Search Results (682)

The human gut microbiota represents a complex and dynamic ecosystem of trillions of microorganisms that play a fundamental role in maintaining physiological homeostasis, regulating metabolism, and modulating the immune system. This narrative review explores the biochemical intricacies of the gut microbiome, focusing on the dominant phyla (Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Verrucomicrobia, Fusobacteria) and their specific contributions to host health. A critical emphasis is placed on the metabolic outputs of these microorganisms, such as short-chain fatty acids (SCFAs) like butyrate, which serve as vital energy sources and anti-inflammatory signaling molecules. Conversely, the review examines how dysbiosis, the disruption of microbial balance, is mechanistically linked to the pathogenesis of diverse conditions, including obesity, diabetes mellitus, inflammatory bowel disease (IBD), and gout. Furthermore, it highlights the profound impact of dietary interventions on microbial architecture, notably, how non-digestible carbohydrates promote beneficial taxa and eubiosis, while high-fat and high-sugar diets drive metabolic endotoxemia and systemic inflammation. By synthesizing current knowledge on microbial biotransformations of proteins and polyphenols, this work underscores the bidirectional relationship between nutrition and the microbiome. Ultimately, understanding these biochemical interactions is essential for developing targeted probiotic, prebiotic, and nutritional strategies to prevent and manage chronic metabolic and inflammatory disorders. Full article

Objective: The objective of this study was to characterize real-world distributions of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) across major rheumatic diagnoses and to quantify concordance/discordance patterns and combined CRP-ESR inflammatory phenotypes. Methods: We retrospectively extracted all CRP and ESR tests performed in a tertiary university rheumatology hospital (January 2018–December 2023), including ICD-10-coded diagnoses. Analyses were conducted at the measurement level and patient level (medians across repeated tests). CRP and ESR were expressed as raw values and multiples of ULN and categorized into severity strata. CRP and ESR datasets were merged by patient identifier and calendar date to define same-day pairs; paired analyses used Spearman correlations and ULN-based phenotype classes. Sensitivity analyses tested alternative pairing windows, first-pair-only analyses, phenotype persistence rules, and tertile/quartile discordance definitions. Results: Among 16,921 patients with ≥1 CRP and 17,126 with ≥1 ESR, CRP was more disease-discriminative and only negligibly age-related, whereas ESR increased modestly with age and showed marked sex shifts across severity categories. Inflammatory burden was highest in gout and rheumatoid arthritis, intermediate in psoriatic arthritis and ankylosing spondylitis, and lower in connective tissue diseases (systemic lupus erythematosus, mixed connective tissue disease, Sjogren’s disease, systemic sclerosis, and dermato/polymyositis) and osteoarthritis; CRP distributions were more strongly right-tailed than ESR. Merging yielded 44,427 same-day CRP-ESR pairs from 16,824 patients (99.1% match). CRP and ESR were moderately correlated at measurement and patient levels, yet discordance was common: 27.3% of pairs showed isolated elevation of a single marker. Conclusions: In routine rheumatology care, CRP and ESR provide complementary information. CRP-ESR dissociation is frequent, persists at the patient level, and follows diagnosis-dependent phenotype patterns. Full article

Background/Objectives: Allopurinol, a first-line drug for gout and hyperuricemia, carries a risk of severe cutaneous adverse reactions (SCARs). Studies have established a strong association between HLA-B*58:01 and this adverse reaction. Although pre-treatment genotyping is recommended, the reliability of HLA-B*58:01 genetic testing varies across laboratories. This study aims to assess the performance of HLA-B*58:01 genetic testing of clinical laboratories in Shanghai through an External Quality Assessment (EQA) program, evaluating accuracy and standardization. Methods: The EQA program was carried out twice a year in 2023 and 2024. Each EQA sample panel consisted of five distinct samples, including HLA-B*58:01 allele-positive and -negative cell cultures. Sample panels were distributed to clinical laboratories through the cold chain system and results were analyzed and scored. Results: EQA samples used in this study were optimized for evaluating current HLA-B*58:01 genotyping assays, and the EQA samples were proved to be homogeneous and stable through each EQA period. In 2023, 17 and 16 clinical laboratories participated in the two EQA schemes; in 2024, 34 and 33 laboratories participated. A total of 14/17 (82.4%), 16/16 (100%), 33/34 (97.1%), and 33/33 (100%) laboratories achieved “optimal” scores. Conclusions: EQA results indicate that most of clinical laboratories in Shanghai exhibit constantly satisfactory performance for HLA-B*58:01 genotyping. However, a few laboratories still need further improvement. Additionally, EQA has demonstrated to be an important method for monitoring clinical laboratories’ performance. Full article

