Neurodegenerative diseases,such as Alzheimer’s disease and Parkinson’s disease,are associated with cognitive impairment and impaired brain glucose metabolism,posing significant challenges for the public health.We pr...Neurodegenerative diseases,such as Alzheimer’s disease and Parkinson’s disease,are associated with cognitive impairment and impaired brain glucose metabolism,posing significant challenges for the public health.We previously demonstrated that cyanidin 3-O-β-galactoside(Cy3Gal)from black chokeberry alleviated cognitive impairment in aging mice through regulating brain energy metabolism in a direct way.However,the indirect mechanisms in mitigating brain glucose hypometabolism remain underexplored.Here,we utilized a bilaterally intracerebroventricular injection of streptozotocin(ICV/STZ,3 mg/kg bw)-induced brain glucose hypometabolism model to investigate the effects of Cy3Gal on cognitive impairment alleviation.Our findings revealed that Cy3Gal administration significantly improved memory deficit and cognitive impairment in ICV/STZ-administrated mice.Subsequently,Cy3Gal showed excellent abilities in inhibiting astrocyte overactivation,regulating neurotransmitters metabolism,and promoting synaptic plasticity.Furthermore,Cy3Gal enhanced brain glucose metabolism by improving glycolysis and the TCA cycle.Additionally,Cy3Gal modulated levels of gut microbiota-derived metabolites,including acetate,butyrate,histidine,glutamine,serine,valine and isoleucine,which were closely linked to brain glucose metabolism.The in vitro results further demonstrated that these metabolites played an important role in the neuron-astrocyte energy metabolism,which accounted for the alleviation of glucose hypometabolism.Overall,our findings suggest that Cy3Gal mitigates ICV/STZ-induced cognitive impairment by modulating gut microbiota-derived short-chain fatty acids and amino acids,which in turn improves brain glucose metabolism.展开更多
AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.MET...AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.METHODS:HRMEC dysfunction model was established by 48h glucose(30 mmol/L)treatment and treated with Feno/NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activator(Nigericin).Cell viability/apoptosis were assessed by cell counting kit-8(CCK-8)/terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay(TUNEL)staining and flow cytometry assays.Levels of apoptosis-(Bcl-2-associated X protein,Bax/B-cell lymphoma 2,Bcl-2),vascular permeability-(vascular endothelial growth factor,VEGF)and inflammasome activation-related proteins(NLRP3/cleaved caspase-1/apoptosis-associated speck-like protein containing a CARD,ASC),as well as inflammatory factors(interleukin,IL-6/IL-1β/tumor necrosis factor,TNF-α/IL-18)were determined with Western blot/enzyme linked immunosorbent assay(ELISA).Cell permeability/reactive oxygen species(ROS)level/superoxide dismutase(SOD)activity/malondialdehyde(MDA)content were assessed by Evans blue staining/2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe/SOD kit/MDA kit.RESULTS:HRMEC dysfunction was successfully induced by HG,evidenced by decreased viability(P<0.001),increased apoptosis(P<0.001),permeability(P<0.001),and inflammatory factor levels(P<0.001).Feno treatment significantly ameliorated HG-induced HRMEC dysfunction(P<0.01).Meanwhile,HG induction increased ROS production(P<0.001)and MDA content(P<0.001)in HRMECs,while reducing SOD activity(P<0.001),indicative of oxidative stress.This was,however,abolished by Feno(P<0.05).Moreover,Feno eliminated activation of NLRP3 inflammasomes(P<0.05)in HG-induced HRMECs.Strikingly,activation of NLRP3 inflammasomes partially averted the inhibition of Feno on HG-induced HRMEC dysfunction(P<0.05).CONCLUSION:Feno represses oxidative stress and NLRP3 inflammasome activation,consequently alleviating HG-induced HRMEC dysfunction.展开更多
Fully utilizing renewable biomass energy is important for saving energy,reducing carbon emissions,and mitigating climate change.As the main hydrolysate of cellulose,a primary component of lignocellulose,glucose could ...Fully utilizing renewable biomass energy is important for saving energy,reducing carbon emissions,and mitigating climate change.As the main hydrolysate of cellulose,a primary component of lignocellulose,glucose could be employed as a starting material to prepare some other functional derivatives for improving the value of biomass resources.The isomerization of glucose to produce fructose is an important intermediate process during numerous high-value-added chemical preparations.Therefore,the development of efficient and selective catalysts for glucose isomerization is of great significance.Currently,glucose isomerase catalysts are limited by the harsh conditions required for microbial activity,which restricts further improvements in fructose yield.Additionally,heterogeneous Bronsted-base and Lewis-acid catalysts commonly employed in chemical isomerization methods often lead to the formation of undesirable by-products,resulting in reduced selectivity toward fructose.This study has demonstrated that lithium-loaded heterogeneous catalysts possess excellent isomerization capabilities under mild conditions.A highly efficient Li-C_(3)N_(4) catalyst was developed,achieving a fructose selectivity of 99.9% and a yield of 42.6% at 60℃ within 1.0 h-comparable to the performance of the enzymatic method.Characterization using X-ray photoelectron spectroscopy(XPS),X-ray diffraction(XRD),proton nuclear magnetic resonance(^(1)H NMR),and inductively coupled plasma(ICP)analyses confirmed that lithium was stably incorporated into the g-C_(3)N_(4) framework through the formation of Li-N bonds.Further investigations using CO_(2) temperature-programmed desorption(CO_(2)-TPD),in situ Fourier-transform infrared spectroscopy(FT-IR)and 7Li magic angle spinning nuclear magnetic resonance(^(7)Li MAS NMR)indicated that the isomerization proceeded via a base-catalyzed mechanism.The Li species were found to interact with hydroxyl groups generated through hydrolysis and simultaneously coordinated with nitrogen atoms in the C_(3)N_(4) matrix,resulting in the formation of Li-N_(6)-H_(2)O active sites.These active sites facilitated the deprotonation of glucose to form an enolate intermediate,followed by a proton transfer step that generated fructose.This mechanism not only improved the efficiency of fructose production but also provided valuable insight into the catalytic role of lithium within the isomerization process.展开更多
Unhealthy diets are associated with various diseases that can disrupt brain energy metabolism,which significantly increased the risk of cognitive impairment and chronic neurodegenerative diseases.Early intervention wi...Unhealthy diets are associated with various diseases that can disrupt brain energy metabolism,which significantly increased the risk of cognitive impairment and chronic neurodegenerative diseases.Early intervention with nutritional supplements may have long-lasting positive effects on diet-related glucose metabolism and potentially mediate the progression of neurodegeneration in middle-aged and elderly people.We previously reported that cyanidin 3-O-β-galactoside(Cy3Gal),an anthocyanin from black chokeberry(Aronia melanocarpa(Michx.)Elliott),alleviated cognitive impairment in aging mice through regulating brain energy metabolism.However,it remains unclear whether Cy3Gal can also exert beneficial effects in mice fed with a high-fat/high-sugar diet.Here we revealed that Cy3Gal treatment conserved the health of neurons and synapses,as well as cognitive function of mice.Furthermore,we observed that Cy3Gal effectively improved glucose uptake and metabolism of skeletal muscle by enhancing glycolysis both in vivo and in vitro models,which is essential for maintaining a stable glucose supply to the brain.Additionally,Cy3Gal significantly increased the levels of glucose-derived tricarboxylic acid cycle intermediates in the mice brain(P<0.05),and regulated the activities of mitochondrial respiratory chain complexes(P<0.01).The positive influence on peripheral and brain bioenergetics explained how the Cy3Gal exerted neuroprotective effect.In conclusion,our study illustrated that early dietary intervention of Cy3Gal had significant advantages in terms of neuroprotection and cognition under the challenge of HFHS diet-induced glucose metabolism disorder.展开更多
