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Clinics in Shoulder and Elbow Apr 2024Overhead athletes undergo significant biomechanical adaptations due to repetitive overhead movements, primarily affecting the glenohumeral joint. These adaptations can...
Overhead athletes undergo significant biomechanical adaptations due to repetitive overhead movements, primarily affecting the glenohumeral joint. These adaptations can lead to glenohumeral internal rotation deficit (GIRD), which is characterized by posterior capsule stiffness that results in glenohumeral joint translation and a shift in the center of gravity. The severity of GIRD is dependent upon the presence of asymmetry between gained external and lost internal rotation, which is defined clinically as an asymmetry exceeding 20º; this reduces the total range of motion compared to the unaffected limb or baseline measurements. Diagnosis is challenging, as it can be mistaken for chronic scapular adaptations. To mitigate misdiagnosis, a high clinical suspicion is crucial in overhead athletes, especially those who began performing forceful overhead movements before closure of growth plates. Periodic physical examinations should establish baseline values for glenohumeral rotation and track changes in glenohumeral motion to aid in diagnosis. Symptoms of GIRD include shoulder pain, stiffness, and decreased force exertion. Magnetic resonance imaging is the preferred imaging method for evaluating GIRD and assessing concomitant soft tissue pathologies. Untreated GIRD can lead to rotator cuff strength imbalances. Treatment mainly involves conservative measures, such as physical therapy, to improve internal rotation and alleviate posterior tightness. Surgical interventions are considered when symptoms persist despite conservative treatment with physical therapy or in the presence of concomitant pathologies.
PubMed: 38738331
DOI: 10.5397/cise.2023.00885 -
BMC Musculoskeletal Disorders May 2024Synovitis, characterized by inflammation of the synovial membrane, is commonly induced by meniscus tears. However, significant differences in inflammatory responses and...
BACKGROUND
Synovitis, characterized by inflammation of the synovial membrane, is commonly induced by meniscus tears. However, significant differences in inflammatory responses and the key inflammatory mediators of synovium induced by different types of meniscal tears remain unclear.
METHODS
Magnetic resonance imaging (MRI) was employed to identify the type of meniscus tear, and the quantification of synovial inflammation was assessed through H&E staining assay. Transcription and expression levels of IL-1β and IL-6 were evaluated using bioinformatics, ELISA, RT-qPCR, and IHC of CD68 staining assays. The therapeutic potential of Docosapentaenoic Acid (DPA) was determined through network pharmacology, ELISA, and RT-qPCR assays. The safety of DPA was assessed using colony formation and EdU staining assays.
RESULTS
The results indicate that both IL-1β and IL-6 play pivotal roles in synovitis pathogenesis, with distinct expression levels across various subtypes. Among tested meniscus tears, oblique tear and bucket handle tear induced the most severe inflammation, followed by radial tear and longitudinal tear, while horizontal tear resulted in the least inflammation. Furthermore, in synovial inflammation induced by specific meniscus tears, the anterior medial tissues exhibited significantly higher local inflammation than the anterior lateral and suprapatellar regions, highlighting the clinical relevance and practical guidance of anterior medial tissues' inflammatory levels. Additionally, we identified the essential omega-3 fatty acid DPA as a potential therapeutic agent for synovitis, demonstrating efficacy in blocking the transcription and expression of IL-1β and IL-6 with minimal side effects.
CONCLUSION
These findings provide valuable insights into the nuanced nature of synovial inflammation induced by various meniscal tear classifications and contribute to the development of new adjunctive therapeutic agents in the management of synovitis.
Topics: Tibial Meniscus Injuries; Synovitis; Magnetic Resonance Imaging; Synovial Membrane; Humans; Fatty Acids, Unsaturated; Male; Interleukin-1beta; Animals; Interleukin-6; Female; Menisci, Tibial; Mice; Disease Models, Animal
PubMed: 38734632
DOI: 10.1186/s12891-024-07491-1 -
Journal of Clinical Medicine Apr 2024: Anterior cruciate ligament (ACL) tears account for 40% to 50% of all ligamentous knee injuries. Most patients with ACL ruptures undergo surgical treatment. There is...
