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Evaluation of a Reliable Biomarker in a Cecal Ligation and Puncture-Induced Mouse Model of Sepsis
Published on: December 9, 2022
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DHCR7 Expression Predicts Poor Outcomes and Mortality from Sepsis
Faheem W Guirgis1, Vinitha Jacob2, Dongyuan Wu3
1University of Florida College of Medicine - Jacksonville.
Research Square
|February 13, 2023
Summary
Sepsis patients with poor outcomes show increased expression of the cholesterol gene DHCR7. Inhibiting DHCR7 in a zebrafish model rescued sepsis survival, suggesting a new therapeutic target for sepsis.
Area of Science:
- Biochemistry
- Genetics
- Critical Care Medicine
Background:
- Sepsis leads to severe outcomes like chronic critical illness or death.
- Identifying molecular targets is crucial for improving sepsis patient outcomes.
Approach:
- Analyzed lipid metabolic gene expression in sepsis patients stratified by clinical outcomes.
- Utilized a lipopolysaccharide-induced zebrafish sepsis model for validation and drug discovery.
- Investigated the role of 7-Dehydrocholesterol Reductase (DHCR7) and its inhibition.
Key Points:
- DHCR7 was significantly upregulated in sepsis patients with poor outcomes (chronic critical illness or 90-day non-survival).
- Upregulation of DHCR7 and related lipid genes was confirmed in a zebrafish sepsis model.
- The DHCR7 inhibitor AY9944 demonstrated complete survival rescue in a lethal zebrafish sepsis model.
Conclusions:
- DHCR7 is a potential biomarker for sepsis severity and poor outcomes.
- Targeting the DHCR7 cholesterol pathway offers a promising therapeutic strategy for sepsis.
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