Correlation analysis of serum TLR4 protein levels and TLR4 gene polymorphisms in gouty arthritis patients.

OBJECTIVE: The Toll-like receptor (TLR) 4-mediated nuclear factor kappa B (NF-κB) signaling pathway regulates the production of inflammatory factors and plays a key role in the pathogenesis of gouty arthritis. The aim of the present study was to investigate the link among TLR4 gene polymorphisms at various loci, protein expression, and gouty arthritis susceptibility. METHODS: Between 2016 and 2021, a case-control study was used to collect a total of 1207 study subjects, including 317 male patients with gouty arthritis (gout group) and 890 healthy males (control group). The association between gout susceptibility and different genetic models was analyzed by typing three loci of the TLR4 gene (rs2149356, rs2737191, and rs10759932) using a multiplex point mutation rapid assay, and the association between protein expression and gout was confirmed by measuring TLR4 protein concentrations using enzyme-linked immunosorbent assays (ELISAs). RESULTS: In a codominant models AA and AG, the rs2737191 polymorphism in the gout group increased the risk of gout compared to the AA genotype (OR = 2.249, 95%CI 1.010~5.008), and the risk of gout was higher for those carrying the G allele compared to the A allele (OR = 2.227, 95%CI 1.006~4.932). TLR4 protein expression was different between the two groups with different locus genotypes. The differences in TLR4 protein expression between the gout group and control group were statistically significant between the following genotypes: the GG and GT genotypes of the rs2149356 polymorphism; the AA and AG genotypes of the rs2737191 polymorphism; and the TT and TC genotypes of the rs10759932 polymorphism(P<0.05). The TLR4 protein level in the gout group (19.19±3.09 ng/ml) was significantly higher than that in the control group (15.85±4.75 ng/ml). CONCLUSION: The AG genotype of the TLR4 gene rs2737191 polymorphism may be correlated with the development of gouty arthritis. The level of TLR4 protein expression is significantly higher in patients with gouty arthritis than in controls, and there is a correlation between high TLR4 protein expression and the development of gouty arthritis.

Influence of intervention treatment by "heat-clearing and diuresis-promoting" prescription on NALP3, an inflammatory factor in acute gouty arthritis.

BACKGROUND: To investigate the efficacy of Qingre Lishi Decoction(QLRD), in the treatment of acute gouty arthritis, and its influence on the expression levels of inflammatory factor nucleotide-binding oligomerization domain-like receptor(NALP 3) in patients. METHODS: A total of 78 patients with acute gouty arthritis admitted to our hospital were randomly divided into the control group and the observation group, with 39 cases in each group. The control group was given basic treatment and colchicine tablets, and the observation group was given "heat-clearing and diuresis-promoting" prescription for intervention treatment. The main symptom score, treatment effective rate and laboratory indexes of the two groups were compared 7 days after treatment. RESULTS: After treatment, the scores of joint redness, hot pain, joint flexion and extension disorder, oliguria and constipation were improved in both groups, and the improvement degree in observation group was higher than that in control group (P < 0.05); the clinical effective rate in the observation group (94.87%) was higher than that in the control group (76.92%). The serum uric acid (UA), erythrocyte sedimentation rate (ESR), interleukin-1ß (IL-1ß) and NALP3 showed a decreasing trend, and the decrease degree of each index in observation group was higher than that in control group (P < 0.05). CONCLUSION: The "heat-clearing and diuresis-promoting" prescription for intervention treatment can effectively improve the clinical symptoms of patients with acute gouty arthritis and reduce the level of inflammatory factor NALP3, maintaining remarkable effect.

Characteristics of monosodium urate crystal deposition in the foot in the different stages of gout by dual-energy computed tomography.

