Search

Purines are the building blocks of DNA/RNA, energy substrates, and cofactors. Purine metabolites, including ATP, GTP, NADH, and coenzyme A, are essential molecules in diverse biological processes such as energy metabolism, signal transduction, and enzyme activity. When purine levels increase, excess purines are either recycled to synthesize purine metabolites or catabolized to the end product uric acid. Purine catabolism increases during states of low oxygen tension (hypoxia and ischemia), but this metabolic pathway is incompletely understood in the context of histotoxic hypoxia (i.e., inhibition of oxygen utilization despite normal oxygen tension). In rabbits exposed to cyanide-a classical histotoxic hypoxia agent-we demonstrated significant increases in several concordant metabolites in the purine catabolic pathway (including plasma levels of uric acid, xanthosine, xanthine, hypoxanthine, and inosine) via mass spectrometry-based metabolite profiling. Pharmacological inhibition of the purine catabolic pathway with oxypurinol mitigated the deleterious effects of cyanide on skeletal muscle cytochrome c oxidase redox state, measured by non-invasive diffuse optical spectroscopy. Finally, plasma uric acid levels correlated strongly with those of lactic acid, an established clinical biomarker of cyanide exposure, in addition to a tissue biomarker of cyanide exposure (skeletal muscle cytochrome c oxidase redox state). Cumulatively, these findings not only shed light on the in vivo role(s) of cyanide but also have implications in the field of medical countermeasure (MCM) development.

In this article, we present the first demonstration of a distance-based paper analytical device (dPAD) for uric acid quantification in human urine samples with instrument-free readout and user-friendliness for the rapid diagnosis and prognosis of various related diseases. By employing gold nanoparticles (AuNPs) as a peroxidase-like nanozyme, our proposed technique eliminates the utilization of horseradish peroxidase (HRP), making the device cost-effective and stable. In our dPAD, uric acid in the sample is oxidized by the uricase enzyme and subsequently catalysed with AuNPs in the sample zone, generating hydroxyl radicals (˙OH). Then, the produced ˙OH reacts with 3,3′-diaminobenzidine (DAB) to form poly DAB (oxDAB), resulting in a coloured distance signal in the detection zone of the dPAD. The variation of the distance of the observed red-brown colour is directly proportional to the uric acid concentration. Our sensor exhibited a linear range from 0.50 to 6.0 mmol L−1 (R2 = 0.9922) with a detection limit (LOD) of 0.25 mmol L−1, covering the clinical range of uric acid in urine. Hence, there is no need for additional sample preparation or dilution. Additionally, this assay is highly selective, with no interferences. We also found that this approach could accurately and precisely determine uric acid in human control samples with the recovery ranging from 99.37 to 100.35 with the highest RSD of 4.05%. Our method is comparable with the use of a commercially available uric acid sensor at a 95% confidence interval. Consequently, the developed dPAD offers numerous advantages such as cost-effectiveness, simplicity, and ease of operation with unskilled individuals. Furthermore, this concept can be applied for extensive biosensing applications in monitoring other biomarkers as an alternative analytical point-of-care (POC) device. [ABSTRACT FROM AUTHOR]

ObjectiveMethodsResultsConclusionsThe study aims to explore the relationship between serum uric acid (UA) levels in the first trimester and pregnancy outcomes.The clinical data of 1381 pregnant women who delivered in the Department of Obstetrics and Gynecology of Beijing Chao-Yang Hospital from June 2021 to July 2022 were collected. All patients were categorized into four groups (Q1-Q4) according to quartiles of UA, using the first quartile of UA as the reference group. Logistic regression analysis was used to observe the correlation between UA and pregnancy outcomes. Restricted cubic spline (RCS) was drawn to observe the dose-response relationship between UA and pregnancy outcomes.The numbers of GDM patients in Q1-Q4 were 40 (11.70%), 46 (13.49%), 60 (17.29%) and 83 (23.65%), respectively (p < 0.001). Logistic regression analysis showed that higher quartiles of UA were significantly associated with an increased prevalence of gestational diabetes mellitus (GDM). After adjusting for confounding factors (maternal age, prepregnancy BMI, gestational weight gain, and gestational age), compared with the lowest quartile of UA, the highest quartile of UA had 2.06 times odds of GDM (OR, 2.06; 95% CI, 1.34, 3.18; p = 0.001) in Q4. RCS suggested that the risk of GDM increased slowly until UA levels reached 219.43 µmol/L and then began to increase rapidly afterward (overall p = 0.0037).Increased uric acid concentrations in the first trimester are associated with an increased risk of GDM and gestational hypertension. [ABSTRACT FROM AUTHOR]

Objectives: To explore the association between hyperuricemia and having periodontitis. Materials and methods: A representative cross-sectional dataset of 10,158 adults was extracted from the National Health and Nutrition Examination Survey (NHANES) 2009–2014. The association between hyperuricemia (the primary exposure) and having periodontitis (outcome) were evaluated using weighted logistic regression models. Serum uric acid (UA) levels and the UA to creatinine (UA/Cr) ratio were used as secondary exposures. Their associations with the diagnosis periodontitis were analyzed using weighted logistic regression or restricted cubic spline regression. Results: The prevalence of Stages III/IV periodontitis was 47.7% among individuals with hyperuricemia and 37.4% among those without. After adjustment, individuals with hyperuricemia had 0.281 times higher odds of developing Stages III/IV periodontitis compared to those without hyperuricemia (adjusted OR = 1.286, 95% CI = 1.040 to 1.591, P = 0.024). The increased odds could be explained by a linear relationship with the serum UA/Cr ratio and a U-shaped relationship with serum UA levels. Each unit increase in the serum UA/Cr ratio was associated with 0.048 times higher odds of developing Stages III/IV periodontitis (adjusted OR = 1.048, 95% CI = 1.008 to 1.088, P = 0.021). Additionally, each 1 mg/dL increase in serum UA was associated with 0.156 times higher odds (adjusted OR = 1.156, 95% CI = 1.009 to 1.323, P = 0.038) of developing Stages III/IV periodontitis when UA levels were greater than 5.9 mg/dL, but 0.118 times lower odds when UA levels were 5.9 mg/dL or lower (adjusted OR = 0.882, 95% CI = 0.790 to 0.984, P = 0.027). Sensitivity analyses validated the robustness of the findings. Conclusions: This study provides the first direct evidence that hyperuricemia is associated with Stages III/IV periodontitis. Clinical relevance: Hyperuricemia may represent a new potential comorbidity of periodontitis, possibly contributing directly or indirectly to the disease burden in patients with periodontitis. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Copyright of Baghdad Science Journal is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Numerous observational studies consistently highlight a strong association between serum uric acid (sUA) levels and atrial fibrillation (AF). However, the causal relationship and the direction of this association remain elusive, despite extensive research efforts. Objective: This study aimed to investigate the bidirectional causal relationships between sUA, gout, and the risk of AF using the two-sample Mendelian randomization (MR) approach. Methods: We conducted a comprehensive analysis utilizing publicly available genome-wide association studies (GWAS) summary statistics, employing stringent criteria to meticulously select genetic variants associated with sUA, gout, and AF. Our primary analytical approach was the inverse-variance weighted (IVW) method, complemented by some sensitivity analyses, including MR-Egger, weighted median, simple mode, and weighted mode, to estimate the causal effects. To identify potential violations, we conducted Egger regression and leave-one-SNP-out analyses. We assessed the strength of instrumental variables using F values to evaluate weak instruments. Additionally, we referenced the Phenoscanner database to exclude single nucleotide polymorphisms (SNPs) associated with confounding factors or outcomes. Results: Our forward Mendelian randomization analysis suggests that there is no causal relationship between UA levels/gout from different populations and the risk of AF [IVW OR 1.03, 95% CI: 0.97–1.08; p = 0.335; IVW OR 0.99, 95% CI: 0.97–1.02; p = 0.583; and IVW OR 1.07, 95% CI: 0.84–1.37; p = 0.575], respectively. We did not detect significant heterogeneity or potential pleiotropy, and we also excluded the possibility of weak instrumental variables. Furthermore, we did not find any reverse causal effects of AF on sUA levels and gout risk. Conclusion: Our findings challenge the widely held belief that lowering urate levels is uniformly effective in reducing the risk of atrial fibrillation (AF). Our study fails to substantiate the existence of a causal link between uric acid (UA) levels or gout and the development of AF, regardless of direction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Dual-energy computed tomography (DECT) is a noninvasive diagnostic tool for gouty arthritis. This study aimed to compare two postprocessing techniques for monosodium urate (MSU) detection: conventional two-material decomposition and material map-based decomposition. Methods: A raster phantom and an ex vivo biophantom, embedded with four different MSU concentrations, were scanned in two high-end CT scanners. Scanner 1 used the conventional postprocessing method while scanner 2 employed the material map approach. Volumetric analysis was performed to determine MSU detection, and image quality parameters, such as signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), were computed. Results: The material map-based method demonstrated superior MSU detection. Specifically, scanner 2 yielded total MSU volumes of 5.29 ± 0.28 mL and 4.52 ± 0.29 mL (mean ± standard deviation) in the raster and biophantom, respectively, versus 2.35 ± 0.23 mL and 1.15 ± 0.17 mL for scanner 1. Radiation dose correlated positively with detection for the conventional scanner, while there was no such correlation for the material map-based decomposition method in the biophantom. Despite its higher detection rate, material map-based decomposition was inferior in terms of SNR, CNR, and artifacts. Conclusion: While material map-based decomposition resulted in superior MSU detection, it is limited by challenges such as increased artifacts. Our findings highlight the potential of this method for gout diagnosis while underscoring the need for further research to enhance its clinical reliability. Relevance statement: Advanced postprocessing such as material-map-based two-material decomposition might improve the sensitivity for gouty arthritis in clinical practice, thus, allowing for lower radiation doses or better sensitivity for gouty tophi. Key Points: Dual-energy CT showed limited sensitivity for tophi with low MSU concentrations. Materiel-map-based decomposition increased sensitivity compared to conventional two-material decomposition. The advantages of material-map-based decomposition outweigh lower image quality and increased artifact load. [ABSTRACT FROM AUTHOR]

