Gout Research Articles

Histopathological diagnostics of infections in rheumatology

The histopathological differential diagnoses of inflammatory infectious and inflammatory noninfectious diseases of the musculoskeletal system, particularly infectious and noninfectious arthritis, soft tissue inflammation and osteomyelitis in rheumatology are presented with afocus on the differential diagnostic possibilities and limitations; however, adiverse spectrum of pathogenic mechanisms underly these diseases, which can present with similar inflammatory response patterns. This wide spectrum of inflammatory pathogenesis of infectious and noninfectious diseases includes diseases such as rheumatoid arthritis, gouty arthritis, osteomyelitis and pyoderma gangrenosum, which cannot clinically be manifested thus necessitating a histopathological clarification. In terms of tissue sampling the following general principle applies: the larger the tissue sample and the more diverse the sites of tissue extraction, the more conclusive are the histopathological diagnostics. This diagnostic approach to infections, especially in arheumatological context, is generally considered complementary and even supplementary to microbiological diagnostics. Furthermore, consideration of the virulence-resistance relationship, which can alter the inflammatory pattern, is of additional relevance. Consequently, definitive causal diagnostics are only achievable within the clinical, rheumatological, microbiological, laboratory medical and infectiological context.

Preparation of combined colchicine with loxoprofen sodium loaded in dissolvable microneedles and its anti-gouty arthritis effect

Both colchicine (Col) and loxoprofen sodium (LS) are first-line drugs for gouty arthritis (GA). Dissolvable microneedles (DMNs) represent an innovative transdermal drug delivery system (TDDS) that maximizes the therapeutic effect of drugs. In this paper, a novel TDDS of combined Col with LS loaded in DMNs (Col-LS-DMNS) was prepared to treat GA. To assess the synergistic effects of Col and LS, cell viability assays were conducted using monosodium urate (MSU)-induced HaCaT cells. The optimization of the Col-LS-DMNs formulation was carried out through sealing membrane puncture tests, single-factor experiments, and Box-Behnken response surface methodology. The quality of Col-LS-DMNs was assessed using high-performance liquid chromatography (HPLC), scanning electron microscopy (SEM), sealing membrane puncture tests, in vitro mouse skin puncture experiments, and Franz diffusion cell assays. The therapeutic effect of Col-LS DMNs on GA through animal experiments. Results demonstrated that Col and LS exhibit a synergistic effect, with optimal mass ratio of 1:1. The optimal formulation included PVP K30 and CMC Na at a mass ratio of 10:1, with 63% water content and a mixed dosage of Col and LS of 42 mg. The drug content in Col-LS-DMNs was (19.11±0.65) μg of Col and (20.69±0.89) μg of LS per tablet. SEM imaging revealed that the needle tips were conical. Additionally, Col-LS-DMNs exhibited favorable mechanical properties and caused minimal skin damage. After 24 hours, the cumulative permeation amount was (21.55±19.49) μg/cm2. Col-LS-DMNs significantly reduced MSU-induced ankle swelling and decreased serum concentrations of TNF-α, IL-6, and IL-1β in rats. In conclusion, Col-LS-DMNs represent a promising new treatment modality for GA.

A Study on the Diagnostic Value of Dual‐Energy CT (DECT) Imaging in Patients With Gouty Arthritis

