Oxidative stress in the pathogenesis of systemic scleroderma: An overview

Systemic sclerosis (SSc) is a rare disorder of the connective tissue characterized by fibrosis of the skin, skeletal muscles and visceral organs. Additional manifestations include activation of the immune system and vascular injury. SSc causes disability and death as the result of end-stage organ failure. Two clinical subsets of the SSc are accepted: limited cutaneous SSc (lc-SSc) and diffuse cutaneous SSc (dc-SSc). At present, the aetiology and pathogenesis of SSc remain obscure, and consequently, disease outcome is unpredictable. Numerous studies suggest that reactive oxidizing species (ROS) play an important role in the pathogenesis of scleroderma. Over the years, several reports have supported this hypothesis for both lc-SSc and dc-SSc, although the specific role of oxidative stress in the pathogenesis of vascular injury and fibrosis remains to be clarified. The aim of the present review was to report and comment the recent findings regarding the involvement and role of oxidative stress in SSc pathogenesis. Biomarkers proving the link between ROS and the main pathological features of SSc have been summarized

Gender-Associated Biomarkers in Metabolic Syndrome

Metabolic syndrome (MetS) is a cluster of risk factors for atherosclerosis, including abdominal obesity, hypertension, insulin resistance, dyslipidemia with high triglycerides, and low high-density lipoprotein cholesterol. Affected patients have a significantly increased risk of developing cardiovascular disorders (CVD), that are the leading cause of death in the Western countries. Several epidemiological studies have investigated the evolution of CVD hypothesizing the presence of a gender difference in the pathogenetic and progression determinants detectable in men and women. In this chapter, we will examine new gender-associated bioindicators of possible diagnostic or prognostic value in the MetS. Moreover, we will provide an overview on current knowledge on sex-associated cardiovascular determinants with the aim to improve CVD diagnostic and prognostic clinical courses and to develop new and gender-biased prevention strategies

Single exposure of human fibroblasts (WI-38) to a sub-cytotoxic dose of UVB induces premature senescence

AbstractIn this work, we present a new model of stress-induced premature senescence obtained by exposing human fibroblasts (WI-38) at early passages (passages 2–4) to a single sub-cytotoxic dose of UVB (200mJ/cm2). We show that this treatment leads to the appearance of several biomarkers of senescence such as enlarged and flattened cell morphology, the presence of nuclear heterochromatic foci and β-galactosidase activity. Furthermore, we demonstrate that a mild ROS production and p53 activation are upstream events required for the induction of premature senescence. Our method represents an alternative in vitro model in photoaging research and could be used to test potential anti-photoaging compounds

Functional Estrogen Receptors of Red Blood Cells. Do They Influence Intracellular Signaling?

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Gender issues on occupational safety and health

The increasing proportion of women in the workforce raises a range of gender-related questions about the different effects of work-related risks on men and women. Few studies have characterized gender differences across occupations and industries, although at this time, the gender sensitive approach is starting to acquire relevance in the field of human preventive medicine. The European Agency for Safety and Health at Work has encouraged a policy of gender equality in all European member states. Italy has adopted European provisions with new specific legislation that integrates the previous laws and introduces the gender differences into the workplace. Despite the fact that gender equal legislation opportunities have been enacted in Italy, their application is delayed by some difficulties. This review examines some of these critical aspects

Sex-related biomarkers in cardiovascular and neurodegenerative disorders

Despite considerable advances in the treatment of human inflammatory diseases, such as cardiovascular and neurological disorders, they remain the leading cause of death in developed countries. From a clinical perspective, an active area of investigation focuses on the identification of diagnostic and prognostic biomarkers, because preventing events in those at risk of chronic inflammatory disease is likely to have a substantial impact on the overall public-health burden. The sex difference has not been considered previously as important in the evaluation of biomarkers of human diseases, twithstanding it is now ascertained that the severity of these disorders is correlated with sex hormones which modulate the inflammatory response. The aim of the present brief review is to report and comment the state of art regarding the sex-related biomarkers in cardiovascular and neurodegenerative disorders, focusing on those compounds showing potential prognosticand diagnostic values, and/or acting as indicators of the therapeutic treatment efficacy

Cathepsin B inhibition interferes with metastatic potential of human melanoma: an in vitro and in vivo study

<p>Abstract</p> <p>Background</p> <p>Cathepsins represent a group of proteases involved in determining the metastatic potential of cancer cells. Among these are cysteinyl- (e.g. cathepsin B and cathepsin L) and aspartyl-proteases (e.g. cathepsin D), normally present inside the lysosomes as inactive proenzymes. Once released in the extracellular space, cathepsins contribute to metastatic potential by facilitating cell migration and invasiveness.</p> <p>Results</p> <p>In the present work we first evaluated, by <it>in vitro </it>procedures, the role of cathepsins B, L and D, in the remodeling, spreading and invasiveness of eight different cell lines: four primary and four metastatic melanoma cell lines. Among these, we considered two cell lines derived from a primary cutaneous melanoma and from a supraclavicular lymph node metastasis of the same patient. To this purpose, the effects of specific chemical inhibitors of these proteases, i.e. CA-074 and CA-074Me for cathepsin B, Cathepsin inhibitor II for cathepsin L, and Pepstatin A for cathepsin D, were evaluated. In addition, we also analyzed the effects of the biological inhibitors of these cathepsins, i.e. specific antibodies, on cell invasiveness. We found that i) cathepsin B, but not cathepsins L and D, was highly expressed at the surface of metastatic but not of primary melanoma cell lines and that ii) CA-074, or specific antibodies to cathepsin B, hindered metastatic cell spreading and dissemination, whereas neither chemical nor biological inhibitors of cathepsins D and L had significant effects. Accordingly, <it>in vivo </it>studies, i.e. in murine xenografts, demonstrated that CA-074 significantly reduced human melanoma growth and the number of artificial lung metastases.</p> <p>Conclusions</p> <p>These results suggest a reappraisal of the use of cathepsin B inhibitors (either chemical or biological) as innovative strategy in the management of metastatic melanoma disease.</p

Role of Oxidative Stress in the Cardiovascular Complications of Kawasaki Disease

Kawasaki disease (KD) is a rare and often undiagnosed disease, at least in the western countries. Although its etiology remains unidentified, epidemiological features point to the role of infection and genetic predisposition. KD is characterized by an inflammatory acute febrile vasculitis. Coronary artery involvement is the most important complication of KD and may cause significant coronary stenosis resulting in ischemic heart disease. It has been demonstrated that the major risks in KD progression are the endothelial dysfunction and that systemic oxidative stress together with premature aging of red blood cells and alteration of platelet homeostasis, could play a critical role in the cardiovascular complications associated with KD. This chapter will focus on the role of oxidative stress in endothelial damage and on circulating blood cells of KD patients