scholarly journals Wnt-Signaling Inhibitor Wnt-C59 Suppresses the Cytokine Upregulation in Multiple Organs of Lipopolysaccharide-Induced Endotoxemic Mice via Reducing the Interaction between β-Catenin and NF-κB

2021 ◽  
Vol 22 (12) ◽  
pp. 6249
Author(s):  
Jaewoong Jang ◽  
Jaewon Song ◽  
Inae Sim ◽  
Young V. Kwon ◽  
Yoosik Yoon
Keyword(s):  
Wnt Signaling ◽  
Organ Dysfunction ◽  
Proinflammatory Cytokines ◽  
Host Response ◽  
Organ Damage ◽  
Suppressive Effect ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction ◽  
Multiple Organs

Sepsis is characterized by multiple-organ dysfunction caused by the dysregulated host response to infection. Until now, however, the role of the Wnt signaling has not been fully characterized in multiple organs during sepsis. This study assessed the suppressive effect of a Wnt signaling inhibitor, Wnt-C59, in the kidney, lung, and liver of lipopolysaccharide-induced endotoxemic mice, serving as an animal model of sepsis. We found that Wnt-C59 elevated the survival rate of these mice and decreased their plasma levels of proinflammatory cytokines and organ-damage biomarkers, such as BUN, ALT, and AST. The Wnt/β-catenin and NF-κB pathways were stimulated and proinflammatory cytokines were upregulated in the kidney, lung, and liver of endotoxemic mice. Wnt-C59, as a Wnt signaling inhibitor, inhibited the Wnt/β-catenin pathway, and its interaction with the NF-κB pathway, which resulted in the inhibition of NF-κB activity and proinflammatory cytokine expression. In multiple organs of endotoxemic mice, Wnt-C59 significantly reduced the β-catenin level and interaction with NF-κB. Our findings suggest that the anti-endotoxemic effect of Wnt-C59 is mediated via reducing the interaction between β-catenin and NF-κB, consequently suppressing the associated cytokine upregulation in multiple organs. Thus, Wnt-C59 may be useful for the suppression of the multiple-organ dysfunction during sepsis.

scholarly journals Multiple Organ Dysfunction Reduces In-Hospital Survival in COVID-19 Patients

2020 ◽  
Vol 5 (09) ◽  
pp. 389-394
Author(s):  
Najiba Abdulrazzaq ◽  
Kashif Bin Naeem ◽  
Abdalla Alhajiri ◽  
Ayman Chkhis ◽  
Vinod Choondal ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Organ Dysfunction ◽  
Distress Syndrome ◽  
Cardiac Injury ◽  
Kidney Injury ◽  
Organ Damage ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction ◽  
Hospital Survival ◽  
Multiple Organs

Background: Although primarily a respiratory illness, COVID-19 involves multiple organs when the disease is severe or critical. Hence, we conducted this study to evaluate the incidence of multiple organ dysfunction in COVID-19 patients and its implications on survival. Methods: A retrospective analysis of laboratory-confirmed COVID-19 patients presenting to our center in Dubai, UAE between April 2020 and July 2020. Data was collected from the electronic medical records and analyzed to evaluate multiple organ damage observed during hospital admission. Findings: Five-hundred patients were studied. Overall mean age was 49.5 years (range 13-94), 76% males, 33% diabetics, 31% hypertensives. 97/500 (19.4%) had evidence of single organ damage; 37/500 (7.4%) had two organ damage; and 105/500 (21%) had more than two organ damage. Acute respiratory distress syndrome was the most prevalent organ damage,153/500 (30.6%); followed by acute cardiac injury, 120/500 (24%); acute kidney injury 107/500 (21.4%); acute liver injury 96/500 (19.2%); septic shock 93/500 (18.6%); disseminated intravascular coagulation 27/500 (5.4%), and heart failure 17/500 (3.4%). We found that in-hospital survival reduced as the number of organs involved increased; only 20% patients survived who had more than 2 organ damage. Also, the chances of survival reduced considerably once other organs were involved in addition to the acute respiratory distress syndrome (91.6% survival in ARDS alone vs. 28.6% survival in ARDS with acute kidney injury vs. 10.4% survival in ARDS with shock/acute cardiac injury/acute kidney injury). Conclusion: Multiple organ dysfunction is common in COVID-19 as 21% had evidence of more than two organ damage in our study. The survival in COVID-19 reduces significantly once multiple organs are involved. Early monitoring and recognition of multiple organ dysfunction is necessary to prevent adverse outcomes and improve survival.

