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New disease targets and medicinal chemistry approaches are urgently needed to develop novel therapeutic strategies for treating pulmonary diseases. Emerging evidence suggests that reduced activity of protein phosphatase 2A (PP2A), a complex heterotrimeric enzyme that regulates dephosphorylation of serine and threonine residues from many proteins, is observed in multiple pulmonary diseases, including lung cancer, smoke-induced chronic obstructive pulmonary disease, alpha-1 antitrypsin deficiency, asthma, and idiopathic pulmonary fibrosis. Loss of PP2A responses is linked to many mechanisms associated with disease progressions, such as senescence, proliferation, inflammation, corticosteroid resistance, enhanced protease responses, and mRNA stability. Therefore, chemical restoration of PP2A may represent a novel treatment for these diseases. This review outlines the potential impact of reduced PP2A activity in pulmonary diseases, endogenous and exogenous inhibitors of PP2A, details the possible PP2A-dependent mechanisms observed in these conditions, and outlines potential therapeutic strategies for treatment. Substantial medicinal chemistry efforts are underway to develop therapeutics targeting PP2A activity. The development of specific activators of PP2A that selectively target PP2A holoenzymes could improve our understanding of the function of PP2A in pulmonary diseases. This may lead to the development of therapeutics for restoring normal PP2A responses within the lung. [ABSTRACT FROM AUTHOR]

Background: During the COVID-19 pandemic, the need for judicious use of diagnostic tests and to limit personnel exposure has led to increased use and dependence on point-of-care ultrasound (POCUS) examinations. We reviewed POCUS findings in patients admitted to the intensive care unit (ICU) for acute respiratory failure with COVID-19 and correlated the findings to severity of illness and 30-day outcomes., Methods: Patients admitted to the ICU in March and April 2020 were reviewed for inclusion (acute hypoxemic respiratory failure secondary to COVID-19 pneumonia; documentation of POCUS findings)., Results: Forty-three patients met inclusion criteria. B lines and pleural thickening were associated with a lower PaO 2 /FiO 2 by 71 ( P = .005; adjusted R 2 = 0.24). Right ventricle (RV) dilation was more common in patients with 30-day mortality ( P = .02) and was a predictor of mortality when adjusted for hypertension, diabetes mellitus, and age (odds ratio, 12.0; P = .048). All patients with RV dilation had bilateral B lines with pleural irregularities., Conclusions: Although lung ultrasound abnormalities are prevalent in patients with severe disease, RV involvement seems to be predictive of outcomes. Further studies are needed to discern the etiology and pathophysiology of RV dilation in COVID-19., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest with regard to this article., (Copyright © 2021 Frontline Medical Communications Inc., Parsippany, NJ, USA.)