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Systemic sclerosis (SSc) is a connective tissue disease secondary to three cardinal pathological features: immunesystem alterations, diffuse microangiopathy, and fibrosis involving the skin and internal organs. The etiology of SSc remains quite obscure; it may encompass multiple host genetic and environmental -infectious/chemicalfactors.The present review focused on the potential role of environmental agents in the etiopathogenesis of SSc based on epidemiological, clinical, and laboratory investigations previously published in the world literature.Among infectious agents, some viruses that may persist and reactivate in infected individuals, namely human cytomegalovirus (HCMV), human herpesvirus-6 (HHV-6), and parvovirus B19 (B19V), and retroviruses have been proposed as potential causative agents of SSc. These viruses share a number of biological activities and consequent pathological alterations, such as endothelial dysfunction and/or fibroblast activation.Moreover, the acute worsening of pre-existing interstitial lung involvement observed in SSc patients with symptomatic SARS-CoV-2 infection might suggest a potential role of this virus in the overall disease outcome.A variety of chemical/occupational agents might be regarded as putative etiological factors of SSc. In this setting, the SSc complicating silica dust exposure represents one of the most promising models of study. Considering the complexity of SSc pathogenesis, none of suggested causative factors may explain the appearance of the whole SSc; it is likely that the disease is the result of a multifactorial and multistep pathogenetic process. A variable combination of potential etiological factors may modulate the appearance of different clinical phenotypes detectable in individual scleroderma patients.The in-deep investigations on the SSc etiopathogenesis may provide useful insights in the broad field of human diseases characterized by diffuse microangiopathy or altered fibrogenesis.

Metal-based nanoparticles (NPs), are currently used in many application fields including consumer products, pharmaceuticals, and biomedical treatments. In spite to their wide applications, an in-depth study of their potential toxic effects is still lacking. The aim of the present research was to investigate the potential initiator or promoter-like activity of different metallic NPs such as gold, iron, cobalt, and cerium using the Balb/3T3 two-stage transformation assay. The results indicated that all the selected metallic NPs, except for cobalt, when used as initiators did not induce any transformation in Balb/3T3 cell line. Moreover, Au and Fe3 O4 NPs, when used in place of the tumor promoter treatment TPA, increased significantly the number of Foci/dish as compared to the MCA treatment alone. The number of Foci/dish was 2.6 for Au NPs and 2.13 for Fe3 O4 ones, similar to those obtained by the positive control treatment (MCA + TPA), whereas 1.27 for MCA treatment alone. On the contrary, CeO2 NPs did not show any difference in the number of Foci/dish, as compared to MCA alone, but it decreased the number of foci by 65% in comparison to the positive control (MCA + TPA). As expected, cobalt NPs showed an increased cytotoxicity and only a few surviving cells were found at the time of analysis showing a number of Foci/dish of 0.13. For the first time, our data clearly showed that Au and Fe3 O4 NPs act as promoters in the two stage transformational assay, suggesting the importance to fully investigate the NPs carcinogenic potential with different models.

In addition to HCV infection, MPs and NPs might play an important role in the aetiopathogenesis of MC.

BackgroundSystemic sclerosis (SSc) is a chronic, multisystem connective tissue disease characterised by by immune dys-regulation, obliterative microvasculopathy and fibrosis. Endothelial dysfunction, immune system imbalance and fibroblast activation constitute the three major factors of the pathogenetic process. In this context, oxidative stress could play a significant role through direct damage of endothelial cells and the persistent activation of the immune system.1,2 ObjectivesThis study investigated the presence of advanced protein oxidation products (AOPP) in serum of patients with SSc and its correlation with disease’s features.Methods50 patients with SSc (M:F 1:7, mean age 57.3±11.2 SD, mean duration of disease 10±9.1 SD years), were screened for AOPP in the serum, using the AOPP OxiSelect Kit of CELL BIOLABS (San Diego, Ca, USA). Among 50 SSc patients, 39 had limited cutaneous subset, while 11 had the diffuse one. Anamnestic and clinical data were collected for all SSc patients. As a control group 50 consecutive healthy subjects, sex and age matched, were recruited.ResultsWe found serum levels of AOPP increased in the SSc group compared with the controls (p<0.0001) with mean values of 336.9±167.8 mmol/L and 167.5±59.2 mmol/L, respectively. In addition, higher levels of AOPP directly correlated with the diffuse cutaneous subset (p=0.0242), presence of digital ulcers (p=0.005), esophagopathy (p=0.006) and pulmonary fibrosis (p=0.0128).ConclusionsSerum AOPP levels are significantly higher in patients with SSc than in controls. In addition, the correlations of AOPP with SSc diffuse cutaneous subset, digital ulcers, and pulmonary involvement (indicative of progressive disease and worse prognosis) suggest a possible role of this marker in the identification of the cases with worse clinical evolution. The data of this preliminary study should be confirmed on larger case series and analysed in prospective studies, in order to understand its eventual usefulness during the follow-up of SSc patients.References[1] Ferri C, Valentini G, Cozzi F, Sebastiani M, Michelassi C, La Montagna G, et al. Systemic Sclerosis: Demographic, Clinical, and Serologic Features and Survival in 1,012 Italian Patients. Medicine (Baltimore). 2002; 81:139–153[2] Steen VD. The many faces of scleroderma. Rheum Dis Clin North Am. 2008; 34:1–15Disclosure of InterestNone declared