Monosodium Urate Research Articles (Page 1)

Objective: Monosodium urate (MSU) crystallization in human joints is poorly understood. This study aimed to investigate whether the length of MSU crystals varies in relation to organized ultrasound deposits, which may lead to longer crystals. Methods: Observational, cross-sectional study analyzing MSU crystals from synovial fluid samples of patients with crystal-proven gout. Using light microscopy, we measured crystal lengths (in µm) and noted the presence of long crystals, defined by cutoffs at the 66th, 75th, and 90th percentiles. We evaluated their association with two ultrasound-defined crystal deposition models: (1) grade 2–3 double-contour (DC) sign, tophi, and/or aggregates; and (2) grade 2–3 DC sign and/or tophi. Results: In a total of 1076 MSU crystals from 28 joints, median length was 23.3 µm (95% confidence interval 22.1–24.5). MSU crystal length was similar regardless of ultrasound deposition: in model 1 (20 joints, 71.4%), 22.5 µm in joints with deposits vs. 21.7 µm without; p = 0.42; in model 2 (15 joints, 53.6%), 22.8 µm vs. 21.2 µm, respectively; p = 0.12. Joints fulfilling model 2 criteria had more long crystals (>66th percentile), both in absolute and relative terms. Long crystals mildly correlated with serum urate levels and were numerically more frequent in patients with tophaceous gout. Conclusions: Most MSU crystals in synovial fluid gathered around a common length, regardless of ultrasound deposition. Long crystals were more common in joints with DC signs or tophi. Our finding is in keeping with two different mechanisms of MSU crystallization in humans.

Gout, a prevalent metabolic disorder driven by hyperuricemia, results in pathological deposition of monosodium urate (MSU) crystals in joints and soft tissues, stimulating intense inflammatory responses with systemic health consequences. Emerging evidence highlights dysregulated bile acid (BA) metabolism as a pivotal contributor to gout pathogenesis. Imbalances in BA influence disease progression through multiple mechanisms (1): modulating hepatic urate production via PPAR-α/XOD signaling (2), regulating immune responses through FXR/TGR5-dependent suppression of NLRP3 inflammasome activation, and (3) shaping the gut microbiota composition, which reciprocally affects uric acid homeostasis and inflammation. Despite these advances, the precise mechanistic networks linking BA dysmetabolism to gout remain incompletely understood. In this review, we systematically synthesizes current knowledge on BA-gout interactions, elucidated how BA disturbances exacerbate disease progression, discussed the factors contributing to metabolic disorders of BAs, and evaluated promising therapeutic strategies targeting BA pathways. For example, FXR antagonists facilitate the synthesis of BA by inhibiting the aberrant activation of FXR. TGR5 agonists suppress inflammation. Probiotics help restore the diversity of the gut microbiota and increase the abundance of beneficial bacteria, including Bifidobacterium and Lactobacillus . Moreover, traditional Chinese medicine works by improving structural disorders of the gut microbiota and activating CYP7A1 to enhance the BA synthesis pathway. By integrating metabolic, immunological, and microbial perspectives, this work provides a framework for developing novel, mechanism-based interventions against gout.

Real-time fluorescent and microscopic uricase assay by monitoring the clearance of acridine orange-doped monosodium urate crystals under physiological conditions.

Introduction: The main aim of present study is to evaluate the anti-arthritic potential of Tribulus terrestris seed extract in-vivo in Wistar rats. Methods: The anti-arthritic activity of ethanolic extract of Tribulus terrestris seeds was evaluated by using three in vivo methods. In the formaldehyde-induced arthritis, the disease was induced by injecting 0.1 ml of formaldehyde into the hind paw. In the monosodium urate crystal model of anti-arthritis activity, the crystals were prepared by dissolving monosodium urate in boiling water, and then agitating at normal temperature. The carrageenan/kaolin model was used to induce arthritis by injecting 5% carrageenan/kaolin into the knee joint. The thickness of the paw was measured using a vernier caliper. Results: When compared to the control group, the extract of Tribulus terrestris exhibits strong anti-arthritic effect. The activity increases with the dose concentration. Conclusion: The Tribulus terrestris has anti-arthritic activity, and its efficacy rises in a dose-dependent way.

Commercial and non-commercial cyclodextrin derivatives as a novel therapy to improve gout's disease and hyperuricemia.

