BACKGROUND Coronary heart disease(CHD)and heart failure(HF)are the major causes of morbidity and mortality worldwide.Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis.Howeve...BACKGROUND Coronary heart disease(CHD)and heart failure(HF)are the major causes of morbidity and mortality worldwide.Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis.However,conventional diagnostic methods such as electrocardiography,echocardiography,and cardiac biomarkers have certain limitations,such as low sensitivity,specificity,availability,and cost-effectiveness.Therefore,there is a need for simple,noninvasive,and reliable biomarkers to diagnose CHD and HF.AIM To investigate serum cystatin C(Cys-C),monocyte/high-density lipoprotein cholesterol ratio(MHR),and uric acid(UA)diagnostic values for CHD and HF.METHODS We enrolled 80 patients with suspected CHD or HF who were admitted to our hospital between July 2022 and July 2023.The patients were divided into CHD(n=20),HF(n=20),CHD+HF(n=20),and control groups(n=20).The serum levels of Cys-C,MHR,and UA were measured using immunonephelometry and an enzymatic method,respectively,and the diagnostic values for CHD and HF were evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Serum levels of Cys-C,MHR,and UA were significantly higher in the CHD,HF,and CHD+HF groups than those in the control group.The serum levels of Cys-C,MHR,and UA were significantly higher in the CHD+HF group than those in the CHD or HF group.The ROC curve analysis showed that serum Cys-C,MHR,and UA had good diagnostic performance for CHD and HF,with areas under the curve ranging from 0.78 to 0.93.The optimal cutoff values of serum Cys-C,MHR,and UA for diagnosing CHD,HF,and CHD+HF were 1.2 mg/L,0.9×10^(9),and 389μmol/L;1.4 mg/L,1.0×10^(9),and 449μmol/L;and 1.6 mg/L,1.1×10^(9),and 508μmol/L,respectively.CONCLUSION Serum Cys-C,MHR,and UA are useful biomarkers for diagnosing CHD and HF,and CHD+HF.These can provide information for decision-making and risk stratification in patients with CHD and HF.展开更多
BACKGROUND Patients with chronic heart failure(CHF)frequently develop hyperuricemia,an elevated serum uric acid level,associated with adverse outcomes.Dapagliflozin,a sodium-glucose cotransporter-2 inhibitor,demonstra...BACKGROUND Patients with chronic heart failure(CHF)frequently develop hyperuricemia,an elevated serum uric acid level,associated with adverse outcomes.Dapagliflozin,a sodium-glucose cotransporter-2 inhibitor,demonstrates reduction in cardiovascular mortality and hospitalization in patients with CHF and ejection fraction(HFrEF),irrespective of diabetes.However,dapagliflozin’s effect on the uric acid levels in patients with CHF and hyperuricemia remain unclear.AIM To investigate the effects of dapagliflozin on uric acid levels in CHF patients with hyperuricemia.METHODS We conducted a randomized,double-blind,placebo-controlled trial in 200 patients with CHF and hyperuricemia,with HFrEF and serum uric acid levels≥7 mg/dL(≥416μmol/L).The participants were randomly assigned to receive a daily dose of 10 mg dapagliflozin or placebo for 24 months.The primary endpoint was the change in serum uric acid level from baseline to 24 months.Secondary endpoints included changes in left ventricular ejection fraction(LVEF),Nterminal pro-B-type natriuretic peptide(NT-proBNP),and quality of life(QoL)scores,as well as the incidence of cardiovascular death and hospitalization for heart failure.RESULTS At 24 months,dapagliflozin significantly reduced serum uric acid levels by 1.2 mg/dL(71μmol/L)compared with placebo(95%CI:-1.5 to-0.9;P<0.001).Dapagliflozin also significantly improved LVEF by 3.5%(95%CI:2.1-4.9;P<0.001),NT-proBNP by 25%(95%CI:18-32;P<0.001),and QoL scores by 10 points(95%CI:7-13;P<0.001)and reduced the risk of cardiovascular death and hospitalization for heart failure by 35%(95%CI:15–50;P=0.002)compared with the placebo.Adverse events were similar between the two groups,except for a higher rate of genital infections in the dapagliflozin group(10%vs 2%,P=0.01).CONCLUSION Dapagliflozin significantly lowered serum uric acid levels and improved the clinical outcomes in patients with CHF and hyperuricemia.Therefore,dapagliflozin may be a useful therapeutic option for this high-risk population.展开更多
Objective:To investigate and analyze the annual physical examination results of retired employees from a unit in the civil aviation system,focusing on blood lipids,blood glucose,blood uric acid,and blood routine resul...Objective:To investigate and analyze the annual physical examination results of retired employees from a unit in the civil aviation system,focusing on blood lipids,blood glucose,blood uric acid,and blood routine results.The study aims to provide relevant references for formulating reasonable disease management measures for preventing and controlling hyperlipidemia,hyperuricemia,and other conditions in retired employees.Methods:The examination results of 231 participants were collected and analyzed.The participants were divided into four groups based on age:middle-aged group,young-old group,middle-old group,and old-old group.The blood test results were compared across these groups,and an assessment of atherosclerotic cardiovascular disease(ASCVD)risk levels was completed in conjunction with medical history.Blood test results were also compared by gender.Results:There were no significant statistical differences in blood test results when grouped by age.However,the prevalence of hyperuricemia was higher in males than in females,while the prevalence of hypercholesterolemia was higher in females than in males.The LDL-C target achievement rate was lower in the moderate-and-high-risk group as well as the very high-risk group as defined by ASCVD risk levels.Conclusion:Management of hyperuricemia and hyperlipidemia in retired employees(elderly patients)should be strengthened to reduce the risk of ASCVD events and alleviate the potential medical burden associated with disease progression.展开更多
Objective:To develop the missing link between hyperuricemia and hypertension.Methods:The study was conducted in Department of Biochemistry in collaboration with Nephrology Unit of Internal Medicine Department.Hyperten...Objective:To develop the missing link between hyperuricemia and hypertension.Methods:The study was conducted in Department of Biochemistry in collaboration with Nephrology Unit of Internal Medicine Department.Hypertension was defined according to blood pressure readings by definitions of the Seventh Report of the Joint National Committee.Totally 205newly diagnosed and untreated essential hypertensive cases and age-sex matched nonnotensive controls were enrolled in the study.The potential confounding factors of hyperuricemia and hypertension in both cases and controls were controlled.Uric acid levels in all participants were analyzed.Results:Renal function between newly diagnosed hypertensive cases and nonnotensive healthy controls were adjusted.The mean serum uric acid observed in newly diagnosed hypertensive cases and in nonnotensive healthy controls were(290.05±87.03)μmol/L and(245.24±09.38)μmol/L respectively.A total of 59(28.8%)participants of cases and 28(13.7%)participants of controls had hyperuricemia(odds ratio 2.555(95%CI:1.549-4.213),P<0.00l).Conclusions:The mean serum uric acid leveb and number of hyperuricemic subjects were found to be significantly higher in cases when compared to controls.展开更多
