Gout Research Articles

ZnO Nanocages Decorated with Au@AgAu Yolk-Shell Nanomaterials for SERS-Based Detection of Hyperuricemia.

Surface-enhanced Raman scattering (SERS) is widely recognized as a highly sensitive technology for chemical detection and biological sensing. In SERS-based biomedical applications, developing highly efficient sensing platforms based on SERS plays a pivotal role in monitoring disease biomarker levels and facilitating the early detection of cancer biomarkers. Hyperuricemia, characterized by abnormally high concentrations of uric acid (UA) in the blood, was associated with a range of diseases, such as gouty arthritis, heart disease, and acute kidney injury. Recent reports have demonstrated the correlation between UA concentrations in blood and tears. In this work, we report the fabrication of SERS substrates utilizing ZnO nanocages and yolk-shell-structured plasmonic nanomaterials for the noninvasive detection of UA in tears. This innovative SERS substrate enables noninvasive and sensitive detection of UA to prevent hyperuricemia-related diseases.

THE MULTIFUNCTIONAL ROLE OF HERBAL PRODUCTS IN THE MANAGEMENT OF GOUT (VATARAKTA): A COMPREHENSIVE REVIEW

Introduction: Vatarakta is a Vata Vyadhi that occurs due to exacerbated Vata and Rakta Dosha by their causa-tive factors. It can occur in the whole body but since joints of the hand and foot are more affected it resembles gouty arthritis as described in allopathic science. Gout is a disease described in conventional medicine that has similarities to the Vatarakta. It is a type of inflammatory arthritis that is triggered by the crystallization of uric acid within the joints and is often associated with hyperuricemia. Hyperuricemia can be caused by overproduc-tion of uric acid, or, more commonly by inefficient excretion by the kidneys. The clinical presentation of gout ranges from the typical episodic acute inflammation of the joint to chronic tophaceous gout, chronic polyarticular arthritis, urate nephrolithiasis, and interstitial nephropathies. Several herbal drugs are well known for their thera-peutic effects and lower toxicity and are important substances for new drug development. Objective: The objective of this systematic review was to explore and validate the efficacy of herbal medicines in the management of gout. This review aims to update some research findings regarding the biological activities of the herbal ingredients of Ayurvedic medicines used in gout and also to collect an adequate basis for the opti-mal integration of Ayurvedic medicines into the conventional health system (Allopath). Materials & Methods: Systematic literature searches were carried out and the available information on Vatarak-ta and gout was collected via electronic search and a library search for articles published in peer-reviewed jour-nals and locally available books. Literature searches were also carried out to find the biochemical effects of vari-ous herbs mentioned in the management of hyperuricemia and gout. Conclusion: It has been demonstrated that plant-derived biochemicals have a potential effect on gout. These ef-fects comprise XOD inhibitory action, uricosuric, anti-inflammatory, anti-oxidant effects, etc. During the analy-sis of the literature available in Ayurveda, Allopathy, and related other branches of health science it was found that integrative medicine would be the optimal strategy to develop more effective agents in the treatment of gout (Vatarakta) and a combination of therapies may be very effective in reducing both the effect and frequency of disease.

Comparison of efficacy of acupuncture-related therapies in treating Acute Gouty Arthritis: A Network Meta-Analysis of Randomized Controlled Trials

