Detoxification of T-2 toxin in human chondrocytes due to its hydroxylation by carboxylesterases and arylacetamide deacetylase in the liver.

To report low-field standing MRI findings and, when available, postmortem findings of 25 thoracic limbs with degenerative joint disease of the distal interphalangeal joint (DIPJ) characterized by narrowing of the joint space suggestive of cartilage loss. Medical records from September 2015 to July 2022 were reviewed for clinical history, signalment, MRI, and postmortem findings. The study retrospectively analyzed cases in which lameness was linked to DIPJ joint space narrowing using a partially nested comparative design. Width was measured at 4 DIPJ sites, as well as a ratio to the proximal interphalangeal joint. Affected limbs were compared to contralateral and randomly selected control limbs. Statistically significant differences in measurements were found between affected and control groups. In the affected group, subjective DIPJ narrowing, synovial effusion, heterogeneous dorsal recess material, periarticular osteophytosis, and STIR hyperintense signal within the foot were graded. Standing low-field MRI identified DIPJ degenerative joint disease with joint space narrowing and cartilage loss. A dorsomedial DIPJ width measurement of < 3 mm suggests cartilage damage. Narrowing of the DIPJ may occur without marked effusion, periarticular osteophytosis, or adjacent bone STIR hyperintensity. Measurements of the joint space on standing low-field MRI can be supportive for the identification of cartilage loss in the DIPJ, which may occur without other concomitant findings. Low-field standing MRI is valuable for assessing DIPJ narrowing. Prognosis appears to be poor for cartilage loss, as 22 of 25 horses did not return to performance.

Ferroptosis has been shown to play a significant role in the pathophysiological progression of knee osteoarthritis (KOA). In this study, we sought to investigate the biological role of Ubiquitin C-terminal hydrolase 1 (UCHL1) in KOA and elucidate its underlying molecular mechanisms. An in vitro KOA cell model was established by stimulating C28/I2 chondrocytes with IL-1β, and UCHL1 expression was decreased in IL-1β-treated chondrocytes. Notably, overexpression of UCHL1 significantly alleviated IL-1β-induced ferroptosis and extracellular matrix (ECM) degradation. Mechanistically, UCHL1 facilitated the deubiquitination and stabilization of FOXO1. Knockdown of FOXO1 partially reversed the inhibitory effects of UCHL1 on ferroptosis and ECM degradation. Furthermore, FOXO1 was found to bind to the Tuberous Sclerosis Complex 1 (TSC1) promoter, enhancing TSC1 transcription. Intriguingly, knockdown of FOXO1 counteracted the inhibitory effects of UCHL1 overexpression on ferroptosis and ECM degradation, while these effects were rescued by TSC1 overexpression. In vivo experiments demonstrated that UCHL1 alleviated cartilage damage in KOA rats by inhibiting ferroptosis and ECM degradation through the FOXO1/TSC1 axis. These findings demonstrate the pivotal role of UCHL1 in regulating ferroptosis and maintaining ECM homeostasis, offering novel insights into the molecular mechanisms driving KOA progression.

Articular cartilage injury represents a significant clinical challenge, with traditional treatments providing limited efficacy. Advances in regenerative medicine and digital education have created new opportunities for both cartilage repair therapies and innovations in medical education. This study aims to systematically analyze the research status, hotspots, and development trends in these two fields from 2013 to 2024 using bibliometric and visualization methods. Literature was retrieved from the PubMed, Embase, and Scopus databases for English articles published between January 1, 2013, and December 1, 2024. A search strategy combining Medical Subject Headings (MeSH) and free-text keywords was employed, resulting in 5,589 included articles. CiteSpace 5.8.R3 was used for keyword co-occurrence, co-citation, collaboration network, and burst detection analyses, with time slicing to reveal dynamic trends. Annual publications in cartilage repair treatment showed steady growth, with research hotspots focusing on stem cell therapy, tissue engineering, 3D printing, and biomaterials. In medical education innovation, research concentrated on educational reform, virtual learning, and flipped classrooms. The collaboration network analysis indicated that the United States and Germany played central roles in cartilage repair, while the United States and the Netherlands were central in medical education innovation. Burst keyword analysis revealed a shift in cartilage repair toward personalized therapies and bioprinting, and in medical education toward virtual reality and blended learning models. The study found that cartilage repair research was moving toward interdisciplinary integration, with personalized and intelligent repair serving as its main development directions. Medical education, leveraging virtual reality and augmented reality technologies, promoted the reconstruction of teaching scenarios and the optimization of learning pathways. Future research should enhance clinical translation, integrate educational technologies, and foster cross-institutional collaboration to promote synergistic innovation in both fields.