Objective To examine the association between serum uric acid levels and cardiovascular disease risk among individuals without diabetes.Methods We investigated the association between serum uric acid levels and the ris...Objective To examine the association between serum uric acid levels and cardiovascular disease risk among individuals without diabetes.Methods We investigated the association between serum uric acid levels and the risk of prevalent cardiometabolic diseases, 10-year Framingham risk for coronary heart disease, and 10-year risk for atherosclerotic cardiovascular diseases (ASCVD) among 8,252 participants aged 〉 40 years without diabetes from Jiading district, Shanghai, China.Results Body mass index, waist circumference, blood glucose, glycated hemoglobin, blood pressure, and serum lipids increased progressively across the sex-specific quartiles of uric acid (all P trend 〈 0.05). Compared with individuals in the lowest quartile, those in the higher quartiles had a significantly higher prevalence of obesity, hypertension, and dyslipidemia (all P trend 〈 0.05). A fully adjusted logistic regression analysis revealed that individuals in the highest quartile had an increased risk of predicted cardiovascular disease compared with those in the lowest quartile of uric acid. The multivariate adjusted odds ratios (ORs) [95% confidence intervals (C/s)] for the highest quartiles for high Framingham risk were 3.00 (2.00-4.50) in men and 2.95 (1.08-8.43) in women. The multivariate adjusted ORs (95% C/s) for the highest quartile for high ASCVD risk were 1.93 [1.17-3.17) in men and 4.53 (2.57-7.98) in women.Conclusion Serum uric acid level is associated with an increased risk of prevalent obesity, hypertension, dystipidemia, 10-year Framingham risk for coronary heart disease, and lO-year risk for ASCVD among Chinese adults without diabetes.展开更多
Objective To determine whether elevated serum uric acid(UA)levels are associated with type 2 diabetes diagnosed using Hb A1 c levels among Chinese adults.Methods We conducted two population-based cross-sectional studi...Objective To determine whether elevated serum uric acid(UA)levels are associated with type 2 diabetes diagnosed using Hb A1 c levels among Chinese adults.Methods We conducted two population-based cross-sectional studies in Qingdao in China in 2006 and 2009.A total of 6894(39.4% men)subjects aged 35-74 years were included in the data analysis.Newly diagnosed diabetes was defined as Hb A1 c level of ≥6.5%,and prediabetes was classified as Hb A1 c level between 5.7% and 6.4% according to the International Diabetes Federation criteria.Multivariate logistic regression was employed to assess the association between UA and prevalence of type 2 diabetes defined using Glycated hemoglobin A1c(Hb A1 c levels.Results Subjects with prediabetes had higher UA levels than those with normal glucose tolerance,newly diagnosed diabetes,and known diabetes,with corresponding values of 325.1(82.5)μmol/L,310.9(84.2)μmol/L,291.3(81.7)μmol/L,305.2(83.6)μmol/L,respectively(P<0.001 for all comparisons).Binary logistic regression analysis showed that UA was a possible predictor for the prevalence of type 2 diabetes diagnosed using Hb A1 c levels,and the second quartile of UA levels had a higher odds ratio(OR:4.088;95% CI:2.900-5.765)for Hb A1 c than the other quartiles after adjusting for age,body mass index,sex,marital status,education,income,alcohol consumption,smoking,and cardiometabolic parameters.Conclusion Serum UA is significantly associated with type 2 diabetes diagnosed using Hb A1 c levels,independent of other cardiometabolic parameters.展开更多
Background Many epidemiological studies analyze the relationship between hyperuricemia and cardiovascular outcomes. This observational prospective study investigates the association of serum uric acid (SUA) levels w...Background Many epidemiological studies analyze the relationship between hyperuricemia and cardiovascular outcomes. This observational prospective study investigates the association of serum uric acid (SUA) levels with adverse cardiovascular events and deaths in an elderly population affected by advanced atherosclerosis. Methods Two hundred and seventy six elderly patients affected by advanced atherosclerosis (217 males and 59 females; aged 71.2 ±7.8 years) were included. All patients were assessed for history of cardiovascular disease, cancer, obesity and traditional risk factors. Patients were followed for approximately 31 ±11 months. Major events were recorded during follow-up, defined as myocardial infarction, cerebral isehemia, myocardial and/or peripheral revascularization and death. Results Mean SUA level was 5.47 ±1.43 mg/dL; then we further divided the population in two groups, according to the median value (5.36 mg/dL). During a median follow up of 31 months (5 to 49 months), 66 cardiovascular events, 9 fatal cardiovascular events and 14 cancer-related deaths have occurred. The patients with increased SUA level presented a higher significant incidence of total cardiovascular events (HR: 1.867, P = 0.014, 95% CI: 1.134-3.074), The same patients showed a significant increased risk of cancer-related death (HR: 4.335, P = 0.025, 95% CI: 1.204-15.606). Conclusions Increased SUA levels are independently and significantly associated with risk of cardiovascular events and cancer related death in a population of mainly elderly patients affected by peripheral vasculopathy.展开更多
Uric acid is the end product of purine catabolism and its plasma levels are maintained below its maximum solubility in water(6–7 mg/dl).The plasma levels are tightly regulated as the balance between the rate of produ...Uric acid is the end product of purine catabolism and its plasma levels are maintained below its maximum solubility in water(6–7 mg/dl).The plasma levels are tightly regulated as the balance between the rate of production and the rate of excretion,the latter occurring in urine(kidney),bile(liver)and feces(intestinal tract).Reabsorption in kidney is also an important component of this process.Both excretion and reabsorption are mediated by specific transporters.Disruption of the balance between production and excretion leads to hyperuricemia,which increases the risk of uric acid crystallization as monosodium urate with subsequent deposition of the crystals in joints causing gouty arthritis.Loss-of-function mutations in the transporters that mediate uric acid excretion are associated with gout.The ATP-Binding Cassette exporter ABCG2 is important in uric acid excretion at all three sites:kidney(urine),liver(bile),and intestine(feces).Mutations in this transporter cause gout and these mutations occur at significant prevalence in general population.However,mutations that are most prevalent result only in partial loss of transport function.Therefore,if the expression of these partially defective transporters could be induced,the increased number of the transporter molecules would compensate for the mutation-associated decrease in transport function and hence increase uric acid excretion.As such,pharmacologic agents with ability to induce the expression of ABCG2 represent potentially a novel class of drugs for treatment of gouty arthritis.展开更多
Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase(XDH/XO) is ...Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase(XDH/XO) is rate-limiting enzyme of uric acid generation, and allopurinol was developed as a uric acid(UA) generation inhibitor in the 1950 s and has been routinely used for gout prevention since then. Serum UA levels are an important risk factor of disease progression for various diseases, including those related to lifestyle. Recently, other UA generation inhibitors such as febuxostat and topiroxostat were launched. The emergence of these novel medications has promoted new research in the field. Lifestyle-related diseases, such as metabolic syndrome or type 2 diabetes mellitus, often have a common pathological foundation. As such, hyperuricemia is often present among these patients. Many in vitro and animal studies have implicated inflammation and oxidative stress in UA metabolism and vascular injury because XDH/XO act as one of the major source of reactive oxygen species Many studies on UA levels and associated diseases implicate involvement of UA generation in disease onset and/or progression. Interventional studies for UA generation, not UA excretion revealed XDH/XO can be the therapeutic target forvascular injury and renal dysfunction. In this review, the relationship between UA metabolism and diabetic complications is highlighted.展开更多
