Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that affects the spine and sacroiliac joints. Early detection of axSpA is crucial to slow disease progression and maintain remission or low disease activity. However, current biomarkers are insufficient for diagnosing axSpA or distinguishing between its radiographic (r-axSpA) and non-radiographic (nr-axSpA) subsets. To address this, we conducted a study using miRNA profiling with massive parallel sequencing (MPS) and SmartChip qRT-PCR validation. The goal was to identify differentially expressed miRNAs in axSpA patients, specifically those subdiagnosed with nr-axSpA or r-axSpA. Disease activity was measured using C-reactive protein (CRP) and the Ankylosing Spondylitis Disease Activity Score (ASDAS). Radiographic assessments of the cervical and lumbar spine were performed at baseline and after two years. Out of the initial 432 miRNAs, 90 met the selection criteria, and 45 were validated out of which miR-1-3p was upregulated, whereas miR-1248 and miR-1246 were downregulated in axSpA patients. The expression of miR-1-3p correlated with interleukin (IL)-17 and tumour necrosis factor (TNF) levels, indicating its significant role in axSpA pathogenesis. Although specific miRNAs distinguishing disease subtypes or correlating with disease activity or spinal changes were not found, the study identified three dysregulated miRNAs in axSpA patients, with miR-1-3p linked to IL-17 and TNF, underscoring its pathogenetic significance. These findings could help improve the early detection and treatment of axSpA.
- Publikační typ
- časopisecké články MeSH
Osteoarthritis (OA) is a frequent musculoskeletal disorder affecting millions of people worldwide. Despite advances in understanding the pathogenesis of OA, prognostic biomarkers or effective targeted treatment are not currently available. Research on epigenetic factors has yielded some new insights as new technologies for their detection continue to emerge. In this context, non-coding RNAs, including microRNAs, long non-coding RNAs, circular RNAs, piwi-interacting RNAs, and small nucleolar RNAs, regulate intracellular signaling pathways and biological processes that have a crucial role in the development of several diseases. In this review, we present current knowledge on the role of epigenetic factors with a focus on non-coding RNAs in the development, prediction and treatment of OA. This article is categorized under: RNA in Disease and Development > RNA in Disease.
- MeSH
- kruhová RNA MeSH
- lidé MeSH
- mikro RNA * genetika MeSH
- osteoartróza * genetika MeSH
- Piwi-interagující RNA MeSH
- RNA dlouhá nekódující * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Objective: Osteoporosis is associated with an impaired balance between bone resorption and formation, which in turn leads to bone loss and fractures. Many recent studies have underlined the regulatory role of microRNAs (miRNAs) in bone remodeling processes and their potential as biomarkers of osteoporosis. The purpose of this study was to prospectively examine the association of circulating miRNAs and bone biomarkers with estrogen status in women before and after oophorectomy, as well as in oophorectomized women on estrogen therapy. Methods: In this prospective study, we included 11 women before oophorectomy and hysterectomy and at 201 ± 24 days after the surgery. Another 11 women were evaluated 508 ± 127 days after oophorectomy and hysterectomy and after an additional 203 ± 71 days of estradiol treatment. Serum miRNAs were profiled by sequencing. Estrogen status and biomarkers of bone metabolism were quantified. Bone mineral density was assessed in the lumbar spine. Results: Our analysis revealed 17 miRNAs associated with estrogen levels. Of those miRNAs that were upregulated with estrogen deficiency and downregulated after estrogen therapy, miR-422a correlated with serum beta-carboxy-terminal type I collagen crosslinks (β-CTX) and procollagen 1 N-terminal propeptide (P1NP); and miR-1278 correlated with serum β-CTX, P1NP, osteocalcin, sclerostin, and Dickkopf-1(Dkk1). In contrast, we found an inverse association of miR-24-1-5p with estrogen status and a negative correlation with serum β-CTX, P1NP, osteoprotegerin, and sclerostin levels. Conclusion: The reported miRNAs associated with estrogen status and bone metabolism could be potential biomarkers of bone pathophysiology and would facilitate studies on the prevention of postmenopausal osteoporosis. Our findings require validation in an extended cohort.
