Search Results (3,532)

Background: Wugeng San (WGS) is a traditional Tibetan medicinal preparation that has long been used to treat inflammatory and arthritic conditions. However, its contemporary pharmacological validation and the mechanisms underlying its action in rheumatoid arthritis (RA) have not been fully investigated. Objective: For the first time, this study aimed to systematically investigate the therapeutic effects of WGS on RA, identify its potential targets, and elucidate its action mechanisms. Methods: This study, as the first comprehensive investigation of WGS in RA, employed integrated multiple approaches including chemical component identification via UPLC-Q-TOF/MS, network pharmacology, bioinformatics, machine learning, and in vivo efficacy assessment and mechanism verification in a collagen-induced arthritis (CIA) rat model, a widely accepted experimental model that mimics the key pathological features of RA. Results: The results demonstrated that WGS reduced the severity of arthritis in a dose-dependent manner, as evidenced by decreased paw swelling, normalized body weight, and restored levels of pro- and anti-inflammatory cytokines. The high dose of WGS (252 mg/kg) showed an effect comparable to that of methotrexate (0.2 mg/kg). Histological analysis revealed that WGS reduced synovial hyperplasia, cartilage erosion and bone destruction, decreased osteoclast numbers, and promoted osteoblast activity. Eighty-four compounds were identified using UPLC-Q-TOF/MS. Network pharmacology and machine learning analyses indicated SYK as a key target enriched in the NF-κB signaling and osteoclast differentiation pathways. Experimental validation confirmed that WGS suppressed the phosphorylation of SYK and NF-κB pathway components (p65, IκBα, and IKKα/β), decreased MMP1/MMP3 levels, and modulated the Bax/Bcl-2 ratio to promote apoptosis. Conclusions: In conclusion, WGS exhibits strong anti-arthritic effects through “multi-component, multi-target, and multi-pathway” mechanisms, likely attributable to the inhibition of the SYK/NF-κB signaling axis, suppression of matrix degradation, and regulation of cellular apoptosis. This research offers a pharmacological basis for repurposing WGS as a promising natural candidate for RA therapy. Full article

Objectives: To evaluate the effectiveness and durability of matrix-associated autologous chondrocyte implantation with periosteal flap (pMACI) in treating knee cartilage defects using clinical scores and MRI evaluations. Methods: Data were collected from 37 knees of 17 patients, with a mean follow-up of 5 years (range: 0.1–20 years). Clinical outcomes were assessed using the Lysholm Knee Scoring Scale (LKS) and Knee Injury and Osteoarthritis Outcome Score (KOOS). Tissue quality was quantitatively evaluated using MRI T1ρ and T2 mapping (biochemical) and MR observation of cartilage repair tissue: MOCART 2.0 (morphological). A linear mixed model was used to identify factors affecting outcomes, including etiology (trauma, OCD, OA), graft site, and defect size. Results: At the 20-year follow-up, clinical scores remained significantly improved from baseline (mean LKS: 55.6 to 86.5; KOOS: 37.8 to 70.8). The biochemical MRI parameters (T1ρ and T2 values) stabilized at levels comparable to native cartilage across all etiologies and sites (p = 0.326 and 0.412, respectively), indicating stable long-term tissue quality. In contrast, the MOCART 2.0 scores significantly declined over time (annual rate: −1.14 points; p < 0.001). Etiology was a significant factor; the OA group showed significantly lower clinical and MOCART scores compared to the trauma/OCD groups (p < 0.05). However, no significant differences were found in LKS and KOOS based on graft site (p = 0.489) or defect size (p > 0.05). Conclusions: pMACI may be a highly durable treatment capable of maintaining biological tissue quality and providing clinical benefits for two decades. The observed morphological deterioration after 20 years likely reflects joint-wide aging—especially in OA cases—rather than graft failure, highlighting the importance of long-term MRI monitoring. Full article

