Search Results (482)

In this report of two cases, we describe two patients with spinal involvement of gout. The first case involved a 67-year-old female who presented to the emergency department with a one-week history of weakness in both the upper and lower limbs, despite no prior history of gout. Cervical spine MRI revealed spinal cord compression at the C4 level from a posterior lesion. During surgery, chalky white deposits consistent with gouty tophi were observed in the ligamentum flavum within the epidural space at C4. These intraoperative findings correlated with elevated serum uric acid levels. The second case concerned a 68-year-old male who presented with a five-day history of right lower limb pain along with bilateral knee discomfort. Radiologic and laboratory evaluations revealed elevated inflammatory markers, negatively birefringent crystals in knee joint aspirate, spondylodiscitis at the L5-S1 level, and a right-sided synovial cyst at the T10–T11 level causing spinal cord compression. Following the initiation of anti-gout therapy, the patient experienced significant clinical improvement, normalization of inflammatory markers, and radiologic resolution of the thoracic synovial cyst. Full article

Membranous nephropathy (MN) is the most prevalent cause of nephrotic syndrome (NS) in adults, and it can be primary (idiopathic) with an unknown cause or secondary due to a variety of conditions (lupus, infections, malignancies, medications, etc.). It progresses to chronic kidney disease (CKD) in up to 60% of patients, and 10 to 30% develop end-stage kidney disease (ESKD). This retrospective study examines the importance of specific factors, including baseline demographic and clinical data, kidney biopsy PH findings, and selected biochemical parameters, influencing MN outcomes after 10 years of follow-up. The cohort included 94 individuals in whom a diagnosis of MN was established by percutaneous biopsy of the left kidney’s lower pole at the University Clinical Center of Serbia (UCCS) between 2008 and 2013. According to the outcomes, patients were divided into three groups: the recovery (Rec) group, with complete remission, including normal serum creatinine (Scr) and proteinuria (Prt), the group with development of chronic kidney disease (CKD), and the group with development of end-stage kidney disease (ESKD). Nephropathologists graded pathohistological (PH) results from I to III based on the observed PH findings. During the follow-up period, 33 patients were in the Rec group, CKD developed in 53 patients, and ESKD developed in 8 patients. Baseline creatinine clearance levels (Ccr), Scr, and uric acid (urate) were found to be significantly associated with the outcomes (p < 0.001). The lowest values of baseline Scr and urate were observed in the Rec group. The presence of acute kidney injury (AKI) or CKD at the time of kidney biopsy was associated with the more frequent development of ESKD (p = 0.02). Lower Ccr was associated with a higher likelihood of progressing to CKD (B = −0.021, p = 0.014), whereas older age independently predicted progression to ESKD (B = 0.02, p = 0.032). Based on this study, it was concluded that the most important biochemical and clinical factors that are associated with the outcomes of this disease are the values of Scr, Ccr, and urate and the existence of CKD at the time of kidney biopsy. Unlike most previous studies, the presence of HTN had no statistical significance in the outcome of the disease. Full article

Background/Objectives: Elevated serum uric acid levels are associated with the occurrence, development, and adverse events of coronary heart disease (CHD) and CHD risk factors. However, the extent of any pathogenic effect of the serum uric acid on CHD and whether CHD risk factors play a confounding or mediating role are still unclear. Methods: The potential causal associations of serum uric acid with CHD were evaluated via cross-trait linkage disequilibrium score regression analysis and Mendelian randomization. The pleiotropy of genetic tools was analyzed via a Bayesian colocalization approach. Moreover, we utilized two-step MR to identify risk factors mediating the relationship between uric acid and CHD. Results: Mendelian randomization results derived from two genetic instrument selection strategies support that serum uric acid levels have a significant causal relationship with coronary artery disease, stable angina pectoris, and myocardial infarction. This causal relationship was partially mediated by diastolic blood pressure, mean arterial pressure, and serum triglycerides. Transcriptomic analysis revealed that serum uric acid may directly contribute to the development of atherosclerosis by inducing transcriptomic changes in macrophages. Conclusions: Our findings highlight that the control of serum urate concentration in the long-term management of CHD patients may be necessary. Well-designed clinical trials and foundational research are presently required to furnish conclusive proof regarding the specific clinical scenarios in which adequate reduction in urate concentrations can confer cardiovascular advantages. Full article

