Hyperuricemia Research Articles

Elucidating the role of gut microbiota dysbiosis in hyperuricemia and gout: Insights and therapeutic strategies

Hyperuricemia (HUA) is a condition associated with a high concentration of uric acid (UA) in the bloodstream and can cause gout and chronic kidney disease. The gut microbiota of patients with gout and HUA is significantly altered compared to that of healthy people. This article focused on the complex interconnection between alterations in the gut microbiota and the development of this disorder. Some studies have suggested that changes in the composition, diversity, and activity of microbes play a key role in establishing and progressing HUA and gout pathogenesis. Therefore, we discussed how the gut microbiota contributes to HUA through purine metabolism, UA excretion, and intestinal inflammatory responses. We examined specific changes in the composition of the gut microbiota associated with gout and HUA, highlighting key bacterial taxa and the metabolic pathways involved. Additionally, we discussed the effect of conventional gout treatments on the gut microbiota composition, along with emerging therapeutic approaches that target the gut microbiome, such as the use of probiotics and prebiotics. We also provided insights into a study regarding the gut microbiota as a possible novel therapeutic intervention for gout treatment and dysbiosis-related diagnosis.

Clinical and instrumental characteristics of osteoarthritis in hyperuricemia

Objective: to investigate in a multicentre single-stage study the relationships between hyperuricemia (HU) and clinical, instrumental and laboratory parameters of osteoarthritis (OA).Material and methods. The study included 200 patients aged 40 to 75 years with a definite diagnosis of knee (KN) OA that met ACR criteria, with stage I–III OA by Kellgren–Lawrence. The mean age of the patients was 55.9±10.3 years and the body mass index (BMI) was 29.4±6.2 kg/m2. An individual chart was completed for each patient, including anthropometric parameters, medical history and clinical examination data, visual analogue scale (VAS) assessment of KN pain, WOMAC, patient's general health assessment (GHA) and information on comorbidities. All patients underwent standard radiography and magnetic resonance imaging (MRI) of the KN (WORMS), dual-energy X-ray absorptiometry of the lumbar spine and femoral neck, and laboratory examination.Results and discussion. HU was diagnosed in 57 (28.5) patients when the serum uric acid (UA) level was above 360 μmol/L. Patients were divided into two groups according to the presence or absence of HU. The age of the patients in the two groups was comparable, but they differed significantly in terms of disease duration, BMI, waist and hip circumference, which were greater in the HU group (p <0.05). Statistically significant differences were also found in the assessment of the severity of OA course: there were higher pain indices according to VAS, WOMAC total score and its components (pain and functional impairment, FI), GHA in the HU group. On MRI, osteitis was more common in the medial aspect of the tibia (odds ratio 5.75; 95% confidence interval 1.29–25.6; p=0.03). Patients with HU had higher concentrations of CRP, COMP, leptin, insulin, triglycerides and creatinine (p <0.05 for all values).Spearman correlation analysis confirmed the association between HU and duration and radiological stage of OA, the presence of osteitis in the medial aspect of tibia detected by MRI, pain according to VAS and WOMAC, FI according to WOMAC and GHA (p<0.05).Conclusion. At high UA levels, pain values according to VAS and WOMAC are higher, GHA is worse, and CRP and COMP levels are elevated. MRI shows more frequent osteitis in the medial aspect of the tibia in patients with HU. Deciphering the mechanisms that determine the relationship between HU and OA is important for the development of new methods for the prevention and treatment of these diseases.

Febuxostat in patients with hyperuricemia and gout: is the nephroprotective effect real?

Hyperuricemia (HU) and gout are independent risk factors for chronic kidney disease (CKD). Worldwide, the increasing prevalence of CKD leads to a deterioration in the quality and duration of life of patients and an increase in mortality. If HU plays a significant role in the development of renal failure, then lowering high uric acid (UA) levels should theoretically contribute to the improvement of kidney function. The main method of lowering UA levels is administration of a urate-lowering therapy – xanthine oxidase (XO) inhibitors. The nephroprotective effect of one of the XO inhibitors, febuxostat has been demonstrated in animal models.The article analyzes the currently available data on the use of febuxostat in patients with HU and gout and different levels of renal function impairment and discusses the possible mechanisms of the drug's nephroprotective effect.

