Identification and validation of m6A RNA methylation and ferroptosis-related biomarkers in sepsis: transcriptome combined with single-cell RNA sequencing

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

Published: March 7, 2025

Background Sepsis, a systemic inflammatory response syndrome triggered by infection, is associated with high mortality rates and an increasing global incidence. While N 6 -methyladenosine (m A) RNA methylation ferroptosis are implicated in diseases, their specific genes mechanisms sepsis remain unclear. Methods Transcriptomic datasets of sepsis, along m A-related A-RGs) ferroptosis-related (FRGs), were sourced from public databases. Differentially expressed (DEGs) identified between the control groups, A-RGs analyzed through weighted gene co-expression network analysis (WGCNA) to uncover A module genes. These then intersected DEGs FRGs identify candidate Biomarkers using two machine learning methods, receiver operating characteristic (ROC) curves, expression validation, followed development nomogram. Further in-depth analyses biomarkers performed, including functional enrichment, immune infiltration, drug prediction, molecular docking. Single-cell was conducted distinct cell clusters evaluate biomarker at single-cell level. Finally, reverse transcription–quantitative PCR (RT-qPCR) employed validate clinical samples. Results DPP4 TXN as key biomarkers, showing higher samples, respectively. The nomogram incorporating these demonstrated strong diagnostic potential. Enrichment highlighted involvement spliceosome function antigen processing presentation. Differential types revealed significant correlations cells, such macrophages activated dendritic cells. Drug predictions gambogenic acid valacyclovir potential treatments, which successfully docked biomarkers. that predominantly CD4 + memory CD16 CD14 monocytes. further validated Conclusions for insights into infiltration therapeutic level, offering novel perspectives treatment.

Language: Английский

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Immunoglobulin G N-Glycome as a biomarker of mortality risk in Escherichia coli induced sepsis

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

Published: March 17, 2025

Sepsis is a life-threatening syndrome caused by an imbalance in the inflammatory response to infection that can lead high mortality rate. Escherichia coli common pathogen causes sepsis. The role of immunoglobulin G N-glycome estimating patients with sepsis remains unknown. This study aims reveal clinical application as potentially novel biomarker predict risk coli-induced serum levels 100 adult septic patient samples on day intensive care unit (ICU) admission, and healthy volunteers were measured analyzed. Immunoglobulin was compared existing scores predicting in-hospital death. We identified fucosylation level significantly decreased patients. Importantly, bisecting GlcNAc, sialylation, galactosylation have different between control groups. In addition, AUC values SOFA score combined GP4, GP5, GP9 0.76 (95%CI: 0.61 0.90), 0.58 0.40 0.7) 0.57 0.38 0.76). value GP4 GP7 0.85 0.93) concentrations at ICU admission are valuable for sepsis, suggesting may be biomarker.

Language: Английский

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Machine learning-based transcriptmics analysis reveals BMX, GRB10, and GADD45A as crucial biomarkers and therapeutic targets in sepsis

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

Published: March 31, 2025

Sepsis is a life-threatening condition characterized by dysregulated host response to infection, resulting in high mortality rates and complex clinical management. This study leverages transcriptomics machine learning (ML) identify critical biomarkers therapeutic targets sepsis. Analyzing microarray data from the Gene Expression Omnibus (GEO) datasets GSE28750, GSE26440, GSE13205, GSE9960, we discovered three pivotal that BMX (bone marrow tyrosine kinase gene on chromosome X), GRB10 (growth factor receptor bound protein 10), GADD45A arrest DNA damage inducible alpha), exhibiting exceptional diagnostic accuracy (AUC >0.9). Functional enrichment analyses revealed these genes play key roles reactive oxygen species metabolism immune regulation. Specifically, was positively correlated with eosinophils inversely associated activated NK cells, CD8 T memory CD4 cells. showed positive correlations eosinophils, mast neutrophils, while linked M2 macrophages. Additionally, constructed comprehensive mRNA-miRNA-lncRNA regulatory network, identifying interactions may drive sepsis pathogenesis. Molecular docking dynamics simulations validated Bendroflumethiazide, Cianidanol, Hexamidine as promising agents targeting biomarkers. In conclusion, this integrated approach provides profound insights into molecular mechanisms underlying sepsis, pinpointing BMX, GRB10, targets. These findings significantly enhance our understanding of pathophysiology lay groundwork for developing personalized strategies aimed at improving patient outcomes.

