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
Stroke,a major cerebrovascular disease,has high morbidity and mortality.Effective methods to reduce the risk and improve the prognosis are lacking.Currently,uric acid(UA)is associated with the pathological mechanism,p...Stroke,a major cerebrovascular disease,has high morbidity and mortality.Effective methods to reduce the risk and improve the prognosis are lacking.Currently,uric acid(UA)is associated with the pathological mechanism,prognosis,and therapy of stroke.UA plays pro/anti-oxidative and pro-inflammatory roles in vivo.The specific role of UA in stroke,which may have both neuroprotective and damaging effects,remains unclear.There is a U-shaped association between serum uric acid(SUA)levels and ischemic stroke(IS).UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke(AIS).Urate-lowering therapy(ULT)plays a protective role in IS with hyperuricemia or gout.SUA levels are associated with the cerebrovascular injury mechanism,risk,and outcomes of hemorrhagic stroke.In this review,we summarize the current research on the role of UA in stroke,providing potential targets for its prediction and treatment.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 The association between the uric acid-to-high-density lipoprotein cholesterol ratio(UHR)and mental health among individuals with type 2 diabetes mellitus(T2DM)has not been thoroughly investigated.AIM To exa...BACKGROUND The association between the uric acid-to-high-density lipoprotein cholesterol ratio(UHR)and mental health among individuals with type 2 diabetes mellitus(T2DM)has not been thoroughly investigated.AIM To examine the link between UHR and symptoms of depression and anxiety in patients with T2DM.METHODS A cross-sectional analysis was carried out from March 2023 to April 2024,involving participants diagnosed with T2DM.Data on sociodemographic characteristics,clinical parameters,and UHR values were systematically gathered.The Self-Rating Depression Scale(SDS)and Self-Rating Anxiety Scale(SAS)were utilized to evaluate depressive and anxiety symptoms,respectively.To assess the relationships between UHR and SDS/SAS scores,linear regression models were employed,incorporating adjustments for potential confounding variables.Additionally,smooth curve fitting and threshold effect analyses were conducted to explore potential nonlinear relationships.RESULTS A total of 285 patients with T2DM were included.Initial univariate analysis demonstrated a significant positive correlation between elevated UHR levels and higher SDS and SAS scores.Multivariate regression analysis revealed that a one-unit rise in UHR was associated with a 1.13-point increase in SDS scores(95%CI:0.69-1.58)and a 0.57-point increase in SAS scores(95%CI:0.20-0.93).After controlling for confounders,UHR remained positively correlated with SDS(β=1.55,95%CI:0.57-2.53)and SAS(β=0.72,95%CI:0.35-1.09).Nonlinear analysis identified critical thresholds at UHR values of 5.02 for SDS and 4.00 for SAS,beyond which the relationships between UHR and psychological symptom scores became markedly stronger(P<0.05).CONCLUSION Higher UHR levels are significantly linked to exacerbated depressive and anxiety symptoms in patients with T2DM.These results indicate that UHR may function as a promising biomarker to identify individuals at greater risk of mental health complications within this population.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
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
Probiotics have been demonstrated to be effective and safe for hyperuricemia(HUA)and gout treatment.Hence,identifying microbes with high uric acid-or purine-metabolizing ability is highly important.Due to the high loa...Probiotics have been demonstrated to be effective and safe for hyperuricemia(HUA)and gout treatment.Hence,identifying microbes with high uric acid-or purine-metabolizing ability is highly important.Due to the high load of uric acid in chicken feces,we hypothesized that the chicken gut would be an excellent source for new uric acid or purine-metabolizing microbes.In this study,we examined chicken gut contents to isolate an Enterococcus faecalis strain(designated CML390)that displayed high uric acid-degrading ability.In vitro experiments indicated that E.faecalis CML390 could effectively metabolize uric acid under both aerobic and anaerobic conditions,and the richer the nutrients,the higher the rate of uric acid degradation.By integrating genomics,transcriptomics,and metabolomics analyses,we revealed two pathways involved in aerobic and anaerobic uric acid degradation,respectively,in this isolate.E.faecalis CML390 relies on oxygen to metabolize uric acid into substances such as allantoin under aerobic conditions,while it also harbors a conserved uric acid-inducible gene cluster for anaerobic uric acid metabolism.An in vivo experiment showed that gavage with live E.faecalis CML390 in a mouse model of HUA(established using a combination of uric acid and potassium oxonate)significantly reduced serum uric acid levels and alleviated HUA.Our findings contribute to the exploration of the pathways and mechanisms of uric acid metabolism in intestinal microorganisms and provide a candidate probiotic for the treatment of HUA and gout.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
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