The alleviating effects and mechanisms of Lactiplantibacillus plantarum MC14 on hyperuricemia in mice

Hyperuricemia (HUA) is a chronic disorder resulting from purine metabolic dysregulation. This research explored the alleviating effects and potential mechanisms of Lactiplantibacillus plantarum MC14 on HUA in a mouse model. Further, it investigated the impact of MC14 intervention on the intestinal flora and metabolites of HUA model mice. Results indicated that the activity of MC14 in alleviating HUA may be linked to its abilities to lower serum levels of uric acid, creatinine, and blood urea nitrogen, reduce inflammation, alleviate renal tissue damage, enhance uric acid excretion, inhibit the overactivation of the PI3K/AKT/mTOR signaling pathway, suppress hepatic adenosine deaminase and xanthine oxidase activities, competitively absorb nucleosides and nucleobases, and regulate the intestinal flora. Our research demonstrates that MC14 is a potential candidate for developing novel therapeutics for hyperuricemia.

Study on risk factor analysis and model prediction of hyperuricemia in different populations.

The purpose of the present study was to explore the influencing factors of hyperuricemia (HUA) in different populations in Shandong Province based on clinical biochemical indicators. A prediction model for HUA was constructed to aid in the early prevention and screening of HUA. In total, 705 cases were collected from five hospitals, and the risk factors were analyzed by Pearson correlation analysis, binary logistic regression, and receiver operating characteristic (ROC) curve in the gender and age groups. All data were divided into a training set and test set (7:3). The training set included age, gender, total protein (TP), low-density lipoprotein cholesterol (LDL-C), and 15 other indicators. The random forest (RF) and support vector machine (SVM) methods were used to build the HUA model, and model performances were evaluated through 10-fold cross-validation to select the optimal method. Finally, features were extracted, and the ROC curve of the test set was generated. TP, LDL-C, and glucose (GLU) were risk factors for HUA, and the area under the curve (AUC) value of the SVM validation set was 0.875. The SVM model based on clinical biochemical indicators has good predictive ability for HUA, thus providing a reference for the diagnosis of HUA and the development of an HUA prediction model.

Association of dietary patterns with serum uric acid and hyperuricemia in Chinese adults

Objective: To analyze the dietary patterns of Chinese adults and explore the relationship with serum uric acid (SUA) and hyperuricemia (HUA). Methods: A total of 9 358 adults were selected in the 2018 China Health and Nutrition Survey. Dietary intake data were collected by three consecutive 24-hour dietary recalls and weighing method. The social demographic information of the survey subjects was obtained through questionnaire surveys. The dietary patterns were extracted using factor analysis, and the relationship between dietary patterns and SUA was analyzed using multiple linear regression analysis. The correlation between HUA and dietary patterns was analyzed using logistic regression analysis models. Results: Four dietary patterns were identified: northern (high intakes of wheat, other cereals,and tubers); modern (high intakes of fruit, dairy, eggs, and nuts); southern (high intakes of rice and vegetables);animal food-wine (high intake of organ meats, seafood, and wine). The multiple linear regression analysis results showed that the northern pattern was negatively correlated with SUA (β=-0.438, 95%CI: -0.500--0.376); the modern pattern was negatively correlated with SUA (β=-0.134, 95%CI: -0.219--0.049); the southern model was significantly correlated with higher SUA (β=0.146, 95%CI: 0.079-0.214); the animal food-wine pattern was positively correlated with SUA (β=0.188, 95%CI: 0.123-0.252). Logistic regression analysis showed that compared with the northern model score Q1 group, the risk of developing HUA was reduced in Q3 and Q4 groups, with ORs values of 0.777 (95%CI: 0.650-0.929) and 0.509 (95%CI: 0.423-0.613), respectively; and compared with the modern model score Q1 group, the higher the scores in Q3 and Q4 groups, the HUA was lower, with ORs of 0.793 (95%CI: 0.660-0.953) and 0.768 (95%CI: 0.631-0.934), respectively. Compared with the animal food-wine pattern score Q1 group, the risk of developing HUA was increased in both Q3 and Q4 groups (Q3 group: OR=1.224, 95%CI: 1.012-1.480; Q4 group: OR=1.312, 95%CI: 1.086-1.584). Conclusions: Dietary patterns are associated with HUA. The northern and modern patterns are related to lower SUA levels and reduced risk of HUA, while the animal food-wine pattern increases the risk of HUA.