(1) Background: The urate-lowering effects of three iridoid glycosides, which are paederosidic acid, paederosidic acid methyl ester, and paederoside, isolated from Paederia foetida and the protection they provide against hyperuricemia-induced kidney injury were investigated in a rat model. (2) Methods: A hyperuricemia (HUA) rat model was established in Sprague-Dawley (SD) rats through intraperitoneal potassium oxonate (PO) and intragastrical adenine for 2 weeks. Subsequently, rats in the pharmaceutical intervention groups received corresponding drug treatments at a concentration of 40 mg/kg/day, maintained consistently for 7 days. (3) Results: The results showed that three compounds reduced serum urate (SU), creatinine (CRE), and blood urea nitrogen (BUN) levels and that the urinary excretion levels of uric acid, urine urea nitrogen, and creatinine increased. Furthermore, the administration of three iridoid glycosides enhanced renal filtration capacity, as demonstrated by the elevated 24 h creatinine clearance rate (CCR) and 24 h uric acid clearance rate (CUA); improved the fraction excretion of uric acid (FEUA); and attenuated renal damage. Finally, three iridoid glycosides promoted uric acid excretion in HUA rats by downregulating URAT1 and GLUT9 and upregulating ABCG2, OAT1, and OAT3. Moreover, the molecular docking results further corroborated the finding that the three compounds can bind to multiple sites of the uric acid transporter via hydrogen, P-π, and hydrophobic bonds. (4) Conclusions: The three iridoid glycosides were found to lower SU levels by increasing uric acid excretion. They are promising natural products for the prevention of HUA and HUA-induced kidney injury. Full article

Objectives: This study aimed to investigate both the linear and non-linear associations between serum 25-hydroxyvitamin D [25(OH)D] levels and serum uric acid concentrations in Korean adults, with a particular focus on the vitamin D-insufficient range (<30 ng/mL), and to explore the potential metabolic implications of this relationship. Methods: Using data from the Korea National Health and Nutrition Examination Survey (KNHANES), we analyzed 10,864 adults aged 19 years and older. Serum vitamin D levels were categorized into quartiles (Q1–Q4), and their relationships with uric acid concentrations were examined using Pearson correlation, analysis of variance (ANOVA), and restricted cubic spline regression. Multivariate models were adjusted for potential confounders including age, sex, body mass index (BMI), kidney function, chronic disease status, and macronutrient intake. Results: In unadjusted analysis, a statistically significant but weak negative correlation was observed between serum 25(OH)D and uric acid levels (Pearson’s r = −0.092, p < 0.001). However, in multivariate regression adjusting for confounders, a weak positive association emerged. Restricted cubic spline analysis revealed significant positive associations in the lower quartiles (Q1–Q3), with the strongest association in Q3 (β = 0.769, 95% CI: 0.34–1.19, p < 0.001). No significant association was observed in the highest quartile (Q4). Conclusions: Serum vitamin D and uric acid concentrations show a non-linear relationship, with a significant positive association within the vitamin D-insufficient range (<30 ng/mL). These findings provide new insights into the potential metabolic role of vitamin D and highlight the need for longitudinal and interventional studies to clarify causality and clinical significance. Full article

Background: Serum uric acid (UA) in end-stage kidney disease (ESKD) patients serves as a critical indicator for nutrition and inflammation, showing a U-shaped association with all-cause mortality. Methods: Our study assessed UA’s survival predictive value in 2615 ESKD patients, stratified by the Charlson Comorbidity Index (CCI) into groups of <4 (n = 1107) and ≥4 (n = 1508). Results: Cox regression revealed distinct patterns. For ESKD patients with CCI < 4, UA levels > 8.6 mg/dL were a mortality risk factor (HR: 1.61, 95% CI: 1.01–2.38) compared to 7.1–7.7 mg/dL. Conversely, in patients with CCI ≥ 4, UA levels < 5.8 mg/dL were a mortality risk factor (HR: 1.53, 95% CI: 1.20–1.95) compared to >8.6 mg/dL. Conclusions: Higher serum UA in ESKD patients with high comorbidities (CCI ≥ 4) is not a risk factor. Low UA should be prevented across all ESKD patients. A personalized approach using CCI and corresponding serum UA levels offers a key reference for managing UA in hemodialysis patients. Full article

Hyperuricemia, defined as elevated serum uric acid (SUA) levels (>6.8 mg/dL), is traditionally linked to gout and nephrolithiasis but is increasingly implicated in insulin resistance (IR) and type 2 diabetes mellitus (T2DM). Epidemiological studies, such as NHANES, suggest hyperuricemia increases the risk of T2DM by 1.6 to 2.5 times. Mechanistically, uric acid promotes IR via oxidative stress, chronic inflammation, endothelial dysfunction, and adipocyte dysregulation. Despite growing evidence, significant gaps remain in understanding these pathways, with existing studies often limited by observational designs and short intervention durations. A bibliographic analysis of studies from 2004–2024 using Web of Science and VOSviewer highlights a growing focus on hyperuricemia’s interplay with inflammation, oxidative stress, and metabolic disorders. However, inconsistencies in therapeutic outcomes and limited exploration of causality underscore the need for further research. We also explored the importance of gender stratification and the limitations of the binary model for the relationship between hyperuricemia and insulin resistance. This review emphasizes the importance of addressing these gaps to optimize hyperuricemia management as a potential strategy for diabetes prevention and metabolic health improvement. Full article

