Carbon-based nanomaterials have important research significance in various disciplines,such as composite materials,nanoelectronic devices,biosensors,biological imaging,and drug delivery.Recently,the human and ecologic...Carbon-based nanomaterials have important research significance in various disciplines,such as composite materials,nanoelectronic devices,biosensors,biological imaging,and drug delivery.Recently,the human and ecological risks associated with carbon-based nanomaterials have received increasing attention.However,the biological safety of carbon based nanomaterials has not been systematically studied.In this study,we used different types of carbon materials,namely,graphene oxide(GO),single-walled carbon nanotubes(SWCNTs),and multiwalled carbon nanotubes(MWCNTs),as models to observe their distribution and oxidative damage in vivo.The results of Histopathological and ultrastructural examinations indicated that the liver and lungs were the main accumulation targets of these nanomaterials.SR-μ-XRF analysis revealed that SWCNTs and MWCNTs might be present in the brain.This shows that the three types of carbon-based nanomaterials could cross the gas-blood barrier and eventually reach the liver tissue.In addition,SWCNTs and MWCNTs could cross the blood-brain barrier and accumulate in the cerebral cortex.The increase in ROS and MDA levels and the decrease in GSH,SOD,and CAT levels indicated that the three types of nanomaterials might cause oxidative stress in the liver.This suggests that direct instillation of these carbon-based nanomaterials into rats could induce ROS generation.In addition,iron(Fe)contaminants in these nanomaterials were a definite source of free radicals.However,these nanomaterials did not cause obvious damage to the rat brain tissue.The deposition of selenoprotein in the rat brain was found to be related to oxidative stress and Fe deficiency.This information may support the development of secure and reasonable applications of the studied carbon-based nanomaterials.展开更多
Three novel acidic polysaccharide fractions(OFPP-1,OFPP-2,OFPP-3)with different m olecular weights(803.7,555.1 and 414.5 k Da)were isolated from the peeled Opuntia dillenii Haw.fruits by alkali-extraction,graded alcoh...Three novel acidic polysaccharide fractions(OFPP-1,OFPP-2,OFPP-3)with different m olecular weights(803.7,555.1 and 414.5 k Da)were isolated from the peeled Opuntia dillenii Haw.fruits by alkali-extraction,graded alcohol precipitation and column chromatography.Structural analysis indicated that OFPPs were pectic polysaccharides consisting of rhamnose,arabinose and galactose residues.The backbone of OFPP-1 consisted of a repeating unit→6-α-D-Galp A-(1→2)-α-L-Rhap-(1→with T-α-D-Galp A-(1→6)-α-D-Galp A-(1→4)-α-D-Glcp-(1→,T-β-D-Xylp-(1→6)-α-D-Galp A-(1→4)-α-D-Glcp-(1→or T-α-D-Galp A-(1→3)-α-L-Araf-(1→as the side chains.The backbone of OFPP-2 consisted of a disaccharide repeating unit→2)-α-L-Rhap-(1→4)-β-D-Galp A-(1→with T-β-L-Araf-(1→as the branches substituted at the O-4 position of→2,4)-α-LRhap-(1→.Whereas the backbone of OFPP-3 was→2,4)-α-L-Rhap-(1→2)-α-L-Rhap-(1→3)-β-L-Araf-(1→or→2,4)-α-L-Rhap-(1→2)-α-L-Rhap-(1→4)-β-D-Galp A-(1→,which was branched at the O-4 position of→2,4)-α-L-Rhap-(1→.Moreover,these three polysaccharide fractions could protect Huh-7 cells against H2O2-induced oxidative stress to different extents by decreasing the MDA content and increasing the SOD,CAT,GSH-Px activities and the GSH level in the Huh-7 cells.These results suggest that OFPPs have the potential to be used as natural antioxidants.展开更多
Probiotics could effectively eliminate excess reactive oxygen species(ROS)generated during aging or lipid metabolism disorders,but their mechanism is unclear.The major purpose of this study was to investigate the mech...Probiotics could effectively eliminate excess reactive oxygen species(ROS)generated during aging or lipid metabolism disorders,but their mechanism is unclear.The major purpose of this study was to investigate the mechanism of Lactiplantibacillus plantarun AR113 alleviating oxidative stress injury in the D-galactose induced aging mice.The result showed that pretreatment with L.plantarun AR113 significantly relieving H_(2)O_(2)induced cytotoxicity in HepG2 cells by maintain cell membrane integrity and increasing antioxidant enzyme activities.In D-galactose induced aging mice,L.plantarun AR113 could significantly attenuate liver damage and inflammatory infiltration by promoting endogenous glutathione(GSH)synthesis and activating the Nrf2/Keap1 signaling pathway in mice,and increasing the expression of regulated phaseⅡdetoxification enzymes and antioxidant enzymes.Further analysis shown that gavage of L.plantarun AR113 could significantly reduce the expression of G protein-coupled receptor 78(GPR78)and C/EBP homologous protein(CHOP)proteins,and promote the restoration of endoplasmic reticulum(ER)homeostasis,thereby activating cell anti-apoptotic pathways.These results were also confirmed in H_(2)O_(2)-treated HepG2 experiments.It indicated that L.plantarun AR113 could inhibit D-galactose-induced liver injury through dual inhibition of ER stress and oxidative stress.L.plantarun AR113 have good application potential in anti-aging and alleviating metabolic disorders.展开更多
Non-enzymatic glycation reaction in food can produce diet-derived advanced glycation end products(dAGEs),which have potential health risks.Thus,it is of great significance to find efficient substances to improve the n...Non-enzymatic glycation reaction in food can produce diet-derived advanced glycation end products(dAGEs),which have potential health risks.Thus,it is of great significance to find efficient substances to improve the negative effects induced by dAGEs on human health.This study investigated the intervening effects of peanut skin procyanidins(PSP)on the dAGEs-induced oxidative stress and systemic inflammation in experimental mice model.Results showed that the accumulation of AGEs in serum,liver,and kidney was significantly increased after mice were fed dAGEs(P<0.05).The expression of advanced glycation product receptor(RAGE)was also significantly increased in liver and kidney(P<0.05).PSP could not only effectively reduce the accumulation of AGEs in serum,liver and kidney of mice,but also reduce the expression of RAGE in liver and kidney of mice.And the levels of pro-inflammatory cytokines interleukin-6(IL-6),tumor necrosis factor(TNF-α),and IL-1βin serum of mice were significantly decreased(P<0.05),while the levels of antiinflammatory factor IL-10 were increased,and the inflammatory injury in mice was improved.In addition,the levels of superoxide dismutase(SOD),glutathione(GSH),catalase(CAT)in liver and kidney of mice were increased(P<0.05),and the level of malondialdehyde(MDA)was decreased(P<0.05),which enhanced the antioxidant capacity of mice in vivo,and improved the oxidative damage of liver and kidney.Molecular docking technique was used to confirm that the parent compound of procyanidins and its main metabolites,such as 3-hydroxyphenylacetic acid,could interact with RAGE,which might inhibit the activation of nuclear transcription factor(NF-κB),and ultimately reduce oxidative stress and inflammation in mice.展开更多
Glycidol is a common lipid-derived foodborne toxicant mainly presents in refined oils and related foodstuffs.Vascular endothelial cells may be potential targets of the deleterious effects associated with glycidol expo...Glycidol is a common lipid-derived foodborne toxicant mainly presents in refined oils and related foodstuffs.Vascular endothelial cells may be potential targets of the deleterious effects associated with glycidol exposure.In human umbilical vein endothelial cells(HUVECs),we found that glycidol treatment promoted endothelialto-mesenchymal transition(EndMT)at a lower concentration(0.5 mmol/L),while induced apoptosis and inflammation at a higher concentration(1 mmol/L).These harmful effects were achieved by the activation of NF-κB/MAPK signaling pathway and were mediated by reactive oxygen species(ROS).In addition,the protective potential of 6-C-(E-2-fluorostyryl)naringenin(6-CEFN)against glycidol was evaluated and compared with naringenin.HUVECs pre-treated with 6-CEFN,but not naringenin,displayed resistance to endothelial dysfunction caused by glycidol.展开更多
Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine ...Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine particulate matter(PM2.5).Methods Forty eight male Wistar rats were randomly divided into six groups:blank control group(C1),water drip control group(C2),PM2.5 exposed group(P),low-dose NAC treated and PM2.5 exposed group(L),middle-dose NAC treated and PM2.5 exposed group(M),and high-dose NAC treated and PM2.5 exposed group(H).PM2.5 suspension(7.5 mg/kg)was administered tracheally once a week for four times.NAC of 125 mg/kg,250 mg/kg and 500 mg/kg was delivered intragastrically to L,M and H group respectively by gavage(10 ml/kg)for six days before PM2.5 exposure.The histopathological changes and human mucin 5 subtype AC(MUC5AC)content in lung tissue of rats were evaluated.We investigated IL-6 in serum and bronchoalveolar lavage fluid(BALF)by Enzyme-linked immunosorbent assay(ELISA),MUC5AC in lung tissue homogenate by ELISA,glutathione peroxidase(GSH-PX)in serum and BALF by spectrophotometry,and the expression of p-ERK1/2,p-JNK1/2 and p-p38 proteins by Western blot.All the measurements were analyzed and compared statistically.Results Lung tissue of rats exposed to PM2.5 showed histological destruction and increased mucus secretion of bronchial epithelial cells.Rats receiving NAC treatment showed less histological destruction and mucus secretion.Of P,L,M and H group,MUC5AC in lung tissue,IL-6 in serum and BALF were higher than controls(C1 and C2)(all P<0.05),with the highest levels found in the P group and a decreasing trend with increase of NAC dose.The activity of GSH-PX in serum and BALF of PM2.5 exposed rats(P,L,M and H)was lower than that of controls(all P<0.05),with higher activities found in NAC treated rats(L,M,and H),and an increasing trend with increase of NAC dose.The expressions of p-ERK1/2,p-JNK1/2 and p-p38 proteins in PM2.5 exposed lung tissue(P,L,M and H)was higher than controls(all P<0.05),with decreased levels and dose dependent downregulation found in NAC treated rats.Conclusion NAC can antagonize major MAPK pathway activation,lung oxidative stress and inflammatory injury induced by PM2.5 in rats.展开更多
Baekgound Recent studies have suggested a potential role for liraglutide in the prevention and stabilization ofatherosclerotic vascular disease. However, the molecular mechanisms underlying the effect of liraglutide o...Baekgound Recent studies have suggested a potential role for liraglutide in the prevention and stabilization ofatherosclerotic vascular disease. However, the molecular mechanisms underlying the effect of liraglutide on atherosclerosis have not been well elucidated. The pur- pose of this study was to examine whether liraglutide protects against oxidative stress and fatty degeneration via modulation of AMP-activated protein kinase （AMPK）/sterol regulatory element binding transcription factor 1 （SREBP1） signaling pathway in foam ceils. Methods Mouse macrophages Raw264.7 cells were exposed to oxidized low density lipoprotein （oxLDL） to induce the formation of foam cells. The cells were incubated with oxLDL （50 μg/mL）, liraglutide （0.1, 0.5, 1 and 2 nmol/L） or exendin-3 （9-39） （1, 10 and 100 nmol/L） alone, or in combination. Oil Red O staining was used to detect intracellular lipid droplets. The levels of TG and cholesterol were measured using the commercial kits. Oxidative stress was determined by measuring intracellular reactive oxygen species （ROS）, malondialdehyde （MDA） and superoxide dismutase 1 （SOD）. Western blot analysis was used to examine the expression of AMPKal, SREBP1, phosphory- lated AMPKal, phosphorylated SREBP1, glucagon-like peptide-1 （GLP-1） and GLP-1 receptor （GLP-1R）. Results Oil Red O staining showed that the cytoplasmic lipid droplet accumulation was visibly decreased in foam cells by treatment with liraglutide. The TG and cholesterol content in the liraglutide-treated foam cells was significantly decreased. In addition, foam ceils manifested an impaired oxidative stress following liraglutide treatment, as evidenced by increased SOD, and decreased ROS and MDA. However, these effects of liraglutide on foam cells were attenuated by the use of GLP-IR antagonist exendin-3 （9-39）. Furthermore, we found that the expression level of AMPKa 1 and phosphorylated AMPKct 1 was significantly increased while the expression level of SREBP 1 and phosphorylated SREBP 1 was significantly decreased in foam cells following treatment with liraglutide. Conclusions This study for the first time demonstrated that the effect of liraglutide on reducing oxidative stress and fatty degeneration in oxLDL-induced Raw264.7 cells is accompanied by the alteration of AMPK/SREBP1 pathway. This study provided a potential molecular mechanism for the effect of liraglutide on reducing oxidative stress and fatty degeneration.展开更多
BACKGROUND:We aimed to investigate the gene expression of myocardial ischemia/reperfusion injury(MIRI)in patients with acute ST-elevation myocardial infarction(STEMI)using stress and toxicity pathway gene chip technol...BACKGROUND:We aimed to investigate the gene expression of myocardial ischemia/reperfusion injury(MIRI)in patients with acute ST-elevation myocardial infarction(STEMI)using stress and toxicity pathway gene chip technology and try to determine the underlying mechanism.METHODS:The mononuclear cells were separated by ficoll centrifugation,and plasma total antioxidant capacity(T-AOC)was determined by the ferric reducing ability of plasma(FRAP)assay.The expression of toxic oxidative stress genes was determined and verified by oligo gene chip and quantitative real-time polymerase chain reaction(qRT-PCR).Additionally,gene ontology(GO)enrichment analysis was performed on DAVID website to analyze the potential mechanism further.RESULTS:The total numbers of white blood cells(WBC)and neutrophils(N)in the peripheral blood of STEMI patients(the AMI group)were significantly higher than those in the control group(WBC:11.67±4.85×10^(9)/L vs.6.41±0.72×10^(9)/L,P<0.05;N:9.27±4.75×10^(9)/L vs.3.89±0.81×10^(9)/L,P<0.05),and WBCs were significantly associated with creatine kinase-myocardial band(CK-MB)on the first day(Y=8.945+0.018X,P<0.05).In addition,the T-AOC was significantly lower in the AMI group comparing to the control group(12.80±1.79 U/mL vs.20.48±2.55 U/mL,P<0.05).According to the gene analysis,eight up-regulated differentially expressed genes(DEGs)included GADD45A,PRDX2,HSPD1,DNAJB1,DNAJB2,RAD50,TNFSF6,and TRADD.Four down-regulated DEGs contained CCNG1,CAT,CYP1A1,and ATM.TNFSF6 and CYP1A1 were detected by polymerase chain reaction(PCR)to verify the expression at different time points,and the results showed that TNFSF6 was up-regulated and CYP1A1 was down-regulated as the total expression.GO and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis suggested that the oxidative stress genes mediate MIRI via various ways such as unfolded protein response(UPR)and apoptosis.CONCLUSIONS:WBCs,especially neutrophils,were the critical cells that mediating reperfusion injury.MIRI was regulated by various genes,including oxidative metabolic stress,heat shock,DNA damage and repair,and apoptosis-related genes.The underlying pathway may be associated with UPR and apoptosis,which may be the novel therapeutic target.展开更多
Auricularia auricula(AA)and Auricularia polytricha(AP)are popular edible fungi.This study successfully produced hypoglycemic polysaccharides from un-smashed or smashing and sieving(through a 10-mesh sieve)AA and AP(te...Auricularia auricula(AA)and Auricularia polytricha(AP)are popular edible fungi.This study successfully produced hypoglycemic polysaccharides from un-smashed or smashing and sieving(through a 10-mesh sieve)AA and AP(termed as AAP/AAP-10 and APP/APP-10)via scalable processes(water extraction,ethanolic precipitation and deproteinization).This is the first report to compare the effectiveness of AAP and APP in combating streptozotocin-induced oxidative stress and diabetes-related changes in mice(body weight,fasting blood glucose,serum insulin,proinflammatory mediator and cytokines,oxidative stress-related products,antioxidant enzymes).APP and AAP with different molecular weights and monosaccharide molar ratios could be therapeutic options for diabetes with a low dose(100 mg/kg/day)likely working better.At the same dose,APP generally performed more effective than AAP,and AAP-10/APP-10 seemed slightly more beneficial than AAP/APP.One mechanism underlying these antidiabetic functions might involve the NF-κB and associated signalling pathways.AP is cheaper than AA,thereby representing a favorable source of functional polysaccharides.展开更多
Many studies on oxidative stress,insulin resistance,and antioxidant treatment have shown that increased oxidative stress may accelerate the development of diabetic complications through the excessive glucose and free ...Many studies on oxidative stress,insulin resistance,and antioxidant treatment have shown that increased oxidative stress may accelerate the development of diabetic complications through the excessive glucose and free fatty acids metabolism in diabetic and insulin-resistant states.Many pathogenic mechanisms such as insulin receptor substrate phosphorylation are involved in insulin resistance induced by oxidative stress.And antioxidant treatments can show benefits in animal models of diabetes mellitus and insulin resistance.However,negative evidence from large clinical trials suggests that new and more powerful antioxidants need to be studied to demonstrate whether antioxidants can be effective in treating diabetic complications.Furthermore,it appears that oxidative stress is only one of the factors contributing to diabetic complications.Thus,antioxidant treatment would most likely be more effective if it were coupled with other treatments for diabetic complications.展开更多
