Lower Uric Acid Research Articles

Reno-protective effects of xanthine oxidase inhibitors in patients with type 2 diabetes and chronic kidney disease: a systematic review and meta-analysis.

The effect of lowering uric acid levels on renal function in patients with diabetic kidney disease remains unclear. Previous randomized controlled trials (RCTs) have reported conflicting results regarding the effects of xanthine oxidase inhibitors on renal function. This study aimed to examine the renoprotective effects of xanthine oxidase inhibitors (febuxostat and topiroxostat) in patients with diabetic kidney disease. Relevant RCTs were searched using PubMed, Embase, and Cochrane Central databases. Ultimately, five RCTs were included in the meta-analysis. The assessed renal endpoints included changes in the estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio. The meta-analysis was conducted using Review Manager version 5.4. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated for changes in renal endpoints between the groups after the study period. A subgroup analysis was conducted based on the type of intervention, results of the risk of bias assessment, and baseline renal function. Although the use of febuxostat or topiroxostat did not induce a significant change in eGFR compared with the placebo, it showed a tendency to delay renal function decline (SMD = 0.32, 95% CI = [-0.00; 0.64]). There was no significant difference in albuminuria between the two groups (SMD = 0.26, 95% CI = [-0.10; 0.62]). This study suggests the potential of febuxostat or topiroxostat to delay renal function decline in patients with diabetes and underlying renal impairment, that needs to be confirmed in further studies. INPLASY registration number 202450024.

Sex-based disparities in the association between uric acid levels and anxiety: a cross-sectional analysis of nationwide data in Korea

BackgroundUric acid has antioxidant properties, and several studies have suggested its neuroprotective effects. Despite reports of increased oxidative damage and decreased antioxidants in anxiety disorders, findings remain inconclusive. This study investigated the association between serum uric acid levels and anxiety symptoms, stratified by sex, using nationwide data from South Korea.MethodsData were derived from the Korea National Health and Nutrition Examination Survey, which included 2,228 males and 2,805 females. Presence of anxiety symptoms was defined as a Generalized Anxiety Disorder 7-item scale (GAD-7) score of ≥ 10. Study participants were categorized into three groups based on serum uric acid levels: 1 (lowest) to 3 (highest). Multivariable logistic regression analyzed the association between uric acid levels and anxiety symptoms, stratified by sex.ResultsCompared to reference group 2, females in group 1 had increased anxiety symptoms (odds ratio (OR) 2.28, 95% confidence interval (CI) 1.48–3.49). When anxiety symptoms were defined as a GAD-7 score of ≥ 5, females in groups 1 (OR 1.68, 95% CI 1.30–2.16) and 3 (OR 1.35, 95% CI 1.04–1.74) both showed more anxiety symptoms than group 2, with a U-shaped relationship between uric acid levels and anxiety symptoms. In males, uric acid levels weren't significantly linked to anxiety symptoms.ConclusionsThis study indicates that low serum uric acid levels are associated with a higher prevalence of anxiety symptoms only in females, suggesting involvement of oxidative stress in anxiety disorders and its sex-based variation.

Polysaccharide extracted from Phellinus igniarius attenuated hyperuricemia by modulating bile acid metabolism and inhibiting uric acid synthesis in adenine/potassium oxonate-treated mice.

Phellinus igniarius (Linnearus: Fries) Quelet (Phellinus igniarius) is an edible and medicinal fungi and has been used in China for centuries. It is found to improve organs function and metabolic homeostasis including ameliorating hyperuricemia (HUA). Polysaccharide is a predominant component in P. igniarius. This study aimed to investigate the anti-HUA effects and underlying mechanism of the polysaccharide extracted from P. igniarius (PPI). PPI was extracted and characterized by molecular weight, monosaccharide composition and FT-IR spectroscopy. HUA was induced in C57BL/6 male mice by gavage of adenine/potassium oxonate for 14 days. PPI (2.2, 4.4 or 8.8 mg/kg) was orally given to HUA mice and its effects on HUA were determined. Compared to HUA group, PPI significantly reduced the serum levels of uric acid (UA), creatinine, blood urea nitrogen (BUN), AST, ALT, and total cholesterol. In the liver of HUA mice, PPI notably inhibited the activity of xanthine oxidase (XOD) and its expression mediated by peroxisome proliferator-activated receptor α (PPARα), suggesting a decrease in UA synthesis. Furthermore, PPI was found to modulate enterohepatic bile acid (BA) metabolism. The profile of BAs showed that PPI significantly elevated the TUDCA+THDCA levels in the liver of HUA mice. In the hepatocytes HepG2, TUDCA decreased the expression of PPARα/XOD and reduced UA production, whereas THDCA did not present similar effects. The anti-HUA effects of TUDCA was further confirmed in HUA mice, where it lowered serum UA level and inhibited XOD expression and activity. This study demonstrates that PPI ameliorates HUA in vivo, and this effect may be mediated by the regulation of bile acid metabolism, particularly through the function of TUDCA in suppressing UA production in the liver.

