Browsing by Author "Silva, Tiago"
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- Can digital technologies change schizophrenia care?: Opportunities and challengesPublication . Simões de Almeida, Raquel; Silva, TiagoDigital technologies like mobile applications, chatbots, virtual reality, and other technological solutions are already revolutionizing mental health care, including schizophrenia care. Digital mental health interventions are not intended to replace mental health professionals, in fact, they are a contribution to enhance prevention, improve diagnosis, and democratize monitoring and treatment. These systems usually handle large-scale sensitive data and require modern solutions to safely process and store data. Cloud-based services can respond to this challenge, but it is important to be aware of the current technical boundaries as well of dangers of health data handling. This chapter provides a review on the subject, presenting several data-driven applications for schizophrenia care and addressing some concerns such as efficacy, privacy and confidentiality, data security, accountability, engagement, ethical implications, and education and training. Some recommendations on clinical integration are also presented.
- Development of Blood−Brain Barrier Permeable Nitrocatechol-Based Catechol O‑Methyltransferase Inhibitors with Reduced Potential for HepatotoxicityPublication . Silva, Tiago; Mohamed, Tarek; Shakeri, Arash; Rao, Praveen P. N.; Martínez-González, Loreto; Pérez, Daniel I.; Martínez, Ana; Valente, Maria João; Garrido, Jorge; Uriarte, Eugenio; Serrão, Paula; Soares-da-Silva, Patrício; Remião, Fernando; Borges, FernandaRecent efforts have been focused on the development of centrally active COMT inhibitors, which can be valuable assets for neurological disorders such as Parkinson’s disease, due to the severe hepatotoxicity risk associated with tolcapone. New nitrocatechol COMT inhibitors based on naturally occurring caffeic acid and caffeic acid phenethyl ester were developed. All nitrocatechol derivatives displayed potent inhibition of peripheral and cerebral COMT within the nanomolar range. Druglike derivatives 13, 15, and 16 were predicted to cross the blood−brain barrier in vitro and were significantly less toxic than tolcapone and entacapone when incubated at 50 μM with rat primary hepatocytes. Moreover, their unique acidity and electrochemical properties decreased the chances of formation of reactive quinone-imines and, as such, the potential for hepatotoxicity. The binding mode of 16 confirmed that the major interactions with COMT were established via the nitrocatechol ring, allowing derivatization of the side chain for future lead optimization efforts.
- Effects of Chlorophenoxy Herbicides and Their Main Transformation Products on DNA Damage and Acetylcholinesterase ActivityPublication . Benfeito, Sofia; Silva, Tiago; Garrido, Jorge; Andrade, Paula B.; Sottomayor, M. J.; Borges, Fernanda; Garrido, E. ManuelaPersistent pesticide transformation products (TPs) are increasingly being detected among different environmental compartments, including groundwater and surface water. However, there is no sufficient experimental data on their toxicological potential to assess the risk associated with TPs, even if their occurrence is known. In this study, the interaction of chlorophenoxy herbicides (MCPA, mecoprop, 2,4-D and dichlorprop) and their main transformation products with calf thymus DNA by UV-visible absorption spectroscopy has been assessed. Additionally, the toxicity of the chlorophenoxy herbicides and TPs was also assessed evaluating the inhibition of acetylcholinesterase activity. On the basis of the results found, it seems that AChE is not the main target of chlorophenoxy herbicides and their TPs. However, the results found showed that the transformation products displayed a higher inhibitory activity when compared with the parent herbicides. The results obtained in the DNA interaction studies showed, in general, a slight effect on the stability of the double helix. However, the data found for 4-chloro-2-methyl-6-nitrophenol suggest that this transformation product can interact with DNA through a noncovalent mode.
- Exploring cinnamic acid scaffold: development of promising neuroprotective lipophilic antioxidantsPublication . Chavarria, Daniel; Silva, Tiago; Martins, Daniel; Bravo, Joana; Summavielle, Teresa; Garrido, Jorge; Borges, FernandaNew lipophilic hydroxycinnamic acid based derivatives were designed and synthesized and their antioxidant and neuroprotective activities evaluated. The chemical modification introduced in the cinnamic acid scaffold leads to compounds with amplified lipophilicity and in general with increased antioxidant activity when compared to natural models (caffeic and ferulic acids). The compounds did not display cytotoxicity and present a significant neuroprotective effect against 6-OH-DA induced damage to SH-SY5Y cells. Compound 6 stands out as an efficient radical scavenger and iron(II) chelator that ensures drug-like properties. Moreover, neuroprotection against oxidative damage was observed even at low concentration (1 μM). Therefore, compound 6 developed by a biology-oriented approach displays a combination of important features for a further optimization process that will generate a new effective antioxidant with therapeutic application for oxidative-stress-related events, namely neurodegenerative diseases.
- Exploring nature profits: development of novel and potent lipophilic antioxidants based on galloylecinnamic hybridsPublication . Teixeira, José; Silva, Tiago; Benfeito, Sofia; Gaspar, Alexandra; Garrido, E. Manuela; Garrido, Jorge; Borges, FernandaPhenolic acids are ubiquitous antioxidants accounting for approximately one third of the phenolic compounds in our diet. Their importance was supported by epidemiological studies that suggest an inverse relationship between dietary intake of phenolic antioxidants and the occurrence of diseases, such as cancer and neurodegenerative disorders. However, until now, most of natural antioxidants have limited therapeutic success a fact that could be related with their limited distribution throughout the body and with the inherent difficulties to attain the target sites. The development of phenolic antioxidants based on a hybrid concept and structurally based on natural hydroxybenzoic (gallic acid) and hydroxycinnamic (caffeic acid) scaffolds seems to be a suitable solution to surpass the mentioned drawbacks. Galloylecinnamic hybrids were synthesized and their antioxidant activity as well as partition coefficients and redox potentials evaluated. The structureepropertyeactivity relationship (SPAR) study revealed the existence of a correlation between the redox potentials and antioxidant activity. The galloylecinnamic acid hybrid stands out as the best antioxidant supplementing the effect of a blend of gallic acid plus caffeic acid endorsing the hypothesis that the whole is greater than the sum of the parts. In addition, some hybrid compounds possess an appropriate lipophilicity allowing their application as chain-breaking antioxidant in biomembranes or other type of lipidic systems. Their predicted ADME properties are also in accordance with the general requirements for drug-like compounds. Accordingly, these phenolic hybrids can be seen as potential antioxidants for tackling the oxidative status linked to the neurodegenerative, inflammatory or cancer processes.
