Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanis...Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides(ADBP)on HUA-induced kidney damage.In the present study,we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents.In vitro results found that ADBP protected uric acid(UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense.In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice,evidenced by a remarkable decrease in serum UA,creatinine and blood urea nitrogen,improving kidney UA excretion,antioxidant defense and histological kidney deterioration.Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction.Intriguingly,ADBP restored the gut microbiome homeostasis in CKD mice,especially with respect to the elevated helpful microbial abundance,and the decreased harmful bacterial abundance.This study demonstrated that ADBP displayed great nephroprotective effects,and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.展开更多
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
Hyperuricemia,a metabolic disorder related to uric acid metabolism dysregulation,has become a common metabolic disease worldwide,due to changes in lifestyle and dietary structure.In recent years,owing to their high ac...Hyperuricemia,a metabolic disorder related to uric acid metabolism dysregulation,has become a common metabolic disease worldwide,due to changes in lifestyle and dietary structure.In recent years,owing to their high activity and few adverse effects,food-derived active peptides used as functional foods against hyperuricemia have attracted increasing attention.This article aims to focus on the challenge associated with peptide-specific preparation methods development,functional components identification,action mechanism(s)clarification,and bioavailability improvement.The current review proposed recent advances in producing the food-derived peptides with high anti-hyperuricemia activity by protein source screening and matched enzymatic hydrolysis condition adjusting,increased the knowledge about strategies to search antihyperuricemia peptides with definite structure,and emphasized the necessity of combining computer-aided approaches and activity evaluations.In addition,novel action mechanism mediated by gut microbiota was discussed,providing different insights from classical mechanism.Moreover,considering that little attention was paid previously on the structure-activity relationships of anti-hyperuricemia peptides,we collected the sequences from published studies and make a preliminary summary about the structure-activity relationships,which in turn provided guides for enzymatic hydrolysis optimization and bioavailability improvement.Hopefully,this article could promote the development,application and commercialization of food-derived anti-hyperuricemia peptides in the future.展开更多
Hyperuricemia(HUA)is a condition associated with a high concentration of uric acid(UA)in the bloodstream and can cause gout and chronic kidney disease.The gut microbiota of patients with gout and HUA is significantly ...Hyperuricemia(HUA)is a condition associated with a high concentration of uric acid(UA)in the bloodstream and can cause gout and chronic kidney disease.The gut microbiota of patients with gout and HUA is significantly altered compared to that of healthy people.This article focused on the complex interconnection between alterations in the gut microbiota and the development of this disorder.Some studies have suggested that changes in the composition,diversity,and activity of microbes play a key role in establishing and progressing HUA and gout pathogenesis.Therefore,we discussed how the gut microbiota contributes to HUA through purine metabolism,UA excretion,and intestinal inflammatory responses.We examined specific changes in the composition of the gut microbiota associated with gout and HUA,highlighting key bacterial taxa and the metabolic pathways involved.Additionally,we discussed the effect of conventional gout treatments on the gut microbiota composition,along with emerging therapeutic approaches that target the gut microbiome,such as the use of probiotics and prebiotics.We also provided insights into a study regarding the gut microbiota as a possible novel therapeutic intervention for gout treatment and dysbiosis-related diagnosis.展开更多
