BACKGROUND Major adverse cardiovascular(CV)events(MACEs)are the primary cause of morbidity and mortality in kidney transplantation(KT)recipients.The risk for MACEs is impacted by an array of traditional and transplant...BACKGROUND Major adverse cardiovascular(CV)events(MACEs)are the primary cause of morbidity and mortality in kidney transplantation(KT)recipients.The risk for MACEs is impacted by an array of traditional and transplant-related non-traditional CV risk factors.AIM To investigate the association between potential CV risk factors related to KT and MACEs,and their potential modification by hyperuricemia(HU).METHODS The relationship between CV risk factors related to KT and MACEs was examined in a cohort of 545 patients who underwent transplantation between 2008 and 2019.The mean age of patients at KT was 55.0 years±14.2 years(range 15.0–89.0 years).Univariate and multivariate logistic regression models were constructed to identify risk factors influencing MACEs.To explore the potential effect modification by uric acid(UA),patients were categorized into groups based on UA levels:(1)Low(<356μmol/L);(2)Normal(356–416μmol/L);(3)High(416–475μmol/L);and(4)Very high(>475μmol/L).RESULTS MACEs occurred in 145 of 545(26.6%)KT recipients.The most prevalent comorbidities were hypertension(87%),dyslipidemia(78%),secondary hyperparathyroidism(68%),HU(63%)and anemia(33%).In the multivariate logistic regression model,the most significant factors associated with MACEs were previous CV events[odds ratio(OR)=70.6,95%CI:24.9–200.1],left ventricular hypertrophy(LVH)(OR=12.6,95%CI:2.7–58.3),HU treatment(OR=4.3,95%CI:2.4–7.6),and anemia(OR=5.3,95%CI:2.9–9.8).Effect modification by the presence of HU revealed that independent factors associated with MACEs were age(OR=1.03,95%CI:1.0–1.1),previous CV events(OR=41.7,95%CI:13.6–127.6),LVH(OR=15.3,95%CI:2.0–116.6),HU treatment(OR=2.5,95%CI:1.3–4.6)and anemia(OR=5.4,95%CI:2.8–10.5).Effect modification by UA levels dichotomized at 475μmol/L(very high level of UA)revealed that HU treatment was not associated with MACEs in groups with or without very high UA levels.CONCLUSION A very high level of UA was observed to act as an effect-modifying factor for MACEs,especially when combined with other risk factors such as age,previous CV events,LVH,and anemia.展开更多
The associations of polycyclic aromatic hydrocarbon(PAH)exposure with serum uric acid(SUA)or hyperuricemia have been rarely assessed.We aimed to investigate the relationships between urinary PAH metabolites and SUA or...The associations of polycyclic aromatic hydrocarbon(PAH)exposure with serum uric acid(SUA)or hyperuricemia have been rarely assessed.We aimed to investigate the relationships between urinary PAH metabolites and SUA or hyperuricemia among US adults and to explore the mediating role of systemic inflammation in the associations.A total of 10,307 US adults were conducted to assess the associations of seven urinary hydroxy–PAH with SUA and hyperuricemia and evaluate the role of C-reactive protein(CRP),a biomarker of systemic inflammation,in such associations.Results showed that each 1-unit increase in ln-transformed 2-hydroxynaphthalene(2-OHNa),1-hydroxyphenanthrene(1-OHPh),2&3-hydroxyphenanthrene(2&3-OHPh)and total hydroxyphenanthrene(OHPh)was associated with a 1.68(95%confidence interval(CI):0.19 to 3.17),2.46(0.78 to 4.13),3.34(1.59 to 5.09),and 2.99(1.23 to 4.75)μmol/L increase in SUA,and a 8%(odds ratio(OR):1.08,1.02 to 1.15),9%(OR:1.09,1.02 to 1.18),13%(OR:1.13,1.05 to 1.22),and 12%(OR:1.12,95%CI:1.03,1.21)increase in hyperuricemia,respectively.Co-exposure of seven PAHs was positively associated with SUA and hyperuricemia,with 2&3-OHPh showing the highest weight(components weights:0.83 and 0.78,respectively).The CRP mediated 11.47%and 10.44%of the associations ofΣOHPh and 2&3-OHPh with SUA and mediated 8.60%and 8.62%in associations ofΣOHPh and 2&3-OHPh with hyperuricemia,respectively.In conclusion,internal levels of PAH metabolites were associated with elevated SUA levels and the increased risk of hyperuricemia among US adults,and CRP played a mediating role in the associations.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
Hyperuricemia is a prevalent metabolic disorder resulting from dysregulation of purine metabolism,often accompanied by inflammation.It is characterized by an abnormal elevation in uric acid(UA)levels.In our investigat...Hyperuricemia is a prevalent metabolic disorder resulting from dysregulation of purine metabolism,often accompanied by inflammation.It is characterized by an abnormal elevation in uric acid(UA)levels.In our investigation,the combined treatment with Lactiplantibacillus plantarum DY1 and quercetin suppressed the activity of xanthine oxidase and adenosine deaminase,decreased the levels of UA,tumor necrosis factor alpha(TNF-α)and interleukin 1β(IL-β),downregulated gene expression of urate transporter 1(URAT1)and glucose transporter 9(GLUT9),and upregulated organic anion transporter 1(OAT1)and ATP-binding cassette transporter subfamily G member 2(ABCG2).The combination increased the abundance of Lactobacillus and decreased the abundance of norank_f_norank_o__Clostridia_UCG-014 and Roseburia.Metabolomics analysis revealed that the combination of probiotics and quercetin exhibited distinct metabolic pathways compared to their individual administrations.When compared to probiotics alone,the combination led to alterations in glutathione metabolism(oxidized glutathione and glutathione)as well as sphingolipid metabolism(sphingosine and sphinganine).When compared to quercetin alone,the combination resulted in variations in tryptophan metabolism(indole-3-acetamide,5-hydroxy-L-tryptophan,indoleacetaldehyde,3-(3-indolyl)-2-oxopropanoic acid,3-indoleacetic acid and 3-methylindole)along with purine metabolism(UA,xanthosine,cyclic adenosine monophosphate(cAMP),adenosine diphosphate(ADP)and adenosine monophosphate(AMP)).The subsequent fecal microbiota transplantation proved that the effect of the combination on reducing UA levels was mediated by the gut microbiota.Therefore,this new combination can be considered a promising adjuvant therapy capable of synergistically alleviating hyperuricemia.展开更多
