Advanced lipoxidation end products(ALEs)are formed by modifying proteins with lipid oxidation products.ALEs formed in the body have been linked to diabetes and hepatic disease.However,it is not known whether ALEs form...Advanced lipoxidation end products(ALEs)are formed by modifying proteins with lipid oxidation products.ALEs formed in the body have been linked to diabetes and hepatic disease.However,it is not known whether ALEs formed in heat-processed foods can induce metabolic diseases.Our results indicate that dietary ALEs induce lipid accumulation in the liver of mice at an early stage and continuous feeding of ALEs induces inflammation,oxidative stress and hepatic insulin resistance.The core reason for these adverse reactions is the damage to the intestinal barrier caused by ALEs.Due to the damage to the intestinal barrier,there is an increase in lipopolysaccharides(LPS)in the liver that induces hepatic lipid accumulation by modulating hepatic lipid metabolism.Furthermore,ALEs plays a major role in the regulation of metabolic diseases by directly or indirectly inhibiting AMP activated protein kinase(AMPK)/Sirtuin 1(SIRT1)signaling through LPS.展开更多
Background Homocysteine(Hcy)is a risk factor for hypertension,although the mechanisms are poorly understood.Methods We first explored the relationship between Hcy levels and blood pressure(BP)by analyzing the clinical...Background Homocysteine(Hcy)is a risk factor for hypertension,although the mechanisms are poorly understood.Methods We first explored the relationship between Hcy levels and blood pressure(BP)by analyzing the clinical data of primary hypertensive patients admitted to our hospital.Secondly,we explored a rat model to study the effect of Hcy on blood pressure and the role of H2S.An hyperhomocysteinemia(HHcy)rat model was induced to explore the effect of Hcy on blood pressure and the possible mechanism.We carried out tissue histology,extraction and examination of RNA and protein.Finally,we conducted cell experiments to determine a likely mechanism through renin-angiotensin-aldosterone system(RAAS)and extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway.Results In primary hypertensive inpatients with HHcy,blood pressure was significantly higher as compared with inpatient counterparts lacking HHcy.In the rat model,blood pressure of the Wistar rats was significantly increased with increases in serum Hcy levels and decreased after folate treatment.Angiotensin converting enzyme 1(ACE1)expression in the Wistar Hcy group was enhanced comparing to controls,but was decreased in the Wistar folate group.Angiotensin II receptor type 1(AGTR1)levels in the kidney tissue increased in the Wistar folate group.Both serum H2S and kidney cystathionineγ-lyase decreased with elevated levels of serum Hcy.In vitro,increased concentrations and treatment times for Hcy were associated with increased expression of collagen type 1 and AGTR1.This dose and time dependent response was also observed for p-STAT3 and p-ERK1/2 expression.Conclusion Endogenous H2S might mediate the process of altered blood pressure in response to changes in serum Hcy levels,in a process that is partly dependent on activated RAAS and ERK1/2-STAT3 signaling pathway.展开更多
