Hyperuricemia is a metabolic disorder caused by abnormal purine metabolism,resulting in abnormally high serum uric acid.In this study,a novel Levilactobacillus brevis PDD-5 isolated from salty vegetables was verified ...Hyperuricemia is a metabolic disorder caused by abnormal purine metabolism,resulting in abnormally high serum uric acid.In this study,a novel Levilactobacillus brevis PDD-5 isolated from salty vegetables was verified with the function of alleviating hyperuricemia.The relevant effects of L.brevis PDD-5 in lowering uric acid were analyzed by in vitro and in vivo experiments.The results showed that the L.brevis PDD-5 has(68.86±15.46)%of inosine uptake capacity and(95.75±3.30)%of guanosine uptake capacity in vitro.Oral administration of L.brevis PDD-5 to hyperuricemia rats reduced uric acid,creatinine,and urea nitrogen in serum,as well as decreased inosine and guanosine levels in the intestinal contents of rats.Analysis of relevant markers in the kidney by ELISA kits revealed that L.brevis PDD-5 alleviated oxidative stress and inflammation.Moreover,the gene expression of uric acid transporter 1(URAT1)and glucose transporter 9(GLUT9)was down-regulated,and the gene expression of organic anion transporter 1(OAT1)was up-regulated after treatment with L.brevis PDD-5.Western blot analysis showed that L.brevis PDD-5 alleviated hyperuricemia-induced kidney injury through the NLRP3 pathway.The se findings suggest that L.brevis PDD-5 can lower uric acid,repair kidney damage,and also has the potential to prevent uric acid nephropathy.展开更多
This study aimed to evaluate the alleviating effect of Chimonanthus nitens Oliv.leaves flavonoids(CLF)on hyperuricemia induced by potassium oxonate in mice.The results showed that CLF lowered the serum levels of uric ...This study aimed to evaluate the alleviating effect of Chimonanthus nitens Oliv.leaves flavonoids(CLF)on hyperuricemia induced by potassium oxonate in mice.The results showed that CLF lowered the serum levels of uric acid(UA),creatinine and blood urea nitrogen,downregulated hepatic mRNA expressions of xanthine oxidase(XO),phosphate ribose pyrophosphate synthetase(PRPS)and adenosine deaminase(ADA)in hyperuricemia mice.In addition,CLF repaired renal injury by significantly down-regulating mRNA and protein expressions of renal UA reabsorption-related proteins and up-regulating the mRNA and protein expressions of UA secretory-related proteins.Finally,CLF inhibited UA synthesis and promoted UA excretion to alleviate hyperuricemia.Besides,CLF supplementation repaired the intestinal barrier function as demonstrated by significant increased mRNA levels of intestinal zonula occludens-1(ZO-1),Occludin,mucin 2(MUC2)and mucin 4(MUC4),as well as decreased mRNA levels of toll-like receptor 4(TLR4)and myeloid differentiation factor 88(MyD88)in mice.Further research showed that CLF treatment restored intestinal homeostasis mediated by improving the composition of gut microbiota and elevating the abundance of beneficial bacteria like Lactobacillus,Alistipes,Prevotellaceae_UCG-001 and Parasutterella.Overall,our findings revealed a novel function of CLF as a promising therapeutic candidate for the treatment of hyperuricemia.展开更多
Hyperuricemia is a critical threat to human health,and a high inosine diet can increase the prevalence of it.Lacticaseibacillus rhamnosus Fmb14 was isolated from traditional fermented Chinese yogurt,and its inosine de...Hyperuricemia is a critical threat to human health,and a high inosine diet can increase the prevalence of it.Lacticaseibacillus rhamnosus Fmb14 was isolated from traditional fermented Chinese yogurt,and its inosine degradation rate reached 36.3%at 109 CFU/mL for 24 h.LC-MS analysis revealed that high concentrations of inosine could activate compensatory metabolic pathways of L.rhamnosus Fmb14 to catalyse inosine as an energy source and produce intracellular folic acid and riboflavin.The contents of folic acid and riboflavin were 6.0 and 4.3 fold increased after inosine treatment in the cell-free extracts(CFE).L.rhamnosus Fmb14 CFE treatment ameliorates hyperuricemia through xanthine oxidase(XOD)inhibition and ATP-binding cassette subfamily G member 2(ABCG2)promotion,both of which are responsible for uric acid(UA)synthesis and secretion in HepG2 and Caco2 cells,respectively.The in vivo results showed that the serum UA level decreased from 236.28 to 149.28μmol/L after 8 weeks of oral administration of L.rhamnosus Fmb14 in inosine-induced hyperuricemia model mice.Our results revealed that L.rhamnosus Fmb14 has a potential as a biological therapeutic agent in hyperuricemia prevention.展开更多
Objective:To explore the pharmacodynamic and renal protective effects of Poriae cutis extract on hyperuricemia(HUA)mice.Methods:The active components from the Poriae cutis were extracted with Alcohol solvent and aqueo...Objective:To explore the pharmacodynamic and renal protective effects of Poriae cutis extract on hyperuricemia(HUA)mice.Methods:The active components from the Poriae cutis were extracted with Alcohol solvent and aqueous solvent,HUA mice were established by hypoxanthine with potassium oxonate.Totally70 male Kunming mice were randomly divided into normal,model(500 mg/kg hypoxanthine+250 mg/kg potassium oxonate),Poriae cutis ethanol(PCE)and water extract(PCW)with high and low dose(388 mg/kg and 97mg/kg),benzbromarone(BEN)groups(7.5 mg/kg),all mice were administered with corresponding medication for 16 d.After the last administration,collected the 24 h urine volume,the urine uric acid(UUA)and urine creatinine(UCr)were determined.The morphological changes of the left kidney were viewed and the pathological changes in right kidneys were observed by hematoxylin-eosin(HE)staining.The serum contents of uric acid(SUA),creatinine(SCr)and urea nitrogen(BUN)were measured.Uric acid excretion index include fractional uric acid excretion(FEUA)and uric acid clearance rate(CUr)were calculated.The contents of OAT1,URAT1,GLUT9,TNF-αand IL-6 in the kidney were detected by ELISA.Results:PCE and PCW could increase UUA,UCr,FEUA,CUr and OAT1(P<0.05,P<0.01),reduce SUA,SCr,BUN,URAT1,GLUT9,TNF-αand IL-6(P<0.05,P<0.01).The pathological and morphological changes of kidneys in HUA mice were improved and the effect is better than BEN.Conclusion:Poriae cutis extractscould lower uric acid and possessed a protective effect on the kidney of mice with HUA,which was achieved by promoting uric acid excretion,regulating the expression of uric acid transporters and reducing the level of inflammatory factors.展开更多
Objective:To explore the epidemiological characteristics of hyperuricemia(HUA)in the metabolic syndrome(MS)and its different components in the physical examination population.Methods:Subjects who underwent medical che...Objective:To explore the epidemiological characteristics of hyperuricemia(HUA)in the metabolic syndrome(MS)and its different components in the physical examination population.Methods:Subjects who underwent medical check-ups at a hospital health management center from June 2021 to March 2023 were included in the study.To analyze the prevalence of HUA in MS and its different components,further,stratify the study population by gender and assess the serum uric acid(SUA)levels and prevalence of HUA in people with different numbers of MS components and the combination of MS components with the highest prevalence of HUA in both sexes.Logistic regression was used to analyze the risk of HUA in people with different numbers of MS components.Result:A total of 66,520 individuals were enrolled in the study.SUA levels(t=-82.947,P<0.001)and HUA prevalence(χ^(2)=3421.632,P<0.001)were significantly higher in the MS group than in the Non-MS group.SUA levels and prevalence of HUA were significantly higher in abdominal obesity,hypertension,decreased HDL-C and evaluated TG than in normal subjects(P<0.001),while there were gender differences in SUA levels and HUA prevalence in diabetic patients,with significantly lower SUA levels and HUA prevalence in men with diabetes than in those with normal blood glucose,an opposite result in women.SUA levels and HUA prevalence gradually increased with the increasing number of MS components in women,whereas in men,such a trend was only observed in MS1-MS4.The combination of MS components with the highest prevalence of HUA was abdominal obesity+hypertension+decreased HDL-C+evaluated TG(54.35%)in men and abdominal obesity+hypertension+diabetes+decreased HDL-C+evaluated TG(41.46%)in women.Logistic regression analysis showed that after adjusting for gender,age and ethnicity,the risk of HUA increased with the number of MS components in women,while in men,the risk of HUA increased continuously from MS1-MS4.Further adjustment for BMI,elevated TC,elevated LDL-C,and coronary artery disease,the results remained consistent.Conclusion:MS and its components are risk factors for HUA in the physical examination population,with different combinations of MS components having different correlations with HUA,and the risk of developing HUA correlates with the number of abnormal MS components.展开更多
