As an active component extracted from Chinese herb moutan cortex and roots of paeonia lactiflora pallas, paeonol possesses many biological activities, including anti-inflammatory and vascular protection activities. In...As an active component extracted from Chinese herb moutan cortex and roots of paeonia lactiflora pallas, paeonol possesses many biological activities, including anti-inflammatory and vascular protection activities. In this study, athero-protective effects of paeonol were investigated in apoliprotein E deficient（Apo E^–/–） mice through the entire course of atherosclerotic development. Apo E^–/– mice were divided into five groups and fed a high-cholesterol diet（HCD） for 5, 15 and 25 weeks. Then they were fed either paeonol or atorvastatin for 6 weeks. The methods, such as ELISA for serum lipid and cytokine analyses, Western blotting for protein expressions, and HE and oil-red o-staining method, were used for evaluation of thoracic aorta lesion area. The results showed that paeonol could significantly reduce body weight, blood lipid, total cholesterol（TC）, triglyceride（TG） and low density lipoprotein（LDL-C） in Apo E^–/– mice at all stages of the atherosclerosis process. Paeonol also reduced the levels of anti-inflammation factors, such as tumor necrosis factor-α（TNF-α）, interleukin（IL）-6, oxidized LDL cholesterol（ox-LDL）, in serum. In paeonol groups, SOD was significantly increased, whereas MDA was decreased compared with the HCD group（P0.01）. Paeonol markedly attenuated the thickness of the lipid-rich plaque and down-regulated the expressions of VCAM-1 and MMP-9 in aorta of mice, suggesting that paeonol could inhibit formation of plaque and stabilize plaques. Taken together, paeonol appeared to have anti-dyslipidemia and anti-atherosclerotic effects by lipid regulation, and it could inhibit the effects of inflammation and oxidative stress on HCD-fed Apo E^–/– mice through the entire course of atherosclerotic development.展开更多
Aberration of lipid storage in lipid droplets (LD) has been linked with the development and progression of several common metabolic diseases including obesity, type II diabetes,
In the context of a surging demand for functional foods,this study utilized Sophora japonica L.(SL)and Rosa rugosa Thunb.(RT),which are rich in polyphenols(with flavonoids as the core subclass).High-purity extracts(SL...In the context of a surging demand for functional foods,this study utilized Sophora japonica L.(SL)and Rosa rugosa Thunb.(RT),which are rich in polyphenols(with flavonoids as the core subclass).High-purity extracts(SLE and RTE)were obtained through ethanol reflux extraction and macroporous resin purification,and then formulated with maltodextrin and erythritol to prepare a composite solid beverage.This beverage exhibited excellent antioxidant capabilities.At a concentration of 1 mg/mL,the scavenging rates of DPPH,ABTS,and hydroxyl radicals reached 82.4%,94.6%,and 49.2%,respectively.Network pharmacology indicated that quercetin andβ-sitosterol could modulate lipid metabolism pathways.Moreover,the beverage showed potential for lipid-lowering.Its cholate adsorption capacity was 589.4±2.9 mg/g at pH 7.0,and the IC50 value for pancreatic lipase inhibition was 32.55 mg/mL.However,a 60-day storage stability test revealed that the moisture content approached 5%,likely due to polyphenol-flavonoid reactivity,extending dissolution time to 30.88 s.These changes were attributed to polyphenols(with flavonoids as the core active subclass,and non-flavonoids such as phenolic acids as auxiliary),resulting in color alterations and reduced solubility.This study confirmed the dual functions of the SL-RT beverage in antioxidant and lipid-lowering aspects.Nevertheless,it also pointed out the need to optimize the formula and process to enhance stability,providing an important basis for the development of stable functional beverages.展开更多