Associations of Dietary Magnesium Intake with All-Cause and Cause-Specific Mortality Among Individuals with Gout and Hyperuricemia.

We aimed to evaluate the relationship of dietary magnesium intake with all-cause and cause-specific mortality among patients with gout and hyperuricemia (HUA). We analyzed data of 1171 gout patients and 6707 HUA patients from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 and 2001-2018, respectively. Dietary intake data were obtained from 24-h dietary recall interviews. Mortality status was determined using the NHANES public-use linked mortality fill. We used Cox regression model and restricted cubic spline analysis to probe the association of dietary magnesium intake and mortality among gout and HUA patients. During 7081 person-years of follow-up, 257 deaths were documented in gout patients, among which 74 died from cardiovascular disease (CVD) and 48 died from cancer. For HUA patients followed up for 58,216 person-years, 1315 all-cause deaths occurred, including 411 CVD deaths and 224 cancer deaths. After multifactorial adjustments, higher dietary magnesium intake was associated with lower risk of all-cause mortality. Nonlinear negative associations were found between dietary magnesium intake and CVD mortality among gout and HUA patients, with inflection points of 152.5mg/day and 303mg/day, respectively, and cancer mortality among HUA patients, with the inflection point of 232mg/day. The results were robust in subgroup and sensitivity analyses. High dietary magnesium intake is linearly related to all-cause mortality, and nonlinearly associated with cause-specific mortality among gout and HUA patients.

Integrated microbiome and metabolome analysis reveals the key role of taurohyocholate in the treatment of hyperuricemia with Lacticaseibacillus rhamnosus 2016SWU.05.0601

The incidence of hyperuricemia (HUA) is on the rise, posing a significant threat to human health. Several probiotics have shown potential in treating HUA; however, the critical role of intestinal metabolites in this therapy remains inadequately understood. Our study demonstrated that Lacticaseibacillus rhamnosus 2016SWU.05.0601 not only reduced the expression levels of xanthine dehydrogenase and the content and activity of xanthine oxidase in the liver but also regulated the uric acid transporters expression in the kidney, thereby attenuating HUA in mice. Additionally, L. rhamnosus 2016SWU.05.0601 modulated the gut microbiota and metabolite abundance in HUA mice. Correlation analysis revealed that the gut microbiota metabolite taurohyocholate played a vital role in the treatment of HUA by L. rhamnosus 2016SWU.05.0601, as confirmed in HUA cell models. Our research provides a significant theoretical basis for elucidating the mechanisms by which probiotics alleviate HUA and for developing functional ingredients for HUA treatment.

Sleeve gastrectomy ameliorates renal injury in obesity-combined hyperuricemic nephropathy mice by modulating the AMPK/Nrf2/ABCG2 pathway

Hyperuricemic nephropathy (HN) is renal injury caused by hyperuricemia (HUA). While sleeve gastrectomy (SG) has shown promise in improving renal injury in patients with obesity-related HN, the mechanisms are not fully understood. This study induced an obesity-combined HN model in male ob/ob mice and measured serum uric acid (SUA), creatinine, and other biochemical indicators 6 weeks post-surgery. Renal histological changes were evaluated through staining techniques, and the study also assessed renal adenosine monophosphate-activated protein kinase (AMPK) and nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation levels and urate transporter ABCG2 expression. In vitro experiments involved Nrf2 knockdown in AMPK-activated HK-2 cells and ChIP to confirm Nrf2 binding to the ABCG2 promoter. Results showed that SG reduced SUA levels, serum creatinine, and blood urea nitrogen, increased p-AMPK, p-Nrf2 protein, and ABCG2 expression, and alleviated renal fibrosis and inflammation. In vitro, Nrf2 knockdown down-regulated ABCG2 expression, and ChIP confirmed Nrf2’s role in ABCG2 transcription. The study suggests that SG may improve renal injury in HN mice by modulating the AMPK/Nrf2 pathway and upregulating ABCG2 transcription.

