Search Results (195)

Inflammatory arthritis (IA) is a chronic condition marked by joint dysfunction and pain, posing significant challenges for effective drug delivery. This study separated Perilla frutescens leaf-derived exosome-like nanovesicles (PFE) to effectively penetrate the stratum corneum barrier. These nanovesicles and indomethacin (IND) were subsequently developed into a nanogel designed for topical drug delivery systems (PFE-IND-GEL). PFE exhibited a typical vesicular structure with a mean diameter of 98.4 ± 1.3 nm. The hydrodynamic size and zeta potential of PFE-IND-GEL were 129.6 ± 5.9 nm and −17.4 ± 1.9 mV, respectively. Mechanistic investigations in HaCaT keratinocytes showed that PFE significantly downregulated tight junction proteins (ZO-1 and Occludin, p < 0.01) via modulation of the IL-17 signaling pathway, as evidenced by transcriptomic analysis. In a sodium urea crystal-induced rat IA model, the topical application of PFE-IND-GEL significantly reduced joint swelling (p < 0.05) and serum levels of inflammatory cytokines (IL-6, IL-1α, TNF-α) compared to control groups. Histopathological analysis confirmed the marked attenuation of synovial inflammation and cartilage preservation in treated animals. These findings underscore the dual role of PFE as both a topical permeation enhancer and an anti-inflammatory agent, presenting a promising strategy for managing IA. Full article

Rheumatoid arthritis (RA) is a progressive and systemic autoimmune disease, characterized by a chronic inflammatory process, affecting the lining of the synovial joints, many body organs/systems, and blood vessels. Its pathological hallmarks are hyperplasic synovium, bone erosion, and progressive joint destruction. Rheumatoid arthritis affects over 20 million people, with a worldwide prevalence of 0.5–1.0%, exhibiting gender, ethnic, and geographical differences. The progressive disability severely impairs physical motion and quality of life and is finally leading to a shortened life span. The pathogenesis of RA is a complex and still poorly understood process in which genetic and environmental factors are principally associated. Current treatment mostly relies on conventional/non-biological disease-modifying anti-rheumatic drugs (cDMARDs), analgesics, non-steroidal anti-inflammatory drugs, glucocorticoids, steroids, immunosuppresants, and biologic DMARDs, which only control inflammation and pain. Along with side effects (drug toxicity and intolerance), these anti-rheumatic drugs possess limited efficacy. Therefore, the discovery of novel multi-target therapeutics with an improved safety profile that function as inhibitors of RA-linked signaling systems are in high demand, and this is in the interest of both patients and clinicians. Plant-derived extracts, nutritional supplements, dietary medicine, and molecules with anti-inflammatory activity represent promising adjuvant agents or alternatives for RA therapeutics. This review not only aims to discuss the basic features of RA pathogenesis, risk factors, and signaling pathways but also highlights the research progress in pre-clinical RA in in vitro and in vivo models, revealing new avenues in the management of the disease in terms of comprehensive multidisciplinary strategies originating from medicinal plants and plant-derived molecules. Full article

Background/Objectives: The aim of this study was to compare the clinical outcomes of cyst excision alone and the combination of excision and unilateral dynamic instrumentation in the surgical treatment of lumbar synovial cysts at the L4–L5 level and to determine which surgical approach is more effective. Methods: Thirty-three patients who underwent operations on the L4–L5-level synovial cyst in a single center between January 2015 and January 2021 were included in this retrospective study. Patients were divided into two groups: cyst excision only (n = 18) and excision with unilateral dynamic instrumentation (n = 15). The pain levels of the patients were assessed by VAS score, and their functional status was assessed by the Oswestry Disability Index. The mean follow-up period was 28.2 ± 4.0 months in the excision group and 27.6 ± 4.4 months in the instrumentation group. Results: VAS and ODI scores improved significantly in both groups (p < 0.001). The improvement in low back pain VAS scores was more significant in the instrumentation group (delta VAS: −5.8 ± 1.3 vs. −5.0 ± 1.2, p = 0.042). The complication rate was 27.8% in the excision group and 13.3% in the instrumentation group. The development of listhesis was significantly more frequent in the excision group (16.7% vs. 0%, p = 0.028). Reoperation rates were 16.7% in the excision group and 6.7% in the instrumentation group. Conclusion: Although both surgical approaches are effective in the treatment of synovial cysts at the L4–L5 level, the addition of dynamic instrumentation unilaterally seems to be more advantageous, especially in the control of low back pain and prevention of listhesis risk. The choice of surgical technique should be individualized by considering patient-specific factors. Full article