Purely ligamentous Lisfranc injuries are challenging to manage. Traditional open reduction and internal fixation provides rigid stability but risks cartilage damage, hardware failure, and the need for removal. Flexible fixation methods such as the suture-button (SB) and InternalBrace (IB) systems aim to maintain reduction while allowing physiological motion. This study compared clinical and radiographic outcomes of SB and IB fixation for these injuries. A retrospective comparative study included 64 patients (SB, n = 34; IB, n = 30) with acute, purely ligamentous Lisfranc injuries and ≥24-month follow-up. Primary outcomes were American Orthopaedic Foot & Ankle Society (AOFAS) midfoot and visual analog scale (VAS) pain scores; radiographic outcomes included maintenance of the first cuneiform to second metatarsal (C1-M2) interval. Secondary measures were time to full weight bearing, return to sport, and complications. Both groups demonstrated significant improvements in AOFAS and VAS scores from preoperative to final follow-up (P < .001). There was no statistically significant difference between the SB and IB groups in mean final AOFAS scores (92.4 vs 91.5, respectively; P = .58) or VAS scores (1.5 vs 1.2, respectively; P = .21). Both techniques effectively maintained anatomic reduction, with no significant difference in the final C1-M2 diastasis (P = .75) and no clinically significant loss of reduction at final follow-up. SB and IB fixation provide excellent function, stable radiographic results, and low complication rates for purely ligamentous Lisfranc injuries, offering reliable alternatives to rigid fixation.

Background: Osteoarthritis (OA) is a prevalent degenerative joint disease marked by the continuous deterioration of cartilage and functional limitations, impacting millions, with few disease-modifying treatments available. The extracellular matrix protein hyaluronan and proteoglycan link protein 1 (HAPLN1) stabilises aggrecan-hyaluronan complexes in cartilage; nonetheless, its function in osteoarthritis pathogenesis is inadequately comprehended. This research examined HAPLN1 expression in osteoarthritis models and its impact on chondrocyte senescence. Methods: Primary articular mouse chondrocytes were extracted from neonatal C57BL/6 mice and grown in DMEM/F12 conditions. OA-like conditions were produced by TNF-α (10 ng/ml) or tert-butyl hydroperoxide (TBHP, 50 μM). HAPLN1 knockdown was accomplished using lentiviral shRNA transfection. Recombinant mouse HAPLN1 (rmHAPLN1, 2.5 ng/ml) was employed for rescue. SA-β-Gal staining, p16/p21 expression, and telomerase activity were used to measure senescence. Matrix breakdown indicators (MMP-13, Col2a1) and inflammatory cytokines (CXCL10, IL-1β, MCP-1) were evaluated by qPCR, Western blot, and ELISA. Oxidative stress was measured by ROS levels, γ-H2AX, SOD/CAT activity, and Foxo3a phosphorylation/localization. In vivo , post-traumatic OA was generated by destabilisation of the medial meniscus (DMM) in 8-week-old male mice, with intra-articular lentiviral HAPLN1 administration at weeks 1 and 4. Krenn’s approach was used to assess synovitis, whereas OARSI grading was used to score cartilage integrity. Results: TNF-α and TBHP-stimulated chondrocytes and cartilage from DMM-operated animals showed significantly lower levels of HAPLN1 mRNA and protein. Silencing HAPLN1 dramatically accelerated extracellular matrix breakdown, inflammatory cytokine release, cellular senescence, and oxidative stress, which was mediated by increased Foxo3a phosphorylation at Ser253/Thr32 and cytoplasmic retention. In contrast, supplementation with rmHAPLN1 or intra-articular lentiviral-mediated HAPLN1 overexpression improved these changes both in vitro and in vivo , considerably decreasing OARSI cartilage damage and synovitis scores when compared to untreated OA controls. Conclusion: Our results show that HAPLN1 protects against OA by reducing Foxo3a-induced chondrocyte senescence and oxidative stress, making it a suitable therapeutic target.

