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

Background/Aims: 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. Methods: 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. Results: 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). Conclusions: Patients with gout who frequently consumed vegetables and exercised regularly experienced less impact of gout, exhibiting a better GIS that represented HRQOL.

Anti-rheumatic property and physiological safety of KMU-11342 in in vitro and in vivo models.

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder characterized by joint destruction due to synovial hypertrophy and the infiltration of inflammatory cells. Despite substantial progress in RA treatment, challenges persist, including suboptimal treatment responses and adverse effects associated with current therapies. This study investigates the anti-rheumatic capabilities of the newly identified multi-protein kinase inhibitor, KMU-11342, aiming to develop innovative agents targeting RA. In this study, we synthesized the novel multi-protein kinase inhibitor KMU-11342, based on indolin-2-one. We assessed its cardiac electrophysiological safety using the Langendorff system in rat hearts and evaluated its toxicity in zebrafish in vivo. Additionally, we examined the anti-rheumatic effects of KMU-11342 on human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS), THP-1 cells, and osteoclastogenesis in RAW264.7 cells. KMU-11342 demonstrated the ability to inhibit LPS-induced chemokine inhibition and the upregulation of pro-inflammatory cytokines, cyclooxygenase-2, inducible nitric oxide synthase, p-IKKα/ß, p-NF-κB p65, and the nuclear translocation of NF-κB p65 in RA-FLS. It effectively suppressed the upregulation of NLR family pyrin domain containing 3 (NLRP3) and caspase-1 cleavage. Furthermore, KMU-11342 hindered the activation of osteoclast differentiation factors such as RANKL-induced TRAP, cathepsin K, NFATc-1, and c-Fos in RAW264.7 cells. KMU-11342 mitigates LPS-mediated inflammatory responses in THP-1 cells by inhibiting the activation of NLRP3 inflammasome. Notably, KMU-11342 exhibited minimal cytotoxicity in vivo and electrophysiological cardiotoxicity ex vivo. Consequently, KMU-11342 holds promise for development as a therapeutic agent in RA treatment.

Real-world effectiveness of a single conventional disease-modifying anti-rheumatic drug (cDMARD) plus an anti-TNF agent versus multiple cDMARDs in rheumatoid arthritis: a prospective observational study.

Objective: The objective of this prospective, observational multicenter study (NCT03264703) was to compare the effectiveness of single conventional disease-modifying anti-rheumatic drug (cDMARD) plus anti-tumor necrosis factor (TNF) therapy versus multiple cDMARD treatments in patients with moderate-to-severe rheumatoid arthritis (RA) following cDMARD failure in the real-world setting in South Korea. Methods: At the treating physicians' discretion, patients received single cDMARD plus anti-TNF therapy or multiple cDMARDs. Changes from baseline in disease activity score 28-joint count with erythrocyte sedimentation rate (DAS28-ESR), corticosteroid use, and Korean Health Assessment Questionnaire (KHAQ-20) scores were evaluated at 3, 6, and 12 months. Results: Of 207 enrollees, the final analysis included 45 of 73 cDMARD plus anti-TNF and 91 of 134 multiple-cDMARD recipients. There were no significant between-group differences (BGDs) in ANCOVA-adjusted changes from baseline in DAS28-ESR at 3, 6 (primary endpoint), and 12 months (BGDs -0.18, -0.38, and -0.03, respectively). More cDMARD plus anti-TNF than multiple-cDMARD recipients achieved a >50% reduction from baseline in corticosteroid dosage at 12 months (35.7% vs 14.6%; p=0.007). Changes from baseline in KHAQ-20 scores at 3, 6, and 12 months were significantly better with cDMARD plus anti-TNF therapy than with multiple cDMARDs (BGD -0.18, -0.19, and -0.19 points, respectively; all p≤0.024). Conclusion: In the real-world setting, relative to multiple cDMARDs, single cDMARD plus anti-TNF therapy significantly improved quality-of-life scores and reduced corticosteroid use, with no significant BGD in disease activity, in RA patients in whom previous cDMARD therapy had failed.

Effect of recombinant human bone morphogenetic protein-2 and osteoprotegerin-Fc in MC3T3-E1 cells.

