University of Oklahoma Health Sciences Center

Afghan refugees in the US face significant challenges, including limited access to healthcare. This study investigates the relationship between social determinants of health (SDOH), including-material circumstances, psychosocial circumstances, behavioral and/or biological factors - and self-rated health among recently resettled Afghan refugees (who received Special Immigrant Visas) in Oklahoma. Data were collected from 348 Afghan refugees using a community-based survey administered in English, Pashto, or Dari in 2022. Measures included sociodemographic characteristics, SDOH, and self-rated health (assessed using a single-item question asking participants to rate their health as poor, fair, good, very good, or excellent). Multivariable logistic regression analyses examined the associations between sociodemographic factors, SDOH, and self-rated health. Of the 348 participants, 59.5% of participants were male, with an average age of 31.5 years. In terms of behavioral factors, high rates of inadequate fruit and vegetable consumption (55.2%), insufficient sleep (58.0%), and insufficient physical activity (83.6%) were observed. With regard to material circumstances-defined based on the World Health Organization's Commission on Social Determinants of Health (CSDH) framework as physical and economic living conditions-chronic health conditions (12.6%) and disabilities (7.8%) were noted. In adjusted models, chronic health conditions (AOR = 0.41, 95% CI: 0.19-0.86), disability (AOR = 0.31, 95% CI: 0.12-0.79), and inadequate sleep (AOR = 0.46, 95% CI: 0.24-0.89) were significantly associated with poor self-rated health. There were no significant associations found between psychosocial factors and self-rated health. This study highlights the significant impact of SDOH, especially material circumstances and behavioral factors on the well-being of Afghan refugees. Future interventions aimed to improve Afghan refugee health need to consider the roles of SDOH in order to optimize their care.

Brain vascular aging is increasingly recognized as a critical therapeutic target for age-related cognitive decline. Oxidative stress, bioenergetic dysfunction, and molecular damage play central roles in the progression of vascular aging, contributing to cerebrovascular dysfunction and impaired cognitive function. While naturally occurring polyphenols such as resveratrol (RSV) have demonstrated potential in mitigating aging-related pathologies, their poor bioavailability and limited brain targeting efficiency significantly constrain their therapeutic impact. As a result, high doses or advanced drug delivery strategies are necessary to achieve meaningful physiological effects. We introduce a novel nanocarrier system designed to enhance RSV delivery to the cerebral endothelium by leveraging the natural formation of an apolipoprotein E (ApoE)-enriched protein corona around fusogenic liposomes (FL) in vivo . These nanoparticles directly fuse with cytoplasmic cell membranes and thus evade endocytosis. We found that once in the circulation FL spontaneously acquire a protein corona, which is highly enriched in ApoE, a key ligand for brain endothelial low-density lipoprotein receptors (LDLR). Based on this observation, we engineered an ApoE-functionalized protein corona around FL (ApoE-FL) to systematically evaluate whether this mechanism could be exploited for targeted brain delivery. Following optimization and physicochemical characterization, the RSV-loaded liposomes were evaluated in vitro using human cerebral microvascular endothelial cells and in vivo C57BL/6 aged mice to assess their therapeutic potential. Both FL and engineered ApoE-FL liposomal delivery systems exhibited a strong affinity for endothelial cell membranes in vitro . The knockdown of the ApoE receptor, low-density lipoprotein receptor-related protein 1 (LRP1), significantly reduced liposomal docking. Microscopy analysis revealed that both ApoE-FL and non-functionalized FL directly fused with endothelial plasma membranes, thus bypassing intracellular organelles and minimizing lysosomal degradation. This suggests that the naturally formed ApoE corona in vivo may contribute to efficient cerebrovascular targeting, a property successfully replicated by the engineered ApoE corona strategy. In vivo biodistribution and kinetic studies demonstrated that especially ApoE-FL achieved enhanced brain-targeting efficiency, prolonged cerebrovascular retention, and extended targeting distance along the arteriovenous axis. This emphasizes that fusogenic liposomes effectively engage almost the entire microvascular network, including capillaries and post-capillary venules. Functionally, fusogenic liposome-delivered RSV improved blood-brain barrier (BBB) integrity, enhanced neurovascular coupling (NVC) responses, and promoted brain vascularization in aged mice. Single-cell RNA sequencing (scRNA-seq) revealed enhanced endothelial angiogenesis and barrier protective transcriptional profiles in cerebrovascular cells treated with ApoE-FL/RSV, suggesting a molecular basis for the observed vascular benefits. Liposomal RSV delivery achieved near-complete cerebrovascular and cognitive rejuvenation in aged mice applying a 2000-fold lower RSV dose than oral administration used as control sample. Thus, ApoE-FL liposomes exhibited exceptionally high delivery efficiency in deeper brain regions, further expanding their therapeutic potential. These findings underscore the importance of targeted drug delivery in optimizing therapeutic outcomes and establish ApoE-functionalized fusogenic liposomes as a promising strategy for mitigating brain vascular aging and cognitive decline.