Hyperuricemia(HUA)and gout became typical metabolic disorders characterized by multiple pathogenic factors.Their incidence increased annually,affecting younger populations.Given that uric acid(UA)and inflammation were...Hyperuricemia(HUA)and gout became typical metabolic disorders characterized by multiple pathogenic factors.Their incidence increased annually,affecting younger populations.Given that uric acid(UA)and inflammation were the primary disease mechanisms,the search for effective and low-side-effect UA-lowering and anti-inflammatory drugs became a pressing scientific priority.Traditional Chinese medicine(TCM)encompassed a rich array of theoretical and practical experience,along with a diverse range of chemical substances,making herbs or their components potential sources for therapeutic drugs.Despite the significant role that modern herbal medicines played in treating HUA and gout,the existing research literature remained fragmented,lacking comprehensive and systematic reviews.In this review,we focused on the regulation of UA and summarized the discovery of UA-lowering pharmacodynamic components or ingredients derived from herbs and formulas,as well as their multi-targeted mechanisms of action.Emphasizing this focus,we proposed that,compared to acute inflammation,low-grade inflammation may play a relatively“unnoticed”role in the disease process.In contrast to Western medicine,we discussed the risks and benefits of herbal medicines and their ingredients for treatment,drawing from theoretical insights and clinical practice.This review offered comprehensive perspectives on the research into anti-HUA and gout treatments using herbal medicines and their natural products.Additionally,it provided a forward-looking view on natural product discovery,the exploration of therapeutic strategies,and new drug research in this field.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
Volatile organic chemicals(VOC)have been identified as hazardous pollutants impairing human health.While whether the VOC exposure was associated with hyperuricemia is yet clarified.All the data was acquired from 6 sur...Volatile organic chemicals(VOC)have been identified as hazardous pollutants impairing human health.While whether the VOC exposure was associated with hyperuricemia is yet clarified.All the data was acquired from 6 survey cycles of the National Health and Nutrition Examination Survey(NHANES)program(2005–2006,2011–2012,2013–2014,2015–2016,2017–2018,2017–2020).Hyperuricemia was defined as a serum uric acid(SUA)concentration exceeding 7 mg/mL in men or 6 mg/mL in women.Three quantile logistic regression modelswith varied covariateswere developed to analyze the correlation between hyperuricemia and volatile organic chemical metabolites(VOCs)in urine,and three quantile linear regression models were used for examining the correlation between VOCs and SUA.N-acetyl-S-(2-carboxyethyl)-l-cysteine(CEMA),N-acetyl-S-(3,4-dihydroxybutyl)-l-cysteine(DHBM),and phenylglyoxylic acid(PHGA)were identified to associated positively with increased hyperuricemia risk and uric acid level.Meanwhile,the weighted quantile sum(WQS)model suggested a positive association between VOCs exposure and hyperuricemia.These data indicate that VOC exposure potentially increases hyperuricemia risk,necessitating policies to mitigate VOC exposure.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
BACKGROUND Lower salivary uric acid concentrations,the most abundant antioxidant agent in saliva,have been observed in patients with periodontitis compared to individuals with periodontal health.However,the independen...BACKGROUND Lower salivary uric acid concentrations,the most abundant antioxidant agent in saliva,have been observed in patients with periodontitis compared to individuals with periodontal health.However,the independent association of salivary uric acid levels with periodontitis,accounting for other risk factors,as well as its association with periodontitis severity,has not been investigated.AIM To the independent association of salivary uric acid levels with periodontitis and the association of salivary uric acid levels with the severity of periodontitis.METHODS This observational and prospective study measured salivary uric acid levels in subjects with periodontitis(characterized by periodontal loss of tissue)and in subjects without periodontitis(periodontal health or localized gingivitis in<30%of sites).Multivariate regression analysis was performed to determine independent factors associated with periodontitis.Spearman’s rho correlation coefficient was used to assess the relationship between salivary uric acid levels and periodontitis severity.A receiver operating characteristic analysis was carried out to evaluate the diagnostic performance of salivary uric acid levels in periodontitis,reporting the area under curve(AUC)and its 95%CI.RESULTS We included 121 subjects,61 of them with periodontitis and 60 without periodontitis(39 with periodontal health and 21 with local gingivitis).Subjects with periodontitis compared to those without periodontitis were older(P<0.001),had higher salivary uric acid levels(P=0.002),higher rate of arterial hypertension history(P=0.001)and higher rate of never-smoker history(P<0.001).The AUC for periodontitis diagnosis by salivary uric acid levels was 66%(95%CI:57%-75%;P<0.001)and the better cut-off point was 111 nmol/mL.Multiple logistic regression analysis showed an independent association of salivary uric acid levels<111 nmol/mL(OR=6.14;95%CI:2.015-18.721;P=0.001)with periodontitis after controlling for age,never-smoker history and arterial hypertension.A negative correlation of salivary uric acid levels and periodontitis severity was observed(rho=-0.32;P<0.001).CONCLUSION The two novel findings of our research were,first,that low salivary uric acid concentrations are independently associated with periodontitis,even after accounting for established risk factors.Second,salivary uric acid levels show a negative correlation with periodontitis severity.展开更多
