Treatment Of Rheumatoid Arthritis Research Articles

Mechanism of Jinteng Qingbi granules in the treatment of rheumatoid arthritis using metabolomics analysis.

This study investigated the differential metabolites after rheumatoid arthritis (RA) rats were treated with Jinteng Qingbi granules. Collagen-induced arthritis rats were divided into three groups, namely normal group, model group, and Jinteng Qingbi granules group. Serum compounds were identified, annotated, and classified using metabolomics to explain the physicochemical properties and biological functions. The metabolites were screened using univariate and multivariate statistical analyses. There were differences in serum metabolites between RA and normal rats; Jinteng Qingbi granules improved RA and recovered the metabolite levels to normal. Compared to the normal group, 51 differential ions were screened, and 108 ions were changed in the Jinteng Qingbi granules group compared to the RA model. Eight metabolites were upregulated in the RA model group compared to the normal group, whereas 10 metabolites were downregulated. Treatment with Jinteng Qingbi granules increased the levels of 12 metabolites such as cinnamate and decreased the levels of 16 metabolites such as allamandin in the RA model. Differential ion enrichment was mainly related to the histidine metabolic pathway in amino acid metabolism. Jinteng Qingbi granules resulted in improvements in the RA model, which were mainly associated with lipids and lipid-like molecules, organic acids, and derivatives, providing a new possibility and basis for screening biomarkers for the diagnosis and treatment of RA.

Factors contributing to the improvement in J-HAQ after 3 years of treatment with abatacept in biologic-naïve rheumatoid arthritis patients: Interim results of a long-term, observational, multicentre study in Japan (ORIGAMI).

We investigated the long-term effectiveness, safety, and factors affecting Japanese Health Assessment Questionnaire (J-HAQ) improvement during abatacept treatment in Japanese rheumatoid arthritis (RA) patients. The ORIGAMI study is an ongoing observational study of biologic-naïve RA patients with moderate disease activity treated with subcutaneous abatacept (125 mg, once-weekly). Patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) registry as an historical, weighted control group. The primary endpoint for this interim analysis was the proportion of patients with J-HAQ remission (score ≤0.5) at 3 years. Among 279 abatacept-treated and 220 csDMARD-treated patients, J-HAQ remission was achieved at 3 years in 40.5% (95% confidence interval [CI] 34.7%-46.2%) and 28.9% (95% CI 9.9%-47.8%), respectively. Age, RA duration <1 year, baseline J-HAQ score, and Simplified Disease Activity Index remission at 6 months were associated with 3-year J-HAQ remission in the abatacept group. Overall, 24/298 patients (8.1%; safety analysis set) experienced serious adverse drug reactions with an incidence of 5.3 per 100 person-years. This study confirmed the 3-year effectiveness and safety, and revealed potential factors associated with J-HAQ remission in biologic-naïve RA patients treated with abatacept in real-world clinical practice.

Tocilizumab in the treatment of hyperferritinemic syndrome and capillary leak syndrome secondary to rheumatoid arthritis: Case report and literature review.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease, which is mainly characterized by joint swelling, pressure pain and joint destruction. Some patients may suffer from a variety of serious complications, which require prompt diagnosis and treatment. Otherwise, the patient condition may deteriorate rapidly, leading to premature death. We reported a case of RA combined with hyperferritinemic syndrome and capillary leak syndrome (CLS) that was successfully treated with tocilizumab (TCZ), with the aim of improving diagnostic ideas for clinicians and consequently improving the diagnosis and treatment of the hyperferritinemic syndrome and CLS. A 55-year-old female patient was admitted to the Department of Infectious Diseases of our hospital due to "recurrent fever for more than 1 month and aggravation for 3 days." The patient was diagnosed with fever of unknown origin (lung infection?) and received anti-infective therapy with large encirclement of anti-bacterial, antifungal and empirical anti-tuberculosis successively during hospitalization in the Department of Infectious Diseases. Yet her condition continues to progress. The patient was eventually diagnosed with RA combined with hyperferritinemic syndrome and CLS. Then she received glucocorticoids (GC) (160 mg qd) combined with intravenous immunoglobulin (IVIG, 20 g/d, for 3 days). We considered that the patient also had an overwhelming proinflammatory cytokine storm, so she received a strong anti-inflammatory treatment with TCZ (400 mg qm). The patient symptoms and follow-up chest CT showed significant improvement following treatment. TCZ has good efficacy in the treatment of RA combined with hyperferritinemic syndrome and CLS and is expected to be a promising treatment.