Current osteoarthritis (OA) therapies fail to yield long-term clinical benefits, due in part to the lack of a mechanism for the targeted and confined delivery of therapeutics to OA joints. This study evaluates if M2 macrophages are effective cell vehicles for the targeted and confined delivery of therapeutic genes to OA joints. CT bioluminescence in vivo cell tracing and fluorescent microscopy reveal that intraarticularly injected M2 macrophages were recruited to and retained at inflamed synovia. The feasibility of an M2 macrophage-based adoptive gene transfer strategy for OA was assessed using IL-1Ra as the therapeutic gene in a mouse tibial plateau injury model. Mouse M2 macrophages were transduced with lentiviral vectors expressing IL-1Ra or GFP. The transduced macrophages were intraarticularly injected into injured joints at 7 days post-injury and OA progression was monitored with plasma COMP and histology at 4 weeks. The IL-1Ra-expressing M2 macrophage treatment reduced plasma COMP, increased the area and width of the articular cartilage layer, decreased synovium thickness, and reduced the OARSI OA score without affecting the osteophyte maturity and meniscus scores when compared to the GFP-expressing M2 macrophage-treated or PBS-treated controls. When the treatment was given at 5 weeks post-injury, at which time OA should have developed, the IL-1Ra-M2 macrophage treatment also reduced plasma COMP, had a greater articular cartilage area and width, decreased synovial thickness, and reduced the OARSI OA score without an effect on the meniscus and osteophyte maturity scores at 8 weeks post-injury. In conclusion, the IL-1Ra-M2 macrophage treatment, given before or after OA was developed, delayed OA progression, indicating that the M2 macrophage-based adoptive gene transfer strategy for OA is tenable. Full article

This article presents a comprehensive review of assistive devices for synovial joints, addressing their definitions, classifications, and technological advancements. The historical evolution of artificial exoskeletons, orthoses, prostheses, and splints is analyzed, emphasizing their impact on rehabilitation and the enhancement of human mobility. Through a systematic compilation of scientific literature, patents, and medical regulations, the study clarifies terminology and classifications that have often been imprecisely used in scientific discourse. The review examines the biomechanical principles of the musculoskeletal system and the kinematics of synovial joints, providing a reference framework for the optimization and design of these devices. Furthermore, it explores the various types of artificial exoskeletons, and their classification based on structure, mobility, power source, and control system, as well as their applications in medical, industrial, and military domains. Finally, this study highlights the necessity of a systematic approach in the design and categorization of these technologies to facilitate their development, comparison, and effective implementation, ultimately improving users’ quality of life. Full article