Background/Objectives: Anthracyclines such as doxorubicin (DOX) are integral to pediatric cancer protocols, yet little is known about how juvenile DOX exposure shapes the long-term trajectory of bone growth, microarchitectural connectivity, and the functional balance of bone turnover after treatment cessation. This study aimed to define how juvenile DOX exposure remodels trabecular architecture and bone homeostasis both acutely and after recovery. Methods: Four-week-old female BALB/c mice were treated with 6 mg/kg DOX or saline once weekly for four weeks. Bone parameters were analyzed immediately after treatment and after a 4-week drug-free recovery period. Assessments included high-resolution µCT for bone structure and connectivity, H&E and TRAP staining for histological evaluation, and ELISA for bone turnover markers (PINP, OC/BGP, TRACP-5b) in both serum and bone marrow. Results: DOX exposure significantly compromised trabecular bone mass and network connectivity, with persistent bone loss extending into the recovery period. Histologically, DOX caused marked degeneration in the epiphyseal growth plate and calcified zones, alongside a marked increase in osteoclast numbers. Functionally, an acute increase in circulating bone formation markers was observed post-treatment. However, during the recovery phase, this transitioned to a significant suppression of these systemic markers, coupled with significantly increased localized bone resorption. Conclusions: Juvenile DOX exposure produces sustained trabecular network impairment and growth plate degeneration. This durable structural deterioration is functionally associated with the establishment of a localized, pathologically uncoupled remodeling environment. Full article

Synovitis is a key contributor to the development of OA, and early modulation of the synovial environment may help limit downstream cartilage damage. This study compared the clinical and biochemical effects of intra-articular triamcinolone acetonide (TA) and autologous conditioned serum (ACS) in an equine model of IL-1β–induced synovitis. Six healthy adult horses were used in a crossover design involving five groups: PBS (negative control), IL-1β (positive control), IL-1β + ACS, IL-1β + TA, and an exploratory ACS-alone group administered post hoc to isolate its effects without IL-1β interference. Both TA and ACS mitigated inflammation through distinct profiles. TA was superior in reducing joint heat, swelling, and effusion. Conversely, IL-1β + ACS provided greater lameness improvement at 24, 36, and 72 h compared to IL-1β. ACS demonstrated potential chondroprotective advantages, as it did not increase synovial glycosaminoglycan (GAG) concentrations, which were highest in the IL-1β + TA group. ACS treatment resulted in significantly higher synovial total nucleated cell counts and total protein, driven primarily by monocyte enrichment. This cellular profile suggests that ACS may support the restoration of joint homeostasis. While TA remains highly effective for visual inflammatory signs, ACS offers a promising biological alternative for modulating the synovial environment and protecting cartilage during acute synovitis. Full article

This study focuses on the development and comprehensive evaluation of the physicochemical, mechanical, and biological properties of composites based on polyhydroxybutyrate (PHB), chitosan (Ch), and hydroxyapatite (HA) for biomedical applications. DSC and FTIR spectroscopy showed that the addition of hydroxyapatite did not significantly affect the structure of the materials, but AFM data revealed a change in the surface morphology. Variations in RMS roughness ranging from 13 to 150 nm were observed for chitosan and the composites. The density of the HA-containing samples was 0.06–0.067 g/cm³, which is higher than that of the unfilled composite (0.056 g/cm³). Optimal hydrophilic properties (contact angle 38.9°) and elasticity (damping factor 0.064) were recorded for the sample with 10% HA (PChHA10). The water absorption varied: the addition of chitosan increased the value to 7.5 g/g, compared to 2.7 g/g for pure PHB, while HA slowed the swelling kinetics (more than 180 min). A biodegradation study revealed that samples containing 10–20% HA exhibited the highest stability in an enzymatic environment, while further increases in HA content resulted in increased degradation rates. The PChHA10 is considered to offer the balanced combination of properties. The potential applications of this material in medicine include its use as a scaffold for the in vitro cultivation of osteoblasts and chondrocytes, as well as for implantation in models of bone and cartilage defects in vivo. Full article

Background: Cytokine-like receptor family 1 (CRLF1) has been implicated in tumor progression, yet its prognostic function and mechanistic actions in prostate cancer (PCa) remain elusive. Objective: This investigation sought to clarify the functional role, molecular mechanisms, and clinical relevance of CRLF1 in the progression of PCa. Methods: We conducted extensive bioinformatics analyses utilizing the protein interaction networks and the TCGA-PRAD dataset. CRLF1 and cartilage oligomeric matrix protein (COMP) expression were validated in clinical samples by qRT-PCR and Western blot (WB). Functional assessments, including Transwell invasion, flow cytometry, CCK-8, and wound healing, were conducted in vitro. An in vivo xenograft tumor model was used for further validation. Mechanistic investigations involved genetic perturbation (overexpression and inhibition) of CRLF1 and COMP. Results: Compared to benign tissues, the levels of CRLF1 and COMP were markedly elevated in PCa tissues. Bioinformatics assessments illustrated a robust positive relationship between CRLF1 and COMP, suggesting COMP may function as a downstream mediator. In vitro and in vivo investigations illustrated that silencing CRLF1 significantly suppressed PCa cell growth, invasion, and tumor progression, while enhancing apoptosis. Importantly, suppressing COMP counteracted the cancer-promoting effects triggered by CRLF1 overexpression. At the mechanistic level, CRLF1 facilitates tumor progression by modulating COMP to activate the FAK/PI3K/AKT signaling cascade. Conclusions: Our outcomes demonstrate that CRLF1 promotes PCa progression by targeting COMP to stimulate the FAK/PI3K/AKT signaling axis. This newly identified CRLF1/COMP/FAK/PI3K/AKT pathway underscores CRLF1 as a potential biomarker and therapeutic target for PCa. Full article

