Exposure to airborne particulate matter (PM) has been associated with detrimental health effects. DNA methylation represents the most well-studied epigenetic factor among the possible mechanisms underlying this association. Interestingly, changes of DNA methylation in response to environmental stimuli are being considered for their role in the pathogenic mechanism, but also as mediators of the body adaptation to air pollutants. Several studies have evaluated both global and gene-specific methylation in relation to PM exposure in different clinical conditions and life stages. The purpose of the present literature review is to evaluate the most relevant and recent studies in the field in order to analyze the available evidences on long- and short-term PM exposure and DNA methylation changes, with a particular focus on the different life stages when the alteration occurs. PM exposure modulates DNA methylation affecting several biological mechanisms with marked effects on health, especially during susceptible life stages such as pregnancy, childhood, and the older age. Although many cross-sectional investigations have been conducted so far, only a limited number of prospective studies have explored the potential role of DNA methylation. Future studies are needed in order to evaluate whether these changes might be reverted.

Growing evidences have shown that particulate matter (PM) exposures during pregnancy are associated with impaired fetal development and adverse birth outcomes, possibly as a result of an exaggerated systemic oxidative stress and inflammation. Telomere length (TL) is strongly linked to biological age and is impacted by oxidative stress. We hypothesized that PM exposure during different time windows in the first trimester of pregnancy influences both mitochondrial DNA copy number (mtDNAcn), an established biomarker for oxidative stress, and TL. Maternal blood TL and mtDNAcn were analysed in 199 healthy pregnant women recruited at the 11th week of pregnancy by quantitative polymerase chain reaction. We also examined whether maternal mtDNAcn and TL were associated with fetal growth outcomes measured at the end of the first trimester of pregnancy (fetal heart rate, FHR; crown‐rump length, CRL; and nuchal translucency, NT) and at delivery (birth weight, length, head circumference). The possible modifying effect of prepregnancy maternal body mass index was evaluated. PM₁₀ exposure during the first pregnancy trimester was associated with an increased maternal mtDNAcn and a reduced TL. As regards ultrasound fetal outcomes, both FHR and CRL were positively associated with PM_2.5, whereas the association with FHR was confirmed only when examining PM₁₀ exposure. PM₁₀ was also associated with a reduced birth weight. While no association was found between mtDNAcn and CRL, we found a negative relationship between mtDNAcn and fetal CRL only in overweight women, whereas normal‐weight women exhibited a positive, albeit nonsignificant, association. As abnormalities of growth in utero have been associated with postnatal childhood and adulthood onset diseases and as PM is a widespread pollutant relevant to the large majority of the human population and obesity a rising risk factor, our results, if confirmed in a larger population, might represent an important contribution towards the development of more targeted public health strategies.

Cornelia de Lange Syndrome is a severe genetic disorder characterized by malformations affecting multiple systems, with a common feature of severe mental retardation. Genetic variants within four genes (NIPBL (Nipped-B-like), SMC1A, SMC3, and HDAC8) are believed to be responsible for the majority of cases; all these genes encode proteins that are part of the ‘cohesin complex’. Cohesins exhibit two temporally separated major roles in cells: one controlling the cell cycle and the other involved in regulating the gene expression. The present study focuses on the role of the zebrafish nipblb paralog during neural development, examining its expression in the central nervous system, and analyzing the consequences of nipblb loss of function. Neural development was impaired by the knockdown of nipblb in zebrafish. nipblb-loss-of-function embryos presented with increased apoptosis in the developing neural tissues, downregulation of canonical Wnt pathway genes, and subsequent decreased Cyclin D1 (Ccnd1) levels. Importantly, the same pattern of canonical WNT pathway and CCND1 downregulation was observed in NIPBL-mutated patient-specific fibroblasts. Finally, chemical activation of the pathway in nipblb-loss-of-function embryos rescued the adverse phenotype and restored the physiological levels of cell death.

OBJECTIVE: Skull base chordomas (SBCs) are rare dysembryogenetic invasive tumors with a variable tendency for recurrence. According to previous studies, the recurrence rate seems to be affected by both clinical variables and tumor biological features. The authors present the results of treatment of SBCs in a large series of patients and investigate the role of 1p36 chromosomal region loss of heterozygosity (LOH) as a prognostic factor. METHODS: Between 1990 and 2011, 45 patients were treated for SBCs. The mean follow-up was 76 months (range 1–240 months). An LOH analysis was performed in 27 cases. Survival analysis was performed to determine clinical and biological parameters correlating with clinical outcome. RESULTS: The 5- and 10-year overall survival rates were 67% and 57%, respectively. Five- and 10-year progression-free survival rates were 58% and 44%, respectively. Multivariate analysis showed that extent of resection, adjuvant radiation therapy, and absence of rhinopharynx invasion were positive independent predictors of overall survival. The latter 2 variables and a younger patient age were positive independent predictors of progression-free survival. Twenty-one patients showed 1p36 LOH. All events of recurrence and death clustered in the group of patients with 1p36 LOH; however, this biological marker was not statistically significant on multivariate analysis. CONCLUSIONS: Resection is the treatment of choice in primary and recurrent SBC. Patient age, rhinopharynx invasion at diagnosis, extent of tumor removal, and postoperative radiation therapy influence SBC prognosis. Genetic analysis, even while showing interesting results, did not reveal 1p36 LOH as an independent predictor of clinical outcome.

Essential hypertension is the leading preventable cause of death in the world. Epidemiological studies have shown that physical training can reduce blood pressure (BP), both in hypertensive and healthy individuals. Increasing evidence is emerging that DNA methylation is involved in alteration of the phenotype and of vascular function in response to environmental stimuli. We evaluated repetitive element and gene-specific DNA methylation in peripheral blood leukocytes of 68 volunteers, taken before (T0) and after (T1) a three-month intervention protocol of continuative aerobic physical exercise. DNA methylation was assessed by bisulfite-PCR and pyrosequencing. Comparing T0 and T1 measurements, we found an increase in oxygen consumption at peak of exercise (VO_2peak) and a decrease in diastolic BP at rest. Exercise increased the levels of ALU and Long Interspersed Nuclear Element 1 (LINE-1) repetitive elements methylation, and of Endothelin-1 (EDN1), Inducible Nitric Oxide Synthase (NOS2), and Tumour Necrosis Factor Alpha (TNF) gene-specific methylation. VO_2peak was positively associated with methylation of ALU, EDN1, NOS2, and TNF; systolic BP at rest was inversely associated with LINE-1, EDN1, and NOS2 methylation; diastolic BP was inversely associated with EDN1 and NOS2 methylation. Our findings suggest a possible role of DNA methylation for lowering systemic BP induced by the continuative aerobic physical training program.