Using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification for acute ischemic stroke, 371 patients with either acute large-artery atherosclerosis or small-artery oc-clusion cerebral infarction wer...Using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification for acute ischemic stroke, 371 patients with either acute large-artery atherosclerosis or small-artery oc-clusion cerebral infarction were recruited to investigate the potential impact of elevated serum uric acid on cerebrovascular disorders. The results showed that patients who have suffered from large-artery atherosclerosis, relative to small-artery occlusion patients, were characterized by elevated serum uric acid but reduced high-density lipoprotein cholesterol and triglyceride levels. Logistic regression showed that elevated uric acid and lower triglyceride levels were the main risk factors for patients with large-artery atherosclerosis. The findings of this study suggest that hyperuricemia may be a risk factor for stroke.展开更多
The electrochemical behavior of vitamin C(ascorbic acid or AA) is investigated on the surface of a carbon-paste electrode modified with TiO2 nanoparticles and 2,2'-(1,2 butanediylbis(nitriloethylidyne))-bis-hyd...The electrochemical behavior of vitamin C(ascorbic acid or AA) is investigated on the surface of a carbon-paste electrode modified with TiO2 nanoparticles and 2,2'-(1,2 butanediylbis(nitriloethylidyne))-bis-hydroquinone(BBNBH).The prepared modified electrode showed an efficient catalytic role in the electrochemical oxidation of AA,leading to remarkable decrease in oxidation overpotential and enhancement of the kinetics of the electrode reaction.This modified electrode exhibits well-separated oxidation peaks for AA and uric acid(UA).The modified electrode is successfully applied for the accurate determination of AA in pharmaceutical preparations.展开更多
A patented kinetic uricase method was evaluated for serum uric acid assay. Initial absorbance of the reaction mixture before uricase action (A0) was obtained by correcting the absorbance at 293 nm measured before th...A patented kinetic uricase method was evaluated for serum uric acid assay. Initial absorbance of the reaction mixture before uricase action (A0) was obtained by correcting the absorbance at 293 nm measured before the addition of uricase solution, and background absorbance (Ab) was predicted by an integrated method. Uric acid concentration in reaction solution was calculated from AA, the difference between A0 and Ab, using the absorptivity preset for uric acid. This kinetic uricase method exhibited CV〈4.3% and recovery of 100%. Lipids, bilirubin, hemoglobin, ascorbic acid, reduced glutathione and xanthine 〈0.32 mmol/L in serum had no significant effects. △A linearly responded to 1.2 to 37.5 μmol/L uric acid in reaction solution containing 15 μl serum. The slope of linear response was consistent with the absorptivity preset for uric acid while the intercept was consistent with that for serum alone. Uric acid concentrations in clinic sera by different uricase methods positively correlated to each other. By Bland-Altman analysis, this kinetic uricase method accorded with that by quantifying the total change of UV absorbance on the completion of uricase reaction. These results demonstrated that this kinetic uricase method is reliable for serum uric acid assay with enhanced resistance to both xanthine and other common errors, wider range of linear response and much lower cost.展开更多
We read the article entitled Serum uric' acid as a prognostic marker in the setting of advanced vascular disease: a prospective study in the elderly by Stolfo, et al. with great interest. The authors evaluated the a...We read the article entitled Serum uric' acid as a prognostic marker in the setting of advanced vascular disease: a prospective study in the elderly by Stolfo, et al. with great interest. The authors evaluated the association of serum uric acid (SUA) levels with adverse cardiovascular events and deaths in an elderly population affected by advanced atherosclerosis. They founded meaningful association between SUA levels and of cardiovascular events and cancer related death. We believe that these findings will lead for further studies on uric acid.展开更多
Background Hyperuricemia is frequently present in patients with heart failure. Many pathological conditions, such as tissue ischemia, renal function impairment, cardiac function impairment, metabolic syndrome, and inf...Background Hyperuricemia is frequently present in patients with heart failure. Many pathological conditions, such as tissue ischemia, renal function impairment, cardiac function impairment, metabolic syndrome, and inflammatory status, may impact uric acid (UA) metabolism. This study was to assess their potential relations to UA metabolism in heart failure. Methods We retrospectively assessed clinical charac- teristics, echocardiological, renal, metabolic and inflammatory variables selected on the basis of previous evidence of their involvement in cardiovascular diseases and UA metabolism in a large cohort of randomly selected adults with congestive heart failure (n = 553). By clustering of indices, those variables were explored using factor analysis. Results In factor analysis, serum uric acid (SUA) formed part of a principal cluster of renal functional variables which included serum creatinine (SCr) and blood urea nitrogen (BUN). Univariate correlation coefficients between variables of patients with congestive heart failure showed that the strongest correlations for SUA were with BUN (r = 0.48, P 〈 0.001) and SCr (r = 0.47, P 〈 0.001). Conclusions There was an inverse relationship between SUA levels and measures of renal function in patients with congestive heart failure. The strong correlation between SUA and SCr and BUN levels suggests that elevated SUA concentrations reflect an impairment of renal function in heart failure.展开更多
OBJECTIVE Eurycoma longifolia is a tropical medicinal plant belonging to Simaroubaceae distributed in South East Asia.The aim of this study is to explore the effect and mechanism of E.longifolia stem 70%ethanol extrac...OBJECTIVE Eurycoma longifolia is a tropical medicinal plant belonging to Simaroubaceae distributed in South East Asia.The aim of this study is to explore the effect and mechanism of E.longifolia stem 70%ethanol extract(EL)and its active com⁃poundson uric acid excretion.METHODS Potassium oxonate(PO)induced hyperuricemia rats and adenine-PO induced hyperuricemia mouse model were used to evaluate the effects of EL.Ultra Performance Liquid Chromatography was used to determine the levels of plasma or serum uric acid and creatinine.Hematoxylin-eosin staining was applied to observe kidney pathological changes,Western blot⁃ting was applied to detect protein expression levels of uric acid transporters.Effects of constituents on urate uptake were tested in hU⁃RAT1-expressing HEK293T cells.RESULTS EL significantly reduced serum and plasma uric acid levels at dosages of 100,200 and 400 mg·kg^-1 in hyperuricemia rats and mice,and increased the clearance rate of uric acid and creatinine,improved therenal pathological injury.The protein expression levels of urate reabsorption transporter 1(URAT1)and glucose transporter 9 were down-regulated while sodium-dependent phosphate transporter 1 and ATP-binding cassette transporter G2 were up-regulated in the kidney after EL treat⁃ment.The diterpenes(50μmol·L^-1)isolated from EL showed inhibitory effects on urate uptake in hURAT1-expressing HEK293T cells,and the effect of eurycomanol was further confirmed in vivo.CONCLUSION EL significantly reduced blood uric acid levels and prevented pathological changes of kidney in PO induced hyperuricemia animal model,improved renal urate transports.We partly clarified the mechanism was related to suppressing effect of URAT1 by diterpene in EL.This study is the first to demonstrate that EL plays a role in hyperuricemia by promoting renal uric acid excretion.展开更多
