How the Plants for Joints multidisciplinary lifestyle intervention achieved its effects: a mixed methods process evaluation.

BACKGROUND: Plants for Joints (PFJ) is a multidisciplinary intervention centered around a whole-food plant-based diet, physical activity, and sleep and stress management. The PFJ intervention successfully improved disease activity and symptoms in people with rheumatoid arthritis (RA) or osteoarthritis (OA), respectively, and metabolic health. To investigate how these effects were achieved a mixed methods process evaluation was conducted to understand the context, implementation, and mechanism of impact of the PFJ intervention. Also, the relationship between degree of implementation and lifestyle changes was explored. METHODS: Quantitative and qualitative data were collected across the evaluation domains context (i.e. reach), implementation (i.e. recruitment and delivery), and mechanism of impact (i.e. responsiveness) of both the participants and coaches (incl. dietitians, sport coaches) according to the UK MRC guidelines for process evaluations. Data was collected from the participants via focus groups and questionnaires after the intervention, and interviews with coaches. Qualitative data were analyzed thematically, and quantitative data were assessed with descriptive statistics and linear regression analyses. Degree of implementation was quantified using a theory-driven implementation index score composed of different process evaluation constructs. RESULTS: Of the 155 participants who participated in the PFJ intervention, 106 (68%) took part in the questionnaire and 34 (22%) attended a focus group. Participants felt the intervention was complete, coherent, and would recommend the intervention to others (mean score 9.2 (SD 1.4) out of 10). Participants felt heard and empowered to take control of their lifestyle and health outcomes. Components perceived as most useful were self-monitoring, social support, practical and theoretical information, and (individual) guidance by the multidisciplinary team. Participants perceived the intervention as feasible, and many indicated it effectively improved their health outcomes. In an explorative analysis there was no significant difference in healthy lifestyle changes across implementation index score groups. CONCLUSION: This process evaluation offers important insights into why the PFJ intervention works and how the intervention can be optimized for future implementation. Results indicating the intervention's high satisfaction, feasibility, and perceived effectiveness, further support the use of plant-based lifestyle interventions as an additional treatment option for patients with RA, OA, or other chronic diseases. TRIAL REGISTRATION: International Clinical Trial Registry Platform numbers: NL7800, NL7801, and NL7802, all registered 17-06-2019.

Rapid Selenoprotein Activation by Selenium Nanoparticles to Suppresses Osteoclastogenesis and Pathological Bone Loss.

Osteoclast hyperactivation stands as a significant pathological factor contributing to the emergence of bone disorders driven by heightened oxidative stress levels. The modulation of the redox balance to scavenge reactive oxygen species (ROS) emerges as a viable approach in addressing this concern. Selenoproteins, characterized by selenocysteine (SeCys2) as the active center, are crucial for selenium-based antioxidative stress therapy for inflammatory diseases. This study reveals that surface-active elemental selenium (Se) nanoparticles, particularly those derived from lentinan (LNT-Se), exhibit enhanced cellular accumulation and accelerated metabolism to SeCys2, the primary active Se form in biological systems. Consequently, LNT-Se demonstrates significant inhibition of RANKL-induced osteoclastogenesis and osteoclastic activity when compared to alternative Se species. Furthermore, in vivo studies underscore the superior therapeutic efficacy of LNT-Se over SeCys2, potentially attributable to the enhanced stability and safety profile of LNT-Se. Specifically, LNT-Se effectively modulates the expression of the selenoprotein GPx1, thereby exerting regulatory control over macrophage polarization, osteoclast activity inhibition, and the prevention of CIA/OVX-induced osteolysis. In summary, these results suggest that the prompt activation of selenoproteins by Se nanoparticles serves to suppress osteoclastogenesis and pathological bone loss by upregulating GPx1 to re-polarize macrophages. Moreover, the utilization of bioactive Se species presents a promising avenue for effectively managing bone disorders, with considerable potential for clinical translation. This article is protected by copyright. All rights reserved.

