28 research outputs found

    Gene expression profiles modulated by the human carcinogen aristolochic acid I in human cancer cells and their dependence on TP53

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    Aristolochic acid (AA) is the Causative agent of urothelial tumours associated with aristolochic acid nephropathy. These tumours contain TP53 mutations and over-express TP53. We compared transcriptional and translational responses of two isogenic HCT116 cell lines, one expressing TP53 (p53-WT) and the other with this gene knocked out (p53-null), to treatment with aristolochic acid I (AAI) (50-100 mu M) lor 6-48 h. Modulation of 118 genes was observed in p53-WT cells ad 123 genes in p53-null cells. Some genes, including INSIG1, EGR1, CAV1, LCN2 arid CCNG1, were differentially expressed in the two cell lines. CDKN1A was selectively Up-regulated in p53-WT cells, leading to accumulation of TP53 and CDKN1A. Apoptotic signalling, measured by caspase-3 and -7 activity, was TP53-dependent. Both cell types accumulated in S phase, suggesting that AAI-DNA adducts interfere with DNA replication, independently of TP53 Status. The oncogene MYC, frequently over expressed ill urothelial turnouts, Was Up-regulated by AAI, whereas FOS was down-regulated. Observed modulation of genes involved in endocytosis, e.g. RAB5A, may be relevant to the known inhibition of receptor-mediated endocytosis, an early sign of AA-mediated proximal tubule injury. AAI-DNA adduct Formation was significantly greater in p53-WT cells than in p53-null cells. Collectively, phenotypic anchoring of the AAI-induced expression profiles to DNA adduct formation, cell-cycle parameters, TP53 expression arid apoptosis identified several genes linked to these biological outcomes, some of which are TP53-dependent. These results strengthen the importance of TP53 in AA-induced cancer, arid indicate that other alterations, e.g. to MYC oncogenic pathways, may also contribute. (C) 2008 Elsevier Inc. All rights reserved

    Protein-based structures for food applications: from macro to nanoscale

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    Novel food structures' development through handling of macroscopic and microscopic properties of bio-based materials (e.g., size, shape, and texture) is receiving a lot of attention since it allows controlling or changing structures' functionality. Proteins are among the most abundant and employed biomaterials in food technology. They are excellent candidates for creating novel food structures due to their nutritional value, biodegradability, biocompatibility, generally recognized as safe (GRAS) status and molecular characteristics. Additionally, the exploitation of proteins' gelation and aggregation properties can be used to encapsulate bioactive compounds inside their network and produce consistent delivery systems at macro-, micro-, and nanoscale. Consequently, bioactive compounds which are exposed to harsh storage and processing conditions and digestion environment may be protected and their bioavailability could be enhanced. In this review, a range of functional and structural properties of proteins which can be explored to develop macro-, micro-, and nanostructures with numerous promising food applications was discussed. Also, this review points out the relevance of scale on these structures' properties, allowing appropriate tailoring of protein-based systems such as hydrogels and micro- or nanocapsules to be used as bioactive compounds delivery systems. Finally, the behavior of these systems in the gastrointestinal tract (GIT) and the impact on bioactive compound bioavailability are thoroughly discussed.JM and AP acknowledge the Portuguese Foundation for Science and Technology (FCT) for their fellowships (SFRH/BPD/89992/2012 and SFRH/BPD/101181/2014). This work was supported by Portuguese FCT under the scope of the Project PTDC/AGR-TEC/5215/2014, of the strategic funding of UID/BIO/04469 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684), and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020—Programa Operacional Regional do Norte.info:eu-repo/semantics/publishedVersio

    Optimizing electrode positioning in 3-lead ECG chest devices

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    Although the 12-lead electrocardiogram has become an essential medical and research tool, many current and envisaged applications would ben- efit from simpler devices, using 3-lead ECG configuration. This is particularly true for Ambient Assisted Living (in a broad perspective). However, the chest anatomy of female patients, namely during pregnancy, can hamper the adequate placement of a 3-lead ECG device and, very often, electrodes are placed below the chest rather than at the precise thoracic landmarks. Thus, the aim of this study was to compare the effect of electrode positioning on the ECG signal of pregnant women and provide guidelines for device development. The effect of breast tissue on the ECG signal was investigated by relating breast size with the signal-to-noise ratio, root mean square and R-wave amplitude. Results show that the 3-lead ECG should be placed on the breast rather than under the breast and indicate positive correlation between breast size and signal-to-noise ratio.(undefined

    Proteína bruta da farinha de minhoca da espécie Eisenia fetida (Savigny, 1826) submetida a diferentes tratamentos térmicos

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    A trial was carried out to evaluate crude protein of earthworm meal, specie Eisenia fetida, subjected to different thermic treatments. A total of 480 adult and clitellum earthworms were fed with dairy cattle manure from Dutch breed. A completely randomized design was used with two treatments: earthworms dehydrated in microwave oven (T1) and earthworms dehydrated in conventional forced air oven (T2). Each treatment had six replications. Crude protein data were subjected to ANOVA and the averages were compared with the Tukey test at 5%. The results showed that microwave oven method did not alter the crude protein content of earthworm meat. Therefore, it might be used for the preparation of earthworm meal. The utilization of conventional forced air oven at 150ºC for 2 hours does not lead to the enzymatic darkness of earthworm meat. The substitution of forced air oven with microwave oven for the preparation of Eisenia fetida meal speeds up the dehydration process.Objetivou-se avaliar a proteína bruta da farinha de minhoca da espécie Eisenia fetida submetida a diferentes tratamentos térmicos. Foram coletadas 480 minhocas adultas e cliteladas, alimentadas com esterco de bovinos leiteiros da raça Holandês. O delineamento experimental utilizado foi o inteiramente casualizado, com dois tratamentos, constituídos por minhocas desidratadas em forno de microondas (T1) e minhocas desidratadas em forno convencional (T2), cada um com seis repetições. Os dados referentes à proteína bruta foram submetidos à análise de variância (ANOVA) e as médias comparadas pelo teste de Tukey a 5%. Os resultados mostraram que o método em forno de microondas pode ser utilizado na preparação de farinha de minhoca por não alterar o teor de proteína da carne de minhoca. A estufa com circulação de ar forçado à mantida a temperatura de 150ºC por 2 horas não promove o escurecimento enzimático da carne de minhoca. A substituição da estufa com circulação de ar forçado pelo forno de microondas na preparação da farinha de minhoca da espécie Eisenia fetida acelera o processo de desidratação.
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