Titanium and Zirconium Levels Are Associated with Changes in MicroRNAs Expression: Results from a Human Cross-Sectional Study on Obese Population

<div><p>Objectives</p><p>In this study on 90 individuals we aimed at evaluating the microRNAs (miRNAs) expression profile associated with personal levels of Titanium (Ti) and Zirconium (Zr) traced in hair samples. Ti and Zr materials are broadly used for dental implants but the biological reactions triggered by a long term presence of these materials in the oral cavity still need to be assessed. MiRNAs are mechanisms that need to be investigated as they play a fundamental role in the control of gene expression following external stimuli and contribute to a wide range of pathophysiological processes.</p><p>Methods</p><p>Using the TaqMan^® Low-Density Array, we assessed the expression levels of 377 human miRNAs in peripheral blood of 90 subjects. Hair samples were analyzed for Ti and Zr content using Inductively Coupled Plasma-Mass Spectrometry. We performed multivariable regression analysis to investigate the effects of Ti and Zr exposure on miRNA expression levels. We used the Ingenuity Pathway Analysis (IPA) software to explore the functional role of the investigated miRNAs and the related target genes.</p><p>Results</p><p>Seven miRNAs (miR-99b, miR-142-5p, miR-152, miR-193a-5p, miR-323-3p, miR-335, miR-494) resulted specifically associated with Zr levels. The functional target analysis showed that miRNAs are involved in mechanisms such as inflammation, skeletal and connective tissue disorders.</p><p>Conclusions</p><p>Our data suggest that Zr is more bioactive than Ti and show that miRNAs are relevant molecular mechanisms sensitive to Zr exposure.</p></div

List of miRNAs associated with Zirconium levels.

<p>List of miRNAs associated with Zirconium levels.</p

Characteristics of the study participants and exposure levels (n = 90).

<p>Characteristics of the study participants and exposure levels (n = 90).</p

Disease and biological function associated with target genes selected with IPA for 7 miRNAs.

<p>Disease and biological function associated with target genes selected with IPA for 7 miRNAs.</p

Cellular location of targets shared by miR-152, miR-335 and miR-494.

<p>Cellular location of targets shared by miR-152, miR-335 and miR-494.</p

microRNA expression in the cervix during pregnancy is associated with length of gestation

<div><p>Preterm birth is a leading cause of infant mortality and can lead to poor life-long health and adverse neurodevelopmental outcomes. The pathophysiologic mechanisms that precede preterm labor remain elusive, and the role that epigenetic phenomena play is largely unstudied. The objective of this study was to assess the association between microRNA (miRNA) expression levels in cervical cells obtained from swabs collected during pregnancy and the length of gestation. We analyzed cervical samples obtained between 16 and 19 weeks of gestation from 53 women in a prospective cohort from Mexico City, and followed them until delivery. Cervical miRNA was extracted and expression was quantified using the NanoString nCounter Analysis System. Linear regression models were used to examine the association between miRNA expression levels and gestational age at delivery, adjusted for maternal age, education, parity, body mass index, smoke exposure, and inflammation assessed on a Papanicolaou smear. We identified 6 miRNAs that were significantly associated with gestational age at the time of delivery, including miR-21, 30e, 142, 148b, 29b, and 223. Notably, per each doubling in miR-21 expression, gestations were 0.9 (95% CI: 0.2–1.5) days shorter on average (<i>P</i> = 0.009). Per each doubling in miR-30e, 142, 148b, 29b, and 223 expression, gestations were shorter by 1.0 to 1.6 days. The predicted targets of the miRNAs were enriched for molecules involved in DNA replication and inflammatory processes. The levels of specific miRNAs in the human cervix during pregnancy are predictive of gestational age at delivery, and should be validated in future studies as potential biomarkers of preterm birth risk.</p></div

Pre-work blood pressure by participant characteristics.

<p>Pre-work blood pressure by participant characteristics.</p

Number of miRNAs associated with BP measured pre- and post-work, in all participants and by strata of occupation and characteristics at FDR <0.05.

<p>Number of miRNAs associated with BP measured pre- and post-work, in all participants and by strata of occupation and characteristics at FDR <0.05.</p

Post-work blood pressure by participant characteristics.

<p>Post-work blood pressure by participant characteristics.</p