Background: The relationship between serum uric acid (SUA) levels and prostate cancer (PCa) remains controversial. This cross-sectional study investigated the association between SUA levels and PCa incidence. Methods: A total of 9,776 participants aged ≥40 from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2020 were included, 503 of whom had PCa. Weighted univariate logistic regression, multivariate logistic regression, and smooth-fitting curve analyses were used to analyze the association between SUA and PCa incidence. Concurrently, the fitted smoothing curves were used to explore the potential non-linear relationships. If non-linearity was observed, a recursive algorithm further calculated the inflection point. Results: Three models were used to analyze the correlation between SUA levels and PCa incidence. All regression models demonstrated a negative correlation between SUA levels and PCa incidence (model 1: OR = 0.88, 95% CI=0.80–0.97; model 2: OR = 0.87, 95% CI=0.80–0.96; model 3: OR = 0.87, 95% CI=0.78–0.96). According to the trend test, with increasing SUA, the risk of PCa showed a downward trend (three models P for trend = 0.037, 0.015, 0.016). According to the subgroup analysis, a significant negative correlation between SUA and PCa was detected in individuals aged >60 years, non-Hispanic whites, those of other races, and those with hypertension. Moreover, the association between SUA and PCa followed a U-shaped curve among participants without hypertension, and the inflection point of SUA was 5.1 mg/dl. Conclusions: This cross-sectional study revealed a negative relationship between SUA levels and the risk of PCa, particularly in specific demographic groups. These findings offer a fresh perspective on the role of SUA in PCa patients, potentially paving the way for new approaches for the prevention and treatment of PCa. However, further studies are necessary to validate these findings. [ABSTRACT FROM AUTHOR]

Background: Hyperuricemia is considered as an independent risk factor for acute ischemic stroke (AIS), and some AIS patients are accompanied by an increase in serum uric acid. Recent studies have highlighted the important role of gut microbiota in both hyperuricemia and AIS, but there is little available data on the relationship between gut microbiota and the pathogenesis of AIS with hyperuricemia (HAS). Methods: Here we profiled the gut microbiota composition in 63 HAS patients and 269 non-HAS patients through 16s rRNA sequencing. Male rat with hyperuricemia were subjected to middle cerebral artery occlusion (MCAO) to establish HAS model and were then treated with Parabacteroides distasonis. Subsequently, the neurological deficit, pathological damages and blood-brain barrier disruption were evaluated. Moreover, the levels of ROS, inflammatory cytokines, NF-휿B pathway related protein, and vascular density markers were determined. Results: There were significant differences of gut microbiota composition between HAS patients and non-HAS patients, and a significant decrease in the abundance of Parabacteroides in HAS patients compared to non-HAS patients. Animal experiments showed that supplementation with P. distasonis increased beneficial commensal bacteria, significantly improved neurological deficits, pathological damages and BBB disruption, as well as reduced the level of serum uric acid in HAS rats. We further demonstrated that P. distasonis treatment decreased ROS level and increased SOD2 level, thereby reducing oxidative stress. Meanwhile, P. distasonis effectively inhibited NF-휿B signal pathway and reduced the production of inflammatory cytokines, including TNF-α and IL-1β, alleviating the inflammatory response. Notably, P. distasonis treatment increased the levels of vascular density markers including cluster of differentiation 31 (CD31) and alpha-smooth muscle actin (α-SMA), ameliorating vascular damage in HAS rats. Conclusions: Together, these findings highlighted the important role of P. distasonis in the pathogenesis of HAS, and its mechanism was involved in the regulation of gut microbiota-gut-brain axis, which implied a novel strategy against HAS. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is a cluster of conditions that increase the risk of cardiovascular disease and diabetes. This study aimed to investigate the association between Neutrophil-Percentage-to-Albumin Ratio (NPAR) and MetS in a large, nationally representative US population. We analyzed data from 28,178 participants in the National Health and Nutrition Examination Survey (NHANES) 2005–2018. Logistic regression models were used to evaluate the association between NPAR and MetS. Restricted cubic spline (RCS) models were employed to assess the dose-response relationship. Mediation analyses were conducted to explore potential mediating effects of serum uric acid and triglyceride-glucose (TyG) index. After adjusting for confounders, participants in the highest NPAR quartile had a 14% higher risk of MetS compared to those in the lowest quartile (OR 1.14, 95%CI 1.03–1.27, P = 0.010). RCS models revealed a monotonic increasing trend between NPAR and MetS risk (P for overall association = 0.002). Mediation analyses showed that serum uric acid and TyG index mediated 14.93% and 29.45% of the total effect of NPAR on MetS, respectively. Subgroup analyses indicated that the positive association between NPAR and MetS was more pronounced in Mexican Americans, individuals aged 20–65 years, those with lower income, males, current smokers, and moderate drinkers. Higher NPAR is associated with increased risk of MetS in the US adult population. This association is partially mediated by serum uric acid and TyG index. These findings suggest that NPAR may serve as a novel biomarker for MetS risk assessment and provide insights into potential mechanisms linking inflammation and metabolic disorders. [ABSTRACT FROM AUTHOR]

The relationship between serum uric acid (SUA) and mortality in patients with cardiovascular disease (CVD) remains controversial. We aimed to explore the relationship between SUA and all-cause mortality (ACM) and cardiovascular mortality (CVM) in adult patients with CVD. This cohort study included 3977 patients with CVD from the National Health and Nutrition Examination Survey (2005–2018). Death outcomes were determined by linking National Death Index (NDI) records through December 31, 2019. We explored the association of SUA with mortality using weighted Cox proportional hazards regression models, subgroup analysis, Kaplan-Meier survival curves, weighted restricted cubic spline (RCS) models, and weighted threshold effect analysis among patients with CVD. During a median follow-up of 68 months (interquartile range, 34–110 months), 1,360 (34.2%) of the 3,977 patients with cardiovascular disease died, of which 536 (13.5%) died of cardiovascular deaths and 824 (20.7%) died of non-cardiovascular deaths. In a multivariable-adjusted model (Model 3), the risk of ACM (HR 1.38, 95% CI 1.16–1.64) and the risk of CVM (HR 1.39, 95% CI 1.04–1.86) for participants in the SUA Q4 group were significantly higher. In patients with CVD, RCS regression analysis revealed a nonlinear association (p < 0.001 for all nonlinearities) between SUA, ACM, and CVM in the overall population and in men. Subgroup analysis showed a nonlinear association between ACM and CVM with SUA in patients with CVD combined with chronic kidney disease (CKD), with thresholds of 5.49 and 5.64, respectively. Time-dependent ROC curves indicated areas under the curve of 0.61, 0.60, 0.58, and 0.55 for 1-, 3-, 5-, and 10-year survival for ACM and 0.69, 0.61, 0.59, and 0.56 for CVM, respectively. We demonstrate that SUA is an independent prognostic factor for the risk of ACM and CVM in patients with CVD, supporting a U-shaped association between SUA and mortality, with thresholds of 5.49 and 5.64, respectively. In patients with CVD combined with CKD, the association of the ACM and the CVM with SUA remains nonlinear. [ABSTRACT FROM AUTHOR]