Objective:To evaluate the impact of hyperuricemia on the occurrence of contrast agentrelated acute kidney injury after percutaneous coronary intervention.Methods:Retrieve PubMed,Embase,Cochrane Library,Web of Science,...Objective:To evaluate the impact of hyperuricemia on the occurrence of contrast agentrelated acute kidney injury after percutaneous coronary intervention.Methods:Retrieve PubMed,Embase,Cochrane Library,Web of Science,CNKI,Wanfang,and VIP databases,and publish articles on the correlation between hyperuricemia and contrast agent-related acute kidney damage after percutaneous coronary intervention from the establishment of the database to August 162023.Two researchers independently conducted literature screening and data extraction to evaluate the bias risk of inclusion in the study,and conducted metaanalysis using Review Manager 5.4 software.Results:A total of 12 articles were included,including 11676 patients.The meta-analysis results showed that compared with patients without hyperuricemia,patients with hyperuricemia had a higher risk of developing PC-AKI,with an incidence rate of 22.3%.Hyperuricemia was a risk factor for the occurrence of PCAKI(OR=2.03,95%CI:1.58-2.61);Patients with hyperuricemia have a higher risk of death after PC-AKI,with a mortality rate of 7.5%.Hyperuricemia is a risk factor for early death in PC-AKI patients(OR=2.33,95%CI:1.81-3.00);The probability of CRRT treatment after PCAKI in patients with hyperuricemia is higher,at 3.14%.Hyperuricemia is an influencing factor for CRRT treatment in PC-AKI patients(OR=7,95%CI:2.83-17.30).Conclusion:Existing research evidence suggests that the presence of hyperuricemia is an independent risk factor for the occurrence of PC-AKI,and it significantly increases the hospital mortality rate and the risk of renal replacement therapy in PC-AKI patients.展开更多
Hyperuricemia(HUA)mainly occurs because of purine metabolism disorders.We recently proposed that limonin from Simiao pill may have therapeutic effects on nitric oxide synthase 3(NOS3)that is related to HUA.Concurrentl...Hyperuricemia(HUA)mainly occurs because of purine metabolism disorders.We recently proposed that limonin from Simiao pill may have therapeutic effects on nitric oxide synthase 3(NOS3)that is related to HUA.Concurrently,our previous work employed a new method,structure-based multi-ligand molecular modeling,to identify potential agents from a herbal formula that may produce synergistic effects and may have the potential to develop combination drugs.Therefore,we employed multi-ligand modeling to seek compounds with potential synergistic effects with limonin against NOS3.We obtained 403 multi-ligand docking results between 403 compounds and the limonin-NOS3 complex(average affinity–8.297 kcal/mol).Then we selected the top 10 highest binding affinity compounds for virtual pharmacokinetic and toxicity screening and we found that only obacunone passed all filters.We further subjected obacunone,bound to limonin and NOS3,to molecular dynamics simulations.We found that the NOS3-limonin-obacunone complex was more stable than the NOS3-limonin complex,based on the root mean square deviation of backbone Cαatoms and root mean square fluctuation,which suggests that synergistic effects may exist between limonin and obacunone.Further cell and animal experimental research is required to verify our results.展开更多
To investigate the possible targets and mechanisms of polyphenols in perilla in the treatment of hyperuricemia(HUA)Batman-TCM,TCMSP,PubMed,and CNKI databases were used to obtain the main components of perilla and comp...To investigate the possible targets and mechanisms of polyphenols in perilla in the treatment of hyperuricemia(HUA)Batman-TCM,TCMSP,PubMed,and CNKI databases were used to obtain the main components of perilla and component-related targets.HUA targets were collected through GeneCards and OMIM online platforms.The HUA target and the perilla component target were crossed to obtain a common target.Protein interaction networks were constructed using the STRING database,and the compound-target-pathway network was constructed by Cytoscape software.The GO and KEGG enrichment analysis was performed using the DAVID database.Molecular docking was used to verify the results.Thirteen potential active components,101 component targets,901 HUA-related targets,and 36 common targets were screened out.Through network topology analysis,core targets such as TP53,TNF,CASP3,and PPARG and active components such as luteolin,β-carotene,cyanidin,catechin,and linolenic acid ethyl ester were obtained.The topology analysis of the“compound-target-pathway”network showed that the polyphenolic compounds luteolin,cyanidin,and catechin were the main active components of the perilla in the treatment of HUA.This study showed that the treatment of HUA with perilla had the characteristics of a multi-component,multi-target,and multi-signal pathway,which provided a scientific basis for further study on the molecular mechanism of the treatment of HUA with the potential active components of perilla.展开更多
Objective:This paper aims to study the clinical characteristics of patients with different types of primary hyperuricemia(HUA).Methods:Using a retrospective research method,200 patients with primary HUA in the hospita...Objective:This paper aims to study the clinical characteristics of patients with different types of primary hyperuricemia(HUA).Methods:Using a retrospective research method,200 patients with primary HUA in the hospital from June 2020 to January 2023 were selected as the research objects.Patients were grouped according to the detection results of 24-hour urinary uric acid excretion(UUE)and fractional excretion of uric acid(FEUA)(renal insufficiency type,renal overload type,mixed type,and other types).The general information of patients in the four groups(gender,age,body mass index,living habits,etc.),underlying diseases(hypertension,diabetes),blood test results[uric acid(UA),creatinine(Cre)],urine test results(24-hour urine UA,24-hour urine Cre)were summarized and the differences between the groups were analyzed.Results:The 200 cases of HUA patients were divided into 54.00%with renal insufficiency type,38.50%with mixed type,6.00%with renal overload type,and 1.50%with other types.The age of patients with mixed HUA was younger than that of patients with other types,renal overload type,and renal insufficiency type,and the difference was statistically significant(P<0.05).The UA level of patients with other types of HUA was lower than that of patients with mixed type HUA,and there was statistical significance(P<0.05).The Cre level of patients with mixed type HUA was lower than that of patients with renal insufficiency type and renal overload type,and the difference was statistically significant(P<0.05).The 24-hour urinary UA level in patients with renal insufficiency type HUA was lower than that in patients with renal overload type and mixed type HUA,and the difference was statistically significant(P<0.05).The 24-hour urinary Cre level of patients with other types of HUA was lower than that of patients with renal overload type and mixed HUA,the difference was statistically significant(P<0.05).The estimated glomerular filtration rate(eGFR)level of patients with other types of HUA was lower than that of patients with mixed type HUA,and the difference was statistically significant(P<0.05).There was no significant difference in the proportions of hypertension,diabetes,coronary heart disease,and urinary calculi among patients with renal insufficiency type,renal overload type,mixed type,and other types of HUA(P>0.05).Conclusion:The primary HUA patients are mainly of renal insufficiency type,followed by mixed type.There are significant differences in the clinical characteristics of patients with different types of HUA.Among them,patients with other types of HUA are the oldest and have the lowest uric acid levels.Patients with mixed HUA had the best renal function but the highest 24-hour urine creatinine level.This study can be used as a basis for rational selection of urate-lowering drugs for different HUA patients.展开更多