In this letter,we delve into the groundbreaking research by Lorente et al,which sheds light on the intricate relationship between low salivary uric acid levels and periodontitis.The study not only confirms previous ob...In this letter,we delve into the groundbreaking research by Lorente et al,which sheds light on the intricate relationship between low salivary uric acid levels and periodontitis.The study not only confirms previous observations of reduced salivary uric acid concentrations in periodontitis patients but also establishes,for the first time,an independent association between these two factors,even when controlling for traditional risk factors such as age,smoking status,and arterial hypertension.Moreover,the findings reveal a significant negative correlation between salivary uric acid levels and the severity of periodontitis,suggesting that this biomarker may serve as a valuable indicator of disease progression.These discoveries open new avenues for understanding the pathophysiology of period-ontitis and pave the way for innovative diagnostic and therapeutic strategies.The potential clinical applications of salivary uric acid measurement,such as guiding personalized treatment plans and monitoring disease activity,warrant further exploration to enhance patient care and improve outcomes in this prevalent inflammatory condition.展开更多
OBJECTIVE:To elucidate the potential mechanisms of Shizhi Fang(SZF,矢志方)in the treatment of uric acid nephropathy(UAN).METHODS:SZF-containing serum was prepared from six male rats and analyzed using ultra-high-perfo...OBJECTIVE:To elucidate the potential mechanisms of Shizhi Fang(SZF,矢志方)in the treatment of uric acid nephropathy(UAN).METHODS:SZF-containing serum was prepared from six male rats and analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS).Network pharmacology was employed was integrated with UPLC-Q-TOF-MS to predict SZF targets for the treatment of UAN,which were subsequently validated through in vivo experiments.Sixty male Bagg Albino Laboratory-Bred Mouse,substrain c mice were randomly allocated into six groups:Normal,Model,Febuxostat,and three SZF dosage groups.Except for the Normal group,all mice were administered potassium oxonate(250 mg/kg)and adenine(50 mg/kg)via gavage to induce UAN.Four hours postadministration,the Febuxostat group received Febuxostat(6 mg/kg),while the SZF groups received low(0.234 g/kg),medium(0.468 g/kg),or high(0.936 g/kg)doses of SZF.The Normal and Model groups were given an equivalent volume of saline.All treatments were conducted over a period of four weeks.Urine and blood samples were collected for biochemical analysis,and kidney tissues were subjected to histopathological examination and Western blot analysis.RESULTS:Nine prototype compounds and 30 metabolites were identified in SZF serum.Network pharmacology analysis revealed 195 drug targets and 1608 disease targets,with 76 common drug-disease targets,including signal transducer and activator of transcription 3(STAT3),proto-oncogene tyrosine-protein kinase Src(SRC),matrix metalloproteinase-9(MMP9),Caspase 3,and toll-like receptor 4(TLR4)as key targets.Gene Ontology analysis identified 325 biological processes,48 cellular components,and 72 molecular functions,while Kyoto Encyclopedia of Genes and Genomes analysis identified 113 pathways.Molecular docking demonstrated strong binding affinities between active compounds and their targets.In the animal study,SZF treatment alleviated pathological damage and improved serum and urine biochemical markers compared to the Model group(P<0.05,P<0.01,P<0.001).Western blot analysis showed a significant reduction in phosphorylated-STAT3,phosphorylatedSRC,MMP9,TLR4,and Caspase3 expression in renal tissues of SZF-treated mice(P<0.001).CONCLUSION:SZF may exert therapeutic effects on UAN through multiple targets and pathways.展开更多
This article explores the association between salivary uric acid(UA)and periodontitis,systematically analyzing its dual roles and research progress.Studies indicate that UA acts as a primary antioxidant in saliva unde...This article explores the association between salivary uric acid(UA)and periodontitis,systematically analyzing its dual roles and research progress.Studies indicate that UA acts as a primary antioxidant in saliva under physiological conditions(accounting for 70%),protecting periodontal tissues by scavenging reactive oxygen species.However,when gum disease becomes severe,UA can switch roles and fuel inflammation,worsening tissue damage.Lorente et al’s research found an independent inverse correlation between salivary UA levels and periodontitis severity(odds ratio=6.14,P=0.001),establishing 111 nmol/mL as a diagnostic threshold(area under the curve=66%).Nevertheless,limitations include sample heterogeneity and failure to distinguish between gingivitis and periodontitis.Mechanistically,three hypotheses are proposed:The Antioxidant Depletion Hypothesis(UA oxidation consumption leading to feedback loops),the Microbial Metabolic Hijacking Hypothesis(pathogens utilizing UA as a carbon source to disrupt redox balance),and the Epithelial Barrier Dysfunction Hypothesis(UA deficiency causing downregulation of tight junction proteins).Future research should prioritize longitudinal cohorts to validate predictive value,integrate multi-omics to explore dysregulated signatures,and develop UA supplementation or targeted antioxidant therapies.This study provides novel insights into periodontitis diagnosis and mechanisms,advancing the application of salivary biomarkers in precision periodontics.展开更多