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder that predominantly affects synovial joints, leading to inflammation, pain, and progressive joint damage. Despite therapeutic advancements, the molecular basis of established RA remains poorly defined. Methods: In this study, we conducted an untargeted plasma proteomic analysis using two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in samples from RA patients and healthy controls in the discovery phase. Results: Significantly (ANOVA, p ≤ 0.05, fold change > 1.5) differentially abundant proteins (DAPs) were identified. Notably, upregulated proteins included mitochondrial dicarboxylate carrier, hemopexin, and 28S ribosomal protein S18c, while CCDC124, osteocalcin, apolipoproteins A-I and A-IV, and haptoglobin were downregulated. Receiver operating characteristic (ROC) analysis identified CCDC124, osteocalcin, and metallothionein-2 with high diagnostic potential (AUC = 0.98). Proteins with the highest selected frequency were quantitatively verified by multiple reaction monitoring (MRM) analysis in the validation cohort. Bioinformatic analysis using Ingenuity Pathway Analysis (IPA) revealed the underlying molecular pathways and key interaction networks involved STAT1, TNF, and CD40. These central nodes were associated with immune regulation, cell-to-cell signaling, and hematological system development. Conclusions: Our combined proteomic and bioinformatic approaches underscore the involvement of dysregulated immune pathways in RA pathogenesis and highlight potential diagnostic biomarkers. The utility of these markers needs to be evaluated in further studies and in a larger cohort of patients. Full article

Background/Objectives: Osteoarthritis is a degenerative joint disease that affects people worldwide. It is characterized by joint pain, synovial inflammation, and the degradation of articular cartilage with subchondral bone. Presently, there is no known cure, and pharmacological treatment options are limited. Blueberries contain phytochemicals, which have been linked to positive health benefits and may offer therapeutic benefits. Therefore, the purpose of this study was to examine the dose-dependent effects of whole blueberries on arthritis symptoms in a monosodium iodoacetate (MIA)-induced rat model of osteoarthritis. Methods: Forty female rats were used for this study. Thirty were injected with MIA to induce joint degradation associated with osteoarthritis. Ten served as controls without MIA induction. The MIA-induced rats were randomized into three groups. All groups were fed a casein-based diet, with two of the MIA-induced groups receiving an addition of whole-blueberry powder at 5% and 10%. Fasted blood specimens and tissues of interest were collected post-euthanasia for analysis. Mechanical allodynia and joint widths were assessed throughout this study. Results: MIA induction resulted in changes in pain behaviors and the development of mechanical allodynia. The MIA injection produced inflammation, pain symptoms, and behaviors that are representative of those observed in humans with osteoarthritis. The incorporation of whole blueberries into diets reduced pain behaviors and inflammation. Conclusions: Overall, whole blueberries showed limited, non-dose-dependent effects in the MIA-induced rat model of osteoarthritis. While some outcomes improved in blueberry-treated groups, the overall results were not consistently significant. These preliminary findings suggest potential biological activity and support the further investigation of blueberries’ therapeutic efficacy. Full article

In this study, we investigated the inhibitory effects of emodin on pyroptosis in rheumatoid arthritis (RA) synovial cells by modulating the HIF-1α/NLRP3 inflammasome pathway and mitochondrial autophagy. By employing a chemically induced hypoxia model with CoCl₂, we established experimental groups including normal control, model group, and emodin-treated groups at different concentrations (5 μM, 10 μM, and 20 μM). We optimized the CoCl₂ concentration via CCK-8 assay to ensure cell viability. ELISA, Western blotting, transmission electron microscopy, and immunofluorescence were employed to assess HIF-1α, IL-1β, and IL-18 levels, pyroptosis-related proteins, autophagy markers, and NLRP3 fluorescence intensity. Statistical analysis revealed that increased CoCl₂ concentrations led to a significant cell viability reduction (p < 0.05), with 300 μM CoCl₂ causing ~50% inhibition at 24 h. Transmission electron microscopy confirmed autophagosome formation in emodin-treated groups, while Western blotting showed dose-dependent downregulation of HIF-1α, NLRP3, BNIP3, and related proteins. Immunofluorescence revealed reduced NLRP3 fluorescence intensity with increasing emodin doses (p < 0.05), alongside dose-dependent cell viability recovery (p < 0.05). Our findings demonstrate that emodin alleviates RA synovitis through dual mechanisms: inhibition of mitochondrial autophagy to regulate the balance between mitochondrial autophagy and pyroptosis, and suppression of HIF-1α/NLRP3-mediated pyroptosis signaling, thereby reducing IL-1β and IL-18 release and inhibiting synovial cell proliferation. This study provides innovative approaches for targeted RA therapy. Full article

