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Riveiro-Naveira R.R.,Institute Investigacion Biomedica Of A Coruna | Valcarcel-Ares M.N.,Institute Investigacion Biomedica Of A Coruna | Almonte-Becerril M.,Institute Investigacion Biomedica Of A Coruna | Almonte-Becerril M.,CINVESTAV | And 7 more authors.
Rheumatology (United Kingdom) | Year: 2016

Objective. The present study aimed to determine the protective effects of dietary supplementation with resveratrol (RSV) in an acute antigen-induced arthritis (AIA) model.Methods. Rats were randomly divided into three groups: control, AIA and RSV-treated AIA group. RSV (12.5 mg/kg/day) was given orally for 8 weeks before induction of AIA and until the end of the experiment (48 h after intra-articular injection). The control and AIA animals were administered 100 μl of water. Results were evaluated by macroscopic observation, histopathology and immunohistochemistry for anti-PCNA, macrophages (CD68), T lymphocytes (CD3), monocyte chemoattractant protein-1 and 8-oxo-7,8-dihydro-2'-deoxyguanine (a marker of DNA damage). Cytokine-induced neutrophil chemoattractant-1 in serum and peroxidase activity in synovial tissue were measured using commercial kits.Results. At the end of the study, RSV significantly reduced knee swelling. Likewise, the histological score of synovial tissue also reduced significantly. The arthritis-protective effects were associated with a significant decrease in PCNA, CD68, CD3 and monocyte chemoattractant protein-1 staining, as well as a reduction in serum concentrations of cytokine-induced neutrophil chemoattractant-1. RSV treatment also decreased the level of the marker of DNA damage, 8-oxo-7,8-dihydro-2'-deoxyguanine. Accordingly, peroxidase activity in the synovial tissue was up-regulated.Conclusion. Dietary supplementation with RSV lowers the main pathological hallmarks of RA disease in an acute model of AIA. RSV may represent a promising strategy in controlling the severity of RA. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

Abella V.,Complexo Hospitalario Universitario runa SERGAS | Valladares M.,Complexo Hospitalario Universitario runa SERGAS | Valladares M.,Medical Oncology Unit | Rodriguez T.,Complexo Hospitalario Universitario runa SERGAS | And 7 more authors.
PLoS ONE | Year: 2012

Gene expression is potently regulated through the action of microRNAs (miRNAs). Here, we present evidence of a miRNA regulating Hakai protein. Hakai was discovered as an E3 ubiquitin-ligase that mediates the posttranslational downregulation of E-cadherin, a major component of adherens junctions in epithelial cells and a potent tumour suppressor. Recent data have provided evidence that Hakai affects cell proliferation in an E-cadherin-independent manner, thus revealing a role for Hakai in the early stages of tumour progression. Furthermore, Hakai is highly up-regulated in human colon adenocarcinomas compared to normal tissues. However, the molecular mechanisms that regulate Hakai abundance are unknown. We identified two putative sites of miR-203 interaction on the Hakai mRNA, in its 3′-untranslated region (UTR). In several human carcinoma cell lines tested, overexpression of a miR-203 precursor (Pre-miR-203) reduced Hakai abundance, while inhibiting miR-203 by using an antisense RNA (Anti-miR-203) elevated Hakai levels. The repressive influence of miR-203 on the Hakai 3′-UTR was confirmed using heterologous reporter constructs. In keeping with Hakai's proliferative influence, Anti-miR-203 significantly increased cell number and BrdU incorporation, while Pre-miR-203 reduced these parameters. Importantly, the growth-promoting effects of anti-miR-203 required the presence of Hakai, because downregulation of Hakai by siRNA suppressed its proliferative action. Finally, in situ hybridization showed that miR-203 expression is attenuated in colon tumour tissues compared to normal colon tissues, suggesting that miR-203 could be a potential new prognostic marker and therapeutic target to explore in colon cancer. In conclusion, our findings reveal, for the first time, a post-transcriptional regulator of Hakai expression. Furthermore, by lowering Hakai abundance, miR-203 also reduces Hakai-regulated-cell division. © 2012 Abella et al.

Lopez-Armada M.J.,Complexo Hospitalario Universitario runa SERGAS | Riveiro-Naveira R.R.,Complexo Hospitalario Universitario runa SERGAS | Vaamonde-Garcia C.,Complexo Hospitalario Universitario runa SERGAS | Valcarcel-Ares M.N.,Complexo Hospitalario Universitario runa SERGAS
Mitochondrion | Year: 2013

Inflammation has been linked to multiple degenerative and acute diseases as well as the aging process. Moreover, mitochondrial alterations play a central role in these processes. Mitochondria have an important role in pro-inflammatory signaling; similarly, pro-inflammatory mediators may also alter mitochondrial function. Both of these processes increase mitochondrial oxidative stress, promoting a vicious inflammatory cycle. Additionally, damage-associated molecular patterns derived from mitochondria could contribute to inflammasome formation and caspase-1 activation, while alterations in mitochondrial autophagy may cause inflammation. Strategies aimed at controlling excessive oxidative stress within mitochondria may represent both preventive and therapeutic interventions in inflammation. © 2012 Elsevier B.V. and Mitochondria Research Society.

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