Hyperuricemia (HUA) is a metabolic disorder characterized by abnormal purine metabolism and/or reduced uric acid (UA) excretion. Chicory (Cichorium intybus L.), recognized in Traditional Chinese Medicine, is noted for its anti-HUA effects, particularly in enhancing intestinal UA excretion, though the underlying mechanisms remain unclear. Studies indicate that disruptions in gut microbiota and its metabolites are associated with HUA, and chicory has been demonstrated to ameliorate gut microbiota dysbiosis. Among gut microbiota-derived metabolites, butyrate, a short-chain fatty acid, plays a crucial role in gut functions and is linked to HUA. Therefore, butyrate may be pivotal in elucidating the mechanism by which chicory promotes intestinal UA excretion. This study aims to investigate whether chicory facilitates intestinal UA excretion through gut microbiota-derived butyrate and to elucidate the underlying mechanism. We employed an integrated methodology combining network biology with the NHANES database analysis to explore the pathological relationship between butyrate and HUA. Our findings were subsequently validated through animal experiments. We administered chicory to rats with HUA to ascertain whether butyrate serves as the key gut microbiota metabolite through which chicory promotes intestinal UA excretion. Furthermore, we utilized western blotting to assess the expression of core targets within the PPARγ-ABCG2 pathway associated with butyrate under conditions where animals received butyrate supplements and PPARγ agonists separately. The network biology indicates that butyrate is a crucial short-chain fatty acid influencing HUA. Analyses of NHANES data and animal experiments further confirm a significant negative correlation between butyrate and serum uric acid (SUA) levels. HUA rats exhibited intestinal barrier damage, impaired intestinal UA excretion, reduced butyrate levels, and decreased expression of PPARγ and ABCG2 proteins. Intervention with chicory in HUA rats repaired intestinal barrier damage, enhanced intestinal UA excretion, and increased both butyrate levels and the expression of PPARγ and ABCG2 proteins. Similarly, interventions with butyrate supplements or PPARγ agonists in HUA rats effectively promoted intestinal UA excretion and increased the expression of PPARγ and ABCG2 proteins. This study demonstrates that butyrate is a key metabolite produced by gut microbiota, through which chicory regulates gut microbiota to enhance intestinal UA excretion. The underlying mechanism involves the activation of the PPARγ-ABCG2 pathway, which is facilitated by elevated butyrate levels in the intestine. Full article

Gout, a metabolic and autoinflammatory disease, is the most common form of inflammatory arthritis worldwide. Hyperuricemia may result in monosodium urate (MSU) crystals forming and depositing in joints and surrounding tissues, triggering an autoinflammatory response. Effective urate-lowering therapies, as well as anti-inflammatory medications, are used to treat gout. Over the past few decades, new antihyperglycemic drug classes with different modes of action have been added to treat hyperglycemia in type 2 diabetes mellitus (T2DM). Two of these drug classes, sodium–glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), have reduced cardiovascular and renal events and mortality. Several clinical studies have demonstrated that SGLT2 inhibitors possess urate-lowering properties, which may be beneficial for treating gout patients, particularly those with comorbid T2DM. Regarding SGLT2 inhibitors, some researchers have suggested that their benefits are partly explained by their ability to reduce serum urate (SU) levels, probably through increased urinary uric acid excretion. The effect of GLP-1 RA on SU levels and urinary excretion of uric acid in humans is unclear. This paper reviews the mechanisms of action of SGLT2 inhibitors and GLP-1RA, both approved and in development. Additionally, it examines what is known about their structure–activity relationships, uricosuric effects, pharmacokinetic profiles, and adverse effects. Full article

