Application Value of Myocardial Segmental Thickness Variability Measured by Echocardiography in Distinguishing Ischemic and Nonischemic Dilated Cardiomyopathy

Journal of Clinical Ultrasound, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

ABSTRACT Purpose The aim of this study is to evaluate the clinical value myocardial segmental thickness variability (STV) measured by echocardiography in distinguishing ischemic cardiomyopathy (ICM) from nonischemic dilated (NIDCM). Methods This included 120 patients diagnosed with cardiomyopathy, divided into ICM ( n = 43) and NIDCM 77) groups based on coronary angiography. Traditional echocardiographic parameters, STV, regional wall motion abnormalities (RWMA) were compared. diagnostic STV was assessed using receiver operating characteristic (ROC) curve analysis. Results There no significant differences traditional parameters between groups. group had a significantly higher mean compared group. An threshold 0.768 provided sensitivity 86.0% specificity 94.8% for NIDCM. Combining RWMA improved accuracy. Conclusion valuable, noninvasive tool differentiating NIDCM, offering high specificity. approach enhances precision, supporting its use practice guide appropriate treatment strategies.

Language: Английский

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Potential Therapeutic Targets of PANoptosis for Myocardial Infarction: A Summary-Data-Based Mendelian Randomization Study Integrating eQTL, mQTL, and Multi-GWAS Data

Cardiovascular Innovations and Applications, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 1, 2025

Language: Английский

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Causal relationship between drug target genes of LDL-cholesterol and coronary artery disease: drug target Mendelian randomization study

Lipids in Health and Disease, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 13, 2025

High LDL-cholesterol (LDL-C) is a well-known risk factor for coronary artery disease (CAD). PCSK9, HMGCR, NPC1L1, ACLY, and LDLR gene have been reported as lipid lowering drug genes related to LDL-C lowering. However relevant Asian studies were rare. We examined the causality between LDL-c target CAD using Korean Japanese data two sample Mendelian Randomization (MR) method. conducted two-sample MR analysis of (7 Single-nucleotide polymorphisms (SNP) in 6 SNPs 5 9 3 LDLR) CAD. used summary statistics from Genome Epidemiology Study (KOGES) data, Biobank Japan (BBJ) data. For every 10 mg/dl decrease determined by four significant PCSK9 gene, decreased approximately 20% (OR = 0.80, 95% CI: 0.75–0.86). The 10% due six HMGCR 0.90, 0.86–0.94). Due LDLR, 26% 0.74, 0.66–0.82). combined effect on showed largest size reduced induced these together was OR 0.78 (95%CI, 0.74–0.83). Finally, all three (PCSK9, 0.85 0.79–0.91). reduction estimated significantly found potential proxy research design clinical trials drugs.

Language: Английский

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Multi‐Omic Insight Into the Molecular Networks in the Pathogenesis of Coronary Artery Disease

Journal of the American Heart Association, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Background Genome‐wide association studies have revealed numerous loci associated with coronary artery disease (CAD). However, some potential causal/risk genes remain unidentified, and causal therapies are lacking. Methods Results We integrated multi‐omics data from gene methylation, expression, protein levels using summary data‐based Mendelian randomization colocalization analysis. Candidate were prioritized based on protein‐level associations, probability, links to methylation expression. Single‐cell RNA sequencing used assess differential expression in the arteries of patients CAD. TAGLN2 ( Transgelin 2 ), APOB Apolipoprotein B GIP Glucose‐dependent insulinotropic polypeptide ) identified as most strongly CAD, exhibiting significant association. Higher at specific Cytosine‐phosphate‐Guanine sites negatively correlated its a lower risk whereas higher circulating positively CAD (odds ratio,1.66 [95% CI, 1.32–2.08). These results suggest distinct regulatory mechanisms for . In contrast, showed positive associations risk, DHX58 DExH‐box helicase 58 SWAP70 Switch‐associated 70 decreased risk. Conclusions Our findings provide evidence suggesting that , This work provides novel insights into molecular highlights integrating uncover relationships cannot be fully captured by traditional genome‐wide studies.

Language: Английский

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Therapeutic Target Discovery for Multiple Myeloma: Identifying Druggable Genes via Mendelian Randomization

Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 885 - 885

Published: April 5, 2025

Background: Multiple myeloma (MM) is a hematological malignancy originating from the plasma cells present in bone marrow. Despite significant therapeutic advancements, relapse and drug resistance remain major clinical challenges, highlighting urgent need for novel targets. Methods: To identify potential druggable genes associated with MM, we performed Mendelian randomization (MR) analysis. Causal candidates were further validated using single-tissue transcriptome-wide association study (TWAS), colocalization analysis was conducted to assess shared genetic signals between gene expression disease risk. Potential off-target effects assessed through an MR phenome-wide (MR-PheWAS). Additionally, molecular docking functional assays used evaluate candidate efficacy. Results: The identified nine (FDR < 0.05), among which Orosomucoid 1 (ORM1) Oviductal Glycoprotein (OVGP1) supported by both TWAS evidence (PPH4 > 0.75). Experimental validation demonstrated downregulation of ORM1 OVGP1 MM (p 0.05). Pregnenolone irinotecan, as agonists OVGP1, respectively, significantly inhibited cell viability, while upregulating their Conclusions: Our highlights targets MM. efficacy pregnenolone irinotecan suppressing growth suggests application. These findings provide insights into pathogenesis offer promising strategy overcoming resistance.