Objective: We compared the osteoblastogenesis by serially administrating recombinant human bone morphogenetic protein-2 (rhBMP-2) and osteoprotegerin-immunoglobulin Fc segment complex (OPG-Fc). Methods: The MC3T3-E1 preosteoblast cell line was differentiated for 1, 3, and 7 days with a treatment of OPG-Fc in 10~200 ng/mL concentration and the cell viability was evaluated by Cell Counting Kit-8 analysis. The level of differentiation from MC3T3-E1 cells to osteoblasts was determined by alkaline phosphatase activity. The level of runt domain-containing transcription factor 2 (Runx2) and osteopontin (OPN) manifestation, involved in osteoblast differentiation, was examined by real-time polymerase chain reaction and western blotting. Results: During MC3T3-E1 cell differentiation, the differentiation level was high with 1-day treatment using 100 ng/mL OPG-Fc. The treatment with 50 ng/mL rhBMP-2 for 7 days, followed by 1-day treatment with 100 ng/mL OPG-Fc produced the highest differentiation level, which was approximately 5.3 times that of the control group (p<0.05). The expression of Runx2 mRNA significantly increased, reaching 2.5 times the level of the control group under the condition of 7-day treatment with rhBMP-2 and 1-day treatment with OPG-Fc (p<0.001). The expression of Runx2 protein significantly increased to approximately 5.7 times that of the control group under the condition of 7-day treatment with rhBMP-2, followed by 1-day treatment with OPG-Fc (p<0.01). The expression of OPN protein showed no change from that of the control group under various conditions of rhBMP-2 and OPG-Fc combinations. Conclusion: These results imply that the treating preosteoblasts with rhBMP-2 first and then with OPG-Fc increased osteoblast differentiation efficacy.

The complement factor H-related protein-5 (CFHR5) exacerbates pathological bone formation in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease, characterized by excessive new bone formation. We previously reported that the complement factor H-related protein-5 (CFHR5), a member of the human factor H protein family, is significantly elevated in patients with AS compared to other rheumatic diseases. However, the pathophysiological mechanism underlying new bone formation by CFHR5 is not fully understood. In this study, we revealed that CFHR5 and proinflammatory cytokines (TNF, IL-6, IL-17A, and IL-23) were elevated in the AS group compared to the HC group. Correlation analysis revealed that CFHR5 levels were not significantly associated with proinflammatory cytokines, while CFHR5 levels in AS were only positively correlated with the high CRP group. Notably, treatment with soluble CFHR5 has no effect on clinical arthritis scores and thickness at hind paw in curdlan-injected SKG, but significantly increased the ectopic bone formation at the calcaneus and tibia bones of the ankle as revealed by micro-CT image and quantification. Basal CFHR5 expression was upregulated in AS-osteoprogenitors compared to control cells. Also, treatment with CFHR5 remarkedly induced bone mineralization status of AS-osteoprogenitors during osteogenic differentiation accompanied by MMP13 expression. We provide the first evidence demonstrating that CFHR5 can exacerbate the pathological bone formation of AS. Therapeutic modulation of CFHR5 could be promising for future treatment of AS. KEY MESSAGES: Serum level of CFHR5 is elevated and positively correlated with high CRP group of AS patients. Recombinant CFHR5 protein contributes to pathological bone formation in in vivo model of AS. CFHR5 is highly expressed in AS-osteoprogenitors compared to disease control. Recombinant CFHR5 protein increased bone mineralization accompanied by MMP13 in vitro model of AS.

GCSB-5 regulates inflammatory arthritis and pain by modulating the mitogen-activated protein kinase signaling pathway in a murine model of rheumatoid arthritis.