BACKGROUND Hyperuricemia(HUA)is a public health concern that needs to be solved urgently.The lyophilized powder of Poecilobdella manillensis has been shown to significantly alleviate HUA;however,its underlying metabol...BACKGROUND Hyperuricemia(HUA)is a public health concern that needs to be solved urgently.The lyophilized powder of Poecilobdella manillensis has been shown to significantly alleviate HUA;however,its underlying metabolic regulation remains unclear.AIM To explore the underlying mechanisms of Poecilobdella manillensis in HUA based on modulation of the gut microbiota and host metabolism.METHODS A mouse model of rapid HUA was established using a high-purine diet and potassium oxonate injections.The mice received oral drugs or saline.Additionally,16S rRNA sequencing and ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry-based untargeted metabolomics were performed to identify changes in the microbiome and host metabolome,respectively.The levels of uric acid transporters and epithelial tight junction proteins in the renal and intestinal tissues were analyzed using an enzyme-linked immunosorbent assay.RESULTS The protein extract of Poecilobdella manillensis lyophilized powder(49 mg/kg)showed an enhanced anti-trioxypurine ability than that of allopurinol(5 mg/kg)(P<0.05).A total of nine bacterial genera were identified to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder,which included the genera of Prevotella,Delftia,Dialister,Akkermansia,Lactococcus,Escherichia_Shigella,Enterococcus,and Bacteroides.Furthermore,22 metabolites in the serum were found to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder,which correlated to the Kyoto Encyclopedia of Genes and Genomes pathways of cysteine and methionine metabolism,sphingolipid metabolism,galactose metabolism,and phenylalanine,tyrosine,and tryptophan biosynthesis.Correlation analysis found that changes in the gut microbiota were significantly related to these metabolites.CONCLUSION The proteins in Poecilobdella manillensis powder were effective for HUA.Mechanistically,they are associated with improvements in gut microbiota dysbiosis and the regulation of sphingolipid and galactose metabolism.展开更多
Hyperuricemia is a high-risk factor for the development of gout and renal fibrosis,but the adverse effects of hyperuricemia on the liver have been seriously neglected.This research investigated the ameliorating effect...Hyperuricemia is a high-risk factor for the development of gout and renal fibrosis,but the adverse effects of hyperuricemia on the liver have been seriously neglected.This research investigated the ameliorating effect of Lacticaseibacillus rhamnosus Fmb14 on hyperuricemia induced liver dysfunction both in vitro and in vivo.Cell free extracts of high dose L.rhamnosus Fmb14 treatment reduced the death rate of HepG2 cell lines from 24.1%to 14.9%by inhibiting NLRP3 recruitment,which was mainly activated by reactive oxygen species release and mitochondrial membrane potential disorder.In purine dietary induced hyperuricemia(PDIH)mice model,liver oedema and pyroptosis were ameliorated after L.rhamnosus Fmb14 administration through downregulating the expression levels of NLRP3,caspase-1 and gasdermin-D from 1.61 to 0.86,3.15 to 1.01 and 5.63 to 2.02,respectively.L.rhamnosus Fmb14 administration restored mitochondrial inner membrane protein(MPV17)and connexin 43 from 2.83 and 0.73 to 0.80 and 0.98 respectively in PDIH mice,indicating that dysbiosis of mitochondrial membrane potential was restored in liver.Intriguingly,PDIH pyroptosis stimulates the process of apoptosis,which leads to severe leakage of hepatocytes,and both of pyroptosis and apoptosis were decreased after L.rhamnosus Fmb14 treatment.Therefore,L.rhamnosus Fmb14 is a promising biological resource to maintain homeostasis of the liver in hyperuricemia and the prevention of subsequent complications.展开更多
Background:Simiaowan(SMW),a well-known traditional Chinese medicine,has been employed to treat hyperuricemia(HUA)and gout for centuries.However,the bioactive components and underlying mechanisms have not been elucidat...Background:Simiaowan(SMW),a well-known traditional Chinese medicine,has been employed to treat hyperuricemia(HUA)and gout for centuries.However,the bioactive components and underlying mechanisms have not been elucidated.The objective of this study was to identify the active components and potential mechanisms of SMW by integrating pharmacological experimentation,serum pharmacochemistry,network pharmacology and molecular docking.Methods:HUA rats modelling by high-fat/high-sugar diet and potassium oxonate/adenine oral administration were used to evaluate the pharmacodynamic effects of SMW.UPLC-Q-Exactive-MS/MS was employed to detect the bioactive components present in SMW-containing serum.Network pharmacology and molecular docking were utilized to elucidate the potential targets and underlying mechanisms.Results:SMW effectively ameliorated HUA rats via the inhibition of uric acid(UA)production,promotion of UA excretion,improvement of lipid and glucose metabolic abnormalities,antioxidant,anti-inflammatory and anti-insulin resistance effects.A total of 73 compounds detected in SMW-containing serum were identified as potential active components,with alkaloids,flavonoids,organic acids,and terpenoids emerging as the primary active ingredients.Totally 203 corresponding targets were obtained as SMW anti-HUA/gout targets,which mainly participated in