Introduction Microplastics (MPs) are ubiquitous environmental particles with emerging immunotoxic and pro-inflammatory potential. Their persistence in water, food chains and air leads to continuous low-dose human exposure. Increasing evidence suggests MPs may act as environmental cofactors capable of triggering immune dysregulation, oxidative stress and chronic low-grade inflammation. These mechanisms raise concern that MPs could contribute to the initiation or exacerbation of autoimmune inflammation. The study aims to synthesise peer-reviewed evidence on MPs exposure and its potential role in the development and worsening of autoimmune pathology, with a focus on rheumatic diseases and their underlying immunopathogenic mechanisms. Material and Methods Narrative review based on structured searches of PubMed/MEDLINE, Scopus and Web of Science, enhanced by manual reference screening. Experimental, translational and clinical studies evaluating MPs exposure in relation to rheumatic outcomes were qualitatively integrated. Exclusion criteria included non-peerreviewed publications, conference abstracts, and studies lacking immune or clinical outcome assessment. Results In murine models, oral MPs exposure induced lupus-like manifestations in C57BL/6 mice and aggravated spontaneous lupus in MRL/lpr mice. These effects were associated with expansion of splenic double-negative T cells and plasma cells, increased anti-dsDNA and anti-nuclear antibodies titres, elevated interleukin-6 and tumour necrosis factor levels, and renal injury with proteomic signatures consistent with lupus-associated pathways and complement-mediated damage. In rheumatoid arthritis models, MPs were internalised by fibroblast-like synoviocytes, enhancing proliferation, migration and invasion, increasing inflammatory mediator release, and promoting cartilage damage. Discussion Across experimental systems, MPs appear to function as pro-inflammatory adjuvant-like particles, activating stromal effector cells, amplifying cytokine and protease cascades, and potentially enhancing complement-driven tissue injury. However, human causality remains uncertain due to heterogeneity in exposure assessment, particle composition and size variability, and predominance of high-dose experimental models. Conclusions Current evidence, largely preclinical, supports a plausible role of MPs in promoting initiation and progression of autoimmune rheumatic phenotypes. Standardised exposure assessment, biomonitoring strategies and prospective human studies are required to define attributable risk and identify preventive public health interventions.

SaintGSE: Transformer-based efficient and explainable gene set enrichment analysis.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovial hyperplasia, progressive osteoarticular destruction, and systemic inflammatory complications. β-Sitosterol (BSS), a plant-derived phytosterol, exhibits anti-inflammatory and antioxidant properties; however, its therapeutic utility is limited by poor aqueous solubility and low oral bioavailability. This study aimed to enhance the oral delivery of BSS using Leciplex nanocarriers (BSS-LPXs) and to investigate their effects on key inflammatory pathways in Complete Freund's Adjuvant (CFA)-induced RA in rats. BSS-LPXs were optimized using a Box-Behnken design to achieve optimal vesicle size, entrapment efficiency, and sustained drug release. Pharmacokinetic parameters were assessed following oral administration in rats. Anti-arthritic pharmacodynamics were evaluated via clinical arthritis scoring, serum cytokine levels (TNF-α, IL-6), oxidative stress markers (GSH, SOD, MDA), and histopathological examination. Mechanistic studies focused on the modulation of JAK2/STAT3, NF-κB, and p38 MAPK signaling pathways. Optimized BSS-LPXs had an average size of ~ 146 nm, 66% entrapment efficiency, and sustained release characteristics. Oral administration of BSS-LPXs significantly increased bioavailability by 3.8-fold compared to the conventional suspension (p < 0.05), with higher Cmax and prolonged half-life. In vivo, BSS-LPXs attenuated arthritis progression, preserved body weight, lowered TNF-α and IL-6 levels, restored antioxidant defenses, and decreased lipid peroxidation. Mechanistically, the formulation downregulated JAK2/STAT3 expression and suppressed the activation of NF-κB and p38 MAPK signaling. Histopathological analysis confirmed reduced synovial hyperplasia and cartilage damage. Leciplexes improved oral bioavailability and systemic exposure of BSS compared with conventional suspension, while enhancing anti-arthritic efficacy by modulating key inflammatory pathways, reducing oxidative stress, and protecting joint structure. This combined pharmacokinetic and pharmacodynamic profile highlights the potential of LPXs as an effective strategy to improve the delivery and anti-arthritic activity of hydrophobic phytoconstituents.

