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Nicotinamide adenine dinucleotide (NAD) depletion has been postulated as a contributor to the severity of COVID-19; however, no study has prospectively characterized NAD and its metabolites in relation to disease severity in patients with COVID-19. We measured NAD and its metabolites in 56 hospitalized patients with COVID-19 and in two control groups without COVID-19: (1) 31 age- and sex-matched adults with comorbidities, and (2) 30 adults without comorbidities. Blood NAD concentrations in COVID-19 group were only slightly lower than in the control groups (p < 0.05); however, plasma 1-methylnicotinamide concentrations were significantly higher in patients with COVID-19 (439.7 ng/mL, 95% CI: 234.0, 645.4 ng/mL) than in age- and sex-matched controls (44.5 ng/mL, 95% CI: 15.6, 73.4) and in healthy controls (18.1 ng/mL, 95% CI 15.4, 20.8; p < 0.001 for each comparison). Plasma nicotinamide concentrations were also higher in COVID-19 group and in controls with comorbidities than in healthy control group. Plasma concentrations of 2-methyl-2-pyridone-5-carboxamide (2-PY), but not NAD, were significantly associated with increased risk of death (HR = 3.65; 95% CI 1.09, 12.2; p = 0.036) and escalation in level of care (HR = 2.90, 95% CI 1.01, 8.38, p = 0.049). RNAseq and RTqPCR analyses of PBMC mRNA found upregulation of multiple genes involved in NAD synthesis as well as degradation, and dysregulation of NAD-dependent processes including immune response, DNA repair, metabolism, apoptosis/autophagy, redox reactions, and mitochondrial function. Blood NAD concentrations are modestly reduced in COVID-19; however, NAD turnover is substantially increased with upregulation of genes involved in both NAD biosynthesis and degradation, supporting the rationale for NAD+ augmentation to attenuate disease severity.
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http://dx.doi.org/10.1111/acel.14326 | DOI Listing |
J Physiol Biochem
December 2024
Department of Exercise Physiology, Faculty of Sport Sciences, Shahid Rajaee Teacher Training University, Tehran, Iran.
The circadian clock regulates mitochondrial function and affects time-dependent metabolic responses to exercise. The present study aimed to determine the effects of aerobic exercise timing at the light-dark phase on the proteins expression of the circadian clock, mitochondrial dynamics, and, NAD-SIRT1-PPARα axis in skeletal muscle of high-fat diet-induced diabetic mice. In this experimental study, thirty male mice were randomly assigned into two groups based on time: the early light phase, ZT3, and the early dark phase, ZT15, and three groups at each time: (1) Healthy Control (HC), (2) Diabetic Control (DC), and (3) Diabetic + Exercise (DE).
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
Ruhr University Bochum, Analytische Chemie, Universitätsstr 150, 44780, Bochum, GERMANY.
We propose a hybrid electrocatalytic-bioelectrocatalytic reaction cascade integrated on a gas diffusion electrode for CO2 reduction under selective formation of methanol. Ag-Bi2O3 selectively reduces gaseous CO2 to formate at neutral pH conditions. A subsequent enzymatic cascade comprising formaldehyde dehydro-genase and alcohol dehydrogenase, which are both nicotinamide adenine dinucleotide (NAD)-dependent, further reduce formate sequentially to formaldehyde and methanol.
View Article and Find Full Text PDFAgeing Res Rev
December 2024
Institute for Sports Medicine, Alpine Medicine and Health Tourism (ISAG), UMIT TIROL - Private University for Health Sciences and Health Technology, Hall in Tirol, Austria.
Nicotinamide adenine dinucleotide (NAD) is an essential regulator of cellular metabolism and redox processes. NAD levels and the dynamics of NAD metabolism change with increasing age but can be modulated via the diet or medication. Because NAD metabolism is complex and its regulation still insufficiently understood, achieving specific outcomes without perturbing delicate balances through targeted pharmacological interventions remains challenging.
View Article and Find Full Text PDFJ Hazard Mater
December 2024
School of Civil Engineering and Architecture, Taizhou University, Taizhou 318000, China. Electronic address:
The removal of selenite (Se(IV)) and cadmium (Cd(II)) from low-carbon wastewater presents significant challenges. However, the addition of external organic carbon sources is limited in application due to the high cost and potential for secondary pollution. This study introduced a "hibernation-like microbial survival strategy", enabling efficient removal of Se(IV) and Cd(II) in sulfur autotrophic reactor, with S acting as the electron donor.
View Article and Find Full Text PDFAm J Cardiovasc Drugs
December 2024
Department of Pharmacy, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China.
Nicotinamide adenine dinucleotide (NAD) is a promising anti-aging molecule that plays a role in cellular energy metabolism and maintains redox homeostasis. Additionally, NAD is involved in regulating deacetylases, DNA repair enzymes, inflammation, and epigenetics, making it indispensable in maintaining the basic functions of cells. Research on NAD has become a hotspot, particularly regarding its potential in cardiovascular disease (CVD).
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