Spatiotemporal landscape of kidney in a mouse model of hyperuricemia at single-cell level.

Serum uric acid is an end-product of purine metabolism. Uric acid concentrations in excess of the physiological range may lead to diseases such as gout, cardiovascular disease, and kidney injury. The kidney includes a variety of cell types with specialized functions such as fluid and electrolyte homeostasis, detoxification, and endocrine functions. Two-thirds of uric acid is excreted through kidney, however, the exploration of markers and new therapeutic targets in renal tissue of hyperuricemia is still lacking. Single-cell and spatial omics techniques represent major milestones in life sciences. The combined measurement of the physical structure and molecular characteristics of tissues facilitates the exploration of the pathophysiological processes underlying disease development and the discovery of possible therapeutic targets. Here, the spatiotemporal atlas of hyperuricemic nephropathy was investigated using single-cell RNA sequencing, spatial transcriptomics, spatial proteomics, and spatial metabolomics in a urate oxidase knockout mouse model. Several emerging targets and pathways especially ribosome and metabolism related to uric acid excretion were discovered and will be investigated further in studies on lowering uric acid.

Serum Urate and Atrial Fibrillation: A Bidirectional Mendelian Randomization Study.

Observational studies indicate that serum urate level is associated with atrial fibrillation (AF). However, whether this association is causal remains controversial, due to confounding factors and reverse causality. We aim to evaluate the causal relationship of genetically predicted serum urate level with AF. A bidirectional Mendelian randomization (MR) study was performed. Instrumental variables were obtained from the Global Urate Genetics Consortium (110347 individuals). We obtained summary statistics of AF from two genome-wide association studies (GWAS) data sets for AF. Inverse-variance-weighted method was applied to obtain MR estimates and other statistical methods were conducted in the sensitivity analyses. The reverse MR analysis was performed to evaluate the effect of AF on serum urate levels. Genetically determined serum urate level was not associated with AF in two studies (OR, 1.03; 95% CI, 0.95-1.11; p = 0.47); (OR, 1.06; 95% CI, 0.99-1.12; p = 0.09). The main results kept robust in the most sensitivity analyses. Multivariable MR analyses suggested that the association pattern did not change, after adjusting for body mass index (BMI), HbA1c: hemoglobin A1c (HbA1c), hypertension, low-density lipoprotein cholesterol (LDL-C) and coronary heart disease. No causal effect of AF on serum urate levels was found in two studies (OR, 1.02; 95% CI, 0.98-1.05; p = 0.30); (OR, 1.00; 95% CI, 0.98-1.03; p = 0.95). Our MR study supports no bidirectional causal effect of serum urate levels and AF. This implies that treatments aimed at lowering uric acid may not reduce the risk of AF.

The Material Basis for the Beneficial Effects of Paidu Powder on Hyperuricemia: A Network Pharmacology and Clinical Study

