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      Plasma Gelsolin: Indicator of Inflammation and Its Potential as a Diagnostic Tool and Therapeutic Target

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          Abstract

          Gelsolin, an actin-depolymerizing protein expressed both in extracellular fluids and in the cytoplasm of a majority of human cells, has been recently implicated in a variety of both physiological and pathological processes. Its extracellular isoform, called plasma gelsolin (pGSN), is present in blood, cerebrospinal fluid, milk, urine, and other extracellular fluids. This isoform has been recognized as a potential biomarker of inflammatory-associated medical conditions, allowing for the prediction of illness severity, recovery, efficacy of treatment, and clinical outcome. A compelling number of animal studies also demonstrate a broad spectrum of beneficial effects mediated by gelsolin, suggesting therapeutic utility for extracellular recombinant gelsolin. In the review, we summarize the current data related to the potential of pGSN as an inflammatory predictor and therapeutic target, discuss gelsolin-mediated mechanisms of action, and highlight recent progress in the clinical use of pGSN.

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          Most cited references187

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          Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis.

          Procalcitonin is widely reported as a useful biochemical marker to differentiate sepsis from other non-infectious causes of systemic inflammatory response syndrome. In this systematic review, we estimated the diagnostic accuracy of procalcitonin in sepsis diagnosis in critically ill patients. 18 studies were included in the review. Overall, the diagnostic performance of procalcitonin was low, with mean values of both sensitivity and specificity being 71% (95% CI 67-76) and an area under the summary receiver operator characteristic curve of 0.78 (95% CI 0.73-0.83). Studies were grouped into phase 2 studies (n=14) and phase 3 studies (n=4) by use of Sackett and Haynes' classification. Phase 2 studies had a low pooled diagnostic odds ratio of 7.79 (95% CI 5.86-10.35). Phase 3 studies showed significant heterogeneity because of variability in sample size (meta-regression coefficient -0.592, p=0.017), with diagnostic performance upwardly biased in smaller studies, but moving towards a null effect in larger studies. Procalcitonin cannot reliably differentiate sepsis from other non-infectious causes of systemic inflammatory response syndrome in critically ill adult patients. The findings from this study do not lend support to the widespread use of the procalcitonin test in critical care settings.
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            Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis.

            The caspase-3 (CPP32, apopain, YAMA) family of cysteinyl proteases has been implicated as key mediators of apoptosis in mammalian cells. Gelsolin was identified as a substrate for caspase-3 by screening the translation products of small complementary DNA pools for sensitivity to cleavage by caspase-3. Gelsolin was cleaved in vivo in a caspase-dependent manner in cells stimulated by Fas. Caspase-cleaved gelsolin severed actin filaments in vitro in a Ca2+-independent manner. Expression of the gelsolin cleavage product in multiple cell types caused the cells to round up, detach from the plate, and undergo nuclear fragmentation. Neutrophils isolated from mice lacking gelsolin had delayed onset of both blebbing and DNA fragmentation, following apoptosis induction, compared with wild-type neutrophils. Thus, cleaved gelsolin may be one physiological effector of morphologic change during apoptosis.
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              Gelsolin superfamily proteins: key regulators of cellular functions.

              Cytoskeletal rearrangement occurs in a variety of cellular processes and involves a wide spectrum of proteins. Among these, the gelsolin superfamily proteins control actin organization by severing filaments, capping filament ends and nucleating actin assembly [1]. Gelsolin is the founding member of this family, which now contains at least another six members: villin, adseverin, capG, advillin, supervillin and flightless I. In addition to their respective role in actin filament remodeling, these proteins have some specific and apparently non-overlapping particular roles in several cellular processes, including cell motility, control of apoptosis and regulation of phagocytosis (summarized in table 1). Evidence suggests that proteins belonging to the gelsolin superfamily may be involved in other processes, including gene expression regulation. This review will focus on some of the known functions of the gelsolin superfamily proteins, thus providing a basis for reflection on other possible and as yet incompletely understood roles for these proteins.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                25 August 2018
                September 2018
                : 19
                : 9
                : 2516
                Affiliations
                [1 ]Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2c, 15-222 Bialystok, Poland; ewelina.piktel@ 123456wp.pl
                [2 ]McGovern Medical School, University of Texas Health Science Center, Houston MSB 4.202A, 6431 Fannin St, Houston, TX 77096, USA; Ilya.Levental@ 123456uth.tmc.edu
                [3 ]Department of Microbiology and Immunology, The Faculty of Medicine and Health Sciences of the Jan Kochanowski University in Kielce, Aleja IX Wieków Kielc, 25-317 Kielce, Poland; Bonita.Durnas@ 123456onkol.kielce.pl
                [4 ]Institute for Medicine and Engineering, University of Pennsylvania, 3340 Smith Walk, Philadelphia, PA 19104, USA; janmey@ 123456mail.med.upenn.edu
                Author notes
                [* ]Correspondence: buckirobert@ 123456gmail.com ; Tel.: +48-85-7485483
                Article
                ijms-19-02516
                10.3390/ijms19092516
                6164782
                30149613
                a5c597d7-cf0b-4617-b6eb-2c7e29f1f2ae
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 18 July 2018
                : 18 August 2018
                Categories
                Review

                Molecular biology
                plasma gelsolin,inflammation,biomarker,extracellular recombinant gelsolin,actin
                Molecular biology
                plasma gelsolin, inflammation, biomarker, extracellular recombinant gelsolin, actin

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