This study aimed to test the effects of five single nucleotide polymorphisms within SLC2A9 on uric acid level in a special ethnic population,the Uygurs in Xinjiang,China.According to our inclusion and exclusion criter...This study aimed to test the effects of five single nucleotide polymorphisms within SLC2A9 on uric acid level in a special ethnic population,the Uygurs in Xinjiang,China.According to our inclusion and exclusion criteria,Uygur adults from Xinjiang constituted the study population.There were 1053 Uygur adults with hyperuricemia and 1373 normal Uygur adults who served as controls.Five single nucleotide polymorphisms within SLC2A9(rs938557,rs7679916,rs7349721,rsl3101785,and rs 13137343)were selected with the HapMap dataset and TaqMan assays.We found that,in normouricemia group,rs938557 was significantly correlated with uric acid(β=11.39±3.74,P=0.0024)adjusting for age,gender and BMI;rs7679916 and rsl3137343 were marginally associated with uric acid concentration(β=5.77±3.O9,P=0.0626;p=-5.99±3.08,P=0.0520).In the hyperuricemia group,no SNP was found to possibly influence uric acid concentration.None of these SNPs showed significant association with hyperuricemia after controlling for age,gender and BMI.There were significant or marginal correlations between certain single nucleotide polymorphisms in the SLC2A9 region and uric acid concentration in Uygur normouricemia samples.In turn,some of these single nucleotide polymorphisms in SLC2A9 may increase the risk of hyperuricemia.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
Hyperuricemia(HUA) is a common metabolic disease caused by increased formation or reduced excretion of uric acid. Although HUA does not cause direct damage to the body, it is closely related to the occurrence of vario...Hyperuricemia(HUA) is a common metabolic disease caused by increased formation or reduced excretion of uric acid. Although HUA does not cause direct damage to the body, it is closely related to the occurrence of various diseases, including gout,hypertension, diabetes mellitus, metabolic syndrome, and chronic kidney disease.展开更多
Objective The purpose of this study was to determine the serum uric acid levels and the prevalence of hyperuricemia among Chinese adults in 2015 and compare the differences between urban and rural areas,as well as the...Objective The purpose of this study was to determine the serum uric acid levels and the prevalence of hyperuricemia among Chinese adults in 2015 and compare the differences between urban and rural areas,as well as the differences between eastern,central,and western regions.Methods A national representative sample of 180,208 participants were included using a stratified,multistage,and random sampling method.The demographic characteristics and blood samples were collected to determine the serum uric acid levels and prevalence of hyperuricemia among subgroups using complicated sampling weight.A t-test or ANOVA was used for normally-distributed data.The Kruskal-Wallis rank test was used for skewed-distributed data.The Mantel-Haenszel chi-square test was used to compare the difference in categorical variables.Results The weighted mean uric acid level in Chinese adults was 310.4μmol/L(317.5μmol/L in urban areas and 302.9μmol/L in rural areas).The weighted average values of uric acid in eastern,central,and western China were 315.5μmol/L,303.5μmol/L,and 310.4μmol/L,respectively.The weighted prevalence of hyperuricemia in Chinese adults was 14.6%,with a prevalence of 16.5%in urban areas and12.5%in rural areas.The weighted prevalence of hyperuricemia in eastern,central,and western China was 16.0%,12.5%,and 14.8%,respectively.Conclusion The uric acid level in Chinese adults is relatively high.Effective actions are warranted to improve this metabolic abnormality.展开更多
The aim of the present study was to observe the protective effects of α-lipoic acid(ALA)on vascular injury in rats with hyperuricemia(HUA).The ALA treatment groups(10,30 and 90 mg/kg,respectively)were administered wi...The aim of the present study was to observe the protective effects of α-lipoic acid(ALA)on vascular injury in rats with hyperuricemia(HUA).The ALA treatment groups(10,30 and 90 mg/kg,respectively)were administered with ALA via gavage for 2 weeks.Subsequently,the levels of blood urea nitrogen(BUN),creatinine(CREA),uric acid(UA),total cholesterol(TC),high density lipoprotein-C(HDL-C)and low density lipoprotein-C(LDL-C)were measured;the activities of glutathione peroxidase(GSH-Px),catalase(CAT),malonaldehyde(MDA),superoxide dismutase(SOD)and xanthine oxidase(XOD)were also determined.The thoracic aorta of rats in each experimental group was observed under a light microscope;ultrastructural analysis was performed.SOD and CAT protein contents were investigated by Western blotting.The results revealed that:i)Compared with the model group,the levels of UA were decreased in the ALA groups and the levels of BUN,CREA,TC,and LDL-C decreased in the 30 and 90 mg/kg ALA groups(P<0.05);ii)compared with the model group,the activities of GSH-Px,SOD and XOD were increased and the levels of MDA were reduced in the 90 mg/kg ALA group (P<0.05);and iii)in the model and 10 mg/kg ALA groups,edema and shedding were observed in endothelial cells.Compared with the model and 10 mg/kg ALA groups,the 30 and 90 mg/kg ALA groups exhibited fewer swollen endothelial cells.In summary,the results of the present study indicated that HUA resulted in vascular oxidative stress injury and decreased the activity of antioxidative enzymes,which leads to endothelial cell damage and vascular lesions.ALA may serve as a therapeutic agent for the treatment of HUA-induced endothelial dysfunction.展开更多
Objective:Hyperuricemia is an excess of urate in blood.The kidneys play important parts in urate excretion,which involves handling reabsorption and secretion.A series of urate transporters is responsible for this proc...Objective:Hyperuricemia is an excess of urate in blood.The kidneys play important parts in urate excretion,which involves handling reabsorption and secretion.A series of urate transporters is responsible for this process:urate transporter (URAT)1,glucose transporter (GLUT)9,organic anion transporter (OAT)1 and OAT3.Excessive fructose intake may result in increased serum urate levels.Chicory (Cichorium intybus L.) has been used as an edible vegetable and traditional Chinese medicine.Studies have shown that chicory is a promising anti-hyperuricemia agent and we explored the mechanism of its uricosuric effect via a renal pathway.Methods:Hyperuricemia was induced in rats by administration of 10% fructose.The uricosuric effect was evaluated by determining the serum urate level.Renal excretory function was detected by the clearance rate of creatinine,clearance rate of uric acid and histology.The location and expression of URAT1,GLUT9,OAT1 and OAT3 their mRNA expression in kidneys were analyzed.Results:Chicory decreased serum levels of urate and creatinine significantly,and promoted the clearance of creatinine and urate,as well as improving renal pathologic changes due to hyperuricemia.Chicory inhibited expression of URAT1 and GLUT9 markedly in a dosedependent manner,but showed no influence on expression of OAT1 or OAT3.Conclusion:Chicory might be a promising anti-hyperuricemia agent.It can promote renal excretion of urate by inhibiting urate reabsorption,which may be related to downregulation of mRNA and protein expression of URAT1 and GLUT9.展开更多