Background: Paidu powder (PDP) is a formula that is used in traditional Chinese medicine (TCM) practices and has been demonstrated to be effective to lower blood uric acid (UA) level.Methods: Network pharmacology was employed to probe the mechanistic basis for the beneficial effects of PDP. Then, PDP was subjected to Aspergillus oryza AS3.042 fermentation, and the primary bioactive compounds in the resultant samples were analyzed via HPLC. A clinical study was then performed to test the therapeutic effects of unfermented and fermented PDP on HUA.Results: Network pharmacology strategies identified 122 active compounds and 924 HUA‐related target genes, with 61 overlapping targets relative to PDP and HUA ultimately being selected. These target genes were associated with 474 GO biological process terms and 136 KEGG pathways. Moreover, good binding was observed between three main bioactive compounds of interest and nine primary target proteins. Notably, the levels of the top three bioactive compounds (quercetin, kaempferol, and naringenin) were significantly elevated by 308.96%, 1386.44%, and 719.21%, respectively, following fermentation. Clinical analyses indicated that both PDP and fermented PDP treatment significantly reduced UA, CRE, and BUN levels (p < 0.01), with a higher overall efficacy rate in the fermented PDP group relative to the unfermented PDP group (p < 0.01). Fewer adverse reactions were also observed in the fermented PDP group.Conclusion: These results offer novel insights into the putative mechanisms through which PDP can exert its beneficial effects against HUA, offering a novel basis for the identification of the pharmacological effects of this popular TCM prescription.

Assessment of Serum Uric Acid to Albumin Ratio as A Prognostic Indicator for Short - Term Mortality in Acute Kidney Injury: A Prospective Study

Background: Acute kidney injury is diagnosed via rapid increase in renal function parameters. Hyperuricemia have been associated with acute kidney injury and result in increased mortality. Objective: To assess the uric acid to albumin ratio as a prognostic indicator for short-term mortality in acute kidney injury. Material and Methods: This observational prospective cohort study was conducted in the Department of Nephrology at Akbar Niazi Teaching Hospital from November 2023 to February 2024. 80 patients, aged 18 and above who presented to the emergency service, developed acute kidney injury, and subsequently received follow-up and treatment. Results: 80 patients having themean age of 58.35±14.18 years (35% female and 65% male) were assessed. The mean uric acid to albumin ratio was 3.57±1.6 mg/g in the non-survivor group and 2.84±1.2 mg/g in survivor group (p=0.001).The optimal cutoff for the uric acid to albumin ratio correlated with mortality was found to be 2.5 mg/g, with specificity 82% and sensitivity 78%.The 30 days cumulatively survival rate for the low was 88.1% ± 3% and high uric acid to albumin ratio was 66.3% ± 4%.The assessed survival time was 25.6 days (95% CI: 24 to 30) for the low uric acid to albumin ratio group and 21.5 days (95% CI: 20 to 23) for the high uric acid to albumin ratio group. Conclusion: The study observed a clear relationship between 30 days mortality and the uric acid to albumin ratio at the initial manifestation in AKI patients, independent age, and clinical findings.

Impact of Uric Acid Levels on Mortality and Cardiovascular Outcomes in Relation to Kidney Function.

Background: Uric acid levels are linked to cardiovascular outcomes and mortality, especially in chronic kidney disease (CKD). However, their impact across varying kidney function remains unclear. Methods: We conducted a retrospective cohort study using the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM) database from a single center. Adult patients with at least one serum uric acid measurement between 2002 and 2021 were included and categorized by estimated glomerular filtration rate (eGFR): normal kidney function (≥90 mL/min/1.73 m2), mild dysfunction (60-89 mL/min/1.73 m2), moderate dysfunction (30-59 mL/min/1.73 m2), and advanced dysfunction (<30 mL/min/1.73 m2). The primary outcome was all-cause mortality with secondary outcomes being myocardial infarction (MI) and heart failure (HF). Results: A total of 242,793 participants were analyzed. Uric acid levels showed a U-shaped association with all-cause mortality in advanced kidney dysfunction, where both low (<3 mg/dL) and high (>10 mg/dL) levels increased mortality risk. In mild kidney dysfunction, lower uric acid levels were linked to better survival. HF risk increased linearly with higher uric acid, particularly in normal kidney function, while no significant association was found between uric acid and MI in any group. Conclusions: Uric acid levels are associated with mortality in a U-shaped pattern for advanced kidney dysfunction, while lower levels appear protective in mild dysfunction. These findings suggest the need for personalized uric acid management in CKD patients based on their kidney function.

Lower serum uric acid levels are associated with depressive symptoms in a Japanese general population: A population-based cross-sectional study.

