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Objective To investigate he intervention effect of knockdown of activating transcription factor 4(ATF-4)on fructose-induced lipid accumulation in liver cells. Methods HepG2 cells were divided into the control group(C),high fructose group(F),high-fructose+negative control group(F+NC)and high-fructose+ATF-4 siRNA group(F+ATF-4-). The mRNA level of gens of the upstream transcriptional factors and ERS markers was detected. The protein level of ACC,FAS and SCD-1 was also detected. Results Compared with group C,the mRNA expression of SREBP-1c,ChREBP,GRP78 and CHOP was increased(P < 0.01),while ATF-4 knock-down decreased the expression of the above genes(P < 0.01 ,respectively). Compared with group C ,the protein expression of ACC,FAS and SCD-1 was increased in group F(P<0.01,respectively). While ATF-4 knockdown decreased the protein expression of ACC ,FAS and SCD-1. Conclusions ATF-4 knockdown can improve the lipid steatosis induced by fructose through down-regulating lipid lipogenesis ,indicating ATF-4 possesses a regulatory effect on lipogenesis.
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Objective To explore the impact of high-fat diet on bone marrow-originated endothelial progenitor cells(EPCs),oxidative stress and glutathione peroxidase-1 (GPx-1) expression in rats.Methods 23 male Wistar rats were randomly divided into normal control group (NC goup,n=13) and high-fat fed group (HF group,n=10).Rats in NC group were fed with a standard lab diet,and rats in HF group were fed with a high-fat diet (502 kcal/100 g).Lee's index,body weight were measured to evaluate whether the obese rat model was established at 16 weeks after feeding.Blood samples were collected via carotid arterial cannula.Serum insulin,lipids and oxidative stress index were measured.Perirenal and epididymis adipose tissues were obtained and weighed.EPCs were detached,cultivated and evaluated by multi-wave laser confocal microscopy.Protein and gene expressions of GPx-1 were determined by Western blot and reverse transcription real time polymerase chain reaction(RT real-time PCR).Results After 16 weeks of high-fat diet,the body weight,Lee's index and visceral adipose tissue were increased in HF group as compared with NC group [(465.11 ±27.69) gvs.(404.38±17.01) g,(312.08±9.82) vs.(297.74±8.75),(20.07±1.94) g vs.(5.31±1.11) g,all P＜0.001].The levels of fasting blood glucose,cholesterol,triglyceride were increased in HE group as compared with NC group[(5.85±0.77) mmol/L vs.(4.285±0.74)mmol/L,(1.35±0.21) mmol/L vs.(0.95±0.14) mmol/L,(1.02±0.21) mmol/L vs.(0.65±0.19)mmol/L,all P＜0.01].The levels of fasting insulin(FIns)and HOMA-IR were higher in HF group than in NCgroup [(3.46±0.77) mmol/L vs.(2.04±0.51) mmol/L,(0.90±0.24) vs.(0.40±0.19),both P＜0.001].Levels of serum glutathion peroxidase(GSH-Px)and erythrocuprein SOD,and total anti-oxidative capacity were decreased in HF group as compared with NC group [(759.13 ±60.71) mU/L vs.(826.26±65.83) mU/L,(72.76±5.41)mU/L vs.(80.44±7.91) mU/L,(5.18±0.35) mU/L vs.(6.01±0.93) mU/L,all P＜0.05].Malonaldehyde (MDA) level was increased,EPCs count and protein and mRNA expressions of GPx-1 were decreased in HF group as compared withNC group [(6.09±0.96) mol/L vs.(5.14±0.89) μmol/L,(62.55 ± 4.85) vs.(71.19±5.95),(0.50±0.13) vs.(1.29±0.42),(0.50±0.13) vs.(1.29±0.42),all P＜0.05 or 0.01].Multiple linear regression analysis showed that MDA was an influential factor for EPCs,Lee's index was an influential factor for GSH-Px,total cholesterol (TC) was an influential factor for TAO-C and SOD,and FINs was an influential factor for MDA.Conclusions High-fat diet can induce obesity and insulin resistance,increase the visceral adiposity,decrease the quantity of EPCs and protein and mRNA expressions of GPx-1 in rats.Oxidative stress is one of influential factors for the decrease of EPCs quantity in high fat diet induced obese rats.
