{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:18:57Z","timestamp":1791872337025,"version":"4.3.4"},"reference-count":97,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Severe COVID-19 cases often progress to life-threatening conditions such as acute respiratory distress syndrome (ARDS), sepsis, and multiple organ dysfunction syndrome (MODS). Gelsolin (GSN), an actin-binding protein with anti-inflammatory and immunomodulatory properties, is a promising therapeutic target for severe COVID-19. Plasma GSN levels are significantly decreased in critical illnesses, including COVID-19, correlating with dysregulated immune responses and poor outcomes. GSN supplementation may mitigate acute lung injury, ARDS, and sepsis, which share pathophysiological features with severe COVID-19, by scavenging actin, modulating cytokine production, enhancing macrophage phagocytosis, and stabilizing the alveolar-capillary barrier. Preliminary data indicate that recombinant human plasma GSN improves oxygenation and lung function in severe COVID-19 patients with ARDS. Although further research is needed to optimize GSN therapy, current evidence supports its potential to mitigate severe consequences of COVID-19 and improve patient outcomes. This review provides a comprehensive analysis of the biological characteristics, mechanisms, and therapeutic value of GSN in severe COVID-19.<\/jats:p>","DOI":"10.3389\/fphar.2024.1447403","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T04:19:06Z","timestamp":1721967546000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["The therapeutic potential of gelsolin in attenuating cytokine storm, ARDS, and ALI in severe COVID-19"],"prefix":"10.3389","volume":"15","author":[{"given":"Juan","family":"Zhi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Xuan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju-Hui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ming","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"S195","DOI":"10.1097\/01.CCM.0000057843.47705.E8","article-title":"Neutrophils and acute lung injury","volume":"31","author":"Abraham","year":"2003","journal-title":"Crit. Care Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1056\/NEJMoa2015432","article-title":"Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19","volume":"383","author":"Ackermann","year":"","journal-title":"N. Engl. J. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1056\/NEJMoa2015432","article-title":"Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19","volume":"383","author":"Ackermann","year":"","journal-title":"N. Engl. J. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/s1570-0232(02)00572-x","article-title":"Quantitation of tryptophan, kynurenine and kynurenic acid in human plasma by capillary liquid chromatography-electrospray ionization tandem mass spectrometry","volume":"780","author":"Amirkhani","year":"2002","journal-title":"J. Chromatogr. B"},{"key":"B5","doi-asserted-by":"publisher","first-page":"5175","DOI":"10.1091\/mbc.e05-07-0648","article-title":"Separate functions of gelsolin mediate sequential steps of collagen phagocytosis","volume":"16","author":"Arora","year":"2005","journal-title":"Mol. Biol. Cell."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e0231889","DOI":"10.1371\/journal.pone.0231889","article-title":"Gestational weight gain and its effect on birth outcomes in sub-Saharan Africa: systematic review and meta-analysis","volume":"15","author":"Asare-Werehene","year":"2020","journal-title":"PloS one"},{"key":"B7","doi-asserted-by":"publisher","first-page":"e799","DOI":"10.1097\/CCM.0000000000004457","article-title":"ICU and ventilator mortality among critically ill adults with coronavirus disease 2019","volume":"48","author":"Auld","year":"2020","journal-title":"Crit. Care Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1165\/rcmb.2002-0024OC","article-title":"Pulmonary vascular permeability and ischemic injury in gelsolin-deficient mice","volume":"28","author":"Becker","year":"2003","journal-title":"Am. J. Respir. Cell. Mol. Biol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2451","DOI":"10.1056\/NEJMcp2009575","article-title":"Severe Covid-19","volume":"383","author":"Berlin","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1164\/ajrccm.149.3.7509706","article-title":"The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination","volume":"149","author":"Bernard","year":"1994","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"9590","DOI":"10.1021\/bi0503504","article-title":"Inactivation of endotoxin by human plasma gelsolin","volume":"44","author":"Bucki","year":"2005","journal-title":"Biochemistry"},{"key":"B12","doi-asserted-by":"publisher","first-page":"541","DOI":"10.2174\/138920308786733912","article-title":"Plasma gelsolin: function, prognostic value, and potential therapeutic use","volume":"9","author":"Bucki","year":"2008","journal-title":"Curr. Protein Peptide Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/S0092-8674(00)80527-9","article-title":"The crystal structure of plasma gelsolin: implications for actin severing, capping, and nucleation","volume":"90","author":"Burtnick","year":"1997","journal-title":"Cell."