-
Cells May 2024Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterised by the formation of a hyperplastic pannus, as well as cartilage and bone damage. The... (Review)
Review
Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterised by the formation of a hyperplastic pannus, as well as cartilage and bone damage. The pathogenesis of RA is complex and involves broad interactions between various cells present in the inflamed synovium, including fibroblast-like synoviocytes (FLSs), macrophages, and T cells, among others. Under inflammatory conditions, these cells are activated, further enhancing inflammatory responses and angiogenesis and promoting bone and cartilage degradation. Novel treatment methods for RA are greatly needed, and mesenchymal stromal cells (MSCs) have been suggested as a promising new regenerative and immunomodulatory treatment. In this paper, we present the interactions between MSCs and RA-FLSs, and macrophages and T cells, and summarise studies examining the use of MSCs in preclinical and clinical RA studies.
Topics: Humans; Arthritis, Rheumatoid; Mesenchymal Stem Cells; Mesenchymal Stem Cell Transplantation; Animals; Macrophages; T-Lymphocytes; Synovial Membrane; Synoviocytes
PubMed: 38891047
DOI: 10.3390/cells13110915 -
European Journal of Radiology Open Jun 2024The present study aimed to compare the computed tomography (CT) and magnetic resonance imaging (MRI) features of solid pseudopapillary neoplasms (SPNs) and pancreatic...
PURPOSE
The present study aimed to compare the computed tomography (CT) and magnetic resonance imaging (MRI) features of solid pseudopapillary neoplasms (SPNs) and pancreatic neuroendocrine neoplasms (pNENs).
METHOD
Lesion imaging features of 39 patients with SPNs and 127 patients with pNENs were retrospectively extracted from 104 CT and 91 MRI scans.
RESULTS
Compared to pNEN patients, SPN patients were significantly younger (mean age 51.8 yrs versus 32.7 yrs) and more often female (female: male ratio, 5.50:1 versus 1.19:1). Most SPNs and pNENs presented as well-defined lesions with an expansive growth pattern. SPNs more often appeared as round or ovoid lesions, compared to pNENs which showed a lobulated or irregular shape in more than half of cases (p<0.01). A surrounding capsule was detected in the majority of SPNs, but only in a minority of pNENs (<0.01). Hemorrhage occurred non-significantly more often in SPNs (p=0.09). Signal inhomogeneity in T1-fat-saturated (p<0.01) and T2-weighted imaging (p=0.046) as well as cystic degeneration (p<0.01) were more often observed in SPNs. Hyperenhancement in the arterial and portal-venous phase was more common in pNENs (p<0.01). Enlargement of locoregional lymph nodes (p<0.01) and liver metastases (p=0.03) were observed in some pNEN patients, but not in SPN patients. Multivariate logistic regression identified the presence of a capsule (p<0.01), absence of arterial hyperenhancement (p<0.01), and low patient age (p<0.01), as independent predictors for SPN.
CONCLUSIONS
The present study provides three key features for differentiating SPNs from pNENs extracted from a large patient cohort: presence of a capsule, absence of arterial hyperenhancement, and low patient age.
PubMed: 38882634
DOI: 10.1016/j.ejro.2024.100576 -
Experimental Biology and Medicine... 2024Rheumatoid fibroblast-like synoviocytes (RFLS) have an important role in the inflammatory pathogenesis of rheumatoid arthritis (RA). Toll-like receptor 3 (TLR3) is...
Rheumatoid fibroblast-like synoviocytes (RFLS) have an important role in the inflammatory pathogenesis of rheumatoid arthritis (RA). Toll-like receptor 3 (TLR3) is upregulated in RFLS; its activation leads to the production of interferon-β (IFN-β), a type I IFN. IFN-stimulated gene 56 (ISG56) is induced by IFN and is involved in innate immune responses; however, its role in RA remains unknown. Therefore, the purpose of this study was to investigate the role of TLR3-induced ISG56 in human RFLS. RFLS were treated with polyinosinic-polycytidylic acid (poly I:C), which served as a TLR3 ligand. ISG56, melanoma differentiation-associated gene 5 (MDA5), and C-X-C motif chemokine ligand 10 (CXCL10) expression were measured using quantitative reverse transcription-polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. Using immunohistochemistry, we found that ISG56 was expressed in synovial tissues of patients with RA and osteoarthritis. Under poly I:C treatment, ISG56 was upregulated in RFLS. In addition, we found that the type I IFN-neutralizing antibody mixture suppressed ISG56 expression. ISG56 knockdown decreased CXCL10 expression and MDA5 knockdown decreased ISG56 expression. In addition, we found that ISG56 was strongly expressed in the synovial cells of patients with RA. TLR3 signaling induced ISG56 expression in RFLS and type I IFN was involved in ISG56 expression. ISG56 was also found to be associated with CXCL10 expression, suggesting that ISG56 may be involved in TLR3/type I IFN/CXCL10 axis, and play a role in RA synovial inflammation.