Traditional Herbal Medicine: Therapeutic Potential in Acute Gouty Arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute Gouty Arthritis (AGA) is characterized by a rapid inflammatory reaction caused by the build-up of monosodium urate (MSU) crystals in the tissues surrounding the joints. This condition often associated with hyperuricemia, is distinguished by its symptoms of intense pain, active inflammation, and swelling of the joints. Traditional approaches in AGA management often fall short of desired outcomes in clinical settings. However, recent ethnopharmacological investigations have been focusing on the potential of Traditional Herbal Medicine (THM) in various forms, exploring their therapeutic impact and targets in AGA treatment. AIM OF THE REVIEW: This review briefly summarizes the current potential pharmacological mechanisms of THMs - including active ingredients, extracts, and prescriptions -in the treatment of AGA, and discusses the relevant potential mechanisms and molecular targets in depth. The objective of this study is to offer extensive information and a reference point for the exploration of targeted AGA treatment using THMs. MATERIALS AND METHODS: This review obtained scientific publications focused on in vitro and in vivo studies of anti-AGA Traditional Herbal Medicines (THMs) conducted between 2013 and 2023. The literature was collected from various journals and electronic databases, including PubMed, Elsevier, ScienceDirect, Web of Science, and Google Scholar. The retrieval and analysis of relevant articles were guided by keywords such as "acute gouty arthritis and Chinese herbal medicine," "acute gouty arthritis herbal prescription," "acute gouty arthritis and immune cells," "acute gouty arthritis and inflammation," "acute gouty arthritis and NLRP3," "acute gouty arthritis and miRNA," and "acute gouty arthritis and oxidative stress." RESULTS: We found that AGA has a large number of therapeutic targets, highlighting the effectiveness the potential of THMs in AGA treatment through in vitro and in vivo studies. THMs and their active ingredients can mitigate AGA symptoms through a variety of therapeutic targets, such as influencing macrophage polarization, neutrophils, T cells, natural killer (NK) cells, and addressing factors like inflammation, NLRP3 inflammasome, signaling pathways, oxidative stress, and miRNA multi-target interactions. The anti-AGA properties of THMs, including their active components and prescriptions, were systematically summarized and categorized based on their respective therapeutic targets. CONCLUSION: phenolic, flavonoid, terpenoid and alkaloid compounds in THMs are considered the key ingredients to improve AGA. THMs and their active ingredients achieve enhanced efficacy through interactions with multiple targets, of which NLRP3 is a main therapeutic target. Nonetheless, given the intricate composition of traditional Chinese medicine, additional research is required to unravel the underlying mechanisms and molecular targets through which THMs alleviate AGA.

Evaluation of inflammatory biomarkers and the ratio of hemoglobin-red cell distribution width in patients with rheumatoid arthritis treated with tumor necrosis factor-alpha inhibitors.

BACKGROUND: The aim of this study was to examine pre-treatment and post-treatment hemogram-derived inflammatory biomarkers in patients with rheumatoid arthritis (RA) who received anti-tumor necrosis factor (TNF)-α treatment. MATERIAL AND METHODS: The data of 1182 patients with RA were screened. Among them, 207 patients who met the eligibility criteria were included in the retrospective study. Demographic parameters, disease activity, and blood cell-derived indexes were evaluated. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and hemoglobin-red cell distribution width (Hb/RDW) rates were evaluated before treatment and at the third month of treatment in patients with RA who received anti-TNF-α treatment. RESULTS: According to the EULAR response criteria, 12.6% of the 207 patients responded to anti-TNF-α treatment as none, 21.3% as good, and 66.2% as moderate, respectively. Post-treatment NLR and PLR values were significantly lower than pre-treatment values (p < 0.001), whereas post-treatment LMR and Hb/RDW values were significantly higher than pre-treatment values (respectively, p = 0.001 and p = 0.012). The difference between pre-treatment and post-treatment values of LMR and Hb/RDW was significantly higher when compared to the moderate + good response groups than the none-response group (p = 0.002 and p = 0.014, respectively). However, in the receiver operating characteristic curve analysis, these parameters were not found to be significant in predicting treatment response. CONCLUSION: Significant changes were detected in hemogram-derived inflammatory markers of the groups responding to anti-TNF-α treatment. They can be used as a guide during treatment follow-up. Yet, they do not predict treatment response. Key Points • RA may manifest with periods of remission and activation, and regular follow-up is essential. • There is a demand for readily available, reproducible, and cost-effective parameters to assess treatment response. • Hemogram-derived inflammatory markers differ in relation to anti-TNF-α treatment response in RA. • None of those markers demonstrate an acceptable predictive performance in distinguishing patients based on their response to TNF-α inhibitors.

