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      Long non‐coding RNA THRIL predicts increased acute respiratory distress syndrome risk and positively correlates with disease severity, inflammation, and mortality in sepsis patients

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          Abstract

          Background

          This present study aimed to investigate the correlation of long non‐coding RNA THRIL (lnc‐THRIL) with acute respiratory distress syndrome (ARDS) risk, disease severity, inflammation, and mortality in sepsis patients.

          Methods

          A total of 109 sepsis patients admitted to intensive care units were consecutively recruited, and their blood samples were collected. After admission, patients were supervised and screened daily to identify the occurrence of ARDS. Clinical characteristics, routine laboratory testing, and disease severity were recorded, and all enrolled patients were followed up until death in the hospital or discharge for mortality records. Lnc‐THRIL was detected by quantitative polymerase chain reaction, and inflammatory cytokine levels were measured by human enzyme‐linked immunoassay.

          Results

          A total of 32 (29.4%) sepsis patients occurred ARDS and 77 (71.6%) did not. Lnc‐THRIL was upregulated in ARDS group compared with non‐ARDS group, and it had good value in distinguishing ARDS from non‐ARDS in sepsis patients (AUC: 0.706; 95%CI: 0.602‐0.809). Besides, lnc‐THRIL, smoke, and chronic obstructive pulmonary disease independently predicted increased risk of ARDS. As for disease severity, lnc‐THRIL positively correlated with APACHE II score and SOFA score in sepsis patients. Regarding inflammation, lnc‐THRIL was positively associated with CRP, PCT, TNF‐α, and IL‐1β levels in sepsis patients. Additionally, the mortality rate was 30.2%, and lnc‐THRIL was upregulated in non‐survivors compared with survivors, presenting a good value (AUC: 0.780; 95%CI: 0.683‐0.876) in predicting mortality in sepsis patients.

          Conclusion

          Lnc‐THRIL predicts increased risk of ARDS and positively correlates with disease severity, inflammation, and mortality in sepsis patients.

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          Most cited references4

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          Expression Analysis of Long Non-coding RNAs in the Blood of Multiple Sclerosis Patients.

          Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system (CNS) with multiple genetic and environmental risk factors. Long non-coding RNAs (lncRNAs) have been recently reported to participate in the regulation of immune responses. Consequently, aberrant expression of lncRNAs has been suggested as an underlying cause of MS. In the present study, we evaluated the expression of three lncRNAs with putative roles in the regulation of immune response, namely TNF-α and heterogeneous nuclear ribonucleoprotein L (THRIL), Fas cell surface death receptor- antisense 1 (FAS-AS1), and plasmacytoma variant translocation 1 (PVT1) in circulating blood cells of 50 Iranian relapsing-remitting multiple sclerosis (RRMS) patients compared with healthy subjects by means of quantitative real-time polymerase chain reaction (PCR). We detected a significant downregulation of PVT1 and FAS-AS1 expressions in RRMS patients while a significant upregulation of THRIL in patients compared with controls (P < 0.001). Correlation analyses between lncRNA expression levels and clinical data of MS patients revealed no significant correlation between lncRNAs expression levels and Expanded Disability Status Scale (EDSS), a moderate correlation between PVT1 expression levels and duration of the disorder and no significant correlation between lncRNAs expression levels and age at onset. In addition, we demonstrated correlations between the expression levels of PVT1 and THRIL as well as expression levels of THRIL and FAS-AS1 in RRMS patients. In brief, we have demonstrated dysregulation of three lncRNAs in MS patients. Further studies are needed to explore the exact mechanisms by which these lncRNAs participate in regulation of immune responses.
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            The long noncoding RNA THRIL knockdown protects hypoxia-induced injuries of H9C2 cells through regulating miR-99a

            Background Myocardial infarction (MI) is a leading cause of disease with high morbidity and mortality worldwide. Recent studies have revealed that long non-coding RNAs (lncRNAs) are involved in heart disease pathogenesis. This study aimed to investigate the effect and the molecular basis of THRIL on hypoxia-injured H9C2 cells. Methods THRIL, miR-99a and Brahma-related gene 1 (Brg1) expressions in H9C2 cells were altered by transient transfections. The cells were subjected to hypoxia for 4 h, and then the levels of THRIL, miR-99a and Brg1 were investigated. Cell viability, migration and invasion, and apoptotic cells were respectively measured by trypan blue exclusion assay, transwell migration assay and flow cytometry assay. Dual luciferase reporter assay was conducted to verify the interaction between miR-99a and THRIL. Furthermore, levels of apoptosis-, PI3K/AKT and mTOR pathways-related factors were measured by western blotting. Results Hypoxia induced an increase of THRIL but a reduction of miR-99a and Brg1. THRIL inhibition significantly attenuated hypoxia-induced cell injuries, as increased cell viability, migration and invasion, and decreased cell apoptosis. THRIL negatively regulated miR-99a expression through sponging with miR-99a binding site, and miR-99a inhibition abolished the protective effects of THRIL knockdown against hypoxia-induced injury in H9C2 cells. Furthermore, miR-99a positively regulated the expression of Brg1. Brg1 inhibition promoted hypoxia-induced cell injuries, while Brg1 overexpression alleviated hypoxia-induced cell injuries. Moreover, Brg1 overexpression activated PI3K/AKT and mTOR pathways. Conclusions This study demonstrated that THRIL inhibition represented a protective effect against hypoxia-induced injuries in H9C2 cells by up-regulating miR-99a expression.
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              Enhancing recovery from sepsis: A review

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                Author and article information

                Contributors
                fenmenjiesc@163.com
                Journal
                J Clin Lab Anal
                J. Clin. Lab. Anal
                10.1002/(ISSN)1098-2825
                JCLA
                Journal of Clinical Laboratory Analysis
                John Wiley and Sons Inc. (Hoboken )
                0887-8013
                1098-2825
                01 July 2019
                July 2019
                : 33
                : 6 ( doiID: 10.1002/jcla.2019.33.issue-6 )
                : e22882
                Affiliations
                [ 1 ] Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College Huazhong University of Science and Technology Wuhan China
                Author notes
                [*] [* ] Correspondence

                Fen Ai, Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

                Email: fenmenjiesc@ 123456163.com

                Author information
                https://orcid.org/0000-0001-9843-4891
                Article
                JCLA22882
                10.1002/jcla.22882
                6642293
                31257645
                a61c6061-073d-4abd-93f2-e4177087bc8d
                © 2019 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 January 2019
                : 17 February 2019
                : 22 February 2019
                Page count
                Figures: 5, Tables: 3, Pages: 8, Words: 4739
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                jcla22882
                July 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.7.0 mode:remove_FC converted:24.10.2019

                Clinical chemistry
                disease severity,inflammation,lnc‐thril,sepsis,survival
                Clinical chemistry
                disease severity, inflammation, lnc‐thril, sepsis, survival

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