Abstract Introduction Gout is a very common inflammatory arthritis caused by the deposition of monosodium urate crystals in the joint, which is normally managed by urate-lowering therapy like allopurinol or febuxostat. A major therapeutic challenge is refractory gout, especially in older patients who have renal impairment, gastrointestinal sensitivity, and cardiovascular disease. This case is particularly challenging due to the elderly patient having multiple comorbidities and drug intolerances, which highlights the limitations of conventional therapy and the need to consider biologic agents for difficult-to-treat cases. Case description We report the case of a 70-year-old gentleman referred to the rheumatology clinic for management of refractory gouty arthritis. The patient had a history of intolerance to standard urate-lowering therapies, including allopurinol and colchicine, both of which caused severe diarrhoea. His extensive comorbidities included type 2 diabetes mellitus, ischaemic heart disease (status post-CABG and stenting), hypertension, hyperlipidaemia, osteoporosis, heart failure, irritable bowel syndrome, and a prior stroke. Following a recent myocardial infarction, he developed multiple gout flares during his hospital stay and was treated with prednisolone 40 mg, resulting in symptomatic improvement. However, he declined benzbromarone initially. At a routine two-year follow-up, he was tried on probenecid, which resulted in a severe itchy rash over the bilateral lower limbs. A subsequent trial of benzbromarone again led to severe diarrhoea. Sulfinpyrazone was also attempted but resulted in similar gastrointestinal intolerance. His serum uric acid remained elevated at 516 µmol/L. Allopurinol was cautiously reintroduced, along with low-dose prednisolone (5 mg), but he continued to experience diarrhoea and frequent flareups affecting the knees, ankles, hands, and shoulders. He required intermittent courses of prednisolone (up to 30 mg), which he tapered but was unable to discontinue completely due to recurrent attacks. He then had a fall and sustained a vertebra fracture. Three months later, he still reports two additional flares managed with a tapering course of prednisolone. Examination revealed ankle tenderness without active synovitis; serum urate remained elevated at 489 µmol/L. Due to the patient’s refractory disease and treatment intolerance, biologic therapies such as anakinra or rasburicase were considered. Tragically, before these could be initiated, the patient suffered a right thalamic haemorrhage and passed away several months later. This case highlights the significant management challenges in treating refractory gout in patients with multiple comorbidities and limited pharmacological options. Discussion Gout is a treatable inflammatory arthritis caused by urate crystal deposition in joints. The long-term management of gout involves urate-lowering therapy with a xanthine oxidase inhibitor, allopurinol, or febuxostat. This patient poses a clinical challenge as he develops gastrointestinal manifestations with the first-line treatment allopurinol and colchicine. Given his multiple comorbidities, non-steroidal agents would be risky, and he was intolerant to colchicine too, leaving only steroids as options for flares. Febuxostat was not initiated due to ischaemic heart disease. The second challenge arises when he develops a cutaneous reaction to probenecid, followed by a gastrointestinal reaction to benzbromarone and sulfinpyrazone. Despite a cautious rechallenge with allopurinol, the patient was still unable to tolerate it. Interleukin-1 inhibitor may be considered for this patient. However, this treatment might not be feasible for a frail elderly patient with multiple comorbidities. The limited therapeutic option in this patient led to steroid dependence, which led to vertebra fractures and frequent gouty flares. This case demonstrates the need for early identification of treatment intolerance, close monitoring of urate levels, and a tailored approach. Unfortunately, before advanced therapies could be initiated, the patient suffered a fatal thalamic haemorrhage—likely influenced by underlying vascular disease and prolonged steroid exposure. Key learning points Management of gout can be challenging, especially in patients with multiple comorbidities and intolerant to first-line treatment. Steroid-dependent individuals demonstrate poor disease control and can lead to multiple complications, including fractures and cardiovascular risk. A personalised, multidisciplinary approach is very crucial for managing complex gout cases, especially for elderly patients with polypharmacy.

