Colonic Dopaminergic Neurons Changed Reversely With Those in the Midbrain via Gut Microbiota-Mediated Autophagy in a Chronic Parkinson's Disease Mice Model.

The role of gut-brain axis in the pathogenesis of Parkinson's disease (PD) have become a research hotspot, appropriate animal model to study gut-brain axis in PD is yet to be confirmed. Our study employed a classical PD mice model achieved by chronic MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) injection to study concurrent changes of dopaminergic neurons in the midbrain and the colon of mice. Our results showed such a PD model exhibited apparent locomotor deficits but not gastrointestinal dysfunction. Tyrosine hydroxylase expressions and dopamine content reduced greatly in the substantia nigra pars compacta (SNpc) or striatum, but increased in the colon of PD mice. Mechanism investigation indicated autophagy activity and apoptosis were stimulated in the SNpc, but inhibited in the colon of PD mice. Interplay of gut microbiota (GM) and autophagy in response to chronic MPTP injection led to GM dysbiosis and defective autophagy in mice colon. Meanwhile, fecal short chain fatty acids (SCFAs), acetate and propionate in particular, declined greatly in PD mice, which could be attributed to the decreased bacteria abundance of phylum Bacteroidetes, but increased abundance of phylum Firmicutes. GM dysbiosis derived fecal SCFAs might be one of the mediators of downregulated autophagy in the colon of PD mice. In conclusion, colonic dopaminergic neurons changed in the opposition direction with those in the midbrain via GM dysbiosis-mediated autophagy inhibition followed by suppressed apoptosis in response to chronic MPTP injection. Such a chronic PD mice model might not be an ideal model to study role of gut-brain axis in PD progression.

Potentiation of in Vivo Anticancer Efficacy of Selenium Nanoparticles by Mushroom Polysaccharides Surface Decoration.

Selenium nanoparticles (SeNPs) are recently emerging as promising anticancer agents because of their high bioavailability, low toxicity and remarkable anticancer activities. However, the effects of surface physicochemical properties on the biological actions remain elusive. Herein we decorated SeNPs with various water-soluble polysaccharides extracted from various mushrooms, to compare physical characteristics and anticancer profile of these SeNPs. The results showed that the prepared spherical SeNPs displayed particle sizes at 91-102 nm, and kept stable in aqueous solution for up to 13 weeks. However, different decoration altered the tumor selectivity of the SeNPs, while gastric adenocarcinoma AGS cells showed relative highest sensitivity. Moreover, PTR-SeNPs demonstrated potent in vivo antitumor, by inducing caspases- and mitochondria-mediated apoptosis, but showed no obvious toxicity to nomal organs. Taken together, this study offers insights into how surface decoration can tune the cancer selectivity of SeNPs and provides a basis for engineering particles with increased anticancer efficacy.

Autophagy is an important action mode for functionalized selenium nanoparticles to exhibit anti-colorectal cancer activity.

Selenium nanoparticles (SeNPs) have attracted much interest as potential anticancer nanodrugs. Our previous studies also demonstrated that SeNPs could be developed as carriers of clinically used anticancer drugs to achieve synergistic efficacy. Here, we describe the synthesis of Pleurotus tuber-regium (PTR)-conjugated SeNPs (PTR-SeNPs) and their application in the treatment of colorectal cancer (CRC), which is one of the principal causes of cancer morbidity and mortality in the world. PTR-SeNPs were absorbed by cancer cells via clathrin-mediated endocytosis into lysosomes and caveolae-mediated endocytosis into the Golgi apparatus. Internalized PTR-SeNPs trigger intracellular dose- and time-dependent G2/M phase arrest and apoptosis. Moreover, as shown by using a pEGFP-LC3 plasmid transfection model, PTR-SeNPs activate autophagy to promote the death of cancer cells via upregulation of beclin 1-related signaling pathways. In summary, this study demonstrates the high efficacy of functionalized SeNPs for therapy of colorectal cancer and reveals the important role of autophagy in promoting apoptosis and cell cycle arrest to induce cell death.

Polysaccharide-protein complex-decorated selenium nanosystem as an efficient bone-formation therapeutic.

Polysaccharide-protein complex-coated selenium nanoparticles (PTR-SeNPs) system has been rationally designed and identified as a potent bone-formation therapeutic to antagonize osteoporosis. The nanosystem presents high cellular uptake in osteoblast cells and significantly enhances bone formation in vitro and in vivo, mainly through BMP-2/Smad-mediated signalling pathways.