Gout predominantly stems from hyperuricemia, precipitating the accumulation of urate crystals and consequent joint inflammation, swelling, and pain, thereby compromising the quality of life and presenting a formidable medical dilemma. Although conventional treatments like allopurinol and febuxostat target uric acid reduction via xanthine oxidase (XO) inhibition, they often entail adverse effects, prompting the exploration of safer alternatives. Resveratrol, a polyphenolic compound abundant in fruits and vegetables, has emerged as a potential XO inhibitor. However, its precise inhibitory mechanisms remain poorly understood. This study aims to comprehensively investigate resveratrol's XO inhibition through mechanistic insights, molecular docking simulations, animal model experiments, and biochemical analysis, contributing valuable insights to the development of novel therapeutics for hyperuricemia and gout. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical significance and level changes of uric acid (UA)/albumin(ALB) ratio (UAR) in patients with chronic kidney disease (CKD) complicated with coronary heart disease (CHD). Methods A total of 175 patients with CKD were divided into the simple CKD group (control group, n=94) and the CKD complicated with CHD group (experimental group, n=81). The differences of blood routine, blood lipid, renal function and UAR were compared between the two groups. The influencing factors of CKD complicated with CHD were analyzed by binary Logistic regression. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of each index for CKD complicated with CHD. Results There were no significant differences in white blood cell count (WBC), monocytes (Mon), total cholesterol (TC), total triglyceride (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) between the two groups. The levels of neutrophils (Neu), red cell distribution width variation coefficient (RDW-CV), blood urea nitrogen (BUN), creatinine (Cr), UA and UAR levels were higher in the experimental group than those in the control group (R＜0.05). The levels of lymphocyte (Lym), red blood cell count (RBC), mean corpuscular hemoglobin concentration (MCHC), platelet (PLT), estimated glomerular filtration rate (eGFR) and albumin (Alb) were lower in the experimental group than those in the control group (R＜0.05). Logistic regression analysis showed that lower levels of RBC and MCHC, and higher levels of UAR were independent risk factors for CKD complicated with CHD. ROC curve showed that the area under the UAR curve was the largest in RBC, MCHC and UAR detection, which was 0.912 (95%CI: 0.870-0.953), the sensitivity was 90.10%, the specificity was 77.70%, the Yoden index was 0.678 and the cutoff value was 10.935. The AUC of combined detection of RBC, MCHC and UAR was 0.987 (95%CI: 0.974-0.999), the sensitivity was 93.80% and the specificity was 97.90%. Conclusion The increased serum UAR level in patients with CKD is a predictor of CHD. The combined detection of UAR, RBC and MCHC has higher prediction efficiency. [ABSTRACT FROM AUTHOR]

Hyperuricemia and its development to gout have reached epidemic proportions. Systemic hyperuricemia is facilitated by elevated activity of xanthine oxidase (XO), the sole source of uric acid in mammals. Here, we aim to investigate the role of bilirubin in maintaining circulating uric acid homeostasis. We observed serum bilirubin concentrations were inversely correlated with uric acid levels in humans with new-onset hyperuricemia and advanced gout in a clinical cohort consisting of 891 participants. We confirmed that bilirubin biosynthesis impairment recapitulated traits of hyperuricemia symptoms, exemplified by raised circulating uric acid levels and accumulated hepatic XO, and exacerbated mouse hyperuricemia development. Bilirubin administration significantly decreased circulating uric acid levels in hyperuricemia-inducing (HUA) mice receiving potassium oxonate (a uricase inhibitor) or fed with a high fructose diet. Finally, we proved that bilirubin ameliorated mouse hyperuricemia by increasing hepatic autophagy, restoring antioxidant defense and normalizing mitochondrial function in a manner dependent on AMPK pathway. Hepatocyte-specific AMPKα knockdown via adeno-associated virus (AAV) 8-TBG-mediated gene delivery compromised the efficacy of bilirubin in HUA mice. Our study demonstrates the deficiency of bilirubin in hyperuricemia progression, and the protective effects exerted by bilirubin against mouse hyperuricemia development, which may potentiate clinical management of hyperuricemia. [Display omitted] • Serum bilirubin levels are associated with human hyperuricemia progression. • Bilirubin deficiency recapitulates traits of mouse hyperuricemia symptoms. • Bilirubin exhibits potent effect on uric acid regulation in mouse HUA models. • Bilirubin enhances hepatic autophagy and antioxidant defense via AMPK activation. [ABSTRACT FROM AUTHOR]

