hucMSC-derived exosomes attenuate colitis by regulating macrophage pyroptosis via the miR-378a-5p/NLRP3 axis.

BACKGROUND: Human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes are recognized as novel cell-free therapeutic agents for inflammatory bowel disease (IBD), a condition caused by dysregulated intestinal mucosal immunity. In this event, macrophage pyroptosis, a process of cell death following the activation of NLRP3 (NOD-like receptor family, pyrin domain-containing 3) inflammasomes, is believed to partially account for inflammatory reactions. However, the role of macrophage pyroptosis in the process of hucMSC-derived exosomes alleviating colitis remains unknown. This study aimed at exploring the therapeutic effect and mechanism of hucMSC-derived exosomes on colitis repair. METHODS: In vivo, we used BALB/c mice to establish a dextran sulfate sodium (DSS)-induced colitis model and administrated hucMSC-derived exosomes intravenously to estimate its curative effect. Human myeloid leukemia mononuclear (THP-1) cells and mouse peritoneal macrophages (MPMs) were stimulated with lipopolysaccharides (LPS) and Nigericin to activate NLRP3 inflammasomes, which simulated an inflammation environment in vitro. A microRNA mimic was used to verify the role of miR-378a-5p/NLRP3 axis in the colitis repair. RESULTS: hucMSC-derived exosomes inhibited the activation of NLRP3 inflammasomes in the mouse colon. The secretion of interleukin (IL)-18, IL-1ß, and Caspase-1 cleavage was suppressed, resulting in reduced cell pyroptosis. The same outcome was observed in the in vitro cell experiments, where the co-culture of THP-1 cells and MPMs with hucMSC-derived exosomes caused decreased expression of NLRP3 inflammasomes and increased cell survival. Furthermore, miR-378a-5p was highly expressed in hucMSC-derived exosomes and played a vital function in colitis repair. CONCLUSION: hucMSC-derived exosomes carrying miR-378a-5p inhibited NLRP3 inflammasomes and abrogated cell pyroptosis to protect against DSS-induced colitis.

Preparation, Surface Modification, and Characteristic of α-Fe2O3 Nanoparticles.

The α-Fe2O3 nanoparticles were prepared via the co-precipitation process, and they were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and selected area electron diffraction (SAED). The effect of the water bath temperature on the average grain size of the α-Fe2O3 nanoparticles was investigated. The minimum grain size of the α-Fe2O3 nanoparticles was 19.6 nm when the water bath temperature was 40 °C. Furthermore, the α-Fe2O3 nanoparticles were successfully modified with silica (SiO2) and chitosan (CTS) using the idea of nanoarchitectonics. the experimental results showed that, the average diameter of the as-prepared α-Fe2O3/SiO2 nanocomposites was around 65 nm; while, the average hydrodynamic diameter of the α-Fe2O3/CTS nanocomposites increased gradually with the increase of chitosan in solution. When the mass ratio of chitosan and the α-Fe2O3 nanoparticles reached 40:1, the diameter distribution range of the α-Fe2O3/CTS nanocomposites was very wide of 100- 900 nm, so the mass ratio of chitosan and the α-Fe2O3 nanoparticles was selected from 10:1 to 20:1 to be applied.