Uncomplicated hypertension (UH) during pregnancy represents a common condition, worsening maternal and fetal prognosis. However, no single biomarker has proven optimal for determining the risk of UH. We developed an early risk multivariate model for UH, integrating hemodynamics with biochemistry, focusing on the relationship between blood pressure (BP) indices, uric acid (UA), and angiogenesis-related factors (AF). We collected and analyzed data on 24 h ambulatory BP monitoring, demographic, epidemiological, clinical, and laboratory variables from 132 pregnancies. The main predictors were BP indices and serum UA and AF levels. Uncomplicated hypertension, defined as the presence of gestational hypertension or worsening of essential hypertension beyond the 20th week, was the main outcome. The combined second-degree polynomial transformation of UA and the AF (sFlt-1/PIGF) ratio, called the UA-AF Index, consistently showed a positive association with UH. The models incorporating nighttime BP indices combined with the UA-AF Index outperformed the others, with the best-performing model based on the nocturnal systolic BP (SBP). Specifically, in the best-fitting model (nighttime SBP + UA-AF Index as predictors), each 1 mmHg increase in nocturnal SBP was associated with a 10% higher risk of UH, while each one-unit increase in the UA-AF Index raised the likelihood of UH by more than twofold (accuracy: 0.830, AUC 0. 874, SE 0.032, p-value < 0.001, 95%CI 0.811–0.938). The combination of nighttime blood pressure indices, serum uric acid, and angiogenesis-related factors may provide added value in the assessment of uncomplicated hypertension during pregnancy. Full article

Objectives: Hyperuricemia (HUA) is a metabolic disorder linked to serious complications, yet current treatments face safety limitations. This study aimed to identify novel probiotic strains from Chinese Baijiu fermentation grains with dual-action mechanisms for HUA management—direct uric acid (UA) reduction and gut microbiota restoration. Methods: Two Lactiplantibacillus plantarum strains (LTJ1/LTJ48) were screened for purine/nucleoside degradation using HPLC. Their efficacy was evaluated in HepG2 cells and HUA mice. Key assessments included UA levels, renal/hepatic markers (AST, CRE, BUN), ADA/XOD activity, UA transporter expression (URAT1, GLUT9, ABCG2), and 16S rRNA-based microbiota analysis. Results: LTJ1/LTJ48 degraded >97% of purines/nucleosides in vitro. In HUA mice, they reduced serum UA by 31.0% (LTJ1) and 51.5% (LTJ48), improved renal/hepatic function, and suppressed ADA activity. They modulated UA transporters and restored gut microbiota. Conclusions: LTJ1/LTJ48 exhibit multi-target HUA alleviation via purine degradation, ADA inhibition, UA transporter regulation, and microbiota remodeling, offering a safer probiotic-based alternative to conventional therapies. Their translational potential warrants further clinical exploration. Full article

Hyperuricemia (HUA), a metabolic disorder characterized by elevated serum uric acid (UA) levels, often leads to renal and hepatic complications. This study evaluated the synergistic effects of Pediococcus acidilactici GQ01, a probiotic strain isolated from naturally fermented wolfberry, in combination with a complex (T) composed of buckwheat-fermented postbiotics, collagen peptide and multiple medicinal food blends in a murine HUA model. The combination therapy (T + GQ01) not only significantly reduced serum UA levels more effectively than T or GQ01 alone but also demonstrated superior inhibition of XOD activity and enhanced ADA activity, both of which are key regulators of purine metabolism. Additionally, T + GQ01 ameliorated kidney injury, as evidenced by reduced serum CRE and BUN levels, and improved liver function, indicated by decreased ALT and AST activities. Histopathological analysis further confirmed the protective effects of T + GQ01 on renal and hepatic tissues. Moreover, T + GQ01 modulated intestinal flora composition, promoted beneficial genera such as Weissella and Bacteroides, and enhanced the production of SCFAs, particularly propionic and butyric acids, which play critical roles in maintaining intestinal health. These findings suggest that the cocktail-like microecological regulator combining P. acidilactici GQ01, buckwheat-fermented postbiotics, collagen peptide and multiple medicinal food blends represents a promising therapeutic strategy for HUA by targeting multiple metabolic pathways, underscoring its potential as a novel intervention for HUA and its complications. Full article

