Design, synthesis, and biological evaluation of 3-phenyl substituted pyridine derivatives as potential dual inhibitors of XOR and URAT1.

Xanthine oxidoreductase (XOR) and uric acid transporter 1 (URAT1) are two most widely studied targets involved in production and reabsorption of uric acid, respectively. Marketed drugs almost target XOR or URAT1, but sometimes, single agents might not achieve aim of lowering uric acid to ideal value in clinic. Thus, therapeutic strategies of combining XOR inhibitors with uricosuric drugs were proposed and implemented. Based on our initial work of virtual screening, A and B were potential hits for dual-targeted inhibitors on XOR/URAT1. By docking A/B with XOR/URAT1 respectively, compounds I1-7 were designed to get different degree of inhibition effect on XOR and URAT1, and I7 showed the best inhibitory effect on XOR (IC50 = 0.037 ± 0.001 µM) and URAT1 (IC50 = 546.70 ± 32.60 µM). Further docking research on I7 with XOR/URAT1 led to the design of compounds II with the significantly improved inhibitory activity on XOR and URAT1, such as II11 and II15. Especially, for II15, the IC50 of XOR is 0.006 ± 0.000 µM, superior to that of febuxostat (IC50 = 0.008 ± 0.000 µM), IC50 of URAT1 is 12.90 ± 2.30 µM, superior to that of benzbromarone (IC50 = 27.04 ± 2.55 µM). In acute hyperuricemia mouse model, II15 showed significant uric acid lowering effect. The results suggest that II15 had good inhibitory effect on XOR/URAT1, with the possibility for further investigation in in-vivo models of hyperuricemia.

Association of hyperuricemia with metabolic syndrome and its components in an adult population of Faisalabad, Pakistan.

BACKGROUND AND AIMS: The rising prevalence of metabolic syndrome (MetS) is a matter of serious concern worldwide. Hyperuricemia has been observed as an independent risk factor in the development of MetS and each of its individual components in different populations. This study aims to determine the association of hyperuricemia with MetS and its individual components in a Pakistani cohort. METHODS AND RESULTS: A cross-sectional study was performed in a public sector hospital in Faisalabad, Pakistan. Total 204 participants were studied along with their anthropometric measurements and blood sample analysis for clinically important parameters. MetS was defined according to the NCEP-criteria. Independent sample t-test, Binomial logistic regression and Linear regression analyses were used to determine the association between hyperuricemia and metabolic syndrome. The prevalence of MetS and hyperuricemia in our study was 42.6% and 31.9% respectively. As compared to the normo-uricemic group, the hyperuricemic group had a significantly higher systolic blood pressure, BMI and lower HDL-C level (p < 0.05). After adjusting for age, gender, BMI and LDL-C, hyperuricemia was observed to increase the risk of MetS, increased systolic blood pressure and reduce HDL-C respectively by 1.34, 1.23 and 1.20 folds respectively. CONCLUSION: In this study, a significant association between hyperuricemia and metabolic syndrome, systolic hypertension, blood glucose and decreased HDL-C was observed.

A Comprehensive Review on Serum Lactate Dehydrogenase (LDH) and Uric Acid in Preeclampsia: Implications for Maternal Health and Disease Severity.

Preeclampsia, a hypertensive disorder unique to pregnancy, remains a significant cause of maternal and fetal morbidity and mortality worldwide. Serum lactate dehydrogenase (LDH) and uric acid have garnered attention as potential biomarkers in understanding preeclampsia's pathophysiology and clinical management. Elevated LDH and uric acid levels have been associated with disease severity and adverse outcomes, highlighting their potential utility in risk stratification and guiding management strategies. This comprehensive review explores the roles of LDH and uric acid in preeclampsia, summarizing current evidence regarding their diagnostic, prognostic, and therapeutic implications. Future research directions are also discussed, including understanding and validation studies. Integrating LDH and uric acid measurements into routine clinical practice may facilitate early detection and intervention, ultimately improving outcomes for preeclamptic pregnancies. This review underscores the importance of serum biomarkers in enhancing our understanding and managing preeclampsia, aiming to optimize maternal and fetal health.