Backgroundd The uric acid to albumin ratio(UAR)has emerged as a potential biomarker for systemic inflammation and oxidative stress,both of which are implicated in adverse outcomes following cardiac surgery.This study ...Backgroundd The uric acid to albumin ratio(UAR)has emerged as a potential biomarker for systemic inflammation and oxidative stress,both of which are implicated in adverse outcomes following cardiac surgery.This study aimed to explore the association between UAR and long-Term mortality in elderly patients undergoing heart valve surgery.MethodsA retrospective cohort study was conducted on 202 elderly patients who underwent valve surgery in the Cardiac Surgery Intensive Care Unit(CSICU)between January 2013 and April 2014.Patients were stratified into three groups based on UAR level(low:5.66-10.26;middle:10.29-13.47;high:13.48-31.88).The multivariable cox regression analysis with covariate adjustment and subgroup analyses were performed to evaluate the association between UAR and long-term mortality,with a median follow-up period of 7.9 years.Smooth curve fitting was used to evaluate the potential linear association between UAR and long-term follow-up mortality.Kaplan-Meier curves with log-rank tests were generated to compare survival distributions among UAR groups.Results In multivariate regression models,UAR demonstrated a significant positive association with long-term follow-up mortality after comprehensive covariates adjustment.The adjusted hazard ratios(HR)for long-term follow-up mortality was 1.22(95%CI:1.10-1.34,P<0.0001)per 1-unit increase in UAR.We further performed exploratory subgroup analyses which confirmed a higher UAR levels were independently associated with a higher risk of mortality.Kaplan-Meier analysis for event-free survival revealed higher occurrence of long-term follow-up mortality in the high UAR group(P=0.013).Conclusions Elevated UAR levels in elderly patients who underwent valvular surgery in the CSICU demonstrated an positivecorrelation with mortality risk.展开更多
BACKGROUND Uric acid(UA),a key antioxidant metabolite,demonstrates dual roles in cancer.Unfortunately,studies on its role in colon cancer risk are uncommon,and the limited results are inconsistent.AIM To elucidate the...BACKGROUND Uric acid(UA),a key antioxidant metabolite,demonstrates dual roles in cancer.Unfortunately,studies on its role in colon cancer risk are uncommon,and the limited results are inconsistent.AIM To elucidate the association between UA and colon cancer risk and its me-chanisms.METHODS Multivariate logistic regression analysis evaluated the association between UA levels and colon cancer risk.Non-linear relationships were illustrated using restricted cubic splines.The threshold effect was performed to identify cut-off points.Human colon cancer cell lines(HCT-116 and HT29)were exposed to UA for 48 hours.Cell viability was assessed via the cell counting kit-8 assay.The evaluation of cell migration involved wound healing and transwell migration assays.HCT-116 cells were exposed to 4 mg/dL UA for 48 hours.The impact of the subsequent treatment with a phosphoinositide 3-kinases(PI3K)agonist and UA was assessed.RESULTS After adjusting for potential confounders,an inverse association was observed between UA and colon cancer risk(odds ratio=0.65,P<0.05).A non-linear relationship was identified,with a 4.79 mg/dL cut-off point(P<0.05).UA inhibited colon cancer cell proliferation and migration.These effects were mediated by the induction of reactive oxygen species and the suppression of the PI3K/protein kinase B/mammalian target of rapamycin pathway.CONCLUSION UA acts as a protective agent against colon cancer by inhibiting cell proliferation and migration through increased reactive oxygen species production and modulation of the PI3K/protein kinase B/mammalian target of rapamycin pathway.展开更多
Growing evidences showed that heavy metals exposure may be associated with metabolic diseases.Nevertheless,themechanism underlying arsenic(As)exposure and metabolic syndrome(MetS)risk has not been fully elucidated.So ...Growing evidences showed that heavy metals exposure may be associated with metabolic diseases.Nevertheless,themechanism underlying arsenic(As)exposure and metabolic syndrome(MetS)risk has not been fully elucidated.So we aimed to prospectively investigate the role of serum uric acid(SUA)on the association between blood As exposure and incident MetS.A sample of 1045 older participants in a community in China was analyzed.We determined As at baseline and SUA concentration at follow-up in the Yiwu Elderly Cohort.MetS events were defined according to the criteria of the International Diabetes Federation(IDF).Generalized linear model with log-binominal regression model was applied to estimate the association of As with incident MetS.To investigate the role of SUA in the association between As andMetS,amediation analysiswas conducted.In the fully adjusted log-binominal model,per interquartile range increment of As,the risk of MetS increased 1.25-fold.Compared with the lowest quartile of As,the adjusted relative risk(RR)of MetS in the highest quartile was 1.42(95%confidence interval,CI:1.03,2.00).Additionally,blood As was positively associated with SUA,while SUA had significant association with MetS risk.Further mediation analysis demonstrated that the association of As and MetS risk was mediated by SUA,with the proportion of 15.7%.Our study found higher As was remarkably associated with the elevated risk of MetS in the Chinese older adults population.Mediation analysis indicated that SUA might be a mediator in the association between As exposure and MetS.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 National Natural Science Foundation of China(82371300)Zhejiang Provincial Natural Science Foundation of China(LY23H090014)Zhejiang Province Traditional Chinese Medicine Science and Technology Project(2024ZL1215).