OBJECTIVE: To compare the characteristics of monosodium urate (MSU) crystal deposition at specific anatomical sites of the foot detected by dual-energy computed tomography in patients with different stages of gout. MATERIALS AND METHODS: This study included 101 patients with gout, 64 had early gout (<3 years) and 37 had late gout (>3 years). We retrospectively compared the total volumes of MSU crystals, the detection rates, and the morphology of MSU crystals at specific anatomical sites in the foot of the patients with different gout durations. RESULTS: The total volume of MSU crystals in patients with early gout was significantly smaller than that in patients with late gout (P < 0.05). The detection rates and morphology of MSU crystals in the anterior calf tendons, ankle joints, tarsometatarsal joints, and metatarsophalangeal joints differed significantly between the patients with early and late gout (P < 0.05). There were no significant differences in the detection rates of submillimeter MSU crystals at the other specific anatomical sites, except for the tendons of the anterior calf, the ankle joint, and the metatarsal joint (P > 0.05). The submillimeter MSU crystal deposition was most common in the tendons of the posterior calf, the proportions in patients with early gout and late gout were 85.9% and 70.3%. Only submillimeter deposition existed in 52 patients (81.3%) with early gout and 11 patients (29.7%) with late gout at all sites of the foot. CONCLUSION: Dual-energy computed tomography detection of submillimeter MSU crystal deposits in the foot is of great significance for the diagnosis of gout, especially along tendons.

Profile of serum cytokine concentrations in patients with gouty arthritis.

OBJECTIVE: This study aimed to analyze the changes in serum inflammatory cytokines and anti-inflammatory cytokines in patients with gouty arthritis (GA). METHODS: The clinical data and serum samples in patients with gouty arthritis and those in healthy volunteers were collected in China-Japan Friendship Hospital from July 2018 to January 2019. Serum cytokine concentrations in patients with GA and volunteers (controls) were determined by a chemiluminescence method. The differences in cytokine concentrations were compared between the two groups. RESULTS: Concentrations of serum interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), IL-6, IL-8, and IL-4 were significantly higher in patients with acute GA than in controls. Serum concentrations of IL-1ß, TNF-α, IL-6, IL-8, and immunoglobulin E in patients with remission of GA were significantly lower, whereas concentrations of IL-10 and interferon-γ were significantly higher, compared with those in patients with acute GA. CONCLUSION: This study shows that serum concentrations of IL-1ß, TNF-α, IL-6, IL-8, and IL-4 are significantly elevated in patients with GA, and may be involved in the pathogenesis of GA.

MiR-192-5p suppresses M1 macrophage polarization via epiregulin (EREG) downregulation in gouty arthritis.

Gouty arthritis (GA) is a chronic inflammatory disease characterized by the deposition of monosodium urate (MSU) crystals within joints. MiR-192-5p is shown to be low-expressed in GA patients. However, the potential mechanism involving miR-192-5p in GA remains unclear. In the current study, a significant reduction in miR-192-5p and an increase in epiregulin (EREG) were observed in serum of GA patients, suggesting that miR-192-5p and EREG were involved in the pathogenic process of GA. A mouse GA model was established via 0.5 mg/20 µL MSU crystal administration. To investigate the effect of miR-192-5p on GA, mice were injected with miR-192-5p agomir or NC agomir before modeling. We found that miR-192-5p overexpression induced by miR-192-5p agomir reduced EREG expression, attenuated ankle joint swelling and synovial inflammatory cell infiltration and improved bone erosion in MSU-induced GA mice. MiR-192-5p decreased CD16/32+ (M1 marker) macrophages, but increased CD206 (M2 marker) expression in synovium of GA models. In vitro, RAW264.7 macrophages were stimulated with miR-192-5p mimic or NC mimic under IFNγ plus LPS-stimulated M1 polarization condition. MiR-192-5p reduced the release of inflammatory cytokines TNF-α and IL-1ß, decreased iNOS expression, and inhibited CD16/32 expression, indicating the blockade of M1 macrophage activation. Luciferase reporter system revealed the target interaction between miR-192-5p and EREG. Further rescue experiments demonstrated that EREG overexpression partly reversed the inhibitory role of miR-192-5p on M1 macrophage polarization manifested by elevated iNOS and CD16/32 levels. Collectively, miR-192-5p ameliorates inflammatory response in GA by inhibiting M1 macrophage activation via inhibiting EREG protein.

Combining Calcitonin and Procalcitonin and Rheumatoid Arthritis-Related Biomarkers Improve Diagnostic Outcomes in Early Rheumatoid Arthritis.