Backgroundand purpose: Acupuncture and moxibustion, as a complementary and alternative therapy, has been widely used in the treatment of acute gouty arthritis (AGA). However, there are various forms of acupuncture and moxibustion, and the curative effect of different forms is different. This study evaluated the clinical efficacy of different acupuncture therapies in treating AGA by network meta-analysis. MethodsComputer searches of English databases (including PubMed, The Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Embase) and Chinese databases (including China National Knowledge Infrastructure (CNKI), VIP Database, Wanfang Database and China Biomedical Literature Database) were conducted for randomized controlled trials (RCTs) of acupuncture therapies in treating AGA. We set the search time from the database establishment to May 2022. Data analysis was performed using Stata14.2 software. ResultsThirty-two RCTs involving 2434 patients with AGA were screened out. The results showed that in terms of the improvement of pain visual analogue scale (VAS) scores, the top ones were acupoint application (100%), electroacupuncture + Western medicine (73.5%) and acupuncture + Western medicine (69.2%); In terms of total effective rate, acupoint application (85.2%), acupuncture (75.2%) and acupuncture + Western medicine (63%) ranked the top; In terms of reducing serum uric acid (SUA) levels, the top ones were acupoint application (95%), acupuncture + Western medicine (87.5%) and acupuncture (66.2%); In terms of the reduction of erythrocyte sedimentation rate (ESR), acupuncture (95%), acupoint application (84.7%), and electroacupuncture + Western medicine (52.8%) were the most prominent. ConclusionThe existing evidence shows that acupoint application has more advantages in improving the total effective rate, improving pain and reduce SUA levels, and acupuncture has an advantage in reducing ESR levels and adverse events. However, due to the low qualities of the original studies, the quality of this evidence is poor. Therefore, it is recommended that more scientific research be performed to confirm the efficacy of acupuncture.

WN1703 alleviates gout symptoms via inflammatory signaling pathways in an acute gout rat model

We previously synthesized the xanthine oxidoreductase (XOR) inhibitor WN1703. In addition to showing XOR inhibitory effects, WN1703 also showed anti-inflammatory effects in a rat hyperuricemia model. Here, we studied WN1703's anti-inflammatory effects on gout and explored the underlying mechanisms. Tohoku Hospital Pediatrics-1 (THP-1) cells were stimulated by lipopolysaccharide/interferon-γ/monosodium urate (MSU). The levels of inflammatory cytokines in the supernatant and protein expression in THP-1 cells were detected using enzyme-linked immunosorbent assay (ELISA) kits and western blotting, respectively, to verify the inhibitory effects of WN1703 and its mechanism. Potassium oxonate, hypoxanthine, and MSU were administered to establish a hyperuricemia rat model complicated by acute gouty arthritis. At 1–24 h after MSU injection, the degree of ankle swelling was recorded to compare the anti-inflammatory effects at each time point. The potential mechanism was further explored using immunohistochemistry and ELISA. WN1703 significantly downregulated expression of nucleotide-binding oligomerization domain-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, toll-like receptor-4 (TLR4), myeloid differentiation primary response protein 88 (MyD88), nuclear factor-kappa B (NF-κB), and relevant cytokine levels in THP-1 cells. Identical doses of WN1703 and febuxostat had comparable effects on these proteins and cytokines. In the gout rats, the same dose of WN1703 and febuxostat showed equivalent inhibitory effects on NLRP3, ASC, and NF-κB; however, WN1703 showed weaker impacts on alleviating ankle swelling than febuxostat showed. In conclusion, WN1703 showed significant anti-inflammatory effects in hyperuricemic rats with acute gout. Such effects were related to the inhibition of the NLRP3/ASC/Caspase-1 and TLR4/MyD88/NF-κB signaling pathways, thereby downregulating inflammation-related protein expression and decreasing inflammatory cytokine secretion.

Analyzing chemical composition of Sargentodoxae caulis water extract and their hypouricemia effect in hyperuricemic mice

Hyperuricemia (HUA) is a metabolic disease characterized by the increase of serum uric acid (UA) level. Sargentodoxae Caulis (SC) is a commonly used herbal medicine for the treatment of gouty arthritis, traumatic swelling, and rheumatic arthritis in clinic. In this study, a total of fifteen compounds were identified in SC water extract using UHPLC-Q-TOF-MS/MS, including three phenolic acids, seven phenolic glycosides, four organic acids, and one lignan. Then, to study the hypouricemia effect of SC, a HUA mouse model was induced using a combination of PO, HX, and 20% yeast feed. After 14 days of treatment with the SC water extract, the levels of serum UA, creatinine (CRE), blood urea nitrogen (BUN) were reduced significantly, and the organ indexes were restored, the xanthine oxidase (XOD) activity were inhibited as well. Meanwhile, SC water extract could ameliorate the pathological status of kidneys and intestine of HUA mice. Additionally, quantitative real-time PCR (qRT-PCR) and western blotting results showed that SC water extract could increase the expression of ATP binding cassette subfamily G member 2 (ABCG2), organic cation transporter 1 (OCT1), organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3), whereas decrease the expression of glucose transporter 9 (GLUT9). This study provided a data support for the clinical application of SC in the treatment of HUA.

