Search Results (421)

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder primarily targeting joints, leading to pain, swelling, and stiffness. RA results from the body’s own immune system attacking its own tissues. Currently, there are various treatments available for RA including disease-modifying antirheumatic drugs (DMARDs) and NSAIDs. Leflunomide (LEF) is a USFDA-approved synthetic DMARD which is being widely prescribed for the management of RA; however, it faces several challenges such as prolonged drug elimination, hepatotoxicity, and others. LEF exerts its therapeutic effects by inhibiting dihydroorotate dehydrogenase (DHODH), thereby suppressing pyrimidine synthesis and modulating immune responses. Emerging nanotechnology-based therapies help in encountering the current challenges faced in LEF delivery to RA patients. This review enlists the LEF’s pharmacokinetics, mechanism of action, and clinical efficacy in RA management. A comparative analysis with methotrexate, biologics, and other targeted therapies, highlighting its role in monotherapy and combination regimens and the safety concerns, including hepatotoxicity, gastrointestinal effects, and teratogenicity, is discussed alongside recommended monitoring strategies. Additionally, emerging trends in novel formulations and drug delivery approaches are explored to enhance efficacy and minimize adverse effects. Overall, LEF remains a perfect remedy for RA patients, specifically individuals contraindicated with drugs like methotrexate. The therapeutic applicability of LEF could be enhanced by developing more customized treatments and advanced drug delivery approaches. Full article

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

Temporomandibular disorders (TMDs) encompass a heterogeneous group of musculoskeletal and neuromuscular conditions affecting the temporomandibular joint (TMJ) and masticatory system. Due to academic stress and parafunctional habits, dental students may be particularly vulnerable to TMD. Objective: To determine the prevalence of TMD symptoms and their psychosocial and functional correlates among students at the Faculty of Dental Medicine, UMPh Iasi, Romania, using the diagnostic criteria for TMD (DC/TMD) self-report axis and axis II instruments. Methods: In this cross-sectional survey, 356 volunteer students (66.0% female; mean age, 22.9 ± 3.6 years) out of a total population of 1874 completed an online DC/TMD–based questionnaire. Axis I assessed orofacial pain, joint noises, and mandibular locking. Axis II instruments included the Graded Chronic Pain Scale (GCPS), Jaw Functional Limitation Scale (JFLS-20), Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Oral Behaviors Checklist (OBC). Descriptive statistics summarized frequencies, means, and standard deviations; χ² tests and t-tests compared subgroups by sex; Pearson correlations explored relationships among continuous measures (α = 0.05). Results: A total of 5% of respondents reported orofacial pain in the past 30 days; 41.6% observed TMJ noises; 19.7% experienced locking episodes. Mean JFLS score was 28.3 ± 30.5, with 4.8% scoring > 80 (severe limitation). Mean PHQ-9 was 5.96 ± 5.37 (mild depression); 15.5% scored ≥ 10. Mean GAD-7 was 5.20 ± 4.95 (mild anxiety); 16.0% scored ≥ 10. Mean OBC score was 12.3 ± 8.5; 30.1% scored ≥ 16, indicating frequent parafunctional habits. Symptom prevalence was similar by sex, except temporal headache (43.4% females vs. 24.3% males; p = 0.0008). Females reported higher mean scores for pain intensity (2.09 vs. 1.55; p = 0.0013), JFLS (32.5 vs. 18.0; p < 0.001), PHQ-9 (6.43 vs. 5.16; p = 0.048), and OBC (13.9 vs. 9.7; p = 0.0014). Strong correlation was observed between PHQ-9 and GAD-7 (r = 0.74; p < 0.001); moderate correlations were observed between pain intensity and PHQ-9 (r = 0.31) or GAD-7 (r = 0.30), between JFLS and pain intensity (r = 0.33), and between OBC and PHQ-9 (r = 0.39) (all p < 0.001). Conclusions: Nearly half of dental students reported TMD symptoms, with appreciable functional limitation and psychosocial impact. Parafunctional behaviors and psychological distress were significantly associated with pain and dysfunction. These findings underscore the need for early screening, stress-management interventions, and interdisciplinary care strategies in the dental student population. 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 and aims: Rheumatic diseases are chronic, progressive conditions associated with severe pain, joint damage, disability, and even death. Healthcare interventions play a critical role in symptom management, patient education, and adherence to treatment plans. This study evaluates the role of healthcare interventions in the management of patients with rheumatic diseases, focusing on pain management, functional rehabilitation, patient education, and multidisciplinary collaboration. In addition, barriers to optimal care and potential solutions, including digital health technologies, are explored. Materials and methods: We conducted a narrative review of the scientific literature. Studies published between 2014 and 2025 were selected from PubMed, Scopus, Web of Science, Elsevier, Springer, Frontiers, and Wiley Online Library. Key areas of review included nurse-led pain management, education programs, and the impact of interdisciplinary care on patient outcomes. Results: Nursing interventions significantly improve pain control, treatment adherence, and self-management skills in patients with rheumatic diseases. Multidisciplinary approaches improve functional rehabilitation and increase quality of life in patients with rheumatic conditions. However, barriers such as insufficient health care resources, lack of patient awareness, and disparities in the availability of services hinder effective care delivery. Conclusions: A structured, multidisciplinary approach integrating healthcare interventions, digital health solutions, and patient-centered education is essential to optimize the management of rheumatic diseases. Future research should focus on improving access to non-pharmacological therapies and standardizing healthcare protocols for better patient outcomes. Full article