The number of confiscated CITES-listed animals has increased dramatically worldwide, creating significant health, logistical, and resource challenges for responsible authorities. Rescue centers represent a scientific and humanitarian response to this challenge, providing solutions through rehabilitation, research, and environmental education. This postmortem survey provides information on disease and mortality during a four-year period, in confiscated CITES-listed birds and reptiles housed in an authorized rescue center. A total of 29 animals (17 birds and 12 reptiles) were examined by necropsy and histopathology. Infectious disease accounted for the mortality of 58.8% of birds and 49.8% of reptiles, with overrepresentation of bacterial disease in both groups. Lesions consisted mainly of granulomas in multiple organs. Suspected viral disease occurred in 23.3% of birds, and protozoal infections were found in 17.3% of birds. Systemic disease caused by an unknown haemosporozoan was the cause of death in a Lonchura oryzivora. An unknown infectious agent was associated with renal disease in a Ctenosaura sp. Gout secondary to dehydration was overrepresented in reptiles (33.3%). This study highlights the complexity of disease processes affecting confiscated birds and reptiles in CITES rescue settings and provides invaluable information for other rescue centers that may impact the success of conservation strategies. Full article

Hyperuricemia, a common metabolic disorder characterized by elevated serum uric acid (UA) levels, can lead to severe complications such as gout and renal impairment. Conventional therapies, while effective, are frequently accompanied by significant adverse effects, underscoring the urgent need for safer therapeutic alternatives. Recent evidence identifies the intestine as a novel, pivotal regulator of UA homeostasis, presenting a promising therapeutic axis. This review delineates the intestinal mechanisms governing UA regulation and evaluates the therapeutic potential of natural active substances that target these pathways. We conducted a comprehensive review of recent preclinical studies focusing on intestinal mechanisms involved in UA metabolism, including the roles of gut microbiota, urate transport proteins, intestinal barrier function, and inflammation. Studies evaluating natural active substances—such as polyphenols, polysaccharides, peptides, and plant extracts—were systematically analyzed for their effects on gut-mediated UA regulation. Natural active substances have been shown to effectively alleviate hyperuricemia by modulating gut microbiota, enhancing UA intestinal excretion, reinforcing intestinal barrier function, and suppressing inflammatory pathways. Collectively, these findings demonstrate the multi-target efficacy of natural active substances within the intestines, offering a promising therapeutic strategy that warrants further investigation into nutrition-based intestinal interventions and novel pharmacological treatments for hyperuricemia. Full article

Gout is the most common form of inflammatory arthritis in men, driven by hyperuricemia and the deposition of monosodium urate (MSU) crystals. The innate immune response to these crystals leads to acute inflammatory episodes, called flares, characterized by intense joint pain, swelling, and temporary disability. Although gout flares are self-limiting, they impose a considerable burden on patients’ quality of life and contribute to increased healthcare utilization. A detailed understanding of the inflammatory processes triggered by MSU crystals is critical for developing targeted therapies to prevent and manage flares effectively. This review provides an overview of experimental models used to study the inflammatory phase of gout, with a focus on both in vivo and in vitro models of MSU crystal-induced inflammation. We concentrate on models that reproduce the acute inflammatory response following MSU crystal deposition, including the air pouch, intraarticular injection, and peritonitis rodent models, alongside the larval zebrafish model. In addition, we discuss in vitro approaches using primary immune cells and cell lines. We discuss the strengths, limitations, and translational relevance of these models and highlight some examples of how they have contributed to our understanding of the etiology of gout. Of note, models of hyperuricemia are not included here as these have been extensively reviewed elsewhere. Full article

