Reactive oxygen species: a merging solution for two unmerging problems

Malignant mesothelioma is a rare cancer arising from the serosal surfaces of the body, mainly from the pleural layer. The primary cause of pleural mesothelioma is exposure to asbestos fibers, a group of naturally occurring fibrous minerals with excellent physical and electrochemical insulating properties and a long history of industrial applications. Despite a progressive ban on asbestos production and usage in over 50 countries worldwide since the 1980s, the incidence of pleural mesothelioma continues to rise due to the long latency period (20 to 50 years) between asbestos exposure and the development of the tumor. When asbestos fibers are inhaled or ingested, they can become lodged in the body, leading to inflammation and scarring of the mesothelium over time, which can eventually result in the development of mesothelioma. Asbestos mining, manufacture of asbestos-containing products (most important, asbestos- cement) and installation of asbestos containing materials in a wide range of industrial and residential settings have accompanied the industrialization of Italy for most of the twentieth century. In this frame, Piemonte was one of the most affected Italian regions, since it hosted the main European chrysotile quarry (Balangero, operating from 1917 through 1990) and the largest facility for the manufacture of asbestos-cement products (Casale Monferrato, operating from 1907 through 1985). Therefore, our research group (working in this high-risk area of mesothelioma, near Casale Monferrato) is strongly committed to promoting efforts to understand new details about the biology of mesothelioma and the development of new therapeutic strategies. 3 Wound repair is the natural process by which the body heals itself after injury. It involves a complex series of events, including inflammation, proliferation, and remodelling, that work together to repair damaged tissue and restore its structure and function. Wound repair is essential for maintaining the integrity of the body and preventing infection and other complications. There is no direct relationship between mesothelioma and wound repair. Mesothelioma is a form of cancer caused by asbestos exposure, while wound repair is a normal physiological process that occurs in response to tissue injury. During my PhD thesis activity, in the Cellular Physiology (CellPhy) laboratory, I dealt with using cellular and molecular biology techniques to these two different types of scientific problems. In particular, given the scarcity of therapeutic strategies for mesothelioma, we were interested in characterising endoplasmic reticulum stress, the role of the chaperone GRP78 and of a compound, BOLD-100, and its ability to induce cell death in mesothelioma cell lines. Another part of the activity I carried out was to use natural compounds, in particular beehive derivatives, such as honey and propolis, to understand their positive mechanism of action on cellular systems. In recent years, our laboratory has understood how the mechanism of action of these compounds depends on the ability to produce H2O2 in the extracellular space. We therefore used endothelial cells as a model to verify how honey acts, confirming the important presence of hydrogen peroxide and the involvement of intracellular calcium. However, honey is not only useful in repairing wounds, but can become a very important compound for a "green" approach in the field of chemistry. 4 Honey has been recognized not only as a natural sweetener but also for its potential use in various biomaterial applications.