Fibulin-1(FBLN-1),an elastin-associated extracellular matrix protein,has been found in blood and may play a role in the pathophysiological processes leading to cardiovascular disease(CVD).We aimed to investigate the r...Fibulin-1(FBLN-1),an elastin-associated extracellular matrix protein,has been found in blood and may play a role in the pathophysiological processes leading to cardiovascular disease(CVD).We aimed to investigate the relationship between fibulin-1 levels and the risk of CVD by evaluating vascular age derived from the Framingham Heart Study and brachial-ankle Pulse Wave Velocity(baPWV)in patients with asymptomatic hyperuricemia(AHU).In total,66 patients with AHU and 66 gender-and age-matched healthy individuals were enrolled.The plasma fibulin-1 levels were measured by immunochemistry.Patients with AHU presented significantly higher vascular age[median(interquartile range):54(22)vs.48(14)years,P=0.01]and baPWV[mean±SD:1373±223 vs.1291±177 cm/s,P=0.02]than the healthy subjects;however,no significant difference was observed in the plasma fibulin-1 level between the patients with AHU and healthy subjects[median(interquartile range):4018(3838)vs.3099(3405)ng/mL,P=0.31].A correlation between fibulin-1 levels and baPWV was observed only in patients with AHU(r=0.29,P=0.02);and there was also a suggestively statistically significant correlation between fibulin-1 levels and vascular age(r=0.22,P=0.08).However,these associations were rendered insignificant after adjustments for potential confounders.In healthy subjects,no correlation was observed between fibulin-1 levels and CVD risk.This study reveals that plasma fibulin-1 levels may reflect the CVD risk in patients with AHU,but the relationship is not robust.展开更多
Background: More and more chronic kidney disease (CKD) patients are accompanied with hyperuricaemia. As is known, hyperuricaemia is an independent hazard of both cardiovascular diseases (CVD) and chronic kidney diseas...Background: More and more chronic kidney disease (CKD) patients are accompanied with hyperuricaemia. As is known, hyperuricaemia is an independent hazard of both cardiovascular diseases (CVD) and chronic kidney diseases. We aim at identifying Single Nucleotide Polymorphism (SNP) difference of hURAT1 (rs7932775) and ABCG2 (rs3825016) on CKD patient with hyperuricemia and/or gout. Methods: All forty-two CKD patients were divided into two groups: hyperuricemia, and control group. 24 hours urine sample and serum were prepared for testing biochemistry parameters. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method is used to analyze hURAT1 and ABCG2 single nucleotide polymorphisms in different groups. Results: 17 patients have CT SNP of hURAT1 (rs7932775) and 13 patients have CT SNP of ABCG2 (rs3825016) in hyperuricemia group, while only 5 persons and 6 persons have the same mutations in control group respectively. 7 patients have CT SNP of both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group, while only 2 persons have the same mutations in control group. CT mutation rates of hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 60.7% (17/28) and 50% (13/28) respectively, higher than that of control group (35.7% (5/14) and 42.8% (6/14)). What is more, Double SNP mutations in both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 25% (7/28), higher than that of control group (14.2%, 2/14). Conclusion: There are higher mutation rates of CT SNP in hURAT1 (rs7932775) and/or ABCG2 (rs3825016) in hyperuricemia group. We can conclude that hyperuricemia is a high risk factor in progress of CKD, which is necessary to take measures of decreasing serum uric acid to delay CKD progress.展开更多
There are few data available on the prevalence of hyperuricemia among elderly and its possible association with metabolic syndrome (MetS) so the aim of this study was to assess prevalence of hyperuricemia among hospit...There are few data available on the prevalence of hyperuricemia among elderly and its possible association with metabolic syndrome (MetS) so the aim of this study was to assess prevalence of hyperuricemia among hospitalized elderly patients as well as to assess its association with MetS. Cross sectional data from 200 hospitalized elderly patients were analyzed and the results were as follows: the prevalence of hyperuricemia was 21.0% in elderly men and 15.1% in elderly women. Multivariate logistic regression analysis revealed that BMI ≥ 30 (p = 0.031, OR = 1.1), hypertension (p = 0.019, OR = 1.8), high triglycerides level (p = 0.018, OR = 2.9) and hyperuricemia (p = 0.023, OR = 3.7) were independently associated with MetS. The study concluded that the prevalence of hyperuricemia among hospitalized elderly patients was 21.0% in elderly men and 15.1% in elderly women. There was an independent association between hyperuricemia and metabolic syndrome.展开更多
Gout is a common of inflammatory arthritis and is caused by the deposition of monosodium urate(MSU)crystals as a result of hyperuricemia(HUA).Although HUA is considered to be the main risk factor for gout,only approxi...Gout is a common of inflammatory arthritis and is caused by the deposition of monosodium urate(MSU)crystals as a result of hyperuricemia(HUA).Although HUA is considered to be the main risk factor for gout,only approximately 10%of the individuals with HUA will eventually experience a gout attack.In this review,we first briefly introduce the development of gout and then summarize several possible reasons for its development.Genetic factors play a more prominent role in gout than in other diseases;functional mutations related to urate control and innate immunity components have been found to be associated with gout.Here,we list some of the most prominent genes involved in the pathogenesis of gout.In joints with MSU deposition,mature macrophages may uptake MSU crystals without causing inflammation,and this helps to maintain joints in an asymptomatic state.As an auxiliary inflammation pathway,the ATP-P2X7R-NLRP3 axis may contribute to the amplification of MSU-induced inflammation to affect the development of gout.Finally,this review summarizes the research progress on natural products that can be used in the treatment of HUA and gout.展开更多