Receptor for Advanced Glycation End-products(RAGE) binds to a number of ligand families to display important roles in hyperglycemia, senescence, inflammation, neurodegeneration and cancer. It is reported that RAGE reg...Receptor for Advanced Glycation End-products(RAGE) binds to a number of ligand families to display important roles in hyperglycemia, senescence, inflammation, neurodegeneration and cancer. It is reported that RAGE regulates the related biological processes via homo-dimerization by the transmembrane(TM) domain, and evidence further shows that the intracellular domain of RAGE has an influence on the dimerization activity of RAGE. In this study, we explored the underlying interaction mechanism of RAGE TM domains by multiscale coarse-grained(CG) dynamic simulations. Two switching packing modes of the TM dimeric conformations were observed. Through a series of site-directed mutations, we further emphasized the key roles of the A342xxxG346xxG349xxxT353xxL356xxxV360motif in the left-handed configuration and the L345xxxG349xxG352xxxL356motif in the right-handed configuration. In addition, we revealed that the juxtamembrane(JM) domain within JM-A375 can determine the RAGE TM dimeric structure. Overall, we provide the molecular insights into the switching dimerization of RAGE TM domains, as well as the regulation from the JM domains mediated by the anionic lipids.展开更多
Lipid catabolism in germinating seeds provides energy and substrates for initial seedling growth,but how this process is regulated is not well understood.Here,we show that an AT-hook motif-containing nuclear localized...Lipid catabolism in germinating seeds provides energy and substrates for initial seedling growth,but how this process is regulated is not well understood.Here,we show that an AT-hook motif-containing nuclear localized(AHL)protein regulates lipid mobilization and fatty acid p-oxidation during seed germination and seedling establishment.AHL4 was identified to directly interact with the lipid mediator phosphatidic acid(PA).Knockout(KO)of AHL4 enhanced,but overexpression(OE)of AHL4 attenuated,triacylglycerol(TAG)degradation and seedling growth.Normal seedling growth of the OE lines was restored by sucrose supplementation to the growth medium.AHL4-OE seedlings displayed decreased expression of genes involved in TAG hydrolysis and fatty acid oxidation,whereas the opposite was observed in AHL4-KOs.These genes contained AHL4-binding cis elements,and AHL4 was shown to bind to the promoter regions of genes encoding the TAG lipases SDP1 and DALL5 and acyl-thioesterase KAT5.These AHL4-DNA interactions were suppressed by PA species that bound to AHL4.These results indicate that AHL4 suppresses lipid catabolism by repressing the expression of specific genes involved in TAG hydrolysis and fatty acid oxidation,and that PA relieves AHL4-mediated suppression and promotes TAG degradation.Thus,AHL4 and PA together regulate lipid degradation during seed germination and seedling establishment.展开更多
Foam cells play a pivotal role in the progression of atherosclerosis progression by triggering inflammation within arterial walls.They release inflammatory molecules that attract additional immune cells,leading to fur...Foam cells play a pivotal role in the progression of atherosclerosis progression by triggering inflammation within arterial walls.They release inflammatory molecules that attract additional immune cells,leading to further macrophage recruitment and plaque development.In this study,we develop an osteopontin(OPN)antibody-conjugated niobium carbide(Nb_(2)C-aOPN)MXenzyme designed to selectively target and mildly ablate foam cells while reducing inflammation in the plaque microenvironment.This approach utilizes photonic hyperthermia to decrease plaque size by enhancing cholesterol regulation through both passive cholesterol outflow and positive cholesterol efflux.Nb_(2)C-aOPN MXenzyme exhibits multiple enzyme-mimicking properties,including catalase,superoxide dismutase,peroxidase and glutathione peroxidase,and acts as a scavenger for reactive oxygen and nitrogen species.The inhibition of reactive oxygen and nitrogen species synergizes with photothermal ablation to promote positive cholesterol efflux,leading to reduced macrophage recruitment and a shift in macrophage phenotype from M1 to M2.This integrative strategy on cholesterol regulation and anti-inflammation highlights the potential of multifunctional 2D MXenzyme-based nanomedicine in advancing atherosclerotic regression.展开更多
