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      Transcriptome Sequencing Unravels Potential Biomarkers at Different Stages of Cerebral Ischemic Stroke

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          Abstract

          Ischemic stroke, which accounts for 87% of all strokes, constitutes the leading cause of morbidity and mortality in China. Although the genetics and epigenetics of stroke have been extensively investigated, few studies have examined their relationships at different stages of stroke. This study assessed the characteristics of transcriptome changes at different stages of ischemic stroke using a mouse model of transient middle cerebral artery occlusion (tMCAO) and bioinformatics analyses. Cerebral cortex tissues from tMCAO mice at days 1, 3, 7, 14, and 28 were removed for RNA-Seq and small RNA-Seq library construction, sequencing, and bioinformatics analysis. We identified differentially expressed (DE) genes and miRNAs and revealed an association of the up-regulated or down-regulated DEmiRNAs with the correspondingly altered DEgene targets at each time point. In addition, different biological pathways were activated at different time points; thus, three groups of miRNAs were verified that may represent potential clinical biomarkers corresponding to days 1, 3, and 7 after ischemic stroke. Notably, this represents the first functional association of some of these miRNAs with stroke, e.g., miR-2137, miR-874-5p, and miR-5099. Together, our findings lay the foundation for the transition from a single-point, single-drug stroke treatment approach to multiple-time-point multi-drug combination therapies.

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          Cutadapt removes adapter sequences from high-throughput sequencing reads

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            miRDB: an online resource for microRNA target prediction and functional annotations

            MicroRNAs (miRNAs) are small non-coding RNAs that are extensively involved in many physiological and disease processes. One major challenge in miRNA studies is the identification of genes regulated by miRNAs. To this end, we have developed an online resource, miRDB (http://mirdb.org), for miRNA target prediction and functional annotations. Here, we describe recently updated features of miRDB, including 2.1 million predicted gene targets regulated by 6709 miRNAs. In addition to presenting precompiled prediction data, a new feature is the web server interface that allows submission of user-provided sequences for miRNA target prediction. In this way, users have the flexibility to study any custom miRNAs or target genes of interest. Another major update of miRDB is related to functional miRNA annotations. Although thousands of miRNAs have been identified, many of the reported miRNAs are not likely to play active functional roles or may even have been falsely identified as miRNAs from high-throughput studies. To address this issue, we have performed combined computational analyses and literature mining, and identified 568 and 452 functional miRNAs in humans and mice, respectively. These miRNAs, as well as associated functional annotations, are presented in the FuncMir Collection in miRDB.
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              Update on the Global Burden of Ischemic and Hemorrhagic Stroke in 1990-2013: The GBD 2013 Study

              Background: Global stroke epidemiology is changing rapidly. Although age-standardized rates of stroke mortality have decreased worldwide in the past 2 decades, the absolute numbers of people who have a stroke every year, and live with the consequences of stroke or die from their stroke, are increasing. Regular updates on the current level of stroke burden are important for advancing our knowledge on stroke epidemiology and facilitate organization and planning of evidence-based stroke care. Objectives: This study aims to estimate incidence, prevalence, mortality, disability-adjusted life years (DALYs) and years lived with disability (YLDs) and their trends for ischemic stroke (IS) and hemorrhagic stroke (HS) for 188 countries from 1990 to 2013. Methodology: Stroke incidence, prevalence, mortality, DALYs and YLDs were estimated using all available data on mortality and stroke incidence, prevalence and excess mortality. Statistical models and country-level covariate data were employed, and all rates were age-standardized to a global population. All estimates were produced with 95% uncertainty intervals (UIs). Results: In 2013, there were globally almost 25.7 million stroke survivors (71% with IS), 6.5 million deaths from stroke (51% died from IS), 113 million DALYs due to stroke (58% due to IS) and 10.3 million new strokes (67% IS). Over the 1990-2013 period, there was a significant increase in the absolute number of DALYs due to IS, and of deaths from IS and HS, survivors and incident events for both IS and HS. The preponderance of the burden of stroke continued to reside in developing countries, comprising 75.2% of deaths from stroke and 81.0% of stroke-related DALYs. Globally, the proportional contribution of stroke-related DALYs and deaths due to stroke compared to all diseases increased from 1990 (3.54% (95% UI 3.11-4.00) and 9.66% (95% UI 8.47-10.70), respectively) to 2013 (4.62% (95% UI 4.01-5.30) and 11.75% (95% UI 10.45-13.31), respectively), but there was a diverging trend in developed and developing countries with a significant increase in DALYs and deaths in developing countries, and no measurable change in the proportional contribution of DALYs and deaths from stroke in developed countries. Conclusion: Global stroke burden continues to increase globally. More efficient stroke prevention and management strategies are urgently needed to halt and eventually reverse the stroke pandemic, while universal access to organized stroke services should be a priority.
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                Author and article information

                Contributors
                Journal
                Front Genet
                Front Genet
                Front. Genet.
                Frontiers in Genetics
                Frontiers Media S.A.
                1664-8021
                24 September 2019
                2019
                : 10
                : 814
                Affiliations
                [1] 1Department of Pathology and Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
                [2] 2The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology , Wuhan, China
                [3] 3Department of Neurobiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
                [4] 4Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji College of Medicine, Huazhong University of Science & Technology , Wuhan, China
                [5] 5Department of Neurology, Union Hospital, Tongji College of Medicine, Huazhong University of Science and Technology , Wuhan, China
                [6] 6Department of Pathology, Maternal and Child Health Hospital of Hubei Province , Wuhan, China
                [7] 7Medical School, Institute of Reproductive Medicine, Nantong University , Nantong, China
                [8] 8Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children’s Hospital of Philadelphia , Philadelphia, PA, United States
                [9] 9Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
                [10] 10Department of Physiology, School of Medicine, Jianghan University , Wuhan, China
                Author notes

                Edited by: Sanjeev Kumar Srivastava, Mitchell Cancer Institute, United States

                Reviewed by: Jihong Hu, Oil Crops Research Institute (CAAS), China; Manoj N. Sonavane, University of South Alabama, United States

                *Correspondence: Lei Pei, peilei@ 123456hust.edu.cn ; Youming Lu, lym@ 123456hust.edu.cn

                This article was submitted to RNA, a section of the journal Frontiers in Genetics

                Article
                10.3389/fgene.2019.00814
                6798056
                31681398
                fee6e4a9-832a-4bb7-871c-6420d46992e4
                Copyright © 2019 Cai, Zhang, Ke, Guo, Yao, Tang, Pang, Xie, Fang, Zhang, Li, Fan, He, Wen, Pei and Lu

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 May 2019
                : 06 August 2019
                Page count
                Figures: 6, Tables: 1, Equations: 0, References: 55, Pages: 13, Words: 5277
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 91632306, 81870932, 31721002, 81571078
                Funded by: China Scholarship Council 10.13039/501100004543
                Award ID: 201706160023
                Categories
                Genetics
                Original Research

                Genetics
                ischemic stroke,rna-seq,small rna-seq,microrna,biomarker
                Genetics
                ischemic stroke, rna-seq, small rna-seq, microrna, biomarker

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