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ID PMID Title PublicationDate abstract
35054104 Diagnosis, Clinical Features and Management of Interstitial Lung Diseases in Rheumatic Dis 2022 Jan 14 Interstitial lung disease (ILD) is one of the most frequent pulmonary complications of autoimmune rheumatic diseases (ARDs), and it is mainly associated with connective tissue diseases (CTDs) and rheumatoid arthritis (RA) [...].
35616586 Risk of malignant melanoma and non-melanoma skin cancer in rheumatoid arthritis patients i 2022 May 10 OBJECTIVES: To characterise the incidence rate of skin cancer associated with methotrexate and hydroxychloroquine in older adults with rheumatoid arthritis (RA). METHODS: RA patients aged ≥65 years who initiated methotrexate or hydroxychloroquine as their first disease modifying antirheumatic drugs (DMARDs). The primary outcome was new occurrence of any skin cancer (i.e. malignant melanoma or non-melanoma skin cancer; NMSC) based on validated algorithms (positive predictive value >83%). Secondary outcomes were malignant melanoma, NMSC, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). We estimated the incidence rates (IRs) and hazard ratios (HRs) for each outcome in the 1:1 propensity score (PS)-matched methotrexate and hydroxychloroquine groups. RESULTS: We included 24,577 PS-matched pairs of methotrexate and hydroxychloroquine initiators. Compared with hydroxychloroquine (IR 25.20/1,000 person-years), methotrexate initiators (IR 26.21/1,000 person-years) had a similar risk of any skin cancer [HR 1.03 -(95%CI 0.92, 1.14)] over a mean follow-up of 388 days. The HR (95%CI) associated with methotrexate was 1.39 (0.87, 2.21) for malignant melanoma, 1.01(0.90, 1.12) for NMSC, 1.37 (1.13, 1.66) for BCC, and 0.79 (0.63, 0.99) for SCC compared with hydroxychloroquine. CONCLUSIONS: In this large cohort of older RA patients initiating methotrexate or hydroxychloroquine as their first DMARD, we found no difference in the risk of skin cancer including malignant melanoma and NMSC. However, for specific components of NMSC, methotrexate initiators had higher risk of BCC but lower risk of SCC compared with hydroxychloroquine initiators.
35367137 A National Catalog of Mapped Short-Form Six-Dimension Utility Scores for Chronic Condition 2022 Mar 30 OBJECTIVES: This study examined health preference utility weights and utility decrements associated with different types of chronic conditions in the United States. METHODS: We used the 2010-2015 Medical Expenditure Panel Survey data for persons aged ≥ 18 years with 12-Item Short-Form Survey Physical and Mental Component Summary scores. 12-Item Short-Form Survey scores were converted to Short-Form Six-Dimension (SF-6D) preference scores to measure utilities of different chronic diseases. We used the Clinical Classification Code to identify 30 chronic diseases from 12 categories, such as cardiovascular diseases, cerebrovascular diseases, hypertension, hyperlipidemia, obesity, cancers, musculoskeletal diseases, endocrine or metabolic diseases, oral diseases, respiratory diseases, and mental disorders. A generalized linear model was used to quantify the utility decrements for 30 chronic diseases, controlling for demographic characteristics. RESULTS: We identified 132 737 adults (mean age 47.2 years, 52.2% female, 80% white); 73% had at least one identified chronic disease, and the mean SF-6D was 0.786. Among 30 chronic diseases, the unadjusted mean SF-6D scores of patients with cognitive disorder (0.607) were the lowest, followed by congestive heart failure (0.629), rheumatoid arthritis (0.654), and lung cancer (0.662). After controlling for demographic variables (ie, age, sex) and comorbidities, cognitive disorders (-0.116), mood disorders (-0.099), rheumatoid arthritis (-0.090), liver cancer (-0.078), and stroke (-0.063) showed the highest decrements in the SF-6D scores (P < .05). CONCLUSIONS: This study provides a nationally representative catalog of utility weights for major chronic diseases in the US general population. The utility decrements will enable researchers to calculate the health utilities of patients with multiple comorbid diseases.