Language: Английский

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Clinical value of Lp-PLA2, LDL-C, HDL-C, hs-CRP, leukocyte, FPG and HbA1c in type 2 diabetes mellitus patients with acute ischemic stroke

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

Published: April 17, 2025

To evaluate the clinical significance of human plasma lipoprotein-associated phospholipase A2 (Lp-PLA2), low-density lipoprotein cholesterol (LDL-C), high-density (HDL-C), high-sensitivity C-reactive protein (hs-CRP), leukocyte count, fasting glucose (FPG), and glycated hemoglobin (HbA1c) in patients with Type 2 diabetes mellitus (T2DM) acute ischemic stroke (AIS). A total 155 T2DM AIS, admitted to Second Affiliated Hospital Shantou University Medical College between October 2023 2024, were included group. Additionally, 86 subjects from same period control Serum levels Lp-PLA2, LDL-C, HDL-C, hs-CRP, FPG, HbA1c compared T2DM-AIS group group, as well among different infarct sizes degrees neurological impairment. The value above indexes diagnosis AIS was analyzed by receiver operating characteristic curve (ROC curve). Lp-PLA2 (142.9 [115.8, 178.3] ng/L), LDL-C (3.4 [2.6, 4.2] mmol/L), hs-CRP (3.6 [1.5, 11.2] mg/L), leukocytes (8.0 [6.8, 10.3] × 10^9/L), FPG (10.2 [7.5, 14.4] %) significantly higher (Lp-PLA2: 102.1 [76.6, 121.9] ng/L, LDL-C: 3.2 [2.4, 3.7] mmol/L, hs-CRP: 2.4 [0.9, 5.2] mg/L, leukocytes: 7.0 [6.1, 8.1] 10^9/L, FPG: 7.4 HbA1c: [6.4, 8.2] %). In contrast, serum HDL-C (1.1 1.3] mmol/L) lower than those (1.3 [1.1, 1.5] which correlated larger size greater injury. ROC analysis indicated that combined use seven tests had an AUC 0.906, a sensitivity 77.40% specificity 95.30%. Monitoring provides comprehensive assessment cerebral infarction serves auxiliary indicators for evaluating disease severity.

Language: Английский

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Development of a ferroptosis-related gene prognostic model and molecular subgroups characterization in sepsis

Molecular Immunology, Journal Year: 2025, Volume and Issue: 178, P. 1 - 11

Published: Jan. 6, 2025

Language: Английский

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Association between Advanced lung cancer inflammation index and all- cause mortality in critically ill patients with sepsis: analysis of the MIMIC- IV database

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Background This study aimed to explore the association between advanced lung cancer inflammation (ALI) index and risk of mortality in critically ill patients with sepsis. Methods retrospective included 6489 sepsis from Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. The participants were grouped into four groups according ALI quartiles. outcome was in-hospital ICU mortality. Cox proportional hazards regression analysis restricted cubic spline used evaluate clinical outcomes Results A total (59.1% male) study. intensive care unit (ICU) 25.4% 19.0%, respectively. Multivariate showed that independently associated all-cause After confounders adjusting, an elevated had a significant hospital (adjusted hazard ratio, 0.990; 95% confidence interval, 0.985–0.996; P < 0.001) 0.991; 0.985–0.997; = 0.004). Restricted splines revealed non-linear patients. Conclusion Our indicates has However, further confirmation these findings necessitates larger prospective studies.

Language: Английский

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The Efficacy of a Novel Medical Artificial Intelligence Large Model(MedGo)-Guided Identification and Personalized Treatment of Sepsis: Study Protocol for a Single- centered Randomized Controlled Trial

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Background Sepsis, a life-threatening organ dysfunction resulting from dysregulated host response to infection, remains major global health challenge with high morbility and mortality. Current diagnostic management frameworks still lack the satisfied sensitivity specificity for early detection personalized treatment. In this study, we aim evaluate efficacy of MedGo-Sepsis, novel large language model developed by our collaborating team us that integrates clinical immunological data, guide identification treatment sepsis in emergency department. Methods This single-center, randomized controlled trial will enroll adult patients presenting department suspected sepsis. Participants be 1:1 at physician level either intervention group receiving standard care augmented MedGo-Sepsis guidance or control alone. provides real-time risk assessments, detailed immune parameter profiling, stratification based on phenotypes, recommendations. The primary outcome is 28-day all-cause Secondary outcomes include changes Sequential Organ Failure Assessment (SOFA) score, accuracy, time appropriate antibiotic administration, resource utilization, patient-reported outcomes, workload. Discussion assess whether through integration individualized data technology, improves compared care. combination enhanced diagnostics tailored therapeutic strategies has potential advance precision critical setting. Trial registration been prospectively registered Chinese Clinical Trial Registry (ChiCTR2400094116) December 17, 2024.