apoptosis,insulin resistance,TNF,PI3K-Akt,HIF-1,NF-κB,MAPK,IL-17 and TLR signaling pathways.Molecular docking indicated that active compounds(e.g.berberine,phellodendrine,quercetin,formononetin,ferulic acid)had superior binding abilities to the key targets(e.g.solute carrier family 22 member 12(URAT1),solute carrier family 22 member 6(OAT1),ATP-binding cassette sub-family G member 2(ABCG2),solute carrier family 2,facilitated glucose transporter member 9(GLUT9),xanthine dehydrogenase/oxidase(XDH),transcription factor p65(RELA),toll-like receptor 4(TLR4),prostaglandin G/H synthase 2(PTGS2),caspase-3(CASP3),insulin(INS)).Conclusion:SMW exerted regulatory influence over the disease network of HUA and gout through a multiplicity of components,targets,and pathways.Alkaloids,flavonoids,organic acids,and terpenoids were the primary active components,exerting anti-HUA/gout effects via antioxidant,anti-inflammatory,anti-insulin resistance,anti-apoptosis,inhibition of UA production,and promotion of UA excretion.This study revealed the active components and molecular mechanisms of SMW,providing insights into the development of natural products derived from SMW.展开更多
Traditional Chinese medicine has a long and illustrious history,and with the development of modern science and technology,the research and application of traditional Chinese medicines have continued to progress signif...Traditional Chinese medicine has a long and illustrious history,and with the development of modern science and technology,the research and application of traditional Chinese medicines have continued to progress significantly.Many traditional Chinese medicinal herbs have undergone scientific validation,reinvi-gorating with new life and vitality,and contributing unique strengths to the advancement of human health.Recently,the discovery that leech total protein extracted from Poecilobdella manillensis lyophilized powder reduces blood uric acid(UA)levels by inhibiting the activity of xanthine oxidase to decrease UA synthesis and promotes UA excretion by regulating different UA transporters in the kidney and intestine has undoubtedly injected new vitality and hope into this field of research.The purpose of this editorial is to comment on this study,explore its strengths and weaknesses,and there is a hope to treat a range of metabolic-related syndromes,including hyperuricemia,by targeting the gut microbiota.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
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
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
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
Objective: To investigate the relationship between metabolic syndrome and hyperuricemia. Methods: A total of 2 374 subjects who received health examination in our hospital from Jan. 2004 to Dec. 2006 were enrolled in ...Objective: To investigate the relationship between metabolic syndrome and hyperuricemia. Methods: A total of 2 374 subjects who received health examination in our hospital from Jan. 2004 to Dec. 2006 were enrolled in our study. Hyperuricemia is defined as ≥7 mg/dl (in men) or ≥6.0 mg/dl (in women). Metabolic syndrome was defined using AHA/NHLBI (American Heart Association/National Heart, Lung, and Blood Institute) criteria. Results: (1) The overall prevalence of hyperuricemia was 13.10%. The condition was more common in men than in women (19.07% vs 3.42%). (2) Among men, uric acid concentration is statistically significantly positively correlated with waist circumference, blood pressure, and triglyceride. Uric acid is negatively correlated with serum high-density lipoprotein-cholesterol (HDL-C). Uric acid concentration is most strongly correlated with serum triglyceride (r=0.379) and waist circumference (r=0.297). Among women, statistically significant positive correlations were noted for the serum uric acid concentrations with waist circumference, triglyceride and fasting plasma glucose. Serum triglyceride (r=0.329) and waist circumference (r=0.234) are most strongly correlated with uric acid concentrations. (3) Men with hyperuricemia had a 1.634-fold increased risk of metabolic syndrome as compared with those without hyperuricemia odds ratio (OR)=1.634, P=0.000. Women with hyperuricemia had a 1.626-fold increased risk of metabolic syndrome (OR=1.626, P=0.000) as compared with those without hyperuricemia. Conclusion: Hyperuricemia is prevalent among Chinese population. Additionally, serum uric acid is positively associated with metabolic syndrome.展开更多