ABSTRACTObjectivesTo explore the diagnostic value of dual‐energy computed tomography (DECT) in patients with gouty arthritis.MethodsA total of 160 patients with gouty arthritis who were treated in our hospital from January 2023 to October 2023 were selected as the research subjects. The participants were randomly divided into two groups: an observation group and a control group. Each group had 80 cases. Observation group performed DECT examination and control group performed X‐ray examination. The researchers recorded the general information of the participants in both groups and conducted single‐factor analysis. They compared the detection of positive diseased joints between the two groups, as well as compared the distribution of positive diseased joints. In addition, the number of joint lesions was compared in the two groups.ResultsThere were not any statistically great differences between the two groups in gender, age, BMI, disease duration, blood uric acid, and erythrocyte sedimentation rate (p > 0.05). During the DECT examination, a total of 82 positive diseased joints were identified in the observation group. The observation group also had a positive rate of 85.42% (82/96) in the DECT examination. While the control group had a total of 55 positive diseased joints during the X‐ray examination with a positive rate of 59.78% (55/92). The difference between the two groups of patients in the positive rate of two kinds of examination was statistically significant (χ2 = 15.616, p < 0.001). No statistical significance was found in the distribution of the number of positive diseased joints between two groups (χ2 = 1.986, p = 0.851). Both DECT and X‐ray examinations of patients in the two groups revealed that the lesions were primarily located in the soft tissues or ligaments surrounding the distal small joints of the limbs, such as metatarsophalangeal joints, ankle joints, and proximal interphalangeal joints. Compared with the X‐ray examination of the patients, the DECT examination of the patients showed a great increase in the number of bone destruction, gout nodules, and soft tissue swelling (χ2 = 7.712, 10.441, 5.389, p = 0.005, 0.001, 0.020). Moreover, the DECT examination of patients showed the presence of urate crystals and joint effusion, while the X‐ray examination of patients in the control group did not show any.ConclusionsSiemens dual‐source 64‐slice CT dual‐energy imaging has better diagnostic value for gouty arthritis than X‐ray and has higher specificity for detecting urate crystals and joint effusion. Therefore, Siemens dual‐source 64‐slice CT dual‐energy imaging examination may serve as a promising new noninvasive technique for early diagnosis, clinical screening, and follow‐up of gout in the future.

Evaluation indicators of Traditional Chinese Medicine syndromes for gouty arthritis with damp heat accumulation and the effect of administering Tongfeng Qingxiao formula.

Evaluation indicators of Traditional Chinese Medicine syndromes for gouty arthritis with damp heat accumulation and the effect of administering Tongfeng Qingxiao formula.

Quality-of-life and clinical gout assessments during pegloticase with and without methotrexate co-therapy: MIRROR randomized controlled trial exploratory findings

Abstract Objectives Pegloticase lowers serum urate (SU) but is limited by anti-drug antibodies. Methotrexate co-administration increases urate-lowering response rate and decreases infusion reaction risk. This is of importance in uncontrolled gout patients who have few treatment options and highly impacted quality-of-life (QOL). Here, we report exploratory QOL/clinical endpoints of MIRROR RCT (NCT03994731). Methods Patients with uncontrolled gout (sUA ≥ 7mg/dl, ULT-failure/intolerance, and ≥1 gout sign/symptom [≥1 tophus, ≥2 flares in past year, chronic gouty arthritis]) were administered pegloticase (biweekly 8 mg infusion; 52-weeks) with oral MTX (15 mg/week) or placebo co-therapy. Key exploratory outcomes included change-from-baseline (CFB) in Physician Global Assessment of Gout [PhGA, score: 0–10], CFB in tender/swollen joint counts [TJC/SJC, score: 0–68/0–66], and gout-chronic-response rate (GCR50, GCR70; 50%/70% reduction in ≥ 3 of TJC, SJC, HAQ-Health, HAQ-Pain). Least-square mean (±SE) CFB to Week 52 was estimated using a mixed-model for repeated measures. Results 100 patients were randomized to pegloticase+MTX; 52 to pegloticase+PBO. At baseline, patients had poor overall health (HAQ-Health [MTX, PBO]: 44.9 ± 28.6, 39.1 ± 27.4; PhGA: 5.5 ± 2.1, 5.4 ± 2.2) and many affected joints (TJC: 5.4 ± 7.8, 6.7 ± 8.4; SJC: 8.3 ± 12.2, 11.0 ± 15.9). QOL progressively improved during treatment, with similar CFB at Week 52 in MTX vs.s PBO groups in PhGA (-4.2 ± 0.2 vs.s-3.8 ± 0.3) and TJC/SJC (-6.1 ± 0.5 vs.s -7.0 ± 0.8/-5.1 ± 0.4 vs.s -6.0 ± 0.6). However, at Week 52, more MTX patients met GCR50 (58.0% vs.s 38.5%) and GCR70 (52.0% vs.s 30.8%) criteria. Conclusion In the MIRROR RCT, pegloticase treatment with or without MTX co-therapy led to meaningful clinical/QOL improvements in uncontrolled gout patients. However, patients receiving MTX co-therapy had greater benefit because of a higher sustained SU-lowering rate (60.0% vs.s 30.8% in the PBO group at Week 52). Trial registration ClinicalTrials.gov, NCT03994731