<strong>Introduction:</strong> Uric acid is a product of purine metabolism and elevated serum concentration are very common in, and linked with hypertension and chronic kidney disease, conditions associate...<strong>Introduction:</strong> Uric acid is a product of purine metabolism and elevated serum concentration are very common in, and linked with hypertension and chronic kidney disease, conditions associated with heavy health burden and cardiovascular complications particularly in sub Sahara Africa. An assessment of factors relating hyperuricemia to hypertension and chronic kidney disease would therefore be necessary as way of mitigating the poor quality of life, morbidity and mortality associated with these diseases in low income nations. <strong>Methods:</strong> A single centre, descriptive comparative study in which the demographic, clinical and laboratory data of hypertensive and non-dialyzed chronic kidney disease (CKD) patients were analyzed. Serum biochemical parameters with uric acid, hematocrit and urine dip strip protein were assessed. Predictors of hyperuricemia were determined using multivariate analysis. <strong>Results:</strong> One hundred and thirty nine hypertensives and 69 CKD were studied. The mean age of the participants was 54.3 ± 11.7 years, hypertensives (52.9 ± 15.7 years) and CKD (57.3 ± 16.1 years). Both groups had more males, P = 0.8. Majority (78.3%) of the CKD cohorts had stage 4 or 5 (non-dialyzed) disease. The systolic and diastolic blood pressure, creatinine and uric acid were lower in hypertension than in CKD, P = 0.07, P = 0.05, P < 0.001 and P = 0.004 respectively. The hematocrit, albumin and GFR were higher in HTN than CKD, P < 0.001, P < 0.001 and P < 0.001 respectively. The prevalence of hyperuricemia was 56.2%. The mean uric acid was 505.9 ± 23.6 mmol/L, 382 7 ± 10.5 mmol/L for hypertensive and 755.9 ± 14.8 mmol/L for CKD, P < 0.001. The prevalence of systolic HTN, proteinuria, hypoalbuminemia and anemia were 51%, 75%, 46% and 59%, and were higher in males. Hyperuricemia was related to advancing age, proteinuria, elevated creatinine, hypoalbuminemia, anemia and hypertriglyceridemia. Proteinuria (OR—4.66, 95% CI—2.42 - 9.65), elevated creatinine (OR—3.12, 95% CI—2.40 - 6.92), hypoalbuminemia (OR—2.92, 95% CI—1.83 - 5.78) and anemia (OR—4.01, 95% CI—3.78 - 7.99) independently predicted hyperuricemia.<strong> Conclusion:</strong> Hyperuricemia is commoner in CKD than hypertension and was higher in males and positively correlated with the blood pressure, proteinuria and creatinine, but negatively related to hematocrit, albumin and glomerular filtration rate. Independent predictors of hyperuricemia were proteinuria, elevated creatinine, hypoalbuminemia and anemia. Measures are needed to prevent and treat hyperuricemia to reduce the health burden associated with hypertension and CKD.展开更多
基金the National Natural Science Foundation of China(31972048,32272339)the National Key R&D Program of China(2021YFD2100104)for financial support。
文摘Hyperuricemia is a metabolic disorder caused by abnormal purine metabolism,resulting in abnormally high serum uric acid.In this study,a novel Levilactobacillus brevis PDD-5 isolated from salty vegetables was verified with the function of alleviating hyperuricemia.The relevant effects of L.brevis PDD-5 in lowering uric acid were analyzed by in vitro and in vivo experiments.The results showed that the L.brevis PDD-5 has(68.86±15.46)%of inosine uptake capacity and(95.75±3.30)%of guanosine uptake capacity in vitro.Oral administration of L.brevis PDD-5 to hyperuricemia rats reduced uric acid,creatinine,and urea nitrogen in serum,as well as decreased inosine and guanosine levels in the intestinal contents of rats.Analysis of relevant markers in the kidney by ELISA kits revealed that L.brevis PDD-5 alleviated oxidative stress and inflammation.Moreover,the gene expression of uric acid transporter 1(URAT1)and glucose transporter 9(GLUT9)was down-regulated,and the gene expression of organic anion transporter 1(OAT1)was up-regulated after treatment with L.brevis PDD-5.Western blot analysis showed that L.brevis PDD-5 alleviated hyperuricemia-induced kidney injury through the NLRP3 pathway.The se findings suggest that L.brevis PDD-5 can lower uric acid,repair kidney damage,and also has the potential to prevent uric acid nephropathy.
基金the financial supports by National Natural Science Foundation of China (31560459)Major Discipline Academic and Technical Leaders Training Program of Jiangxi Province (20182BCB22003)+1 种基金the Earmarked Fund for Jiangxi Agriculture Research System (JXARS-13)the Graduate Innovative Special Fund Projects of Jiangxi Province, China (YC2021-S343)。
文摘This study aimed to evaluate the alleviating effect of Chimonanthus nitens Oliv.leaves flavonoids(CLF)on hyperuricemia induced by potassium oxonate in mice.The results showed that CLF lowered the serum levels of uric acid(UA),creatinine and blood urea nitrogen,downregulated hepatic mRNA expressions of xanthine oxidase(XO),phosphate ribose pyrophosphate synthetase(PRPS)and adenosine deaminase(ADA)in hyperuricemia mice.In addition,CLF repaired renal injury by significantly down-regulating mRNA and protein expressions of renal UA reabsorption-related proteins and up-regulating the mRNA and protein expressions of UA secretory-related proteins.Finally,CLF inhibited UA synthesis and promoted UA excretion to alleviate hyperuricemia.Besides,CLF supplementation repaired the intestinal barrier function as demonstrated by significant increased mRNA levels of intestinal zonula occludens-1(ZO-1),Occludin,mucin 2(MUC2)and mucin 4(MUC4),as well as decreased mRNA levels of toll-like receptor 4(TLR4)and myeloid differentiation factor 88(MyD88)in mice.Further research showed that CLF treatment restored intestinal homeostasis mediated by improving the composition of gut microbiota and elevating the abundance of beneficial bacteria like Lactobacillus,Alistipes,Prevotellaceae_UCG-001 and Parasutterella.Overall,our findings revealed a novel function of CLF as a promising therapeutic candidate for the treatment of hyperuricemia.
基金the National Natural Science Foundation of China(32072182).
文摘Hyperuricemia is a critical threat to human health,and a high inosine diet can increase the prevalence of it.Lacticaseibacillus rhamnosus Fmb14 was isolated from traditional fermented Chinese yogurt,and its inosine degradation rate reached 36.3%at 109 CFU/mL for 24 h.LC-MS analysis revealed that high concentrations of inosine could activate compensatory metabolic pathways of L.rhamnosus Fmb14 to catalyse inosine as an energy source and produce intracellular folic acid and riboflavin.The contents of folic acid and riboflavin were 6.0 and 4.3 fold increased after inosine treatment in the cell-free extracts(CFE).L.rhamnosus Fmb14 CFE treatment ameliorates hyperuricemia through xanthine oxidase(XOD)inhibition and ATP-binding cassette subfamily G member 2(ABCG2)promotion,both of which are responsible for uric acid(UA)synthesis and secretion in HepG2 and Caco2 cells,respectively.The in vivo results showed that the serum UA level decreased from 236.28 to 149.28μmol/L after 8 weeks of oral administration of L.rhamnosus Fmb14 in inosine-induced hyperuricemia model mice.Our results revealed that L.rhamnosus Fmb14 has a potential as a biological therapeutic agent in hyperuricemia prevention.
基金Anhui University Collaborative Project(GXXT-2019-043)Key Project of Anhui University Scientific Research Project(KJ2020A0608)。
文摘Objective:To explore the pharmacodynamic and renal protective effects of Poriae cutis extract on hyperuricemia(HUA)mice.Methods:The active components from the Poriae cutis were extracted with Alcohol solvent and aqueous solvent,HUA mice were established by hypoxanthine with potassium oxonate.Totally70 male Kunming mice were randomly divided into normal,model(500 mg/kg hypoxanthine+250 mg/kg potassium oxonate),Poriae cutis ethanol(PCE)and water extract(PCW)with high and low dose(388 mg/kg and 97mg/kg),benzbromarone(BEN)groups(7.5 mg/kg),all mice were administered with corresponding medication for 16 d.After the last administration,collected the 24 h urine volume,the urine uric acid(UUA)and urine creatinine(UCr)were determined.The morphological changes of the left kidney were viewed and the pathological changes in right kidneys were observed by hematoxylin-eosin(HE)staining.The serum contents of uric acid(SUA),creatinine(SCr)and urea nitrogen(BUN)were measured.Uric acid excretion index include fractional uric acid excretion(FEUA)and uric acid clearance rate(CUr)were calculated.The contents of OAT1,URAT1,GLUT9,TNF-αand IL-6 in the kidney were detected by ELISA.Results:PCE and PCW could increase UUA,UCr,FEUA,CUr and OAT1(P<0.05,P<0.01),reduce SUA,SCr,BUN,URAT1,GLUT9,TNF-αand IL-6(P<0.05,P<0.01).The pathological and morphological changes of kidneys in HUA mice were improved and the effect is better than BEN.Conclusion:Poriae cutis extractscould lower uric acid and possessed a protective effect on the kidney of mice with HUA,which was achieved by promoting uric acid excretion,regulating the expression of uric acid transporters and reducing the level of inflammatory factors.