Hormonal Imbalance in Obesity and Arthritis: Points of Contact.

Obesity is a growing global health crisis intricately connected to various chronic conditions, including arthritis. This paper explores the intricate web of hormonal changes in the context of obesity and their profound influence on the development and progression of arthritis. Hormones, such as leptin, insulin, cortisol, and estrogen, all altered in obesity, play pivotal roles in inflammation, cartilage degradation, mechanical stress, and pain associated with obesity-related arthritis. Additionally, the mechanical stress placed on weight-bearing joints by excess body weight accelerates joint wear and tear, contributing to arthritis. Genetic factors, shared biomarkers, and pathways further link these conditions. Recognizing these connections is vital for healthcare professionals and individuals facing the challenges of obesity and arthritis, offering insights into strategies for prevention, management, and intervention. This comprehensive understanding of the complex interplay between hormonal changes, obesity, and arthritis sheds light on multifaceted mechanisms underlying this intricate relationship.

Patient-reported outcomes of curcumin supplementation in rheumatoid arthritis and psoriatic arthritis: a cross-sectional survey.

Curcumin is suggested to possess potent anti-inflammatory properties. This study focuses on determining the prevalence and perceived efficacy of curcumin supplementation in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) population. We conducted a cross-sectional study on patients with RA and PsA who visited a rheumatology outpatient clinic from October 2019 to March 2020. A brief, voluntary, and anonymous Qualtrics survey of specific questions regarding curcumin use, source, form, method, dosage, side effects, and perceived efficacy was distributed to the patients. Descriptive and correlation analyses were performed. Among the 291 patients included, 46.4% of patients reported taking curcumin supplementation. Majority patients supplemented once a day (53.4%) and took dosages ranging from less than 200 mg/day to around 1000 mg/day of curcumin. Pain scores decreased significantly after starting curcumin therapy (p < 0.0001). Patients who were taking curcumin for years reported better symptomatic control when compared with patients taking it for months (p 0.01), weeks (p 0.02), or days (p 0.02). There was a significant difference in symptom improvement in patients taking 200-1000 mg compared to patients taking less than 200 mg (p 0.01). Patients taking curcumin once or twice a day reported significant symptom improvement compared to patients taking it sporadically. Symptomatic improvement was reported as pain (35.7%), swelling (25%), stiffness (23.21%), and fatigue (16.07%). An interesting correlation exists between the symptom relief and the frequency, dosages (200-1000 mg), and duration (years) of curcumin supplementation. Our study indicates that curcumin supplementation positively influenced outcomes in 46.4% of individuals with RA and PsA, reducing pain, swelling, stiffness, and fatigue. This suggests curcumin's potential as an adjunct therapy for these conditions.

Efficacy and Safety of Secukinumab in US Patients with Psoriatic Arthritis: A Subgroup Analysis of the Phase 3 FUTURE Studies.

INTRODUCTION: The aim of this work is to evaluate secukinumab vs. placebo in a challenging-to-treat and smaller US patient subpopulation of the international FUTURE 2-5 studies in patients with psoriatic arthritis (PsA). METHODS: Data were pooled from US patients enrolled in the phase 3 FUTURE 2-5 studies (NCT01752634, NCT01989468, NCT02294227, and NCT02404350). Patients received secukinumab 300 or 150 mg with subcutaneous loading dose, secukinumab 150 mg without subcutaneous loading dose, or placebo. Categorical efficacy and health-related quality-of-life (QoL) outcomes and safety were evaluated at week 16. Subgroup analyses were performed based on tumor necrosis factor inhibitor (TNFi) status and body mass index (BMI). For hypothesis generation, odds ratios (ORs) for American College of Rheumatology (ACR) 20/50/70 and Psoriasis Area and Severity Index (PASI) 75/90/100 responses by treatment were estimated using logistic regression without adjustment for multiple comparisons. RESULTS: Of 2148 international patients originally randomized, 279 US patients were included in this pooled analysis. Mean BMI was > 30 kg/m2 and 55.2% had prior TNFi treatment. ORs for ACR20/50/70 significantly favored patients receiving secukinumab 300 mg and 150 mg with loading dose vs. placebo (P < 0.05), but not those receiving secukinumab 150 mg without loading dose vs. placebo. For PASI75, ORs favored all secukinumab groups over placebo (P < 0.05); for PASI90 and PASI100, only the secukinumab 300-mg group was significantly favored over placebo (P < 0.05). CONCLUSIONS: In this challenging sub-population of US patients with PsA, secukinumab provided rapid improvements in disease activity and QoL. Patients with PsA and active psoriasis might benefit more from secukinumab 300 mg than 150 mg.

