RESUMEN
Mature microRNAs are short non-coding RNA sequences which upon incorporation into the RISC ribonucleoprotein complex, play a crucial role in regulation of gene expression. However, miRNAs can exist within the cell also as free molecules fulfilling their biological activity. Therefore, it is emerging that in addition to sequence even the structure adopted by mature miRNAs might play an important role to reach the target. Indeed, we analysed by several spectroscopic techniques the secondary structures of two artificial miRNAs selected by computational tool (miR-Synth) as best candidates to silence c-MET and EGFR genes and of two endogenous miRNAs (miR-15a and miR-15b) having the same seed region, but different biological activity. Our results demonstrate that both endogenous and artificial miRNAs can arrange in several 3D-structures which affect their activity and selectivity toward the targets.
Asunto(s)
MicroARNs/química , MicroARNs/genética , Secuencia de Bases , Receptores ErbB/deficiencia , Receptores ErbB/genética , Silenciador del Gen , Conformación de Ácido Nucleico , Proteínas Proto-Oncogénicas c-met/deficiencia , Proteínas Proto-Oncogénicas c-met/genética , Análisis de Secuencia de ARNRESUMEN
BACKGROUND AND AIMS: The diagnosis of heart failure (HF) in elderly patients is often difficult, due to overlap of typical signs and symptoms with those of comorbidities. B-type Natriuretic Peptide (BNP) predicts diagnosis and prognosis of HF, but little is known on its predictive role of short-term prognosis when admission diagnosis is other than HF. METHODS AND RESULTS: We prospectively recruited 404 consecutive patients (aged≥65 years) hospitalized in the Unit of Internal Medicine, University of Catania, Catania, Italy, with an admission diagnosis other than HF. Clinical examination, laboratory data and BNP were evaluated at the admission. The predictive value of BNP and other variables for in-hospital mortality, thirty-day mortality and three month re-hospitalization was assessed. During hospitalization 48 (12%) patients died; by logistic regression analysis, in-hospital mortality was not predicted by BNP>600 pg/ml (OR = 1.36; CI 95% = 0.60-2.80; p = 0.4), while it was by chronic kidney disease (CKD, p < 0.001), WBC count (p < 0.001), immobilization syndrome (p < 0.008) and age (p = 0.012). After discharge, 54 patients (15%) died within 30 days; in these patients thirty-day mortality was significantly predicted by BNP>600 pg/ml (OR = 2.70; CI 95% = 1.40-5.00; p = 0.001), CKD (p < 0.001), malnutrition (p = 0.029) and age (p = 0.033). Re-hospitalized patients were 97 (32%); three month re-hospitalization was predicted by BNP>600 pg/ml (OR = 12.28; CI 95% = 6.00-24.90; p < 0.001) and anamnestic HF (p = 0.002). CONCLUSIONS: Our study shows that BNP>600 pg/ml, CKD, malnutrition and age predict thirty-day mortality after discharge in elderly patients with an admission diagnosis other than HF, while CKD, WBC count, immobilization syndrome and age predict in-hospital mortality. Three-month re-hospitalization was predicted by BNP>600 pg/ml and anamnestic HF.
Asunto(s)
Insuficiencia Cardíaca/diagnóstico , Desnutrición/sangre , Péptido Natriurético Encefálico/sangre , Admisión del Paciente , Insuficiencia Renal Crónica/sangre , Factores de Edad , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Comorbilidad , Femenino , Evaluación Geriátrica/métodos , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/terapia , Mortalidad Hospitalaria , Humanos , Italia , Recuento de Leucocitos , Masculino , Desnutrición/diagnóstico , Desnutrición/mortalidad , Desnutrición/terapia , Evaluación Nutricional , Estado Nutricional , Readmisión del Paciente , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/terapia , Factores de Riesgo , Factores de TiempoRESUMEN
BACKGROUND AND AIMS: The Neutrophil-to-Lymphocyte Ratio (NLR), an index of systemic inflammation, has been reported to be associated with subclinical atherosclerosis, but its predictive role of the presence of carotid atherosclerotic plaques remains undefined. This study aims to assess this association which gives additional value to this biomarker, with respect to the main risk factors, in the prediction of carotid atherosclerosis in older adults. METHODS AND RESULTS: We recruited 324 patients, aged ≥65 years, without hematopoietic disorders, and/or history of malignancies, evidence of acute infections, chronic inflammatory status, and history of glucocorticoid therapy within the past three months, hospitalized in the Unit of Internal Medicine, University of Catania, Catania, Italy from January 2014 to December 2016. All patients underwent blood sampling for white blood cell, neutrophil, lymphocyte and platelet counts, and for measurements of inflammatory markers, NLR was calculated as the ratio of the absolute neutrophil count to the absolute lymphocyte count. Patients also underwent carotid scan by ultrasonography (US) to evaluate abnormalities of carotid wall. NLR resulted a strong predictor of the presence of carotid plaques. NLR > 2.4 predicted with 80% probability carotid plaques (p < 0.01), while NLR > 3.68 gave 97% probability (p = 0.013). Furthermore, NLR > 2.4 was associated with an average presence of 2.86 carotid plaques (p < 0.001). Fibrinogen and CRP performed well, but with lesser significance, as predictors of the presence of carotid plaques (p = 0.002). CONCLUSION: NLR is a strong predictor of the presence and the number of carotid atherosclerotic plaques. Its use could be useful to identify the risk of harboring carotid plaques.