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Vaping has risen substantially in recent years, particularly among young adults. While e-hookah vaping acutely reduces endothelial function, the role of nicotine and the mechanisms by which it may impairs endothelial function remain understudied. In a randomized cross-over study, we investigated the acute effects of vaping e-hookah, with and without nicotine, as compared to sham on endothelial function assessed by brachial artery flow-mediated dilation (FMD), among 18 overtly healthy young adults. To determine the role of changes in circulating factors in plasma on endothelial cell function, human umbilical vein endothelial cells (HUVECs) were cultured with participants' plasma and acetylcholine-stimulated NO production and basal ROS bioactivity were assessed. E-hookah vaping with nicotine, which acutely increased heart rate (HR) 6±3 bpm and mean arterial pressure (MAP) 7±2 mm Hg (mean±SE; p<0.001), decreased endothelial-dependent FMD by 1.57±0.19%Δ (p=0.001), indicating impairment in endothelial function. Vaping e-hookah without nicotine, which mildly increased hemodynamics (p=ns), did not significantly impair endothelial function. No changes were observed after sham vaping. HUVECs cultured with participants' plasma after vs. before e-hookah vaping with nicotine, but not without nicotine or sham vaping, exhibited reductions in endothelial cell NO bioavailability and increases in ROS bioactivity (p<0.05). Plasma nicotine concentrations increased after vaping e-hookah with nicotine (6.7±1.8 ng/mL; p<0.001), whereas no changes were observed after e-hookah without nicotine or sham (p=ns). Acute e-hookah vaping induces endothelial dysfunction by impairing NO-bioavailability associated with increased ROS production, and these effects are attributable to nicotine, not to non-nicotine constituents, present in the flavored e-liquid.
Vaping has risen substantially in recent years, particularly among young adults. While e-hookah vaping acutely reduces endothelial function, the role of nicotine and the mechanisms by which it may impairs endothelial function remain understudied. In a randomized cross-over study, we investigated the acute effects of vaping e-hookah, with and without nicotine, as compared to sham on endothelial function assessed by brachial artery flow-mediated dilation (FMD), among 18 overtly healthy young adults. To determine the role of changes in circulating factors in plasma on endothelial cell function, human umbilical vein endothelial cells (HUVECs) were cultured with participants' plasma and acetylcholine-stimulated NO production and basal ROS bioactivity were assessed. E-hookah vaping with nicotine, which acutely increased heart rate (HR) 6±3 bpm and mean arterial pressure (MAP) 7±2 mm Hg (mean±SE; p<0.001), decreased endothelial-dependent FMD by 1.57±0.19%Δ (p=0.001), indicating impairment in endothelial function. Vaping e-hookah without nicotine, which mildly increased hemodynamics (p=ns), did not significantly impair endothelial function. No changes were observed after sham vaping. HUVECs cultured with participants' plasma after vs. before e-hookah vaping with nicotine, but not without nicotine or sham vaping, exhibited reductions in endothelial cell NO bioavailability and increases in ROS bioactivity (p<0.05). Plasma nicotine concentrations increased after vaping e-hookah with nicotine (6.7±1.8 ng/mL; p<0.001), whereas no changes were observed after e-hookah without nicotine or sham (p=ns). Acute e-hookah vaping induces endothelial dysfunction by impairing NO-bioavailability associated with increased ROS production, and these effects are attributable to nicotine, not to non-nicotine constituents, present in the flavored e-liquid.
The rapid development of the COVID-19 pandemic resulted in a closer analysis of cell functioning during β-coronavirus infection. This review will describe evidence for COVID-19 as a syndrome with a strong, albeit still underestimated, mitochondrial component. Due to the sensitivity of host mitochondria to coronavirus infection, SARS-CoV-2 affects mitochondrial signaling, modulates the immune response, modifies cellular energy metabolism, induces apoptosis and ageing, worsening COVID-19 symptoms which can sometimes be fatal. Various aberrations across human systems and tissues and their relationships with mitochondria were reported. In this review, particular attention is given to characterization of multiple alterations in gene expression pattern and mitochondrial metabolism in COVID-19; the complexity of interactions between SARS-CoV-2 and mitochondrial proteins is presented. The participation of mitogenome fragments in cell signaling and the occurrence of SARS-CoV-2 subgenomic RNA within membranous compartments, including mitochondria is widely discussed. As SARS-CoV-2 severely affects the quality system of mitochondria, the cellular background for aberrations in mitochondrial dynamics in COVID-19 is additionally characterized. Finally, perspectives on the mitigation of COVID-19 symptoms by affecting mitochondrial biogenesis by numerous compounds and therapeutic treatments are briefly outlined.
The persistent threat of COVID-19, particularly with the emergence of new variants, underscores the urgency for innovative therapeutic strategies beyond conventional antiviral treatments. Current immunotherapies, including IL-6/IL-6R monoclonal antibodies and JAK inhibitors, exhibit suboptimal efficacy, necessitating alternative approaches. Our review delves into the significance of NAD+ metabolism in COVID-19 pathology, marked by decreased NAD+ levels and upregulated NAD+-consuming enzymes such as CD38 and poly (ADP-ribose) polymerases (PARPs). Recognizing NAD+’s pivotal role in energy metabolism and immune modulation, we propose modulating NAD+ homeostasis could bolster the host’s defensive capabilities against the virus. The article reviews the scientific rationale behind targeting NAD+ pathways for therapeutic benefit, utilizing strategies such as NAD+ precursor supplementation and enzyme inhibition to modulate immune function. While preliminary data are encouraging, the challenge lies in optimizing these interventions for clinical use. Future research should aim to unravel the intricate roles of key metabolites and enzymes in NAD+ metabolism and to elucidate their specific mechanisms of action. This will be essential for developing targeted NAD+ therapies, potentially transforming the management of COVID-19 and setting a precedent for addressing other infectious diseases.
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