The Impact of mHealth-Based Continuous Care on Disease Knowledge, Treatment Compliance, and Serum Uric Acid Levels in Chinese Patients With Gout: Randomized Controlled Trial.

Background: In patients with gout, suboptimal management refers to a lack of disease knowledge, low treatment compliance, and inadequate control of serum uric acid (SUA) levels. Several studies have shown that continuous care is recommended for disease management in patients with gout. However, in China, the continuous care model commonly used for patients with gout requires significant labor and time costs, and its efficiency and coverage remain low. Mobile health (mHealth) may be able to address these issues. Objective: This study aimed to explore the impact of mHealth-based continuous care on improving gout knowledge and treatment compliance and reducing SUA levels. Methods: This study was a single-center, single-blind, and parallel-group randomized controlled trial. Participants were recruited at the West China Hospital of Sichuan University in Chengdu, China, between February 2021 and July 2021 and were randomly assigned to the intervention and control groups. The intervention group received continuous care via an mHealth app, which includes modules for health records, 24 weeks of gout-related health education materials, and interactive support. The control group received routine continuous care, including face-to-face health education, paper-based health education materials consistent with the content for the intervention group, and telephone consultations initiated by the patient. Follow-up was conducted at 6 months. Participants' gout knowledge levels and treatment compliance were measured at baseline and the 12th and 24th weeks, and participants' SUA levels were measured at baseline and the 24th week. The intention-to-treat principle and a generalized estimating equation model were used to test the effect of the intervention. Results: Overall, 258 potential participants underwent eligibility assessments, and 120 were recruited and randomized into the intervention (n=60, 50%) and control (n=60, 50%) groups. Of the 120 participants, 93 (77.5%) completed the 24-week study. The 2 groups had no significant differences in sociodemographic or clinical characteristics, and the baseline measurements were comparable (all P>.05). Compared with the control group, the intervention group exhibited a significant improvement in gout knowledge levels over time (ß=0.617, 95% CI 0.104-1.129; P=.02 and ß=1.300, 95% CI 0.669-1.931; P<.001 at the 12th and 24th weeks, respectively). There was no significant difference in treatment adherence between the 2 groups at the 12th week (ß=1.667, 95% CI -3.283 to 6.617; P=.51), while a statistical difference was observed at the 24th week (ß=6.287, 95% CI 1.357-11.216; P=.01). At the 24th week, SUA levels in both the intervention and control groups were below baseline, but there was no significant difference in SUA changes between the 2 groups (P=.43). Conclusions: Continuous care based on the mHealth app improved knowledge levels and treatment compliance among patients with gout. We suggest incorporating this intervention modality into standard continuous care for patients with gout.

Gender differences in the relationship between serum uric acid and the long-term prognosis in heart failure: a nationwide study.

