Hyperlipidemia remains a leading modifiable risk factor for cardiovascular morbidity and mortality. Statins are considered the cornerstone of treatment; however, their adverse effects and limited effi Show more
Hyperlipidemia remains a leading modifiable risk factor for cardiovascular morbidity and mortality. Statins are considered the cornerstone of treatment; however, their adverse effects and limited efficacy in certain patient populations necessitate exploration of novel therapeutic avenues. Epiafzelechin (EZN), a flavanol with established antioxidant and anti-inflammatory properties, was investigated for its potential role in lipid metabolism using an integrative approach combining network pharmacology, molecular docking, and in vivo validation. Putative EZN targets were predicted through SuperPred, Way2Drug, and PharmMapper, and intersected with hyperlipidemia-related genes from GeneCards, DisGeNET, and CTD. Overlapping genes were subjected to protein-protein interaction (PPI) mapping, hub gene identification, and pathway enrichment analysis. Molecular docking was conducted to assess the binding affinity of EZN to lipid-regulating proteins. Therapeutic efficacy of EZN was also evaluated in a TWR-1339-induced hyperlipidemic rat model using biochemical assays and real-time PCR for gene expression profiling. A total of 105 genes were identified, involved in lipid transport, inflammatory signaling, and metabolic regulation. Functional enrichment and PPI analysis highlighted HMGCR, PCSK9, PPAR- Show less
To determine whether long-term residential air pollution [AP; ozone (O₃) and fine particulate matter (PM₂.₅)] is associated with (1) incident mild cognitive impairment (MCI) or Alzheimer’s disease (AD Show more
To determine whether long-term residential air pollution [AP; ozone (O₃) and fine particulate matter (PM₂.₅)] is associated with (1) incident mild cognitive impairment (MCI) or Alzheimer’s disease (AD), (2) biomarkers of core and AD-relevant pathology, and (3) whether these relationships are moderated by APOE4+/- (carrier/non-carrier of one or both ε4 alleles) status or mediated by neuroinflammation. Sample included 795 participants (Mage 68.7 ± 7.9; 68% female) from the Wisconsin Alzheimer’s Disease Research Center and Wisconsin Registry for Alzheimer’s Prevention parent studies, both enriched for AD risk at enrollment based on parental AD history. Residential zip code and 2009–2021 EPA-based annual AP reports were used to estimate individual exposure. Cox proportional hazards models assessed MCI/AD risk. Linear regressions examined the relationships between AP exposure and biomarkers of core and AD-relevant pathology, with and without APOE4 + stratification. Causal mediation analysis examined whether markers of inflammation mediated the AP-AD pathology relationships. Neither O₃ nor PM₂.₅ exposure predicted MCI/AD incidence nor core AD pathology (Ps > 0.05). Higher PM₂.₅ was associated with higher CSF GFAP levels ( Show less