OBJECTIVE: To demonstrate whether procalcitonin (PCT) combined with calcitonin (CT) could provide additional diagnostic value to other clinically available rheumatoid arthritis- (RA-) related biomarkers in the early diagnosis of RA. METHOD: The blood samples aseptically collected by venipuncture were centrifuged within 1 hour and frozen at -80°C. PCT and CT levels were measured using electrochemiluminescence immunoassay (ECLIA) in 260 subjects (48 patients with early RA, 34 patients with established RA, 37 patients with systemic lupus erythematosus, 30 with osteoarthritis, 31 with gouty arthritis, and 80 healthy participants). Anti-cyclic citrullinated peptide (Anti-CCP) and anti-RA33 antibodies (Anti-RA33) were analyzed by ELISA. RF was detected by transmission immunoturbidimetry. Mann-Whitney U tests and Kruskal-Wallis tests compared differences among groups. Spearman's rank correlation analysis determined the relationship between biomarkers. Receiver-operator characteristic (ROC) curves were generated, and diagnostic performance was assessed by area under the curve (AUC), as well as specificity, sensitivity, likelihood ratios (LR). RESULTS: Median serum PCT concentrations were significantly higher (p < 0.0001) in patients with early RA (0.065 ng/ml) when compared with healthy controls (0.024 ng/ml), and patients with osteoarthritis (0.025 ng/ml). When compared with gouty arthritis (GA) controls (0.072 ng/ml) and systemic lupus erythematosus (SLE) controls (0.093 ng/ml), median serum PCT concentrations were not significant in patients with early RA (0.065 ng/ml). Median serum CT concentrations were significantly lower (p < 0.0001) in patients with early RA (0.880 pg/ml) compared with healthy controls (3.159 pg/ml), patients with SLE (2.480 pg/ml), and patients with GA (2.550 pg/ml). When compared with osteoarthritis controls (0.586 pg/ml), median serum CT concentrations were not significant in patients with early RA (0.880 pg/ml). ROC curve analysis comparing early RA with healthy controls demonstrated that the AUC of RF, anti-CCP, and anti-RA33 were 0.66, 0.73, and 0.64, respectively; the additions of PCT and CT further improved the diagnostic ability of early RA with the AUC of 0.97, 0.98, and 0.97, respectively (p < 0.01). The sensitivities of RF, anti-CCP, and anti-RA33 for early RA were 33.33%, 44.74%, and 58.33%, respectively, and the additions of PCT and CT showed very high sensitivities of 83.33%, 92.11%, and 87.50%. The high-value groups of PCT moderately correlated with the anti-RA33 levels (r = 0.417, p < 0.05). CT had no significant correlation with disease duration, radiographic progression, or clinical/serological variables, such as ESR levels, CRP levels, RF, anti-CCP, and anti-RA33 levels in early RA. CONCLUSIONS: Serum PCT and CT combined with clinically available RA-related biomarkers could further improve the diagnostic efficiency of early RA.

Melatonin Alleviates Acute Gouty Inflammation In Vivo and In Vitro.

The aim of this study was to identify the effects of melatonin on acute gouty inflammation and to investigate the underlying mechanisms. We found significantly lower serum melatonin levels in gout patients in the acute phase than in those in the remission phase or in normal individuals. The mRNA expression of melatonin receptor 2 (MT2) was also lower in gout patients than in normal individuals. To verify the in-vivo role of melatonin, a gouty arthritis model was established by intraarticular injection of monosodium urate (MSU, 1 mg) crystals into the paws of C57BL/6 mice. Joint inflammation in the mouse model was evaluated by measuring the thickness of the right paw/left paw, and the inflammation index was determined by examining infiltrating neutrophils with haematoxylin and eosin (H&E) staining. Melatonin was found to reduce both paw thickness and the inflammation index in the mouse model, and melatonin also reduced the mRNA levels of interleukin-1 beta (IL-1ß), IL-6 and NLR family pyrin domain containing 3 (NLRP3) inflammasome. To mimic gouty inflammation in vitro, mouse peritoneal macrophages were stimulated with lipopolysaccharides (LPS) plus MSU. Melatonin was revealed to reduce IL-1ß secretion by stimulated macrophages. The mRNA expression levels of IL-1ß and IL-6 were also inhibited by melatonin. Western blot analysis showed that the expression of NLRP3, caspase-1 and pro-IL-1ß was also inhibited by melatonin. In conclusion, our study demonstrated that melatonin alleviated gouty inflammation in vivo and in vitro, and the underlying mechanism may involve inhibiting the assembly of the NLRP3 inflammasome.

MiR-221-5p is involved in the regulation of inflammatory responses in acute gouty arthritis by targeting IL-1ß.