Objective To investigate the association of retinal vascular calibers with hyperuricemia in a middle‐aged and elderly population. Methods A cross‐sectional design was applied in this study and 869 participants aged ...Objective To investigate the association of retinal vascular calibers with hyperuricemia in a middle‐aged and elderly population. Methods A cross‐sectional design was applied in this study and 869 participants aged ≥40 years from a high‐risk group for diabetes were recruited. All participants received the anthropometrical measurements and laboratory tests. Retinal arteriolar and venular caliber of the participants were measured with a semi‐automated system. Hyperuricemia was defined as a serum uric acid level 420 μmol/L in men and 360 μmol/L in women. Linear regression models were used to assess the association of hyperuricemia with retinal vascular calibers. These models were additionally adjusted for age, central obesity, hypertension, dyslipidemia, weekly activity, smoking status, and education. Results Among the 869 participants, 133 (15.3%) suffered from hyperuricemia. The crude mean serum uric acid level was 312.3 μmol/L (Standard Deviation 79.5); mean concentration was 355.0 μmol/L (SD 75.5) in male participants, and 288.0 μmol/L (SD 71.1) in female participants (age‐adjusted difference 58.1 μmol/L, 95% Confidence Internal 48.5, 67.6). After adjusting for additional covariates, male participants with hyperuricemia had 3.77 μm (95% CI ‐0.46, 8.00) smaller arteriolar caliber and 6.20 μm (95% CI 0.36, 12.04) larger venule than those without hyperuricemia; the corresponding numbers among female participants were 1.57 μm (95% CI ‐1.07, 4.21) for retinal arteriolar caliber and 2.28 μm (95% CI ‐1.72, 6.27) for retinal venular caliber. Conclusion Hyperuricemia was associated with smaller retinal arteriolar caliber and larger venular caliber mainly in male participants in this study.展开更多
Objective To establish abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model fed with high fat diet. And then to investigate the pathological characteristics of this quail model. Methods ...Objective To establish abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model fed with high fat diet. And then to investigate the pathological characteristics of this quail model. Methods Thirty Longcheng quails were randomly divided into two groups: control group and model group (n=15). The control group quails were fed with normal diet and model group quails were fed with high fat diet for 14 days. After a 12-hour overnight fast, liver and abdominal fat at euthanasia as well as serum were collected. The levels of serum uric acid, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride, free fatty acid (FFA), and blood glucose were assayed. The activity changes of adenosine deaminase (ADA), xanthine oxidase (XOD), lipoprotein lipase (LPL), hepatic lipase (HL), and fatty acid synthetase (FAS) were analyzed. Results Compared with control group, the abdominal fat content (0.74±0.63 vs. 1.36±0.65 g, P〈0.05) and abdominal fat index (0.44%±0.30% vs. 0.85%±0.30%, P〈0.01) as well as live lipid index (3.61%±0.65% vs. 11.33%±2.14%, P〈0.01) in model group significantly increased; the levels of serum uric acid (210.61±94,76 vs. 304.25±141.94 /amol/L, P〈0.05), total cholesterol (4.20±0.51 vs. 20.10±11.25 mmol/L, P〈0.01), LDL-C (1.16±0.29 vs. 10.78±6.48 mmol/L, P〈0.01), and FFA (0.39±0.14 vs. 0.55±0.15 mmol/L, P〈0.01) in model group significantly increased; HDL-C (5.85±0.95 vs. 4.14±2.03 mmol/L, P〈0.05) significantly decreased; the levels of triglyceride and blood glucose had no significant changes (P〉0.05); the activities of ADA (9.71±3.05 vs. 17.19±5.10 U/ml, P〈0.01) and XOD (10.58±6,88 vs. 19.22+9.44 U/L, P〈0.01) in model group significantly increased; and FAS, LPL, HL had no significant changes (P〉0.05). Conclusions High fat diet can induce abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model. The changes of uric acid and lipid metabolic enzyme activities may he the pathological mechanism of abdominal fat accumulation with hyperuricemia and hypercholesterolemia.展开更多
基金financially supported by Shenzhen Agricultural Development Special Fund(Fishery)Agricultural High-Tech Project([2021]735)the Shenzhen Science and Technology Innovation Commission(KCXFZ20201221173207022)Youth Science Foundation Project(32101936)。
文摘Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides(ADBP)on HUA-induced kidney damage.In the present study,we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents.In vitro results found that ADBP protected uric acid(UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense.In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice,evidenced by a remarkable decrease in serum UA,creatinine and blood urea nitrogen,improving kidney UA excretion,antioxidant defense and histological kidney deterioration.Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction.Intriguingly,ADBP restored the gut microbiome homeostasis in CKD mice,especially with respect to the elevated helpful microbial abundance,and the decreased harmful bacterial abundance.This study demonstrated that ADBP displayed great nephroprotective effects,and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.
