Publicaciones Nanomedicina

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08

Oct 2018

MiR-873-5p acts as an epigenetic regulator in early stages of liver fibrosis and cirrhosis

Posted by / in Publicaciones Destacadas, Publicaciones Nanomedicina, Publications 2018, Publications Nanomedicine 2018, Últimas Publicaciones CINN / No comments yet

Glycine N-methyltransferase (GNMT) is the most abundant methyltransferase in the liver and a master regulator of the transmethylation flux. GNMT downregulation leads to loss of liver function progressing to fibrosis, cirrhosis, and hepatocellular carcinoma. Moreover, GNMT deficiency aggravates cholestasis-induced fibrogenesis. To date, little is known about the mechanisms underlying downregulation of GNMT levels in hepatic fibrosis and cirrhosis. On this basis, microRNAs are epigenetic regulatory elements that play important roles in liver pathology. In this work, we aim to study the regulation of GNMT by microRNAs during liver fibrosis and cirrhosis. Luciferase assay on the 3ʹUTR-Gnmt was used to confirm in silico analysis showing that GNMT is potentially targeted by the microRNA miR-873-5p. Correlation between GNMT and miR-873-5p in human cholestasis and cirrhosis together with miR-873-5p inhibition in vivo in different mouse models of liver cholestasis and fibrosis [bile duct ligation and Mdr2 (Abcb4)-/- mouse] were then assessed. The analysis of liver tissue from cirrhotic and cholestatic patients, as well as from the animal models, showed that miR-873-5p inversely correlated with the expression of GNMT. Importantly, high circulating miR-873-5p was also detected in cholestastic and cirrhotic patients. Preclinical studies with anti-miR-873-5p treatment in bile duct ligation and Mdr2-/- mice recovered GNMT levels in association with ameliorated inflammation and fibrosis mainly by counteracting hepatocyte apoptosis and cholangiocyte proliferation. In conclusion, miR-873-5p emerges as a novel marker for liver fibrosis, cholestasis, and cirrhosis and therapeutic approaches based on anti-miR-873-5p may be effective treatments for liver fibrosis and cholestatic liver disease.

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03

Sep 2018

Prevention of periodontitis by the addition of a bactericidal particulate glass/glass-ceramic to a dental resin: A pilot study in dogs

Posted by / in Publicaciones Nanomedicina, Publications 2018, Publications Nanomedicine 2018, Últimas Publicaciones CINN / No comments yet

The aim of the study is to evaluate, in a ligature-induced periodontitis model, the efficacy of a commercially available dental resin containing different antimicrobial glass/glass-ceramic additions (0–26 wt.%). It has been proved that a 26 wt.% glass addition to a conventional dental resin matrix does not alter neither its workability nor its adhesion to the surface of teeth; however, it does confer notable antimicrobial properties when tested in vitro. Moreover, in vivo tests in Beagle dogs demonstrated the prevention of bone loss in ligature-induced plaque accumulation around teeth. Particularly, the glass-ceramic filler resin composite has shown excellent antimicrobial control since it displays the same bone loss as that of the negative control. The results obtained in the present investigation have shown that a conventional dental resin containing a fraction of glass/glass-ceramic (≥26 wt.%) can prevent periodontitis, which is considered to be a most serious dental disease.

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26

Jul 2018

Epigenome-wide analysis reveals specific DNA hypermethylation of T cells during human hematopoietic differentiation

Posted by / in Publicaciones Nanomedicina, Publications 2018, Publications Nanomedicine 2018, Últimas Publicaciones CINN / No comments yet

Aim: Epigenetic regulation plays an important role in cellular development and differentiation. A detailed map of the DNA methylation dynamics that occur during cell differentiation would contribute to decipher the molecular networks governing cell fate commitment. Methods: Illumina MethylationEPIC BeadChip platform was used to describe the genome-wide DNA methylation changes observed throughout hematopoietic maturation by analyzing multiple myeloid and lymphoid hematopoietic cell types. Results: We identified a plethora of DNA methylation changes that occur during human hematopoietic differentiation. We observed that T lymphocytes display substantial enhancement of de novo CpG hypermethylation as compared with other hematopoietic cell populations. T-cell-specific hypermethylated regions were strongly associated with open chromatin marks and enhancer elements, as well as binding sites of specific key transcription factors involved in hematopoietic differentiation, such as PU.1 and TAL1. Conclusion: These results provide novel insights into the role of DNA methylation at enhancer elements in T-cell development.

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