MicroRNA maturation: stepwise processing and subcellular localization

MicroRNAs (miRNAs) constitute a novel, phylogenetically extensive family of small RNAs (∼22 nucleotides) with potential roles in gene regulation. Apart from the finding 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 first 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

Downregulation of GFAP, TSP-1, and p53 in human glioblastoma cell line, U373MG, by IE1 protein from human cytomegalovirus

Human cytomegalovirus (HCMV) is a member of the beta-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 TE1-expressing glioblastoma cells by real-time quantitative reverse transcription-polymerase 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. (C) 2005 Wiley-Liss, Inc

Glycated Albumin, a Novel Biomarker for Short-Term Functional Outcomes in Acute Ischemic Stroke

Background: There is growing interest in the use of new biomarkers such as glycated albumin (GA), but data are limited in acute ischemic stroke. We explored the impact of GA on short-term functional outcomes as measured using the modified Rankin Scale (mRS) at 3 months compared to glycated hemoglobin (HbA1c). Methods: A total of 1163 AIS patients from two hospitals between 2016 and 2019 were included. Patients were divided into two groups according to GA levels (GA < 16% versus GA ≥ 16%). Results: A total of 518 patients (44.5%) were included in the GA ≥ 16% group. After adjusting for multiple covariates, the higher GA group (GA ≥ 16%) had a 1.4-fold risk of having unfavorable mRS (95% CI 1.02–1.847). However, HbA1c was not significantly associated with 3-month mRS. In addition, GA ≥ 16% was independently associated with unfavorable short-term outcomes only in patients without diabetes. Conclusions: In light of these results, GA level might be a novel prognostic biomarker compared to HbA1c for short-term stroke outcome. Although the impact of GA is undervalued in the current stroke guidelines, GA monitoring should be considered in addition to HbA1c monitoring

Glycated Albumin, a Novel Biomarker for Short-Term Functional Outcomes in Acute Ischemic Stroke

Background: There is growing interest in the use of new biomarkers such as glycated albumin (GA), but data are limited in acute ischemic stroke. We explored the impact of GA on short-term functional outcomes as measured using the modified Rankin Scale (mRS) at 3 months compared to glycated hemoglobin (HbA1c). Methods: A total of 1163 AIS patients from two hospitals between 2016 and 2019 were included. Patients were divided into two groups according to GA levels (GA Results: A total of 518 patients (44.5%) were included in the GA ≥ 16% group. After adjusting for multiple covariates, the higher GA group (GA ≥ 16%) had a 1.4-fold risk of having unfavorable mRS (95% CI 1.02–1.847). However, HbA1c was not significantly associated with 3-month mRS. In addition, GA ≥ 16% was independently associated with unfavorable short-term outcomes only in patients without diabetes. Conclusions: In light of these results, GA level might be a novel prognostic biomarker compared to HbA1c for short-term stroke outcome. Although the impact of GA is undervalued in the current stroke guidelines, GA monitoring should be considered in addition to HbA1c monitoring

Changes in Stroke Patients' Health-Seeking Behavior by COVID-19 Epidemic Regions: Data from the Korean Stroke Registry

© 2021 The Author(s) Published by S. Karger AG, Basel.Introduction: The coronavirus disease 2019 (COVID-19) pandemic has led to changes in stroke patients' healthcare use. This study evaluated changes in Korean stroke patients' health-seeking behaviors and stroke care services using data from the Korean Stroke Registry (KSR). Methods: We reviewed data from patients with acute stroke and transient ischemic attack (TIA) during 2019 (before COVID-19 period) and 2020 (COVID-19 period). Outcomes included patient characteristics, time from stroke onset to hospital arrival, and in-hospital stroke pathways. Subgroup analyses were performed for an epidemic region (Daegu city and Gyeongsangbuk-do region, the D-G region). Results: The study included 1,792 patients from the pre-COVID-19 period and 1,555 patients from the COVID-19 period who visited hospitals that contribute to the KSR. During the COVID-19 period, the D-G region had two-thirds the number of cases (vs. the pre-CO-VID-19 period) and a significant decrease in the proportion of patients with TIA (9.97%-2.91%). Unlike other regions, the median onset-to-door time increased significantly in the D-G region (361 min vs. 526.5 min, p = 0.016), and longer onset-to-door times were common for patients with mild symptoms and who were in their 60s or 70s. The number of patients who underwent intravenous thrombolysis also decreased during the COVID-19 period, although the treatment times were not significantly different between the 2 periods. Discussion/Conclusion: Korean stroke patients in a CO-VID-19 epidemic region exhibited distinct changes in health-seeking behaviors. Appropriate triage system and public education regarding the importance of early treatment are needed during the COVID-19 pandemic.Y

Modification of Acute Stroke Pathway in Korea After the Coronavirus Disease 2019 Outbreak

Background: Since the global pandemic of coronavirus disease 2019 (COVID-19), the process of emergency medical services has been modified to ensure the safety of healthcare professionals as well as patients, possibly leading to a negative impact on the timely delivery of acute stroke care. This study aimed to assess the impact of the COVID-19 pandemic on the acute stroke care processes and outcomes in tertiary COVID-19-dedicated centers in South Korea. Methods: We included 1,213 patients with acute stroke admitted to three centers in three cities (Seoul, Seongnam, and Daegu) through the stroke critical pathway between September 2019 and May 2020 (before and during the COVID-19 pandemic). In all three centers, we collected baseline characteristics and parameters regarding the stroke critical pathway, including the number of admitted patients diagnosed with acute stroke through the stroke critical pathway, door to brain imaging time, door to intravenous recombinant tissue plasminogen activator time, door to groin puncture time, and door to admission time. We performed an interrupted time series analysis to determine the impact of the COVID-19 outbreak on outcomes and critical pathway parameters. Results: Three centers modified the protocol of the stroke critical pathway during the COVID-19 pandemic. There was an immediate decrease in the number of patients admitted with acute ischemic stroke after the outbreak of COVID-19 in Korea, especially in the center of Daegu, an epicenter of the COVID-19 outbreak. However, the number of patients with stroke soon increased to equal that before the Covid-19 outbreak. In several critical pathway parameters, door to imaging time showed a temporary increase, and door to admission was transiently decreased after the COVID-19 outbreak. However, there was no significant effect on the timely trend. Moreover, there was no significant difference in the baseline characteristics and clinical outcomes between the periods before and during the COVID-19 pandemic. Conclusion: This study demonstrated that the COVID-19 outbreak immediately affected the management process. However, it did not have a significant overall impact on the trends of stroke treatment processes and outcomes. The stroke management process should be modified according to changing situations for optimal acute management.Y