BACKGROUND Tumor necrosis factor-α(TNF-α)has been implicated in the development of diabetes following chronic pancreatitis.However,its role in abnormal glucose metabolism(AGM)after acute pancreatitis(AP)and post-pan...BACKGROUND Tumor necrosis factor-α(TNF-α)has been implicated in the development of diabetes following chronic pancreatitis.However,its role in abnormal glucose metabolism(AGM)after acute pancreatitis(AP)and post-pancreatitis diabetes mellitus remains unclear.AIM To investigate the role of TNF-αin AP-associated AGM and its effects on isletβ-cell apoptosis,focusing on the underlying molecular mechanisms.METHODS Clinical data were collected to assess AGM’s incidence and identify the characteristics in 369 AP patients.In vitro,AP models were established using lipopolysaccharide in 266-6 acinar cells and MIN-6β-cells.Cell proliferation,apoptosis,and protein expression were analyzed using the Cell Counting Kit-8 assay,terminal deoxynucleotidyl transferase dUTP nick-end labeling assay,and western blotting.The TNF-αand insulin concentration in co-culture medium was measured by enzyme-linked immunosorbent assay.In vivo,an AP mouse model was induced using sodium taurocholate,and pancreatic tissues were analyzed through hematoxylin and eosin staining,terminal deoxynucleotidyl transferase dUTP nick-end labeling,and western blotting.TNF-αlevels were assessed by enzyme-linked immunosorbent assay.A TNF-αinhibitor was applied to the AP cell model to reassess apoptosis and protein expression.RESULTS AGM occurred in 40.38%of AP patients.Body mass index,severity grade,recurrence frequency,and lung injury were significantly associated with AGM.AP models in 266-6 and MIN-6 cells showed reducedβ-cell proliferation,insulin secretion,and increased apoptosis,which correlated with inflammation severity.Similar findings ofβ-cell apoptosis were confirmed in the mouse model.TNF-αlevels were significantly elevated in AP models,with higher levels in severe inflammation.Increased Bax and caspase-3 expression and decreased Bcl-2 expression were observed in both in vitro and in vivo models.These changes intensified with increasing inflammation.TNF-αinhibition reduced apoptosis and altered protein expression patterns,decreasing Bax and caspase-3,while increasing Bcl-2 in MIN-6 cells.CONCLUSION TNF-αcontributes toβ-cell apoptosis and AGM in AP through the Bax/Bcl-2/caspase-3 signaling pathway,suggesting TNF-αas a potential therapeutic target for preventing AP-associated AGM.展开更多
Recent research has indicated that sialic acid,such as free sialic acid(N-acetylneuraminic acid,Neu5Ac)and bound sialic acid(3ʹ-sialyllactose,3ʹ-SL),can ameliorate disorders associated with glycolipid metabolism,altho...Recent research has indicated that sialic acid,such as free sialic acid(N-acetylneuraminic acid,Neu5Ac)and bound sialic acid(3ʹ-sialyllactose,3ʹ-SL),can ameliorate disorders associated with glycolipid metabolism,although the underlying mechanisms have yet to be determined.We examined the effects of 3ʹ-SL on glycolipid metabolism in mice fed a high-fat diet.Male C57BL/6J mice were divided into 6 groups:2 model control groups(normal and high-fat diets)and 4 intervention groups(Neu5Ac,and low,moderate,and high-dose 3ʹ-SL).After 8 weeks of continuous gavage intervention,mice in the 3ʹ-SL intervention groups had lower body weight and total fat content;reduced fasting blood glucose,triglycerides,low-density lipoproteins and oxidized-low-density lipoproteins;and increased high-density lipoproteins,but no dosage-dependent of 3ʹ-SL intervention was found,moderate-dose 3ʹ-SL intervention as optimal for further exploration.3ʹ-SL intervention could increase respiratory exchange ratio,energy expenditure,and amount of exercise performed.3ʹ-SL increased the colonic abundances of Akkermansia,Lactobacillus,and Bacteroides,and reduced those of Erysipelatoclostridium,Faecalibaculum,and Aldercreutzia.Changes were also observed in colonic metabolites,and liver gene transcript and metabolites,which were mainly enriched in bile secretion,taurine and hypotaurine metabolism,and insulin resistance.Additionally,3ʹ-SL was observed to regulate genes associated with physiological rhythms,including Clock,Per2,Cry1,and Bhihe41.Collectively,our findings indicate that 3ʹ-SL can contribute to the prevention and control of disorders associated with glucose and lipid metabolism caused by high-fat diets.Compared with Neu5Ac,3ʹ-SL intervention can more effectively ameliorate intestinal flora disorders,enhance bile acid circulation,increase tissue energy expenditure,and reduce lipid synthesis,thereby promoting lipid-lowering effects mediated via the gut-liver axis,and can also enhance energy metabolism and alleviate disorders of glucolipid metabolism by altering physiological rhythms in high fat-diet mice.展开更多
Objective Endothelial dysfunction is a central contributor to the vascular complications observed in individuals with diabetes.cAMP response element-binding protein(CREB)plays a crucial role in mediating hyperglycemia...Objective Endothelial dysfunction is a central contributor to the vascular complications observed in individuals with diabetes.cAMP response element-binding protein(CREB)plays a crucial role in mediating hyperglycemia-induced endothelial dysfunction.Phosphatase and tensin homolog(PTEN)has been implicated in the regulation of endothelial inflammation,yet the precise mechanism by which CREB modulates PTEN to protect endothelial cells under high glucose conditions remains unknown.This study aims to elucidate this potential mechanism.Methods Human umbilical vein endothelial cells(HUVECs)were exposed to high glucose(30 mM)or normal glucose(5.5 mM)for 6 days.Cell viability and apoptosis were assessed via the Cell Counting Kit-8 and flow cytometry.To evaluate oxidative stress,the levels of reactive oxygen species(ROS),lactate dehydrogenase(LDH),and malondialdehyde(MDA)were measured via commercial assay kits.The interaction between CREB and endothelial specific molecule 1(ESE-1)was assessed via coimmunoprecipitation.Chromatin immunoprecipitation and luciferase reporter assays were used to investigate the transcriptional regulation of PTEN by ESE-1 and CREB.Western blotting was performed to analyze the expression of intercellular adhesion molecule-1 and E-selectin.The adhesion of HUVECs was evaluated via monocyte‒endothelial cell adhesion assays.Results Our findings revealed a direct interaction between CREB and ESE-1,which together regulate PTEN expression to activate the phosphoinositide 3-kinase/protein kinase B pathway.Under high-glucose conditions,we observed significant increases in oxidative stress,inflammatory responses,and adhesion in HUVECs.ESE-1 knockdown reversed these effects,restoring endothelial cell function.Moreover,the overexpression of PTEN in high glucose–treated HUVECs rescued the endothelial injury induced by ESE-1 knockdown,suggesting that PTEN plays a pivotal role in mediating the protective effects.Conclusion ESE-1,through the regulation of CREB-mediated PTEN expression,activates the PI3K/AKT pathway and modulates key processes such as oxidative stress,inflammation,and adhesion in endothelial cells under high-glucose stress.展开更多
目的探讨星状神经节阻滞(SGB)通过长链非编码RNA(lncRNA)牛磺酸上调基因1(TUG1)-NOD样受体热蛋白结构域相关蛋白3(NLRP3)轴在体外脑缺血再灌注模型中对炎症反应和自噬溶酶体形成的调节作用。方法培养大鼠海马神经元细胞系H19-7,并将细...目的探讨星状神经节阻滞(SGB)通过长链非编码RNA(lncRNA)牛磺酸上调基因1(TUG1)-NOD样受体热蛋白结构域相关蛋白3(NLRP3)轴在体外脑缺血再灌注模型中对炎症反应和自噬溶酶体形成的调节作用。方法培养大鼠海马神经元细胞系H19-7,并将细胞分为8组:(i)正常对照组:正常培养的神经元细胞;(ii)氧-糖剥夺/复氧(OGD/R)组:采用氧-糖剥夺/复氧法模拟脑缺血再灌注损伤;(iii)OGD/R+SGB组:OGD/R联合麻醉药0.5%布比卡因用于体外模拟SGB;(iv)OGD/R+SGB+TUG1过表达阴性对照组:OGD/R联合布比卡因并联合TUG1过表达阴性对照质粒转染细胞;(v)OGD/R+SGB+TUG1过表达组:OGD/R联合布比卡因并联合TUG1过表达质粒转染细胞;(vi)OGD/R+SGB+TUG1过表达+MCC950组:OGD/R联合布比卡因、TUG1过表达质粒转染及NLRP3抑制剂MCC950处理细胞;(vii)OGD/R+TUG1过表达组:OGD/R联合TUG1过表达质粒转染细胞;(viii)OGD/R+MCC950组:OGD/R联合NLRP3抑制剂MCC950处理细胞。进一步通过实时定量PCR(Quantitative Real Time PCR,qRTPCR)实验检测细胞中lncRNATUG1的表达;利用Western blot法检测细胞中NLRP3、微管相关蛋白1轻链3(LC3)-I、LC3-II、自噬相关基因5(Atg5)、苄氯素1(beclin1)、自噬接头蛋白(p62)、溶酶体相关膜蛋白1(LAMP1)的表达水平;利用透射电镜(TEM)检测自噬溶酶体的数量;并用酶联免疫吸附测定(ELISA)法检测细胞培养上清中白细胞介素(IL)-1β、IL-6、IL-18、肿瘤坏死因子(TNF)-α的含量。结果与正常对照组相比,OGD/R组lncRNA TUG1、NLRP3、Atg5、beclin1、p62、LAMP1的表达水平以及LC3-II/I比值均显著上调(^(均)P<0.05),自噬溶酶体数量增加(P<0.05),IL-1β、IL-6、IL-18、TNF-α的含量显著升高(^(均)P<0.05)。与OGD/R组相比,OGD/R+SGB组的上述指标均显著下调(P<0.05)。与OGD/R+SGB+TUG1过表达阴性对照组相比,OGD/R+SGB+TUG1过表达组的lncRNA TUG1、NLRP3、Atg5、beclin1、p62、LAMP1的表达水平以及LC3-II/I比值均显著上调(^(均)P<0.05),自噬溶酶体数量增加(P<0.05),IL-1β、IL-6、IL-18、TNF-α的含量显著升高(^(均)P<0.05),然而,加入NLRP3的抑制剂MCC950后,除lncRNA TUG1外其余指标均显著下调(^(均)P<0.05)。另外,与OGD/R组比,OGD/R+TUG1过表达组的上述指标进一步上调(^(均)P<0.05)。与OGD/R组比,OGD/R+MCC950组则抑制了除lncRNA TUG1外的其余指标(^(均)P<0.05)。结论星状神经节阻滞通过调节lncRNA TUG1-NLRP3轴有效减轻体外脑缺血再灌注损伤引起的炎症反应和自噬溶酶体形成,提示其可能作为治疗缺血性脑损伤的潜在策略。展开更多