35591865 A Systematic Review and Network Meta-Analysis about the Efficacy and Safety of Tripterygiu 2022 OBJECTIVE: This study aims to evaluate the efficacy of various conventional synthetic DMARDs, including Tripterygium wilfordii Hook F (TwHF) for treating rheumatoid arthritis (RA) by network meta-analysis. METHODS: We retrieved the related literature from online databases and supplemented it by using a manual retrieval method. Data was extracted from the literature and analyzed with STATA software. RESULTS: A total of 21 trials (5,039 participants) were identified. Assessment of ACR20 response found that TwHF combined with methotrexate (MTX) had the greatest probability for being the best treatment option among the treatments involved, while TwHF used singly was second only to TwHF combined with MTX. Assessment of ACR50 response found that TwHF combined with MTX ranked second in all treatment options after cyclosporine A (CsA) combined with leflunomide (LEF) and TwHF alone, followed by TwHF combined with MTX. Assessment of ACR70 response found that CsA combined with LEF ranked first, TwHF combined with LEF ranked second, TwHF combined with MTX ranked third, and TwHF used singly ranked fourth. In the safety analysis, TwHF had the least probability of adverse event occurrence, followed by TwHF combined with MTX, which ranked first and second, respectively. CONCLUSION: Compared with the current csDMARDs for treating RA, the efficacy of TwHF was clear, and TwHF combined with MTX performed well under various endpoints. In the future, large, rigorous, and high-quality RCTs are still needed to confirm the benefits of TwHF therapy on RA.
34806341 Fatigue Is Not Associated With Objective Assessments of Inflammation During Tocilizumab Tr 2022 Mar OBJECTIVE: In patients with rheumatoid arthritis (RA), the relation between fatigue and disease activity is not established, and our objective was to explore in post hoc analyses the associations between fatigue and subjective as well as objective assessments of inflammation during follow-up of patients with RA initiating biologic treatment. METHODS: In a Nordic multicenter study, patients with RA starting tocilizumab were examined for fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue sum score) as well as patient-reported outcome measures (PROMs) (patient's global disease activity, joint pain, and Health Assessment Questionnaire Disability Index), clinical examinations (examiner's global disease activity, 28 tender/swollen joint counts), laboratory variables (erythrocyte sedimentation rate, C-reactive protein), and ultrasound assessments (semiquantitative scoring [0-3]) of gray scale and Doppler of 36 joints and 4 tendons) at baseline and 4, 12, and 24 weeks. The associations were explored by using nonparametric tests, including the Wilcoxon rank test, the Mann-Whitney U test, Spearman correlations, and a linear regression and linear mixed model. RESULTS: One hundred ten patients were included (83% female, mean [SD] age 55.6 [12.1] years, mean [SD] RA duration 8.7 [9.5] years, 81% anti-cyclic citrullinated peptide positive). Fatigue, PROMs, and clinical, laboratory, and ultrasound variables all decreased significantly during follow-up, already at 4 weeks (P < 0.001). Fatigue was both cross-sectionally and longitudinally associated with PROMs, whereas there were no or low associations with clinical, laboratory, or ultrasound assessments of inflammation. Baseline fatigue was predictive of PROMs at 12 and 24 weeks (P < 0.05 and P < 0.001, respectively) but not of any objective assessments. CONCLUSION: Fatigue was primarily associated with subjective assessments of disease activity. Thus, the present study supports fatigue to reflect other aspects of RA disease activity than inflammation.
35628185 Activation and Function of NLRP3 Inflammasome in Bone and Joint-Related Diseases. 2022 May 11 Inflammation is a pivotal response to a variety of stimuli, and inflammatory molecules such as cytokines have central roles in the pathogenesis of various diseases, including bone and joint diseases. Proinflammatory cytokines are mainly produced by immune cells and mediate inflammatory and innate immune responses. Additionally, proinflammatory cytokines accelerate bone resorption and cartilage destruction, resulting in the destruction of bone and joint tissues. Thus, proinflammatory cytokines are involved in regulating the pathogenesis of bone and joint diseases. Interleukin (IL)-1 is a representative inflammatory cytokine that strongly promotes bone and cartilage destruction, and elucidating the regulation of IL-1 will advance our understanding of the onset and progression of bone and joint diseases. IL-1 has two isoforms, IL-1α and IL-1β. Both isoforms signal through the same IL-1 receptor type 1, but the activation mechanisms are completely different. In particular, IL-1β is tightly regulated by protein complexes termed inflammasomes. Recent research using innovative technologies has led to a series of discoveries about inflammasomes. This review highlights the current understanding of the activation and function of the NLRP3 (NOD-like receptor family, pyrin domain-containing 3) inflammasome in bone and joint diseases.