Modern lifestyle and diet have increased the incidence rate of uric acid(UA)metabolism-related diseases like hyperuricemia(HUA)and gout,posing heavy economic burden to individual patients and their families and the so...Modern lifestyle and diet have increased the incidence rate of uric acid(UA)metabolism-related diseases like hyperuricemia(HUA)and gout,posing heavy economic burden to individual patients and their families and the society.UA metabolism is a complex physiological process involving the kidney,intestine,and other organs.A number of factors together regulate UA metabolism,including genetics,diet,hormones,and the gut microbiota.This review summaries the gut microbiota features in subjects with HUA and gout,and the therapeutic effects of implementing microecological therapies(probiotics,prebiotics,or fecal microbiota transplant)that target modulate the gut microbiota and its downstream metabolism on the disease.Current evidence shows that these strategies are safe and promising in alleviate inflammation,reduce UA,and restoring a healthy gut microbiota in subjects with UA metabolism-related diseases.However,most clinical data are generated by animal studies.Therefore,we propose that vigorous human intervention trials should be conducted in the future to evaluate the therapeutic effects of microecological therapies in managing HUA and gout.展开更多
Hyperuricemia(HUA)is a metabolic disease characterized by high levels of uric acid(UA)in the blood and varying degrees of kidney damage.Desirable nanoliposomes should simultaneously exhibit efficient biocompatibility ...Hyperuricemia(HUA)is a metabolic disease characterized by high levels of uric acid(UA)in the blood and varying degrees of kidney damage.Desirable nanoliposomes should simultaneously exhibit efficient biocompatibility and effective drug delivery.However,they both usually require special structural properties.Herein,we propose a strategy to prepare nanoliposomes with varying rigidity by replacing cholesterol(CH)with phytosterol esters(PE).The results showed that the particle size of PE naringenin nanoliposomes(PE-NAR)was 179.5 nm,and the encapsulation efficiency(EE)was 79.93%.In atomic force microscopy(AFM)tests,PE-NAR showed a 1-fold increase in rigidity compared to CH naringenin nanoliposomes(CH-NAR).By observing the effects of naringenin nanoliposomes(NAR-NLs)on the physiological and biochemical indicators in HUA mice,we explore its impact on kidney damage and inflammatory pathways in HUA mice.The results show that NAR-NLs significantly inhibit UA levels and improve kidney damage.Compared to oral naringenin,NAR-NLs generally enhance the in vivo antioxidant effects of naringenin.Furthermore,high-rigidity PE-NAR downregulated the renal inflammatory factor interleukin-1β(IL-1β)to 6.67%,demonstrating the highest inhibitory effect.Further experiments have demonstrated that naringenin exerts a protective effect in kidney injury by inhibiting the activation of NOD like receptor protein 3(NLRP3)inflammasome and reducing oxidative stress within the body.In summary,by adjusting the rigidity of the nanoliposomes,the oral administration of naringenin can effectively improve the alleviation of HUA.展开更多
BACKGROUND Gut microbiota play a crucial role in metabolic diseases,including type 2 diabetes(T2DM)and hyperuricemia(HUA).One-third of uric acid is excreted into the intestinal tract and further metabolized by gut mic...BACKGROUND Gut microbiota play a crucial role in metabolic diseases,including type 2 diabetes(T2DM)and hyperuricemia(HUA).One-third of uric acid is excreted into the intestinal tract and further metabolized by gut microbiota.Thus,the gut microbiota might be a new therapeutic target for HUA.Empagliflozin significantly lowers serum uric acid levels and contributes to cardiovascular benefits which are partly attributed to altered gut microbiota.We hypothesize that gut dysbiosis in patients with diabetes and HUA,and the reduction of uric acid by empagliflozin,may be mediated by gut microbiota.AIM To investigate dysbiosis in patients with T2DM and HUA,and the effect of empagliflozin on gut microbiota associated with purine metabolism.METHODS In this age and sex-matched,case-control study,we recruited 30 patients with T2DM and HUA;30 with T2DM;and 30 healthy controls at the Henan Provincial People’s Hospital between February 2019 and August 2023.Nine patients with T2DM and HUA were treated with empagliflozin for three months.Gut microbiota profiles were assessed using the 16S rRNA gene.RESULTS Patients with T2DM and HUA had the highest total triglycerides(1.09 mmol/L in heathy control vs 1.56 mmol/L in T2DM vs 2.82 mmol/L in T2DM+HUA)and uric acid levels(302.50μmol/L in heathy control vs 288.50μmol/L in T2DM vs 466.50μmol/L in T2DM+HUA)among the three groups.The composition of the gut microbiota differed significantly between patients with T2DM and HUA,and those with T2DM/healthy controls(P<0.05).Notably,patients with T2DM and HUA demonstrated a deficiency of uric acid-degrading bacteria such as Romboutsia,Blautia,Clostridium sensu stricto 1(P<0.05).Empagliflozin treatment was associated with significantly reduced serum uric acid levels and purine metabolism-related pathways and genes in patients with T2DM and HUA(P<0.05).CONCLUSION Gut dysbiosis may contribute to the pathogenesis of HUA in T2DM,and empagliflozin may partly restore the gut microbiota related to uric acid metabolism.展开更多
To elucidate the mechanisms underlying the therapeutic effects of the herbal medicine pair Smilax Glabra and Semen Coicis in treating gout and hyperuricemia,a comprehensive analysis was conducted using network pharmac...To elucidate the mechanisms underlying the therapeutic effects of the herbal medicine pair Smilax Glabra and Semen Coicis in treating gout and hyperuricemia,a comprehensive analysis was conducted using network pharmacology and molecular docking methods.Disease-associated targets for gout and hyperuricemia were identified from the GeneCards,OMIM,Disgenet,and TTD databases,while the key active components and their corresponding targets for Smilax Glabra and Semen Coicis were obtained from the TCSMP database.The intersection of these targets enabled the construction of a protein-protein interaction(PPI)network,which was subsequently visualized and analyzed.Core targets were further subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses to elucidate the biological processes and pathways involved.Molecular docking was then employed to validate the reliability of the interactions between the active components and the identified targets.The analysis revealed that Smilax Glabra and Semen Coicis contained 15 bioactive components that interacted with 393 potential targets,while gout and hyperuricemia were associated with 660 targets in total.The primary active compounds implicated in treating these conditions included diosgenin,quercetin,and naringenin,which were found to interact with crucial hub targets such as BCL2,CASP3,and MAPK3.These interactions suggested that the herbal medicine pair modulated several biological processes,including gland development and the regulation of body fluid levels,through pathways involving membrane rafts,membrane microdomains,and nuclear receptor activities.Enrichment analyses highlighted their involvement in multiple signaling pathways,such as EGFR tyrosine kinase inhibitor resistance,phospholipase D signaling,and platelet activation.Molecular docking confirmed the strong binding affinities between the hub genes and the major active components,supporting their potential role in therapeutic efficacy.This study demonstrated that Smilax Glabra and Semen Coicis might offer a promising therapeutic strategy for gout and hyperuricemia by targeting multiple molecular components,biological functions,and pathways.The findings underscored the unique potential of traditional Chinese medicine(TCM)in managing complex diseases by leveraging synergistic effects across diverse biological mechanisms.展开更多