Polymerized Network-Based Artificial Peroxisome Reprogramming Macrophages for Photoacoustic Imaging-Guided Treatment of Rheumatoid Arthritis.

Artificial peroxisomes (AP) with enzyme-mimetic catalytic activity and recruitment ability have drawn a great deal of attention in fabricating protocell systems for scavenging reactive oxygen species (ROS), modulating the inflammatory microenvironment, and reprogramming macrophages, which is of great potential in treating inflammatory diseases such as rheumatoid arthritis (RA). Herein, a macrophage membrane-cloaked Cu-coordinated polyphthalocyanine-based AP (CuAP) is prepared with a macrocyclic conjugated polymerized network and embedded Cu-single atomic active center, which mimics the catalytic activity and coordination environment of natural superoxide dismutase and catalase, possesses the inflammatory recruitment ability of macrophages, and performs photoacoustic imaging (PAI)-guided treatment. The results of both in vitro cellular and in vivo animal experiments demonstrated that the CuAP under ultrasound and microbubbles could efficiently scavenge excess ROS in cells and tissues, modulate microenvironmental inflammatory cytokines such as interleukin-1β, tumor necrosis factor-α, and arginase-1, and reprogram macrophages by polarization of M1 (proinflammatory phenotype) to M2 (anti-inflammatory phenotype). We believe this study offers a proof of concept for engineering multifaceted AP and a promising approach for a PAI-guided treatment platform for RA.

Natural biomimetic nano-system for drug delivery in the treatment of rheumatoid arthritis: a literature review of the last 5 years

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized primarily by synovitis, leading to the destruction of articular cartilage and bone and ultimately resulting in joint deformity, loss of function, and a significant impact on patients’ quality of life. Currently, a combination of anti-rheumatic drugs, hormonal drugs, and biologics is used to mitigate disease progression. However, conventional drug therapy has limited bioavailability, and long-term use often leads to drug resistance and toxic side effects. Therefore, exploring new therapeutic approaches for RA is of great clinical importance. Nanodrug delivery systems offer promising solutions to overcome the limitations of conventional drugs. Among them, liposomes, the first nanodrug delivery system to be approved for clinical application and still widely studied, demonstrate the ability to enhance therapeutic efficacy with fewer adverse effects through passive or active targeting mechanisms. In this review, we provide a review of the research progress on the targeting mechanisms of various natural biomimetic nano-delivery systems in RA therapy. Additionally, we predict the development trends and application prospects of these systems, offering new directions for precision treatment of RA.

Exploring the therapeutic opportunities of potassium channels for the treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects the synovial joint, which leads to inflammation, loss of function, joint destruction, and disability. The disease biology of RA involves complex interactions between genetic and environmental factors and is strongly associated with various immune cells, and each of the cell types contributes differently to disease pathogenesis. Several immunomodulatory molecules, such as cytokines, are secreted from the immune cells and intervene in the pathogenesis of RA. In immune cells, membrane proteins such as ion channels and transporters mediate the transport of charged ions to regulate intracellular signaling pathways. Ion channels control the membrane potential and effector functions such as cytotoxic activity. Moreover, clinical studies investigating patients with mutations and alterations in ion channels and transporters revealed their importance in effective immune responses. Recent studies have shown that voltage-gated potassium channels and calcium-activated potassium channels and their subtypes are involved in the regulation of immune cells and RA. Due to the role of these channels in the pathogenesis of RA and from multiple pieces of clinical evidence, they can be considered therapeutic targets for the treatment of RA. Here, we describe the role of voltage-gated and calcium-activated potassium channels and their subtypes in RA and their pharmacological application as drug targets.

Incident Use of Hydroxychloroquine for the Treatment of Rheumatoid Arthritis and Systemic Lupus Erythematosus During the COVID-19 Pandemic.