35403370 Time-Varying Association of Rheumatoid Arthritis Disease Activity to Subsequent Cardiovasc 2022 Apr 10 OBJECTIVE: It is unknown how the relationship between disease activity in rheumatoid arthritis (RA) and cardiovascular (CV) events may change over time. We examined the potentially time-varying association of RA disease activity to CV events. METHODS: We used the CorEvitas prevalent RA registry. The Clinical Disease Activity Index (CDAI) score category, averaged within each 6-month window since enrollment, was the exposure, and the outcome was major adverse CV events (MACEs). We used marginal structural models to estimate the hazard ratio (HR), comparing each CDAI score category with remission, allowing for differential association over time. We predicted MACE-free survival under several CDAI score scenarios. RESULTS: We found 44,816 eligible patients (77% female; mean age 58 years) with a crude event rate of 5.3/1000 person-years (median follow-up 3.4 years). The strongest association between higher CDAI score and MACEs was observed during the first 6 months of enrollment (HR for CDAI score low 2.29 [95% CI: 1.21-4.36], moderate 2.81 [95% CI: 1.46-5.43], and high 2.99 [95% CI: 1.48-6.02]). These estimates gradually diminished; by year 5, the HRs were 1.00 (95% CI: 0.49-2.05) for low, 1.18 (95% CI: 0.51-2.71) for moderate, and 1.04 (95% CI: 0.45-2.40) for high CDAI score. Predicted MACE-free survival suggested a potential decrease in MACEs with a hypothetical earlier transition to remission. CONCLUSION: The association of higher disease activity with CV events may be stronger earlier in the disease course of RA. Interventional studies may be warranted to precisely determine the effect of disease activity suppression on CV events in RA.
35384021 Comparison of efficacy and cost-efficiency of an immunologically targeted low dose rituxim 2022 Apr 5 BACKGROUND: Various dosing protocols of rituximab have been used in pemphigus. B-cell repopulation post-rituximab can be considered a forerunner of clinical relapse. Immunologically-guided dosing may obviate the need of fixed timepoint maintenance dosing, hence proving more cost-effective and perhaps safer. OBJECTIVE: Comparison of overall efficacy and cost-efficiency of low dose rituximab with immunologically-guided ultra-low (200mg) top-up infusions versus rheumatoid arthritis (RA) protocol with 500mg repeat infusion upon clinical relapse, in severe pemphigus over one-year period. METHODS: 23 patients of severe pemphigus were randomized into Group-A (RA protocol: 1000mg, 2 doses, 2 weeks apart) and Group-B (low-dose rituximab: 500mg, 2 doses, 2 weeks apart). Both groups also received short-term oral corticosteroids and were followed clinically and immunologically (3-monthly flowcytometric assessments of B-cell subtypes). While Group-A got a 500mg rituximab top-up upon clinical relapse; Group-B received an ultra-low top-up (200mg) on B-cell repopulation, intended to prevent clinical relapse. Outcome parameters [complete remission off treatment (CROT), relapse (clinical and immunological), total corticosteroid dose and direct cost of therapy] were compared. RESULTS: Time to CROT (Group-A: 27±1.6 weeks; Group-B: 26±1.2 weeks, p=0.09) and cumulative prednisolone dose (p=0.28) were comparable. 10/11 (90.9%) patients in Group-B had B-cell repopulation (8.4±2.4 months) and a single 200mg top-up dose successfully prevented clinical relapse. In Group-A, 3/9 (33.3%) patients had clinical relapse (9.3±0.4 months). Overall cost of therapy was 37.4% cheaper in Group-B. CONCLUSION: An immunologically- guided low dose rituximab regimen can be an equally effective yet affordable alternative to conventional rituximab regimens in pemphigus.