BACKGROUND: Serum uric acid (SUA) is an important pathogenetic and prognostic factor for heart failure (HF). Gender differences are apparent in HF. Furthermore, gender differences also exist in the association between SUA and prognosis in various cardiovascular diseases. However, the gender difference for SUA in the prediction of long-term prognosis in HF is still ambiguous. METHODS: A total of 1593 HF patients (897 men, 696 women) from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 cycle were enrolled in our final analysis. Participants were categorized according to gender-specific SUA tertile. We assessed the association between SUA and long-term prognosis of HF patients, defined as all-cause mortality and cardiovascular mortality, in different genders via Kaplan-Meier curve analysis, Cox proportional hazard model, and Fine-Gray competing risk model. The restricted cubic spline (RCS) was performed to investigate the dose-response relationship between SUA and outcomes. RESULTS: Gender differences exist in demographic characteristics, clinical parameters, laboratory tests, and medication of HF patients. After a median follow-up of 127 months (95% CI 120-134 months), there were 853 all-cause deaths (493 events in men, 360 events in women) and 361 cardiovascular deaths (206 events in men, 155 events in women). Kaplan-Meier analysis showed that SUA had gender difference in the prediction of cardiovascular mortality (Log-rank p < 0.001, for male, Log-rank p = 0.150, for female), but not in all-cause mortality. Multivariate Cox regression analysis revealed that elevated SUA levels were associated with higher all-cause mortality and cardiovascular mortality in men (HR 1.11, 95% CI 1.05-1.18, p < 0.001, for all-cause death; HR 1.18, 95% CI 1.09-1.28, p < 0.001, for cardiovascular death), but not in women (HR 1.05, 95% CI 0.98-1.12, p = 0.186, for all-cause death; HR 1.01, 95% CI 0.91-1.12, p = 0.902, for cardiovascular death). Even using non-cardiovascular death as a competitive risk, adjusted Fine-Gray model also illustrated that SUA was an independent predictor of cardiovascular death in men (SHR 1.17, 95% CI 1.08-1.27, p < 0.001), but not in women (SHR 0.98, 95% CI 0.87 - 1.10, p = 0.690). CONCLUSIONS: Gender differences in the association between SUA and long-term prognosis of HF existed. SUA was an independent prognostic predictor for long-term outcomes of HF in men, but not in women.

The Prevalence of Hyperuricemia and the Association Between Hyperuricemia and Age in Patients with Psychiatric Disorders to a General Hospital: A Cross-Section Study.

Purpose: In clinical work, it has been found that the prevalence of hyperuricemia (HUA) is significantly higher in younger patients with psychiatric disorders, but there are few studies in this area. The present study aims to evaluate the prevalence of HUA and the relationship between the HUA and age in hospitalized patients with psychiatric disorders in the real world, and to provide a theoretical basis for clinical staff to pay attention to the metabolic indicators of younger patients and for future related studies. Methods: This is a cross-sectional evaluation of a cohort of 1761 patients with psychiatric disorders of hospitalized. The categories of disorders designed for study included: Depression, Bipolar disorder, Schizophrenia, Anxiety, Obsessive-Compulsive disorder, Acute and transient psychotic disorder, Dissociative(conversion) disorders, Conduct disorders and Tic disorders. In addition, based on age, the participants are stratified into three groups. The authors used Kruskal-Wallis tests, chi-square tests, and multiple linear logistic regression to verify the relationship between HUA and age among hospitalized patients with psychiatric disorders. Results: Overall, the estimated prevalence of HUA was 35.4%. The prevalence of HUA was significantly higher in individuals with 17 years and under compared to those with 45 years and above (P < 0.001). After adjusting for confounders, the prevalence of HUA remained higher at 17 years and under than at 45 years and above. Bipolar disorder can lead to an increased prevalence of HUA (P<0.05). Conclusion: The prevalence of HUA was higher in hospitalized patients with psychiatric disorders, and the prevalence was inversely proportional to age.

Relationship Between Asymptomatic Hyperuricemia and the Hypertriglyceridemic-Waist Phenotype in Korean Adults: A Cross-Sectional Study.