We studied whether the use of hydroxychloroquine (HCQ) for COVID-19 resulted in supply shortages for patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We used US claims data (IQVIA PHARMETRICS®Plus for Academics [PHARMETRICS]) and hospital electronic records from Spain (Institut Municipal d'Assistència Sanitària Information System [IMASIS]) to estimate monthly rates of HCQ use between January 2019 and March 2022, in the general population and in patients with RA and SLE. Methotrexate (MTX) use was estimated as a control. More than 13.5 million individuals (13,311,811 PHARMETRICS, 207,646 IMASIS) were included in the general population cohort. RA and SLE cohorts enrolled 135,259 and 39,295 patients, respectively, in PHARMETRICS. Incidence of MTX and HCQ were stable before March 2020. On March 2020, the incidence of HCQ increased by 9- and 67-fold in PHARMETRICS and IMASIS, respectively, and decreased in May 2020. Usage rates of HCQ went back to prepandemic trends in Spain but remained high in the United States, mimicking waves of COVID-19. No significant changes in HCQ use were noted among patients with RA and SLE. MTX use rates decreased during HCQ approval period for COVID-19 treatment. Use of HCQ increased dramatically in the general population in both Spain and the United States during March and April 2020. Whereas Spain returned to prepandemic rates after the first wave, use of HCQ remained high and followed waves of COVID-19 in the United States. However, we found no evidence of general shortages in the use of HCQ for both RA and SLE in the United States.

ECM-mimetic, NSAIDs loaded thermo-responsive, immunomodulatory hydrogel for rheumatoid arthritis treatment

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and it leads to irreversible inflammation in intra-articular joints. Current treatment approaches for RA include non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids, and biological agents. To overcome the drug-associated toxicity of conventional therapy and transdermal tissue barrier, an injectable NSAID-loaded hydrogel system was developed and explored its efficacy.ResultsThe surface morphology and porosity of the hydrogels indicate that they mimic the natural ECM, which is greatly beneficial for tissue healing. Further, NSAIDs, i.e., diclofenac sodium, were loaded into the hydrogel, and the in vitro drug release pattern was found to be burst release for 24 h and subsequently sustainable release of 50% drug up to 10 days. The DPPH assay revealed that the hydrogels have good radical scavenging activity. The biocompatibility study carried out by MTT assay proved good biocompatibility and anti-inflammatory activity of the hydrogels was carried out by gene expression study in RAW 264.7 cells, which indicate the downregulation of several key inflammatory genes such as COX-2, TNF-α & 18s.ConclusionIn summary, the proposed ECM-mimetic, thermo-sensitive in situ hydrogels may be utilized for intra-articular inflammation modulation and can be beneficial by reducing the frequency of medication and providing optimum lubrication at intra-articular joints.Graphical

Melanin nanoparticles scavenging reactive oxygen and nitrogen radicals for rheumatoid arthritis treatment

Rheumatoid arthritis (RA) is a complex and chronic disease that often causes long-term pain and joint swelling in patients, and even causes joint deformity and dysfunction. The pathogenesis of this disease involves abnormal activity of the immune system, causing immune cells to attack the bodys joint tissues, which triggers an inflammatory response. During these inflammatory processes, the accumulation of reactive oxygen and nitrogen species (RONS) is considered to be one of the key factors that aggravate inflammation and damage joint tissues. To address this problem, we designed a method that takes advantage of the targeting properties of melanin nanoparticles. These nanoparticles have excellent biocompatibility, can remain stable in the body, and can be accurately targeted to the site of inflammation. In addition, these nanoparticles also have strong free radical scavenging ability, which can effectively neutralize excessive RONS, reduce the inflammatory response and weaken joint tissue damage. The promise of this treatment strategy is encouraging and offers new hope for patients with RA. By reducing inflammation, protecting joint tissue, and possibly even reversing the disease process to some extent, this melanin nanoparticle holds great promise.

