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Parkinson's disease (PD) is a common neurodegenerative disease with limited treatment and no cure, hence, broadening PD drug spectrum is of great significance. At present, engineered microorganisms are attracting increasing attention. In this study, we constructed an engineered strain of Clostridium butyricum-GLP-1, a C. butyricum (a probiotic) that consistently expresses glucagon-like peptide-1 (GLP-1, a peptide-based hormone with neurological advantage) in anticipation of its use in PD treatment. We further investigated the neuroprotective mechanism of C. butyricum-GLP-1 on PD mice models induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The results indicated that C. butyricum-GLP-1 could improve motor dysfunction and ameliorate neuropathological changes by increasing TH expression and reducing the expression of α-syn. Moreover, we confirmed that C. butyricum-GLP-1 improved microbiome imbalance of PD mice by decreasing the relative abundance of Bifidobacterium at the genus level, improved gut integrity, and upregulated the levels of GPR41/43. Surprisingly, we found it could exert its neuroprotective effects via promoting PINK1/Parkin mediated mitophagy and attenuating oxidative stress. Together, our work showed that C. butyricum-GLP-1 improves PD by promoting mitophagy, which provides an alternative therapeutic modality for PD.
RESUMO
AIM: To elucidate the effect of histone deacetylase(HDAC)inhibitor suberoylanilide hydroxamic acid(SAHA)on the proliferation of choroidal melanoma(CM)cell line C918 and to explore the related mechanism.METHODS: Inverted fluorescence microscope was used to observe the effect of different concentrations of SAHA(0.625, 1.25 or 2.5 μmol/L)on the morphology of C918 cell. The cell viability was detected by cholecystokinin octapeptide(CCK-8)assay. Plate clone formation assay and EdU staining were carried out to measure the effect of SAHA on the cell proliferation. Meanwhile, the expressions of cell proliferation-related proteins including c-Myc, CyclinA2 and CDK2, and histone deacetylase 7(HDAC7)and fibroblast growth factor 18(FGF18)were detected by Western blot.RESULTS: Compared with the control group, the cell density was reduced in SAHA. SAHA could also promote cell shrinkage, and the inhibition on cell was in a concentration-dependent manner. CCK-8 assay showed that SAHA treatment decreased cell viability in a dose-dependent manner and the inhibition rate was 80% when SAHA at 2.5 μmol/L. Compared with the control group, Western blot showed that SAHA could suppress the expression of cell proliferation proteins including c-Myc, CyclinA2 and CDK2 in a dose-dependent manner. In addition, 1.25 μmol/L SAHA significantly decreased the numbers of EdU staining positive cells and cell clones. More importantly, SAHA could dose-dependently decrease the expression of HDAC7 and FGF18 compared with control group.CONCLUSION: SAHA could inhibit the proliferation of CM cell line C918 by inhibiting the HDAC7/FGF18 signaling pathway.
RESUMO
<p><b>OBJECTIVE</b>To further study the binding character of hepatitis B surface antigen (HBsAg) and beta 2-glycoprotein I (beta2GP I) and to explore whether beta2GP I plays an important role in the hepatotropism of hepatitis B virus.</p><p><b>METHODS</b>Using Western blot technique, we observed the binding character of the HBsAg with reduced and non-reduced beta2GP I.</p><p><b>RESULTS</b>rHBsAgs with reduced and non-reduced beta2GP I showed identical binding activity.</p><p><b>CONCLUSIONS</b>The binding activity of HBsAg is dependent on tandem residues, but not on conformational structures of beta2GP I. There is a specific binding between HBV and beta2GP I, which may play an important role in HBV infection and is one of the reasons of hepatotropism of HBV.</p>
