scholarly journals Extracellular Vesicles: A Double-Edged Sword in Sepsis

2021 ◽  
Vol 14 (8) ◽  
pp. 829
Author(s):  
Marlies Burgelman ◽  
Charysse Vandendriessche ◽  
Roosmarijn E. Vandenbroucke
Keyword(s):  
Clinical Outcome ◽  
Organ Dysfunction ◽  
Extracellular Vesicles ◽  
Host Response ◽  
Current Knowledge ◽  
Healthy Controls ◽  
Lymphocyte Apoptosis ◽  
Cellular Source ◽  
Life Threatening

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection. Several studies on mouse and patient sepsis samples have revealed that the level of extracellular vesicles (EVs) in the blood is altered compared to healthy controls, but the different functions of EVs during sepsis pathology are not yet completely understood. Sepsis EVs are described as modulators of inflammation, lymphocyte apoptosis, coagulation and organ dysfunction. Furthermore, EVs can influence clinical outcome and it is suggested that EVs can predict survival. Both detrimental and beneficial roles for EVs have been described in sepsis, depending on the EV cellular source and the disease phase during which the EVs are studied. In this review, we summarize the current knowledge of EV sources and functions during sepsis pathology based on in vitro and mouse models, as well as patient samples.

scholarly journals Inflammatory cytokines and organ dysfunction associate with the aberrant DNA methylome of monocytes in sepsis

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Clara Lorente-Sorolla ◽  
Antonio Garcia-Gomez ◽  
Francesc Català-Moll ◽  
Víctor Toledano ◽  
Laura Ciudad ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Organ Dysfunction ◽  
Inflammatory Cytokines ◽  
Healthy Controls ◽  
Toll Like Receptors ◽  
Transcriptional Dysregulation ◽  
Organic Dysfunction ◽  
Life Threatening ◽  
Gains And Losses

Abstract Background Sepsis, a life-threatening organ dysfunction caused by a dysregulated systemic immune response to infection, associates with reduced responsiveness to subsequent infections. How such tolerance is acquired is not well understood but is known to involve epigenetic and transcriptional dysregulation. Methods Bead arrays were used to compare global DNA methylation changes in patients with sepsis, non-infectious systemic inflammatory response syndrome, and healthy controls. Bioinformatic analyses were performed to dissect functional reprogramming and signaling pathways related to the acquisition of these specific DNA methylation alterations. Finally, in vitro experiments using human monocytes were performed to test the induction of similar DNA methylation reprogramming. Results Here, we focused on DNA methylation changes associated with sepsis, given their potential role in stabilizing altered phenotypes. Tolerized monocytes from patients with sepsis display changes in their DNA methylomes with respect to those from healthy controls, affecting critical monocyte-related genes. DNA methylation profiles correlate with IL-10 and IL-6 levels, significantly increased in monocytes in sepsis, as well as with the Sequential Organ Failure Assessment score; the observed changes associate with TFs and pathways downstream to toll-like receptors and inflammatory cytokines. In fact, in vitro stimulation of toll-like receptors in monocytes results in similar gains and losses of methylation together with the acquisition of tolerance. Conclusion We have identified a DNA methylation signature associated with sepsis that is downstream to the response of monocytes to inflammatory signals associated with the acquisition of a tolerized phenotype and organic dysfunction.

scholarly journals The Therapeutic Effect of Extracellular Vesicles on Asthma in Pre-Clinical Models: A Systematic Review Protocol

2021 ◽  
Vol 1 (1) ◽  
pp. 84-95
Author(s):  
Patience O. Obi ◽  
Jennifer E. Kent ◽  
Maya M. Jeyaraman ◽  
Nicole Askin ◽  
Taiana M. Pierdoná ◽  
...  
Keyword(s):  
Systematic Review ◽  
Extracellular Vesicles ◽  
Current Knowledge ◽  
Grey Literature ◽  
Specific Treatment ◽  
Therapeutic Effects ◽  
Management Options ◽  
Paracrine Signalling