Diaphragmatic morgagni in adult: a case report

A 70-year-old male patient with a history of systemic hypertension, gouty arthritis, and possible chronic kidney disease presented with right flank pain, nausea, and decreased appetite. Examinations revealed a right-sided incarcerated diaphragmatic hernia in the anterior region, with protrusion of adipose tissue and loops of small intestine. A laparoscopic surgery was performed, during which the herniated contents were reduced, and a hernia defect approximately 4 cm in size was found and repaired. Post-surgery, he developed complications including pulmonary thromboembolism, intestinal perforation, and fistula, which required reoperation, and progressive clinical deterioration, ultimately leading to death. This case report presents a rare instance of congenital hernia diagnosed through imaging after the onset of nonspecific clinical symptoms. It emphasizes the importance of considering this pathology among differential diagnoses of acute abdomen for prompt diagnosis and appropriate management through surgical intervention.

Resolution of acute inflammation induced by monosodium urate crystals (MSU) through neutrophil extracellular trap-MSU aggregate-mediated negative signaling

BackgroundPolymorphonuclear neutrophils (PMN) activation by monosodium urate crystals (MSU) is crucial to acute gouty arthritis and subsequent spontaneous remission within 7–10 days. Activated PMNs release neutrophil extracellular traps (NETs) that entrap MSU crystals, forming NET-MSU aggregates. Whether NET-MSU aggregates contribute to the resolution of acute inflammation remains to be elucidated. This study uses a cell-based approach to unveil their molecular bases.MethodsAll-trans retinoic acid-differentiated HL-60 cells (dHL-60) served as surrogate PMNs. NET release from MSU-activated dHL-60 was confirmed by detecting DNA, neutrophil elastase, and citrullinated histone 3, forming large NET-MSU aggregates. NET area was measured with Fiji software after SYTOX Green staining. Released pro-inflammatory cytokines IL-8 and TNF-α, and the anti-inflammatory cytokine IL-1RA in culture supernatants were quantified to calculate the estimate inflammation score (EIS). Cellular redox state was determined by a FRET-based sensor. Expression of intracellular positive (ERK1/2) and negative (SHP-1 and SHIP-1) cytokine signaling regulators was detected by western blot. qPCR detected mRNA expressions of CISH and SOCS1–SOCS7. Flow cytometry measured neutrophil N1 (CD54) and N2 (CD182) surface markers after staining with fluorescent-conjugated antibodies.ResultsIncubating dHL-60 with MSU for 4 h maximized NET-MSU aggregate formation and acute inflammation with an EIS of 11.6. Prolonging the incubation of dHL-60 + MSU to 22 h gradually raised the EIS to 19.40 without increasing NET area, due to reduced cellular redox capacity. Adding both new dHL-60 and new MSU crystals to the culture, mimicking the clinical scenario, increased NET area but conversely suppressed EIS to 1.53, indicating acute inflammation resolution. The resolution of acute inflammation following prolonged incubation was attributed to decreases in P-ERK and increases in P-SHP-1, SOCS2, SOCS3, and CISH gene expressions, which may suppress pro-inflammatory and enhance anti-inflammatory cytokine production. Moreover, the large NET-MSU aggregates facilitated N1 to N2 polarization, crucial for accelerating inflammation resolution.ConclusionWe explored the potential molecular basis for the spontaneous resolution of MSU induced acute inflammation using a cell-based model in that huge NET-MSU aggregates frustrate the transformation of newly entering PMNs to the N2 phenotype, enhancing the production of the anti-inflammatory cytokine IL-1RA.