Globally,hyperuricemia is a growing health,social,and economic problem which could cause gout,chronic kidney diseases and other diseases.There are increasing evidences that a sensible diet makes sense to reduce the ri...Globally,hyperuricemia is a growing health,social,and economic problem which could cause gout,chronic kidney diseases and other diseases.There are increasing evidences that a sensible diet makes sense to reduce the risk of hyperuricemia.This review aims to explore the metabolic mechanism of dietary factors and effects of dietary types associated with hyperuricemia.Recommendations for dietary modification to prevent hyperuricemia are as following:decreasing intake of animal organs,seafood,sugar-sweetened,and alcohol beverages is essential;choosing water or unsweetened tea and coffee instead of sweetened beverages is beneficial;and increasing intake of vegetables,reduced-fat dairy products,foods containing fiber,micronutrients and unsaturated fatty acids is helpful.In addition,consumption of fruits and legumes in moderation is advantageous,and low-fructose of fruits and low-purine of non-soy beans are recommended.Moreover,personalized diet needs to be emphasized for hyperuricemic patients accompanied with diverse metabolic diseases.展开更多
Hyperuricemia(HUA)is a metabolic disorder characterized by elevated levels of uric acid in the blood,resulting from either increased production or decreased excretion of uric acid.This condition has reached epidemic p...Hyperuricemia(HUA)is a metabolic disorder characterized by elevated levels of uric acid in the blood,resulting from either increased production or decreased excretion of uric acid.This condition has reached epidemic proportions.Conventional Western medical treatments often come with a range of adverse effects.According to traditional Chinese medicine(TCM),the root cause of HUA lies in the spleen’s insufficient healthy movement,with phlegm,dampness,turbidity,and stasis being symptomatic manifestations.Research has shown that spleen-strengthening herbal remedies can effectively treat HUA by inhibiting uric acid synthesis enzymes,promoting uric acid excretion,reducing inflammation,providing antioxidant benefits,regulating gut microbiota,and modulating cellular processes.Clinical applications have substantiated these findings.Therefore,from the standpoint of symptomatic treatment of HUA,spleen-strengthening therapies hold significant importance and potential.展开更多
Hyperuricemia(HUA)refers to a condition where fasting serum uric acid levels exceed 420μmol/L in men and 350μmol/L in women,affecting 17.4%of China’s general population,showing increasing prevalence among younger i...Hyperuricemia(HUA)refers to a condition where fasting serum uric acid levels exceed 420μmol/L in men and 350μmol/L in women,affecting 17.4%of China’s general population,showing increasing prevalence among younger individuals.Luteolin,a common flavonoid compound,exhibits multiple biological effects,including inhibition of tumor proliferation and inflammatory responses.It also suppresses the activity of urate transporter 1(URAT1),promoting uric acid excretion.This study is the first to integrate network toxicology and network pharmacology approaches to systematically analyze the multi-target mechanisms of adenine-induced HUA and luteolin-treated HUA,with molecular docking validation of interaction targets.We constructed compound-pathway-intersection gene networks and a dual-group PPI network to analyze the mechanisms of adenine-induced HUA and luteolin-treated HUA.The dual-group PPI network identified 7 shared targets,namely XDH,PYGL,IL10,PPARG,TNF,VEGFA,and MAOA,involving core intersecting pathways such as purine-xanthine metabolism and insulin resistance.Luteolin may activate PPARG to regulate inflammation and uric acid excretion modules in the adenine network.GO-KEGG analysis indicates that intersection genes for adenine pathogenesis involve diverse biological processes,cellular components,and molecular functions,with core target KEGG analysis revealing 15 signaling pathways.Luteolin’s therapeutic targets are associated with more entries,and its core target KEGG analysis identified 46 signaling pathways.Molecular docking shows TNF,PPARG,and PYGL bind to both luteolin and adenine with negative binding energies,and luteolin’s binding energies are all below 5 kJ/mol,confirming stable binding.Luteolin’s anti-HUA mechanism is characterized by inhibition of production,promotion of excretion,anti-inflammation and metabolic regulation,but interactions with gut microbiota metabolites require further study.展开更多
The health effects of traffic-derived pollutants have gathered increasing concerns.Our objectives were to evaluate the associations of traffic-related heavy metal exposure with serum uric acid(SUA)and hyperuricemia an...The health effects of traffic-derived pollutants have gathered increasing concerns.Our objectives were to evaluate the associations of traffic-related heavy metal exposure with serum uric acid(SUA)and hyperuricemia and to explore the underlying mechanism.Traffic-related heavy metals(including zinc,iron,manganese,copper,lead,cadmium,antimony,and barium)and SUA were determined among 3909 community-based adults from the Wuhan-Zhuhai cohort.Various regression methods were applied to assess the association of heavy metals with SUA and hyperuricemia.Furthermore,mediation analyses were employed to evaluate the potential role of systemic inflammation in these associations.In single metal analyses,positive dose-response relationships between urinary zinc,iron,manganese,and antimony and SUA were observed.Furthermore,each 1-unit increase of ln-transformed urinary zinc levels was related to a 37.9%(OR=1.379,95%CI:1.148 to 1.657)increase in the hyperuricemia risk.In multiple metal analyses,both Bayesian kernel machine regression(BKMR)and weighted quantile sum regression(WQS)models showed positive associations of heavy metals mixture with SUA and hyperuricemia risk,and WQS analyses further revealed that zinc was the dominant metal(component weight:0.611 and 0.594,respectively).Additionally,plasma C-reactive protein(CRP)mediated 4.919%and 8.417%of the association of urinary zinc with SUA and hyperuricemia,respectively.In conclusion,exposure to several traffic-related heavy metals or traffic-related heavy metal mixtures were positively associated with SUA and hyperuricemia risk in the general Chinese population,in which zinc played a dominating role.Plasma CRP might partly mediate the association of urinary zinc with SUA and hyperuricemia risk.展开更多