35076904 Treatment Patterns Among Patients with Rheumatoid Arthritis in Puerto Rico. 2022 Apr INTRODUCTION: Racial and ethnic disparities in rheumatoid arthritis (RA) have been identified in the United States, with higher levels of disease activity and worse functional status reported in Hispanic patients compared with their white counterparts. Although RA is one of the most prevalent health conditions in Puerto Rico, few studies have previously examined the characteristics or treatment patterns of patients receiving biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) in this population. METHODS: This was a retrospective cohort study using data extracted from the Advanced Business Management Organization database, which represents around 70% of pharmacy claims in Puerto Rico. Patients with RA were included if they had ≥ 1 prescription for any approved b/tsDMARD during the index period (January 2016 to July 2018), and ≥ 2 years of follow-up. The objective was to describe and compare the demographic and clinical characteristics of patients with RA being treated with b/tsDMARD therapy in Puerto Rico, and to evaluate the treatment patterns among these patients. RESULTS: Most patients (74%) received tumor necrosis factor inhibitors (TNFis) as index therapy, followed by abatacept (17%), Janus kinase inhibitors (JAKis; 5%), and other non-TNFis (4%). Similar trends were observed in subsequent lines of therapy, although abatacept was more frequently used in these later lines versus index therapy. At 2 years, 62% of patients had discontinued their index therapy and 17% had switched to an alternative b/tsDMARD; only 21% persisted with index therapy. The percentage of patients who were persistent with their index therapy at the end of year 2 was 28% for JAKis, 36% for abatacept, 41% for TNFis, and 45% for other non-TNFis. CONCLUSIONS: These findings demonstrate that despite the availability of several b/tsDMARDs, patients with RA in Puerto Rico still experience substantial treatment disruption, with almost two-thirds of patients discontinuing their index therapy within 2 years.
35038643 The role of whole-body MRI in musculoskeletal inflammation detection and treatment respons 2022 Feb OBJECTIVE: To evaluate the relation between whole-body MRI (WBMRI) outcomes and disease activity measures, including clinical examination, composite scores, and other imaging outcomes, and the ability of WBMRI to detect treatment response in patients with inflammatory arthritis (IA) across age. METHODS: Human studies published as full text or abstract in the PubMed and MEDLINE and Cochrane databases from inception to 11th April 2021 were systematically and independently searched by two reviewers. Studies including patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), spondyloarthritis (SpA), juvenile idiopathic arthritis (JIA) or unclassified inflammatory arthritis (UA) who underwent WBMRI and which reported on disease outcomes were included. RESULTS: Nineteen full-text studies were eligible for inclusion: 2 interventional, 7 retrospective and 10 prospective observational studies, comprising 540 participants (SpA 38.7%, RA 24.8%, JIA 17.8%, PsA 11.5%, healthy controls 5.9%, UA 1.3%). Abstracts of 6 conference papers were reported separately. Five studies in PsA and SpA and 4 in RA measured the frequency of WBMRI-detected and clinically-detected synovitis, and all found the former to be more frequent. Less enthesitis was detected by WBMRI than clinical examination in 5/8 studies. After biologic treatment, the WBMRI inflammation scores declined in 3 studies in SpA and 2 in RA, whilst in 3 studies the results were equivocal. CONCLUSION: The ability of WBMRI to assess disease activity and treatment response in IA was adequate overall. Further studies are needed to corroborate WBMRI findings with IA outcomes and investigate the clinical value of subclinical inflammation.
35622172 Comparison and correlation study of synovial ultrasound indices and serum VEGF in rheumato 2022 May 27 OBJECTIVE: Rheumatoid wrist arthritis is a chronic autoimmune disease, resulting in joint deformity and functional impairment. We aimed to compare the wrist synovial ultrasound indices and serum vascular endothelial growth factor (VEGF) level in patients with RA before and after treatment, and to explore the correlation between the two. METHODS: Forty patients with RA in wrist underwent ultrasound examination to determine wrist synovial thickness, synovial blood flow grade, and synovial artery resistive index (RI) before and after treatment. The serum level of VEGF was detected by enzyme-linked immunosorbent assay. Correlation between synovial ultrasound indices and serum VEGF level was assessed. RESULTS: Pre-treatment synovial thickness, synovial artery RI, and serum VEGF level were 8.60 ± 2.82 mm, 0.62 ± 0.07, and 419.49 ± 19.27 pg/mL, respectively. The corresponding post-treatment levels were 4.05 ± 1.89 mm, 0.83 ± 0.10, and 199.30 ± 16.18 pg/mL. Pre-treatment distribution of synovial blood flow grades was as follows: grade 0, nil; grade I, 1 case; grade II, 17 cases; grade III, 22 cases. The post-treatment distribution was as follows: grade 0, 6 cases; grade I, 23 cases; grade II, 11 cases; and grade III, nil. There were significant differences between pre- and post-treatment wrist synovial thickness, artery RI, and blood flow grading. Wrist synovial thickness and synovial blood flow grade showed a strong positive correlation with serum VEGF level (P < 0.01). There was strong negative correlation between wrist synovial artery RI and serum VEGF level (P < 0.01). CONCLUSION: The strong correlation between wrist synovial ultrasound indicators and serum VEGF may be clinically useful for diagnosis and therapy.
