Punicalagin has been demonstrated to exhibit anti-oxidant and anti-inflammatory properties,but whether and how it could impact hypercholesterolemia remains not fully explored.The aim of this study was to investigate t...Punicalagin has been demonstrated to exhibit anti-oxidant and anti-inflammatory properties,but whether and how it could impact hypercholesterolemia remains not fully explored.The aim of this study was to investigate the influence of punicalagin on hypercholesterolemia in mice and its related mechanisms.After 6 weeks'intervention,punicalagin significantly reduced serum total cholesterol and low-density lipoprotein cholesterol(LDL-C)levels in mice fed a high-fat high-cholesterol(HFHC)diet.Meanwhile,punicalagin supplementation lowered hepatic cholesterol level,which corresponded to the down-regulation of cholesterol synthesis genes(Fdps,Cyp51)and up-regulated bile acid synthesis genes(Cyp7a1,Cyp27a1).In addition,bile acid reabsorption was retarded in punicalagin-fed mice through down-regulating ileal apical sodium-dependent BA transporter(ASBT).Furthermore,intestinal farnesoid X receptor(FXR)-fibroblast growth factor 15(Fgf15)pathway was inhibited while hepatic FXR-small heterodimeric partner(SHP)pathway was activated in punicalagin group.Microbiota analysis and targeted metabolomics showed that punicalagin decreased the abundance of bile-salt hydrolase(BSH)-producing bacteria(Clostridiaceae and Bifidobacteriaceae)and the ratio of primary BAs to secondary BAs.In conclusion,the cholesterol-lowering effect of punicalagin partly through down-regulating cholesterol synthesis and increasing cholesterol catabolism,which could be achieved by regulating gut microbiota,altering bile acid composition and modulating FXR signaling pathway.These findings indicate the potential application of punicalagin-related products as an alternative strategy for hypercholesterolemia prevention and mitigation.展开更多
The aim of this paper was to study the effect of combination of Lactobacillus strains and tryptophan(Trp)-rich diet on the intestinal barrier function of Balb/c mice exposed to a cocktail of antibiotics and dextran so...The aim of this paper was to study the effect of combination of Lactobacillus strains and tryptophan(Trp)-rich diet on the intestinal barrier function of Balb/c mice exposed to a cocktail of antibiotics and dextran sodium sulfate.Several Lactobacillus strains isolated from the healthy human fecal sample was found to utilize Trp to produce indole derivatives.The results of Trp metabolism indicated that the ability of Lactobacillus to metabolize Trp to produce indole-3-lactic acid(ILA),indole-3-carboxaldehyde(I3C),and indole-3-acetic acid varies in vitro and in vivo.The effect of Lactobacillus with high-yielding indole derivatives on disease activity index,colon length,and intestinal permeability was significantly better than that of Lactobacillus with low-yielding indole derivatives in a high Trp diet.And Lactobacillus combined with Trp intervention also had a certain regulatory effect on the intestinal flora of male BALB/c mice.Among them,Lactiplantibacillus plantarum DPUL-S164 produced more ILA both in vivo and in vitro,and the combination of L.plantarum DPUL-S164 and Trp significantly decreased the expression level of the serum pro-inflammatory cytokine interleukin(IL)-6 and increased the expression level of the anti-inflammatory cytokine IL-10,significantly improved the number of goblet cells in the mouse mucous layer and increased mucin and tight junction protein expression.Furthermore,L.plantarum DPUL-S164 combined with Trp intervention activated the aryl hydrocarbon receptors(Ah R)signaling pathway.Furthermore,we found that the expression of colonic tight junction protein was positively correlated with the expression of colonic Ah R,and the expression of Ah R was positively correlated with the concentrations of ILA and I3C in vivo.Therefore,we conclude that the ILA as Ah R ligand produced by L.plantarum DPUL-S164 regulated the Ah R pathway,thus up-regulating the expression of the tight junction protein and protecting the integrity of the epithelial barrier.展开更多