Bioinformatics and molecular docking reveal Cryptotanshinone as the active anti-inflammation component of Qu-Shi-Xie-Zhuo decoction by inhibiting S100A8/A9-NLRP3-IL-1β signaling

BackgroundGout is a common type of arthritis marked by monosodium urate (MSU) crystal deposition in joints, triggering an inflammatory response. Qu-Shi-Xie-Zhuo (QSXZ), a traditional Chinese medicine (TCM) formula, has been clinically used for the treatment of gouty arthritis (GA). PurposeThe study sought to examine the impact of QSXZ on GA and to delve into the pharmacological mechanisms that underlie its effects. MethodsThe chemical constituents of QSXZ were analyzed through UPLC-MS. MSU-induced acute gouty arthritis (AGA) and subcutaneous (SC) air pouch models in mice were employed to evaluate the anti-inflammatory properties of QSXZ and its primary active compound, Cryptotanshinone (CTS). To investigate the therapeutic mechanisms of QSXZ, we used MS-based network pharmacology, transcriptomic analysis, molecular docking and multiscale bioassays. ResultsTreatment of QSXZ revealed a significant reduction of inflammatory cell infiltration and the expression of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin -1β (IL-1β). Based on UPLC/MS/MS results, 49 components were considered the active ingredients of QSXZ. Network pharmacology analysis indicated that QSXZ regulates multiple inflammation-related pathways. Subsequent transcriptomic analysis showed that QSXZ regulates gene expression of S100A8 and S100A9. Our investigation observed an increased expression of S100A8 and S100A9 in monocytes derived from gout patients. Molecular docking and molecular dynamics simulation analysis revealed the binding pattern and interaction between QSXZ active compound CTS and S100A8/A9, and subsequent surface plasmon resonance (SPR) and cell thermal shift assay (CETSA) experiments verified the direct interaction between them. To investigate the mechanisms of action, we conducted RT-PCR, Western blotting, immunohistochemistry, flow cytometry, and measured the inflammatory response. Our findings highlight the pathogenic role of S100A8/A9 mediated TLR4-NLRP3 axis in gout and review outstanding therapeutic effects of QSXZ and its primary active compound CTS on MSU-induced experimental models. ConclusionsIn summary, this study substantiates the therapeutic potential of QSXZ and its primary active compound CTS, as promising alternative treatments for GA. Our findings provide valuable insight into the critical pharmacological mechanism of QSXZ in regulating inflammation, highlighting its potential therapeutic effects in GA management.

Novel Macrocyclic NLRP3 Inhibitors.

Aberrant activation of NLRP3 due to persistent tissue damage, misfolded proteins or crystal deposits has been linked to multiple chronic inflammatory disorders such as cryopyrin-associated periodic syndrome (CAPS), neurodegenerative diseases, gouty arthritis, and numerous others. Hence, there has been an increasing interest in NLRP3 inhibitors as therapeutics. A first generation of NLRP3 inhibitors bearing a sulfonylurea core such as MCC950 (developed by Pfizer) were discovered by phenotypic screening, however their mode of action was only elucidated later. Based on MCC950, second-generation inhibitors were developed, aiming to overcome some liabilities such as moderate potency and drug induced liver injury. During the optimization of these (second-generation) inhibitors, conformational studies led to the design of novel macrocycles. Here we report the discovery and optimization of this class of NLRP3 inhibitors.

Imaging comparative analysis of familial and sporadic gout in Chinese men by multijoint ultrasonography.

This study aimed to compare the imaging features of bilateral knees, ankles, and the first metatarsophalangeal joint using high-frequency ultrasonography in male patients with familial and sporadic primary gout and sought to elucidate the relationship between the presence of tophi and various clinical indicators. Male patients with primary gouty arthritis (GA) in the acute phase presenting to the Department of Rheumatology and Immunology at the First Affiliated Hospital of Chengdu Medical College from November 2020 to June 2022 were enrolled and classified into familial and sporadic gout groups. Comparative analyses of their clinical data and ultrasonographic imaging findings of the knees, ankles, and first metatarsophalangeal joints were performed between the groups. Univariate and multivariate logistic regression analyses, as well as receiver operating characteristic (ROC) analysis, were conducted to determine the effectiveness of significant factors in the prediction of tophi. In comparison to male patients with sporadic gout, those with familial primary gout exhibited lower age, body mass index, disease duration, and serum uric acid (SUA) levels. However, they demonstrated higher incidences of tophi and bone erosion (54.6% in familial gout vs. 35.1% in sporadic gout, p < 0.05; 71.2% in familial gout vs. 48.1% in sporadic gout, p < 0.05, respectively), with a greater prevalence of tophi in the right first metatarsophalangeal joint (44.2% in familial gout vs. 32.3% in sporadic gout, p < 0.05). Independent risk factors for tophi included family history (OR = 6.712), age (OR = 1.049), disease duration (OR = 1.134), and SUA levels (OR = 1.006). ROC analysis yielded an area under the curve of 0.883 (p < 0.05) for predicting joint tophi using these factors. Male patients with familial primary GA in the acute phase experienced earlier onset, shorter disease duration compared to those with sporadic gout. They also had more affected joints, more frequent and a wider distribution of tophi, especially in the right first metatarsophalangeal joint. Family history, age, disease duration, and SUA levels are predictive of tophi formation.