‘Irregular gout’ is an obsolete term that was used in the past to describe both trivial and serious health issues seemingly related to gouty arthritis. This article looks back at what physicians such as George Cheyne, William Oliver, William Cullen and William Heberden thought about ‘irregular gout’. It examines to what degree the concept is still relevant, knowing what we now know about uric acid and the local and systemic inflammatory effects of urate crystal formation. In parallel, the article traces the trajectory from Cullen’s ‘asthenic gout’ to nineteenth century ‘uric acid poisoning’ and thence to possible hidden consequences of asymptomatic hyperuricaemia. ‘Irregular gout’ in its various guises has greatly influenced both orthodox and unorthodox treatments over the years. Although the term is no longer used, the concept is by no means dead. Full article

Background: Inflammatory bowel disease (IBD) and gout are both chronic inflammatory conditions. Emerging evidence suggests a potential link between IBD and gout through shared inflammatory and metabolic pathways; however, epidemiological findings remain limited and inconsistent, and the temporal direction of this association has not been clearly established. Methods: Through the use of the South Korean National Health Insurance database, we conducted a nationwide bidirectional matched cohort study. In Study I, 10,793 patients with IBD were matched 1:4 to controls without IBD. In Study II, 25,624 patients with gout were matched 1:4 to nongout controls. Exact matching was performed on age, sex, income level, and region of residence, followed by propensity score overlap weighting. Overlap-weighted Cox proportional hazards models were employed to measure adjusted hazard ratios (aHRs) for incident gout (Study I) and incident IBD (Study II). Results: In Study I, patients with IBD experienced a greater occurrence of gout than matched controls (28.40 vs. 24.20 per 10,000 person-years). IBD was linked to a higher likelihood of gout (aHR, 1.16; 95% CI, 1.04–1.29). When stratified by subtype, Crohn’s disease (CD) revealed a significant relationship with gout (aHR, 1.25; 95% CI, 1.05–1.48), whereas ulcerative colitis (UC) did not. Notably, the association between IBD (including CD and UC) and gout was consistently significant among participants younger than 45 years. In Study II, gout was not related to an elevated likelihood of IBD (aHR, 1.04; 95% CI, 0.91–1.21) or its subtypes. Conclusions: IBD, particularly CD, was linked to a greater likelihood of gout, especially among younger adults, whereas gout was not associated with subsequent IBD, suggesting an asymmetric association between IBD and gout. Full article

Objectives: The variable clustering of comorbidities in gout, including diabetes mellitus (DM), remains poorly understood. We analyzed the frequency and impact of DM in a nationwide Spanish hospitalized population with gout. Methods: Observational, multicenter, longitudinal study assessing 192,062 hospitalizations with gout in Spain from 2005 to 2015 (Minimal Basic Data Set, ICD-9 coding). We estimated the prevalence of DM with 95% confidence intervals (CIs), stratified by DM type and related complications. A logistic regression analysis identified characteristics of patients with both gout and DM. We also matched recurrent admissions in the first tercile (2005–2008) to assess cardiovascular, renal, infectious, and thromboembolic comorbidities in the subsequent terciles (2009–2012 and 2012–2015). Results: DM was identified in 27.72% of the hospital-based gout population, predominantly type 2 DM, with 19.76% having complications. DM was associated with older age, female gender, and conditions such as dyslipidemia, obesity, cardiovascular and kidney diseases, liver disease, obstructive pulmonary disease, urinary tract infections, and dementia. In contrast, non-DM patients showed higher rates of venous thromboembolism and other rheumatic diseases. Readmissions were significantly more common in DM patients, who experienced +10% more cardiovascular and renal issues, similar infections, and fewer venous thromboembolism cases. Conclusions: DM is prevalent in gout and associated with older patients, women, and a particular comorbidity profile. The presence of DM increases the risks of readmission and the development of cardiovascular and renal diseases. Fewer venous thromboses were noted. Thus, diagnosing and managing DM in patients with gout is likely a more pressing issue. Full article

