Ironing out Macrophage Immunometabolism

Over the last decade, increasing evidence has reinforced the key role of metabolic reprogramming in macrophage activation. In addition to supporting the specific immune response of different subsets of macrophages, intracellular metabolic pathways also directly control the specialized effector functions of immune cells. In this context, iron metabolism has been recognized as an important component of macrophage plasticity. Since macrophages control the availability of this essential metal, changes in the expression of genes coding for the major proteins of iron metabolism may result in different iron availability for the macrophage itself and for other cells in the microenvironment. In this review, we discuss how macrophage iron can also play a role in immunometabolism

New perspectives on the molecular basis of the interaction between oxygen homeostasis and iron metabolism

Oxygen and iron are two elements closely related from a (bio)chemical point of view. Moreover, they share the characteristic of being indispensable for life, while also being potentially toxic. Therefore, their level is strictly monitored, and sophisticated pathways have evolved to face variations in either element. In addition, the expression of proteins involved in iron and oxygen metabolism is mainly controlled by a complex interplay of proteins that sense both iron levels and oxygen availability (ie, prolyl hydroxylases, hypoxia inducible factors, and iron regulatory proteins), and in turn activate feedback mechanisms to re-establish homeostasis. In this review, we describe how cells and organisms utilize these intricate networks to regulate responses to changes in oxygen and iron levels. We also explore the role of these pathways in some pathophysiological settings

COVID-19–related skin manifestations: Update on therapy

An increasing body of evidence has been produced in a very limited period to improve the understanding of skin involvement in the current coronavirus 2019 disease pandemic, and how this novel disease affects the management of dermatologic patients. A little explored area is represented by the therapeutic approach adopted for the different skin manifestations associated with the infection. An overview of the current scenario is provided, through review of the English-language literature published until October 30, 2020, and comparison with the personal experience of the authors. As dermatologists, our primary aim is to support patients with the highest standard of care and relieve suffering, even with lesions not life-threatening. With asymptomatic COVID-19 patients, patient discomfort related to skin lesions should not be undervalued and intervention to accelerate healing should be provided. Consensus protocols are warranted to assess the best skin-targeted treatments in COVID-19 patients

Dual Role of ROS as Signal and Stress Agents : Iron Tips the Balance in favor of Toxic Effects

Iron is essential for life, while also being potentially harmful. Therefore, its level is strictly monitored and complex pathways have evolved to keep iron safely bound to transport or storage proteins, thereby maintaining homeostasis at the cellular and systemic levels. These sequestration mechanisms ensure that mildly reactive oxygen species like anion superoxide and hydrogen peroxide, which are continuously generated in cells living under aerobic conditions, keep their physiologic role in cell signaling while escaping iron-catalyzed transformation in the highly toxic hydroxyl radical. In this review, we describe the multifaceted systems regulating cellular and body iron homeostasis and discuss how altered iron balance may lead to oxidative damage in some pathophysiological settings

Influence of block versus random monomer distribution on the cellular uptake of hydrophilic copolymers

The use of polymers has revolutionized the field of drug delivery in the past two decades. Properties such as polymer size, charge, hydrophilicity, or branching have all been shown to play an important role in the cellular internalization of polymeric systems. In contrast, the fundamental impact of monomer distribution on the resulting biological properties of copolymers remains poorly studied and is always only investigated for biologically active self-assembling polymeric systems. Here, we explore the fundamental influence of monomer distribution on the cellular uptake of nonaggregating and biologically passive copolymers. Reversible addition–fragmentation chain-transfer (RAFT) polymerization was used to prepare precisely defined copolymers of three hydrophilic acrylamide monomers. The cellular internalization of block copolymers was compared with the uptake of a random copolymer where monomers are statistically distributed along the chain. The results demonstrate that monomer distribution in itself has a negligible impact on copolymer uptake

Macrophages : central regulators of iron balance

Macrophages are important to immune function and also actively participate in iron homeostasis. The involvement of splenic and liver macrophages in the processing of effete erythrocytes and the subsequent return of iron to the circulation is well established, and the molecular details of iron recycling have been characterized recently. Another important aspect regarding iron handling by macrophages is their capacity to act as immune cells, which involves the inflammatory response, as well as other pathological conditions in which macrophages are central. This review discusses the latest advances in macrophage iron trafficking and the pathophysiological consequences of altered iron homeostasis in these cells

Vegetating nodules following erosions on the oral cavity : a quiz

Acta Derm Venereol 95 © 2015 The Authors. doi: 10.2340/00015555-1936 Journal Compilation © 2015 Acta Dermato-Venereologica. ISSN 0001-5555 A 68-year-old Italian man presented with a 7-month history of multiple erosions on the trunk as well as lips and oral cavity. Before admission to our department, he was treated in another institution with systemic corticosteroids (oral prednisone at the initial dose of 1 mg/kg/day, with progressively tapering dosages for 2 months) and other immunosuppressants, such as azathioprine (1.25 mg/kg/ day for 2 months), intravenous immunoglobulins (one cycle consisting of one infusion of 400 mg/kg/day for 5 consecutive days), and rituximab (one cycle consisting of one infusion of 375 mg/m2/every week for 4 weeks), achieving resolution of the cutaneous manifestations but without control of the oral involvement. Upon admission, he had multiple lip and oral erosions (Fig. 1a). In the following days, he developed erythematous-violaceous vegetating nodules that coalesced into ulcerated plaques on the lips and tongue (Fig. 1b). The patient's general condition was compromised; he was asthenic and, due to dysphagia, had lost about 15 kg in the last 3 months. Staging fibroscopy revealed nodules that induced marked stenosis of the larynx and pharynx (Fig. 1c). Within a few days, an emergency tracheotomy was required because of acute dyspnea. Biopsy specimens from a nodule were submitted for histology (Fig. 1d)

Iron-induced damage in cardiomyopathy: oxidative-dependent and independent mechanisms

The high incidence of cardiomyopathy in patients with hemosiderosis, particularly in transfusional iron overload, strongly indicates that iron accumulation in the heart plays a major role in the process leading to heart failure. In this context, iron-mediated generation of noxious reactive oxygen species is believed to be the most important pathogenetic mechanism determining cardiomyocyte damage, the initiating event of a pathologic progression involving apoptosis, fibrosis, and ultimately cardiac dysfunction. However, recent findings suggest that additional mechanisms involving subcellular organelles and inflammatory mediators are important factors in the development of this disease. Moreover, excess iron can amplify the cardiotoxic effect of other agents or events. Finally, subcellular misdistribution of iron within cardiomyocytes may represent an additional pathway leading to cardiac injury. Recent advances in imaging techniques and chelators development remarkably improved cardiac iron overload detection and treatment, respectively. However, increased understanding of the pathogenic mechanisms of iron overload cardiomyopathy is needed to pave the way for the development of improved therapeutic strategies