Elevated Uric Acid Levels Research Articles

Difficult-to-treat psoriatic arthritis. Data from the All-Russian registry of patients with psoriatic arthritis

Objective: to characterize patients with difficult-to-treat (D2T) psoriatic arthritis (PsA) and to assess risk factors for its development.Material and methods. The study included 263 PsA patients treated with biologic disease- modifying antirheumatic drugs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) and followed up for ≥2 years in the All-Russian Registry of PsA Patients. All patients underwent a standard clinical and laboratory examination, and concomitant diseases were recorded. PsA activity was assessed using DAPSA index and minimal disease activity criteria.Results and discussion. 152 (57.8%) patients who received 1 bDMARD/tsDMARD for 2 years achieved remission/low disease activity (LDA) according to DAPSA and were categorized as having non-D2T PsA. Other 111 (42.2%) patients switched ≥2 bDMARDs/tsDMARDs within 2 years, 71 (27%) of them achieved remission/LDS, and 40 (15.2%) patients who continued to have high or moderate PsA activity met the D2T criteria. A comparative analysis of 40 patients (20 men and 20 women) with D2T PsA and 152 patients (78 men and 74 women) with PsA who did not fulfil the D2T criteria was performed. It was found that patients with D2T PsA had a significantly longer duration of PsA (p=0.017), more frequent polyarthritis (p=0.014), dactylitis (p=0.004), enthesitis (p=0.001), BSA >10% (p=0.008), onycholysis (p=0.001), HAQ >0.5 (p=0.039), depression (p=0.007) and elevated blood uric acid levels (p=0.023).Conclusion. In real-life clinical practice, the D2T variant of PsA is reported in 15% of cases. Treatment-resistant PsA patients are characterized by a longer duration of PsA, more widespread severe psoriasis with onycholysis and are more likely to have polyarthritis, dactylitis, enthesitis and functional disorders at the time of bDMARD prescription, as well as concomitant diseases, especially depression and hyperuricaemia.

Uric acid is associated with increased risk of myocardial infarction: results from NHANES 2009-2018 and bidirectional two-sample Mendelian randomization analysis

AimAlthough 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.MethodsWe 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.ResultsAfter 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).ConclusionBased 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.

The role of uric acid in the risk of hypertension developed from prehypertension: a five-year Chinese urban cohort study

BackgroundUric acid as a prominent causal factor in the pathogenesis of hypertension is well recognized. Nevertheless, the influence of uric acid on the transition from prehypertension to hypertension within the Chinese population remains understudied.MethodsA cohort of 1,516 prehypertensive individuals, aged 35 to 84 years, underwent recruitment following a comprehensive health assessment in 2017 and subsequent re-evaluation in 2022. Baseline characteristics and relevant clinical data were collected. The analytical approach encompassed multiple logistic regression and propensity score matching.ResultsOver 5 years, the cumulative incidence of hypertension amounted to 35.1%, with 33.9% in males and 37.3% in females, respectively. Notably, prehypertensive subjects concomitant with hyperuricemia exhibited a higher cumulative incidence of hypertension in comparison to the non-hyperuricemic counterparts (40.7% vs. 34.0%, p = 0.041). Multiple logistic regression unveiled a significant association between hyperuricemia and heightened hypertension risk (adjusted odds ratio [OR] = 1.44; 95% confidence interval [CI], 1.05–1.98; p = 0.022). Nonetheless, this association did not reach statistical significance when examining female subjects (adjusted OR = 1.10; 95% CI, 0.58–2.09; p = 0.781) or participants aged ≥ 60 years (adjusted OR = 1.07; 95% CI, 0.61–1.88; p = 0.814). Further validation through propensity score matching affirmed that subjects afflicted by hyperuricemia experienced a substantially elevated risk of transitioning from prehypertension to hypertension over the course of five years compared with the non-hyperuricemic counterparts (41.3% vs. 32.3%, p = 0.045), after adjusting for 12 covariates including age and gender. Hyperuricemia emerged as an independent risk factor predisposing individuals to the development of hypertension from a prehypertensive state.ConclusionThis observation prompted the formulation of a hypothesis suggesting that ameliorating elevated uric acid levels may potentially mitigate the progression from prehypertension to hypertension.