基金Tianshan Talent Program Phase II Tier 2 Project (No.201720277)。
文摘Objective:To explore the epidemiological characteristics of hyperuricemia(HUA)in the metabolic syndrome(MS)and its different components in the physical examination population.Methods:Subjects who underwent medical check-ups at a hospital health management center from June 2021 to March 2023 were included in the study.To analyze the prevalence of HUA in MS and its different components,further,stratify the study population by gender and assess the serum uric acid(SUA)levels and prevalence of HUA in people with different numbers of MS components and the combination of MS components with the highest prevalence of HUA in both sexes.Logistic regression was used to analyze the risk of HUA in people with different numbers of MS components.Result:A total of 66,520 individuals were enrolled in the study.SUA levels(t=-82.947,P<0.001)and HUA prevalence(χ^(2)=3421.632,P<0.001)were significantly higher in the MS group than in the Non-MS group.SUA levels and prevalence of HUA were significantly higher in abdominal obesity,hypertension,decreased HDL-C and evaluated TG than in normal subjects(P<0.001),while there were gender differences in SUA levels and HUA prevalence in diabetic patients,with significantly lower SUA levels and HUA prevalence in men with diabetes than in those with normal blood glucose,an opposite result in women.SUA levels and HUA prevalence gradually increased with the increasing number of MS components in women,whereas in men,such a trend was only observed in MS1-MS4.The combination of MS components with the highest prevalence of HUA was abdominal obesity+hypertension+decreased HDL-C+evaluated TG(54.35%)in men and abdominal obesity+hypertension+diabetes+decreased HDL-C+evaluated TG(41.46%)in women.Logistic regression analysis showed that after adjusting for gender,age and ethnicity,the risk of HUA increased with the number of MS components in women,while in men,the risk of HUA increased continuously from MS1-MS4.Further adjustment for BMI,elevated TC,elevated LDL-C,and coronary artery disease,the results remained consistent.Conclusion:MS and its components are risk factors for HUA in the physical examination population,with different combinations of MS components having different correlations with HUA,and the risk of developing HUA correlates with the number of abnormal MS components.
基金Key Research and Development Program of the Ministry of Science and Technology(No.2018YFC1704304)。
文摘Objective:To evaluate the impact of hyperuricemia on the occurrence of contrast agentrelated acute kidney injury after percutaneous coronary intervention.Methods:Retrieve PubMed,Embase,Cochrane Library,Web of Science,CNKI,Wanfang,and VIP databases,and publish articles on the correlation between hyperuricemia and contrast agent-related acute kidney damage after percutaneous coronary intervention from the establishment of the database to August 162023.Two researchers independently conducted literature screening and data extraction to evaluate the bias risk of inclusion in the study,and conducted metaanalysis using Review Manager 5.4 software.Results:A total of 12 articles were included,including 11676 patients.The meta-analysis results showed that compared with patients without hyperuricemia,patients with hyperuricemia had a higher risk of developing PC-AKI,with an incidence rate of 22.3%.Hyperuricemia was a risk factor for the occurrence of PCAKI(OR=2.03,95%CI:1.58-2.61);Patients with hyperuricemia have a higher risk of death after PC-AKI,with a mortality rate of 7.5%.Hyperuricemia is a risk factor for early death in PC-AKI patients(OR=2.33,95%CI:1.81-3.00);The probability of CRRT treatment after PCAKI in patients with hyperuricemia is higher,at 3.14%.Hyperuricemia is an influencing factor for CRRT treatment in PC-AKI patients(OR=7,95%CI:2.83-17.30).Conclusion:Existing research evidence suggests that the presence of hyperuricemia is an independent risk factor for the occurrence of PC-AKI,and it significantly increases the hospital mortality rate and the risk of renal replacement therapy in PC-AKI patients.
基金This work was funded by the Key Project of National Natural Science Foundation of China[grant number 81830117]Joint Funds of National Natural Science Foundation of China[grant number U22A20365]+3 种基金National Natural Science Foundation of China[grant numbers 8220140209,82274499]Guangdong Basic and Applied Basic Research Foundation[grant number 2021A1515110082]China Postdoctoral Science Foundation[grant number 2022M711534]Science&Technical Plan of Guangzhou,Guangdong,China[grant number 201903010069].
文摘Hyperuricemia(HUA)mainly occurs because of purine metabolism disorders.We recently proposed that limonin from Simiao pill may have therapeutic effects on nitric oxide synthase 3(NOS3)that is related to HUA.Concurrently,our previous work employed a new method,structure-based multi-ligand molecular modeling,to identify potential agents from a herbal formula that may produce synergistic effects and may have the potential to develop combination drugs.Therefore,we employed multi-ligand modeling to seek compounds with potential synergistic effects with limonin against NOS3.We obtained 403 multi-ligand docking results between 403 compounds and the limonin-NOS3 complex(average affinity–8.297 kcal/mol).Then we selected the top 10 highest binding affinity compounds for virtual pharmacokinetic and toxicity screening and we found that only obacunone passed all filters.We further subjected obacunone,bound to limonin and NOS3,to molecular dynamics simulations.We found that the NOS3-limonin-obacunone complex was more stable than the NOS3-limonin complex,based on the root mean square deviation of backbone Cαatoms and root mean square fluctuation,which suggests that synergistic effects may exist between limonin and obacunone.Further cell and animal experimental research is required to verify our results.
文摘To investigate the possible targets and mechanisms of polyphenols in perilla in the treatment of hyperuricemia(HUA)Batman-TCM,TCMSP,PubMed,and CNKI databases were used to obtain the main components of perilla and component-related targets.HUA targets were collected through GeneCards and OMIM online platforms.The HUA target and the perilla component target were crossed to obtain a common target.Protein interaction networks were constructed using the STRING database,and the compound-target-pathway network was constructed by Cytoscape software.The GO and KEGG enrichment analysis was performed using the DAVID database.Molecular docking was used to verify the results.Thirteen potential active components,101 component targets,901 HUA-related targets,and 36 common targets were screened out.Through network topology analysis,core targets such as TP53,TNF,CASP3,and PPARG and active components such as luteolin,β-carotene,cyanidin,catechin,and linolenic acid ethyl ester were obtained.The topology analysis of the“compound-target-pathway”network showed that the polyphenolic compounds luteolin,cyanidin,and catechin were the main active components of the perilla in the treatment of HUA.This study showed that the treatment of HUA with perilla had the characteristics of a multi-component,multi-target,and multi-signal pathway,which provided a scientific basis for further study on the molecular mechanism of the treatment of HUA with the potential active components of perilla.
文摘Objective:This paper aims to study the clinical characteristics of patients with different types of primary hyperuricemia(HUA).Methods:Using a retrospective research method,200 patients with primary HUA in the hospital from June 2020 to January 2023 were selected as the research objects.Patients were grouped according to the detection results of 24-hour urinary uric acid excretion(UUE)and fractional excretion of uric acid(FEUA)(renal insufficiency type,renal overload type,mixed type,and other types).The general information of patients in the four groups(gender,age,body mass index,living habits,etc.),underlying diseases(hypertension,diabetes),blood test results[uric acid(UA),creatinine(Cre)],urine test results(24-hour urine UA,24-hour urine Cre)were summarized and the differences between the groups were analyzed.Results:The 200 cases of HUA patients were divided into 54.00%with renal insufficiency type,38.50%with mixed type,6.00%with renal overload type,and 1.50%with other types.The age of patients with mixed HUA was younger than that of patients with other types,renal overload type,and renal insufficiency type,and the difference was statistically significant(P<0.05).The UA level of patients with other types of HUA was lower than that of patients with mixed type HUA,and there was statistical significance(P<0.05).The Cre level of patients with mixed type HUA was lower than that of patients with renal insufficiency type and renal overload type,and the difference was statistically significant(P<0.05).The 24-hour urinary UA level in patients with renal insufficiency type HUA was lower than that in patients with renal overload type and mixed type HUA,and the difference was statistically significant(P<0.05).The 24-hour urinary Cre level of patients with other types of HUA was lower than that of patients with renal overload type and mixed HUA,the difference was statistically significant(P<0.05).The estimated glomerular filtration rate(eGFR)level of patients with other types of HUA was lower than that of patients with mixed type HUA,and the difference was statistically significant(P<0.05).There was no significant difference in the proportions of hypertension,diabetes,coronary heart disease,and urinary calculi among patients with renal insufficiency type,renal overload type,mixed type,and other types of HUA(P>0.05).Conclusion:The primary HUA patients are mainly of renal insufficiency type,followed by mixed type.There are significant differences in the clinical characteristics of patients with different types of HUA.Among them,patients with other types of HUA are the oldest and have the lowest uric acid levels.Patients with mixed HUA had the best renal function but the highest 24-hour urine creatinine level.This study can be used as a basis for rational selection of urate-lowering drugs for different HUA patients.
