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Este trabalho pretende rever o uso da epigenética, particularmente da metilação do DNA, na predição de idade em contexto forense. Este mecanismo é caracterizado pela adição de um grupo metil na citosina, impedindo a expressão dos genes e criando padrões de metilação. Com o envelhecimento, observaram-se alterações nestes padrões, que tem sido investigadas em diferentes amostras com o intuito de se alcançar um modelo de estimativa de idade preciso.

“This is an Accepted Manuscript of an article published by Taylor & Francis in Biotechnic and Histochemistry on 10 Sep 2019, available at http://www.tandfonline.com/10.1080/10520295.2019.1651901."

Ellagitannins have been gaining attention as potential anticancer molecules. However, the low bioavailability of ellagitannins and their extensive metabolization in the gastrointestinal tract into ellagic acid and urolithins suggest that the health benefits of consuming ellagitannins rely on the direct effects of their metabolites. Recently, chemopreventive and chemotherapeutic activities were ascribed to urolithins. Nonetheless, there is still a need to screen and evaluate the selectivity of these molecules and to elucidate their cellular mechanisms of action. Therefore, this work focused on the antiproliferative effects of urolithins A, B and C and ellagic acid on different human tumor cell lines. The evaluation of cell viability and the determination of the half-maximal inhibitory concentrations indicated that the sensitivity to the studied urolithins varied markedly between the different cell lines, with the bladder cancer cells (UMUC3) being the most susceptible. In UMUC3 cells, urolithin A was the most active molecule, promoting cell cycle arrest at the G2/M checkpoint, increasing apoptotic cell death and inhibiting PI3K/Akt and MAPK signaling. Overall, the present study emphasizes the chemopreventive/chemotherapeutic potential of urolithins, highlighting the stronger effects of urolithin A and its potential to target transitional bladder cancer cells.

Calcium dobesilate (CaD) has been prescribed to some patients in the early stages of diabetic retinopathy to delay its progression. We previously reported that the treatment of diabetic animals (4 weeks of diabetes) with CaD, during the last 10 days of diabetes, prevents blood-retinal barrier breakdown. Here, we aimed to investigate whether later treatment of diabetic rats with CaD would reverse inflammatory processes in the retina. Diabetes was induced with streptozotocin, and 6 weeks after diabetes onset, CaD (100 mg/kg/day) was administered for 2 weeks. The treatment with CaD significantly increased glial fibrillary acidic protein (GFAP) levels in the retina of nondiabetic animals (138.6 ± 12.8% of control) and enhanced the diabetes-induced increase in GFAP levels (174.8 ± 5.6% of control). In addition, CaD prevented the increase in mRNA and protein expression of tumor necrosis factor and interleukin-1β, as well as the formation of oxidized carbonyl residues and the increase in nitrotyrosine immunoreactivity, particularly in the ganglion cell layer of diabetic animals. We demonstrate that the treatment of diabetic animals with CaD can reverse the established proinflammatory processes in the retina. These beneficial effects appear to be attributed, at least partially, to the antioxidant properties of CaD.

info:eu-repo/semantics/publishedVersion

Agrimony (Agrimonia eupatoria L.) (Ae) is used in traditional medicine to treat inflammatory and oxidative related diseases. Therefore, this study focuses on the anti-inflammatory and analgesic potential of Ae infusion (AeI). Phenolic compounds characterization was achieved by HPLC-PDA-ESI/MS (n) . To evaluate antioxidant potential, 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion, hydroxyl radical, and SNAP assays were used. In vitro anti-inflammatory activity of AeI was investigated in LPS-stimulated macrophages by measuring the NO production. In vivo anti-inflammatory activity was validated using the mouse carrageenan-induced paw edema model. Peripheral and central analgesic potential was evaluated using the acetic acid-induced writhing and hot-plate tests, respectively, as well as the formalin assay to assess both activities. The safety profile was disclosed in vitro and in vivo, using MTT and hematoxylin assays, respectively. Vitexin, quercetin O-galloyl-hexoside, and kaempferol O-acetyl-hexosyl-rhamnoside were referred to in this species for the first time. AeI and mainly AePF (Ae polyphenolic fraction) showed a significant antiradical activity against all tested radicals. Both AeI and AePF decreased NO levels in vitro, AePF being more active than AeI. In vivo anti-inflammatory and analgesic activities were verified for both samples at concentrations devoid of toxicity. Agrimony infusion and, mainly, AePF are potential sources of antiradical and anti-inflammatory polyphenols.

A new C15-acetogenin, sagonenyne (20), exhibiting an unusual single tetrahydropyran ring was isolated from an ethyl acetate extract of Laurencia obtusa collected on the Corsican coastline. Its structure was established by detailed NMR spectroscopic analysis, mass spectrometry, and comparison with literature data. Twenty-three known compounds were identified in the same extract by means of column chromatography steps, using a (13)C-NMR computer aided method developed in our laboratory. In addition to sesquiterpenes, which represent the main chemical class of this extract, diterpenes, sterols, and C15-acetogenins were identified. The crude extract was submitted to a cytotoxicity assay and was particularly active against THP-1 cells, a human leukemia monocytic cell line.