Objective To evaluate the effect of angiotensin-converting enzyme inhibitor(ACEI)/angiotensin Ⅱ receptor blocker(ARB)therapy on the prognosis of patients with atrial fibrillation(AF).Methods A total of 1,991 AF patie...Objective To evaluate the effect of angiotensin-converting enzyme inhibitor(ACEI)/angiotensin Ⅱ receptor blocker(ARB)therapy on the prognosis of patients with atrial fibrillation(AF).Methods A total of 1,991 AF patients from the AF registry were divided into two groups according to whether they were treated with ACEI/ARB at recruitment.Baseline characteristics were carefully collected and analyzed.Logistic regression was utilized to identify the predictors of ACEI/ARB therapy.The primary endpoint was all-cause mortality,while the secondary endpoints included cardiovascular mortality,stroke and major adverse events(MAEs)during the one-year follow-up period.Univariable and multivariable Cox regression were performed to identify the association between ACEI/ARB therapy and the one-year outcomes.Results In total,759 AF patients(38.1%)were treated with ACEI/ARB.Compared with AF patients without ACEI/ARB therapy,patients treated with ACEI/ARB tended to be older and had a higher rate of permanent AF,hypertension,diabetes mellitus,heart failure(HF),left ventricular ejection fraction(LVEF)<40%,coronary artery disease(CAD),prior myocardial infarction(MI),left ventricular hypertrophy,tobacco use and concomitant medications(all P<0.05).Hypertension,HF,LVEF<40%,CAD,prior MI and tobacco use were determined to be predictors of ACEI/ARB treatment.Multivariable analysis showed that ACEI/ARB therapy was associated with a significantly lower risk of one-year all-cause mortality[hazard ratio(HR)(95%CI):0.682(0.527-0.882),P=0.003],cardiovascular mortality[HR(95%CI):0.713(0.514-0.988),P=0.042]and MAEs[HR(95%CI):0.698(0.568-0.859),P=0.001].The association between ACEI/ARB therapy and reduced mortality was consistent in the subgroup analysis.Conclusions In patients with AF,ACEI/ARB was related to significantly reduced one-year all-cause mortality,cardiovascular mortality and MAEs despite the high burden of cardiovascular comorbidities.展开更多
Bitterness,one of the 5“basic tastes”,is usually undesired by humans.However,abundant literature reported that bitter fruits and vegetables have beneficial health effects due to their bitter contributors.This review...Bitterness,one of the 5“basic tastes”,is usually undesired by humans.However,abundant literature reported that bitter fruits and vegetables have beneficial health effects due to their bitter contributors.This review provided an updated overview of the main bitter contributors of typical bitter fruits and vegetables and their health benefits.The main bitter contributors,including phenolics,terpenoids,alkaloids,amino acids,nucleosides and purines,were summarized.The bioactivities and wide range of beneficial effects of them on anti-cancers,anti-inflammations,anti-microbes,neuroprotection,inhibiting chronic and acute injury in organs,as well as regulating behavior performance and metabolism were reported.Furthermore,not only did the bitter taste receptors(taste receptor type 2 family,T2Rs)show taste effects,but extra-oral T2Rs could also be activated by binding with bitter components,regulating physiological activities via modulating hormone secretion,immunity,metabolism,and cell proliferation.This review provided a new perspective on exploring and explaining the nutrition of bitter foods,revealing the relationship between the functions of bitter contributors from food and T2Rs.Future trends may focus on revealing the possibility of T2Rs being targets for the treatment of diseases,exploring the mechanism of T2Rs mediating the bioactivities,and making bitter foods more acceptable without getting rid of bitter contributors.展开更多
目的探讨白血病抑制因子受体(leukemia inhibitory factor receptor,LIFR)在非ST段抬高型心肌梗死(non-ST-segment elevation myocardial infarction,NSTEMI)患者中的表达情况及其与心肌重构的可能关联。方法前瞻性选取2023年1月至2024...目的探讨白血病抑制因子受体(leukemia inhibitory factor receptor,LIFR)在非ST段抬高型心肌梗死(non-ST-segment elevation myocardial infarction,NSTEMI)患者中的表达情况及其与心肌重构的可能关联。方法前瞻性选取2023年1月至2024年11月于武汉大学人民医院行冠状动脉造影的急性心肌梗死患者188例,根据是否诊断为NSTEMI分为对照组94例和NSTEMI组94例。收集患者一般临床资料,采用线性回归分析LIFR及与其他指标的相关性。结果与对照组比较,NSTEMI组吸烟史、LIFR、N末端B型钠尿肽前体、肌钙蛋白I、肌酐、尿酸、白细胞计数显著升高,左心室射血分数显著降低,差异有统计学意义[48.94%vs 13.83%,P<0.01;5.82(4.23,8.11)mmol/L vs 0.97(0.60,1.41)mmol/L,P<0.01;2.53(1.24,9.71)pg/L vs 0.03(0.02,0.04),P<0.01;18.57(4.11,250.00)ng/L vs 0.00(0.00,0.00)ng/L,P<0.01;82.50(68.00,121.25)μmol/L vs 68.50(53.00,88.25)μmol/L,P<0.01;411.00(349.00,521.25)μmol/L vs 337.00(286.75,406.00)μmol/L,P<0.01;10.21(8.71,13.09)×10~9/L vs 6.22(4.67,7.46)×10~9/L,P<0.01;47.00(38.00,54.00)%vs 59.00(56.00,60.00)%,P<0.01]。心肌梗死患者血清LIFR与N末端B型钠尿肽前体、肌钙蛋白I及白细胞计数呈正相关(β=1.403,95%CI:10597.867~17327.087,P=0.000;β=0.232,95%CI:114.558~1769.808,P=0.026;β=0.336,95%CI:0.164~0.617,P=0.001)。结论LIFR可能通过炎症参与心肌梗死后心肌重构和心力衰竭的发展。展开更多