Flavonoids from Verbascum thapsus Protect Against Nephrotoxicity in Rats

General Background: Nephrotoxicity induced by carbon tetrachloride (CCl4) poses significant health risks, prompting the exploration of natural antioxidants for renal protection. Specific Background: Verbascum thapsus, a plant known for its flavonoid content, has shown potential in mitigating oxidative stress, but its specific protective effects against CCl4-induced nephrotoxicity remain under-investigated. Knowledge Gap: While previous studies have indicated antioxidant properties of flavonoids, their efficacy in renal preservation in vivo has not been fully elucidated. Aims: The study evaluated the antioxidative and nephroprotective properties of flavonoids from Verbascum thapsus leaves in a rat model of CCl4-induced nephrotoxicity.Results: Rats were divided into three groups: control, CCl4-treated, and flavonoid plus CCl4-treated. Biochemical analyses revealed that CCl4 significantly elevated malondialdehyde (MDA), urea, creatinine, and uric acid levels while decreasing superoxide dismutase (SOD) and glutathione (GSH) levels. Notably, flavonoid administration markedly reduced MDA, urea, creatinine, and uric acid levels and enhanced SOD and GSH levels compared to the CCl4-only group. Novelty: This study uniquely highlights the protective role of flavonoids from Verbascum thapsus against nephrotoxicity, demonstrating both their antioxidative capacity and renal preservation in an experimental model. Implications: The findings support the potential use of Verbascum thapsus as a therapeutic agent in the management of kidney diseases, suggesting further investigation into its application in clinical settings to address nephrotoxicity and related renal disorders. Highlights: Nephroprotective: Flavonoids significantly protect against CCl4-induced kidney damage. Biochemical Enhancement: Improved antioxidant levels; reduced harmful biochemical indicators. Therapeutic Potential: Supports natural treatments for kidney diseases. Keywords: Verbascum thapsus, flavonoids, nephrotoxicity, antioxidants, carbon tetrachloride

Elevated uric acid levels as a risk factor for new-onset hypertension in newly enrolled Japanese university students (JSH46-0100).

This study aimed to determine the association between serum uric acid (UA) levels and new-onset hypertension (HTN) in newly enrolled students (aged 18 to 20 years) at a university in Gifu, Japan. We analyzed data collected over a 12-year period from April 2010 to March 2022. From this dataset, we selected individuals who were normotensive at admission and underwent a follow-up examination four years later, at the time of their progression to a master's course (n = 2859). Among these participants, 75 (2.6%) developed HTN by the second visit. Their serum UA levels (mg/dL) were significantly higher compared to those who remained HTN-free, both at baseline (6.02 ± 1.06 vs. 5.42 ± 1.17) and at the second visit (6.10 ± 1.20 vs 5.46 ± 1.22). Logistic regression analysis revealed that the odds of developing HTN were higher when considering the mean UA level across both visits (odds ratio: 1.63 per 1 mg/dL increase) compared to either the first or second visit alone. Further analysis of the relationship between elevated mean UA levels (above the cutoff value of 5.7 mg/dL) and the risk of new-onset HTN demonstrated a significant odds ratio of 3.39, which remained significant after adjusting for body mass index and sex. In summary, elevated UA levels are an independent risk factor for future HTN in young adults.

Antilithiatic Activity of Arbutus Pavarii (Shemeri) Extract on Ethylene Glycol Induced Lithiasis in Rats

Objectives. The objective of this study was to investigate the antilithiatic activity of shemeri (Arbutus Pavarii) on ethylene glycol-induced urolithiasis in male albino rats. Methods. 24 healthy male albino rats were divided into 4 groups. The rats in group A served as the normal control group. Group B (EG-treated group) rats received 0.75% ethylene glycol for three weeks followed by drinking water for the next 3 weeks. Group C (preventive group) rats received 0.75% ethylene glycol along with shemeri for six weeks. Group D (treatment group) rats received 0.75% ethylene glycol for three weeks then supplemented with shemeri aqueous solution. After six weeks, various levels of oxalate, calcium, and phosphate in urine and serum levels of creatinine, urea, uric acid, phosphate, calcium, and sodium were measured. Histopathological examination for kidney samples was also conducted. Results. In comparison to the EG-treated group, oral administration of Arbutus Pavarii (shemeri) significantly lowered elevated levels of creatinine, urea, and uric acid while, significantly increased levels of phosphate, calcium, and sodium in the serum. Shemeri also reduced elevated levels of urinary oxalate, calcium, and phosphate. Histopathological examination showed noticeable kidney lesions in group (B), but these lesions improved in groups (C, and D). Conclusion. This study suggests that shemeri is a promising and effective plant in prevention and treatment of Ethylene glycol-induced urolithiasis in male albino rats.

