Promising gas therapies for severe COVID-19.

The novel coronavirus disease 2019 (COVID-19) pandemic is a worldwide catastrophe, thoroughly challenging the healthcare systems. A growing number of victims suffer from a remarkable acute respiratory distress syndrome (ARDS) that necessitates admission to the intensive care unit (ICU), but there are no satisfactory treatments. Various gas therapies including nitric oxide, ozone, hyperbaric oxygen, hydrogen, and heliox have been employed in the fight against the pandemic and have improved clinical outcomes. However, the potential roles of these gases in COVID-19 treatment need to be verified in well-designed randomized controlled trials. This paper reviews advances in gaseous therapy of COVID-19.

Heart-targeted amelioration of sepsis-induced myocardial dysfunction by microenvironment responsive nitric oxide nanogenerators in situ.

BACKGROUND: A balanced endogenous level of bioavailable nitric oxide (NO) plays a key role in maintaining cardiovascular homeostasis. The bioactive NO level in the cardiomyocytes was much reduced during sepsis. However, it is clinically challenging for the NO gas therapy due to the lack of spatial and temporal release system with precise control. The purpose of this study is to design a NO-releasing biomaterial with heart-targeted capability responsive to the infectious microenvironment, thus ameliorating lipopolysaccharide (LPS)-induced cardiac dysfunction. RESULTS: The heart-targeted NO delivery and in situ releasing system, PCM-MSN@LA, was synthesized using hollow mesoporous silica nanoparticles (MSN) as the carrier, and L-arginine (LA) as the NO donor. The myocardial delivery was successfully directed to heart by specific peptide (PCM) combined with low-intensity focused ultrasound (LIFU) guidance. The myocardial system synthesized NO from the LA released from PCM-MSN@LA in the presence of increased endogenous nitric oxide synthase (NOS) activity induced by LPS. This targeted NO release in situ achieved extraordinary protective effects against LPS-challenged myocardial injury by reducing the recruitment of inflammatory cells, inhibiting oxidative stress and maintaining the mitochondria integrity. In particular, this protection was not compromised by simultaneous circulation collapse as an adverse event in the context. CONCLUSIONS: PCM-MSN@LA + LIFU exhibited extraordinary cardioprotective effects against severe sepsis in the hearts of LPS-treated animals without the side effect of NO diffusion. This technology has great potential to be served as a novel therapeutic strategy for sepsis-induced myocardial injury.