Cholesterol (CH) plays a crucial role in enhancing the membrane stability of drug delivery systems (DDS). However, its association with conditions such as hyperlipidemia often leads to criticism, overshadowing its influence on the biological effects of formulations. In this study, we reevaluated the delivery effect of CH using widely applied lipid microspheres (LM) as a model DDS. We conducted comprehensive investigations into the impact of CH on the distribution, cell uptake, and protein corona (PC) of LM at sites of cardiovascular inflammatory injury. The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage. Then, the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy. Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in vascular endothelial cells and estrogen receptor alpha (ERα) protein levels in myocardial cells, thereby enhancing LM uptake at cardiovascular inflammation sites. Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V (Apoa5); this may be a major contributing factor to their prolonged circulation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites. It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations. The findings enhance the conceptualization of CH and LM delivery, providing novel strategies for investigating prescription factors' bioactivity.

Objective To investigate gene pathways associated with severe acne.Methods Kyoto encyclopedia of genes and genomes (KEGG)-based pathway analysis was conducted using the genome-wide association study (GWAS) data on 1 056 patients with severe acne and 1 056 healthy controls,and each testee was tested for 900 015 SNPs.A hypergeometric distribution test was used to analyze the relationship between each pathway and severe acne,and the false discovery rate (FDR) to correct for multiple testing.Any pathway with an adjusted P value of ＜ 0.05 was considered to be associated with severe acne.Results Twelve genes were identified to be associated with severe acne (P ＜ 0.001),including TMPRSS11E,DDB2,RIC1,CLLU1OS,IL3,PLA2G4B,SLC16A14,SOX17,FAHD2A,ENTPD7,MRPL50 and TXLNB.Pathway analysis revealed 5 pathways associated with severe acne (adjusted P ＜ 0.05),including the prolactin signaling pathway,hepatitis C,renal cell carcinoma,high affinity receptor for immunoglobulin E (Fc epsilon RI) signaling pathway,and tyrosine metabolism.Conclusion The 5 identified pathways are associated with severe acne,which affect the endocrine,immune and metabolic processes in the human body.

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