RÉSUMÉ
This study investigated the protective effect and related mechanisms of Xinhui citrus fermentation liquor on mice with ulcerative colitis. Animal experiments follow the rules of Animal Ethics Committee of Southern Medical University. C57BL/6 mice were given 3% dextran sodium sulfate (DSS) for 6 days to induce acute ulcerative colitis. During this period, Xinhui citrus fermentation liquor, decoction of Citrus reticulata blanco (both orally administrated with 300 mg·kg-1·d-1 crude polysaccharide) or positive drug 5-aminosalicylic acid (100 mg·kg-1·d-1) were gavaged continuously for 9 days. Cecal contents were collected for 16S rRNA sequencing analysis. The levels of inflammatory factors, tight junction proteins and nuclear factor erythroid 2 related factor 2 / Nod-like receptor protein 3 (Nrf2/NLRP3) pathway related proteins in the colon were detected by real-time PCR (RT-PCR), immunofluorescence and Western blot. Our results showed that Xinhui citrus fermentation liquor and Citrus reticulata blanco protected against UC-induced weight loss, diarrhea, bloody stool, and colon shortening. The mRNA and protein levels of pro-inflammatory factors, such as interleukin 6 (Il-6) and CXC chemokine ligand 10 (Cxcl10) and NLRP3 inflammasome were significantly decreased; the mRNA levels of colon anti-inflammatory factor (Il-10), tight junction protein [zonula occludens-1 (Zo-1), occludin, claudin-1], mucin 2 (Muc2), Nrf2, as well as the mRNA and protein levels of NAD(P)H quinine oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) were significantly increased. In addition, Xinhui citrus fermentation liquor increased the abundance of Akkermansia and reduced the abundance of harmful bacteria Enterococcus and Streptococcus. The correlation analysis showed that the abundance of Akkermansia was positively correlated with anti-inflammatory factors, tight junction protein and the related genes levels of Nrf2 signaling pathway. In summary, Xinhui citrus fermentation liquor ameliorates acute ulcerative colitis in mice via regulating intestinal bacteria homeostasis and Nrf2/NLRP3 pathway to repair intestinal mucosa.
RÉSUMÉ
BACKGROUND:To date,no single material can completely meet the clinical requirements.However,the composite materials characterized by good biodegradability,biocompatibility and osteoconductivity have become a highlight of the artificial bone materials.OBJECTIVE:To synthesize the basic fibroblast growth factor (bFGF)-poly(lactic-co-glycolic acid) (PLGA) microspheres/hydroxyapatite (HA)/poly(I-lactic acid) (PLLA) porous bone scaffolds,and to observe the physicochemical properties and biocompatibility of the composite material.METHODS:The bFGF-PLGA microspheres were prepared by double emulsion method,and then six kinds of materials were made including PLLA,PLLNHA,PLLAJPLGA,PLLNHNPLGA,PLLNHA/bFGF,and bFGF-PLGA microspheres/PLLA/HA.The characterization of the materials were observed by particle size analyzer,transmission electron microscopy,X-ray diffraction,Fourier transform infrared spectrometer,microcomputer differential thermal balance,and scanning electron microscope.Toxicity of these materials and proliferation of bone marrow mesechymal stem cells seeded onto these materials were analyzed and compared.RESULTS AND CONCLUSION:The average particle size of bFGF-PLGA microspheres was about 250 nm,the average drug-loading capacity was (26.03±0.17)％,and the entrapment percentage was (90.65±2.68)％.The prepared bFGF-PLGA microspheres were spherical and had good dispersibility.In addition,all the six kinds of materials had a porous structure with similar pore diameter,in which the microspheres and particles exhibited a rational distribution.The toxic level of bFGF-PLGA microspheres/PLLNHA,bFGF/HNPLLA and HAP/PLLA was graded as 1 (with a relative survival rate ≥ 80％),indicating no obvious toxicity or slight toxicity.All these six kinds of composite materials can promote the proliferation of bone marrow mesenchymal stem cells,and the bFGF-PLGA microspheres/PLLNHA shows the best effects on cell proliferation and has good biocompatibility.