Allopurinol, the most used urate-lowering drug for the treatment of gout, is associated with rare but life-threatening severe cutaneous adverse reactions (SCARs) such as Stevens–Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, but not Acute Generalised Exanthematous Pustulosis (AGEP). They are characterised by severe skin and systemic involvement and are associated with substantial morbidity and a high risk of mortality. This narrative review summarises evidence on the clinical presentation, epidemiology, risk factors, and preventive strategies for allopurinol-induced SCARs. Key risk factors include the presence of the HLA-B*58:01 allele, renal impairment, older age, female sex, heart disease, higher starting doses of allopurinol, and certain ethnicities, e.g., South Asian, Han Chinese, and African populations likely due to the higher prevalence of the HLA-B*58:01 allele. Risk mitigation strategies include genetic testing for HLA-B*58:01 in high-risk ethnic groups and avoiding allopurinol in those that are positive for the HLA-B*58:01 allele, starting allopurinol at a low-dose (e.g., 50–100 mg/day) and up-titrating it gradually at 4-week intervals, and avoiding high-dose allopurinol in those with risk factors (e.g., chronic kidney disease stage ≥3). In addition, risk stratification using prediction tools may enable a safer use of allopurinol. Full article

Autoinflammatory diseases are characterized by inappropriate activation of innate immunity resulting in excessive or persistent inflammation in the absence of infection. γδ T cells possess innate-like properties, including rapid responsiveness to stress-induced self-molecules, phosphoantigens, and inflammasome-derived cytokines, while retaining adaptive effector functions. Neutrophils and macrophages are well-established drivers of autoinflammatory disease, but increasing evidence implicates γδ T cells as key intermediaries by linking innate immune activation to tissue-specific inflammatory pathology. Here, we review evidence that in both monogenic and multifactorial autoinflammatory diseases—including, for example, familial Mediterranean fever, hyper-immunoglobulin (Ig) D syndrome, gout, Behçet’s disease, Still’s disease, atherosclerosis, and neurodegenerative disorders—γδ T cells display altered frequencies, activation states, cytokine polarization, and tissue recruitment. In inflammasome-driven diseases, skewing of γδ T cells toward interleukin (IL)-17 production has been observed, often accompanied by reduced interferon (IFN)γ secretion, thereby amplifying neutrophilic inflammation and tissue damage. In other diseases, e.g., Behcet’s disease, IFNγ and tumor necrosis factor (TNF)α producton predominate. Transcriptomic and tissue-based analyses support the accumulation and functional specialization of γδ T cells at sites of sterile inflammation. Collectively, these findings position γδ T cells as central amplifiers and modulators of inappropriate innate immune activation in the context of autoinflammatory diseases. Improved understanding of γδ T cell subset-specific regulation may inform novel therapeutic strategies targeting autoinflammatory diseases. Full article