AIM To investigate the relationship between glucose metabolism and glypican-3(GPc3)expression in hepatocellular carcinoma(Hcc).METHODSImmunohistochemical staining of pathological samples for GPc3 and glucose transport...AIM To investigate the relationship between glucose metabolism and glypican-3(GPc3)expression in hepatocellular carcinoma(Hcc).METHODSImmunohistochemical staining of pathological samples for GPc3 and glucose transporter 1(GLUT1),and whole-body ^(18)F-FDG PET/c T for measuring tumour glucose uptake were performed in 55 newly diagnosed Hcc patients.The maximum standard uptake value(s UVmax)and tumour-to-non-tumourous liver uptake(T/NT)ratio were used to quantify ^(18)F-FDG uptake.In vitro ^(18)F-FDG uptake assay of GPc3-expressing Hep G2 and non-GPc3-expressing RH7777 cel ls was used to examine the effect of GPc3 in cellular glucose metabolism.The relationships between GPc3 expression and ^(18)F-FDG uptake,GLUT1 expression,tumour differentiation,and other clinical indicators were analysed using spearman rank correlation,univariateand multiple logistic regression analyses.RESULTSPositive GPc3 expression was observed in 67.3%of Hcc patients,including 75.0%of those with well or moderately differentiated Hcc and 36.4%of those with poorly differentiated Hcc.There was an inverse relationship between GPc3 expression and s UVmax(Spearman correlation coefficient=-0.281,P=0.038)and a positive relationship between GLUT1 expression and sU Vmax(Spearman correlation coefficient=0.681,P<0.001)in patients with Hcc.Univariate analysis showed that two glucose metabolic parameters(sU Vmax and T/NT ratio),tumour differentiation,lymph node metastasis,and TNM stage were all significantly associated with GPc3 expression(P<0.05),whereas GLUT1 expression,sex,age,tumour size,intrahepatic lesion number,and distant metastasis showed no statistical association(P>0.05).Further multivariate analysis revealed that only the T/N ratio was significantly correlated with GPC3 expression in patients with Hcc(P<0.05).In vitro assay revealed that the uptake of ^(18)F-FDG in GPc3-expressing HepG2 cells was significantly lower than that of non-GPc3-expressing RH7777 cells(t=-20.352,P<0.001).CONCLUSIONThe present study demonstrated that GPc3 expression is inversely associated with glucose metabolism,suggesting that GPc3 may play a role in regulating glucose metabolism in Hcc.展开更多
In the present study, we investigated the role of reactive oxygen species（ROS） elevation induced by an anti-diabetic vanadium compound, vanadyl acetylacetonate（VO（acac）2）, in the regulation of lipolysis and gluc...In the present study, we investigated the role of reactive oxygen species（ROS） elevation induced by an anti-diabetic vanadium compound, vanadyl acetylacetonate（VO（acac）2）, in the regulation of lipolysis and glucose metabolism using differentiated 3T3L1 adipocytes as a model system. By confocal laser scanning microscopy, we found that VO（acac）2 induced ROS generation under high glucose stimulation, and the pretreatment of NADPH oxidase inhibitors could significantly reduce the elevated ROS level. Meanwhile, the decreased phosphorylated levels of AKT and the two key modulators of lipolysis（HSL and perilipin） were observed by western blot analysis. We also found that the contents of glycerol release were further reduced as well. In addition, the levels of key regulatory proteins, AS160 and GSK3β, in glucose metabolism pathway were correspondingly reduced. These findings demonstrated that ROS induced by vanadium compounds could act as a metabolic signal to activate AKT pathway to inhibit lipolysis and promote glucose transport and glycogen synthesis rather than by direct action by themselves. Our study contributed to elucidate the anti-diabetic effects of vanadium compounds and provided a theoretical basis for the further development of new vanadium complexes in the prevention and therapeutics of diabetes.展开更多
Compositions of glycerolipids and fatty acid compositions of glycerolipids were compared among Synechocystis sp. PCC 6803 cells grown in the BG-11 medium containing different concentrations of glucose and Na2S2O3 in t...Compositions of glycerolipids and fatty acid compositions of glycerolipids were compared among Synechocystis sp. PCC 6803 cells grown in the BG-11 medium containing different concentrations of glucose and Na2S2O3 in this study. It was found that Na2S2O3 can effectively increase the percentage of sulphoquinovosyl diacylglycerol (SQDG) and phosphatidylglycerol (PG) to total membrane lipids and the simultaneous application of glucose with Na2S2O3 can counteract the effect of Na2S2O3. In addition, Na2S2O3 can significantly increase the percentage of palmitic acid (C, 16:0) in fatty acid composition of monogalactosyl diacylglycerol (MGDG) and digalactosyl diacylglycerol (DGDG) and decrease the fatty acid unsaturation degree accordingly, and these effects can also be eliminated by glucose. These results indicate that Na2S2O3 can take as a reductant to make membrane lipids in a low unsaturated state, and the simultaneous application of glucose can decrease the reducing power of Na2S2O3. In addition, Na2S2O3 can take as a sulfur donor for the synthesis of SQDG.展开更多
AIM To investigate the role of embryonic liver fordin(ELF) in liver fibrosis by regulating hepatic stellate cells(HSCs) glucose glycolysis.METHODS The expression of ELF and the glucose glycolysisrelated proteins were ...AIM To investigate the role of embryonic liver fordin(ELF) in liver fibrosis by regulating hepatic stellate cells(HSCs) glucose glycolysis.METHODS The expression of ELF and the glucose glycolysisrelated proteins were evaluated in activated HSCs. si RNA was used to silence ELF expression in activated HSCs in vitro and the subsequent changes in PI3K/Akt signaling and glucose glycolysis-related proteins were observed.RESULTS The expression of ELF increased remarkably in HSCs of the fibrosis mouse model and HSCs that were cultured for 3 wk in vitro. Glucose glycolysis-related proteins showed an obvious increase in the activated HSCs, such as phosphofructokinase, platelet and glucose transporter 1. ELF-si RNA, which perfectly silenced the expression of ELF in activated HSCs, led to the induction of glucose glycolysis-related proteins and extracellular matrix(ECM) components. Moreover, p Akt, which is an important downstream factor in PI3K/Akt signaling, showed a significant change in response to the ELF silencing. The expression of glucose glycolysisrelated proteins and ECM components decreased remarkably when the PI3K/Akt signaling was blocked by Ly294002 in the activated HSCs. CONCLUSION ELF is involved in HSC glucose glycolysis by regulating PI3K/Akt signaling.展开更多
In this study, we investigated the effects of adenovirus-mediated transfection of PC12 cells with glucose transporter 3 after ischemic injury. The results of flow cytometry and TUNEL showed that exogenous glucose tran...In this study, we investigated the effects of adenovirus-mediated transfection of PC12 cells with glucose transporter 3 after ischemic injury. The results of flow cytometry and TUNEL showed that exogenous glucose transporter 3 significantly suppressed PC12 cell apoptosis induced by ischemic injury. The results of isotopic scintiscan and western blot assays showed that, the glucose uptake rate was significantly increased and nuclear factor kappaB expression was significantly decreased after adenovirus-mediated transfection of ischemic PC12 cells with glucose transporter 3. These results suggest that adenovirus-mediated transfection of cells with glucose transporter 3 elevates the energy metabolism of PC12 cells with ischemic injury, and inhibits cell apoptosis.展开更多
Objective High glucose(HG)can influence the osteogenic differentiation ability of periodontal ligament stem cells(PDLSCs).Human umbilical cord mesenchymal stem cell-derived exosomes(hUCMSC-exo)have broad application p...Objective High glucose(HG)can influence the osteogenic differentiation ability of periodontal ligament stem cells(PDLSCs).Human umbilical cord mesenchymal stem cell-derived exosomes(hUCMSC-exo)have broad application prospects in tissue healing.The current study aimed to explore whether hUCMSC-exo could promote the osteogenic differentiation of hPDLSCs under HG conditions and the underlying mechanism.Methods We used a 30 mmol/L glucose concentration to simulate HG conditions.CCK-8 assay was performed to evaluate the effect of hUCMSC-exo on the proliferation of hPDLSCs.Alkaline phosphatase(ALP)staining,ALP activity,and qRT-PCR were performed to evaluate the pro-osteogenic effect of hUCMSC-exo on hPDLSCs.Western blot analysis was conducted to evaluate the underlying mechanism.Results The results of the CCK-8 assay,ALP staining,ALP activity,and qRT-PCR assay showed that hUCMSC-exo significantly promoted cell proliferation and osteogenic differentiation in a dosedependent manner.The Western blot results revealed that hUCMSC-exo significantly increased the levels of p-PI3K and p-AKT in cells,and the effect was inhibited by LY294002(PI3K inhibitor)or MK2206(AKT inhibitor),respectively.Moreover,the increases in osteogenic indicators induced by hUCMSC-exo were significantly suppressed by LY294002 and MK2206.Conclusion hUCMSC-exo promote the osteogenic differentiation of hPDLSCs under HG conditions through the PI3K/AKT signaling pathway.展开更多
