Angiotensin-converting enzyme 2 (ACE2) is a receptor for the spike protein of SARS-COV-2 that allows viral binding and entry and is expressed on the surface of several pulmonary and non-pulmonary cell types, with induction of a “cytokine storm” upon binding. Other cell types present the receptor and can be infected, including cardiac, renal, intestinal, and endothelial cells. High ACE2 levels protect from inflammation. Despite the relevance of ACE2 levels in COVID-19 pathogenesis, experimental studies to comprehensively address the question of ACE2 regulations are still limited. A relevant observation from the clinic is that, besides the pro-inflammatory cytokines, such as IL-6 and IL-1β, the anti-inflammatory cytokine IL-10 is also elevated in worse prognosis patients. This could represent somehow a “danger signal”, an alarmin from the host organism, given the immuno-regulatory properties of the cytokine. Here, we investigated whether IL-10 could increase ACE2 expression in the lung-derived Calu-3 cell line. We provided preliminary evidence of ACE2 mRNA increase in cells of lung origin in vitro, following IL-10 treatment. Endothelial cell infection by SARS-COV-2 is associated with vasculitis, thromboembolism, and disseminated intravascular coagulation. We confirmed ACE2 expression enhancement by IL-10 treatment also on endothelial cells. The sartans (olmesartan and losartan) showed non-statistically significant ACE2 modulation in Calu-3 and endothelial cells, as compared to untreated control cells. We observed that the antidiabetic biguanide metformin, a putative anti-inflammatory agent, also upregulates ACE2 expression in Calu-3 and endothelial cells. We hypothesized that IL-10 could be a danger signal, and its elevation could possibly represent a feedback mechanism fighting inflammation. Although further confirmatory studies are required, inducing IL-10 upregulation could be clinically relevant in COVID-19-associated acute respiratory distress syndrome (ARDS) and vasculitis, by reinforcing ACE2 levels.

Graphical AbstractThe cartoon summarized the major approaches and insights of the manuscript: (A) the possibility to recover waste material from extra-virgin olive oil (EVOO) processing that allows the repurposing of polyphenol-rich extracts characterized by (B) antiangiogenic activities in vivo, antiproliferative activities in vitro on BC cell lines (C), cardioprotective activities on rat and human cardiomyocytes (HCMs) (D), and in vivo on the zebrafish embryo heart (E).

In questo articolo č riportata l'esperienza di un gruppo a termine per padri di adolescenti seguiti presso un ambulatorio ASL che si occupa di etŕ evolutiva in Torino. L'obiettivo č offrire sostegno ai padri attraverso l'intervento gruppale in un momento in cui la figura paterna č messa in discussione a livello familiare dalle criticitŕ dell'adolescenza cui si accompagna un disagio psicologico e dai grandi cambiamenti macrosociali. Il gruppo rende fruibili le connessioni e le discontinuitŕ tra i ruoli genitoriali e i bisogni dei figli del nostro tempo; contemporaneamente agevola il superamento dell'impasse sintomatologica attraverso una rivisitazione transgenerazionale del rapporto padre-figlio.

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