Objectives: This study aimed to determine whether GCSB-5 has anti-inflammatory and antinociceptive effects in mice with collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis (RA), and investigate the influence of GCSB-5 on the mitogen-activated protein kinase (MAPK) pathway. Materials and methods: The experimental animal study was designed to include five groups: CIA mice treated with GCSB-5 (300 mg/kg), GCSB-5 (600 mg/kg), celecoxib (60 mg/kg), or saline for four weeks, and nontreated control mice. The clinical severity of arthritis was scored. Nociceptive thresholds were measured by using a von Frey dynamic plantar analgesimeter. The MAPK pathway was evaluated in mouse synovium. The expression of channels associated with pain signaling was assessed by western blot and immunohistochemical staining. Results: GCSB-5 treatment diminished the severity of clinical arthritis and increased the nociceptive threshold in mice with CIA. Celecoxib, a positive control drug, also showed comparable changes. Clinical arthritis scores were inversely related to mechanical thresholds. GCSB-5 administration decreased the levels of anti-type II collagen antibody and inflammatory cytokines in the sera of mice with CIA. Furthermore, ERK, p38 MAPK, and JNK phosphorylation were downregulated and TRPV1 and ASIC3 expression were decreased in the synovium of GCSB-5-treated mice compared to salinetreated mice. Interleukin-6-induced TRPV1 and ASIC3 upregulation were also inhibited by GCSB-5 in human RA fibroblast-like synoviocytes in vitro. Conclusion: GCSB-5 decreased inflammatory arthritis and pain in a murine model of RA. The results present evidence that GCSB-5 may be beneficial for relieving pain as well as decreasing inflammation in autoimmune arthritis, such as RA.

Factors for achieving target serum uric acid levels after initiating urate-lowering therapy in patients with gout: results from the ULTRA registry.

Achieving target serum uric acid (SUA) levels is important in gout management. Guidelines recommend lowering SUA levels to < 6 mg/dL; however, many patients fail to reach this target, even with uric acid-lowering therapy (ULT). This study investigated clinical characteristics of target SUA achievers among Korean patients with gout. This study used data from the ULTRA registry, a nationwide inception cohort established in September 2021 that enrolls patients with gout who initiate ULT. Demographic, clinical, and laboratory data were collected at baseline; the 6-month follow-up. Patients were divided into two groups: target achievers (SUA level < 6 mg/dL at 6 months) and non-achievers. The mean participant (N = 117) age was 56.1 years, and 88.0% were male. At 6 months, 83 patients (70.9%) reached target SUA levels. Target achievers had better drug adherence (≥ 80%) to ULT (97.6% vs. 76.5%; p < 0.01) than non-achievers. Target non-achievers had a higher percentage of a family history of gout (32.4% vs. 10.8%; p < 0.01) and less antihypertensive agent use (38.2% vs. 59.0%; p = 0.03) than target achievers. Multivariate regression analysis revealed that good adherence to ULT, the absence of a family history of gout, and antihypertensive agent use were key factors associated with achieving target SUA levels at 6 months.

Urate-lowering efficacy and renal safety of febuxostat in patients with hyperuricemia and stage 4-5 chronic kidney disease not yet on dialysis: A meta-analysis of observational studies.

OBJECTIVE: The efficacy and safety of febuxostat in patients with stage 4-5 chronic kidney disease (CKD) remains unclear. We evaluated the urate-lowering efficacy and renal safety of febuxostat in patients with stage 4-5 CKD not yet on dialysis, through a meta-analysis of observational studies. METHODS: We performed a systematic search in PubMed, Ovid MEDLINE, Embase, and the Cochrane Library databases for observational studies of patients with advanced CKD starting febuxostat. Articles describing changes in serum urate levels and/or renal function assessed by the estimated glomerular filtration rate (eGFR) were included. RESULTS: Among 148 retrieved studies, five relevant observational studies with 327 patients were included in the meta-analysis. Febuxostat was administered daily at 10-120 mg for 3-12 months. Serum urate reduced in response to febuxostat (weighted mean difference, -1.85 mg/dL; 95% CI, -2.04--1.67 mg/dL; I2; 0%). Three studies involving 145 patients included eGFR assessments. Renal function, assessed through the eGFR, did not change after febuxostat use (weighted mean difference, 0.11 mL/min/1.73m2; 95% CI, -0.25-0.47 mL/min/1.73m2; I2; 45%). CONCLUSION: Overall, febuxostat has acceptable urate-lowering efficacy and renal safety in patients with hyperuricemia and stage 4-5 CKD who are not yet on dialysis.

Melanoma Detection by AFM Indentation of Histological Specimens.