Uric acid (UA) is a final product of purine metabolism and has neuroprotective effects. It has not been established whether serum UA levels are associated with depressive disorder. Thus, we investigated whether serum UA levels are associated with depressive symptoms in a Japanese general population. We used the Iwaki Health Promotion Project 2022 data (737 subjects) in this cross-sectional study. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess the prevalence of depressive symptoms. Subjects with CES-D scores ≥16 were assigned to the Depression group. We compared characteristics and laboratory data (including serum UA) between the Depression and Non-depression groups and performed a multivariable logistic regression analysis to investigate whether their serum UA levels were associated with depressive symptoms, after adjusting for possible confounding factors. We analyzed the cases of 705 subjects: the Depression group (n = 142) and the Non-depression group (n = 563). The Depression group's serum UA levels were significantly lower than those of the Non-depression group. The multivariable logistic regression analysis demonstrated that lower serum UA levels were significantly associated with the depressive symptoms. In conclusion, lower serum UA levels in this Japanese general population were significantly associated with the depressive symptoms.

Potential candidates from a functional food Zanthoxyli Pericarpium (Sichuan pepper) for the management of hyperuricemia: high-through virtual screening, network pharmacology and dynamics simulations.

Hyperuricemia (HUA) is a metabolic syndrome caused by purine metabolism disorders. Zanthoxyli Pericarpium (ZP) is a medicinal and food homologous plant, and its ripe peel is used to treat diseases and as a spice for cooking. Some studies have shown that ZP can inhibit the formation of xanthine oxidase and reduce the production of uric acid. Through network pharmacology, ZP's potential targets and mechanisms for HUA treatment were identified. Databases like TCMSP, UniProt, and Swiss Target Prediction were utilized for ZP's active ingredients and targets. HUA-related targets were filtered using GeneCards, Drugbank, and Open Targets. Core targets for ZP's HUA treatment were mapped in a PPI network and analyzed with Cytoscape. GO and KEGG pathway enrichments were conducted on intersected targets via DAVID. Molecular docking and virtual screening were performed to find optimal binding pockets, and ADMET screening assessed compound safety. Molecular dynamics simulations confirmed compound stability in binding sites. We identified 81 ZP active ingredient targets, 140 HUA-related targets, and 6 drug targets, with xanthine dehydrogenase (XDH) as the top core target. Molecular docking revealed ZP's active ingredients had strong binding to XDH. Virtual screening via Protein plus identified 48 compounds near the optimal binding pocket, with 2'-methylacetophenone, ledol, beta-sitosterol, and ethyl geranate as the most promising. Molecular dynamics simulations confirmed binding stability, suggesting ZP's potential in HUA prevention and the need for further experimental validation. Our study provides foundations for exploring the mechanism of the lowering of uric acid by ZP and developing new products of ZP. The role of ZP in the diet may provide a new dietary strategy for the prevention of HUA, and more experimental studies are needed to confirm our results in the future.

Changes in serum uric acid, glutathione, and amyloid-β1-42 levels in Parkinson’s disease patients and their association with disease progression and cognitive decline

Objective This study aims to evaluate the diagnostic significance of serum uric acid (UA), glutathione (GSH), and amyloid-β1-42 (Aβ1-42) levels in relation to disease progression and cognitive impairment in patients with Parkinson’s disease (PD). Methods A total of 209 PD patients with disease duration ranging from 4.0 to 6.8 years were enrolled. Based on the Hoehn-Yahr staging system, patients were classified into Early (n = 67), Medium-term (n = 70), and Advanced (n = 72) stages. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), dividing the cohort into CD (cognitive dysfunction, n = 94) and NO-CD (no cognitive dysfunction, n = 115) groups. Serum UA, GSH, and Aβ1-42 levels were analyzed for correlations with clinical data. Independent risk factors and diagnostic value were determined through multivariable logistic regression models and receiver operating characteristic curve analysis. Results Serum UA and GSH levels progressively declined with advancing disease stage, while Aβ1-42 increased. Compared to the NO-CD group, the CD group showed lower serum UA and GSH levels, and higher Aβ1-42 levels. Serum UA and GSH were inversely correlated with disease duration, levodopa equivalent daily dose, and Unified Parkinson’s Disease Rating Scale scores, while Aβ1-42 showed positive correlations. UA (p = 0.006), GSH (p < 0.001), and Aβ1-42 (p = 0.040) were independent predictors of disease stage. Similarly, UA (p = 0.003), GSH (p < 0.001), and Aβ1-42 (p < 0.001) were independent predictors of cognitive dysfunction. The combined assessment of these markers demonstrated a higher area under the curve (AUC) than individual markers for disease and cognitive decline identification. Conclusions Serum UA, GSH, and Aβ1-42 are independent predictors of disease progression and cognitive decline in PD patients. Their combined use offers enhanced diagnostic accuracy for disease staging and cognitive impairment in PD.