Background: Hyperuricemia has been linked to various adverse clinical outcomes. Data on the clinical outcomes and the relationship between hyperuricemia and sepsis remain limited. The aim of this study was to evaluate the impact of hyperuricemia on clinical outcomes in sepsis patients and to identify whether it can predict the mortality in this patient population. Methods: This was a retrospective cohort study of adult patients with sepsis admitted to the intensive care unit (ICU) from 1 January 2021 to 31 December 2023. The patients were divided into hyperuricemia and non-hyperuricemia groups. Hyperuricemia was defined as a serum uric acid level > 416.4 µmol/L (7.0 mg/dL) in males or >357.0 µmol/L (6.0 mg/dL) in females based on the first serum uric acid reading within 24 h of ICU admission. The primary outcome of this study was ICU mortality. Secondary outcomes included in-hospital mortality, progression to septic shock, and ICU and hospital lengths of stay (LOSs). Results: A total of 599 patients were included in the study. Among these, 303 were in hyperuricemia group, while 296 were in the non-hyperuricemia group. The incidence of ICU and in-hospital mortality was higher in the hyperuricemia group compared to the non-hyperuricemia group (26.7% vs. 18.9% (p < 0.001) and 34.7% vs. 19.3% (p < 0.001), respectively). After adjusting for cofounders, hyperuricemia was not a predictor of ICU mortality (OR 1.52, 95% CI 0.95–2.43, p = 0.083). Most secondary outcomes were similar between the groups. However, the hyperuricemia group had a higher incidence of progression to septic shock (67.3% vs. 50.7%, p < 0.001), and hospital LOS was significantly longer in the hyperuricemia group (384 vs. 264 h, p = 0.004). Conclusions: Our findings demonstrated that hyperuricemia in sepsis patients was associated with worse clinical outcomes such as higher ICU and hospital mortality. Moreover, there was a higher incidence of septic shock progression and longer hospital LOS. The other outcomes were not statistically significantly different. Further prospective research is warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to show the relationship between the serum uric acid level measured at diagnosis and the BRAF mutation status in the primary tumor tissue in patients with metastatic colorectal cancer. Methods: In this retrospective cross-sectional study, 264 patients (64% male) whose serum uric acid level was measured at the time of diagnosis and whose BRAF mutation status in the primary tumor was determined were included. Results: The BRAF mutation rate was 14% (n = 37). The median serum uric acid levels of all patients were 6.9 mg/dL (25%, 75% percentile range 3.7, 8.2). The serum uric acid level cut-off value was 6.6 mg/dL. Sensitivity and specificity for BRAF mutated patients were 84% and 27%, respectively. These rates were calculated as 85% and 70% in BRAF-mutated patients aged 65 and over. There was a significant correlation between BRAF mutation and high serum uric acid level, female gender, tumor located in the ascending colon, and multiple metastatic sites. The independent factors affecting BRAF mutation were age 65 and over, tumor in the ascending colon, and high serum uric acid level. Conclusion: As a result, we concluded that high serum uric acid level measured during diagnosis in metastatic colorectal cancer is an accessible and economical biomarker that can predict BRAF mutation in patients aged 65 and over. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is there a relationship between serum uric acid and fructose levels in polycystic ovary syndrome (PCOS)? SUMMARY ANSWER Elevated serum uric acid levels in women with PCOS positively correlate with serum fructose levels, and elevated serum fructose levels are an independent risk factor for hyperuricemia in women with PCOS. WHAT IS KNOWN ALREADY Our previous study suggested a link between elevated serum fructose levels and PCOS. Fructose is unique as it generates uric acid during metabolism, and high uric acid levels are associated with metabolic disorders and an increased risk of anovulation. However, the relationship between serum uric acid and fructose levels in women with PCOS remains unclear. STUDY DESIGN, SIZE, DURATION In a case-control study of 774 women (482 controls and 292 patients with PCOS) between May and October 2020 at the Shengjing Hospital of China Medical University, the relationship between uric acid and fructose levels in women with PCOS was examined. Participants were divided into subgroups based on various factors, including BMI, insulin resistance, dyslipidemia, metabolic syndrome, and hyperuricemia. PARTICIPANTS/MATERIALS, SETTING, METHODS Serum uric acid concentrations were measured using enzymatic assays, and serum fructose levels were determined using a fluorescent enzyme immunoassay. Dietary fructose data were collected through a validated food-frequency questionnaire of 81 food items. We applied restricted cubic splines to a flexibly model and visualized the linear/nonlinear relationships between serum uric acid and fructose levels in PCOS. Multivariate logistic analysis was executed to assess the association between serum fructose levels and hyperuricemia in PCOS. Human granulosa cell and oocyte mRNA profile sequencing data were downloaded for mapping uric acid and fructose metabolism genes in PCOS. Further downstream analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and protein–protein interactions were then carried out on the differentially expressed genes (DEGs). The correlation between uric acid and fructose metabolism genes was calculated using the Pearson correlation coefficient. The GeneCards database was used to identify DEGs related to uric acid and fructose metabolism in PCOS, and then several DEGs were confirmed by quantitative real-time PCR. MAIN RESULTS AND THE ROLE OF CHANCE Both serum fructose and uric acid levels were significantly increased in women with PCOS compared with the control women (P   <    0.001), and there was no statistically significant difference in dietary fructose intake between PCOS and controls, regardless of metabolic status. There was a positive linear correlation between serum uric acid and fructose levels in women with PCOS (P overall < 0.001, P non-linear = 0.30). In contrast, no correlation was found in control women (P overall = 0.712, P non-linear = 0.43). Additionally, a non-linear association was observed in the obese subgroup of patients with PCOS (P overall < 0.001, P non-linear = 0.02). Serum uric acid levels were linearly and positively associated with serum fructose levels in patients with PCOS with insulin resistance, dyslipidemia, and metabolic syndrome. Furthermore, even after adjusting for confounding factors, elevated serum fructose levels were an independent risk factor for hyperuricemia in patients with PCOS (P   =    0.001; OR, 1.380; 95% CI, 1.207–1.577). There were 28 uric acid and 25 fructose metabolism genes which showed a significant correlation in PCOS. Seven upregulated genes (CAT, CRP, CCL2, TNF, MMP9, GCG, and APOB) related to uric acid and fructose metabolism in PCOS ovarian granulosa cells were ultimately successfully validated using quantitative real-time PCR. LIMITATIONS, REASONS FOR CAUTION Due to limited conditions, more possible covariates (such as smoking and ethnicity) were not included, and the underlying molecular mechanism between fructose and uric acid levels in women with PCOS remains to be further investigated. WIDER IMPLICATIONS OF THE FINDINGS The results of this study and our previous research indicate that the high uric acid status of PCOS may be mediated by fructose metabolism disorders, highlighting the importance of analyzing fructose metabolism, and especially its metabolic byproduct uric acid, during the clinical diagnosis of PCOS. These results suggest the adverse effects of high uric acid in PCOS, and the importance of taking early interventions regarding uric acid levels to reduce the occurrence and development of further clinical signs, such as metabolic disorders in women with PCOS. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by: the National Natural Science Foundation of China (No. 82371647, No. 82071607, and No. 32100691); LiaoNing Revitalization Talents Program (No. XLYC1907071); Fok Ying Tung Education Foundation (No. 151039); and Outstanding Scientific Fund of Shengjing Hospital (No. 202003). No competing interests were declared. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Objectives Despite the well-established association between prediabetes and hyperuricaemia, knowledge about serum urate (SU) trends during the prediabetic phase is limited. Therefore, we aimed to assess the longitudinal changes of SU in individuals with prediabetes. Methods Individuals with prediabetes, defined by initial haemoglobin A1c (HbA1c) levels between 5.7% and 6.4%, were identified using electronic health records from an academic health system (2007–2022). We required at least one SU test before and after the prediabetes diagnosis. The primary outcome was the longitudinal SU trends during the follow-up period, estimated with a multivariable mixed-effects model. Patients were censored at diabetes onset. Marginal effects of covariates on SU changes were estimated. Subsequent analyses examined SU variations in subgroups stratified by age, sex, BMI, HbA1c, estimated glomerular filtration rate and metformin use. Results Out of 25 526 individuals with prediabetes, 1521 met the SU cohort requirements, contributing to 6832 SU observations. At baseline, median age was 63 years and 40% were female. Median values were SU 6.3 mg/dl, HbA1c 5.9% and BMI 30 kg/m2. Median follow-up was 7.4 years. Older age, male sex, greater BMI and higher HbA1c were significant predictors of increased longitudinal SU levels. Individuals with a BMI ≥30 kg/m2 exhibited higher SU levels compared with those with lower BMI values. Conclusion Among individuals with prediabetes, several baseline variables were significant predictors of increased SU levels over time. These longitudinal trends in SU, support the potential for early intervention during the prediabetic phase, possibly reducing the risk of gout. [ABSTRACT FROM AUTHOR]

Objectives The minor allele of the common rs2231142 ABCG2 variant predicts inadequate response to allopurinol urate lowering therapy. We hypothesize that additional variants in genes encoding urate transporters and allopurinol-to-oxypurinol metabolic enzymes also predict allopurinol response. Methods This study included a subset of participants with gout from the Long-term Allopurinol Safety Study Evaluating Outcomes in Gout Patients (LASSO), whose whole genome was sequenced (n  = 563). Good responders had a 4:1 or 5:1 ratio of good [serum urate (SU) <0.36 mmol/l on allopurinol ≤300 mg/day] to poor (SU ≥0.36 mmol/l despite allopurinol >300 mg/day) responses over five to six time points, while inadequate responders had a 1:4 or 1:5 ratio of good to poor responses. Adherence to allopurinol was determined by pill counts, and for a subgroup (n  = 303), by plasma oxypurinol >20μmol/l. Using the sequence kernel association test (SKAT), we estimated the combined effect of rare and common variants in urate secretory (ABCC4 , ABCC5 , ABCG2 , SLC17A1 , SLC17A3 , SLC22A6 , SLC22A8) and reuptake genes (SLC2A9 , SLC22A11) and in allopurinol-to-oxypurinol metabolic genes (AOX1 , MOCOS , XDH) on allopurinol response. Results There was an association of rare and common variants in the allopurinol-to-oxypurinol gene group (P SKAT-C = 0.019), and in MOCOS , encoding molybdenum cofactor sulfurase, with allopurinol response (P SKAT-C = 0.011). Evidence for genetic association with allopurinol response in the allopurinol-to-oxypurinol gene group (P SKAT-C = 0.002) and MOCOS (P SKAT-C < 0.001) was stronger when adherence to allopurinol therapy was confirmed by plasma oxypurinol. Conclusion We provide evidence for common and rare genetic variation in MOCOS associating with allopurinol response. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The prevalence of uric acid (UA) stones increases regularly due to its high correlation with obesity, hypertension, metabolic syndrome, type 2 diabetes, and aging. Uric acid stone formation is mainly due to an acidic urinary pH secondary to an impaired urinary ammonium availability responsible for UA rather than soluble urate excretion. Alkalization of urine is therefore advocated to prevent UA crystallization and considered effective therapy. METHODS: We report a large series of 120 patients with UA lithiasis who were successfully treated with potassium (K)-citrate for stone dissolution (n=75) and/or stone recurrence prevention (n=45) without any urologic intervention, with a median 3.14 years followup. The K-citrate was diluted in 1.5 L of water, avoiding gastrointestinal disorders. RESULTS: Among 75 patients having stones in their kidney at initiation of therapy, a complete chemolysis was obtained in 88% of cases. Stone risk factors decreased under treatment, mainly due to increased diuresis, urinary pH, and citrate excretion. Treatment was stopped in only 2% of patients due to side effects, with no hyperkalemia onset despite a median urinary potassium increase of 44 mmol/day. CONCLUSIONS: Contrary to other reports, our data show that medical treatment of UA kidney stones is well-tolerated and efficient if regular monitoring of urinary pH is performed. [ABSTRACT FROM AUTHOR]