Melanoma is visible unlike other types of cancer, but it is still challenging to diagnose correctly because of the difficulty in distinguishing between benign nevus and melanoma. We conducted a robust investigation of melanoma, identifying considerable differences in local elastic properties between nevus and melanoma tissues by using atomic force microscopy (AFM) indentation of histological specimens. Specifically, the histograms of the elastic modulus of melanoma displayed multimodal Gaussian distributions, exhibiting heterogeneous mechanical properties, in contrast with the unimodal distributions of elastic modulus in the benign nevus. We identified this notable signature was consistent regardless of blotch incidence by sex, age, anatomical site (e.g., thigh, calf, arm, eyelid, and cheek), or cancer stage (I, IV, and V). In addition, we found that the non-linearity of the force-distance curves for melanoma is increased compared to benign nevus. We believe that AFM indentation of histological specimens may technically complement conventional histopathological analysis for earlier and more precise melanoma detection.

Grape seed proanthocyanidin extract induces apoptotic and autophagic cell death in rheumatoid arthritis fibroblast-like synoviocytes.

Objectives: In this study, we aimed to evaluate the association between grape seed proanthocyanidin extract (GSPE) and rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLSs) and to investigate whether GSPE induces cell death in RA-FLSs. Materials and methods: The FLSs were isolated from RA synovial tissues. Cell viability and cell cycle staging were analyzed using a hemocytometer and flow cytometry. Caspase 3 and poly (ADP-ribose) polymerase (PARP) proteins were analyzed using Western blotting with z-VAD-fmk. Protein LC3 and polyubiquitin-binding protein p62 that were degraded by autophagy were evaluated using Western blotting with 3-methyladenine and chloroquine. Reactive oxygen species (ROS) were also evaluated. Results: When RA-FLSs were treated with GSPE, cell viability decreased, the number of cells in sub-G1 and G2/M phases increased, and the expression of pro-PARP and pro-caspase 3 proteins decreased in a concentration-dependent manner. This result was offset, when the cells were co-treated with the pan-caspase inhibitor z-VAD-fmk. The reduced cell viability, increased expression of LC3-II protein, and reduced expression of p62 protein with GSPE treatment were offset, when RA-FLSs were co-treated with GSPE and autophagy inhibitors 3-methyladenine and chloroquine. The level of ROS in RA-FLSs treated with GSPE was significantly lower than treatment with N-acetyl-cysteine, a ROS inhibitor. Conclusion: Our study results show that GSPE induces apoptotic and autophagic cell death and inhibites reactive oxygen species in RA-FLSs.

Serial administration of rhBMP-2 and alendronate enhances the differentiation of osteoblasts.

AIM: The incorporation of growth factors is an effective strategy to accelerate bone induction. Bone morphogenetic protein-2 (BMP-2) promotes osteoblast differentiation and induces bone formation. Alendronate (ALN) is an osteoclast deactivation drug. We investigated the effect of serial administration of recombinant human BMP-2 (rhBMP-2) and ALN on osteoblast differentiation. METHODS: The effect of serial administration of rhBMP-2 (0-150 ng/mL) and ALN (0-15 µmol/L) on the viability and differentiation of a clonal murine calvarial cell line, MC3T3-E1, was evaluated at various concentrations and for different periods. The Cell Counting Kit-8 assay was used to assess cell viability. The alkaline phosphatase activity was evaluated as an indicator of osteogenic differentiation. The expression levels of runt domain-containing transcription factor 2 (Runx2) and osteopontin (OPN) were analyzed by real-time polymerase chain reaction and western blotting. Statistical analyses were performed using Student's t test. RESULTS: The serial treatment with rhBMP-2 and ALN increased the expression of the differentiation-related factors Runx2 and OPN, as well as the differentiation ability of osteoblasts compared with individual or simultaneous treatment. The osteoblasts treated with rhBMP-2 followed by ALN showed the highest differentiation. The degree of differentiation in the group treated with rhBMP-2 for 7 days followed by ALN for 3 days was increased by 1.5 times compared with that of the group treated with rhBMP-2 alone (P < .01). CONCLUSION: These findings indicate that the serial administration of rhBMP-2 and ALN may exert osteogenic effects on osteoblastic cells via the upregulation of Runx2 and OPN.

KMU-1170, a Novel Multi-Protein Kinase Inhibitor, Suppresses Inflammatory Signal Transduction in THP-1 Cells and Human Osteoarthritic Fibroblast-Like Synoviocytes by Suppressing Activation of NF-κB and NLRP3 Inflammasome Signaling Pathway.

