Gout Therapy Research Articles

Harnessing Nanotechnology for Gout Therapy: Colchicine-Loaded Nanoparticles Regulate Macrophage Polarization and Reduce Inflammation

Harnessing Nanotechnology for Gout Therapy: Colchicine-Loaded Nanoparticles Regulate Macrophage Polarization and Reduce Inflammation

Effective xanthine oxidase inhibitor urate lowering therapy in gout is linked to an emergent serum protein interactome of complement and inflammation modulators

Urate-lowering treatment (ULT) to target with xanthine oxidase inhibitors (XOIs) paradoxically causes early increase in gouty arthritis flares. Because delayed reduction in flare burden is mechanistically unclear, we tested for ULT inflammation responsiveness markers. Unbiased proteomics analyzed blood samples (baseline, 48 weeks ULT) in two, independent ULT out trial cohorts (n = 19, n = 30). STRING-db and multivariate analyses supplemented determinations of altered proteins via Wilcoxon matched pairs signed rank testing in XOI ULT responders. Mechanistic studies characterized proteomes of cultured XOI-treated murine bone marrow macrophages (BMDMs). At 48 weeks ULT, serum urate normalized in all gout patients, and flares declined in association with significantly altered proteins (p < 0.05) in clustering and proteome networks in sera and peripheral blood mononuclear cells. Sera demonstrated altered complement activation and regulatory gene ontology biologic processes. In both cohorts, a treatment-emergent serum interactome included key gouty inflammation mediators (C5, IL-1B, CXCL8, IL6). Last, febuxostat treatment decreased complement activation biologic process proteins in cultured BMDMs. Reduced gout flares are linked with a XOI treatment-emergent serum protein interactome that includes inflammation regulators, associated with altered complement activation and regulatory biologic processes. Serum and leukocyte proteomics could help identify when gouty inflammatory processes begin to subside in response to ULT.Trial Registration: ClinicalTrials.gov Identifier NCT02579096, posted October 19, 2015.

Self-assembled mixed nanomicelles based hydrogel for enhanced transdermal bioavailability of allopurinol in gout therapy: In vitro and In vivo evaluation

Allopurinol (ALP), a preferred first line medication for the treatment of gout and hyperuricemia, exhibits poor solubility, a short half-life, and undergoes the hepatic first-pass effect, thus resulting in low oral bioavailability. Additionally, ALP is associated with several adverse effects, including hypersensitivity reactions, gastrointestinal issues, and hepatotoxicity. Here, we developed methoxy poly (ethylene glycol)- poly(lactide) (mPEG-PLA)/D-tocopherol polyethylene glycol 1000 succinate (TPGS) mixed nanomicelles (MNs)-based hydrogel for transdermal delivery of ALP to enhance its bioavailability, In vivo safety, and efficacy for gout treatment. To this end, mPEG-PLA diblock copolymer was synthesized via ring-opening copolymerization and characterized using Fourier transform infrared spectroscopy (FTIR), SEM micrograph, proton nuclear magnetic resonance (1H NMR) and Differential scanning calorimetric thermograms (DSC) analysis. Self-assembled mixed nanomicelles were formulated by thin film dispersed technique. The optimized mixed nanomicelles were analyzed for their physicochemical properties and subjected to in vitro, ex vivo and in vivo investigations. The final formulation (ALP-loaded MNs) exhibited a size of 59.12 nm, an encapsulation efficiency (EE) of 87 %, a PDI of 0.053, and a zeta potential of −22.3 mV. In Vitro release kinetics of the ALP-loaded MNs exhibited a sustained and site-specific release profile (p < 0.001). As compared with the ALP based hydrogel, 32-fold higher permeation flux was noticed from ALP-MNs loaded hydrogel with argan oil (ALP-MNs-AO-HG). The in vivo skin irritation study showed that the ALP-MNs-HG was well-tolerated with minimal signs of edema or erythema. ALP-MNs-AO-HG notably enhanced ALP bioavailability with a 7.67 ± 0.01 fold higher AUC0−t, 4.8 ± 0.03 fold longer mean residence time, and a 6 ± 0.04 fold extension in half-life as compared to the oral drug suspension. These results indicate that ALP-MNs based transdermal hydrogels exhibit the potential to enhance therapeutic outcomes by increasing bioavailability and abating the adverse effects associated with oral administration.