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2713","DOI":"10.1038\/sj.emboj.7600280","article-title":"Structure of the N-terminal half of gelsolin bound to actin: roles in severing, apoptosis and FAF","volume":"23","author":"Burtnick","year":"2004","journal-title":"EMBO J."},{"key":"B15","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.pcl.2012.03.002","article-title":"Making sense of the cytokine storm: a conceptual framework for understanding, diagnosing, and treating hemophagocytic syndromes","volume":"59","author":"Canna","year":"2012","journal-title":"Pediatr. Clin. N. Am."},{"key":"B16","doi-asserted-by":"publisher","first-page":"100088","DOI":"10.1016\/j.clinpr.2021.100088","article-title":"Recombinant human plasma gelsolin (rhu-pGSN) in a patient hospitalized with critical COVID-19 pneumonia","volume":"12","author":"Catteeuw","year":"2021","journal-title":"Clin. Infect. Dis. Pract."},{"key":"B17","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1007\/s00281-017-0629-x","article-title":"Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology","volume":"39","author":"Channappanavar","year":"2017","journal-title":"Seminars Immunopathol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2620","DOI":"10.1172\/JCI137244","article-title":"Clinical and immunological features of severe and moderate coronavirus disease 2019","volume":"130","author":"Chen","year":"2020","journal-title":"J. Clin. Investigation"},{"key":"B19","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1002\/med.21311","article-title":"The unique pharmacological characteristics of mifepristone (RU486): from terminating pregnancy to preventing cancer metastasis","volume":"34","author":"Chen","year":"2014","journal-title":"Med. Res. Rev."},{"key":"B20","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1159\/000456043","article-title":"Gelsolin inhibits the inflammatory process induced by LPS","volume":"41","author":"Cheng","year":"2017","journal-title":"Cell. Biol. Int."},{"key":"B21","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/S0022-2836(02)01131-2","article-title":"The calcium activation of gelsolin: insights from the 3\u00c5 structure of the G4-G6\/actin complex","volume":"324","author":"Choe","year":"2002","journal-title":"J. Mol. Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"6585","DOI":"10.1073\/pnas.1015674108","article-title":"Leptin is an effective treatment for hypothalamic amenorrhea","volume":"108","author":"Chou","year":"2011","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1007\/s00281-017-0639-8","article-title":"Cytokine storm and sepsis disease pathogenesis","volume":"39","author":"Chousterman","year":"2017","journal-title":"Seminars Immunopathol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"54","DOI":"10.2310\/6650.2002.33518","article-title":"Recombinant plasma gelsolin diminishes the acute inflammatory response to hyperoxia in mice","volume":"51","author":"Christofidou-Solomidou","year":"","journal-title":"J. Investigative Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s004080000084","article-title":"Changes in plasma gelsolin concentration during acute oxidant lung injury in mice","volume":"180","author":"Christofidou-Solomidou","year":"2002","journal-title":"Lung"},{"key":"B26","doi-asserted-by":"publisher","first-page":"L283","DOI":"10.1152\/ajplung.00021.2003","article-title":"PECAM-directed delivery of catalase to endothelium protects against pulmonary vascular oxidative stress","volume":"285","author":"Christofidou-Solomidou","year":"","journal-title":"Am. J. Physiology-Lung Cell. Mol. Physiology"},{"key":"B27","doi-asserted-by":"publisher","first-page":"6781","DOI":"10.1093\/emboj\/cdf680","article-title":"Gelsolin-induced epithelial cell invasion is dependent on Ras-Rac signaling","volume":"21","author":"De Corte","year":"2002","journal-title":"EMBO J."