Nanosurgical and Bioengineering Treatment of Human Anterior Cruciate Ligament Tears with Ultrasound-Guided Injection of Modified Platelet-Rich Plasma Using Human Cell Memory Based on Clinical, Ultrasound, MRI, and Nanoscope Analyses: A Double-Blind Randomized Trial.
: Anterior cruciate ligament (ACL) tears account for 40% to 50% of all ligamentous knee injuries. Most patients with ACL ruptures undergo surgical treatment. There is currently no objective, well-documented, repeatable, and standardized nonsurgical method for ACL tear treatment. This study aimed to investigate ACL outcomes in patients who underwent a novel nanosurgery and bioengineering treatment (NSBT) for an ACL tear. : This was a double-blind randomized trial including 44 patients with a history of traumatic knee injury and a confirmed ACL tear. The final sample comprised 40 patients who met all the eligibility criteria. The patients were divided into two groups: the treatment group (n = 30) and the control group (n = 10). The treatment group underwent nanosurgery with an ultrasound-guided injection of modified platelet-rich plasma (PRP) using human cell memory (RP-hCM). The control group was treated with an ultrasound-guided PRP injection into the joint capsule. At baseline and post-treatment, all patients underwent both ultrasonography and magnetic resonance imaging (MRI), and the following clinical variables were assessed: the WOMAC score, the Lysholm knee score, the visual analog scale score, and knee instability. In most patients, the clinical outcome was verified using nanoscopy. : The median WOMAC, VAS, and LKS scores, as well as knee instability, improved significantly 12 weeks after the procedure in the treatment group ( < 0.001). We found a significantly larger improvement in the assessed parameters in the treatment group compared to the control group ( < 0.001). In the treatment group, all the patients had good and very good clinical outcomes, while 90% of the patients had a normal ACL signal in a follow-up MRI scan. In the control group, a physical examination revealed no changes in knee stability after treatment. : This study showed that there is a significant difference in patient experience and the duration of recovery for patients with ACL tears treated with NSBT. The novel nonsurgical method was shown to be repeatable, objective, well documented, standardized, and highly effective.
PubMed: 38731004
DOI: 10.3390/jcm13092475 -
Cells Apr 2024Rheumatoid arthritis (RA) is a chronic autoimmune disorder which can lead to long-term joint damage and significantly reduced quality of life if not promptly diagnosed... (Review)
Review
Rheumatoid arthritis (RA) is a chronic autoimmune disorder which can lead to long-term joint damage and significantly reduced quality of life if not promptly diagnosed and adequately treated. Despite significant advances in treatment, about 40% of patients with RA do not respond to individual pharmacological agents and up to 20% do not respond to any of the available medications. To address this large unmet clinical need, several recent studies have focussed on an in-depth histological and molecular characterisation of the synovial tissue to drive the application of precision medicine to RA. Currently, RA patients are clinically divided into "seropositive" or "seronegative" RA, depending on the presence of routinely checked antibodies. Recent work has suggested that over the last two decades, long-term outcomes have improved significantly in seropositive RA but not in seronegative RA. Here, we present up-to-date differences in epidemiology, clinical features, and serological biomarkers in seronegative versus seropositive RA and discuss how histological and molecular synovial signatures, revealed by recent large synovial biopsy-based clinical trials, may be exploited to refine the classification of RA patients, especially in the seronegative group.
Topics: Humans; Arthritis, Rheumatoid; Biomarkers; Synovial Membrane; Phenotype
PubMed: 38727279
DOI: 10.3390/cells13090743 -
Journal of Ethnopharmacology Oct 2024Di-Long (Pheretima vulgaris) is a classic animal sourced traditional Chinese medicine. It has been used for the treatment of joint inflammation and arthralgia for over...