Purpose: Visceral fat accumulation can negatively affect uric acid metabolism in healthy adults. The hypertriglyceridemic-waist (HTGW) phenotype is a predictor of diabetes and cardiometabolic risk. This study aimed to investigate the association between the HTGW phenotype and asymptomatic hyperuricemia in Korean adults. Patients and Methods: The study included 23,240 adults, aged 20-80 years who underwent comprehensive health examinations at a general hospital in Gyeonggi Province, Korea, from January 2020 to December 2022. The HTGW phenotype was defined as the simultaneous presence of elevated serum triglyceride (TG) levels and increased waist circumference (WC). The diagnostic capability of the HTGW phenotype for hyperuricemia and its association with the condition were assessed using the receiver operating characteristic (ROC) curve and logistic regression analysis. Results: The prevalence of hyperuricemia in the HTGW phenotype was 3.44 times higher than that in the normal TG normal waist (NTNW) phenotype. Compared with those in the NTNW group, the hazard ratios for developing hyperuricemia in the HTGW group were 2.887 (2.566-3.249, P <0.001) for men and 7.341 (5.139-10.487, P <0.001) for women, and these values remained significant after adjusting for potential confounders. The stratified analysis revealed that the HTGW phenotype, coupled with diabetes, had the highest probability of developing asymptomatic hyperuricemia (2.55 times). ROC curve analysis revealed that the area under the curve values of the WC*TG index for hyperuricemia diagnosis were 0.702, 0.627, and 0.685 for all participants, men, and women, respectively. Conclusion: Among Korean adults, the HTGW phenotype was closely related to hyperuricemia in both men and women and showed a particularly strong association in patients with diabetes. It may be used in combination with an indicator that can complement its accuracy for identifying individuals at high risk of hyperuricemia.

Association of time-averaged serum uric acid level with clinicopathological information and long-term outcomes in patients with IgA nephropathy.

Objective: Whether serum uric acid (SUA) at baseline could been identiûed as a risk factor for progression in IgA nephropathy (IgAN) patients remains unclear, therefore, long- term SUA control levels must be monitored. We aimed to investigate the relevant factors affecting time-averaged SUA (TA-SUA) and to assess the prognostic value of TA-SUA in IgAN. Methods: This retrospective study included 152 patients with IgAN. The relationships between TA-SUA and clinicopathological features and renal outcomes (defined as the doubling of the baseline serum creatinine level or end-stage renal disease) were analyzed in groups divided by quartiles of TA-SUA levels, the presence of hyperuricemia, and sex. Results: Patients with high TA-SUA levels had higher levels of baseline SUA, blood urea nitrogen (BUN), triglycerides, serum C3 and serum C4 and were more likely to be male and have hypertension, proteinuria, poor renal function, and pathological injuries including high grades of tubular atrophy/interstitial fibrosis (T1-T2). These patients had a poorer prognosis compared with patients with low TA-SUA levels. The TA-SUA level was positively correlated with baseline age and BUN, triglycerides, serum C3, and serum C4 levels, and negatively correlated with baseline eGFR. Survival curve analysis indicated that persistent hyperuricemia was associated with significantly poorer renal outcomes than normo-uricemia in both men and women. The TA-SUA level also was an independent predictor of renal outcome in patients with IgAN, with optimal cutoû values of 451.38 µmol/L (area under the curve (AUC) = 0.934) for men and 492.83 µmol/L (AUC = 0.768) for women. Conclusions: The TA-SUA level is associated with triglyceride level, complement component levels, renal function, and pathological severity of IgAN, and it may be a prognostic indicator in male and female patients with IgAN.

Kidney function decline mediates the adverse effects of per- and poly-fluoroalkyl substances (PFAS) on uric acid levels and hyperuricemia risk.

Previous studies indicated per- and poly-fluoroalkyl substances (PFAS) were related to uric acid and hyperuricemia risk, but evidence for the exposure-response (E-R) curves and combined effect of PFAS mixture is limited. Moreover, the potential mediation effect of kidney function was not assessed. Hence, we conducted a national cross-sectional study involving 13,979 US adults in NHANES 2003-2018 to examine the associations of serum PFAS with uric acid and hyperuricemia risk, and the mediation effects of kidney function. Generalized linear models and E-R curves showed positive associations of individual PFAS with uric acid and hyperuricemia risk, and nearly linear E-R curves indicated no safe threshold for PFAS. Weighted quantile sum regression found positive associations of PFAS mixture with uric acid and hyperuricemia risk, and PFOA was the dominant contributor to the adverse effect of PFAS on uric acid and hyperuricemia risk. Causal mediation analysis indicated significant mediation effects of kidney function decline in the associations of PFAS with uric acid and hyperuricemia risk, with the mediated proportion ranging from 19 % to 57 %. Our findings suggested that PFAS, especially PFOA, may cause increased uric acid and hyperuricemia risk increase even at low levels, and kidney function decline plays a crucial mediation effect.