Alterations in articular cartilage frictional properties in the setting of acute gouty arthritis.

The tribological behaviour of articular cartilage plays a key role in joint motion; however, there is a gap in research on the effect of hyperuricemic joint fluid on cartilage friction behaviour in acute gouty arthritis. In this study, we carried out a fixed-load scratch experiment to compare the friction and wear of articular cartilage under the lubrication of gouty arthritis arthritic fluid and normal human arthritic fluid, and the results showed that the cartilage friction coefficient of patients with acute gouty arthritis was significantly larger than that of normal human beings, and that the cartilage friction coefficient decreased with the elevation of normal load and sliding speed, and the change with the sliding speed varied more differently from that of normal human beings, and that the cartilage surface wear was more severe after prolonged friction. The wear and tear of the cartilage surface is more severe after prolonged friction. Patients with gouty arthritis should reduce the sudden speed changes such as fast running and variable speed running to maintain the stability of the cartilage surface friction coefficient.

Diagnostic values of different musculoskeletal ultrasound signs, serum uric acid, and their combined detection for gouty arthritis.

The study aimed to investigate the diagnostic values of different musculoskeletal ultrasound (MSUS) signs, serum uric acid (SUA), and their combined detection for gouty arthritis (GA). In this retrospective study, 70 patients (62 males, 8 females; mean age: 46.1±14.1 years; range, 25 to 86 years) diagnosed with GA (the GA group) between August 2022 and March 2023 and 70 patients (54 females, 16 males; mean age: 49.0±14.1 years; range, 21 to 75 years) diagnosed with rheumatoid arthritis and osteoarthritis during the same period (the non-GA group) were included. The positive rate of MSUS signs and SUA in both groups was recorded to compare the differences. The correlations of MSUS signs and SUA with GA were analyzed using Spearman's rank correlation analysis. The diagnostic values of different MSUS signs, SUA, and their combined detection for GA were analyzed using a receiver operating characteristic, the area under the curve (AUC), sensitivity, specificity, and the Youden index. The positive rate of the double contour (DC) sign (chi-squared [χ2 ]=102.935, p<0.001), hyperechoic spots (χ2=56.395, p<0.001), bone erosions (χ2 =10.080, p<0.001), and SUA (χ2 =41.117, p <0.001) were higher in the GA group than in the non-GA group. The positive rate of the DC sign (rs=0.829, p=0.001), hyperechoic spots (rs=0.631, p<0.001), bone erosion (rs=0.268, p=0.001), and SUA (rs=0.542, p<0.001) were positively correlated with GA. Among the single-indicator measures, the DC sign exhibited the highest diagnostic value (AUC=0.907, sensitivity=81.4%, specificity=100%, p<0.001). Among the combined-indicator measures, the DC sign combined with SUA exhibited the highest diagnostic value (AUC=0.929, sensitivity=91.4%, specificity=94.3%, p<0.001), higher than DC sign detection alone. The DC sign combined with SUA yielded a high diagnostic value and can thus provide a reliable basis for effectively and efficiently diagnosing GA.