Identifying reliable obesity indices for hyperuricemia among middle-aged and elderly populations: a longitudinal study

BackgroundGiven the established link between obesity and hyperuricemia (HUA), the research want to investigate the relationship between different obesity indices and HUA, and further analyze which obesity index can better predict HUA.MethodsThe data were obtained from a longitudinal study involving middle-aged and elderly populations in Dalian, China. The research encompassed individuals who exhibited typical uric acid levels initially and tracked their progress over a three-year period. 8 obesity indices were evaluated retrospectively. Subgroup analyses were conducted to identify susceptible populations. Restricted cubic splines (RCS) were utilized to model the dose-response relationships between obesity indices and HUA. Receiver operating characteristic (ROC) curves were applied to visualize and compare the predictive value of both traditional and new obesity indices for HUA.ResultsAmong 4,112 individuals with normal baseline uric acid levels, 950 developed HUA. Significant associations with HUA were observed for body mass index (BMI), waist circumference (WC), body roundness index (BRI), cardiometabolic index (CMI), visceral adiposity index (VAI), Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP), and abdominal volume index (AVI). Subgroup analysis indicated that all obesity indices proved more effective in assessing the onset of HUA in women without Metabolic Syndrome (MetS). Further analysis using RCS revealed non-linear dose-response relationships between LAP, CMI, VAI, and HUA in males, with similar non-linear relationships observed for all indices in females. The results from the ROC curves indicate that LAP may serve as a better predictor of HUA in males, and CVAI may serve as a better predictor in females.ConclusionHUA is closely associated with obesity indices. Among females, CVAI emerges as the preferred predictive index for HUA. In males, LAP emerges as the preferred predictive index for HUA.

Comparison of the predictive value of four insulin resistance surrogates and hyperuricemia in women with recurrent pregnancy loss: A cross-sectional study.

Insulin resistance (IR), hyperuricemia (HUA), and recurrent pregnancy loss (RPL) elevate the risk of cardiovascular disease and metabolic disorders, while also impacting reproductive health. The relationship between IR, HUA, and RPL has not been thoroughly investigated. This study investigates the relationship between four IR surrogates and the risk of HUA in RPL patients. Data from a real-world study on RPL in China were analyzed using multivariable regression to determine the relationship between HUA and triglyceride and glucose (TyG) index, triglyceride glucose-body mass index (TyG-BMI), triglyceride to high-density lipoprotein cholesterol (TG/HDL-c) ratio, and metabolic score for insulin resistance (METS-IR). The predictive ability of these surrogates for detecting HUA in RPL patients was evaluated using the area under the curve and receiver operating characteristic analysis. Sensitivity analysis was performed using bootstrapping resampling. The study included 769 patients with a mean age of 30 ± 4 years old, 8.32% of whom had HUA. Four IR surrogates were closely related to HUA in patients of RPL after adjusting for age, menstrual cycle, creatinine, alanine transaminase, aspartate transaminase, total cholesterol, homocysteine, and low-density lipoprotein, with area under the curve values of TyG index (OR = 0.693, 95% confidence interval [CI]: 0.626, 0.759), TyG-BMI (OR = 0.731 95% CI: 0.657, 0.805), TG/HDL-C (OR = 0.703, 95% CI: 0.641, 0.764), and METS-IR (OR = 0.728, 95% CI: 0.655, 0.799). Bootstrap resampling yielded similar results. The TyG index, TyG-BMI, TG/HDL-c, and METS-IR significantly correlated with HUA in patients with RPL. The TyG-BMI had the highest predictive value of the four IR surrogates.