基金the National Natural Science Foundation of China(No.81560153 and No.81760169)the Natural Science Foundation of the Xinjiang Uygur Autonomous Region(No.2017D01C234)the Open Project of Shanghai Six People,Hospital and Shanghai Key Laboratory of Diabetes Mellitus(No.SHKLD-KF-1502).
文摘This study aimed to test the effects of five single nucleotide polymorphisms within SLC2A9 on uric acid level in a special ethnic population,the Uygurs in Xinjiang,China.According to our inclusion and exclusion criteria,Uygur adults from Xinjiang constituted the study population.There were 1053 Uygur adults with hyperuricemia and 1373 normal Uygur adults who served as controls.Five single nucleotide polymorphisms within SLC2A9(rs938557,rs7679916,rs7349721,rsl3101785,and rs 13137343)were selected with the HapMap dataset and TaqMan assays.We found that,in normouricemia group,rs938557 was significantly correlated with uric acid(β=11.39±3.74,P=0.0024)adjusting for age,gender and BMI;rs7679916 and rsl3137343 were marginally associated with uric acid concentration(β=5.77±3.O9,P=0.0626;p=-5.99±3.08,P=0.0520).In the hyperuricemia group,no SNP was found to possibly influence uric acid concentration.None of these SNPs showed significant association with hyperuricemia after controlling for age,gender and BMI.There were significant or marginal correlations between certain single nucleotide polymorphisms in the SLC2A9 region and uric acid concentration in Uygur normouricemia samples.In turn,some of these single nucleotide polymorphisms in SLC2A9 may increase the risk of hyperuricemia.
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.
文摘Hyperuricemia(HUA) is a common metabolic disease caused by increased formation or reduced excretion of uric acid. Although HUA does not cause direct damage to the body, it is closely related to the occurrence of various diseases, including gout,hypertension, diabetes mellitus, metabolic syndrome, and chronic kidney disease.
基金supported by the Chinese Adults Chronic Diseases and Nutrition Surveillance(2015)
文摘Objective The purpose of this study was to determine the serum uric acid levels and the prevalence of hyperuricemia among Chinese adults in 2015 and compare the differences between urban and rural areas,as well as the differences between eastern,central,and western regions.Methods A national representative sample of 180,208 participants were included using a stratified,multistage,and random sampling method.The demographic characteristics and blood samples were collected to determine the serum uric acid levels and prevalence of hyperuricemia among subgroups using complicated sampling weight.A t-test or ANOVA was used for normally-distributed data.The Kruskal-Wallis rank test was used for skewed-distributed data.The Mantel-Haenszel chi-square test was used to compare the difference in categorical variables.Results The weighted mean uric acid level in Chinese adults was 310.4μmol/L(317.5μmol/L in urban areas and 302.9μmol/L in rural areas).The weighted average values of uric acid in eastern,central,and western China were 315.5μmol/L,303.5μmol/L,and 310.4μmol/L,respectively.The weighted prevalence of hyperuricemia in Chinese adults was 14.6%,with a prevalence of 16.5%in urban areas and12.5%in rural areas.The weighted prevalence of hyperuricemia in eastern,central,and western China was 16.0%,12.5%,and 14.8%,respectively.Conclusion The uric acid level in Chinese adults is relatively high.Effective actions are warranted to improve this metabolic abnormality.
文摘The aim of the present study was to observe the protective effects of α-lipoic acid(ALA)on vascular injury in rats with hyperuricemia(HUA).The ALA treatment groups(10,30 and 90 mg/kg,respectively)were administered with ALA via gavage for 2 weeks.Subsequently,the levels of blood urea nitrogen(BUN),creatinine(CREA),uric acid(UA),total cholesterol(TC),high density lipoprotein-C(HDL-C)and low density lipoprotein-C(LDL-C)were measured;the activities of glutathione peroxidase(GSH-Px),catalase(CAT),malonaldehyde(MDA),superoxide dismutase(SOD)and xanthine oxidase(XOD)were also determined.The thoracic aorta of rats in each experimental group was observed under a light microscope;ultrastructural analysis was performed.SOD and CAT protein contents were investigated by Western blotting.The results revealed that:i)Compared with the model group,the levels of UA were decreased in the ALA groups and the levels of BUN,CREA,TC,and LDL-C decreased in the 30 and 90 mg/kg ALA groups(P<0.05);ii)compared with the model group,the activities of GSH-Px,SOD and XOD were increased and the levels of MDA were reduced in the 90 mg/kg ALA group (P<0.05);and iii)in the model and 10 mg/kg ALA groups,edema and shedding were observed in endothelial cells.Compared with the model and 10 mg/kg ALA groups,the 30 and 90 mg/kg ALA groups exhibited fewer swollen endothelial cells.In summary,the results of the present study indicated that HUA resulted in vascular oxidative stress injury and decreased the activity of antioxidative enzymes,which leads to endothelial cell damage and vascular lesions.ALA may serve as a therapeutic agent for the treatment of HUA-induced endothelial dysfunction.
基金The authors thank Mrs.Meijuan Yang for her technical support on the preparation of paraffin sections.This work was supported by National Natural Science Foundation of China(81673618)Beijing Natural Science Foundation(7162117)National Science and Technology Major Projects for'Major New Drugs Innovation and Development'(2017ZX09301024).
文摘Objective:Hyperuricemia is an excess of urate in blood.The kidneys play important parts in urate excretion,which involves handling reabsorption and secretion.A series of urate transporters is responsible for this process:urate transporter (URAT)1,glucose transporter (GLUT)9,organic anion transporter (OAT)1 and OAT3.Excessive fructose intake may result in increased serum urate levels.Chicory (Cichorium intybus L.) has been used as an edible vegetable and traditional Chinese medicine.Studies have shown that chicory is a promising anti-hyperuricemia agent and we explored the mechanism of its uricosuric effect via a renal pathway.Methods:Hyperuricemia was induced in rats by administration of 10% fructose.The uricosuric effect was evaluated by determining the serum urate level.Renal excretory function was detected by the clearance rate of creatinine,clearance rate of uric acid and histology.The location and expression of URAT1,GLUT9,OAT1 and OAT3 their mRNA expression in kidneys were analyzed.Results:Chicory decreased serum levels of urate and creatinine significantly,and promoted the clearance of creatinine and urate,as well as improving renal pathologic changes due to hyperuricemia.Chicory inhibited expression of URAT1 and GLUT9 markedly in a dosedependent manner,but showed no influence on expression of OAT1 or OAT3.Conclusion:Chicory might be a promising anti-hyperuricemia agent.It can promote renal excretion of urate by inhibiting urate reabsorption,which may be related to downregulation of mRNA and protein expression of URAT1 and GLUT9.