Language: Английский

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Identification of Novel Protein Biomarkers for Intrahepatic Cholangiocarcinoma by Integrating Human Plasma Proteome with Genome

Journal of Gastrointestinal Cancer, Journal Year: 2025, Volume and Issue: 56(1)

Published: April 17, 2025

Language: Английский

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Proteome Alterations in Cardiac Fibroblasts: Insights from Experimental Myocardial Infarction and Clinical Ischaemic Cardiomyopathy

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3846 - 3846

Published: April 18, 2025

Ischaemic heart disease (IHD) is a chronic condition that can cause pathological cardiac remodelling and failure (HF). In this study, we sought to determine how fibroblasts were altered post-experimental myocardial infarction (MI). Female C57BL6 mice underwent experimental MI by permanent left coronary artery ligation. Cardiac isolated from extracted tissue of subsequently treated with the pro-fibrotic cytokine, TGF-β, for 24 h analysed using high throughput LC-MS/MS analysis. Findings validated mass spectrometry data generated human ventricular analysis, which collected patients ischaemic cardiomyopathy (ISCM) age/sex-matched without clinical HF (NF). Proteomic analysis revealed significant protein expression changes in mouse after MI. These most pronounced at 1 month post-MI, compared earlier time points (3 days week). TGF-β treatment profoundly affected fibroblast cells mice, indicating heightened sensitivity factors injury. Extracellular matrix (ECM) proteins significantly following associated remodelling. Notably, Lox was changed both experiment ISCM. Isolated are more susceptible developing pathogenic traits than normal tissue. ECM these enhanced activities functions evident. may play functional role MI-associated dysfunction.

Language: Английский

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Unveiling causal relationships between addiction phenotypes and inflammatory cytokines: insights from bidirectional mendelian randomization and bibliometric analysis

European Archives of Psychiatry and Clinical Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 26, 2024

Language: Английский

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Identification of Plasma Protein Targets in Sepsis through Integrative Genomic and Proteomic Analysis

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 10, 2024

Objective: To identify plasma protein targets with potential therapeutic implications for sepsis using genetic and proteomic data integration. Methods: We explored proteomics from deCODE Genetics, which measured 4,719 proteins in 35,559 Icelandic individuals, genomics on 361,141 participants the UK Biobank. Utilizing cis-pQTLs as instrumental variables, we conducted Mendelian Randomization to circulating causally linked risk of sepsis. After adjusting false discovery rate (FDR), associated were further analyzed through Protein-Protein Interaction analysis Bayesian colocalization. Ultimately, exhibiting strongest colocalization evidence was subjected molecular docking targeted therapeutics Results: From 229 initial proteins, 27 significant pass FDR correction. Among these, 11 showed positive associations 16 demonstrated negative risk. Interactions indicated strong interactions among 15 related immune inflammatory responses. identified GFER having stable binding nicotinamide, positioning them high-potential drug targets. Conclusion: Our results highlight effectiveness integrating new is particularly promising candidates development.

Language: Английский

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Application of large-scale and multicohort plasma proteomics data to discover novel causal proteins in gastric cancer

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 18, 2024

Gastric cancer (GC) is one of the most common malignant tumors threatening human beings and has a poor prognosis. Therefore, exploring unveiled biomarkers or therapeutic targets for diagnosis treatment GC crucial. A total 5772 protein quantitative trait loci (pQTL) were aggregated from four latest large-scale proteomics cohorts. Two-sample Mendelian randomization (two-sample MR) was utilized to identify causal effect blood plasma proteins on GC. Heterogeneity, pleiotropy, directionality analyses employed evaluate identified via two-sample MR. The robustness results further validated colocalization. drug evaluated reveal compounds that can interfere with these proteins. Ten potential causations in relation identified: LY6D, SLURP1, MLN, PSCA, THSD1, CFTR, PPM1B, KDM3A, TSC1, HCG22. Among proteins, THSD1 considered as reliable due their significant H4 posterior probabilities colocalization analysis absence pleiotropy. Compound 35, nitrosamide, 0175029-0000 drugs small molecules targeting respectively. This study several provided data support new insights into early diagnosis, intervention,

Language: Английский

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