Publications: Nanomedicine

Publications of the research group on nanomedicine

08

Nov 2018

Loss of 5hmC identifies a new type of aberrant DNA hypermethylation in glioma

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Aberrant DNA hypermethylation is a hallmark of cancer although the underlying molecular mechanisms are still poorly understood. To study the possible role of 5-hydroxymethylcytosine (5hmC) in this process we analyzed the global and locus-specific genome-wide levels of 5hmC and 5-methylcytosine (5mC) in human primary samples from 12 non-tumoral brains and 53 gliomas. We found that the levels of 5hmC identified in non-tumoral samples were significantly reduced in gliomas. Strikingly, hypo-hydroxymethylation at 4627 (9.3%) CpG sites was associated with aberrant DNA hypermethylation and was strongly enriched in CpG island shores. The DNA regions containing these CpG sites were enriched in H3K4me2 and presented a different genuine chromatin signature to that characteristic of the genes classically aberrantly hypermethylated in cancer. As this 5mC gain is inversely correlated with loss of 5hmC and has not been identified with classical sodium bisulfite-based technologies, we conclude that our data identifies a novel 5hmC-dependent type of aberrant DNA hypermethylation in glioma.

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08

Oct 2018

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

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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 Latest CINN Publications, Publications 2018, Publications Nanomedicine, Publications Nanomedicine 2018 / 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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