Search Results (260)

Proper joint function has a significant impact on people’s quality of life. Joints are the point of connection between two or more bones and consist of at least three elements: joint surfaces, the joint capsule, and the joint cavity. Joint diseases are a serious social problem. Risk factors for the development of these diseases include overweight and obesity, gender, and intestinal microbiome disorders. Another factor that is considered to influence joint diseases is trace elements. Under normal conditions, elements such as iron (Fe), copper (Cu), cobalt (Co), iodine (I), manganese (Mn), zinc (Zn), silver (Ag), cadmium (Cd), mercury (Hg), lead (Pb), nickel (Ni) selenium (Se), boron (B), and silicon (Si) are part of enzymes involved in reactions that determine the proper functioning of cells, regulate redox metabolism, and determine the maturation of cells that build joint components. However, when the normal concentration of the above-mentioned elements is disturbed and toxic elements are present, dangerous joint diseases can develop. In this article, we focus on the role of trace elements in joint function. We describe the molecular mechanisms that explain their interaction with chondrocytes, osteocytes, osteoblasts, osteoclasts, and synoviocytes, as well as their proliferation, apoptosis, and extracellular matrix synthesis. We also focus on the role of these trace elements in the pathogenesis of joint diseases: rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and systemic lupus erythematosus (SLE). We describe the roles of increased or decreased concentrations of individual elements in the pathogenesis and development of joint diseases and their impact on inflammation and disease progression, referring to molecular mechanisms. We also discuss their potential application in the treatment of joint diseases. Full article

Human T-lymphotropic virus 1 (HTLV-1) infection has been associated with inflammatory, autoimmune, and lymphoproliferative diseases with a wide spectrum of clinical manifestations. Among patients with inflammatory rheumatological disease manifestations, cases of rheumatoid arthritis, Sjögren’s syndrome, polymyositis, and fibromyalgia, among others, have been reported. Another common feature of rheumatological diseases is the presence of joint manifestations, such as arthralgia and arthritis. In the present study, we sought to determine the laboratory profile and clinical rheumatological manifestations of people living with HTLV-1/2 residing in a metropolitan area in the Brazilian Amazon. A total of 957 individuals were screened for HTLV-1/2 infection by enzyme-linked immunosorbent assay (ELISA), and samples from seropositive individuals were subjected to infection confirmation by Western blotting or quantitative polymerase chain reaction (qPCR). Individuals with confirmed HTLV-1 and HTLV-2 infection were clinically evaluated for signs and symptoms of rheumatological diseases. Of the 957 individuals tested, 69 were positive for HTLV-1/2 infection, with 56 confirmed cases of HTLV-1 infection (5.9%), 12 of HTLV-2 infection (1.2%), and 1 classified as undetermined (0.1%). After clinical screening, 15 infected individuals with complaints suggestive of rheumatological disease were selected for evaluation by a rheumatologist (11 with HTLV-1 infection (1.1%) and 4 with HTLV-2 infection (0.4%)). The predominant pain pattern was symmetrical polyarthralgia, with large joints predominantly being affected. The diseases diagnosed were psoriatic arthritis, osteoarthritis, fibromyalgia, and regional pain syndromes. Antinuclear antibody (ANA) positivity was observed in two patients. Our findings confirm that HTLV-1 infection is associated with rheumatological disease manifestations and highlight the novel finding of cases of HTLV-2 infection in patients with rheumatoid arthritis symptoms. Full article

Inflammatory arthritis, including rheumatoid arthritis (RA) and osteoarthritis (OA), is a group of degenerative joint diseases that result in reduced mobility and a prevalent cause of disability. Despite differing etiologies, both conditions involve inflammation, affecting only the joints in OA and systemic in RA due to its autoimmune nature. Regenerative medicine offers promising alternatives, with a focus on the therapy with mesenchymal stem cell (MSC) and their secreted extracellular vesicles (EVs). MSC-derived EVs have shown great potential in modulating inflammatory pathways and promoting tissue repair in the preclinical models of RA and OA. Additionally, EVs from immune cells exhibit strong anti-inflammatory effects, reducing cartilage and bone degeneration. This review highlights the recent progress in MSC-based and EV-based therapies for OA and RA, discussing the bioengineering approaches that enhance the therapeutic efficacy, stability, and targeting of EV. It also addresses the major challenges in translating EV therapy from the laboratory to clinical practice and discusses strategies to overcome these obstacles in the treatment of inflammatory arthritis. Full article