Objective To determine whether transforming growth factor betal (TGF-β1)/Smad signaling pathway mediates p53-dependent apoptosis in hepatoma cell lines.Methods Three human hepatic carcinoma cell lines, HepG2, Huh-7, ...Objective To determine whether transforming growth factor betal (TGF-β1)/Smad signaling pathway mediates p53-dependent apoptosis in hepatoma cell lines.Methods Three human hepatic carcinoma cell lines, HepG2, Huh-7, and Hep3B, were used in this study.TGF-β1-induced apoptosis in hepatic carcinoma cell lines was analyzed using TUNEL assay.For identifying the mechanism of apoptosis induced by TGF-β1, cell lines were transfected with a TGF-β1-inducible luciferase reportor plasmid containing Smad4 binding elements.After transfection, cells were treated with TGF-β1, then assayed for luciferase activity.Results The apoptosis rate of HepG2 cell lines (48.51%± 8.21%) was significantly higher than control ( 12.72%±2.18%, P<0.05).But TGF-β1 was not able to induce apoptosis of Huh-7 and Hep3B cell lines.The relative luciferase activity of TGF-β1-treated HepG2 cell lines (4.38) was significantly higher than control (1.00, P< 0.05).But the relative luciferase activity of TGF-β1-treated Huh-7 and Hep3B cell lines less increased compared with control.Conclusions HepG2 cells seem to be highly susceptible to TGF-β1-induced apoptosis compared with Hep3B and Huh-7 cell lines.Smad4 is a central mediator of TGF-β1 signaling transdution pathway.TGF-β1/Smad signaling pathway might mediate p53-dependent apoptosis in hepatoma cell lines.展开更多
目的探讨脱氧核苷酸转移酶末端相互作用蛋白1(deoxynucleotidyltransferase,terminal,interacting protein 1,DNTTIP1)通过细胞外调节蛋白激酶(extracellular regulated protein kinases,ERK)信号通路促进鼻咽癌侵袭及转移机制。方法选...目的探讨脱氧核苷酸转移酶末端相互作用蛋白1(deoxynucleotidyltransferase,terminal,interacting protein 1,DNTTIP1)通过细胞外调节蛋白激酶(extracellular regulated protein kinases,ERK)信号通路促进鼻咽癌侵袭及转移机制。方法选用人鼻咽癌细胞系(HK1)作为研究对象,分为观察组与对照组,观察组中细胞转入含有DNTTIP1基因的载体,对照组转入空白载体。采用Trizol法提取细胞中的总RNA,细胞划痕及Transwell小室实验检测细胞的迁移及侵袭能力,Western blot法检测ERK信号通路相关蛋白的表达情况。结果DNTTIP1在观察组HK1细胞中的表达水平明显高于对照组(2.75±0.43 vs.1.00±0.01),差异有统计学意义(t=9.966,P<0.05)。观察组中HK1细胞迁移及侵袭明显增强,差异有统计学意义(P<0.05)。与对照组比较,观察组HK1细胞中的p-ERKl/2蛋白表达水平明显上升(0.64±0.13 vs.1.26±0.15),差异有统计学意义(t=7.651,P<0.05)。ERK+3'-UTR+DNTTIP1组中ERK相对表达量明显高于ERK+3'-UTR组(1.71±0.21 vs.1.00±0.01),差异有统计学意义(t=8.272,P<0.05)。结论DNTTIP1通过ERK信号通路促进鼻咽癌侵袭及转移,该通路对鼻咽癌相关疾病的治疗具有潜在的医学价值。展开更多
Heat processing of food has been well validated as the trigger to generate heat-processing side product of advanced lipoxidation end products(ALEs),which potentially engenders the threat on systemic health or progress...Heat processing of food has been well validated as the trigger to generate heat-processing side product of advanced lipoxidation end products(ALEs),which potentially engenders the threat on systemic health or progression of diseases,especially the accumulated effect after long-term intake.Thus,the study was proposed to evaluate the effect of dietary ALEs on health after long-term ingestion,specifically through simulating the intake of dietary ALE in mice within 9 months to investigate the intervention effect and underlying mechanism.The unexpected observation of renal insufficiency or impairment after long-term intake of dietary ALEs indicated the negative impact on renal health,which has been verified by the pathological analysis.Further studies revealed that a high-ALEs diet disrupted the intestinal barrier,with enhanced impact after disturbing the gut microbiota to potentially lower the abundance of beneficial microbiome through producing nephrotoxic metabolites.Correlation analysis showed that the proliferation of harmful bacteria and the reduction of beneficial bacteria were strongly correlated with intestinal barrier damage and the development of renal insufficiency.Furthermore,the underlying mechanism was unveiled as that ALEs could inhibit AMPK/SIRT1 signaling to fundamentally induce renal inflammation and oxidative stress.Thus,it was revealed that long-term intake of dietary ALE could result in renal impairment,and the results emphasized the control or intervention on dietary ALE to decrease to accumulated impairment on systemic health.展开更多
