Association of Plasma Irisin Levels with Circulating Endothelial Microparticles (EMPs) and Endothelial Progenitor Cells (EPCs) in Children Born Prematurely.

Prematurity has been linked with endothelial dysfunction in later life. The purpose of this study was to evaluate the association between plasma irisin, an adipomyokine reported to protect the functional integrity of vascular endothelium, and circulating endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs), consisting early biomarkers of endothelial dysfunction, in preterm-born children. We studied 131 prepubertal children; 61 preterm and 70 born at term (controls). Plasma irisin was determined by ELISA. Circulating CD62E(+), CD144(+) and CD31(+)/CD42b(-) EMPs, and CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs, were determined by flow cytometry. Body mass index, waist-to-hip ratio, neck circumference, systolic and diastolic blood pressure, and biochemical parameters (glucose, lipids, insulin, HOMA-IR) were also evaluated. Plasma irisin was significantly lower (p = 0.001), whereas circulating EMPs and EPCs were higher, in children born prematurely compared to controls. Irisin was recognized as independent predictor for CD144(+) and CD31(+)/CD42b(-) EMPs, CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs in the total study population, and for CD31(+)/CD42b(-) EMPs in the preterm group. In conclusion, plasma irisin correlates independently with circulating EMP and EPC subpopulations in prepubertal children and in preterm-born ones. Further studies in children will potentially elucidate the link between irisin and the primary stages of prematurity-related endothelial dysfunction.

Elevated circulating endothelial microparticles (EMPs) in prepubertal children born preterm.

BACKGROUND: Endothelial microparticles (EMPs) act as early biomarkers of endothelial activation and damage. No studies have investigated EMPs in preterm-born individuals. METHODS: Sixty-three preterm-born children and 52 children born full-term (controls) were studied. Circulating CD62E(+), CD144(+), and CD31(+)/CD42b(-) EMPs were measured in preterm-born children compared to controls; possible associations with cardiovascular risk factors and endothelial function parameters were also assessed. RESULTS: Circulating CD62E(+), CD144(+), and CD31(+)/CD42b(-) EMPs were significantly higher in preterm-born children compared to controls (p = 0.003, p < 0.001, and p < 0.001, respectively). Preterm birth was recognized as an independent predictor of each EMP subpopulation studied; moreover, the mean pressure and velocity of pulmonary artery were independently correlated with CD62E(+) (ß = 0.20, p = 0.04) and CD144(+) EMPs (ß = 0.22, p = 0.02), respectively, whereas age (ß = 0.21, p = 0.03) and being born SGA (ß = 0.26, p = 0.01) correlated independently with CD31(+)/CD42b(-) EMPs in the study population. Furthermore, diastolic blood pressure (ß = 0.24, p = 0.04), being born SGA (ß = 0.24, p = 0.04) and the hyperemic peak velocity of the brachial artery (ß = -0.65, p = 0.02) were independently associated with CD31(+)/CD42b(-) EMPs in the preterm-born group. CONCLUSION: Circulating EMPs were higher in preterm-born children compared to children born full-term. Whether EMPs could act, in clinical practice, as a complementary tool for non-invasive evaluation of endothelium in preterm-born children, remains under investigation. IMPACT: Circulating endothelial microparticles (EMPs) are small membrane vesicles released from endothelial cells and they act as novel biomarkers of endothelial activation and damage. No studies have investigated circulating EMPs in preterm-born individuals. Circulating EMPs were significantly higher in prepubertal preterm-born children compared to children born at term. In the preterm-born group, the hyperemic peak velocity of the brachial artery was independently associated with CD31(+)/CD42b(-) EMPs. Whether assessment of circulating EMPs could act, in clinical practice, as a complementary tool for non-invasive evaluation of endothelium in preterm-born children, remains to be defined in future investigations.

Increased circulating endothelial progenitor cells (EPCs) in prepubertal children born prematurely: a possible link between prematurity and cardiovascular risk.

BACKGROUND: Endothelial progenitor cells (EPCs) ensure vascular integrity and neovascularization. No studies have investigated EPCs in preterm-born children beyond infancy. METHODS: One hundred and thirty-six prepubertal children were enrolled: 63 preterm and 73 born at term (controls). Circulating CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs were measured in preterm-born children compared to controls. Body mass index (BMI), waist-to-hip ratio (WHR), neck circumference, systolic and diastolic blood pressure (SBP and DBP, respectively), fasting glucose, insulin, lipid profile, common carotid and abdominal aortic intima-media thickness (cIMT and aIMT, respectively), endothelium-dependent brachial artery flow-mediated dilation (FMD), and echocardiographic parameters were also assessed. RESULTS: Circulating CD34(+)/VEGFR-2(+)/CD45(-) and CD34(+)/VEGFR-2(+)/CD45dim EPCs were significantly higher in preterm-born children compared to controls (p < 0.001 and p < 0.001, respectively). In total study population and in the preterm-born group, EPCs were significantly lower in children born to mothers with gestational diabetes compared to non-diabetic mothers. Prematurity was associated with higher WHR, neck circumference, SBP, DBP, cIMT, aIMT, mean pressure, and velocity of pulmonary artery; the peak velocity of the brachial artery was significantly lower in children born prematurely. In multiple regression analysis, preterm birth and maternal gestational diabetes were recognized as independent predictors of EPCs. CONCLUSIONS: Circulating EPCs were increased in prepubertal preterm-born children in comparison with peers born full-term. Maternal gestational diabetes was associated with a decrease in EPCs. IMPACT: Mounting evidence supports the adverse effect of prematurity on cardiovascular health. However, the underlying mechanisms that could lead to endothelial dysfunction in preterm-born individuals are not fully understood. Endothelial progenitor cells (EPCs) ensure vascular integrity, normal endothelial function and neovascularization. No studies have investigated the EPCs counts in peripheral blood beyond infancy in children born prematurely. Circulating EPCs were significantly higher in preterm-born prepubertal children compared to controls, thus indicating that prematurity is possibly associated with endothelial damage. In total study population and in the preterm-born group, maternal gestational diabetes was associated with decreased EPCs concentrations.

