BackgroundNAD+, nicotinamide adenine dinucleotide, is mostly described to associate with the aging process. We aimed to investigate the association between human whole blood NAD+ contents and aging in a relative large-scale community-based population and further to address the gender impact on this association.MethodsWe recruited 1,518 participants aged over 18 years old and free of cardiovascular and any type of cancer from the Jidong community from 2019 to 2020. Whole blood NAD+ level was measured by cycling assay and LC-mass spectroscopy assay. The chronological age and clinical data were collected using standard questionnaires. The participants were divided into five groups according to their chronological age. General liner regression model was performed to analyze the association between NAD+ contents and aging. In addition, we also conducted subgroup analysis by gender.ResultsThe mean age of included 1,518 participants was 43.0 years, and 52.6% of them were men. The average levels of whole blood NAD+ of total participants was 33.0 ± 5.5 μmol/L. The whole blood NAD+ contents in men were significantly higher than that in women (34.5 vs. 31.3 μmol/L). There was significant difference in the meat diet among NAD+ quartile groups (p = 0.01). We observed a decline trend of NAD+ contents with aging before 50 years in total participants with significant level in 40–49 years old group (β coefficients with 95% confidence interval (95% CI): −1.12 (−2.18, −0.06)), while this trend disappeared after the 50 years. In addition, this association was significantly altered by gender (p for interaction = 0.003). In men, as compared with ≤29 years group, adjusted β coefficient decreased with aging but was only significant in the ≥60 year group (β,−2.16; 95% CI, −4.16 to −0.15). In females, the level of whole blood NAD+ did not significantly differ among five age groups and without the trend as males.ConclusionsAssociation of whole blood NAD+ contents with aging significantly differed in males and females. The loss of blood NAD+ with aging only was observed in males, especially in the male middle-aged population. It is crucial to consider the gender difference in further NAD+ related studies in the future.

Nicotinamide adenine dinucleotide (NAD+) level is the protective factor of cardiovascular diseases (CVDs). In addition, anaemia is a risk factor of adverse cardiovascular outcomes in women. However, there are limited data about the association between NAD+ and anaemia. The aim of this study was to evaluate association of NAD+ with anaemia among women. A total of 727 females from Jidong community were included in the current analysis. NAD+ levels were tested by the cycling assay and HPLC assay using whole blood samples. Anaemia was determined by haemoglobin (Hb) concentration, and the subtypes of anaemia were further defined according to mean corpuscular volume (MCV) in blood. Multivariable logistic analysis was used to analyse the association between NAD+ levels and anaemia or its subtypes. The mean age of recruited subjects was 42.7 years. The proportion of anaemia by NAD+ levels quartiles were 19.7% (35/178), 4.8% (9/189), 3.4% (6/178) and 2.7% (5/182). Haematological parameters including haemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and red blood count (RBC) increased over NAD+ quartiles. Red cell volume distribution width (RDW) decreased over NAD+ quartiles. Compared with the lowest quartile of NAD+ levels (<27.6μM), the adjusted odds ratios with 95% confidence intervals of the top quartile were 0.15 (0.06–0.41) for anaemia, 0.05 (0.01–0.36) for microcytic anaemia and 0.37 (0.10–1.36) for normocytic anaemia respectively. Higher NAD+ levels were significantly associated with lower prevalence of anaemia among women, especially microcytic anaemia and normocytic anaemia. Haematological parameters might serve as a predictor of the blood NAD+ levels.