Abstract Introduction Gout is a common crystal arthropathy that typically presents with acute monoarthritis of peripheral joints. Extra-articular tophaceous disease is rarely seen as the initial manifestation. We present an unusual case of a young man with a family history of gout who developed supraclavicular masses causing thoracic outlet syndrome (TOS). Initial surgical excision was undertaken due to concerns about malignancy. Only on recurrence and re-excision was the diagnosis of urate crystal deposition confirmed. This case highlights the importance of considering gout in atypical locations and the role of advanced imaging and surgical pathology in diagnosis. Case description A 30-year-old male with a known family history of gout (twin brother and uncle) presented with subacute onset of right shoulder and neck pain. Examination revealed a firm supraclavicular mass. Imaging confirmed compressive masses behind the right clavicle, raising concern for malignancy or a vascular anomaly. He underwent thoracic outlet decompression including 1st rib and pectoralis minor excision with subclavian vein bypass. Intraoperatively, chalky white material was noted. Histology suggested a granulomatous foreign body reaction, but no definitive diagnosis was made. The patient recovered but re-presented with recurrence of the mass six months later. A second surgery revealed similar chalky material and a fluid analysis confirmed monosodium urate crystals on polarised light microscopy. This was further confirmed with a dual-energy CT (DECT) scan showing multifocal urate deposition at the sternoclavicular and acromioclavicular joints (see attached DECT images – urate crystals denoted in green). Subsequently, he reported a new self-limiting attack of podagra. Serum urate was also elevated at 480 µmol/L. Allopurinol was initiated at 200 mg daily, with a repeat level of 328 µmol/L. The patient remains under rheumatology follow-up. Allopurinol was titrated to 400 mg to achieve a serum urate target <300 µmol/L as per BSR guidelines. Naproxen and gastroprotection were prescribed for future flares. The DECT scan of the right shoulder area shows the appearance of multifocal urate crystal deposition along the capsular attachments of the sternoclavicular and AC joints on the right side (green denotes urate crystals; purple can be ignored - cartilage). Discussion This case illustrates an unusual presentation of gout, masquerading initially as a sinister supraclavicular mass with compressive features mimicking TOS. The initial surgical exploration, although essential due to clinical suspicion, did not yield a diagnosis until the recurrence provided the opportunity for more targeted crystal analysis. The presence of chalky material intraoperatively should prompt consideration of gout, even in atypical locations. The patient had a suggestive family history and prior peripheral joint symptoms, but the rarity of axial gout meant this was not initially suspected. Serum urate was normal at first presentation, which likely contributed to diagnostic delay. This reflects the known limitation that serum urate can be normal during active disease. The diagnosis was ultimately confirmed using a combination of repeat histology and polarised microscopy, supported by DECT imaging which offered non-invasive localisation of urate deposits. The DECT findings were instrumental in guiding ongoing management and reassuring both patient and team regarding the nature of the recurrence. Treatment has focused on achieving urate lowering below target thresholds, consistent with BSR guidelines. Given prior surgical morbidity, a conservative approach is preferred for any recurrence. This case underscores the diagnostic challenge in atypical gout presentations and supports a lower threshold for crystal evaluation in unexplained masses. Questions for further discussion include: Should DECT be used earlier in diagnostic work-up for atypical soft tissue masses? What is the optimal surveillance strategy for extra-articular gout post-surgery? Key learning points • Gout can rarely present as a soft tissue mass in axial locations, mimicking malignancy or causing structural compression such as thoracic outlet syndrome. • DECT is a valuable diagnostic tool in atypical presentations, providing non-invasive localisation of urate deposits and confirming diagnosis where aspiration is not feasible.

To develop and validate a model that integrates dual-energy computed tomography (DECT) and clinical features for the prediction of the risk of frequent gout flares (FrGF). This retrospective cohort study included 1204 patients with gout who were randomly divided into training and validation cohorts and followed for 12 months after DECT. The patients were categorized into an FrGF group (≥ 2 flares, n = 606) and an infrequent gout flares (InGF) group (< 2 flares, n = 598) based on flare frequency during follow-up. Clinicoradiological features that were significant in univariate analysis were dimensionally reduced via least absolute shrinkage and selection operator regression, followed by multivariate logistic regression to identify independent risk factors for FrGF. An integrated clinicoradiological model was constructed using a nomogram. Model performance was evaluated using the receiver-operating characteristic (ROC) curve and clinical utility by decision curve analysis. The integrated model was compared with the clinical model using the DeLong test to evaluate the incremental value of radiological features. Independent risk factors for FrGF were chronic arthritis, recurrent gout at baseline, intermittent medication, non-adherence to a low-purine diet, high monosodium urate burden, elevated Sharp/van der Heijde score, and tarsal bone erosion. The integrated model had an area under the ROC curve (AUC) of 0.95 (95% CI 0.92-0.97) in the validation cohort, outperforming the clinical model (AUC 0.83, 95% CI 0.79-0.87), demonstrating the incremental diagnostic value of DECT. The integrated model demonstrated excellent discriminative ability, calibration, and clinical value, enabling accurate prediction of the risk of FrGF. Question Frequent gout and infrequent gout differ in treatment strategies, but how can clinicians prospectively and accurately identify frequent gout? Findings Based on clinical and DECT features, this study identified 7 independent risk factors for frequent gout and developed and validated a predictive model. Clinical relevance This study's predictive model exhibits favorable predictive performance, and its web-based calculator helps clinicians assess the risk of frequent gout flares and predict clinical intervention efficacy, thus providing valuable evidence for formulating individualized clinical treatment plans.