Topics: Humans; Toll-Like Receptor 3; Arthritis, Rheumatoid; Poly I-C; Signal Transduction; Synoviocytes; Chemokine CXCL10; Interferon-Induced Helicase, IFIH1; Cells, Cultured; Synovial Membrane; Adaptor Proteins, Vesicular Transport; RNA-Binding Proteins; Adaptor Proteins, Signal Transducing; Apoptosis Regulatory Proteins
PubMed: 38881847
DOI: 10.3389/ebm.2024.10122 -
Journal of Orthopaedic Surgery and... Jun 2024This study aimed to validate alterations in the gene expression of DNA methylation-related enzymes and global methylation in the peripheral blood mononuclear cell (PBMC)...
BACKGROUND
This study aimed to validate alterations in the gene expression of DNA methylation-related enzymes and global methylation in the peripheral blood mononuclear cell (PBMC) and synovial tissues of animal hip osteoarthritis (OA) models.
METHODS
Animals were assigned to the control (no treatment), sham (25 µL of sterile saline), and OA (25 µL of sterile saline and 2 mg of monoiodoacetate) groups. Microcomputed tomography scan, histopathological assessment and pain threshold measurement were performed after induction. The mRNA expression of the DNA methylation machinery genes and global DNA methylation in the PBMC and hip synovial tissue were evaluated.
RESULTS
The OA group presented with hip joint OA histopathologically and radiologically and decreased pain threshold. The mRNA expression of DNA methyltransferase (Dnmt 3a), ten-eleven translocation (Tet) 1 and Tet 3 in the synovial tissue of the OA group was significantly upregulated. Global DNA methylation in the synovial tissue of the OA group was significantly higher than that of the control and sham groups.
CONCLUSIONS
The intra-articular administration of monoiodoacetate induced hip joint OA and decreased pain threshold. The DNA methylation machinery in the synovial tissues of hip OA was altered.
Topics: DNA Methylation; Animals; Osteoarthritis, Hip; Disease Models, Animal; Male; Rats; Iodoacetic Acid; Synovial Membrane; Leukocytes, Mononuclear; Rats, Sprague-Dawley; DNA Methyltransferase 3A; Pain Threshold
PubMed: 38880910
DOI: 10.1186/s13018-024-04847-0 -
Medical Science Monitor : International... Jun 2024BACKGROUND Osteoarthritis (OA) is a chronic degenerative disease characterized by synovitis and has been implicated in sphingolipid metabolism disorder. However, the...
BACKGROUND Osteoarthritis (OA) is a chronic degenerative disease characterized by synovitis and has been implicated in sphingolipid metabolism disorder. However, the role of sphingolipid metabolism pathway (SMP)-related genes in the occurrence of OA and synovial immune dysregulation remains unclear. MATERIAL AND METHODS In this study, we obtained synovium-related databases from GEO (n=40 for both healthy controls and OA) and analyzed the expression levels of SMP-related genes. Using 2 algorithms, we identified hub genes and developed a diagnostic model incorporating these hub genes to predict the occurrence of OA. Subsequently, the hub genes were further validated in peripheral blood samples from OA patients. Additionally, CIBERSORT and MCP-counter analyses were employed to explore the correlation between hub genes and immune dysregulation in OA synovium. WGCNA was used to determine enriched modules in different clusters. RESULTS Overall, the expression levels of SMP genes were upregulated in OA synovium. We identified 6 hub genes of SMP and constructed an excellent diagnostic model (AUC=0.976). The expression of re-confirmed hub genes showed associations with immune-related cell infiltration and levels of inflammatory cytokines. Furthermore, we observed heterogeneity in the expression patterns of hub genes across different clusters of OA. Notably, older patients displayed increased susceptibility to elevated levels of pain-related inflammatory cytokines and infiltration of immune cells. CONCLUSIONS The SMP-related hub genes have the potential to serve as diagnostic markers for OA patients. Moreover, the 4 hub genes of SMP demonstrate wide participation in immune dysregulation in OA synovium. The activation of different pathways is observed among different populations of patients with OA.
Topics: Humans; Synovial Membrane; Osteoarthritis; Sphingolipids; Gene Expression Profiling; Gene Regulatory Networks; Male; Female; Transcriptome; Databases, Genetic; Middle Aged; Case-Control Studies
PubMed: 38877693
DOI: 10.12659/MSM.943369 -
Medicine Jun 2024Spontaneously ruptured hepatocellular carcinoma (srHCC) is a life-threatening disease. The prognosis of patients with srHCC after hepatectomy remains unclear. This study...
