Integration of Mendelian Randomization to explore the genetic influences of pediatric sepsis: a focus on RGL4, ATP9A, MAP3K7CL, and DDX11L2

BMC Pediatrics, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 27, 2025

This study aims to explore the genetic characteristics of pediatric sepsis through a combined analysis multiple methods, including Mendelian Randomization (MR), differential gene expression analysis, and immune cell infiltration assessment. It explores their potential as biomarkers for risk involvement in immune-related pathways. Differential was performed using public datasets identify genes with significant changes between patients healthy controls. MR utilized genome-wide SNPs instrumental variables assess causal relationships risk. Bi-directional conducted both forward reverse causality. FDR correction applied adjust comparisons results. Immune investigate genes' roles responses, findings were validated independent datasets. ROC curves constructed predictive performance. identified RGL4,ATP9A,MAP3K7CL, DDX11L2. revealed associations these risk, RGL4 ATP9A upregulated (inflammatory roles), MAP3K7CL DDX11L2 downregulated (protective roles). found no showed key types, demonstrated strong potential. play important response regulation, offering insights into mechanisms that may inform future research treatment.

Language: Английский

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Innovative nanoparticle-based approaches for modulating neutrophil extracellular traps in diseases: from mechanisms to therapeutics

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 6, 2025

Neutrophil extracellular traps (NETs) participate in both host defense and the pathogenesis of various diseases, such as infections, thrombosis, tumors. While they help capture eliminate pathogens, NETs' excessive or dysregulated formation can lead to tissue damage disease progression. Therapeutic strategies targeting NET modulation have shown potential, but challenges remain, particularly achieving precise drug delivery maintaining stability. Nanoparticle (NP)-based systems offer innovative solutions for overcoming limitations conventional therapies. This review explores biological mechanisms formation, their interactions with NPs, therapeutic applications NP-based modulating NETs. We discuss how NPs be designed either promote inhibit provide a comprehensive analysis potential treating NET-related diseases. Additionally, we address current future prospects therapies research, aiming bridge gap between nanotechnology development novel approaches.

Language: Английский

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Association Between Plasma Granzyme B Levels, Organ Failure, and 28-Day Mortality Prediction in Patients with Sepsis

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(5), P. 1461 - 1461

Published: Feb. 21, 2025

Background/Objectives: Sepsis is basically an inflammatory disease that involves the host’s immune response. Granzyme B, a cytotoxic protease, has garnered attention for its involvement in modulating responses. This study aimed to elucidate clinical implications of granzyme B critically ill patients with sepsis, focusing on plasma levels as potential prognostic marker. Methods: We conducted retrospective analysis sequentially collected blood samples from 57 sepsis admitted medical intensive care unit at Severance Hospital, tertiary hospital Seoul, South Korea. Clinical and laboratory data were comparatively analyzed between 28-day survivors nonsurvivors. Results: The number survivor nonsurvivor groups was 32 (56.1%) 25 (43.9%), respectively. Compared survivors, nonsurvivors had higher APACHE II (23.5 vs. 34, p = 0.007) SOFA (10 15, 0.001) scores, well increased serum lactate (1.8 9.2 mmol/L, < (28.2 71 pg/mL, 0.001). exhibited robust area under receiving operating characteristic (AUROC) predicting mortality (AUROC 0.794), comparable (0.804), (0.764), (0.709). combined index demonstrated highest AUROC (0.838) among all investigated predictors. Significant positive correlations observed log various cytokines, including IFN-γ (r 0.780), IL-4 0.540), IL-10 0.534), IL-6 0.520). Conclusions: Plasma fair short-term prediction ICU, suggesting utility risk stratification managing sepsis.

Language: Английский

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Bulk and Single‐Cell Transcriptomic Reveals Shared Key Genes and Patterns of Immune Dysregulation in Both Intestinal Inflammatory Disease and Sepsis

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(4)

Published: Feb. 1, 2025

ABSTRACT Inflammatory bowel disease (IBD) and Sepsis are both characterised by immune dysregulation. Notably, IBD is a factor in the increase septic infections. However, these two conditions' shared molecular pathophysiological mechanisms remain unclear. We used ‘limma’ ‘WGCNA’ analyses to identify common DEGs between conditions. Single‐cell RNA sequencing further assessed cell heterogeneity. machine learning algorithms construct diagnostic markers for Sepsis, which we then validated using receiver operating characteristic curve (ROC) analysis. A mouse model of combined with was constructed, real‐time PCR western blot expression BCL2A1 CEBPB. It found that 58 identified were highly enriched inflammation‐related pathways. analysis revealed CD14 + monocytes (or IL1B macrophages) primarily express hub genes. Both conditions significantly increased proportion this type compared healthy controls. Finally, CEBPB as potential biomarkers have strong potential. Furthermore, confirmed levels elevated mice complicated through observed exacerbates progression Sepsis. conclude macrophages expressing high genes play key role dysregulation associated The overlapping gene pathway alterations cells indicate mechanisms, suggesting new strategies targeted therapeutic interventions.

Language: Английский

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Noninvasive Vagus Nerve Electrical Stimulation for Immune Modulation in Sepsis Therapy

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Sepsis presents a significant medical challenge due to its intense inflammatory response infection, often resulting in high mortality rates. A promising therapeutic strategy targets the cholinergic anti-inflammatory pathway (CAIP), which regulates immune responses. This study investigates ingestion of piezoelectric particles that adhere stomach lining, specifically targeting TRPV1 receptors. In mouse model sepsis, these particles, when activated by low-intensity pulsed ultrasound, generate mild electrical pulses. These pulses stimulate vagal afferent fibers, transmitting signals brain and modulating neural-immune network via CAIP. Consequently, this leads reduction systemic inflammation, mitigating weight loss, alleviating multiple tissue injuries, preventing death cells spleen. approach addresses critical need for noninvasive sepsis therapies, potentially improving patient outcomes. Utilizing portable ultrasound equipment with minimal thermal effects, technique offers safe convenient treatment option, even home use.