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1038\/s41591-020-1051-9","article-title":"An inflammatory cytokine signature predicts COVID-19 severity and survival","volume":"26","author":"Del Valle","year":"2020","journal-title":"Nat. Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/ar2547","article-title":"Plasma gelsolin as a biomarker of inflammation","volume":"10","author":"DiNubile","year":"2008","journal-title":"Arthritis Res. Ther."},{"key":"B30","doi-asserted-by":"publisher","first-page":"4367","DOI":"10.1182\/blood-2002-06-1672","article-title":"Prognostic implications of declining plasma gelsolin levels after allogeneic stem cell transplantation","volume":"100","author":"DiNubile","year":"2002","journal-title":"Blood"},{"key":"B31","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1016\/j.intimp.2013.09.003","article-title":"Increased expression of heat shock protein 70 in chronic obstructive pulmonary disease","volume":"17","author":"Dong","year":"2013","journal-title":"Int. Immunopharmacol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1172\/JCI4953","article-title":"Neuroprotective effects of gelsolin during murine stroke","volume":"103","author":"Endres","year":"1999","journal-title":"J. Clin. Investigation"},{"key":"B33","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.1056\/NEJMra2026131","article-title":"Cytokine storm","volume":"383","author":"Fajgenbaum","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1038\/s41576-018-0055-5","article-title":"The phylogenomics of evolving virus virulence","volume":"19","author":"Geoghegan","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"B35","doi-asserted-by":"publisher","first-page":"14573","DOI":"10.1074\/jbc.275.19.14573","article-title":"Gelsolin binding and cellular presentation of lysophosphatidic acid","volume":"275","author":"Goetzl","year":"2000","journal-title":"J. Biol. Chem."},{"key":"B36","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/S1359-6101(03)00059-5","article-title":"Cytokine-mediated inflammation in acute lung injury","volume":"14","author":"Goodman","year":"2003","journal-title":"Cytokine and Growth Factor Rev."},{"key":"B37","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s41232-020-00146-3","article-title":"How COVID-19 induces cytokine storm with high mortality","volume":"40","author":"Hojyo","year":"2020","journal-title":"Inflamm. Regen."},{"key":"B38","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.omtm.2020.06.013","article-title":"Characteristics of the coronavirus disease 2019 and related therapeutic options","volume":"18","author":"Huang","year":"","journal-title":"Mol. Therapy-Methods Clin. Dev."},{"key":"B39","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"","journal-title":"Lancet"},{"key":"B40","doi-asserted-by":"publisher","first-page":"11818","DOI":"10.1016\/s0021-9258(19)49772-x","article-title":"Phosphoinositide-binding peptides derived from the sequences of gelsolin and villin","volume":"267","author":"Janmey","year":"1992","journal-title":"J. Biol. Chem."},{"key":"B41","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1038\/325362a0","article-title":"Modulation of gelsolin function by phosphatidylinositol 4,5-bisphosphate","volume":"325","author":"Janmey","year":"1987","journal-title":"Nature"},{"key":"B42","doi-asserted-by":"publisher","first-page":"e0178648","DOI":"10.1371\/journal.pone.0178648","article-title":"A versatile cell-penetrating peptide-adaptor system for efficient delivery of molecular cargos to subcellular destinations","volume":"12","author":"Kang","year":"2017","journal-title":"PloS One"},{"key":"B43","doi-asserted-by":"publisher","first-page":"8683","DOI":"10.1016\/s0021-9258(18)52929-x","article-title":"Nucleotide binding to actin: cation dependence of nucleotide dissociation and exchange rates","volume":"268","author":"Kinosian","year":"1993","journal-title":"J. Biol. Chem."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1001\/jama.2020.17052","article-title":"Cytokine levels in critically ill patients with COVID-19 and other conditions","volume":"324","author":"Kox","year":"2020","journal-title":"JAMA"},{"key":"B45","doi-asserted-by":"publisher","first-page":"15343","DOI":"10.1074\/jbc.275.20.15343","article-title":"Gelsolin inhibits apoptosis by blocking mitochondrial membrane potential loss and cytochrome c release","volume":"275","author":"Koya","year":"2000","journal-title":"J. Biol. Chem."