Prevalence of neutropenia in US residents: a population based analysis of NHANES 2011-2018.

AIMS: Neutrophils play a pivotal in immunity and inflammation. We aim to investigate the prevalence of neutropenia in the United States. METHODS: In this cross-sectional study, participants from the National Health and Nutrition Examination Survey (NHANES) (2011-2018) were enrolled. Demographic information, hematologic measurements, smoking status of all participants were collected for all participants. All statistical analyses were performed utilizing the NHANES survey weights. Covariate-adjusted linear regression was used to compare hematologic indices in different population grouped by age, sex, ethnicity, and smoking. We also employed multivariate-logistic regression to estimate the weighted odds ratio with a 95% confidence interval and predict the neutropenia risk among. RESULTS: 32,102 participants from NHANES survey were included, represented 286.6 million multiracial population in the United States. Black participants had lower mean leukocyte count (mean difference (MD): 0.71 × 109/L; P < 0.001) and lower neutrophil count (MD: 0.83 × 109/L; P < 0.001) compared with white participants after adjusting for age and sex. Furthermore, t a notable observation was the significant downward shift in the distribution curves of leukocyte count and neutrophil count among black participants. Smokers had a higher mean leukocyte count (MD: 1.10 × 109 cells/L; P < 0.001) and a higher mean neutrophil count (MD: 0.75 × 109 cells/L; P < 0.001) comparing with nonsmokers. The estimated prevalence of neutropenia was 1.24% (95% CI: 1.11 - 1.37%), which corresponds to approximately 35.5 million individuals in the United States. The prevalence of neutropenia in black participants was significantly higher than other races. Results of logistic regression analysis showed that black individuals, male individuals, and children younger than 5 years had a higher risk of neutropenia. CONCLUSIONS: Neutropenia is more common in the general population than we thought, especially in black individuals and children. More attention should be paid to neutropenia.

The dietary inflammatory index and its association with the prevalence of hypertension: A cross-sectional study.

Aims: We aim to investigate the association of the Dietary Inflammatory Index (DII) with the prevalence of hypertension in a large multiracial population in the United States. Methods: Participants from the National Health and Nutrition Examination Survey (NHANES) (1999-2018) were included in this cross-sectional study. Dietary information was obtained and used to calculate DII. Blood pressures of participants were measured by experienced examiners. The NHANES used the method of "stratified multistage probability sampling," and this study is a weight analysis following the NHANES analytic guidance. Weight logistic regression analysis was adopted to investigate the association of hypertension with DII. Least Absolute Shrinkage and Selection Operator (LASSO) regression was carried out to screen the most important dietary factors associated with the risk of hypertension. Moreover, a nomogram model based on key dietary factors was established; the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic power of the nomogram model for screening hypertension risk. Results: A total of 45,023 participants were included in this study, representing 191 million residents in the United States. Participants with hypertension had an elevated DII compared with those without hypertension. Weight logistic regression showed that an increment of DII was strongly associated with hypertension after adjusting for confounding factors. The nomogram model, based on key dietary factors screened by LASSO regression, showed a favorable discriminatory power with an area under the curve (AUC) of 78.5% (95% CI: 78.5%-79.3%). Results of the sensitivity analysis excluding participants who received any drug treatment were consistent with those in the main analysis. Conclusion: An increment of DII is associated with the risk of hypertension. For better prevention and treatment of hypertension, more attention should be paid to controlling dietary inflammation.

MicroRNA profiling of human myeloid angiogenic cells derived from peripheral blood mononuclear cells.

Human myeloid angiogenic cells (MACs), also termed early endothelial progenitor cells, play an important role in neovascularization and vascular repair. MicroRNAs (miRNAs) are a class of naturally occurring, noncoding, short (∼22 nucleotides), single-stranded RNAs that regulate gene expression post-transcriptionally. MiRNAs have been shown to regulate MAC function. A miRNA signature of MACs was described approximately a decade ago, and many new miRNAs have been discovered in recent years. In this study, we aimed to provide an up-to-date miRNA signature for human MACs. MACs were obtained by culture of human peripheral blood mononuclear cells in endothelial medium for 7 days. Using qPCR array analysis we identified 72 highly expressed miRNAs (CT value < 30) in human MACs. RT-qPCR quantification of select miRNAs revealed a strong correlation between the CT values detected by the array analysis and RT-qPCR, suggesting the miRNA signature generated by the qPCR array assay is accurate and reliable. Experimentally validated target genes of the 10 most highly expressed miRNAs were retrieved. Only a few of the targets and their respective miRNAs have been studied for their role in MAC biology. Our study therefore provides a valuable repository of miRNAs for future exploration of miRNA function in MACs.