Disruption of survivin protein expression by treatment with YM155 accelerates the resolution of neutrophilic inflammation.

Prolonged survival of neutrophils is essential for determining the progression and severity of inflammatory and immune-mediated disorders, including gouty arthritis. Survivin, an anti-apoptotic molecule, has been described as a regulator of cell survival. This study aims to examine the effects of YM155 treatment, a survivin selective suppressant, in maintaining neutrophil survival in vitro and in vivo experimental settings of neutrophilic inflammation. BALB/c mice were injected with monosodium urate (MSU) crystals and treated with YM155 (intra-articularly) at the peak of inflammatory response. Leukocyte recruitment, apoptosis neutrophil and efferocytosis were determined by knee joint wash cell morphology counting and flow cytometry. Resolution interval (Ri) was quantified by neutrophil infiltration, monitoring the amplitude and duration of the inflammation. Cytokine production was measured by ELISA. Mechanical hypernociception was assessed using an electronic von Frey aesthesiometer. Efferocytosis was evaluated in zymosan-induced neutrophilic peritonitis. Survivin and cleaved caspase-3 expression was determined in human neutrophils by flow cytometry. Survivin was expressed in neutrophils during MSU-induced gout, and the treatment with YM155 reduced survivin expression and shortened Ri from ∼8 h observed in vehicle-treated mice to ∼5.5 h, effect accompanied by increased neutrophil apoptosis and efferocytosis, both crucial for the inflammation resolution. Reduced IL-1β and CXCL1 levels were also observed in periarticular tissue. YM155 reduced histopathological score and hypernociceptive response. In human neutrophils, lipopolysaccharide (LPS) increased survivin expression, whereas survivin inhibition with YM155 induced neutrophil apoptosis, with activation of caspase-3. Survivin may be a promising therapeutic target to control neutrophilic inflammation.

Performance of novel multiparametric second-generation dual-layer spectral detector CT in gouty arthritis.

This study aimed to compare the performance of different dual-energy computed tomography (DECT) technologies in detecting monosodium urate (MSU) crystals and evaluate the potential clinical value of novel second-generation dual-layer spectral detector CT (dlDECT) in gouty arthritis. Using data collected from a tertiary hospital, we examined the diagnostic accuracy of different DECT technologies for the diagnosis of MSU. We used two standards: (1) demonstration of MSU crystals in synovial fluid (gold) and (2) 2015 ACR/EULAR gout classification criteria (silver). Furthermore, six novel spectral parameters derived from dlDECT were quantitatively calculated and analyzed for MSU diagnostic efficiency. Of the 243 patients with 387 joints, 68 (27.98%) had synovial fluid analysis. Compared with the gold standard, MSU diagnostic accuracy statistics for dlDECT, dual-source DECT (dsDECT) and rapid kilovolt peak switching DECT (rsDECT) were as follows: area under the curve (AUC): 0.85, 0.80 and 0.75, respectively. Findings were replicated compared with the silver standard. Multiparametric analysis in dlDECT demonstrated the highest MSU detection rate (92.86%), significantly higher than rsDECT (42.08%) and dsDECT (85.80%). Among novel parameters in dlDECT, Calcium-suppressed index 25 (CaSupp-I 25) exhibited the best performance in distinguishing materials (MSU, muscle, and bone), with an AUC of 0.992. The differentiation was also aided by histograms, scatter plots, and attenuation curves. The novel dlDECT is likely not inferior to other DECT technologies in MSU detection, especially its spectral parameter CaSupp-I 25. Multiparameter analysis showed the potential value for detecting MSU crystals in gouty arthritis, providing valuable clinical insights for gout diagnosis. Question The performance of different DECT technologies in detecting monosodium urate (MSU), and the value of dual-layer spectral detector CT (dlDECT) in gouty arthritis remains unclear. Findings The dlDECT was likely not inferior to other DECT technologies in MSU detection, and its multiparametric analysis provided valuable information for MSU diagnosis. Clinical relevance Novel dlDECT may improve the accurate detection of MSU crystals in gouty arthritis compared to other DECT technologies, providing valuable clinical insights and potentially improving patient outcomes for more precise gout diagnosis.