This study aimed to identify preoperative and postoperative risk factors associated with the development of arthrogenic muscle inhibition (AMI) in patients undergoing anterior cruciate ligament reconstruction (ACLR). The hypothesis was that distinct risk factors contribute to the occurrence of preoperative and postoperative AMI. A retrospective cohort study included 169 patients who underwent ACLR using a hamstring autograft combined with anterolateral ligament reconstruction between November 2022 and December 2023. AMI was clinically assessed preoperatively (t0), and at 45 days (D45) and 90 days (D90) postoperatively. Demographic, clinical and perioperative variables were collected. A combination of descriptive statistics and inferential tests was used, followed by univariate and stepwise multivariable logistic regression to identify independent predictors of AMI. AMI was observed in 33.7% of patients. Its prevalence was 15% at t0, 22% at D45 and 18% at D90. Preoperatively, patients with AMI demonstrated reduced knee flexion range (p < 0.001) and a shorter delay between injury and consultation (p < 0.001); AMI was significantly associated with joint effusion (odds ratio [OR] = 8.97; p < 0.001) and bucket-handle meniscal tears (OR = 5.24; p = 0.016). Postoperatively, significant predictors included female sex (OR = 2.98; p = 0.009), lateral femorotibial cartilage lesions (OR = 8.63; p = 0.004) and preoperative AMI (OR = 3.56; p = 0.008). Pain intensity was not significantly associated with AMI at any assessment point (not significant [n.s.]). AMI affects approximately one-third of patients undergoing ACLR and may persist for at least three months postoperatively. Distinct preoperative and postoperative risk factors were identified, with preoperative AMI strongly predicting its persistence. Joint effusion and specific meniscal lesions appear to act as preoperative triggers, whereas cartilage damage and sex may influence postoperative evolution. Early identification and management of modifiable risk factors, particularly before surgery, may help optimize rehabilitation and limit the persistence of AMI after ACLR. Level III.

Reactive oxygen species (ROS) play a crucial role in the occurrence and development of osteoarthritis (OA). The homeostasis of the joint environment becomes imbalanced when joints are affected by various adverse factors, such as long-term excessive wear, trauma, and aging. Excessive accumulation of ROS in the joint can cause a series of harmful chain reactions and affect the normal function of joints. Traditional drugs are mainly used to relieve patient symptoms and cannot repair damaged cartilage or prevent the destruction process. Long-term use of these drugs may cause side effects. With the vigorous development of modern medicine and materials science, metal-based nanozymes have shown therapeutic effects in clearing ROS, anti-inflammatory effects, and promoting cartilage protection due to their unique physical and chemical properties. Metal-based nanozymes demonstrate the advantages of simulating various natural enzyme activities, multitarget synergy, and reshaping the microenvironment of joint lesions. In this review, the dynamic balance mechanism of chondrocytes in joints was introduced, followed by ROS-driven OA cartilage and synovial injury. Emphasis was placed on the application of metal-based nanozymes including Cu, Mn, Fe, Ce, Au, Pt, PB, and Ag in the field of OA. Finally, preclinical safety evaluation was discussed, confirming the efficacy of some metal-based nanozymes in the joint. We hope to provide useful references for future research and promote the progress of nanomedicine in the field of OA.

ALOX5 knockdown alleviates cartilage damage in osteoarthritis by inhibiting the NF-κB signaling pathway.

