Liver cancer cells as the model for developing liver-targeted RNAi therapeutics

Biochemical and Biophysical Research Communications, Journal Year: 2023, Volume and Issue: 644, P. 85 - 94

Published: Jan. 6, 2023

Language: Английский

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Genetic insights into repurposing statins for hyperthyroidism prevention: a drug-target Mendelian randomization study

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

Published: Feb. 15, 2024

Background Current therapeutic measures for thyroid dysfunction are limited and often accompanied by adverse effects. The use of lipid-lowering drugs like statins has recently been associated with lower eye diseases risk. Objective To investigate the implications genetically proxied on dysfunction. Methods In this drug-target Mendelian randomization (MR) study, we utilized genetic variants within drug target genes low-density lipoprotein (LDL) or triglyceride (TG), derived from a genome-wide association study (GWAS) meta-analysis (N ≤ 188,577), to simulate lifelong interventions. Genetic summary statistics outcomes were retrieved GWAS datasets Thyroid Omics Consortium 54,288) UK Biobank = 484,598). Inverse-variance-weighted MR (IVW-MR) method was performed as primary analysis, followed validation in colocalization analysis. A subsequent two-step analysis conducted identify biomarkers mediating identified drug-outcome association. Results IVW-MR mimicry 3-hydroxy-3-methylglutarylcoenzyme reductase (HMGCR) inhibitors (e.g. statins) significantly risk hyperthyroidism two independent (OR 1 , 0.417 per 1-mmol/L LDL-C; 95% CI 0.262 0.664; P 2.262 × 10 -4 ; OR 2 0.996; 0.993-0.998; 0.002). Two-step revealed eighteen linked HMGCR inhibition, insulin-like growth factor (IGF-1) levels 2.108% negative causal relationship between inhibition hyperthyroidism. Conclusion This supports promising strategy suggests its underlying mechanisms may extend beyond lipid metabolism. Further investigations through laboratory studies clinical trials necessary confirm elucidate these findings.

Language: Английский

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Causal association between remnant cholesterol level and risk of cardiovascular diseases: a bidirectional two sample mendelian randomization study

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 7, 2024

Serum lipids have been associated with an increased risk of various cardiovascular diseases (CVDs) in several observational studies, but the causal inference between remnant cholesterol (RC) levels and CVDs has not established. The purpose this study was to investigate whether there is a relationship RC developing by bidirectional two-sample Mendelian randomization (TSMR) analysis. One TSMR analysis performed using publicly released large-scale genome-wide association (GWAS) data. Inverse variance weighted (IVW) method chosen as main method, MR-Egger, median, simple mode, mode were used supplementary methods. We conducted series sensitivity analyses assess robustness results, including Cochran's Q test, MR-Egger intercept leave-one-out analysis, funnel plot. IVW revealed that genetically predicted serum level significantly ischemic heart disease (OR = 1.409, 95%CI 1.284-1.546, P value 4.753E-13), unstable angina pectoris 1.621, 1.398-1.880, 1.672E-10), myocardial infarction 1.526, 1.337-1.741, 3.771E-10), cardiac arrest 1.595, 1.322-1.924, 1.076E-06), failure 1.086, 1.009-1.169, 0.028), hypertension 1.089, 1.043-1.136, 9.458E-05), major coronary (CHD) events 1.515, 1.376-1.669, 3.217E-17), atherosclerosis 1.388, 1.231-1.564, 7.739E-08), arrhythmias 1.067, 1.008-1.130, 0.025), atrial fibrillation flutter 1.122, 1.039-1.211, 0.003). Additionally, associations these remained significant after correcting for false discovery rate (all < 0.05). However, did find any cardiomyopathy pericarditis (both > Heterogeneity existed IVs disease, pectoris, infarction, failure, hypertension, CHD events, cardiomyopathy, atherosclerosis, test Moreover, no horizontal pleiotropy showed effects (except arrhythmias) are driven single SNP. plots obvious potential bias our study. In replication positively 43.12% higher artery disease. This present supported link heightened CVDs, indicating RC-lowering treatment might be effective preventing CVDs.

Language: Английский

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A bibliometric analysis of immunotherapy for atherosclerosis: trends and hotspots prediction

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

Published: Nov. 19, 2024

An increasing number of studies have demonstrated that immunotherapy may play a significant role in treating Atherosclerosis and has emerged as promising therapy this field. The aim study is to provide comprehensive perspective through bibliometric analysis investigate the existing hotspots frontiers.

Language: Английский

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Cholesterol-modifying strategies for alzheimer disease: promise or fallacy?

Expert Review of Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

As the world population ages, Alzheimer disease (AD) prevalence increases. However, understanding of AD etiology continues to evolve, and pathophysiological processes involved are only partially elucidated. One compound suspected play a role in development progression is cholesterol. Several lines evidence support this connection, yet it remains unclear whether cholesterol-modifying strategies have potential applications clinical management AD. A deep literature search using PubMed was performed prepare narrative review. The search, early 2024, inclusive from 1990 2024. After providing an overview cholesterol metabolism, study summarizes key preclinical studies that investigated therapies laboratory models It also past current trials testing specific targets modulated by anti-cholesterol patients. Based on epidemiological mechanistic studies, likely plays etiology. use could be promising treatment approach if administered at presymptomatic phases, but unlikely efficient mild, moderate, late stages. recommendations provided for hypercholesterolemia

Language: Английский

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