Association between serum uric acid and all-cause and cardiovascular-related mortality in hemodialysis patients.

The association between serum uric acid (UA) and all-cause and cardiovascular-related mortality in hemodialysis (HD) patients is conflicting. We investigated this association and explored the effect modification of underlying nutritional status, as reflected in the lean tissue index (LTI) and the Geriatric Nutritional Risk Index (GNRI), which serve as markers of muscle mass and nutritional risk in HD patients. A retrospective cohort study was conducted from January 2019 to December 2023. We investigated the association between serum UA and the outcomes using the Cox proportional hazards regression and restricted cubic splines. Subgroup analyses based on the LTI and GNRI were conducted to explore possible effect modification. During a mean follow-up of 32.9 months, 876 patients who underwent HD were included in the analysis. The association between serum UA and all-cause mortality showed a non-linear U-shaped pattern (p = 0.007), with a survival benefit observed for the patients with serum UA levels between 3.4 and 6.8 mg/dL. In the multivariable-adjusted model, the low and high UA groups were associated with a greater risk of all-cause mortality compared to the reference UA group (hazard ratio (HR) =1.24, confidence interval (CI) 1.03-2.12, p = 0.027; HR = 1.09; CI 1.05-2.08. p = 0.012). In the low UA group, a greater risk of mortality was observed in patients with low LTI (<12.3; HR 1.56, 95% CI 1.22-1.82) and GNRI values (<102.1; HR 1.43, 95% CI 1.12-1.76), but not in those with high LTI and GNRI values. There was no significant association between serum UA and cardiovascular disease-related mortality. Our study showed that lower and higher serum UA levels increase the risk of all-cause mortality in HD patients. Among the patients with lower UA levels, low LTI and GNRI values showed a greater risk of mortality. This finding suggested that better nutritional status, rather than elevated UA levels, is likely to improve long-term survival in HD patients.

Transcriptomic Analysis Reveals the Potential Mechanism of Cardamine circaeoides Hook.f. & Thomson in Lowering Serum Uric Acid by Reducing Inflammatory State Through CCR7 Target.

Cardamine circaeoides Hook.f. & Thomson (CC) is a traditional medicinal herb with multiple biological activities. In previous studies, we have identified its serum uric acid (SUA) lowering effects and speculated that Cardamine circaeoides water extract (CCE) may exert anti-hyperuricemia effects related to its anti-inflammatory activity. This study aims to further investigate the molecular mechanism underlying these effects at the mRNA level through transcriptomic analysis, quantitative reverse transcription polymerase chain reaction (RT-qPCR), molecular docking, and Western blotting. CCE effectively reduced SUA and improved renal function in a dose-dependent manner in hyperuricemia rats. Cytokine-cytokine receptor interaction pathway was significantly altered by CCE. An additional study identified a number of genes (IL27, Inhbe, CCR7, CXCR3, IL12RB1, CXCR5, Mstn, and GDF5) as regulators of the inflammatory response. Meanwhile, three key targets (IL27, Inhbe, and CCR7) were found to be significantly expressed at the mRNA level and have strong binding affinity with 22 components, among which Kaempferol 3-sophoroside 7-glucoside, Kaempferol-3-O-sophoroside, and Quercetin 3-sophoroside 7-glucoside have strong binding activities. Following this, Western blotting showed a significant increase in CCR7 expression. Our findings indicated that CCE regulated the cytokine-cytokine receptor interaction pathway through CCR7 to reduce the inflammatory state and exert an SUA-lowering effect.

