Exploring the role of palmitoylation in sepsis: mechanistic insights and future perspectives DOI Creative Commons
Susu Cao, Wenyan Xiao,

Sinong Pan

и другие.

Molecular Medicine, Год журнала: 2025, Номер 31(1)

Опубликована: Июнь 3, 2025

The palmitoylation system is intricate, multidimensional, and plays a crucial role in various inflammatory immune-related disorders. Palmitoylation controls protein stability, cargo sorting, signal transmission, as well cell differentiation death. Notably, growing body of studies has highlighted its participation processes, either directly or indirectly, indicating broad complex involvement the development sepsis. Understanding mechanisms underlying essential for advancing research on We began this review with brief summary related to sepsis progression. Second, we went over recent palmitoylation. Third, compiled described palmitoylation-related alterations vital molecules biological processes involved Lastly, outlined promising features proposed hopeful outlook future

Язык: Английский

Endothelial dysfunction and immunothrombosis in sepsis DOI Creative Commons
Eleni Maneta, Evmorfia Aivalioti, Simon Tual‐Chalot

и другие.

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Апрель 4, 2023

Sepsis is a life-threatening clinical syndrome characterized by multiorgan dysfunction caused dysregulated or over-reactive host response to infection. During sepsis, the coagulation cascade triggered activated cells of innate immune system, such as neutrophils and monocytes, resulting in clot formation mainly microcirculation, process known immunothrombosis. Although this aims protect through inhibition pathogen’s dissemination survival, endothelial microthrombotic complications can rapidly lead multiple organ dysfunction. The development treatments targeting responses immunothrombosis could be great significance for reducing morbidity mortality patients with sepsis. Medications modifying cell-specific inhibiting platelet–endothelial interaction platelet activation have been proposed. Herein, we discuss underlying mechanisms organ-specific sepsis its complications, while highlighting recent advances new therapeutic approaches aiming at improving short- long-term prognosis

Язык: Английский

Процитировано

75
The pathophysiology, diagnosis, and management of sepsis-associated disseminated intravascular coagulation DOI Creative Commons
Toshiaki Iba, Julie Helms, Jean M. Connors

и другие.

Journal of Intensive Care, Год журнала: 2023, Номер 11(1)

Опубликована: Май 23, 2023

Abstract Background The International Society on Thrombosis and Haemostasis (ISTH) released overt disseminated intravascular coagulation (DIC) diagnostic criteria in 2001. Since then, DIC has been understood as the end-stage consumptive coagulopathy not therapeutic target. However, is merely a decompensated disorder, but also includes early stages with systemic activation coagulation. Thus, ISTH recently sepsis-induced (SIC) that can diagnose compensated-phase of readily available biomarkers. Main body laboratory-based diagnosis due to various critical conditions, although sepsis most common underlying disease. pathophysiology sepsis-associated multifactorial, addition suppressed fibrinolysis, multiple inflammatory responses are initiated by activated leukocytes, platelets, vascular endothelial cells part thromboinflammation. Although were established advanced stage DIC, additional detect an earlier needed for potential considerations. Accordingly, introduced SIC 2019 easy use require only platelet count, prothrombin time-international normalized ratio, Sequential Organ Failure Assessment Score. score be used evaluate disease severity determine timing interventions. One major disadvantages treating lack availability specific approaches beyond infection. Clinical trials date have failed because included patients who coagulopathic. Nevertheless, infection control, anticoagulant therapy will choice DIC. Therefore, efficacy heparin, antithrombin, recombinant thrombomodulin proven future clinical studies. Conclusion It necessary develop novel strategy against improve outcomes. Consequently, we recommend screening monitoring using scoring system.

Язык: Английский

Процитировано

60
Neutrophil extracellular traps in homeostasis and disease DOI Creative Commons

Han Wang,

Susan J. Kim,

Lei Yu

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Сен. 20, 2024

Язык: Английский

Процитировано

43
Intracellular communication and immunothrombosis in sepsis DOI Creative Commons
Toshiaki Iba, Marcel Levi, Jerrold H. Levy

и другие.

Journal of Thrombosis and Haemostasis, Год журнала: 2022, Номер 20(11), С. 2475 - 2484

Опубликована: Авг. 18, 2022

Abstract

Inflammation and coagulation are the critical responses to infection that include leukocytes, platelets, vascular endothelial cells responding in concert eradicate invading pathogen. In sepsis, a variety of cell surface receptors, including toll‐like Fcγ‐receptors, G‐protein‐coupled adhesion detect pathogens elicit thromboinflammatory responses. Concurrently, molecular patterns released from host damaged accelerate immune through binding same pattern recognition receptors. Cytokines, chemokines, extracellular vesicles important mediators for amplifying distant as part systemic response infections. At time, communicate with each other via direct contact, molecules, paracrine mediators, tunneling nanotubes, which regulating inflammation thrombus formation. Despite increasing attention immunothrombosis these close communication systems less understood but play role defense mechanisms. this review, cellular activation intercellular sepsis focus on will be considered.