Hemophagocytic lymphohistiocytosis and macrophage activation syndrome: two rare sides of the same devastating coin.

Hemophagocytic lymphohistiocytosis (HLH) is a rare genetic hyperinflammatory syndrome that occurs early in life. Macrophage activation syndrome (MAS) usually refers to a secondary form of HLH associated with autoimmunity, although there are other causes of secondary HLH, such as infections and malignancy. In this article, we reviewed the concepts, epidemiology, clinical and laboratory features, diagnosis, differential diagnosis, prognosis, and treatment of HLH and MAS. We also reviewed the presence of MAS in the most common autoimmune diseases that affect children. Both are severe diseases that require prompt diagnosis and treatment to avoid morbidity and mortality.

Detection of common pathogenesis of rheumatoid arthritis and atherosclerosis via microarray data analysis.

Despite extensive research reveal rheumatoid arthritis (RA) is related to atherosclerosis (AS), common pathogenesis between these two diseases still needs to be explored. In current study, we explored the common pathogenesis between rheumatoid arthritis (RA) and atherosclerosis (AS) by identifying 297 Differentially Expressed Genes (DEGs) associated with both diseases. Through KEGG and GO functional analysis, we highlighted the correlation of these DEGs with crucial biological processes such as the vesicle transport, immune system process, signaling receptor binding, chemokine signaling and many others. Employing Protein-Protein Interaction (PPI) network analysis, we elucidated the associations between DEGs, revealing three gene modules enriched in immune system process, vesicle, signaling receptor binding, Pertussis, and among others. Additionally, through CytoHubba analysis, we pinpointed 11 hub genes integral to intergrin-mediated signaling pathway, plasma membrane, phosphotyrosine binding, chemokine signaling pathway and so on. Further investigation via the TRRUST database identified two key Transcription Factors (TFs), SPI1 and RELA, closely linked with these hub genes, shedding light on their regulatory roles. Finally, leveraging the collective insights from hub genes and TFs, we proposed 10 potential drug candidates targeting the molecular mechanisms underlying RA and AS pathogenesis. Further investigation on xCell revealed that 14 types of cells were all different in both AS and RA. This study underscores the shared pathogenic mechanisms, pivotal genes, and potential therapeutic interventions bridging RA and AS, offering valuable insights for future research and clinical management strategies.

The role and mechanism of TXNDC5 in disease progression.

Thioredoxin domain containing protein-5 (TXNDC5), also known as endothelial protein-disulfide isomerase (Endo-PDI), is confined to the endoplasmic reticulum through the structural endoplasmic reticulum retention signal (KDEL), is a member of the PDI protein family and is highly expressed in the hypoxic state. TXNDC5 can regulate the rate of disulfide bond formation, isomerization and degradation of target proteins through its function as a protein disulfide isomerase (PDI), thereby altering protein conformation, activity and improving protein stability. Several studies have shown that there is a significant correlation between TXNDC5 gene polymorphisms and genetic susceptibility to inflammatory diseases such as rheumatoid, fibrosis and tumors. In this paper, we detail the expression characteristics of TXNDC5 in a variety of diseases, summarize the mechanisms by which TXNDC5 promotes malignant disease progression, and summarize potential therapeutic strategies to target TXNDC5 for disease treatment.

Higher odds of periodontitis in systemic lupus erythematosus compared to controls and rheumatoid arthritis: a systematic review, meta-analysis and network meta-analysis.