Investigation of Chemical Compounds and Effect of Astragalus Galactites (Pall.) on MSU Crystal-Induced Acute Gouty Arthritis in Rats

The objective of the present investigation is to identify the biologically active components of Astragalus galactites (AG) and examine their effect on rats of acute gouty arthritis induced by crystals of the compound monosodium urate (MSU). Analyses of AG chemical constituents and their antioxidant activity were performed using both UV spectrophotometric and HPLC methods. Twenty-five adult Wistar rat males in total were assigned at random to a choice of five groups: AG 160 mg/kg, AG 330 mg/kg, MSU group, control group, and normal group. We reported the contents of Formononetin 1.97 µg/mL, Astragaloside IV 0.56 mg/mL, and total flavonoid 0.22±0.07% in the aerial part of our sample AG. In the DPPH scavenging assay, methanol and ethanol extracts established antioxidant properties with an IC50 concentration of 91.04 µg/mL and 93.13 µg/mL, respectively. In the ABTS scavenging assay, IC50 concentrations of 387.2 µg/mL (methanol extract) and 436.2 µg/mL (ethanol extract) were also shown. This investigation also looked at the histopathological characteristics related to MSU-induced gouty arthritis in order to assess the preventive effects of the AG plant on inflammatory mediator levels. In the AG 330 mg/kg group, the level of PGE2 significantly reduced (p&lt;0.001). Our results showed that the AG 330 mg/kg group was relatively effective in the treatment of gouty arthritis compared to other groups, which appears to be mediated by inhibiting the release of cytokines that pro-inflammation. The main compounds of the AG medicine plant, flavonoids and saponins, are acutely anti-gout due to the resulting decrease in PGE2 levels. We have hypothesized that it is able to treat acute gouty arthritis by reducing levels of UA and PGE2, providing an anti-inflammatory effect. This study contributes to the body of evidence that AG can be utilized in preventing and treating hyperuricemia.

Efficacy and safety of Huzhang Granule, a compound Chinese herbal medicine, for acute gouty arthritis: A double-blind, randomized controlled trial

BackgroundAcute gouty arthritis (AGA) is an inflammatory joint disease with a high prevalence. Typical medical interventions, including nonsteroidal anti-inflammatory drugs, colchicine and glucocorticoids, can have serious adverse reactions. Huzhang Granule (HZG), a compound Chinese herbal medicine, has been used to treat AGA for more than 30 years with satisfactory effects and no significant adverse reactions. However, the efficacy and safety of HZG in AGA patients remains unknown. ObjectiveThe present investigation was designed to examine the efficacy and safety profile of HZG in managing AGA patients. Design, setting, participants and interventionsThe current study was conducted as a noninferiority, randomized controlled clinical trial on 180 eligible enrolled participants. Participants were randomly assigned into the HZG and etoricoxib groups. Treatments were administered for 5 d, during which the HZG group received HZG and placebo etoricoxib, while the etoricoxib group received etoricoxib and placebo HZG in the same ratio (1:1). Main outcome measuresThe primary outcome was pain experienced by the patient in the gout-afflicted joint from days 2 to 5 of the treatment window. The pain level was measured via a visual analogue scale, ranging from 0 mm to 100 mm. The secondary outcomes comprised joint tenderness and swelling, reduction of inflammatory biomarkers, and the patient’s and investigator’s global evaluations of therapeutic response. ResultsThe mean reduction in pain was −51.22 mm (95% confidence interval [CI], [−53.42, −49.03] mm) for the HZG and −52.00 mm (95% CI, [−54.06, −49.94] mm) for the etoricoxib groups. The mean difference between the two groups was 0.78 mm (95% CI, [−2.25, 3.81] mm). All additional efficacy endpoints, covering decreased inflammation and pain relief, yielded compelling proof of noninferiority. Patients in the HZG group exhibited a comparatively lower rate of adverse events compared to those in the etoricoxib group (4.44% vs 13.33%; P ≤ 0.05). ConclusionHZG and etoricoxib groups demonstrated similar levels of analgesic effectiveness. The safety and efficacy of HZG indicates that it can be used as a potential therapeutic option for treating AGA. Trial registrationChinese Clinical Trial Registry (ChiCTR2000036970).Please cite this article as: Wang H, Chen ST, Ding XJ, Kuai L, Hua L, Li X, Wang YF, Zhang M, Li B, Wang RP, Zhou M. Efficacy and safety of Huzhang Granule, a compound Chinese herbal medicine, for acute gouty arthritis: A double-blind, randomized controlled trial. J Integr Med. 2024; 22(3): 270–278.

