Metallothioneins are peculiar cysteine rich, heat resistant, small cellular plasma proteins expressed through almost all life forms. The currently established biological functions of metallothioneins are the homeostasis of essential metals and protection against toxic transitional metals (TM) alongside defence from oxidative stress by direct scavenging of reactive oxygen and nitrogen species (ROS and RNS). In mammals, among the four main evolutionary conserved forms, only the ubiquitously expressed metallothionein 1 and 2 (here abbreviated as MT) are inducible by TM, oxidative stress, glucocorticoids and starvation among various other stimuli. However, more than sixty years after being discovered, metallothioneins still bear unresolved issues about their possible physiological function and regulation. The biological function of MTs has still not been associated with the in vitro-demonstrated capacity of MT interaction with cellular molecules glutathione (GSH) or adenosine triphosphate (ATP), or with the possibility of direct iron-MT binding in the reducing intracellular environment of some organelles, e.g. lysosomes. Iron as the most abundant cellular TM is also one of the main physiological sources of ROS. Moreover, iron exhibits strain, sex and age differences that reflected ROS generation and MT induction in (patho)physiology and toxicology studies. A recent study showed that iron sex differences follows expression of both ferritin and MT leading to wide implications from essential TM interconnectivity to aging. This review places emphasis on biochemically proven but physiologically ignored interactions of MT with iron to stimulate advanced research for establishing a wide frame of the biological roles of MTs important for health and longevity.
Psoriasis is a common chronic inflammatory skin disease which affects 0.5–1 % of children and 2–3 % of the adult population. In Croatia, 1.6 % of the population suffer from psoriasis. Distribution of the disease is bimodal, with the first peak at the age of 20–30, and the second at the age of 50–60. The etiopathogenesis of the disease is multifactorial, the key factors being genetic predisposition combined with immunological disorders, environmental factors and skin barrier damage. There are several clinical variants of the disease. The main signalling pathways in psoriasis include TNF-α, IL-23 and IL-17. Topical agents are used for the treatment of the mild form, and the systemic conventional therapy is used for the treatment of moderate to severe forms of the disease. In cases where’s no response, or intolerance or contraindications are present, new targeted medications are to be administered. Development in the field of immunogenetics of psoriasis leads to personalized medicine.
Many personal care products on the market contain endocrine disrupting chemicals, including parabens. Parabens are well known chemical additives used as preservatives. They have been found in mammary glands and breast cancer tissues. At the same time, the general public is increasingly exposed to plastic micro- and nanoparticles generated during plastic production and waste disposal. Exposure to chemical cocktails is a realistic scenario of high public health interest, in which many types of compounds such as these two may exhibit synergistic or additive adverse effects. This study evaluated the effects of plastic nanoparticles, parabens, and their mixture on the viability and proliferation of two human breast cancer cell lines: MDA-MB 231, which lacks oestrogen receptors, and MCF-7, which expresses these receptors. Parabens increased proliferation of oestrogen-sensitive breast cancer cells, and this effect became synergistic in the presence of plastic nanoparticles. The mechanism behind synergy may be related to the translocation and adsorption properties of nanoplastics, which served as a Trojan horse to expose cells to parabens more efficiently. These preliminary findings support growing evidence warning about the urgent problem of human exposure to combinations of plastic waste and contingent chemicals.