This study endeavors to investigate the effects of Bifidobacterium breve CCFM1078 on bone formation and resorption balance in growing BALB/c mice.Newborn BALB/c mice were assigned to the control group(administration s...This study endeavors to investigate the effects of Bifidobacterium breve CCFM1078 on bone formation and resorption balance in growing BALB/c mice.Newborn BALB/c mice were assigned to the control group(administration saline)and the CCFM1078 group(administration B.breve CCFM1078,3×10^(9) CFU/day)in 3-,4-,and 5-week tests.All the groups have male and female distinctions.Our findings demonstrate that B.breve CCFM1078 exerts on the dynamic equilibrium between bone formation and resorption during the critical period of growth in mice by modulating the composition of gut microbiota and metabolites(hexadecanamide,linoleoyl ethanolamide,and palmitoyl ethanolamide),the genes and proteins expression related to the growth hormone(GH)/insulin-like growth factors-1(IGF-1)axis and Gs/PKA/CREB signaling pathways,as well as downstream osteogenic and osteoclastic differentiation factors.The effects of B.breve CCFM1078 were different with age and gender dependent.This finding suggests B.breve CCFM1078 may have potential applications in regulating bone metabolism in the growth period population.展开更多
Reactive oxygen species(ROS)-induced oxidative damage is strongly associated with the pathogenesis of chronic diseases,and natural antioxidant peptides have good abilities of scavenging ROS.The antioxidant activity of...Reactive oxygen species(ROS)-induced oxidative damage is strongly associated with the pathogenesis of chronic diseases,and natural antioxidant peptides have good abilities of scavenging ROS.The antioxidant activity of peptide Lys-Ser-Pro-Leu-Tyr(KSPLY)derived from Hericium erinaceus remains unclear.In the present study,the antioxidant effect and mechanism of KSPLY on H_(2)O_(2)-induced oxidative damage in HepG2 cells were investigated.The results indicated that KSPLY exhibited the antioxidant capacity in H_(2)O_(2)-induced HepG2 cells by enhancing superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and catalase(CAT)activities.In comparison with the H_(2)O_(2)-treated damage group,the apoptosis rate,ROS level,and malondialdehyde(MDA)content of HepG2 cells treated with KSPLY were significantly decreased.The H.erinaceus-derived peptide KSPLY pretreatment promoted the expression of detoxification and antioxidant enzymes via the Keap1/Nrf2 signal pathway,thereby inhibiting the generation of ROS and MDA.In conclusion,the H.erinaceus-derived peptide KSPLY effectively protected HepG2 cells against H_(2)O_(2)-induced oxidative damage,and it provided a theoretical basis for the further development of new natural antioxidants.展开更多
基金supported by grants from the National Natural Science Foundation of China(32030083)。
文摘Advanced lipoxidation end products(ALEs)are formed by modifying proteins with lipid oxidation products.ALEs formed in the body have been linked to diabetes and hepatic disease.However,it is not known whether ALEs formed in heat-processed foods can induce metabolic diseases.Our results indicate that dietary ALEs induce lipid accumulation in the liver of mice at an early stage and continuous feeding of ALEs induces inflammation,oxidative stress and hepatic insulin resistance.The core reason for these adverse reactions is the damage to the intestinal barrier caused by ALEs.Due to the damage to the intestinal barrier,there is an increase in lipopolysaccharides(LPS)in the liver that induces hepatic lipid accumulation by modulating hepatic lipid metabolism.Furthermore,ALEs plays a major role in the regulation of metabolic diseases by directly or indirectly inhibiting AMP activated protein kinase(AMPK)/Sirtuin 1(SIRT1)signaling through LPS.
