No abstract

In October 2019, a viral infectious disease appeared in the city of Wuhan in China. A new betacoronavirus, SARS-CoV-2, has been recognized as the responsible pathogen in this infection. Although coronavirus disease is principally expressed as a pulmonary infection, critical SARS-CoV-2 infection is frequently complicated with coagulopathy, and thromboembolic events are recognizable in several patients. Dehydration, acute inflammatory condition, protracted immobilization during disease, existence of multiple cardiovascular risk factors such as diabetes, obesity or hypertension, previous coronary artery disease, ischemic stroke, peripheral artery disease are frequent comorbidities in SARS-CoV-2 hospitalized subjects, which possibly augment thrombo-embolic risk. However, other causal factors can still be identified such as unrestricted angiotensin II action, the use of immunoglobulins, an increased production of adhesion molecules able to induce vascular inflammation and endothelial activation, complement stimulation, excessive production of neutrophil extracellular traps (NETs), and increased platelet count. Low-molecular-weight heparin should be chosen as early treatment because of its anti-inflammatory action and its ability to antagonize histones and so defend the endothelium. However, several therapeutic possibilities have also been proposed such as fibrinolytic treatment, drugs that target NETs, and complement inhibition. Nevertheless, although the violence of the pandemic may suggest the use of heroic treatments to reduce the frightening mortality that accompanies SARS-CoV-2 infection, we believe that experimental treatments should only be used within approved and controlled protocols, the only ones that can provide useful and specify information on the validity of the treatments.

Our findings suggest that ASA: 1) is only effective to treat the very transient TxB2-induced pulmonary vasoconstriction resulting in hydrostatic edema, and it is ineffective, even accentuates, the subsequent major pulmonary endothelial cell injury leading to alveolar flooding that is unrelated to TxB2; 2) has a transient protective effect on the TxB2-induced early bronchospasm; 3) has a biphasic behaviour on gas exchange, with a benefit which lasts only one hour and then results in a worse gas exchange; 4) has an immediate, stabilizing, persisting effect on R, contrasting with its transient effect on pulmonary hemodynamics and PaO2.

Background The importance of the role of MicroRNAs (or miRNAs) has been emphasised by the large number of studies in human tumour cells, underlining the high impact of post‐transcriptional processes in cancer onset, progression, invasion and metastatisation. Currently known as oncomiR, real databases are collecting all the smaller fragments of RNA capable of participating in the oncogenesis. Aims With the aim to collect for the first time the most important acquisitions in literature about antagomiRs in oncology, our narrative review is born with the purpose of showing that specific antisense oligonucleotides, capable to bind and antagonise single or multiple miRNAs, are effective as therapeutic compounds. Results Peptide or locked nucleic acids, miRNA sponges or antagomiRs attached to plasmid or lentiviral vectors carrying miRNA sequences to its target are objects of our analysis, demonstrating their effectiveness in a large number and types of tumours. We have also tried how to overcome their high immunogenicity, which remains its greatest limit for clinical use. Conclusions They are ambitious but fascinating promise to alter the promotion of the tumour growth by binding specific molecular targets, with high precision and low toxicity, leaving the scientists the chance of development as anti‐cancer drugs and not just.

No abstract