Maintaining chondrocyte homeostasis is crucial for the effective treatment of osteoarthritis. Chondrocytes reside in a hypoxic environment under physiological conditions. This study, conducted exclusively in male mice, examines the association between epigenetics and chondrocyte homeostasis and observes significant alterations in histone acetylation in chondrocytes under hypoxic conditions. We identify a key enhancer element that regulates the long non-coding RNA CADM1-AS1, which is essential for cartilage homeostasis. This work elucidates a mechanism of epigenetic modulation that contributes to chondrocyte dysfunction in osteoarthritis. Further mechanistic investigations show that CADM1-AS1 recruits histone deacetylase complexes to suppress the transcriptional activation of NOS2, thereby affecting amino acid metabolism in chondrocytes. Conditional knockout of CADM1-AS1 in chondrocytes accelerates osteoarthritis development in mice. Using a hybrid exosome delivery system, we successfully modulate the expression of CADM1-AS1 and effectively reduce cartilage damage. Collectively, these findings reveal the importance of epigenetic regulation via CADM1-AS1-mediated histone deacetylation in the pathogenesis of osteoarthritis. Thus, CADM1-AS1 represents a potential therapeutic target for reducing cartilage damage in osteoarthritis and improving disease management.

Femoroacetabular impingement (FAI) is one of the major causes of hip pain. The pathogenesis of FAI remains unclear, and few animal models are available to study its mechanisms. To evaluate bone deformity formation, labrum, and articular cartilage injury induced by mechanical and exercise stimulation, and to establish an FAI model in New Zealand White rabbits. Controlled laboratory study. 6-month-old (6M) and 1-month-old (1M) male rabbits were used. Three-dimensional printed polylactic acid scaffolds were surgically fixed to the acetabular rim, followed by postoperative treadmill training. Specimens were collected at 8 and 12 weeks. Bone deformities were assessed by micro-computed tomography. Histological evaluation included hematoxylin and eosin staining for morphology, Safranin O/Fast Green (SO/FG), and toluidine blue staining for proteoglycan and glycosaminoglycan deposition, and immunofluorescence for SRY-box transcription factor 9 (SOX9), aggrecan (ACAN), runt-related transcription factor 2 (RUNX2), and cluster of differentiation 31 (CD31) expression. Mechanical properties of the labrum and cartilage were evaluated by nanoindentation, with the Young's modulus as the stiffness parameter. Gross evaluation (control [Ctrl] vs FAI, 6M: P < .0001, 1M: P < 0001) and micro-CT revealed significant bone deformities and cartilage damage in the FAI group. SO/FG staining showed reduced proteoglycan deposition (Ctrl vs FAI, 6M: P = .0001, 1M: P = .0006), accompanied by decreased SOX9 (Sham vs FAI, 6M: P < .0001, 1M: P < .0001), ACAN (Sham vs FAI, 6M: P = .0392, 1M: P < .0001) expression, and increased RUNX2 (Sham vs FAI, 6M: P = .0007, 1M: P = .0014) and CD31 (Sham vs FAI, 6M: P = .0018, 1M: P = .0071) expression. The Young's modulus of both the labrum (Ctrl vs FAI, 6M: P < .0001, 1M: P = .0061) and femoral head cartilage was reduced. A stable, reproducible, and easily operable rabbit model of FAI was established using combined mechanical and exercise stimulation, providing a practical platform for investigating the pathogenesis of FAI. FAI animal models established through acetabular overcoverage surgery are expected to provide an effective tool for subsequent research into the pathogenesis of FAI, thereby laying a theoretical foundation for its early targeted treatment.

Pyrroloquinoline quinone alleviates age-related osteoarthritis via nuclear factor erythroid 2-related factor 2-mediated stress response and insulin-like growth factor 1 receptor upregulation.