The relationship between hyperuricemia(HUA)and erectile dysfunction(ED)remains inadequately understood.Given that HUA is often associated with various metabolic disorders,this study aims to explore the multivariate li...The relationship between hyperuricemia(HUA)and erectile dysfunction(ED)remains inadequately understood.Given that HUA is often associated with various metabolic disorders,this study aims to explore the multivariate linear impacts of metabolic parameters on erectile function in ED patients with HUA.A cross-sectional analysis was conducted involving 514 ED patients with HUA in the Department of Andrology,Jiangsu Province Hospital of Chinese Medicine(Nanjing,China),aged 18 to 60 years.General demographic information,medical history,and laboratory results were collected to assess metabolic disturbances.Sexual function was evaluated using the 5-item version of the International Index of Erectile Function(IIEF-5)questionnaire.Based on univariate analysis,variables associated with IIEF-5 scores were identified,and the correlations between them were evaluated.The effects of these variables on IIEF-5 scores were further explored by multiple linear regression models.Fasting plasma glucose(β=−0.628,P<0.001),uric acid(β=−0.552,P<0.001),triglycerides(β=−0.088,P=0.047),low-density lipoprotein cholesterol(β=−0.164,P=0.027),glycated hemoglobin(HbA1c;β=−0.562,P=0.012),and smoking history(β=−0.074,P=0.037)exhibited significant negative impacts on erectile function.The coefficient of determination(R²)for the model was 0.239,and the adjusted R²was 0.230,indicating overall statistical significance(F-statistic=26.52,P<0.001).Metabolic parameters play a crucial role in the development of ED.Maintaining normal metabolic indices may aid in the prevention and improvement of erectile function in ED patients with HUA.展开更多
Objective:Hyperuricemia(HUA)is a metabolic disease that threatens human health.The role of Penthorum chinense Pursh.(PCP)in the treatment of HUA has begun to receive attention in recent years.This study aimed to inves...Objective:Hyperuricemia(HUA)is a metabolic disease that threatens human health.The role of Penthorum chinense Pursh.(PCP)in the treatment of HUA has begun to receive attention in recent years.This study aimed to investigate the effects and potential mechanisms of PCP in HUA treatment.Methods:A HUA murine model was induced in C57/BL6 mice using potassium oxonate(PO)and adenine(AD).Serum uric acid(SUA)was measured using ultra-performance liquid chromatography(UPLC).Serum creatinine(Scr)was detected using a creatine oxidase assay kit,and serum blood urea nitrogen(BUN)was detected using a urease indophenol blue assay kit.Protein expression levels were detected using western blotting,and gut microbiota were detected using 16S rRNA.Results:PCP substantially improved the serum contents of SUA,Scr,and BUN and alleviated kidney injury.PCP promotes renal uric acid excretion by downregulating GLUT9 and URAT1 expression and upregulating ABCG2 and OAT1 expression PCP also regulated the NOD-like receptor family,pyrin domain-containing protein 3(NLRP3)pathway and reduced the expression of inflammatory factors,thus attenuating kidney injury in HUA mice.PCP regulated the structure of the gut microbiota,including the relative abundance of beneficial bacteria,such as Lactobacillus and Alistipes,which promoted uric acid metabolism and antiinflammatory effects.Conclusions:PCP can reduce uric acid levels by promoting renal uric acid excretion and regulating the gut microbiota.PCP improves kidney injury by inhibiting the activation of the NLRP3 signaling pathway and reducing the levels of inflammatory factors.展开更多
Hyperuricemia(HUA)is characterized by elevated levels of uric acid(UA)in the bloodstream,resulting from either excessive production or insufficient excretion of UA within the body.If left untreated,progressive or pers...Hyperuricemia(HUA)is characterized by elevated levels of uric acid(UA)in the bloodstream,resulting from either excessive production or insufficient excretion of UA within the body.If left untreated,progressive or persistent HUA can lead to gout,causing significant harm to human health.Lactic acid bacteria(LAB),generally recognized as safe(GRAS)probiotics,have been shown to alleviate symptoms associated with gastrointestinal disorders such as irritable bowel syndrome and inflammatory bowel disease while supporting overall bodily functions and health.Recently,LAB has emerged as a potentially safe,cost-effective and efficient treatment for HUA.This comprehensive review aims to explore the current literature on the mechanisms through which LAB controls HUA.These mechanisms include suppressing purine metabolism,absorbing purine compounds,modulating microbiota to maintain host global purine homeostasis,reducing intestinal permeability,producing metabolites that alleviate HUA symptoms,promoting the expression of urate excretory proteins and inhibiting the expression of urate reabsorption proteins.The findings presented in this review provide a framework for further investigation into how probiotic LAB can alleviate HUA by influencing UA metabolism and elucidating their underlying action mechanisms.展开更多
Objective:Evidence pertaining to the associations between hyperuricemia and diabetic microvascular complications is limited and inconclusive.In this study,we aimed to prospectively investigate the independent associat...Objective:Evidence pertaining to the associations between hyperuricemia and diabetic microvascular complications is limited and inconclusive.In this study,we aimed to prospectively investigate the independent associations of hyperuricemia and retinopathy,nephropathy and neuropathy in individuals with type 2 diabetes mellitus(T2DM).Methods:This cohort study enrolled 25,094 participants from UK Biobank with T2DM and without microvascular complications at baseline.Hyperuricemia was defined as serum uric acid(SUA)higher than 420μmol/L.The incidence of diabetic microvascular complications was identified from hospital inpatient records that were coded according to the International Classification of Diseases(ICD)-10 coding system.Multivariable adjusted Cox proportional hazards regression models were used to calculate adjusted hazard ratios(aHR).Results:Among all participants,3,844(15.3%)were classified as having hyperuricemia at baseline.During a median follow-up of 14.0 years,555(14.4%)individuals with hyperuricemia developed diabetic microvascular complications,compared with 12.6%of individuals without hyperuricemia(P=0.002).In the multivariable-adjusted model accounted for socioeconomic status,lifestyle factors,physical and biochemical measurements,and medication use,when compared with individuals of T2DM who had a normal SUA level,those with hyperuricemia had an 82.9%higher risk of developing diabetic nephropathy(95%CI:1.41-2.38,P<0.001),and a 30.2%higher risk of diabetic neuropathy(95%CI:1.06-1.60,P=0.011).However,the association between hyperuricemia and diabetic retinopathy was not statistically significant(aHR:1.070,95%CI:0.94-1.22,P=0.320).Conclusions:Hyperuricemia was independently associated with diabetic nephropathy and neuropathy but not retinopathy in individuals with T2DM.These findings underscore the importance of monitoring SUA level in prevention of certain microvascular complications.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
