Association between NAD<sup>+</sup> levels and anaemia among women in community‐based study

Yang, Fan; Zhang, Xuguang; Hu, Feifei; Yu, Ye; Luo, Lei; Zhao, Yuzheng; Pan, Bo; Qiu, Yugang; Guo, Jun; Feng, Xiao; Xie, Xiaomei; Ju, Zhenyu; Zhou, Yingling

doi:10.1111/jcmm.17281

Cited by 7 publications

(4 citation statements)

References 42 publications

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“…These complexities necessitate thorough optimization of LC/MS methods to produce reliable results for plasma eNAD + quantification (54). Yet, it is important to note that while LC/MS has been a robust and validated technique for NAD + measurements in whole blood, correlating well with enzymatic assays (55)(56)(57), such an equivalence has yet to be established for blood plasma. Nevertheless, the data is novel, and the inclusion of healthy volunteers has ruled out surrogate parameters of age or disease, which is the case for many other studies.…”

Section: Discussionmentioning

confidence: 99%

Optimized protocol for quantification of extracellular nicotinamide adenine dinucleotide: evaluating clinical parameters and pre-analytical factors for translational research

Saqr,

Kamali,

Brunnbauer

et al. 2024

Front. Med.

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Nicotinamide adenine dinucleotide (NAD+), a coenzyme for more than 500 enzymes, plays a central role in energy production, metabolism, cellular signaling, and DNA repair. Until recently, NAD+ was primarily considered to be an intracellular molecule (iNAD+), however, its extracellular species (eNAD+) has recently been discovered and has since been associated with a multitude of pathological conditions. Therefore, accurate quantification of eNAD+ in bodily fluids such as plasma is paramount to answer important research questions. In order to create a clinically meaningful and reliable quantitation method, we analyzed the relationship of cell lysis, routine clinical laboratory parameters, blood collection techniques, and pre-analytical processing steps with measured plasma eNAD+ concentrations. Initially, NAD+ levels were assessed both intracellularly and extracellularly. Intriguingly, the concentration of eNAD+ in plasma was found to be approximately 500 times lower than iNAD+ in peripheral blood mononuclear cells (0.253 ± 0.02 μM vs. 131.8 ± 27.4 μM, p = 0.007, respectively). This stark contrast suggests that cellular damage or cell lysis could potentially affect the levels of eNAD+ in plasma. However, systemic lactate dehydrogenase in patient plasma, a marker of cell damage, did not significantly correlate with eNAD+ (n = 33; r = −0.397; p = 0.102). Furthermore, eNAD+ was negatively correlated with increasing c-reactive protein (CRP, n = 33; r = −0.451; p = 0.020), while eNAD+ was positively correlated with increasing hemoglobin (n = 33; r = 0.482; p = 0.005). Next, variations in blood drawing, sample handling and pre-analytical processes were examined. Sample storage durations at 4°C (0–120 min), temperature (0° to 25°C), cannula sizes for blood collection and tourniquet times (0 – 120 s) had no statistically significant effect on eNAD+ (p > 0.05). On the other hand, prolonged centrifugation (> 5 min) and a faster braking mode of the centrifuge rotor (< 4 min) resulted in a significant decrease in eNAD+ levels (p < 0.05). Taken together, CRP and hemoglobin appeared to be mildly correlated with eNAD+ levels whereas cell damage was not correlated significantly to eNAD+ levels. The blood drawing trial did not show any influence on eNAD+, in contrast, the preanalytical steps need to be standardized for accurate eNAD+ measurement. This work paves the way towards robust eNAD+ measurements, for use in future clinical and translational research, and provides an optimized hands-on protocol for reliable eNAD+ quantification in plasma.

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Section: Discussionmentioning

confidence: 99%

Optimized protocol for quantification of extracellular nicotinamide adenine dinucleotide: evaluating clinical parameters and pre-analytical factors for translational research

Saqr,

Kamali,

Brunnbauer

et al. 2024

Front. Med.

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“…There are other factors that could affect our findings on the association between RDW and mortality. (3) We are unable to link laboratory data to other potentially confounding variables, such as past history and treatment history. (4) Although we have adjusted for chronic conditions that may affect the results, we do not have information on cases of death due to complications from drug use in patients.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, RDW has been used for the diagnosis and differential diagnosis of different types of anemia (2). Red blood cell distribution width values are often seen in cases of nutrient deficiency, hemolysis, and anemia, and have been used to diagnose and classify anemia from various causes (3)(4)(5). An increase in RDW values is usually associated with an increase in the rate of erythrocyte proliferation.…”

Section: Introductionmentioning

confidence: 99%

Association between red blood cell distribution width and all-cause mortality in unselected critically ill patients: Analysis of the MIMIC-III database

Peng

2023

Front. Med.