Traditional Chinese preserved egg products have exhibited some anti-inflammatory effects,but their mechanisms of action remain unknown.This study aimed to investigate the anti-inflammatory effects of preserved egg whi...Traditional Chinese preserved egg products have exhibited some anti-inflammatory effects,but their mechanisms of action remain unknown.This study aimed to investigate the anti-inflammatory effects of preserved egg white(PEW)treatment on dextran sulfate sodium(DSS)-induced colitis in mice and the underlying mechanisms.The results showed that treatment with PEW in mice with DSS-induced colitis for 14 days effectively improved the clinical signs,inhibited the secretion and gene expression of pro-inflammatory cytokines,and reduced myeloperoxidase(MPO)activity and oxidative stress levels.In addition,western blotting results showed that PEW significantly suppressed DSS-induced phosphorylation levels of nuclear factor-kappa B(NF-κB)p65 and p38 mitogen-activated protein kinase(MAPK)in colon tissues of mice with colitis.PEW also enhanced the production of short-chain fatty acids(SCFAs)and modulated gut microbiota composition in mice with DSS-induced colitis,including increasing the relative abundance of beneficial bacteria Lachnospiraceae,Ruminococcaceae and Muribaculaceae,and reducing the relative abundance of harmful bacteria Proteobacteria.Taken together,our study demonstrated that preserved egg white could alleviate DSS-induced colitis in mice through the reduction of oxidative stress,modulation of inflammatory cytokines,NF-κB,MAPK and gut microbiota composition.展开更多
BACKGROUND： Ulinastatin （UTI） is a urinary trypsin inhibitor extracted and purified from urine of males. This study aimed to explore the effects of UTI on paraquat-induced-oxidative stress in human type II alveolar...BACKGROUND： Ulinastatin （UTI） is a urinary trypsin inhibitor extracted and purified from urine of males. This study aimed to explore the effects of UTI on paraquat-induced-oxidative stress in human type II alveolar epithelial cells. METHODS： The human type II alveolar epithelial cells, A549 cells, were cultured in vitro. The A549 cells were treated with different concentrations of paraquat （200, 400, 600, 800, 1 000, 1 200 pmol/L） and ulinastatin（0, 2 000, 4 000, 6 000, 8 000 U/mL） for 24 hours, the cell viability was measured by cell counting kit-8 and the median lethal concentration was selected. In order to establish an in vitro model of paraquat intoxication and to determine the safe dose of ulinastatin, we calculated LD50 using cell counting kit-8 to determine the survival rate of the cells. A549 cells were divided into normal control group, paraquat group and paraquat＋ulinastatin group. The levels of malondialdehyde （MDA） and myeloperoxidase （MPO） were detected by biochemistry colorimetry, while the level of reactive oxygen spies （ROS） was detected by DCFH-DA assay. RESULTS： The survival rate of A549 cells treated with different concentrations of paraquat decreased in a concentration-dependent manner. Whereas there was no decrease in the survival rate of cells treated with 0-4 000 U/mL ulinastatin. The levels of MDA, MPO, and ROS were significantly higher in the paraquat group than in the normal control group after 24-hour-exposure. And the survival rate of the paraquat＋ulinastatin group was higher than that of the paraquat group, but lower than that of the normal control group. The levels of MDA, MPO, and ROS were lower than those of the paraquat group. CONCLUSION： Ulinastatin can alleviate the paraquat-induced A549 cell damage by reducing oxidative stress.展开更多
Reducing oxidative stress and hepatoprotective effect of Pu-erh tea water extracts on rats fed with high-fat diet were researched for explaining health care of Pu-erh tea.Fifty SD rats were divided into five groups.Th...Reducing oxidative stress and hepatoprotective effect of Pu-erh tea water extracts on rats fed with high-fat diet were researched for explaining health care of Pu-erh tea.Fifty SD rats were divided into five groups.The body weight was measured once a day.The malondialdehyde(MDA)and glucose(Glu)levels and the activities of alanine aminotransferase(ALT),aspartate aminotransferase(AST),nitric oxide synthase(NOS),and pyruvate kinase(PK)in serum were determined.Furthermore,the hepatic glycogen level(HGL)and the activities of hepatic total superoxide dismutase(T-SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)were also measured after continuous administration for 12 weeks.The result demonstrated that Pu-erh extract caused the decreases in body weight,fat index,MDA and NOS levels,and the increases in hepatic T-SOD,CAT and GSH-Px activities,indicating that the extract may be due to inhibiting the increases of body weight and fat index,reducing oxidant stress state and inhibiting lipid peroxidation,thus decreasing the activities of ALT and AST,and protecting the liver in rat.Meanwhile,the extracts could increase the production of hepatic glycogen and the activity of PK,and reduce glucose level,protecting the liver from the diseases associated with type II diabetes.展开更多
Background Cilostazol is a type 3 phosphodiesterase inhibitor which has been previously demonstrated to prevent the occurrence of tachyarrhythmia and improve defibrillation efficacy. However, the mechanism for this be...Background Cilostazol is a type 3 phosphodiesterase inhibitor which has been previously demonstrated to prevent the occurrence of tachyarrhythmia and improve defibrillation efficacy. However, the mechanism for this beneficial effect is still unclear. Since cardiac mito-chondria have been shown to play a crucial role in fatal cardiac arrhythmias and that oxidative stress is one of the main contributors to arr-hythmia generation, we tested the effects of cilostazol on cardiac mitochondria under severe oxidative stress. Methods Mitochondria were isolated from rat hearts and treated with H2O2 to induce oxidative stress. Cilostazol, at various concentrations, was used to study its protective effects. Pharmacological interventions, including a mitochondrial permeability transition pore （mPTP） blocker, cyclosporine A （CsA）, and an inner membrane anion channel （IMAC） blocker, 4＇-chlorodiazepam （CDP）, were used to investigate the mechanistic role of cilostazol on cardiac mitochondria. Cardiac mitochondrial reactive oxygen species （ROS） production, mitochondrial membrane potential change and mi-tochondrial swelling were determined as indicators of cardiac mitochondrial function. Results Cilostazol preserved cardiac mitochondrial function when exposed to oxidative stress by preventing mitochondrial depolarization, mitochondrial swelling, and decreasing ROS produc-tion. Conclusions Our findings suggest that cardioprotective effects of cilostazol reported previously could be due to its prevention of car-diac mitochondrial dysfunction caused by severe oxidative stress.展开更多
Objective To investigate the role of oxidative stress, inflammation, hypercoagulability and neuroendocrine activation in the transition of hypertensive heart disease to heart failure with preserved ejection fraction ...Objective To investigate the role of oxidative stress, inflammation, hypercoagulability and neuroendocrine activation in the transition of hypertensive heart disease to heart failure with preserved ejection fraction （HFPEF）. Methods We performed echocardiography for 112 patients （≥ 60 years old） with normal EF （18 controls and 94 with hypertension）, and determined protein carbonylation （PC）, and tetrahydrobiopterin （BH4）, C-reactive protein （CRP）, interleukin-6 （IL-6）, tumor necrosis factor-α （TNF-α）, fibrinogen, plasminogen activator inhibitor type-I （PAI-I）, von Willebrand factor, chromogranin A （cGA） and B-type natriuretic peptide （BNP） levels from their blood samples. Results We found that 40% （38/94） of the patients with hypertension （HT） had no diastolic dysfunction （HTDD-）, and 60% （56/94） had diastolic dysfunction （HTDD＋）. Compared to the controls, both patient groups had increased PC and BH4, TNF-α, PAI-I and BNP levels, while the HTDD＋ group had elevated cGA and CRP levels. Decreased atrial and longitudinal left ventficular （LV） systolic and diastolic myocardial deformation （strain and strain rate） was demonstrated in both patient groups versus the control. Patients whose LV diastolic function deteriorated during the follow-up had elevated PC and IL-6 level compared to their own baseline values, and to the respective values of patients whose LV diastolic function remained unchanged. Oxidative stress, inflammation, BNP and PAI-I levels inversely correlated with LV systolic, diastolic and atrial function. Conclusions In patients with HT and normal EF, the most common HFPEF precursor condition, oxidative stress and inflammation may be responsible for LV systolic, diastolic and atrial dysfunction, which are important determinants of the transition of liT to HFPEF.展开更多