The NADase CD38 is a central regulator in gouty inflammation and a novel druggable therapeutic target

ObjectivesCellular NAD+ declines in inflammatory states associated with increased activity of the leukocyte-expressed NADase CD38. In this study, we tested the potential role of therapeutically targeting CD38 and NAD+ in gout.MethodsWe studied cultured mouse wild type and CD38 knockout (KO) murine bone marrow derived macrophages (BMDMs) stimulated by monosodium urate (MSU) crystals and used the air pouch gouty inflammation model.ResultsMSU crystals induced CD38 in BMDMs in vitro, associated with NAD+ depletion, and IL-1β and CXCL1 release, effects reversed by pharmacologic CD38 inhibitors (apigenin, 78c). Mouse air pouch inflammatory responses to MSU crystals were blunted by CD38 KO and apigenin. Pharmacologic CD38 inhibition suppressed MSU crystal-induced NLRP3 inflammasome activation and increased anti-inflammatory SIRT3–SOD2 activity in macrophages. BMDM RNA-seq analysis of differentially expressed genes (DEGs) revealed CD38 to control multiple MSU crystal-modulated inflammation pathways. Top DEGs included the circadian rhythm modulator GRP176, and the metalloreductase STEAP4 that mediates iron homeostasis, and promotes oxidative stress and NF-κB activation when it is overexpressed.ConclusionsCD38 and NAD+ depletion are druggable targets controlling the MSU crystal- induced inflammation program. Targeting CD38 and NAD+ are potentially novel selective molecular approaches to limit gouty arthritis.

Clinical study to Evaluate Safety and Efficacy of Boozidaan (Pyrethrum indicum) in the management of Niqris Muzmin (Chronic Gout)

Objectives: The objectives of this study were to observe the Efficacy of unani pharmacopoeial formulation Boozidan (Pyrethrum indicum) for the management of Niqris Muzmin (Chronic gout) and to observe any concomitant and adverse effects of formulation.&#x0D; Methods: This single blind, randomized and standard control clinical study was conducted between April 2021 to October 2021 for a period of 28 days. 60 patients diagnosed with chronic gout were divided into two groups, 30 Test group and 30 Control group. The test group was administered with 5g boozidaan in powder form once daily with water and the patients of control group were given tablet febuxostat 80mg once daily. Patients were followed up and improvements in subjective parameters were assessed weekly at 7th, 14th, 21st, and 29th day. Objective parameters were assessed at the baseline and at 29th day. The data obtained was subjected to statistical analysis.&#x0D; Results: Both the test and control drug were effective in reducing Serum uric acid level, ESR and CRP levels. A significant improvement in subjective and objective parameters was observed in both test and control groups and no adverse effects were observed during and after the study.&#x0D; However, the test drug had superior efficacy in reducing the objective parameters and it was statistically significant (p-value&lt;0.0001).&#x0D; Conclusion: Both Boozidaan and Febuxostat were safe and significantly effective in resolving the symptoms and signs of gouty arthritis and both have significant effect on reducing serum uric acid level.&#x0D; Keywords: Boozidaan, Chronic gout, Niqris, Febuxostat, serum uric acid, unani medicine

Urolithiasis in Primary Gout, Incidence of Clinically Presented and Asymptomatic Kidney Stones: Identification of Significant Risk Factors