Effect of konjac glucomannan on gut microbiota from hyperuricemia subjects in vitro: fermentation characteristics and inhibitory xanthine oxidase activity.

The disorder of uric acid metabolism is closely associated with gut microbiota and short-chain fatty acids (SCFAs) dysregulation, but the biological mechanism is unclear, limiting the development of uric acid-lowering active polysaccharides. Konjac glucomannan (KGM) could attenuate metabolic disturbance of uric acid and modulate the gut microbiota. However, the relationship between uric acid metabolism and gut microbiota is still unknown. In this study, The fecal samples were provided by healthy volunteers and hyperuricemia (HUA) patients. Fecal samples from healthy volunteers was regarded as the NOR group. Similarly, 10% HUA fecal suspension was named as the HUA group. Then, fecal supernatant was inoculated into a growth basal medium containing glucose or KGM, and healthy fecal samples were designated as the NOR-GLU and NOR-KGM groups, while HUA fecal samples were designated as the HUA-GLU and HUA-KGM groups. All samples were cultured in an anaerobic bag system. After fermentation for 24 h, the samples were collected for further analysis of composition of intestinal microbiota, SCFAs concentration and XOD enzyme activity. The results showed that KGM could be utilized and degraded by the gut microbiota from HUA subjects, and it could modulate the composition and structure of their HUA gut microbiota to more closely resemble that of a healthy group. In addition, KGM showed a superior modulated effect on HUA gut microbiota by increasing Megasphaera, Faecalibacterium, Lachnoclostridium, Lachnospiraceae, Anaerostipes, and Ruminococcus levels and decreasing Butyricicoccus, Eisenbergiella, and Enterococcus levels. Furthermore, the fermentation solution of KGM showed an inhibitory effect on xanthine oxidase (XOD) enzyme activity, which might be due to metabolites such as SCFAs. In conclusion, the effect of KGM on hyperuricemia subjects was investigated based on the gut microbiota in vitro. In the present study. It was found that KGM could be metabolized into SCFAs by HUA gut microbiota. Furthermore, KGM could modulate the structure of HUA gut microbiota. At the genus level, KGM could decrease the relative abundances of Butyricicoccus, Eisenbergiella, and Enterococcus, while Lachnoclostridium and Lachnospiraceae in HUA gut microbiota were significantly increased by the addition of KGM. The metabolites of gut microbiota, such as SCFAs, might be responsible for the inhibition of XOD activity. Thus, KGM exhibited a superior probiotic function on the HUA gut microbiota, which is expected as a promising candidate for remodeling the HUA gut microbiota.

Shield-armed probiotic delivery system based on co-deposition of poly-dopamine and poly-l-lysine helps Lactiplantibacillus plantarum relieve hyperuricemia

Hyperuricemia (HUA) is a disease characterized by an abnormal metabolism of purine. Lactic acid bacteria (LAB) have attracted much attention for their safe and effective treatment of HUA by inhibiting xanthine oxidase (XOD) and regulating gut microbiota. However, the effectiveness of probiotics can be compromised by the harsh environment of the gastrointestinal tract. In preliminary experiments, Lactiplantibacillus plantarum DY1, which is generally regarded as safe (GRAS), can lower uric acid. We have devised a straightforward and efficient technique for encapsulating DY1 using a coating comprising polydopamine (PDA) co-deposited with poly-l-lysine (PLL) to obtain DY1@PDLL. TEM, SEM, FT-IR and DLS tests showed that DY1 was successfully coated. Incubate at SGF or SIF for 3 h, the number of viable bacteria of free probiotics and DY1@PDLL decreased by 0.92 and 0.46 log cfu/mL, 1.66 and 0.66 log cfu/mL, respectively. The fluorescence intensity of the intestines of the DY1@PDLL treated mice was 3.96 times that of free probiotic. Notably, DY1@PDLL can reduce the uric acid levels of HUA mice by 31.63 % and free probiotics by 18.72 % (≈1.69 times). DY1@PDLL could also regulate gut microbiota and serum metabolic profile. These findings unequivocally highlight the remarkable potential of DY1@PDLL as an exceptional oral probiotic delivery system.

