Oxidative stress plays a fundamental role in many conditions. Specifically, redox imbalance inhibits endothelial cell (EC) growth, inducing cell death and senescence. We used global transcriptome profiling to investigate the involvement of noncoding-RNAs in these phenotypes. By RNA-sequencing, transcriptome changes were analyzed in human ECs exposed to H2O2, highlighting a pivotal role of p53-signaling. Bioinformatic analysis and validation in p53-silenced ECs, identified several p53-targets among both mRNAs and long noncoding-RNAs (lncRNAs), including MALAT1 and NEAT1. Among microRNAs (miRNAs), miR-192-5p was the most induced by H2O2 treatment, in a p53-dependent manner. Down-modulated mRNA-targets of miR-192-5p were involved in cell cycle, DNA repair and stress response. Accordingly, miR-192-5p overexpression significantly decreased EC proliferation, inducing cell death. A central role of the p53-pathway was also confirmed by the analysis of differential exon usage: Upon H2O2 treatment, the expression of p53-dependent 5'-isoforms of MDM2 and PVT1 increased selectively. The transcriptomic alterations identified in H2O2-treated ECs were also observed in other physiological and pathological conditions where redox control plays a fundamental role, such as ECs undergoing replicative senescence, skeletal muscles of critical limb-ischemia patients and the peripheral-blood mononuclear cells of long-living individuals. Collectively, these findings indicate a prominent role of noncoding-RNAs in oxidative stress response.

Nt an opportunity to diagnostically characterize acute or chronic aortic processes. We examined the potential diagnostic role of MMP-9 and MMP-2 in different phases of aortic dissection. Methods Plasma levels of MMPs were evaluated by enzyme-linked immunosorbent assay technique in 13 patients affected by acute aortic dissection (nine type A, four type B). Ten healthy subjects were used as controls. In patients with type B aortic dissection treated medically, plasma curves (1, 3, 6, 12, 24, 48 and 96 h; 1 and 2 weeks; and 2 months from symptom onset) were also assessed. Aortic tissue samples obtained during surgery were evaluated by immunohistochemistry and western blot for MM-9 and tissue inhibitor of metalloproteinase-1 expression. Results MMP-9 plasma levels were increased in patients affected by type A and type B aortic dissection presenting within 1 h from onset of symptoms compared to controls (29.3 ± 16.1 and 16.7 ± 2.1 ng/ml versus 7.74 ± 1.6 ng/ml, P < 0.03, respectively). No differences were detected in MMP-2 plasma levels compared to controls (4.84 ± 1.2 ng/ml for type A and 6.16 ± 0.6 ng/ml versus 3.17 ± 1.0 ng/ml for controls, P = NS, respectively). In type B aortic dissection, mean MMP-9 plasma levels increased significantly from hospital admission to 2-month follow-up (16.7 ± 2.1 ng/ml versus 58.0 ± 8.2 ng/ml, P < 0.0001). Conversely, no difference in MMP-2 plasma levels was evident during follow-up (6.16 ± 0.6 ng/ml versus 4.28 ± 0.4 ng/ml, P = NS, respectively). Low-moderate (+/++) expression of MMP-9 was evident at immunohistochemistry in the acute phase whereas a marked expression (++++) was detected in the subacute phase. Conclusions This pilot study suggests that the acute and subacute phase of both type A and type B aortic dissection is characterized by an increase of MMP-9 plasma levels. A marked increase is also evident in the subacute phase of medically treated type B aortic dissection as an expression of aortic wall remodelling. An increase of proteolytic activity could accompany attempts of the dissected aorta to heal itself but such a phenomena might further weaken the aortic wall, predisposing it to dilation and/or rupture....

Introduction: Aim of the study is to assess the occurrence of early stage coagulopathy and disseminated intravascular coagulation (DIC) in patients with mild to moderate respiratory distress secondary to SARS-CoV-2 infection. Materials and methods: Data of patients hospitalized from 18 March 2020 to 20 April 2020 were retrospectively reviewed. Two scores for the screening of coagulopathy (SIC and non-overt DIC scores) were calculated. The occurrence of thrombotic complication, death, and worsening respiratory function requiring non-invasive ventilation (NIV) or admission to ICU were recorded, and these outcomes were correlated with the results of each score. Chi-square test, receiver-operating characteristic curve, and logistic regression analysis were used as appropriate. p Values < 0.05 were considered statistically significant. Results: Data of 32 patients were analyzed. Overt-DIC was diagnosed in two patients (6.2%), while 26 (81.2%) met the criteria for non-overt DIC. Non-overt DIC score values ≥4 significantly correlated with the need of NIV/ICU (p = 0.02) and with the occurrence of thrombotic complications (p = 0.04). A score ≥4 was the optimal cut-off value, performing better than SIC score (p = 0.0018). Values ≥4 in patients with thrombotic complications were predictive of death (p = 0.03). Conclusions: Overt DIC occurred in 6.2% of non-ICU patients hospitalized for a mild to moderate COVID-19 respiratory distress, while 81.2% fulfilled the criteria for non-overt DIC. The non-overt DIC score performed better than the SIC score in predicting the need of NIV/ICU and the occurrence of thrombotic complications, as well as in predicting mortality in patients with thrombotic complications, with a score ≥4 being detected as the optimal cut-off.