Background The aim of this study is to explore the prevalence of urolithiasis in patients with primary gout as well as its correlation with other associated risk factors. Methods The study was conducted on 102 patients with primary gout, they underwent ultrasonography examination and their general, clinical, and urinalysis data were recorded for further assessment and statistical analysis. Results There were 102 patients with primary gout included in our study, 69 (67.6%) males, mean age of patients was 64.3±9.7. The overall prevalence of urolithiasis in our patients with primary gout is 37.3% and 15.7% have “silent” urolithiasis. Patients with urolithiasis (Group 1) are significantly older, 68.9±7.4-years, had a long history of gout 10.3±4.5-years, presence of tophi in 9 (23.6%) patients and more than 3 gouty arthritis attacks per year in 17(44.7%) patients. Also, patients in Group 1 have a significantly lower urine pH of 5.2±0.4 compared to patients without urolithiasis (Group 2) who have a urine pH of 6.6±0.2. Results showed that obesity, diabetes, and hyperlipidemia are significantly more common in patients with urolithiasis (Group 1) while the presence of hypertension is not significantly different between groups. Correlation between urolithiasis and parameters related to disease (duration, tophi, and more than three attacks per year) and parameters related to urinalysis (pH and crystalluria) was tested and found statistically significant. Logistic regression analyses (univariate and multivariate) of tested parameters confirmed that obesity, diabetes mellitus, and hyperlipidemia are predictive factors for the presence of urolithiasis in patients with primary gout. Conclusion There is a high prevalence of urolithiasis in patients with primary gout including asymptomatic urolithiasis, associated with the age of patients, duration, and severity of gout, obesity, diabetes, and hyperlipidemia. Therefore, ultrasonographic screening as harmless and available should be recommended in order to prevent complications.

Ascorbic acid-mediated selenium nanoparticles as potential antihyperuricemic, antioxidant, anticoagulant, and thrombolytic agents

Abstract Selenium (Se) is an important trace element that is involved in controlling oxidative stress and inflammatory disorders. Gouty arthritis is the inflammation and pain within the joints and tissues caused due to the accumulation of monosodium urate (MSU) crystals. This study aimed to investigate the antigout, antioxidant, anticoagulant, and thrombolytic potential of ascorbic acid-mediated Se nanoparticles (A-SeNPs). Different analytical techniques were used to investigate the formation of A-SeNPs. The antigout potential of the nanoparticles was carried out using MSU crystal dissolution, uric acid (UA) degradation assay, and xanthine oxidase inhibition (XOI). A-SeNPs exhibited excellent antihyperurecemic activity in a concentration-dependent manner. It was observed that at the tested concentration of 20 mg·mL−1, the A-SeNPs demonstrated significant breakage and dissolution of MSU crystals and resulted in UA degradation of 67.76%. Similarly, A-SeNPs resulted in 76% XOI with an excellent IC50 of 140 µg·mL−1. Furthermore, considerable antioxidant activity was noted for the A-SeNPs as evaluated with multiple antioxidant assays. Finally, the NPs were found to have significant anticoagulant and thrombolytic potential. Thus, it was concluded that A-SeNPs have potent antihyperuricemic, antioxidant, anticoagulant, and thrombolytic activities, making them an ideal choice for future biomedical applications.

Targeting Neutrophil Extracellular Traps in Gouty Arthritis: Insights into Pathogenesis and Therapeutic Potential.

Gouty arthritis (GA) is an immune-mediated disorder characterized by severe inflammation due to the deposition of monosodium urate (MSU) crystals in the joints. The pathophysiological mechanisms of GA are not yet fully understood, and therefore, the identification of effective therapeutic targets is of paramount importance. Neutrophil extracellular traps (NETs), an intricate structure of DNA scaffold, encompassing myeloperoxidase, histones, and elastases - have gained significant attention as a prospective therapeutic target for gouty arthritis, due to their innate antimicrobial and immunomodulatory properties. Hence, exploring the therapeutic potential of NETs in gouty arthritis remains an enticing avenue for further investigation. During the process of gouty arthritis, the formation of NETs triggers the release of inflammatory cytokines, thereby contributing to the inflammatory response, while MSU crystals and cytokines are sequestered and degraded by the aggregation of NETs. Here, we provide a concise summary of the inflammatory processes underlying the initiation and resolution of gouty arthritis mediated by NETs. Furthermore, this review presents an overview of the current pharmacological approaches for treating gouty arthritis and summarizes the potential of natural and synthetic product-based inhibitors that target NET formation as novel therapeutic options, alongside elucidating the intrinsic challenges of these inhibitors in NETs research. Lastly, the limitations of HL-60 cell as a suitable substitute of neutrophils in NETs research are summarized and discussed. Series of recommendations are provided, strategically oriented towards guiding future investigations to effectively address these concerns. These findings will contribute to an enhanced comprehension of the interplay between NETs and GA, facilitating the proposition of innovative therapeutic strategies and novel approaches for the management of GA.