Non-adherence to urate lowering therapy in gout after 5 years is related to poor outcomes-results from the NOR-Gout study.

Patients with gout need to adhere to medication over time to achieve good outcomes. We assessed self-reported adherence to medication with urate lowering therapy (ULT) 5 years after a treat-to-target intervention and studied how non-adherence was related to baseline demographic and disease variables. Patients in the NOR-Gout observational study were included after a recent gout flare and serum urate >360 µmol/L. Patients (mean age 56.2 (S.D. 13.6), 94.5% males, 17.2% with tophi) attended tight-control visits over one year with escalating urate lowering therapy using a treat-to-target strategy. Five-year follow-up included the Medication Adherence Report Scale (MARS-5) questionnaire (range 5-25) for adherence. Flares and SUA target achievement were compared for 5-year adherence to medication. At 5-years most of the 163 patients used ULT (95.1%). MARS-5 adherence scores after 5 years were high (median 24, interquartile range 22-25). Patients in the lowest MARS-5 quartile had, compared to the highest quartile, more often a flare during the last year of follow-up (33.3% vs. 9.5%, P=0.004), and reached the 5-yr serum urate treatment target less frequently (45.2% vs. 87.5%, P<0.001). Baseline lower age (OR 0.56, 95%CI 0.39-0.79), non-European origin (OR 0.22, 95%CI 0.06-0.80), lower SF-36 mental health scores (OR 0.94, 95%CI 0.91-0.98) and less joint pain during last flare (OR 0.73, 95%CI 0.58-0.92) were independent risk factors for non-adherence to medication. Patients reported after 5 years high adherence to medication. Non-adherence was related to more flares and less urate target achievement. Younger age and non-European origin were associated with non-adherence.

Comprehensive Screening and Evaluation of Anti-gout Activity of Plantago asiatica L. through Integrated In vivo and In vitro Methodologies

Abstract Objective: This study aimed to elucidate the active components and mechanisms of Plantago asiatica L. (PAL) in the treatment of gout. Materials and Methods: Based on its polarity, PAL was partitioned into three parts, P1, P2, and P3, through gradient elution using AB-8 macroporous resin columns. The primary constituents of these fractions include iridoids, phenylethanoid glucosides, and flavonoids. Subsequently, a comprehensive in vitro and in vivo screening and evaluation model was developed considering the fundamental pathological processes of gout, including the inhibition of uric acid (UA) production, augmentation of UA excretion, and anti-inflammatory effects. This model was used to analyze the anti-gout activity of P1, P2, P3, and the overall extracts derived from PAL. Results: All the PAL parts exhibited specific therapeutic properties as part of gout therapy. Specifically, the P2 part demonstrated the ability to diminish interleukin-1 beta levels, lower UA concentrations, suppress joint inflammation in rats, and restore abnormal parameters associated with gout, such as creatinine and urea nitrogen. These findings highlight the significant effect of P2 on gout treatment. Conclusions: Following a thorough assessment of the outcomes derived from diverse anti-gout experiments, P2 exhibited superior anti-gout properties compared to the remaining parts. P2 demonstrated a restorative effect on the aberrant parameters associated with gout, thereby comprehensively elucidating the therapeutic mechanism of P2 against gout. This study provides substantial evidence and serves as a reference for future investigations regarding the material foundation of PAL in gout treatment.

Current Challenges and Emerging Therapies in the Treatment of Gout.

Gout is a common form of inflammatory arthritis characterized by the deposition of MSU in the joints and surrounding tissues, which results in inflammation and recurrent painful attacks. Currently, xanthine oxidase inhibitors, i.e., Allopurinol and Febuxostat, are used in the therapy. Recently, nanoparticles (NPs) containing metal oxides and non-metal oxides have also been developed to better manage gout. This comprehensive review summarizes the pathophysiology of gout, currently used drugs in the treatment, followed by emerging therapies for gout.