AIM: Gout is caused by the accumulation of deposited monosodium urate (MSU) crystals in the joints. Recent studies have shown that interleukin-1ß (IL-1ß) is a key inflammatory mediator of acute gouty arthritis (AGA), and its level is regulated by microRNAs (miRNAs). The purpose of this study was to study the role of miR-221-5p in the pathogenesis of AGA. METHODS: One hundred patients with AGA and 94 healthy individuals were recruited. The expression of serum miR-221-5p was determined by quantitative real-time polymerase chain reaction. The receiver operating curve (ROC) was applied for diagnostic value analysis. A luciferase reporter assay was performed to confirm the interaction of miRNA and the 3'-untranslated region (UTR) of IL-1ß. Enzyme-linked immunosorbent assay was used to detect serum and proinflammatory factors. RESULTS: miR-221-5p had lower expression in the serum of AGA patients. The area under the curve was 0.884, the sensitivity was 82.0%, and the specificity was 80.9%. Serum miR-221-5p was negatively correlated with the expression levels of visual analog scale and IL-1ß. Cell experiments showed that overexpression of miR-221-5p significantly inhibited the expression of inflammatory factors tumor necrosis factor-α, IL-8, and IL-1ß, while down-regulation of miR-221-5p was the opposite. Luciferase analysis showed that IL-1ß was the target gene of miR-221-5p. CONCLUSIONS: This study confirmed that miR-221-5p regulates the production of inflammatory cytokines during the pathogenesis of AGA. These results suggested that miR-221-5p could be used as a potential therapeutic target for the treatment of AGA.

PD-1 mRNA expression in peripheral blood mononuclear cells as a biomarker for different stages of primary gouty arthritis.

There is currently a lack of biomarkers to assist the diagnosis and prediction of primary gouty arthritis (PG). Therefore, we evaluated the clinical value of programmed cell death protein 1 (PD-1) mRNA expression in peripheral blood mononuclear cells (PBMCs) of patients with PG. This study included 36 patients with acute phase PG (APPG), 48 with non-acute phase PG (NAPPG), 42 with asymptomatic hyperuricemia (AH) and 79 normal controls (NCs). PD-1 mRNA expression levels were detected by qRT-PCR. PD-1 mRNA expression was statistically analysed by ANOVA or t tests, while correlations between PD-1 mRNA and clinical variables were assessed using Pearson correlation tests. Receiver operator characteristic (ROC) curve analysis was used to evaluate the diagnostic value of PD-1 in different PG stages. PD-1 mRNA expression was significantly lower in patients with APPG than that in NAPPG, AH and NCs (P < 0.01). Correlation analysis revealed that PD-1 mRNA levels correlated negatively with T-score (r = -0.209, P < 0.01). ROC curve analysis showed that serum uric acid (SUA), PD-1 mRNA and both combined displayed higher diagnostic value in patients with PG, NAPPG and APPG compared to that in NCs and patients with non-PG arthritis (NPG). Moreover, ROC curve analysis showed that SUA and PD-1 mRNA had good diagnostic value in APPG, with the greatest diagnostic power when combined. PD-1 mRNA could be a clinical auxiliary diagnostic biomarker for APPG, and the combined use of PD-1 mRNA and SUA is better than that of SUA alone.

Serum CA72-4 is specifically elevated in gout patients and predicts flares.

OBJECTIVES: Serum CA72-4 levels are elevated in some gout patients but this has not been comprehensively described. The present study profiled serum CA72-4 expression in gout patients and verified the hypothesis that CA72-4 is a predictor of future flares in a prospective gout cohort. METHODS: To profile CA72-4 expression, a cross-sectional study was conducted in subjects with gouty arthritis, asymptomatic hyperuricaemia, four major arthritis types (OA, RA, SpA, septic arthritis) and healthy controls. A prospective gout cohort study was initiated to test the value of CA72-4 for predicting gout flares. During a 6-month follow-up, gout flares, CA72-4 levels and other gout-related clinical variables were observed at 1, 3 and 6 months. RESULTS: CA72-4 was highly expressed in patients with gouty arthritis [median (interquartile range) 4.55 (1.56, 32.64) U/ml] compared with hyperuricaemia patients [1.47 (0.87, 3.29) U/ml], healthy subjects [1.59 (0.99, 3.39) U/ml] and other arthritis patients [septic arthritis, 1.38 (0.99, 2.66) U/ml; RA, 1.58 (0.95, 3.37) U/ml; SpA, 1.56 (0.98, 2.85) U/ml; OA, 1.54 (0.94, 3.34) U/ml; P < 0.001, respectively]. Gout patients with frequent flares (twice or more in the last year) had higher CA72-4 levels than patients with fewer flares (fewer than twice in the last year). High CA72-4 level (>6.9 U/ml) was the strongest predictor of gout flares (hazard ratio = 3.889). Prophylactic colchicine was effective, especially for patients with high CA72-4 levels (P = 0.014). CONCLUSION: CA72-4 levels were upregulated in gout patients who experienced frequent flares and CA72-4 was a useful biomarker to predict future flares.