In the field of glucose sensors,the development of inexpensive and high-efficiency electrochemical glucose sensors is the current research hotspot.In this paper,CuO-Co_(3)O_(4)composite with a prickly-sphere-like morp...In the field of glucose sensors,the development of inexpensive and high-efficiency electrochemical glucose sensors is the current research hotspot.In this paper,CuO-Co_(3)O_(4)composite with a prickly-sphere-like morphology is prepared by the facile hydrothermal method for the non-enzymatic electrochemical glucose detection.X-ray diffraction,scanning electron microscopy,transmission electron microscopy,energy-dispersive X-ray spec-troscopy,and X-ray photoelectron spectroscopy are used to analyze the structure,composition,and morphology of the material.In addition,the electrochemical catalytic perfor-mance of CuO-Co_(3)O_(4)to glucose is obtained by cyclic voltammetry and chronoamperometry.The excellent elec-trochemical sensing performance may be attributed to the large number of catalytic sites in the prickly-sphere-like composite and the synergistic effect of Cu and Co.Under an applied voltage of 0.55 V,CuO-Co_(3)O_(4)composite shows sensitivity to glucose(1503.45μA·(mmol·L^(-1))^(-1)-cm^(-2)),a low detection limit(21.95μmol·L^(-1)),excellent selectivity,a high level of reproducibility,and good sta-bility.This indicates that the CuO-Co_(3)O_(4)composite has a broad prospect of non-enzymatic glucose sensing application.展开更多
Background:Hyperglycemia is a typical symptom of diabetes.High glucose induces apoptosis of isletβcells.While autophagy functions in cytoprotection and autophagic cell death.The interaction between autophagy and apop...Background:Hyperglycemia is a typical symptom of diabetes.High glucose induces apoptosis of isletβcells.While autophagy functions in cytoprotection and autophagic cell death.The interaction between autophagy and apoptosis is important in the modulation of the function of isletβcells.Vitamin B3 can induce autophagy and inhibit isletβapoptosis.Method:The mechanism of vitamin B3-mediated protective effect on the function of isletβcells was explored by the method of western blot,immunofluorescence and flow cytometry.Results:In the present study,high glucose stress increased the apoptosis rate,while vitamin B3 reduced the apoptosis rate.The effect of vitamin B3 on autophagy flux under normal and high glucose stress was also investigated.Vitamin B3 increased the number of autophagosomes and increased the light chain(LC)3-II/LC3-I ratio.In contrast,vitamin B3 decreased sequestosome 1(SQSTM1)/p62 protein expression and inhibited the phosphorylation of mammalian ribosomal protein S6 kinaseβ-1(p70S6K/S6K1),which was a substrate of mammalian target of rapamycin(mTOR)under normal and high glucose stress.To further verify the protective effect of vitamin B3 on apoptosis,we treated isletβcell RIN-m5F with autophagy inhibitor 3-methyladenine(3-MA).Vitamin B3 decreased the apoptosis rate under high glucose stress,while the inhibition of apoptosis by vitamin B3 was blocked after adding 3-MA.Conclusion:Our data suggested that vitamin B3 reduced the apoptosis rate ofβcells,possibly through inducing autophagy under high glucose stress.展开更多
Nanocomposite of Co3O4 and multiwalled carbon nanotube (MCNT) was synthesised using one step solvothermal method, and an electrochemical non-enzymatic glucose sensor (Co3O4-MCNT/GCE) was successfully constructed by a ...Nanocomposite of Co3O4 and multiwalled carbon nanotube (MCNT) was synthesised using one step solvothermal method, and an electrochemical non-enzymatic glucose sensor (Co3O4-MCNT/GCE) was successfully constructed by a dropping method. The obtained Co3O4 and Co3O4- MCNT were characterized and investigated by transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDS). Quantitative analysis of glucose was performed using the amperometric (i–t) method, and plot of current difference versus concentration of glucose was linear in the range of 1.0–122μmol/L, with a linear correlation coefficient (R^2) of 0.9983 and limit of detection (LOD) of 0.28μmol/L. Sensitivity of this sensor was evaluated as 2550μA L mmol^-1 cm^-2. This new sensor produced satisfactory reproducibility and stability and was applied to monitor trace amounts of glucose in human serum samples.展开更多
BACKGROUND Colorectal cancer(CRC)is a worldwide problem,which has been associated with changes in diet and lifestyle pattern.As a result of colonic fermentation of dietary fibres,short chain free fatty acids are gener...BACKGROUND Colorectal cancer(CRC)is a worldwide problem,which has been associated with changes in diet and lifestyle pattern.As a result of colonic fermentation of dietary fibres,short chain free fatty acids are generated which activate free fatty acid receptors(FFAR)2 and 3.FFAR2 and FFAR3 genes are abundantly expressed in colonic epithelium and play an important role in the metabolic homeostasis of colonic epithelial cells.Earlier studies point to the involvement of FFAR2 in colorectal carcinogenesis.AIM To understand the role of short chain FFARs in CRC.METHODS Transcriptome analysis console software was used to analyse microarray data from CRC patients and cell lines.We employed short-hairpin RNA mediated down regulation of FFAR2 and FFAR3 genes,which was validated using quantitative real time polymerase chain reaction.Assays for glucose uptake and cyclic adenosine monophosphate(cAMP)generation was done along with immunofluorescence studies to study the effects of FFAR2/FFAR3 knockdown.For measuring cell proliferation,we employed real time electrical impedancebased assay available from xCELLigence.RESULTS Microarray data analysis of CRC patient samples showed a significant down regulation of FFAR2 gene expression.This prompted us to study the FFAR2 in CRC.Since,FFAR3 shares significant structural and functional homology with FFAR2,we knocked down both these receptors in CRC cell line HCT 116.These modified cell lines exhibited higher proliferation rate and were found to have increased glucose uptake as well as increased level of glucose transporter 1.Since,FFAR2 and FFAR3 signal through G protein subunit(Gαi),knockdown of these receptors was associated with increased cAMP.Inhibition of protein kinase A(PKA)did not alter the growth and proliferation of these cells indicating a mechanism independent of cAMP/PKA pathway.CONCLUSION Our results suggest role of FFAR2/FFAR3 genes in increased proliferation of colon cancer cells via enhanced glucose uptake and exclude the role of PKA mediated cAMP signalling.Alternate pathways could be involved that would ultimately result in increased cell proliferation as a result of down regulated FFAR2/FFAR3 genes.This study paves the way to understand the mechanism of action of short chain FFARs in CRC.展开更多
There has been substantial interest in designing and fabricating electrochemical non-enzyme sensors for glucose detection with a focus on the nanocomposites used between metal oxide and the two-dimensional material.In...There has been substantial interest in designing and fabricating electrochemical non-enzyme sensors for glucose detection with a focus on the nanocomposites used between metal oxide and the two-dimensional material.In this work,Co_(3)O_(4)/reduced graphene oxide(rGO)nanocomposite was obtained and used as a modified electrochemical electrode for the detection of trace glucose.According to the results,the electrocatalytic performances of Co_(3)O_(4)nanoparticles for the oxidation of glucose were substantially enhanced with the addition of a small amount of r GO.Specifically,the Co_(3)O_(4)/r GO modified electrode exhibited a sensitivity of 82μA·mmol^(-1)·cm^(-2),a detection limit of 50μmol·L^(-1)(signal noise ratio(S/N)=3),and a fast response time of about 1 s under optimal conditions.The enhanced performances of the Co_(3)O_(4)/r GO modified electrode are attributable to the high absorption oxygen(O_(Ads))and synergistic effect between Co_(3)O_(4)and r GO.The results indicate that Co_(3)O_(4)/r GO nanocomposite is a promising candidate for being used as the active material in real-world electrochemical biosensors.展开更多
基金supported by the National Natural Science Foundation of China(32172210)the Shandong Provincial Natural Science Foundation(ZR2025QC295).