Objective: Although Global Postural Re-education (GPR) is widely used for musculoskeletal conditions, its specific benefits for this population remain unclear due to inconsistent findings across studies. This systematic review aims to analyze the effects of GPR on pain intensity, functionality, and range of motion (ROM) in individuals with chronic non-specific neck pain. Methods: Computerized search was performed in the Cochrane CENTRAL, Lilacs, EBSCO, PEDro, Pubmed, RCAAP and Scielo databases using the keyword combination (“Global Postural Rehabilitation” OR “Global Postural Reeducation” OR “Global Posture Reeducation” OR “Global Postural Re-education” OR “GPR”) AND (“Neck Pain” OR “Cervicalgia”). Methodological quality was assessed using the Physiotherapy Evidence Database Scale. Results: Six studies with a total of 393 participants (322 women, aged 18–80) were included. The methodological quality was moderate (average PEDro score: 6.7/10), with frequent limitations related to lack of blinding and allocation concealment. Risk of bias was rated as “some concerns” in four studies and “high” in two. GPR was associated with improvements in pain intensity, functionality, and cervical ROM (flexion/extension). While three studies found no significant differences between GPR and static stretching or specific cervical exercises, the remaining three studies reported greater improvements with GPR compared to manual therapy or traditional neck education and exercise therapy. No adverse effects were reported in any of the included trials. Conclusions: GPR appears to be a safe and potentially effective intervention for individuals with chronic non-specific neck pain, particularly in improving pain, function, and cervical ROM. Nonetheless, further high-quality randomized controlled trials are needed to confirm its superiority over other physiotherapeutic interventions and to determine the optimal treatment parameters. PROSPERO registration: CRD420251068974. Full article

