Causal relationship between immune cells and risk of heart failure: evidence from a Mendelian randomization study

Frontiers in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 11

Published: Jan. 23, 2025

Background Heart failure (HF) is a clinical syndrome resulting from structural damage or dysfunction of the heart. Previous investigations have highlighted critical involvement immune cells in progression heart failure, with distinct roles attributed to different types cells. The objective current research was explore potential connections between characteristics and development HF, as well ascertain nature causality these factors. Methods To assess causal association immunological profiles HF based on publicly available genome-wide studies, we employed two-sample Mendelian randomization technique, utilizing inverse variance weighted (IVW) method our primary analytical approach. In addition, assessed heterogeneity cross-sectional pleiotropy through sensitivity analyses. Results A (MR) analysis conducted using IVW method. At significance level 0.001, identified 40 immunophenotypes that significant relationship HF. There phenotypes failure. These immunophenotypes, 8 which were B cells, 5 cDC, 2 T cell maturation stage, monocytes, 3 myeloid 7 TBNK 13 Treg. Sensitivity analyses validate strength reliability MR findings. Conclusions Our study suggests there appears be effect multiple This discovery provides new avenue for therapeutic treatments target drug development.

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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Integrating network pharmacology and multi-omics to explore the potentiating effect and mechanism of Shenlingcao oral liquid on cisplatin chemotherapy in Lewis lung cancer mice

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119843 - 119843

Published: April 1, 2025

Language: Английский

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Improving precision management of anxiety disorders: a Mendelian randomization study targeting specific gut microbiota and associated metabolites

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: April 9, 2024

Background There is growing evidence of associations between the gut microbiota and anxiety disorders, where changes in microbiotas may affect brain function behavior via microbiota-gut-brain axis. However, population-level studies offering a higher level for causality are lacking. Our aim was to investigate specific associated metabolites that closely related disorders provide mechanistic insights novel management perspectives disorders. Method This study used summary-level data from publicly available Genome-Wide Association Studies (GWAS) 119 bacterial genera phenotype “All disorders” reveal causal effects on identify with A two-sample, bidirectional Mendelian randomization (MR) design deployed, followed by comprehensive sensitivity analyses validate robustness results. We further conducted multivariable MR (MVMR) analysis potential impact neurotransmitter-associated metabolites, bacteria-associated dietary patterns, drug use or alcohol consumption, lifestyle factors such as smoking physical activity observed associations. Results Bidirectional identified three causally disorders: genus Eubacterium nodatum group Ruminococcaceae UCG011 were protective, while an increased risk Further MVMR suggested metabolite-dependent mechanism, primarily driven tryptophan, tyrosine, phenylalanine, glycine cortisol, which consistent previous research findings, probably played significant role mediating these Furthermore, modifying pattern salt, sugar processed meat intake, adjusting state levels, appears be effective approaches targeting manage Conclusion findings offer avenues developing precise metabolites.

Language: Английский

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Causal relationship between immune cells and risk of myocardial infarction: evidence from a Mendelian randomization study

Frontiers in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Aug. 27, 2024

Background Atherosclerotic plaque rupture is a major cause of heart attack. Previous studies have shown that immune cells are involved in the development atherosclerosis, but different play roles. The aim this study was to investigate causal relationship between immunological traits and myocardial infarction (MI). Methods To assess association profiles with based on publicly available genome-wide studies, we used two-sample mendelian randomization (MR) approach inverse variance weighted (IVW) as main analytical method. Sensitivity analyses were heterogeneity horizontal pleiotropy. Results A MR analysis conducted using IVW primary At significance level 0.001, identified 47 immunophenotypes significant MI. Seven these present B cells, five cDC, four T at maturation stage, six monocytes, myeloid 12 TBNK eight Treg cells. performed confirm robustness results. Conclusions Our results provide strong evidence multiple effect risk infarction. This discovery provides new avenue for therapeutic treatments target drug development.

Language: Английский

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An atlas on risk factors for gastrointestinal cancers: A systematic review of Mendelian randomization studies

Preventive Medicine, Journal Year: 2024, Volume and Issue: 189, P. 108147 - 108147

Published: Oct. 3, 2024

Language: Английский

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Gut Microbiota’s role in lipoma development: evidence from mendelian randomization

Frontiers in Genetics, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 15, 2024

Background Lipoma, a benign tumor derived from mesenchymal tissue, significantly affects patients’ physical and psychological wellbeing. Increasing evidence points to strong link between the gut microbiome (GM) lipoma incidence. This study utilizes Mendelian Randomization (MR) assess potential causal relationships GM development. Methods We conducted two-sample MR analysis using genome-wide association (GWAS) data MiBioGen FinnGen explore relationship lipoma. The dataset included 18,340 participants with 14,587 single nucleotide polymorphisms (SNPs), while comprised 412,181 21,306,349 SNPs. employed 5 methods: Inverse Variance Weighted (IVW), Median, Simple Mode, MR-Egger, Mode. Additional assessments Cochran’s Q test for result heterogeneity, PRESSO horizontal pleiotropy, sensitivity analyses through scatter plots, leave-one-out analyses, funnel forest plots. Results IVW method identified 18 gene predictors trans-genus associated risk. Protective effects against (BL) were observed in Eubacterium rectale group, Desulfovibrio, Ruminococcus1, Clostridium sensu stricto1, Lachnospiraceae UCG001; conversely, UCG008 was linked increased BL Desulfovibrio provided protection TS-BL; however, Family XIII AD3011 coprostanoligenes NK4A136 Parasutterella an TS-BL innocuum Anaerotruncus, Ruminiclostridium6, UCG001 offered LS-BL, LS-BL brachy Odoribacter, Butyricimonas, Subdoligranulum, stricto1 protective HFNS-BL; Ruminococcaceae UCG005 HFNS-BL Conclusion Compared malignant tumors, research on lipomas has been relatively limited. study, analysis, new of specific development lipomas. Certain bacterial species may act as or harmful factors formation, offering avenues future treatment strategies. However, additional is required unravel complexity how influences pathogenesis

Language: Английский

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