- MeSH
- biologické markery MeSH
- estrogeny MeSH
- lidé MeSH
- menopauza MeSH
- mikro RNA * genetika MeSH
- osteoporóza * MeSH
- prospektivní studie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Germline mutations in ETV6 gene cause inherited thrombocytopenia with leukemia predisposition. Here, we report on functional validation of ETV6 W380R mutation segregating with thrombocytopenia in a family where two family members also suffered from acute lymphoblastic leukemia (ALL) or essential thrombocythemia (ET). In-silico analysis predicted impaired DNA binding due to W380R mutation. Functional analysis showed that this mutation prevents the ETV6 protein from localizing into the cell nucleus and impairs the transcriptional repression activity of ETV6. Based on the germline ETV6 mutation, ET probably started with somatic JAK2 V617F mutation, whereas ALL could be caused by diverse mechanisms: high-hyperdiploidity; somatic deletion of exon 1 IKZF1 gene; or somatic mutations of other genes found by exome sequencing of the ALL sample taken at the diagnosis.
- MeSH
- akutní lymfatická leukemie genetika MeSH
- esenciální trombocytemie genetika MeSH
- lidé MeSH
- protoonkogenní proteiny c-ets metabolismus MeSH
- represorové proteiny metabolismus MeSH
- trombocytopenie metabolismus MeSH
- zárodečné mutace genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Temporal lobe epilepsy (TLE) is the most common epilepsy type. TLE onset in infancy aggravates features like severity, drug responsiveness, or development of comorbidities. These aggravations may arise from altered micro RNA (miRNA) expression specific to the early onset of the disease. Although the miRNA involvement in TLE is widely studied, the relationship between the onset-age and miRNA expression has not been addressed. Here, we investigated the miRNA profile of infantile and adult-onset TLE in rats combining sequencing and PCR. Since miRNA expression changes with the disease progression, we scrutinized miRNA dynamics across three stages: acute, latent, and chronic. We report that infantile-onset TLE leads to changes in the expression of fewer miRNAs across these stages. Interestingly, the miRNA profile in the acute stage of infantile-onset TLE overlaps in dysregulation of miR-132-5p, -205, and -211-3p with the chronic stage of the disease starting in adulthood. The analysis of putative targets linked the majority of dysregulated miRNAs with pathways involved in epilepsy. Our profiling uncovered miRNA expression characteristic for infantile and adulthood-onset epileptogenesis, suggesting the distinct biology underlying TLE in the onset age-dependent matter. Our results indicate the necessity of addressing the onset age as an important parameter in future epilepsy research.
- MeSH
- biologické modely MeSH
- dospělí MeSH
- epilepsie temporálního laloku etiologie metabolismus MeSH
- hipokampus metabolismus MeSH
- kojenec MeSH
- krysa rodu rattus MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé MeSH
- mikro RNA metabolismus MeSH
- potkani Wistar MeSH
- regulace genové exprese MeSH
- status epilepticus metabolismus MeSH
- transkriptom MeSH
- věk při počátku nemoci MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- kojenec MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
S100A11 (calgizzarin), a member of S100 family, is associated with several autoimmune diseases, including rheumatoid arthritis (RA). Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of RA and in the externalization of some S100 family members. Therefore, we aimed to determine the association between S100A11 and NETs in RA. For this purpose, the levels of S100A11 and NETosis markers were detected in the RA synovial fluid by immunoassays. The expression of S100A11 by neutrophils in the RA synovial tissue was assessed. Neutrophils isolated from peripheral blood were exposed to S100A11 or stimulated to release NETs. The levels of NETosis- and inflammation-associated proteins were analysed by immunoassays. NETs were visualized by immunofluorescence. We showed that S100A11 was expressed by the neutrophils in the RA synovial tissue. Moreover, S100A11 in the RA synovial fluid correlated with several NETosis markers. In vitro, S100A11 was abundantly released by neutrophils undergoing NETosis compared to untreated cells (p < 0.001). Extracellular S100A11 increased the secretion of IL-6 (p < 0.05) and TNF (p < 0.05) by neutrophils but did not induce NETosis. This study demonstrates, for the first time, that the release of S100A11 is dependent on NETosis and that extracellular S100A11 augments the inflammatory response by inducing pro-inflammatory cytokines in neutrophils.
- MeSH
- dospělí MeSH
- extracelulární pasti metabolismus MeSH
- interleukin-6 metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- neutrofily metabolismus patologie MeSH
- proteiny S100 metabolismus MeSH
- revmatoidní artritida metabolismus patologie MeSH
- senioři MeSH
- synoviální tekutina metabolismus MeSH
- TNF-alfa metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