Tetrandrine alleviates inflammation and promotes macrophage M2 polarization in gouty arthritis by NF-κB-mediated Lcp1.

Gouty arthritis (GA) is an inflammatory disease caused by the deposition of monosodium urate (MSU) crystals into joints. Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid extracted from the root of Stephania tetrandra and can exert an anti-inflammatory function in different diseases. Nevertheless, the specific function of TET in GA remains unclear. We established the GA mouse model by MSU injection into joints of mice. Paw volume and gait score were detected for measuring the degree of joint swelling and the situation of joint dysfunction. Western blot were utilized to test the alterations of M1-related factors (IL-6, IL-1β, TNF-α, IL-12, and iNOS) and M2-related factors (Mgl1, Mgl2, Pgc1-β, Arg-1, and IL-10). The activity of NF-κB p65 in tissues was determined. The interaction of NF-κB p65 and Lcp1 was measured by ChIP and luciferase reporter assay. Lcp1 KO mice were utilized to detect the effect of Lcp1 depletion on GA process. TET treatment markedly suppressed MSU-induced joint swelling, joint dysfunction, and joint injury in GA mice. TET can also reduce inflammatory reactions in MUS-induced mice. Furthermore, we proved that TET facilitated M2 macrophage polarization and inhibited M1 macrophage polarization in GA mice. In addition, TET was found to inhibit NF-κB activity and NF-κB-mediated Lcp1 expression. Lcp1 knockdown can improve joint injury and promote M2 macrophage polarization in GA mice, while this effect was further enhanced by TET. TET alleviates inflammation and facilitates macrophage M2 polarization in GA by NF-κB-mediated Lcp1.

Osteostatin Mitigates Gouty Arthritis through the Inhibition of Caspase-1 Activation and Upregulation of Nrf2 Expression.

Gouty arthritis results from monosodium urate (MSU) crystal deposition in joints, initiating (pro)-interleukin (IL)-1β maturation, inflammatory mediator release, and neutrophil infiltration, leading to joint swelling and pain. Parathyroid hormone-related protein (107-111) C-terminal peptide (osteostatin) has shown anti-inflammatory properties in osteoblasts and collagen-induced arthritis in mice, but its impact in gouty arthritis models remains unexplored. We investigated the effect of osteostatin on pyroptosis, inflammation, and oxidation in macrophages, as well as its role in the formation of calcium pyrophosphate dihydrate crystals and MSU-induced gouty arthritis in mice models. Osteostatin ameliorated pyroptosis induced by lipopolysaccharide and adenosine 5'-triphosphate (LPS + ATP) in mice peritoneal macrophages by reducing the expression of caspase-1, lactate dehydrogenase release, and IL-1β and IL-18 secretion. Additionally, IL-6 and tumor necrosis factor-α (TNF-α) were also decreased due to the reduced activation of the NF-κB pathway. Furthermore, osteostatin displayed antioxidant properties in LPS + ATP-stimulated macrophages, resulting in reduced production of mitochondrial and extracellular reactive oxygen species and enhanced Nrf2 translocation to the nuclei. In both models of gouty arthritis, osteostatin administration resulted in reduced pro-inflammatory cytokine production, decreased leukocyte migration, and reduced caspase-1 and NF-κB activation. These results highlight the potential of osteostatin as a therapeutic option for gouty arthritis.

Gut-immunity-joint axis: a new therapeutic target for gouty arthritis.

Gouty arthritis (GA) is an inflammatory disease characterized by pain. The primary goal of current treatment strategies during GA flares remains the reduction of inflammation and pain. Research suggests that the gut microbiota and microbial metabolites contribute to the modulation of the inflammatory mechanism associated with GA, particularly through their effect on macrophage polarization. The increasing understanding of the gut-joint axis emphasizes the importance of this interaction. The primary objective of this review is to summarize existing research on the gut-immune-joint axis in GA, aiming to enhance understanding of the intricate processes and pathogenic pathways associated with pain and inflammation in GA, as documented in the published literature. The refined comprehension of the gut-joint axis may potentially contribute to the future development of analgesic drugs targeting gut microbes for GA.