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ObjectiveTo compare the effects of streamlined liner pharynx airway(SLIPA) and endotracheal intubation in the radical mastectomy under general anesthesia,and to evaluate the efficacy and safety.MethodsSixty patients scheduled for radical mastectomy were randomly divided into 2 groups.SLIPA group( S,n =30 ) and endotracheal intubation group(T,n =30).The data were kept regarding the insertion time and successful rate,MAP,HR,BIS were recorded at 6 time points:before induction ( T0 ),during SLIPA incursion or trachel intubation ( T1 ),3min after intubation( T2 ),before extubation( T3 ),after extubation ( T4 ),3 min after extubation ( Ts ).Ppeak,PetCO2 and SpO2 were measured after successful airway placement at 10min,30min,60min and to observe intraoperative and postoperative throat complications.ResultsThe time of endotracheal intubation group is significantly longer than SLIPA group (P ＜0.05).In group T,MAP and HR at T1,T2,T4,T5 were higer than at T0 and the same time points in group S(all P ＜ 0.05 ).No regurgitation and aspiration was found in two groups ( all P ＞ 0.05 ).The incidence of complicaton in group T is significantly higher than that in group S ( all P ＜ 0.05 ).ConclusionSLIPA is easier placement,safety and efficacy when it is used for the radical mastectomy under general anesthesia without significant influences on hemodynamics and fewer complications of throat after operation.
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Objective To study the relationship between oxidative stress and endothelial progenitor cells(EPCs)count in the first-degree relatives of diabetes mellitus(FDRs).Methods Three groups were evaluated with 40 type 2 diabetes mellitus(T2DM)patients,38 FDRs and 30 healthy individuals as the control(NC).Fasting plasma glucose(FPG),glycosylated hemoglobin(HbA1c),TG,TC and fasting plasma insulin concentrations were measured and homeostasis model assessment-insulin resistance(HOMAIR)was calculated.Quantity of EPCs and flow-mediated dilation(FMD)were evaluated.Malonaldehyde(MDA),glutathion peroxidase(GSH-Px),erythrocuprein(SOD)and total anti-oxidative capacity(TAO-C)were measured.Results In T2DM group FPG[(7.86 ±0.77)mmol/L]and HbA1c[(7.24 ±0.20)％]were significantly higher than those in NC[FPG(4.90 ± 0.35)mmol/L,HbA1 c(5.34 ± 0.37)％]and FDRsgroup[FPG(5.13±0.95)mmol/L,HbA1c(5.36 ±0.36)％](all P values ＜0.05).TC in T2DM group[(5.88 ±0.76)mmol/L]was higher than in NC[(4.66±0.90)mmol/L]and FDRs [(4.95 ± 0.76)mmol/L].HOMA-IR was 0.48 ± 0.25 in NC,0.81 ± 0.46 in FDRs and 1.47 ± 0.24 in T2DM group,P ＜ 0.01.In T2DM group,the plasma levels of SOD[(69.30 ± 2.21)U/ml],TAO-C [(7.30 ± 0.29)U/ml]and GSH-Px[(856.5 ± 9.01)U/ml]were significantly lower than those in NC [SOD(75.33 ±3.63)U/ml,TAO-C(8.17 ±0.58)U/ml and GSH-Px(938.1 ± 19.35)U/ml]and FDRs group[SOD(74.91 ±4.53)U/ml,TAO-C(8.24 ±0.46)U/ml and GSH-Px(936.9 ± 15.78)U/ml](all P values ＜ 0.01).Serum level of MDA was(2.87 ± 0.63)μmol/L in NC,(3.28 ± 0.71)μmol/L in FDRs and(3.69 ± 0.39)μmol/L in T2DM group(P ＜ 0.01).The quantity of EPCs and FMD％ were 96.75 ±8.11 and 8.36 ± 2.21 in NC,83.34 ± 12.43 and 6.78 ± 0.98 in FDRs and 58.45 ± 7.58 and 2.86 ± 0.35 in T2DM group with statistical differences between different groups(all P values ＜ 0.05).Pearson correlation analysis showed that lnHOMA-IR was positively correlated with MDA(r =0.486,P ＜0.05)and negatively correlated with SOD,TAO-C,GSH-Px(r =-0.426,-0.601,-0.524,all P values ＜ 0.05)in FDRs group.Conclusions Insulin resistance,oxidative stress,decreased quantity of EPCs and impairment of endovascular function have already occurred in the FDRs of T2DM with normal glucose tolerance and they are correlated with each other.