Association of Serum Bilirubin and Serum Uric Acid with Glycemic Status in Type 2 Diabetes Mellitus

Background: Type 2 diabetes mellitus (T2DM) is a major public health problem affecting millions of people worldwide and its magnitude in developing countries including Bangladesh is rising rapidly. It is associated with multiple metabolic derangements that result in the excessive production of reactive oxygen species and oxidative stress. The major concern of health management in T2DM patients is to prevent diabetes-related complications which can only be achieved via strict glycemic control. Over the recent past it had been evident that serum bilirubin acts as a powerful antioxidant and upper limit of physiological ranges of serum bilirubin levels are beneficial and negatively associated with oxidative stress and glycemic status. Moreover, high serum uric acid plays an important role as an oxidative stress agent that is associated with poor glycemic control in diabetic subjects. Low serum bilirubin and high uric acid predicted a higher incidence for the development of T2DM and also had adverse impact on glycemic status. So, this study was designed to find out the association of serum bilirubin and uric acid with glycemic status among Type 2 diabetes mellitus subjects. Objective: To evaluate the association of serum bilirubin and uric acid with glycemic status in Type 2 diabetes mellitus. Materials and Methods: This cross-sectional analytical study was carried out in the department of Biochemistry, Sir Salimullah Medical College (SSMC), Dhaka from March, 2021 to February, 2022. A total number of 100 subjects were included in this study. Among them, 50 apparently healthy non-diabetic subjects age ranged from 30-59 years were considered as control group (Group A). Another 50 age and gender matched Type 2 diabetes mellitus patients without any complication were selected as study group (Group B). Ethical permission was taken from the Ethical Review Committee (ERC) of SSMC. All the study subjects were selected from the outpatient department of Medicine and Endocrinology, Sir Salimullah Medical College and Mitford Hospital, Dhaka. The study parameters were FPG, HbA1c, Serum bilirubin and serum uric acid. Estimation of study parameters were done in the Department of Biochemistry of SSMC, Dhaka. Statistical analysis was done by using SPSS version-22. Unpaired t test, Chi Square test, Pearson’s correlation test and Binary logistic regression were performed to analyze the data as applicable. Results: Serum bilirubin level was significantly lower and uric acid level was significantly higher among diabetic subjects in comparison to healthy controls. Comparison of glycemic status (FPG and HbA1c) in between different quartiles of serum bilirubin and uric acid in diabetic subjects were observed. FPG and HbA1c levels were significantly higher in Q1 &amp; Q2 compared to Q3 &amp; Q4 of serum bilirubin. However, FPG and HbA1c levels found high in Q3 &amp; Q4 than Q1 &amp; Q2 of uric acid. Pearson’s correlation analysis showed significant negative correlation of serum bilirubin with FPG and HbA1c, whereas significant positive correlation of serum uric acid with FPG and HbA1c were observed in study subjects. Binary logistic regression was performed to show the association between several factors and diabetes which were expressed by the coefficients of logistic regression. The risk of diabetes for each factor was expressed as odds ratio (OR). Coefficient for serum bilirubin (showing inverse relation) was significant. In case of serum uric acid, coefficient showed significant positive relationship. Where serum uric acid was strongest predictor of diabetes with an odds ratio of 3.709. Conclusion: Type 2 diabetic subjects have lower serum bilirubin and higher uric acid level than that of healthy subjects. Serum bilirubin has an inverse relationship with glycemic status (FPG and HbA1c), whereas uric acid shows positive correlation with glycemic status in diabetic subjects. Hyperuricemia appears to be a risk factor for development of Type 2 diabetes mellitus.

Clerodendranthus spicatus [Orthosiphon aristatus (Blume) Miq.] maintains uric acid homeostasis via regulating gut microbiota and restrains renal inflammation in hyperuricemic nephropathy.