[Differentially expressed inflammatory proteins in acute gouty arthritis based on protein chip].

OBJECTIVE: To detect the differentially expressed inflammatory proteins in acute gouty arthritis (AGA) with protein chip. METHODS: The Raybiotech cytokine antibody chip was used to screen the proteomic expression in serum samples of 10 AGA patients and 10 healthy individuals. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were applied to determine the biological function annotation of differentially expressed proteins and the enrichment of signal pathways. ELISA method was used to verify the differential protein expression in 60 AGA patients and 60 healthy subjects. The ROC curve was employed to evaluate the diagnostic value of differential proteins in AGA patients. RESULTS: According to|log2FC|>log2 1.2 and corrected P<0.01, 4 most differentially expressed proteins in AGA patients were identified, including tumor necrosis factor receptor super family members Ⅱ (TNF RⅡ), macrophage inflammatory protein 1ß (MIP-1ß), interleukin-8 (IL-8), and granulocyte-macrophage colony stimulating factor (GM-CSF). GO and KEGG enrichment analysis showed that the differentially expressed proteins were related to inflammation, metabolism and cytokine pathways. The ELISA results showed that serum levels of differentially expressed proteins were significantly different between AGA patients and healthy subjects(all P<0.01). ROC curve analysis showed that the areas under the curve (AUCs) of GM-CSF, IL-8, MIP-1ß and TNF RⅡ for predicting AGA were 0.657 (95% CI: 0.560-0.760, sensitivity: 68.33%, specificity: 50.00%), 0.994 (95% CI: 0.980-1.000, sensitivity: 100.00%, specificity: 61.67%), 0.980 (95% CI: 0.712-0.985, sensitivity: 95.00%, specificity: 98.33%) and 0.965 (95% CI: 0.928-1.000, sensitivity: 100.00%, specificity: 10.00%), respectively. CONCLUSIONS: Proteomics can be applied to identify the biomarkers of AGA, which may be used for risk prediction and diagnosis of AGA patients.

Impact of the Synbiotics and Urate-Lowering Therapy on Gut Microbiota and Cytokine Profile in Patients with Chronic Gouty Arthritis.

The main goal of our study is the impact evaluation of complex urate-lowering therapy with the synbiotic addition on fecal microbiota and cytokine profile in patients with primary gout. During our study, 130 men (mean age 55.5 ± 9.4 years) with gout (duration 7.7 ± 7.1 years) were examined. All patients were divided into two treatment groups. The main group (n = 68) was taking allopurinol at 300 mg per day dose and additionally a synbiotic. The comparison group (n = 62) received allopurinol monotherapy without synbiotic intake. The therapy duration was 3 months. Evaluation of therapy efficiency was marked by blood uric acid changes, cytokine levels, CRP and fecal microbiota condition. After treatment, stabilization of the gut microbiota parameters was observed, which was leading to normalization uricemia levels (40.3% vs. 21%, p <0.01) in the main group patients. Addition of synbiotic to allopurinol leads to a blood uric acid lowering (18.7% vs. 13.3%, p <0.01), CRP reduction (75% vs. 26.3%, p <0.01) as well as decrease of cytokines level: IL-1ß, IL-6, IL-8, IL-10 and TNFα (all p <0.001). After a 3-month gout treatment, a group of patients who received complex therapy with synbiotic inclusion showed signs of disease remission characterized by inflammation activity reducing, fecal microbiota condition normalization and a more pronounced decrease in laboratory markers comparing to control group.

