33 research outputs found
Alpha-2-macroglobulin loaded microcapsules enhance human leukocyte functions and innate immune response
Synthetic microstructures can be engineered to deliver bioactive compounds impacting on their pharmacokinetics and pharmacodynamics. Herein, we applied dextran-based layer-by-layer (LbL) microcapsules to deliver alpha-2-macroglobulin (α2MG), a protein with modulatory properties in inflammation. Extending recent observations made with dextran-microcapsules loaded with α2MG in experimental sepsis, we focused on the physical and chemical characteristics of these microstructures and determined their biology on rodent and human cells. We report an efficient encapsulation of α2MG into microcapsules, which enhanced i) human leukocyte recruitment to inflamed endothelium and ii) human macrophage phagocytosis: in both settings microcapsules were more effective than soluble α2MG or empty microcapsules (devoid of active protein). Translation of these findings revealed that intravenous administration of α2MG-microcapsules (but not empty microcapsules) promoted neutrophil migration into peritoneal exudates and augmented macrophage phagocytic functions, the latter response being associated with alteration of bioactive lipid mediators as assessed by mass spectrometry. The present study indicates that microencapsulation can be an effective strategy to harness the complex biology of α2MG with enhancing outcomes on fundamental processes of the innate immune response paving the way to potential future development in the control of sepsis
Sex in basic research – Concepts in the cardiovascular field
Women and men, female and male animals and cells are biologically different, and acknowledgement of
this fact is critical to advancing medicine. However, incorporating concepts of sex-specific
analysis in basic research is largely neglected, introducing bias into translational findings, clinical concepts and drug
development.Research funding agencies recently approached these issues but implementation of policy
changes in the scientific community is still limited probably due to deficits in concepts, knowledge and proper methodology. This expert review is based on the EUGenMed project (www.eugenmed.eu) developing a roadmap for implementing sex and gender in biomedical and health research. For sake of clarity and conciseness, examples are mainly taken from the cardiovascular field that may serve as a paradigm for others, since a significant amount of knowledge how sex and estrogen determine the manifestation of many
cardiovascular diseases (CVD) has been accumulated. As main concepts for implementation of sex in
basic research, the study of primary cell and animals of both sexes, the study of the influence of genetic
versus hormonal factors and the analysis of sex chromosomes and sex specific statistics in genome wide
association studies (GWAS) are discussed. The review also discusses methodological issues, and analyses
strength, weaknesses, opportunities and threats in implementing sex-sensitive aspects into basic
research