Introduction: Periodontitis as a comorbidity in systemic lupus erythematosus (SLE) is still not well recognized in the dental and rheumatology communities. A meta-analysis and network meta-analysis were thus performed to compare the (i) prevalence of periodontitis in SLE patients compared to those with rheumatoid arthritis (RA) and (ii) odds of developing periodontitis in controls, RA, and SLE. Methods: Pooled prevalence of and odds ratio (OR) for periodontitis were compared using meta-analysis and network meta-analysis (NMA). Results: Forty-three observational studies involving 7,800 SLE patients, 49,388 RA patients, and 766,323 controls were included in this meta-analysis. The pooled prevalence of periodontitis in SLE patients (67.0%, 95% confidence interval [CI] 57.0-77.0%) was comparable to that of RA (65%, 95% CI 55.0-75.0%) (p>0.05). Compared to controls, patients with SLE (OR=2.64, 95% CI 1.24-5.62, p<0.01) and RA (OR=1.81, 95% CI 1.25-2.64, p<0.01) were more likely to have periodontitis. Indirect comparisons through the NMA demonstrated that the odds of having periodontitis in SLE was 1.49 times higher compared to RA (OR=1.49, 95% CI 1.09-2.05, p<0.05). Discussion: Given that RA is the autoimmune disease classically associated with periodontal disease, the higher odds of having periodontitis in SLE are striking. These results highlight the importance of addressing the dental health needs of patients with SLE. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/ identifier CRD42021272876.

A Case of Adult-onset Still's Disease (AOSD) with Gastrointestinal Lesions.

A 51-year-old woman with fever was admitted to our hospital. A computed tomography (CT) scan showed thickened colonic walls. Colonoscopy revealed erosion in the ileum and colon. Adult-onset Still's disease (AOSD) was diagnosed due to a subsequent sore throat and skin rash. Following AOSD treatment, methylprednisolone pulse therapy, followed by prednisolone and cyclosporine, was initiated. Despite achieving a temporary improvement, relapse occurred with fever, abdominal pain, with worsening CT and endoscopic findings. The reappearance of a skin rash confirmed an exacerbation of AOSD. Tocilizumab treatment alleviated the symptoms and improved the endoscopic findings. Considering their correlation with the symptoms and endoscopic findings, the observed gastrointestinal lesions may be linked to AOSD.

Relationships among gut microbiota, plasma metabolites, and juvenile idiopathic arthritis: a mediation Mendelian randomization study.

Objective: The objective of this study is to investigate the causal relationship between gut microbiota and juvenile idiopathic arthritis, and to identify and quantify the potential role of plasma metabolites as mediators. Methods: Using summary-level data from genome-wide association studies, a two-sample Mendelian randomization was conducted involving 131 gut microbiota genus, 1,400 plasma metabolites, and juvenile idiopathic arthritis. Additionally, a two-step approach was employed to quantify the proportion of the effect of gut microbiota on juvenile idiopathic arthritis mediated by plasma metabolites. Effect estimation primarily utilized Inverse Variance Weighting, with further validation using Bayesian weighted Mendelian randomization. Results: In our MR analysis, a positive correlation was observed between Rikenellaceae and the risk of juvenile idiopathic arthritis, while Dorea showed a negative correlation with juvenile idiopathic arthritis risk. Mediation analysis indicated that Furaneol sulfate levels acted as a mediator between Dorea and juvenile idiopathic arthritis, with an indirect effect proportion of 19.94, 95% CI [8.86-31.03%]. Conclusion: Our study confirms a causal relationship between specific microbial genus and juvenile idiopathic arthritis, and computes the proportion of the effect mediated by plasma metabolites, offering novel insights for clinical interventions in juvenile idiopathic arthritis.

Upadacitinib sustained-release tablets for the treatment of chronic refractory gouty arthritis: a case report and literature review.