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sponsored by the National Natural Science Foundation China(32270115)National Key R&D Program of China(2018YFD0901102)+1 种基金Fundamental Research Funds for the Provincial Universities of Zhejiang(SJLY2021015)K.C.Wong Magna Fund of Ningbo University。
文摘Hyperuricemia,a metabolic disorder related to uric acid metabolism dysregulation,has become a common metabolic disease worldwide,due to changes in lifestyle and dietary structure.In recent years,owing to their high activity and few adverse effects,food-derived active peptides used as functional foods against hyperuricemia have attracted increasing attention.This article aims to focus on the challenge associated with peptide-specific preparation methods development,functional components identification,action mechanism(s)clarification,and bioavailability improvement.The current review proposed recent advances in producing the food-derived peptides with high anti-hyperuricemia activity by protein source screening and matched enzymatic hydrolysis condition adjusting,increased the knowledge about strategies to search antihyperuricemia peptides with definite structure,and emphasized the necessity of combining computer-aided approaches and activity evaluations.In addition,novel action mechanism mediated by gut microbiota was discussed,providing different insights from classical mechanism.Moreover,considering that little attention was paid previously on the structure-activity relationships of anti-hyperuricemia peptides,we collected the sequences from published studies and make a preliminary summary about the structure-activity relationships,which in turn provided guides for enzymatic hydrolysis optimization and bioavailability improvement.Hopefully,this article could promote the development,application and commercialization of food-derived anti-hyperuricemia peptides in the future.
文摘Hyperuricemia(HUA)is a condition associated with a high concentration of uric acid(UA)in the bloodstream and can cause gout and chronic kidney disease.The gut microbiota of patients with gout and HUA is significantly altered compared to that of healthy people.This article focused on the complex interconnection between alterations in the gut microbiota and the development of this disorder.Some studies have suggested that changes in the composition,diversity,and activity of microbes play a key role in establishing and progressing HUA and gout pathogenesis.Therefore,we discussed how the gut microbiota contributes to HUA through purine metabolism,UA excretion,and intestinal inflammatory responses.We examined specific changes in the composition of the gut microbiota associated with gout and HUA,highlighting key bacterial taxa and the metabolic pathways involved.Additionally,we discussed the effect of conventional gout treatments on the gut microbiota composition,along with emerging therapeutic approaches that target the gut microbiome,such as the use of probiotics and prebiotics.We also provided insights into a study regarding the gut microbiota as a possible novel therapeutic intervention for gout treatment and dysbiosis-related diagnosis.
基金Supported by National Natural Science Foundation of China,No.82160843.