Medial patellofemoral ligament (MPFL) reconstruction is frequently used to manage recurrent patellar instability. Diagnostic arthroscopy is commonly performed before MPFL reconstruction to identify, confirm, and address intra-articular pathology. However, when preoperative magnetic resonance imaging (MRI) does not demonstrate intra-articular lesions, it is unclear how often diagnostic arthroscopy in pediatric patients alters surgical management. To determine the utility of diagnostic arthroscopy in young patients undergoing MPFL reconstruction who had no intra-articular chondral or osteochondral pathology, meniscal tears, or loose bodies identified on preoperative MRI, and to characterize intra-articular pathology detected on arthroscopy but not identified on MRI. Case series; Level of evidence, 4. This was a retrospective cohort study of patients who underwent MPFL reconstruction from 2014 to 2025. Inclusion criteria were age ≤18 years at the time of surgery, available preoperative MRI without intra-articular chondral or osteochondral pathology, meniscal tears, or loose bodies; and MPFL reconstruction with concomitant diagnostic arthroscopy. Exclusion criteria were congenital or syndromic patellar instability, prior ipsilateral knee surgery, absence of diagnostic arthroscopy, and MRI with intra-articular cartilage damage, osteochondral fractures, subchondral fractures, loose bodies, or meniscal tears. A total of 626 knees were initially identified. After application of exclusion criteria, the final cohort included 81 knees. The mean age was 14.9 years, and 77% patients were female. Of the knees excluded for operative MRI findings, the most common were loose bodies, articular cartilage injuries, and osteochondral fractures. In the final cohort, 35 of 81 (43.2%) knees had arthroscopic pathology, which included chondral changes in multiple sites (n = 35; 43%), loose bodies (n = 3; 4%), and meniscal tears (n = 1; 1%). Overall, 10 of 81 (12.3%) knees underwent changes in management based on arthroscopic findings, including chondroplasty (n = 8; 10%) and loose-body removal (n = 3; 4%). Diagnostic arthroscopy altered management in 12.3% of pediatric MPFL reconstructions in the absence of intra-articular chondral or osteochondral pathology, meniscal tears, or loose bodies on MRI. These results suggest that routine diagnostic arthroscopy may provide clinically meaningful value only in a subset of patients by identifying pathology not appreciated on MRI.

Articular cartilage injury often leads to progressive degeneration, necessitating advanced strategies that integrate immunomodulation, stem cell recruitment, and microenvironment regulation. Traditional hydrogels face limitations in spatiotemporal drug release and mechanical adaptability for dynamic joint environments. This study introduces an injectable, self-healing nanocomposite hydrogel engineered through dynamic boronate ester bonds between carboxymethyl chitosan and polyvinyl alcohol, synergizing macrophage-targeted curcumin nanomicelle and chondroinductive icariin. The hydrogel's reversible network enables shear-thinning injectability and reactive oxygen species (ROS)-responsive degradation, ensuring localized anti-inflammatory and pro-regenerative drug release. Curcumin-loaded mannose-functionalized micelles enhance macrophage uptake, polarizing macrophages toward an anti-inflammatory phenotype, while icariin promotes bone marrow mesenchymal stem cell (BMSC) migration and chondrogenic differentiation via Wnt/β-catenin and BMP/Smad pathway activation. In vitro studies demonstrated the hydrogel's capacity to scavenge ROS, suppress pro-inflammatory cytokines, and enhance BMSC recruitment and cartilage-specific matrix synthesis. In vivo evaluation in a rat full-thickness cartilage defect model revealed accelerated repair with organized neocartilage formation, reduced inflammation, and restored subchondral bone architecture. Histological and immunohistochemical analyses confirmed significant collagen II deposition and M2 macrophage polarization, aligning with native tissue regeneration. The hydrogel's biocompatibility and absence of systemic toxicity were validated through hematological and organ histopathology assessments. By dynamically coupling early-stage immunomodulation with sustained chondroinductive signaling, this dual-drug hydrogel disrupts the inflammation-degeneration cycle, offering a cell-free therapeutic platform for functional cartilage restoration. Its design principles provide a blueprint for intelligent biomaterials addressing complex tissue repair challenges.

A BSTRACT Pinna abscess is a severe condition that can lead to lasting cosmetic issues. The pinna, often the most affected part of the ear in mechanical injuries, is particularly susceptible to perichondritis. If auricular perichondritis is not properly treated, it can progress to a sub-perichondrial abscess, potentially causing cartilage damage and significant cosmetic deformity. Pseudomonas aeruginosa is commonly associated with pinna abscesses, typically started from injury. Swift surgical drainage of the abscess and suitable antibiotic therapy are crucial in managing pinna abscesses. Here, we illustrate a case where a pinna abscess was triggered by an exceptionally rare cause: a mosquito bite.

A self-perpetuating cycle of Type H vessel proliferation and T-2 induced inflammation drives KBD pathogenesis.

Nanomaterial-based strategies to modulate macrophage polarization in osteoarthritis: A systematic review.