Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in hig...Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.展开更多
Oxidative stress leads to chondrocyte apoptosis and extracellular matrix(ECM)degradation,thus contributing to the pathogenesis of osteoarthritis(OA).Herein,curcumin with remarkable antioxidant and anti-inflammatory ac...Oxidative stress leads to chondrocyte apoptosis and extracellular matrix(ECM)degradation,thus contributing to the pathogenesis of osteoarthritis(OA).Herein,curcumin with remarkable antioxidant and anti-inflammatory activities has been employed as an organic ligand to coordinate ferric ions for enhancing the water-solubility and biocompatibility of natural product curcumin.The obtained iron-curcumin-based coordination nanoparticles(Fe-Cur NPs)exhibit great water-solubility and efficient reactive oxygen/nitrogen species(ROS/RNS)scavenging ability.In vitro chondrocyte evaluation experiments indicated that the intracellular ROS/RNS induced by interleukin 1β(IL-1β)could be efficiently scavenged by these Fe-Cur NPs and oxidative-stressinduced cell death could be preserved as well.In addition,post intra-articular(i.a.)injection into OA rat joints,Fe-Cur NPs could greatly inhibit OA progression via activating the nuclear factor-erythroid 2 related factor-2(Nrf2)and inhibiting nod-like receptor protein-3(NLRP3)inflammasome activation in primary rat chondrocytes,as well as decrease the production of matrix degrading proteases and other inflammatory mediators.The efficient antioxidation and anti-inflammation performance of Fe-Cur NPs endow them as a promising nanoplatform for treatment of various inflammatory diseases,and more detailed researches will be conducted in the future.展开更多
Objective: Reactive oxygen species(ROS) are involved in a variety of biological phenomena and serve both deleterious and beneficial roles. ROS quantification and assessment of reaction networks are desirable but diffi...Objective: Reactive oxygen species(ROS) are involved in a variety of biological phenomena and serve both deleterious and beneficial roles. ROS quantification and assessment of reaction networks are desirable but difficult because of their short half-life and high reactivity. Here, we describe a pro-oxidative model in a single human lung carcinoma SPC-A-1 cell that was created by application of extracellular H2O2 stimuli. Methods: Modified microfluidics and imaging techniques were used to determine O2·- levels and construct an O2^·- reaction network. To elucidate the consequences of increased O2^·- input, the mitochondria were given a central role in the oxidative stress mode, by manipulating mitochondria-interrelated cytosolic Ca2+ levels, mitochondrial Ca^2+ uptake, auto-amplification of intracellular ROS and the intrinsic apoptotic pathway. Results and conclusions: Results from a modified microchip demonstrated that 1 mmol/L H·-2 O2 induced a rapid increase in cellular O2 levels(>27 vs.>406 amol in 20 min), leading to increased cellular oxidizing power(evaluated by ROS levels) and decreased reducing power(evaluated by glutathione(GSH) levels). In addition, we examined the dynamics of cytosolic Ca^2+ and mitochondrial Ca^2+ by confocal laser scanning microscopy and confirmed that Ca^2+ stores in the endoplasmic reticulum were the primary source of H2O2-induced cytosolic Ca^2+ bursts. It is clear that mitochondria have pivotal roles in determining how exogenous oxidative stress affects cell fate. The stress response involves the transfer of Ca^2+ signals between organelles,ROS auto-amplification, mitochondrial dysfunction, and a caspase-dependent apoptotic pathway.展开更多
基金supported by National Natural Science Foundation of China(32072212)Multi-Year Research Grant of University of Macao(MYRG2018-00169-ICMS)+5 种基金Science and Technology Development Fund of Macao(FDCT)(0098/2020/A)MICINN supporting the Ramón y Cajal grant for M.A.Prieto(RYC-201722891)Jianbo Xiao(RYC2020-030365-I)Xunta de Galicia supporting the Axudas Conecta Peme,the IN852A 2018/58 Neuro Food Project,the program EXCELENCIA-ED431F 2020/12the pre-doctoral grants of P.García-Oliveira(ED481A-2019/295)to Ibero-American Program on Science and Technology(CYTED-AQUA-CIBUS,P317RT0003).
