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BMC Musculoskeletal Disorders May 2023The aim of this study was to search for key genes in ankylosing spondylitis (AS) through comprehensive bioinformatics analysis, thus providing some theoretical support...
OBJECTIVE
The aim of this study was to search for key genes in ankylosing spondylitis (AS) through comprehensive bioinformatics analysis, thus providing some theoretical support for future diagnosis and treatment of AS and further research.
METHODS
Gene expression profiles were collected from Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/ ) by searching for the term "ankylosing spondylitis". Ultimately, two microarray datasets (GSE73754 and GSE11886) were downloaded from the GEO database. A bioinformatic approach was used to screen differentially expressed genes and perform functional enrichment analysis to obtain biological functions and signalling pathways associated with the disease. Weighted correlation network analysis (WGCNA) was used to further obtain key genes. Immune infiltration analysis was performed using the CIBERSORT algorithm to conduct a correlation analysis of key genes with immune cells. The GWAS data of AS were analysed to identify the pathogenic regions of key genes in AS. Finally, potential therapeutic agents for AS were predicted using these key genes.
RESULTS
A total of 7 potential biomarkers were identified: DYSF, BASP1, PYGL, SPI1, C5AR1, ANPEP and SORL1. ROC curves showed good prediction for each gene. T cell, CD4 naïve cell, and neutrophil levels were significantly higher in the disease group than in the paired normal group, and key gene expression was strongly correlated with immune cells. CMap results showed that the expression profiles of ibuprofen, forskolin, bongkrek-acid, and cimaterol showed the most significant negative correlation with the expression profiles of disease perturbations, suggesting that these drugs may play a role in AS treatment.
CONCLUSION
The potential biomarkers of AS screened in this study are closely related to the level of immune cell infiltration and play an important role in the immune microenvironment. This may provide help in the clinical diagnosis and treatment of AS and provide new ideas for further research.
Topics: Humans; Spondylitis, Ankylosing; Ibuprofen; Algorithms; Biomarkers; Computational Biology; LDL-Receptor Related Proteins; Membrane Transport Proteins
PubMed: 37226132
DOI: 10.1186/s12891-023-06550-3 -
International Journal of Rheumatic... Nov 2023
Topics: Humans; Spondylitis, Ankylosing
PubMed: 37910030
DOI: 10.1111/1756-185X.14846 -
Rheumatology International Oct 2016The ankylosed spine is prone to fracture even after minor trauma due to its changed biomechanical properties. The two central features of ankylosing spondylitis (AS)... (Review)
Review
The ankylosed spine is prone to fracture even after minor trauma due to its changed biomechanical properties. The two central features of ankylosing spondylitis (AS) that promote the pathological remodeling of the spine are inflammation and new bone formation. AS is also associated with osteoporosis that is attributed to an uncoupling of the bone formation and bone resorption processes. Therefore, bone resorption occurs and promotes weakening of the spine as well as increased risk of vertebral fractures which can be hugely different in terms of clinical relevance. Even in the presence of symptomatic clinical vertebral fractures, the diagnosis can be overruled by attributing the pain to disease activity. Furthermore, given the highly abnormal structure of the spine, vertebral fracture diagnosis can be difficult on the basis of radiography alone. CT can show the fractures in detail. Magnetic resonance imaging is considered the method of choice for the imaging of spinal cord injuries, and a reasonable option for exclusion of occult fractures undetected by CT. Since it is equally important for radiologists and clinicians to have a common knowledge base rather than a compartmentalized view, the aim of this review article was to provide the required clinical knowledge that radiologists need to know and the relevant radiological semiotics that clinicians require in diagnosing clinically significant injury to the ankylosed spine.