In vitro gut microbiota fermentation characteristics and anti-adipogenic effect of Bangia fusco-purpurea polysaccharide extracted with ultra-high pressure assisted extraction(UBFP)were investigated.Compared with polys...In vitro gut microbiota fermentation characteristics and anti-adipogenic effect of Bangia fusco-purpurea polysaccharide extracted with ultra-high pressure assisted extraction(UBFP)were investigated.Compared with polysaccharide obtained with traditional hot water extraction(BFP),UBFP significantly increased intestinal flora diversity and induced a beneficial shift in the microbial composition,which could suppress the growth of opportunistic pathogens such as Escherichia-Shigella and Streptococcus,while enriching the abundance of bene-ficial bacteria such as Enterococcus.Both BFP and UBFP increased short-chain fatty acids(SCFAs)production,particularly acetic acid.The total SCFAs content in the UBFP group showed a 1.83-fold greater increase than that in the BFP group relative to the control.Furthermore,UBFP fermented products could better inhibit 3T3-L1 preadipocytes from differentiating into mature adipocytes as well as lowering triglyceride and total choles-terol contents and inhibiting lipid droplet formation.Notably,the reduction of TG content by UBFP fermented products showed 1.07-to 2.87-fold greater efficacy than BFP fermented products(p<0.05).Western blot analysis revealed that UBFP fermentation products upregulated the pAMPK/AMPK ratio and downregulated PPARγexpression in 3T3-L1 cells,suggesting that the anti-adipogenic effect may be mediated through activation of the AMPK signaling pathway and inhibition of PPARγexpression.Although these bioactivities of UBFP were assessed using in vitro models and requires further validation through in vivo studies,this research nevertheless provided valuable insights into the potential role of UBFP in promoting intestinal health and regulating lipid metabolism.展开更多
基金National Natural Science Foundation of China(Grant No.81473386,81773937)Natural Science Fund of Education Department of Anhui Province(Grant No.KJ2015A061)Excellent Researcher Award Program of Anhui Province(Grant No.gxyq ZD2016135)
文摘As an active component extracted from Chinese herb moutan cortex and roots of paeonia lactiflora pallas, paeonol possesses many biological activities, including anti-inflammatory and vascular protection activities. In this study, athero-protective effects of paeonol were investigated in apoliprotein E deficient（Apo E^–/–） mice through the entire course of atherosclerotic development. Apo E^–/– mice were divided into five groups and fed a high-cholesterol diet（HCD） for 5, 15 and 25 weeks. Then they were fed either paeonol or atorvastatin for 6 weeks. The methods, such as ELISA for serum lipid and cytokine analyses, Western blotting for protein expressions, and HE and oil-red o-staining method, were used for evaluation of thoracic aorta lesion area. The results showed that paeonol could significantly reduce body weight, blood lipid, total cholesterol（TC）, triglyceride（TG） and low density lipoprotein（LDL-C） in Apo E^–/– mice at all stages of the atherosclerosis process. Paeonol also reduced the levels of anti-inflammation factors, such as tumor necrosis factor-α（TNF-α）, interleukin（IL）-6, oxidized LDL cholesterol（ox-LDL）, in serum. In paeonol groups, SOD was significantly increased, whereas MDA was decreased compared with the HCD group（P0.01）. Paeonol markedly attenuated the thickness of the lipid-rich plaque and down-regulated the expressions of VCAM-1 and MMP-9 in aorta of mice, suggesting that paeonol could inhibit formation of plaque and stabilize plaques. Taken together, paeonol appeared to have anti-dyslipidemia and anti-atherosclerotic effects by lipid regulation, and it could inhibit the effects of inflammation and oxidative stress on HCD-fed Apo E^–/– mice through the entire course of atherosclerotic development.