BACKGROUND:Pulmonary fibrosis(PF)is one of the main causes of death in patients with paraquat(PQ)poisoning.This study aimed to evaluate the relationship between mitochondrial fi ssion and oxidative stress in PQ-induce...BACKGROUND:Pulmonary fibrosis(PF)is one of the main causes of death in patients with paraquat(PQ)poisoning.This study aimed to evaluate the relationship between mitochondrial fi ssion and oxidative stress in PQ-induced epithelial-mesenchymal transition(EMT)and PF.METHODS:C57BL/6 mice and MLE-12 cells were exposed to PQ to construct a PF model in vivo and in vitro.Histological changes in the lungs were examined by hematoxylin and eosin(H&E)staining.Mitochondrial morphology was detected by MitoTracker®Deep Red FM or transmission electron microscopy(TEM).Western blotting and immunofluorescence were used to determine the expression of protein.The migration ability of the cells was detected by the cell scratch test.Mitochondrial DNA(mtDNA)levels were assessed by real-time polymerase chain reaction(PCR).Enzyme-linked immunosorbent assay(ELISA)was applied to detect cytokine levels.Superoxide dismutase(SOD)activity and the levels of glutathione(GSH)and malondialdehyde(MDA)were detected by chemichromatometry.RESULTS:PQ exposure caused EMT and PF in vivo and in vitro.PQ destroyed mitochondrial structure and enhanced the expression of dynamin-related protein 1(Drp1),which were accompanied by oxidative stress.Inhibiting mitochondrial fission using mitochondrial division inhibitor-1(Mdivi-1),a selective inhibitor of Drp1,attenuated PQ-induced EMT and oxidative damage.Treatment with N-acetyl-L-cysteine(NAC),an antioxidant,reduced Drp1 expression,attenuated mitochondrial structure damage and inhibited PQ-induced EMT and PF.Both Mdivi-1 and NAC treatment markedly suppressed mtDNA release,the expression of Toll-like receptor 9(TLR9)and phosphorylation(P)-NF-κB p65 as well as cytokines(interleukin 6[IL-6],interleukin-1β[IL-1β],and tumor necrosis factor-α[TNF-α])production.CONCLUSION:Mutual promotion of mitochondrial fission and oxidative stress contributes to EMT in PQ-induced PF,which is associated with the mtDNA/TLR9/NF-κB pathway.展开更多
Curculigoside(CCG)is a phenolic glycoside compound extracted from the root of a natural plant called Curculigo orchioides Gaertn.In this study,the neuroprotective effect of CCG through oxidative stress mediated mitoch...Curculigoside(CCG)is a phenolic glycoside compound extracted from the root of a natural plant called Curculigo orchioides Gaertn.In this study,the neuroprotective effect of CCG through oxidative stress mediated mitochondrial dysfunction on L-glutamate(L-Glu)-damaged hippocampal neuron cell line(HT22)and APPswe/PSEN1dE9 transgenic(APP/PS1)mice were investigated.Observably,CCG in L-Glu-damaged HT22 cells suppressed apoptosis,reduced the accumulation of reactive oxygen species,balanced the mitochondrial membrane potential and prevented the over-influx of calcium.In APP/PS1 mice,4-week CCG administration significantly improved their memory and behavioral impairments,enhanced the function of cholinergic system,reduced the deposition of Aβand neurofibrillary fiber tangles caused by tau phosphorylation,and suppressed the development and progression of oxidative stress in brains of APP/PS1 mice.Based on the screening of proteomic analysis on hippocampus,CCG were confirmed that it could regulate the expression levels of proteins related to mitochondrial dysfunction,mainly through activating on AMPK/Nrf2 signaling,in APP/PS1 mice and L-Glu-exposed HT22 cells.CCG has a prominent neuroprotective effect on regulate the AMPK/Nrf2-mediated mitochondrial dysfunction in cells APP/PS1 mice support CCG is a potentially potent drug for AD treatment and merits further investigation.展开更多
Soluble fiber-rich fenugreek seeds(Trigonella foenum-graecum)and garlic(Allium sativum)are understood to exert cholesterol-lowering and antioxidant effects.The cardioprotective influence of a combination of fenugreek ...Soluble fiber-rich fenugreek seeds(Trigonella foenum-graecum)and garlic(Allium sativum)are understood to exert cholesterol-lowering and antioxidant effects.The cardioprotective influence of a combination of fenugreek seeds and garlic by their antioxidant influence was evaluated in hypercholesterolemic rats administered isoproterenol.Wistar rats were maintained on high-cholesterol diet for 8 weeks along with dietary interventions of fenugreek(10%),garlic(2%)and their combination.Myocardial infarction was induced with isoproterenol injection.Increased circulatory troponin,disturbed activities of cardiac ATPases,increased serum iron and decreased ceruloplasmin confirmed myocardial infarction.Elevated lipid peroxides accompanied with reduced antioxidant molecules caused by isoproterenol and altered activities of antioxidant enzymes in serum and heart in induced myocardial necrosis were countered by dietary fenugreek,garlic,and fenugreek+garlic.Dietary fenugreek seeds and garlic ameliorated isoproterenol-induced compromised antioxidant status,the cardioprotective effect being higher by the combination of fenugreek seeds and garlic.展开更多
Carbon tetrachloride(CCl4)is a hepatotoxin that triggers liver damage.This study aimed to evaluate the protective effect of phytochemicals detected in Moringa oleifera Lam.leaf extract(MOLE)on CCl4-induced hepatotoxic...Carbon tetrachloride(CCl4)is a hepatotoxin that triggers liver damage.This study aimed to evaluate the protective effect of phytochemicals detected in Moringa oleifera Lam.leaf extract(MOLE)on CCl4-induced hepatotoxicity in mice.Phytochemicals,total phenolics,and total fl avonoids were detected in MOLE.MOLE markedly decreased the elevation of serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in consistence with the ameliorating effect on CCl4-induced histopathological abnormalities.Moreover,MOLE significantly alleviated the decrease in the antioxidant defense mechanism induced by CCl4.The suppressing effect of MOLE on the boosted inflammatory pathway triggered by CCl4 was detected by measuring the protein levels of nuclear factor kappa-light-chain-enhancer of activated B-cells(NF-κB-p65),toll-like receptor 4(TLR4),tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-1β,and IL-8 as well as the relative expressions of nuclear factor kappa B(NF-κB),TNF-α,IL-1β,and TLR4 genes.Apoptosis and genotoxicity induced by CCl4 were signifi cantly alleviated by MOLE.MOLE co-administration modulated TLR4/NF-κB pathway as presented by the suppressed gene expression of TLR4 and NF-κB as well as by the reduced protein expression of TLR4 and NF-κB-p65.In conclusion,MOLE has a multifarious protective role against hepatotoxicity through control of oxidative stress and modulation of TLR4/NF-κB.展开更多
This study aimed to evaluate the anti-hyperglycemic and antioxidant role of Actinidia deliciosa(kiwifruits)aqueous extract in streptozotocin-treated rats.Animals were distributed into;control,A.deliciosa aqueous extra...This study aimed to evaluate the anti-hyperglycemic and antioxidant role of Actinidia deliciosa(kiwifruits)aqueous extract in streptozotocin-treated rats.Animals were distributed into;control,A.deliciosa aqueous extract(ADAE;1 g/kg orally),streptozotocin(STZ;50 mg/kg,i.p,single dose),and STZ plus ADAE,respectively.Results showed that ADAE had high antioxidant and radical scavenging potency.Elevation in blood sugar level,lipid peroxidation(LPO),kidney function biomarkers,and perturbations in hematological parameters were observed in diabetic rats.While,enzymatic and non-enzymatic antioxidants,protein content,and alkaline phosphatase(ALP)activity declined.Furthermore,histological,immunohistochemical alpha-smooth muscle actin immunoreactivity(α-SMA-ir)and histochemical(collagen,total protein,DNA,and RNA)alterations were observed in rat kidneys.Moreover,STZ produced upregulation of inflammatory associated genes(tumor necrosis factor-alpha;TNF-αand transforming growth factorβ1;TGF-β1)and triggered apoptosis by upregulating apoptotic related gene[Bcl2-associated X protein(Bax)]and downregulating anti-apoptotic related gene B-cell lymphoma-2(Bcl-2)based on real-time PCR data.Moreover,diabetic rats administered with ADAE showed significant restoration in LPO,antioxidant status,and biochemical indices besides tissue architecture,and genes improvement regarding STZ group.Conclusively,A.deliciosa has a valuable ameliorative infl uence and can restore glucose levels and improve kidney dysfunction in diabetic rats.展开更多
基金the National Natural Science Foundation of the Henan University(21IRTSTHN011).