Unraveling the impact of miRNAs on gouty arthritis: diagnostic significance and therapeutic opportunities.

Gouty arthritis is a prevalent inflammatory illness. Gout attacks begin when there is an imbalance in the body's uric acid metabolism, which leads to urate buildup and the development of the ailment. A family of conserved, short non-coding RNAs known as microRNAs (miRNAs) can regulate post-transcriptional protein synthesis by attaching to the 3' untranslated region (UTR) of messenger RNA (mRNA). An increasing amount of research is pointing to miRNAs as potential players in several inflammatory diseases, including gouty arthritis. miRNAs may influence the progression of the disease by regulating immune function and inflammatory responses. This review mainly focused on miRNAs and how they contribute to gouty arthritis. It also looked at how miRNAs could be used as diagnostic, prognostic, and potential therapeutic targets.

Research hotspots and trends related to pain in gouty arthritis from 2014 to 2024: A bibliometric analysis.

Gouty arthritis is a metabolic condition caused by disordered purine metabolism and elevated uric acid levels. This study adopts a bibliometric approach to analyze current research on pain in gouty arthritis and forecast future research trends. Retrieve relevant research on gouty arthritis pain in the Web of Science core collection database, screen literature, and use visualization software such as CiteSpace, Vosviewers, and R package "Bibliometrix" for analysis. The total number of documents included was 1133, with 909 articles and 224 reviews. Between 2014 and 2024, there was an overall upward trend in the number of publications about pain in gouty arthritis, with the United States of America and China ranking first and second, respectively, in terms of publication volume. The UNIVERSITY OF ALABAMA BIRMINGHAM had the most publications, and Professor DALBETH N played a key role in this field. According to the keyword analysis, disease management and treatment, particularly methods for enhancing patients' quality of life and reducing symptoms, are research hotspots. For a deeper understanding, attention is also being paid to the epidemiology and pathological mechanisms of the disease. Emerging keywords such as "gut microbiota" and "urate-lowering therapies" indicate growing interest in the interrelationship between gut microbiota and gout, and the development of new treatment methods. This bibliometric study reveals that research on gouty arthritis pain is actively developing. Current hot topics reflect investigations into the deeper pathological mechanisms of gouty arthritis and the development of new treatment methods, including urate-lowering therapies. There is also increasing attention on the role of gut microbiota in the disease. Despite limitations such as the preliminary nature of research methods and insufficient interdisciplinary collaboration, future research directions aim to improve the rigor of research design, strengthen international cooperation, promote unified treatment guidelines, and optimize the diagnosis and treatment of gouty arthritis with new technologies like artificial intelligence, precision medicine, and nanomedicine. This will drive the field towards a deeper scientific understanding, more effective treatment methods, and more comprehensive disease management, ultimately improving patients' prognosis and quality of life.