35470716 Identification in synovial fluid of a new potential pathogenic player in arthropathies. 2022 Apr 26 STING (stimulator of interferon genes) has been recognized as an important signaling molecule in the innate immune response to cytosolic nucleic acids. Although it has been proposed that STING signaling pathway may play a pathogenic role in developing autoimmune and autoinflammatory diseases, its involvement in rheumatic disease processes remains to be elucidated. Here, we evaluated STING protein levels, expression and relationship with inflammatory parameters in synovial fluid (SF) of patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), gout, calcium pyrophosphate crystal-induced arthritis (CPP-IA), osteoarthritis (OA), and OA with CPP crystals (OA + CPP). The correlation with its negative regulator, nuclear factor erythroid 2-related factor 2 (Nrf2), was also investigated. SFs from 72 patients were analyzed for white blood cell (WBC) count, polymorphonuclear cell percentage (PMN%), and IL-1β, IL-6, IL-8, extra- and intracellular STING levels. STING and Nrf2 expression was also determined. WBC count and PMN% were greater in SF from inflammatory arthritis, while they were lower in OA groups. RA and gouty SFs have the highest levels of IL-1β, IL-8, and IL-6; while OA and OA + CPP showed the lowest concentrations. Gout and RA had the highest intracellular STING levels, while extracellular STING was greater in CPP-IA and OA SFs. STING was not detectable in PsA. STING mRNA was lower in PsA than other arthritides. Nrf2 mRNA was not detectable in OA. This study determines the presence of STING in SF of different arthritides, except for PsA, and suggests that it may be involved in pathogenesis and progression of arthropathies.
35293336 Presence of Autoantibodies in Males and Females With Rheumatoid Arthritis: A Systematic Re 2022 Mar 15 OBJECTIVE: Rheumatoid arthritis (RA) is more common in females, and although the cause of RA is unknown, it is characterized by the production of autoantibodies. The aims of this study were to determine whether RA-associated autoantibodies are more often found in females than males and to identify factors that influence the relationship between sex and seropositivity. METHODS: Databases were searched and studies of RA (N ≥ 100) were included if they reported proportion of seropositive patients with RA by sex. Metaanalyses and metaregression were conducted using the random-effects model. Covariates regressed were smoking, age, BMI, Health Assessment Questionnaire-Disability Index (HAQ-DI), and the Disease Activity Score in 28 joints (DAS28). RESULTS: Eighty-four studies with a total of 141,381 subjects with rheumatoid factor (RF) seropositivity and 95,749 subjects with anticitrullinated protein antibody (ACPA) seropositivity met inclusion criteria. The mean age of participants ranged from 37 to 68 years and the proportion of female subjects ranged from 9% to 92%. Results indicated that females were less likely than males to be seropositive: odds ratio (OR) 0.84 [95% CI 0.77-0.91] for RF and OR 0.88 [95% CI 0.81-0.95] for ACPA. BMI, smoking, mean age, DAS28, and HAQ-DI did not affect the relationship between sex and seropositivity. CONCLUSION: Although studies report that females have higher RA disease activity than males and that seropositivity predicts worse outcomes, females were less likely to be seropositive than males.