Elevated uric acid causes direct injury to pancreatic β-cells. In this study, we examined the effects of luteolin, an important antioxidant, on uric acid-induced β-cell dysfunction. We first evaluated the effect of ...Elevated uric acid causes direct injury to pancreatic β-cells. In this study, we examined the effects of luteolin, an important antioxidant, on uric acid-induced β-cell dysfunction. We first evaluated the effect of luteolin on nitric oxide (NO) formation in uric acid-stimulated Min6 cells using the Griess method. Next, we performed transient transfection and reporter assays to measure transcriptional activity of nuclear factor (NF)-κB. Western blotting assays were also performed to assess the effect of luteolin on the expression of MafA and inducible NO synthase (iNOS) in uric acid-treated cells. Finally, we evaluated the effect of luteolin on uric acidinduced inhibition of glucose-stimulated insulin secretion (GSIS) in Min6 cells and freshly isolated mouse pancreatic islets. We found that luteolin significantly inhibited uric acid-induced NO production, which was well correlated with reduced expression of iNOS mRNA and protein. Furthermore, decreased activity of NF-κB was implicated in inhibition by luteolin of increased iNOS expression induced by uric acid. Besides, luteolin significantly increased MafA expression in Min6 cells exposed to uric acid, which was reversed by overexpression of iNOS. Moreover, luteolin prevented uric acidinduced inhibition of GSIS in both Min6 cells and mouse islets. In conclusion, luteolin protects pancreatic β-cells from uric acid-induced dysfunction and may confer benefit on the protection of pancreatic β-cells in hyperuricemiaassociated diabetes.展开更多
A novel covalently modified glassy carbon electrode with β-cyclodextrin was prepared via electropolymerization technique for the simultaneous determination of uric acid(UA),xanthine(XA),hypoxanthine(HX) and dop...A novel covalently modified glassy carbon electrode with β-cyclodextrin was prepared via electropolymerization technique for the simultaneous determination of uric acid(UA),xanthine(XA),hypoxanthine(HX) and dopamine(DA).This new electrode presented an excellent electrocatalytic activity towards the oxidation of UA,XA,HX and DA by cyclic voltammetry(CV) method.The oxidation peaks of the four compounds were well defined and had the enhanced peak currents.The separation potentials of the oxidation peaks for DA-UA,UA-XA and XA-HX were 150,390 and 360 mV in CV,respectively.By means of differential pulse voltammetry(DPV) method,the calibration curves in the ranges of 10―225,5―105,10―170 and 5―150 μmol/L were obtained for UA,XA,HX and DA,respectively.The lowest detection limits(S/N=3) were 5,1.25,5 and 1.5 μmol/L for UA,XA,HX and DA,respectively.The practical application of the modified electrode was demonstrated by the determination of DA in hydrochloride injection and UA,XA,HX in human urine samples.展开更多
Uric acid(UA)detection is essential in diagnosis of arthritis,preeclampsia,renal disorder,and cardiovascular diseases,but it is very challenging to realize the required wide detection range and low detection limit.We ...Uric acid(UA)detection is essential in diagnosis of arthritis,preeclampsia,renal disorder,and cardiovascular diseases,but it is very challenging to realize the required wide detection range and low detection limit.We present here a single-atom catalyst consisting of Co(Ⅱ)atoms coordinated by an average of 3.4 N atoms on an N-doped graphene matrix(A-Co-NG)to build an electrochemical biomimetic sensor for UA detection.The A-Co-NG sensor achieves a wide detection range over 0.4-41,950μM and an extremely low detection limit of 33.3±0.024 nM,which are much better than previously reported sensors based on various nanostructured materials.Besides,the A-Co-NG sensor also demonstrates its accurate serum diagnosis for UA for its practical application.Combination of experimental and theoretical calculation discovers that the catalytic process of the A-Co-NG toward UA starts from the oxidation of Co species to form a Co^3+-OH-UA*,followed by the generation of Co^3+-OH+^*UA_H,eventually leading to N-H bond dissociation for the formation of oxidized UA molecule and reduction of oxidized Co^3+to Co^2+for the regenerated A-Co-NG.This work provides a promising material to realize UA detection with wide detection range and low detection limit to meet the practical diagnosis requirements,and the proposed sensing mechanism sheds light on fundamental insights for guiding exploration of other biosensing processes.展开更多
BACKGROUND Uric acid is the end product of purine metabolism.Previous studies have found that serum uric acid(SUA)levels are associated with the total cancer risk.However,due to the dual effect of uric acid on cancer,...BACKGROUND Uric acid is the end product of purine metabolism.Previous studies have found that serum uric acid(SUA)levels are associated with the total cancer risk.However,due to the dual effect of uric acid on cancer,the relationship between the SUA levels and most specific-site cancer remains unclear.AIM To investigate the associations between the SUA levels and incidence of hepatobiliary-pancreatic cancer.METHODS In this prospective cohort study,444462 participants free of cancer from the UK Biobank were included.The SUA levels were measured at baseline,and the incidence of hepatobiliary-pancreatic cancer was determined by contacting the cancer registry.The hazard ratios(HRs)and 95%confidence intervals(CIs)between the SUA levels and hepatobiliary-pancreatic cancer were investigated using multiple adjusted Cox regression models adjusted for potential confounders.RESULTS In total,920 participants developed liver,gallbladder,biliary tract or pancreatic cancer during a median of 6.6 yrs of follow-up.We found that the HR of pancreatic cancer in the highest SUA group was 1.77(95%CI:1.29-2.42)compared with that in the lowest group.After stratifying by gender,we further found that SUA was associated with an increased risk of pancreatic cancer only among the females(highest quartile vs lowest quartile HR 2.04,95%CI:1.35-3.08).Among the males,the SUA levels were positively associated with the gallbladder cancer risk(highest quartile vs lowest quartile HR 3.09,95%CI:1.28-7.46),but a U-shaped association with the liver cancer risk was observed(P-nonlinear=0.03).CONCLUSION SUA is likely to have gender-specific effects on hepatobiliary-pancreatic cancer.High SUA levels are a risk factor for pancreatic cancer in females and gallbladder cancer in males.A U-shaped association with the liver cancer risk was identified.展开更多
