Metabolic syndrome(Met S)is a chronic disease associated with the disturbance of gut microbiota homeostasis.Metabolites derived from gut microbes play essential roles in Met S prevention and therapy.Here,we focused on...Metabolic syndrome(Met S)is a chronic disease associated with the disturbance of gut microbiota homeostasis.Metabolites derived from gut microbes play essential roles in Met S prevention and therapy.Here,we focused on the inhibitory effect of the extract of millet bran protein(EMBP)on a high-fat diet(HFD)-induced Met S,aiming to identify gut microbiota and their metabolites that involve in the anti-Met S activity of EMBP.The obesity,chronic inflammation,insulin resistance in Met S mouse models were abolished after EMBP treatment.The protective mechanism of EMBP against HFD-induced Met S may depend on improved gut barrier function.Using microbiome analysis,we found that EMBP supplementation improved gut microbiome dysbiosis in Met S mice,specifically upregulating Bacteroides acidifaciens.The fecal microbiota transplantation(FMT)also demonstrated this phenomenon.In addition,metabolomic analysis showed that EMBP mediates metabolic profiling reprogramming in Met S mice.Notably,a microbiota-derived metabolite,gamma-aminobutyric acid(GABA),is enriched by EMBP.In addition,exogenous GABA treatment produced a similar protective effect to EMBP by improving NRF2-dependent gut barrier function to protect HFDinduced Met S.The results suggest that EMBP suppress host Met S by remodeling of gut microbiota as an effective candidate for next-generation medicine food dual purpose dietary supplement to intervene in MetS.展开更多
Molecular targeted therapy has become an emerging promising strategy in cancer treatment,and screening the agents targeting at cancer cell specific targets is very desirable for cancer treatment.Our previous study fir...Molecular targeted therapy has become an emerging promising strategy in cancer treatment,and screening the agents targeting at cancer cell specific targets is very desirable for cancer treatment.Our previous study firstly found that a secretory peroxidase of class III derived from foxtail millet bran(FMBP)exhibited excellent targeting anti-colorectal cancer(CRC)activity in vivo and in vitro,whereas its underlying target remains unclear.The highlight of present study focuses on the finding that cell surface glucose-regulated protein 78(cs GRP78)abnormally located on CRC is positively correlated with the anti-CRC effects of FMBP,indicating it serves as a potential target of FMBP against CRC.Further,we demonstrated that the combination of FMBP with the nucleotide binding domain(NBD)of cs GRP78interfered with the downstream activation of signal transducer and activator of transcription 3(STAT3)in CRC cells,thus promoting the intracellular accumulation of reactive oxygen species(ROS)and cell grown inhibition.These phenomena were further confirmed in nude mice tumor model.Collectively,our study highlights cs GRP78 acts as an underlying target of FMBP against CRC,uncovering the clinical potential of FMBP as a targeted agent for CRC in the future.展开更多
基金supported by National Natural Science Foundation of China(32270420,32072220)National Key Research and Development Project(2020YFD1001405)+2 种基金Shanxi Province Science Foundation(202103021224011)Shanxi Key Laboratory for Research and Development of Regional PlantsShanxi Province“136”Revitalization Medical Project Construction Funds。
文摘Metabolic syndrome(Met S)is a chronic disease associated with the disturbance of gut microbiota homeostasis.Metabolites derived from gut microbes play essential roles in Met S prevention and therapy.Here,we focused on the inhibitory effect of the extract of millet bran protein(EMBP)on a high-fat diet(HFD)-induced Met S,aiming to identify gut microbiota and their metabolites that involve in the anti-Met S activity of EMBP.The obesity,chronic inflammation,insulin resistance in Met S mouse models were abolished after EMBP treatment.The protective mechanism of EMBP against HFD-induced Met S may depend on improved gut barrier function.Using microbiome analysis,we found that EMBP supplementation improved gut microbiome dysbiosis in Met S mice,specifically upregulating Bacteroides acidifaciens.The fecal microbiota transplantation(FMT)also demonstrated this phenomenon.In addition,metabolomic analysis showed that EMBP mediates metabolic profiling reprogramming in Met S mice.Notably,a microbiota-derived metabolite,gamma-aminobutyric acid(GABA),is enriched by EMBP.In addition,exogenous GABA treatment produced a similar protective effect to EMBP by improving NRF2-dependent gut barrier function to protect HFDinduced Met S.The results suggest that EMBP suppress host Met S by remodeling of gut microbiota as an effective candidate for next-generation medicine food dual purpose dietary supplement to intervene in MetS.
基金supported by National Natural Science Foundation of China(Nos.31500630,31770382,32072220,and 81803238)“1331 Project”Key Innovation Center and Team,National Key Research and Development Project(No.2020YFD1001405,China)+1 种基金Shanxi Key Laboratory for Research and Development of Regional Plants,Higher Education Institution Project of Shanxi Province:Ecological Remediation of Soil Pollution Disciplines Group(No.20181401,China)the Open Project Program of Xinghuacun College of Shanxi University[Shanxi Institute of Brewing Technology and Industry(Preparation)](No.XCSXUKF-202004,China)。
文摘Molecular targeted therapy has become an emerging promising strategy in cancer treatment,and screening the agents targeting at cancer cell specific targets is very desirable for cancer treatment.Our previous study firstly found that a secretory peroxidase of class III derived from foxtail millet bran(FMBP)exhibited excellent targeting anti-colorectal cancer(CRC)activity in vivo and in vitro,whereas its underlying target remains unclear.The highlight of present study focuses on the finding that cell surface glucose-regulated protein 78(cs GRP78)abnormally located on CRC is positively correlated with the anti-CRC effects of FMBP,indicating it serves as a potential target of FMBP against CRC.Further,we demonstrated that the combination of FMBP with the nucleotide binding domain(NBD)of cs GRP78interfered with the downstream activation of signal transducer and activator of transcription 3(STAT3)in CRC cells,thus promoting the intracellular accumulation of reactive oxygen species(ROS)and cell grown inhibition.These phenomena were further confirmed in nude mice tumor model.Collectively,our study highlights cs GRP78 acts as an underlying target of FMBP against CRC,uncovering the clinical potential of FMBP as a targeted agent for CRC in the future.
