Asunto(s)
Quiste Mediastínico , Quiste Tirogloso , Humanos , Quiste Tirogloso/diagnóstico por imagen , Quiste Tirogloso/cirugía , Quiste Tirogloso/patología , Quiste Mediastínico/diagnóstico por imagen , Quiste Mediastínico/cirugía , Quiste Mediastínico/complicaciones , Tomografía Computarizada por Rayos X , Femenino , Masculino , Coristoma/diagnóstico por imagen , Coristoma/cirugíaRESUMEN
BACKGROUND AND PURPOSE: Dysregulation of the miR-15a/16-1 cluster in plasma has been reported in patients with stroke as a potential biomarker for diagnostic and prognostic use. However, the essential role and therapeutic potential of the miR-15a/16-1 cluster in ischemic stroke are poorly understood. This study is aimed at investigating the regulatory role of the miR-15a/16-1 cluster in ischemic brain injury and insight mechanisms. METHODS: Adult male miR-15a/16-1 knockout and wild-type mice, or adult male C57 BL/6J mice injected via tail vein with the miR-15a/16-1-specific inhibitor (antagomir, 30 pmol/g), were subjected to 1 hour of middle cerebral artery occlusion and 72 hours of reperfusion. The neurological scores, brain infarct volume, brain water content, and neurobehavioral tests were then evaluated and analyzed. To explore underlying signaling pathways associated with alteration of miR-15a/16-1 activity, major proinflammatory cytokines were measured by quantitative polymerase chain reaction or ELISA and antiapoptotic proteins were examined by Western blotting. RESULTS: Genetic deletion of the miR-15a/16-1 cluster or intravenous delivery of miR-15a/16-1 antagomir significantly reduced cerebral infarct size, decreased brain water content, and improved neurological outcomes in stroke mice. Inhibition of miR-15a/16-1 significantly decreased the expression of the proinflammatory cytokines interleukin-6, monocyte chemoattractant protein-1, vascular cell adhesion molecule 1, tumor necrosis factor alpha, and increased Bcl-2 and Bcl-w levels in the ischemic brain regions. CONCLUSIONS: Our data indicate that pharmacological inhibition of the miR-15a/16-1 cluster reduces ischemic brain injury via both upregulation of antiapoptotic proteins and suppression of proinflammatory molecules. These results suggest that the miR-15a/16-1 cluster is a novel therapeutic target for ischemic stroke.
Asunto(s)
Antagomirs/farmacología , Isquemia Encefálica/tratamiento farmacológico , MicroARNs/antagonistas & inhibidores , Accidente Cerebrovascular/tratamiento farmacológico , Animales , Antagomirs/administración & dosificación , Isquemia Encefálica/inmunología , Isquemia Encefálica/metabolismo , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Accidente Cerebrovascular/inmunología , Accidente Cerebrovascular/metabolismoRESUMEN
The northern pike (Esox lucius L.), an important predatory freshwater species, is undergoing significant population decline. In this study, 18 novel polymorphic microsatellite loci were isolated and used for assessing genetic variation in the Chinese Ulungur and Hungarian Balaton populations of the species. The number of alleles ranged from 2 to 13, observed heterozygosity from 0.154 to 0.920 and expected heterozygosity from 0.145 to 0.921, thereby indicating the specific usefulness of these suites of markers for investigating genetic variability.
RESUMEN
The northern pike (Esox lucius L.), an important predatory freshwater species, is undergoing significant population decline. In this study, 18 novel polymorphic microsatellite loci were isolated and used for assessing genetic variation in the Chinese Ulungur and Hungarian Balaton populations of the species. The number of alleles ranged from 2 to 13, observed heterozygosity from 0.154 to 0.920 and expected heterozygosity from 0.145 to 0.921, thereby indicating the specific usefulness of these suites of markers for investigating genetic variability.