Complex Case: Acute-on-Chronic Gouty Arthritis, Septic Arthritis, and Severe Joint Deformities in a Young Adult Patient

Background: Gout is the most prevalent type of inflammatory arthritis, which can lead to inflammation in the joints. However, septic arthritis is unusual in gout.&#x0D; Case presentation: A 34-year-old male presented with lumps on the right ankle with cloudy white fluid discharge for 5 days prior to admission. The patient also has lumps observed on the left pedis, and manus bilateral. The patient regularly takes Allopurinol daily and Piroxicam prior to admission. The physical examination had a limited range of movement. Laboratory examinations found elevated uric acid, impaired renal function, elevated white blood cells, and elevated erythrocyte sedimentation rate. The patient was then referred for surgical debridement.&#x0D; Conclusion: Chronic gout marked by persistent polyarticular engagement and the formation of tophi. In individuals left untreated, septic arthritis and gout may manifest, followed by deformities of joints, which need further diagnosis and management.

Vegetarian diet induced new onset acute gouty arthritis in a middle-aged genetically predisposed male: A rare presentation

Gout is a metabolic disease characterised by acute or chronic arthritis which is due to deposition of Monosodium urate (MSU) crystals in joints and soft tissues. Classically described as a disease associated with hyperuricemia which may be due to metabolic defect in uric acid production or due to impaired renal excretion.We present a case of 45 year old nondiabetic, non-alcoholic, non-smoker male presented to orthopaedic OPD with complain of pain in right hand and left leg with restriction of joint mobility for past 14 hours.On carefully eliciting the dietary history patient revealed that he was a vegetarian and was on high purine rich diet for past 2 weeks due to family functions and various gatherings. Patient gave the history of consumption of cauliflower, mushrooms, beans along with sweetened carbonated drinks on two consecutive days before the onset of these symptoms.Serum uric acid 4.5 mg/dl, C-reactive protein was 9 mg/dl. To best of our knowledge this is the first case being reported in literatures where purine rich vegetarian diet has induced new case of gout.This kind of gout precipitation after consuming vegetarian diet is rarely reported in literature. This case report emphasizes upon the need of special caution to be taken by persons who are genetically predisposed to gout, while consuming purine rich diet like red meat, seafood, cauliflowers, spinach, rajma, Bengal gram, mushrooms, soft drinks sweetened with fructose.

Roles of the Caspase-11 Non-Canonical Inflammasome in Rheumatic Diseases.

Inflammasomes are intracellular multiprotein complexes that activate inflammatory signaling pathways. Inflammasomes comprise two major classes: canonical inflammasomes, which were discovered first and are activated in response to a variety of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), and non-canonical inflammasomes, which were discovered recently and are only activated in response to intracellular lipopolysaccharide (LPS). Although a larger number of studies have successfully demonstrated that canonical inflammasomes, particularly the NLRP3 inflammasome, play roles in various rheumatic diseases, including rheumatoid arthritis (RA), infectious arthritis (IR), gouty arthritis (GA), osteoarthritis (OA), systemic lupus erythematosus (SLE), psoriatic arthritis (PA), ankylosing spondylitis (AS), and Sjögren's syndrome (SjS), the regulatory roles of non-canonical inflammasomes, such as mouse caspase-11 and human caspase-4 non-canonical inflammasomes, in these diseases are still largely unknown. Interestingly, an increasing number of studies have reported possible roles for non-canonical inflammasomes in the pathogenesis of various mouse models of rheumatic disease. This review comprehensively summarizes and discusses recent emerging studies demonstrating the regulatory roles of non-canonical inflammasomes, particularly focusing on the caspase-11 non-canonical inflammasome, in the pathogenesis and progression of various types of rheumatic diseases and provides new insights into strategies for developing potential therapeutics to prevent and treat rheumatic diseases as well as associated diseases by targeting non-canonical inflammasomes.