Novel insights in endocrine and metabolic pathways in sepsis and gaps for future research

Téblick, Arno; Gunst, Jan; Langouche, Lies; Berghe, Greet Van den

doi:10.1042/cs20211003

Cited by 8 publications

(8 citation statements)

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“…Immune and endothelial cell dysfunction, impaired neural mechanisms, cellular and metabolic dysregulation, microvascular dysfunction, compromised oxygen delivery or utilization, endocrinopathy, mitochondrial dysfunction, and abnormalities in transcellular signal transduction have all been implicated in the pathobiology of sepsis-induced organ injury and dysfunction (multiple organ dysfunction score [MODS]) (36–39). Studies in cells, animals, and humans suggest that endothelial cells contribute to the host response to sepsis and that sepsis induces endothelial dysfunction that promotes organ injury and failure (40, 41).…”

Section: Resultsmentioning

confidence: 99%

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Surviving Sepsis Campaign Research Priorities 2023

De Backer,

Deutschman,

Hellman

et al. 2024

Critical Care Medicine

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OBJECTIVES: To identify research priorities in the management, epidemiology, outcome, and pathophysiology of sepsis and septic shock. DESIGN: Shortly after publication of the most recent Surviving Sepsis Campaign Guidelines, the Surviving Sepsis Research Committee, a multiprofessional group of 16 international experts representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, convened virtually and iteratively developed the article and recommendations, which represents an update from the 2018 Surviving Sepsis Campaign Research Priorities. METHODS: Each task force member submitted five research questions on any sepsis-related subject. Committee members then independently ranked their top three priorities from the list generated. The highest rated clinical and basic science questions were developed into the current article. RESULTS: A total of 81 questions were submitted. After merging similar questions, there were 34 clinical and ten basic science research questions submitted for voting. The five top clinical priorities were as follows: 1) what is the best strategy for screening and identification of patients with sepsis, and can predictive modeling assist in real-time recognition of sepsis? 2) what causes organ injury and dysfunction in sepsis, how should it be defined, and how can it be detected? 3) how should fluid resuscitation be individualized initially and beyond? 4) what is the best vasopressor approach for treating the different phases of septic shock? and 5) can a personalized/precision medicine approach identify optimal therapies to improve patient outcomes? The five top basic science priorities were as follows: 1) How can we improve animal models so that they more closely resemble sepsis in humans? 2) What outcome variables maximize correlations between human sepsis and animal models and are therefore most appropriate to use in both? 3) How does sepsis affect the brain, and how do sepsis-induced brain alterations contribute to organ dysfunction? How does sepsis affect interactions between neural, endocrine, and immune systems? 4) How does the microbiome affect sepsis pathobiology? 5) How do genetics and epigenetics influence the development of sepsis, the course of sepsis and the response to treatments for sepsis? CONCLUSIONS: Knowledge advances in multiple clinical domains have been incorporated in progressive iterations of the Surviving Sepsis Campaign guidelines, allowing for evidence-based recommendations for short- and long-term management of sepsis. However, the strength of existing evidence is modest with significant knowledge gaps and mortality from sepsis remains high. The priorities identified represent a roadmap for research in sepsis and septic shock.

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Section: Resultsmentioning

confidence: 99%

“…and 5) how is sepsis screening best implemented in lower resourced settings? (36)(37)(38)(39). Studies in cells, animals, and humans suggest that endothelial cells contribute to the host response to sepsis and that sepsis induces endothelial dysfunction that promotes organ injury and failure (40,41).…”

Section: Gaps In Knowledge/critique Of Evidencementioning

confidence: 99%

Surviving Sepsis Campaign Research Priorities 2023

De Backer,

Deutschman,

Hellman

et al. 2024

Critical Care Medicine

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“…Evidence has demonstrated that sepsis could lead to sepsis-induced dysfunction and mitochondrial damage, which is suggested as a major cause of cell metabolism disorders in these patients ( Wasyluk & Zwolak, 2021 ). Likewise, Téblick et al (2022) also highlighted sepsis contributed to the development of severe metabolic alterations. Therefore, we have reason to believe that the DEPs are significantly ( P < 0.05) enriched into metabolic pathways consistent with previous findings.…”

Section: Discussionmentioning

confidence: 99%

Liver proteomic analysis reveals the key proteins involved in host immune response to sepsis

