Evidence map›Paper›PMID 41784867›Full record

ArticleMolecular and cellular pediatrics2026

Time-resolved urinary proteomics reveals heme-associated oxidative stress responses in neonatal hypoxic-ischaemic encephalopathy.

Magdalena Zasada, Maciej Suski, Marta Olszewska, Aleksandra Kowalik, Natalia Łapińska, Weronika Pogoda, Przemko Kwinta

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Article in Molecular and cellular pediatrics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Magdalena Zasada *Department of Pediatrics, Jagiellonian University Medical College, University Children's Hospital, Wielicka 265 Street, Krakow, 30- 663, Poland. magdalena.zasada@uj.edu.pl.
Maciej Suski *Department of Pharmacology, Faculty of Medicine, Jagiellonian University Medical College, Grzegórzecka 16 Street, Krakow, 31-531, Poland.
Marta OlszewskaDepartment of Pediatrics, Jagiellonian University Medical College, University Children's Hospital, Wielicka 265 Street, Krakow, 30- 663, Poland.
Aleksandra KowalikDepartment of Pediatrics, Jagiellonian University Medical College, University Children's Hospital, Wielicka 265 Street, Krakow, 30- 663, Poland.
Natalia ŁapińskaDepartment of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 Street, Krakow, 30-688, Poland.
Weronika PogodaProteomics Laboratory, Centre for the Development of Therapies for Civilization and Age- Related Diseases CDT-CARD, Jagiellonian University Medical College, Skawińska 8 Street, Krakow, 31- 066, Poland.
Przemko KwintaDepartment of Pediatrics, Jagiellonian University Medical College, University Children's Hospital, Wielicka 265 Street, Krakow, 30- 663, Poland.

Funding

Narodowe Centrum Nauki 2020/37/B/NZ5/01099
6 · The paper itself

Abstract

backgroundNeonatal hypoxic-ischemic encephalopathy (HIE) triggers systemic oxidative stress and redox imbalance, contributing to multi-organ injury. Urine is a noninvasive matrix for longitudinal profiling of molecular responses, yet time-resolved proteomic studies in HIE are limited.

methodsWe performed longitudinal SWATH-MS proteomic profiling of urine from term neonates with moderate-to-severe HIE treated with therapeutic hypothermia (n = 16) and non-asphyxiated controls (n = 19) at six time points during the first eight days of life. Proteins identified in ≥ 80% of samples were quantified, and differential abundance, temporal clustering, pathway enrichment, and upstream regulatory networks were analyzed.

resultsApproximately 1,000 proteins were quantified per sample. A total of 438 proteins were differentially abundant, with most changes transient and ten persistent. Early HIE urine showed marked elevation of hemoglobin subunits and sequential induction of haptoglobin and hemopexin, indicating staged heme scavenging and oxidative stress responses. Pathway enrichment revealed inhibition of neutrophil-associated innate immunity and activation of heme detoxification, lipoprotein remodeling, and PPAR signaling. Temporal clustering demonstrated stage-specific proteomic transitions, with partial normalization toward controls by days 6-8. Ingenuity Pathway Analysis identified six upstream regulators: Interleukin-1 alpha (IL1A), Tumor Necrosis Factor (TNF), ETS Homologous Factor (EHF), Peroxisome Proliferator-Activated Receptor Delta (PPARD), Thioredoxin-Interacting Protein (TXNIP), and Solute Carrier Family 2 Member 3 (SLC2A3), coordinating inflammation, redox control, and metabolic adaptation.

conclusionsWe identified transient and sustained proteomic shifts that trace coordinated changes in oxidative stress, heme metabolism, and metabolic adaptation, alongside key regulators such as IL1A, TNF, EHF, PPARD, and TXNIP. The progression from early injury-related divergence to partial recovery by day 8 highlights the dynamic nature of post-insult remodeling. These findings support urinary proteomics as a robust, non-invasive tool for probing HIE pathophysiology and point to promising biomarker and pathway candidates for future studies.

Indexed as

HemeHypoxic-ischemic encephalopathyInflammationInnate immunityNeonateOxidative stressProteomeUrine

Identifiers

PMID41784867
PMCPMC12963591

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