Comparison of Gout Flares With the Initiation of Treat-to-Target Allopurinol and Febuxostat: A Post-Hoc Analysis of a Randomized Multicenter Trial.

Initiating urate-lowering therapy (ULT) in gout can precipitate arthritis flares. There have been limited comparisons of flare risk during the initiation and escalation of allopurinol and febuxostat, administered as a treat-to-target strategy with optimal anti-inflammatory prophylaxis. This was a post-hoc analysis of a 72-week randomized, double-blind, placebo-controlled, noninferiority trial comparing the efficacy of allopurinol and febuxostat. For this analysis, the occurrence of flares was examined during weeks 0 to 24 when ULT was initiated and titrated to a serum urate (sUA) goal of less than 6 mg/dl (<5 mg/dl if tophi). Flares were assessed at regular intervals through structured participant interviews. Predictors of flare, including treatment assignment, were examined using multivariable Cox proportional hazards regression. Study participants (n = 940) were predominantly male (98.4%) and had a mean age of 62.1 years with approximately equal proportions receiving allopurinol or febuxostat. Mean baseline sUA was 8.5 mg/dl and all participants received anti-inflammatory prophylaxis (90% colchicine). In a multivariable model, there were no significant associations of ULT treatment (hazard ratio [HR] 1.17; febuxostat vs allopurinol), ULT-dose escalation (HR 1.18 vs no escalation), prophylaxis type, or individual comorbidity with flare and no evidence of ULT-dose escalation interaction. Factors independently associated with flare risk during ULT initiation/escalation included younger age, higher baseline sUA, and absence of tophi. These results demonstrate that gout flare risk during the initiation and titration of allopurinol is similar to febuxostat when these agents are administered according to a treat-to-target strategy using gradual ULT-dose titration and best practice gout flare prophylaxis.

High vegetable consumption and regular exercise are associated with better quality of life in patients with gout.

The Gout Impact Scale (GIS), a part of the Gout Assessment Questionnaire 2.0, is used to measure gout-specific health-related quality of life (HRQOL). Although several studies have been conducted on the factors affecting the HRQOL of patients with gout, few have focused on lifestyle factors. This study aimed to investigate the correlation between lifestyle habits and HRQOL using the GIS in patients with gout. We used data from the Urate-Lowering TheRApy in Gout (ULTRA) registry, a prospective cohort of Korean patients with gout treated at multiple centers nationwide. The patients were aged ≥18 years and met the 2015 American College of Rheumatology/European League Against Rheumatism gout classification criteria. They were asked to complete a GIS and questions regarding their lifestyle habits at enrollment. The study included 232 patients. 'Gout concern overall' scores in the GIS were significantly lower in patients who exercised more frequently and consumed soft drinks and meat less, and 'well-being during attack' scores were significantly lower in patients who consumed vegetables and exercised more frequently. The frequency of vegetable consumption had a negative linear relationship with the 'well-being during attack' and 'gout concern during attack' scores (p = 0.01, p = 0.001, respectively). The frequency of exercise had a negative linear relationship with the 'gout concern overall' and 'gout concern during attack' scores (p = 0.04 and p = 0.002, respectively). Patients with gout who frequently consumed vegetables and exercised regularly experienced less impact of gout, exhibiting a better GIS that represented HRQOL.

Battle of the strategies: diet versus drug therapy for gout

The best results in combating gout are achieved through a combination of diet and drug therapy. Urate-lowering therapy, which includes febuxostat, has been shown to be more effective and convenient than diet when it comes to achieving and maintaining target uric acid (UA) levels in gout patients. Febuxostat, a xanthine oxidase inhibitor, helps to reduce UA levels in the blood by blocking its formation. This helps prevent the deposition of urate crystals in joints and tissues and reduces the frequency and severity of gout attacks. At the same time, a diet of low purine foods may also have some effect on UA levels. Diet can improve the results of drug treatment by reducing the need for medications and minimizing the risk of side effects. However, without adequate drug therapy, diet will not produce the desired results. Therefore, febuxostat remains the preferred urate-lowering treatment option for gout, especially given its proven efficacy in these patients.