文摘Stroke,a major cerebrovascular disease,has high morbidity and mortality.Effective methods to reduce the risk and improve the prognosis are lacking.Currently,uric acid(UA)is associated with the pathological mechanism,prognosis,and therapy of stroke.UA plays pro/anti-oxidative and pro-inflammatory roles in vivo.The specific role of UA in stroke,which may have both neuroprotective and damaging effects,remains unclear.There is a U-shaped association between serum uric acid(SUA)levels and ischemic stroke(IS).UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke(AIS).Urate-lowering therapy(ULT)plays a protective role in IS with hyperuricemia or gout.SUA levels are associated with the cerebrovascular injury mechanism,risk,and outcomes of hemorrhagic stroke.In this review,we summarize the current research on the role of UA in stroke,providing potential targets for its prediction and treatment.
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 Science and Technology Program of Quzhou,China,No.2022K67Zhejiang Medical Association Clinical Research Fund Project,No.2024ZYC-A526and the Research Project of Quzhou People’s Hospital,No.KYQD2024-006.
文摘BACKGROUND The association between the uric acid-to-high-density lipoprotein cholesterol ratio(UHR)and mental health among individuals with type 2 diabetes mellitus(T2DM)has not been thoroughly investigated.AIM To examine the link between UHR and symptoms of depression and anxiety in patients with T2DM.METHODS A cross-sectional analysis was carried out from March 2023 to April 2024,involving participants diagnosed with T2DM.Data on sociodemographic characteristics,clinical parameters,and UHR values were systematically gathered.The Self-Rating Depression Scale(SDS)and Self-Rating Anxiety Scale(SAS)were utilized to evaluate depressive and anxiety symptoms,respectively.To assess the relationships between UHR and SDS/SAS scores,linear regression models were employed,incorporating adjustments for potential confounding variables.Additionally,smooth curve fitting and threshold effect analyses were conducted to explore potential nonlinear relationships.RESULTS A total of 285 patients with T2DM were included.Initial univariate analysis demonstrated a significant positive correlation between elevated UHR levels and higher SDS and SAS scores.Multivariate regression analysis revealed that a one-unit rise in UHR was associated with a 1.13-point increase in SDS scores(95%CI:0.69-1.58)and a 0.57-point increase in SAS scores(95%CI:0.20-0.93).After controlling for confounders,UHR remained positively correlated with SDS(β=1.55,95%CI:0.57-2.53)and SAS(β=0.72,95%CI:0.35-1.09).Nonlinear analysis identified critical thresholds at UHR values of 5.02 for SDS and 4.00 for SAS,beyond which the relationships between UHR and psychological symptom scores became markedly stronger(P<0.05).CONCLUSION Higher UHR levels are significantly linked to exacerbated depressive and anxiety symptoms in patients with T2DM.These results indicate that UHR may function as a promising biomarker to identify individuals at greater risk of mental health complications within this population.
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 the National Key Research and Development Program of China(2022YFA1304200)the Beijing Natural Science Foundation(6222032)the Starting Grants Program for Young Talents at China Agricultural University,the 2115 Talent Development Program of China Agricultural University,and Chinese Universities Scientific Fund.
文摘Probiotics have been demonstrated to be effective and safe for hyperuricemia(HUA)and gout treatment.Hence,identifying microbes with high uric acid-or purine-metabolizing ability is highly important.Due to the high load of uric acid in chicken feces,we hypothesized that the chicken gut would be an excellent source for new uric acid or purine-metabolizing microbes.In this study,we examined chicken gut contents to isolate an Enterococcus faecalis strain(designated CML390)that displayed high uric acid-degrading ability.In vitro experiments indicated that E.faecalis CML390 could effectively metabolize uric acid under both aerobic and anaerobic conditions,and the richer the nutrients,the higher the rate of uric acid degradation.By integrating genomics,transcriptomics,and metabolomics analyses,we revealed two pathways involved in aerobic and anaerobic uric acid degradation,respectively,in this isolate.E.faecalis CML390 relies on oxygen to metabolize uric acid into substances such as allantoin under aerobic conditions,while it also harbors a conserved uric acid-inducible gene cluster for anaerobic uric acid metabolism.An in vivo experiment showed that gavage with live E.faecalis CML390 in a mouse model of HUA(established using a combination of uric acid and potassium oxonate)significantly reduced serum uric acid levels and alleviated HUA.Our findings contribute to the exploration of the pathways and mechanisms of uric acid metabolism in intestinal microorganisms and provide a candidate probiotic for the treatment of HUA and gout.
