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Translational Research : the Journal of... Dec 2019RNA interference (RNAi) is a cellular mechanism for post-transcriptional gene regulation mediated by small interfering RNA (siRNA) and microRNA. siRNA-based therapy... (Review)
Review
RNA interference (RNAi) is a cellular mechanism for post-transcriptional gene regulation mediated by small interfering RNA (siRNA) and microRNA. siRNA-based therapy holds significant promise for the treatment of a wide-range of arthritic diseases. siRNA selectively suppresses the expression of a gene product and can thus achieve the specificity that is lacking in small molecule inhibitors. The potential use of siRNA-based therapy in arthritis, however, has not progressed to clinical trials despite ample evidence for efficacy in preclinical studies. One of the main challenges to clinical translation is the lack of a suitable delivery vehicle to efficiently and safely access diverse pathologies. Moreover, the ideal targets in treatment of arthritides remain elusive given the complexity and heterogeneity of these disease pathogeneses. Herein, we review recent preclinical studies that use RNAi-based drug delivery systems to mitigate inflammation in models of rheumatoid arthritis and osteoarthritis. We discuss a self-assembling peptide-based nanostructure that demonstrates the potential of overcoming many of the critical barriers preventing the translation of this technology to the clinic.
Topics: Animals; Arthritis; Cell Engineering; Gene Transfer Techniques; Humans; Inflammation; RNA Interference; Signal Transduction
PubMed: 31351032
DOI: 10.1016/j.trsl.2019.07.002 -
Journal of Translational Medicine Aug 2016Only recently, the scientific community gained insights on the importance of the intestinal resident flora for the host's health and disease. Gut microbiota in fact... (Review)
Review
BACKGROUND
Only recently, the scientific community gained insights on the importance of the intestinal resident flora for the host's health and disease. Gut microbiota in fact plays a crucial role in modulating innate and acquired immune responses and thus interferes with the fragile balance inflammation versus tolerance.
MAIN BODY
Correlations between gut bacteria composition and the severity of inflammation have been studied in inflammatory bowel diseases. More recently similar alterations in the gut microbiota have been reported in patients with spondyloarthritis, whereas in rheumatoid arthritis an accumulating body of evidence evokes a pathogenic role for the altered oral microbiota in disease development and course. In the context of dysbiosis it is also important to remember that different environmental factors like stress, smoke and dietary components can induce strong bacterial changes and consequent exposure of the intestinal epithelium to a variety of different metabolites, many of which have an unknown function. In this perspective, and in complex disorders like autoimmune diseases, not only the genetic makeup, sex and immunologic context of the individual but also the structure of his microbial community should be taken into account.
CONCLUSIONS
Here we provide a review of the role of the microbiota in the onset, severity and progression of chronic inflammatory arthritis as well as its impact on the therapeutic management of these patients. Furthermore we point-out the complex interwoven link between gut-joint-brain and immune system by reviewing the most recent data on the literature on the importance of environmental factors such as diet, smoke and stress.
Topics: Animals; Arthritis; Chronic Disease; Environment; Humans; Inflammation; Microbiota
PubMed: 27492386
DOI: 10.1186/s12967-016-0989-3 -
Journal of Psychosomatic Research Dec 2023This study aimed to compare the health-related quality of life scores among rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis and to evaluate...
OBJECTIVES
This study aimed to compare the health-related quality of life scores among rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis and to evaluate socio-demographic and clinical determinantes of quality of life across diseases.
METHODS
The sample comprised 490 patients with rheumatoid arthritis, 198 with psoriatic arthritis, and 119 with spondyloarthritis who completed a series of health examinations and self-reported questionnaires. Quality of life was evaluated using the Short-Form 36 Health Survey, disease activity by DAS28-CRP, DAPSA, and ASDAS-CRP (for rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis, respectively), depression and anxiety using the Hospital Anxiety and Depression Scale. ANOVA was used to compare the quality of life dimensions and their physical and mental summary measures among rheumatic diseases, and multivariate analysis was used to explore their potential determinants.
RESULTS
Rheumatoid arthritis had significantly worse scores than spondyloarthritis in the following dimensions: physical functioning, role limitation due to physical health, physical component score, and mental health. Psoriatic arthritis was not significantly different from the other two diseases. Multivariate analysis revealed that physical quality of life was mainly associated with disease activity across rheumatic diseases, rheumatological treatment and depression in rheumatoid arthritis and psoriatic arthritis. Mental quality of life is primarily associated with depression and anxiety across rheumatic diseases.
CONCLUSION
There were differences in quality of life among patients with inflammatory rheumatic diseases, but overall, approximately uniform factors explained the variance in quality of life across diseases. Clinicians should develop general approaches and strategies for inflammatory rheumatic diseases to improve patients' quality of life.