Objective: The aim was to investigate the relationship between metabolic indices and abnormal bone mass (ABM), analyse the association between osteoprotegerin (OPG) gene mutations and ABM, and explore the interaction effect of type 2 diabetes mellitus (T2DM) and OPG gene mutations on bone mineral density (BMD) in postmenopausal women to provide a new supplementary index and a reliable basis for the early identification of osteoporosis (OP) in postmenopausal women in the clinical setting. Methods: Postmenopausal women hospitalized within the Department of Endocrinology of the First Affiliated Sanatorium of Shihezi University from June 2021 to March 2023 were retrospectively analysed, and the bone mineral density of lumbar vertebrae 1–4 (BMD (L1-4)) of the studied subjects was measured once via twin-energy X-ray absorptiometry. The studied subjects were divided into a normal bone mass (NBM) group and an ABM group according to their bone mineral density, and the general data of the studied subjects were recorded once. Blood biochemical indices were determined, and genotyping of the rs4355801 locus of the OPG gene was performed. Differences in the overall data and biochemical indices of the two groups were evaluated via the rank-sum test, and the relationship between blood glucose levels and mutations of the rs4355801 locus of the OPG gene and ABM or BMD (L1-4) was evaluated via binary logistic regression analysis or linear regression analysis. A bootstrap test was performed to test whether uric acid (UA) levels mediate the association between blood glucose levels and BMD (L1-4). Simple effect analysis was performed to analyse the interaction between T2DM and mutations at the rs4355801 locus of the OPG gene on BMD (L1-4). Results: ① After adjusting for confounding factors, the risk of ABM increased by 50% (95% CI 21–85%) for each unit increase in fasting plasma glucose (FPG) levels and 31% (95% CI 2–69%) for each unit increase in glycosylated haemoglobin (HbA1c) levels (both P < 0.05). FPG levels were negatively correlated with BMD (L1-4) (both P < 0.05), and uric acid in blood sugar and BMD (L1-4) played a significant mediating role in the model; this mediation accounted for 21% of the variance. ② After adjusting for confounding factors, women with the mutant genotypes GA and GG + GA of the OPG gene rs4355801 locus had a lower risk of ABM than did those with the wild-type genotype AA (OR = 0.71, 95% CI = 0.52–1.00; OR = 0.51, 95% CI = 0.28–0.92, P < 0.05). The mutant genotypes GG, GA and GG + GA were positively correlated with BMD (L1–4) (all P < 0.05). The interaction between T2DM and mutations in the OPG gene rs4355801 locus had an effect on BMD (L1-4), and this site mutation weakened the increase in blood glucose levels and led to an increase in the risk of ABM (P < 0.05). Conclusion: Elevated blood glucose levels in postmenopausal women were associated with an increased risk of ABM, and UA played a mediating role in the relationship FPG levels and BMD (L1-4), accounting for 21% of the variance. Mutations at the rs4355801 locus of the OPG gene were associated with a reduced risk of ABM in postmenopausal women. The interaction between T2DM and mutations at the rs4355801 locus of the OPG gene in postmenopausal women affects BMD (L1-4), and mutations at this locus attenuate the increased risk of ABM due to elevated blood glucose levels. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is associated with a heightened risk of cardiovascular and renal complications. While glycemic control remains essential, newer therapeutic options, such as SGLT2 inhibitors, offer additional benefits beyond glucose reduction. This review delves into the mechanisms underlying the cardio-renal protective effects of SGLT2 inhibitors. By inducing relative hypoglycemia, these agents promote ketogenesis, optimize myocardial energy metabolism, and reduce lipotoxicity. Additionally, SGLT2 inhibitors exert renoprotective actions by enhancing renal perfusion, attenuating inflammation, and improving iron metabolism. These pleiotropic effects, including modulation of blood pressure, reduction of uric acid, and improved endothelial function, collectively contribute to the cardiovascular and renal benefits observed with SGLT2 inhibitor therapy. This review will provide clinicians with essential knowledge, understanding, and a clear recollection of this pharmacological group's mechanism of action. [ABSTRACT FROM AUTHOR]

To address the limitations in existing urinary stone recurrence (USR) models, including failure to account for changes in 24-hour urine (24U) parameters over time and ignoring multiplicity of stone recurrences, we presented a novel statistical method to jointly model temporal trends in 24U parameters and multiple recurrent stone events. The MSTONE database spanning May 2001 to April 2015 was analyzed. A joint recurrent model was employed, combining a linear mixed-effects model for longitudinal 24U parameters and a recurrent event model with a dynamic first-order Autoregressive (AR(1)) structure. A mixture cure component was included to handle patient heterogeneity. Comparisons were made with existing methods, multivariable Cox regression and conditional Prentice-Williams-Peterson regression, both applied to established nomograms. Among 396 patients (median follow-up of 2.93 years; IQR, 1.53–4.36 years), 34.6% remained free of stone recurrence throughout the study period, 30.0% experienced a single recurrence, and 35.4% had multiple recurrences. The joint recurrent model with a mixture cure component identified significant associations between 24U parameters - including urine pH (adjusted HR = 1.991; 95% CI 1.490–2.660; p < 0.001), total volume (adjusted HR = 0.700; 95% CI 0.501–0.977; p = 0.036), potassium (adjusted HR = 0.983; 95% CI 0.974–0.991; p < 0.001), uric acid (adjusted HR = 1.528; 95% CI 1.105–2.113, p = 0.010), calcium (adjusted HR = 1.164; 95% CI 1.052–1.289; p = 0.003), and citrate (adjusted HR = 0.796; 95% CI 0.706–0.897; p < 0.001), and USR, achieving better predictive performance compared to existing methods. 24U parameters play an important role in prevention of USR, and therefore, patients with a history of stones are recommended to closely monitor for future recurrence by regularly conducting 24U tests. [ABSTRACT FROM AUTHOR]

Psoriasis mimics uric acid in terms of inflammation, but the association has not been well defined. This study aimed to identify the causal link between serum uric acid (SUA) and psoriasis in an observational study using the National Health and Nutrition Examination Survey (NHANES, 2004–2006, and 2011–2014) and transethnic Mendelian randomization (MR) analyses. We utilized weighted multivariable-adjusted logistic regression and transethnic MR in European and East Asian populations to assess the association. Inverse variance weighted (IVW) was the main analysis. To test the robustness and pleiotropy, further sensitivity analyses were also conducted. Weighted regression analysis suggested that SUA positively related to psoriasis risk (OR = 1.339, 95% CI: 1.092–1.642, P = 0.006) in women. For all participants and males, neither association was significant. IVW showed that SUA levels were not significantly associated with psoriasis in Europeans (OR = 1.099, 95% CI: 0.963–1.254, P = 0.159) or East Asians (OR = 1.297, 95% CI: 0.576–2.918, P = 0.528). Furthermore, sensitivity analyses confirmed the robustness of the present MR results. In females, SUA and psoriasis were significantly correlated; findings from transethnic MR analysis did not indicate a causal relationship between SUA and psoriasis. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative condition marked by the gradual depletion of dopaminergic neurons in the substantia nigra. Despite substantial strides in comprehending potential causative mechanisms, the validation of biomarkers with unequivocal evidence for routine clinical application remains elusive. Consequently, the diagnosis heavily relies on patients' clinical assessments and medical backgrounds. The imperative need for diagnostic and prognostic biomarkers arises due to the prevailing limitations of treatments, which predominantly address symptoms without modifying the disease course. This comprehensive review aims to elucidate the existing landscape of diagnostic and prognostic biomarkers for PD, drawing insights from contemporary literature. [ABSTRACT FROM AUTHOR]