Material decomposition approaches for monosodium urate (MSU) quantification in gouty arthritis: a (bio)phantom study

BackgroundDual-energy computed tomography (DECT) is a noninvasive diagnostic tool for gouty arthritis. This study aimed to compare two postprocessing techniques for monosodium urate (MSU) detection: conventional two-material decomposition and material map-based decomposition.MethodsA raster phantom and an ex vivo biophantom, embedded with four different MSU concentrations, were scanned in two high-end CT scanners. Scanner 1 used the conventional postprocessing method while scanner 2 employed the material map approach. Volumetric analysis was performed to determine MSU detection, and image quality parameters, such as signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), were computed.ResultsThe material map-based method demonstrated superior MSU detection. Specifically, scanner 2 yielded total MSU volumes of 5.29 ± 0.28 mL and 4.52 ± 0.29 mL (mean ± standard deviation) in the raster and biophantom, respectively, versus 2.35 ± 0.23 mL and 1.15 ± 0.17 mL for scanner 1. Radiation dose correlated positively with detection for the conventional scanner, while there was no such correlation for the material map-based decomposition method in the biophantom. Despite its higher detection rate, material map-based decomposition was inferior in terms of SNR, CNR, and artifacts.ConclusionWhile material map-based decomposition resulted in superior MSU detection, it is limited by challenges such as increased artifacts. Our findings highlight the potential of this method for gout diagnosis while underscoring the need for further research to enhance its clinical reliability.Relevance statementAdvanced postprocessing such as material-map-based two-material decomposition might improve the sensitivity for gouty arthritis in clinical practice, thus, allowing for lower radiation doses or better sensitivity for gouty tophi.Key PointsDual-energy CT showed limited sensitivity for tophi with low MSU concentrations.Materiel-map-based decomposition increased sensitivity compared to conventional two-material decomposition.The advantages of material-map-based decomposition outweigh lower image quality and increased artifact load.Graphical

Co-regulated ceRNA network mediated by circRNA and lncRNA in patients with gouty arthritis

Numerous studies have demonstrated the involvement of messenger RNAs (mRNAs) and non-coding RNAs, including long non-coding RNAs (lncRNA), circular RNAs (circRNAs) and microRNA (miRNAs), in gouty arthritis onset; however, the regulatory mechanism has not yet been elucidated. Here, we applied whole-transcriptome sequencing to identify the differentially expressed circRNAs, lncRNAs, miRNAs and mRNAs between the gout patients and normal people, and constructed co-regulated networks of circRNAs and lncRNAs according to the competitive endogenous RNA (ceRNA) theory for gouty arthritis onset to improve our understanding of the pathogenesis of this disease. The most significant finding of this study is the co-regulated ceRNA network of circRNAs and lncRNAs in gouty arthritis. The circRNA novel_circ_0030384 and the lncRNAs AAMP, TRIM16, PKN1, XLOC_184579 and XLOC_189826 were upstream genes in the co-regulated network. These upstream genes upregulated miR550a-5p and miR550a-3-5p, which downregulated PSME1 and FERMT3 expression. These mRNAs participated in proteasome dynamics, antigen processing and presentation, and platelet activation, which are associated with inflammation in gouty arthritis. In addition, the circRNA and lncRNAs upregulated miR550a-5p, which downregulated GRK2 and OS9 expression. Also, it proved that the down-regulated of PSME1, FERMT3, GRK2 and OS9 can aggravate gouty arthritis in vitro. In summary, these genes mediate inflammation in gouty arthritis through chemokine signaling to regulate neutrophil function.

Network pharmacology and transcriptomics explore the therapeutic effects of Ermiao Wan categorized formulas for diabetes in mice

Ermiao wan (EMW) is a classical traditional Chinese medicine formula, with two modified versions including Sanmiao wan (SMW) and Simiao wan (FMW). These Ermiao wan categorized formulas (ECFs) are traditionally used to treat gouty arthritis and hyperuricemia. However, their potential benefits and mechanisms on diabetes remain to be explored. This study aims to investigate the overall effects and biological differences of ECFs in high fat diet (HFD)-fed mice based on network pharmacology and transcriptomics. ECFs significantly reduced body weight, improved oral glucose tolerance, decreased fat accumulation, and lowered serum insulin and inflammatory cytokine levels in HFD-fed mice. FMW had better efficacy than EMW and SMW. Network pharmacology analysis revealed that ECFs targeted functional modules associated with chronic inflammation, lipid metabolism, and glucose metabolism. Transcriptome results also showed ECFs could inhibit genes associated with inflammation and upregulated some genes in lipid metabolism. Comprehensive analysis and QPCR verification indicated the beneficial effects of ECFs on diabetes might be attributed to the regulation of Ddit3, Ccl2, Esr1, and Cyp7a1. This study provides a theoretical basis for the clinical use of ECFs.