文摘BACKGROUND Hyperuricemia(HUA)is a public health concern that needs to be solved urgently.The lyophilized powder of Poecilobdella manillensis has been shown to significantly alleviate HUA;however,its underlying metabolic regulation remains unclear.AIM To explore the underlying mechanisms of Poecilobdella manillensis in HUA based on modulation of the gut microbiota and host metabolism.METHODS A mouse model of rapid HUA was established using a high-purine diet and potassium oxonate injections.The mice received oral drugs or saline.Additionally,16S rRNA sequencing and ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry-based untargeted metabolomics were performed to identify changes in the microbiome and host metabolome,respectively.The levels of uric acid transporters and epithelial tight junction proteins in the renal and intestinal tissues were analyzed using an enzyme-linked immunosorbent assay.RESULTS The protein extract of Poecilobdella manillensis lyophilized powder(49 mg/kg)showed an enhanced anti-trioxypurine ability than that of allopurinol(5 mg/kg)(P<0.05).A total of nine bacterial genera were identified to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder,which included the genera of Prevotella,Delftia,Dialister,Akkermansia,Lactococcus,Escherichia_Shigella,Enterococcus,and Bacteroides.Furthermore,22 metabolites in the serum were found to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder,which correlated to the Kyoto Encyclopedia of Genes and Genomes pathways of cysteine and methionine metabolism,sphingolipid metabolism,galactose metabolism,and phenylalanine,tyrosine,and tryptophan biosynthesis.Correlation analysis found that changes in the gut microbiota were significantly related to these metabolites.CONCLUSION The proteins in Poecilobdella manillensis powder were effective for HUA.Mechanistically,they are associated with improvements in gut microbiota dysbiosis and the regulation of sphingolipid and galactose metabolism.
基金Grant support was received from the National Natural Science Foundation of China(32072182).
文摘Hyperuricemia is a high-risk factor for the development of gout and renal fibrosis,but the adverse effects of hyperuricemia on the liver have been seriously neglected.This research investigated the ameliorating effect of Lacticaseibacillus rhamnosus Fmb14 on hyperuricemia induced liver dysfunction both in vitro and in vivo.Cell free extracts of high dose L.rhamnosus Fmb14 treatment reduced the death rate of HepG2 cell lines from 24.1%to 14.9%by inhibiting NLRP3 recruitment,which was mainly activated by reactive oxygen species release and mitochondrial membrane potential disorder.In purine dietary induced hyperuricemia(PDIH)mice model,liver oedema and pyroptosis were ameliorated after L.rhamnosus Fmb14 administration through downregulating the expression levels of NLRP3,caspase-1 and gasdermin-D from 1.61 to 0.86,3.15 to 1.01 and 5.63 to 2.02,respectively.L.rhamnosus Fmb14 administration restored mitochondrial inner membrane protein(MPV17)and connexin 43 from 2.83 and 0.73 to 0.80 and 0.98 respectively in PDIH mice,indicating that dysbiosis of mitochondrial membrane potential was restored in liver.Intriguingly,PDIH pyroptosis stimulates the process of apoptosis,which leads to severe leakage of hepatocytes,and both of pyroptosis and apoptosis were decreased after L.rhamnosus Fmb14 treatment.Therefore,L.rhamnosus Fmb14 is a promising biological resource to maintain homeostasis of the liver in hyperuricemia and the prevention of subsequent complications.
基金supported by Natural Science Foundation of Guangdong Province(2021A1515010978 and 2021A1515012474)Basic research project of Shenzhen Science and Innovation Commission(JCYJ20210324121610029)Guangdong Provincial Key Areas Research and Development Program project Lingnan TCM Modernization(2020B1111120003).