Postprandial effects following a semielemental critical-care diet lead to changes in uric acid, bile acids, and glucose in the central bearded dragon (Pogona vitticeps).

OBJECTIVE: To assess the prandial effects of a semielemental diet on plasma uric acid, bile acid, and glucose concentrations in the central bearded dragon (Pogona vitticeps). ANIMALS: 13 healthy adult male bearded dragons. METHODS: Following a 72-hour fasting period, blood was collected to measure preprandial uric acid, bile acid, and glucose concentrations. The animals were then gavage fed 1.2% body weight of an omnivore critical-care diet containing 20% protein, 9.5% fat, 2.5% fiber, and 2.39 kcal/mL. Blood was collected for repeat concentrations at 4 and 24 hours. RESULTS: Median (IQR) uric acid concentration (mg/dL) increased from 3.8 preprandial (2.8 to 4.3) to 4.7 4 hours postprandial (4 to 7; P = .0001). Median (IQR) bile acid concentration (mg/dL) increased from 1.8 preprandial (1 to 3.4) to 9.5 24 hours postprandial (5.6 to 10.4; P = .004). Median (IQR) glucose concentration (mg/dL) was 209 at time 0 (193 to 216), 287 at 4 hours (258 to 312), and 393 at 24 hours (361 to 464). Significant increases were seen between pre- and 4-hours-postprandial (P < .0001), pre- and 24-hours-postprandial (P < .0001), and 4-hours- and 24-hours-postprandial (P < .0001) glucose concentrations. CLINICAL RELEVANCE: Results suggest that postprandial status and diet composition should be considered during the interpretation of some biochemical analytes in the bearded dragon.

Iron-carbon dots embedded in molybdenum single-atom nanoflowers as multifunctional nanozyme for dual-mode detection of hydrogen peroxide and uric acid.

Single-atom catalysts (SACs) have attracted extensive attention in the field of catalysis due to their excellent catalytic ability and enhanced atomic utilization, but the multi-mode single-atom nanozymes for biosensors remain a challenging issue. In this work, iron-doped carbon dots (Fe CDs) were loaded onto the edges and pores of Mo SACs with nanoflower morphology; accordingly, a composite material Fe CDs/Mo SACs was prepared successfully, which improves the catalytic performance and develops a fluorescence mode without changing the original morphology. The steady-state kinetic data indicates that the material prepared have better affinity for substrates and faster reaction rates under optimized conditions. The specific kinetic parameters Km and Vmax were calculated as 0.39 mM and 7.502×10-7 M·s-1 respectively. The excellent peroxidase-like activity of Fe CDs/Mo SACs allows H2O2 to decompose into •OH, which in turn oxidizes colorless o-phenylenediamine (OPD) to yellow 2,3-diaminophenazine (DAP). At the same time, the fluorescence signal of Fe CDs/Mo SACs quenches obviously by DAP at 460 nm through internal filtration effect (IFE), while the characteristic fluorescence response of DAP gradually increases at 590 nm. Based on this sensing mechanism, a sensitive and accurate dual-mode (colorimetric and ratiometric fluorescent) sensor was constructed to detect H2O2 and uric acid, and the rate of recovery and linearity were acceptable for the detection of UA in human serum and urine samples. This method provides a new strategy for rapid and sensitive detection of UA, and also broadens the development of SACs in the field of biosensors.

A high level of uric acid is associated with long-term adverse cardiovascular outcomes in patients who received fractional flow reserve with coronary intermediate stenosis.

