Causal Associations Between Immune Cell Phenotypes and Varicose Veins: A Mendelian Randomization Analysis

Annals of Vascular Surgery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Circulating cell-free DNA methylation analysis of pancreatic cancer patients for early noninvasive diagnosis

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: March 10, 2025

Background Aberrant hypermethylation of genomic DNA CpG islands (CGIs) is frequently observed in human pancreatic cancer (PAC). A plasma cell-free (cfDNA) methylation analysis method can be utilized for the early and noninvasive detection PAC. This study also aimed to differentiate PAC from other types. Methods We employed methylated tandem amplification sequencing (MCTA-Seq) method, which targets approximately one-third CGIs, on samples patients (n = 50) healthy controls 52), as well cancerous adjacent noncancerous tissue 66). The method’s efficacy detecting distinguishing it hepatocellular carcinoma (HCC), colorectal (CRC), gastric (GC) was evaluated. Additionally, a score typing system established. Results identified total 120 cfDNA biomarkers, including IRX4 , KCNS2 RIMS4 blood. panel comprising these biomarkers achieved sensitivity 97% 86% discovery validation cohorts, respectively, with specificity 100% both cohorts. scoring systems were clinically applicable. Furthermore, we hundreds differentially between HCC, CRC, GC. Certain combinations markers used highly specific (approximately 100%) algorithm GC Conclusions Our PAC, offering novel approach early, diagnosis

Language: Английский

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Metabolic reprogramming shapes the immune microenvironment in pancreatic adenocarcinoma: prognostic implications and therapeutic targets

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

Published: March 21, 2025

Introduction Pancreatic adenocarcinoma (PAAD) is characterized by a profoundly immunosuppressive tumor microenvironment (TME) that limits the efficacy of immunotherapy. Emerging evidence suggests tumor-specific metabolic reprogramming may drive disease progression and shape immune landscape in PAAD. Methods We integrated multi-omics data from TCGA, GEO, ICGC to identify key metabolism-related genes (MRGs) influence cell infiltration, progression, patient survival. Based on nine pivotal MRGs (including ANLN, PKMYT1, HMGA1), we developed validated novel metabolic-prognostic index (MPI). Functional enrichment analyses were conducted elucidate pathways associated with different MPI risk groups. In vitro experiments drug sensitivity performed confirm oncogenic role selected explore their therapeutic implications. Results The effectively stratified patients into high- low-risk High-MPI scores correlated poor overall survival, elevated mutation burden (TMB), an TME, evidenced reduced CD8⁺ T-cell infiltration increased expression checkpoints (PD-L1, TGF-β). revealed glycolysis folate biosynthesis as dominant high-MPI groups, whereas fatty acid metabolism prevailed low-MPI Experimental validation underscored ANLN promoting epithelial-mesenchymal transition (EMT) evasion via NF-κB signaling. knockdown significantly glycolytic activity, migration, evasion. Drug indicated resistance gemcitabine but afatinib patients. Although TIDE analysis predicted checkpoint inhibitor (ICI) tumors, subset showed favorable responses anti-PD-L1 therapy. Discussion These findings provide comprehensive framework for understanding how shapes PAAD’s TME affects treatment outcomes. By accurately stratifying patients, serves promising tool guide decisions, including targeted therapy selection immunotherapy prediction, ultimately offering potential more personalized management

Language: Английский

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Immune cells mediate the effect of plasma lipidomes on IgA nephropathy: a Mendelian randomization study

Renal Failure, Journal Year: 2025, Volume and Issue: 47(1)

Published: May 6, 2025

IgA nephropathy (IgAN) is a leading cause of chronic kidney disease, often associated with dyslipidemia and immune dysfunction. This study employs Mendelian randomization (MR) to investigate the causal relationship between plasma lipidomes IgAN, focus on potential mediating role cells. We analyzed 179 genetically predicted IgAN gene using two-sample (TSMR) multivariable MR based summary-level data from genome-wide association study, results were validated by liquid chromatography-mass spectrometry. Furthermore, we quantified proportional effect cell-mediated TSMR. identified significant relationships 3 risk examining lipidome traits as exposures. To whether impact lipid groups specific, performed TSMR analyses exposure factors 4 nephritides outcomes. Specifically, only phosphatidylinositol (18:1_20:4) was found have negative incidence (IVW method, p = 0.01, OR 0.71, 95% CI 0.55 - 0.92). Our further analysis focused 8 cells IgAN. 2 cell phenotypes that may contribute (18:1_20:4)-mediated careful screening. findings provide robust genetic evidence supporting link acting mediators. Phosphatidylinositol emerges promising biomarker for stratification, early detection, therapeutic intervention. Modulating its levels offer novel avenues management.

Language: Английский

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