RESUMO
Lipid-lowering drugs, especially statins, are extensively utilized in clinical settings for the prevention of hyperlipidemia. Nevertheless, prolonged usage of current lipid-lowering medications is associated with significant adverse reactions. Therefore, it is imperative to develop novel therapeutic agents for lipid-lowering therapy. In this study, a chenodeoxycholic acid and lactobionic acid double-modified polyethyleneimine (PDL) nanocomposite as a gene delivery vehicle for lipid-lowering therapy by targeting the liver, are synthesized. Results from the in vitro experiments demonstrate that PDL exhibits superior transfection efficiency compared to polyethyleneimine in alpha mouse liver 12 (AML12) cells and effectively carries plasmids. Moreover, PDL can be internalized by AML12 cells and rapidly escape lysosomal entrapment. Intravenous administration of cyanine5.5 (Cy5.5)-conjugated PDL nanocomposites reveals their preferential accumulation in the liver compared to polyethyleneimine counterparts. Systemic delivery of low-density lipoprotein receptor plasmid-loaded PDL nanocomposites into mice leads to reduced levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TC) in the bloodstream without any observed adverse effects on mouse health or well-being. Collectively, these findings suggest that low-density lipoprotein receptor plasmid-loaded PDL nanocomposites hold promise as potential therapeutics for lipid-lowering therapy.
RESUMO
AIM: To examine trends in public awareness and knowledge of drinking guidelines in the UK since their revision in 2016, which had moved from a daily to a weekly guideline, made the guideline the same for men and women, and reduced the guideline for men by around one-third. METHOD: Data were from a representative, repeat cross-sectional survey. We analysed changes in awareness and knowledge of drinking guidelines among 8168 adult drinkers between 2016 and 2022 and associations with sociodemographic characteristics, smoking status and level of alcohol consumption. RESULTS: The proportion of drinkers aware of guidelines declined from 86.0% (95%CI 84.0-88.0%) in 2016 to 81.7% (79.5-84.0%) in 2019, then increased during the COVID-19 pandemic, peaking at 91.6% (90.1-93.1%) in 2020. The proportion who correctly identified the guideline as a maximum of exactly 14 units/week remained at around a quarter from 2016 (25.0%, 22.4-27.5%) to 2018 (25.8%, 23.2-28.3%), whereas the proportion who gave a figure of 14 units or fewer rose from 52.1 (49.2-55.0%) to 57.4% (54.6-60.3%). However, by 2022, guideline knowledge had worsened significantly, with these figures falling to 19.7 (17.4-21.9%) and 46.5% (43.6-49.4%), respectively. Changes over time were similar across subgroups. Odds of guideline awareness and knowledge were higher among drinkers who were aged ≥35, female, more educated and from more advantaged social grades. CONCLUSIONS: The majority of adult drinkers in the UK are aware of low-risk drinking guidelines. However, 6 years since their announcement, knowledge of the revised drinking guidelines remains poor. Less than a quarter know the recommended weekly limit and only around half think it is 14 units or less. Inequalities have persisted over time, such that disadvantaged groups remain less likely to know the guidelines.