35622871 Performance of a rapid immuno-chromatographic test (Schistosoma ICT IgG-IgM) for detecting 2022 May 27 BACKGROUND: Schistosomiasis, an acute and chronic parasitic disease caused by human pathogenic Schistosoma species, is a neglected tropical disease affecting more than 220 million people worldwide. For diagnosis of schistosomiasis, stool and urine microscopy for egg detection is still the recommended method, however sensitivity of these methods is limited. Therefore, other methods like molecular detection of DNA in stool, detection of circulating cathodic antigen in urine or circulating anodic antigen in urine and serum, as well as serological tests have gained more attention. This study examines the sensitivity and specificity of a rapid diagnostic test based on immunochromatography (Schistosoma ICT IgG-IgM, LD Bio, Lyon, France) for simultaneous detection of specific IgG and IgM antibodies in serum, against Schistosoma spp. in endemic and non-endemic populations. METHODOLOGY/PRINCIPAL FINDINGS: Frozen banked serum samples from patients with confirmed schistosomiasis, patients with other helminth infections, patients with seropositive rheumatoid arthritis and healthy blood donors were used to assess the sensitivity and the specificity of the Schistosoma ICT IgG-IgM rapid diagnostic test. The test showed a sensitivity of 100% in patients with parasitologically confirmed schistosomiasis, irrespective of the species (S. mansoni, S. haematobium, S. japonicum, S. mekongi). In healthy blood donors and patients with rheumatoid factor positive rheumatoid arthritis from Europe, specificity was 100%. However, in serum samples of patients with other tissue invasive helminth infections, the test showed some cross-reactivity, resulting in a specificity of 85%. CONCLUSION/SIGNIFICANCE: With its high sensitivity, the Schistosoma ICT IgG-IgM rapid diagnostic test is a suitable screening test for detection of Schistosoma specific antibodies, including S. mekongi. However, in populations with a high prevalence of co-infection with other tissue invasive helminths, positive results should be confirmed with other diagnostic assays due to the test's imperfect specificity.
35254584 Berberis lycium fruit extract and its phytoconstituents berberine and rutin mitigate colla 2022 Apr Rheumatoid arthritis (RA), a chronic auto-immune disease, is often result of persistent and misdirectional inflammation and cannot be effectually resolved by single-target selective drugs. Present study attempted to uncover anti-arthritic efficacy and governing molecular mechanism of BLFE and its phytoconstituents berberine and rutin, with focus on dysregulated oxi-inflammation and structural integrity during articular damage using Collagen II-CFA-induced RA mice model. NMR-based phytometabolomic analysis revealed presence of phenolics and alkaloids such as berberine and rutin. BLFE, rutin and berberine remarkably mitigated Collagen II-CFA-induced disease severity index, articular damage, immune cells influx and pannus formation. An effective decrease in levels of TNF-α, IL-6, IL-1β, IFN-γ, IL-13, IL-17, MMPs, RORγt, Ob-cadherin, Cox-2, iNOS and enhancement in IL-10, IL-4 and IL-5, BMP-6/7 was observed in BLFE, rutin and berberine treatments. Molecular mechanistic analysis demonstrated reduction in expression of p-STAT-1/3, p-PI3K, p-Akt, p-JNK, p-p38, p-IκB, p-NF-κB and β-catenin via BLFE, rutin and berberine. Furthermore, reduced activation of p-ERK and p-GSK3β and enhanced splenic Tregs was only noticed in BLFE and berberine. Thus, the signifying presence of these phytoconstituents could contribute to the above-mentioned findings. These findings imply that BLFE could be beneficial for assuaging deleterious aspects of RA mediated via perturbed inflammation.
35335915 Polymeric Hydrogels for Controlled Drug Delivery to Treat Arthritis. 2022 Feb 28 Rheumatoid arthritis (RA) and osteoarthritis (OA) are disabling musculoskeletal disorders that affect joints and cartilage and may lead to bone degeneration. Conventional delivery of anti-arthritic agents is limited due to short intra-articular half-life and toxicities. Innovations in polymer chemistry have led to advancements in hydrogel technology, offering a versatile drug delivery platform exhibiting tissue-like properties with tunable drug loading and high residence time properties This review discusses the advantages and drawbacks of polymeric materials along with their modifications as well as their applications for fabricating hydrogels loaded with therapeutic agents (small molecule drugs, immunotherapeutic agents, and cells). Emphasis is given to the biological potentialities of hydrogel hybrid systems/micro-and nanotechnology-integrated hydrogels as promising tools. Applications for facile tuning of therapeutic drug loading, maintaining long-term release, and consequently improving therapeutic outcome and patient compliance in arthritis are detailed. This review also suggests the advantages, challenges, and future perspectives of hydrogels loaded with anti-arthritic agents with high therapeutic potential that may alter the landscape of currently available arthritis treatment modalities.