基金supported in part by the National Key Research and Development Program of China(2022YFD2100104)the Science and Technology Program of Shaanxi Province,China(2022JM-111)Graduate Innovation Fund of Dalian Polytechnic University。
文摘Punicalagin has been demonstrated to exhibit anti-oxidant and anti-inflammatory properties,but whether and how it could impact hypercholesterolemia remains not fully explored.The aim of this study was to investigate the influence of punicalagin on hypercholesterolemia in mice and its related mechanisms.After 6 weeks'intervention,punicalagin significantly reduced serum total cholesterol and low-density lipoprotein cholesterol(LDL-C)levels in mice fed a high-fat high-cholesterol(HFHC)diet.Meanwhile,punicalagin supplementation lowered hepatic cholesterol level,which corresponded to the down-regulation of cholesterol synthesis genes(Fdps,Cyp51)and up-regulated bile acid synthesis genes(Cyp7a1,Cyp27a1).In addition,bile acid reabsorption was retarded in punicalagin-fed mice through down-regulating ileal apical sodium-dependent BA transporter(ASBT).Furthermore,intestinal farnesoid X receptor(FXR)-fibroblast growth factor 15(Fgf15)pathway was inhibited while hepatic FXR-small heterodimeric partner(SHP)pathway was activated in punicalagin group.Microbiota analysis and targeted metabolomics showed that punicalagin decreased the abundance of bile-salt hydrolase(BSH)-producing bacteria(Clostridiaceae and Bifidobacteriaceae)and the ratio of primary BAs to secondary BAs.In conclusion,the cholesterol-lowering effect of punicalagin partly through down-regulating cholesterol synthesis and increasing cholesterol catabolism,which could be achieved by regulating gut microbiota,altering bile acid composition and modulating FXR signaling pathway.These findings indicate the potential application of punicalagin-related products as an alternative strategy for hypercholesterolemia prevention and mitigation.
基金project was supported by the National Key Research and Development Program(2021YFD2100700)。
文摘The aim of this paper was to study the effect of combination of Lactobacillus strains and tryptophan(Trp)-rich diet on the intestinal barrier function of Balb/c mice exposed to a cocktail of antibiotics and dextran sodium sulfate.Several Lactobacillus strains isolated from the healthy human fecal sample was found to utilize Trp to produce indole derivatives.The results of Trp metabolism indicated that the ability of Lactobacillus to metabolize Trp to produce indole-3-lactic acid(ILA),indole-3-carboxaldehyde(I3C),and indole-3-acetic acid varies in vitro and in vivo.The effect of Lactobacillus with high-yielding indole derivatives on disease activity index,colon length,and intestinal permeability was significantly better than that of Lactobacillus with low-yielding indole derivatives in a high Trp diet.And Lactobacillus combined with Trp intervention also had a certain regulatory effect on the intestinal flora of male BALB/c mice.Among them,Lactiplantibacillus plantarum DPUL-S164 produced more ILA both in vivo and in vitro,and the combination of L.plantarum DPUL-S164 and Trp significantly decreased the expression level of the serum pro-inflammatory cytokine interleukin(IL)-6 and increased the expression level of the anti-inflammatory cytokine IL-10,significantly improved the number of goblet cells in the mouse mucous layer and increased mucin and tight junction protein expression.Furthermore,L.plantarum DPUL-S164 combined with Trp intervention activated the aryl hydrocarbon receptors(Ah R)signaling pathway.Furthermore,we found that the expression of colonic tight junction protein was positively correlated with the expression of colonic Ah R,and the expression of Ah R was positively correlated with the concentrations of ILA and I3C in vivo.Therefore,we conclude that the ILA as Ah R ligand produced by L.plantarum DPUL-S164 regulated the Ah R pathway,thus up-regulating the expression of the tight junction protein and protecting the integrity of the epithelial barrier.
基金the National Key Research and Develop Program of China(2017YFC0908802).