Objective: Caffeine, an adenosine receptor antagonist, is a potent central nervous system stimulant that also impairs insulin signaling. Recent studies have suggested that coffee consumption lowers serum urate (SU) and protects against gout by unknown mechanisms. We hypothesized that caffeine lowers SU by affecting activity of urate transporters. Methods: We examined the effect of caffeine and adenosine on basal and insulin stimulation of net 14C‐urate uptake in the human renal proximal tubule cell line PTC‐05 and on individual urate transporters expressed in Xenopus laevis oocytes. Results: We found that caffeine and adenosine efficiently inhibited both basal and insulin stimulation of net 14C‐urate uptake mediated by endogenous urate transporters in PTC‐05 cells. In oocytes expressing individual urate transporters, caffeine (>0.2 mM) more efficiently inhibited the basal urate transport activity of GLUT9 isoforms, OAT4, OAT1, OAT3, NPT1, ABCG2, and ABCC4 than did adenosine without significantly affecting URAT1 and OAT10. However, unlike adenosine, caffeine at lower concentrations (<0.2 mM) very effectively inhibited insulin activation of urate transport activity of GLUT9, OAT10, OAT1, OAT3, NPT1, ABCG2, and ABCC4 by blocking activation of Akt and extracellular signal–regulated kinase. Conclusion: We postulate that inhibition of urate transport activity of the re‐absorptive transporters GLUT9, OAT10, and OAT4 by caffeine is a key mechanism in its urate‐lowering effects. Additionally, the ability of caffeine to block insulin‐activated urate transport by GLUT9a and OAT10 suggests greater relative inhibition of these transporters in hyperinsulinemia. [ABSTRACT FROM AUTHOR]

Perfluoroalkyl and polyfluoroalkyl(PFAS) substances are the most common environmental pollutants, which has an inconsistent association with hyperuricemia across different populations. This study explored the relationship between hyperuricemia and different gender PFAS and PFAS mixtures, using data from two cycles of the NHANES from 2015-2018. Weighted logistic regression results showed that the correlation between individual PFAS and hyperuricemia was significant only in men. Compared to the reference quartile, the fourth quartile of n-PFOA increased the risk of hyperuricemia in men (OR: 2.79, 95% CI: 1.50, 5.18). The Qgcomp model results showed that each quartile increase in the serum concentration of PFAS mixtures was associated with an increased likelihood of hyperuricemia in the total population, with odds ratios (OR) for men and women being 1.74 (95% CI: 1.26, 2.40), and 2.04 (95% CI: 1.35, 3.16), respectively. we concluded that PFAS might increase the risk of hyperuricemia in adults. [ABSTRACT FROM AUTHOR]

Background: Gouty arthritis is a metabolic disease characterized by the deposition of monosodium urate crystals in the joints, which triggers the release of interleukin-1β (IL-β) by activating the NLRP3 inflammasome. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor involved in IL-β production and as a regulator of NLRP3. Objectives: The aims were to analyze the association of HIF1A rs11549465, rs11549467, and rs2057482 variants in patients with gouty arthritis, and to evaluate the correlation between urate and HIF-1α levels according to the associated genotypes. Methods: Cases and controls were genotyped using TaqMan probes, and urate and HIF-1α levels were quantified. Data were analyzed using SPSS v21 software and P-values < 0.05 were considered statistically significant. Results: Urate and HIF-1α levels were higher in patients than in controls (P < 0.05). Under the three inheritance models (codominant, dominant, and recessive), the AA genotype of the rs11549467 variant was associated with gout risk (OR = 5.74, P = 0.009, OR = 3.33, P = 0.024, and OR = 9.09, P = 0.003, respectively). There were significant differences in the distribution of serum levels of both HIF-1α (P < 0.0001) and urate (P = 0.016) according to the genotypes of the rs11549467 variant. Conclusion: These results suggest that the HIF1A rs11549467 variant may play a key role in the pathogenesis of gouty arthritis. Key Points • The pathogenesis of gouty arthritis involves the HIF1A gene. • In patients with gout, the AA genotype of the rs11549467 (HIF1A) variant is associated with increased serum levels of urate and HIF-1α. • HIF-1α is involved in the regulation of IL-1β and NLRP3. [ABSTRACT FROM AUTHOR]

Perenniporia fraxinea is a type of wild macrofungus that is widely distributed globally. This study aimed to explore and understand its medicinal value and potential as a functional food by evaluating the effects of its active ingredients. Specifically, we assessed their hypoglycemic, hypolipidemic, hypouricemic, and anti-nitrite properties. The highest concentrations of flavonoids, polyphenols, triterpenes, and sterols were found in the ethyl acetate extract of the fruiting body, followed by the n-butanol extract. The petroleum ether extract of the mycelium exhibited higher hypoglycemic activity than that of the fruiting body. The water extract of the fruiting body showed the highest ability to lower uric acid, while the petroleum ether extract exhibited the lowest. Lipid-lowering effects were stronger in all extracts except the water extract of the mycelium compared to those of the fruiting body. Additionally, the anti-nitrite activity of the water extract of the mycelium was higher than that of the fruiting body, whereas it was lower in all other extracts. [ABSTRACT FROM AUTHOR]

Introduction: The role of uric acid (UA) on bone metabolism is controversially discussed. Higher UA levels have been associated with higher T-scores and a reduced incidence of fractures in postmenopausal women. However, in the context of rheumatoid arthritis (RA), the role of UA remains unclear. This pilot study aimed to investigate the association of UA levels with bone mineral density in RA female and male patients. Methods: This pilot study analyzed patients with RA to explore preliminary associations. We utilized data from the Rh-GIOP cohort, a prospective monocentric observational study focusing on bone health in chronic rheumatic diseases. To assess the association between UA levels and the lowest T-scores measured at the lumbar spine, hip, or femur, we used linear regression with adjustment for various confounders. An interaction term was included to evaluate differential associations in pre- and postmenopausal women. Results: Data on dual X-ray absorptiometry (DXA) measurements and serum UA levels were analyzed in a total of 206 patients. Among the 167 women 16 were premenopausal (age 40 ± 8 years) and 149 postmenopausal (age 65 ± 10 years). As expected, postmenopausal had lower T-scores than premenopausal patients (-1.53 ± 1.01 versus − 0.41 ± 1.29, respectively). No association of UA levels with T-scores was found when analyzing the whole cohort (Slope β: -0.04; p = 0.45). However, a significant negative correlation of UA with T-scores in premenopausal (Slope β: -0.98; p = 0.014), but not postmenopausal (Slope β: -0.04; p > 0.05) women was found. Conclusion: Uric acid appears to be negatively associated with bone mineral density in premenopausal but not in postmenopausal women with RA. Thus, the impact of UA on bone health seems to depend on the hormonal status of women. Further investigations are required to validate these results in a larger cohort of patients and to investigate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Monomers: gentian violet (GV), brilliant green (BG), aniline, and methyl violet (MV), as well as their copolymers, were electropolymerized and used to modify glassy carbon electrode (GCE) by enhancing the sensitivity of the electrode. This is due to their special characteristics of sensing ability of the electropolymerized polymers. The electropolymerization and characterization of these monomers and their copolymers were done using cyclic voltammetry (CV) on GCE as a working electrode against Ag/AgCl reference electrode and platinum wire as the counter electrode. The copolymers showed higher current peaks than their corresponding homopolymers. The electrochemical characterization of these polymers and copolymers was studied by scan rate effect each between 10 and 300 mV/s and pH effect between 1.56 and 5.30. After being modified by the copolymers: poly(BG-GV) and poly(BG-MV), the modified GCE showed good results in resolving the peaks of ascorbic acid and uric acid which otherwise showed an overlapped broad peak on bare GCE. The CV in bare GCE was scanned at different scan rates of 4 mM K3[Fe(CN)6] in 1 M KNO3 solution. The square root of scan rate dependence of peak current was plotted and the Randles–Sevcik equation was applied to determine the diffusion coefficient of Fe(CN)63− ion and which was 1.13 × 10–14 cm2/s. This was used to determine the area of the modified electrode after running the CV of 4 mM K3[Fe(CN)6] in 1 M KNO3 at different scan rates. Therefore, the electrochemical polymerization of organic dye polymers was able to increase the sensitivity of the electrode by increasing its area. [ABSTRACT FROM AUTHOR]

