ArticleThe journal of trauma and acute care surgery2014
Histone deacetylase III as a potential therapeutic target for the treatment of lethal sepsis.
Article in The journal of trauma and acute care surgery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Epigenetic mechanisms of Immune remodeling in sepsis: targeting histone modification.Cell death & disease · 2023Pooled it
- Lactylated Histone H3K18 as a Potential Biomarker for the Diagnosis and Predicting the Severity of Septic Shock.Frontiers in immunology · 2021Trial
- Protein acylation in inflammatory diseases: from mechanisms to therapeutic strategies.Cell communication and signaling : CCS · 2025Review
- The Epigenetics of Sepsis: How Gene Modulation Shapes Outcomes.Biomedicines · 2025Review
- Molecular mechanisms and functions of protein acetylation in sepsis and sepsis-associated organ dysfunction.Cellular & molecular biology letters · 2025Review
- An Fgr kinase inhibitor attenuates sepsis-associated encephalopathy by ameliorating mitochondrial dysfunction, oxidative stress, and neuroinflammation via the SIRT1/PGC-1α signaling pathway.Journal of translational medicine · 2023Article
- Histone Deacetylase Inhibitors: A Novel Strategy in Trauma and Sepsis.Shock (Augusta, Ga.) · 2019Review
- Histone Deacetylation Inhibitors as Therapy Concept in Sepsis.International journal of molecular sciences · 2019Review
- Inhibition of SIRT1 promotes taste bud stem cell survival and mitigates radiation-induced oral mucositis in mice.American journal of translational research · 2019Article
- Epigenetics in Sepsis: Understanding Its Role in Endothelial Dysfunction, Immunosuppression, and Potential Therapeutics.Frontiers in immunology · 2019Review
- Histone deacetylase inhibitors: Isoform selectivity improves survival in a hemorrhagic shock model.The journal of trauma and acute care surgery · 2018Article
- Emerging Evidence concerning the Role of Sirtuins in Sepsis.Critical care research and practice · 2018Review
- Protective effect of Cl-amidine against CLP-induced lethal septic shock in mice.Scientific reports · 2016Article
- Propagation of errors in citation networks: a study involving the entire citation network of a widely cited paper published in, and later retracted from, the journal Nature.Research integrity and peer review · 2016Article
- Inhibition of histone deacetylase 6 restores innate immune cells in the bone marrow in a lethal septic model.The journal of trauma and acute care surgery · 2016Article
- Creating a "Prosurvival Phenotype" Through Histone Deacetylase Inhibition: Past, Present, and Future.Shock (Augusta, Ga.) · 2015Review
- Selective histone deacetylase 6 inhibition prolongs survival in a lethal two-hit model.The Journal of surgical research · 2015Article
- Hypothermia and valproic acid activate prosurvival pathways after hemorrhage.The Journal of surgical research · 2015Article
- Inhibition of histone deacetylase 6 improves long-term survival in a lethal septic model.The journal of trauma and acute care surgery · 2015Article
- Selective Inhibition of SIRT2 Improves Outcomes in a Lethal Septic Model.Current molecular medicine · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundWe have recently demonstrated that inhibition of histone deacetylase (HDAC) Class I, II, and IV with nonspecific HDAC inhibitors improves survival in a mouse model of lethal cecal ligation and puncture (CLP). However, the consequence of HDAC Class III inhibition is unknown in this model. The aims of the present study were to explore the effect of EX-527, a selective Sirtuin 1 (SIRT1) inhibitor, on survival in the lethal model of CLP-sepsis and to assess the impact of the treatment on inflammatory cytokine production, coagulopathy, and bone marrow atrophy during severe sepsis.
methodsFor Experiment I, C57BL/6J mice were subjected to CLP and, 1 hour later, intraperitoneally injected with either EX-527 dissolved in dimethyl sulfoxide (DMSO) or DMSO only. Survival was monitored for 10 days. For Experiment II, 1 hour after CLP animals were randomly treated with (1) DMSO vehicle and (2) EX-527. Peritoneal fluid and blood samples were collected for measurement of cytokines, and blood was also used to evaluate coagulation status using thrombelastography. In addition, long bones (femurs and tibias) were examined to determine morphologic changes in the marrow by hematoxylin and eosin staining. For Experiment III, normal primary splenocytes were cultured and treated with lipopolysaccharide in the presence or absence of EX-527 to assess cytokine production.
resultsEX-527 significantly improved survival (50% vs. 0% survival as compared to vehicle, p = 0.0007) and attenuated levels of cytokines tumor necrosis factor α and interleukin 6 in the blood and the peritoneal fluid compared with the vehicle control. It also decreased tumor necrosis factor α and interleukin 6 production by splenocytes in vitro. Selective inhibition of SIRT1 was associated with significant improvements in fibrin cross-linkage, platelet function, and clot rigidity but had no significant impact on the clot initiation parameters. Moreover, inhibition of SIRT1 was associated with a significant decrease in bone marrow atrophy.
conclusionSelective inhibition of Class III HDAC SIRT1 significantly improves survival, attenuates cytokine levels and sepsis-associated coagulopathy, and decreases bone marrow atrophy in a lethal mouse septic model.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.