Inhibition of Prostaglandin F2α Receptors Exaggerates HCl-Induced Lung Inflammation in Mice.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe respiratory disorders that are caused by aspiration, sepsis, trauma, and pneumonia. A clinical feature of ALI/ARDS is the acute onset of severe hypoxemia, and the mortality rate, which is estimated at 38-50%, remains high. Although prostaglandins (PGs) are detected in the bronchoalveolar lavage fluid of patients with ALI/ARDS, the role of PGF2α in ALI remains unclear. We aimed to clarify the role of PGF2α/PGF2α receptor (FP) signaling in acid-induced ALI using an FP receptor antagonist, AL8810. Intratracheal injection of hydrochloric acid (HCl) increased neutrophil migration into the lungs, leading to respiratory dysfunction. Pre-administration of AL8810 further increased these features. Moreover, pre-treatment with AL8810 enhanced the HCl-induced expression of pro-inflammatory cytokines and neutrophil migratory factors in the lungs. Administration of HCl decreased the gene expression of lung surfactant proteins, which was further reduced by co-administration of AL8810. Administration of AL8810 also increased lung edema and reduced mRNA expression of epithelial sodium channel in the lungs, indicating that AL8810 reduced fluid clearance. Furthermore, AL8810 also increased lipopolysaccharide-induced expression of adhesion molecules such as intracellular adhesion molecule-1 and E-selectin in human umbilical vein endothelial cells. These results indicate that inhibition of FP receptors by AL8810 exacerbated HCl-induced ALI.

Cracking the Chloroquine Conundrum: The Application of Defective UiO-66 Metal-Organic Framework Materials to Prevent the Onset of Heart Defects-In Vivo and In Vitro.

In this study, we present a modulated synthesis nanocrystalline defective UiO-66 metal-organic framework as a potential chloroquine diphosphate (CQ) delivery system. Increasing the concentration of hydrochloric acid during the modulated synthesis resulted in a considerable increase of pore volume, which enhanced the CQ loading in CQ@UiO-66 composites. Drug release tests for CQ@UiO-66 composites have confirmed prolonged CQ release in comparison with pure CQ. In vivo tests on a Danio reiro model organism have revealed that CQ released from CQ@UiO-66 25% showed lower toxicity and fewer cardiotoxic effects manifested by cardiac malformations and arrhythmia in comparison to analogous doses of CQ. Cytotoxicity tests proved that the CQ loaded on the defective UiO-66 cargo resulted in increased viability of cardiac cells (H9C2) as compared to incubation with pure CQ. The experimental results presented here may be a step forward in the context of reducing the cardiotoxicity CQ.

Can volcanic trace elements facilitate Covid-19 diffusion? A hypothesis stemming from the Mount Etna area, Sicily.

In December 2019, severe cases of pneumonia of unknown aetiology were reported in Wuhan city, in China. Lately, the pneumonia was related to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and the diseases was termed coronavirus disease-2019 (COVID-19). At the end of January 2020, the infection spread all over Italy, but with high infection rates and mortality in the northern part, especially in Lombardy, the most industrialized and polluted region of the country. It is noteworthy that a strong association between severe viral respiratory disease and air pollution has been described. Air pollutant could be solid particles, liquid droplets, or gases and can be of natural origin (such as ash from a volcanic eruption) or released from motor vehicle depletes (carbon monoxide gas) or factories (sulfur dioxide). Volcanic eruptions release large amounts of sulphuric acid, hydrogen sulfide, and hydrochloric acid into the atmosphere. Pulmunary diseases spreadby means of small droplets in thebreath, also called aerosols, and air pollution may facilitate the outside survival of viruses. We suppose that ash and gases emitted from the Mount Etna contributed to air pollution, potentially favouring the major contagion of COVID-19 in the eastern flank of the mountain, as in Catania city. In fact, ash and gases (with regard to radon) are usually particularly intense in winter, with a reduction of emission of specific metals with warmer weather. This is the first paper that elaborates the hypothesis of a potential role of volcanic gases and heavy metals-related air pollution, combined to specific climatic conditions and regional topography, in favouring severe COVID-19 diffusion in Sicily. Clinical and epidemiological studies are needed to support the hypothesis and plan the due prevention and awareness-raising campaigns.