It has been demonstrated in a number of studies that high levels of uric acid can cause crystal deposition in the tendons of the lower extremities, which in turn can impair the Achilles tendon. This study aimed to interpret whether hyperuricemia is relevant with Achilles tendon rupture. Patients diagnosed with Achilles tendon rupture at the same institution between 2013 and 2022 were included in the case group. Healthy subjects who had physical examinations during the same period were included in the control group. Propensity score matching was used to match in a 1:1 ratio. Demographic and clinical characteristics of patients in both groups were compared. Five hundred and fourteen patients were included in the study (ATR=257; Control group=257). The proportion of individuals with hyperuricemia varied significantly between the 2 groups (Achilles tendon rupture group=43.6%; control group=27.6%; p <0.001). The Achilles tendon rupture and hyperuricemia were linked by conditional logistic regression (p <0.001; OR=2.036; 95CI%=1.400-2.961). Compared with healthy subjects, patients with hyperuricemia have a higher risk of Achilles tendon rupture. Further studies are required to verify the effects of hyperuricemia and monosodium urate crystals on Achilles tendon structure. [ABSTRACT FROM AUTHOR]

• Mendelian randomization is a method that employs genetic variants as instrumental variables to explore the causal effects of genetic factors on phenotypes. • Our research revealed a causal link between serum uric acid levels and pulmonary arterial hypertension at the genetic level. • Uric acid is a potential target for future preventive and therapeutic strategies against pulmonary arterial hypertension. Observational studies have suggested a correlation between hyperuricemia and pulmonary arterial hypertension (PAH), yet the causal relationship remains uncertain. We aimed to establish this link using Mendelian Randomization (MR) methods. Based on publicly accessible data, our study employs MR to determine the causal relationship between uric acid (UA) and PAH. MR analysis was conducted among individuals of European descent. Genetic instruments linked to UA (p-value < 5 × 10–8) were extracted from the Chronic Kidney Disease Genetic Consortium and genome-wide association study databases. PAH risk genetic associations were sourced separately. We employed four MR methods (MR-Egger, weighted median, inverse variance weighted, and weighted mode) with selected instrumental variables to assess the causal association between UA and PAH. MR-PRESSO was used to evaluate pleiotropy and outlier Single Nucleotide Polymorphisms (SNPs), while Cochran's Q test and funnel plot assessed SNP heterogeneity. Leave-one-out analysis examined SNP impacts on causal assessment. Two-sample MR analysis revealed a positive, causal relationship between UA levels and PAH. Our MR analysis provides robust evidence of a causal link between serum UA and PAH, suggesting UA's potential as a biomarker and therapeutic target for PAH. [Display omitted] [ABSTRACT FROM AUTHOR]

Aim: Although a growing number of studies have shown that elevated uric acid (UA) levels are associated with multiple cardiovascular risk factors and progression of coronary artery disease, the causal relationship between UA and the occurrence of myocardial infarction (MI) remains uncertain. The aim of this study was to investigate the relationship between UA and the risk of MI. Methods: We screened 23,080 patients in the National Health and Nutrition Examination Survey (NHANES) database for 2009-2018 and explored the association between UA and MI risk using multivariate logistic regression model. In addition, a two-way two-sample Mendelian randomization (TSMR) analysis was performed to examine the causal relationship of UA on MI, and inverse variance-weighted (IVW) results were used as the primary outcome in this study. Sensitivity analysis and horizontal multiple validity test were also performed to verify the reliability of the results. Results: After multivariable adjustment, individuals with the severe elevation of UA levels have a significantly increased risk of MI (OR=2.843, 95%CI: 1.296-6.237, P=0.010). In TSMR analysis, the IVW method demonstrated a significant association between UA and increased risk of MI (OR=1.333, 95%CI: 1.079- 1.647, P=0.008). Results from the MR-Egger intercept test, Cochran’s Q test, and MR-PRESSO test all suggest the reliability of the IVW analysis. Reverse TSMR analysis did not indicate a causal relationship between genetic susceptibility to MI and UA levels (IVW: OR=1.001, 95%CI: 0.989-1.012, P=0.922). Conclusion: Based on cross-sectional study and Mendelian randomization analysis, it has been demonstrated that UA is an independent risk factor for MI. Elevated levels of UA increase the risk of MI, particularly in cases of severe elevation. [ABSTRACT FROM AUTHOR]

To identify rare variants (RVs) of gout, we sequenced the whole genomes of 321 male gout patients and combined these with those of 64 male gout patients and 682 normal controls at Taiwan Biobank. We performed ACAT-O to identify 682 significant RVs (p < 3.8 × 10-8) clustered on chromosomes 1, 7, 10, 16, and 18. To prioritize causal variants effectively, we sifted them by Combined Annotation-Dependent Depletion score >10 or |effect size| ≥ 1.5 for those without CADD scores. In particular, to the best of our knowledge, we identified the rare variants rs559954634, rs186763678, and 13-85340782-G-A for the first time to be associated with gout in Taiwanese males. Importantly, the RV rs559954634 positively affects gout, and its neighboring gene NPHS2 is involved in serum urate and expressed in kidney tissues. The kidneys play a major role in regulating uric acid levels. This suggests that rs559954634 may be involved in gout. Furthermore, rs186763678 is in the intron of NFIA that interacts with SLC2A9, which has the most significant effect on serum urate. Note that gene-gene interaction NFIA-SLC2A9 is significantly associated with serum urate in the Italian MICROS population and a Croatian population. Moreover, 13-85340782-G-A significantly affects gout susceptibility (odds ratio 6.0; P = 0.038). The >1% carrier frequencies of these potentially pathogenic (protective) RVs in cases (controls) suggest the revealed associations may be true; these RVs deserve further studies for the mechanism. Finally, multivariate logistic regression analysis shows that the rare variants rs559954634 and 13-85340782-G-A jointly are significantly associated with gout susceptibility. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to identify the factors most strongly associated with an increased atherosclerotic cardiovascular disease (ASCVD) risk score in patients with type 2 diabetes (T2D). Methods: This cross-sectional study included 4698 patients with T2D over an 11-year period (2010–2021). Patients were categorized into four groups based on their 10-year ASCVD risk score (< 5%, 5–7.5%, 7.5–20%, and > 20%). Multinominal regression analysis was used to evaluate the association between various modifiable and non-modifiable risk factors and the ASCVD risk score. Results: Of the patients, 35.9% had a 10-year ASCVD risk score below 5%, 12.6% had a score between 5% and 7.5%, 30.8% had a score between 7.5% and 20%, and 19.7% had a score above 20%. Higher ASCVD risk scores were significantly associated with elevated waist-to-hip ratio (WHR > 0.93), pulse pressure, uric acid, triglycerides, and decreased glomerular filtration rate (all p-values < 0.05). WHR demonstrated the strongest association with higher ASCVD risk scores (OR: 4.55, 95% CI: 2.94–7.03, p < 0.001) when comparing patients with ASCVD scores > 5% to those with scores < 5%. Conclusion: WHR was independently associated with higher ASCVD risk scores in patients with T2D. Incorporating WHR, along with traditional risk factors, could improve ASCVD risk assessments in this population. [ABSTRACT FROM AUTHOR]

Background: Both serum uric acid (SUA) levels and body mass index (BMI) are recognized as important risk factors for hypertension. The current study aimed to investigate the interaction effects between SUA levels and overweight (defined as BMI ≥ 24 kg/m2 in Chinese) on the incidence of hypertension among Chinese adults. Methods: 1124 hypertensive participants and 7283 non-hypertensive participants, extracted from the China Health and Nutrition Survey (CHNS), were analyzed. Participants were categorized based on their SUA levels and BMI, to investigate the interaction effects between SUA levels and overweight on hypertension. Results: In comparison with the reference group (BMI < 24 kg/m2 and in the 1st quintile of SUA), multivariable adjusted analysis demonstrated that the odds ratio (OR) (95% confidence interval, 95% CI) of hypertension for participants with overweight alone was 2.18 (1.41–3.37); for elevated SUA levels alone, the ORs (95% CIs) were 1.57 (1.08–2.30), 1.84 (1.24–2.74), 2.21 (1.47–3.32), and 2.48 (1.55–3.96) across SUA quintiles; and for the combined effect of higher SUA levels and overweight, the ORs (95% CIs) were 3.25 (2.19–4.82), 3.73 (2.51–5.55), 5.17 (3.42–7.80), and 6.21 (4.01–9.60). The relative excess risk due to interaction (RERI) was 3.26 (1.43–5.09) at the 5th quintile of SUA, indicating the presence of additive interaction between overweight and SUA levels on hypertension. Conclusion: Interaction between SUA levels and overweight on hypertension exists specifically at the highest quintile (Q5, > 6.39 mg/dL) of SUA among Chinese adults. Therefore, strategies to lower SUA levels could be considered as a potential approach to mitigate hypertension risk in overweight individuals within this specific subgroup. [ABSTRACT FROM AUTHOR]