文摘Aberration of lipid storage in lipid droplets (LD) has been linked with the development and progression of several common metabolic diseases including obesity, type II diabetes,
文摘In the context of a surging demand for functional foods,this study utilized Sophora japonica L.(SL)and Rosa rugosa Thunb.(RT),which are rich in polyphenols(with flavonoids as the core subclass).High-purity extracts(SLE and RTE)were obtained through ethanol reflux extraction and macroporous resin purification,and then formulated with maltodextrin and erythritol to prepare a composite solid beverage.This beverage exhibited excellent antioxidant capabilities.At a concentration of 1 mg/mL,the scavenging rates of DPPH,ABTS,and hydroxyl radicals reached 82.4%,94.6%,and 49.2%,respectively.Network pharmacology indicated that quercetin andβ-sitosterol could modulate lipid metabolism pathways.Moreover,the beverage showed potential for lipid-lowering.Its cholate adsorption capacity was 589.4±2.9 mg/g at pH 7.0,and the IC50 value for pancreatic lipase inhibition was 32.55 mg/mL.However,a 60-day storage stability test revealed that the moisture content approached 5%,likely due to polyphenol-flavonoid reactivity,extending dissolution time to 30.88 s.These changes were attributed to polyphenols(with flavonoids as the core active subclass,and non-flavonoids such as phenolic acids as auxiliary),resulting in color alterations and reduced solubility.This study confirmed the dual functions of the SL-RT beverage in antioxidant and lipid-lowering aspects.Nevertheless,it also pointed out the need to optimize the formula and process to enhance stability,providing an important basis for the development of stable functional beverages.
基金supported by the National Natural Science Foundation of China (Nos. 21672019, 21372026, 21402006)the Fundamental Research Funds for the Central Universities (No. XK1701)partly supported by CHEMCLOUDCOMPUTING
文摘Receptor for Advanced Glycation End-products(RAGE) binds to a number of ligand families to display important roles in hyperglycemia, senescence, inflammation, neurodegeneration and cancer. It is reported that RAGE regulates the related biological processes via homo-dimerization by the transmembrane(TM) domain, and evidence further shows that the intracellular domain of RAGE has an influence on the dimerization activity of RAGE. In this study, we explored the underlying interaction mechanism of RAGE TM domains by multiscale coarse-grained(CG) dynamic simulations. Two switching packing modes of the TM dimeric conformations were observed. Through a series of site-directed mutations, we further emphasized the key roles of the A342xxxG346xxG349xxxT353xxL356xxxV360motif in the left-handed configuration and the L345xxxG349xxG352xxxL356motif in the right-handed configuration. In addition, we revealed that the juxtamembrane(JM) domain within JM-A375 can determine the RAGE TM dimeric structure. Overall, we provide the molecular insights into the switching dimerization of RAGE TM domains, as well as the regulation from the JM domains mediated by the anionic lipids.
基金The work is supported by grants from the National Key Research and Development Program of China(2017YFE0104800)National Natural Science Foundation of China(31801029)+1 种基金the U.S.Department of Energy(DESC0001295)the Agriculture and Food Research Initiative(AFRI)(award no.2016-67013-24429,project accession number 1007600)from the USDA National Institute of Food and Agriculture,and the International Postdoctoral Exchange Fellowship Program 2016 of the Office of China Postdoctoral Council(20160034).
文摘Lipid catabolism in germinating seeds provides energy and substrates for initial seedling growth,but how this process is regulated is not well understood.Here,we show that an AT-hook motif-containing nuclear localized(AHL)protein regulates lipid mobilization and fatty acid p-oxidation during seed germination and seedling establishment.AHL4 was identified to directly interact with the lipid mediator phosphatidic acid(PA).Knockout(KO)of AHL4 enhanced,but overexpression(OE)of AHL4 attenuated,triacylglycerol(TAG)degradation and seedling growth.Normal seedling growth of the OE lines was restored by sucrose supplementation to the growth medium.AHL4-OE seedlings displayed decreased expression of genes involved in TAG hydrolysis and fatty acid oxidation,whereas the opposite was observed in AHL4-KOs.These genes contained AHL4-binding cis elements,and AHL4 was shown to bind to the promoter regions of genes encoding the TAG lipases SDP1 and DALL5 and acyl-thioesterase KAT5.These AHL4-DNA interactions were suppressed by PA species that bound to AHL4.These results indicate that AHL4 suppresses lipid catabolism by repressing the expression of specific genes involved in TAG hydrolysis and fatty acid oxidation,and that PA relieves AHL4-mediated suppression and promotes TAG degradation.Thus,AHL4 and PA together regulate lipid degradation during seed germination and seedling establishment.