基金supported by the Beijing Natural Science Foundation Program(Grant number:5102040)the Open Foundation of the Beijing Key Laboratory of Hypertension Research(Grant number:2015GXYB01)
文摘Background Homocysteine(Hcy)is a risk factor for hypertension,although the mechanisms are poorly understood.Methods We first explored the relationship between Hcy levels and blood pressure(BP)by analyzing the clinical data of primary hypertensive patients admitted to our hospital.Secondly,we explored a rat model to study the effect of Hcy on blood pressure and the role of H2S.An hyperhomocysteinemia(HHcy)rat model was induced to explore the effect of Hcy on blood pressure and the possible mechanism.We carried out tissue histology,extraction and examination of RNA and protein.Finally,we conducted cell experiments to determine a likely mechanism through renin-angiotensin-aldosterone system(RAAS)and extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway.Results In primary hypertensive inpatients with HHcy,blood pressure was significantly higher as compared with inpatient counterparts lacking HHcy.In the rat model,blood pressure of the Wistar rats was significantly increased with increases in serum Hcy levels and decreased after folate treatment.Angiotensin converting enzyme 1(ACE1)expression in the Wistar Hcy group was enhanced comparing to controls,but was decreased in the Wistar folate group.Angiotensin II receptor type 1(AGTR1)levels in the kidney tissue increased in the Wistar folate group.Both serum H2S and kidney cystathionineγ-lyase decreased with elevated levels of serum Hcy.In vitro,increased concentrations and treatment times for Hcy were associated with increased expression of collagen type 1 and AGTR1.This dose and time dependent response was also observed for p-STAT3 and p-ERK1/2 expression.Conclusion Endogenous H2S might mediate the process of altered blood pressure in response to changes in serum Hcy levels,in a process that is partly dependent on activated RAAS and ERK1/2-STAT3 signaling pathway.
文摘Objective To determine whether transforming growth factor betal (TGF-β1)/Smad signaling pathway mediates p53-dependent apoptosis in hepatoma cell lines.Methods Three human hepatic carcinoma cell lines, HepG2, Huh-7, and Hep3B, were used in this study.TGF-β1-induced apoptosis in hepatic carcinoma cell lines was analyzed using TUNEL assay.For identifying the mechanism of apoptosis induced by TGF-β1, cell lines were transfected with a TGF-β1-inducible luciferase reportor plasmid containing Smad4 binding elements.After transfection, cells were treated with TGF-β1, then assayed for luciferase activity.Results The apoptosis rate of HepG2 cell lines (48.51%± 8.21%) was significantly higher than control ( 12.72%±2.18%, P<0.05).But TGF-β1 was not able to induce apoptosis of Huh-7 and Hep3B cell lines.The relative luciferase activity of TGF-β1-treated HepG2 cell lines (4.38) was significantly higher than control (1.00, P< 0.05).But the relative luciferase activity of TGF-β1-treated Huh-7 and Hep3B cell lines less increased compared with control.Conclusions HepG2 cells seem to be highly susceptible to TGF-β1-induced apoptosis compared with Hep3B and Huh-7 cell lines.Smad4 is a central mediator of TGF-β1 signaling transdution pathway.TGF-β1/Smad signaling pathway might mediate p53-dependent apoptosis in hepatoma cell lines.
文摘目的探讨脱氧核苷酸转移酶末端相互作用蛋白1(deoxynucleotidyltransferase,terminal,interacting protein 1,DNTTIP1)通过细胞外调节蛋白激酶(extracellular regulated protein kinases,ERK)信号通路促进鼻咽癌侵袭及转移机制。方法选用人鼻咽癌细胞系(HK1)作为研究对象,分为观察组与对照组,观察组中细胞转入含有DNTTIP1基因的载体,对照组转入空白载体。采用Trizol法提取细胞中的总RNA,细胞划痕及Transwell小室实验检测细胞的迁移及侵袭能力,Western blot法检测ERK信号通路相关蛋白的表达情况。结果DNTTIP1在观察组HK1细胞中的表达水平明显高于对照组(2.75±0.43 vs.1.00±0.01),差异有统计学意义(t=9.966,P<0.05)。观察组中HK1细胞迁移及侵袭明显增强,差异有统计学意义(P<0.05)。与对照组比较,观察组HK1细胞中的p-ERKl/2蛋白表达水平明显上升(0.64±0.13 vs.1.26±0.15),差异有统计学意义(t=7.651,P<0.05)。ERK+3'-UTR+DNTTIP1组中ERK相对表达量明显高于ERK+3'-UTR组(1.71±0.21 vs.1.00±0.01),差异有统计学意义(t=8.272,P<0.05)。结论DNTTIP1通过ERK信号通路促进鼻咽癌侵袭及转移,该通路对鼻咽癌相关疾病的治疗具有潜在的医学价值。
基金supported by grants from the National Natural Science Foundation of China(32030083)。