Abstract Introduction Crystal arthropathies are well-known disease entities caused by the deposition of crystals within the articular surface, including monosodium urate, calcium pyrophosphate, basic calcium phosphate, oxalate, and cholesterol crystals. These crystals typically deposit in the joint space but can also affect other tissues, such as the renal tract and cardiopulmonary system. Here, we present a case of a Caucasian male who initially presented with dactylitis, presumed to be gout, despite a normal uric acid level. Later, he was diagnosed with 2,8-dihydroxyadenine crystalline (2,8 DHA) arthropathy and nephropathy. Case description A 68-year-old Caucasian male initially presented with loin pain and hematuria, leading to a diagnosis of bilateral renal stones. A CT scan of the kidneys, ureters, and bladder revealed multiple high-density foci in the urinary bladder, with the largest stone measuring 6 mm. No hydronephrosis or perinephric fat stranding was noted. His CRP was 86gm/L, creatinine 193 µmol/L, and eGFR 30 mL/min. Eighteen months prior, he had been diagnosed with gout after presenting with dactylitis in both his hands and toes. X-rays of his hands demonstrated osteoarthritis changes at the proximal and distal interphalangeal joints of both hands and a chest x-ray was normal. He was started on allopurinol which was uptitrated to 300 mg and colchicine as and when required. His urate level at that time was 416 µmol/L, and subsequent measurements ranged from 246 to 338 µmol/L, with ongoing flare-ups. The patient had no children and one healthy sister. He was a non-smoker with occasional alcohol use, and had a history of scalp folliculitis treated with isotretinoin. Over the following 12 months, he continued to experience recurrent flares of dactylitis, often in an asymmetrical pattern affecting his hands. He also had recurring renal colic. Further investigations, including exclusion of seronegative inflammatory arthritis and atypical infections (e.g., tuberculosis), led to a renal biopsy, which revealed 2,8-dihydroxyadenine crystalline deposits. Genetic testing confirmed an APRT deficiency with a heterozygous mutation. The patient remains on allopurinol and has received lifestyle advice to increase fluid intake. He is being closely monitored by both rheumatology and renal services due to his risk of end-stage renal failure. Discussion 2,8-dihydroxyadenine crystalline nephropathy is a rare but preventable cause of end-stage renal failure. It is caused by adenine phosphoribosyltransferase (APRT) deficiency, an autosomal recessive disorder in purine metabolism, which can often mimic gout. Characteristic features include recurrent renal stones, dactylitis, and metatarsophalangeal (MTP) joint swelling. Diagnosis is confirmed through urine analysis, which reveals the presence of 2,8-DHA crystals, and joint aspiration, which typically shows birefringence and a distinctive Maltese cross appearance. APRT deficiency impairs the purine salvage pathway, leading to the accumulation of 2,8-DHA, similar to the pathophysiology of gout. Management includes allopurinol or febuxostat, although no “treat-to-target” approach has been established. In the absence of biomarkers, uric acid has been used as a surrogate marker, as it is a downstream product in this pathway. Case series have reported the accumulation of 2,8-DHA in various organ systems, including the liver, kidney, and lymph nodes, and post-transplant renal allografts. Key learning points 2,8 DHA crystalline arthropathy is a rare condition that can mimic gout occurring due to an APRT deficiency. Although primarily a renal disease it can cause joint involvement including dactylitis and MTP swelling. The true incidence of this crystal arthritis is unknown but should be considered in anyone with renal disease and a crystal arthritis. The diagnostic process simple, urine analysis will demonstrate the presence of 2,8 DHA crystals and joint aspiration will show a characteristic Maltese cross bifringence pattern. Confirmation can be sought with a renal biopsy and genetic testing. The management is generally supportive with allopurinol or febuxostat and hydration alongside monitoring Wednesday renal failure.