Inflammation is a complicated physiological process that contributes to a variety of disorders including osteoarthritis (OA) and rheumatoid arthritis (RA). Endocannabinoids and the endocannabinoid system (ECS) play a pivotal role in the physiological response to pain and inflammation. A clinical study to investigate the role of the endocannabinoid system and related lipids in pain and inflammation in OA and RA was performed. In total, 80 subjects, namely, 25 patients with RA, 18 with OA, and 37 healthy participants, were included. Sixteen endocannabinoids and congeners, as well as 129 oxylipins, were quantified in plasma using specific, quantitative LC-MS/MS assays. The endocannabinoid analysis revealed significantly lower levels of 2-arachidonoylglycerol (2-AG) in RA and OA patients compared to healthy participants. In contrast, the EC levels of the ethanolamide group (anandamide, docosahexaenoyl-EA, palmitoleoyl-EA, and other ethanolamides) were higher in the RA study cohort and to a lesser extent also in the OA cohort. This analysis of oxylipins revealed lower levels of the pro-resolving lipid 9-oxo-octadecadienoic acid (9-oxoODE) and the ω-3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) in RA compared to all other study cohorts. 2-AG is a key regulator of nociception and inflammation, and its relatively low levels might be a mechanistic contributor to residual pain and inflammation in RA and OA. Several changes in pro- and anti-inflammatory lipid mediators were detected, including lower levels of EPA and DHA in RA, which might reveal the potential for nutritional supplementation with these anti-inflammatory fatty acids. Full article

Herein, a simple and effective analytical method was developed to monitor etoricoxib concentrations in human urine samples. Etoricoxib is a nonsteroidal anti-inflammatory drug for pain and inflammation relief in conditions such as osteoarthritis and rheumatoid arthritis. To determine its concentration, fabric phase sorptive extraction (FPSE) was combined with high-performance liquid chromatography and diode array detection (HPLC-DAD). FPSE is a green sample preparation technique that utilizes sol–gel-coated fabric substrates as extraction devices, offering numerous benefits in bioanalysis. Initially, different materials were tested for their affinity towards etoricoxib. The most critical FPSE parameters (i.e., sample amount, stirring rate, and adsorption time) were optimized using a face-centered central composite design (FC-CCD), while the remaining ones were explored by means of the one-variable-at-a-time approach. Afterwards, the analytical method was validated in terms of its selectivity, linearity, sensitivity, accuracy, and precision, while the environmental sustainability and the practicality of the method were also examined. The limit of detection was 0.03 μg mL⁻¹, and the lower limit of quantification was 0.10 μg mL⁻¹. The relative standard deviation was less than 7.2% in all cases, showing good precision. The proposed approach was successfully used to monitor urinary etoricoxib concentrations in real samples obtained from a volunteer after oral drug administration. Full article

Objectives: The objective of this study was to evaluate the relationship between interleukin-17 (IL-17) serum levels, musculoskeletal ultrasound (MSUS) observations, and clinical disease activity in patients with rheumatoid arthritis (RA) and hand osteoarthritis (OA). Methods: This case–control study involved 120 participants, with 40 individuals assigned to each of the three groups: RA, OA, and control. IL-17 serum levels were quantified in all participants. MSUS of the hand joints was performed on all RA and OA patients. Disease activity in patients with RA was assessed using the Clinical Disease Activity Score (CDAS). Both RA and OA patients completed a Visual Analog Scale (VAS) to evaluate pain intensity. Functional status was evaluated using the Health Assessment Questionnaire (HAQ) for RA patients, while the Australian/Canadian (AUSCAN) Osteoarthritis Hand Index was utilized for OA patients. Results: Serum levels of IL-17 were significantly higher in both the RA and OA groups compared to the control group. Among RA patients, a positive correlation was identified between the CDAS and the VAS for pain. In OA patients, a significant correlation was observed between VAS scores and serum IL-17 levels. Additionally, serum IL-17 levels were associated with the presence of synovitis in both RA and OA groups; however, no significant association was found between IL-17 levels and bony changes such as erosions or osteophytes. In terms of functional evaluation, serum IL-17 levels correlated with HAQ in the RA group, but not with AUSCAN in the OA group. Conclusions: Elevated IL-17 serum levels are linked to inflammatory changes identified by MSUS but not to bony changes. These findings suggest that the rise in IL-17 levels in both OA and RA is primarily driven by underlying inflammatory processes, positioning IL-17 as a potential therapeutic target for both conditions. Full article