Mechanism of Biqi capsules in the treatment of gout based on network pharmacology and experimental verification

Ethnopharmacological relevanceGout is a crystal-related arthropathy caused by monosodium urate (MSU) deposition, resulting from purine metabolism disorders and hyperuricemia (HUA). Gout belongs to the traditional medicine category of Bi syndrome. Biqi capsules (BQ) is a traditional Chinese medicine formula used to treat Bi syndrome. The BQ prescription is derived from the ancient prescription of Hua Tuo, a famous physician in the Han Dynasty. Aim of the studyTo study the effect and mechanism of BQ in treating acute gouty arthritis (AGA) and HUA. Materials and methodsAnalyzing BQ's signaling pathways for gout treatment via network pharmacology. The HUA model was induced orally with adenine and potassium oxonate. The rat AGA model was established by MSU injection. In vitro, MH7A and RAW 246.7 cells were treated with LPS and MSU. Serum uric acid, creatinine, and urea nitrogen levels were evaluated. Kidney and ankle joint pathology was observed via HE staining. Inflammatory signaling pathway proteins, epithelial-mesenchymal transition (EMT) pathway proteins, and uric acid metabolism-related proteins were detected by Western blot. Results1780 potential targets for gout treatment were identified, and 1039 target proteins corresponding to BQ's active ingredients were obtained. Pathway enrichment analysis revealed BQ improved gout mainly through inflammatory pathways. Experimental results showed BQ could reduce serum uric acid level and increase uric acid clearance rate by regulating the expression of adenosine deaminase (ADA), and organic anion transporter 1 (OAT1) and glucose transporter 9 (GLUT9) in HUA mice. BQ could improve renal function and injury by inhibiting the NLRP3 pathway in HUA mice' kidneys. Additionally, BQ could alleviate ankle joint swelling and synovial injury, inhibit the TLR4/NLRP3 pathway, and reduce levels of inflammatory factors including interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) in AGA rats. The main component of BQ, brucine, could inhibit the activation of NLRP3/NF-κB pathway induced by MSU and reduce the expression level of inflammatory factors (IL-6, IL-1β, and TNF-α) in macrophages. Brucine could inhibit the activation of the EMT pathway and reduce the expression level of inflammatory factors (IL-6, TNF-α) in human fibroblast-like synoviocytes (MH7A cells) induced by MSU. ConclusionsBQ effectively reduced serum uric acid levels, improved kidney and joint damage, and ameliorated the inflammatory response caused by MSU. Its main component, brucine, effectively improved the inflammatory response and reduced the invasive ability of synoviocytes induced by MSU.

Association between cardiovascular health assessed by life's essential 8 and hyperuricemia in U.S. adults: the NHANES 2009-2020.

This study presented the new Life's Essential 8 (LE8) framework for examining cardiovascular health (CVH) to analyze the potential relationship between the latter and hyperuricemia (HUA) in the U.S. population. Data on individuals aged at least 20 years were collected from the National Health and Nutrition Examination Survey (NHANES) 2009-2020. Smoothed curve fitting and multivariate logistic regression analyses were then performed on a sample of 25,681 adults to explore the association between LE8 and HUA. A sensitivity analysis was conducted to examine the robustness of the research findings. The study found a strong negative association between LE8 and HUA, with an odds ratio (OR) of 0.71 and a 95% confidence interval (CI) from 0.69 to 0.73 after adjusting for multiple confounding factors. The sensitivity analysis further validated the robustness of this association. This analysis consistently showed negative associations across different genders, ages, races, and education levels (p < 0.05), but there were no significant relationships with marital status. The association between uric acid levels and LE8 displayed an inverted L-shaped curve, with an inflection point around 41.43. The findings indicate a strong negative relationship between LE8 and HUA among the U.S. population, suggesting that higher scores on the LE8, which assesses CVH, were associated with reduced uric acid levels. The consistent negative association underscores the LE8 framework's potential as a valuable tool for understanding and managing HUA in CVH.