Chen

Gong

Tang

et al. 2023

PeerJ

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Background Sepsis is a serious infection-induced response in the host, which can result in life-threatening organ dysfunction. It is of great importance to unravel the relationship between sepsis and host immune response and its mechanisms of action. Liver is one of the most vulnerable organs in sepsis, however, the specific pathogenesis of septic liver injury has not been well understood at the protein level. Methods A total of 12 healthy Sprague–Dawley (SD) male rats aged from 6 to 8 weeks were adaptively housed in individual cages in the specific pathogen free animal room. These lab rats were grouped into two groups: treatment (N = 9) and control (N = 3) groups; only three mice from the treatment group survived and were used for subsequent experiments. A TMT-based proteomic analysis for liver tissue was performed in the septic rat model. Results A total of 37,012 unique peptides were identified, and then 6,166 proteins were determined, among which 5,701 were quantifiable. Compared to the healthy control group, the septic rat group exhibited 162 upregulated and 103 downregulated differentially expressed proteins (DEPs). The upregulated and downregulated DEPs were the most significantly enriched into the complement and coagulation cascades and metabolic pathways. Protein-protein interaction (PPI) analysis further revealed that the upregulated and downregulated DEPs each clustered in a PPI network. Several highly connected upregulated and downregulated DEPs were also enriched into the complement and coagulation cascades pathways and metabolic pathways, respectively. The parallel reaction monitoring (PRM) results of the selected DEPs were consistent with the results of the TMT analysis, supporting the proteomic data. Conclusion Our findings highlight the roles of complement and coagulation cascades and metabolic pathways that may play vital roles in the host immune response. The DEPs may serve as clinically potential treatment targets for septic liver injury.

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“…Neuroendocrine organs play an important role in maintaining the survival of the human body, regulating the balance of the environment, protecting human tissue from emergency responses, and avoiding external infection[ 1 ]. Major brain trauma, vascular diseases, tumors, and other insults can lead to loss of function of neurosecretory organs, which leaves patients prone to infection, hormone imbalance, systemic complications, and even death due to low hormones[ 2 ]. Even partial removal of endocrine organs can cause loss of endocrine function, which often necessitates long-term additional hormone drug replacement therapy in affected individuals.…”

Section: Introductionmentioning

confidence: 99%

Hybrid biofabrication of neurosecretory structures as a model for neurosecretion

Tian¹,

Gu²,

Yang³

et al. 2022

IJB

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The present study aimed to combine extrusion-based three-dimensional (3D) bioprinting and polymer nanofiber electrospinning technology to fabricate tissue-like structures with neurosecretory function in vitro. Using neurosecretory cells as cell resources, sodium alginate/gelatin/fibrinogen as matrix, polylactic acid/gelatin electrospun nanofibers as diaphragm, and neurosecretory cells-loaded 3D hydrogel scaffolds were bioprinted and then covered with electrospun nanofibers layer-by-layer. The morphology was observed by scanning electron microscopy and transmission electron microscopy (TEM), and the mechanical characteristics and cytotoxicity of the hybrid biofabricated scaffold structure were evaluated. The 3D-bioprinted tissue activity, including cell death and proliferation, was verified. Western blotting and ELISA experiments were used to confirm the cell phenotype and secretory function, while animal in vivo transplantation experiments confirmed the histocompatibility, inflammatory reaction, and tissue remodeling ability of the heterozygous tissue structures. Neurosecretory structures with 3D structures were successfully prepared by hybrid biofabrication in vitro. The mechanical strength of the composite biofabricated structures was significantly higher than that of the hydrogel system (P < 0.05). The survival rate of PC12 cells in the 3D-bioprinted model was 92.849 ± 2.995%. Hematoxylin and eosin-stained pathological sections showed that the cells grew in clumps, and there was no significant difference in the expression of MAP2 and tubulin-β between 3D organoids and PC12 cells. The results of ELISA showed that the PC12 cells in 3D structures retained the ability to continuously secrete noradrenaline and met-enkephalin, and the secretory vesicles around and within the cells could be observed by TEM. In in vivo transplantation, PC12 cells gathered and grew in clusters, maintained high activity, neovascularization, and tissue remodeling in 3D structures. The neurosecretory structures were biofabricated by 3D bioprinting and nanofiber electrospinning in vitro, which had high activity and neurosecretory function. In vivo transplantation of neurosecretory structures showed active proliferation of cells and potential for tissue remodeling. Our research provides a new method for biological manufacture of neurosecretory structures in vitro, which maintains neurosecretory function and lays the foundation for the clinical application of neuroendocrine tissues.

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Novel insights in endocrine and metabolic pathways in sepsis and gaps for future research

Cited by 8 publications

References 174 publications

Surviving Sepsis Campaign Research Priorities 2023

Surviving Sepsis Campaign Research Priorities 2023

Liver proteomic analysis reveals the key proteins involved in host immune response to sepsis

Hybrid biofabrication of neurosecretory structures as a model for neurosecretion

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