基金the Shanghai General Hospital Clinical Center Laboratory Animal Welfare&Ethics Committee(License number:2023AW017).
文摘Foam cells play a pivotal role in the progression of atherosclerosis progression by triggering inflammation within arterial walls.They release inflammatory molecules that attract additional immune cells,leading to further macrophage recruitment and plaque development.In this study,we develop an osteopontin(OPN)antibody-conjugated niobium carbide(Nb_(2)C-aOPN)MXenzyme designed to selectively target and mildly ablate foam cells while reducing inflammation in the plaque microenvironment.This approach utilizes photonic hyperthermia to decrease plaque size by enhancing cholesterol regulation through both passive cholesterol outflow and positive cholesterol efflux.Nb_(2)C-aOPN MXenzyme exhibits multiple enzyme-mimicking properties,including catalase,superoxide dismutase,peroxidase and glutathione peroxidase,and acts as a scavenger for reactive oxygen and nitrogen species.The inhibition of reactive oxygen and nitrogen species synergizes with photothermal ablation to promote positive cholesterol efflux,leading to reduced macrophage recruitment and a shift in macrophage phenotype from M1 to M2.This integrative strategy on cholesterol regulation and anti-inflammation highlights the potential of multifunctional 2D MXenzyme-based nanomedicine in advancing atherosclerotic regression.
基金supported by Natural Science Foundation of Fujian Youth Fund,China(No.2024J09041)National Natural Science Foundation of China(No.32372338)+1 种基金Fuzhou-Xiamen-Quanzhou National Independent Innovation Demonstration Zone Collaborative Innovation Platform Project(No.2024-P-005)the Scientific Research Foundation of Jimei University,China(No.ZQ2022040).
文摘In vitro gut microbiota fermentation characteristics and anti-adipogenic effect of Bangia fusco-purpurea polysaccharide extracted with ultra-high pressure assisted extraction(UBFP)were investigated.Compared with polysaccharide obtained with traditional hot water extraction(BFP),UBFP significantly increased intestinal flora diversity and induced a beneficial shift in the microbial composition,which could suppress the growth of opportunistic pathogens such as Escherichia-Shigella and Streptococcus,while enriching the abundance of bene-ficial bacteria such as Enterococcus.Both BFP and UBFP increased short-chain fatty acids(SCFAs)production,particularly acetic acid.The total SCFAs content in the UBFP group showed a 1.83-fold greater increase than that in the BFP group relative to the control.Furthermore,UBFP fermented products could better inhibit 3T3-L1 preadipocytes from differentiating into mature adipocytes as well as lowering triglyceride and total choles-terol contents and inhibiting lipid droplet formation.Notably,the reduction of TG content by UBFP fermented products showed 1.07-to 2.87-fold greater efficacy than BFP fermented products(p<0.05).Western blot analysis revealed that UBFP fermentation products upregulated the pAMPK/AMPK ratio and downregulated PPARγexpression in 3T3-L1 cells,suggesting that the anti-adipogenic effect may be mediated through activation of the AMPK signaling pathway and inhibition of PPARγexpression.Although these bioactivities of UBFP were assessed using in vitro models and requires further validation through in vivo studies,this research nevertheless provided valuable insights into the potential role of UBFP in promoting intestinal health and regulating lipid metabolism.