Effects of Acute and One-Week Supplementation with Montmorency Tart Cherry Powder on Food-Induced Uremic Response and Markers of Health: A Proof-of-Concept Study

Metabolic conditions, such as gout, can result from elevated uric acid (UA) levels. Consuming high-purine meals increases UA levels. Therefore, people with hyperuricemia typically must avoid ingesting such foods. Polyphenols have been shown to reduce uric acid levels and tart cherries (TCs) are a rich source of phenolic and anthocyanin compounds. This proof-of-concept study evaluated whether ingesting TCs with a purine-rich meal affects the uricemic response. Methods: A total of 25 adults (15 males and 10 females, 85.0 ± 17 kg, 40.6 ± 9 years, 29.1 ± 4.9 kg/m2) with elevated fasting UA levels (5.8 ± 1.3 mg/dL) donated a fasting blood sample. In a randomized, double-blind, crossover, placebo-controlled, counterbalanced manner, participants ingested capsules containing 960 mg of a placebo (PLA) or concentrated TC powder containing 20.7 mg of proanthocyanins with a serving of hot soup (10 g of carbohydrate, 2 g protein, and 1 g fat) containing 3 g of purines (1 g of adenosine 5′-monophosphate, 1 g of disodium 5′-guanylate, and 1 g of disodium 5′-inosinate). Blood samples were obtained at 0, 60, 120, 180, and 240 min after ingestion to assess changes in uric acid levels and pharmacokinetic profiles. Cell blood counts, a comprehensive metabolic panel, cytokines, inflammatory markers, and subjective side effects ratings were analyzed on baseline (0 min) and post-treatment (240 min) samples. Participants continued consuming two capsules/day of the assigned treatment for one week and then repeated the experiment. Participants observed a 14-day washout and then repeated the experiment while ingesting the alternate treatment. Data were analyzed using general linear model (GLM) statistics with repeated measures, pairwise comparisons, and percentage change from baseline with 95% confidence intervals (CIs). Results: No statistically significant interaction effects or differences between treatments were seen in uric acid levels or PK profiles. Analysis of percent changes from baseline revealed that TC ingestion reduced the blood glucose levels following the ingestion of the high-purine meal (−4.2% [−7.7, −0.7], p = 0017). Additionally, there was some evidence that TC ingestion attenuated the increase from baseline in IL-1β and IL-10 and increased INF-γ. No significant differences were seen in the remaining health markers or subjective side effects ratings. Conclusions: Acute and one-week TC supplementation did not affect the uricemic response to ingesting a high-purine meal in individuals with mildly elevated UA levels. However, there was some evidence that TC supplementation may blunt the glycemic response to ingesting a meal and influence some inflammatory cytokines. Registered clinical trial NCT04837274.

Integrating metabolomics with network pharmacology to reveal the mechanism of Poria cocos in hyperuricemia treatment

