Modulation of LPS-Induced Neurodegeneration by Intestinal Helminth Infection in Ageing Mice.

Parasitic helminths induce a transient, short-term inflammation at the beginning of infection, but in persistent infection may suppress the systemic immune response by enhancing the activity of regulatory M2 macrophages. The aim of the study was to determine how nematode infection affects age-related neuroinflammation, especially macrophages in the nervous tissue. Here, intraperitoneal LPS-induced systemic inflammation resulting in brain neurodegeneration was enhanced by prolonged Heligmosomoides polygyrus infection in C57BL/6 mice. The changes in the brain coincided with the increase in M1 macrophages, reduced survivin level, enhanced APP and GFAP expression, chitin-like chains deposition in the brain and deterioration behaviour manifestations. These changes were also observed in transgenic C57BL/6 mice predisposed to develop neurodegeneration typical for Alzheimer's disease in response to pathogenic stimuli. Interestingly, in mice infected with the nematode only, the greater M2 macrophage population resulted in better results in the forced swim test. Given the growing burden of neurodegenerative diseases, understanding such interactive associations can have significant implications for ageing health strategies and disease monitoring.

High Hemin Concentration Induces Escape from Senescence of Normoxic and Hypoxic Colon Cancer Cells.

Hemoglobin from either red meat or bowel bleeding may promote oxidative stress and increase the risk of colorectal cancer (CRC). Additionally, solid cancers or their metastases may be present with localized bruising. Escape from therapy-induced senescence (TIS) might be one of the mechanisms of tumor re-growth. Therefore, we sought to study whether hemin can cause escape from TIS in CRC. To induce senescence, human colon cancer cells were exposed to a chemotherapeutic agent irinotecan (IRINO). Cells treated with IRINO exhibited common hallmarks of TIS. To mimic bleeding, colon cancer cells were additionally treated with hemin. High hemin concentration activated heme oxygenase-1 (HO-1), induced escape from TIS and epithelial-to-mesenchymal transition, and augmented progeny production. The effect was even stronger in hypoxic conditions. Similar results were obtained when TIS cells were treated with another prooxidant agent, H2O2. Silencing of antioxidative enzymes such as catalase (CAT) or glutathione peroxidase-1 (GPx-1) maintained colon cancer cells in a senescent state. Our study demonstrates that a high hemin concentration combined with an increased activity of antioxidative enzymes, especially HO-1, leads to escape from the senescence of colon cancer cells. Therefore, our observations could be used in targeted anti-cancer therapy.