RESUMEN
Chemical modification of lysozyme was carried out using benzaldehyde and anisaldehyde. It was shown that chemical modification affects only 1-2 amino groups of the protein molecule which does not prevent further covalent immobilization of lysozyme using the remaining free amino groups. The bacteriolytic activity of lysozyme is preserved after chemical modification and after subsequent covalent immobilization. As a result of chemical modification immobilized lysozyme more effectively adsorbs bacterial lipopolysaccharides (endotoxins). Adsorption of immunoglobulin G does not increase after modification. The sorbents obtained in this work can be used for the future development of new medical material for the extracorporeal treatment of sepsis. The proposed scheme for the modification and immobilization of lysozyme can be used with various aldehydes for the preparation of sorbents with different properties.
RESUMEN
The tumor microenvironment offers multiple targets for cancer therapy, including pro-tumorigenic inflammation. Natural compounds represent an enormous source of new anti-inflammatory and anticancer agents. We previously showed that the styryl lactone goniothalamin (GTN) has promising antiproliferative and anti-inflammatory activities. Because inflammation is a major driver of colorectal cancer (CRC), we therefore evaluated the therapeutic and preventive potentials of GTN in colitis, colitis-associated cancer (CAC) and spontaneous CRC. First, in a simplistic model of inflammation in vitro, GTN was able to inhibit cytokine production in bone marrow-derived macrophages induced by lipopolysaccharide. Next, in dextran sulfate sodium (DSS) induced-colitis model, mice treated with GTN displayed restored tissue architecture, increased cell proliferation in the colonic crypts and reduced epithelial damage. Moreover, colon tissue from GTN-treated mice had significantly less expression of the inflammatory genes interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), S100A9, interleukin 23A (IL-23A), IL-22 and IL-17A In the azoxymethane/DSS model of CAC, GTN reduced tumor multiplicity, load and size. Additionally, GTN suppressed production of IL-6, IL-17 and TNF-α in tumor tissue, as well as abrogated stromal immune cell activation and nuclear translocation of NF-κB. Finally, in a tamoxifen inducible model of sporadic CRC, GTN-treated mice had significantly fewer tumors and decreased levels of IL-17A, IL-6, S100A9 and TNF-α protein within the tumors. These results suggest that GTN possesses anti-inflammatory and antitumor activities and represents a preventive and therapeutic agent modulating the inflammatory environment in the colon during colitis as well as CAC and CRC development.