Increase uric acid levels have been found in oxidative stress. Urate radicals do not react with oxygen to form another peroxy radical, thus increasing the efficacy of uric acid as an antioxidant. Therefore, this study...Increase uric acid levels have been found in oxidative stress. Urate radicals do not react with oxygen to form another peroxy radical, thus increasing the efficacy of uric acid as an antioxidant. Therefore, this study is designed to measure the level of uric acids and find out the relationship of uric acid with superoxide dismutase in induced hyperuricemic model. Forty male albino rats with an average weight of 180 ± 2 g were selected. The rats were grouped. The animals were fed on standard diet and given tap water ad libitum until treatment. Albino rats were divided into four groups. Group A(10)-control given only standard diet, group B(10) fed on 60% fructose with standard diet , group C(10) fed on fructose, standard diet and intraperitonially oxonic acid 250 mg/kg and group D (10) only on injection intraperotonially oxonic acid 250 mg/kg. At the end of study 10 mL of blood was drawn from heart of rats. Then blood was estimated for superoxide dismutase and uric acids done by kit methods randox-manual/Rx monza UA230/UA 233. Results: In Group C superoxide dismutase was found to be 32 % (244 mg/dL ± 2.23) more than control. In the same group the uric acid concentration was highly significantly correlated with control. Conclusion: The uric acid concentration increases when we take fructose up to 60% in our diet. It also increases superoxide dismutase concentration. More than this value may have inverse effect on the uric acid level and its role as an antioxidant may become inversed.展开更多
文摘BACKGROUND Coronary heart disease(CHD)and heart failure(HF)are the major causes of morbidity and mortality worldwide.Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis.However,conventional diagnostic methods such as electrocardiography,echocardiography,and cardiac biomarkers have certain limitations,such as low sensitivity,specificity,availability,and cost-effectiveness.Therefore,there is a need for simple,noninvasive,and reliable biomarkers to diagnose CHD and HF.AIM To investigate serum cystatin C(Cys-C),monocyte/high-density lipoprotein cholesterol ratio(MHR),and uric acid(UA)diagnostic values for CHD and HF.METHODS We enrolled 80 patients with suspected CHD or HF who were admitted to our hospital between July 2022 and July 2023.The patients were divided into CHD(n=20),HF(n=20),CHD+HF(n=20),and control groups(n=20).The serum levels of Cys-C,MHR,and UA were measured using immunonephelometry and an enzymatic method,respectively,and the diagnostic values for CHD and HF were evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Serum levels of Cys-C,MHR,and UA were significantly higher in the CHD,HF,and CHD+HF groups than those in the control group.The serum levels of Cys-C,MHR,and UA were significantly higher in the CHD+HF group than those in the CHD or HF group.The ROC curve analysis showed that serum Cys-C,MHR,and UA had good diagnostic performance for CHD and HF,with areas under the curve ranging from 0.78 to 0.93.The optimal cutoff values of serum Cys-C,MHR,and UA for diagnosing CHD,HF,and CHD+HF were 1.2 mg/L,0.9×10^(9),and 389μmol/L;1.4 mg/L,1.0×10^(9),and 449μmol/L;and 1.6 mg/L,1.1×10^(9),and 508μmol/L,respectively.CONCLUSION Serum Cys-C,MHR,and UA are useful biomarkers for diagnosing CHD and HF,and CHD+HF.These can provide information for decision-making and risk stratification in patients with CHD and HF.
基金Supported by General Medical Research Fund Project,No.TYYLKYJJ-2022-025.
文摘BACKGROUND Patients with chronic heart failure(CHF)frequently develop hyperuricemia,an elevated serum uric acid level,associated with adverse outcomes.Dapagliflozin,a sodium-glucose cotransporter-2 inhibitor,demonstrates reduction in cardiovascular mortality and hospitalization in patients with CHF and ejection fraction(HFrEF),irrespective of diabetes.However,dapagliflozin’s effect on the uric acid levels in patients with CHF and hyperuricemia remain unclear.AIM To investigate the effects of dapagliflozin on uric acid levels in CHF patients with hyperuricemia.METHODS We conducted a randomized,double-blind,placebo-controlled trial in 200 patients with CHF and hyperuricemia,with HFrEF and serum uric acid levels≥7 mg/dL(≥416μmol/L).The participants were randomly assigned to receive a daily dose of 10 mg dapagliflozin or placebo for 24 months.The primary endpoint was the change in serum uric acid level from baseline to 24 months.Secondary endpoints included changes in left ventricular ejection fraction(LVEF),Nterminal pro-B-type natriuretic peptide(NT-proBNP),and quality of life(QoL)scores,as well as the incidence of cardiovascular death and hospitalization for heart failure.RESULTS At 24 months,dapagliflozin significantly reduced serum uric acid levels by 1.2 mg/dL(71μmol/L)compared with placebo(95%CI:-1.5 to-0.9;P<0.001).Dapagliflozin also significantly improved LVEF by 3.5%(95%CI:2.1-4.9;P<0.001),NT-proBNP by 25%(95%CI:18-32;P<0.001),and QoL scores by 10 points(95%CI:7-13;P<0.001)and reduced the risk of cardiovascular death and hospitalization for heart failure by 35%(95%CI:15–50;P=0.002)compared with the placebo.Adverse events were similar between the two groups,except for a higher rate of genital infections in the dapagliflozin group(10%vs 2%,P=0.01).CONCLUSION Dapagliflozin significantly lowered serum uric acid levels and improved the clinical outcomes in patients with CHF and hyperuricemia.Therefore,dapagliflozin may be a useful therapeutic option for this high-risk population.
文摘Objective:To investigate and analyze the annual physical examination results of retired employees from a unit in the civil aviation system,focusing on blood lipids,blood glucose,blood uric acid,and blood routine results.The study aims to provide relevant references for formulating reasonable disease management measures for preventing and controlling hyperlipidemia,hyperuricemia,and other conditions in retired employees.Methods:The examination results of 231 participants were collected and analyzed.The participants were divided into four groups based on age:middle-aged group,young-old group,middle-old group,and old-old group.The blood test results were compared across these groups,and an assessment of atherosclerotic cardiovascular disease(ASCVD)risk levels was completed in conjunction with medical history.Blood test results were also compared by gender.Results:There were no significant statistical differences in blood test results when grouped by age.However,the prevalence of hyperuricemia was higher in males than in females,while the prevalence of hypercholesterolemia was higher in females than in males.The LDL-C target achievement rate was lower in the moderate-and-high-risk group as well as the very high-risk group as defined by ASCVD risk levels.Conclusion:Management of hyperuricemia and hyperlipidemia in retired employees(elderly patients)should be strengthened to reduce the risk of ASCVD events and alleviate the potential medical burden associated with disease progression.
基金Supported by Department of Biochemistry,Institute of Medicine.Tribhuvan University Teaching Hospital,Kathmandu.Nepal(Grant No.30-956/2013CEA)
文摘Objective:To develop the missing link between hyperuricemia and hypertension.Methods:The study was conducted in Department of Biochemistry in collaboration with Nephrology Unit of Internal Medicine Department.Hypertension was defined according to blood pressure readings by definitions of the Seventh Report of the Joint National Committee.Totally 205newly diagnosed and untreated essential hypertensive cases and age-sex matched nonnotensive controls were enrolled in the study.The potential confounding factors of hyperuricemia and hypertension in both cases and controls were controlled.Uric acid levels in all participants were analyzed.Results:Renal function between newly diagnosed hypertensive cases and nonnotensive healthy controls were adjusted.The mean serum uric acid observed in newly diagnosed hypertensive cases and in nonnotensive healthy controls were(290.05±87.03)μmol/L and(245.24±09.38)μmol/L respectively.A total of 59(28.8%)participants of cases and 28(13.7%)participants of controls had hyperuricemia(odds ratio 2.555(95%CI:1.549-4.213),P<0.00l).Conclusions:The mean serum uric acid leveb and number of hyperuricemic subjects were found to be significantly higher in cases when compared to controls.