The performance of dual-energy CT in the classification criteria of gout: a prospective study in subjects with unclassified arthritis.

OBJECTIVE: To establish the performance of (subsets of) the 2015 ACR/EULAR gout classification criteria in patients with unclassified arthritis, and to determine the value of dual-energy CT (DECT) herein. Reference was the MSU crystal detection result in SF at polarization microscopy. METHODS: We included subjects with acute, unclassified mono or oligoarthritis, who underwent SF analysis and DECT. Performance was assessed by calculating area under the receiver operating characteristic curve of (i) the clinical criteria subset, (ii) the clinical+serum urate subset and (iii) the full set (including DECT). RESULTS: Of the 89 subjects enrolled, 40 met the clinical+serum urate subset criteria, and 49 (55%) subjects did not. Of these 49, 30 had a negative microscopy result, of whom 15 had positive DECT; of these 15, 14 met the full set criteria only after adding the positive DECT result. For the clinical-only subset, the areas under the curves (AUCs) were 0.68 and 0.69 without and with DECT result, respectively, and for the clinical+serum urate subset without and with DECT, AUCs were 0.81 and 0.81, respectively (results not significant). CONCLUSION: Adding the serum urate results to the clinical subset improves the performance, but adding the DECT result does not, neither does adding the DECT results to the clinical+serum urate subset. However, DECT seems to have an additive value in gout classification, especially when microscopy of SF is negative; 14/89 of patients (16%) only met the classification criteria with the use of DECT. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT03038386.

Plasma Metabolic Profiling Analysis of Gout Party on Acute Gout Arthritis Rats Based on UHPLC-Q-TOF/MS Combined with Multivariate Statistical Analysis.

Gout Party is a Chinese medicine prescription composed of Aconiti Lateralis Radix Praeparaia, Aconiti Radix Cocta, Cremastrae Pseudobulbus Pleiones Pseudobulbus, Smilacis Glabrae Rhizoma, Rehmanniae Radix, and Glycyrrhizae Radix et Rhizoma, which can relieve joint pain caused by gouty arthritis (GA) and rheumatoid, and has a therapeutic effect on acute gouty arthritis (AGA). However, little information is available on the molecular biological basis and therapeutic mechanism of Gout Party for the treatment of AGA. AGA model was established by injecting sodium urate, and colchicine served as a positive control drug. We established a metabolomic method based on ultra-high-performance liquid chromatography-tandem quadrupole/time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) to analyze the plasma samples of model group rats and blank group rats. Multiple statistical analyses, including principal component analysis (PCA) and partial least square discrimination analysis (PLS-DA), were used to examine metabolite profile changes in plasma samples. Finally, we identified 2-ketobutyric acid, 3-hexenedioic acid, but-2-enoic acid, and so on; 22 endogenous metabolites associated with AGA. After successful molding, we found that 2-ketobutyric acid, 3-hexenedioic acid, but-2-enoic acid, argininic acid, galactonic acid, lactic acid, equol 4'-O-glucuronide, deoxycholic acid glycine conjugate, glycocholic acid, sphinganine 1-phosphate, LPE (0:0/20:3), LPE (0:0/16:0), LPC (15:0) decreased significantly (p < 0.05 or p < 0.01), alanine, erythrulose, 3-dehydrocarnitine, m-methylhippuric acid, 3-hydroxyoctanoic acid, p-cresol sulfate, estriol 3-sulfate 16-glucuronide, 10-hydroxy-9-(phosphonooxy)octadecenoate, docosahexaenoic acid increased significantly (p < 0.05 or p < 0.01). After Gout Party treatment, 14 biomarkers had a tendency to normal conditions. These above biomarkers were mainly involved in fatty acid metabolism, bile acid metabolism, amino acid metabolism, and energy metabolism pathways. These results suggested that Gout Party exerted therapeutic effects of treating AGA by improving energy metabolism disorder and amino acid metabolism dysfunction, and attenuating fatty acid metabolism abnormal and inflammation. The results of this experiment provided a reference for revealing the metabolic mechanism produced by Gout Party in the treatment of AGA, but the subsequent studies need to be further improved and supported by relevant cell experiments and clinical experiments.

Monocyte to Lymphocyte Ratio, Neutrophil to Lymphocyte Ratio, and Red Cell Distribution Width are the Associates with Gouty Arthritis.