Introduction: Total temporomandibular joint replacement (TMJR) is a well-established surgical solution for patients with severe TMJ disorders. It aims to relieve chronic pain, restore jaw mobility, and significantly enhance quality of life. This systematic review evaluates QoL outcomes following TMJR, analyzes complication profiles, compares custom versus stock prostheses, explores pediatric applications, and highlights technological innovations shaping the future of TMJ reconstruction. Methods: A systematic search of PubMed, Embase, and the Cochrane Library was conducted throughout April 2025 in accordance with PRISMA 2020 guidelines. Sixty-four studies were included, comprising 2387 patients. Results: Primary outcomes assessed were QoL improvement, pain reduction, and functional gains such as maximum interincisal opening (MIO). Secondary outcomes included complication rates and technological integration. TMJR consistently led to significant pain reduction (75–87%), average MIO increases of 26–36 mm, and measurable QoL improvements across physical, social, and psychological domains. Custom prostheses were particularly beneficial in anatomically complex or revision cases, while stock devices generally performed well for standard anatomical conditions. Pediatric TMJR demonstrated functional and airway benefits with no clear evidence of growth inhibition over short- to medium-term follow-up. Complications such as heterotopic ossification (~20%, reduced to <5% with fat grafting), infection (3–4.9%), and chronic postoperative pain (~20–30%) were reported but were largely preventable or manageable. Recent advancements, including CAD/CAM planning, 3D-printed prostheses, augmented-reality-assisted surgery, and biofilm-resistant materials, are enhancing personalization, precision, and implant longevity. Conclusions: TMJR is a safe and transformative treatment that consistently improves QoL in patients with end-stage TMJ disease. Future directions include long-term registry tracking, growth-accommodating prosthesis design, and biologically integrated smart implants. 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: The joint presence of chronic pain (CP) and depression is frequent, exacerbating symptoms of both conditions. Although tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors are effective treatments, they are frequently not well tolerated, and selective serotonin reuptake inhibitors are not useful for controlling CP. This study investigated vortioxetine’s effectiveness in relieving CP in patients with any degree of depression. Methods: Patient data with any degree of depression and with CP (Visual Analog Scale [VAS] score ≥ 4) were collected and analyzed. Included patients (n = 142) were initially treated with vortioxetine 10 mg/day for 3 months. Improvement of patients’ pain and condition was measured with the VAS, Patient Global Impression (PGI), and Clinical Global Impression (CGI) scales at 1 and 3 months. Brief Pain Inventory (BPI) was measured at baseline and 3 months. Additionally, at baseline and after 3 months of treatment, the Satisfaction with Medicines Questionnaire (SATMED-Q) and 9-item Patient Health Questionnaire (PHQ-9) were evaluated. Adverse Events (AEs) were recorded. Results: Patients showed significant improvement (p < 0.001) in VAS from baseline to 1 and 3 months (mean [SD]: 7.19 [0.62], 6.23 [0.80], and 5.41 [1.15], respectively). BPI and PHQ-9 scores also showed a significant decrease from baseline (mean [SD] of 6.05 [0.75] and 11.73 [4.89], respectively) to 3 months (5.11 [1.04] and 6.95 [2.52], respectively). Clinical improvement with the CGI and PGI scales were reported. According to the SATMED-Q, patients were satisfied with the treatment. Only a few mild EAs were recorded. Conclusions: Vortioxetine can improve both the severity and intensity of CP in patients with any degree of depression. Full article

Background/Objectives: Chronic stress has an undeniable effect in generating emotional disorders and physiological changes. It results in excessive muscle tension throughout the body, also in the masticatory system. A situation of chronic stress was the COVID-19 pandemic. The aim of this paper was to assess the prevalence of specific masticatory pain symptoms, their severity, and the co-occurrence of associated symptoms (otological symptoms and headaches) in patients diagnosed before and during the COVID-19 pandemic. Methods: A total of 202 patients were divided into two groups: Group A (mean age of 36.46; F = 64; and M = 37) and B (mean age of 26.04; F = 70; and M = 31) included patients who presented for the study before and after the COVID-19 pandemic, respectively. The Oral Behaviours Checklist (OBC) questionnaire was used: patients with result ≥2 scores in the OBC were evaluated by DC/TMD. To evaluate the intensity of pain in masticatory structures, the elements of the RDC-TMD questionnaire were used. Otologic symptoms and headaches were assessed as coexisted complaints. Results: A significant increase in pain occurrence was observed in Group B mainly for masseter muscles (p < 0.0001), temporalis (p = 0.0044), and medial pterygoid muscles (p = 0.0153). A significantly more frequent reporting of pain/tenderness was observed among men in most of the evaluated muscles. For the lateral pterygoid muscles, changes in palpation pain did not reach statistical significance. There was a statistically significant difference in the intensity of pain in the temporomandibular joint area between both the entire groups A and B (p = 0.000152), as well as between women in Group A and B (p = 0.006453) and men in the study groups (p = 0.007990). An increase in the incidence of headaches was observed among men in Group B (Group A with 40.6% vs. Group B with 67.3%). The most commonly reported otological symptom in both groups was ear pain and/or discomfort in the preauricular region, with the frequency of otological symptoms being higher in Group B. Conclusions: (1) The COVID-19 pandemic affected the incidence and severity of masticatory muscle pain and associated complaints. (2) A decrease in the age of patients reporting complaints of masticatory mm pain was observed during the COVID-19 pandemic. (3) An increase in the frequency of headaches was observed in the male group during the pan-demic, while in women there was an increase in palpation tenderness of masticatory muscles. Full article