Temporomandibular disorders (TMDs) impact quality of life and present diagnostic and treatment challenges. Biomarkers may serve as an additional tool to support diagnosis and monitor disease progression, offering supplementary information for treatment strategies in specific and selected patients. This systematic review aimed to assess the role of biomarkers in diagnosing TMD and guiding personalized treatment. It also examined key biomarkers linked to chronic temporomandibular joint (TMJ) pain and how therapies affect biomarker levels and clinical outcomes. A comprehensive search was conducted in PubMed, Scopus, and Web of Science to identify observational and interventional studies assessing the role of biomarkers in synovial fluid/tissue, saliva, and blood. The research was registered in PROSPERO, adhered to PRISMA guidelines, and employed Cochrane Risk of Bias tools. To assess the effect, only studies examining biomarker levels were considered. A total of forty-six studies met the inclusion criteria: three randomized controlled trials were rated as having some concerns, as were most of the observational studies. Elevated levels of interleukins (1ß and 6), tumour necrosis factor alpha, and prostaglandin E2 in synovial fluid were correlated with temporomandibular joint (TMJ) inflammation. Increased matrix metalloproteinases (2, 7, and 9) indicated cartilage deterioration, while oxidative stress markers such as malondialdehyde were higher in TMD patients. Treatments including hyaluronic acid, platelet-rich plasma, and low-level laser therapy effectively reduced inflammatory biomarkers and improved symptoms. Biomarkers show potential to contribute to the understanding of pathophysiological mechanisms in TMD and may support future diagnostic and therapeutic strategies for selected patients. After high-quality studies confirm these findings, this approach will enable personalized medicine by tailoring treatments to individual patient profiles, ultimately leading to improved outcomes and quality of life. Full article

Objective: Inflammatory arthritis (IA) has been linked to a number of adverse pregnancy outcomes (APOs), but the mechanisms linking IA-related immune dysregulation to compromised reproductive success remain poorly understood. This project will examine how IA affects pregnancy outcomes and alters the associated immune microenvironment using SKG (ZAP70^W163C) mice, a mouse model that suffers from arthritis resembling human IA. Methods: IA was induced in SKG mice on a C57BL/6J background via mannan exposure. Wild-type C57BL/6 mice served as controls. Pregnancy rates, conception time, embryo resorption rates, and immune parameters (cytokine levels and splenic/lymph node/placental immune cell subsets) were analyzed. Joint pathology was evaluated via histology (HE is staining) and anti-CCP antibody levels. Flow cytometry was used to analyze immune populations within the spleen along with the associated lymphatic nodes. Results: Synovial hyperplasia, elevated anti-CCP, and systemic inflammation were all observed in IA mice. Compared to controls, IA mice demonstrated a reduced mating success rate, prolonged conception time, decreased pregnancy rates, and increased embryo resorption. IA mice showed elevated Th1/Th17 cytokines-IFN-γ, TNF-α, and IL-17, and an expansion of pro-inflammatory immune cells, including NK cells, CD11b+ myeloid cells, neutrophils, M1 macrophages, and Tc1, in the spleen/lymph nodes. Placental immune dysregulation featured increased NKT, NK, and CD4+ cell infiltration. Conversely, anti-inflammatory subsets, such as M2 macrophages and dendritic cells, were reduced. Conclusions: IA increased APOs and skewed the immune microenvironment toward a pro-inflammatory state dominated by Th1/Th17/Tc1 responses and cytotoxic cell activation. These findings highlight immune dysregulation as a key driver of IA-associated pregnancy complications, providing mechanistic insights for therapeutic intervention. Full article