Ethnopharmacological relevanceHyperuricemia is a chronic condition characterized by persistently elevated uric acid levels, often leading to gouty arthritis and renal insufficiency. Poria cocos F.A.Wolf, a traditional Chinese medicinal herb, possesses notable diuretic and anti-inflammatory properties and is widely used to treat edema, inflammation, viral infections, and tumors. Recent studies suggest that Poria cocos has the potential to lower uric acid levels and mitigate kidney damage, making it a promising candidate for hyperuricemia treatment. However, its pharmacological mechanisms require further exploration. Aim of the studyThis study aims to elucidate the mechanisms by which Poria cocos alleviates hyperuricemia, using metabolomics and network pharmacology approaches. Materials and methodsHyperuricemia was induced in rats via a high-yeast diet combined with potassium oxonate. The effects of Poria cocos were assessed by measuring serum uric acid, creatinine, urea nitrogen levels, hepatic xanthine oxidase activity, and renal tissue morphology. Non-targeted metabolomics was employed to identify differential metabolites and explore the metabolic pathways involved in its therapeutic effects. Network pharmacology was utilized to analyze potential targets and signaling pathways, which were validated through molecular docking and ELISA analysis. ResultsPoria cocos extract significantly reduced serum uric acid, creatinine, and urea nitrogen levels, inhibited xanthine oxidase activity, and attenuated kidney damage. Metabolomics combined with network pharmacology identified xanthine dehydrogenase and fatty acid synthase as key targets, while purine metabolism, fatty acid biosynthesis, and primary bile acid biosynthesis were identified as critical pathways. ELISA confirmed that Poria cocos suppressed xanthine dehydrogenase and fatty acid synthase expression in hyperuricemic rats. Molecular docking further verified strong binding interactions between core compounds and key targets. ConclusionsPoria cocos alleviates hyperuricemia by modulating multiple compounds, targets, and pathways. Through network pharmacology and metabolomics, it reveals that Poria cocos selectively regulates xanthine dehydrogenase and fatty acid synthase, influencing purine metabolism, fatty acid biosynthesis, and primary bile acid biosynthesis pathways. These findings provide insights into its therapeutic mechanisms, supporting the clinical application of Poria cocos in treating metabolic disorders and kidney damage associated with hyperuricemia.

Serum Uric Acid Level and its Association with Severity in Acute Ischemic Stroke

Background: Cerebrovascular diseases (CVDs) are a major public health issue around the world. Elevated serum uric acid levels may predict an increased risk for cerebrovascular events particularly acute ischemic stroke. Aim of the study: The aim of our study was to assess the association between serum uric acid level and severity of acute ischemic stroke. Methods: This observational case control study was conducted at the department of Neurology and at the department of Medicine in Dhaka Medical College Hospital from July 2018 to June 2020. This study included 50 acute ischemic stroke patients and 50 age and gender matched healthy controls. Along with the routine investigations, estimation of serum uric acid was done in all participants. The severity of stroke was assessed as per national institutes of health stroke scale (NIHSS). After collection of all the required data, analysis was done by SPSS 23.0. Results: The mean age and distribution of the age in different age group were matched between case and control groups (p=0.607 and 0.763 respectively). The mean age of the ischemic stroke cases was 62.14±9.77 years. The mean NIHSS score of the patients was 16.34±10.34. Of all, 18% had minor stroke, 32% had moderate stroke, 20% had moderate to severe stroke and 30% had severe stroke. Among stroke patients 58% had elevated uric acid level and among controls 20% had raised uric acid in serum. The number of patients having elevated serum uric acid is statistically significantly higher in case group than control group (p<0.001). Multivariate regression analysis showed hypertension (OR 4.046; 95% CI 1.432–11.432; p=0.008), DM (OR 3.063; 95% CI 1.030-9.105; p=0.044), dyslipidemia (OR 3.031; 95% CI 1.062-8.654; p=0.038) and elevated serum uric acid level (OR 6.019, 95% CI 2.220–16.317; p<0.001) independently associated with acute ischemic stroke (p<0.05). Conclusion: This study shows elevated serum uric acid level significantly associated with severity of acute...........

Investigation of dual inhibition of antibacterial and antiarthritic drug candidates using combined approach including molecular dynamics, docking and quantum chemical methods

Emerging antibiotic resistance in bacteria threatens immune efficacy and increases susceptibility to bone degradation and arthritic disorders. In our current study, we utilized a three-layer in-silico screening approach, employing quantum chemical methods, molecular docking, and molecular dynamic methods to explore the novel drug candidates similar in structure to floroquinolone (ciprofloxacin). We investigated the interaction of novel similar compounds of ciprofloxacin with both a bacterial protein S. aureus TyrRS (1JIJ) and a protein associated with gout arthritis Neutrophil collagenase (3DPE). UTIs and gout are interconnected through the elevation of uric acid levels. We aimed to identify compounds with dual functionality: antibacterial activity against UTIs and antirheumatic properties. Our screening based on several methods, sorted out six promising ligands. Four of these (L1, L2, L3, and L6) demonstrated favorable hydrogen bonding with both proteins and were selected for further analysis. These ligands showed binding affinities of −8.3 to −9.1 kcal/mol with both proteins, indicating strong interaction potential. Notably, L6 exhibited highest binding energies of −9.10 and −9.01 kcal/mol with S. aureus TyrRS and Neutrophil collagenase respectively. Additionally, the pkCSM online database conducted ADMET analysis on all lead ligand suggested that L6 might exhibit the highest intestinal absorption and justified total clearance rate. Moreover, L6 showed a best predicted inhibition constant with both proteins. The average RMSF values for all complex systems, namely L1, L2, L3 and L6 are 0.43 Å, 0.57 Å, 0.55 Å, and 0.51 Å, respectively where the ligand residues show maximum stability. The smaller energy gap of 3.85 eV between the HOMO and LUMO of the optimized molecule L1 and L6 suggests that these are biologically active compound. All the selected four drugs show considerable stabilization energy ranging from 44.78 to 103.87 kcal/mol, which means all four compounds are chemically and physically stable. Overall, this research opens exciting avenues for the development of new therapeutic agents with dual functionalities for antibacterial and antiarthritic drug designing.

