We aimed to explore the mechanism of pramipexole (PPX) actions in the treatment of Parkinson’s disease (PD). Genes related to PD and PPX were screened through bioinformatics retrieval. The PD model was constructed by applying 1-methyl-4-phenylpyridinium (MMP+). The RNA expression levels of circSNCA, SNCA, apoptosis-related genes (BCL2, CASP3, BAX, PTEN and P53) and miR-7 were detected by qRT-PCR. Protein expression was determined by western blot. The interactions between circSNCA-miR-7-SNCA were verified by dual luciferase assay and immunofluorescence localization. Cell viability was determined by MTT assay. SNCA and circSNCA expression levels in PD were downregulated after PPX treatment, consistent with the levels of pro-apoptotic genes. CircSNCA increased SNCA expression by downregulating miR-7 in PD as a competitive endogenous RNA (ceRNA). Lower circSNCA expression was associated with the reduced expression of pro-apoptotic (CASP3, BAX, PTEN and P53) proteins. CircSNCA downregulation could decrease apoptosis and induce autophagy in PD. In conclusion, the downregulation of circSNCA by PPX treatment reduced cell apoptosis and promoted cell autophagy in PD via a mechanism that served as a miR-7 sponge to upregulate SNCA.

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Background/Aims: We aimed to explore the protective role of curcumin (Cur) in a cell model of Parkinson’s disease (PD) and its underlying mechanism. Methods: In this study, genes concerned with PD-related keywords were screened within DiGSeE database. The association network between Cur and selected genes was downloaded from STITCH, with the interactions analyzed by STRING. We built a mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP⁺)-induced SH-SY5Y cell model of PD. Cell morphology was observed under an electron microscope. MTT assay was applied to detect cell proliferation rate. Western blot assay was conducted to determine the level of apoptotic markers, including cleaved caspase 3, Bcl-2-associated X protein (Bax) and B-cell lymphoma-extra-large (Bcl-xl). Tyrosine hydroxylase (TH), dopamine transporter (DAT) protein levels and dopamine (DA) concentration were identified as dopaminergic neuron markers and measured by western blotting or Enzyme-linked immunosorbent assay (ELISA). Results: Cur rescued the toxicity effects of MPP⁺ on SH-SY5Y cells, by controlling morphological change, promoting cell proliferation and inhibiting apoptosis. Of all PD-related genes, HSP90 played an important role in Cur-gene network. HSP90 protein level was elevated by MPP⁺, whereas Cur could reverse this effect. Silencing of HSP90 significantly attenuated the curative effect introduced by Cur, while HSP90 overexpression enhanced the impact of Cur on PD. Conclusion: Cur can effectively inhibit the toxic effect of MPP⁺ on SH-SY5Y cells and significantly reduce the adverse effects of MPP⁺ on dopaminergic neurons via up-regulation of HSP90.

Background and objectivesMicroRNA-613 (miR-613), a novel cancer-related microRNA, has been shown to be responsible for the inhibition of tumor development and progression in various cancers. We aimed to investigate the biological function and regulatory mechanisms of miR-613 in gliomas.Materials and methodsmiR-613 expression were detected by qRT-PCR assays in glioma tissues and cell lines. Cell Counting Kit-8 (CCK-8) assay, colony formation analysis, wound healing and transwell invasion assays were performed to evaluate cell proliferation, colony formation, migration and invasion abilities. Luciferase reporter assays, qRT-PCR and Western blot were performed to explore the potential targets of miR-613. Xenograft mice model was established to evaluate the effect of miR-613 in vivo.ResultThe expression levels of miR-613 were significantly downregulated in the glioma tissues and cell lines, and the decreased level was significantly negatively associated with the overall disease-free survival of the patients. Functionally, ectopic expression of miR-613 in glioma cells suppressed the proliferation, colony formation, and migration and invasion of the cells. The sex-determining region Y-box 9 (SOX9) was identified as a direct functional target of miR-613, and its expression was inversely correlated with miR-613 expression in glioma tissues. Moreover, rescue of SOX9 could partially reverse the inhibitory effects of miR-613 on glioma cell proliferation, colony formation, migration, and invasion. Importantly, miR-613 also suppressed tumor growth in vivo by targeting SOX9.ConclusionTaken together, these findings demonstrate that miR-613 functions as a tumor suppressor in glioma cells by directly targeting SOX9.

Periodic paralysis (PP) is an uncommon inherited disorder causing recurrent episodes of muscle weakness, with an incidence of 0.001%. Normokalemic periodic paralysis (NormoKPP) as the rarest subtype of PP contains both familial and sporadic. Familial NormoKPP caused by the p.M1592V mutation of the skeletal muscle sodium channel alpha subunit (SCN4A) gene is rarely reported. Only three pedigrees of NormoKPP related to mutations in the SCN4A p.M1592V have been previously reported. We herein presented a family case of NormoKPP associated with the SCN4A p.M1592V mutation, in which respiratory muscle paralysis occurred in the proband while not in his children. Moreover, we conducted a thorough literature review. To our knowledge, this is the first report of respiratory muscle paralysis as a symptom of NormoKPP associated with mutation in the SCN4A p.M1592V.