Omics-based pharmacological evaluation reveals Yuanhu Zhitong oral liquid ameliorates arthritis by regulating PKC/ERK/NF-κB signaling pathway

Ethnopharmacological relevanceSuccessful use of herbal medicine in the treatment of rheumatoid arthritis (RA) creates opportunities for alternative therapies. Yuanhu Zhitong oral liquid (YZOL) is an herbal preparation known for its potent analgesic and anti-inflammatory properties in traditional use. However, the pharmacological mechanism of YZOL for treating RA remains unclear. Aim of the studyThe aim of this study was to evaluate the efficacy of YZOL in the treatment of RA and to explore its potential mechanisms through omics analysis. Materials and methodsType II collagen was used to induce an arthritis rat model. The effects of YZOL on paw swelling, inflammatory cytokines, oxidative stress, and histopathological changes were systematically investigated. A pathway-driven transcriptomic analysis was performed to identify key signaling pathways associated with YZOL therapy. The key alterations were validated by qRT-PCR, Western blot, and immunohistochemistry assays. ResultsYZOL significantly attenuated arthritis progression, reduced paw swelling rate, and lowered arthritis score in CIA rats. YZOL also inhibited systemic inflammation and associated oxidative stress during RA. Transcriptomic analysis identified 341 genes with significantly altered expression following YZOL treatment. These genes were enriched in inflammation-related pathways, particularly in the NF-κB and MAPK signaling pathways. In addition, we discovered that YZOL can alleviate inflammation in the local synovial tissue. The effect of YZOL was confirmed by the suppression of PKC/ERK/NF-κB p65 signaling at systemic and local levels. ConclusionsThis study provides novel evidence that YZOL treatment ameliorates RA by suppressing the PKC/ERK/NF-κB pathway, suggesting its potential as an alternative therapy for RA.

Epi-revolution in rheumatology: the potential of histone deacetylase inhibitors for targeted rheumatoid arthritis intervention.

Autoimmune diseases hold significant importance in the realm of medical research, prompting a thorough exploration of potential therapeutic interventions. One crucial aspect of this exploration involves understanding the intricate processes of histone acetylation and deacetylation. Histone acetylation, facilitated by histone acetyl transferases (HATs), is instrumental in rendering DNA transcriptionally active. Conversely, histone deacetylases (HDACs) are responsible for the removal of acetyl groups, influencing gene expression regulation. The upregulation of HDACs, observed in various cancers, has steered attention towards histone deacetylase inhibitors (HDACi) as promising anti-cancer agents. Beyond cancer, HDACi has demonstrated anti-inflammatory properties, prompting interest in their potential therapeutic applications for inflammatory diseases such as rheumatoid arthritis (RA). RA, characterized by the immune system erroneously attacking healthy cells, leads to joint inflammation. Recent studies suggest that HDACi could offer a viable therapeutic strategy for RA, with potential mechanisms including the inhibition of synovial tissue growth and suppression of pro-inflammatory cytokines. Furthermore, HDACi may exert protective effects on bone and cartilage, common targets in RA pathology. In-depth investigations through in vivo and histopathology studies contribute to the ongoing discourse on the therapeutic benefits of HDACis in the context of RA treatment.

Potential Role of Dietary Phenolic Compounds in the Prevention and Treatment of Rheumatoid Arthritis: Current Reports

Rheumatoid arthritis (RA) is a complex illness with both hereditary and environmental components. Globally, in 2019, 18 million people had RA. RA is characterized by persistent inflammation of the synovial membrane that lines the joints, cartilage loss, and bone erosion. Phenolic molecules are the most prevalent secondary metabolites in plants, with a diverse spectrum of biological actions that benefit functional meals and nutraceuticals. These compounds have received a lot of attention recently because they have antioxidant, anti-inflammatory, immunomodulatory, and anti-rheumatoid activity by modulating tumor necrosis factor, mitogen-activated protein kinase, nuclear factor kappa-light-chain-enhancer of activated B cells, and c-Jun N-terminal kinases, as well as other preventative properties. This article discusses dietary polyphenols, their pharmacological properties, and innovative delivery technologies for the treatment of RA, with a focus on their possible biological activities. Nonetheless, commercialization of polyphenols may be achievable only after confirming their safety profile and completing successful clinical trials.

Enhanced efficacy of brucine dissolving-microneedles as a targeted delivery system in rheumatoid arthritis treatment: a comprehensive pharmacokinetic-pharmacodynamic analysis.