Developmental dysplasia of the hip (DDH) is a multifactorial and polygenic abnormal hip joint development, with a prognosis influenced by environmental and genetic factors, potentially leading to complete dislocation. Growth differentiation factor 5 is a signaling molecule, encoded by a polymorphic gene (GDF5), promoting the development, repair, and maintenance of bone, cartilage, and other synovial joint tissues. The GDF5 rs143384 G>A polymorphism affects GDF5 expression and may be associated with a susceptibility to DDH. The aim of this study was to determine the frequency of the GDF5 rs143384 polymorphism in Brazilian individuals and its influence on the development of DDH. This case–control study included 50 DDH cases and 150 controls without hip disease. Genotyping was performed by real-time PCR using the TaqMan system. The GDF5 AA variant genotype frequency was significantly higher in DDH cases (32%) compared to controls (14%, p-value = 0.01) and showed a marginal association with disease risk (OR = 1.47; CI 95% = 0.96–2.26). The GDF5 rs143384 polymorphism could be useful in identifying individuals at risk, guiding personalized treatment strategies, and contributing to diagnosis and clinical management. Full article

Background/Objectives: Gouty arthritis (GA) is a chronic inflammatory condition characterized by hyperuricemia and NLRP3 inflammasome activation, leading to joint damage and systemic inflammation. Although allopurinol (ALP), a xanthine oxidase inhibitor, effectively lowers serum urate levels, it has limited anti-inflammatory effects. This study investigated whether combining disulfiram (DSF), a known NLRP3 inflammasome inhibitor, with ALP enhances therapeutic outcomes in a rat model of gout. Methods: Thirty male Albino Wistar rats (150–200 g) were randomly assigned to five groups (n = 6): control, disease control, ALP-treated, DSF-treated, and ALP + DSF combination. Hyperuricemia was induced using potassium oxonate, followed by MSU crystal injection to trigger acute gout. Treatment lasted 30 days. Efficacy was assessed through clinical scoring, paw swelling, serum uric acid levels, ELISA-based cytokine profiling (IL-1β, TNF-α, IL-6), renal function tests, radiography, and histopathology. Results: Combination therapy with ALP + DSF significantly reduced paw swelling (p < 0.05), inflammation index (p < 0.001), serum uric acid (p < 0.001), and pro-inflammatory cytokines compared to monotherapy. Histopathology revealed preserved synovial architecture and reduced inflammatory infiltration. Radiographic imaging showed attenuated soft tissue swelling and joint erosion. Renal function markers were also improved in the combination group. Conclusions: The combination of ALP and DSF provided superior anti-inflammatory and urate-lowering effects compared to individual treatments. These findings support the potential of disulfiram as an adjunct to conventional ULTs in gout management through dual modulation of urate metabolism and inflammasome-driven inflammation. Full article

Background/Objectives: Intra-articularly administered hyaluronic acid (HA) products improve the mechanical properties of the synovial fluid (SF) in an osteoarthritic (OA) joint and thus improve joint motion quality. However, current diagnostic methods, used to assess the clinical effectiveness of HA-based therapy are based on subjective tools, and are unable to deliver solid data about the actual impact of this molecule on joint functioning. Consequently, the aim of this study was to objectively assess the effect of HA IA injection on joint motion quality with vibroarthrography (VAG) and the subsequent evaluation of patient clinical status. Methods: A total of 40 patients with knee OA and 50 healthy individuals as the control group were enrolled in this non-randomized clinical and were subjected to therapy consisting of a single IA administration of highly concentrated HA gel (Biolevox™ HA ONE). The therapy assessment included an evaluation of joint motion quality with the VAG method and a subsequent evaluation of the knee joint function using the WOMAC questionnaire for up to 60 days after the therapy. Results: A single IA injection of HA led to an immediate and sustained improvement of the motion quality of OA-affected synovial joints, as proven by the significant reduction in all measured vibroacoustic emissions (VMS, R4, P1, and P2). Furthermore, this was followed by a significant improvement in all WOMAC sub-scales, observed at 30 and 60 days after the therapy. Conclusions: The results of this study demonstrate that an IA-HA injection can improve the motion quality of OA-affected joints. Importantly, the observed improvement in joint motion quality is directly correlated with early recovery of joint function. These findings provide objective evidence that HA effectively enhances OA-affected joint biomechanics, contributing to a better understanding of the actual impact of this prevalent OA therapy on knee joint motion quality. Full article