Topics: Bone Density; Humans; Magnetic Resonance Imaging; Osteoporosis; Spinal Fractures; Spondylitis, Ankylosing
PubMed: 27379763
DOI: 10.1007/s00296-016-3524-1 -
Rheumatic Diseases Clinics of North... May 2022Spondyloarthritis is a common rheumatologic disease, present in up to 2% of the population, characterized by inflammatory arthritis, often with enthesitis, dactylitis,... (Review)
Review
Spondyloarthritis is a common rheumatologic disease, present in up to 2% of the population, characterized by inflammatory arthritis, often with enthesitis, dactylitis, spondylitis, and skin disease. It has historically been characterized as ankylosing spondylitis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, reactive arthritis, and undifferentiated spondyloarthritis. These subsets are now classified as axial-predominant and peripheral-predominant spondyloarthritis. This article provides an updated understanding of disease classification and practical advice about diagnosis to aid in the determination of which patients should be referred to rheumatology. It is important to provide patients the opportunity to have early and effective therapy.
Topics: Arthritis, Psoriatic; Enthesopathy; Humans; Rheumatology; Spondylarthritis; Spondylitis, Ankylosing
PubMed: 35400375
DOI: 10.1016/j.rdc.2022.02.008 -
International Journal of Rheumatic... Jan 2024
Topics: Humans; Spondylitis, Ankylosing; HLA-B27 Antigen; Genetic Predisposition to Disease; Causality; Risk Factors
PubMed: 38151980
DOI: 10.1111/1756-185X.15023 -
QJM : Monthly Journal of the... Nov 2023
Topics: Humans; Spondylitis, Ankylosing; Osteogenesis; Ossification, Heterotopic
PubMed: 37335876
DOI: 10.1093/qjmed/hcad141 -
ACS Nano Dec 2023Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease that leads to serious spinal deformity and ankylosis. Persistent inflammation and progressive...
Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease that leads to serious spinal deformity and ankylosis. Persistent inflammation and progressive ankylosis lead to loss of spinal flexibility in patients with AS. Tetrahedral framework nucleic acids (tFNAs) have emerged as a one kind of nanomaterial composed of four specially designed complementary DNA single strands with outstanding biological properties. Results from experiments demonstrated that tFNAs treatment could inhibit inflammatory responses and heterotopic ossification to halt disease progression. , tFNAs were proved to influence the biological behavior of AS primary chondrocytes and inhibit the secretion of pro-inflammatory cytokines through interleukin-17 pathway. The osteogenic process of chondrocytes was as well inhibited at the transcriptional level to regulate the expression of related proteins. Therefore, we believe tFNAs had a strong therapeutic effect and could serve as a nonsurgical remedy in the future to help patients suffering from AS.
Topics: Humans; Spondylitis, Ankylosing; Interleukin-17; Nucleic Acids; Ossification, Heterotopic; Inflammation
PubMed: 37983164
DOI: 10.1021/acsnano.3c09480 -
Human Immunology Jan 2022To study whether Vitamin D levels are causally associated with ankylosing spondylitis (AS).
OBJECTIVES
To study whether Vitamin D levels are causally associated with ankylosing spondylitis (AS).
METHODS
Two-sample Mendelian randomization (TSMR) analysis was performed by employing MR-Egger regression, weighted median (WM), inverse-variance weighted (IVW), and weight mode (WM) methods. The odds ratio (OR) with 95% confidence intervals (CIs) was used to evaluate this association.
RESULTS
The results of IVW show that no causal association between vitamin D and AS (OR = 0.999, 95%CI = 0.997, 1.002, P = 0.724). The MR-Egger regression results show that genetic pleiotropy does not bias the results (intercept = -4.474E-05, SE = 2.830E-05, P = 0.255). The MR-Egger method no supported causal association between vitamin D and AS (OR = 1.000, 95%CI = 0.996, 1.005, P = 0.879). WM (OR = 1.002, 95%CI = 0.999, 1.005, P = 0.837) and WM (OR = 0.998, 95%CI = 0.996, 1.002, P = 0.910) approach also not found a causal relationship between vitamin D levels and AS. The significant heterogeneity was not observed by Cochran's Q test. The "leave-one-out" analysis also proved lack of a single SNP affected the robustness of our results.