33034255 Ligand-based pharmacophore modeling of TNF-α to design novel inhibitors using virtual scr 2022 Mar Tumor necrosis factor-α (TNF-α) is one of the promising targets for treating inflammatory (Crohn disease, psoriasis, psoriatic arthritis, rheumatoid arthritis) and various other diseases. Commercially available TNF-α inhibitors are associated with several risks and limitations. In the present study, we have identified small TNF-α inhibitors using in silico approaches, namely pharmacophore modeling, virtual screening, molecular docking, molecular dynamics simulation and free binding energy calculations. The study yielded better and potent hits that bind to TNF-α with significant affinity. The best pharmacophore model generated using LigandScout has an efficient hit rate and Area Under the operating Curve. High throughput virtual screening of SPECS database molecules against crystal structure of TNF-α protein, coupled with physicochemical filtration, PAINS test. Virtual hit compounds used for molecular docking enabled the identification of 20 compounds with better binding energies when compared with previously known TNF-α inhibitors. MD simulation analysis on 20 virtual identified hits showed that ligand binding with TNF-α protein is stable and protein-ligand conformation remains unchanged. Further, 16 compounds passed ADMET analysis suggesting these identified hit compounds are suitable for designing a future class of potent TNF-α inhibitors.Communicated by Ramaswamy H. Sarma.
35592040 Hansen's disease masquerading as rheumatoid arthritis: A case report. 2022 May Hansen's disease, a chronic granulomatous disease, classically has cutaneous and neurological manifestations. Musculoskeletal manifestation of the disease is underappreciated. This case report conveys that musculoskeletal manifestation of the disease should not be missed, as sometimes it is the only presenting symptom, to avoid delay in correct diagnosis and treatment.
35200127 Il-34 regulates MAPKs, PI3K/Akt, JAK and NF-κ B pathways and induces the expression of in 2022 Feb 1 OBJECTIVES: To explore the role of interleukin 34 (IL-34) in rheumatoid arthritis (RA) and its related signalling pathways as well as the expression levels of IL-34 in collagen-induced arthritis (CIA) modelling mice. METHODS: Recombination IL-34 was used to stimulate cultured RA fibroblast-like synoviocytes (RA-FLS). The expression levels of inflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA), and the levels of phosphorylation signalling molecules were detected by western blotting assay (WB). After the establishment of the CIA model, paw indexes and serum IL-34 expression levels of mice were evaluated. RESULTS: IL-34 significantly increased the secretion of IL-8 and TNF-α but had no significant effect on IL-6, and this effect could be impaired by signal inhibitors. At the same time, IL-34 activated multiple signalling pathways, whereas treating with inhibitors could reduce phosphorylation intensity. In animal experiments, mice in the model group had lost weight, and their paws were obviously swollen, ulcerous, and even stiffened. The hyperplasia of synovial tissue, infiltration of many inflammatory cells, and destruction of bone and cartilage from the typical pannus formation were also apparently observed. CONCLUSIONS: IL-34 can mediate the production and secretion of IL-8 and TNF-α in RA-FLS cells through MAPKs, PI3K/Akt, JAK and NF-κB signalling pathways, while the expression of serum IL-34 in collagen-induced arthritis mice is also upregulated.
35636705 Sustained DMARD-free remission in rheumatoid arthritis - concepts and moving towards pract 2022 May 27 Sustained DMARD-free remission (SDFR) is the best possible outcome in RA. It is characterized by sustained absence of clinical arthritis, which is accompanied by resolution of symptoms and restoration of normal physical functioning. Therefore it's the best proxy for cure in RA. The mechanisms underlying SDFR-development are yet unidentified. Hypothetically, there are two possible scenarios. The first hypothesis is based on the concept of regaining immune-tolerance, which implies that RA-patients are similar at diagnosis and that disease-processes during the disease-course shift into a favorable direction, resulting in regaining a state in which arthritis is persistently absent. This could imply that SDFR is theoretically achievable for all RA-patients. The alternative hypothesis is that RA-patients who achieve SDFR are intrinsically different from those who cannot. This would imply that DMARD-cessation could be restricted to a subgroup of RA-patients. Since the 1990s, DMARD-discontinuation and SDFR have been increasingly studied as long-term-outcome in RA. In this review, we describe hitherto results of clinical, genetic, serological, histological and imaging studies and looked for arguments for the first or second hypothesis in both autoantibody-positive and autoantibody-negative RA. In autoantibody-negative-RA, SDFR is presumably restricted to a subgroup of patients with high serological-markers of inflammation at diagnosis and a rapid and sustained decrease in inflammation after treatment-start. Identifying these RA-patients could be helpful in realizing personalized-medicine. In autoantibody-positive RA, only few patients achieve SDFR and no definite conclusions can be drawn, but data could suggest that SDFR-patients might be a subgroup with relatively low inflammation from disease-presentation onwards.