RESUMEN
Parabacteroides distasonis (P. distasonis) plays an important role in human health, including diabetes, colorectal cancer and inflammatory bowel disease. Here, we show that P. distasonis is decreased in patients with hepatic fibrosis, and that administration of P. distasonis to male mice improves thioacetamide (TAA)- and methionine and choline-deficient (MCD) diet-induced hepatic fibrosis. Administration of P. distasonis also leads to increased bile salt hydrolase (BSH) activity, inhibition of intestinal farnesoid X receptor (FXR) signaling and decreased taurochenodeoxycholic acid (TCDCA) levels in liver. TCDCA produces toxicity in mouse primary hepatic cells (HSCs) and induces mitochondrial permeability transition (MPT) and Caspase-11 pyroptosis in mice. The decrease of TCDCA by P. distasonis improves activation of HSCs through decreasing MPT-Caspase-11 pyroptosis in hepatocytes. Celastrol, a compound reported to increase P. distasonis abundance in mice, promotes the growth of P. distasonis with concomitant enhancement of bile acid excretion and improvement of hepatic fibrosis in male mice. These data suggest that supplementation of P. distasonis may be a promising means to ameliorate hepatic fibrosis.
Asunto(s)
Cirrosis Hepática , Piroptosis , Humanos , Ratones , Masculino , Animales , Cirrosis Hepática/metabolismo , Hígado/metabolismo , Hepatocitos/metabolismo , Ácidos y Sales Biliares/metabolismo , Caspasas/metabolismo , Ratones Endogámicos C57BLRESUMEN
Chitosan/poloxamer-based thermosensitive hydrogels containing zinc gluconate/recombinant human epidermal growth factor (ZnG/rhEGF@Chit/Polo) were developed as a convenient, safe and effective dressing for skin wound treatment. Their fabrication procedure and characterization were reported, and their morphology was examined by a scanning electron microscope. Antibacterial and biofilms activities were evaluated by in vitro tests to reveal the inhibitory effects and scavenging activity on the biofilms of Staphylococcus aureus and Pseudomonas aeruginosa. ZnG/rhEGF@Chit/Polo was also investigated as a potential therapeutic agent for wound healing therapy. In vivo wound healing studies on rats for 21 days proves that ZnG/rhEGF@Chit/Polo supplements the requisite Zn2+ and rhEGF for wound healing to promote the vascular remodeling and collagen deposition, facilitate fibrogenesis, and reduce the level of interleukin 6 for wound basement repair, and thus is a good wound therapy.
Asunto(s)
Quitosano , Animales , Antibacterianos/farmacología , Quitosano/farmacología , Factor de Crecimiento Epidérmico , Gluconatos , Humanos , Hidrogeles/farmacología , Poloxámero , Ratas , Cicatrización de HeridasRESUMEN
OBJECTIVE: This study aimed to determine the optimal extraction process and examine whether the combination of Flos Sophorae Immaturus (FSI) and Yupingfeng san (YPS) has a synergistic effect on free radical scavenging capacity. DESIGN AND METHODS: The time of immersion and extraction and the ratios (material/solvent) of the combination of YPS and FSI were optimized on the basis of polysaccharide and flavonoid yields via orthogonal design. The optimal result was used in the 1,1-diphenyl-1-picrylhydrazyl (DPPH) assay and animal experiments to test the antioxidant activity, which is reflected by superoxide dismutase, malondialdehyde, glutathione peroxidase, and total antioxidant capacity serum levels. The optimal extraction process was determined using various ingredients to obtain complex extracts with high active ingredient content and antioxidant activity. DPPH assay results showed that the optimized ingredients have antioxidant effects, and the combination had better antioxidation function than YPS in vitro. The combination also showed synergistic antioxidant activity compared with YPS in vivo. CONCLUSIONS: The combination of YPS and FSI had a synergistic antioxidant effect in vitro. The optimized extracts had antioxidant effects in vivo. These results indicated that YPS could be used with FSI to improve its antioxidant capacity in the body on the basis of free radical scavenging capacity.