SARS-CoV-2 Causes Lung Inflammation through Metabolic Reprogramming and RAGE

Clinical studies indicate that patients infected with SARS-CoV-2 develop hyperinflammation, which correlates with increased mortality. The SARS-CoV-2/COVID-19-dependent inflammation is thought to occur via increased cytokine production and hyperactivity of RAGE in several cell types, a phenomenon observed for other disorders and diseases. Metabolic reprogramming has been shown to contribute to inflammation and is considered a hallmark of cancer, neurodegenerative diseases, and viral infections. Malfunctioning glycolysis, which normally aims to convert glucose into pyruvate, leads to the accumulation of advanced glycation end products (AGEs). Being aberrantly generated, AGEs then bind to their receptor, RAGE, and activate several pro-inflammatory genes, such as IL-1b and IL-6, thus, increasing hypoxia and inducing senescence. Using the lung epithelial cell (BEAS-2B) line, we demonstrated that SARS-CoV-2 proteins reprogram the cellular metabolism and increase pyruvate kinase muscle isoform 2 (PKM2). This deregulation promotes the accumulation of AGEs and senescence induction. We showed the ability of the PKM2 stabilizer, Tepp-46, to reverse the observed glycolysis changes/alterations and restore this essential metabolic process

Preparation of Novel Silicone Multicompartment Particles by Multiple Emulsion Templating and Their Use As Encapsulating Systems

Multicompartment poly(dimethylsiloxane) particles were produced for the first time using water-in-oil-in-water (W1/O/W2) emulsions as templates. Multiple silicone W1/O/W2 emulsions were successfully prepared by using silicone precursors with a low viscosity. Several formulation parameters were studied to determine their effect on the properties of emulsions and derived particles. It was observed that the mass fraction of the inner aqueous phase (φ(W1)) and the concentration of both the hydrophobic and hydrophilic surfactants played a crucial role in the morphology and stability of the emulsions. Thus, the derived silicone porous particles also showed different characteristics depending on the emulsion formulation because of the templating effect. At low φ(W1) or high concentrations of the hydrophobic surfactant, particles showed smaller pore sizes as a result of more stable inner droplets. On the other hand, high concentrations of the hydrophobic surfactant resulted in an increase in the size of the derived particles, whereas high concentrations of the hydrophilic surfactant caused the opposite effect. In addition, fluorescein was encapsulated into the hydrophobic particles during the synthesis process and released in a controlled manner. The possibility to encapsulate simultaneously but independently two different hydrophilic components inside the same globule was also tested. On the basis of these results, the obtained silicone porous particles are envisioned to have applications in several advanced fields, for instance, as hydrophobic delivery systems.The authors gratefully acknowledge the Ministerio de Economia y Competitividad (Grant CTQ2011-29336-C03- 01/PPQ) and Generalitat de Catalunya (Grant 2009 SGR-961) for the financial support. C. Rodríguez-Abreu is grateful to the European Union’s Seventh Framework Programme (FP7/2007-2013) under COOPERATION program NMP-theme (Grant 314212) and Xunta de Galicia (PGIDIT, 2010/PX168) for research funding. N. Vilanova thanks CSIC for a JAE-predoctoral scholarship.Peer reviewe