},{"key":"B46","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1083\/jcb.106.2.375","article-title":"Genomic organization and biosynthesis of secreted and cytoplasmic forms of gelsolin","volume":"106","author":"Kwiatkowski","year":"1988","journal-title":"J. Cell. Biol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1038\/s41591-020-1038-6","article-title":"A dynamic COVID-19 immune signature includes associations with poor prognosis","volume":"26","author":"Laing","year":"2020","journal-title":"Nat. Med."},{"key":"B48","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1097\/01.sla.0000201798.77133.55","article-title":"Relationship of plasma gelsolin levels to outcomes in critically ill surgical patients","volume":"243","author":"Lee","year":"2006","journal-title":"Ann. Surg."},{"key":"B49","doi-asserted-by":"publisher","first-page":"e3712","DOI":"10.1371\/journal.pone.0003712","article-title":"Plasma gelsolin depletion and circulating actin in sepsis: a pilot study","volume":"3","author":"Lee","year":"2008","journal-title":"PloS One"},{"key":"B50","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1097\/01.CCM.0000253815.26311.24","article-title":"Plasma gelsolin is a marker and therapeutic agent in animal sepsis","volume":"35","author":"Lee","year":"2007","journal-title":"Crit. Care Med."},{"key":"B51","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1002\/med.20231","article-title":"Multifunctional roles of gelsolin in health and diseases","volume":"32","author":"Li","year":"2012","journal-title":"Med. Res. Rev."},{"key":"B52","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1002\/ctm2.16","article-title":"Acute lung injury in patients with COVID\u201019 infection","volume":"10","author":"Li","year":"2020","journal-title":"Clin. Transl. Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1172\/JCI112634","article-title":"Role of plasma gelsolin and the vitamin D-binding protein in clearing actin from the circulation","volume":"78","author":"Lind","year":"1986","journal-title":"J. Clin. Investigation"},{"key":"B54","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1165\/rcmb.2008-0144OC","article-title":"A critical role for gelsolin in ventilator-induced lung injury","volume":"41","author":"Maniatis","year":"2009","journal-title":"Am. J. Respir. Cell. Mol. Biol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"2731","DOI":"10.1172\/JCI60331","article-title":"The acute respiratory distress syndrome","volume":"122","author":"Matthay","year":"2012","journal-title":"J. Clin. Investigation"},{"key":"B56","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1165\/rcmb.F305","article-title":"Acute lung injury and the acute respiratory distress syndrome: four decades of inquiry into pathogenesis and rational management","volume":"33","author":"Matthay","year":"2005","journal-title":"Am. J. Respir. Cell. Mol. Biol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/S0014-5793(03)00932-3","article-title":"The gelsolin family of actin regulatory proteins: modular structures, versatile functions","volume":"552","author":"McGough","year":"2003","journal-title":"FEBS Lett."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1016\/S0140-6736(20)30628-0","article-title":"COVID-19: consider cytokine storm syndromes and immunosuppression","volume":"395","author":"Mehta","year":"2020","journal-title":"Lancet"},{"key":"B59","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/s41577-020-0331-4","article-title":"Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages","volume":"20","author":"Merad","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1242\/jcs.115.8.1591","article-title":"Human CAP1 is a key factor in the recycling of cofilin and actin for rapid actin turnover","volume":"115","author":"Moriyama","year":"2002","journal-title":"J. Cell. Sci."},{"key":"B61","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1002\/cm.21117","article-title":"Gelsolin: the tail of a molecular gymnast","volume":"70","author":"Nag","year":"2013","journal-title":"Cytoskeleton"},{"key":"B62","doi-asserted-by":"publisher","first-page":"13713","DOI":"10.1073\/pnas.0812374106","article-title":"Ca2+ binding by domain 2 plays a critical role in the activation and stabilization of gelsolin","volume":"106","author":"Nag","year":"2009","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B63","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1038\/s41591-021-01283-z","article-title":"Post-acute COVID-19 syndrome","volume":"27","author":"Nalbandian","year":"2021","journal-title":"Nat. Med."