Evidence map›Paper›PMID 41101738›Full record

ArticleThe Journal of allergy and clinical immunology2026

Radical-induced lipid oxidation produces a torrent of leukotriene-like agonists in severe asthma.

Si-Yang Liu, Mikhail Linetsky, Abby Hite, Yu-Shiuan Cheng, Masaru Miyagi, Serena C Zhu, Hong Zeng, Siqi Huang, Myra Qin, Emma Sintic and 8 more

Abstract read
In one paragraph

Article in The Journal of allergy and clinical immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Si-Yang LiuDepartment of Chemistry, Case Western Reserve University, Cleveland, Ohio.
Mikhail LinetskyDepartment of Chemistry, Case Western Reserve University, Cleveland, Ohio.
Abby HiteDepartment of Chemistry, Case Western Reserve University, Cleveland, Ohio.
Yu-Shiuan ChengDepartment of Chemistry, Case Western Reserve University, Cleveland, Ohio.
Masaru MiyagiDepartment of Pharmacology, Case Western Reserve University, Cleveland, Ohio.
Serena C ZhuDepartment of Chemistry, Case Western Reserve University, Cleveland, Ohio.
Hong ZengDepartment of Chemistry, Case Western Reserve University, Cleveland, Ohio.
Siqi HuangDepartment of Chemistry, Case Western Reserve University, Cleveland, Ohio.
Myra QinDepartment of Chemistry, Case Western Reserve University, Cleveland, Ohio.
Emma SinticDepartment of Chemistry, Case Western Reserve University, Cleveland, Ohio.
Carolyn M KouturesDepartment of Chemistry, Case Western Reserve University, Cleveland, Ohio.
Abigail MenesesDepartment of Chemistry, Case Western Reserve University, Cleveland, Ohio.
Olivia R LaniakDepartment of Chemistry, Case Western Reserve University, Cleveland, Ohio.
Sailaja ParuchuriDepartment of Physiology and Pharmacology, The University of Toledo, Toledo, Ohio.
Lakshminarayan R TeegalaDepartment of Physiology and Pharmacology, The University of Toledo, Toledo, Ohio.
Kaixi CuiDepartment of Chemistry, Case Western Reserve University, Cleveland, Ohio.
Fariba RezaeeDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Robert G SalomonDepartment of Chemistry, Case Western Reserve University, Cleveland, Ohio. Electronic address: rgs@case.edu.

Funding

TISSUE CULTURE AND HYBRIDOMA MODULEP30EY011373 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI Irina A Pikuleva · 1997 to 2026
$17.7M
REACTIVE INTERMEDIATES OF OXIDATIVE LIPID FRAGMENTATIONR01EY016813 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI SALOMON, ROBERT GERD · 2006 to 2018
$3.9M
Mechanisms of Airway Epithelial Barrier Dysfunction by Respiratory Syncytial Virus and Environmental StimuliR01HL148057 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI REZAEE, FARIBA · 2019 to 2023
$2.2M
Integration of Leukotriene and Prostaglandin Receptor Signaling in Mast Cell Activation and Pulmonary Inflammation during AsthmaR01AI144115 · NIAID · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI PARUCHURI, SAILAJA · 2019 to 2023
$1.8M
Glutathionylated Products of Radical-Induced Lipid Oxidation in Inflammatory DiseaseR01EY034075 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI Robert Gerd Salomon · 2023 to 2026
$1.7M
NEI NIH HHS P30 EY011373NEI NIH HHS R01 EY016813NEI NIH HHS R01 EY034075NHLBI NIH HHS R01 HL148057NIAID NIH HHS R01 AI144115
6 · The paper itself

Abstract

backgroundWe discovered a family of cysteinyl leukotriene (CysLT)-like biomolecules, pseudo leukotrienes (øLTs), produced through radical-induced oxidation of arachidonate.

objectiveWe sought to test hypotheses that øLT levels are elevated in asthma and that øLTs induce CysLT receptor-dependent inflammatory signaling in bronchial epithelial cells.

methodsLiquid chromatography-tandem mass spectrometry analysis determined levels of øLTs in urine from human subjects and in lung samples from mice exposed to house dust mite extract. Inflammatory signaling induced by øLTs and CysLTs in human bronchial epithelial cells were compared.

resultsMean urinary øLTC and øLTD concentrations were elevated 4-fold (P = .004) to 5-fold (P = .0015) in severe asthma. Adding øLTC+øLTD improved the statistical significance of the differences between controls and moderate (P = .0004) or severe (P = .00008) asthma. Pulmonary øLT concentrations were elevated 100% in mice after allergen exposure. øLTs induced phosphorylation of extracellular signal-regulated kinase and protein kinase B (Akt) in bronchial epithelial cells, which was inhibited by CysLT receptor antagonists.

conclusionsUrinary øLTs are new biomarkers that may facilitate noninvasive assessment of asthma severity and the efficacy of therapeutic measures. Presumably øLTs contribute to CysLT receptor-mediated inflammation through CysLT-like inflammatory biological activities previously ascribed uniquely to CysLTs. øLTs provide a mechanistic link between radical-induced biochemistry, activation of the extracellular signal-regulated kinase/Akt pathway, and asthma. These discoveries require re-examination of long-held disease paradigms for the involvement of CysLTs in asthma pathology and reconsideration of the mechanistic basis for the efficacy of CysLT receptor antagonists for ameliorating chronic asthma. Inhibiting the biosynthesis of øLTs may provide new therapeutic strategies for preventing asthmatic inflammation.

Indexed as

AsthmaLeukotrienesAdultAllergensAnimalsCysteineEpithelial CellsFemaleHumansMaleMiceMiddle AgedOxidation-ReductionProto-Oncogene Proteins c-aktReceptors, LeukotrieneSignal TransductionAllergensCysteinecysteinyl-leukotrieneLeukotrienesProto-Oncogene Proteins c-aktReceptors, LeukotrieneAktasthmabiomarkercysteinyl leukotriene receptorERKinflammationmontelukastPseudo leukotrienezafirlukast

Identifiers

PMID41101738
PMCPMC13446106

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.