Abstract Introduction This case presents a diagnostically challenging journey of a young female with intermittent joint pain and swelling, initially suspected to be related to hypermobility syndrome, ultimately diagnosed as gout. Her diagnosis was complicated by rarity of gout in young females, normal inflammatory indices, and normal joint ultrasound on most occasions. The diagnosis was confirmed through joint aspiration revealing monosodium urate crystals and raised uric acid levels. The case is significant due to the rarity of gout in premenopausal women. It highlights the importance of thorough clinical reassessment. Case description A 40-year-old female with a background of asthma, arrhythmia (with loop recorder in situ), childhood joint dislocations, two miscarriages, and a son with reflux nephropathy and autism, presented with a complex history of intermittent joint pain and swelling since 2020. She is a social smoker and has reported low alcohol intake at presentation. Her symptoms began in February 2020 with left ankle pain and swelling. Ultrasound demonstrated inflammatory changes, but serological markers (ANA, RF, CCP) were negative and inflammatory markers were normal. Initial management included steroid injection with partial relief. By October 2020, she reported intermittent polyarticular joint pain and swelling (MCP, shoulder, wrists, knees, and ankle) with systemic symptoms such as fatigue and weight loss. Despite this, no objective inflammation was noted on examination or ultrasound. She was managed symptomatically with analgesics. In November 2020, hypermobility syndrome was diagnosed based on clinical features and Beighton score, without any evidence of synovitis on ultrasound. However, symptoms escalated, particularly affecting the left ankle. By April 2021, joint aspiration of the left ankle revealed monosodium urate crystals, confirming gout. Uric acid was elevated at 0.75 mmol/L. She was started on prednisolone and allopurinol. After discussion with genetic experts, genetic testing for inherited causes (Bartter’s, Gitelman’s, ADPKD) was not performed due to unlikeliness and the identification of under-excretion of uric acid on 24 hour urine test. Despite escalation of allopurinol dose to 400 mg OD, she continued to have flares through 2022, with persistently elevated uric acid levels. In November 2023, a further ankle flare led to aspiration confirming abundant urate crystals. She was subsequently switched from allopurinol to febuxostat. This case illustrates a diagnostic challenge in a young female with crystal arthropathy, complicated by hypermobility. Discussion This case is clinically intriguing due to the patient’s atypical presentation of gout in a young, premenopausal woman, compounded by a background of joint hypermobility. Initial clinical decisions focused on joint hypermobility as the main cause of joint pain. This decision was emphasised by negative autoimmune serologies (ANA, RF, CCP), low inflammatory markers, and joint ultrasound which did not persistently show active synovitis, directing us toward a non-inflammatory or mechanical aetiology. The turning point came when aspiration of a swollen ankle revealed monosodium urate crystals, confirming a diagnosis of gout. Although this is an uncommon diagnosis in women of her demographic, the discovery prompted further investigation into potential secondary causes. Discussion with genetic experts excluded inherited metabolic conditions, and it was ultimately determined that her hyperuricaemia resulted from under-excretion of uric acid. Escalation of urate-lowering therapy from allopurinol to febuxostat was warranted due to persistent flares and elevated uric acid levels, despite increasing allopurinol doses. This case raises this key question: • Should young women with atypical joint pain and negative autoimmune work-up be screened earlier for crystal arthropathy? Ultimately, this case has highlighted the importance of reassessment, keeping an open differential, and not dismissing gout purely based on age or gender. It reinforces the value of diagnostic joint aspiration and tailoring management to the individual’s unique social and clinical context. Key learning points 1. Atypical presentation of gout in young women: Although gout is more common in older men, it can occur in young, premenopausal women and should be considered in the differential diagnosis of unexplained joint pain and swelling. 2. Challenges in diagnosing gout with coexisting hypermobility: Joint hypermobility can mimic or mask inflammatory joint symptoms, complicating clinical assessment and potentially delaying diagnosis. 3. Importance of joint aspiration for definitive diagnosis: Identification of monosodium urate crystals through joint aspiration remains the gold standard for confirming gout, especially when clinical and serological findings are inconclusive. 4. Negative autoimmune serologies do not exclude inflammatory joint disease: Normal ANA, RF, and CCP, along with absent synovitis on imaging, do not rule out crystal arthropathies or other inflammatory conditions.