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(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
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
文摘BACKGROUND Major adverse cardiovascular(CV)events(MACEs)are the primary cause of morbidity and mortality in kidney transplantation(KT)recipients.The risk for MACEs is impacted by an array of traditional and transplant-related non-traditional CV risk factors.AIM To investigate the association between potential CV risk factors related to KT and MACEs,and their potential modification by hyperuricemia(HU).METHODS The relationship between CV risk factors related to KT and MACEs was examined in a cohort of 545 patients who underwent transplantation between 2008 and 2019.The mean age of patients at KT was 55.0 years±14.2 years(range 15.0–89.0 years).Univariate and multivariate logistic regression models were constructed to identify risk factors influencing MACEs.To explore the potential effect modification by uric acid(UA),patients were categorized into groups based on UA levels:(1)Low(<356μmol/L);(2)Normal(356–416μmol/L);(3)High(416–475μmol/L);and(4)Very high(>475μmol/L).RESULTS MACEs occurred in 145 of 545(26.6%)KT recipients.The most prevalent comorbidities were hypertension(87%),dyslipidemia(78%),secondary hyperparathyroidism(68%),HU(63%)and anemia(33%).In the multivariate logistic regression model,the most significant factors associated with MACEs were previous CV events[odds ratio(OR)=70.6,95%CI:24.9–200.1],left ventricular hypertrophy(LVH)(OR=12.6,95%CI:2.7–58.3),HU treatment(OR=4.3,95%CI:2.4–7.6),and anemia(OR=5.3,95%CI:2.9–9.8).Effect modification by the presence of HU revealed that independent factors associated with MACEs were age(OR=1.03,95%CI:1.0–1.1),previous CV events(OR=41.7,95%CI:13.6–127.6),LVH(OR=15.3,95%CI:2.0–116.6),HU treatment(OR=2.5,95%CI:1.3–4.6)and anemia(OR=5.4,95%CI:2.8–10.5).Effect modification by UA levels dichotomized at 475μmol/L(very high level of UA)revealed that HU treatment was not associated with MACEs in groups with or without very high UA levels.CONCLUSION A very high level of UA was observed to act as an effect-modifying factor for MACEs,especially when combined with other risk factors such as age,previous CV events,LVH,and anemia.
基金supported by the Key Program of National Natural Science Foundation of China(No.82241088)the Natural Science Foundation of Hubei Province(No.2022CFB813).
文摘The associations of polycyclic aromatic hydrocarbon(PAH)exposure with serum uric acid(SUA)or hyperuricemia have been rarely assessed.We aimed to investigate the relationships between urinary PAH metabolites and SUA or hyperuricemia among US adults and to explore the mediating role of systemic inflammation in the associations.A total of 10,307 US adults were conducted to assess the associations of seven urinary hydroxy–PAH with SUA and hyperuricemia and evaluate the role of C-reactive protein(CRP),a biomarker of systemic inflammation,in such associations.Results showed that each 1-unit increase in ln-transformed 2-hydroxynaphthalene(2-OHNa),1-hydroxyphenanthrene(1-OHPh),2&3-hydroxyphenanthrene(2&3-OHPh)and total hydroxyphenanthrene(OHPh)was associated with a 1.68(95%confidence interval(CI):0.19 to 3.17),2.46(0.78 to 4.13),3.34(1.59 to 5.09),and 2.99(1.23 to 4.75)μmol/L increase in SUA,and a 8%(odds ratio(OR):1.08,1.02 to 1.15),9%(OR:1.09,1.02 to 1.18),13%(OR:1.13,1.05 to 1.22),and 12%(OR:1.12,95%CI:1.03,1.21)increase in hyperuricemia,respectively.Co-exposure of seven PAHs was positively associated with SUA and hyperuricemia,with 2&3-OHPh showing the highest weight(components weights:0.83 and 0.78,respectively).The CRP mediated 11.47%and 10.44%of the associations ofΣOHPh and 2&3-OHPh with SUA and mediated 8.60%and 8.62%in associations ofΣOHPh and 2&3-OHPh with hyperuricemia,respectively.In conclusion,internal levels of PAH metabolites were associated with elevated SUA levels and the increased risk of hyperuricemia among US adults,and CRP played a mediating role in the associations.
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.
基金supported by National Science and Technology Fundamental Resources Investigation Program of China(2019FY100700).
文摘Hyperuricemia is a prevalent metabolic disorder resulting from dysregulation of purine metabolism,often accompanied by inflammation.It is characterized by an abnormal elevation in uric acid(UA)levels.In our investigation,the combined treatment with Lactiplantibacillus plantarum DY1 and quercetin suppressed the activity of xanthine oxidase and adenosine deaminase,decreased the levels of UA,tumor necrosis factor alpha(TNF-α)and interleukin 1β(IL-β),downregulated gene expression of urate transporter 1(URAT1)and glucose transporter 9(GLUT9),and upregulated organic anion transporter 1(OAT1)and ATP-binding cassette transporter subfamily G member 2(ABCG2).The combination increased the abundance of Lactobacillus and decreased the abundance of norank_f_norank_o__Clostridia_UCG-014 and Roseburia.Metabolomics analysis revealed that the combination of probiotics and quercetin exhibited distinct metabolic pathways compared to their individual administrations.When compared to probiotics alone,the combination led to alterations in glutathione metabolism(oxidized glutathione and glutathione)as well as sphingolipid metabolism(sphingosine and sphinganine).When compared to quercetin alone,the combination resulted in variations in tryptophan metabolism(indole-3-acetamide,5-hydroxy-L-tryptophan,indoleacetaldehyde,3-(3-indolyl)-2-oxopropanoic acid,3-indoleacetic acid and 3-methylindole)along with purine metabolism(UA,xanthosine,cyclic adenosine monophosphate(cAMP),adenosine diphosphate(ADP)and adenosine monophosphate(AMP)).The subsequent fecal microbiota transplantation proved that the effect of the combination on reducing UA levels was mediated by the gut microbiota.Therefore,this new combination can be considered a promising adjuvant therapy capable of synergistically alleviating hyperuricemia.
基金the National Natural Science Foundation of China(32325040)the Research Fund for the National Key R&D Program of China(2022YFD2100700).