文摘Background:Simiaowan(SMW),a well-known traditional Chinese medicine,has been employed to treat hyperuricemia(HUA)and gout for centuries.However,the bioactive components and underlying mechanisms have not been elucidated.The objective of this study was to identify the active components and potential mechanisms of SMW by integrating pharmacological experimentation,serum pharmacochemistry,network pharmacology and molecular docking.Methods:HUA rats modelling by high-fat/high-sugar diet and potassium oxonate/adenine oral administration were used to evaluate the pharmacodynamic effects of SMW.UPLC-Q-Exactive-MS/MS was employed to detect the bioactive components present in SMW-containing serum.Network pharmacology and molecular docking were utilized to elucidate the potential targets and underlying mechanisms.Results:SMW effectively ameliorated HUA rats via the inhibition of uric acid(UA)production,promotion of UA excretion,improvement of lipid and glucose metabolic abnormalities,antioxidant,anti-inflammatory and anti-insulin resistance effects.A total of 73 compounds detected in SMW-containing serum were identified as potential active components,with alkaloids,flavonoids,organic acids,and terpenoids emerging as the primary active ingredients.Totally 203 corresponding targets were obtained as SMW anti-HUA/gout targets,which mainly participated in apoptosis,insulin resistance,TNF,PI3K-Akt,HIF-1,NF-κB,MAPK,IL-17 and TLR signaling pathways.Molecular docking indicated that active compounds(e.g.berberine,phellodendrine,quercetin,formononetin,ferulic acid)had superior binding abilities to the key targets(e.g.solute carrier family 22 member 12(URAT1),solute carrier family 22 member 6(OAT1),ATP-binding cassette sub-family G member 2(ABCG2),solute carrier family 2,facilitated glucose transporter member 9(GLUT9),xanthine dehydrogenase/oxidase(XDH),transcription factor p65(RELA),toll-like receptor 4(TLR4),prostaglandin G/H synthase 2(PTGS2),caspase-3(CASP3),insulin(INS)).Conclusion:SMW exerted regulatory influence over the disease network of HUA and gout through a multiplicity of components,targets,and pathways.Alkaloids,flavonoids,organic acids,and terpenoids were the primary active components,exerting anti-HUA/gout effects via antioxidant,anti-inflammatory,anti-insulin resistance,anti-apoptosis,inhibition of UA production,and promotion of UA excretion.This study revealed the active components and molecular mechanisms of SMW,providing insights into the development of natural products derived from SMW.
文摘Traditional Chinese medicine has a long and illustrious history,and with the development of modern science and technology,the research and application of traditional Chinese medicines have continued to progress significantly.Many traditional Chinese medicinal herbs have undergone scientific validation,reinvi-gorating with new life and vitality,and contributing unique strengths to the advancement of human health.Recently,the discovery that leech total protein extracted from Poecilobdella manillensis lyophilized powder reduces blood uric acid(UA)levels by inhibiting the activity of xanthine oxidase to decrease UA synthesis and promotes UA excretion by regulating different UA transporters in the kidney and intestine has undoubtedly injected new vitality and hope into this field of research.The purpose of this editorial is to comment on this study,explore its strengths and weaknesses,and there is a hope to treat a range of metabolic-related syndromes,including hyperuricemia,by targeting the gut microbiota.
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.
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Project supported by the Health Promotion Center in Sir Run RunShaw Hospital, the Affiliated Hospital of Zhejiang University, China
文摘Objective: To investigate the relationship between metabolic syndrome and hyperuricemia. Methods: A total of 2 374 subjects who received health examination in our hospital from Jan. 2004 to Dec. 2006 were enrolled in our study. Hyperuricemia is defined as ≥7 mg/dl (in men) or ≥6.0 mg/dl (in women). Metabolic syndrome was defined using AHA/NHLBI (American Heart Association/National Heart, Lung, and Blood Institute) criteria. Results: (1) The overall prevalence of hyperuricemia was 13.10%. The condition was more common in men than in women (19.07% vs 3.42%). (2) Among men, uric acid concentration is statistically significantly positively correlated with waist circumference, blood pressure, and triglyceride. Uric acid is negatively correlated with serum high-density lipoprotein-cholesterol (HDL-C). Uric acid concentration is most strongly correlated with serum triglyceride (r=0.379) and waist circumference (r=0.297). Among women, statistically significant positive correlations were noted for the serum uric acid concentrations with waist circumference, triglyceride and fasting plasma glucose. Serum triglyceride (r=0.329) and waist circumference (r=0.234) are most strongly correlated with uric acid concentrations. (3) Men with hyperuricemia had a 1.634-fold increased risk of metabolic syndrome as compared with those without hyperuricemia odds ratio (OR)=1.634, P=0.000. Women with hyperuricemia had a 1.626-fold increased risk of metabolic syndrome (OR=1.626, P=0.000) as compared with those without hyperuricemia. Conclusion: Hyperuricemia is prevalent among Chinese population. Additionally, serum uric acid is positively associated with metabolic syndrome.