The impact of psychological stress on physiological indicators in healthcare workers: a cross-sectional study.

Medical health workers play an essential role in the healthcare system and face unique workplace stressors. However, the impact of psychological stress on their physical health has received less attention compared to the general population. We retrospectively analyzed the Self-rating Depression Scale (SDS) questionnaires and blood testing results from 1963 medical health workers. Multivariate linear regression analysis using a backward stepwise selection strategy to identify physical examination indicators that were significantly affected by depression. Depression severity, as measured by SDS index score, was positively correlated with the levels of hemoglobin (coefficient 0.0027, p = 0.0412), platelet count (coefficient 0.0005, p = 0.0198), and uric acid (coefficient 0.0004, p = 0.0492), while negatively correlated with red blood cell count (coefficient-0.0895, p = 0.0406). Similar results were observed in the subgroup analysis stratified by age and sex. Our study found a significant association between higher levels of depression and specific physiological indicators in healthcare professionals, including elevated hemoglobin, platelet counts, and uric acid levels, as well as decreased red blood cell counts. These changes in blood parameters may reflect underlying physiological stress and inflammation, potentially increasing overall health risks for healthcare workers. Addressing these physiological changes may be crucial for mitigating the health risks associated with depression. To validate our findings and develop targeted interventions, larger multi-center studies are needed to further explore the relationship between depression severity and blood parameters in healthcare professionals.

Utility of serum uric acid levels in excluding pulmonary hypertension in severe chronic lung disease: insights from a tertiary care center

Hyperuricemia is a known predictor of World Health Organization (WHO) Group 1 pulmonary hypertension (PH) (pulmonary arterial hypertension), but its role in excluding PH secondary to chronic lung diseases (WHO Group 3) remains unclear. We retrospectively analyzed data from 323 patients with severe chronic pulmonary diseases who underwent evaluation for lung transplantation at a tertiary medical center between June 2017 and February 2023. We examined the association between hyperuricemia (serum uric acid > 6 mg/dL or > 0.357 mmol/L) and PH [mean pulmonary arterial pressure (MPAP) > 20 mmHg]. Compared to the normouricemia group (n = 211), hyperuricemic patients (n = 112) were more likely to be younger (P = 0.02), male (P < 0.001), and present with PH (P = 0.001) and severe PH (MPAP > 35 mmHg; P < 0.001). These patients also had a higher body mass index (P = 0.004), plasma N-terminal pro-B-type natriuretic peptide (P < 0.001), serum creatinine (P < 0.001), and C-reactive protein levels (P = 0.03). Significant associations with PH included higher body mass index (P = 0.005), uric acid levels (P < 0.001), total lung capacity (P = 0.02), and residual volume (P = 0.01); shorter 6-min walk test distance (P = 0.005); and lower forced expiratory volume in one second (P = 0.006) and diffusing capacity for carbon monoxide (P < 0.001). Multivariate analysis showed elevated uric acid levels remained significantly associated with PH (OR 1.29, 95% CI 1.05–1.58, P = 0.01). In conclusion, normal serum uric acid levels serve as a significant predictor for excluding pulmonary hypertension in patients with severe chronic lung diseases.