文摘Carbon-based nanomaterials have important research significance in various disciplines,such as composite materials,nanoelectronic devices,biosensors,biological imaging,and drug delivery.Recently,the human and ecological risks associated with carbon-based nanomaterials have received increasing attention.However,the biological safety of carbon based nanomaterials has not been systematically studied.In this study,we used different types of carbon materials,namely,graphene oxide(GO),single-walled carbon nanotubes(SWCNTs),and multiwalled carbon nanotubes(MWCNTs),as models to observe their distribution and oxidative damage in vivo.The results of Histopathological and ultrastructural examinations indicated that the liver and lungs were the main accumulation targets of these nanomaterials.SR-μ-XRF analysis revealed that SWCNTs and MWCNTs might be present in the brain.This shows that the three types of carbon-based nanomaterials could cross the gas-blood barrier and eventually reach the liver tissue.In addition,SWCNTs and MWCNTs could cross the blood-brain barrier and accumulate in the cerebral cortex.The increase in ROS and MDA levels and the decrease in GSH,SOD,and CAT levels indicated that the three types of nanomaterials might cause oxidative stress in the liver.This suggests that direct instillation of these carbon-based nanomaterials into rats could induce ROS generation.In addition,iron(Fe)contaminants in these nanomaterials were a definite source of free radicals.However,these nanomaterials did not cause obvious damage to the rat brain tissue.The deposition of selenoprotein in the rat brain was found to be related to oxidative stress and Fe deficiency.This information may support the development of secure and reasonable applications of the studied carbon-based nanomaterials.
基金supported by the National Natural Science Foundation of China(No.31972977)。
文摘Three novel acidic polysaccharide fractions(OFPP-1,OFPP-2,OFPP-3)with different m olecular weights(803.7,555.1 and 414.5 k Da)were isolated from the peeled Opuntia dillenii Haw.fruits by alkali-extraction,graded alcohol precipitation and column chromatography.Structural analysis indicated that OFPPs were pectic polysaccharides consisting of rhamnose,arabinose and galactose residues.The backbone of OFPP-1 consisted of a repeating unit→6-α-D-Galp A-(1→2)-α-L-Rhap-(1→with T-α-D-Galp A-(1→6)-α-D-Galp A-(1→4)-α-D-Glcp-(1→,T-β-D-Xylp-(1→6)-α-D-Galp A-(1→4)-α-D-Glcp-(1→or T-α-D-Galp A-(1→3)-α-L-Araf-(1→as the side chains.The backbone of OFPP-2 consisted of a disaccharide repeating unit→2)-α-L-Rhap-(1→4)-β-D-Galp A-(1→with T-β-L-Araf-(1→as the branches substituted at the O-4 position of→2,4)-α-LRhap-(1→.Whereas the backbone of OFPP-3 was→2,4)-α-L-Rhap-(1→2)-α-L-Rhap-(1→3)-β-L-Araf-(1→or→2,4)-α-L-Rhap-(1→2)-α-L-Rhap-(1→4)-β-D-Galp A-(1→,which was branched at the O-4 position of→2,4)-α-L-Rhap-(1→.Moreover,these three polysaccharide fractions could protect Huh-7 cells against H2O2-induced oxidative stress to different extents by decreasing the MDA content and increasing the SOD,CAT,GSH-Px activities and the GSH level in the Huh-7 cells.These results suggest that OFPPs have the potential to be used as natural antioxidants.
基金supported by the National Science Fund for Distinguished Young Scholars(32025029)the Shanghai Education Committee Scientific Research Innovation Projects(2101070007800120)+1 种基金the Yili Health Science Foundation of Chinese Institute of Food Science and Technology(2021-Y06)the Shanghai Engineering Research Center of food microbiology program(19DZ2281100)。
文摘Probiotics could effectively eliminate excess reactive oxygen species(ROS)generated during aging or lipid metabolism disorders,but their mechanism is unclear.The major purpose of this study was to investigate the mechanism of Lactiplantibacillus plantarun AR113 alleviating oxidative stress injury in the D-galactose induced aging mice.The result showed that pretreatment with L.plantarun AR113 significantly relieving H_(2)O_(2)induced cytotoxicity in HepG2 cells by maintain cell membrane integrity and increasing antioxidant enzyme activities.In D-galactose induced aging mice,L.plantarun AR113 could significantly attenuate liver damage and inflammatory infiltration by promoting endogenous glutathione(GSH)synthesis and activating the Nrf2/Keap1 signaling pathway in mice,and increasing the expression of regulated phaseⅡdetoxification enzymes and antioxidant enzymes.Further analysis shown that gavage of L.plantarun AR113 could significantly reduce the expression of G protein-coupled receptor 78(GPR78)and C/EBP homologous protein(CHOP)proteins,and promote the restoration of endoplasmic reticulum(ER)homeostasis,thereby activating cell anti-apoptotic pathways.These results were also confirmed in H_(2)O_(2)-treated HepG2 experiments.It indicated that L.plantarun AR113 could inhibit D-galactose-induced liver injury through dual inhibition of ER stress and oxidative stress.L.plantarun AR113 have good application potential in anti-aging and alleviating metabolic disorders.
基金supported by the Doctoral Science Foundation of Shanxi Agricultural University(2023BQ34)Shanxi Province Work Award Fund Research Project(SXBYKY2022116).
文摘Non-enzymatic glycation reaction in food can produce diet-derived advanced glycation end products(dAGEs),which have potential health risks.Thus,it is of great significance to find efficient substances to improve the negative effects induced by dAGEs on human health.This study investigated the intervening effects of peanut skin procyanidins(PSP)on the dAGEs-induced oxidative stress and systemic inflammation in experimental mice model.Results showed that the accumulation of AGEs in serum,liver,and kidney was significantly increased after mice were fed dAGEs(P<0.05).The expression of advanced glycation product receptor(RAGE)was also significantly increased in liver and kidney(P<0.05).PSP could not only effectively reduce the accumulation of AGEs in serum,liver and kidney of mice,but also reduce the expression of RAGE in liver and kidney of mice.And the levels of pro-inflammatory cytokines interleukin-6(IL-6),tumor necrosis factor(TNF-α),and IL-1βin serum of mice were significantly decreased(P<0.05),while the levels of antiinflammatory factor IL-10 were increased,and the inflammatory injury in mice was improved.In addition,the levels of superoxide dismutase(SOD),glutathione(GSH),catalase(CAT)in liver and kidney of mice were increased(P<0.05),and the level of malondialdehyde(MDA)was decreased(P<0.05),which enhanced the antioxidant capacity of mice in vivo,and improved the oxidative damage of liver and kidney.Molecular docking technique was used to confirm that the parent compound of procyanidins and its main metabolites,such as 3-hydroxyphenylacetic acid,could interact with RAGE,which might inhibit the activation of nuclear transcription factor(NF-κB),and ultimately reduce oxidative stress and inflammation in mice.
基金supported by the National Key R&D Program of China(2021YFD2100103)the National Natural Science Foundation of China(32101935).