Our previous studies have shown the therapeutic efficacy of brucine dissolving-microneedles (Bru-DMNs) in treating rheumatoid arthritis (RA). Bru delivered via the DMNs can bypass some of the issues related to oral and systemic delivery, including extensive enzymatic activity, liver metabolism and in the case of systemic delivery via hypodermic needles, pain resulting from injections and needle stick injury. However, the underlying mechanism of Bru-DMNs against RA has not been investigated in depth at the pharmacokinetic-pharmacodynamic (PK-PD) level. In this study, a microdialysis-based method combined with ultra-performance liquid chromatography-tandem mass spectrometry was developed for the simultaneous and continuous sampling and quantitative analysis of blood and joint cavities in fully awake RA rats. The acquired data were analyzed by the PK-PD analysis method. Bru delivered via microneedles showed enhanced distribution and prolonged retention in the joint cavity compared to its administration in blood. The correlation between the effect of Bru and its concentration at the action site was indirect. In this study, we explored the mechanism of Bru-DMNs against RA and established a visualization method to express the PK-PD relationship of Bru-DMNs against RA. This study provides insights into the mechanism of action of drugs with potential side effects administered transdermally for RA treatment.

Amrita: The ancient herb with modern healing potential and safety features

Tinospora cordifolia Willd commonly known, as “Amrita” or “Guduchi”, is a large deciduous, extensively spreading climbing shrub with several coiling branches, a dioecious medicinal herb. It is designated as Rasayana in Ayurveda as it enhances general body resistance and promotes longevity, an anti-stress, adaptogen, and a potential plant for providing resistance against infections. The plant is well known as Indian bitter and is generally prescribed for fever, diabetes, dyspepsia, jaundice, urinary problems, skin diseases, gastrointestinal diseases including dyspepsia, flatulence, gastritis, jaundice, chronic diarrhea and dysentery, splenomegaly, and hemorrhoids. The herb has been reported to be significant for the management of cardiovascular diseases (CVDs), and the treatment of leprosy, helminthiasis, and rheumatoid arthritis. Some of the most significant formulations in which Guduchi is prime ingredient are Guduchyadi churn, Guduchi taila, Dashmoolarishtha, Sanjivani vati, Punchnimba churana, Guduchi ghrita, Amritaguggulu, Amritashtaka churna, Kantakari avaleha, Chyavanaprasha, Guduchi sattva, Brihat guduchi taila, Stanyashodhana kashaya churana. The most dominant constituents in guduchi include terpenoids, alkaloids, tannins, cardiac glycosides, flavonoids, saponins, lignans, steroids, C6-C3 derivatives and polysaccharides along with other components. There are no adverse effects of any kind reported so far as prescribed under reasonable dose application. It has promising potential as a tonic in infants and stimulates immunity in children besides facilitating growth. Due to the presence of immense medicinal properties, this plant has been over-exploited by pharmaceutical companies and folk people for traditional remedies. This in turn has led to the acute scarcity of this plant. Therefore, it is of prime importance and urgent need for its conservation.

CGAS-STING pathway in pathogenesis and treatment of osteoarthritis and rheumatoid arthritis

Osteoarthritis (OA) and Rheumatoid Arthritis (RA) are significant health concerns with notable prevalence and economic impact. RA, affecting 0.5% to 1.0% of the global population, leads to chronic joint damage and comorbidities. OA, primarily afflicting the elderly, results in joint degradation and severe pain. Both conditions incur substantial healthcare expenses and productivity losses. The cGAS-STING pathway, consisting of cyclic GMP–AMP synthase (cGAS) and stimulator of interferon genes (STING), is a crucial component of mammalian immunity. This pathway is responsible for detecting foreign DNA, particularly double-stranded DNA (dsDNA), triggering innate immune defense responses. When cGAS recognizes dsDNA, it catalyzes the synthesis of cyclic GMP–AMP (cGAMP), which then binds to and activates STING. Activated STING, in turn, initiates downstream signaling events leading to the production of interferons and other immune mediators. The cGAS-STING pathway is essential for defending against viral infections and maintaining cellular balance. Dysregulation of this pathway has been implicated in various inflammatory diseases, including arthritis, making it a target for potential therapeutic interventions. Understanding the intricate molecular signaling network of cGAS-STING in these arthritis forms offers potential avenues for targeted therapies. Addressing these challenges through improved early detection, comprehensive management, and interventions targeting the cGAS-STING pathway is crucial for alleviating the impact of OA and RA on individuals and healthcare systems. This review offers an up-to-date comprehension of the cGAS-STING pathway’s role in the development and therapeutic approaches for these arthritis types.