BACKGROUND: Neutrophils, monocytes, and macrophages activations are associated with a gout attack. Monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), red cell distribution width (RDW), and mean platelet volume (MPV) are well-known inflammation markers. In this study, we aimed to investigate whether they could be a predictive marker to the gout attack. MATERIAL AND METHODS: A hundred and ten gout patients (male/female, 86/24) and 90 (male/female, 64/26) age-, gender-, and body mass index-matched volunteer controls were included in the study. Blood samples were obtained in the intercritical and attack period of the patients. Hemogram, serum uric acid (SUA), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) values were studied. RESULTS: In the attack period NLR (p < 0.001), PLR (p < 0.05), MLR (p < 0.001), RDW (p < 0.05), MPV (p < 0.05), ESR (p < 0.001), CRP (p < 0.001) and SUA (p < 0.001) values were significantly higher than intercritical period values. According to the results of regression analysis; There was an independent strong relationship between the gout attack and SUA, (Beta [ß] = 0.352, p < 0.001), ESR (ß = 0.329, p < 0.001), CRP (ß = 0.286, p < 0.001), MLR (ß = 0.126, p < 0.001), RDW (ß = 0.100, p = 0.003) and NLR (ß = 0.082, p = 0.014). CONCLUSIONS: MLR, RDW, and NLR may be a strong predictive marker for a gout attack. MPV and PLR values in the gout attack may be associated with systemic inflammation.

LC-MS Analysis of Serum for the Metabolomic Investigation of the Effects of Pulchinenoside b4 Administration in Monosodium Urate Crystal-Induced Gouty Arthritis Rat Model.

Gouty arthritis (GA) is commonly caused by deposition of monosodium urate (MSU) crystals within the joint capsule, bursa, cartilage, bone, or other periarticular tissues after chronic hyperuricemia. Clinically, GA is characterized by acute episodes of joint inflammation, which is most frequently encountered in the major joints, and also has a significant impact on quality of life. Pulchinenoside b4(P-b4) has a wide range of biological activities, including antitumor, anti-inflammatory, antiviral and immunomodulatory activities. Currently, the anti-GA activity and metabolomic profiles after being treated by P-b4 have not been reported. In this paper, for the first time, we have performed a non-targeted metabolomics analysis of serum obtained from an MSU crystal-induced GA rat model intervened by P-b4, using ultra-performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry. In this study, the main pharmacodynamics of different dosing methods and dosages of P-b4 was firstly investigated. Results have shown that P-b4 possesses high anti-inflammatory activity. These results demonstrated changes in serum metabolites with 32 potential biomarkers. Arachidonic acid, sphingolipid, and glycerophospholipid metabolism are considered to be the most relevant metabolic pathway with P-b4 treatment effect in this study. Moreover, the changes of metabolites and the self-extinction of model effects within 24 h reveals important information for GA diagnostic criteria: The regression of clinical symptoms or the decline of some biochemical indicators cannot be regarded as the end point of GA treatment. Furthermore, our research group plans to conduct further metabolomics research on the clinical course of GA.

Association between serum uric acid and chronic kidney disease in patients with hypertension: A multicenter nationwide cross-sectional study.

INTRODUCTION: Current data on the role of hyperuricemia as a risk factor for renal progression in patients with hypertension is inconclusive. This study aimed to assess the association of uric acid and chronic kidney disease (CKD) in hypertensive patients using a nationwide patient sample. METHODS: We conducted a nationwide cross-sectional study based on the DM/HT study of the Medical Research Network of the Consortium of Thai Medical Schools. This study evaluated adult patients with hypertension from 831 Thailand public hospitals in the year 2014. Serum uric acid (SUA) was categorized into quintiles (≤4.5, 4.6 to 5.4, 5.5 to 6.2, 6.3 to 7.4, ≥7.5 mg/dL). CKD was defined as estimated glomerular filtration rate of ≤ 60 mL/min/1.73 m2 . Multivariate logistic regression was performed to assess the association between SUA and CKD using uric acid of ≤4.5 mg/dL as the reference group. RESULTS: A total of 9776 hypertensive patients with available SUA were included in the analysis. The mean SUA was 6.1±1.8 mg/dL. The prevalence of CKD in hypertensive patients was 31.8%. SUA of 4.6 to 5.4, 5.5 to 6.2, 6.3 to 7.4, and ≥7.5 mg/dL were associated with an increased CKD with ORs of 1.57 (95% CI 1.28 to 1.92), 2.15 (95% CI 1.74 to 2.66), 3.31 (95% CI 2.72 to 4.04), and 7.11 (95% CI 5.76 to 8.78), respectively. The restricted cubic spline showed significant increased CKD prevalence when uric acid ≥4.6 mg/dL. CONCLUSION: Higher SUA was associated with increased CKD prevalence in patients with hypertension. SUA should be monitored in hypertensive patients for CKD prevention.