文摘Glycidol is a common lipid-derived foodborne toxicant mainly presents in refined oils and related foodstuffs.Vascular endothelial cells may be potential targets of the deleterious effects associated with glycidol exposure.In human umbilical vein endothelial cells(HUVECs),we found that glycidol treatment promoted endothelialto-mesenchymal transition(EndMT)at a lower concentration(0.5 mmol/L),while induced apoptosis and inflammation at a higher concentration(1 mmol/L).These harmful effects were achieved by the activation of NF-κB/MAPK signaling pathway and were mediated by reactive oxygen species(ROS).In addition,the protective potential of 6-C-(E-2-fluorostyryl)naringenin(6-CEFN)against glycidol was evaluated and compared with naringenin.HUVECs pre-treated with 6-CEFN,but not naringenin,displayed resistance to endothelial dysfunction caused by glycidol.
文摘Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine particulate matter(PM2.5).Methods Forty eight male Wistar rats were randomly divided into six groups:blank control group(C1),water drip control group(C2),PM2.5 exposed group(P),low-dose NAC treated and PM2.5 exposed group(L),middle-dose NAC treated and PM2.5 exposed group(M),and high-dose NAC treated and PM2.5 exposed group(H).PM2.5 suspension(7.5 mg/kg)was administered tracheally once a week for four times.NAC of 125 mg/kg,250 mg/kg and 500 mg/kg was delivered intragastrically to L,M and H group respectively by gavage(10 ml/kg)for six days before PM2.5 exposure.The histopathological changes and human mucin 5 subtype AC(MUC5AC)content in lung tissue of rats were evaluated.We investigated IL-6 in serum and bronchoalveolar lavage fluid(BALF)by Enzyme-linked immunosorbent assay(ELISA),MUC5AC in lung tissue homogenate by ELISA,glutathione peroxidase(GSH-PX)in serum and BALF by spectrophotometry,and the expression of p-ERK1/2,p-JNK1/2 and p-p38 proteins by Western blot.All the measurements were analyzed and compared statistically.Results Lung tissue of rats exposed to PM2.5 showed histological destruction and increased mucus secretion of bronchial epithelial cells.Rats receiving NAC treatment showed less histological destruction and mucus secretion.Of P,L,M and H group,MUC5AC in lung tissue,IL-6 in serum and BALF were higher than controls(C1 and C2)(all P<0.05),with the highest levels found in the P group and a decreasing trend with increase of NAC dose.The activity of GSH-PX in serum and BALF of PM2.5 exposed rats(P,L,M and H)was lower than that of controls(all P<0.05),with higher activities found in NAC treated rats(L,M,and H),and an increasing trend with increase of NAC dose.The expressions of p-ERK1/2,p-JNK1/2 and p-p38 proteins in PM2.5 exposed lung tissue(P,L,M and H)was higher than controls(all P<0.05),with decreased levels and dose dependent downregulation found in NAC treated rats.Conclusion NAC can antagonize major MAPK pathway activation,lung oxidative stress and inflammatory injury induced by PM2.5 in rats.
文摘Baekgound Recent studies have suggested a potential role for liraglutide in the prevention and stabilization ofatherosclerotic vascular disease. However, the molecular mechanisms underlying the effect of liraglutide on atherosclerosis have not been well elucidated. The pur- pose of this study was to examine whether liraglutide protects against oxidative stress and fatty degeneration via modulation of AMP-activated protein kinase （AMPK）/sterol regulatory element binding transcription factor 1 （SREBP1） signaling pathway in foam ceils. Methods Mouse macrophages Raw264.7 cells were exposed to oxidized low density lipoprotein （oxLDL） to induce the formation of foam cells. The cells were incubated with oxLDL （50 μg/mL）, liraglutide （0.1, 0.5, 1 and 2 nmol/L） or exendin-3 （9-39） （1, 10 and 100 nmol/L） alone, or in combination. Oil Red O staining was used to detect intracellular lipid droplets. The levels of TG and cholesterol were measured using the commercial kits. Oxidative stress was determined by measuring intracellular reactive oxygen species （ROS）, malondialdehyde （MDA） and superoxide dismutase 1 （SOD）. Western blot analysis was used to examine the expression of AMPKal, SREBP1, phosphory- lated AMPKal, phosphorylated SREBP1, glucagon-like peptide-1 （GLP-1） and GLP-1 receptor （GLP-1R）. Results Oil Red O staining showed that the cytoplasmic lipid droplet accumulation was visibly decreased in foam cells by treatment with liraglutide. The TG and cholesterol content in the liraglutide-treated foam cells was significantly decreased. In addition, foam ceils manifested an impaired oxidative stress following liraglutide treatment, as evidenced by increased SOD, and decreased ROS and MDA. However, these effects of liraglutide on foam cells were attenuated by the use of GLP-IR antagonist exendin-3 （9-39）. Furthermore, we found that the expression level of AMPKa 1 and phosphorylated AMPKct 1 was significantly increased while the expression level of SREBP 1 and phosphorylated SREBP 1 was significantly decreased in foam cells following treatment with liraglutide. Conclusions This study for the first time demonstrated that the effect of liraglutide on reducing oxidative stress and fatty degeneration in oxLDL-induced Raw264.7 cells is accompanied by the alteration of AMPK/SREBP1 pathway. This study provided a potential molecular mechanism for the effect of liraglutide on reducing oxidative stress and fatty degeneration.
基金National Natural Science Foundation of China(81670220,31270992,and 30800215)Guangdong Provincial Natural Science Foundation(2014A030313086)+2 种基金Guangdong Provincial Science and Technology Plan Project(2015A020212013)Guangzhou Science and Technology Project(201804010007)This research was approved by the Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University([2019]176).
文摘BACKGROUND:We aimed to investigate the gene expression of myocardial ischemia/reperfusion injury(MIRI)in patients with acute ST-elevation myocardial infarction(STEMI)using stress and toxicity pathway gene chip technology and try to determine the underlying mechanism.METHODS:The mononuclear cells were separated by ficoll centrifugation,and plasma total antioxidant capacity(T-AOC)was determined by the ferric reducing ability of plasma(FRAP)assay.The expression of toxic oxidative stress genes was determined and verified by oligo gene chip and quantitative real-time polymerase chain reaction(qRT-PCR).Additionally,gene ontology(GO)enrichment analysis was performed on DAVID website to analyze the potential mechanism further.RESULTS:The total numbers of white blood cells(WBC)and neutrophils(N)in the peripheral blood of STEMI patients(the AMI group)were significantly higher than those in the control group(WBC:11.67±4.85×10^(9)/L vs.6.41±0.72×10^(9)/L,P<0.05;N:9.27±4.75×10^(9)/L vs.3.89±0.81×10^(9)/L,P<0.05),and WBCs were significantly associated with creatine kinase-myocardial band(CK-MB)on the first day(Y=8.945+0.018X,P<0.05).In addition,the T-AOC was significantly lower in the AMI group comparing to the control group(12.80±1.79 U/mL vs.20.48±2.55 U/mL,P<0.05).According to the gene analysis,eight up-regulated differentially expressed genes(DEGs)included GADD45A,PRDX2,HSPD1,DNAJB1,DNAJB2,RAD50,TNFSF6,and TRADD.Four down-regulated DEGs contained CCNG1,CAT,CYP1A1,and ATM.TNFSF6 and CYP1A1 were detected by polymerase chain reaction(PCR)to verify the expression at different time points,and the results showed that TNFSF6 was up-regulated and CYP1A1 was down-regulated as the total expression.GO and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis suggested that the oxidative stress genes mediate MIRI via various ways such as unfolded protein response(UPR)and apoptosis.CONCLUSIONS:WBCs,especially neutrophils,were the critical cells that mediating reperfusion injury.MIRI was regulated by various genes,including oxidative metabolic stress,heat shock,DNA damage and repair,and apoptosis-related genes.The underlying pathway may be associated with UPR and apoptosis,which may be the novel therapeutic target.
基金the financial support from National key Technologies R&D Program for 13th Five-year Plan(2016YFD0400803)National Natural Science Foundation of China(No.31201416)Science and Technology Plan of Guangdong Province(2017ZD093).
文摘Auricularia auricula(AA)and Auricularia polytricha(AP)are popular edible fungi.This study successfully produced hypoglycemic polysaccharides from un-smashed or smashing and sieving(through a 10-mesh sieve)AA and AP(termed as AAP/AAP-10 and APP/APP-10)via scalable processes(water extraction,ethanolic precipitation and deproteinization).This is the first report to compare the effectiveness of AAP and APP in combating streptozotocin-induced oxidative stress and diabetes-related changes in mice(body weight,fasting blood glucose,serum insulin,proinflammatory mediator and cytokines,oxidative stress-related products,antioxidant enzymes).APP and AAP with different molecular weights and monosaccharide molar ratios could be therapeutic options for diabetes with a low dose(100 mg/kg/day)likely working better.At the same dose,APP generally performed more effective than AAP,and AAP-10/APP-10 seemed slightly more beneficial than AAP/APP.One mechanism underlying these antidiabetic functions might involve the NF-κB and associated signalling pathways.AP is cheaper than AA,thereby representing a favorable source of functional polysaccharides.