Asthma is the most common pediatric disease, characterized by chronic airway inflammation and airway hyperresponsiveness. There are several management options for asthma, but no specific treatment. Extracellular vesicles (EVs) are powerful cellular mediators of endocrine, autocrine and paracrine signalling, and can modulate biophysiological function in vitro and in vivo. A thorough investigation of therapeutic effects of EVs in asthma has not been conducted. Therefore, this systematic review is designed to synthesize recent literature on the therapeutic effects of EVs on physiological and biological outcomes of asthma in pre-clinical studies. An electronic search of Web of Science, EMBASE, MEDLINE, and Scopus will be conducted on manuscripts published in the last five years that adhere to standardized guidelines for EV research. Grey literature will also be included. Two reviewers will independently screen the selected studies for title and abstract, and full text based on the eligibility criteria. Data will be extracted, narratively synthesized and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review will summarize the current knowledge from preclinical studies investigating the therapeutic effects of EVs on asthma. The results will delineate whether EVs can mitigate biological hallmarks of asthma, and if so, describe the underlying mechanisms involved in the process. This insight is crucial for identifying key pathways that can be targeted to alleviate the burden of asthma. The data will also reveal the origin, dosage and biophysical characteristics of beneficial EVs. Overall, our results will provide a scaffold for future intervention and translational studies on asthma treatment.

scholarly journals The Role and Mechanism of Pyroptosis and Potential Therapeutic Targets in Sepsis: A Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiangtao Zheng ◽  
Weiwei Chen ◽  
Fangchen Gong ◽  
Ying Chen ◽  
Erzhen Chen
Keyword(s):  
Immune Response ◽  
Organ Dysfunction ◽  
Host Response ◽  
Therapeutic Targets ◽  
Host Immune Response ◽  
Unique Form ◽  
Pathogen Infection ◽  
Programmed Death ◽  
Life Threatening ◽  
Future Direction

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Recently was been found that pyroptosis is a unique form of proinflammatory programmed death, that is different from apoptosis. A growing number of studies have investigated pyroptosis and its relationship with sepsis, including the mechanisms, role, and relevant targets of pyroptosis in sepsis. While moderate pyroptosis in sepsis can control pathogen infection, excessive pyroptosis can lead to a dysregulated host immune response and even organ dysfunction. This review provides an overview of the mechanisms and potential therapeutic targets underlying pyroptosis in sepsis identified in recent decades, looking forward to the future direction of treatment for sepsis.

scholarly journals CXCL5-mediated recruitment of neutrophils into the peritoneal cavity ofGdf15-deficient mice protects against abdominal sepsis

2020 ◽  
Vol 117 (22) ◽  
pp. 12281-12287 ◽  
Author(s):  
Isa Santos ◽  
Henrique G. Colaço ◽  
Ana Neves-Costa ◽  
Elsa Seixas ◽  
Tiago R. Velho ◽  
...  
Keyword(s):  
Septic Shock ◽  
Organ Dysfunction ◽  
Peritoneal Cavity ◽  
Host Response ◽  
Abdominal Sepsis ◽  
Neutrophil Recruitment ◽  
Life Threatening ◽  
Pathogen Control ◽  
Circulating Levels ◽  
Deficient Mice

Sepsis is a life-threatening organ dysfunction condition caused by a dysregulated host response to an infection. Here we report that the circulating levels of growth and differentiation factor-15 (GDF15) are strongly increased in septic shock patients and correlate with mortality. In mice, we find that peptidoglycan is a potent ligand that signals through the TLR2-Myd88 axis for the secretion of GDF15, and thatGdf15-deficient mice are protected against abdominal sepsis due to increased chemokine CXC ligand 5 (CXCL5)-mediated recruitment of neutrophils into the peritoneum, leading to better local bacterial control. Our results identify GDF15 as a potential target to improve sepsis treatment. Its inhibition should increase neutrophil recruitment to the site of infection and consequently lead to better pathogen control and clearance.

scholarly journals Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Potential Therapeutic Strategy for Acute Kidney Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Jia-Kun Li ◽  
Cheng Yang ◽  
Ying Su ◽  
Jing-Chao Luo ◽  
Ming-Hao Luo ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Extracellular Vesicles ◽  
Cellular Therapy ◽  
Supportive Therapy ◽  
Kidney Injury ◽  
Therapeutic Effects ◽  
Life Threatening ◽  
Stage Renal Disease ◽  
End Stage

