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Three-dimensional culture alters cancer cell signaling; however, the underlying mechanisms and importance of these changes on tumor vascularization remain unclear. A hydrogel system was used to examine the role of the transition from 2D to 3D culture, with and without integrin engagement, on cancer cell angiogenic capability. Threedimensional culture recreated tumor microenvironmental cues and led to enhanced interleukin 8 (IL-8) secretion that depended on integrin engagement with adhesion peptides coupled to the polymer. In contrast, vascular endothelial growth factor (VEGF) secretion was unaffected by 3D culture with or without substrate adhesion. IL-8 diffused greater distances and was present in higher concentrations in the systemic circulation, relative to VEGF. Implantation of a polymeric IL-8 delivery system into GFP bone marrow-transplanted mice revealed that localized IL-8 up-regulation was critical to both the local and systemic control of tumor vascularization in vivo. In summary, 3D integrin engagement within tumor microenvironments regulates cancer cell angiogenic signaling, and controlled local and systemic blockade of both IL-8 and VEGF signaling may improve antiangiogenic therapies.ECM ͉ microenvironment ͉ tumor vascularization ͉ drug delivery ͉ IL-8

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Superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with antimicrobial agents are promising infection-targeted therapeutic platforms when coupled with external magnetic stimuli. These antimicrobial nanoparticles (NPs) may offer advantages in fighting intracellular pathogens as well as biomaterial-associated infections. This requires the development of NPs with high antimicrobial activity without interfering with the biology of mammalian cells. Here, we report the preparation of biocompatible antimicrobial SPION@gold core-shell NPs based on covalent immobilization of the antimicrobial peptide (AMP) cecropin melittin (CM) (the conjugate is named AMP-NP). The minimal inhibitory concentration (MIC) of the AMP-NP for Escherichia coli was 0.4 μg/mL, 10-times lower than the MIC of soluble CM. The antimicrobial activity of CM depends on the length of the spacer between the CM and the NP. AMP-NPs are taken up by endothelial (between 60 and 170 pg of NPs per cell) and macrophage (between 18 and 36 pg of NPs per cell) cells and accumulate preferentially in endolysosomes. These NPs have no significant cytotoxic and pro-inflammatory activities for concentrations up to 200 μg/mL (at least 100 times higher than the MIC of soluble CM). Our results in membrane models suggest that the selectivity of AMP-NPs for bacteria and not eukaryotic membranes is due to their membrane compositions. The AMP-NPs developed here open new opportunities for infection-site targeting.

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This study assessed the contribution of sociodemographic and psychological variables to quality of life (QoL) in male and female users of anti-aging cosmetic products and procedures, and the moderator role of age and sex in those relationships. Methods: 382 participants were evaluated on appearance schemes, aging perceptions, self-esteem, psychological morbidity, perfectionism and QoL. Results: Being male, married, professionally active and having a higher household income was associated with better QoL, while the usage of cosmetic products was negatively associated with QoL. Appearance schemes, psychological morbidity, perfectionism and aging perceptions (timeline chronic and emotional representations) were associated with worse QoL, and self-esteem was associated with better QoL. Sex moderated the relationship between perfectionism and psychological morbidity in both men and women but stronger in the latter, while the relationship between chronic aging perceptions and negative QoL was only significant in men. Age moderated the relationship between perfectionism and psychological morbidity, between psychological morbidity and QoL, and between aging perceptions and QoL. Conclusions: Findings may help guide psychological interventions targeted on the adaptation to the aging experience as means of promoting QoL. Thus, psychological intervention programs should address perfectionism, psychological morbidity and aging perceptions, being differentiated according to participants' sex and age in order to promote a better adaptation to the aging process.