基金Supported by grant from the National Basic Research Program (973Program) (2006CB503903)
文摘Many studies on oxidative stress,insulin resistance,and antioxidant treatment have shown that increased oxidative stress may accelerate the development of diabetic complications through the excessive glucose and free fatty acids metabolism in diabetic and insulin-resistant states.Many pathogenic mechanisms such as insulin receptor substrate phosphorylation are involved in insulin resistance induced by oxidative stress.And antioxidant treatments can show benefits in animal models of diabetes mellitus and insulin resistance.However,negative evidence from large clinical trials suggests that new and more powerful antioxidants need to be studied to demonstrate whether antioxidants can be effective in treating diabetic complications.Furthermore,it appears that oxidative stress is only one of the factors contributing to diabetic complications.Thus,antioxidant treatment would most likely be more effective if it were coupled with other treatments for diabetic complications.
基金financially supported by the Chinese National Natural Science Funds (31772043)the Fundamental Research Funds for the Central Universities (2662018JC021)
文摘Traditional Chinese preserved egg products have exhibited some anti-inflammatory effects,but their mechanisms of action remain unknown.This study aimed to investigate the anti-inflammatory effects of preserved egg white(PEW)treatment on dextran sulfate sodium(DSS)-induced colitis in mice and the underlying mechanisms.The results showed that treatment with PEW in mice with DSS-induced colitis for 14 days effectively improved the clinical signs,inhibited the secretion and gene expression of pro-inflammatory cytokines,and reduced myeloperoxidase(MPO)activity and oxidative stress levels.In addition,western blotting results showed that PEW significantly suppressed DSS-induced phosphorylation levels of nuclear factor-kappa B(NF-κB)p65 and p38 mitogen-activated protein kinase(MAPK)in colon tissues of mice with colitis.PEW also enhanced the production of short-chain fatty acids(SCFAs)and modulated gut microbiota composition in mice with DSS-induced colitis,including increasing the relative abundance of beneficial bacteria Lachnospiraceae,Ruminococcaceae and Muribaculaceae,and reducing the relative abundance of harmful bacteria Proteobacteria.Taken together,our study demonstrated that preserved egg white could alleviate DSS-induced colitis in mice through the reduction of oxidative stress,modulation of inflammatory cytokines,NF-κB,MAPK and gut microbiota composition.
基金supported by grants from National Natural Science Foundation(81272071)Techpool Foundation(01201111)
文摘BACKGROUND： Ulinastatin （UTI） is a urinary trypsin inhibitor extracted and purified from urine of males. This study aimed to explore the effects of UTI on paraquat-induced-oxidative stress in human type II alveolar epithelial cells. METHODS： The human type II alveolar epithelial cells, A549 cells, were cultured in vitro. The A549 cells were treated with different concentrations of paraquat （200, 400, 600, 800, 1 000, 1 200 pmol/L） and ulinastatin（0, 2 000, 4 000, 6 000, 8 000 U/mL） for 24 hours, the cell viability was measured by cell counting kit-8 and the median lethal concentration was selected. In order to establish an in vitro model of paraquat intoxication and to determine the safe dose of ulinastatin, we calculated LD50 using cell counting kit-8 to determine the survival rate of the cells. A549 cells were divided into normal control group, paraquat group and paraquat＋ulinastatin group. The levels of malondialdehyde （MDA） and myeloperoxidase （MPO） were detected by biochemistry colorimetry, while the level of reactive oxygen spies （ROS） was detected by DCFH-DA assay. RESULTS： The survival rate of A549 cells treated with different concentrations of paraquat decreased in a concentration-dependent manner. Whereas there was no decrease in the survival rate of cells treated with 0-4 000 U/mL ulinastatin. The levels of MDA, MPO, and ROS were significantly higher in the paraquat group than in the normal control group after 24-hour-exposure. And the survival rate of the paraquat＋ulinastatin group was higher than that of the paraquat group, but lower than that of the normal control group. The levels of MDA, MPO, and ROS were lower than those of the paraquat group. CONCLUSION： Ulinastatin can alleviate the paraquat-induced A549 cell damage by reducing oxidative stress.
文摘Reducing oxidative stress and hepatoprotective effect of Pu-erh tea water extracts on rats fed with high-fat diet were researched for explaining health care of Pu-erh tea.Fifty SD rats were divided into five groups.The body weight was measured once a day.The malondialdehyde(MDA)and glucose(Glu)levels and the activities of alanine aminotransferase(ALT),aspartate aminotransferase(AST),nitric oxide synthase(NOS),and pyruvate kinase(PK)in serum were determined.Furthermore,the hepatic glycogen level(HGL)and the activities of hepatic total superoxide dismutase(T-SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)were also measured after continuous administration for 12 weeks.The result demonstrated that Pu-erh extract caused the decreases in body weight,fat index,MDA and NOS levels,and the increases in hepatic T-SOD,CAT and GSH-Px activities,indicating that the extract may be due to inhibiting the increases of body weight and fat index,reducing oxidant stress state and inhibiting lipid peroxidation,thus decreasing the activities of ALT and AST,and protecting the liver in rat.Meanwhile,the extracts could increase the production of hepatic glycogen and the activity of PK,and reduce glucose level,protecting the liver from the diseases associated with type II diabetes.
文摘Background Cilostazol is a type 3 phosphodiesterase inhibitor which has been previously demonstrated to prevent the occurrence of tachyarrhythmia and improve defibrillation efficacy. However, the mechanism for this beneficial effect is still unclear. Since cardiac mito-chondria have been shown to play a crucial role in fatal cardiac arrhythmias and that oxidative stress is one of the main contributors to arr-hythmia generation, we tested the effects of cilostazol on cardiac mitochondria under severe oxidative stress. Methods Mitochondria were isolated from rat hearts and treated with H2O2 to induce oxidative stress. Cilostazol, at various concentrations, was used to study its protective effects. Pharmacological interventions, including a mitochondrial permeability transition pore （mPTP） blocker, cyclosporine A （CsA）, and an inner membrane anion channel （IMAC） blocker, 4＇-chlorodiazepam （CDP）, were used to investigate the mechanistic role of cilostazol on cardiac mitochondria. Cardiac mitochondrial reactive oxygen species （ROS） production, mitochondrial membrane potential change and mi-tochondrial swelling were determined as indicators of cardiac mitochondrial function. Results Cilostazol preserved cardiac mitochondrial function when exposed to oxidative stress by preventing mitochondrial depolarization, mitochondrial swelling, and decreasing ROS produc-tion. Conclusions Our findings suggest that cardioprotective effects of cilostazol reported previously could be due to its prevention of car-diac mitochondrial dysfunction caused by severe oxidative stress.
文摘Objective To investigate the role of oxidative stress, inflammation, hypercoagulability and neuroendocrine activation in the transition of hypertensive heart disease to heart failure with preserved ejection fraction （HFPEF）. Methods We performed echocardiography for 112 patients （≥ 60 years old） with normal EF （18 controls and 94 with hypertension）, and determined protein carbonylation （PC）, and tetrahydrobiopterin （BH4）, C-reactive protein （CRP）, interleukin-6 （IL-6）, tumor necrosis factor-α （TNF-α）, fibrinogen, plasminogen activator inhibitor type-I （PAI-I）, von Willebrand factor, chromogranin A （cGA） and B-type natriuretic peptide （BNP） levels from their blood samples. Results We found that 40% （38/94） of the patients with hypertension （HT） had no diastolic dysfunction （HTDD-）, and 60% （56/94） had diastolic dysfunction （HTDD＋）. Compared to the controls, both patient groups had increased PC and BH4, TNF-α, PAI-I and BNP levels, while the HTDD＋ group had elevated cGA and CRP levels. Decreased atrial and longitudinal left ventficular （LV） systolic and diastolic myocardial deformation （strain and strain rate） was demonstrated in both patient groups versus the control. Patients whose LV diastolic function deteriorated during the follow-up had elevated PC and IL-6 level compared to their own baseline values, and to the respective values of patients whose LV diastolic function remained unchanged. Oxidative stress, inflammation, BNP and PAI-I levels inversely correlated with LV systolic, diastolic and atrial function. Conclusions In patients with HT and normal EF, the most common HFPEF precursor condition, oxidative stress and inflammation may be responsible for LV systolic, diastolic and atrial dysfunction, which are important determinants of the transition of liT to HFPEF.