Background: The main feature of osteoarthritis (OA) is the deterioration of articular cartilage, but numerous studies have demonstrated the role of synovial inflammation in the early stages of the disease, leading to further progression of OA. The WNT signaling pathway is involved in numerous activities in joint tissue, but there is a lack of evidence considering the role of WNT in OA synovitis. Our research aims to investigate the expression of WNT Family Member 5A/B (WNT5A/B), β-catenin, acetyl-α-tubulin, Dishevelled-1 (DVL-1), and Inversin (INV) in the synovial membrane of osteoarthritis (OA) hips. Methods: The immunohistochemical expressions of the aforementioned proteins in the synovial membrane were analyzed and compared with samples of control group participants with fractured femoral necks. Results: The immunoexpression of acetyl-α-tubulin was significantly increased in the intima (p < 0.0001) and subintima (p < 0.0001) of the group with OA compared with the intima and subintima of the control group. At the same time, acetyl-α-tubulin was also more highly expressed in the intima of the OA group than in the subintima of the OA group (p < 0.05); we found the same expression pattern in the control group (p < 0.0001). The differential analysis of the GEO dataset did not show significant differences between the osteoarthritis (OA) and control groups in the expression of TUBA1A. β-catenin was significantly increased in the subintima (p < 0.01) of the group with OA compared to the subintima of the control group. WNT expression has significantly higher positivity in the subintima than in the intima, especially in the control group (p < 0.01). WNT5A and WNT5B were significantly down-regulated in OA compared to the control in the differential analysis of the GEO dataset. The expression of INV and DVL-1 in our study and the differential analysis of the GEO dataset did not differ significantly between the osteoarthritis (OA) and control groups. Conclusions: Based on our results, we suggest that acetyl-α-tubulin and β-catenin might be involved in synovial membrane inflammation in OA and serve as potential therapeutic targets. Full article

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by the inflammation of synovial fluid. The incidence of cardiovascular diseases (CVDs) is increasing in RA patients. This research is the first report to investigate the anti-arthritic effect of avocado peel nutraceutical (APN) and its potential in mitigating the cardiovascular risk associated with RA. The antioxidant activity and phytochemical composition of APN were assessed. The potential interaction of APN’s active compounds with protein tyrosine phosphatase non-receptor type 22 (PTPN22) was studied using molecular docking. The impact of APN on the plasma lipid profile, oxidative and inflammatory markers, and the indices of coronary risk and atherogenicity as CVD markers were evaluated. The gene expression of COX-2, IL-6, IL-1β, IL-10, and TNF-α in liver and spleen tissues were measured. The rat gut microbiota profile was investigated using 16S rRNA amplicon sequencing. APN exhibited high antioxidant activity, low atherogenicity and thrombogenicity indices, and a high ratio of hypocholesterolemic to hypercholesterolemic fatty acids indicating its cardioprotective potential. The administration of APN led to a reduction in oxidative stress markers, inflammatory markers, dyslipidemia, and CVD markers. APN administration downregulated the expression of COX-2, IL-6, IL-1β, and TNF-α genes, while the IL-10 gene was significantly upregulated in the liver and spleen. Treatment with APN was favorable in restoring eubiosis in the gut by modulating RA-associated bacterial taxa linked to impaired immune function and cardiometabolic diseases. In molecular docking, β-amyrin and ellagic acid showed the highest binding affinity for PTPN22. APN may represent a promising approach to ameliorating the cardiovascular risk of RA. The present results will be offering a foundation for future in-depth research in nutraceuticals from agriculture by-products. Additionally, they will be supporting the public health policies aimed at preventing and controlling rheumatoid arthritis. Full article