ETHNOPHARMACOLOGICAL RELEVANCE
Di-Long (Pheretima vulgaris) is a classic animal sourced traditional Chinese medicine. It has been used for the treatment of joint inflammation and arthralgia for over two thousand years due to its effects of Tong-Luo-Zhi-Tong (dredging collaterals and alleviating pain). Our previous study showed that Chinese medicine Di-Long has significant anti-rheumatoid arthritis (RA) effects.
AIM OF THE STUDY
Considering Di-Long as a potential source of active compounds with specific anti-RA therapeutic effects, this research was to obtain the anti-RA target-specific active fraction from Di-Long extracts (DL), and to further explore the chemical basis and verify the anti-RA mechanism of this active fraction.
MATERIALS AND METHODS
Transcriptomic was applied to obtain the main anti-RA targets of DL on human RA fibroblast-like synoviocytes (FLS) and validated by qPCR. The target-corresponding active fraction was isolated from DL by ethanol precipitation and gel chromatography, and analyzed by nanoliter chromatography-mass spectrometry. Anti-RA effects of this active fraction was investigated by collagen-induced arthritis (CIA) in mice, and anti-RA mechanisms were verified in cocultured model of rat FLS and peripheral blood lymphocytes.
RESULTS
We confirmed that CXCL10/CXCR3 was the main anti-RA target of DL. The active fraction - A (2182 - 890 Da) was isolated from DL based on its CXCL10 inhibiting effects in RA-FLS. Fraction A contains 195 peptides (192 were newly discovered), 26 of which might be bioactive and were considered to be the chemical basis of its anti-RA effects. Fraction A significantly ameliorated the joint destruction and overall inflammation in CIA mice, and downregulated CXCR3 expression in mice joint. Fraction A inhibited the chemotaxis of Th-cells in rat peripheral blood lymphocytes towards the TNF-α-induced rat FLS through CXCL10/CXCR3 pathway.
CONCLUSIONS
Our work indicated that active fraction from DL containing small peptides exhibits promising therapeutic effects for RA through inhibiting CXCL10/CXCR3 chemotaxis.
Topics: Animals; Receptors, CXCR3; Chemokine CXCL10; Arthritis, Experimental; Arthritis, Rheumatoid; Male; Antirheumatic Agents; Rats; Humans; Chemotaxis; Synovial Membrane; Mice; Mice, Inbred DBA; Drugs, Chinese Herbal; Synoviocytes
PubMed: 38723919
DOI: 10.1016/j.jep.2024.118286 -
Scientific Reports May 2024Histone lysine methylation is thought to play a role in the pathogenesis of rheumatoid arthritis (RA). We previously reported aberrant expression of the gene encoding...
Histone lysine methylation is thought to play a role in the pathogenesis of rheumatoid arthritis (RA). We previously reported aberrant expression of the gene encoding mixed-lineage leukemia 1 (MLL1), which catalyzes methylation of histone H3 lysine 4 (H3K4), in RA synovial fibroblasts (SFs). The aim of this study was to elucidate the involvement of MLL1 in the activated phenotype of RASFs. SFs were isolated from synovial tissues obtained from patients with RA or osteoarthritis (OA) during total knee joint replacement. MLL1 mRNA and protein levels were determined after stimulation with tumor necrosis factor α (TNFα). We also examined changes in trimethylation of H3K4 (H3K4me3) levels in the promoters of RA-associated genes (matrix-degrading enzymes, cytokines, and chemokines) and the mRNA levels upon small interfering RNA-mediated depletion of MLL1 in RASFs. We then determined the levels of H3K4me3 and mRNAs following treatment with the WD repeat domain 5 (WDR5)/MLL1 inhibitor MM-102. H3K4me3 levels in the gene promoters were also compared between RASFs and OASFs. After TNFα stimulation, MLL1 mRNA and protein levels were higher in RASFs than OASFs. Silencing of MLL1 significantly reduced H3K4me3 levels in the promoters of several cytokine (interleukin-6 [IL-6], IL-15) and chemokine (C-C motif chemokine ligand 2 [CCL2], CCL5, C-X-C motif chemokine ligand 9 [CXCL9], CXCL10, CXCL11, and C-X3-C motif chemokine ligand 1 [CX3CL1]) genes in RASFs. Correspondingly, the mRNA levels of these genes were significantly decreased. MM-102 significantly reduced the promoter H3K4me3 and mRNA levels of the CCL5, CXCL9, CXCL10, and CXCL11 genes in RASFs. In addition, H3K4me3 levels in the promoters of the IL-6, IL-15, CCL2, CCL5, CXCL9, CXCL10, CXCL11, and CX3CL1 genes were significantly higher in RASFs than OASFs. Our findings suggest that MLL1 regulates the expression of particular cytokines and chemokines in RASFs and is associated with the pathogenesis of RA. These results could lead to new therapies for RA.