The kidney damage caused by the deposition of uric acid in the kidneys is of urgent need for new treatment drugs due to its complex pathogenesis. Orthosiphon aristatus (Blume) Miq. Also known as C. spicatus, which has a significant therapeutic effect on hyperuricemia nephropathy (HN), however, the specific mechanism of its action is still unknown. The HN mice model was constructed using adenine (AD) and potassium oxonate (PO), and serum biochemical indexes, kidney pathological changes, xanthine oxidase (XOD) activity in the liver, and renal protein expressions of phosphoribose pyrophosphate synthetase (PRPS) and uric acid transporter were detected. The effects of C. spicatus on uric acid lowering, anti-inflammation, and renal protection of HN mice were verified. The effect of C. spicatus on gut microbiota was assessed by 16S rRNA sequencing. Establish pseudo-sterile mice through the combined treatment of ampicillin, neomycin, and vancomycin to verify the role of gut microbiota in improving HN in C. spicatus. In HN mice, C. spicatus could significantly reduce serum uric acid levels and improve renal function. In addition, C. spicatus modulated gut microbiota and decreased the relative abundance of Bacteroides, Prevotellaceae_UCG-001 and Alistipes, and increased the abundance of Alloprevotella and Lachnospiraceae_NK4A136_group.C.spicatus altered the expression of the renal urate transporter and key enzymes in hepatic urate synthesis, leading to a decrease in serum uric acid levels. C. spicatus alleviated kidney inflammation by inhibiting the activation of the NLRP3 and TLR4/MYD88 inflammatory pathways, and reduced the level of kidney inflammatory factors. It also improved kidney damage by inhibiting the process of renal epithelial-mesenchymal transition, and improved kidney fibrosis. In pseudo-sterile HN mice, without the effect of gut microbiota, the uric acid lowering, anti-inflammatory, and renal fibrosis improving effects of C. spicatus were significantly reduced. Our results demonstrated that C. spicatus could reduce uric acid levels, anti-inflammatory effects, and improve HN by regulating the gut microbiota. This provides a novel scientific basis for the clinical application of C. spicatus.

Mechanism of targeted uric acid reduction by soybean protein peptide SHECN in hyperuricemia mice and improvement of liver injury

Hyperuricemia (HUA) is a chronic condition characterized by abnormal purine metabolism. SHECN (Ser-His-Glus-Cys-Asn), a soy-derived peptide, has demonstrated uric acid (UA) lowering and antioxidant properties in vitro. The aim of this study was to further explore its uric acid lowering potential in hyperuricemia mice. The results indicated that UA level in SHECN-H group (40 mg/kg) was reduced to 32.80 ± 1.23 μmol/L compared with that in HUA group (104.46 ± 7.30 μmol/L). SHECN group decreased serum xanthine oxidase (XO) and adenosine deaminase (ADA) activities, AST and ALT activities. Additionally, SHECN significantly ameliorated fiber damage observed in mouse liver tissue. We also found that under the action of SHECN, the active expression of XO and ADA in serum and liver was down-regulated, and the expression of hypoxanthine-guanine phosphoribosyl transferase (HGPRT) was up-regulated. Notably, SHECN effectively mimics interactions with XO-associated target proteins as well as key liver transporter receptor proteins. This study further confirmed that SHECN can affect the activity level of the key receptor protein of uric acid synthesis in the liver of mice, and ultimately reduce the serum uric acid level and alleviate liver injury (P < 0.05).

Plasma uric acid levels and risk of dementia in a population-based cohort study

BackgroundGiven the opposing properties of uric acid (UA), which are intracellular prooxidant action and extracellular antioxidant action, the association of circulating UA levels with dementia remains controversial. We aimed to ascertain whether both lower and higher plasma UA levels are associated with the risk of incident dementia among middle-aged and older population. Methods1685 participants (530 men and 1155 women) aged 40–69 years at baseline (1990–1993) were randomly selected for plasma UA measurement from base cohort participants who responded to the baseline questionnaire and provided blood samples. They were followed for dementia (disabling dementia requiring care; hereinafter dementia) from 2006 to 2016 using certification records for national long-term care insurance in Japan. A Cox proportional hazards model adjusted for various lifestyle factors and past medical history (cardiometabolic disease) was applied for overall participants and sex. ResultsDementia was diagnosed in 240 participants (14.2 % overall: 16.0 % in men and 13.4 % in women). No statistically significant association with plasma UA was found in overall participants. Compared to participants with UA of 5.1–6.0 mg/dL, men with ≥6.1 mg/dL showed fully adjusted hazard ratios of 1.46 (95 % confidence interval: 0.78–2.75) for 6.1–7.0 mg/dL and 1.89 (0.97–3.66) for ≥7.1 mg/dL, while women with ≥6.1 mg/dL showed 1.13 (0.54–2.38). ConclusionsNo statistically significant association between plasma UA level and risk of dementia was found in overall participants or by sex.