MicroRNA signature of human blood mononuclear cells.

MicroRNAs (miRNAs) regulate a wide range of cellular processes and functions. Blood mononuclear cells (BMNCs) participate in the immune response, inflammatory reaction and angiogenesis. In 2010, a total of 157 miRNAs were quantified by RT-qPCR and a miRNA signature was determined for human peripheral BMNCs. With the advent of technologies such as RNA sequencing, many new miRNAs have been identified. This study was designed to provide an up-to-date miRNA signature for human BMNCs. Peripheral BMNCs were isolated by Ficoll density gradient centrifugation. Using the qPCR array assay, we identified 108 highly expressed miRNAs (Ct value < 30) in human BMNCs. Further validation of the array results by quantifying select miRNAs with RT-qPCR revealed a strong correlation between Ct values derived from array analysis and RT-qPCR, suggesting the array results presented in this study are accurate and reliable. Of note, the function of the majority of the highly expressed miRNAs we have identified has not yet been studied. Our findings may help direct further studies of the regulatory roles of miRNAs in BMNC function.

Decreased levels of miR-28-5p and miR-361-3p and increased levels of insulin-like growth factor 1 mRNA in mononuclear cells from patients with hereditary hemorrhagic telangiectasia 1.

Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular disorder inherited in an autosomal dominant manner. Patients with HHT can develop vascular dysplasias called telangiectasias and arteriovenous malformations (AVMs). Our objective was to profile and characterize micro-RNAs (miRNAs), short noncoding RNAs that regulate gene expression posttranscriptionally, in HHT patient-derived peripheral blood mononuclear cells (PBMCs). PBMCs, comprised mostly of lymphocytes and monocytes, have been reported to be dysfunctional in HHT. A total of 40 clinically confirmed HHT patients and 22 controls were enrolled in this study. PBMCs were isolated from 16 mL of peripheral blood and purified for total RNA. MiRNA expression profiling was conducted with a human miRNA array analysis. Select dysregulated miRNAs and miRNA targets were validated with reverse transcription-quantitative polymerase chain reaction. Of the 377 miRNAs screened, 41 dysregulated miRNAs were identified. Both miR-28-5p and miR-361-3p, known to target insulin-like growth factor 1 (IGF1), a potent angiogenic growth factor, were found to be significantly downregulated in HHT patients. Consequently, IGF1 mRNA levels were found to be significantly elevated. Our research successfully identified miRNA dysregulation and elevated IGF1 mRNA levels in PBMCs from HHT patients. This novel discovery represents a potential pathogenic mechanism that could be targeted to alleviate clinical manifestations of HHT.

Dysfunction and Therapeutic Potential of Endothelial Progenitor Cells in Diabetes Mellitus.

Diabetes mellitus (DM) is a chronic, multifactorial metabolic disease whereby insulin deficiency or resistance results in hyperglycemia. Endothelial cells (ECs) form the innermost layer of the blood vessel and produce and release a variety of vasoactive substances and growth factors to regulate vascular homeostasis and angiogenesis. Hyperglycemia and insulin resistance can cause endothelial dysfunction, leading to vascular complications such as coronary artery disease, peripheral arterial disease, diabetic nephropathy, neuropathy and retinopathy. The detrimental effect exerted on ECs by hyperglycemia and insulin resistance underlines the importance of reparatory mechanisms in DM. Endothelial progenitor cells (EPCs), derived from bone marrow, have been recognized as endogenous cells involved in endothelial repair and new blood vessel formation. Initially isolated from a subset of circulating CD34+ mononuclear cells, EPCs were found to possess the ability to differentiate into ECs when cultured in vitro and incorporate into newly formed vessels upon transplantation in animal models of ischemia. Due to the low frequency of CD34+ cells in circulation, the vast majority of studies investigating EPC actions have used cells that are generated through the culture of peripheral blood mononuclear cells (PBMNCs) for 4 - 7 days in endothelial selective medium. These cells, mainly of myeloid hematopoietic cell origin, were termed "Early EPCs," of which, few expressed stem/progenitor-cell markers. Therefore, early EPCs were also termed "myeloid angiogenic cells" (MACs). When PBMNCs are cultured for over 2 weeks, early EPCs gradually diminish while so-called late EPCs appear. Late EPCs share phenotypic features with mature ECs and are therefore also termed blood-derived ECs; they will not be addressed in this review. MAC dysfunction has been observed in a variety of disease conditions including DM. In this article we review the activities and therapeutic potential of MACs in DM. We will interchangeably use "EPCs" and "MACs" to refer to the cells procured by culture of PBMNCs in EC selective medium for approximately 7 days.