Triptolide regulates neutrophil function through the Hippo signaling pathway to alleviate rheumatoid arthritis disease progression

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammatory changes in the joints, the etiology of which is unclear. It is now well established that regulated cell death (RCD) and migration of neutrophils play an important role in the pathogenesis of RA. Tripterygium wilfordii Hook.f (TwHF) is a total saponin extracted from the root of Tripterygium wilfordii Hook.f, a plant of the family Wesleyanaceae, which has strong anti-inflammatory and immunomodulatory effects and has been used as a basic drug in the clinical treatment of RA. Despite the good efficacy of TwHF treatment, the mechanism of action of TwHF remains unclear. Several studies have demonstrated that the drug tripterygium glycosides, in which TwHF is the main ingredient, has achieved excellent efficacy in the clinical treatment of RA. Investigations have also found that TwHF can affect cellular RCD, cell migration, cell proliferation, and the apoptosis-related Hippo signaling pathway. In this study, we first analyzed the RCD and migration differences of neutrophils in patients with RA through network pharmacology and transcriptome analysis. Subsequently, we used electron microscopy, immunofluorescence, and other methods to identify the RCD phenotype of neutrophils. In collagen-induced arthritis (CIA) model, we demonstrated that Triptolide (the main active ingredient in TwHF) could alleviate the progression of arthritis by reducing the bone destruction and the infiltration of neutrophils. Furthermore, in vitro experiments showed that Triptolide induced neutrophil apoptosis, inhibited the formation of neutrophil extracellular traps (NETs), and impeded the neutrophil migration process in a Hippo pathway-dependent manner. Taken together, these findings indicate that Triptolide has potential for treating RA and provide theoretical support for the clinical application of TwHF, as a traditional Chinese medicine, in RA.

A reconfigurable integrated smart device for real-time monitoring and synergistic treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a global autoimmune disease that requires long-term management. Ambulatory monitoring and treatment of RA favors remission and rehabilitation. Here, we developed a wearable reconfigurable integrated smart device (ISD) for real-time inflammatory monitoring and synergistic therapy of RA. The device establishes an electrical-coupling and substance delivery interfaces with the skin through template-free conductive polymer microneedles that exhibit high capacitance, low impedance, and appropriate mechanical properties. The reconfigurable electronics drive the microneedle-skin interfaces to monitor tissue impedance and on-demand drug delivery. Studies in vitro demonstrated the anti-inflammatory effect of electrical stimulation on macrophages and revealed the molecular mechanism. In a rodent model, impedance sensing was validated to hint inflammation condition and facilitate diagnosis through machine learning model. The outcome of subsequent synergistic therapy showed notable relief of symptoms, elimination of synovial inflammation, and avoidance of bone destruction.

IGF2BP2 regulates the inflammation of fibroblast-like synoviocytes via GSTM5 in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease with an unknown etiology. RA cannot be fully cured and requires lengthy treatment, imposing a significant burden on both individuals and society. Due to the lack of specific drugs available for treating RA, exploring a key new therapeutic target for RA is currently an important task. Activated fibroblast-like synoviocytes (FLSs) play a crucial role in the progression of RA, which release interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α resulting in abnormal inflammatory reaction in the synovium. A previous study has highlighted the correlation of m6A reader insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) with inflammation-related diseases in human. However, the role of IGF2BP2 in the inflammatory reaction of FLSs during RA progression has not been assessed. In this study, IGF2BP2 expression was decreased in the synovial tissues of RA patients and collagen-induced arthritis (CIA) rats. Intra-articular injection of an adeno-associated virus (AAV) vector overexpressing IGF2BP2 relieved paw swelling, synovial hyperplasia and cartilage destruction in CIA rats. IGF2BP2 overexpression also inhibited lipopolysaccharide (LPS)-mediated RA fibroblast-like synoviocytes (RA-FLSs) migration and invasion accompanied by a decreased level of inflammatory factors in vitro. Conversely, IGF2BP2 suppression promoted RA-FLSs migration and invasion with an elevated level of inflammatory factors in vitro. The sequencing result showed that glutathione S-transferase Mu 5 (GSTM5), a key antioxidant gene, was the target mRNA of IGF2BP2. Further experiments demonstrated that IGF2BP2 strengthened the stability of GSTM5 mRNA, leading to weakened inflammatory reaction and reduced expression of matrix metalloproteinase 9 and 13 (MMP9, MMP13). Therefore, IGF2BP2-GSTM5 axis may represent a potential therapeutic target for RA treatment.