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Objective To observe the effects of high-fat diet on liver steatosis and liver endoplasm reticulum stress in mice and to investigate the interventional effect of metfomin on them.Methods Forth-five male C57BL/J6 mice were divided into healthy control group,high-fat group and metformin group.High fat group and metformin group were fed with high-fat diet.Mice in metformin group were given metformin since the fourth week of high-fat feeding.After feeding for eight weeks,subperitoneal glucose tolerance test was performed in mice.After mice were sacrificed,liver triglyceride (TG) content and the expression of endoplasmic reticulum stress related factors at gene and protein levels were measured.One-way ANOVA was applied for analysis between groups.Results Compared with healthy control group,area under curve (AUC) of glucose tolerance and TG contents in liver tissues significantly increased in high-fat group [998±87 vs 1409±106,(10.05±0.29) μmol/g vs (27.11 ±4.76) μmol/g].Glucose tolerance and liver steatosis were improved in metformin group,AUC and TG of metformin group were significantly lower than those of high-fat group in metformin group [1178±90,(15.12±2.11) μmol/g,F=55.328,89.212,both P ＜0.01].Compared with healthy control group,the expression of glucose-regulated protein 94 (GRP94)at mRNA level significantly increased in high-fat group.Meanwhile,the expression of phosphorylated eukaryotic translation initiation factor 2α at protein level,which indicated endoplasmic reticulum stress,significantly increased.However,the expression of those endoplasmic reticulum stress markers at mRNA and protein level of metformin group were both lower than those of high fat group (F=84.002,137.321,both P＜0.05).Conclusions High fat diet caused liver steatosis in mice and accompanied by endoplasmic reticulum stress.Fatty liver was significantly improved by metformin treatment in high-fat-fed mice.The mechanism may be related with the improvement of endoplasmic reticulum stress by metformin.
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The effect of oxymatrine on high-fructose-feeding induced insulin resistance and liver steatosis in rats was observed and the underlying mechanism in improving the hepatic lipid metabolism was explored.The results demonstrated that high fructose feeding decreased the glucose tolerance and increased hepatic lipid accumulation in rats,while oxymatrine could improve glucose tolerance and alleviate hepatic steatosis in rats.High fructose feeding stimulated the protein expressions of key lipid-synthesis enzymes,which were decreased by oxymatrine intervention.Both high fructose feeding and oxymatrine intervention had no significant effect on protein expressions of mitochondrial fatty acid oxidation enzymes.
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Objective To explore and compare the mechanism of high-fructose and high-fat diet induced triglyceride excessive accumulation in mice liver and its relationship with endoplasmic reticulum (ER) stress.Methods 45 Adult male C57BL/J6 mice,weight arranged from 25 gram to 30 gram were randomly divided into control group,high-fructose group and high-fat group,15 mice in each group.Common food was fed in control group,high-fructose food was fed in high-fructose group,high-fat food was fed in high-fat group,and the everyday calories consumption in 3 groups was almost equal.Intraperitoneal glucose tolerance test (ipGTT) was performed after feeding for 8 weeks.After mice were sacrificed,triglyceride content,lipogenic enzymes and ER stress markers expression in liver tissues of each group were measured.Results After feeding with different food for 8 weeks,the fat content of epididymis in high-fructose group and high-fat group both was (2.0±0.1) g/100 g (body weight),which was significantly higher than that of control group (1.2 ± 0.1) g/100 g (body weight),P＜0.01).After ipGTT test,the area under curve of blood glucose in high-fructose group and high-fat group was significantly higher than that in control group (P＜0.01).Compared with control group,triglyceride contents of liver tissues in high-fructose group and high-fat group were significantly increased,of those triglyceride contents in high-fructose group increased more obviously,and triglyceride contents in high-fructose group was significantly higher than that of high-fat group (P＜0.01).Compared with control group,the expression of acylCoA carboxylase (ACC),fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD-1) increased in high-fructose group (P＜0.01),while decreased in high-fat group (P＜0.05) ; meanwhile,the expression of phosphorylated pancreatic ER kinase (p-PERK),inositol requiring enzyme 1 (p-IRE-1/t-IRE-1)and glucose-regulated protein 78 (GRP78) was up-regulated in both high-fructose group and high-fat group (all P＜0.01).Conclusion Both high-fructose diet and high-fat diet can induce fatty liver through different mechanisms.High-frucose diet promotes endogenous lipogenesis while high-fat diet inhibits endogenous lipogenesis.Both dietary factors can induce ER stress,which indicate that ER stress is associated with pathogenesis and development of food factors induced fatty liver.