Language: Английский

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Identification of CD38^high Monocyte as a Candidate Diagnostic Biomarker and Therapeutic Target for Sepsis

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Abstract Sepsis is characterized by a systemic host response to infection. Monocytes, as major mediators of acute infection, are implicated in complications among critically ill patients. Identifying key monocyte subsets and their activation states essential for diagnosis delineating new therapeutic targets sepsis. Here, single cell transcriptome sequencing mass cytometry used assess alterations the composition function peripheral monocytes patients with sepsis, CD38 high circulation specifically accumulated within first 24 h detectable conventional flow discriminate sepsis sterile inflammation, associated 28‐day mortality bacterial Targeting therapy markedly reduces inflammatory primary mice model. Mechanistically, exhibit hyperactivated glycolysis hypoxia‐inducible factor‐1α (HIF‐1α) due NAD + consumption. Glycolytic metabolite methylglyoxal (MGO) found regulate expression CD38, establishing CD38‐HIF‐1α/glycolysis/MGO loop that exacerbates sepsis‐induced immune dysregulation. These findings demonstrate might serve candidate diagnostic biomarker target

Language: Английский

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Prognostic Value of the Lactate/Albumin Ratio in Sepsis-Related Mortality: An Exploratory Study in a Tertiary Care Center with Limited Resources in Western Mexico

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(8), P. 2825 - 2825

Published: April 19, 2025

Background and Objectives: Sepsis is a critical condition with high mortality rates worldwide. The early identification of patients at an elevated risk remains significant clinical challenge. lactate/albumin (L/A) ratio has emerged as potential prognostic biomarker in critically ill patients. This exploratory study aimed to evaluate the L/A predictor sepsis or septic shock describe demographic characteristics affected tertiary referral hospital Western Mexico. Materials Methods: A retrospective cross-sectional was conducted including diagnosed between January 2022 June 2023. Clinical biochemical data, serum lactate albumin levels, were collected from medical records calculate ratio. primary outcome in-hospital mortality. statistical analysis included receiver operating characteristic (ROC) curves ratio’s discriminative capacity, bivariate analysis, multivariate logistic regression identify independent factors for Results: total 141 study, median significantly higher non-survivors compared survivors (0.95 vs. 0.60, p = 0.003). ROC showed area under curve (AUC) 0.651, sensitivity 36.5% specificity 82% cutoff value 1.12. identified levels vasopressor use predictors Conclusions: demonstrates simple accessible sepsis, though its utility requires further validation larger prospective studies.

Language: Английский

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HNL Dimer in plasma is a unique and useful biomarker for the monitoring of antibiotic treatment in sepsis

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(9), P. e0310987 - e0310987

Published: Sept. 26, 2024

Introduction Sepsis is a growing problem worldwide and associated with high mortality morbidity. The early accurate diagnosis effective supportive therapy are critical for combating mortality. aim of the study was to compare kinetics four biomarkers in plasma patients admitted ICU including sepsis during antibiotics treatment. Methods evaluated were HBP (Heparin-binding protein), HNL Dimer (Human Neutrophil Lipocalin), Total PCT (Procalcitonin). Plasma obtained at admission follow-up days 2 3. Antibiotic treatment started or reviewed on ICU. results compared SOFA KDIGO-scores survival. 277 included which 30% had sepsis. other groups categorized as miscellaneous, medical trauma. Results concentrations all highly elevated highest patients. During period decreased already day further so 3 (p<0.00001) contrast unchanged three biomarkers. showed strongest relationships clinical scores (p<0.0001) by multiples regression analysis independently related these scores. Conclusion Our data supports confirms our earlier findings being novel potentially useful tool antibiotic stewardship reflects epithelial cell activity body an interesting biomarker management organ failure such

Language: Английский

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