BACKGROUND Inflammatory bowel disease(IBD)is a common chronic intestinal inflammatory disease.High oxidative stress is a treatment target for IBD.Cerium oxide(CeO2)nanomaterials as nanozymes with antioxidant activity ...BACKGROUND Inflammatory bowel disease(IBD)is a common chronic intestinal inflammatory disease.High oxidative stress is a treatment target for IBD.Cerium oxide(CeO2)nanomaterials as nanozymes with antioxidant activity are potential drugs for the treatment of colitis.AIM To synthesize hollow cerium(H-CeO2)nanoparticles by one-step method and to validate the therapeutic efficacy of H-CeO2 in IBD.METHODS H-CeO2 was synthesized by one-step method and examined its characterization and nanoenzymatic activity.Subsequently,we constructed dextran sulfate so-dium(DSS)-induced colitis in mice to observe the effects of H-CeO2 on colonic inflammation.The effects of H-CeO2 on colon inflammation and reactive oxygen species(ROS)levels in IBD mice were detected by hematoxylin and eosin staining and dichlorofluorescein diacetate staining,respectively.Finally,the biological sa-fety of H-CeO2 on mice was evaluated by hematoxylin and eosin staining,blood routine,and blood biochemistry.RESULTS H-CeO2 nanoparticles prepared by the one-step method were uniform,monodi-sperse and hollow.H-CeO2 had a good ability to scavenge ROS,∙OH and∙OOH.H-CeO2 reduced DSS-induced decreases in body weight and colon length,colonic epithelial damage,inflammatory infiltration,and ROS accumulation.H-CeO2 administration reduced the disease activity index of DSS-induced animals from about 8 to 5.H-CeO2 had no significant effect on body weight,total platelet count,hemoglobin,white blood cell,and red blood cell counts in healthy mice.No significant damage to major organs was observed in healthy mice following H-CeO2 administration.CONCLUSION The one-step synthesis of H-CeO2 nanomaterials had good antioxidant activity,biosafety,and inhibited deve-lopment of DSS-induced IBD in mice by scavenging ROS.展开更多
Skeletal muscle plays a key role in metabolic homeostasis. Brg1/Brm-associated factor (Baf) 60c, a subunit of the mating type switching/sucrose non-fermenting (SWI/SNF) chromatin remodeling complexes, was previously i...Skeletal muscle plays a key role in metabolic homeostasis. Brg1/Brm-associated factor (Baf) 60c, a subunit of the mating type switching/sucrose non-fermenting (SWI/SNF) chromatin remodeling complexes, was previously identified to be robustly involved in glycolytic muscle function and systemic metabolic balance. However, whether Baf60c regulates the secreted factors and couples the skeletal muscle function to systemic metabolism remains unclear. Here, we uncover that Baf60c regulates the expression of a series of secreted factors, among which Musclin, a recently identified negative regulator of beige adipocyte thermogenesis, was top-ranked in the upregulated factors in Baf60c-deficient muscle. Mechanistically, Baf60c physically interacts with the transcription factor myocyte enhancer factor 2c (Mef2c) and modulates the chromatin accessibility at the proximal promoter regions upstream of the Musclin gene transcription start site (TSS), therefore negatively regulating Musclin gene expression in the skeletal muscle. Further in vivo metabolic assays demonstrate that muscle-specific Baf60c ablation inhibits thermogenesis and elevates blood glucose. Conversely, muscle-specific overexpression of Baf60c increases thermogenesis and energy expenditure and improves systemic glucose metabolism. Together, this work uncovers Baf60c/Mef2c-mediated chromatin remodeling signaling in myocytes that control adipose tissue thermogenesis and systemic metabolism through Musclin-mediated muscle-fat crosstalk.展开更多
文摘BACKGROUND Inflammatory bowel disease(IBD)is a common chronic intestinal inflammatory disease.High oxidative stress is a treatment target for IBD.Cerium oxide(CeO2)nanomaterials as nanozymes with antioxidant activity are potential drugs for the treatment of colitis.AIM To synthesize hollow cerium(H-CeO2)nanoparticles by one-step method and to validate the therapeutic efficacy of H-CeO2 in IBD.METHODS H-CeO2 was synthesized by one-step method and examined its characterization and nanoenzymatic activity.Subsequently,we constructed dextran sulfate so-dium(DSS)-induced colitis in mice to observe the effects of H-CeO2 on colonic inflammation.The effects of H-CeO2 on colon inflammation and reactive oxygen species(ROS)levels in IBD mice were detected by hematoxylin and eosin staining and dichlorofluorescein diacetate staining,respectively.Finally,the biological sa-fety of H-CeO2 on mice was evaluated by hematoxylin and eosin staining,blood routine,and blood biochemistry.RESULTS H-CeO2 nanoparticles prepared by the one-step method were uniform,monodi-sperse and hollow.H-CeO2 had a good ability to scavenge ROS,∙OH and∙OOH.H-CeO2 reduced DSS-induced decreases in body weight and colon length,colonic epithelial damage,inflammatory infiltration,and ROS accumulation.H-CeO2 administration reduced the disease activity index of DSS-induced animals from about 8 to 5.H-CeO2 had no significant effect on body weight,total platelet count,hemoglobin,white blood cell,and red blood cell counts in healthy mice.No significant damage to major organs was observed in healthy mice following H-CeO2 administration.CONCLUSION The one-step synthesis of H-CeO2 nanomaterials had good antioxidant activity,biosafety,and inhibited deve-lopment of DSS-induced IBD in mice by scavenging ROS.
基金supported by the grants from the National Natural Science Foundation of China(82100904,81670740,82300910,82425012,32471170,and 92457301)the Zhejiang Provincial Natural Science Foundation of China(LQ21C110001 and LQ23H070005).
文摘Skeletal muscle plays a key role in metabolic homeostasis. Brg1/Brm-associated factor (Baf) 60c, a subunit of the mating type switching/sucrose non-fermenting (SWI/SNF) chromatin remodeling complexes, was previously identified to be robustly involved in glycolytic muscle function and systemic metabolic balance. However, whether Baf60c regulates the secreted factors and couples the skeletal muscle function to systemic metabolism remains unclear. Here, we uncover that Baf60c regulates the expression of a series of secreted factors, among which Musclin, a recently identified negative regulator of beige adipocyte thermogenesis, was top-ranked in the upregulated factors in Baf60c-deficient muscle. Mechanistically, Baf60c physically interacts with the transcription factor myocyte enhancer factor 2c (Mef2c) and modulates the chromatin accessibility at the proximal promoter regions upstream of the Musclin gene transcription start site (TSS), therefore negatively regulating Musclin gene expression in the skeletal muscle. Further in vivo metabolic assays demonstrate that muscle-specific Baf60c ablation inhibits thermogenesis and elevates blood glucose. Conversely, muscle-specific overexpression of Baf60c increases thermogenesis and energy expenditure and improves systemic glucose metabolism. Together, this work uncovers Baf60c/Mef2c-mediated chromatin remodeling signaling in myocytes that control adipose tissue thermogenesis and systemic metabolism through Musclin-mediated muscle-fat crosstalk.