CONCLUSION
Based on our analysis, there is lack of a strong evidence to support a causal inverse association between vitamin D levels and ankylosing spondylitis.
Topics: Genome-Wide Association Study; Humans; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Spondylitis, Ankylosing; Vitamin D
PubMed: 34521568
DOI: 10.1016/j.humimm.2021.09.003 -
Seminars in Arthritis and Rheumatism Aug 2014Ankylosing spondylitis (AS) is associated with increased mortality largely due to cardiovascular disease. Diastolic left ventricular (LV) dysfunction serves as a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Ankylosing spondylitis (AS) is associated with increased mortality largely due to cardiovascular disease. Diastolic left ventricular (LV) dysfunction serves as a precursor to chronic heart failure and may cause morbidity and mortality. A systematic literature search was conducted to determine the prevalence of diastolic LV dysfunction in patients with AS.
METHODS
We identified all echocardiographic studies investigating diastolic LV function in patients with AS. The initial search yielded 166 studies of which 11 met the inclusion criteria.
RESULTS
Compared to control subjects, AS patients had a worse E/A ratio [mean difference -0.13 m/s (95% CI: -0.19 to -0.07)], a prolonged deceleration time [mean difference 13.90 ms (95% CI: 6.03-21.78)], and a prolonged mean isovolumetric relaxation time [mean difference 8.06 ms (95% CI: 3.23-12.89)], all suggestive of diastolic LV dysfunction. The best way to establish diastolic LV dysfunction, however, is to combine E/A ratio, deceleration time, and isovolumetric relaxation time. The latter has been done in 3 studies, all reaffirming an increased prevalence rate of diastolic LV dysfunction in AS patients as compared with control subjects, i.e., 9% versus 0%, 30% versus 12%, and 45% versus 18%, respectively.
CONCLUSIONS
Our observations support the current evidence base for an increased risk of diastolic LV dysfunction in AS. However, larger studies are needed to investigate the exact magnitude of diastolic LV dysfunction and its clinical relevance in patients with AS.
Topics: Humans; Prognosis; Spondylitis, Ankylosing; Ventricular Dysfunction, Left
PubMed: 24655534
DOI: 10.1016/j.semarthrit.2014.02.004 -
Scientific Reports Sep 2023Methazolamide is a carbonic anhydrase (CA) inhibitor with satisfactory safety. Our previous studies have demonstrated the elevation of CA1 expression and the therapeutic...
Methazolamide is a carbonic anhydrase (CA) inhibitor with satisfactory safety. Our previous studies have demonstrated the elevation of CA1 expression and the therapeutic effect of Methazolamide in Ankylosing spondylitis (AS). In this study, we explored the pathogenic role of CA1 and the pharmacological mechanism of Methazolamide in AS through Gene Set Enrichment Analysis (GSEA) and network pharmacology. Seven out of twelve CA1 related gene sets were enriched in AS group. CA1 was core enriched in above seven gene sets involving zinc ion binding, arylesterase activity and one carbon metabolic process. Functional analysis of the candidate target genes obtained from the intersection of AS associated genes and Methazolamide target genes indicated that Methazolamide exerts therapeutic effects on AS mainly through inflammatory pathways which regulate the production of tumor necrosis factor, IL-6 and nitric oxide. PTGS2, ESR1, GSK3β, JAK2, NOS2 and CA1 were selected as therapeutic targets of Methazolamide in AS. Molecular docking and molecular dynamics simulations were performed successfully. In addition, we innovatively obtained the intersection of Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and GSEA results, and found that 18 GO terms and 5 KEGG terms were indicated in the pharmacological mechanism of Methazolamide in AS, involving bone mineralization, angiogenesis, inflammation, and chemokine signaling pathways. Nevertheless, validation for these mechanisms is needed in vivo/vitro experiments.
Topics: Humans; Methazolamide; Spondylitis, Ankylosing; Network Pharmacology; Molecular Docking Simulation; Carbonic Anhydrase Inhibitors
PubMed: 37717047
DOI: 10.1038/s41598-023-42721-x