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

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

MSU crystallization promotes fibroblast proliferation and renal fibrosis in diabetic nephropathy via the ROS/SHP2/TGFβ pathway

Monosodium urate (MSU) crystallisation deposited in local tissues and organs induce inflammatory reactions, resulting in diseases such as gout. MSU has been recognized as a common and prevalent pathology in various clinical conditions. In this study, we investigated the role of MSU in the pathogenesis of diabetic kidney disease (DKD). We induced renal injury in diabetic kidney disease mice using streptozotocin (STZ) and assessed renal histopathological damage using Masson's trichrome staining and Collagen III immunofluorescence staining. We measured the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and uric acid (UA) using ELISA. Protein expression levels of NLRP3, p-NF-κB, SHP2, p-STAT3, and p-ERK1/2 were analyzed by Western blot. To further investigate the role of MSU in diabetic kidney disease, we conducted in vitro experiments. In our in vivo experiments, we found that compared to the Model group, there was a significant increase in interstitial fibrosis in the kidneys of mice after treatment with MSU, accompanied by elevated levels of MDA, SOD, and UA. Furthermore, the protein expression of NLRP3, p-NF-NB, SHP2, p-STAT3, and p-ERK1/2 was upregulated. In our subsequent studies on mouse fibroblasts (L929 cells), we discovered that high glucose, MSU, and TGF-β could promote the expression of P22, GP91, NLRP3, NF-κB, p-NF-κB, p-SHP2, p-EGFR, p-STAT3, and Collagen-III proteins. Additionally, we found that SHP2 could counteract the upregulation trend induced by MSU on the expression of p-SHP2, p-EGFR, p-STAT3, and Collagen-III proteins, and inhibitors YQ128, NAC, and Cetuximab exhibited similar effects. Furthermore, immunofluorescence results indicated that SHP2 could inhibit the expression of the fibrosis marker α-SMA in L929 cells. These findings suggest that MSU can promote renal fibroblast SHP2 expression, induce oxidative stress, activate the NLRP3/NF-κB pathway, and enhance diabetic kidney disease fibroblast proliferation through the TGFβ/STAT3/ERK1/2 signaling pathway, leading to renal fibrosis.

High Uric Acid Orchestrates Ferroptosis to Promote Cardiomyopathy Via ROS-GPX4 Signaling.

Aims: High uric acid (HUA), as a pro-oxidant, plays a significant role in the pathophysiology of cardiovascular disease. Studies have indicated that elevated uric acid levels can adversely affect cardiovascular health. Nevertheless, the impact of hyperuricemia on cardiomyopathy remains uncertain. Further research is needed to elucidate the relationship between HUA and cardiomyopathy, shedding light on its potential implications for heart health. Results: We demonstrated that uricase knockout (Uox-KO) mice accelerated the development of cardiomyopathy, causing significantly impaired cardiac function and myocardial fibrosis. Meanwhile, the mitochondrial morphology was destroyed, the lipid peroxidation products increased in number and the antioxidant function was weakened. In addition, we evaluated the effects of ferrostatin-1 (Fer-1), the ferroptosis inhibitor. Myocardial damage can be reversed by the Fer-1 treatment caused by HUA combined with doxorubicin (DOX) treatment. Benzbromarone, a uric acid-lowering drug, decreases myocardial fibrosis, and ferroptosis by alleviating hyperuricemia in Uox-KO mice by DOX administration. In vitro, we observed that the activity of cardiomyocytes treated with HUA combined with DOX decreased significantly, and lipid reactive oxygen species (ROS) increased significantly. Afterward, we demonstrated that HUA can promote oxidative stress in DOX, characterized by increased mitochondrial ROS, and downregulate protein levels of glutathione peroxidase 4 (GPX4). N-acetyl-l-cysteine, an antioxidant, inhibits the process by which HUA promotes DOX-induced ferroptosis by increasing the GPX4 expression. Innovation: We verified that HUA can exacerbate myocardial damage. This has clinical implications for the treatment of cardiac damage in patients with hyperuricemia. Conclusions: Our data suggested that HUA promotes the cardiomyopathy. HUA promotes DOX-induced ferroptosis by increasing oxidative stress and downregulating GPX4. Antioxid. Redox Signal. 00, 00-00.

