Metabolomics- and proteomics-based multi-omics integration reveals early metabolite alterations in sepsis-associated acute kidney injury

BMC Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 11, 2025

Abstract Background Sepsis-associated acute kidney injury (SA-AKI) is a frequent complication in patients with sepsis and associated high mortality. Therefore, early recognition of SA-AKI essential for administering supportive treatment preventing further damage. This study aimed to identify validate metabolite biomarkers assist clinical diagnosis. Methods Untargeted renal proteomic metabolomic analyses were performed on the tissues LPS-induced mice. Glomerular filtration rate (GFR) monitoring technology was used evaluate real-time function To elucidate distinctive characteristics SA-AKI, multi-omics Spearman correlation network constructed integrating core metabolites, proteins, function. Subsequently, metabolomics analysis explore dynamic changes metabolites serum mice at 0, 8, 24 h. Finally, cohort (28 vs. 28 sepsis) quantitative carried out build diagnostic model via logistic regression (LR). Results Thirteen differential 112 proteins identified through highlight five i.e., 3-hydroxybutyric acid, 3-hydroxymethylglutaric creatine, myristic inosine, which then observed time series experiments The levels creatine increased significantly h, acid 8 while inosine decreased Ultimately, based we recruited 56 named IC3, using (AUC = 0.90). Conclusions We proposed blood consisting screening SA-AKI. Future studies will observe performance these other populations their role.

Language: Английский

Programmed cell death markers in COVID-19 survivors with and without sepsis

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 20, 2025

Sepsis remains a leading cause of mortality, especially in COVID-19 patients, due to delayed diagnosis and limited therapeutic options. While the mechanisms programmed cell death (PCD) sepsis are complex, understanding molecular markers involved these processes may aid assessing disease severity. This study aimed investigate roles PCD markers, inflammatory cytokines, MHC molecules distinguishing severity patients with without sepsis. The adult (≥18 years) who survived COVID-19, grouped into four cohorts: (C19wSepsis), (C19NoSepsis), alone, healthy controls. Serum peripheral blood mononuclear cells (PBMCs) from each cohort were analyzed using enzyme-linked immunosorbent assay (ELISA) flow cytometry. (caspase-3, caspase-1, MLKL, LC3B, p62/SQSTM1), cytokines (IL-1-beta, IFN-gamma), (MHC I-A, II-DRB1) assessed. Statistical analyses performed evaluate differences marker levels between within cohorts. analysis identified two distinct signatures associated first signature, characterized by elevated secreted PCD, IL-1-beta, IFN-gamma, I-A II-DRB1, was common C19wSepsis C19NoSepsis second which more prominent cellular (caspase-1, caspase-3, uniquely cohort. These findings provide insight immune responses COVID-19-related serve as valuable biomarkers for severity, while guiding interventions critical care settings.

Language: Английский

Selenium-Doped Carbon Dots as a Multipronged Nanoplatform to Alleviate Oxidative Stress and Ferroptosis for the Reversal of Acute Kidney Injury

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: May 2, 2025

Acute kidney injury (AKI) is a life-threatening condition characterized by rapid decline in the renal function, primarily caused oxidative stress, inflammation, and ferroptosis. Herein, we present selenium-doped carbon dots (Zt-SeCDs) that integrate antioxidant activity with controlled release of Zileuton, 5-lipoxygenase (ALOX5) inhibitor, under high reactive oxygen species (ROS) conditions. This nanoplatform can efficiently deliver leveraging its inherent properties to achieve targeted prevention treatment AKI. In vitro studies have confirmed Zt-SeCDs eliminate excessive ROS, prevent ferroptotic cell death, modulate inflammatory responses reducing expression key pro-inflammatory cytokines. Additionally, regulate ferroptosis through suppression ALOX5 upregulation glutathione peroxidase 4 (GPX4) expression. The significantly improves promotes regeneration damaged tissue, alleviates processes, death. Moreover, monitoring serum indicators observing pathological changes further potential preventing Notably, activate AMPK/FoxO1 signaling pathway, enhancing endogenous defenses protect tissue from damage. promising not only holds significant promise for AKI, but also aims facilitate clinical application.

Language: Английский