Purpose: Uric acid stones (UAS) can be treated non-invasively by oral chemolysis. However, it is crucial to identify individuals who are most likely to benefit from this approach, specifically, patients with pure UAS. The aim of this study was to develop a nomogram that can differentiate between pure and mixed UAS. Methods: A retrospective analysis of demographic, clinical and stone composition data of patients with a predominant UAS composition (≥ 50%) treated between 2014 and 2022. Results: A total of 135 patients were included in the analysis, 37.8% had mixed UAS (50–90% UA) and 62.2% had pure UAS (≥ 95% UA). The mean stone density and the percentage of radiopaque stones in the pure UAS group were significantly lower than those in the mixed UAS group (450 Hounsfield Units [HU] vs. 600 HU, and 24% vs. 58%, respectively). A stepwise multivariate logistic regression revealed that lower stone density, bigger size, decreased stone opacity and older age are predictive variables for pure UAS. Accordingly, a nomogram was generated with a receiver operating characteristic (ROC) curve that showed an area under the curve (AUC) of 0.78. A patient with a total score of 156 has a probability of > 95% for pure UAS. Conclusion: Imaging and demographic data can be used to identify patients with pure UAS. The nomogram may be useful for counseling patients regarding oral chemolysis. Future validation of the nomogram with a different data set is required to assess its efficacy. [ABSTRACT FROM AUTHOR]

Background: Interleukin (IL)-38 is a newly discovered anti-inflammatory cytokine. However, its concentration and clinical significance in patients with gout remain unclear. This study aimed to investigate the levels of IL-38 in patients with gout and evaluate their clinical significance. Methods: Thirty-two patients with active gout, 27 patients with inactive gout, and 20 negative controls (NCs) were included in the study. Clinical parameters, including white blood cell count, C-reactive protein, serum amyloid A, erythrocyte sedimentation rate, uric acid, urea, creatinine, alanine aminotransferase, aspartate aminotransferase, glutamyl transpeptidase, and glycoserated serum protein, were obtained from laboratory tests of blood samples. The serum concentration of IL-38 was determined using enzyme-linked immunosorbent assay. Spearman’s correlation analysis and receiver operating characteristic curve assessments were used to investigate the role and diagnostic value of IL-38 in gout. Results: Patients with active and inactive gout exhibited significantly lower serum IL-38 levels than NCs. No significant differences were observed between the two gout groups. A negative correlation was observed between IL-38 and white blood cell counts, whereas a positive correlation was found between IL-38 and creatinine levels. Furthermore, IL-38, either alone or in combination with uric acid, demonstrated substantial diagnostic potential. Conclusion: The findings suggest that the decreased serum levels of IL-38 in patients with gout compared to that in NCs indicates that IL-38 may have immunomodulatory effects on gout inflammation and possesses clinical application value. [ABSTRACT FROM AUTHOR]

Background: The prevalence of hyperuricemia is increasing globally. The health check‐up population is a group of people dedicated to disease prevention in public health. This study aims to estimate the current prevalence of hyperuricemia among the health check‐up population in economically developed areas of China using a healthcare database. Method: Healthcare data from 48,988 subjects in 12 provinces of China who had an annual health check‐up in 2021 were used. Hyperuricemia was defined as a serum urate level > 420 mmol/L and/or a history of physician‐diagnosed gout. An alternative definition of serum urate level > 420 mmol/L in men and > 360 mmol/L in women was used. The stratified prevalence of hyperuricemia by sex, age, region, and comorbidity group was reported. The association between hyperuricemia and sex, age, region, and comorbidities was analyzed in the multivariate logistic regression model. Results: In 2021, the sex‐ and age‐adjusted prevalence of hyperuricemia was 13.6% in the total population (24.3% in men and 2.6% in women) based on the definition of serum urate level > 420 mmol/L. Regional prevalence varied considerably across the country, with the highest prevalence found in Fujian and the lowest in Liaoning Province (21.6% vs. 7.3%). Male sex, aging, hypertension, obesity, abdominal obesity, hypertriglyceridemia, and hypercholesterolemia were likely to be associated with hyperuricemia. Conclusions: This is the largest study using a healthcare database to indicate the prevalence of hyperuricemia in a health check‐up population in an economically developed area of China. The current prevalence among the Chinese health check‐up population was substantial, with a higher prevalence in males and in the eastern region. Hyperuricemia and its comorbidities warrant greater attention in the developed areas of China. [ABSTRACT FROM AUTHOR]

The causal link between serum uric acid (SUA) levels and gastric cancer susceptibility remains inadequately elucidated. This investigation employed a two-sample Mendelian randomization (MR) framework to assess the potential causative link between SUA concentrations and the propensity for developing gastric cancer. To further explore potential racial differences, this MR analysis was conducted on cohorts of both European and East Asian descent. Data from a large-scale GWAS in 343,836 Europeans and 92,615 East Asians were screened for 206 and 45 SNPs significantly linked to SUA levels, respectively, as genetic variants. Subsequently, four distinct MR methodologies were deployed to determine how SUA levels affected gastric cancer risk. Using the fixed-effects IVW approach, our analysis revealed no significant association between SUA levels and gastric cancer risk, with P-values exceeding the threshold of significance in both populations (European P = 0.778; East Asian P = 0.245). The findings were supported by three additional MR methods. The reliability of these results was substantiated by comprehensive sensitivity analyses. In summary, our data do not support a significant causal linkage between SUA levels and gastric cancer risk. [ABSTRACT FROM AUTHOR]

Aims The stress hyperglycemia ratio (SHR) is a valuable biomarker of acute hyperglycemia, significantly correlated with unfavorable prognosis in various conditions. However, its impact on Psoriasis has not been studied. We explored the association between SHR and long-term mortality in psoriasis patients. Methods We conducted a prospective cohort study with 288 psoriasis patients from the 2003–2006 and 2009–2014 NHANES. Participants were divided into three groups based on SHR tertiles: T1 (SHR ≤ 0.870), T2 (SHR 0.870–0.958), and T3 (SHR ≥ 0.958). Cox regression and Kaplan-Meier analyses assessed the correlation between SHR and mortality, while restricted cubic splines explored non-linear correlations. ROC analyses determined the optimal SHR cut-off value for predicting clinical outcomes. Results Out of 288 Psoriasis patients, 38 all-cause deaths occurred during an average follow-up of 112.13 ± 45.154 months. Kaplan-Meier analysis indicated that higher SHR values were linked to an increased risk of all-cause mortality (log-rank P = 0.049). A U-shaped relationship was observed between SHR and all-cause mortality (P for non-linear = 0.028). Spearman correlation revealed significant associations between SHR and WC, BMI, neutrophil, monocyte, lymphocyte counts, SCr, uric acid, DM and MetS (all P < 0.05). After adjusting for confounders, multivariate Cox regression showed that SHR was associated with a 10.937-fold risk of all-cause mortality. ROC curve analysis identified an optimal SHR cut-off value of 1.045 for predicting long-term all-cause mortality in psoriasis patients. Conclusions Elevated SHR value independently correlates with all-cause mortality in Psoriasis patients, displaying a U-shaped relationship with clinical endpoints. An optimal SHR cut-off value of 1.045 has been determined for predicting clinical outcomes. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionsThis 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).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.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.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. [ABSTRACT FROM AUTHOR]

Background: Rasburicase, a recombinant urate oxidase enzyme, has potent efficacy in controlling uric acid and is widely used to prevent tumor lysis syndrome in high-risk patients owing to its low toxicity profile. However, it has been associated with a risk of anaphylaxis, especially on re-exposure, owing to its immunogenic potential. Case presentation: A 71-year-old Japanese female diagnosed with diffuse large B cell lymphoma with a large tumor burden experienced anaphylactic shock leading to death upon initial administration of rasburicase. The pre-and postmortem examination revealed that the cause of death was a cascade of events starting with anaphylaxis-induced distributive shock leading to obstructive shock due to the collapse of the heart, which was compressed by the post-mediastinal tumor. This was further compounded by massive bleeding from the tumor and tension hemothorax, resulting in circulatory collapse. Conclusions: Although extremely rare, rasburicase can cause fatal anaphylaxis, even on first exposure. [ABSTRACT FROM AUTHOR]