Gout is a prevalent inflammatory arthritis resulting from the deposition of monosodium urate (MSU) crystals in tissues, typically characterized by severe pain and swelling at the affected joints. This review article aims to understand the reasons for the global rise in gout cases through examining the underlying mechanism and evaluating available treatments. Four treatmentsNSAIDs, colchicine, glucocorticoids, and xanthine oxidase inhibitorsare evaluated based on mechanisms of action, commonly used drugs, and associated safety issues. NSAIDs, with ibuprofen, aspirin, and naproxen sodium as the most used drugs, exert their effect by inhibiting prostaglandin production from the COX enzyme, although their adverse effects of gastrointestinal disorders warrant attention. Colchicine has long been used to relieve joint pain and swelling by inhibiting microtubules, blocking NLRP3 activation, and reducing neutrophil recruitment. However, it has comparatively narrow therapeutic uses as high doses may lead to severe toxicity. Glucocorticoids relieve acute gout by inhibiting leukocyte recruitment and by suppressing inflammation and vascular permeability. Prednisone, methylprednisolone, and triamcinolone are used depending on disease severity and sites of onset. They are recommended only for short-term treatment due to the risks of ulcers. Lastly, xanthine oxidase inhibitors, allopurinol and febuxostat, focus on maintaining serum urate levels to prevent crystal formation. However, side effects include allopurinol leading to allopurinol hypersensitivity syndrome and febuxostat causing cardiovascular events. The major issues lie in drug safety and knowledge gaps. Future research should focus on eliminating side effects; professionals and patients should be educated on gout treatment and prevention.

BackgroundGout, an inflammatory arthritis characterized by monosodium urate crystal deposition, affects 1–4% of the global population and demonstrates strong associations with metabolic syndrome. Metabolic dysfunction-associated fatty liver disease (MASLD), affecting 38% of adults worldwide, represents a multisystem disorder with substantial morbidity and mortality. This first European prospective cohort study systematically examines the association between MASLD and incident gout risk.MethodUtilizing UK Biobank data (n = 402,083 after exclusions), we conducted a prospective cohort analysis excluding participants with baseline gout, arthritis, hepatitis B/C, alcohol-related liver disease, or events within the initial 2-year follow-up. Cox proportional hazards models evaluated MASLD–gout associations, with Kaplan–Meier curves illustrating cumulative incidence.ResultMASLD patients exhibited a 71% elevated gout risk versus non-MASLD counterparts (HR = 1.71, 95% CI 1.59–1.83, P < 0.0001). Subgroup analyses revealed consistent associations across demographics, with attenuated risk in older adults (≥ 65 years: HR = 1.55 vs. < 65 years: HR = 1.86). Paradoxically, individuals without diabetes, hypertension, or central obesity demonstrated a higher gout risk than those with these comorbidities. MASLD patients showed significantly greater cumulative gout incidence over time (P < 0.001).ConclusionMASLD independently associates with increased gout risk, persisting after comprehensive confounder adjustment. These findings underscore MASLD’s potential role in gout pathogenesis and highlight the clinical relevance of targeted MASLD interventions for gout prevention. Mechanistic and causal investigations remain warranted.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40001-025-03298-5.

PurposeGout is a chronic disease caused by the deposition of monosodium urate crystals in joints and tissues. The Qifu Huazhuo (QFHZ) Formula has shown effectiveness and safety in the management of gout. However, the role of QFHZ in the mitigation of gout needs to be further explored.Materials and methodsUHPLC-MS/MS was used to identify potential metabolites of QFHZ. Then we conducted a midpoint evaluation of the clinical study on the treatment of gout with QFHZ formula. The clinical study was a monocenter, open-label, randomized controlled trial. Eligible participants were allocated to TM, WM and TWM three groups in random. Participants in TM, WM and TWM group were received QFHZ (250 mL/dose, twice daily, oral), febuxostat (40 mg/dose, once daily, oral) and combination of febuxostat (40 mg/dose, once daily, oral) with QFHZ (250 mL/dose, twice daily, oral) for 12 weeks respectively. The primary efficacy endpoint is the percentage change in serum uric acid. The secondary efficacy endpoint include frequency of gout attacks, the change in estimated glomerular filtration rate (eGRF) and serum creatinine from baseline. Proteomic and metabolomic profiling was performed on paired pre- and post-treatment plasma samples.ResultsPharmacological studies have indicated that QFHZ contains 14 major metabolites. Clinical research has found that, TM can reduce the frequency of gout attacks compared to WM (p = 0.0006), while no significant differences were observed in the percentage change of serum uric acid levels across the three groups. Combined with proteomics and metabolomics analysis, it was discovered that QFHZ may regulate neutrophil extracellular trap (NET) formation, complement, lysosomes, phagosomes, and ferroptosis related biomolecules.ConclusionQFHZ shows distinct advantages in preventing gout recurrence over urate-lowering therapy alone, with multi-omics profiling revealing its potential multi-target effects. Future studies should validate these findings in larger cohorts and further elucidate the underlying molecular mechanisms.Clinical Trial Registrationhttps://www.chictr.org.cn/showproj.html?proj=198890, identifier ChiCTR2300073188.

