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Sepsis: Molecular Research

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 3123

Special Issue Editor

Special Issue Information

Dear Colleagues,

Sepsis has always been a major challenge for emergency physicians and intensivists. Over the years, the definition of sepsis has evolved from a simple description of the main symptoms due to infection to the presence of damage to an organ distant from the site of infection due to an inappropriate response. The understanding of the basic mechanisms has also progressively evolved. Starting from the search for factors related to the causative microorganism and host, it has been recognized that the components related to sepsis include the pathogen, the immune system, the endothelia and microcirculation, blood coagulation, and the nervous system with microglia and neurons. However, knowledge of physiopathologic mechanisms has evolved without finding new therapies. Sepsis is still treated with fluids, antibiotics, vasopressors, and, when possible, surgical removal of the focus of infection. For this reason, the search for physiopathologic molecular mechanisms that may lead to early diagnosis or more effective treatment must continue. Therefore, I invite all investigators working on sepsis to contribute with original papers or a literature review on all molecular mechanisms related to this topic, from those related to the responsible pathogens to those related to the host.

Dr. Marcello Candelli
Guest Editor

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Keywords

  • sepsis
  • septic shock
  • virulence
  • bacteria
  • immunodepressin
  • inflammation
  • sirs
  • organ disfunction
  • infection
  • biomarkers

Published Papers (2 papers)

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Research

18 pages, 3453 KiB  
Article
Myristica fragrans Extract Inhibits Platelet Desialylation and Activation to Ameliorate Sepsis-Associated Thrombocytopenia in a Murine CLP-Induced Sepsis Model
Int. J. Mol. Sci. 2023, 24(10), 8863; https://doi.org/10.3390/ijms24108863 - 16 May 2023
Cited by 1 | Viewed by 1311
Abstract
Sepsis, characterized by an uncontrolled host inflammatory response to infections, remains a leading cause of death in critically ill patients worldwide. Sepsis-associated thrombocytopenia (SAT), a common disease in patients with sepsis, is an indicator of disease severity. Therefore, alleviating SAT is an important [...] Read more.
Sepsis, characterized by an uncontrolled host inflammatory response to infections, remains a leading cause of death in critically ill patients worldwide. Sepsis-associated thrombocytopenia (SAT), a common disease in patients with sepsis, is an indicator of disease severity. Therefore, alleviating SAT is an important aspect of sepsis treatment; however, platelet transfusion is the only available treatment strategy for SAT. The pathogenesis of SAT involves increased platelet desialylation and activation. In this study, we investigated the effects of Myristica fragrans ethanol extract (MF) on sepsis and SAT. Desialylation and activation of platelets treated with sialidase and adenosine diphosphate (platelet agonist) were assessed using flow cytometry. The extract inhibited platelet desialylation and activation via inhibiting bacterial sialidase activity in washed platelets. Moreover, MF improved survival and reduced organ damage and inflammation in a mouse model of cecal ligation and puncture (CLP)-induced sepsis. It also prevented platelet desialylation and activation via inhibiting circulating sialidase activity, while maintaining platelet count. Inhibition of platelet desialylation reduces hepatic Ashwell–Morell receptor-mediated platelet clearance, thereby reducing hepatic JAK2/STAT3 phosphorylation and thrombopoietin mRNA expression. This study lays a foundation for the development of plant-derived therapeutics for sepsis and SAT and provides insights into sialidase-inhibition-based sepsis treatment strategies. Full article
(This article belongs to the Special Issue Sepsis: Molecular Research)
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14 pages, 2208 KiB  
Article
Thiosulfinate-Enriched Allium sativum Extract Exhibits Differential Effects between Healthy and Sepsis Patients: The Implication of HIF-1α
Int. J. Mol. Sci. 2023, 24(7), 6234; https://doi.org/10.3390/ijms24076234 - 25 Mar 2023
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Abstract
Garlic (Allium sativum) has historically been associated with antioxidant, immunomodulatory, and microbiocidal properties, mainly due to its richness in thiosulfates and sulfur-containing phytoconstituents. Sepsis patients could benefit from these properties because it involves both inflammatory and refractory processes. We evaluated the [...] Read more.
Garlic (Allium sativum) has historically been associated with antioxidant, immunomodulatory, and microbiocidal properties, mainly due to its richness in thiosulfates and sulfur-containing phytoconstituents. Sepsis patients could benefit from these properties because it involves both inflammatory and refractory processes. We evaluated the effects of thiosulfinate-enriched Allium sativum extract (TASE) on the immune response to bacterial lipopolysaccharide (LPS) by monocytes from healthy volunteers (HVs) and patients with sepsis. We also explored the TASE effects in HIF-1α, described as the key transcription factor leading to endotoxin tolerance in sepsis monocytes through IRAK-M expression. Our results showed TASE reduced the LPS-triggered reactive oxygen species (ROS) production in monocytes from both patients with sepsis and HVs. Moreover, this extract significantly reduced tumor necrosis factor (TNF)-α, interleukin-1β, and interleukin-6 production in LPS-stimulated monocytes from HVs. However, TASE enhanced the inflammatory response in monocytes from patients with sepsis along with increased expression of human leukocyte antigen-DR. Curiously, these dual effects of TASE on immune response were also found when the HV cohort was divided into low- and high-LPS responders. Although TASE enhanced TNFα production in the LPS-low responders, it decreased the inflammatory response in the LPS-high responders. Furthermore, TASE decreased the HIF-1α pathway-associated genes IRAK-M, VEGFA and PD-L1 in sepsis cells, suggesting HIF-1α inhibition by TASE leads to higher cytokine production in these cells as a consequence of IRAK-M downregulation. The suppression of this pathway by TASE was confirmed in vitro with the prolyl hydroxylase inhibitor dimethyloxalylglycine. Our data revealed TASE’s dual effect on monocyte response according to status/phenotype and suggested the HIF-1α suppression as the possible underlying mechanism. Full article
(This article belongs to the Special Issue Sepsis: Molecular Research)
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