BACKGROUND AND AIMS: The role of fractional flow reserve (FFR) in coronary intermediate lesions is widely recommended by guidelines. The effect of uric acid (UA) on cardiovascular events is also well known. However, the relationship between UA and long-term cardiovascular outcomes in patients who received FFR with intermediate lesions remains unknown. METHODS AND RESULTS: We retrospectively included 428 patients who underwent both coronary angiography (CAG) and FFR. Participants were stratified into two groups based on the median UA. The primary endpoint was the composite of major adverse cardiovascular and cerebrovascular events (MACCEs), including repeat revascularization, nonfatal stroke, nonfatal myocardial infarction, and all-cause death. A Cox proportional hazards model was utilized to analyze the association between UA and the prevalence of MACCEs. During a median follow-up of 5.8 years, a higher MACCEs rate occurred in the high UA group compared to the low UA group (16.8% vs. 5.1%, p log-rank<0.01). Elevated UA was independently linked to a higher incidence of MACCEs, whether UA was treated as a categorical or continuous variable (hazard ratio [HR] 2.76, 95% confidence interval [CI] 1.27-6.03 or HR 1.01, 95% CI 1.01-1.02). The restricted cubic spline (RCS) analysis illustrated that the HR for MACCEs increased with increasing UA. CONCLUSION: The present study demonstrates that UA is associated with MACCEs risk and suggests that UA is a reliable predictor of long-term cardiovascular events in coronary intermediate stenosis patients.

Spontaneous Tumor Lysis Syndrome Secondary to Metastatic Pancreatic Adenocarcinoma.

Spontaneous tumor lysis syndrome (STLS) secondary to metastatic pancreatic adenocarcinoma is a rare clinical phenomenon. An 86-year-old woman with a history of pancreatic cysts presented to the emergency department with progressive fatigue, transaminitis, elevated lactate dehydrogenase, and acute kidney injury of unclear etiology. Abdominal imaging and celiac lymph node biopsy were consistent with metastatic pancreatic adenocarcinoma. Her clinical status deteriorated requiring intensive care unit transfer, and her laboratory results were found to be consistent with STLS. Despite treatment, she entered multisystem organ failure and died shortly after. This case adds to the literature of STLS in pancreatic adenocarcinomas.

Elevated uric acid in gestational diabetes and its risk on pregnancy outcomes.

Background: Over the past few years, gestational diabetes mellitus has become more common. According to earlier research, gestational diabetes mellitus is linked to higher uric acid levels, and gestational hyperuricemia is linked to poor maternal and neonatal outcomes. Aim and objectives: To assess the influence of elevated uric acid >5 mg/dl on pregnancy outcomes such as neonatal weight, respiratory distress, preterm delivery, neonatal intensive care unit admission, premature membrane rupture, oligohydramnios, cesarean section, and intensive care admission for mothers. Setting and methods: It is a prospective cohort study, carried out at obstetric/family medicine outpatient clinics, Cairo University Hospitals on 221 pregnant females with gestational diabetes mellitus in their third trimester of pregnancy, selected by random sampling, performed structured interviews, and tested for serum uric acid level and were separated into two groups, those with elevated uric acid >5 mg/dl (121) and those without elevated uric acid ⩽5 mg/dl (100) patients and then followed up until delivery in Cairo University Hospitals for collecting pregnancy outcome data. Results: There were statistically significant differences between the antepartum uric acid and neonatal complications, maternal complications, preterm, macrosomia, neonatal intensive care unit admission, premature rupture of membranes, oligohydramnios, and cesarean section between both groups. Conclusions: This study showed that elevated serum uric acid >5 mg/dl can predict the incidence of maternal and neonatal problems in gestational diabetes mellitus including preterm, macrosomia, neonatal intensive care unit admission, premature rupture of membranes, oligohydramnios, and cesarean section.

Bioinspired mp20 mimicking uricase in ZIF-8: Metal ion dependent for controllable activity.

