Pre-B-Cell Colony-Enhancing Factor and Its Clinical Correlates With Acute Lung Injury and Sepsis

Lee, Kathleen A.; Gong, Michelle N.

doi:10.1378/chest.10-3100

Cited by 35 publications

(22 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…63 High eNAMPT levels at the time of admission to the intensive care unit correlate with disease severity and may predict mortality in patients with sepsis and ARDS. 76,77 Unfortunately, no single biomarker has been shown to reliably provide information about the patient's overall disease outcome and thus stratify patients for enrollment in clinical trials. However, recent efforts to combine biomarkers demonstrate that prognostic ability can be greatly enhanced.…”

Section: Ards Biomarkers By Categorymentioning

confidence: 99%

The acute respiratory distress syndrome biomarker pipeline: crippling gaps between discovery and clinical utility

Bime

Camp

Casanova

et al. 2020

Translational Research

View full text Add to dashboard Cite

Recent innovations in translational research have ushered an exponential increase in the discovery of novel biomarkers, thereby elevating the hope for deeper insights into "personalized" medicine approaches to disease phenotyping and care. However, a critical gap exists between the fast pace of biomarker discovery and the successful translation to clinical use. This gap underscores the fundamental biomarker conundrum across various acute and chronic disorders: how does a biomarker address a specific unmet need? Additionally, the gap highlights the need to shift the paradigm from a focus on biomarker discovery to greater translational impact and the need for a more streamlined drug approval process. The unmet need for biomarkers in acute respiratory distress syndrome (ARDS) is for reliable and validated biomarkers that minimize heterogeneity and allow for stratification of subject selection for enrollment in clinical trials of tailored therapies. This unmet need is particularly highlighted by the ongoing SARS-CoV-2/COVID-19 pandemic. The unprecedented numbers of COVID-19-induced ARDS cases has strained health care systems across the world and exposed the need for biomarkers that would accelerate drug development and the successful phenotyping of COVID-19infected patients at risk for development of ARDS and ARDS mortality. Accordingly, this review discusses the current state of ARDS biomarkers in the context of the drug development pipeline and highlight gaps between biomarker discovery and clinical implementation while proposing potential paths forward. We discuss potential ARDS biomarkers by category and by context of use, highlighting progress in the development continuum. We conclude by discussing challenges to successful translation of biomarker candidates to clinical impact and proposing possible novel strategies.

show abstract

Section: Ards Biomarkers By Categorymentioning

confidence: 99%

The acute respiratory distress syndrome biomarker pipeline: crippling gaps between discovery and clinical utility

Bime

Camp

Casanova

et al. 2020

Translational Research

View full text Add to dashboard Cite

show abstract

“…Recent studies have shown that visfatin is also closely related to immune processes and is a major proinflammatory cytokine in a variety of inflammatory processes (e.g., acute inflammation of the lung and sepsis) (ref. [12][13][14] ). In these conditions, adiponectin has antagonistic properties.…”

Section: Introductionmentioning

confidence: 99%

Early changes in serum visfatin after abdominal surgery: a new pro-inflammatory marker in diagnosis?

et al. 2015

View full text Add to dashboard Cite

“…Heterozygous Nampt 1/2 mice showed reductions in both inflammatory markers and lung injury when subjected to preclinical models of ventilator-induced lung injury (27). Furthermore, plasma concentrations of eNAMPT are a biomarker for acute respiratory distress syndrome and correlate with acute respiratory distress syndrome mortality (27)(28)(29). Recently, we clarified the mechanism by which eNAMPT exerts proinflammatory properties, and we identified Toll-like receptor 4 (TLR4) as the novel receptor for eNAMPT leading to the downstream activation of NF-kBdependent signaling (30).…”

mentioning

confidence: 99%

Novel Mechanism for Nicotinamide Phosphoribosyltransferase Inhibition of TNF-α–mediated Apoptosis in Human Lung Endothelial Cells

Oita

Camp

et al. 2018

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Nicotinamide phosphoribosyltransferase (NAMPT) exists as both intracellular NAMPT and extracellular NAMPT (eNAMPT) proteins. eNAMPT is secreted into the blood and functions as a cytokine/enzyme (cytozyme) that activates NF-κB signaling via ligation of Toll-like receptor 4 (TLR4), further serving as a biomarker for inflammatory lung disorders such as acute respiratory distress syndrome. In contrast, intracellular NAMPT is involved in nicotinamide mononucleotide synthesis and has been implicated in the regulation of cellular apoptosis, although the exact mechanisms for this regulation are poorly understood. We examined the role of NAMPT in TNF-α-induced human lung endothelial cell (EC) apoptosis and demonstrated that reduced NAMPT expression (siRNA) increases EC susceptibility to TNF-α-induced apoptosis as reflected by PARP-1 cleavage and caspase-3 activation. In contrast, overexpression of NAMPT served to reduce degrees of TNF-α-induced EC apoptosis. Inhibition of nicotinamide mononucleotide synthesis by FK866 (a selective NAMPT enzymatic inhibitor) failed to alter TNF-α-induced human lung EC apoptosis, suggesting that NAMPT-dependent NAD generation is unlikely to be involved in regulation of TNF-α-induced EC apoptosis. We next confirmed that TNF-α-induced EC apoptosis is attributable to NAMPT secretion into the EC culture media and subsequent eNAMPT ligation of TLR4 on the EC membrane surface. Silencing of NAMPT expression, direct neutralization of secreted eNAMPT by an NAMPT-specific polyclonal antibody (preventing TLR4 ligation), or direct TLR4 antagonism all served to significantly increase EC susceptibility to TNF-α-induced EC apoptosis. Together, these studies provide novel insights into NAMPT contributions to lung inflammatory events and to novel mechanisms of EC apoptosis regulation.

show abstract

Pre-B-Cell Colony-Enhancing Factor and Its Clinical Correlates With Acute Lung Injury and Sepsis

Cited by 35 publications

References 49 publications

The acute respiratory distress syndrome biomarker pipeline: crippling gaps between discovery and clinical utility

The acute respiratory distress syndrome biomarker pipeline: crippling gaps between discovery and clinical utility

Early changes in serum visfatin after abdominal surgery: a new pro-inflammatory marker in diagnosis?

Novel Mechanism for Nicotinamide Phosphoribosyltransferase Inhibition of TNF-α–mediated Apoptosis in Human Lung Endothelial Cells

Contact Info

Product

Resources

About