Systemic autoimmune rheumatic diseases (SARDs), such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren’s syndrome (SS), are traditionally characterized by chronic inflammation and immune-mediated damage to joints and other tissues. However, many patients also experience symptoms such as widespread pain, persistent fatigue, cognitive dysfunction, and autonomic disturbances that cannot be attributed directly or entirely to peripheral inflammation or structural pathology. These conditions suggest the involvement of interactions between the nervous and immune systems, which probably include both peripheral and central components. This review summarizes the current knowledge of neurological and neuroimmune mechanisms that may contribute to these symptoms in SARDs. Glial cell activation and neuroinflammation within the central nervous system (CNS), small-fiber neuropathy (SFN) affecting peripheral nociceptive pathways, central pain sensitization, and autonomic nervous system dysfunction will be discussed. In addition, the role of molecular mediators, including cytokines, neuropeptides, and microRNAs, that could potentially modulate neuroimmune signaling will be highlighted. Integrating findings from pathology, immunology, and neuroscience, this review seeks to provide a useful framework for understanding neuroimmune dysregulation in SARDs. It also highlights the clinical relevance of these mechanisms and summarizes new directions for diagnosis and treatment. Full article

Osteoarthritis (OA) is a prevalent and disabling joint disorder characterized by progressive cartilage degradation, subchondral bone changes, synovial inflammation, and chronic pain. While traditionally attributed to mechanical and age-related factors, increasing attention has been directed toward the role of nutritional components in disease modulation. This article critically examines the emerging role of three essential trace elements, zinc, copper, and selenium, in the pathophysiology of OA. These micronutrients are fundamental to antioxidant defense, immune modulation, and extracellular matrix (ECM) integrity. Altered systemic or local levels of zinc, copper, and selenium have been associated with oxidative stress, inflammation, and dysregulated cartilage metabolism in OA. Drawing on clinical studies, in vivo and in vitro experimental models, and population-based data, we synthesize evidence on trace element status in OA patients, mechanistic pathways, and therapeutic potential, including emerging nanomedicine strategies that enhance the targeted delivery and therapeutic efficacy of trace elements in joint tissues. This review highlights the need for integrated trace element profiling in OA research and clinical care and supports the exploration of targeted nutritional interventions in OA prevention and management. 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

Background: Joint pain can impair joint function and limit a person’s ability to perform basic tasks and quality of life. The most used treatment is the pharmacological one. An alternative is the use of collagen-based food supplements. However, it remains a challenge to continue to develop new formulations to improve their efficacy. Objectives: The aim was to evaluate the long-term effectiveness of a food supplement based on hydrolyzed collagen alongside other active ingredients on knee joint pain, range of motion, and quality of life questionnaires in a moderately active population. Methods: A randomized, double-blind, and controlled study with two arms was completed with 80 participants, who took the prescribed supplementation (Curarti^® Selectium) or placebo for 40 days. Results: The supplement group showed a reduction of pain felt just after waking up in the morning. A statistically significant reduction in felt pain 3 h after exercise was observed at week 6 for the new product formula group compared to the placebo group. The symptoms associated with knee problems (KOOS) showed significant differences between groups. In functional capacity (WOMAC), it was found that the improvement was greater in the group treated with investigational formula (IF) than in the placebo group. The 36-item short form health survey (SF-36) about quality of life showed that the individuals who took IF improved with respect to those who took a placebo. Conclusions: The intake of Curarti^® Selectium for 40 days is effective in reducing joint pain at rest and after physical exercise, as well as maintaining the perception of quality of life, while allowing the physical functionality of the joint. Full article

Regional anesthesia techniques targeting articular nerve branches offer promising avenues for managing articular pain. This study developed and compared the success rates of an ultrasound-guided versus a blind pericapsular knee desensitization (PKD) technique in canine cadavers. In Phase I, gross dissection and ultrasound evaluations were performed in eight limbs to characterize the anatomy of the medial (MAN), lateral (LAN), and posterior (PAN) articular branches of the saphenous, common fibular, and tibial nerves, respectively, and to identify suitable anatomical and ultrasonographic landmarks. In Phase II, ultrasound-guided and blind PKD injections of a dye solution were randomly performed in 10 cadavers (20 limbs), followed by dissection and histological assessment of staining accuracy. The ultrasound-guided technique achieved a significantly higher overall success rate (96.7%) than the blind technique (73.3%; p = 0.02). The MAN was successfully stained in 100% of ultrasound-guided and 50% of blind injections (p = 0.03), while the LAN and PAN were stained with high but comparable success. Parent nerve involvement was minimal for MAN and PAN but frequent for the common fibular nerve following LAN injections. Histological confirmation supported the anatomical findings, although PAN identification remained inconsistent. These results support the feasibility and increased precision of ultrasound-guided PKD, providing a foundation for further clinical evaluation. Full article