Solution electrospinning (SES) and melt electrowriting (MEW) are complementary fiber-based fabrication platforms extensively investigated in tissue engineering. SES generates fibers typically ranging from the nanometer to the low-micrometer scale, producing fibrous networks that mimic the native extracellular matrix (ECM) and support key cellular functions. MEW, by contrast, operates solvent-free and enables precise, layer-by-layer deposition of microfibers with well-controlled geometry, conferring the mechanical integrity and open-pore architecture that SES constructs inherently lack. Despite growing interest, the body of peer-reviewed literature reporting original hybrid SES–MEW fabrication and biological outcome data remains limited, with no comprehensive cross-tissue synthesis available to date. This narrative review examines the current state of SES–MEW hybrid strategies across five tissue engineering targets selected for their clinical relevance: skin, vascular grafts, bone, cartilage, cardiac valves, and skeletal muscle. For each application, the architectural rationale, the fabrication approach, and the in vitro and in vivo biological outcomes are discussed in an integrated manner, with attention to how the spatial organization of nano- and microfibers translates into tissue-specific functional responses. A comparative analysis across tissue types highlights both the versatility of hybrid constructs and their persistent limitations, including suture retention values that remain below clinically accepted thresholds in vascular applications, incomplete cellular infiltration through dense nanofibrous layers, and the absence of validated, reproducible scale-up protocols compatible with clinical-grade manufacturing. The review concludes by identifying the most critical open questions in the field, encompassing process standardization, regulatory classification, and the emerging role of machine learning in closed-loop MEW process optimization. This work aims to provide an evidence-based perspective on the current state of hybrid SES–MEW scaffold engineering and the key translational gaps limiting clinical application. Full article

Background/Objectives: Proximal phalangeal fractures account for 38% of all phalangeal fractures, with unstable patterns requiring surgical intervention. Various modalities have been explored, including open reduction and internal fixation, percutaneous K-wire fixation, and intramedullary techniques. This study explores the technical nuances, indication, and outcomes of antegrade cannulated compressive screw (CCS) fixation of proximal phalangeal fractures. Methods: This retrospective case series involved 18 closed proximal phalangeal fractures in 16 patients who underwent intramedullary headless screw fixation between January 2018 and December 2023. Records were reviewed for demographics, fracture characteristics, and screw type. With the metacarpophalangeal joint flexed at 60–75°, a 1 cm longitudinal incision was made, the extensor tendon split, and a 0.9 mm guidewire advanced anterogradely along the phalangeal axis under fluoroscopy. A 2.2 mm or 3.0 mm SpeedTip CCS was selected based on phalanx size and advanced until fully buried below the cartilage line. Postoperatively, patients were immobilized in a volar intrinsic-plus splint, transitioned to a gutter splint within five to seven days, and commenced on range of motion (ROM) exercises within one week. Primary outcomes included radiographic union, Total Active Motion (TAM), QuickDASH scores, and postoperative complications. Results: All fractures were healed within acceptable radiological parameters and with no postoperative complications. Mean TAM was measured to be 216.0° (SD 7.7°, range 200–230°) and mean QuickDASH was 10.1 (SD 2.8, range 5–16). Conclusions: Antegrade intramedullary headless screw fixation demonstrates feasibility, short-term safety, and excellent early functional outcomes for carefully selected unstable proximal phalanx fractures, supporting its role as a minimally invasive alternative in appropriately indicated cases. Full article