Ammodaucus Leucotrichus Seed Extract as a Potential Therapy in Animal Models of Rheumatoid Arthritis Induced by Complete Freund Adjuvant and Chicken Cartilage Collagen.

This study assessed the efficacy of an Ammodaucus leucotrichus seed extract to treat rheumatoid arthritis in rat models of this disease. Rheumatoid arthritis was induced in rats using two methods: immunization with 100 µL of Complete Freund Adjuvant (CFA) and immunization with 100 µL of a 3mg/ml solution of type II collagen (CII) from chicken cartilage. The therapeutic potential of the extract was assessed at different doses (150, 300, and 600mg/kg/day for 21 days in the CII-induced arthritis model and for 14 days in the CFA-induced arthritis model) and compared with methotrexate (MTX; 0.2mg/kg for the same periods), a commonly used drug for rheumatoid arthritis treatment in humans. In both models (CII-induced arthritis and CFA-induced arthritis), walking distance, step length, intra-step distance and footprint area were improved following treatment with the A. leucotrichus seed extract (all concentrations) and MTX compared with untreated animals. Both treatments increased the serum concentration of glutathione and reduced that of complement C3, malondialdehyde and myeloperoxidase. Radiographic data and histological analysis indicated that cartilage destruction was reduced already with the lowest dose of the extract (100mg/kg/dose) in both models. These results show the substantial antiarthritic potential of the A. leucotrichus seed extract, even at the lowest dose, suggesting that it may be a promising alternative therapy for rheumatoid arthritis and joint inflammation. They also emphasize its efficacy at various doses, providing impetus for more research on this extract as a potential therapeutic agent for arthritis.

Tofacitinib as a means of optimizing the treatment of rheumatoid arthritis at the outpatient stage (clinical cases)

Two clinical cases of tofacitinib use in the management of rheumatoid arthritis (RA) patients by a rheumatologist at the outpatient stage within the framework of the “Treatment to Target” strategy are presented. The first clinical case describes the case history of a female patient (age 48 years, RA duration 20 years), which demonstrates the difficulties in selecting pathogenetic therapy for late-stage RA. Consecutively prescribed four synthetic baseline anti-inflammatory drugs (methotrexate, sulfasalazine, cyclophosphamide, leflunomide) and two genetically engineered biological drugs (infliximab, rituximab) failed to achieve remission of the disease in the patient. Decrease in disease activity was noted after connection of the third biological drug – etanercept, treatment with which had to be interrupted due to pregnancy planning. The return to the combined treatment after childbirth did not lead to repeated “success”. A positive result was achieved 12 weeks after tofacitinib at a dose of 10 mg/day, which provided a decrease in RA activity to moderate and complete withdrawal of glucocorticoids. Given the incomplete clinical effect, tofacitinib dose was increased to 20 mg/day by the outpatient rheumatologist, which resulted in achieving low RA activity persisting for 5 years. The second case demonstrates the effectiveness of tofacitinib inclusion in the RA treatment regimen as a “second-line” drug. A patient (age 46 years, RA duration 10 years) with long-term drug (methotrexate 25 mg/week) clinical and laboratory remission of RA after an upper respiratory tract infection developed an exacerbation of the disease. Despite three-component therapy with baseline anti-inflammatory drugs, the patient had persistence of high RA activity, which led to the revision of pathogenetic therapy – tofacitinib at a dose of 10 mg/day with clinical effect of the drug after 4 weeks. The achieved clinical and laboratory remission of the disease has been maintained for two years. In outpatient practice tofacitinib can be an effective tool for optimizing RA treatment.