Associations between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and hyperuricemia: a cross-sectional study

Background and objectiveThe value of the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) assessment in the context of metabolic abnormalities is growing in importance. Nevertheless, the relationship between NHHR and hyperuricemia (HUA) is unknown. This study seeks to investigate the relationship between NHHR and HUA.MethodsThe data derived from the 2017–2020 National Health and Nutrition Examination Survey (NHANES) included 7,876 adult participants. The multivariable logistic regression model, subgroup analysis and smooth fitting curve were utilized in order to investigate the association between NHHR and HUA.ResultsIn the fully adjusted model 3, NHHR was significantly associated with HUA. Specifically, participants in the highest quartile of NHHR had 1.95 times higher odds of HUA prevalence compared to those in the lowest quartile [2.95 (2.39, 3.64), P < 0.0001]. Although the overall trend suggested a positive association, further analysis using smooth fitting curves and threshold effect analysis indicated that this association was nonlinear, with an inflection point at 5.8. The positive association persisted across different HUA definitions and after removing outliers. Subgroup analysis showed significant interactions between NHHR and HUA in different races and diabetes statuses. The odds of HUA prevalence were higher among non-diabetic participants [1.40 (1.32, 1.49), P < 0.0001] compared to diabetic participants [1.18 (1.06, 1.32), P = 0.0031]. Mexican Americans had the lowest odds of HUA prevalence [1.09 (0.92, 1.27), P = 0.2413] compared to other races.ConclusionsThere is a significant positive association between NHHR and HUA, indicating that NHHR may serve as a potential risk assessment maker for HUA, although further prospective studies are needed for validation.

Uric acid reference values for children and adolescents should be stratified by pubertal stage

Background and AimTo establish reference values for hyperuricemia (HUA) in children and adolescents. Methods and ResultsThe study enrolled 4,807 students from "The Evaluation and Monitoring on School-based Nutrition and Growth in Shenzhen study." Utilizing quantile regression, associations between age, body mass index (BMI), pubertal stage, and serum uric acid (SUA) were examined, alongside the relationship between SUA and cardiovascular disease (CVD) risk factors. Reference values for SUA were explored using receiver operating characteristic analysis, considering sex and pubertal stage. The prevalence of HUA was 34.3% for boys and 29% for girls (using the adult HUA diagnostic criteria: >420 μmol/L for males, >360 μmol/L for females), increasing with higher BMI, age, and pubertal stage. Pubertal stage had the largest influence on SUA in boys, while nutritional status was the most significant factor affecting SUA in girls. Adjusting for age and pubertal stage, higher SUA levels correlated with an increased risk of CVD risk factors. Proposed reference values included > 360 μmol/L for girls ages 6–17 years and prepubertal boys. For pubertal boys, reference values varied based on age: >392 μmol/L for ages 9–11 in early-middle puberty, >429 μmol/L for ages 12–14 in early-middle puberty, >478 μmol/L for ages 12–14 in late puberty, and >505 μmol/L for ages 15–17 in late puberty. ConclusionsStratifying HUA reference values by pubertal stage, particularly for boys, is crucial. Long-term follow-up of individuals with high SUA levels may aid in refining SUA reference values.

Linoleyl acetate and mandenol alleviate HUA-induced ED via NLRP3 inflammasome and JAK2/STAT3 signalling conduction in rats.

Hyperuricemia (HUA) is characterized by elevated blood uric acid levels, which can increase the risk of erectile dysfunction (ED). Clinical studies have demonstrated satisfactory efficacy of a traditional Chinese medicine formula QYHT decoction in improving ED. Furthermore, the main monomeric components of this formula, linoleyl acetate and mandenol, demonstrate promise in the treatment of ED. This study established an ED rat model induced by HUA and the animals were administered with linoleyl acetate and mandenol. HE and TUNEL were performed to detect tissue changes, ELISA to measure the levels of serum testosterone (T), MDA, NO, CRP, and TNF-α and qPCR and WB to assess the expression levels of NLRP3, ASC, Caspase-1, JAK2, and STAT3 in whole blood. The findings showed that linoleyl acetate and mandenol improved kidney tissue morphology, reduced cell apoptosis in penile tissue, significantly increased T and NO levels, while substantially decreasing levels of MDA, CRP, and TNF-α. Meanwhile, the expression of NLRP3, ASC, and Caspase-1 mRNAs and proteins was markedly reduced, and the phosphorylation of JAK2 and STAT3 was inhibited. These findings were further validated through faecal microbiota transplantation results. Taken together, linoleyl acetate and mandenol could inhibit NLRP3 inflammasome activation, reduce inflammatory and oxidative stress responses, suppress the activity of JAK-STAT signalling pathway, ultimately providing a potential treatment for HUA-induced ED.

