Percorrer por autor "Costa, P. P."
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- Circulating microRNAs as potential biomarkers for genetic generalized epilepsies: a three microRNA panelPublication . Martins‐Ferreira, R.; Chaves, J.; Carvalho, C.; Bettencourt, A.; Chorão, R.; Freitas, J.; Samões, R.; Boleixa, D.; Lopes, J.; Ramalheira, J.; Silva, B.M.; Martins da Silva, A.; Costa, P. P.; Leal, B.Background and purpose: Genetic generalized epilepsies (GGEs) encompass a group of syndromes of mainly genetic causes, characterized by the involvement of both hemispheres. MicroRNAs (miRNAs) are small non-coding RNAs with a critical role in the regulation of neuronal biological processes through gene expression modulation. Dysregulated miRNA expression has been shown in epilepsy. Due to their stability in biological fluids like serum, miRNAs have assumed a prominent role in biomarker research. Our aim was to evaluate circulating levels of three miRNAs in GGE patients and assess their putative diagnostic value. Methods: MiR-146a, miR-155 and miR-132 were quantified by real-time polymerase chain reaction in the serum of 79 GGE patients (47 women, 32 men, 35.1 ± 12.4 years) and 67 healthy individuals (41 women, 26 men, 42.4 ± 10.1 years). Relative expression values were calculated using the 2-ΔΔCt method. Receiver operating characteristic curve analysis was performed to assess diagnostic value. MiRNA expression was correlated with clinicopathological features. Results: Serum levels of miR-146a and miR-155 were significantly upregulated in GGE patients relative to controls (3.13 and 6.05, respectively). Combined miR-146a, miR-155 and miR-132 serum levels performed well as a diagnostic biomarker, discriminating GGE patients from controls with an area under the curve of 0.85, 80% specificity and 73% sensitivity. Conclusions: Our results indicate that miR-146a, miR-155 and miR-132 may partake in GGE epileptogenesis. A panel of three circulating miRNAs with potential value as a GGE biomarker is reported for the first time. Novel biomarkers may help to identify new treatment targets and contribute to improved patients' quality of life through earlier diagnosis and a more precise prognosis.
- Expression of miR146-a, an inflammation-associated microRNA, in Mesial Temporal Lobe EpilepsyPublication . Leal, B.; Carvalho, C.; Chaves, J.; Bettencourt, A.; Freitas, J.; Lopes, J.; Ramalheira, J.; Martins da Silva, A.; Costa, P. P.; Martins da Silva, B.Background: Neuroinflammation appears as an important epileptogenic mechanism. MicroRNAs (miRNA) are small non-coding RNA molecules that function as post-transcriptional regulators of gene expression. MicroRNas control different biological process including immune system homeostasis and function. Several evidences, both in patients and animal studies, have demonstrated an abnormal brain expression of miR-146a in Mesial Temporal Lobe Epilepsy. Knowing that miR expression is very stable in biological fluids such as plasma or serum our aim was to characterize miR146a expression in serum of MTLE patients. Methods: Expression levels of miR146a and U6B small nuclear RNA gene (reference gene) were quantified by Real-Time PCR in serum of 14 MTLE patients all with Hippocampal Sclerosis (6F, 8M, mean age= 44.1±11.7 years, age of onset= 13.5±10.6 years, 7 with Febrile Seizures antecedents). A group of 10 healthy individuals was used as control. Relative expression values were calculated using the 2-ΔΔCt method. Results: We observed that expression of miR146a was 2 fold higher in MTLE-HS patients than in controls. Conclusion: The results obtained in serum are in accordance with the results obtained from brain tissue of epileptic patients. This may confirm that miR-146a is a suitable biomarker of epileptogenesis. Additionally, it is thought that miR-146a has a role in fine-tuning the response to cytokines during epileptogenesis. Nevertheless its importance in epilepsy development it is yet not fully understood. The comprehension of this role may be relevant for the development of new therapeutic strategies.