文摘Modern lifestyle and diet have increased the incidence rate of uric acid(UA)metabolism-related diseases like hyperuricemia(HUA)and gout,posing heavy economic burden to individual patients and their families and the society.UA metabolism is a complex physiological process involving the kidney,intestine,and other organs.A number of factors together regulate UA metabolism,including genetics,diet,hormones,and the gut microbiota.This review summaries the gut microbiota features in subjects with HUA and gout,and the therapeutic effects of implementing microecological therapies(probiotics,prebiotics,or fecal microbiota transplant)that target modulate the gut microbiota and its downstream metabolism on the disease.Current evidence shows that these strategies are safe and promising in alleviate inflammation,reduce UA,and restoring a healthy gut microbiota in subjects with UA metabolism-related diseases.However,most clinical data are generated by animal studies.Therefore,we propose that vigorous human intervention trials should be conducted in the future to evaluate the therapeutic effects of microecological therapies in managing HUA and gout.
基金funded by National Key R&D Plan of China(2024YFE0109500)the National Natural Science Foundation of China(32472367,32372249)Key Program of the Natural Science Foundation of Zhejiang Province(HZSZ25C200001).
文摘Hyperuricemia(HUA)is a metabolic disease characterized by high levels of uric acid(UA)in the blood and varying degrees of kidney damage.Desirable nanoliposomes should simultaneously exhibit efficient biocompatibility and effective drug delivery.However,they both usually require special structural properties.Herein,we propose a strategy to prepare nanoliposomes with varying rigidity by replacing cholesterol(CH)with phytosterol esters(PE).The results showed that the particle size of PE naringenin nanoliposomes(PE-NAR)was 179.5 nm,and the encapsulation efficiency(EE)was 79.93%.In atomic force microscopy(AFM)tests,PE-NAR showed a 1-fold increase in rigidity compared to CH naringenin nanoliposomes(CH-NAR).By observing the effects of naringenin nanoliposomes(NAR-NLs)on the physiological and biochemical indicators in HUA mice,we explore its impact on kidney damage and inflammatory pathways in HUA mice.The results show that NAR-NLs significantly inhibit UA levels and improve kidney damage.Compared to oral naringenin,NAR-NLs generally enhance the in vivo antioxidant effects of naringenin.Furthermore,high-rigidity PE-NAR downregulated the renal inflammatory factor interleukin-1β(IL-1β)to 6.67%,demonstrating the highest inhibitory effect.Further experiments have demonstrated that naringenin exerts a protective effect in kidney injury by inhibiting the activation of NOD like receptor protein 3(NLRP3)inflammasome and reducing oxidative stress within the body.In summary,by adjusting the rigidity of the nanoliposomes,the oral administration of naringenin can effectively improve the alleviation of HUA.
基金Supported by the National Natural Science Foundation of China,No.82270865the Henan Provincial Key Research and Development Projects,No.231111313200+1 种基金the Henan Provincial Medical Science and Technology Research Program-the Provincial and Ministerial Major Projects,No.SBGJ202301002the Scientific and Technological Project in Henan Province,No.LHGJ20190614.
文摘BACKGROUND Gut microbiota play a crucial role in metabolic diseases,including type 2 diabetes(T2DM)and hyperuricemia(HUA).One-third of uric acid is excreted into the intestinal tract and further metabolized by gut microbiota.Thus,the gut microbiota might be a new therapeutic target for HUA.Empagliflozin significantly lowers serum uric acid levels and contributes to cardiovascular benefits which are partly attributed to altered gut microbiota.We hypothesize that gut dysbiosis in patients with diabetes and HUA,and the reduction of uric acid by empagliflozin,may be mediated by gut microbiota.AIM To investigate dysbiosis in patients with T2DM and HUA,and the effect of empagliflozin on gut microbiota associated with purine metabolism.METHODS In this age and sex-matched,case-control study,we recruited 30 patients with T2DM and HUA;30 with T2DM;and 30 healthy controls at the Henan Provincial People’s Hospital between February 2019 and August 2023.Nine patients with T2DM and HUA were treated with empagliflozin for three months.Gut microbiota profiles were assessed using the 16S rRNA gene.RESULTS Patients with T2DM and HUA had the highest total triglycerides(1.09 mmol/L in heathy control vs 1.56 mmol/L in T2DM vs 2.82 mmol/L in T2DM+HUA)and uric acid levels(302.50μmol/L in heathy control vs 288.50μmol/L in T2DM vs 466.50μmol/L in T2DM+HUA)among the three groups.The composition of the gut microbiota differed significantly between patients with T2DM and HUA,and those with T2DM/healthy controls(P<0.05).Notably,patients with T2DM and HUA demonstrated a deficiency of uric acid-degrading bacteria such as Romboutsia,Blautia,Clostridium sensu stricto 1(P<0.05).Empagliflozin treatment was associated with significantly reduced serum uric acid levels and purine metabolism-related pathways and genes in patients with T2DM and HUA(P<0.05).CONCLUSION Gut dysbiosis may contribute to the pathogenesis of HUA in T2DM,and empagliflozin may partly restore the gut microbiota related to uric acid metabolism.
文摘To elucidate the mechanisms underlying the therapeutic effects of the herbal medicine pair Smilax Glabra and Semen Coicis in treating gout and hyperuricemia,a comprehensive analysis was conducted using network pharmacology and molecular docking methods.Disease-associated targets for gout and hyperuricemia were identified from the GeneCards,OMIM,Disgenet,and TTD databases,while the key active components and their corresponding targets for Smilax Glabra and Semen Coicis were obtained from the TCSMP database.The intersection of these targets enabled the construction of a protein-protein interaction(PPI)network,which was subsequently visualized and analyzed.Core targets were further subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses to elucidate the biological processes and pathways involved.Molecular docking was then employed to validate the reliability of the interactions between the active components and the identified targets.The analysis revealed that Smilax Glabra and Semen Coicis contained 15 bioactive components that interacted with 393 potential targets,while gout and hyperuricemia were associated with 660 targets in total.The primary active compounds implicated in treating these conditions included diosgenin,quercetin,and naringenin,which were found to interact with crucial hub targets such as BCL2,CASP3,and MAPK3.These interactions suggested that the herbal medicine pair modulated several biological processes,including gland development and the regulation of body fluid levels,through pathways involving membrane rafts,membrane microdomains,and nuclear receptor activities.Enrichment analyses highlighted their involvement in multiple signaling pathways,such as EGFR tyrosine kinase inhibitor resistance,phospholipase D signaling,and platelet activation.Molecular docking confirmed the strong binding affinities between the hub genes and the major active components,supporting their potential role in therapeutic efficacy.This study demonstrated that Smilax Glabra and Semen Coicis might offer a promising therapeutic strategy for gout and hyperuricemia by targeting multiple molecular components,biological functions,and pathways.The findings underscored the unique potential of traditional Chinese medicine(TCM)in managing complex diseases by leveraging synergistic effects across diverse biological mechanisms.