文摘Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.
基金This research was supported by the National Research Program of China(No.2016YFA0201200)the National Natural Science Foundation of China(Nos.U20A20254 and 52072253)+2 种基金the China Postdoctoral Science Foundation(No.2021TQ0229)the Collaborative Innovation Center of Suzhou Nano Science and Technology,the Preponderant Discipline Supporting Project of the Second Affiliated Hospital of Soochow University(No.XKTJXK202003)the Suzhou Special Foundation for the Key Diseases Diagnosis and Treatment(Nos.LCZX201904 and LCZX201708).
文摘Oxidative stress leads to chondrocyte apoptosis and extracellular matrix(ECM)degradation,thus contributing to the pathogenesis of osteoarthritis(OA).Herein,curcumin with remarkable antioxidant and anti-inflammatory activities has been employed as an organic ligand to coordinate ferric ions for enhancing the water-solubility and biocompatibility of natural product curcumin.The obtained iron-curcumin-based coordination nanoparticles(Fe-Cur NPs)exhibit great water-solubility and efficient reactive oxygen/nitrogen species(ROS/RNS)scavenging ability.In vitro chondrocyte evaluation experiments indicated that the intracellular ROS/RNS induced by interleukin 1β(IL-1β)could be efficiently scavenged by these Fe-Cur NPs and oxidative-stressinduced cell death could be preserved as well.In addition,post intra-articular(i.a.)injection into OA rat joints,Fe-Cur NPs could greatly inhibit OA progression via activating the nuclear factor-erythroid 2 related factor-2(Nrf2)and inhibiting nod-like receptor protein-3(NLRP3)inflammasome activation in primary rat chondrocytes,as well as decrease the production of matrix degrading proteases and other inflammatory mediators.The efficient antioxidation and anti-inflammation performance of Fe-Cur NPs endow them as a promising nanoplatform for treatment of various inflammatory diseases,and more detailed researches will be conducted in the future.
基金Project supported by the Zhejiang Provincial Natural Science Foundation of China(No.LY18H300002)the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission(No.2019RC061/2019312897)+1 种基金the Zhejiang Provincial Natural Science Foundation of China(Nos.Y4110212 and LY19H090001)partly by the National Natural Science Foundation of China(Nos.81372301 and 81301113)
文摘Objective: Reactive oxygen species(ROS) are involved in a variety of biological phenomena and serve both deleterious and beneficial roles. ROS quantification and assessment of reaction networks are desirable but difficult because of their short half-life and high reactivity. Here, we describe a pro-oxidative model in a single human lung carcinoma SPC-A-1 cell that was created by application of extracellular H2O2 stimuli. Methods: Modified microfluidics and imaging techniques were used to determine O2·- levels and construct an O2^·- reaction network. To elucidate the consequences of increased O2^·- input, the mitochondria were given a central role in the oxidative stress mode, by manipulating mitochondria-interrelated cytosolic Ca2+ levels, mitochondrial Ca^2+ uptake, auto-amplification of intracellular ROS and the intrinsic apoptotic pathway. Results and conclusions: Results from a modified microchip demonstrated that 1 mmol/L H·-2 O2 induced a rapid increase in cellular O2 levels(>27 vs.>406 amol in 20 min), leading to increased cellular oxidizing power(evaluated by ROS levels) and decreased reducing power(evaluated by glutathione(GSH) levels). In addition, we examined the dynamics of cytosolic Ca^2+ and mitochondrial Ca^2+ by confocal laser scanning microscopy and confirmed that Ca^2+ stores in the endoplasmic reticulum were the primary source of H2O2-induced cytosolic Ca^2+ bursts. It is clear that mitochondria have pivotal roles in determining how exogenous oxidative stress affects cell fate. The stress response involves the transfer of Ca^2+ signals between organelles,ROS auto-amplification, mitochondrial dysfunction, and a caspase-dependent apoptotic pathway.