文摘Neurodegenerative diseases,such as Alzheimer’s disease and Parkinson’s disease,are associated with cognitive impairment and impaired brain glucose metabolism,posing significant challenges for the public health.We previously demonstrated that cyanidin 3-O-β-galactoside(Cy3Gal)from black chokeberry alleviated cognitive impairment in aging mice through regulating brain energy metabolism in a direct way.However,the indirect mechanisms in mitigating brain glucose hypometabolism remain underexplored.Here,we utilized a bilaterally intracerebroventricular injection of streptozotocin(ICV/STZ,3 mg/kg bw)-induced brain glucose hypometabolism model to investigate the effects of Cy3Gal on cognitive impairment alleviation.Our findings revealed that Cy3Gal administration significantly improved memory deficit and cognitive impairment in ICV/STZ-administrated mice.Subsequently,Cy3Gal showed excellent abilities in inhibiting astrocyte overactivation,regulating neurotransmitters metabolism,and promoting synaptic plasticity.Furthermore,Cy3Gal enhanced brain glucose metabolism by improving glycolysis and the TCA cycle.Additionally,Cy3Gal modulated levels of gut microbiota-derived metabolites,including acetate,butyrate,histidine,glutamine,serine,valine and isoleucine,which were closely linked to brain glucose metabolism.The in vitro results further demonstrated that these metabolites played an important role in the neuron-astrocyte energy metabolism,which accounted for the alleviation of glucose hypometabolism.Overall,our findings suggest that Cy3Gal mitigates ICV/STZ-induced cognitive impairment by modulating gut microbiota-derived short-chain fatty acids and amino acids,which in turn improves brain glucose metabolism.
基金Supported by grants from the Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-037A).
文摘AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.METHODS:HRMEC dysfunction model was established by 48h glucose(30 mmol/L)treatment and treated with Feno/NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activator(Nigericin).Cell viability/apoptosis were assessed by cell counting kit-8(CCK-8)/terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay(TUNEL)staining and flow cytometry assays.Levels of apoptosis-(Bcl-2-associated X protein,Bax/B-cell lymphoma 2,Bcl-2),vascular permeability-(vascular endothelial growth factor,VEGF)and inflammasome activation-related proteins(NLRP3/cleaved caspase-1/apoptosis-associated speck-like protein containing a CARD,ASC),as well as inflammatory factors(interleukin,IL-6/IL-1β/tumor necrosis factor,TNF-α/IL-18)were determined with Western blot/enzyme linked immunosorbent assay(ELISA).Cell permeability/reactive oxygen species(ROS)level/superoxide dismutase(SOD)activity/malondialdehyde(MDA)content were assessed by Evans blue staining/2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe/SOD kit/MDA kit.RESULTS:HRMEC dysfunction was successfully induced by HG,evidenced by decreased viability(P<0.001),increased apoptosis(P<0.001),permeability(P<0.001),and inflammatory factor levels(P<0.001).Feno treatment significantly ameliorated HG-induced HRMEC dysfunction(P<0.01).Meanwhile,HG induction increased ROS production(P<0.001)and MDA content(P<0.001)in HRMECs,while reducing SOD activity(P<0.001),indicative of oxidative stress.This was,however,abolished by Feno(P<0.05).Moreover,Feno eliminated activation of NLRP3 inflammasomes(P<0.05)in HG-induced HRMECs.Strikingly,activation of NLRP3 inflammasomes partially averted the inhibition of Feno on HG-induced HRMEC dysfunction(P<0.05).CONCLUSION:Feno represses oxidative stress and NLRP3 inflammasome activation,consequently alleviating HG-induced HRMEC dysfunction.
基金supported by the National Natural Science Foundation of China(22278419)the Key Core Technology Research(Social Development)Foundation of Suzhou(2023ss06)the Suzhou National Joint Laboratory for Green and Low-carbon Wastewater Treatment and Resource Utilization Technology,Suzhou University of Science and Technology(SZLSDT202404).
文摘Fully utilizing renewable biomass energy is important for saving energy,reducing carbon emissions,and mitigating climate change.As the main hydrolysate of cellulose,a primary component of lignocellulose,glucose could be employed as a starting material to prepare some other functional derivatives for improving the value of biomass resources.The isomerization of glucose to produce fructose is an important intermediate process during numerous high-value-added chemical preparations.Therefore,the development of efficient and selective catalysts for glucose isomerization is of great significance.Currently,glucose isomerase catalysts are limited by the harsh conditions required for microbial activity,which restricts further improvements in fructose yield.Additionally,heterogeneous Bronsted-base and Lewis-acid catalysts commonly employed in chemical isomerization methods often lead to the formation of undesirable by-products,resulting in reduced selectivity toward fructose.This study has demonstrated that lithium-loaded heterogeneous catalysts possess excellent isomerization capabilities under mild conditions.A highly efficient Li-C_(3)N_(4) catalyst was developed,achieving a fructose selectivity of 99.9% and a yield of 42.6% at 60℃ within 1.0 h-comparable to the performance of the enzymatic method.Characterization using X-ray photoelectron spectroscopy(XPS),X-ray diffraction(XRD),proton nuclear magnetic resonance(^(1)H NMR),and inductively coupled plasma(ICP)analyses confirmed that lithium was stably incorporated into the g-C_(3)N_(4) framework through the formation of Li-N bonds.Further investigations using CO_(2) temperature-programmed desorption(CO_(2)-TPD),in situ Fourier-transform infrared spectroscopy(FT-IR)and 7Li magic angle spinning nuclear magnetic resonance(^(7)Li MAS NMR)indicated that the isomerization proceeded via a base-catalyzed mechanism.The Li species were found to interact with hydroxyl groups generated through hydrolysis and simultaneously coordinated with nitrogen atoms in the C_(3)N_(4) matrix,resulting in the formation of Li-N_(6)-H_(2)O active sites.These active sites facilitated the deprotonation of glucose to form an enolate intermediate,followed by a proton transfer step that generated fructose.This mechanism not only improved the efficiency of fructose production but also provided valuable insight into the catalytic role of lithium within the isomerization process.
基金supported by the National Natural Science Foundation of China(32172210).
文摘Unhealthy diets are associated with various diseases that can disrupt brain energy metabolism,which significantly increased the risk of cognitive impairment and chronic neurodegenerative diseases.Early intervention with nutritional supplements may have long-lasting positive effects on diet-related glucose metabolism and potentially mediate the progression of neurodegeneration in middle-aged and elderly people.We previously reported that cyanidin 3-O-β-galactoside(Cy3Gal),an anthocyanin from black chokeberry(Aronia melanocarpa(Michx.)Elliott),alleviated cognitive impairment in aging mice through regulating brain energy metabolism.However,it remains unclear whether Cy3Gal can also exert beneficial effects in mice fed with a high-fat/high-sugar diet.Here we revealed that Cy3Gal treatment conserved the health of neurons and synapses,as well as cognitive function of mice.Furthermore,we observed that Cy3Gal effectively improved glucose uptake and metabolism of skeletal muscle by enhancing glycolysis both in vivo and in vitro models,which is essential for maintaining a stable glucose supply to the brain.Additionally,Cy3Gal significantly increased the levels of glucose-derived tricarboxylic acid cycle intermediates in the mice brain(P<0.05),and regulated the activities of mitochondrial respiratory chain complexes(P<0.01).The positive influence on peripheral and brain bioenergetics explained how the Cy3Gal exerted neuroprotective effect.In conclusion,our study illustrated that early dietary intervention of Cy3Gal had significant advantages in terms of neuroprotection and cognition under the challenge of HFHS diet-induced glucose metabolism disorder.