Investigating the mechanisms of resveratrol in the treatment of gouty arthritis through the integration of network pharmacology and metabolics.

This study integrates network pharmacology and metabolomics techniques to explore the potential regulatory mechanisms of Res on gouty arthritis (GA). Network pharmacology was used to predict the mechanism of Res in regulating GA, and methods such as HE staining, ELISA, immunohistochemistry, Real-time PCR, Western blot, and molecular docking were used to verify the role of NF-κB, MAPK, and JAK/STAT inflammatory signaling pathways in the MSU-induced GA rat model. In addition, non-targeted metabolomics techniques were combined to further investigate the mechanism of Res in treating GA. The results of network pharmacology showed that Res may exert its therapeutic effects through the NF-κB signaling pathway. Animal experiments demonstrated that in the MSU-induced GA rat model, pathological damage, serum biochemical indicators, and levels of inflammatory factors were significantly increased, and the NF-κB signaling pathway was activated. The intervention of Res significantly reduced pathological damage, serum biochemical indicators, levels of inflammatory factors, and the activation of NF-κB, MAPK, and JAK/STAT signaling pathways in the model rats. Metabolomics results showed that Res could improve the metabolic trajectory deviations in serum and joint fluid of GA model rats. Through related metabolic pathway analysis, the most affected metabolic pathways were found to be Sphingolipid metabolism, Glycerophospholipid metabolism, Phenylalanine, tyrosine and tryptophan biosynthesis, Pantothenate and CoA, Citrate cycle (TCA cycle), and Arachidonic acid metabolism. Resveratrol can regulate the biosynthetic pathways of arachidonic acid, phenylalanine, tyrosine, and tryptophan, pantothenic acid and CoA biosynthesis pathways, TCA cycle, and other metabolic pathways, thereby regulating the NF-κB, MAPK, and JAK/STAT3 signaling pathways, and inhibiting the acute inflammatory response during GA attacks, showing characteristics of multi-pathway and multi-target action.

Zinc oxide nanoparticles made with Phyla nodiflora leaf extract have anti-hyperuricemic effect on monosodium urate crystal-induced gouty arthritis

Zinc oxide nanoparticles made with Phyla nodiflora leaf extract have anti-hyperuricemic effect on monosodium urate crystal-induced gouty arthritis

Benzoylmesaconine mitigates NLRP3 inflammasome-related diseases by reducing intracellular K+ efflux and disrupting NLRP3 inflammasome assembly

BackgroundBenzoylmesaconine (BMA), a major alkaloid derived from the traditional Chinese medicine Aconitum carmichaeli Debx, exhibits potent anti-inflammatory properties. However, the precise mechanism underlying its action remains unclear. PurposeThis study aimed to investigate the inhibitory mechanism of BMA on the NLRP3 inflammasome and assess its therapeutic efficacy in NLRP3-related metabolic diseases. MethodsA classic NLRP3 inflammasome-activated bone marrow-derived macrophage (BMDM) model was established to evaluate BMA's effects on NLRP3 upstream and downstream protein expression, as well as pyroptosis. Two distinct animal disease models, MSU-induced gouty arthritis and DSS-induced colitis, were utilized to validate BMA's anti-inflammatory activity in vivo. ResultsIn vitro findings revealed that BMA can suppress NLRP3 inflammasome activation by inhibiting interleukin-1β (IL-1β) secretion and GSDMD-N protein expression. This mechanism involved blocking intracellular K+ efflux and interfering with the formation of NLRP3 inflammasomes. In vivo studies demonstrated that BMA significantly alleviated inflammatory symptoms in MSU-induced acute gout and DSS-induced colitis models. ConclusionThese findings suggest that BMA effectively inhibits the activation of the NLRP3 signaling pathway through dual mechanisms: reducing intracellular K+ efflux and disrupting NLRP3 inflammasome assembly. This multifaceted action highlights the therapeutic potential of BMA for NLRP3-related diseases.