文摘Objective To evaluate the effect of angiotensin-converting enzyme inhibitor(ACEI)/angiotensin Ⅱ receptor blocker(ARB)therapy on the prognosis of patients with atrial fibrillation(AF).Methods A total of 1,991 AF patients from the AF registry were divided into two groups according to whether they were treated with ACEI/ARB at recruitment.Baseline characteristics were carefully collected and analyzed.Logistic regression was utilized to identify the predictors of ACEI/ARB therapy.The primary endpoint was all-cause mortality,while the secondary endpoints included cardiovascular mortality,stroke and major adverse events(MAEs)during the one-year follow-up period.Univariable and multivariable Cox regression were performed to identify the association between ACEI/ARB therapy and the one-year outcomes.Results In total,759 AF patients(38.1%)were treated with ACEI/ARB.Compared with AF patients without ACEI/ARB therapy,patients treated with ACEI/ARB tended to be older and had a higher rate of permanent AF,hypertension,diabetes mellitus,heart failure(HF),left ventricular ejection fraction(LVEF)<40%,coronary artery disease(CAD),prior myocardial infarction(MI),left ventricular hypertrophy,tobacco use and concomitant medications(all P<0.05).Hypertension,HF,LVEF<40%,CAD,prior MI and tobacco use were determined to be predictors of ACEI/ARB treatment.Multivariable analysis showed that ACEI/ARB therapy was associated with a significantly lower risk of one-year all-cause mortality[hazard ratio(HR)(95%CI):0.682(0.527-0.882),P=0.003],cardiovascular mortality[HR(95%CI):0.713(0.514-0.988),P=0.042]and MAEs[HR(95%CI):0.698(0.568-0.859),P=0.001].The association between ACEI/ARB therapy and reduced mortality was consistent in the subgroup analysis.Conclusions In patients with AF,ACEI/ARB was related to significantly reduced one-year all-cause mortality,cardiovascular mortality and MAEs despite the high burden of cardiovascular comorbidities.
基金the financial support provided by“Pioneer”and“Leading Goose”R&D Program of Zhejiang(2022C020122022C02078)。
文摘Bitterness,one of the 5“basic tastes”,is usually undesired by humans.However,abundant literature reported that bitter fruits and vegetables have beneficial health effects due to their bitter contributors.This review provided an updated overview of the main bitter contributors of typical bitter fruits and vegetables and their health benefits.The main bitter contributors,including phenolics,terpenoids,alkaloids,amino acids,nucleosides and purines,were summarized.The bioactivities and wide range of beneficial effects of them on anti-cancers,anti-inflammations,anti-microbes,neuroprotection,inhibiting chronic and acute injury in organs,as well as regulating behavior performance and metabolism were reported.Furthermore,not only did the bitter taste receptors(taste receptor type 2 family,T2Rs)show taste effects,but extra-oral T2Rs could also be activated by binding with bitter components,regulating physiological activities via modulating hormone secretion,immunity,metabolism,and cell proliferation.This review provided a new perspective on exploring and explaining the nutrition of bitter foods,revealing the relationship between the functions of bitter contributors from food and T2Rs.Future trends may focus on revealing the possibility of T2Rs being targets for the treatment of diseases,exploring the mechanism of T2Rs mediating the bioactivities,and making bitter foods more acceptable without getting rid of bitter contributors.
文摘目的探讨白血病抑制因子受体(leukemia inhibitory factor receptor,LIFR)在非ST段抬高型心肌梗死(non-ST-segment elevation myocardial infarction,NSTEMI)患者中的表达情况及其与心肌重构的可能关联。方法前瞻性选取2023年1月至2024年11月于武汉大学人民医院行冠状动脉造影的急性心肌梗死患者188例,根据是否诊断为NSTEMI分为对照组94例和NSTEMI组94例。收集患者一般临床资料,采用线性回归分析LIFR及与其他指标的相关性。结果与对照组比较,NSTEMI组吸烟史、LIFR、N末端B型钠尿肽前体、肌钙蛋白I、肌酐、尿酸、白细胞计数显著升高,左心室射血分数显著降低,差异有统计学意义[48.94%vs 13.83%,P<0.01;5.82(4.23,8.11)mmol/L vs 0.97(0.60,1.41)mmol/L,P<0.01;2.53(1.24,9.71)pg/L vs 0.03(0.02,0.04),P<0.01;18.57(4.11,250.00)ng/L vs 0.00(0.00,0.00)ng/L,P<0.01;82.50(68.00,121.25)μmol/L vs 68.50(53.00,88.25)μmol/L,P<0.01;411.00(349.00,521.25)μmol/L vs 337.00(286.75,406.00)μmol/L,P<0.01;10.21(8.71,13.09)×10~9/L vs 6.22(4.67,7.46)×10~9/L,P<0.01;47.00(38.00,54.00)%vs 59.00(56.00,60.00)%,P<0.01]。心肌梗死患者血清LIFR与N末端B型钠尿肽前体、肌钙蛋白I及白细胞计数呈正相关(β=1.403,95%CI:10597.867~17327.087,P=0.000;β=0.232,95%CI:114.558~1769.808,P=0.026;β=0.336,95%CI:0.164~0.617,P=0.001)。结论LIFR可能通过炎症参与心肌梗死后心肌重构和心力衰竭的发展。