基金supported by Science and Technology Commission of Shanghai Municipality (STCSM) and the Key Project of Health Bureau of Shanghai (Grant 04dz19501‐1 and 08GWZX0203 to Xin GAO)
文摘Objective To investigate the association of retinal vascular calibers with hyperuricemia in a middle‐aged and elderly population. Methods A cross‐sectional design was applied in this study and 869 participants aged ≥40 years from a high‐risk group for diabetes were recruited. All participants received the anthropometrical measurements and laboratory tests. Retinal arteriolar and venular caliber of the participants were measured with a semi‐automated system. Hyperuricemia was defined as a serum uric acid level 420 μmol/L in men and 360 μmol/L in women. Linear regression models were used to assess the association of hyperuricemia with retinal vascular calibers. These models were additionally adjusted for age, central obesity, hypertension, dyslipidemia, weekly activity, smoking status, and education. Results Among the 869 participants, 133 (15.3%) suffered from hyperuricemia. The crude mean serum uric acid level was 312.3 μmol/L (Standard Deviation 79.5); mean concentration was 355.0 μmol/L (SD 75.5) in male participants, and 288.0 μmol/L (SD 71.1) in female participants (age‐adjusted difference 58.1 μmol/L, 95% Confidence Internal 48.5, 67.6). After adjusting for additional covariates, male participants with hyperuricemia had 3.77 μm (95% CI ‐0.46, 8.00) smaller arteriolar caliber and 6.20 μm (95% CI 0.36, 12.04) larger venule than those without hyperuricemia; the corresponding numbers among female participants were 1.57 μm (95% CI ‐1.07, 4.21) for retinal arteriolar caliber and 2.28 μm (95% CI ‐1.72, 6.27) for retinal venular caliber. Conclusion Hyperuricemia was associated with smaller retinal arteriolar caliber and larger venular caliber mainly in male participants in this study.
基金Supported by National Nature Science Foundation of China (30472282)Beijing Natural Science Foundation (7052036)Major State Basic Research Development Program of China (973 Program, 2007CB512605)
文摘Objective To establish abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model fed with high fat diet. And then to investigate the pathological characteristics of this quail model. Methods Thirty Longcheng quails were randomly divided into two groups: control group and model group (n=15). The control group quails were fed with normal diet and model group quails were fed with high fat diet for 14 days. After a 12-hour overnight fast, liver and abdominal fat at euthanasia as well as serum were collected. The levels of serum uric acid, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride, free fatty acid (FFA), and blood glucose were assayed. The activity changes of adenosine deaminase (ADA), xanthine oxidase (XOD), lipoprotein lipase (LPL), hepatic lipase (HL), and fatty acid synthetase (FAS) were analyzed. Results Compared with control group, the abdominal fat content (0.74±0.63 vs. 1.36±0.65 g, P〈0.05) and abdominal fat index (0.44%±0.30% vs. 0.85%±0.30%, P〈0.01) as well as live lipid index (3.61%±0.65% vs. 11.33%±2.14%, P〈0.01) in model group significantly increased; the levels of serum uric acid (210.61±94,76 vs. 304.25±141.94 /amol/L, P〈0.05), total cholesterol (4.20±0.51 vs. 20.10±11.25 mmol/L, P〈0.01), LDL-C (1.16±0.29 vs. 10.78±6.48 mmol/L, P〈0.01), and FFA (0.39±0.14 vs. 0.55±0.15 mmol/L, P〈0.01) in model group significantly increased; HDL-C (5.85±0.95 vs. 4.14±2.03 mmol/L, P〈0.05) significantly decreased; the levels of triglyceride and blood glucose had no significant changes (P〉0.05); the activities of ADA (9.71±3.05 vs. 17.19±5.10 U/ml, P〈0.01) and XOD (10.58±6,88 vs. 19.22+9.44 U/L, P〈0.01) in model group significantly increased; and FAS, LPL, HL had no significant changes (P〉0.05). Conclusions High fat diet can induce abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model. The changes of uric acid and lipid metabolic enzyme activities may he the pathological mechanism of abdominal fat accumulation with hyperuricemia and hypercholesterolemia.