Mild hyperthermia enhanced synergistic uric acid degradation and multiple ROS elimination for an effective acute gout therapy.

Acute gouty is caused by the excessive accumulation of Monosodium Urate (MSU) crystals within various parts of the body, which leads to a deterioration of the local microenvironment. This degradation is marked by elevated levels of uric acid (UA), increased reactive oxygen species (ROS) production, hypoxic conditions, an upsurge in pro-inflammatory mediators, and mitochondrial dysfunction. In this study, we developed a multifunctional nanoparticle of polydopamine-platinum (PDA@Pt) to combat acute gout by leveraging mild hyperthermia to synergistically enhance UA degradation and anti-inflammatory effect. Herein, PDA acts as a foundational template that facilitates the growth of a Pt shell on the surface of its nanospheres, leading to the formation of the PDA@Pt nanomedicine. Within this therapeutic agent, the Pt nanoparticle catalyzes the decomposition of UA and actively breaks down endogenous hydrogen peroxide (H2O2) to produce O2, which helps to alleviate hypoxic conditions. Concurrently, the PDA component possesses exceptional capacity for ROS scavenging. Most significantly, Both PDA and Pt shell exhibit absorption in the Near-Infrared-II (NIR-II) region, which not only endow PDA@Pt with superior photothermal conversion efficiency for effective photothermal therapy (PTT) but also substantially enhances the nanomedicine's capacity for UA degradation, O2 production and ROS scavenging enzymatic activities. This photothermally-enhanced approach effectively facilitates the repair of mitochondrial damage and downregulates the NF-κB signaling pathway to inhibit the expression of pro-inflammatory cytokines. The multifunctional nanomedicine PDA@Pt exhibits exceptional efficacy in UA reduction and anti-inflammatory effects, presenting a promising potential therapeutic strategy for the management of acute gout.

PHARMACOLOGICAL EFFECTS OF MELATONIN AND ITS POTENTIAL APPLICATION IN THERAPY OF GOUT AND ASSOCIATED DISEASES

Introduction. The disturbance in biosynthetic activity of pinealocytes of the pineal gland and subsequent melatonin deficiency in the body are linked to the progression of certain chronic diseases. This has prompted research into correcting chrono-biological dysfunctions, particularly in conditions such as gout and its comorbidities. This study aims to analyze the potential use of melatonin in correcting metabolic disorders in gout and to justify its use as a pharmacotherapeutic agent for treating metabolic and cardiovascular diseases. Materials and methods. We conducted a comprehensive analysis of modern scientific literature from specialized domestic and foreign sources. Emphasis was placed on studies exploring the pharmacological and pharmacotherapeutic aspects of melatonin use in both experimental and clinical settings, particularly those conducted in the last 5-6 years. Results. The research data revealed three main aspects of the problem that must be addressed to understand the experimental, biological, pharmacological, and pharmacotherapeutic foundations for the long-term use of melatonin in clinical practice. The first part of the review highlighted the significant impact of melatonin homeostasis disruption on the pathogenesis of gout and its progression in comorbidity with other conditions such as hypertension, obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. The role of chronobiological disorders and desynchronosis in the progression of these diseases was also established. Pharmacological studies demonstrated the pivotal role of melatonin, as an important factor in neuroendocrine regulation, in organizing the circadian rhythm of the body's vital functions under normal and pathological conditions. Melatonin was found to normalize the pathological processes underlying gout development and comorbid diseases, providing a scientific basis for its use in the treatment of gout, cardiovascular diseases, disturbed metabolic processes, and normalization of circadian rhythms in patients with these conditions. Conclusions. This paper presents data on the causes of gout development and progression, as well as some comorbid diseases, from the perspective of chronobiological disruptions in the body's functions. The review sections delve into the pharmacological and pharmacotherapeutic aspects of melatonin's therapeutic action. The findings confirm the importance of melatonin in effectively treating gout and other comorbid diseases and metabolic disorders.