文摘Fibulin-1(FBLN-1),an elastin-associated extracellular matrix protein,has been found in blood and may play a role in the pathophysiological processes leading to cardiovascular disease(CVD).We aimed to investigate the relationship between fibulin-1 levels and the risk of CVD by evaluating vascular age derived from the Framingham Heart Study and brachial-ankle Pulse Wave Velocity(baPWV)in patients with asymptomatic hyperuricemia(AHU).In total,66 patients with AHU and 66 gender-and age-matched healthy individuals were enrolled.The plasma fibulin-1 levels were measured by immunochemistry.Patients with AHU presented significantly higher vascular age[median(interquartile range):54(22)vs.48(14)years,P=0.01]and baPWV[mean±SD:1373±223 vs.1291±177 cm/s,P=0.02]than the healthy subjects;however,no significant difference was observed in the plasma fibulin-1 level between the patients with AHU and healthy subjects[median(interquartile range):4018(3838)vs.3099(3405)ng/mL,P=0.31].A correlation between fibulin-1 levels and baPWV was observed only in patients with AHU(r=0.29,P=0.02);and there was also a suggestively statistically significant correlation between fibulin-1 levels and vascular age(r=0.22,P=0.08).However,these associations were rendered insignificant after adjustments for potential confounders.In healthy subjects,no correlation was observed between fibulin-1 levels and CVD risk.This study reveals that plasma fibulin-1 levels may reflect the CVD risk in patients with AHU,but the relationship is not robust.
文摘Background: More and more chronic kidney disease (CKD) patients are accompanied with hyperuricaemia. As is known, hyperuricaemia is an independent hazard of both cardiovascular diseases (CVD) and chronic kidney diseases. We aim at identifying Single Nucleotide Polymorphism (SNP) difference of hURAT1 (rs7932775) and ABCG2 (rs3825016) on CKD patient with hyperuricemia and/or gout. Methods: All forty-two CKD patients were divided into two groups: hyperuricemia, and control group. 24 hours urine sample and serum were prepared for testing biochemistry parameters. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method is used to analyze hURAT1 and ABCG2 single nucleotide polymorphisms in different groups. Results: 17 patients have CT SNP of hURAT1 (rs7932775) and 13 patients have CT SNP of ABCG2 (rs3825016) in hyperuricemia group, while only 5 persons and 6 persons have the same mutations in control group respectively. 7 patients have CT SNP of both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group, while only 2 persons have the same mutations in control group. CT mutation rates of hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 60.7% (17/28) and 50% (13/28) respectively, higher than that of control group (35.7% (5/14) and 42.8% (6/14)). What is more, Double SNP mutations in both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 25% (7/28), higher than that of control group (14.2%, 2/14). Conclusion: There are higher mutation rates of CT SNP in hURAT1 (rs7932775) and/or ABCG2 (rs3825016) in hyperuricemia group. We can conclude that hyperuricemia is a high risk factor in progress of CKD, which is necessary to take measures of decreasing serum uric acid to delay CKD progress.
文摘There are few data available on the prevalence of hyperuricemia among elderly and its possible association with metabolic syndrome (MetS) so the aim of this study was to assess prevalence of hyperuricemia among hospitalized elderly patients as well as to assess its association with MetS. Cross sectional data from 200 hospitalized elderly patients were analyzed and the results were as follows: the prevalence of hyperuricemia was 21.0% in elderly men and 15.1% in elderly women. Multivariate logistic regression analysis revealed that BMI ≥ 30 (p = 0.031, OR = 1.1), hypertension (p = 0.019, OR = 1.8), high triglycerides level (p = 0.018, OR = 2.9) and hyperuricemia (p = 0.023, OR = 3.7) were independently associated with MetS. The study concluded that the prevalence of hyperuricemia among hospitalized elderly patients was 21.0% in elderly men and 15.1% in elderly women. There was an independent association between hyperuricemia and metabolic syndrome.
基金Important Drug Development Fund,Ministry of Science and Technology of China(2018ZX09735-002)National Natural Science Foundation of China(81173524,81673688)。
文摘Gout is a common of inflammatory arthritis and is caused by the deposition of monosodium urate(MSU)crystals as a result of hyperuricemia(HUA).Although HUA is considered to be the main risk factor for gout,only approximately 10%of the individuals with HUA will eventually experience a gout attack.In this review,we first briefly introduce the development of gout and then summarize several possible reasons for its development.Genetic factors play a more prominent role in gout than in other diseases;functional mutations related to urate control and innate immunity components have been found to be associated with gout.Here,we list some of the most prominent genes involved in the pathogenesis of gout.In joints with MSU deposition,mature macrophages may uptake MSU crystals without causing inflammation,and this helps to maintain joints in an asymptomatic state.As an auxiliary inflammation pathway,the ATP-P2X7R-NLRP3 axis may contribute to the amplification of MSU-induced inflammation to affect the development of gout.Finally,this review summarizes the research progress on natural products that can be used in the treatment of HUA and gout.
文摘<strong>Introduction:</strong> Uric acid is a product of purine metabolism and elevated serum concentration are very common in, and linked with hypertension and chronic kidney disease, conditions associated with heavy health burden and cardiovascular complications particularly in sub Sahara Africa. An assessment of factors relating hyperuricemia to hypertension and chronic kidney disease would therefore be necessary as way of mitigating the poor quality of life, morbidity and mortality associated with these diseases in low income nations. <strong>Methods:</strong> A single centre, descriptive comparative study in which the demographic, clinical and laboratory data of hypertensive and non-dialyzed chronic kidney disease (CKD) patients were analyzed. Serum biochemical parameters with uric acid, hematocrit and urine dip strip protein were assessed. Predictors of hyperuricemia were determined using multivariate analysis. <strong>Results:</strong> One hundred and thirty nine hypertensives and 69 CKD were studied. The mean age of the participants was 54.3 ± 11.7 years, hypertensives (52.9 ± 15.7 years) and CKD (57.3 ± 16.1 years). Both groups had more males, P = 0.8. Majority (78.3%) of the CKD cohorts had stage 4 or 5 (non-dialyzed) disease. The systolic and diastolic blood pressure, creatinine and uric acid were lower in hypertension than in CKD, P = 0.07, P = 0.05, P < 0.001 and P = 0.004 respectively. The hematocrit, albumin and GFR were higher in HTN than CKD, P < 0.001, P < 0.001 and P < 0.001 respectively. The prevalence of hyperuricemia was 56.2%. The mean uric acid was 505.9 ± 23.6 mmol/L, 382 7 ± 10.5 mmol/L for hypertensive and 755.9 ± 14.8 mmol/L for CKD, P < 0.001. The prevalence of systolic HTN, proteinuria, hypoalbuminemia and anemia were 51%, 75%, 46% and 59%, and were higher in males. Hyperuricemia was related to advancing age, proteinuria, elevated creatinine, hypoalbuminemia, anemia and hypertriglyceridemia. Proteinuria (OR—4.66, 95% CI—2.42 - 9.65), elevated creatinine (OR—3.12, 95% CI—2.40 - 6.92), hypoalbuminemia (OR—2.92, 95% CI—1.83 - 5.78) and anemia (OR—4.01, 95% CI—3.78 - 7.99) independently predicted hyperuricemia.<strong> Conclusion:</strong> Hyperuricemia is commoner in CKD than hypertension and was higher in males and positively correlated with the blood pressure, proteinuria and creatinine, but negatively related to hematocrit, albumin and glomerular filtration rate. Independent predictors of hyperuricemia were proteinuria, elevated creatinine, hypoalbuminemia and anemia. Measures are needed to prevent and treat hyperuricemia to reduce the health burden associated with hypertension and CKD.