Background: Elevated serum uric acid (SUA) levels in young people have become a significant public health concern. Dietary habits are a key factor influencing SUA levels. This study aimed to investigate dietary patterns (DPs) of children and adolescents and their associations with SUA. Methods: This cross-sectional study included children and adolescents in Guangzhou, China. We used structured questionnaires to collect data on demographics, lifestyle, and dietary intake, and we collected blood samples for biochemical analysis. DPs were identified by factor analysis. We used robust linear regression to examine the association between these patterns and SUA levels. Parallel mediation analysis was utilized to assess the mediating role of body mass index (BMI) Z-score and waist circumference (WC). Results: The study encompassed 4100 children and adolescents between ages 9–17. The median SUA level was 374 (IQR: 319, 438) μmol/L and the prevalence of hyperuricemia was 41.7%. We identified four DPs, including plant-based, snack–beverage, highprotein, and meat–carbohydrate patterns. There was a positive correlation between the meat–carbohydrate pattern and SUA (β = 3.67 μmol/L, 95% CI: 1.22–6.12). The Q4 group of the highprotein pattern was associated with higher SUA levels (9.17 μmol/L, 95% CI: 2.41–15.93) compared to the Q1 group. BMI Z-score and WC mediated the association between the meat–carbohydrate pattern and SUA. Conclusions: Our findings suggest that BMI Z-score and WC mediated the association between the meat–carbohydrate pattern and SUA. This study emphasizes the significance of targeted dietary interventions for weight control in addressing the increasing SUA levels in children and adolescents. Future research could focus on exploring the molecular mechanisms, developing personalized dietary intervention programs, and conducting multicenter prospective cohort studies. Full article

This study aimed to investigate the effects of dietary ISF:SF ratio on reproductive performance, biochemical parameters, colostrum composition, and fecal microbial composition in gestating sows. A total of 30 multiparous sows were randomly allocated to three dietary treatment groups: 8% inulin diet (ISF:SF 1.14, Inulin group), 8% cotton fiber diet (ISF:SF 6.61, Cotton group), and 4% inulin + 4% cotton fiber diet (ISF:SF 2.37, Inulin + Cotton group). The results showed that, compared to the other groups, the Inulin group had a significantly higher number of piglets born alive, as well as increased plasma concentrations of acetic acid, butyric acid, hexanoic acid, and total short-chain fatty acids (SCFAs) (p < 0.05). Sows in the Inulin group had significantly lower fecal scores than those in the other groups from days 81 to 85 and from days 106 to 110 of gestation (p < 0.05). On day 90 of gestation, the serum levels of albumin, urea, uric acid, calcium, and phosphorus in the Inulin group were significantly lower than those in the other groups (p < 0.05). Additionally, the serum levels of triacylglycerol in the Inulin + Cotton Fiber group were significantly higher than those in the other groups (p < 0.05). However, there were no significant differences in serum concentrations of total protein, creatinine, glucose, cholesterol, HDL-cholesterol, or LDL-cholesterol among the treatments (p > 0.05). On day 110 of gestation, the serum content of urea, uric acid, calcium, and phosphorus in the Inulin group was significantly lower than those in the other groups (p < 0.05). Furthermore, the plasma levels of uric acid, triacylglycerol, and HDL-cholesterol in the Inulin + Cotton Fiber group were significantly higher than those in the Cotton Fiber group (p < 0.05), while the creatinine levels in the Inulin group were higher than those in the other groups (p < 0.05). No differences were observed in the composition and immune performance of colostrum (p > 0.05). Microbial sequencing analysis showed that dietary inulin supplementation to increase the proportion of soluble fiber significantly decreased the abundance of Firmicutes, Clostridia, Clostridiales, Lachnospiraceae, Streptococcaceae, and Streptococcus (p < 0.05). The abundance of short-chain fatty acid-producing microorganisms—Bacteroidetes, Bacteroidia, Bacteroidales, and Muribaculaceae—was significantly increased (p < 0.05). The results indicated that inulin supplementation decreased the dietary ISF:SF ratio, significantly alleviated constipation in sows, increased the number of piglets born alive, regulated intestinal microecology, and increased the plasma concentrations of short-chain fatty acids (SCFAs), including acetic, propionic, and butyric acids. Full article

Recently, compounds of plant origin have been the focus of increased scientific interest. Micromeria frivaldszkyana is a rare species endemic to Bulgaria, whose biological activity remains unknown. This article aims to evaluate the subchronic toxicity of Micromeria frivaldszkyana methanolic extract and its effect on cognition in rats. Following 90 days of oral administration, a histopathological evaluation of brain, kidney, and liver tissues was conducted. Additionally, serum levels of total bilirubin (TB), conjugated bilirubin (CB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CR), uric acid (UA), and urea (U) were measured. Cognitive function was studied after 7 d of treatment using activity cage test, along with tests for active memory, passive memory, anxiety, spatial and working memory, and explorative activity. The experiments showed no toxic effects of the extract in subchronic application. No adverse effects on brain function were observed after 14 days of treatment. While the extract increased the motor activity of the animals, it did not significantly improve the learning and memory processes. In conclusion, the methanolic extract of Micromeria frivaldszkyana in doses 250 and 500 mg/kg bw did not induce toxicity after 90-day treatment in rats. These doses did not significantly affect central nervous system (CNS) functions, although increased motor activity was observed after 14 days of treatment with the extract. Full article