Urate-lowering therapy for gout: Difficulties in goal achieving the and ways to overcome

Urate-lowering therapy for gout: Difficulties in goal achieving the and ways to overcome

P082 Nephrolithiasis associated with uricosuric therapies for the treatment of gout: a systematic review

Abstract Background/Aims Uric acid nephrolithiasis is a recognised side-effect of uricosuric therapies and a contraindication to their use. The objective of this systematic review was to assess the incidence and risk of nephrolithiasis in people with gout receiving uricosuric therapy. Methods A systematic review was undertaken using MEDLINE, Embase, Cochrane Library, Web of Science and Clinical Trials electronic databases from inception to 16th May 2023. Pre-specified search terms relating to ‘gout’, ‘uricosuric drugs’ and ‘nephrolithiasis’ and their synonyms were used. Title/abstract and full-text screening and data extraction were undertaken independently by two reviewers. Randomised controlled trials (RCTs) and observational cohort studies assessing the incidence and risk of nephrolithiasis in adults with gout treated with uricosuric therapies were included (with or without a non-uricosuric urate-lowering therapy (ULT) comparator group). The Cochrane Risk of Bias (RoB)-2 for randomised trials and the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tools were used to assess the quality of included RCTs and cohort studies respectively. Results 507 articles were identified, of which 22 studies (8 RCTs, 14 cohort studies) were eligible for inclusion. The mean age of participants ranged from 51.2 years (standard deviation (SD) 10.9) to 66.8 years (SD 9.1). Participants were predominantly male (range 69-100%). Length of follow-up ranged from three months to 10 years. Eleven studies included participants with a prior history of nephrolithiasis. Ten studies assessed Benzbromarone monotherapy, five Lesinurad plus xanthine oxidase inhibitor (XOI), four Probenecid, three Sulfinpyrazone and one Lesinurad monotherapy (total 3091 participants). Ten studies included a non-uricosuric comparator group(s) (five placebo plus XOI, four XOI only, and one placebo only (total 1386 participants)), whereas 12 had no comparator group. Most studies assessed nephrolithiasis through clinical adverse event reporting rather than systematic assessment. The incidence of nephrolithiasis ranged from 0.0% to 11.8% in people receiving uricosuric therapy (four studies reported no stone events; incidence 0.1%-5% in seven studies, 5.1-10% in 9, and &amp;gt;10% in two). The incidence of nephrolithiasis ranged from 0.0% to 4.2% in those not receiving uricosurics. No studies calculated the risk of nephrolithiasis between uricosuric-treated and untreated groups. Few studies documented renal stone composition or reported the severity of clinical presentation of nephrolithiasis events. Conclusion Nephrolithiasis is a common side-effect of uricosuric therapy for gout. Future studies should provide risk estimates between uricosuric-treated and untreated groups, describe clinical presentation of stone events and, where possible, assess stone composition. Disclosure C. Dahanayake: None. R. Bajpai: Other; Dr Bajpai is a member of the Versus Arthritis College of Experts. K.M. Jordan: Other; Dr Jordan is a Trustee of the UK Gout Society. M. Lambie: Honoraria; Dr Lambie has received speakers honoraria from Baxter Healthcare and Fresenius Medical Care. Grants/research support; Dr Lambie has received an unrestricted research grant from Baxter Healthcare. E. Roddy: None.

Prognostic factors for colchicine prophylaxis-related adverse events when initiating allopurinol for gout: retrospective cohort study.