Interferon Regulatory Factor 5 plays an important role in the regulation of innate immune responses by amplifying the Nuclear Factor κB response, which is critical in gout inflammation. Furthermore, the rs4728141 polymorphism C allele was associated with both increased IRF5 expression and susceptibility to gout. We examine the association between rs4728141 and cytokine production in response to various Toll-Like Receptor ligands and describe the transcriptomic and proteomic changes observed in patients with gout and controls in relation to this polymorphism. We examine the transcriptome of freshly isolated peripheral blood mononuclear cells (PBMCs) from 93 normouricemic donors and 63 gout patients as well as serum inflammatory proteome in 197 control and 195 gout samples. Stimulation experiments of freshly isolated human PBMCs were performed over 24 h, followed by RNA-sequencing in gout patients and cytokine production measurement by ELISA in normouricemic donors and gout patients. The rs4728141 C allele was associated with increased IL-1β expression in unstimulated PBMCs of controls, but not in gout. No association between the polymorphism and serum inflammatory proteome was found. As expected, an increased IRF5 expression was observed in stimulated PBMCs of rs4728141 C allele carriers in response to several stimulations. Interestingly, IL-1β production was specifically enhanced in association to the rs4728141 C allele when cells were stimulated with palmitate with or without monosodium urate crystals. This pattern of cytokine production shows a functional impact of rs4728141 in gout through altered IL-1β production.

Gout is a prevalent and painful form of inflammatory arthritis associated with hyperuricemia, which leads to monosodium urate crystal deposition in joints and surrounding tissues, triggering acute inflammatory responses. This disease is also closely linked to serious comorbidities, including cardiovascular diseases, chronic kidney diseases, diabetes, and increased mortality risk, significantly impacting global health. In this study, we conducted a comprehensive genome-wide association study (GWAS) based on the UK Biobank pain questionnaire 2019, comprising 10 474 gout cases and 140 068 controls, identifying 13 loci associated with gout. These findings were further explored in the FinnGen cohort, with 10 loci being replicated significantly. Sex-stratified analyses revealed notable differences, with 16 loci identified in males and two loci identified in females, reflecting both shared and sex -stratified genetic influences on gout susceptibility. In addition, genetic correlation analyses demonstrated strong associations between gout and traits related to urate levels, specific medication use, and metabolic functions. Transcriptome-wide association studies highlighted several genes, such as SLC16A9 and ASAH2B, which showed significant expression patterns across various tissues, implicating metabolic and immune pathways in gout. Phenome-wide association studies of significant single nucleotide polymorphisms revealed links to metabolic, immunological, and skeletal traits, underscoring the multi-faceted nature of gout. These results contribute valuable insights into the genetic architecture and biological mechanisms underlying gout, suggesting potential avenues for tailored interventions.

Modulation of NLRP3 inflammasome and uric acid metabolism by small molecule pectin from Premna ligustroides Hemsl leaves: Implications for hyperuricemia management.

Endothelial dysfunction is an early driver of atherosclerosis, yet the direct impact of endogenous crystals such as cholesterol crystals and monosodium urate on endothelial activation remains incompletely understood. In this study, we examine how crystalline stimuli modulate human umbilical vein endothelial cells by assessing inflammatory signaling, mitochondrial respiration, and neutrophil recruitment. Using dose- and time-controlled experiments, we show that CC and MSU are internalized by endothelial cells, activating NF-κB and STAT3 signaling pathways and inducing a robust pro-inflammatory cytokine profile. Notably, CC caused marked mitochondrial dysfunction, evidenced by impaired respiratory capacity and loss of membrane potential, revealing a novel bioenergetic vulnerability in endothelial cells. Both direct crystal stimulation and exposure to crystal-primed conditioned media triggered endothelial adhesion molecule expression and promoted neutrophil adhesion, indicating that soluble mediators released upon crystal stimulation can propagate vascular inflammation. These findings demonstrate that crystalline stimuli are potent vascular danger signals capable of driving endothelial inflammation, mitochondrial impairment, and immune cell engagement, which are hallmarks of early atherogenesis. By elucidating these multifaceted endothelial responses, this study provides important mechanistic insights into how crystal-induced signals may contribute to vascular dysfunction and the early stages of atherogenesis.