Topics: Humans; Arthritis, Psoriatic; Quality of Life; Cross-Sectional Studies; Arthritis, Rheumatoid; Spondylarthritis
PubMed: 37844390
DOI: 10.1016/j.jpsychores.2023.111512 -
Journal of ISAKOS : Joint Disorders &... Feb 2024In elbow stiffness, pre-operative assessments should identify the articular and peri-articular tissues involved and, more specifically, they should determine how...
In elbow stiffness, pre-operative assessments should identify the articular and peri-articular tissues involved and, more specifically, they should determine how preserved the articular surfaces and osteo-articular congruity are. We will focus on the most important conditions and tissue reactions after trauma in order to understand the causes of joint stiffness. A logical surgical planning is based upon a deep knowledge of the anatomical obstacles and of the associated lesions that the trauma provoked with. The peri-articular soft tissue contractures. The osteo-articular incongruity.
Topics: Humans; Elbow; Elbow Joint; Elbow Injuries; Treatment Outcome; Joint Dislocations; Arthritis; Ossification, Heterotopic
PubMed: 37879605
DOI: 10.1016/j.jisako.2023.10.009 -
RMD Open Apr 2023
Same, same or different? Commonalities and differences between spondyloarthritis and its subsets of axial and peripheral spondyloarthritis with psoriatic arthritis and its diverse phenotypes.
Topics: Humans; Arthritis, Psoriatic; Spondylarthritis; Spondylitis, Ankylosing; Phenotype
PubMed: 37028815
DOI: 10.1136/rmdopen-2022-002872 -
Journal of Immunology Research 2023The aim of the study was to investigate the landscape of B-cell-related gene expression profiling in rheumatoid arthritis (RA) synovium and explore the biological and...
BACKGROUND
The aim of the study was to investigate the landscape of B-cell-related gene expression profiling in rheumatoid arthritis (RA) synovium and explore the biological and clinical significance of these genes in RA.
METHODS
Expression profiling of synovial biopsies from subjects with 152 RA patients, 22 osteoarthritis (OA) patients, and 28 healthy controls was downloaded from the Gene Expression Omnibus database. Single-sample gene set enrichment analysis (ssGSEA) was performed to evaluate the abundance of infiltrated immune cells, and the results were validated using immunohistochemical staining. GSEA was employed to decipher differences in B-cell-related biological pathways. B-cell-related differential expression genes (BRDEGs) were screened, and BRDEGs-based model was developed by machine learning algorithms and evaluated by an external validation set and clinical RA cohort, then biological functions were further analyzed.
RESULTS
High levels of immune cell infiltration and B-cell-related pathway activation were revealed in RA synovium. BRDEGs were screened, and three key molecular markers consisting of FAS, GPR183, and TFRC were identified. The diagnosis model was established, and these gene markers have good discriminative ability for RA. Molecular pathological evaluation confirmed RA patients with high-risk scores presented higher levels of B-cell activation and RA characteristics. In addition, a competitive endogenous RNA network was established to elucidate the molecular mechanisms of the posttranscriptional network.
CONCLUSIONS
We described the B-cell-related molecular landscape of RA synovium and constructed a molecular diagnostic model in RA. The three genes FAS, GPR183, and TFRC may be potential targets for clinical diagnosis and immunoregulatory therapy of RA.
Topics: Humans; Arthritis, Rheumatoid; Synovial Membrane; Osteoarthritis; Biomarkers
PubMed: 38046263
DOI: 10.1155/2023/9422990 -
Biological Chemistry Aug 2015Cathepsin S is a member of the cysteine cathepsin protease family. It is a lysosomal protease which can promote degradation of damaged or unwanted proteins in the... (Review)
Review
Cathepsin S is a member of the cysteine cathepsin protease family. It is a lysosomal protease which can promote degradation of damaged or unwanted proteins in the endo-lysosomal pathway. Additionally, it has more specific roles such as MHC class II antigen presentation, where it is important in the degradation of the invariant chain. Unsurprisingly, mis-regulation has implicated cathepsin S in a variety of pathological processes including arthritis, cancer, and cardiovascular disease, where it becomes secreted and can act on extracellular substrates. In comparison to many other cysteine cathepsin family members, cathepsin S has uniquely restricted tissue expression and is more stable at a neutral pH, which supports its involvement and importance in localised disease microenvironments. In this review, we examine the known involvement of cathepsin S in disease, particularly with respect to recent work indicating its role in mediating pain, diabetes, and cystic fibrosis. We provide an overview of current literature with regards cathepsin S as a therapeutic target, as well as its role and potential as a predictive diagnostic and/or prognostic marker in these diseases.
Topics: Animals; Arthritis; Cardiovascular Diseases; Cathepsins; Humans; Hydrogen-Ion Concentration; Neoplasms; Prognosis
PubMed: 25872877
DOI: 10.1515/hsz-2015-0114 -
Brain and Behavior Jun 2024Observational studies have found that most patients with arthritis have depression. We aimed to determine the causal relationship between various types of arthritis and...
INTRODUCTION
Observational studies have found that most patients with arthritis have depression. We aimed to determine the causal relationship between various types of arthritis and depression.