基金supported by Grants from the Ministry of Science and Technology of the People’s Republic of China[2016YFC1305202,2016YFC1305601,2016YFC0901201,2016YFC1304904]the National Natural Science Foundation of China[81670795]
文摘Objective To examine the association between serum uric acid levels and cardiovascular disease risk among individuals without diabetes.Methods We investigated the association between serum uric acid levels and the risk of prevalent cardiometabolic diseases, 10-year Framingham risk for coronary heart disease, and 10-year risk for atherosclerotic cardiovascular diseases (ASCVD) among 8,252 participants aged 〉 40 years without diabetes from Jiading district, Shanghai, China.Results Body mass index, waist circumference, blood glucose, glycated hemoglobin, blood pressure, and serum lipids increased progressively across the sex-specific quartiles of uric acid (all P trend 〈 0.05). Compared with individuals in the lowest quartile, those in the higher quartiles had a significantly higher prevalence of obesity, hypertension, and dyslipidemia (all P trend 〈 0.05). A fully adjusted logistic regression analysis revealed that individuals in the highest quartile had an increased risk of predicted cardiovascular disease compared with those in the lowest quartile of uric acid. The multivariate adjusted odds ratios (ORs) [95% confidence intervals (C/s)] for the highest quartiles for high Framingham risk were 3.00 (2.00-4.50) in men and 2.95 (1.08-8.43) in women. The multivariate adjusted ORs (95% C/s) for the highest quartile for high ASCVD risk were 1.93 [1.17-3.17) in men and 4.53 (2.57-7.98) in women.Conclusion Serum uric acid level is associated with an increased risk of prevalent obesity, hypertension, dystipidemia, 10-year Framingham risk for coronary heart disease, and lO-year risk for ASCVD among Chinese adults without diabetes.
基金supported by grants from the World Diabetes Foundation(WDF05-108&07-308)Qingdao Outstanding Health Professional Development Fund and Qingdao Applied Basic Research Project(No.14-2-4-25-jch)
文摘Objective To determine whether elevated serum uric acid(UA)levels are associated with type 2 diabetes diagnosed using Hb A1 c levels among Chinese adults.Methods We conducted two population-based cross-sectional studies in Qingdao in China in 2006 and 2009.A total of 6894(39.4% men)subjects aged 35-74 years were included in the data analysis.Newly diagnosed diabetes was defined as Hb A1 c level of ≥6.5%,and prediabetes was classified as Hb A1 c level between 5.7% and 6.4% according to the International Diabetes Federation criteria.Multivariate logistic regression was employed to assess the association between UA and prevalence of type 2 diabetes defined using Glycated hemoglobin A1c(Hb A1 c levels.Results Subjects with prediabetes had higher UA levels than those with normal glucose tolerance,newly diagnosed diabetes,and known diabetes,with corresponding values of 325.1(82.5)μmol/L,310.9(84.2)μmol/L,291.3(81.7)μmol/L,305.2(83.6)μmol/L,respectively(P<0.001 for all comparisons).Binary logistic regression analysis showed that UA was a possible predictor for the prevalence of type 2 diabetes diagnosed using Hb A1 c levels,and the second quartile of UA levels had a higher odds ratio(OR:4.088;95% CI:2.900-5.765)for Hb A1 c than the other quartiles after adjusting for age,body mass index,sex,marital status,education,income,alcohol consumption,smoking,and cardiometabolic parameters.Conclusion Serum UA is significantly associated with type 2 diabetes diagnosed using Hb A1 c levels,independent of other cardiometabolic parameters.
文摘Background Many epidemiological studies analyze the relationship between hyperuricemia and cardiovascular outcomes. This observational prospective study investigates the association of serum uric acid (SUA) levels with adverse cardiovascular events and deaths in an elderly population affected by advanced atherosclerosis. Methods Two hundred and seventy six elderly patients affected by advanced atherosclerosis (217 males and 59 females; aged 71.2 ±7.8 years) were included. All patients were assessed for history of cardiovascular disease, cancer, obesity and traditional risk factors. Patients were followed for approximately 31 ±11 months. Major events were recorded during follow-up, defined as myocardial infarction, cerebral isehemia, myocardial and/or peripheral revascularization and death. Results Mean SUA level was 5.47 ±1.43 mg/dL; then we further divided the population in two groups, according to the median value (5.36 mg/dL). During a median follow up of 31 months (5 to 49 months), 66 cardiovascular events, 9 fatal cardiovascular events and 14 cancer-related deaths have occurred. The patients with increased SUA level presented a higher significant incidence of total cardiovascular events (HR: 1.867, P = 0.014, 95% CI: 1.134-3.074), The same patients showed a significant increased risk of cancer-related death (HR: 4.335, P = 0.025, 95% CI: 1.204-15.606). Conclusions Increased SUA levels are independently and significantly associated with risk of cardiovascular events and cancer related death in a population of mainly elderly patients affected by peripheral vasculopathy.
基金This work was supported by the National Institutes of Health grant R41 AR074854the Welch Endowed Chair in Biochemistry,Grant No.BI-0028,at Texas Tech University Health Sciences Center.
文摘Uric acid is the end product of purine catabolism and its plasma levels are maintained below its maximum solubility in water(6–7 mg/dl).The plasma levels are tightly regulated as the balance between the rate of production and the rate of excretion,the latter occurring in urine(kidney),bile(liver)and feces(intestinal tract).Reabsorption in kidney is also an important component of this process.Both excretion and reabsorption are mediated by specific transporters.Disruption of the balance between production and excretion leads to hyperuricemia,which increases the risk of uric acid crystallization as monosodium urate with subsequent deposition of the crystals in joints causing gouty arthritis.Loss-of-function mutations in the transporters that mediate uric acid excretion are associated with gout.The ATP-Binding Cassette exporter ABCG2 is important in uric acid excretion at all three sites:kidney(urine),liver(bile),and intestine(feces).Mutations in this transporter cause gout and these mutations occur at significant prevalence in general population.However,mutations that are most prevalent result only in partial loss of transport function.Therefore,if the expression of these partially defective transporters could be induced,the increased number of the transporter molecules would compensate for the mutation-associated decrease in transport function and hence increase uric acid excretion.As such,pharmacologic agents with ability to induce the expression of ABCG2 represent potentially a novel class of drugs for treatment of gouty arthritis.
文摘Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase(XDH/XO) is rate-limiting enzyme of uric acid generation, and allopurinol was developed as a uric acid(UA) generation inhibitor in the 1950 s and has been routinely used for gout prevention since then. Serum UA levels are an important risk factor of disease progression for various diseases, including those related to lifestyle. Recently, other UA generation inhibitors such as febuxostat and topiroxostat were launched. The emergence of these novel medications has promoted new research in the field. Lifestyle-related diseases, such as metabolic syndrome or type 2 diabetes mellitus, often have a common pathological foundation. As such, hyperuricemia is often present among these patients. Many in vitro and animal studies have implicated inflammation and oxidative stress in UA metabolism and vascular injury because XDH/XO act as one of the major source of reactive oxygen species Many studies on UA levels and associated diseases implicate involvement of UA generation in disease onset and/or progression. Interventional studies for UA generation, not UA excretion revealed XDH/XO can be the therapeutic target forvascular injury and renal dysfunction. In this review, the relationship between UA metabolism and diabetic complications is highlighted.