scholarly journals Multiple Organ Dysfunction During Severe Malaria: The Role of the Inflammatory Response

10.5772/65348 ◽  
2016 ◽  
Author(s):  
Mariana Conceição de Souza ◽  
Tatiana Almeida Pádua ◽  
Maria das Graças Henriques
Keyword(s):  
Inflammatory Response ◽  
Severe Malaria ◽  
Organ Dysfunction ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction

Article Commentary: Sepsis, Systemic Inflammatory Response, and Multiple Organ Dysfunction: The Mystery Continues

2012 ◽  
Vol 78 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Donald E. Fry
Keyword(s):  
Clinical Trials ◽  
Inflammatory Response ◽  
Organ Dysfunction ◽  
Multiple Organ ◽  
Systemic Inflammatory Response ◽  
Invasive Infection ◽  
Multiple Organ Dysfunction ◽  
Human Sepsis ◽  
Critical Organ

Human sepsis is thought to be systemic inflammatory response syndrome (SIRS) that is activated by invasive infection. The multiple organ dysfunction syndrome (MODS) is the identified failure of critical organ function in patients that have sustained SIRS. Because SIRS and MODS are consequences of the excessive activation of inflammation, extensive research and numerous clinical trials have pursued treatments that would modify the inflammatory response. This presentation reviews the normal local mechanisms of inflammation and provides a theoretical framework for the transition of the inflammatory process to a systemic level. Clinical trials with biomodulators to block or inhibit inflammation have generally failed to improve the outcomes in patients with severe sepsis, septic shock, and MODS. The role of counter-inflammatory signaling and the newer concept of the cholinergic anti-inflammatory pathway are being investigated, and newer hypotheses are focusing upon the balancing of proinflammatory and counter-inflammatory mechanisms as important directions for newer therapies. It is concluded that failure to define novel and effective treatments reflects fundamental gaps in our understanding of inflammation and its regulation.

scholarly journals Role of Damage-Associated Molecular Patterns and Uncontrolled Inflammation in Pediatric Sepsis-Induced Multiple Organ Dysfunction Syndrome

2018 ◽  
Vol 08 (01) ◽  
pp. 025-031 ◽  
Author(s):  
Diana Pang ◽  
Dalia Bashir ◽  
Joseph Carcillo ◽  
Trung Nguyen ◽  
Rajesh Aneja ◽  
...  
Keyword(s):  
Organ Dysfunction ◽  
Multiple Organ Dysfunction Syndrome ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction ◽  
Risk Of Death ◽  
Pediatric Sepsis ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Stimulation Of

AbstractThe incidence of multiple organ dysfunction syndrome (MODS) in sepsis varies from 17 to 73% and furthermore, increases the risk of death by 60% when controlled for the number of dysfunctional organs. Several MODS phenotypes exist, each unique in presentation and pathophysiology. Common to the phenotypes is the stimulation of the immune response by pathogen-associated molecular patterns (PAMPs), or danger-associated molecular patterns (DAMPs) causing an unremitting inflammation. Two of the MODS phenotypes are discussed in detail, thrombocytopenia-associated multiple organ failure (TAMOF) and the hyperinflammatory phenotype–macrophage activating syndrome (MAS) and hemophagocytic lymphohistiocytosis (HLH). In the end, we will briefly review the role of mitochondrial dysfunction as a significant contributor to the pathogenesis of MODS.

scholarly journals 1657 Mortality in Post-Cardiac Surgery in Children: The role of Multiple Organ Dysfunction

2012 ◽  
Vol 97 (Suppl 2) ◽  
pp. A469-A469
Author(s):  
T. d. Rocha ◽  
A. Botta ◽  
C. Ricachinevsky ◽  
L. Mulle ◽  
P. Carvalho
Keyword(s):  
Cardiac Surgery ◽  
Organ Dysfunction ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction ◽  
Post Cardiac Surgery
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