Protein kinases regulate protein phosphorylation, which are involved in fundamental cellular processes such as inflammatory response. In this study, we discovered a novel multi-protein kinase inhibitor, KMU-1170, a derivative of indolin-2-one, and investigated the mechanisms of its inflammation-inhibiting signaling in both THP-1 cells and human osteoarthritic fibroblast-like synoviocytes (FLS). We demonstrated that in THP-1 cells, KMU-1170 inhibited lipopolysaccharide (LPS)-induced upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and, furthermore, suppressed LPS-induced phosphorylation of transforming growth factor-ß-activated kinase 1, JNK, ERK, inhibitor of NF-κB kinase α/ß (IKKα/ß), and NF-κB p65 as well as nuclear translocation of NF-κB p65. Moreover, KMU-1170 suppressed LPS-induced upregulation of proinflammatory cytokines such as IL-1ß, TNF-α, and IL-6, and, notably, inhibited LPS-induced upregulation of the NLRP3 inflammasome in THP-1 cells. Importantly, KMU-1170 attenuated LPS-mediated inflammatory responses in human osteoarthritic FLS, such as the upregulation of IL-1ß, TNF-α, IL-6, iNOS, and COX-2 and the phosphorylation of IKKα/ß and NF-κB p65. Collectively, these results suggest that KMU-1170 inhibits inflammatory signal transduction and could be developed as a potential anti-inflammatory agent.

A Nationwide Study of Severe Cutaneous Adverse Reactions Based on the Multicenter Registry in Korea.

BACKGROUND: Because severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) rarely occur, clinical data based on large-scale studies are still lacking. OBJECTIVE: To provide information on culprit drugs and clinical characteristics, including morbidity and mortality of SCARs based on a nationwide registry. METHODS: SCAR cases that occurred from 2010 to 2015 were recruited to the Korean SCAR registry from 34 tertiary referral hospitals. Demographics, causative drugs, causality, and clinical outcomes were collected by reviewing the medical record. RESULTS: A total of 745 SCAR cases (384 SJS/TEN cases and 361 DRESS cases) due to 149 drugs were registered. The main causative drugs were allopurinol (14.0%), carbamazepine (9.5%), vancomycin (4.7%), and antituberculous agents (6.3%). A strong preference for SJS/TEN was observed in carbonic anhydrase inhibitors (100%), nonsteroidal anti-inflammatory drugs (84%), and acetaminophen (83%), whereas dapsone (100%), antituberculous agents (81%), and glycopeptide antibacterials (78%) were more likely to cause DRESS. The mortality rate was 6.6% (SJS/TEN 8.9% and DRESS 4.2%). The median time to death was 19 days and 29 days in SJS/TEN and DRESS respectively, and 89.8% of deaths occurred within 60 days after the onset of the skin symptoms. CONCLUSION: Allopurinol, carbamazepine, vancomycin, and antituberculous agents were the leading causes of SCARs in Korea. Some drugs preferentially caused a specific phenotype. The mortality rate of SCARs was 6.6%, and most of the deaths occurred within 2 months.

Bath Ankylosing Spondylitis Disease Activity Index is Associated With the Quality of Sleep in Ankylosing Spondylitis Patients.

Objective: High disease activity of ankylosing spondylitis (AS) is associated with poor sleep quality The purpose of this study was to identify which of the representative tools for evaluating the disease activity of AS best reflect the quality of sleep. Methods: A total of 107 AS patients were enrolled in the study and the sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) Age, sex, concomitant medication, erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) level, Beck Depression Inventory second edition (BDI-II), Bath ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis disease activity score (ASDAS)-ESR, ASDAS-CRP, pain visual analog scale, Insomnia Severity Index (ISI), and Epworth Sleepiness Scale (ESS) were analyzed as covariates. Results: Overall, 65% (70/107) of subjects reported poor sleep quality (PSQI>5) There was a positive correlation between the sleep quality and disease activity as measured by the BASDAI, ASDAS-ESR, and ASDAS-CRP In addition, the BASDAI demonstrated good correlations with ISI, ESS, and BDI-II, respectively However, only BASDAI showed reliable correlation with PSQI among the disease activity parameters of AS (adjusted odd ratio 5.36, p=0.023). Conclusion: BASDAI is the most reliable parameter of disease activity associated with the sleep quality in patients with AS.

