Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption

Osteoclasts are large multinucleated bone-resorbing cells formed by the fusion of monocyte/macrophage-derived precursors that are thought to undergo apoptosis once resorption is complete. Here, by intravital imaging, we reveal that RANKL-stimulated osteoclasts have an alternative cell fate in which they fission into daughter cells called osteomorphs. Inhibiting RANKL blocked this cellular recycling and resulted in osteomorph accumulation. Single-cell RNA sequencing showed that osteomorphs are transcriptionally distinct from osteoclasts and macrophages and express a number of non-canonical osteoclast genes that are associated with structural and functional bone phenotypes when deleted in mice. Furthermore, genetic variation in human orthologs of osteomorph genes causes monogenic skeletal disorders and associates with bone mineral density, a polygenetic skeletal trait. Thus, osteoclasts recycle via osteomorphs, a cell type involved in the regulation of bone resorption that may be targeted for the treatment of skeletal diseases

Antioxidant activity and protecting health effects of common medicinal plants

Medicinal plants are traditionally used in folk medicine as natural healing remedies with therapeutic effects such as prevention of cardiovascular diseases, inflammation disorders, or reducing the risk of cancer. In addition, pharmacological industry utilizes medicinal plants due to the presence of active chemical substances as agents for drug synthesis. They are valuable also for food and cosmetic industry as additives, due to their preservative effects because of the presence of antioxidants and antimicrobial constituents. To commonly used medicinal plants with antioxidant activity known worldwide belong plants from several families, especially Lamiaceae (rosemary, sage, oregano, marjoram, basil, thyme, mints, balm), Apiaceae (cumin, fennel, caraway), and Zingiberaceae (turmeric, ginger). The antioxidant properties of medicinal plants depend on the plant, its variety, environmental conditions, climatic and seasonal variations, geographical regions of growth, degree of ripeness, growing practices, and many other factors such as postharvest treatment and processing. In addition, composition and concentration of present antioxidants, such as phenolic compounds, are related to antioxidant effect. For appropriate determination of antioxidant capacity, the extraction technique, its conditions, solvent used, and particular assay methodology are important