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.
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 the National Natural Science Foundation of China(Grant No:U20A20406).
文摘Hyperuricemia(HUA)and gout became typical metabolic disorders characterized by multiple pathogenic factors.Their incidence increased annually,affecting younger populations.Given that uric acid(UA)and inflammation were the primary disease mechanisms,the search for effective and low-side-effect UA-lowering and anti-inflammatory drugs became a pressing scientific priority.Traditional Chinese medicine(TCM)encompassed a rich array of theoretical and practical experience,along with a diverse range of chemical substances,making herbs or their components potential sources for therapeutic drugs.Despite the significant role that modern herbal medicines played in treating HUA and gout,the existing research literature remained fragmented,lacking comprehensive and systematic reviews.In this review,we focused on the regulation of UA and summarized the discovery of UA-lowering pharmacodynamic components or ingredients derived from herbs and formulas,as well as their multi-targeted mechanisms of action.Emphasizing this focus,we proposed that,compared to acute inflammation,low-grade inflammation may play a relatively“unnoticed”role in the disease process.In contrast to Western medicine,we discussed the risks and benefits of herbal medicines and their ingredients for treatment,drawing from theoretical insights and clinical practice.This review offered comprehensive perspectives on the research into anti-HUA and gout treatments using herbal medicines and their natural products.Additionally,it provided a forward-looking view on natural product discovery,the exploration of therapeutic strategies,and new drug research in this field.
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 National Natural Science Foundation of China(No.82360437)the Key Research and Development Program of Hunan Province(No.2021SK2012).
文摘Volatile organic chemicals(VOC)have been identified as hazardous pollutants impairing human health.While whether the VOC exposure was associated with hyperuricemia is yet clarified.All the data was acquired from 6 survey cycles of the National Health and Nutrition Examination Survey(NHANES)program(2005–2006,2011–2012,2013–2014,2015–2016,2017–2018,2017–2020).Hyperuricemia was defined as a serum uric acid(SUA)concentration exceeding 7 mg/mL in men or 6 mg/mL in women.Three quantile logistic regression modelswith varied covariateswere developed to analyze the correlation between hyperuricemia and volatile organic chemical metabolites(VOCs)in urine,and three quantile linear regression models were used for examining the correlation between VOCs and SUA.N-acetyl-S-(2-carboxyethyl)-l-cysteine(CEMA),N-acetyl-S-(3,4-dihydroxybutyl)-l-cysteine(DHBM),and phenylglyoxylic acid(PHGA)were identified to associated positively with increased hyperuricemia risk and uric acid level.Meanwhile,the weighted quantile sum(WQS)model suggested a positive association between VOCs exposure and hyperuricemia.These data indicate that VOC exposure potentially increases hyperuricemia risk,necessitating policies to mitigate VOC exposure.
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BACKGROUND Lower salivary uric acid concentrations,the most abundant antioxidant agent in saliva,have been observed in patients with periodontitis compared to individuals with periodontal health.However,the independent association of salivary uric acid levels with periodontitis,accounting for other risk factors,as well as its association with periodontitis severity,has not been investigated.AIM To the independent association of salivary uric acid levels with periodontitis and the association of salivary uric acid levels with the severity of periodontitis.METHODS This observational and prospective study measured salivary uric acid levels in subjects with periodontitis(characterized by periodontal loss of tissue)and in subjects without periodontitis(periodontal health or localized gingivitis in<30%of sites).Multivariate regression analysis was performed to determine independent factors associated with periodontitis.Spearman’s rho correlation coefficient was used to assess the relationship between salivary uric acid levels and periodontitis severity.A receiver operating characteristic analysis was carried out to evaluate the diagnostic performance of salivary uric acid levels in periodontitis,reporting the area under curve(AUC)and its 95%CI.RESULTS We included 121 subjects,61 of them with periodontitis and 60 without periodontitis(39 with periodontal health and 21 with local gingivitis).Subjects with periodontitis compared to those without periodontitis were older(P<0.001),had higher salivary uric acid levels(P=0.002),higher rate of arterial hypertension history(P=0.001)and higher rate of never-smoker history(P<0.001).The AUC for periodontitis diagnosis by salivary uric acid levels was 66%(95%CI:57%-75%;P<0.001)and the better cut-off point was 111 nmol/mL.Multiple logistic regression analysis showed an independent association of salivary uric acid levels<111 nmol/mL(OR=6.14;95%CI:2.015-18.721;P=0.001)with periodontitis after controlling for age,never-smoker history and arterial hypertension.A negative correlation of salivary uric acid levels and periodontitis severity was observed(rho=-0.32;P<0.001).CONCLUSION The two novel findings of our research were,first,that low salivary uric acid concentrations are independently associated with periodontitis,even after accounting for established risk factors.Second,salivary uric acid levels show a negative correlation with periodontitis severity.