基金supported by the Wenzhou Municipal Science and Technology Bureau(Y2020092)partly by the Key Specialty of Traditional Chinese Medicine of Zhejiang Province in the 13th Five-Year Plan period(Emergency Department).
文摘BACKGROUND:Pulmonary fibrosis(PF)is one of the main causes of death in patients with paraquat(PQ)poisoning.This study aimed to evaluate the relationship between mitochondrial fi ssion and oxidative stress in PQ-induced epithelial-mesenchymal transition(EMT)and PF.METHODS:C57BL/6 mice and MLE-12 cells were exposed to PQ to construct a PF model in vivo and in vitro.Histological changes in the lungs were examined by hematoxylin and eosin(H&E)staining.Mitochondrial morphology was detected by MitoTracker®Deep Red FM or transmission electron microscopy(TEM).Western blotting and immunofluorescence were used to determine the expression of protein.The migration ability of the cells was detected by the cell scratch test.Mitochondrial DNA(mtDNA)levels were assessed by real-time polymerase chain reaction(PCR).Enzyme-linked immunosorbent assay(ELISA)was applied to detect cytokine levels.Superoxide dismutase(SOD)activity and the levels of glutathione(GSH)and malondialdehyde(MDA)were detected by chemichromatometry.RESULTS:PQ exposure caused EMT and PF in vivo and in vitro.PQ destroyed mitochondrial structure and enhanced the expression of dynamin-related protein 1(Drp1),which were accompanied by oxidative stress.Inhibiting mitochondrial fission using mitochondrial division inhibitor-1(Mdivi-1),a selective inhibitor of Drp1,attenuated PQ-induced EMT and oxidative damage.Treatment with N-acetyl-L-cysteine(NAC),an antioxidant,reduced Drp1 expression,attenuated mitochondrial structure damage and inhibited PQ-induced EMT and PF.Both Mdivi-1 and NAC treatment markedly suppressed mtDNA release,the expression of Toll-like receptor 9(TLR9)and phosphorylation(P)-NF-κB p65 as well as cytokines(interleukin 6[IL-6],interleukin-1β[IL-1β],and tumor necrosis factor-α[TNF-α])production.CONCLUSION:Mutual promotion of mitochondrial fission and oxidative stress contributes to EMT in PQ-induced PF,which is associated with the mtDNA/TLR9/NF-κB pathway.
基金supported by the Science and Technology Develop Project in Jilin Province of China(20200201030JC)the Scientific Research Project of Education Department of Jilin Province in China(JJKH20211461KJ)Characteristic Innovation Project for Guangdong University of China(2019KTSCX221).
文摘Curculigoside(CCG)is a phenolic glycoside compound extracted from the root of a natural plant called Curculigo orchioides Gaertn.In this study,the neuroprotective effect of CCG through oxidative stress mediated mitochondrial dysfunction on L-glutamate(L-Glu)-damaged hippocampal neuron cell line(HT22)and APPswe/PSEN1dE9 transgenic(APP/PS1)mice were investigated.Observably,CCG in L-Glu-damaged HT22 cells suppressed apoptosis,reduced the accumulation of reactive oxygen species,balanced the mitochondrial membrane potential and prevented the over-influx of calcium.In APP/PS1 mice,4-week CCG administration significantly improved their memory and behavioral impairments,enhanced the function of cholinergic system,reduced the deposition of Aβand neurofibrillary fiber tangles caused by tau phosphorylation,and suppressed the development and progression of oxidative stress in brains of APP/PS1 mice.Based on the screening of proteomic analysis on hippocampus,CCG were confirmed that it could regulate the expression levels of proteins related to mitochondrial dysfunction,mainly through activating on AMPK/Nrf2 signaling,in APP/PS1 mice and L-Glu-exposed HT22 cells.CCG has a prominent neuroprotective effect on regulate the AMPK/Nrf2-mediated mitochondrial dysfunction in cells APP/PS1 mice support CCG is a potentially potent drug for AD treatment and merits further investigation.
文摘Soluble fiber-rich fenugreek seeds(Trigonella foenum-graecum)and garlic(Allium sativum)are understood to exert cholesterol-lowering and antioxidant effects.The cardioprotective influence of a combination of fenugreek seeds and garlic by their antioxidant influence was evaluated in hypercholesterolemic rats administered isoproterenol.Wistar rats were maintained on high-cholesterol diet for 8 weeks along with dietary interventions of fenugreek(10%),garlic(2%)and their combination.Myocardial infarction was induced with isoproterenol injection.Increased circulatory troponin,disturbed activities of cardiac ATPases,increased serum iron and decreased ceruloplasmin confirmed myocardial infarction.Elevated lipid peroxides accompanied with reduced antioxidant molecules caused by isoproterenol and altered activities of antioxidant enzymes in serum and heart in induced myocardial necrosis were countered by dietary fenugreek,garlic,and fenugreek+garlic.Dietary fenugreek seeds and garlic ameliorated isoproterenol-induced compromised antioxidant status,the cardioprotective effect being higher by the combination of fenugreek seeds and garlic.
文摘Carbon tetrachloride(CCl4)is a hepatotoxin that triggers liver damage.This study aimed to evaluate the protective effect of phytochemicals detected in Moringa oleifera Lam.leaf extract(MOLE)on CCl4-induced hepatotoxicity in mice.Phytochemicals,total phenolics,and total fl avonoids were detected in MOLE.MOLE markedly decreased the elevation of serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in consistence with the ameliorating effect on CCl4-induced histopathological abnormalities.Moreover,MOLE significantly alleviated the decrease in the antioxidant defense mechanism induced by CCl4.The suppressing effect of MOLE on the boosted inflammatory pathway triggered by CCl4 was detected by measuring the protein levels of nuclear factor kappa-light-chain-enhancer of activated B-cells(NF-κB-p65),toll-like receptor 4(TLR4),tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-1β,and IL-8 as well as the relative expressions of nuclear factor kappa B(NF-κB),TNF-α,IL-1β,and TLR4 genes.Apoptosis and genotoxicity induced by CCl4 were signifi cantly alleviated by MOLE.MOLE co-administration modulated TLR4/NF-κB pathway as presented by the suppressed gene expression of TLR4 and NF-κB as well as by the reduced protein expression of TLR4 and NF-κB-p65.In conclusion,MOLE has a multifarious protective role against hepatotoxicity through control of oxidative stress and modulation of TLR4/NF-κB.
文摘This study aimed to evaluate the anti-hyperglycemic and antioxidant role of Actinidia deliciosa(kiwifruits)aqueous extract in streptozotocin-treated rats.Animals were distributed into;control,A.deliciosa aqueous extract(ADAE;1 g/kg orally),streptozotocin(STZ;50 mg/kg,i.p,single dose),and STZ plus ADAE,respectively.Results showed that ADAE had high antioxidant and radical scavenging potency.Elevation in blood sugar level,lipid peroxidation(LPO),kidney function biomarkers,and perturbations in hematological parameters were observed in diabetic rats.While,enzymatic and non-enzymatic antioxidants,protein content,and alkaline phosphatase(ALP)activity declined.Furthermore,histological,immunohistochemical alpha-smooth muscle actin immunoreactivity(α-SMA-ir)and histochemical(collagen,total protein,DNA,and RNA)alterations were observed in rat kidneys.Moreover,STZ produced upregulation of inflammatory associated genes(tumor necrosis factor-alpha;TNF-αand transforming growth factorβ1;TGF-β1)and triggered apoptosis by upregulating apoptotic related gene[Bcl2-associated X protein(Bax)]and downregulating anti-apoptotic related gene B-cell lymphoma-2(Bcl-2)based on real-time PCR data.Moreover,diabetic rats administered with ADAE showed significant restoration in LPO,antioxidant status,and biochemical indices besides tissue architecture,and genes improvement regarding STZ group.Conclusively,A.deliciosa has a valuable ameliorative infl uence and can restore glucose levels and improve kidney dysfunction in diabetic rats.