Background/Objectives: Rheumatoid arthritis (RA) and osteoarthritis (OA) are highly prevalent diseases and their pathophysiology, diagnosis and treatment continue to be challenging. The aim of this study was to characterize and differentiate the profiles of the serum extracellular vesicles (EVs) isolated from RA and OA patients. Methods: This study included nine patients diagnosed with RA, eight patients with OA during a flare and five healthy controls (HCs). Blood samples were collected and EVs from the serum were isolated for further performance of flow cytometry and proteomic analysis. Results: The extracellular vesicles from HC samples exhibited smaller sizes and were more concentrated than exosomes from RA and OA samples. Surface protein expression was analyzed by flow cytometry. The results showed an enrichment of exosomes derived from antigen-presenting cells in RA samples; this was evidenced by their expression of CD14 and HLA-DR. Proteomic analysis identified 45 differentially expressed proteins between RA and OA patients. Furthermore, Ingenuity Pathway Analysis (IPA) identified inflammatory pathways such as the IL-1β and IL-6 signaling pathways as being enhanced in RA-derived exosomes, while the MYC and ROCK2 signaling pathways were enhanced in OA-derived exosomes. Conclusions: Our results show serum-derived exosomes from RA and OA patients harbor different surface proteins and cargo profiles, mirroring the different pathophysiologic mechanisms underlying these diseases. These results also highlight the promising use of exosomes as disease biomarkers. Full article

Micro-computed tomography assessment of osteochondral microstructural properties of the distal femur and proximal tibia was comprehensively conducted to compare adult patients with knee rheumatoid arthritis (RA) and primary knee osteoarthritis (KOA), with special focus on the effects of knee malalignment. This study encompassed 402 bone samples divided into three groups: the RA group [patients who were subjected to total knee arthroplasty (TKA) due to RA, n = 23, age: 61 ± 10 years], the KOA group [individuals subjected to TKA due to KOA, n = 24, age: 71 ± 9 years] and the control group [sex-matched cadavers without degenerative knee diseases, n = 20, age: 67 ± 11 years]. Our data revealed that the RA, KOA, and control groups differ significantly in osteochondral microstructural properties depending on the knee alignment. Specifically, increasing femoral and tibial cortical porosity, coupled with thinner articular cartilage, were noted in the RA and KOA groups, compared to the controls. Furthermore, larger femoral and tibial cortical pores, lower tibial and femoral subchondral trabecular bone fraction, and thinner tibial articular cartilage were noted in the RA group in comparison to the KOA group, implying that the medial-to-lateral load distribution in the knee joint could be most affected in these patients. Our data illustrated that the thinnest cartilage, a thicker and less porous cortex, along with lower trabecular bone volume, were present in the lateral femoral and tibial condyles of RA individuals with valgus knee alignment. Observed subchondral trabecular microarchitectural alterations could be morphological factors contributing to different effects of surgical treatment and variable implant stability in individuals with RA, warranting further research. Full article

This study systematically evaluates and meta-analyzes Mendelian randomization studies on the bidirectional causal relationship between Alzheimer’s disease (AD) and systemic diseases. We searched five databases, assessed study quality, and extracted data. Diseases were classified using ICD-11, and the meta-analysis was performed with RevMan 5.4. A total of 56 studies identified genetic links between AD susceptibility and systemic diseases. Notably, genetic proxies for hip osteoarthritis (OR = 0.80; p = 0.007) and rheumatoid arthritis (OR = 0.97; p = 0.004) were inversely associated with AD risk, while gout (OR = 1.02; p = 0.049) showed a positive association. Genetic liability to depression (OR = 1.03; p = 0.001) elevated AD risk, and AD genetic risk increased susceptibility to delirium (OR = 1.32; p = 0.0005). Cardiovascular traits, including coronary artery disease (OR = 1.07; p = 0.021) and hypertension (OR = 4.30; p = 0.044), were causally linked to a higher AD risk. Other conditions, such as insomnia, chronic periodontitis, migraine, and certain cancers, exhibited significant genetic correlations. Intriguingly, herpes zoster (OR = 0.87; p = 0.005) and cataracts (OR = 0.96; p = 0.012) demonstrated inverse genetic associations with AD. These findings suggest potential therapeutic targets and preventive strategies, emphasizing the need to address comorbid systemic diseases to reduce AD risk and progression. Full article