基金supported by the National Natural Science Foundation of China(No.32122069)Beijing Outstanding Young Scientist Program(No.BJJWZYJH01201910011025)China Postdoctoral Science Foundation(No.2023M730134)。
文摘Globally,hyperuricemia is a growing health,social,and economic problem which could cause gout,chronic kidney diseases and other diseases.There are increasing evidences that a sensible diet makes sense to reduce the risk of hyperuricemia.This review aims to explore the metabolic mechanism of dietary factors and effects of dietary types associated with hyperuricemia.Recommendations for dietary modification to prevent hyperuricemia are as following:decreasing intake of animal organs,seafood,sugar-sweetened,and alcohol beverages is essential;choosing water or unsweetened tea and coffee instead of sweetened beverages is beneficial;and increasing intake of vegetables,reduced-fat dairy products,foods containing fiber,micronutrients and unsaturated fatty acids is helpful.In addition,consumption of fruits and legumes in moderation is advantageous,and low-fructose of fruits and low-purine of non-soy beans are recommended.Moreover,personalized diet needs to be emphasized for hyperuricemic patients accompanied with diverse metabolic diseases.
基金National Natural Science Foundations of China(Grant No.81960863)the Education Department of Yunnan Province(Grant No.2023Y0463 and 2024Y380)Yunnan Clinical Research Center for rheumatism in Traditional Chinese Medicine(Grant No.202405AJ310004).
文摘Hyperuricemia(HUA)is a metabolic disorder characterized by elevated levels of uric acid in the blood,resulting from either increased production or decreased excretion of uric acid.This condition has reached epidemic proportions.Conventional Western medical treatments often come with a range of adverse effects.According to traditional Chinese medicine(TCM),the root cause of HUA lies in the spleen’s insufficient healthy movement,with phlegm,dampness,turbidity,and stasis being symptomatic manifestations.Research has shown that spleen-strengthening herbal remedies can effectively treat HUA by inhibiting uric acid synthesis enzymes,promoting uric acid excretion,reducing inflammation,providing antioxidant benefits,regulating gut microbiota,and modulating cellular processes.Clinical applications have substantiated these findings.Therefore,from the standpoint of symptomatic treatment of HUA,spleen-strengthening therapies hold significant importance and potential.
基金supported by the National College Student Innovation and Entrepreneurship Project.
文摘Hyperuricemia(HUA)refers to a condition where fasting serum uric acid levels exceed 420μmol/L in men and 350μmol/L in women,affecting 17.4%of China’s general population,showing increasing prevalence among younger individuals.Luteolin,a common flavonoid compound,exhibits multiple biological effects,including inhibition of tumor proliferation and inflammatory responses.It also suppresses the activity of urate transporter 1(URAT1),promoting uric acid excretion.This study is the first to integrate network toxicology and network pharmacology approaches to systematically analyze the multi-target mechanisms of adenine-induced HUA and luteolin-treated HUA,with molecular docking validation of interaction targets.We constructed compound-pathway-intersection gene networks and a dual-group PPI network to analyze the mechanisms of adenine-induced HUA and luteolin-treated HUA.The dual-group PPI network identified 7 shared targets,namely XDH,PYGL,IL10,PPARG,TNF,VEGFA,and MAOA,involving core intersecting pathways such as purine-xanthine metabolism and insulin resistance.Luteolin may activate PPARG to regulate inflammation and uric acid excretion modules in the adenine network.GO-KEGG analysis indicates that intersection genes for adenine pathogenesis involve diverse biological processes,cellular components,and molecular functions,with core target KEGG analysis revealing 15 signaling pathways.Luteolin’s therapeutic targets are associated with more entries,and its core target KEGG analysis identified 46 signaling pathways.Molecular docking shows TNF,PPARG,and PYGL bind to both luteolin and adenine with negative binding energies,and luteolin’s binding energies are all below 5 kJ/mol,confirming stable binding.Luteolin’s anti-HUA mechanism is characterized by inhibition of production,promotion of excretion,anti-inflammation and metabolic regulation,but interactions with gut microbiota metabolites require further study.
基金supported by the Key Program of the National Natural Science Foundation of China(No.82241088).
文摘The health effects of traffic-derived pollutants have gathered increasing concerns.Our objectives were to evaluate the associations of traffic-related heavy metal exposure with serum uric acid(SUA)and hyperuricemia and to explore the underlying mechanism.Traffic-related heavy metals(including zinc,iron,manganese,copper,lead,cadmium,antimony,and barium)and SUA were determined among 3909 community-based adults from the Wuhan-Zhuhai cohort.Various regression methods were applied to assess the association of heavy metals with SUA and hyperuricemia.Furthermore,mediation analyses were employed to evaluate the potential role of systemic inflammation in these associations.In single metal analyses,positive dose-response relationships between urinary zinc,iron,manganese,and antimony and SUA were observed.Furthermore,each 1-unit increase of ln-transformed urinary zinc levels was related to a 37.9%(OR=1.379,95%CI:1.148 to 1.657)increase in the hyperuricemia risk.In multiple metal analyses,both Bayesian kernel machine regression(BKMR)and weighted quantile sum regression(WQS)models showed positive associations of heavy metals mixture with SUA and hyperuricemia risk,and WQS analyses further revealed that zinc was the dominant metal(component weight:0.611 and 0.594,respectively).Additionally,plasma C-reactive protein(CRP)mediated 4.919%and 8.417%of the association of urinary zinc with SUA and hyperuricemia,respectively.In conclusion,exposure to several traffic-related heavy metals or traffic-related heavy metal mixtures were positively associated with SUA and hyperuricemia risk in the general Chinese population,in which zinc played a dominating role.Plasma CRP might partly mediate the association of urinary zinc with SUA and hyperuricemia risk.
基金supported by Jiangsu Provincial Science and Technology Plan Special Project(No.BK20231379)Key Project of Jiangsu Provincial Health Commission(No.ZDA2020025)+1 种基金Jiangsu Traditional Chinese Medicine Science and Technology Development Plan Project(No.MS2022023)Excellent Young Doctor Training Program of Jiangsu Province Hospital of Chinese Medicine(No.2023QB0126).
