This study aimed to explore the effect of Bifidobacterium animalis F1-7 on the improvement of atherosclerotic inflammation.Arteriosclerosis model ApoE^(-/-)mice were orally administered with B.animalis F1-7 for 12 wee...This study aimed to explore the effect of Bifidobacterium animalis F1-7 on the improvement of atherosclerotic inflammation.Arteriosclerosis model ApoE^(-/-)mice were orally administered with B.animalis F1-7 for 12 weeks.The probiotic intervention reduced the plaque areas in aorta and the accumulation of macrophages,and downregulated the expression of toll-like receptor 4(TLR4)/nuclear factorκB(NF-κB)pathway to reduce the levels of inflammatory factors.The widely-targeted metabolomics analysis showed that acetyl-L-carnitine(ALC)in the intestine of atherosclerotic mice was significantly increased after B.animalis F1-7 intervention.Correlation analysis proved that ALC was associated with atherosclerotic inflammatory response.By using oxidized low density lipoprotein induced macrophage foam cells,we further verified that ALC could reduce lipid accumulation and inflammatory response in foam cells by downregulating the TLR4/NF-κB pathway.Finally,our results revealed that B.animalis F1-7 upregulated the metabolite ALC to downregulate the inflammatory responses,leading to the reduction of plaque accumulation of atherosclerosis.展开更多
Background C16:0 and cis-9 C18:1 may have different effects on animal growth and health due to unique metabolism in vivo.This study was investigated to explore the different effects of altering the ratio of C16:0 and ...Background C16:0 and cis-9 C18:1 may have different effects on animal growth and health due to unique metabolism in vivo.This study was investigated to explore the different effects of altering the ratio of C16:0 and cis-9 C18:1 in fat supplements on growth performance,lipid metabolism,intestinal barrier,cecal microbiota,and inflammation in fattening bulls.Thirty finishing Angus bulls(626±69 kg,21±0.5 months)were divided into 3 treatments according to the randomized block design:(1)control diet without additional fat(CON),(2)CON+2.5%palmitic acid calcium salt(PA,90%C16:0),and(3)CON+2.5%mixed fatty acid calcium salt(MA,60%C16:0+30%cis-9 C18:1).The experiment lasted for 104 d,after which all the bulls were slaughtered and sampled for analysis.Results MA tended to reduce 0–52 d dry matter intake compared to PA(DMI,P=0.052).Compared with CON and MA,PA significantly increased 0–52 d average daily gain(ADG,P=0.027).PA tended to improve the 0–52 d feed conversion rate compared with CON(FCR,P=0.088).Both PA and MA had no significant effect on 52–104 days of DMI,ADG and FCR(P>0.05).PA tended to improve plasma triglycerides compared with MA(P=0.077),significantly increased plasma cholesterol(P=0.002)and tended to improve subcutaneous adipose weight(P=0.066)when compared with CON and MA.Both PA and MA increased visceral adipose weight compared with CON(P=0.021).Only PA increased the colonization of Rikenellaceae,Ruminococcus and Proteobacteria in the cecum,and MA increased Akkermansia abundance(P<0.05).Compared with CON,both PA and MA down-regulated the m RNA expression of Claudin-1 in the jejunum(P<0.001),increased plasma diamine oxidase(DAO,P<0.001)and lipopolysaccharide(LPS,P=0.045).Compared with CON and MA,PA down-regulated the ZO-1 in the jejunum(P<0.001)and increased plasma LPS-binding protein(LBP,P<0.001).Compared with CON,only PA down-regulated the Occludin in the jejunum(P=0.013).Compared with CON,PA and MA significantly up-regulated the expression of TLR-4 and NF-κB in the visceral adipose(P<0.001)and increased plasma IL-6(P<0.001).Compared with CON,only PA up-regulated the TNF-αin the visceral adipose(P=0.01).Compared with CON and MA,PA up-regulated IL-6 in the visceral adipose(P<0.001),increased plasma TNF-α(P<0.001),and reduced the Ig G content in plasma(P=0.035).Compared with CON,PA and MA increased C16:0 in subcutaneous fat and longissimus dorsi muscle(P<0.05),while more C16:0 was also deposited by extension and desaturation into C18:0 and cis-9 C18:1.However,neither PA nor MA affected the content of cis-9 C18:1 in longissimus dorsi muscle compared with CON(P>0.05).Conclusions MA containing 30%cis-9 C18:1 reduced the risk of high C16:0 dietary fat induced subcutaneous fat obesity,adipose tissue and systemic low-grade inflammation by accelerating fatty acid oxidative utilization,improving colonization of Akkermansia,reducing intestinal barrier damage,and down-regulating NF-κB activation.展开更多
Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AF...Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AFB_(1)induces podocyte inflammation,proteinuria and renal dysfunction.Studying the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse glomeruli.Reduction of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte inflammation.We also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway activation.Overexpression of miR-9 or deletion of CXCR4 suppressed AFB_(1)-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney dysfunction.Our findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB_(1)-induced glomerular podocyte inflammation.Our study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.展开更多
High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the ex...High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.展开更多
基金supported by Shandong Taishan industry leading talent project(LJNY202101)the National Key R&D of China(2018YFC0311201)。
文摘This study aimed to explore the effect of Bifidobacterium animalis F1-7 on the improvement of atherosclerotic inflammation.Arteriosclerosis model ApoE^(-/-)mice were orally administered with B.animalis F1-7 for 12 weeks.The probiotic intervention reduced the plaque areas in aorta and the accumulation of macrophages,and downregulated the expression of toll-like receptor 4(TLR4)/nuclear factorκB(NF-κB)pathway to reduce the levels of inflammatory factors.The widely-targeted metabolomics analysis showed that acetyl-L-carnitine(ALC)in the intestine of atherosclerotic mice was significantly increased after B.animalis F1-7 intervention.Correlation analysis proved that ALC was associated with atherosclerotic inflammatory response.By using oxidized low density lipoprotein induced macrophage foam cells,we further verified that ALC could reduce lipid accumulation and inflammatory response in foam cells by downregulating the TLR4/NF-κB pathway.Finally,our results revealed that B.animalis F1-7 upregulated the metabolite ALC to downregulate the inflammatory responses,leading to the reduction of plaque accumulation of atherosclerosis.