Background: Inonotus obliquus (Chaga), a medicinal and edible macrofungus abundant in bioactive polyphenols, is a potential source of natural antioxidants and anti-inflammatory agents for functional foods. This study aimed to evaluate the antioxidant capacity of three key polyphenols (osmundacetone [OS], protocatechuic aldehyde [PAH], protocatechuic acid [PA]) from I. obliquus and decipher their anti-inflammatory mechanisms via the MyD88/TLR4/NF-κB pathway in a gout-related model. Methods: Antioxidant activity was assessed by xanthine oxidase (XO) inhibition (IC₅₀), superoxide anion (O₂⁻) scavenging, and structure–activity relationship (SAR) analysis; in a monosodium urate (MSU)-induced acute gout cell model, reactive oxygen species (ROS), nitric oxide (NO), lactate dehydrogenase (LDH), superoxide dismutase (SOD), pro-inflammatory cytokines (TNF-α, IL-1β) were quantified, and MyD88/TLR4/NF-κB pathway proteins were analyzed by Western blot. Results: OS showed the strongest XO inhibition (IC₅₀ = 4.91 mM), followed by PAH (IC₅₀ = 5.92 mM) and PA (IC₅₀ = 26.53 mM); OS exerted dual redox effects by scavenging O₂⁻ and suppressing XO-mediated O₂⁻ generation, with its conjugated C=C-carbonyl system and PAH’s aldehyde group enhancing XO binding. All polyphenols and I. obliquus crude extract significantly reduced ROS, NO, LDH, and cytokines (p < 0.05), increased SOD, and downregulated TLR4, MyD88, and NF-κB expression. Conclusions: I. obliquus-derived polyphenols exhibit obvious antioxidant and xanthine oxidase inhibitory effects, and regulate oxidative stress, pro-inflammatory mediators, and the MyD88/TLR4/NF-κB signaling pathway in monosodium urate-stimulated RAW 264.7 inflammatory macrophages, supporting their development as natural functional food ingredients and potential candidates for gout-related and oxidative stress-associated inflammatory cellular disorders. Full article

Hyperuricemia (HUA) is a metabolic disorder that can easily lead to gout or kidney disease, and it is believed that it can be treated effectively using probiotics. This study evaluated the safety, probiotic, and functional properties of Wickerhamomyces anomalus YFJ252, isolated from pickled vegetables, including its in vitro inhibitory activity against xanthine oxidase (XO) and in vivo uric acid-lowering activity in mice, using virulence factor screening, plate counting, and colorimetric assays. Meanwhile, the potential anti-HUA mechanism was also investigated using untargeted metabolomics and whole-genome analysis. The results show that YFJ252 is non-hemolytic and does not produce DNase, gelatinase, or biogenic amine. It has potential probiotic properties: 85.83% DPPH radical scavenging, 39.94% α-amylase inhibition, 35.32% α-glucosidase inhibition, 20.73% anti-inflammatory ability, and 84.15% XO inhibition capacity. Animal experiments indicated that early intake of YFJ252 could maintain serum uric acid levels at 165.08 μmol/L (p < 0.05), lower than the HUA group (212.19 μmol/L), and significantly decrease creatinine and urea nitrogen levels (p < 0.05). The hypothetical anti-HUA potential of YFJ252 might be due to the production of antioxidant, hypoglycemic, and XO-inhibitory metabolites during growth, as well as a purine-degrading pathway that the strain inherited. This study provides a theoretical basis for using W. anomalus YFJ252 as a food ingredient with preventive effects against HUA. Full article

Hyperuricemia affects approximately 20% of the global adult population and serves as the primary etiological factor for gout. Glucose transporter 9 (GLUT9) plays a critical role in renal urate reabsorption, representing a promising therapeutic target for hyperuricemia treatment. This study employed an integrated computational and experimental approach to identify novel flavonoid-based putative GLUT9 binders, combining molecular docking, molecular dynamics (MD) simulations, ADMET prediction, antioxidant evaluation, and density functional theory (DFT) calculations. Eight structurally diverse flavonoids were docked against the human GLUT9 cryo-EM structure, and antioxidant activities were assessed using DPPH, ABTS, and FRAP assays. All tested flavonoids exhibited favorable binding affinities ranging from −7.67 to −9.10 kcal/mol. Epigallocatechin gallate (EGCG) demonstrated the highest binding affinity (−9.10 kcal/mol) with an extensive hydrogen bonding network, while chrysin exhibited the second-highest affinity (−8.35 kcal/mol) with favorable drug-like properties. MD simulations over 100 ns confirmed the structural stability of the complexes. EGCG displayed exceptional antioxidant capacity (DPPH IC₅₀ = 3.28 μM) superior to ascorbic acid, whereas chrysin showed lower radical scavenging activity despite favorable GLUT9 binding. DFT calculations revealed that higher HOMO energies correlated with enhanced antioxidant activity. These findings suggest that EGCG and chrysin exhibit favorable GLUT9 binding profiles, warranting further functional and pharmacokinetic optimization. Full article