Background: Gouty arthritis (GA) is a crystal-related joint disease caused by the deposition of monosodium urate (MSU) crystals, directly associated with hyperuricemia resulting from purine metabolism disorder and/or reduced uric acid excretion. Acute attacks of typical gouty arthritis are generally relieved through the clinical use of NSAIDs, colchicine, or glucocorticoids. However, managing patients with chronic refractory gout poses challenges due to complications such as multiple tophi, gouty nephropathy, diabetes, and gastrointestinal bleeding. While there have been numerous studies on gout in recent years, research specifically regarding chronic refractory gout remains limited. The management of such cases still faces several unresolved issues, including recurrent disease flare-ups and poor patient compliance leading to inadequate drug utilization and increased risk of side effects. In this report, we present a case of successful improvement in chronic refractory gouty arthritis using the biologic agent upadacitinib sustained-release tablets. Case presentation: Our case report involves a 53 years-old Asian patient with recurrent gouty arthritis who had a history of over 20 years without regular treatment, presenting with tophi and an increasing number of painful episodes. During hospitalization, various analgesics and anti-inflammatory drugs provided inadequate relief, requiring the use of steroids to alleviate symptoms. However, tapering off steroids proved challenging. We decided to add upadacitinib sustained-release tablets to the treatment regimen, which ultimately improved the patient's condition. After 6 months of follow-up, the patient has not experienced any further acute pain episodes. Conclusion: This case highlights the potential therapeutic effect of upadacitinib sustained-release tablets during the acute phase of chronic refractory gouty arthritis.

Inhibition of HDAC1 and 3 in the Presence of Systemic Inflammation Reduces Retinal Degeneration in a Model of Dry Age-Related Macular Degeneration.

Purpose: Previously, we identified increased retinal degeneration and cytokine response in a mouse model of dry age-related macular degeneration (AMD) in the presence of systemic inflammation from rheumatoid arthritis (RA). Histone deacetylases (HDACs) regulate cytokine production by reducing acetylation and are found to be dysregulated in inflammatory diseases, including RA and AMD. Therefore, this current study investigates the effect of HDAC inhibition on AMD progression in the presence of systemic inflammation. Methods: Collagen induced arthritis (CIA) was induced in C57BL6J mice, followed by sodium iodate (NaIO3)-induced retinal degeneration. Mice were treated with a selective HDAC class I inhibitor, MS-275, and retinal structure [optical coherence tomography (OCT)], function (electroretinography), and molecular changes quantitative real-time polymerase chain reaction (RT-qPCR, Western Blot) were assessed. Results: NaIO3 retinal damage was diminished in CIA mice treated with MS-275 (P ≤ 0.05). While no significant difference was observed in retinal pigment epithelium (RPE) function, a trend in increased c-wave amplitude was detected in CIA + NaIO3 mice treated with MS-275. Finally, we identified decreased Hdac1, Hdac3, and Cxcl9 expression in CIA + NaIO3 mouse RPE/choroid when treated with MS-275 (P ≤ 0.05). Conclusions: Our data demonstrate that HDAC inhibition can reduce the additive effect of NaIO3-induced retinal degeneration in the presence of systemic inflammation by CIA as measured by OCT analysis. In addition, HDAC inhibition in CIA + NaIO3 treated mice resulted in reduced cytokine production. These findings are highly innovative and provide additional support to the therapeutic potential of HDAC inhibitors for dry AMD treatment.

Impact of COVID-19 on arthritis with generative AI.

OBJECTIVE: The study aims to examine the effects of the COVID-19 pandemic on the prevalence of arthritis in the US using a specific generative AI tool. METHODS: The AI tool with Bing.com/copilot, designed to generate Python code, uses data from the Centers for Disease Control and Prevention (CDC) to visualize trends and uncover insights in four key areas: (1) The prevalence of arthritis in adults aged 18 years and older who have diabetes, (2) The prevalence of fair or poor health in adults aged 18 years and older who have arthritis, (3) The prevalence of activity limitations due to arthritis in adults aged 18 years and older with doctor-diagnosed arthritis, (4) The prevalence of arthritis in adults aged 18 years and older who are obese. This research did not require approval from an institutional review board or an ethics committee. RESULTS: The findings reveal a significant decline in the prevalence of arthritis among adults with conditions such as diabetes and obesity during the COVID-19 pandemic. There was also an observed improvement in activity limitations among patients with doctor-diagnosed arthritis. CONCLUSION: The study highlights the potential impact of the pandemic on chronic disease management, particularly arthritis. It underscores the importance of continued monitoring and care for patients with arthritis, especially during a global health crisis like the COVID-19 pandemic. The use of AI tools in generating insights from health data proves to be valuable in this context.