Serum Uric Acid as a Biomarker in Patients Admitted with Acute Exacerbation of Chronic Obstructive Pulmonary Disease to a Tertiary Hospital, Kerala

ABSTRACT Background: Chronic obstructive pulmonary disease (COPD) is a highly prevalent and debilitating condition worldwide, imposing significant economic and social burdens on societies. Serum uric acid contributes to inflammation and is often used a biomarker. Aims and Objectives: This study aims to assess the potential role of serum uric acid as a cost-effective biomarker in hospitalized patients experiencing acute exacerbation of COPD. Additionally, it aims to investigate the relationship between the severity of airflow obstruction and serum uric acid levels in patients with COPD. Materials and Methods: The study design is a prospective cohort study involving 144 COPD patients admitted for acute exacerbation, excluding those with concurrent chronic comorbidities or receiving medications known to substantially elevate uric acid levels. Results: Our findings demonstrate elevated serum uric acid levels in patients with advanced-stage COPD and severe airflow obstruction. Furthermore, patients with higher levels of serum uric acid exhibit poorer prognosis compared to those with lower levels in COPD. Conclusion: Serum uric acid can serve as a valuable biomarker to prognosticate COPD patients and assess disease severity in patient admitted with exacerbations.

Effects of Febuxostat Therapy on Circulating Adipokine Profiles in Patients with Overweight or Obesity and Asymptomatic Hyperuricemia: A Randomized Controlled Study

Introduction: Elevated levels of serum uric acid (SUA) are strongly associated with several components of the metabolic syndrome, particularly obesity. Previous studies have reported the correlation between SUA levels, xanthine oxidoreductase (XOR) activity, and the imbalanced adipokine levels that are characteristic of obesity. In this study, we explored the effect of febuxostat on circulating adipokine profiles in patients with overweight or obesity and asymptomatic hyperuricemia. Methods: This study was a single-center, randomized, and controlled clinical trial that enrolled 130 participants with asymptomatic hyperuricemia and obesity. One hundred seventeen participants were included in the final analysis, with 60 participants in the febuxostat group and 57 in the control group. We compared the circulating adipokine levels at 3 and 6 months, including high molecular weight (HMW) adiponectin, chemerin, omentin, monocyte chemotactic protein-1, asprosin, fibroblast growth factor 21, neuregulin-4, leptin, resistin, vaspin, visfatin, adipsin, and assessed the correlation between changes in adipokine levels (Δadipokines) and changes in XOR activity (ΔXOR) after febuxostat treatment. Results: The results showed that an increase in HMW adiponectin and omentin levels and a decrease in chemerin and asprosin levels at 3 or 6 months compared to the control group. Additionally, a positive correlation was observed between ΔXOR activity and Δasprosin. Furthermore, after adjusting for triglyceride (ΔTG) and serum uric acid (ΔSUA) in multiple linear regression analyses, we found that ΔXOR activity was independently correlated with Δasprosin. Conclusion: This study may provide important evidence that febuxostat could alleviate the imbalance in circulating adipokine levels in patients with overweight or obesity and asymptomatic hyperuricemia. Furthermore, we observed a positive correlation between changes in asprosin levels and changes in XOR activity after febuxostat treatment.

Uric Acid as a Biomarker for Mood Disorders: A Comparative Study of Blood Uric Acid Levels Correlating With the Symptom Severity and Treatment Response.