Acute kidney injury (AKI) is a common and potential life-threatening disease in patients admitted to hospital, affecting 10%–15% of all hospitalizations and around 50% of patients in the intensive care unit. Severe, recurrent, and uncontrolled AKI may progress to chronic kidney disease or end-stage renal disease. AKI thus requires more efficient, specific therapies, rather than just supportive therapy. Mesenchymal stem cells (MSCs) are considered to be promising cells for cellular therapy because of their ease of harvesting, low immunogenicity, and ability to expand in vitro. Recent research indicated that the main therapeutic effects of MSCs were mediated by MSC-derived extracellular vesicles (MSC-EVs). Furthermore, compared with MSCs, MSC-EVs have lower immunogenicity, easier storage, no tumorigenesis, and the potential to be artificially modified. We reviewed the therapeutic mechanism of MSCs and MSC-EVs in AKI, and considered recent research on how to improve the efficacy of MSC-EVs in AKI. We also summarized and analyzed the potential and limitations of EVs for the treatment of AKI to provide ideas for future clinical trials and the clinical application of MSC-EVs in AKI.

scholarly journals An assessment of knowledge and education about sepsis among medical students: a multi-university survey

2021 ◽  
Vol 23 (1) ◽  
pp. 117-118
Author(s):  
Rachit Datta ◽  
◽  
Gian Luca Di Tanna ◽  
Amanda Harley ◽  
Luregn J Schlapbach ◽  
...  
Keyword(s):  
Critical Illness ◽  
Medical Students ◽  
Organ Dysfunction ◽  
Host Response ◽  
Medical Schools ◽  
Junior Doctors ◽  
Life Threatening ◽  
Time Critical ◽  
Australian Universities

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection; it affects 55 000 Australians and results in around 8700 deaths annually.1 Studies have shown that junior doctors have reduced awareness of the importance of sepsis as a time-critical illness.2 Whether this deficiency is a consequence of insufficient training on sepsis in medical schools is unknown. This study evaluated the knowledge of sepsis among medical students in two Australian universities

scholarly journals diagnosis and trEatmEnt of patiEnts in sEptiC shoCK

New Medicine ◽  
2017 ◽  
Vol 21 (1) ◽  
pp. 31-36
Author(s):  
Jacek wadełek
Keyword(s):  
Septic Shock ◽  
Organ Dysfunction ◽  
Host Response ◽  
Signs And Symptoms ◽  
Intravenous Fluids ◽  
Failure Assessment ◽  
Acute Change ◽  
Life Threatening ◽  
Sepsis And Septic Shock ◽  
Clinical Emergency

sepsis and septic shock are a clinical emergency. sepsis is defined as a life-threatening organ dysfunction due to a dysregulated host response to infection, and organ dysfunction is defined as an acute change in sequential organ failure assessment (sofa) score greater than 2 points secondary to an infectious cause. septic shock is defined as sepsis with persisting hypotension requiring vasopressors to maintain a mean arterial pressure of 65 mm hg or higher, and blood lactate level greater than 2 mmol/l (18 mg/dl) despite adequate volume resuscitation. the diagnosis of septic shock begins with medical history and physical examination focused on the signs and symptoms of infection, with the aim of recognizing complex physiologic manifestations of shock. Clinicians should understand the importance of prompt administration of antibiotics, vasopressors and intravenous fluids aimed at restoring adequate circulation. they should also be aware of the limitations of the protocol-based therapy.

scholarly journals Recent application of metabolomics in the diagnosis, pathogenesis, treatment, and prognosis of sepsis

2021 ◽  
Keyword(s):  
Early Diagnosis ◽  
Organ Dysfunction ◽  
Host Response ◽  
Clinical Manifestations ◽  
Rapid Diagnosis ◽  
Pathophysiological Mechanism ◽  
Recent Application ◽  
Biochemical Pathways ◽  
Diagnosis And Prognosis ◽  
Life Threatening