},{"key":"B64","doi-asserted-by":"publisher","first-page":"C1323","DOI":"10.1152\/ajpcell.00510.2006","article-title":"Modifications of cellular responses to lysophosphatidic acid and platelet-activating factor by plasma gelsolin","volume":"292","author":"Osborn","year":"2007","journal-title":"Am. J. Physiology-Cell Physiology"},{"key":"B65","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1186\/ar2520","article-title":"Decreased levels of the gelsolin plasma isoform in patients with rheumatoid arthritis","volume":"10","author":"Osborn","year":"2008","journal-title":"Arthritis Res. Ther."},{"key":"B66","doi-asserted-by":"publisher","first-page":"341","DOI":"10.3390\/v15020341","article-title":"Biochemistry of the respiratory syncytial virus L protein embedding RNA polymerase and capping activities","volume":"15","author":"Pathinayake","year":"2023","journal-title":"Viruses"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.3389\/fimmu.2020.01446","article-title":"The COVID-19 cytokine storm; what we know so far","volume":"11","author":"Ragab","year":"2020","journal-title":"Front. Immunol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"1726","DOI":"10.1038\/s41375-020-0887-9","article-title":"SARS-CoV-2 infection and overactivation of Nlrp3 inflammasome as a trigger of cytokine \"storm\" and risk factor for damage of hematopoietic stem cells","volume":"34","author":"Ratajczak","year":"2020","journal-title":"Leukemia"},{"key":"B69","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1152\/japplphysiol.01074.2002","article-title":"Recombinant plasma gelsolin infusion attenuates burn-induced pulmonary microvascular dysfunction","volume":"96","author":"Rothenbach","year":"2004","journal-title":"J. Appl. Physiology"},{"key":"B70","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1007\/s00134-020-05991-x","article-title":"Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China","volume":"46","author":"Ruan","year":"2020","journal-title":"Intensive Care Med."},{"key":"B71","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1055\/s-2008-1063855","article-title":"Cytokines and chemokines in the pathogenesis of interstitial pneumonia","volume":"29","author":"Shimizu","year":"2008","journal-title":"Seminars Respir. Crit. Care Med."},{"key":"B72","doi-asserted-by":"publisher","first-page":"2614","DOI":"10.1007\/s00018-004-4225-6","article-title":"Gelsolin superfamily proteins: key regulators of cellular functions","volume":"61","author":"Silacci","year":"2004","journal-title":"Cell. Mol. Life Sci."},{"key":"B73","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/978-1-4020-6191-2_3","article-title":"Gelsolin and diseases","volume":"45","author":"Spinardi","year":"2007","journal-title":"Subcell. Biochem."},{"key":"B74","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1097\/00003246-199704000-00007","article-title":"Decreased plasma gelsolin concentrations in acute liver failure, myocardial infarction, septic shock, and myonecrosis","volume":"25","author":"Suhler","year":"1997","journal-title":"Crit. Care Med."},{"key":"B75","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/0955-0674(95)80051-4","article-title":"Actin monomer binding proteins","volume":"7","author":"Sun","year":"1995","journal-title":"Curr. Opin. Cell. Biol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"33179","DOI":"10.1074\/jbc.274.47.33179","article-title":"Gelsolin, a multifunctional actin regulatory protein","volume":"274","author":"Sun","year":"1999","journal-title":"J. Biol. Chem."},{"key":"B77","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/0165-3806(93)90217-x","article-title":"Gelsolin is localized in neuronal growth cones","volume":"76","author":"Tanaka","year":"1993","journal-title":"Dev. Brain Res."},{"key":"B78","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1038\/s41577-020-0311-8","article-title":"The trinity of COVID-19: immunity, inflammation and intervention","volume":"20","author":"Tay","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1016\/S0140-6736(20)30937-5","article-title":"Endothelial cell infection and endotheliitis in COVID-19","volume":"395","author":"Varga","year":"2020","journal-title":"Lancet"},{"key":"B80","doi-asserted-by":"publisher","first-page":"R106","DOI":"10.1186\/cc6988","article-title":"Time course of plasma gelsolin concentrations during severe sepsis in critically ill surgical patients","volume":"12","author":"Wang","year":"2008","journal-title":"Crit. Care"},{"key":"B81","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1080\/15548627.2019.1615305","article-title":"Gelsolin inhibits BECN1-mediated autophagy through a calcium-dependent mechanism","volume":"16","author":"Wang","year":"2020","journal-title":"Autophagy"},{"key":"B82","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1056\/NEJM200005043421806","article-title":"The acute respiratory distress syndrome","volume":"342","author":"Ware","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"B83","doi-asserted-by":"publisher","first-page":"9700","DOI":"10.1021\/bi960920n","article-title":"The plasma and cytoplasmic forms of human gelsolin differ in disulfide structure","volume":"35","author":"Wen","year":"1996","journal-title":"Biochemistry"},{"key":"B84","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/0092-8674(95)90369-0","article-title":"Hemostatic, inflammatory, and fibroblast responses are blunted in mice lacking gelsolin","volume":"81","author":"Witke","year":"1995","journal-title":"Cell."