文摘The relationship between hyperuricemia(HUA)and erectile dysfunction(ED)remains inadequately understood.Given that HUA is often associated with various metabolic disorders,this study aims to explore the multivariate linear impacts of metabolic parameters on erectile function in ED patients with HUA.A cross-sectional analysis was conducted involving 514 ED patients with HUA in the Department of Andrology,Jiangsu Province Hospital of Chinese Medicine(Nanjing,China),aged 18 to 60 years.General demographic information,medical history,and laboratory results were collected to assess metabolic disturbances.Sexual function was evaluated using the 5-item version of the International Index of Erectile Function(IIEF-5)questionnaire.Based on univariate analysis,variables associated with IIEF-5 scores were identified,and the correlations between them were evaluated.The effects of these variables on IIEF-5 scores were further explored by multiple linear regression models.Fasting plasma glucose(β=−0.628,P<0.001),uric acid(β=−0.552,P<0.001),triglycerides(β=−0.088,P=0.047),low-density lipoprotein cholesterol(β=−0.164,P=0.027),glycated hemoglobin(HbA1c;β=−0.562,P=0.012),and smoking history(β=−0.074,P=0.037)exhibited significant negative impacts on erectile function.The coefficient of determination(R²)for the model was 0.239,and the adjusted R²was 0.230,indicating overall statistical significance(F-statistic=26.52,P<0.001).Metabolic parameters play a crucial role in the development of ED.Maintaining normal metabolic indices may aid in the prevention and improvement of erectile function in ED patients with HUA.
基金funded by the National Natural Science Foundation of China(82304870)Innovation Team and Talents Cultivation Program of National Administmiceion of Traditional Chinese Medicine(ZYYCXTD-C-202009)+1 种基金Tianjin Municipal Health Commission Project(2024009)Tianjin University Students’Innovation and Entrepreneurship Training Program Project(202410063027).
文摘Objective:Hyperuricemia(HUA)is a metabolic disease that threatens human health.The role of Penthorum chinense Pursh.(PCP)in the treatment of HUA has begun to receive attention in recent years.This study aimed to investigate the effects and potential mechanisms of PCP in HUA treatment.Methods:A HUA murine model was induced in C57/BL6 mice using potassium oxonate(PO)and adenine(AD).Serum uric acid(SUA)was measured using ultra-performance liquid chromatography(UPLC).Serum creatinine(Scr)was detected using a creatine oxidase assay kit,and serum blood urea nitrogen(BUN)was detected using a urease indophenol blue assay kit.Protein expression levels were detected using western blotting,and gut microbiota were detected using 16S rRNA.Results:PCP substantially improved the serum contents of SUA,Scr,and BUN and alleviated kidney injury.PCP promotes renal uric acid excretion by downregulating GLUT9 and URAT1 expression and upregulating ABCG2 and OAT1 expression PCP also regulated the NOD-like receptor family,pyrin domain-containing protein 3(NLRP3)pathway and reduced the expression of inflammatory factors,thus attenuating kidney injury in HUA mice.PCP regulated the structure of the gut microbiota,including the relative abundance of beneficial bacteria,such as Lactobacillus and Alistipes,which promoted uric acid metabolism and antiinflammatory effects.Conclusions:PCP can reduce uric acid levels by promoting renal uric acid excretion and regulating the gut microbiota.PCP improves kidney injury by inhibiting the activation of the NLRP3 signaling pathway and reducing the levels of inflammatory factors.
基金funded by National Natural Science Foundation of China(32360564)the Natural Science and Technology Innovation Development Multiplication Plan of Guangxi University(2022BZRC010)。
文摘Hyperuricemia(HUA)is characterized by elevated levels of uric acid(UA)in the bloodstream,resulting from either excessive production or insufficient excretion of UA within the body.If left untreated,progressive or persistent HUA can lead to gout,causing significant harm to human health.Lactic acid bacteria(LAB),generally recognized as safe(GRAS)probiotics,have been shown to alleviate symptoms associated with gastrointestinal disorders such as irritable bowel syndrome and inflammatory bowel disease while supporting overall bodily functions and health.Recently,LAB has emerged as a potentially safe,cost-effective and efficient treatment for HUA.This comprehensive review aims to explore the current literature on the mechanisms through which LAB controls HUA.These mechanisms include suppressing purine metabolism,absorbing purine compounds,modulating microbiota to maintain host global purine homeostasis,reducing intestinal permeability,producing metabolites that alleviate HUA symptoms,promoting the expression of urate excretory proteins and inhibiting the expression of urate reabsorption proteins.The findings presented in this review provide a framework for further investigation into how probiotic LAB can alleviate HUA by influencing UA metabolism and elucidating their underlying action mechanisms.
基金supported by the Guangzhou Basic Research Program,City&University(Institute)Joint Funding Project(2023A03J0174).
文摘Objective:Evidence pertaining to the associations between hyperuricemia and diabetic microvascular complications is limited and inconclusive.In this study,we aimed to prospectively investigate the independent associations of hyperuricemia and retinopathy,nephropathy and neuropathy in individuals with type 2 diabetes mellitus(T2DM).Methods:This cohort study enrolled 25,094 participants from UK Biobank with T2DM and without microvascular complications at baseline.Hyperuricemia was defined as serum uric acid(SUA)higher than 420μmol/L.The incidence of diabetic microvascular complications was identified from hospital inpatient records that were coded according to the International Classification of Diseases(ICD)-10 coding system.Multivariable adjusted Cox proportional hazards regression models were used to calculate adjusted hazard ratios(aHR).Results:Among all participants,3,844(15.3%)were classified as having hyperuricemia at baseline.During a median follow-up of 14.0 years,555(14.4%)individuals with hyperuricemia developed diabetic microvascular complications,compared with 12.6%of individuals without hyperuricemia(P=0.002).In the multivariable-adjusted model accounted for socioeconomic status,lifestyle factors,physical and biochemical measurements,and medication use,when compared with individuals of T2DM who had a normal SUA level,those with hyperuricemia had an 82.9%higher risk of developing diabetic nephropathy(95%CI:1.41-2.38,P<0.001),and a 30.2%higher risk of diabetic neuropathy(95%CI:1.06-1.60,P=0.011).However,the association between hyperuricemia and diabetic retinopathy was not statistically significant(aHR:1.070,95%CI:0.94-1.22,P=0.320).Conclusions:Hyperuricemia was independently associated with diabetic nephropathy and neuropathy but not retinopathy in individuals with T2DM.These findings underscore the importance of monitoring SUA level in prevention of certain microvascular complications.
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.