Язык: Английский

Процитировано

48
Role of Neutrophil Extracellular Traps in Health and Disease Pathophysiology: Recent Insights and Advances DOI Open Access
M M. Islam, Naoshi Takeyama

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(21), С. 15805 - 15805

Опубликована: Окт. 31, 2023

Neutrophils are the principal trouper of innate immune system. Activated neutrophils undergo a noble cell death termed NETosis and release mesh-like structure called neutrophil extracellular traps (NETs) as part their defensive strategy against microbial pathogen attack. This web-like architecture includes DNA backbone embedded with antimicrobial proteins like myeloperoxidase (MPO), elastase (NE), histones deploys in entrapment clearance encountered pathogens. Thus NETs play an inevitable beneficial role host's protection. However, recent accumulated evidence shows that dysregulated enhanced NET formation has various pathological aspects including promotion sepsis, pulmonary, cardiovascular, hepatic, nephrological, thrombotic, autoimmune, pregnancy, cancer diseases, list is increasing gradually. In this review, we summarize NET-mediated pathophysiology different diseases focus on some updated potential therapeutic approaches NETs.

Язык: Английский

Процитировано

42
Thromboinflammation in acute injury: infections, heatstroke, and trauma DOI Creative Commons
Toshiaki Iba, Julie Helms, Marcel Levi

и другие.

Journal of Thrombosis and Haemostasis, Год журнала: 2023, Номер 22(1), С. 7 - 22

Опубликована: Авг. 3, 2023

Язык: Английский

Процитировано

40
Mechanism and role of mitophagy in the development of severe infection DOI Creative Commons

Lixiu Ma,

Tianyu Han,

Y M Zhan

и другие.

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Фев. 19, 2024

Abstract Mitochondria produce adenosine triphosphate and potentially contribute to proinflammatory responses cell death. Mitophagy, as a conservative phenomenon, scavenges waste mitochondria their components in the cell. Recent studies suggest that severe infections develop alongside mitochondrial dysfunction mitophagy abnormalities. Restoring protects against excessive inflammation multiple organ failure sepsis. Here, we review normal process, its interaction with invading microorganisms immune system, summarize mechanism of during infection. We highlight critical role preventing

Язык: Английский

Процитировано

13
The role of thromboinflammation in acute kidney injury among patients with septic coagulopathy DOI
Toshiaki Iba, Julie Helms, Cheryl L. Maier

и другие.

Journal of Thrombosis and Haemostasis, Год журнала: 2024, Номер 22(6), С. 1530 - 1540

Опубликована: Фев. 19, 2024

Язык: Английский

Процитировано

10
Disrupting the dangerous alliance: Dual anti-inflammatory and anticoagulant strategy targets platelet-neutrophil crosstalk in sepsis DOI

Sa Chen,

Aijia Wu,

Xinran Shen

и другие.

Journal of Controlled Release, Год журнала: 2025, Номер 379, С. 814 - 831

Опубликована: Янв. 28, 2025

Язык: Английский

Процитировано

1
The critical role of neutrophil-endothelial cell interactions in sepsis: new synergistic approaches employing organ-on-chip, omics, immune cell phenotyping and in silico modeling to identify new therapeutics DOI Creative Commons
Dan Liu, Jordan C. Langston,

Balabhaskar Prabhakarpandian

и другие.

Frontiers in Cellular and Infection Microbiology, Год журнала: 2024, Номер 13

Опубликована: Янв. 8, 2024

Sepsis is a global health concern accounting for more than 1 in 5 deaths worldwide. now defined as life-threatening organ dysfunction caused by dysregulated host response to infection. can develop from bacterial (gram negative or gram positive), fungal viral (such COVID) infections. However, therapeutics developed animal models and traditional vitro sepsis have had little success clinical trials, these failed fully replicate the underlying pathophysiology heterogeneity of disease. The current understanding that highly diverse among patients, this impacts immune function Phenotyping classifying patients into specific endotypes needed personalized treatment approach. Neutrophil-endothelium interactions play critical role progression, increased neutrophil influx endothelial barrier disruption important roles early course damage. Understanding mechanism neutrophil-endothelium how interaction help us better manage disease lead discovery new diagnostic prognosis tools effective treatments. In review, we will discuss latest research exploring silico modeling synergistic combination organ-on-chip incorporating human cells/tissue, omics analysis data allow identify relevant signaling pathways characterize phenotypes patients. Emerging technologies such machine learning then be leveraged druggable therapeutic targets relate them infectious agents. This approach development identification FDA approved drugs repurposed sepsis.

Язык: Английский

Процитировано

8