},{"key":"B85","unstructured":"WHO coronavirus (COVID-19) dashboard2023"},{"key":"B86","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1001\/jama.2020.2648","article-title":"Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72,314 cases from the Chinese Center for Disease Control and Prevention","volume":"323","author":"Wu","year":"2020","journal-title":"JAMA"},{"key":"B87","doi-asserted-by":"publisher","first-page":"5a","DOI":"10.1016\/S0006-3495(00)76494-X","article-title":"Dissociation of gelsolin-actin complex by phosphatidylinositol 4, 5-bisphosphate","volume":"78","author":"Xian","year":"2000","journal-title":"Biophysical J."},{"key":"B88","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1016\/S2213-2600(20)30076-X","article-title":"Pathological findings of COVID-19 associated with acute respiratory distress syndrome","volume":"8","author":"Xu","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"B89","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/S2213-2600(20)30079-5","article-title":"Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study","volume":"8","author":"Yang","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"B90","doi-asserted-by":"publisher","first-page":"L11","DOI":"10.1152\/ajplung.00094.2015","article-title":"Plasma gelsolin improves lung host defense against pneumonia by enhancing macrophage NOS3 function","volume":"309","author":"Yang","year":"2015","journal-title":"Am. J. Physiology-Lung Cell. Mol. Physiology"},{"key":"B91","doi-asserted-by":"publisher","first-page":"5271","DOI":"10.1016\/s0021-9258(17)42985-1","article-title":"Structure and biosynthesis of cytoplasmic and secreted variants of gelsolin","volume":"259","author":"Yin","year":"1984","journal-title":"J. Biol. Chem."},{"key":"B92","doi-asserted-by":"publisher","first-page":"1863","DOI":"10.2147\/JIR.S299401","article-title":"Cathepsin B and gelsolin levels are inversely correlated with lung injury progression in a mouse model of acute respiratory distress syndrome","volume":"14","author":"Yin","year":"2021","journal-title":"J. Inflamm. Res."},{"key":"B93","doi-asserted-by":"publisher","first-page":"e13087","DOI":"10.1097\/MD.0000000000013087","article-title":"N-acetylcysteine improves oxidative stress and inflammatory response in patients with community acquired pneumonia: a randomized controlled trial","volume":"97","author":"Zhang","year":"2018","journal-title":"Medicine"},{"key":"B94","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1186\/1742-2094-8-118","article-title":"Treatment with gelsolin reduces brain inflammation and apoptotic signaling in mice following thermal injury","volume":"8","author":"Zhang","year":"2011","journal-title":"J. Neuroinflammation"},{"key":"B95","doi-asserted-by":"publisher","first-page":"e29","DOI":"10.1016\/j.jinf.2021.03.041","article-title":"Plasma gelsolin functions as a treatment for severe COVID-19 and sepsis patients: a cohort study","volume":"83","author":"Zhao","year":"2021","journal-title":"J. Infect."},{"key":"B96","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1016\/S0140-6736(20)30566-3","article-title":"Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study","volume":"395","author":"Zhou","year":"2020","journal-title":"Lancet"},{"key":"B97","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A novel coronavirus from patients with pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N. Engl. J. Med."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1447403\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T04:19:11Z","timestamp":1721967551000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1447403\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,26]]},"references-count":97,"alternative-id":["10.3389\/fphar.2024.1447403"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2024.1447403","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,26]]},"article-number":"1447403"}}