Identifying Differing Intracellular Cargo Release Mechanisms by Monitoring In Vitro Drug Delivery from MOFs in Real Time.

Metal-organic frameworks (MOFs) have been proposed as biocompatible candidates for the targeted intracellular delivery of chemotherapeutic payloads, but the site of drug loading and subsequent effect on intracellular release is often overlooked. Here, we analyze doxorubicin delivery to cancer cells by MIL-101(Cr) and UiO-66 in real time. Having experimentally and computationally verified that doxorubicin is pore loaded in MIL-101(Cr) and surface loaded on UiO-66, different time-dependent cytotoxicity profiles are observed by real-time cell analysis and confocal microscopy. The attenuated release of aggregated doxorubicin from the surface of Dox@UiO-66 results in a 12 to 16 h induction of cytotoxicity, while rapid release of pore-dispersed doxorubicin from Dox@MIL-101(Cr) leads to significantly higher intranuclear localization and rapid cell death. In verifying real-time cell analysis as a versatile tool to assess biocompatibility and drug delivery, we show that the localization of drugs in (or on) MOF nanoparticles controls delivery profiles and is key to understanding in vitro modes of action.

Preterm Birth as a Risk Factor for Metabolic Syndrome and Cardiovascular Disease in Adult Life: A Systematic Review and Meta-Analysis.

OBJECTIVE: To determine if preterm birth is associated with components of the metabolic syndrome in adult life. STUDY DESIGN: A structured literature search was performed using PubMed. All comparative studies reported metabolic and cardiovascular outcomes in adults (≥18 years of age) born preterm (<37 weeks of gestation) compared with adults born at term (37-42 weeks of gestation) and published through March 2018 were included. The major outcomes assessed were body mass index, waist circumference, waist-to-hip ratio, fat mass, systolic blood pressure (SBP), diastolic blood pressure (DBP), 24-hour SBP, 24-hour DBP, endothelium-dependent brachial artery flow-mediated dilation, carotid intima-media thickness, pulse wave velocity, fasting glucose and insulin, Homeostasis Model Assessment-Estimated Insulin Resistance Index, and lipid profiles. Quality appraisal was performed using a modified version of the Newcastle-Ottawa scale. A meta-analysis was performed for comparable studies which reported sufficient data. RESULTS: Forty-three studies were included, including a combined total of 18 295 preterm and 294 063 term-born adults. Prematurity was associated with significantly higher fat mass (P = .03), SBP (P < .0001), DBP (P < .0001), 24-hour SBP (P < .001), and 24-hour DBP (P < .001). Furthermore, preterm-born adults presented higher values of fasting glucose (P = .01), insulin (P = .002), Homeostasis Model Assessment-Estimated Insulin Resistance Index (P = .05), and total cholesterol levels (P = .05) in comparison with adults born at term, in random effect models. No statistically significant difference was found between preterm and term-born adults for the other outcomes studied. CONCLUSIONS: Preterm birth is strongly associated with a number of components of the metabolic syndrome and cardiovascular disease in adult life.

Tellurite-Squarate Driven Assembly of a New Family of Nanoscale Clusters Based on (Mo2 O2 S2 )2.

The preparation and characterization of a new family of four polyoxothiometalate (POTM) clusters are reported, with varying size and complexity, based upon the dimeric [Mo2 O2 S2 (H2 O)6 ]2+ cation with the general formula (NMe4 )a Kb [(Mo2 O2 S2 )c (TeO4 )d (C4 O4 )e (OH)f ] where a,b,c,d,e,f={1,7,14,2,4,10}=1, {Mo28 Te2 }; {2,26,36,12,10,48}=2, {Mo72 Te12 }; {0,11,15,3,3,21}=3, {Mo30 Te3 }; {2,6,12,2,4,16}=4, {Mo24 Te2 }. The incorporation of tellurite anions allowed the fine tuning of the templating and bridging of the available building blocks, leading to new topologies of increased complexity. The structural diversity of this family of compounds ranges from the highly symmetrical cross-shaped {Mo24 Te2 } to the stacked ring structure of {Mo72 Te12 }, which is the largest tellurium-containing POTM cluster reported so far. Also a detailed experimental analysis revealed that the pH isolation window extends from acidic to basic values. ESI-MS analyses not only confirmed the stability of this family in solution but also revealed the stability of the observed virtual building blocks.