Background/Objectives: Inflammatory arthritides includes a range of joint disorders, such as osteoarthritis and rheumatoid arthritis, as well as inflammatory conditions like gout and lupus. This review investigates the pathophysiology, therapeutic challenges, and evolving treatment landscape of arthritis, with a particular focus on the clinical roles of rituximab, apremilast, and upadacitinib. Methods: A comprehensive analysis was undertaken to evaluate the current clinical application, therapeutic efficacy, and safety profiles of selected biosimilar and targeted synthetic disease-modifying antirheumatic drugs (bsDMARDs and tsDMARDs). This overview placed particular emphasis on three key agents—rituximab, apremilast, and upadacitinib—each exemplifying distinct immunomodulatory mechanisms. By focusing on these agents, the analysis highlights the evolving landscape of targeted therapies in rheumatology and underscores the importance of personalized treatment selection based on the disease phenotype, prior therapeutic responses, and comorbid conditions. Results: Rituximab, apremilast, and upadacitinib each present valuable therapeutic options for patients who have shown inadequate response to conventional disease-modifying antirheumatic drugs (DMARDs) or nonsteroidal anti-inflammatory drugs (NSAIDs). Conclusions: Despite the complexity and heterogeneity of arthritis, agents like rituximab, apremilast, and upadacitinib have expanded the therapeutic possibilities in treating this disease and improved its management. Continued research is essential to optimize patient-specific treatment strategies and explore novel molecular targets. Full article

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are known to help resolve inflammation through generation of anti-inflammatory eicosanoids and specialized pro-resolving mediators, including resolvins, protectins, and maresins. Through binding to the GPR120/FFAR4 receptor, their beneficial effects result from phospholipid membrane remodeling, impairment of inflammatory signaling molecules clustering, subsequent inhibition of NF-κB and inflammasome activation, and a reduction in oxidative stress. Obesity, a chronic inflammatory disease that contributes to metabolic disorders, is alleviated by n-3 PUFAs. In the adipose tissue (AT) of individuals with obesity, n-3 PUFAs counteract hypoxia, inhibit immune cell infiltration and AT inflammation, improve insulin sensitivity, and reduce fat mass. Beyond AT, n-3 PUFAs also alleviate other metabolic disorders such as metabolic-associated steatotic liver disease (MASLD), gut dysbiosis, and/or renal dysfunction. In cardiovascular disease (CVD), they are mainly recommended as a secondary prevention for patients with coronary heart disease risks. This review provides an in-depth analysis of the benefits of n-3 PUFAs in obesity and related metabolic diseases, examining both the mechanistic and clinical aspects. Additionally, it also explores the effects of n-3 PUFAs in obesity-related chronic inflammatory conditions, including inflammatory bowel disease, psoriasis, rheumatoid arthritis, osteoarthritis, and multiple sclerosis, by targeting specific pathophysiological mechanisms. Clinical applications and limitations of n-3 PUFAs are discussed based on findings from human clinical trials. Full article

Background/Objectives: This scoping review explores the relationship between ultra-processed food (UPF), bone health, and joint diseases, focusing on its potential impact on bone mineral density (BMD), osteoporosis, osteoarthritis, and inflammatory arthritis, including rheumatoid arthritis (RA), gout, and spondyloarthritis. Methods: A search strategy was developed using key terms such as “ultra-processed food” and related terms like “fast food,” alongside various definitions of bone health impairment, chronic degenerative joint diseases, and inflammatory arthritis. Results: A total of 19 studies were included: 12 on bone health, 3 on osteoarthritis, and 4 on inflammatory arthritis. Preclinical studies showed that UPF consumption negatively affects bone structure and strength. In studies on children and adults, four investigations (2013–2017) found no association between fast food intake and BMD. However, more recent large-scale cross-sectional studies linked higher UPF consumption to lower BMD, increased osteoporosis risk, and greater prevalence of osteopenia, particularly in postmenopausal women. UPF intake was associated with knee osteoarthritis risk, with evidence suggesting an interaction with cartilage thickness, though no association was found for hip osteoarthritis. In inflammatory arthritis, UK Biobank data indicated a higher risk of RA and gout in UPF consumers, while a Brazilian study reported worse metabolic profiles in RA patients. No significant differences in UPF intake were found in spondyloarthritis. Conclusions: This review highlights relevant considerations about the deleterious role of UPF on bone health and joint diseases, providing additional evidence to suggest healthier dietary patterns to patients and to the general population. Full article