Colchicine is commonly used to prevent flares when starting urate-lowering therapy for gout. Patients with gout are frequently concurrently prescribed other medications (such as statins) that may interact with colchicine, increasing the risk of adverse events. The aim of this study was to describe potential prognostic factors for adverse events in patients prescribed colchicine when initiating allopurinol. We conducted a retrospective cohort study in linked UK Clinical Practice Research Datalink and Hospital Episode Statistics datasets. Adults initiating allopurinol for gout with colchicine (01/04/1997-30/11/2016) were included. Potential prognostic factors were defined, and the likelihood of adverse events, including diarrhoea, nausea or vomiting, myocardial infarction (MI), neuropathy, myalgia, myopathy, rhabdomyolysis, and bone marrow suppression, were estimated. From 01/04/1997-30/11/2016, 13 945 people with gout initiated allopurinol with colchicine prophylaxis (mean age 63.9 (SD 14.7) years, 78.2% male). One quarter (26%, 95% CI 25% to 27%) were prescribed ≥1 potentially interacting medicines, most commonly statins (21%, 95% CI 20% to 22%). Statins were not associated with increased adverse events, although other drugs were associated with some adverse outcomes. Diarrhoea and MI were associated with more comorbidities and more severe CKD. People were given colchicine prophylaxis despite commonly having preexisting prescriptions for medications with potential to interact with colchicine. Adverse events were more common in people who had more comorbidities and certain potentially interacting medications. Our findings will provide much-needed information about prognostic factors for colchicine-related adverse events that can inform treatment decisions about prophylaxis when initiating allopurinol.

Spatiotemporal Observation of Monosodium Urate Crystals Deposition in Synovial Organoids Using Label-Free Stimulated Raman Scattering.

Gout, a common form of arthritis, is characterized by the deposition of monosodium urate (MSU) crystals in joints. MSU deposition in synovial tissues would initiate arthritis flares and recurrence, causing irreversible joint damage. However, the dynamic deposition of MSU crystals in tissues lacks experimental observation. In this study, we used chemical-specific, label-free stimulated Raman scattering (SRS) microscopy to investigate the spatiotemporal deposition and morphological characteristics of MSU crystals in human synovial organoids. Our findings revealed a critical 12-h window for MSU deposition in the lining layer of gouty synovium. Moreover, distinctive inflammatory reactions of the lining and sublining synovial layers in gout using SRS microscopy were further verified by immunofluorescence. Importantly, we identified a crucial proinflammatory role of sublining fibroblast-like synoviocytes, indicating a need for targeted medication treatment on these cells. Our work contributes to the fundamental understanding of MSU-based diseases and offers valuable insights for the future development of targeted gout therapies.

Patient-Led Urate Self-Monitoring to Improve Clinical Outcomes in People With Gout: A Feasibility Study.

Self-monitored point-of-care urate-measuring devices are an underexplored strategy to improve adherence to urate-lowering therapy and clinical outcomes in gout. This study observed patient-led urate self-monitoring practice and assessed its influence on allopurinol adherence, urate control, and health-related quality of life. People with gout (n = 31) and prescribed allopurinol self-monitored their urate concentrations (HumaSens2.0plus) at baseline and thereafter monthly for 12 months (3 months per quarter). Adherence to allopurinol was measured using medication event monitoring technology (Medication Event Monitoring System cap). Time spent below the target urate concentration (<0.36 mmol/L) was determined. Health-related quality of life was measured using a survey (EuroQoL EQ-5D-5L). Gout flares were recorded. Two-tailed Spearman correlation and the Wilcoxon matched-pairs signed-rank test (P < 0.05) were used for statistical comparisons. Most participants were male (94%) and had urate concentrations below the target (74%) at baseline. Overall, seven participants demonstrated repeated periods of "missed doses" (two or fewer allopurinol doses missed consecutively) and "drug holidays" (three or more missed doses). Most participants (94%) persisted with allopurinol. Time spent within the target urate concentration increased 1.3-fold (from 79% to 100%; P = 0.346), and the incidence of gout flares decreased 1.6-fold (from 8 to 5; P = 0.25) in the final quarter compared to that in the first quarter of the study. Health-related quality of life was reduced for participants reporting at least one gout flare (median utility values 0.9309 vs 0.9563, P = 0.04). Patient-led urate self-monitoring may support the maintenance of allopurinol adherence and improve urate control, thus reducing the incidence of gout flares. Further research on patient-led urate self-monitoring in a randomized controlled study is warranted.

The effectiveness and safety of lifestyle medicine and integrative therapies in inflammatory arthritis: an umbrella review using a hierarchical evidence gathering approach.