Analysis of a family with hypouricemia due to type Ⅰ xanthinuria

This article reports a patient presenting with"extremely low uric acid levels in blood and urine"clinically along with reviewing relevant literature to consider a diagnosis of xanthinuria. Peripheral blood samples of the patient and her family were further collected for xanthine dehydrogenase(XDH) gene sequencing, showing that the patient had compound heterozygous mutations in exon 19:c.1995_2006del12(p.His666_Gly669del) and exon 10:c.871G>T(p.Glu291*), however no mutations were found in the gene encoding MOCOS on chromosome 18, confirming the diagnosis of hereditary xanthinuria type Ⅰ.The patient's father, son and daughter carried heterozygous mutations in exon 19:c.1995_2006del12(p.His666_Gly669del), and the mother carried heterozygous mutations in exon 10:c.871G>T(p.Glu291*).Mutations in the XDH gene cause a lack of xanthine oxidoreductase function, which hinders the production of uric acid, leading to very low or undetectable levels in blood and urine. Patients present clinically with hematuria, renal colic, urolithiasis, and even acute renal failure. Through the diagnosis and treatment of this patient and literature review, the article aims to deepen the understanding of purine metabolism and uric acid production process, and improve the clinicians' diagnosis and treatment ability of hypouricemia.

Fasciculation potentials are related to the prognosis of amyotrophic lateral sclerosis.

Some prognostic biomarkers of amyotrophic lateral sclerosis (ALS) have been described; however, they are inadequate for satisfactorily predicting individual patient outcomes. Fasciculation potentials (FPs) on electromyography (EMG) are useful for the early diagnosis of ALS, and complex FPs are associated with shorter survival in ALS. In this study, we investigated the relationship between the proportion of muscles with FPs, biochemical markers, and the prognosis of ALS. 89 Patients with ALS were retrospectively classified into three groups based on the interval from onset to death or tracheostomy (less than 1 year: fast progression; from 1 year to less than 3 years: average progression; 3 years or more: slow progression). We performed statistical analysis of the electrophysiological findings, including the percentage of examined muscles with FPs, and biochemical markers evaluated on admission. Patients with fast ALS progression had a higher percentage of muscles with FPs (93.1% vs. 37.9%, P<0.001) and lower uric acid (UA) levels (male: 4.19 mg/dl vs 5.55 mg/dl, P<0.001; female: 3.71 mg/dl vs 5.41 mg/dl, P<0.001) than patients with slow progression. Survival curves demonstrated a relationship between these factors and the survival time in patients with ALS. Furthermore, UA levels were correlated with the percentage of muscles with FPs. Our electrophysiological findings suggest that ALS presents with multisystem neurological manifestations, and these manifestations differed among the groups classified by disease progression. The percentage of muscles with FPs on EMG and serum UA levels were especially associated with the prognosis of ALS.

Rewiring of Uric Acid Metabolism in the Intestine Promotes High-Altitude Hypoxia Adaptation in Humans.

Adaptation to high-altitude hypoxia is characterized by systemic and organ-specific metabolic changes. This study investigates whether intestinal metabolic rewiring is a contributing factor to hypoxia adaptation. We conducted a longitudinal analysis over 108 days, with seven time points, examining fecal metabolomic data from a cohort of 46 healthy male adults traveling from Chongqing (a.s.l. 243 m) to Lhasa (a.s.l. 3,658 m) and back. Our findings reveal that short-term hypoxia exposure significantly alters intestinal metabolic pathways, particularly those involving purines, pyrimidines, and amino acids. A notable observation was the significantly reduced level of intestinal uric acid, the end product of purine metabolism, during acclimatization (also called acclimation) and additional two long-term exposed cohorts (Han Chinese and Tibetans) residing in Shigatse, Xizang (a.s.l. 4,700 m), suggesting that low intestinal uric acid levels facilitate adaptation to high-altitude hypoxia. Integrative analyses with gut metagenomic data showed consistent trends in intestinal uric acid levels and the abundance of key uric acid-degrading bacteria, predominantly from the Lachnospiraceae family. The sustained high abundance of these bacteria in the long-term resident cohorts underscores their essential role in maintaining low intestinal uric acid levels. Collectively, these findings suggest that the rewiring of intestinal uric acid metabolism, potentially orchestrated by gut bacteria, is crucial for enhancing human resilience and adaptability in extreme environments.