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      Long non‐coding RNA MALAT1/microRNA 125a axis presents excellent value in discriminating sepsis patients and exhibits positive association with general disease severity, organ injury, inflammation level, and mortality in sepsis patients

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          Abstract

          Objective

          The present study aimed to investigate the potential value of long non‐coding RNA metastasis‐associated lung adenocarcinoma transcript 1 (lnc‐MALAT1)/microRNA (miR)‐125a axis in disease management and prognosis surveillance of sepsis.

          Methods

          Totally, 196 sepsis patients and 196 healthy controls were enrolled. Blood samples were collected within 24 hours after admission in sepsis patients and were collected at enrollment in healthy controls. The relative expression of lnc‐MALAT1 and miR‐125a in all participants was detected by reverse transcription quantitative polymerase chain reaction, and the inflammatory cytokines in plasma of sepsis patients were measured by enzyme‐linked immunosorbent assay.

          Results

          Lnc‐MALAT1/miR‐125a axis was increased in sepsis patients compared with healthy controls ( P < .001) and was of excellent value in distinguishing septic patients from healthy controls with the area under the curve (AUC) of 0.931 (95% CI: 0.908‐0.954). In sepsis patients, lnc‐MALAT1 was negatively associated with miR‐125a, and lnc‐MALAT1/miR‐125a axis was positively correlated with acute pathologic and chronic health evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, serum creatinine, C‐reactive protein, tumor necrosis factor‐α, interleukin (IL)‐1β, IL‐6, and IL‐8, while negatively associated with albumin. Furthermore, lnc‐MALAT1/miR‐125a axis was of value in predicting increased 28‐day mortality risk to some extent (AUC: 0.678, 95% CI: 0.603‐0.754).

          Conclusion

          Lnc‐MALAT1/miR‐125a axis presents excellent value in differentiating sepsis patients from healthy controls and also exhibits positive association with general disease severity, organ injury, inflammation level, and mortality in sepsis patients.

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          Most cited references16

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          MiRNA-Mediated Macrophage Polarization and its Potential Role in the Regulation of Inflammatory Response.

          Monocytes and macrophages are important components of the immune system, specialized in either removing pathogens as part of innate immunity or contributing to adaptive immunity through antigen presentation. Essential to such functions is classical activation (M1) and alternative activation (M2) of macrophages. M1 polarization of macrophages is characterized by production of pro-inflammatory cytokines, antimicrobial and tumoricidal activity, whereas M2 polarization of macrophages is linked to immunosuppression, tumorigenesis, wound repair, and elimination of parasites. MiRNAs are small non-coding RNAs with the ability to regulate gene expression and network of cellular processes. A number of studies have determined miRNA expression profiles in M1 and M2 polarized human and murine macrophages using microarray and RT-qPCR arrays techniques. More specifically, miR-9, miR-127, miR-155, and miR-125b have been shown to promote M1 polarization while miR-124, miR-223, miR-34a, let-7c, miR-132, miR-146a, and miR-125a-5p induce M2 polarization in macrophages by targeting various transcription factors and adaptor proteins. Further, M1 and M2 phenotypes play distinctive roles in cell growth and progression of inflammation-related diseases such as sepsis, obesity, cancer, and multiple sclerosis. Hence, miRNAs that modulate macrophage polarization may have therapeutic potential in the treatment of inflammation-related diseases. This review highlights recent findings in miRNA expression profiles in polarized macrophages from murine and human sources, and summarizes how these miRNAs regulate macrophage polarization. Last, therapeutic potential of miRNAs in inflammation-related diseases through modulation of macrophage polarization is also discussed.
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            The long noncoding RNA Malat1: Its physiological and pathophysiological functions.

            Recent studies suggest that in humans, DNA sequences responsible for protein coding regions comprise only 2% of the total genome. The rest of the transcripts result in RNA transcripts without protein-coding ability, including long noncoding RNAs (lncRNAs). Different from most members in the lncRNA family, the metastasis-associated lung adenocarcinoma transcript 1 (Malat1) is abundantly expressed and evolutionarily conserved throughout various mammalian species. Malat1 is one of the first identified lncRNAs associated with human disease, and cumulative studies have indicated that Malat1 plays critical roles in the development and progression of various cancers. Malat1 is also actively involved in various physiologic processes, including alternative splicing, epigenetic modification of gene expression, synapse formation, and myogenesis. Furthermore, extensive evidences show that Malat1 plays pivotal roles in multiple pathological conditions as well. In this review, we will summarize latest findings related to the physiologic and pathophysiological processes of Malat1 and discuss its therapeutic potentials.
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              Sepsis: The evolution in definition, pathophysiology, and management

              There has been a significant evolution in the definition and management of sepsis over the last three decades. This is driven in part due to the advances made in our understanding of its pathophysiology. There is evidence to show that the manifestations of sepsis can no longer be attributed only to the infectious agent and the immune response it engenders, but also to significant alterations in coagulation, immunosuppression, and organ dysfunction. A revolutionary change in the way we manage sepsis has been the adoption of early goal-directed therapy. This involves the early identification of at-risk patients and prompt treatment with antibiotics, hemodynamic optimization, and appropriate supportive care. This has contributed significantly to the overall improved outcomes with sepsis. Investigation into clinically relevant biomarkers of sepsis are ongoing and have yet to yield effective results. Scoring systems such as the sequential organ failure assessment and Acute Physiology and Chronic Health Evaluation help risk-stratify patients with sepsis. Advances in precision medicine techniques and the development of targeted therapy directed at limiting the excesses of the inflammatory and coagulatory cascades offer potentially viable avenues for future research. This review summarizes the progress made in the diagnosis and management of sepsis over the past two decades and examines promising avenues for future research.
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                Author and article information

                Contributors
                yuligf@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
                20 April 2020
                June 2020
                : 34
                : 6 ( doiID: 10.1002/jcla.v34.6 )
                : e23222
                Affiliations
                [ 1 ] Department of ICU The Central Hospital of Wuhan Tongji Medical College Huazhong University of Science and Technology Wuhan China
                Author notes
                [*] [* ] Correspondence

                Li Yu, Department of ICU, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 26 Shengli Street, Wuhan 430010, China.

                Email: yuligf@ 123456163.com

                Author information
                https://orcid.org/0000-0001-5944-1888
                https://orcid.org/0000-0002-1526-4514
                https://orcid.org/0000-0002-3367-7072
                Article
                JCLA23222
                10.1002/jcla.23222
                7307338
                32309886
                7404d4ca-88d9-4746-be1e-8106c75161e7
                © 2020 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
                : 19 November 2019
                : 08 January 2020
                : 08 January 2020
                Page count
                Figures: 5, Tables: 2, Pages: 10, Words: 5172
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                June 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.4 mode:remove_FC converted:22.06.2020

                Clinical chemistry
                disease severity,inflammation,long non‐coding rna malat1/micro rna 125a axis,mortality,sepsis

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