基金Supported by Taicang Science and Technology Program,No.TC2021JCYL21“National Tutor System”Training Program for Health Youth Key Talents in Suzhou,No.Qngg2023042Suzhou Science and Technology Bureau,No.SYW2024152.
文摘BACKGROUND Tumor necrosis factor-α(TNF-α)has been implicated in the development of diabetes following chronic pancreatitis.However,its role in abnormal glucose metabolism(AGM)after acute pancreatitis(AP)and post-pancreatitis diabetes mellitus remains unclear.AIM To investigate the role of TNF-αin AP-associated AGM and its effects on isletβ-cell apoptosis,focusing on the underlying molecular mechanisms.METHODS Clinical data were collected to assess AGM’s incidence and identify the characteristics in 369 AP patients.In vitro,AP models were established using lipopolysaccharide in 266-6 acinar cells and MIN-6β-cells.Cell proliferation,apoptosis,and protein expression were analyzed using the Cell Counting Kit-8 assay,terminal deoxynucleotidyl transferase dUTP nick-end labeling assay,and western blotting.The TNF-αand insulin concentration in co-culture medium was measured by enzyme-linked immunosorbent assay.In vivo,an AP mouse model was induced using sodium taurocholate,and pancreatic tissues were analyzed through hematoxylin and eosin staining,terminal deoxynucleotidyl transferase dUTP nick-end labeling,and western blotting.TNF-αlevels were assessed by enzyme-linked immunosorbent assay.A TNF-αinhibitor was applied to the AP cell model to reassess apoptosis and protein expression.RESULTS AGM occurred in 40.38%of AP patients.Body mass index,severity grade,recurrence frequency,and lung injury were significantly associated with AGM.AP models in 266-6 and MIN-6 cells showed reducedβ-cell proliferation,insulin secretion,and increased apoptosis,which correlated with inflammation severity.Similar findings ofβ-cell apoptosis were confirmed in the mouse model.TNF-αlevels were significantly elevated in AP models,with higher levels in severe inflammation.Increased Bax and caspase-3 expression and decreased Bcl-2 expression were observed in both in vitro and in vivo models.These changes intensified with increasing inflammation.TNF-αinhibition reduced apoptosis and altered protein expression patterns,decreasing Bax and caspase-3,while increasing Bcl-2 in MIN-6 cells.CONCLUSION TNF-αcontributes toβ-cell apoptosis and AGM in AP through the Bax/Bcl-2/caspase-3 signaling pathway,suggesting TNF-αas a potential therapeutic target for preventing AP-associated AGM.
基金supported by the Incubation Fund of Zhongshan Hospital,Fudan University(Xiamen Branch)(2020ZSXMYS24).
文摘Recent research has indicated that sialic acid,such as free sialic acid(N-acetylneuraminic acid,Neu5Ac)and bound sialic acid(3ʹ-sialyllactose,3ʹ-SL),can ameliorate disorders associated with glycolipid metabolism,although the underlying mechanisms have yet to be determined.We examined the effects of 3ʹ-SL on glycolipid metabolism in mice fed a high-fat diet.Male C57BL/6J mice were divided into 6 groups:2 model control groups(normal and high-fat diets)and 4 intervention groups(Neu5Ac,and low,moderate,and high-dose 3ʹ-SL).After 8 weeks of continuous gavage intervention,mice in the 3ʹ-SL intervention groups had lower body weight and total fat content;reduced fasting blood glucose,triglycerides,low-density lipoproteins and oxidized-low-density lipoproteins;and increased high-density lipoproteins,but no dosage-dependent of 3ʹ-SL intervention was found,moderate-dose 3ʹ-SL intervention as optimal for further exploration.3ʹ-SL intervention could increase respiratory exchange ratio,energy expenditure,and amount of exercise performed.3ʹ-SL increased the colonic abundances of Akkermansia,Lactobacillus,and Bacteroides,and reduced those of Erysipelatoclostridium,Faecalibaculum,and Aldercreutzia.Changes were also observed in colonic metabolites,and liver gene transcript and metabolites,which were mainly enriched in bile secretion,taurine and hypotaurine metabolism,and insulin resistance.Additionally,3ʹ-SL was observed to regulate genes associated with physiological rhythms,including Clock,Per2,Cry1,and Bhihe41.Collectively,our findings indicate that 3ʹ-SL can contribute to the prevention and control of disorders associated with glucose and lipid metabolism caused by high-fat diets.Compared with Neu5Ac,3ʹ-SL intervention can more effectively ameliorate intestinal flora disorders,enhance bile acid circulation,increase tissue energy expenditure,and reduce lipid synthesis,thereby promoting lipid-lowering effects mediated via the gut-liver axis,and can also enhance energy metabolism and alleviate disorders of glucolipid metabolism by altering physiological rhythms in high fat-diet mice.
基金supported by the Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2020D01C210).
文摘Objective Endothelial dysfunction is a central contributor to the vascular complications observed in individuals with diabetes.cAMP response element-binding protein(CREB)plays a crucial role in mediating hyperglycemia-induced endothelial dysfunction.Phosphatase and tensin homolog(PTEN)has been implicated in the regulation of endothelial inflammation,yet the precise mechanism by which CREB modulates PTEN to protect endothelial cells under high glucose conditions remains unknown.This study aims to elucidate this potential mechanism.Methods Human umbilical vein endothelial cells(HUVECs)were exposed to high glucose(30 mM)or normal glucose(5.5 mM)for 6 days.Cell viability and apoptosis were assessed via the Cell Counting Kit-8 and flow cytometry.To evaluate oxidative stress,the levels of reactive oxygen species(ROS),lactate dehydrogenase(LDH),and malondialdehyde(MDA)were measured via commercial assay kits.The interaction between CREB and endothelial specific molecule 1(ESE-1)was assessed via coimmunoprecipitation.Chromatin immunoprecipitation and luciferase reporter assays were used to investigate the transcriptional regulation of PTEN by ESE-1 and CREB.Western blotting was performed to analyze the expression of intercellular adhesion molecule-1 and E-selectin.The adhesion of HUVECs was evaluated via monocyte‒endothelial cell adhesion assays.Results Our findings revealed a direct interaction between CREB and ESE-1,which together regulate PTEN expression to activate the phosphoinositide 3-kinase/protein kinase B pathway.Under high-glucose conditions,we observed significant increases in oxidative stress,inflammatory responses,and adhesion in HUVECs.ESE-1 knockdown reversed these effects,restoring endothelial cell function.Moreover,the overexpression of PTEN in high glucose–treated HUVECs rescued the endothelial injury induced by ESE-1 knockdown,suggesting that PTEN plays a pivotal role in mediating the protective effects.Conclusion ESE-1,through the regulation of CREB-mediated PTEN expression,activates the PI3K/AKT pathway and modulates key processes such as oxidative stress,inflammation,and adhesion in endothelial cells under high-glucose stress.
