circSCAF11 overexpression. Mechanistically, circSCAF11 was a sponge of miR-145-5p. In addition, ropivacaine was revealed to inhibit tumor growth in vivo by regulating circSCAF11 and miR-145-5p expression. Conclusion Ropivacaine suppressed glioma progression by regulating circSCAF11 and miR-145-5p, which might provide a theoretical foundation in glioma treatment.

AbstractPseudogenes are pivotal funtional non-coding RNAs in tumorigenesis. Cumulative evidences have shown that pituitary tumor-transforming 3, pseudogene (PTTG3P), serves as an oncogene in multiple human cancers. However, its expression pattern, biological function, and potential targets in esophageal squamous cell carcinoma (ESCC) remain unknown. Here, by quantitative real-time polymerase chain reaction (qRT-PCR) in 50 cases of ESCC, we found that the expression of PTTG3P, PTTG1 and PTTG2 in esophageal squamous cancer tissues and cell lines were significantly higher than their normal counterparts (P<0.01). Spearman correlation analysis showed that the PTTG3P expression was positively correlated with the PTTG1 and PTTG2 expression in ESCC tissue samples (P<0.05). Additionally, the high expression of PTTG3P in ESCC was significantly correlated with tumor depth, lymph node invasion and TNM stage (P<0.05). We also assessed the function of PTTG3P in vitro by gain-of-function studies. Results showed that enhanced expression of PTTG3P stimulated the migration and invasion of ESCC cells, and promoted the expression level of PTTG1 and PTTG2 in vitro. Furthermore, PTTG3P fulfilled its oncogenic functions by positively regulating its parent gene PTTG1 and PTTG2. Overall, our study indicated that PTTG3P is distinctly overexpressed and exhibited oncogenic role in a PTTG1 and PTTG2 mediated manner in ESCC.