Background. Oxidative stress (OS) is associated with the development of acute myeloid leukemia (AML). However, there is lack of relevant research to confirm that OS-related genes can guide patients in risk stratification and predict their survival probability. Method. First, we Data from three public databases, respectively. Then, we use batch univariate Cox regression and machine learning to select important characteristic genes; next, we build the model and use receiver operating characteristic curve (ROC) to evaluate the accuracy. Moreover, GSEAs were performed to discover the molecular mechanism and conduct nomogram visualization. In addition, the relative importance value was used to identify the hub gene, and GSE9476 was to validate hub gene difference expression. Finally, we use symptom mapping to predict the candidate herbs, targeting the hub gene, and put these candidate herbs into Traditional Chinese Medicine Systems Pharmacology (TCMSP) to identify the main small molecular ingredients and then docking hub proteins with this small molecular. Results. A total of 313 candidate oxidative stress-related genes could affect patients’ outcomes and machine learning to select six potential genes to construct a gene signature model to predict the overall survival (OS) of AML patients. Patients in a high group will obtain a short survival time when compared with the low-risk group ( HR = 3.97 , 95% CI: 2.48-6.36; p < 0.001 ). ROC results demonstrate the model has better prediction efficiency with AUC 0.873. GSEA suggests that this gene is enriched in several important signaling pathways. Nomogram is constructed and is robust. PLA2G4A is a hub gene of signature and associated with prognosis, and Nobiletin could target PLA2G4A for therapy AML. Conclusion. We use two different machine learning methods to build six oxidative stress-related gene signatures that could assist clinical decisions and identify PLA2G4A as a potential biomarker for AML. Nobiletin, targeting PLA2G4, may provide a third pathway for therapy AML.

Objective. To collect and analyze data of patent foramen ovale (PFO). Methods. This study included a total of 260 patients diagnosed with PFO. We analyzed basic clinical data such as sex, age, transesophageal echocardiography as well as other symptoms. Results. Our data showed that females accounted for the highest proportion of PFO (166 females, 64%), with the highest number of patients (65 patients) having between 45 and 55 years. Transesophageal echocardiography examination demonstrated frequent occurrence of tunnel-like anatomical structures. In addition, PFO was associated with symptoms such as migraine, stroke or TIA, syncope, chest tightness, and palpitations, with dizziness being the most common symptom in the patients with PFO. Conclusion. Our data demonstrated that females accounted for the highest proportion of PFO patients, with those aged between 45 and 55 years being most affected. The most frequently encountered clinical symptom was dizziness. Taken together, these findings may help doctors to better understand and screen for PFO patients.

This study tested the hypothesis that Jagged2/Notches promoted the endothelial‐mesenchymal transition (endMT)‐mediated pulmonary arterial hypertension (PAH) (i.e. induction by monocrotaline [MCT]/63 mg/kg/subcutaneous injection) through increasing the expression of GATA‐binding factors which were inhibited by propylthiouracil (PTU) (i.e. 0.1% in water for daily drinking since Day 5 after PAH induction) in rodent. As compared with the control (i.e. HUVECs), the protein expressions of GATAs (3/4/6) and endMT markers (Snail/Zeb1/N‐cadherin/vimentin/fibronectin/α‐SMA/p‐Smad2) were significantly reduced, whereas the endothelial‐phenotype markers (CD31/E‐cadherin) were significantly increased in silenced JAG2 gene or in silenced GATA3 gene of HUVECs (all p < 0.001). As compared with the control, the protein expressions of intercellular signallings (GATAs [3/4/6], Jagged1/2, notch1/2 and Snail/Zeb1/N‐cadherin/vimentin/fibronectin/α‐SMA/p‐Smad2) were significantly upregulated in TGF‐ß/monocrotaline‐treated HUVECs that were significantly reversed by PTU treatment (all p < 0.001). By Day 42, the results of animal study demonstrated that the right‐ventricular systolic‐blood‐pressure (RVSBP), RV weight (RVW) and lung injury/fibrotic scores were significantly increased in MCT group than sham‐control (SC) that were reversed in MCT + PTU groups, whereas arterial oxygen saturation (%) and vasorelaxation/nitric oxide production of PA exhibited an opposite pattern of RVW among the groups (all p < 0.0001). The protein expressions of hypertrophic (ß‐MHC)/pressure‐overload (BNP)/oxidative‐stress (NOX‐1/NOX‐2) biomarkers in RV and the protein expressions of intercellular signalling (GATAs3/4/6, Jagged1/2, notch1/2) and endMT markers (Snail/Zeb1/N‐cadherin/vimentin/fibronectin/TGF‐ß/α‐SMA/p‐Smad2) in lung parenchyma displayed an identical pattern of RVW among the groups (all p < 0.0001). Jagged‐Notch‐GATAs signalling, endMT markers and RVSBP that were increased in PAH were suppressed by PTU.