Topics: Aged; Female; Humans; Male; Middle Aged; Arthritis, Rheumatoid; Cells, Cultured; Chemokines; Cytokines; Fibroblasts; Gene Expression Regulation; Histone-Lysine N-Methyltransferase; Histones; Myeloid-Lymphoid Leukemia Protein; Osteoarthritis; Promoter Regions, Genetic; RNA, Messenger; Synovial Membrane; Tumor Necrosis Factor-alpha
PubMed: 38719857
DOI: 10.1038/s41598-024-60860-7 -
Diagnostic Microbiology and Infectious... Jul 2024Lecanicillium dimorphum and Lecanicillium psalliotae are fungi that exist naturally in plants or insects, and are generally considered non-pathogenic to humans. However,...
Lecanicillium dimorphum and Lecanicillium psalliotae are fungi that exist naturally in plants or insects, and are generally considered non-pathogenic to humans. However, in this case, we cultured Lecanicillium from the synovial fluid of a patient, and identified it through genome sequencing and sequence alignment as Lecanicillium dimorphum or Lecanicillium psalliotae. Due to the conservation of sequences, we can only identify the genus and not the species. There are very few reports on the human infection and pathogenicity of these two fungi, and this case also cannot completely prove that the pathogenic agent is this fungus. But this case also holds clinical significance, as the discovery of Lecanicillium in a human sample can alert the clinician to the presence of an uncommon mold with unclear clinical significance.
Topics: Humans; Hypocreales; Mycoses; Synovial Fluid; Male; Phylogeny; Sequence Analysis, DNA; DNA, Fungal
PubMed: 38718662
DOI: 10.1016/j.diagmicrobio.2024.116337 -
The Archives of Bone and Joint Surgery 2024Primary idiopathic frozen shoulder (FS) causes pain and stiffness in the shoulder joint. Over time, this disease causes restriction of shoulder motion. We undertook this...
OBJECTIVES
Primary idiopathic frozen shoulder (FS) causes pain and stiffness in the shoulder joint. Over time, this disease causes restriction of shoulder motion. We undertook this study to evaluate possible correlation of MRI findings with outcome of conservative management in FS.
METHODS
A total of 65 cases participated in prospective cohort study. The correlation of MRI findings obtained before commencing the treatment with outcome of non-operative management (Mean of ROM, VAS, SST and OSS) was evaluated.
RESULTS
Anterior extracapsular edema significantly correlated with FF, EXR, VAS (a) and OSS. The effusion in humeral side of axillary recess significantly correlated with ROM restriction in ABD, EXR. Capsular thickness of glenoid portion showed good significance with FF, ABD, VAS (a) and OSS. Increased thickness of CHL showed negative correlation with improvement of EXR (P=0.049) (r=-0.617). Thickening of IGHL showed negative correlation with improvement of ABD (p=0.005 r=-0.862) and FF (p=0.007 r=-0.831). Mean Height of Axillary recess (HAR) was 7.2mm (3.5-11mm). HAR showed negative correlation with VAS pain scale (P=0.036) (r=-0.682) and OSS (P=0.038) (r=-0.668).
CONCLUSION
Thickness of the joint capsule and effusion at the axillary fold are important factors for refractory frozen shoulder. We can recommend MRI for refractive cases and low threshold of expectation can be set for conservative management in patients with above findings.