An umbrella review was conducted to provide a comprehensive evaluation of the evidence on lifestyle medicine and integrative therapies for inflammatory arthritis. Five electronic databases were searched for umbrella reviews, meta-analyses, and systematic reviews of randomised controlled trials on acupuncture, diet, exercise, herbal medicine, nutrient supplements, and mind-body therapies for rheumatoid arthritis, spondyloarthritis, and gout published from January 2012 to December 2022. The primary outcomes were functional status and quality of life. Quality assessment was performed using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) tool, and the certainty of evidence for our primary outcomes was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach where possible. We included 52 reviews. Exercise was beneficial for functional status in both rheumatoid arthritis and spondyloarthritis, with moderate certainty of evidence. Chinese herbal medicine in combination with disease-modifying anti-rheumatic drugs may improve functional status in rheumatoid arthritis (very low certainty evidence). Acupuncture may improve functional status in rheumatoid arthritis and pain in both rheumatoid arthritis and gout; however, the evidence is of very low certainty. Evidence for other therapies was not clinically significant; however, it suggests possible benefits from quercetin and polyunsaturated fatty acids. Yoga may result in a moderate improvement in functional status when used as an adjunct to medication; however, the certainty of evidence is very low. Diet interventions offered inconsistent improvements to functional status in rheumatoid arthritis, spondyloarthritis, and gout with low to very low certainty. Exercise should be prescribed for people with rheumatoid arthritis and spondyloarthritis. More research is needed to confirm or refute evidence for Chinese herbal medicine, acupuncture, yoga, and anti-inflammatory diets.

Diet for gout and hyperuricaemia: some important questions

Diet has traditionally been viewed as playing a leading role in both the pathogenesis and treatment of gout. And although this thesis is controversial today, adherence to certain dietary rules for patients with gout and hyperuricemia (HU) is an integral part of therapy. The review examines the modern theoretical basis of dietary therapy for gout and HU, in particular the mechanisms of increasing serum uric acid levels and the risk of developing arthritis when certain foods are consumed and, conversely, reducing uric acid levels and the risk of gout when a diet containing a range of vitamins and foods in the supplements is followed.

Solving the mysteries of urate transport: structural insights into GLUT9 and URAT1

Recent groundbreaking advances in the structural biology of the glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) have provided critical insights into the molecular mechanisms underlying urate recognition and transport. Using cryo-electron microscopy (cryo-EM), researchers have elucidated the structures of these transporters at high resolution, thus revealing their substrate preferences and interactions with inhibitors. Several studies have highlighted the potential of specific inhibitors, such as apigenin for GLUT9, and have demonstrated the role of chloride-mediated inhibition in URAT1 function. These findings provide an excellent starting point for developing targeted therapies for hyperuricemia and gout, to enable the design of more effective and selective drugs in the future.

Intestine-Targeted Explosive Hydrogel Microsphere Promotes Uric Acid Excretion for Gout Therapy.

Uric acid metabolism disorder triggers metabolic diseases, especially gout. However, increasing uric acid excretion remains a challenge. Here, an accelerative uric acid excretion pathway via an oral intestine-explosive hydrogel microsphere merely containing uricase and dopamine is reported. After oral administration, uricase is exposed and immobilized on intestinal mucosa along with an in situ dopamine polymerization via a cascade reaction triggered by the intestinal specific environment. By this means, trace amount of uricase is required to in situ up-regulate uric acid transporter proteins of intestinal epithelial cells, causing accelerated intestinal uric acid excretion. From in vitro data, the uric acid in fecal samples from gout patients could be significantly reduced by up to 37% by the mimic mucosa-immobilized uricase on the isolated porcine tissues. Both hyperuricemia and acute gouty arthritis in vivo mouse models confirm the uric acid excretion efficacy of intestine-explosive hydrogel microspheres. Fecal uric acid excretion is increased around 30% and blood uric acid is reduced more than 70%. In addition, 16S ribosomal RNA sequencing showed that the microspheres optimized intestinal flora composition as well. In conclusion, a unique pathway via the intestine in situ regulation to realize an efficient uric acid intestinal excretion for gout therapy is developed.