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      Spleen data: Cerium oxide nanoparticles attenuate polymicrobial sepsis induced spenic damage in male Sprague Dawley rats

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          Abstract

          Sepsis is a serious life threatening medical emergency which, if not treated properly, oftentimes results in organ failure and death. Current sepsis treatment protocols are largely centered on the use of antibiotics and supportive care. Recent studies have suggested that antibiotics fail to be effective for sepsis treatment when administered during hypo-dynamic phase of sepsis that is usually characterized by the presence of a cytokine storm. As such, there is an urgent need to develop novel therapeutic drugs that target the inflammatory cytokines that are secreted as a result of increased reactive oxygen species. Cerium oxide nanoparticles (CeO 2) have been shown to act as anti-inflammatory and anti-oxidant agent. More recently, they have been shown to attenuate polymicrobial insult-induced mortality in Sprague Dawley rats. Here, we investigated whether CeO 2 nanoparticles can attenuate splenic damage in this animal model of sepsis. A single intravenous dose (0.5 mg/kg) of CeO 2 nanoparticles attenuated the sepsis-induced loss in splenic cell structural integrity. These improvements in splenic structure were accompanied by a decrease in expression of late phase pro-inflammatory cytokine high mobility group box 1 (HMGB1) along with reduced bacterial load in the blood and peritoneal fluid of septic animals. Taken together these findings suggest that CeO 2 nanoparticles can be used to attenuate polymicrobial insult-induced splenic damage in Sprague dawley rats.

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          Inhibition of MAP kinase/NF-kB mediated signaling and attenuation of lipopolysaccharide induced severe sepsis by cerium oxide nanoparticles.

          Sepsis is a life threatening disease that is associated with high mortality. Existing treatments have failed to improve survivability in septic patients. The purpose of this present study is to evaluate whether cerium oxide nanoparticles (CeO2NPs) can prevent lipopolysaccharide (LPS) induced severe sepsis mortality by preventing hepatic dysfunction in male Sprague Dawley rats. Administration of a single dose (0.5 mg/kg) of CeO2NPs intravenously to septic rats significantly improved survival rates and functioned to restore body temperature, respiratory rate and blood pressure towards baseline. Treatment-induced increases in animal survivability were associated with decreased hepatic damage along with reductions in serum cytokines/chemokines, and diminished inflammatory related signaling. Kupffer cells and macrophage cells exposed to CeO2NPs exhibited decreases in LPS-induced cytokine release (TNF-α, IL-1β, IL-6, HMGB1) which were associated with diminished cellular ROS, reduced levels of nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and decreased nuclear factor-kappa light chain enhancer of activated B cells (NF-kB) transcriptional activity. The findings of this study indicate that CeO2NPs may be useful as a therapeutic agent for sepsis.
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            Prevention of lymphocyte apoptosis--a potential treatment of sepsis?

            Sepsis is the leading cause of death in surgical intensive care units and is a major cause of morbidity and mortality in neonatal and medical intensive care units. The Centers for Disease Control and Prevention estimates that, in the United States alone, approximately 500,000 people develop sepsis and 175,000 people die each year. Sepsis is a growing problem; its incidence has tripled from 1972 to 1992. Recently, apoptosis has been identified as an important mechanism of cell death in animal models of sepsis and endotoxemia. During sepsis, there is extensive apoptotic death of lymphocytes and gastrointestinal epithelial cells. The extensive apoptotic death of lymphocytes is likely an important cause of the profound immunosuppression that is a hallmark of patients with sepsis. The apoptosis of gastrointestinal epithelial cells may compromise the integrity of the bowel wall, resulting in translocation of bacteria or endotoxins into the systemic circulation. The potential importance of apoptosis in the pathophysiology of sepsis is illustrated by results from animal models that demonstrate that blocking lymphocyte apoptosis improves survival in sepsis. A variety of strategies to inhibit apoptosis may ultimately provide an effective therapy for this highly lethal disorder.
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              HMGB1 mediates splenomegaly and expansion of splenic CD11b+ Ly-6Chigh inflammatory monocytes in murine sepsis survivors

              Background More than 500,000 hospitalized patients survive severe sepsis annually in the USA. Recent epidemiological evidence, however, demonstrated that these survivors have significant morbidity and mortality, with 3-year fatality rates higher than 70%. To investigate the mechanisms underlying persistent functional impairment in sepsis survivors, here we developed a model to study severe sepsis survivors following cecal ligation and puncture (CLP). Methods Sepsis was induced in mice by CLP and survivors were followed for twelve weeks. Spleen and blood were collected and analyzed at different time points post-sepsis. Results We observed that sepsis survivors developed significant splenomegaly. Analysis of the splenic cellular compartments revealed a major expansion of the inflammatory CD11b+ Ly-6CHigh pool. Serum high-mobility group box 1 (HMGB1) levels in the sepsis surviving mice were significantly elevated for 4-6 weeks after post-sepsis, and administration of an anti-HMGB1 monoclonal antibody significantly attenuated splenomegaly as well as splenocyte priming. Administration of recombinant HMGB1 to naive mice induced similar splenomegaly, leukocytosis and splenocyte priming as observed in sepsis survivors. Interestingly analysis of circulating HMGB1 from sepsis survivors by mass spectroscopy demonstrated a stepwise increase of reduced form of HMGB1 (with known chemo-attractant properties) during the first 3 weeks, followed by disulphide form (with known inflammatory properties) 4-8 weeks after CLP. Discussion Our results indicate that prolonged elevation of HMGB1 is a necessary and sufficient mediator of splenomegaly and splenocyte expansion, as well as splenocyte inflammatory priming in murine severe sepsis survivors.
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                Author and article information

                Contributors
                Journal
                Data Brief
                Data Brief
                Data in Brief
                Elsevier
                2352-3409
                22 March 2018
                June 2018
                22 March 2018
                : 18
                : 740-746
                Affiliations
                [a ]Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA
                [b ]Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA
                [c ]Biotechnology Graduate Program West Virginia State University, Institute, WV, USA
                [d ]Department of Health and Human Service, School of Kinesiology, Marshall University, Huntington, WV, USA
                [e ]Department of Public Health, Marshall University, Huntington, WV, USA
                [f ]Department of Pharmaceutical Sciences and Research, School of Pharmacy, Marshall University, Huntington, WV, USA
                [g ]Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA
                Author notes
                [* ]Correspondence to: Center for Diagnostic Nanosystems, Marshall University, Room 241D Robert C. Byrd Biotechnology Science Center, 1700 3rd Ave., Huntington, WV 25755-1090, USA. Fax: +304 696 3766. rice9@ 123456marshall.edu
                Article
                S2352-3409(18)30286-5
                10.1016/j.dib.2018.03.073
                5996310
                7d3d8e73-e968-494a-9742-3e4ad7a4192d

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 12 February 2018
                : 2 March 2018
                : 15 March 2018
                Categories
                Medicine and Dentistry

                sepsis,ceo2 nanoparticles,spleen
                sepsis, ceo2 nanoparticles, spleen

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