- Improving the Multi-Brand Channel Distribution of a Fashion RetailerPublication . Silva, Tiago; Pereira, Teresa; Ferreira, Luís Pinto; Silva, F.J.G.One has seen exponential growth in the number of clients and in the quantities ordered in the fashion retailing multi-brand channel. It has, therefore, become essential to improve the channel’s distribution process in order to meet the customers’ orders in the shortest time, and in a cost-effective manner, thus complying with the delivery terms agreed upon with the market. To this end, one studied aspects such as the mapping of the supply flow process, the occupation of space and the spaghetti-dash diagram of four current distribution process activities. Besides these, one also analyzed the calculation of productivity, cycle times, takt time, as well as the service level designed, with the purpose of preparing a system to evaluate company performance. In addition to these studies, one resorted to the ABC and SWOT customers’ analyses in order to develop the improvement proposal, which was characterized by: (a) changes in the layout, (b) improvements in the supply flow, (c) implementation of gravity carriers, as well as more ergonomic forms of transport, and (d) the use of computer applications developed in Visual Basic language for the distribution process. Based on this proposal, one succeeded in increasing the amount sorted out by the distributor in an eight-hour shift to 294 articles (11,23%). Cycle time was reduced from 0,015 minutes/article to 0,013 minutes/article (13,33%), which allows for the segregation of articles in time for the next collections. In addition, the occupied space was reduced to 47 m2 on average per collection (1,39%), which is translated into a reduction of 1 498 468 meters (23,34%) in the average distance covered per collection. Furthermore, the number of workers was reduced, on average, by five employees (12,82%) per collection. The storage capacity of the finished product was also increased by 535 boxes (11,30%). The total investment needed to achieve these changes is established as being 23 754,42 €; yet, the payback time involved will only be six months, resulting in a cumulative profit of 84 504,23 € by the end of the fall/winter 2020 collection.
- Lipophilic Caffeic and Ferulic Acid Derivatives Presenting Cytotoxicity against Human Breast Cancer CellsPublication . Serafim, Teresa L.; Carvalho, Filipa S.; Marques, Maria P. M.; Calheiros, Rita; Silva, Tiago; Garrido, J.M.P.J.; Milhazes, Nuno; Borges, Fernanda; Roleira, Fernanda; Silva, Elisário T.; Holy, Jon; Oliveira, Paulo J.In the present work, lipophilic caffeic and ferulic acid derivatives were synthesized, and their cytotoxicity on cultured breast cancer cells was compared. A total of six compounds were initially evaluated: caffeic acid (CA), hexyl caffeate (HC), caffeoylhexylamide (HCA), ferulic acid (FA), hexyl ferulate (HF), and feruloylhexylamide (HFA). Cell proliferation, cell cycle progression, and apoptotic signaling were investigated in three human breast cancer cell lines, including estrogen-sensitive (MCF-7) and insensitive (MDA-MB-231 and HS578T). Furthermore, direct mitochondrial effects of parent and modified compounds were investigated by using isolated liver mitochondria. The results indicated that although the parent compounds presented no cytotoxicity, the new compounds inhibited cell proliferation and induced cell cycle alterations and cell death, with a predominant effect on MCF-7 cells. Interestingly, cell cyle data indicates that effects on nontumor BJ fibroblasts were predominantly cytostatic and not cytotoxic. The parent compounds and derivatives also promoted direct alterations on hepatic mitochondrial bioenergetics, although the most unexpected and never before reported one was that FA induces the mitochondrial permeability transition. The results show that the new caffeic and ferulic acid lipophilic derivatives show increased cytotoxicity toward human breast cancer cell lines, although the magnitude and type of effects appear to be dependent on the cell type. Mitochondrial data had no direct correspondence with effects on intact cells suggesting that this organelle may not be a critical component of the cellular effects observed. The data provide a rational approach to the design of effective cytotoxic lipophilic hydroxycinnamic derivatives that in the future could be profitably applied for chemopreventive and/or chemotherapeutic purposes.
- Plant derived and dietary phenolic antioxidants: Anticancer propertiesPublication . Roleira, Fernanda M.F.; Tavares-da-Silva, Elisiário J.; Varela, Carla L.; Costa, Saul C.; Silva, Tiago; Garrido, Jorge; Borges, Fernandan this paper, a review of the literature on the phenolic compounds with anticancer activity published between 2008 and 2012 is presented. In this overview only phenolic antioxidant compounds that display significant anticancer activity have been described. In the first part of this review, the oxidative and nitrosative stress relation with cancer are described. In the second part, the plant-derived food extracts, containing identified phenolic antioxidants, the phenolic antioxidants isolated from plants and plant-derived food or commercially available and the synthetic ones, along with the type of cancer and cells where they exert anticancer activity, are described and summarized in tables. The principal mechanisms for their anti-proliferative effects were also described. Finally, a critical analysis of the studies and directions for future research are included in the conclusion.