Mini protein mimicking uricase (mp20) has shown significant potential as a replacement for natural enzymes in the development of uric acid biosensors. However, the design of mp20 has resulted to an inactive form of peptide, causing of loss their catalytic activity. Herein, this paper delineates the impact of various metal cofactors on the catalytic activity of mp20. The metal ion-binding site prediction and docking (MIB) web server was employed to identify the metal ion binding sites and their affinities towards mp20 residues. Among the tested metal ions, Cu2+ displayed the highest docking score, indicating its preference for interaction with Thr16 and Asp17 residues of mp20. To assess the catalytic activity of mp20 in the presence of metal ions, uric acid assays was monitored using a colorimetric method. The presence of Cu2+ in the assays promotes the activation of mp20, resulting in a color change based on quinoid production. Furthermore, the encapsulation of the mp20 within zeolitic imidazolate framework-8 (ZIF-8) notably improved the stability of the biomolecule. In comparison to the naked mp20, the encapsulated ZIFs biocomposite (mp20@ZIF-8) demonstrates superior stability, selectivity and sensitivity. ZIF's porous shells provides excellent protection, broad detection (3-100 µM) with a low limit (4.4 µM), and optimal function across pH (3.4-11.4) and temperature (20-100°C) ranges. Cost-effective and stable mp20@ZIF-8 surpasses native uricase, marking a significant biosensor technology breakthrough. This integration of metal cofactor optimization and robust encapsulation sets new standards for biosensing applications.

Signaling pathways in uric acid homeostasis and gout: From pathogenesis to therapeutic interventions.

Uric acid is a product of purine degradation, and uric acid may have multiple physiologic roles, including the beneficial effects as an antioxidant and neuroprotector, maintenance of blood pressure during low salt ingestion, and modulation of immunity. However, overproduction of metabolic uric acid, and/or imbalance of renal uric acid secretion and reabsorption, and/or underexcretion of extrarenal uric acid, e.g. gut, will contribute to hyperuricemia, which is a common metabolic disease. Long-lasting hyperuricemia can induce the formation and deposition of monosodium urate (MSU) crystals within the joints and periarticular structures. MSU crystals further induce an acute, intensely painful, and sterile inflammation conditions named as gout by NLRP3 inflammasome-mediated cleavage of pro-IL-1ß to bioactive IL-1ß. Moreover, hyperuricemia and gout are associated with multiple cardiovascular and renal disorders, e.g., hypertension, myocardial infarction, stroke, obesity, hyperlipidemia, type 2 diabetes mellitus and chronic kidney disease. Although great efforts have been made by scientists of modern medicine, however, modern therapeutic strategies with a single target are difficult to exert long-term positive effects, and even some of these agents have severe adverse effects. The Chinese have used the ancient classic prescriptions of traditional Chinese medicine (TCM) to treat metabolic diseases, including gout, by multiple targets, for more than 2200 years. In this review, we discuss the current understanding of urate homeostasis, the pathogenesis of hyperuricemia and gout, and both modern medicine and TCM strategies for this commonly metabolic disorder. We hope these will provide the good references for treating hyperuricemia and gout.

Left atrial size modify the association between uric acid and atrial fibrillation in patients with coronary artery disease.

BACKGROUND AND AIMS: The potential influence of left atrial size on the relationship between uric acid and atrial fibrillation has not been fully investigated. This study aims to evaluate the interaction effect of left atrial size on the association between uric acid and atrial fibrillation in patients with coronary artery disease. METHODS AND RESULTS: This retrospective cohort study, conducted from January 2018 to October 2022, included 2004 patients undergoing Drug-Eluting Stent implantation for coronary artery disease. Utilizing logistic regression models with the product of left atrial enlargement (LAE) and uric acid, interaction effects were assessed. Among the participants, 383 had LAE, and 159 experienced atrial fibrillation. After adjusting for covariates, continuous uric acid levels were associated with an increased risk of atrial fibrillation in patients without LAE (OR:1.631, 95% CI: 1.284-2.072), but not in those with LAE (OR:1.069, 95% CI: 0.848-1.348). A significant interaction of uric acid levels was observed between groups with and without LAE (p = 0.046). Restricted cubic spline curves indicated a J-shaped relationship between uric acid and atrial fibrillation in the absence of LAE. However, the association between uric acid levels and atrial fibrillation in the LAE group remained unchanged with increasing uric acid levels. CONCLUSION: The study suggested that left atrial size modified the association between uric acid and atrial fibrillation in patients with coronary artery disease. Uric acid serves as a potential biomarker for atrial fibrillation risk, especially in individuals without LAE.