文摘目的探讨星状神经节阻滞(SGB)通过长链非编码RNA(lncRNA)牛磺酸上调基因1(TUG1)-NOD样受体热蛋白结构域相关蛋白3(NLRP3)轴在体外脑缺血再灌注模型中对炎症反应和自噬溶酶体形成的调节作用。方法培养大鼠海马神经元细胞系H19-7,并将细胞分为8组:(i)正常对照组:正常培养的神经元细胞;(ii)氧-糖剥夺/复氧(OGD/R)组:采用氧-糖剥夺/复氧法模拟脑缺血再灌注损伤;(iii)OGD/R+SGB组:OGD/R联合麻醉药0.5%布比卡因用于体外模拟SGB;(iv)OGD/R+SGB+TUG1过表达阴性对照组:OGD/R联合布比卡因并联合TUG1过表达阴性对照质粒转染细胞;(v)OGD/R+SGB+TUG1过表达组:OGD/R联合布比卡因并联合TUG1过表达质粒转染细胞;(vi)OGD/R+SGB+TUG1过表达+MCC950组:OGD/R联合布比卡因、TUG1过表达质粒转染及NLRP3抑制剂MCC950处理细胞;(vii)OGD/R+TUG1过表达组:OGD/R联合TUG1过表达质粒转染细胞;(viii)OGD/R+MCC950组:OGD/R联合NLRP3抑制剂MCC950处理细胞。进一步通过实时定量PCR(Quantitative Real Time PCR,qRTPCR)实验检测细胞中lncRNATUG1的表达;利用Western blot法检测细胞中NLRP3、微管相关蛋白1轻链3(LC3)-I、LC3-II、自噬相关基因5(Atg5)、苄氯素1(beclin1)、自噬接头蛋白(p62)、溶酶体相关膜蛋白1(LAMP1)的表达水平;利用透射电镜(TEM)检测自噬溶酶体的数量;并用酶联免疫吸附测定(ELISA)法检测细胞培养上清中白细胞介素(IL)-1β、IL-6、IL-18、肿瘤坏死因子(TNF)-α的含量。结果与正常对照组相比,OGD/R组lncRNA TUG1、NLRP3、Atg5、beclin1、p62、LAMP1的表达水平以及LC3-II/I比值均显著上调(^(均)P<0.05),自噬溶酶体数量增加(P<0.05),IL-1β、IL-6、IL-18、TNF-α的含量显著升高(^(均)P<0.05)。与OGD/R组相比,OGD/R+SGB组的上述指标均显著下调(P<0.05)。与OGD/R+SGB+TUG1过表达阴性对照组相比,OGD/R+SGB+TUG1过表达组的lncRNA TUG1、NLRP3、Atg5、beclin1、p62、LAMP1的表达水平以及LC3-II/I比值均显著上调(^(均)P<0.05),自噬溶酶体数量增加(P<0.05),IL-1β、IL-6、IL-18、TNF-α的含量显著升高(^(均)P<0.05),然而,加入NLRP3的抑制剂MCC950后,除lncRNA TUG1外其余指标均显著下调(^(均)P<0.05)。另外,与OGD/R组比,OGD/R+TUG1过表达组的上述指标进一步上调(^(均)P<0.05)。与OGD/R组比,OGD/R+MCC950组则抑制了除lncRNA TUG1外的其余指标(^(均)P<0.05)。结论星状神经节阻滞通过调节lncRNA TUG1-NLRP3轴有效减轻体外脑缺血再灌注损伤引起的炎症反应和自噬溶酶体形成,提示其可能作为治疗缺血性脑损伤的潜在策略。
基金supported by the National Natural Science Foundation of China,No.81371591
文摘AIM To investigate the relationship between glucose metabolism and glypican-3(GPc3)expression in hepatocellular carcinoma(Hcc).METHODSImmunohistochemical staining of pathological samples for GPc3 and glucose transporter 1(GLUT1),and whole-body ^(18)F-FDG PET/c T for measuring tumour glucose uptake were performed in 55 newly diagnosed Hcc patients.The maximum standard uptake value(s UVmax)and tumour-to-non-tumourous liver uptake(T/NT)ratio were used to quantify ^(18)F-FDG uptake.In vitro ^(18)F-FDG uptake assay of GPc3-expressing Hep G2 and non-GPc3-expressing RH7777 cel ls was used to examine the effect of GPc3 in cellular glucose metabolism.The relationships between GPc3 expression and ^(18)F-FDG uptake,GLUT1 expression,tumour differentiation,and other clinical indicators were analysed using spearman rank correlation,univariateand multiple logistic regression analyses.RESULTSPositive GPc3 expression was observed in 67.3%of Hcc patients,including 75.0%of those with well or moderately differentiated Hcc and 36.4%of those with poorly differentiated Hcc.There was an inverse relationship between GPc3 expression and s UVmax(Spearman correlation coefficient=-0.281,P=0.038)and a positive relationship between GLUT1 expression and sU Vmax(Spearman correlation coefficient=0.681,P<0.001)in patients with Hcc.Univariate analysis showed that two glucose metabolic parameters(sU Vmax and T/NT ratio),tumour differentiation,lymph node metastasis,and TNM stage were all significantly associated with GPc3 expression(P<0.05),whereas GLUT1 expression,sex,age,tumour size,intrahepatic lesion number,and distant metastasis showed no statistical association(P>0.05).Further multivariate analysis revealed that only the T/N ratio was significantly correlated with GPC3 expression in patients with Hcc(P<0.05).In vitro assay revealed that the uptake of ^(18)F-FDG in GPc3-expressing HepG2 cells was significantly lower than that of non-GPc3-expressing RH7777 cells(t=-20.352,P<0.001).CONCLUSIONThe present study demonstrated that GPc3 expression is inversely associated with glucose metabolism,suggesting that GPc3 may play a role in regulating glucose metabolism in Hcc.
基金National Natural Science Foundation of China(Grant No.20871008 and 21171011)
文摘In the present study, we investigated the role of reactive oxygen species（ROS） elevation induced by an anti-diabetic vanadium compound, vanadyl acetylacetonate（VO（acac）2）, in the regulation of lipolysis and glucose metabolism using differentiated 3T3L1 adipocytes as a model system. By confocal laser scanning microscopy, we found that VO（acac）2 induced ROS generation under high glucose stimulation, and the pretreatment of NADPH oxidase inhibitors could significantly reduce the elevated ROS level. Meanwhile, the decreased phosphorylated levels of AKT and the two key modulators of lipolysis（HSL and perilipin） were observed by western blot analysis. We also found that the contents of glycerol release were further reduced as well. In addition, the levels of key regulatory proteins, AS160 and GSK3β, in glucose metabolism pathway were correspondingly reduced. These findings demonstrated that ROS induced by vanadium compounds could act as a metabolic signal to activate AKT pathway to inhibit lipolysis and promote glucose transport and glycogen synthesis rather than by direct action by themselves. Our study contributed to elucidate the anti-diabetic effects of vanadium compounds and provided a theoretical basis for the further development of new vanadium complexes in the prevention and therapeutics of diabetes.
文摘Compositions of glycerolipids and fatty acid compositions of glycerolipids were compared among Synechocystis sp. PCC 6803 cells grown in the BG-11 medium containing different concentrations of glucose and Na2S2O3 in this study. It was found that Na2S2O3 can effectively increase the percentage of sulphoquinovosyl diacylglycerol (SQDG) and phosphatidylglycerol (PG) to total membrane lipids and the simultaneous application of glucose with Na2S2O3 can counteract the effect of Na2S2O3. In addition, Na2S2O3 can significantly increase the percentage of palmitic acid (C, 16:0) in fatty acid composition of monogalactosyl diacylglycerol (MGDG) and digalactosyl diacylglycerol (DGDG) and decrease the fatty acid unsaturation degree accordingly, and these effects can also be eliminated by glucose. These results indicate that Na2S2O3 can take as a reductant to make membrane lipids in a low unsaturated state, and the simultaneous application of glucose can decrease the reducing power of Na2S2O3. In addition, Na2S2O3 can take as a sulfur donor for the synthesis of SQDG.
基金Supported by National Natural Science Foundation of China,No.81300329 and No.81401992
文摘AIM To investigate the role of embryonic liver fordin(ELF) in liver fibrosis by regulating hepatic stellate cells(HSCs) glucose glycolysis.METHODS The expression of ELF and the glucose glycolysisrelated proteins were evaluated in activated HSCs. si RNA was used to silence ELF expression in activated HSCs in vitro and the subsequent changes in PI3K/Akt signaling and glucose glycolysis-related proteins were observed.RESULTS The expression of ELF increased remarkably in HSCs of the fibrosis mouse model and HSCs that were cultured for 3 wk in vitro. Glucose glycolysis-related proteins showed an obvious increase in the activated HSCs, such as phosphofructokinase, platelet and glucose transporter 1. ELF-si RNA, which perfectly silenced the expression of ELF in activated HSCs, led to the induction of glucose glycolysis-related proteins and extracellular matrix(ECM) components. Moreover, p Akt, which is an important downstream factor in PI3K/Akt signaling, showed a significant change in response to the ELF silencing. The expression of glucose glycolysisrelated proteins and ECM components decreased remarkably when the PI3K/Akt signaling was blocked by Ly294002 in the activated HSCs. CONCLUSION ELF is involved in HSC glucose glycolysis by regulating PI3K/Akt signaling.
基金funded by the National Natural Science Foundation of China,No. 30770765
文摘In this study, we investigated the effects of adenovirus-mediated transfection of PC12 cells with glucose transporter 3 after ischemic injury. The results of flow cytometry and TUNEL showed that exogenous glucose transporter 3 significantly suppressed PC12 cell apoptosis induced by ischemic injury. The results of isotopic scintiscan and western blot assays showed that, the glucose uptake rate was significantly increased and nuclear factor kappaB expression was significantly decreased after adenovirus-mediated transfection of ischemic PC12 cells with glucose transporter 3. These results suggest that adenovirus-mediated transfection of cells with glucose transporter 3 elevates the energy metabolism of PC12 cells with ischemic injury, and inhibits cell apoptosis.