J-shaped Relationship Between Chronic Kidney Disease and Serum Uric Acid Levels: A Cross-sectional Study on the Korean Population.

Objective: Both hypouricemia and hyperuricemia are reportedly associated with reduced kidney function This study investigated the association between uric acid levels and the risk of reduced renal function in men and women. Methods: We conducted a cross-sectional study using data from a government-funded health examinee cohort of a Korean genome and epidemiological study A total of 172,970 participants (58,981 men, 113,989 women) aged 40∼79 years were included A logistic regression test was performed, and the odds ratio (OR) and 95% confidence interval (CI) were calculated to examine the relationship between stratified uric acid levels and the frequency of chronic kidney disease. Results: As the uric acid level increased, the risk of reduced renal function increased Moreover, for uric acid levels ≤20 mg/dL, the risk of reduced renal function was higher than that of the reference group Among the total, man, and woman groups, a statistically significant association was observed in men (OR 171, 95% CI 0945∼3111, OR 5003, 95% CI 1405∼17809, and OR 1377, 95% CI 0696∼2724, respectively). Conclusion: The OR of reduced renal function according to uric acid levels formed a J-shaped curve in both genders.

Distribution of serum uric acid levels and prevalence of hyper- and hypouricemia in a Korean general population of 172,970.

BACKGROUND/AIMS: We investigated the distribution of serum uric acid (SUA) levels and estimated the prevalence of hyperuricemia and hypouricemia in the Korean population. METHODS: This cross-sectional study used data from the Korean Genome and Epidemiology Study and included 172,970 participants (58,981 men and 113,989 women) aged 40 to 79 years. Hypouricemia and hyperuricemia were defined as SUA level ≤ 2.0 mg/dL and > 7 mg/dL, respectively. The prevalence of hyperuricemia and hypouricemia was evaluated by age and sex. RESULTS: The mean SUA levels were significantly higher in men than in women (5.71 ± 1.27 mg/dL vs. 4.21 ± 0.96 mg/dL, p < 0.001). The mean SUA levels and prevalence of hyperuricemia increased with age in women but not in men. The overall prevalence of hyperuricemia and that in men and women was 50.82, 133.25, and 8.17 per 1,000 persons, respectively; the overall prevalence of hypouricemia and that in men and women was 4.16, 1.10, and 5.75 per 1,000 persons, respectively. The prevalence of hypouricemia in men was similar across all age groups; however, that in women was the highest in the age group of 40 to 49 years and the lowest in the age group of 50 to 59 years. CONCLUSION: The distribution of SUA levels and prevalence of hyperuricemia and hypouricemia differed according to age and sex. Age and sex should be considered in studies on uric acid-related diseases.

Proteomic analysis of human synovial fluid reveals potential diagnostic biomarkers for ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease affecting the axial skeleton and peripheral joints. The etiology of this disease remains poorly understood, but interactions between genetic and environmental factors have been implicated. The present study identified differentially expressed proteins in the synovial fluid (SF) of AS patients to elucidate the underlying cause of AS. METHODS: A cohort of 40 SF samples from 10 AS and 10 each of rheumatoid arthritis (RA), gout, and osteoarthritis (OA) patients were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify differentially expressed proteins specific to AS. The label-free LC-MS/MS results were verified by western blotting. RESULTS: We identified 8 proteins that were > 1.5-fold upregulated in the SF of AS patients compared to that of the disease control groups, including HP, MMP1, MMP3, serum amyloid P-component (APCS), complement factor H-related protein 5 (CFHR5), mannose-binding lectin 2 (MBL2), complement component C9 (C9), and complement C4-A (C4A). CFHR5 and C9 were previously found in serum from AS patients, while APCS was previously found in SF as well as in serum. However, the present study has identified C4A, and MBL2 as potential AS biomarkers for the first time. The expression levels of MMP3, C9, and CFHR5 were verified in AS SF using western blotting. CONCLUSION: We performed quantitative comparative proteomic analysis using by LC-MS/MS of the SF from four disease states: RA, gout, and OA. This systematic comparison revealed novel differentially expressed proteins in AS SF, as well as two previously reported candidate biomarkers. We further verified the expression of MMP3, C9 and CFHR5 by western blot. These proteins may serve as diagnostic or prognostic biomarkers in patients with AS, and may thus improve the clinical outcomes of this serious disease.