Association of the ABCG2 rs2231142 variant with the Framingham Cardiovascular Disease Risk score in the Taiwanese population

BackgroundSerum uric acid (SUA) is an important predictor of cardiovascular events and mortality. The ABCG2 rs2231142 variant (TT genotype) is associated with hyperuricemia (HUA), but the relationship between ABCG2 gene polymorphisms and coronary artery disease (CAD) risk is poorly elucidated. We investigated the association between ABCG2 rs2231142 genetic variants and the Framingham Risk Score for Cardiovascular Disease (FRS-CVD) in a Taiwanese population. MethodsThis cross-sectional study enrolled 139,508 Taiwanese participants aged 30–70 years based on data from the Taiwan Biobank (TWB) database that was obtained from questionnaires, laboratory investigations, anthropometry, and Affymetrix TWB genome-wide single-nucleotide polymorphism (SNP) chip data analysis. The association between ABCG2 rs2231142 and FRS-CVD risk was evaluated using logistic regression analysis. ResultsCompared to those with the GG genotype, participants with the ABCG2 rs2231142 TT genotype had a significantly lower systolic blood pressure, smoking rate, body mass index, triglyceride level, waist circumference, waist–hip ratio, and body fat percentage, but had higher high-density lipoprotein cholesterol level. Despite the same FRS-CVD score, participants with TT genotypes had higher SUA. Even with the same SUA, TT carriers had a lower FRS-CVD than GT and GG carriers. Participants with the TT genotype had significantly lower CVD risk, particularly female participants with HUA and BMI <27 (OR: 0.760, 95 % CI: 0.587–0.985; p = 0.0381) group. ConclusionThe ABCG2 rs2231142 TT genotype is associated with a lower FRS-CVD, particularly in non-obese hyperuricemic female individuals. The complicated interplay among genetic variations, metabolic profile, and CVD risk provides insights for precision health.

Mechanisms of levan in ameliorating hyperuricemia: Insight into levan on serum metabolites, gut microbiota, and function in hyperuricemia rats

This study aims to investigate the effects of levan on the progression of hyperuricemia (HUA) rats and elucidate its underlying mechanisms. After levan intervention, both low and high-dose groups exhibited a significant decrease in serum uric acid (UA) levels, reaching 71.0 % and 77.5 %, respectively, compared to the model group. Furthermore, levan could alleviate renal pathological damage caused by glomerular cell vacuolation, inflammatory infiltration and collagen deposition. The results of enzyme activity assay and real-time fluorescence quantitative PCR showed that levan decreased UA production by inhibiting adenosine deaminase (ADA) activity and gene expression in liver; it upregulated ATP-binding cassette subfamily G member 2 protein (ABCG2) and organic anion transporter 1 (OAT1) transporter gene expression in the kidney, promoting UA excretion. Gut microbiome analysis indicated that levan regulated gut flora dysbiosis induced by HUA, resulting in up-regulated the abundance of beneficial bacteria (Muribaculaceae, Faecalibaculum, Bifidobacterium, and Lactobacillus) and decreased conditioned pathogenic bacteria (Escherichia_Shigella and Proteus). Non-targeted metabolomics showed changes in various serum metabolites associated with glycerophospholipid metabolism, lipid metabolism, and inflammation following oral administration of levan. Therefore, levan may be a promising functional dietary supplement for regulating the gut flora and remodeling of metabolic disorders in individuals with HUA.