基金the Natural Science Foundation of Guangdong Province, No. 10151130001000001, S2011010004708the Science and Technology Projects of Guangdong Province, No. 2010Y1-C191
文摘Using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification for acute ischemic stroke, 371 patients with either acute large-artery atherosclerosis or small-artery oc-clusion cerebral infarction were recruited to investigate the potential impact of elevated serum uric acid on cerebrovascular disorders. The results showed that patients who have suffered from large-artery atherosclerosis, relative to small-artery occlusion patients, were characterized by elevated serum uric acid but reduced high-density lipoprotein cholesterol and triglyceride levels. Logistic regression showed that elevated uric acid and lower triglyceride levels were the main risk factors for patients with large-artery atherosclerosis. The findings of this study suggest that hyperuricemia may be a risk factor for stroke.
文摘The electrochemical behavior of vitamin C(ascorbic acid or AA) is investigated on the surface of a carbon-paste electrode modified with TiO2 nanoparticles and 2,2'-(1,2 butanediylbis(nitriloethylidyne))-bis-hydroquinone(BBNBH).The prepared modified electrode showed an efficient catalytic role in the electrochemical oxidation of AA,leading to remarkable decrease in oxidation overpotential and enhancement of the kinetics of the electrode reaction.This modified electrode exhibits well-separated oxidation peaks for AA and uric acid(UA).The modified electrode is successfully applied for the accurate determination of AA in pharmaceutical preparations.
基金Project (No. 30200266) supported by the National Natural Science Foundation of China
文摘A patented kinetic uricase method was evaluated for serum uric acid assay. Initial absorbance of the reaction mixture before uricase action (A0) was obtained by correcting the absorbance at 293 nm measured before the addition of uricase solution, and background absorbance (Ab) was predicted by an integrated method. Uric acid concentration in reaction solution was calculated from AA, the difference between A0 and Ab, using the absorptivity preset for uric acid. This kinetic uricase method exhibited CV〈4.3% and recovery of 100%. Lipids, bilirubin, hemoglobin, ascorbic acid, reduced glutathione and xanthine 〈0.32 mmol/L in serum had no significant effects. △A linearly responded to 1.2 to 37.5 μmol/L uric acid in reaction solution containing 15 μl serum. The slope of linear response was consistent with the absorptivity preset for uric acid while the intercept was consistent with that for serum alone. Uric acid concentrations in clinic sera by different uricase methods positively correlated to each other. By Bland-Altman analysis, this kinetic uricase method accorded with that by quantifying the total change of UV absorbance on the completion of uricase reaction. These results demonstrated that this kinetic uricase method is reliable for serum uric acid assay with enhanced resistance to both xanthine and other common errors, wider range of linear response and much lower cost.
文摘We read the article entitled Serum uric' acid as a prognostic marker in the setting of advanced vascular disease: a prospective study in the elderly by Stolfo, et al. with great interest. The authors evaluated the association of serum uric acid (SUA) levels with adverse cardiovascular events and deaths in an elderly population affected by advanced atherosclerosis. They founded meaningful association between SUA levels and of cardiovascular events and cancer related death. We believe that these findings will lead for further studies on uric acid.
文摘Background Hyperuricemia is frequently present in patients with heart failure. Many pathological conditions, such as tissue ischemia, renal function impairment, cardiac function impairment, metabolic syndrome, and inflammatory status, may impact uric acid (UA) metabolism. This study was to assess their potential relations to UA metabolism in heart failure. Methods We retrospectively assessed clinical charac- teristics, echocardiological, renal, metabolic and inflammatory variables selected on the basis of previous evidence of their involvement in cardiovascular diseases and UA metabolism in a large cohort of randomly selected adults with congestive heart failure (n = 553). By clustering of indices, those variables were explored using factor analysis. Results In factor analysis, serum uric acid (SUA) formed part of a principal cluster of renal functional variables which included serum creatinine (SCr) and blood urea nitrogen (BUN). Univariate correlation coefficients between variables of patients with congestive heart failure showed that the strongest correlations for SUA were with BUN (r = 0.48, P 〈 0.001) and SCr (r = 0.47, P 〈 0.001). Conclusions There was an inverse relationship between SUA levels and measures of renal function in patients with congestive heart failure. The strong correlation between SUA and SCr and BUN levels suggests that elevated SUA concentrations reflect an impairment of renal function in heart failure.
文摘OBJECTIVE Eurycoma longifolia is a tropical medicinal plant belonging to Simaroubaceae distributed in South East Asia.The aim of this study is to explore the effect and mechanism of E.longifolia stem 70%ethanol extract(EL)and its active com⁃poundson uric acid excretion.METHODS Potassium oxonate(PO)induced hyperuricemia rats and adenine-PO induced hyperuricemia mouse model were used to evaluate the effects of EL.Ultra Performance Liquid Chromatography was used to determine the levels of plasma or serum uric acid and creatinine.Hematoxylin-eosin staining was applied to observe kidney pathological changes,Western blot⁃ting was applied to detect protein expression levels of uric acid transporters.Effects of constituents on urate uptake were tested in hU⁃RAT1-expressing HEK293T cells.RESULTS EL significantly reduced serum and plasma uric acid levels at dosages of 100,200 and 400 mg·kg^-1 in hyperuricemia rats and mice,and increased the clearance rate of uric acid and creatinine,improved therenal pathological injury.The protein expression levels of urate reabsorption transporter 1(URAT1)and glucose transporter 9 were down-regulated while sodium-dependent phosphate transporter 1 and ATP-binding cassette transporter G2 were up-regulated in the kidney after EL treat⁃ment.The diterpenes(50μmol·L^-1)isolated from EL showed inhibitory effects on urate uptake in hURAT1-expressing HEK293T cells,and the effect of eurycomanol was further confirmed in vivo.CONCLUSION EL significantly reduced blood uric acid levels and prevented pathological changes of kidney in PO induced hyperuricemia animal model,improved renal urate transports.We partly clarified the mechanism was related to suppressing effect of URAT1 by diterpene in EL.This study is the first to demonstrate that EL plays a role in hyperuricemia by promoting renal uric acid excretion.