文摘Heat processing of food has been well validated as the trigger to generate heat-processing side product of advanced lipoxidation end products(ALEs),which potentially engenders the threat on systemic health or progression of diseases,especially the accumulated effect after long-term intake.Thus,the study was proposed to evaluate the effect of dietary ALEs on health after long-term ingestion,specifically through simulating the intake of dietary ALE in mice within 9 months to investigate the intervention effect and underlying mechanism.The unexpected observation of renal insufficiency or impairment after long-term intake of dietary ALEs indicated the negative impact on renal health,which has been verified by the pathological analysis.Further studies revealed that a high-ALEs diet disrupted the intestinal barrier,with enhanced impact after disturbing the gut microbiota to potentially lower the abundance of beneficial microbiome through producing nephrotoxic metabolites.Correlation analysis showed that the proliferation of harmful bacteria and the reduction of beneficial bacteria were strongly correlated with intestinal barrier damage and the development of renal insufficiency.Furthermore,the underlying mechanism was unveiled as that ALEs could inhibit AMPK/SIRT1 signaling to fundamentally induce renal inflammation and oxidative stress.Thus,it was revealed that long-term intake of dietary ALE could result in renal impairment,and the results emphasized the control or intervention on dietary ALE to decrease to accumulated impairment on systemic health.
基金supported by the National Key R&D Program of China(2021YFD2100700)National Natural Science Foundation of China(32021005)+1 种基金111 project(BP0719028)Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province。
文摘This study endeavors to investigate the effects of Bifidobacterium breve CCFM1078 on bone formation and resorption balance in growing BALB/c mice.Newborn BALB/c mice were assigned to the control group(administration saline)and the CCFM1078 group(administration B.breve CCFM1078,3×10^(9) CFU/day)in 3-,4-,and 5-week tests.All the groups have male and female distinctions.Our findings demonstrate that B.breve CCFM1078 exerts on the dynamic equilibrium between bone formation and resorption during the critical period of growth in mice by modulating the composition of gut microbiota and metabolites(hexadecanamide,linoleoyl ethanolamide,and palmitoyl ethanolamide),the genes and proteins expression related to the growth hormone(GH)/insulin-like growth factors-1(IGF-1)axis and Gs/PKA/CREB signaling pathways,as well as downstream osteogenic and osteoclastic differentiation factors.The effects of B.breve CCFM1078 were different with age and gender dependent.This finding suggests B.breve CCFM1078 may have potential applications in regulating bone metabolism in the growth period population.
基金supported by the Natural Science Foundation of the Higher Education Institutions of Jiangsu Province(20KJB550016)the National Natural Science Foundation of China(32101944)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘Reactive oxygen species(ROS)-induced oxidative damage is strongly associated with the pathogenesis of chronic diseases,and natural antioxidant peptides have good abilities of scavenging ROS.The antioxidant activity of peptide Lys-Ser-Pro-Leu-Tyr(KSPLY)derived from Hericium erinaceus remains unclear.In the present study,the antioxidant effect and mechanism of KSPLY on H_(2)O_(2)-induced oxidative damage in HepG2 cells were investigated.The results indicated that KSPLY exhibited the antioxidant capacity in H_(2)O_(2)-induced HepG2 cells by enhancing superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and catalase(CAT)activities.In comparison with the H_(2)O_(2)-treated damage group,the apoptosis rate,ROS level,and malondialdehyde(MDA)content of HepG2 cells treated with KSPLY were significantly decreased.The H.erinaceus-derived peptide KSPLY pretreatment promoted the expression of detoxification and antioxidant enzymes via the Keap1/Nrf2 signal pathway,thereby inhibiting the generation of ROS and MDA.In conclusion,the H.erinaceus-derived peptide KSPLY effectively protected HepG2 cells against H_(2)O_(2)-induced oxidative damage,and it provided a theoretical basis for the further development of new natural antioxidants.