文摘In this letter,we delve into the groundbreaking research by Lorente et al,which sheds light on the intricate relationship between low salivary uric acid levels and periodontitis.The study not only confirms previous observations of reduced salivary uric acid concentrations in periodontitis patients but also establishes,for the first time,an independent association between these two factors,even when controlling for traditional risk factors such as age,smoking status,and arterial hypertension.Moreover,the findings reveal a significant negative correlation between salivary uric acid levels and the severity of periodontitis,suggesting that this biomarker may serve as a valuable indicator of disease progression.These discoveries open new avenues for understanding the pathophysiology of period-ontitis and pave the way for innovative diagnostic and therapeutic strategies.The potential clinical applications of salivary uric acid measurement,such as guiding personalized treatment plans and monitoring disease activity,warrant further exploration to enhance patient care and improve outcomes in this prevalent inflammatory condition.
基金National Science Foundation of China:Mechanistic Study on How Shizhi Fang Promotes Mitocytosis of Renal Tubular Epithelial Cells to Alleviate Hyperuricemia-Induced Kidney Injury(82274415)National Science Foundation of China:Mechanistic Study on Shizhi Fang in Lowering Uric Acid Based on Extracellular Signal-regulated Kinases 1 and 2-mediated Transcriptional Regulation of the Uric Acid Transporter Urate Transporter 1(82474434)。
文摘OBJECTIVE:To elucidate the potential mechanisms of Shizhi Fang(SZF,矢志方)in the treatment of uric acid nephropathy(UAN).METHODS:SZF-containing serum was prepared from six male rats and analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS).Network pharmacology was employed was integrated with UPLC-Q-TOF-MS to predict SZF targets for the treatment of UAN,which were subsequently validated through in vivo experiments.Sixty male Bagg Albino Laboratory-Bred Mouse,substrain c mice were randomly allocated into six groups:Normal,Model,Febuxostat,and three SZF dosage groups.Except for the Normal group,all mice were administered potassium oxonate(250 mg/kg)and adenine(50 mg/kg)via gavage to induce UAN.Four hours postadministration,the Febuxostat group received Febuxostat(6 mg/kg),while the SZF groups received low(0.234 g/kg),medium(0.468 g/kg),or high(0.936 g/kg)doses of SZF.The Normal and Model groups were given an equivalent volume of saline.All treatments were conducted over a period of four weeks.Urine and blood samples were collected for biochemical analysis,and kidney tissues were subjected to histopathological examination and Western blot analysis.RESULTS:Nine prototype compounds and 30 metabolites were identified in SZF serum.Network pharmacology analysis revealed 195 drug targets and 1608 disease targets,with 76 common drug-disease targets,including signal transducer and activator of transcription 3(STAT3),proto-oncogene tyrosine-protein kinase Src(SRC),matrix metalloproteinase-9(MMP9),Caspase 3,and toll-like receptor 4(TLR4)as key targets.Gene Ontology analysis identified 325 biological processes,48 cellular components,and 72 molecular functions,while Kyoto Encyclopedia of Genes and Genomes analysis identified 113 pathways.Molecular docking demonstrated strong binding affinities between active compounds and their targets.In the animal study,SZF treatment alleviated pathological damage and improved serum and urine biochemical markers compared to the Model group(P<0.05,P<0.01,P<0.001).Western blot analysis showed a significant reduction in phosphorylated-STAT3,phosphorylatedSRC,MMP9,TLR4,and Caspase3 expression in renal tissues of SZF-treated mice(P<0.001).CONCLUSION:SZF may exert therapeutic effects on UAN through multiple targets and pathways.
文摘This article explores the association between salivary uric acid(UA)and periodontitis,systematically analyzing its dual roles and research progress.Studies indicate that UA acts as a primary antioxidant in saliva under physiological conditions(accounting for 70%),protecting periodontal tissues by scavenging reactive oxygen species.However,when gum disease becomes severe,UA can switch roles and fuel inflammation,worsening tissue damage.Lorente et al’s research found an independent inverse correlation between salivary UA levels and periodontitis severity(odds ratio=6.14,P=0.001),establishing 111 nmol/mL as a diagnostic threshold(area under the curve=66%).Nevertheless,limitations include sample heterogeneity and failure to distinguish between gingivitis and periodontitis.Mechanistically,three hypotheses are proposed:The Antioxidant Depletion Hypothesis(UA oxidation consumption leading to feedback loops),the Microbial Metabolic Hijacking Hypothesis(pathogens utilizing UA as a carbon source to disrupt redox balance),and the Epithelial Barrier Dysfunction Hypothesis(UA deficiency causing downregulation of tight junction proteins).Future research should prioritize longitudinal cohorts to validate predictive value,integrate multi-omics to explore dysregulated signatures,and develop UA supplementation or targeted antioxidant therapies.This study provides novel insights into periodontitis diagnosis and mechanisms,advancing the application of salivary biomarkers in precision periodontics.