基金financially supported by the earmarked fund for CARS36,the Natural Science Foundation of Heilongjiang Province(YQ2023C011)the National Key Research and Development Program of China(2023YFD2000701)the Key Research and Development Program of Heilongjiang Province(GZ20230028)。
文摘Background C16:0 and cis-9 C18:1 may have different effects on animal growth and health due to unique metabolism in vivo.This study was investigated to explore the different effects of altering the ratio of C16:0 and cis-9 C18:1 in fat supplements on growth performance,lipid metabolism,intestinal barrier,cecal microbiota,and inflammation in fattening bulls.Thirty finishing Angus bulls(626±69 kg,21±0.5 months)were divided into 3 treatments according to the randomized block design:(1)control diet without additional fat(CON),(2)CON+2.5%palmitic acid calcium salt(PA,90%C16:0),and(3)CON+2.5%mixed fatty acid calcium salt(MA,60%C16:0+30%cis-9 C18:1).The experiment lasted for 104 d,after which all the bulls were slaughtered and sampled for analysis.Results MA tended to reduce 0–52 d dry matter intake compared to PA(DMI,P=0.052).Compared with CON and MA,PA significantly increased 0–52 d average daily gain(ADG,P=0.027).PA tended to improve the 0–52 d feed conversion rate compared with CON(FCR,P=0.088).Both PA and MA had no significant effect on 52–104 days of DMI,ADG and FCR(P>0.05).PA tended to improve plasma triglycerides compared with MA(P=0.077),significantly increased plasma cholesterol(P=0.002)and tended to improve subcutaneous adipose weight(P=0.066)when compared with CON and MA.Both PA and MA increased visceral adipose weight compared with CON(P=0.021).Only PA increased the colonization of Rikenellaceae,Ruminococcus and Proteobacteria in the cecum,and MA increased Akkermansia abundance(P<0.05).Compared with CON,both PA and MA down-regulated the m RNA expression of Claudin-1 in the jejunum(P<0.001),increased plasma diamine oxidase(DAO,P<0.001)and lipopolysaccharide(LPS,P=0.045).Compared with CON and MA,PA down-regulated the ZO-1 in the jejunum(P<0.001)and increased plasma LPS-binding protein(LBP,P<0.001).Compared with CON,only PA down-regulated the Occludin in the jejunum(P=0.013).Compared with CON,PA and MA significantly up-regulated the expression of TLR-4 and NF-κB in the visceral adipose(P<0.001)and increased plasma IL-6(P<0.001).Compared with CON,only PA up-regulated the TNF-αin the visceral adipose(P=0.01).Compared with CON and MA,PA up-regulated IL-6 in the visceral adipose(P<0.001),increased plasma TNF-α(P<0.001),and reduced the Ig G content in plasma(P=0.035).Compared with CON,PA and MA increased C16:0 in subcutaneous fat and longissimus dorsi muscle(P<0.05),while more C16:0 was also deposited by extension and desaturation into C18:0 and cis-9 C18:1.However,neither PA nor MA affected the content of cis-9 C18:1 in longissimus dorsi muscle compared with CON(P>0.05).Conclusions MA containing 30%cis-9 C18:1 reduced the risk of high C16:0 dietary fat induced subcutaneous fat obesity,adipose tissue and systemic low-grade inflammation by accelerating fatty acid oxidative utilization,improving colonization of Akkermansia,reducing intestinal barrier damage,and down-regulating NF-κB activation.
基金funded by Suzhou Science and Technology Council(SNG201907)Universities Natural Science Foundation of Jiangsu Province(20KJB330002)+6 种基金General Program of China Postdoctoral Science Foundation(2022M711369)the Startup Funding of Soochow University,Jiangsu Province-Suzhou Science and Technology Planning Project(SL T201917)National Natural Science Foundation of China(32172922,31972741)Natural Science Foundation of Jiangsu Province of China(BK20211216,BK20221091)the Startup Funding of Hefei University of Technology(1302003712022058)China-CEEC Joint University Education Project(202010)the Excellence Project PrF UHK(2217/2022-2023)。
文摘Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AFB_(1)induces podocyte inflammation,proteinuria and renal dysfunction.Studying the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse glomeruli.Reduction of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte inflammation.We also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway activation.Overexpression of miR-9 or deletion of CXCR4 suppressed AFB_(1)-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney dysfunction.Our findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB_(1)-induced glomerular podocyte inflammation.Our study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.
基金supported by a grant of the M.D.-Ph.D./Medical Scientist Training Program through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(to HK)+3 种基金supported by National Research Foundation of Korea(NRF)grants funded by the Korean government(MSITMinistry of Science and ICT)(NRF2019R1A5A2026045 and NRF-2021R1F1A1061819)a grant from the Korean Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(HR21C1003)New Faculty Research Fund of Ajou University School of Medicine(to JYC)。
文摘High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.