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infections. It is a leading cause of morbidity and mortality in hospitalized patients. Patients with sepsis often require care in the intensive care unit (ICU) which is costly to the patients and their families. Sepsis has no specific clinical manifestations, and its pathophysiological mechanism is complex. The disease progresses rapidly which makes early diagnosis difficult. Severe forms of the disease, such as septic shock, may lead to organ dysfunction, organ failure, and death. As an emerging “-omics” technology, metabolomics has revolutionized the clinical and research landscape of sepsis. Metabolomics has been applied in the prognosis, diagnosis, and risk stratification in patients with sepsis. This technology provides details on the metabolites and biochemical pathways commonly associated with the pathophysiology of sepsis. At present, it is mostly used to identify metabolites in various diseases. Using this technology, metabolites in body fluids such as blood and urine are detected and analyzed in relation to disease progresssion. The technology therefore helps to understand the pathogenesis of diseases and promote early diagnosis and treatment of the disease. So far, the applicaition of metabolomics in patients with sepsis has not been well defined. This article briefly reviews the application of metabolomics technology in patients with sepsis in recent years, to generate ideas for improving rapid diagnosis and prognosis evaluation of patients with sepsis.

scholarly journals Pathologic Difference between Sepsis and Bloodstream Infections

2019 ◽  
Vol 3 (4) ◽  
pp. 654-663 ◽  
Author(s):  
Luis E Huerta ◽  
Todd W Rice
Keyword(s):  
Mitochondrial Dysfunction ◽  
Organ Dysfunction ◽  
Host Response ◽  
Laboratory Tests ◽  
Bloodstream Infections ◽  
Therapeutic Interventions ◽  
Coagulation Cascade ◽  
Sepsis Diagnosis ◽  
Reactive Protein ◽  
Life Threatening

Abstract Background Sepsis, defined as life-threatening organ failure caused by a dysregulated host response to infection, is a major cause of morbidity and mortality in hospitalized patients. Understanding the features that distinguish sepsis from bloodstream infections (and other types of infection) can help clinicians appropriately and efficiently target their diagnostic workup and therapeutic interventions, especially early in the disease course. Content In this review, sepsis and bloodstream infections are both defined, with a focus on recent changes in the sepsis definition. The molecular and cellular pathways involved in sepsis pathogenesis are described, including cytokines, the coagulation cascade, apoptosis, and mitochondrial dysfunction. Laboratory tests that have been evaluated for their utility in sepsis diagnosis are discussed. Summary Sepsis is defined not only by the presence of an infection, but also by organ dysfunction from a dysregulated host response to that infection. Numerous pathways, including proinflammatory and antiinflammatory cytokines, the coagulation cascade, apoptosis, and mitochondrial dysfunction, help determine if a bloodstream infection (or any other infection) progresses to sepsis. Many biomarkers, including C-reactive protein, procalcitonin, and lactic acid have been evaluated for use in sepsis diagnosis, although none are routinely recommended for that purpose in current clinical practice. While some laboratory tests can help distinguish the 2, the presence of organ dysfunction is what separates sepsis from routine infections.

scholarly journals Sepsis: an update in 2018

2019 ◽  
pp. S99-S101
Author(s):  
Muhammad Fuad Bangash
Keyword(s):  
Organ Dysfunction ◽  
Host Response ◽  
The United States ◽  
Review Article ◽  
Source Control ◽  
Metabolic Dysfunction ◽  
Vasoactive Agents ◽  
Sepsis Management ◽  
Failure Assessment ◽  
Life Threatening

Sepsis remains a major source of morbidity and mortality not only in the United States but worldwide. The key to save lives of these patients is to have a multi-pronged approach to the management of sepsis. In this review article we shall go through the specifics of this approach. Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. The septic shock is a subset of sepsis with circulatory and cellular/metabolic dysfunction. Patients with sepsis (formerly severe sepsis) should still be identified by the same organ dysfunction criteria (including lactate level > 2 mmol/L). Organ dysfunction may also be identified using the ‘quick Sepsis-Related Organ Failure Assessment’ (qSOFA). Appropriate source control and immediate treatment with IV antibiotics is a cornerstone of sepsis management. The next step is to resuscitate patients with sepsis-induced hypoperfusion with at least 30 ml/kg of intravenous crystalloid fluid. If the patient is hypotensive despite adequate fluid resuscitation, then use of vasoactive agents like norepinephrine and vasopressin is indicated.Citation: Bangash MF. Sepsis: an update in 2018. Anaesth Pain & Intensive Care 2018;22 Suppl 1:S99-S101

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