MicroRNAs (miRNAs) constitute a novel, phylogenetically extensive family of small RNAs (~22 nucleotides) with potential roles in gene regulation. Apart from the ®nding that miRNAs are produced by Dicer from the precursors of~70 nucleotides (pre-miRNAs), little is known about miRNA biogenesis. Some miRNA genes have been found in close conjunction, suggesting that they are expressed as single transcriptional units.Here, we present in vivo and in vitro evidence that these clustered miRNAs are expressed polycistronically and are processed through at least two sequential steps: (i) generation of the~70 nucleotide pre-miRNAs from the longer transcripts (termed pri-miRNAs); and (ii) processing of pre-miRNAs into mature miRNAs. Subcellular localization studies showed that the ®rst and second steps are compartmentalized into the nucleus and cytoplasm, respectively, and that the pre-miRNA serves as the substrate for nuclear export. Our study suggests that the regulation of miRNA expression may occur at multiple levels, including the two processing steps and the nuclear export step. These data will provide a framework for further studies on miRNA biogenesis.
Human cytomegalovirus (HCMV) is a member of the b-herpesvirus family, which has tropism for glial cells. It was recently reported that HCMV might play important roles in the pathogenesis of malignant glioma. In this study, we investigated the effects of the HCMV IE1 protein on the gene expression profile in the human glioblastoma cell line, U373MG by employing cDNA microarray technology. Using DNA chips containing approximately 1,000 human cDNAs, RNA samples from U373MG cells stably expressing IE1 were compared with those from the control cells lacking IE1 cDNA. Fluorescence intensities of 13 genes were significantly decreased in IE1-expressing cells, while one gene was found to be upregulated. Among these 14 genes, we chose to work further on glial fibrillary acidic protein (GFAP), thrombospondin-1 (TSP-1), and p53, because of their previously known involvement in tumorigenesis. The mRNA levels of all these genes were found to be decreased in IE1-expressing glioblastoma cells by real-time quantitative reverse transcriptionpolymerase chain reaction (RT-PCR) as well as Northern blot analysis. The decreased expression of these genes was also observed at protein levels as measured by immunocytochemistry or fluorescence-activated cell sorting (FACS) analysis. Our data strongly suggested that HCMV IE1 could modulate the expression of cellular genes that might play important roles in the pathogenesis of glial tumors. '
Background The research about the influence of triglyceride-glucose index on early prognosis in stroke is lacking. Aims In this study, we evaluated the association between triglyceride-glucose index and early neurological deterioration in patients with single subcortical infarctions. Methods Consecutive patients with single subcortical infarctions within 72 h of symptom onset between 2011 and 2015. Early neurological deterioration was defined as an increase of ≥2 in the total NIHSS score or ≥1 in the motor NIHSS score. The triglyceride-glucose index was calculated using the log scale of fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2. Results A total of 305 patients with single subcortical infarctions were evaluated. In multivariable analysis, the triglyceride-glucose index (adjusted odds ratio [aOR] = 2.94, 95% confidence interval [CI] = 1.58–5.45) and age (aOR = 1.05, 95% CI = 1.01–1.09) were associated with early neurological deterioration. In subgroup analysis according to the type of single subcortical infarctions, only patients with proximal single subcortical infarctions showed a significant association between the triglyceride-glucose index and early neurological deterioration (aOR = 2.92, 95% CI = 1.35–6.29). On the other hand, there was no statistical significance in patients with distal single subcortical infarctions. Patients with untreated diabetes also showed the close association between the triglyceride-glucose index and early neurological deterioration (aOR = 3.94, 95% CI = 1.47–10.52). Conclusions The triglyceride-glucose index was associated with early neurological deterioration in single subcortical infarctions. This association differed depending on the location of lesion and the presence of untreated diabetes.
Background: Spontaneous subclavian artery dissection (SAD) is rare. Moreover, there are very few case reports which document spontaneous SAD accompanied by symptomatic neurological deficits related with ischemic stroke. Case Report: A 71-year-old man without any reported history of trauma presented with left facial hypesthesia, left arm ataxia and gait disturbance, subsequently diagnosed as posterior circulation infarction affecting medulla and cerebellum. The computed tomography angiography revealed spontaneous left SAD with left vertebral artery occlusion, atherosclerotic plaque surrounding the origin of left subclavian artery and normal aortic vasculature. His neurological status did not deteriorate further after dual anti-platelet therapy, and intravenous hydration with volume expander were applied. Conclusions: This is an unusual case of spontaneous SAD with lateral medullary infarction as well as cerebellar infarction. Although spontaneous SAD is a distinctly rare disease entity, it should be considered in the differential diagnosis when multiple posterior circulation infarctions are observed.
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