Background Bipolar affective disorder (BPAD) and major depressive disorder (MDD) are two mood disorders whose pathophysiology may involve the purinergic system. Elevated uric acid levels, associated with this system, can impact various behaviors in individuals affected by these conditions. In addition to genetic predisposition, blood uric acid levels can be impacted by various factors, including metabolic syndrome, the consumption of psychoactive medications, and other underlying kidney conditions such as gout. Objective The study aims to investigate the relationship between blood uric acid levels and mental health conditions, specifically BPAD subtypes (manic and depressive) and MDD. The study also examines changes in blood uric acid levels following treatment and evaluates the effectiveness of different treatment approaches in reducing uric acid levels. Methodology To be eligible to participate, individuals must have a confirmed diagnosis of BPAD (manic or depressive type) or MDD, according to the International Classification of Diseases (ICD-10). Blood uric acid levels were measured at both baseline and follow-up assessments. Symptoms were assessed weekly using standardized rating scales (Young Mania Rating Scale (YMRS) and Hamilton Rating Scale for Depression (HAM-D)) until treatment response was achieved, which was defined as a 50% reduction in initial scores on both scales. We used ANOVA to examine the differences among the three patient groups and paired sample t-tests to examine the changes in means before and after treatment conditions. Results A significant positive correlation was found between the severity of illness and serum uric acid levels across all three patient groups: those with BPAD-mania, BPAD-depression, and MDD. Notably, patients with BPAD-mania patients had significantly higher serum uric acid levels (5.2±0.9 mg/dL) compared to those with BPAD-depression (4.8±1.0 mg/dL) and MDD (4.0±1.1 mg/dL). After treatment, all patient groups exhibited a decrease in serum uric acid levels. The reduction in serum uric acid levels was pronounced in all patient groups, with decreases of 3.1±0.8 mg/dL in patients with BPAD-mania, 3.1±0.9 mg/dL in those with BPAD-depression, and 3.5±1.1 mg/dL in those with MDD. The study showed that the reduction in serum uric acid levels was significantly correlated with the severity of illness in patients with BPAD-mania, but not in those with BPAD-depression or MDD. Furthermore, the study found that treatment with lithium carbonate, sodium valproate, or carbamazepine was equally effective in reducing serum uric acid levels, regardless of the mood stabilizer used. Conclusion The study supports that dysfunction in the purine system might play a significant role in the development and progression of BPAD, suggesting that this phenomenon is not solely due to chronicity or medication exposure. This study also introduces a fresh perspective on the underlying biological processes that contribute to the development of BPAD and also sheds light on new treatment regimens targeting uric acid reduction in treating patients with bipolar disorder.

The effect of warm water compresses on gout pain in the elderly at Takalar Community Health Center Makassar

Background: Gout arthritis, commonly referred to as gout, is a chronic non-communicable disease characterized by joint inflammation caused by elevated uric acid levels. This condition can persist for years or even a lifetime, leading to recurrent pain. One non-pharmacological treatment for managing gout pain is the application of warm water compresses, which may help alleviate discomfort by improving blood circulation and reducing inflammation. Purpose: This study aimed to assess the effectiveness of warm water compresses in reducing gout-related pain in elderly patients. Methods: The study used a quasi-experimental design with a control group and a pretest-posttest approach. A total of 32 elderly respondents suffering from gout pain at Takalar Community Health Center Makassar, were selected through purposive sampling. Pain levels were measured before and after the intervention using standardized pain scales. An independent t-test was conducted to analyze the differences between the experimental and control groups. Results: The independent t-test revealed a statistically significant effect of warm water compresses on reducing gout pain, with a p-value of 0.00 (p &lt; 0.05). This indicates that warm water compresses effectively alleviate gout-related pain in the elderly. Conclusion: Warm water compresses significantly reduce gout pain in elderly patients at Takalar Community Health Center, Makassar. These findings suggest that warm water compresses can be a simple, non-invasive, and effective treatment option for managing gout pain in older adults.

The impact of pre-operative uric acid levels on post-operative renal outcomes in off-pump coronary artery bypass grafting patients

Background: Elevated pre-operative uric acid levels significantly impact post-operative renal outcomes in off-pump CABG patients, increasing the risk of acute kidney injury, as evidenced by higher serum creatinine and reduced urine output. Methods: This cross-sectional study was conducted in Department of Cardiac Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka, Bangladesh from January 2021 to December 2022. Total 160 patients undergoing off pump CABG were divided into two groups, group A and group B, each containing 80 patients. In group A, uric acid level was &lt;7 mg/dl for male and &lt;6 mg/dl for female and in group B, it was &gt;7 mg/dl and &gt;6 mg/dL for female. Results: The demographic characteristics, pre-operative serum UA levels and serum creatinine levels between the two groups was not statistically significant. Group A had shorter operative times (mean 265.21±53.33 minutes) compared to Group B (mean 327.04±44.32 minutes), with more patients in Group-B undergoing longer surgeries (&gt;360 minutes). Group-B also had more grafts (mean 4.4 vs 3.6), higher serum creatinine (1.91 vs 1.17 mg/dl), bilirubin (0.8 vs 0.7 mg/dl), and lower urine output (mean 47.52 vs 95.37 ml/hour), all statistically significant (p&lt;0.001). Conclusions: This study concludes that there is significant impact of pre-operative uric acid levels on post-operative renal outcomes in off-pump CABG patients.