Chondrosarcoma (CHS), the second most common primary malignant cartilage tumor, is largely resistant to conventional therapies, making surgical resection the standard treatment. Proton therapy offers a physical advantage through the Bragg peak, enabling targeted irradiation while sparing surrounding tissues. However, differential biological responses between malignant and normal cartilage cells remain poorly understood. In this study, CHS SW1353 cells and normal chondrocytes (MC615) were exposed to proton irradiation. Biological responses were assessed via clonogenic survival, cell viability, apoptosis (caspase 3/7), micronucleus formation, cell cycle profiling, and oxidative stress markers. Proteomic changes were analyzed using mass spectrometry and bioinformatics. CHS cells exhibited higher radioresistance (D₁₀ = 6.45 Gy) than normal chondrocytes (D₁₀ = 5.08 Gy), oxidative stress adaptation, G1 arrest and proteomic plasticity, whereas normal chondrocytes displayed increased oxidative stress, extracellular matrix fragility and impaired integrin signaling. Notably, the tumor-specific increased levels of Tyrosine-protein kinase Fyn and Yes1-associated transcriptional regulator (YAP1) signaling suggest molecular drivers of radioresistance. Overall, proton irradiation elicits distinct biological and proteomic responses in malignant versus normal cartilage cells. These findings highlight potential radiosensitization targets, including Fyn/Src and YAP1/Hippo pathways, while underscoring the need to optimize proton therapy to enhance tumor control while minimizing damage to healthy cartilage. Full article

Background: Eyelid reconstruction is particularly challenging because of the delicate anatomy and its critical functional and aesthetic roles. Although various methods have been described for anterior and posterior lamellar repairs, no standardized approach has been established. We developed a single-stage technique integrating reconstruction of both lamellae. Methods: This retrospective case series included seven consecutive patients who underwent full-thickness eyelid reconstruction between 2012 and 2024. Patients were included if they had full-thickness defects requiring reconstruction of both lamellae, underwent reconstruction using a nasal septal chondromucosal graft combined with a large local flap, and had at least 12 months of follow-up. The posterior lamella was reconstructed using nasal septal chondromucosal grafts, and the anterior lamella using large local flaps. Donor sites were managed using various methods. Results: All patients (7/7) achieved complete graft survival without partial or total graft loss. All patients achieved complete eyelid closure without lagophthalmos, and no cases of ectropion, corneal complications, or graft failure were observed. Buccal mucosal grafting demonstrated the most favorable donor-site outcomes, with uneventful healing and no septal perforation or airway-related complications. Conclusions: This single-stage approach combining chondromucosal grafts and local flaps is a feasible and reproducible option for selected patients, providing reliable structural support and satisfactory functional outcomes. Full article

The increase in older adults and active lifestyles has made chondral and osteochondral lesions common in the population, making them one of the central challenges in orthopedics. Although hydrogel-based regenerative medicine offers an encouraging therapeutic option for these lesions, important obstacles still prevent these therapies from reaching the clinic. In view of these factors, we adopted a risk-based approach for this review, in line with the current legislative requirements in clinical translation and clinical trials. We identified the factors that could undermine patient safety or lead to poor outcomes. Then, we outlined solutions to remedy these problems that integrate hydrogel technology, clinical/pharmaceutical/surgical protocols, and post-operative follow-up. Upcoming studies should give priority to the development of hydrogel scaffolds modified to mimic cartilage’s mechanical and physicochemical properties, together with patient-specific features. Other crucial characteristics are host-tissue integration, long-lasting cartilage tissue regeneration, and a positive outcome. In parallel, to scale complex and costly innovations, efforts should focus on a harmonized, simplified legislative landscape, optimized standards, and established follow-up protocols. Getting through this “valley of death” between research and innovation is strategic for reaching the clinics and the largest number of patients. Full article

Temporomandibular disorders (TMDs) are the prevalent causes of orofacial pain and dysfunction of the temporomandibular joint (TMJ) and masticatory muscles. Previous studies have revealed that proinflammatory cytokines play a key role in promoting inflammation, pain, and degeneration within the TMJ. In this context, the present systematic review synthesizes current evidence on various cytokines involved in the pathophysiology of TMDs and evaluates their associations with clinical signs and structural TMJ damage. A PRISMA-guided search (PROSPERO: CRD420251163290) was conducted in PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library to identify human-based, in vivo, and in vitro studies (January 2014 to September 2025) that assessed the roles of proinflammatory cytokines in TMDs. The following data were extracted from the identified studies: cytokine profiles, sampling methods, clinical outcomes, and TMJ structural changes. Study quality and risk of bias were systematically evaluated. A total of 15 studies (clinical, animal, and mechanistic) were included in the review. Tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-17 (IL-17) consistently emerged as the major contributors to synovitis, cartilage degradation, nociceptive sensitization, and bone resorption. Human studies showed that high levels of TNF-α, IL-1β, and IL-6 and chemokines such as C-C motif chemokine ligand 2 (CCL2) and regulated on activation, normal T-cell expressed and secreted (RANTES) were associated with TMJ pain, restricted mandibular motion, crepitus, malocclusion, and erosive changes on imaging. An increased ratio of TNF to soluble TNF receptor in synovial fluid correlated with both pain and condylar damage, suggesting that loss of cytokine control contributes to progressive joint destruction. TMDs, particularly inflammatory and degenerative subtypes, are cytokine-driven pathologies rather than purely mechanical disorders. TNF-α, IL-1β, and IL-6 are the promising candidate biomarkers of local inflammation and structural joint pathology. Standardized longitudinal studies are required to validate cytokine-based diagnostics and develop anti-cytokine therapeutics. Full article