基金supported by the Guangzhou Science and Technology Program(No.2023A04J0502)。
文摘Backgroundd The uric acid to albumin ratio(UAR)has emerged as a potential biomarker for systemic inflammation and oxidative stress,both of which are implicated in adverse outcomes following cardiac surgery.This study aimed to explore the association between UAR and long-Term mortality in elderly patients undergoing heart valve surgery.MethodsA retrospective cohort study was conducted on 202 elderly patients who underwent valve surgery in the Cardiac Surgery Intensive Care Unit(CSICU)between January 2013 and April 2014.Patients were stratified into three groups based on UAR level(low:5.66-10.26;middle:10.29-13.47;high:13.48-31.88).The multivariable cox regression analysis with covariate adjustment and subgroup analyses were performed to evaluate the association between UAR and long-term mortality,with a median follow-up period of 7.9 years.Smooth curve fitting was used to evaluate the potential linear association between UAR and long-term follow-up mortality.Kaplan-Meier curves with log-rank tests were generated to compare survival distributions among UAR groups.Results In multivariate regression models,UAR demonstrated a significant positive association with long-term follow-up mortality after comprehensive covariates adjustment.The adjusted hazard ratios(HR)for long-term follow-up mortality was 1.22(95%CI:1.10-1.34,P<0.0001)per 1-unit increase in UAR.We further performed exploratory subgroup analyses which confirmed a higher UAR levels were independently associated with a higher risk of mortality.Kaplan-Meier analysis for event-free survival revealed higher occurrence of long-term follow-up mortality in the high UAR group(P=0.013).Conclusions Elevated UAR levels in elderly patients who underwent valvular surgery in the CSICU demonstrated an positivecorrelation with mortality risk.
文摘BACKGROUND Uric acid(UA),a key antioxidant metabolite,demonstrates dual roles in cancer.Unfortunately,studies on its role in colon cancer risk are uncommon,and the limited results are inconsistent.AIM To elucidate the association between UA and colon cancer risk and its me-chanisms.METHODS Multivariate logistic regression analysis evaluated the association between UA levels and colon cancer risk.Non-linear relationships were illustrated using restricted cubic splines.The threshold effect was performed to identify cut-off points.Human colon cancer cell lines(HCT-116 and HT29)were exposed to UA for 48 hours.Cell viability was assessed via the cell counting kit-8 assay.The evaluation of cell migration involved wound healing and transwell migration assays.HCT-116 cells were exposed to 4 mg/dL UA for 48 hours.The impact of the subsequent treatment with a phosphoinositide 3-kinases(PI3K)agonist and UA was assessed.RESULTS After adjusting for potential confounders,an inverse association was observed between UA and colon cancer risk(odds ratio=0.65,P<0.05).A non-linear relationship was identified,with a 4.79 mg/dL cut-off point(P<0.05).UA inhibited colon cancer cell proliferation and migration.These effects were mediated by the induction of reactive oxygen species and the suppression of the PI3K/protein kinase B/mammalian target of rapamycin pathway.CONCLUSION UA acts as a protective agent against colon cancer by inhibiting cell proliferation and migration through increased reactive oxygen species production and modulation of the PI3K/protein kinase B/mammalian target of rapamycin pathway.
基金supported by the Fundamental Research Funds for the Central Universities(Nos.2021FZZX001-39 and 2020QNA7018)the Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province(No.20220204)the Medical Science and Technology Project of Zhejiang Province(No.2023RC037).
文摘Growing evidences showed that heavy metals exposure may be associated with metabolic diseases.Nevertheless,themechanism underlying arsenic(As)exposure and metabolic syndrome(MetS)risk has not been fully elucidated.So we aimed to prospectively investigate the role of serum uric acid(SUA)on the association between blood As exposure and incident MetS.A sample of 1045 older participants in a community in China was analyzed.We determined As at baseline and SUA concentration at follow-up in the Yiwu Elderly Cohort.MetS events were defined according to the criteria of the International Diabetes Federation(IDF).Generalized linear model with log-binominal regression model was applied to estimate the association of As with incident MetS.To investigate the role of SUA in the association between As andMetS,amediation analysiswas conducted.In the fully adjusted log-binominal model,per interquartile range increment of As,the risk of MetS increased 1.25-fold.Compared with the lowest quartile of As,the adjusted relative risk(RR)of MetS in the highest quartile was 1.42(95%confidence interval,CI:1.03,2.00).Additionally,blood As was positively associated with SUA,while SUA had significant association with MetS risk.Further mediation analysis demonstrated that the association of As and MetS risk was mediated by SUA,with the proportion of 15.7%.Our study found higher As was remarkably associated with the elevated risk of MetS in the Chinese older adults population.Mediation analysis indicated that SUA might be a mediator in the association between As exposure and MetS.