Supramolecular Hydrogel Dexamethasone-Diclofenac for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) severely affects patients' quality of life and is commonly treated with glucocorticosteroids injections, like dexamethasone, which may have side effects. This study aimed to create a novel low dose of twin-drug hydrogel containing dexamethasone and diclofenac and explore its potential as a drug delivery system for an enhanced anti-inflammatory effect. Its characterization involved rheology, transmission electron microscope (TEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Furthermore, the hydrogel demonstrated thixotropic properties. The hydrogel exhibited no cytotoxicity against RAW 264.7 macrophages. Furthermore, the hydrogel demonstrated a significant anti-inflammatory efficacy by effectively downregulating the levels of NO, TNF-α, and IL-6 in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. The co-delivery approach, when intra-articularly injected in adjuvant-induced arthritis (AIA) rats, significantly alleviated chronic inflammation leading to reduced synovitis, delayed bone erosion onset, and the downregulation of inflammatory cytokines. The biocompatibility and adverse effect evaluation indicated good biological safety. Furthermore, the hydrogel demonstrated efficacy in reducing NF-κB nuclear translocation in LPS-induced RAW 264.7 macrophages and inhibited p-NF-kB, COX-2, and iNOS expression both in RAW 264.7 macrophages and the joints of AIA rats. In conclusion, the findings indicate that the hydrogel possesses potent anti-inflammatory activity, which effectively addresses the limitations associated with free forms. It presents a promising therapeutic strategy for the management of RA.

Combinational strategy using albumin-based nanoparticles to enable synergetic anti-rheumatic efficacy and reduced hepatotoxicity.

Methotrexate (MTX) is recognized as the golden standard for rheumatoid arthritis (RA) treatment. However, it can cause liver damage in long-term application. Although nanomedicines can target to inflamed sites, most of them tend to accumulate in liver. Glycyrrhizinic acid (GA) holds potential to reverse MTX-associated hepatotoxicity. The combination of GA and MTX might achieve a synergistic anti-inflammatory efficacy and reduced hepatotoxicity. As MTX and GA have totally different in vivo performance, it is necessary to co-encapsulate them in one carrier to coordinate their in vivo fates. Here, we co-delivered MTX and GA to arthritic joints using a human serum albumin-based nanoparticle (HSN). We found the dual drug-loaded albumin nanoparticles (HSN/MTX/GA) could preferentially distribute in inflamed joints, where GA can extend MTX retention by inhibiting the expression of efflux pumps for MTX, thereby exerting synergistic therapeutic effect. In liver tissues, GA was able to reverse the MTX-induced liver damage by activating anti-oxidant defense Nrf2/HO-1 and anti-apoptosis Bcl-2/Bax signaling. We offer a combinational strategy to effectively overcome the MTX-induced hepatotoxicity and enhance the anti-rheumatic efficacy simultaneously. Furthermore, we verified the underlying mechanism about how GA cooperated with MTX in vivo for the first time. Our findings can provide valuable insights for long-term treatment of RA.

Design, optimization, and evaluation of topical gel of Cardiospermum halicacabum and Ricinus communis L. leaves extract for the treatment of rheumatoid arthritis.

This research aims to develop and assess the anti-arthritic properties of a topically herbal gel including leaf extracts from Cardiospermum halicacabum and Ricinus communis L. in rats. Utilizing gelling agents carbopol 940 (2.5, 5, 7.5 g), nine herbal gel compositions were created. Prepared formulations were then assessed for physical appearance, spreadability, viscosity, net content, pH, extrudability, in vitro diffusion profile, and main skin irritant tests. According to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) recommendations, the stability research for the topical herbal gel composition was completed, and Freund's Complete Adjuvant (FCA) induced arthritis technique was used to assess the anti-arthritic efficacy. Additional procedures included measuring the body weight, paw volume, biochemical and hematological variables, histological analysis, and in vitro serum biomarker detection. The prepared gels followed the instructions and were uniform and stable. F5 performed better than the other compositions in terms of release kinetics (97.20%). The gel proved safe and non-toxic since no erythema or edema was seen during the skin irritation test. Comparing the herbal gel F5 comprising carbopol 940 to rats with arthritis, the topical treatment showed considerable (p < .001) anti-arthritic effect. The anti-arthritic action of the gel formulations was confirmed by decreased paw volume, absence of agglutination in reacting protein and rheumatic factor, a decline in TNFα level, restoration to baseline biochemical and hematological characteristics, decrease in thymus and spleen weight, and histopathological study.