Spontaneously ruptured hepatocellular carcinoma (srHCC) is a life-threatening disease. The prognosis of patients with srHCC after hepatectomy remains unclear. This study aimed to investigate the prognosis and recurrence after hepatectomy in patients with srHCC. From 2015 to 2020, a retrospective analysis of patients with srHCC who underwent hepatectomy was performed, and compared with patients with unruptured HCC. Among the 86 patients with HCC who underwent hepatectomy, 11 had srHCC. The median tumor size in the ruptured group was significantly larger than that in the unruptured group (P = .001). The incidence rate of vascular invasion and Glisson capsule invasion in the ruptured group was significantly higher than that in the unruptured group. (P = .012 and P < .001, respectively). The American Joint Committee on Cancer was significantly higher in the ruptured group than in the unruptured group (P < .001). In total, 8 (73%) patients in the ruptured group experienced recurrence, whereas the median recurrence-free survival (RFS) and overall survival (OS) periods in the ruptured group were 15 (11-32) and 23 (17-38) months, respectively. In the unruptured group, 34 (45%) patients experienced recurrence, and the median RFS and OS periods were 20 (8-37, P = .099) and 33 (12-51, P = .394) months, respectively. Patients who developed peritoneal metastases were included in the ruptured group (n = 3). Ruptured HCCs exhibit worse oncological outcomes have poorer survival and higher recurrence rates than unruptured HCCs.
Topics: Humans; Liver Neoplasms; Carcinoma, Hepatocellular; Hepatectomy; Male; Female; Middle Aged; Retrospective Studies; Neoplasm Recurrence, Local; Prognosis; Rupture, Spontaneous; Aged; Adult
PubMed: 38875373
DOI: 10.1097/MD.0000000000038555 -
Arthritis Research & Therapy Jun 2024Kinases are intracellular signalling mediators and key to sustaining the inflammatory process in rheumatoid arthritis (RA). Oral inhibitors of Janus Kinase family (JAKs)...
BACKGROUND
Kinases are intracellular signalling mediators and key to sustaining the inflammatory process in rheumatoid arthritis (RA). Oral inhibitors of Janus Kinase family (JAKs) are widely used in RA, while inhibitors of other kinase families e.g. phosphoinositide 3-kinase (PI3K) are under development. Most current biomarker platforms quantify mRNA/protein levels, but give no direct information on whether proteins are active/inactive. Phosphoproteome analysis has the potential to measure specific enzyme activation status at tissue level.
METHODS
We validated the feasibility of phosphoproteome and total proteome analysis on 8 pre-treatment synovial biopsies from treatment-naive RA patients using label-free mass spectrometry, to identify active cell signalling pathways in synovial tissue which might explain failure to respond to RA therapeutics.
RESULTS
Differential expression analysis and functional enrichment revealed clear separation of phosphoproteome and proteome profiles between lymphoid and myeloid RA pathotypes. Abundance of specific phosphosites was associated with the degree of inflammatory state. The lymphoid pathotype was enriched with lymphoproliferative signalling phosphosites, including Mammalian Target Of Rapamycin (MTOR) signalling, whereas the myeloid pathotype was associated with Mitogen-Activated Protein Kinase (MAPK) and CDK mediated signalling. This analysis also highlighted novel kinases not previously linked to RA, such as Protein Kinase, DNA-Activated, Catalytic Subunit (PRKDC) in the myeloid pathotype. Several phosphosites correlated with clinical features, such as Disease-Activity-Score (DAS)-28, suggesting that phosphosite analysis has potential for identifying novel biomarkers at tissue-level of disease severity and prognosis.
CONCLUSIONS
Specific phosphoproteome/proteome signatures delineate RA pathotypes and may have clinical utility for stratifying patients for personalised medicine in RA.
Topics: Humans; Arthritis, Rheumatoid; Synovial Membrane; Signal Transduction; Proteomics; Female; Phosphoproteins; Middle Aged; Male; Adult; Aged; Proteome
PubMed: 38867295
DOI: 10.1186/s13075-024-03351-4 -
Nature Communications Jun 2024Rheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA and repertoire sequencing on paired...
Rheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA and repertoire sequencing on paired synovial tissue and blood samples from 12 seropositive RA patients. We identify clonally expanded CD4 + T cells, including CCL5+ cells and T peripheral helper (Tph) cells, which show a prominent transcriptomic signature of recent activation and effector function. CD8 + T cells show higher oligoclonality than CD4 + T cells, with the largest synovial clones enriched in GZMK+ cells. CD8 + T cells with possibly virus-reactive TCRs are distributed across transcriptomic clusters. In the B cell compartment, NR4A1+ activated B cells, and plasma cells are enriched in the synovium and demonstrate substantial clonal expansion. We identify synovial plasma cells that share BCRs with synovial ABC, memory, and activated B cells. Receptor-ligand analysis predicted IFNG and TNFRSF members as mediators of synovial Tph-B cell interactions. Together, these results reveal clonal relationships between functionally distinct lymphocyte populations that infiltrate the synovium of patients with RA.
Topics: Humans; Arthritis, Rheumatoid; Synovial Membrane; B-Lymphocytes; Female; Male; Middle Aged; CD8-Positive T-Lymphocytes; Lymphocyte Subsets; CD4-Positive T-Lymphocytes; Single-Cell Analysis; Transcriptome; Plasma Cells; Aged; Lymphocyte Activation; Adult
PubMed: 38862501
DOI: 10.1038/s41467-024-49186-0 -
RMD Open Jun 2024To assess the presence and anatomical distribution of activated fibroblasts in the joints and entheses of patients with psoriasis with arthralgia and to test how...
OBJECTIVES
To assess the presence and anatomical distribution of activated fibroblasts in the joints and entheses of patients with psoriasis with arthralgia and to test how fibroblast activation visualised by gallium-labelled fibroblast activation protein inhibitor-04 (Ga-FAPI-04)-positron emission tomography (PET)/CT correlates with clinical tenderness, musculoskeletal ultrasound findings and progression to psoriatic arthritis (PsA).
METHODS
We conducted a prospective cohort study in patients with psoriasis and arthralgia who underwent clinical and ultrasound evaluation and whole-body PET/CT imaging with Ga-FAPI-04. Ga-FAPI-04 uptake at synovial and entheseal sites was assessed by maximal standardised uptake values (SUVmax) and PET/CT Joint Index (JI); logistic regression models were used to investigate its correlation with clinical and ultrasound findings. Survival analyses were performed on patients with at least 6 months of follow-up.
RESULTS
36 patients with psoriasis were enrolled. Ga-FAPI-04 uptake was found in 318 (7.9%) joints and 369 (7.3%) entheses in 29 (80.6%) participants, with a mean SUVmax (SD) of 3.2 (1.8) for joints and 2.9 (1.6) for entheses. Large joints and the lower limbs were predominantly affected. A significant positive relationship was found between Ga-FAPI-04-PET/CT signal intensity and the 68 tender joint count (SUVmax: p<0.001; PET/CT-JI: p<0.001) and tender entheses count (SUVmax: p<0.001; PET/CT-JI: p=0.002). No correlations were found with ultrasound findings (SUVmax: p=0.969; PET/CT-JI: p=0.720). Patients with relevant synovio-entheseal Ga-FAPI-04 uptake showed a statistically significant higher risk of developing PsA (p=0.02), independent of ultrasound findings.
CONCLUSIONS
Patients with psoriasis presenting with arthralgia show localised signs of resident tissue activation in joints and entheses, which are associated with higher risk of developing PsA.
Topics: Humans; Arthritis, Psoriatic; Male; Female; Middle Aged; Positron Emission Tomography Computed Tomography; Psoriasis; Adult; Prospective Studies; Fibroblasts; Synovial Membrane; Aged; Ultrasonography; Disease Progression
PubMed: 38862244
DOI: 10.1136/rmdopen-2024-004294 -
Cureus May 2024Chronic unreduced dislocations of the proximal interphalangeal joint are uncommon, and management principles for these injuries have not been defined. The dislocation...
Chronic unreduced dislocations of the proximal interphalangeal joint are uncommon, and management principles for these injuries have not been defined. The dislocation can be volar or dorsal and closed reduction is rarely successful owing to soft tissue contractures. Treatment options in literature reviews for such rare injuries included open reduction of pip joint with volar plate arthroplasty, extension block pinning, hemi hamate arthroplasty, pip joint arthrodesis, Suzuki dynamic frame fixation, open reduction and repair of capsule and collateral ligaments with suture anchors. Few cases of amputation following treatment were even reported in literature emphasizing the role of meticulous soft tissue handling in such neglected cases of hand. We report six cases of neglected (more than three months old) dorsal dislocation of the PIP joint of the hand, treated with volar plate arthroplasty and extension block pinning. A functional range of motion with a stable joint can be achieved in such injuries with volar plate arthroplasty, as long as the articular cartilage is relatively preserved and bone loss is <30%.
PubMed: 38860079
DOI: 10.7759/cureus.60077