Calcium pyrophosphate deposition disease (CPPD) has been shown to be associated with inflammatory arthritis such as rheumatoid arthritis. However, few studies have investigated the correlation between CPPD and psoriatic arthritis (PsA). Our study aimed to determine whether there were higher rates of PsA in patients with CPPD than controls. A retrospective cohort study was conducted using the Veterans Affairs’ Corporate Data Warehouse. Individuals with a CPPD ICD code were matched with controls and diagnoses of PsA and psoriasis were collected. A total of 41,084 CPPD patients were matched with 119,192 controls. The proportion of CPPD patients with PsA diagnosis was more than double that of controls (1.07% vs. 0.37%; p < 0.0001), and more CPPD patients were diagnosed with psoriasis (3.05% vs. 2.52%; p < 0.0001). Those with CPPD had higher odds of a PsA diagnosis (OR 3.550, 95% CI 2.602–4.844). A total of 61.59% of PsA diagnoses preceded the CPPD diagnoses by at least one year. This is the first case–control study demonstrating an association between CPPD and PsA, potentially related to the fact that both PsA and CPPD could be triggered by trauma, and are closely associated with osteoarthritis. It also is possible that inflammatory pathways contribute to CPP crystal deposition in joints. Full article

Background/Objectives: Arthritis encompasses a range of joint-related conditions, including osteoarthritis and rheumatoid arthritis, along with inflammatory diseases such as gout and lupus. This research study explores the underlying causes, challenges, and treatment options for arthritis, aiming to enhance the effectiveness of therapies. Methods: This research study evaluated current treatment strategies and examined the effectiveness of selected biological disease-modifying antirheumatic drugs (bDMARDs), i.e., abatacept, golimumab, and sarilumab, with a focus on emerging drug classes and their distinct mechanisms of action. Results: Biologic DMARDs like abatacept, golimumab, and sarilumab offer hopeful treatment alternatives for patients who fail to respond to conventional therapies. However, individual outcomes differ because of the disease’s complexity and the influence of accompanying health conditions. Conclusions: Treating arthritis continues to be challenging due to its numerous underlying causes and the varied ways in which patients respond to treatment. Although biologics and targeted therapies have brought progress, additional research is needed to identify new treatment targets and enhance patient results. Full article

Osteoarthritis (OA) is a chronic joint disease marked by synovial inflammation, cartilage degradation, and persistent pain. Although Netrin-4 (NTN4) has been implicated in pain modulation in rheumatoid arthritis (RA), its role in OA pain remains less understood. Previous research has documented that NTN4 promotes axonal growth in rodent-derived neurons; however, its effects on human sensory neurons are yet to be fully explored. NTN4 also plays a multifactorial role in various non-neuronal cells, such as endothelial cells, tumor cells, and stromal cells. Nevertheless, its specific impact on synovial fibroblasts, which are key components of the synovium and have been linked to OA pain, is still unclear. This study examined the correlation between NTN4 expression levels and pain severity in OA, specifically investigating its effects on human iPSC-derived sensory neurons (iPSC-SNs) and synovial fibroblasts from OA patients. Our findings indicate a positive correlation between synovial NTN4 expression and pain severity. Recombinant human Netrin-4 (rh-NTN4) was also shown to enhance neurite outgrowth in human iPSC-SNs, suggesting a potential role in neuronal sensitization. Additionally, rh-NTN4 stimulated the production of pro-inflammatory cytokines (IL-6, IL-8) and chemokines (CXCL1, CXCL6, CXCL8) in synovium-derived fibroblastic cells, implicating it in synovial inflammation. Collectively, these results suggest that NTN4 may contribute to KOA pathology by promoting synovial inflammation and potentially sensitizing sensory neurons, thereby influencing the mechanisms of underlying pain. Full article