Language: Английский

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Comprehensive integration of diagnostic biomarker analysis and immune cell infiltration features in sepsis via machine learning and bioinformatics techniques

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

Published: March 10, 2025

Introduction Sepsis, a critical medical condition resulting from an irregular immune response to infection, leads life-threatening organ dysfunction. Despite advancements, the need for research into dependable diagnostic markers and precise therapeutic targets. Methods We screened out five gene expression datasets (GSE69063, GSE236713, GSE28750, GSE65682 GSE137340) Gene Expression Omnibus. First, we merged first two datasets. then identified differentially expressed genes (DEGs), which were subjected KEGG GO enrichment analyses. Following this, integrated DEGs with key modules as determined by Weighted Co-expression Network Analysis (WGCNA), identifying 262 overlapping genes. 12 core subsequently selected using three machine-learning algorithms: random forest (RF), Least Absolute Shrinkage Selection Operator (LASSO), Support Vector Machine-Recursive Feature Elimination (SVW-RFE). The utilization of receiver operating characteristic curve in conjunction nomogram model served authenticate discriminatory strength efficacy CIBERSORT was utilized evaluate inflammatory immunological sepsis. Astragalus, Salvia, Safflower are primary elements Xuebijing, commonly used clinical treatment Using Traditional Chinese Medicine Systems Pharmacology Database Platform (TCMSP), chemical constituents these herbs their target Results found that CD40LG is not only one identified, but also common active components quercetin, luteolin, apigenin herbs. extracted structure ingredients -flavonoids. Through docking analysis, further validated interaction between flavonoids CD40LG. Lastly, blood samples collected healthy individuals sepsis patients, without administration extraction peripheral mononuclear cells (PBMCs). By qPCR WB analysis. observed significant differences across groups. In this study, pinpointed candidate hub constructed its diagnosis. Discussion This provides potential evidence diagnosis offers insights pathogenesis disease progression

Language: Английский

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Integrating bioinformatics and machine learning for comprehensive analysis and validation of diagnostic biomarkers and immune cell infiltration characteristics in pediatric septic shock

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 26, 2025

This study aims to predict and diagnose pediatric septic shock through the screening of immune infiltration-related biomarkers. Three gene expression datasets were accessible from Gene Expression Omnibus repository. The differentially expressed genes identified using R 4.3.2 ( https://www.r-project.org/ ), followed by set enrichment analysis. Thereafter, utilizing machine-learning algorithms. receiver operating characteristic curve was employed assess discrimination effectiveness hub genes. inflammatory status evaluated cell-type identification estimating relative subsets RNA transcripts (CIBERSORT). correlation between diagnostic markers infiltrating cells further examined. Overall, we detected 12 CD177, MCEMP1, MMP8, OLAH examined as indicators for shock, revealing statistically significant differences (P < 0.01) efficacy in validation cohort. cell infiltration analysis suggests that various may contribute onset shock. Furthermore, all characteristics exhibit varying degrees with cells. identifies four potential biomarkers—CD177, OLAH—that provide value novel insights into dysregulation Through integration bioinformatics machine learning methodologies, offer a perspective on mechanisms involved potentially facilitating more targeted personalized therapies individual patients.

Language: Английский

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Sepsis subphenotypes, theragnostics and personalized sepsis care

Intensive Care Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 31, 2025

Language: Английский

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Development of Free Testosterone Chemiluminescence Detection Kit and Its Clinical Application

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

Published: April 7, 2025

Background: Free testosterone makes up only 1–2% of the total in blood, but it is active form and enters cells directly to work. The level substantially affected by sex hormone-binding globulin, whereas free can better reflect actual biological activity. clinical detection levels serum important for diagnosis related diseases, such as male hypogonadism, polycystic ovary syndrome, metabolic osteoporosis, Alzheimer's disease, hypogonadism. However, existing methods have problems, insufficient sensitivity, complex operation, high cost, there an urgent need develop efficient accurate technologies. We aimed a chemiluminescence kit conducted comprehensive performance evaluation. Methods: content was quantified using competitive immunoassay method. Free derivatives competed binding biotinylated testosterone-specific antibodies. reaction procedure determined concentration magnetic beads optimized, antibodies were biotinylated, labeled with acridinium ester, working concentrations both fine-tuned. Following determination process, assay evaluated through series tests assessing linearity, limit blank, accuracy, precision, stability, specificity, relevance. Samples collected from 1615 2035 female patients, their measured. Finally, significance diagnostic applications analyzed. Results: The linear r > 0.99, blank 0.021 pg/mL, accuracy deviation < 5%, imprecision stability lasted 12 months. There no cross-reactivity similar substances. In total, 392 samples analysis methodological comparison conducted. correlation coefficient 0.9941, meeting requirements. patient detection. showed significant differences among patients different diagnoses. Prostate malignancy associated lower levels, other diagnoses (such those hair loss) higher levels. Therefore, could serve reference indicator assessment certain diseases. Conclusion: developed this study exhibited excellent performance, low degree automation. It fully meets requirements When tested on samples, be regarded which help doctors make treatments

Language: Английский

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Engineered bioorthogonal cell delivery system for in situ antimicrobial peptide recruitment during systemic bacterial infection

Acta Biomaterialia, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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