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BackgroundAlthough red cell distribution width (RDW) is widely observed in clinical practice, only a few studies have looked at all-cause mortality in unselected critically ill patients, and there are even fewer studies on long-term mortality. The goal of our study was to explore the prediction and inference of mortality in unselected critically ill patients by assessing RDW levels.MethodsWe obtained demographic information, laboratory results, prevalence data, and vital signs from the unselected critically ill patients using the publicly available MIMIC-III database. We then used this information to analyze the association between baseline RDW levels and unselected critically ill patients using Cox proportional risk analysis, smoothed curve fitting, subgroup analysis, and Kaplan–Meier survival curves for short, intermediate, and long-term all-cause mortality in unselected critically ill patients.ResultsA total of 26,818 patients were included in our study for the final data analysis after screening in accordance with acceptable conditions. Our study investigated the relationship between RDW levels and all-cause mortality in a non-selected population by a smoothed curve fit plots and COX proportional risk regression models integrating cubic spline functions reported results about a non-linear relationship. In the fully adjusted model, we found that RDW values were positively associated with 30-day, 90-day, 365-day, and 4-year all-cause mortality in 26,818 non-selected adult patients with HRs of 1.10 95%CIs (1.08, 1.12); 1.11 95%CIs (1.10, 1.13); 1.13 95%CIs (1.12, 1.14); 1.13 95%CIs (1.12, 1.14).ConclusionIn unselected critically ill patients, RDW levels were positively associated with all-cause mortality, with elevated RDW levels increasing all-cause mortality.

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“…1 , 6 , 7 , 8 ). Recent study also suggests that administration of NR [ 130 ] and NAD [ 131 ] may improve anemia, which is a common complication in patients with CKD [ 18 ] . The mechanisms may be associated with increased activation of sirtuins that antagonize HIF-1α, NF-kB, and AHR activity but promote HIF-2α responses [ 17 , 25 , 79 ] (Figs.…”

Section: Introductionmentioning

confidence: 99%

The complexity of nicotinamide adenine dinucleotide (NAD), hypoxic, and aryl hydrocarbon receptor cell signaling in chronic kidney disease

Curran,

Kopp

2023

J Transl Med

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Early-stage detection of chronic kidney diseases (CKD) is important to treatment that may slow and occasionally halt CKD progression. CKD of diverse etiologies share similar histologic patterns of glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Macro-vascular disease and micro-vascular disease promote tissue ischemia, contributing to injury. Tissue ischemia promotes hypoxia, and this in turn activates the hypoxia-inducible transcription factors (HIFs). HIF-1α and HIF-2α, share a dimer partner, HIF-1β, with the aryl hydrocarbon receptor (AHR) and are each activated in CKD and associated with kidney cellular nicotinamide adenine dinucleotide (NAD) depletion. The Preiss-Handler, salvage, and de novo pathways regulate NAD biosynthesis and gap-junctions regulate NAD cellular retention. In the Preiss-Handler pathway, niacin forms NAD. Niacin also exhibits crosstalk with HIF and AHR cell signals in the regulation of insulin sensitivity, which is a complication in CKD. Dysregulated enzyme activity in the NAD de novo pathway increases the levels of circulating tryptophan metabolites that activate AHR, resulting in poly-ADP ribose polymerase activation, thrombosis, endothelial dysfunction, and immunosuppression. Therapeutically, metabolites from the NAD salvage pathway increase NAD production and subsequent sirtuin deacetylase activity, resulting in reduced activation of retinoic acid-inducible gene I, p53, NF-κB and SMAD2 but increased activation of FOXO1, PGC-1α, and DNA methyltransferase-1. These post-translational responses may also be initiated through non-coding RNAs (ncRNAs), which are additionally altered in CKD. Nanoparticles traverse biological systems and can penetrate almost all tissues as disease biomarkers and drug delivery carriers. Targeted delivery of non-coding RNAs or NAD metabolites with nanoparticles may enable the development of more effective diagnostics and therapies to treat CKD.

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Association between NAD⁺ levels and anaemia among women in community‐based study

Cited by 7 publications

References 42 publications

Optimized protocol for quantification of extracellular nicotinamide adenine dinucleotide: evaluating clinical parameters and pre-analytical factors for translational research

Optimized protocol for quantification of extracellular nicotinamide adenine dinucleotide: evaluating clinical parameters and pre-analytical factors for translational research

Association between red blood cell distribution width and all-cause mortality in unselected critically ill patients: Analysis of the MIMIC-III database

The complexity of nicotinamide adenine dinucleotide (NAD), hypoxic, and aryl hydrocarbon receptor cell signaling in chronic kidney disease

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Association between NAD+ levels and anaemia among women in community‐based study

Cited by 7 publications

References 42 publications

Optimized protocol for quantification of extracellular nicotinamide adenine dinucleotide: evaluating clinical parameters and pre-analytical factors for translational research

Optimized protocol for quantification of extracellular nicotinamide adenine dinucleotide: evaluating clinical parameters and pre-analytical factors for translational research

Association between red blood cell distribution width and all-cause mortality in unselected critically ill patients: Analysis of the MIMIC-III database

The complexity of nicotinamide adenine dinucleotide (NAD), hypoxic, and aryl hydrocarbon receptor cell signaling in chronic kidney disease

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Association between NAD⁺ levels and anaemia among women in community‐based study