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative maxillofacial disorder marked by progressive cartilage degradation and subchondral bone resorption, severely compromising patients’ quality of life. Intra-articular injection (IA), a standard route for conservative therapy, offers clinical advantages in safety and efficacy; however, outcomes remain limited due to short drug retention, poor tissue penetration, and variable agent efficacy, necessitating repeated administration. To overcome these limitations, fisetin-loaded poly (lactic-co-glycolic acid) nanoparticles (FST-PNP) were developed as a localized drug delivery system (DDS) for TMJOA treatment. Physicochemical analyses showed FST-PNP had uniform spherical morphology, excellent dispersibility, stability, high encapsulation efficiency, and substantial drug loading capacity. An in vitro study demonstrated more sustained and stable release from FST-PNP than free fisetin. The in vivo IA administration of FST-PNP preserved mandibular condylar osteochondral structures in TMJOA models. Notably, FST-PNP suppressed the expression of metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS5) as catabolic enzymes and downregulated p16 and p21 as senescence markers, indicating synergistic anti-inflammatory and anti-senescent effects. These findings highlight FST-PNP as a DDS integrating controlled-release with multifaceted therapeutic actions, providing a promising strategy for IA therapy of TMJOA. Full article

Mechano-sorptive phenomena (MSP) refer to the coupled mechanical response of polymers under simultaneous mechanical stress and fluid sorption. The most researched MSP are environmental stress cracking (ESC) and mechano-sorptive creep (MSC). ESC initiates at regions of localized stress and solvent sorption, presenting as brittle fracture, while MSC is characterized by large, time-dependent, and partially recoverable creep associated with transient bulk sorption. ESC experiments can however also result in significant plastic deformation, in which case the term environmental stress yielding (ESY) has been used. Similarly, MSC can evolve into tertiary creep followed by rupture, in which case the phenomenon is termed mechano-sorptive creep rupture (MSCR). Both behaviors originate from solvent diffusion into the amorphous phase, leading to disruption of non-covalent interactions between polymer chains. This review bridges seemingly disconnected research to illustrate that ESC and MSC represent extremes on a continuum of MSP, rather than disparate phenomena. We identify the principles of polymer thermodynamics and experimental methods necessary to separate polymer deformation under MSC into reversible stress-induced swelling and irreversible non-equilibrium deformation. Finally, we illustrate how MSP underline the functionality of several biomimetic materials including dentin adhesives, mutable collagenous tissue, spider silk, tendons, and articular cartilage, as well the synthesis of biomimetic materials by solvent vapor annealing assisted by soft shear. Full article

Articular cartilage has a limited capacity for self-repair, and effective strategies for its regeneration remain a major clinical challenge. Full-thickness cartilage defects extending to the subchondral bone induce an enhanced inflammatory response and impair spontaneous healing. This study aimed to evaluate the regenerative potential of autologous chondrocyte transplantation using an insoluble polyethersulfone (PES) scaffold in a rabbit model of grade III articular cartilage lesions. Chondrocytes were isolated and expanded in vitro and subsequently seeded onto PES membranes. Sixty-two rabbit knees with defects extending to the subchondral bone were divided into three groups: group I received chondrocyte-seeded PES scaffolds (n = 25), group II received cell-free PES scaffolds (n = 25), and group III served as an untreated control (n = 12). Cartilage regeneration was evaluated macroscopically and histologically over 52 weeks. In addition, the chondrogenic differentiation potential of cells cultured on PES scaffolds was assessed. This study extends our previous investigations of PES scaffolds in grade IV cartilage defects to a clinically relevant grade III lesion model, enabling evaluation of regenerative outcomes at an earlier stage of cartilage degeneration. The results demonstrated superior tissue regeneration in defects treated with chondrocyte-seeded PES scaffolds compared to both control groups. These findings indicate that synthetic PES scaffolds support cartilage repair and represent a promising biomaterial for the development of cell-based therapies in articular cartilage regeneration. Full article