Dual effects of serum urate on stroke risk and prognosis: insights from Mendelian randomization.

Background: To investigate the causal associations of serum urate (SUA) with stroke risk and prognosis using Mendelian randomization (MR) and the potential mediating role of stroke risk factors in the causal pathways. Methods: We used the random-effects inverse variance weighting (IVW) as our primary method. We initially performed two-sample univariable MR (UVMR) to identify the causal associations of SUA (n = 437,354) with any stroke (AS, FinnGen: n = 311,635; MEGASTROKE: n = 446,696), ischemic stroke (IS, FinnGen: n = 212,774; MEGASTROKE: n = 440,328), intracranial hemorrhage (ICH, FinnGen: n = 343,663; ISGC: n = 3,026), functional outcome after ischemic stroke at 90d (n = 4,363), and motor recovery within 24 months after stroke (n = 488), and then multivariable MR (MVMR) to estimate the direct causal effects of SUA on these outcomes, adjusting for potential confounders. Finally, we further conducted a two-step MR to investigate the potential mediating role of body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and estimated glomerular filtration rate (eGFR) in the identified causal pathways. Results: Genetically predicted elevated SUA levels were significantly associated with increased risk of AS (meta-analysis: OR = 1.09, 95% CI [1.04-1.13], p = 3.69e-05) and IS (meta-analysis: OR = 1.10, 95% CI [1.01-1.19], p = 0.021) and with improved poor functional outcome after ischemic stroke at 90d (OR = 0.81, 95% CI [0.72-0.90], p = 1.79e-04) and motor recovery within 24 months after stroke (OR = 1.42, 95% CI [1.23-1.64], p = 2.15e-06). In MVMR, SBP and DBP significantly attenuated the causal effects of SUA on AS, IS, and functional outcome after ischemic stroke at 90d and motor recovery within 24 months after stroke. Further mediation analyses showed that SBP mediated 52.4 and 34.5% of the effects of SUA on AS and IS, while DBP mediated 28.5 and 23.4% of the causal effects, respectively. Conclusion: This study supports the dual role of genetically predicted SUA in increasing stroke risk, especially ischemic stroke risk, and in improving functional outcome and motor recovery. SBP and DBP are key mediators lying on the causal pathways of SUA with AS and IS.

Gut microbiota plays a significant role in gout.

With the development of social economy, the incidence of gout is increasing, which is closely related to people's increasingly rich diet. Eating a diet high in purine, fat, sugar and low-fibre for a long time further aggravates gout by affecting uric acid metabolism. The renal metabolism mechanism of uric acid has been thoroughly studied. To find a new treatment method for gout, increasing studies have recently been conducted on the mechanism of intestinal excretion, metabolism and absorption of uric acid. The most important research is the relationship between intestinal microbiota and the risk of gout. Gut microbiota represent bacteria that reside in a host's gastrointestinal tract. The composition of the gut microbiota is associated with protection against pathogen colonization and disease occurrence. This review focuses on how gut microbiota affects gout through uric acid and discusses the types of bacteria that may be involved in the occurrence and progression of gout. We also describe potential therapy for gout by restoring gut microbiota homeostasis and reducing uric acid levels. We hold the perspective that changing intestinal microbiota may become a vital method for effectively preventing or treating gout.