基金supported by the National Basic Research Program ofChina(2011CB504000,Program 973)the National Natural ScienceFoundation of China(81070656,81171589)the Colleges andUniversities in Jiangsu Province Plans to Graduate Research andInnovation(No.CXZZ12_0562)and Grant(No.100011)from the HealthDepartment of Sichuan Province to D.W
文摘Elevated uric acid causes direct injury to pancreatic β-cells. In this study, we examined the effects of luteolin, an important antioxidant, on uric acid-induced β-cell dysfunction. We first evaluated the effect of luteolin on nitric oxide (NO) formation in uric acid-stimulated Min6 cells using the Griess method. Next, we performed transient transfection and reporter assays to measure transcriptional activity of nuclear factor (NF)-κB. Western blotting assays were also performed to assess the effect of luteolin on the expression of MafA and inducible NO synthase (iNOS) in uric acid-treated cells. Finally, we evaluated the effect of luteolin on uric acidinduced inhibition of glucose-stimulated insulin secretion (GSIS) in Min6 cells and freshly isolated mouse pancreatic islets. We found that luteolin significantly inhibited uric acid-induced NO production, which was well correlated with reduced expression of iNOS mRNA and protein. Furthermore, decreased activity of NF-κB was implicated in inhibition by luteolin of increased iNOS expression induced by uric acid. Besides, luteolin significantly increased MafA expression in Min6 cells exposed to uric acid, which was reversed by overexpression of iNOS. Moreover, luteolin prevented uric acidinduced inhibition of GSIS in both Min6 cells and mouse islets. In conclusion, luteolin protects pancreatic β-cells from uric acid-induced dysfunction and may confer benefit on the protection of pancreatic β-cells in hyperuricemiaassociated diabetes.
基金Supported by the Natural Science Foundation of Jilin Province,China(No.20090326)
文摘A novel covalently modified glassy carbon electrode with β-cyclodextrin was prepared via electropolymerization technique for the simultaneous determination of uric acid(UA),xanthine(XA),hypoxanthine(HX) and dopamine(DA).This new electrode presented an excellent electrocatalytic activity towards the oxidation of UA,XA,HX and DA by cyclic voltammetry(CV) method.The oxidation peaks of the four compounds were well defined and had the enhanced peak currents.The separation potentials of the oxidation peaks for DA-UA,UA-XA and XA-HX were 150,390 and 360 mV in CV,respectively.By means of differential pulse voltammetry(DPV) method,the calibration curves in the ranges of 10―225,5―105,10―170 and 5―150 μmol/L were obtained for UA,XA,HX and DA,respectively.The lowest detection limits(S/N=3) were 5,1.25,5 and 1.5 μmol/L for UA,XA,HX and DA,respectively.The practical application of the modified electrode was demonstrated by the determination of DA in hydrochloride injection and UA,XA,HX in human urine samples.
基金the National Natural Science Foundation of China(Nos.22075195,21705115,21972102,and 21775122)the Natural Science Foundation of Jiangsu Province of China(BK20170378)+1 种基金Jiangsu Specially Appointed Professor program,the Natural Science research Foundation of Jiangsu Higher Education Institutions(17KJB150036)the Jiangsu Laboratory for Biochemical Sensing and Biochip.Natural Science Foundation of Chongqing(cstc2018jcyjAX0693),China.
文摘Uric acid(UA)detection is essential in diagnosis of arthritis,preeclampsia,renal disorder,and cardiovascular diseases,but it is very challenging to realize the required wide detection range and low detection limit.We present here a single-atom catalyst consisting of Co(Ⅱ)atoms coordinated by an average of 3.4 N atoms on an N-doped graphene matrix(A-Co-NG)to build an electrochemical biomimetic sensor for UA detection.The A-Co-NG sensor achieves a wide detection range over 0.4-41,950μM and an extremely low detection limit of 33.3±0.024 nM,which are much better than previously reported sensors based on various nanostructured materials.Besides,the A-Co-NG sensor also demonstrates its accurate serum diagnosis for UA for its practical application.Combination of experimental and theoretical calculation discovers that the catalytic process of the A-Co-NG toward UA starts from the oxidation of Co species to form a Co^3+-OH-UA*,followed by the generation of Co^3+-OH+^*UA_H,eventually leading to N-H bond dissociation for the formation of oxidized UA molecule and reduction of oxidized Co^3+to Co^2+for the regenerated A-Co-NG.This work provides a promising material to realize UA detection with wide detection range and low detection limit to meet the practical diagnosis requirements,and the proposed sensing mechanism sheds light on fundamental insights for guiding exploration of other biosensing processes.
基金Supported by National Natural Science Foundation of China,No.81872036.
文摘BACKGROUND Uric acid is the end product of purine metabolism.Previous studies have found that serum uric acid(SUA)levels are associated with the total cancer risk.However,due to the dual effect of uric acid on cancer,the relationship between the SUA levels and most specific-site cancer remains unclear.AIM To investigate the associations between the SUA levels and incidence of hepatobiliary-pancreatic cancer.METHODS In this prospective cohort study,444462 participants free of cancer from the UK Biobank were included.The SUA levels were measured at baseline,and the incidence of hepatobiliary-pancreatic cancer was determined by contacting the cancer registry.The hazard ratios(HRs)and 95%confidence intervals(CIs)between the SUA levels and hepatobiliary-pancreatic cancer were investigated using multiple adjusted Cox regression models adjusted for potential confounders.RESULTS In total,920 participants developed liver,gallbladder,biliary tract or pancreatic cancer during a median of 6.6 yrs of follow-up.We found that the HR of pancreatic cancer in the highest SUA group was 1.77(95%CI:1.29-2.42)compared with that in the lowest group.After stratifying by gender,we further found that SUA was associated with an increased risk of pancreatic cancer only among the females(highest quartile vs lowest quartile HR 2.04,95%CI:1.35-3.08).Among the males,the SUA levels were positively associated with the gallbladder cancer risk(highest quartile vs lowest quartile HR 3.09,95%CI:1.28-7.46),but a U-shaped association with the liver cancer risk was observed(P-nonlinear=0.03).CONCLUSION SUA is likely to have gender-specific effects on hepatobiliary-pancreatic cancer.High SUA levels are a risk factor for pancreatic cancer in females and gallbladder cancer in males.A U-shaped association with the liver cancer risk was identified.
文摘Increase uric acid levels have been found in oxidative stress. Urate radicals do not react with oxygen to form another peroxy radical, thus increasing the efficacy of uric acid as an antioxidant. Therefore, this study is designed to measure the level of uric acids and find out the relationship of uric acid with superoxide dismutase in induced hyperuricemic model. Forty male albino rats with an average weight of 180 ± 2 g were selected. The rats were grouped. The animals were fed on standard diet and given tap water ad libitum until treatment. Albino rats were divided into four groups. Group A(10)-control given only standard diet, group B(10) fed on 60% fructose with standard diet , group C(10) fed on fructose, standard diet and intraperitonially oxonic acid 250 mg/kg and group D (10) only on injection intraperotonially oxonic acid 250 mg/kg. At the end of study 10 mL of blood was drawn from heart of rats. Then blood was estimated for superoxide dismutase and uric acids done by kit methods randox-manual/Rx monza UA230/UA 233. Results: In Group C superoxide dismutase was found to be 32 % (244 mg/dL ± 2.23) more than control. In the same group the uric acid concentration was highly significantly correlated with control. Conclusion: The uric acid concentration increases when we take fructose up to 60% in our diet. It also increases superoxide dismutase concentration. More than this value may have inverse effect on the uric acid level and its role as an antioxidant may become inversed.