文摘Objective High glucose(HG)can influence the osteogenic differentiation ability of periodontal ligament stem cells(PDLSCs).Human umbilical cord mesenchymal stem cell-derived exosomes(hUCMSC-exo)have broad application prospects in tissue healing.The current study aimed to explore whether hUCMSC-exo could promote the osteogenic differentiation of hPDLSCs under HG conditions and the underlying mechanism.Methods We used a 30 mmol/L glucose concentration to simulate HG conditions.CCK-8 assay was performed to evaluate the effect of hUCMSC-exo on the proliferation of hPDLSCs.Alkaline phosphatase(ALP)staining,ALP activity,and qRT-PCR were performed to evaluate the pro-osteogenic effect of hUCMSC-exo on hPDLSCs.Western blot analysis was conducted to evaluate the underlying mechanism.Results The results of the CCK-8 assay,ALP staining,ALP activity,and qRT-PCR assay showed that hUCMSC-exo significantly promoted cell proliferation and osteogenic differentiation in a dosedependent manner.The Western blot results revealed that hUCMSC-exo significantly increased the levels of p-PI3K and p-AKT in cells,and the effect was inhibited by LY294002(PI3K inhibitor)or MK2206(AKT inhibitor),respectively.Moreover,the increases in osteogenic indicators induced by hUCMSC-exo were significantly suppressed by LY294002 and MK2206.Conclusion hUCMSC-exo promote the osteogenic differentiation of hPDLSCs under HG conditions through the PI3K/AKT signaling pathway.
基金financially supported by the National Natural Science Foundation of China (Nos.62074018 and 62174015)the Developing Project of Science and Technology of Jilin Province (No.20200301052RQ)+1 种基金the Project of Education Department of Jilin Province (No.JJKH20210831KJ)the Science and Technology Foundation of State Grid Corporation of China (No. SGTJDK00DYJS2000148)
文摘In the field of glucose sensors,the development of inexpensive and high-efficiency electrochemical glucose sensors is the current research hotspot.In this paper,CuO-Co_(3)O_(4)composite with a prickly-sphere-like morphology is prepared by the facile hydrothermal method for the non-enzymatic electrochemical glucose detection.X-ray diffraction,scanning electron microscopy,transmission electron microscopy,energy-dispersive X-ray spec-troscopy,and X-ray photoelectron spectroscopy are used to analyze the structure,composition,and morphology of the material.In addition,the electrochemical catalytic perfor-mance of CuO-Co_(3)O_(4)to glucose is obtained by cyclic voltammetry and chronoamperometry.The excellent elec-trochemical sensing performance may be attributed to the large number of catalytic sites in the prickly-sphere-like composite and the synergistic effect of Cu and Co.Under an applied voltage of 0.55 V,CuO-Co_(3)O_(4)composite shows sensitivity to glucose(1503.45μA·(mmol·L^(-1))^(-1)-cm^(-2)),a low detection limit(21.95μmol·L^(-1)),excellent selectivity,a high level of reproducibility,and good sta-bility.This indicates that the CuO-Co_(3)O_(4)composite has a broad prospect of non-enzymatic glucose sensing application.
基金supported by the National-Natural Science Foundation of China(32072334),the General Project of the Education Department of Hunan Province(20C0959)the Changsha Natural Science Foundation(kq2007020).
文摘Background:Hyperglycemia is a typical symptom of diabetes.High glucose induces apoptosis of isletβcells.While autophagy functions in cytoprotection and autophagic cell death.The interaction between autophagy and apoptosis is important in the modulation of the function of isletβcells.Vitamin B3 can induce autophagy and inhibit isletβapoptosis.Method:The mechanism of vitamin B3-mediated protective effect on the function of isletβcells was explored by the method of western blot,immunofluorescence and flow cytometry.Results:In the present study,high glucose stress increased the apoptosis rate,while vitamin B3 reduced the apoptosis rate.The effect of vitamin B3 on autophagy flux under normal and high glucose stress was also investigated.Vitamin B3 increased the number of autophagosomes and increased the light chain(LC)3-II/LC3-I ratio.In contrast,vitamin B3 decreased sequestosome 1(SQSTM1)/p62 protein expression and inhibited the phosphorylation of mammalian ribosomal protein S6 kinaseβ-1(p70S6K/S6K1),which was a substrate of mammalian target of rapamycin(mTOR)under normal and high glucose stress.To further verify the protective effect of vitamin B3 on apoptosis,we treated isletβcell RIN-m5F with autophagy inhibitor 3-methyladenine(3-MA).Vitamin B3 decreased the apoptosis rate under high glucose stress,while the inhibition of apoptosis by vitamin B3 was blocked after adding 3-MA.Conclusion:Our data suggested that vitamin B3 reduced the apoptosis rate ofβcells,possibly through inducing autophagy under high glucose stress.
基金the financial support of this study by the National Natural Science Foundation of China(NSFC, No. 31860468)
文摘Nanocomposite of Co3O4 and multiwalled carbon nanotube (MCNT) was synthesised using one step solvothermal method, and an electrochemical non-enzymatic glucose sensor (Co3O4-MCNT/GCE) was successfully constructed by a dropping method. The obtained Co3O4 and Co3O4- MCNT were characterized and investigated by transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDS). Quantitative analysis of glucose was performed using the amperometric (i–t) method, and plot of current difference versus concentration of glucose was linear in the range of 1.0–122μmol/L, with a linear correlation coefficient (R^2) of 0.9983 and limit of detection (LOD) of 0.28μmol/L. Sensitivity of this sensor was evaluated as 2550μA L mmol^-1 cm^-2. This new sensor produced satisfactory reproducibility and stability and was applied to monitor trace amounts of glucose in human serum samples.
文摘BACKGROUND Colorectal cancer(CRC)is a worldwide problem,which has been associated with changes in diet and lifestyle pattern.As a result of colonic fermentation of dietary fibres,short chain free fatty acids are generated which activate free fatty acid receptors(FFAR)2 and 3.FFAR2 and FFAR3 genes are abundantly expressed in colonic epithelium and play an important role in the metabolic homeostasis of colonic epithelial cells.Earlier studies point to the involvement of FFAR2 in colorectal carcinogenesis.AIM To understand the role of short chain FFARs in CRC.METHODS Transcriptome analysis console software was used to analyse microarray data from CRC patients and cell lines.We employed short-hairpin RNA mediated down regulation of FFAR2 and FFAR3 genes,which was validated using quantitative real time polymerase chain reaction.Assays for glucose uptake and cyclic adenosine monophosphate(cAMP)generation was done along with immunofluorescence studies to study the effects of FFAR2/FFAR3 knockdown.For measuring cell proliferation,we employed real time electrical impedancebased assay available from xCELLigence.RESULTS Microarray data analysis of CRC patient samples showed a significant down regulation of FFAR2 gene expression.This prompted us to study the FFAR2 in CRC.Since,FFAR3 shares significant structural and functional homology with FFAR2,we knocked down both these receptors in CRC cell line HCT 116.These modified cell lines exhibited higher proliferation rate and were found to have increased glucose uptake as well as increased level of glucose transporter 1.Since,FFAR2 and FFAR3 signal through G protein subunit(Gαi),knockdown of these receptors was associated with increased cAMP.Inhibition of protein kinase A(PKA)did not alter the growth and proliferation of these cells indicating a mechanism independent of cAMP/PKA pathway.CONCLUSION Our results suggest role of FFAR2/FFAR3 genes in increased proliferation of colon cancer cells via enhanced glucose uptake and exclude the role of PKA mediated cAMP signalling.Alternate pathways could be involved that would ultimately result in increased cell proliferation as a result of down regulated FFAR2/FFAR3 genes.This study paves the way to understand the mechanism of action of short chain FFARs in CRC.
基金financially supported by the National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(Nos.2021H1D3A2A01100019 and 2022R1F1074441)supported by the Brain Pool Program funded by the Ministry of Science and ICT through the National Research Foundation of Korea(No.2021H1D3A2A01100019)。
文摘There has been substantial interest in designing and fabricating electrochemical non-enzyme sensors for glucose detection with a focus on the nanocomposites used between metal oxide and the two-dimensional material.In this work,Co_(3)O_(4)/reduced graphene oxide(rGO)nanocomposite was obtained and used as a modified electrochemical electrode for the detection of trace glucose.According to the results,the electrocatalytic performances of Co_(3)O_(4)nanoparticles for the oxidation of glucose were substantially enhanced with the addition of a small amount of r GO.Specifically,the Co_(3)O_(4)/r GO modified electrode exhibited a sensitivity of 82μA·mmol^(-1)·cm^(-2),a detection limit of 50μmol·L^(-1)(signal noise ratio(S/N)=3),and a fast response time of about 1 s under optimal conditions.The enhanced performances of the Co_(3)O_(4)/r GO modified electrode are attributable to the high absorption oxygen(O_(Ads))and synergistic effect between Co_(3)O_(4)and r GO.The results indicate that Co_(3)O_(4)/r GO nanocomposite is a promising candidate for being used as the active material in real-world electrochemical biosensors.