Gout is a common form of inflammatory arthritis and is caused by the deposition of monosodium urate (MSU) crystals as a result of hyperuricemia (HUA). s. Renowned Unani Physician Ibn-Hubal said that Niqras affects mainly those people who have excess of Humors (Akhlat) and their body is unable to excrete them. These humors retain inside the body and accumulate around the joints and other tissues of body.

Background and ObjectivesConcomitant septic and crystal-induced arthritis is a rare condition. Failure to diagnose this condition can result in significant harm to the patient. This study aims to investigate the prevalence and characteristics of concomitant septic and crystal-induced arthritis.MethodsA retrospective study included patients diagnosed with concomitant septic and crystal-induced arthritis confirmed by positive bacterial culture and intracellular crystals in synovial fluid of the same joint, from January 1, 2015, to July 31 ,2024.ResultsA total of 45 cases were defined as having the prevalence of concomitant septic and crystal-induced arthritis among patients with crystal-induced arthritis of 4% (45/1116). Demographic characteristics showed male predominance (73.3%) with a mean ± SD age of 62.8 ± 14.4 years. Acute monoarthritis (66.7%, n = 30), which primarily affected the knee (68.9%, n = 31), was the most common presentation. Fever was present in 95.6% of cases. The median synovial white blood cell (WBC) count was 61, 478 cells/μL (interquartile range: 33, 600–131, 030). The mean ± SD C-reactive protein (CRP) level was 215 ± 96.7 mg/L. Monosodium urate crystals were found in 80% (n = 36) of the cases. The predominant bacteria were Staphylococcus (48.9%, n = 22), with Methicillin-sensitive Staphylococcus aureus (MSSA) being the most common (28.9%, n = 13), followed by Streptococcus dysgalactiae (15.6%, n = 7) and gram-negative bacilli (15.6%, n = 7). The mortality rate was 15.6% (n = 7).ConclusionThe prevalence of concomitant septic and crystal-induced arthritis was 4% among patients with crystal-induced arthritis, especially among those with acute fever and high synovial WBC counts. The chance of concomitant septic and crystal-induced arthritis is very low in cases with synovial WBC < 12,000 cells/μL.

HighlightsWhat are the main findings?Auranofin suppresses NLRP3 inflammasome activation and attenuates the IL-33/ST2–CXCL1 axis, thereby reducing neutrophil recruitment in MSU-based models.Prophylactic dosing mitigates paw and air-pouch inflammation; enforced IL-33 overexpression abrogates these effects, indicating pathway dependency.What is the implication of the main finding?Redox/thioredoxin-reductase targeting offers a dual-action strategy complementary to selective NLRP3 and CXCR2 blockade.The results motivate on-flare dosing and combination regimens (e.g., IL-33/ST2 or CXCR2 inhibition) under clinically aligned, exposure-matched designs.Gout is a form of sterile inflammatory arthritis in which monosodium urate (MSU) crystals deposit and provoke a neutrophil-predominant response, primarily driven by activation of the NACHT, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome. Here, we show that auranofin, a Food and Drug Administration (FDA)-approved anti-rheumatic agent, exerts anti-inflammatory effects in both in vitro and in vivo models of gout. Auranofin inhibited NLRP3 inflammasome activation in human THP-1 cells and murine macrophages, leading to reduced cleavage of caspase-1, interleukin-1β (IL-1β), and interleukin-18 (IL-18). In MSU crystal-induced mouse models, auranofin treatment reduced paw swelling, serum cytokine levels, and tissue inflammation. Notably, auranofin suppressed neutrophil migration and decreased expression of C-X-C motif chemokine ligand 1 (CXCL1) in inflamed foot tissue and air-pouch exudates. Mechanistically, auranofin disrupted the interleukin-33 (IL-33)/suppression of tumorigenicity 2 (ST2) axis, a key signaling pathway promoting neutrophil recruitment. Overexpression of IL-33 abolished the anti-inflammatory effects of auranofin, highlighting the central role of IL-33 in gout pathogenesis. Together, our findings suggest that auranofin alleviates MSU-induced inflammation by concurrently inhibiting NLRP3 inflammasome activation and IL-33-mediated neutrophil recruitment, supporting its potential as a dual-action therapeutic candidate for gout.