Antioxidant and anti-gout effects of orally administered zinc oxide nanoparticles in gouty mice.

BACKGROUND: Zinc is an essential trace element which is involved in controlling oxidative stress, growth and immune system by regulating inflammatory cytokines. Gouty arthritis is the inflammation of joints and tissues caused by the accumulation of monosodium urate crystals. METHOD AND OBJECTIVE: This study involved the oral administration of zinc oxide nanoparticles at a various concentration (5 ppm, 10 ppm, and 20 ppm) and study their antioxidant and anti-gout effects on Balb/C mice. Various parameters such as ROS, superoxide, peroxide, catalase, TBARS, RFTs, LFTs, lipid profile and blood count were studied. RESULTS: ZnO nanoparticles at the concentrations of 10 and 20 ppm were significant (P < 0.001) in reducing serum uric acid concentration thus treating gouty arthritis. Reactive oxygen species and thiobarbituric acid reactive substances were significantly increased in comparison to zinc oxide nanoparticles treated groups. Furthermore, blood count and LFTs also showed the effectiveness of zinc oxide in the reduction of hyperuricemia. Histopathological analysis showed no apparent changes in liver, kidney and muscles tissues. CONCLUSION: Zinc oxide nanoparticles can be effective in reducing oxidative stress and the treatment of gouty arthritis.

Novel findings from determination of common expressed plasma exosomal microRNAs in patients with psoriatic arthritis, psoriasis vulgaris, rheumatoid arthritis, and gouty arthritis.

BACKGROUND: Circulating exosomal microRNAs modulate not only cancer cell metabolism but also the immune response, and therefore plasma exosomal microRNAs might have the potential to be the biomarkers for a number of immune disorders. OBJECTIVE: This study was conducted to identify the common mechanisms among psoriatic arthritis (PsA), psoriasis vulgaris (PV), rheumatoid arthritis (RA), and gouty arthritis (GA). The common expressed plasma exosomal microRNAs in these diseases were determined. METHODS: The expression of microRNAs derived from plasma exosome of patients with PsA (n=30), PV (n=15), RA (n=15), GA (n=15), and healthy controls (n=15) was evaluated via sequencing. Function analysis of common expressed microRNAs was conducted by the Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses. Coexpression analysis was conducted to identify novel and significant genes and proteins by using the Search Tool for the Retrieval of Interacting Genes (STRING). A systematic literature review was conducted to uncover the role of the common microRNAs in the pathogenesis of PsA, PV, RA, and GA. RESULTS: A total of 36 common expressed microRNAs were detected in patients with PsA, PV, RA, and GA. The most significantly enriched biological processes, cellular components, and molecular functions were "homophilic cell adhesion via plasma membrane adhesion molecules," "CCR4-NOT complex," and "calcium ion binding," respectively. "Antigen processing and presentation" was the most significantly enriched pathway. A total of 91 validated coexpressed gene pairs were identified and 16 common expressed microRNAs and 85 potential target genes were screened based on Cytoscape. Of 36 common expressed microRNAs, 5 microRNAs, including hsa-miR-151a-3p, hsa-miR-199a-5p, hsa-miR-370-3p, hsa-miR-589-5p, and hsa-miR-769-5p, were considered to be connected with the common pathogenesis of PsA, PV, RA, and GA. Systemic review revealed that the roles of these 5 microRNAs are related to immune disorder and bone injury, which matches the conclusion from GO and KEGG analyses. CONCLUSION: (1) Both immune disorder and bone metabolic dysregulation could be the shared mechanism in the development of PsA, PV, RA, and GA. (2) Immune dysfunction is involved in GA. Our study may shed new light on the diagnosis and treatment strategy of these autoimmune diseases and GA, which warrants further studies.