METHODS
We conducted a two-sample bidirectional Mendelian randomized (MR) analysis to determine whether there was a significant causal relationship between depression and multiple types of arthritis. The data of our study were derived from the publicly released genome-wide association studies (GWASs) and the largest GWAS meta-analysis. MR analysis mainly used inverse-variance weighted method; supplementary methods included weighted median, weighted mode, and MR-Egger using MR pleiotropy residual sum and outlier to detect and correct for the presence of pleiotropy.
RESULTS
After adjusting for heterogeneity and horizontal pleiotropy, we found that depression was associated with an increased risk of osteoarthritis (OA) (OR = 1.02, 95%CI: 1.01-1.02, p = 2.96 × E - 5). In the reverse analysis, OA was also found to increase the risk of depression (OR = 1.10, 95%CI: 1.04-1.15, p = .0002). Depression only increased the risk of knee OA (KOA) (OR = 1.25, 95%CI: 1.10-1.42, p = 6.46 × E - 4). Depression could potentially increase the risk of spondyloarthritis (OR = 1.52, 95%CI: 1.19-1.94, p ≤ 8.94 × E - 4).
CONCLUSION
There is a bidirectional causal relationship of depression with OA. However, depression only augments the risk of developing KOA. Depression may increase the risk of spondyloarthritis and gout.
Topics: Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Depression; Osteoarthritis; Osteoarthritis, Knee; Arthritis; Arthritis, Rheumatoid; Gout; Risk Factors; Spondylarthritis
PubMed: 38849983
DOI: 10.1002/brb3.3551 -
Clinical and Experimental Rheumatology 2016Musculoskeletal ultrasound (MSUS) has become a relevant part of rheumatology practice and research because it substantially allows us to optimize management of rheumatic... (Review)
Review
Musculoskeletal ultrasound (MSUS) has become a relevant part of rheumatology practice and research because it substantially allows us to optimize management of rheumatic and musculoskeletal diseases. This non-invasive imaging modality is a valuable point-of-care tool to accurately evaluate intra-articular and periarticular structures involved in a wide range of rheumatic diseases in adults and children. In addition, MSUS is an invaluable bedside aid for guiding accurate and safe musculoskeletal aspirations, injections and biopsies. This review provides an overview of the literature of the last year on the role of MSUS in arthritis.
Topics: Adult; Arthritis; Arthritis, Juvenile; Arthritis, Rheumatoid; Child; Echocardiography, Doppler; Humans; Musculoskeletal System; Osteoarthritis; Point-of-Care Systems; Point-of-Care Testing; Predictive Value of Tests; Prognosis; Reproducibility of Results; Severity of Illness Index
PubMed: 26892798
DOI: No ID Found -
Pediatric Rheumatology Online Journal Sep 2020Juvenile spondyloarthritis (JSpA) represents a group of inflammatory arthritides with several distinctive features (enthesitis, involvement of spine and sacroiliac...
BACKGROUND
Juvenile spondyloarthritis (JSpA) represents a group of inflammatory arthritides with several distinctive features (enthesitis, involvement of spine and sacroiliac joint, HLA-B27 association and development of uveitis). There are limited data on the course of uveitis in children with JSpA. This study aims to estimate the prevalence of uveitis and to look at the presence of HLA-B27 in relation to uveitis occurrence and ocular symptoms in a cohort of JSpA patients.
FINDINGS
This is a cross sectional/retrospective study involving patients with JSpA followed in a tertiary referral hospital. Two hundred twenty-three patients were enrolled in the study. The prevalent diagnosis was enthesitis-related arthritis (ERA) (62%) followed by juvenile psoriatic arthritis (PsA), undifferentiated arthritis (UA), and the arthropathies associated with inflammatory bowel disease (IBD-A) (18, 14, 6%, respectively). Uveitis was reported in twenty-four patients (11%) of the JSpA cohort (JSpA-U). ERA patients had the highest uveitis prevalence (ERA-U) (13%) with similar prevalences in UA, PsA and in IBD-A (7% each). The prevalence of HLA-B27 positivity was similar amongst the entire JSpA-U cohort (N = 22, 45%) and those with ERA-U (N = 8, 44%). The overall prevalence of symptomatic uveitis was 79%. Neither the likelihood of uveitis, nor of symptomatic uveitis, varied by HLA-B27 status either in the entire cohort nor in those with ERA.
CONCLUSIONS
About one-tenth of patients developed uveitis, the majority of which was symptomatic. Fewer than half of the patients with uveitis were HLA-B27 positive. HLA-B27 status was not statistically associated with either the development of uveitis or symptomaticity of uveitis.
Topics: Adolescent; Arthritis, Juvenile; Arthritis, Psoriatic; Child; Child, Preschool; Cross-Sectional Studies; Female; HLA-B27 Antigen; Humans; Inflammatory Bowel Diseases; Male; Prevalence; Retrospective Studies; Spondylarthropathies; Uveitis
PubMed: 32912296
DOI: 10.1186/s12969-020-00463-4