PubMed: 38716178
DOI: 10.22038/ABJS.2023.73913.3423 -
Veterinary Research May 2024Klebsiella pneumoniae has become one of the most intractable gram-negative pathogens infecting humans and animals due to its severe antibiotic resistance. Bacteriophages...
Klebsiella pneumoniae has become one of the most intractable gram-negative pathogens infecting humans and animals due to its severe antibiotic resistance. Bacteriophages and protein products derived from them are receiving increasing amounts of attention as potential alternatives to antibiotics. In this study, we isolated and investigated the characteristics of a new lytic phage, P1011, which lyses K5 K. pneumoniae specifically among 26 serotypes. The K5-specific capsular polysaccharide-degrading depolymerase dep1011 was identified and expressed. By establishing murine infection models using bovine strain B16 (capable of supporting phage proliferation) and human strain KP181 (incapable of sustaining phage expansion), we explored the safety and efficacy of phage and dep1011 treatments against K5 K. pneumoniae. Phage P1011 resulted in a 60% survival rate of the mice challenged with K. pneumoniae supporting phage multiplication, concurrently lowering the bacterial burden in their blood, liver, and lungs. Unexpectedly, even when confronted with bacteria impervious to phage multiplication, phage therapy markedly decreased the number of viable organisms. The protective efficacy of the depolymerase was significantly better than that of the phage. The depolymerase achieved 100% survival in both treatment groups regardless of phage propagation compatibility. These findings indicated that P1011 and dep1011 might be used as potential antibacterial agents to control K5 K. pneumoniae infection.
Topics: Animals; Klebsiella pneumoniae; Mice; Klebsiella Infections; Bacteriophages; Disease Models, Animal; Phage Therapy; Female; Glycoside Hydrolases; Cattle
PubMed: 38715095
DOI: 10.1186/s13567-024-01311-z -
Frontiers in Immunology 2024Rheumatoid arthritis (RA) is a systemic immune-related disease characterized by synovial inflammation and destruction of joint cartilage. The pathogenesis of RA remains...
BACKGROUND
Rheumatoid arthritis (RA) is a systemic immune-related disease characterized by synovial inflammation and destruction of joint cartilage. The pathogenesis of RA remains unclear, and diagnostic markers with high sensitivity and specificity are needed urgently. This study aims to identify potential biomarkers in the synovium for diagnosing RA and to investigate their association with immune infiltration.
METHODS
We downloaded four datasets containing 51 RA and 36 healthy synovium samples from the Gene Expression Omnibus database. Differentially expressed genes were identified using R. Then, various enrichment analyses were conducted. Subsequently, weighted gene co-expression network analysis (WGCNA), random forest (RF), support vector machine-recursive feature elimination (SVM-RFE), and least absolute shrinkage and selection operator (LASSO) were used to identify the hub genes for RA diagnosis. Receiver operating characteristic curves and nomogram models were used to validate the specificity and sensitivity of hub genes. Additionally, we analyzed the infiltration levels of 28 immune cells in the expression profile and their relationship with the hub genes using single-sample gene set enrichment analysis.
RESULTS
Three hub genes, namely, ribonucleotide reductase regulatory subunit M2 (), DLG-associated protein 5 (), and kinesin family member 11 (), were identified through WGCNA, LASSO, SVM-RFE, and RF algorithms. These hub genes correlated strongly with T cells, natural killer cells, and macrophage cells as indicated by immune cell infiltration analysis.
CONCLUSION
, , and could serve as potential diagnostic indicators and treatment targets for RA. The infiltration of immune cells offers additional insights into the underlying mechanisms involved in the progression of RA.
Topics: Humans; Arthritis, Rheumatoid; Gene Regulatory Networks; Machine Learning; Gene Expression Profiling; Transcriptome; Synovial Membrane; Kinesins; Biomarkers; Databases, Genetic; Computational Biology; Support Vector Machine; Ribonucleoside Diphosphate Reductase
PubMed: 38711508
DOI: 10.3389/fimmu.2024.1387311