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  • Bdnf-NRF2 crosstalk in depression disorder
    Publication . Santos, Marlene; Caldevilla, Renato; Morais, Stephanie; Carvalho, Serafim; Medeiros, Rui; Barroso, Maria Fátima
    The World Health Organization estimates that major depressive disorder (MDD) affects over 264 million individuals globally, posing a significant public health challenge. Treatment-resistant depression (TRD) represents a severe form of MDD with poor treatment outcomes. Genetic variations are known to impact MDD treatment responses, yet genome-wide association studies have struggled to identify consistent marker alleles. Previous research has linked the Brain Derived Neurotrophic Factor (BDNF) genetic polymorphism with TRD. BDNF is essential for neuronal survival and neuroplasticity, processes influenced by antidepressant treatment, and regulated by transcription factors like Nuclear factor erythroid 2-related factor 2 (NRF2). NRF2 regulates antioxidant and anti-inflammatory responses and plays a crucial role in depression pathogenesis. NRF2 knockout mice exhibit reduced BDNF levels and depression-like behaviors, indicating that NRF2activation enhances BDNF expression and antidepressant efficacy. The BDNF rs6265 (Val66Met) polymorphism is associated with variations in antidepressant response rates. Research suggests that the interaction between BDNF and NRF2 pathways could enhance antidepressant effectiveness. NRF2 activation, such as through the compound sulforaphane, has demonstrated rapid antidepressant effects by increasing BDNF expression. Lower levels of NRF2 and BDNF are observed in stress-induced depression models, and ketamine treatment influences NRF2-related genes. Simultaneously, there is a growing need for efficient genotyping methods, and genosensors offer a promising solution. This presentation will address the interplay between BDNF and NRF2 in depression, explore its relationship in antidepressant response, and present a putative genosensor for BDNF rs6265 (Val66Met) polymorphism identification, improving antidepressant treatment outcome.
  • Toxicity testing of simvastatin, sertraline, 4-MBC propylparaben and triclocarban using zebrafish and sea urchin embryos bioassays
    Publication . Torres, Tiago; Ribeiro, Sílvia; Cunha, Isabel; Martins, Rosário; Santos, Miguel Machado
    In the past decade, many emergent compounds, including some active substances and ingredients of Pharmaceuticals and Personal Care Products (PPCPs) have been detected in water at levels that can negatively impact aquatic ecosystems (Lapworth et al., 2012; Jiang et al., 2013). The recent knowledge of their occurrence has raised concerns about human health effects and ecosystem risks. Although these compounds are frequently detected at concentrations that are not likely to induce adverse effects in humans and may be too low to cause acute effects in other organisms, there is still a serious lack of information about the effects in non-target species, particularly considering chronic exposure or effects resulting from interactions between them (Lapworth et al., 2012). Pharmaceuticals and Personal Care Products enter the aquatic environment from different point and nonpoint sources and wastewater treatments plants cannot ensure complete removal of many compounds, and therefore they may be present at significant concentrations in effluents (Jiang et al., 2013). Hence, it is essential to understand the effects of these substances on aquatic organisms. Owing to the large number of new chemicals that must go through toxicity testing, short-term early-life-stages have been frequently used as an alternative to long-term exposures due to its high sensitivity and logistic advantages.
  • Toxicological assessment of ibuprofen, paracetamol and metformin in terrestrial ecosystems
    Publication . Moreira, Inês; Silva, Cláudia; Barros, Piedade; Nunes, Mafalda
    Pharmaceuticals (PhACs) are a class of emerging contaminants that have, in recent years, been associated with potential risks for the environment (Fent, Weston & Caminada, 2006). Pharmaceutical substances are often engineered for persistence, so they remain unaltered as they pass through the organism. This leads to the persistence of these substances when they are excreted, leading to potential environmental problems (European Environment Agency, 2010). Residues of pharmaceuticals have been detected at trace quantities in aquatic systems, with studies finding over 80 PhACs from various prescription classes in sewage, surface and groundwater, in several countries all over the world (Heberer, 2002). These facts make the evaluations of potential effects of pharmaceuticals on ecosystems relevant and necessary. Acute aquatic toxicity has been more extensively studied since aquatic organisms are more easily identifiable as important targets, as they might be exposed to wastewater over their whole life. However, only little is known about the ecotoxicological effects of pharmaceuticals on terrestrial organisms (Fent et al., 2006). Residues of PhACs may reach the terrestrial environment through several sources/routes (Heberer, 2002) but, since removal of PhACs in Wastewater Treatment Plants (WWTPs) is many times not efficient, contamination comes mostly from applying contaminated sludge in agriculture.
  • Occupational and environmental exposure to anticancer drugs
    Publication . Teles, Luís; Fernandes, Sara; Cruz, Agostinho; Vieira da Silva, Manuela; Amorim, Manuela; Vieira, Mónica; Barros, Piedade
    The use of anticancer drugs is not restricted to a single type of drug (Connor et al. , 1999; Suspiro & Prista, 2012). These are varied and present diverse mechanisms of action, which may be causes of occupational exposure. Despite the restricted and controlled use of cytotoxic agents, the risk involved is not confined to individuals who administer them but also to all health care professionals and general population directly or indirectly in contact with them (Suspiro & Prista, 2012). The presence of pharmaceuticals products in natural surface waters and in the effluent sewage treatment plants have been reported since 1980s. More recently, these products have been detected in ground and drinking water. However, there is little information about the risks these drugs and their metabolites in the water, have, for the human health (Ferrando-Climentet al. , 2013).There are few published studies with detailed information about the significance of pharmaceuticals compounds in water for humans (Ferrando- Climentet al. , 2013). The major concern with genotoxic/carcinogenic pharmaceuticals compounds is a cancer risk, at any level of exposure because there is no threshold dose below which no carcinogenic effect may occur (Garcia-AC et al., 2011). The pharmaceutical compounds are excreted to wastewater and become potential water contaminants. Currently, very little is known about the presence and elimination process of cytostatic drugs in wastewater treatment plants. The lack of methods and knowledge about the specific risk of pharmaceutical products in aquatic environment may be consider a public health problem.
  • Cytotoxity induced by extracts of Pisolithustinctorius spores on human cancer and normal cell lines – evaluation of the anticancer potential
    Publication . Alves, Ricardo; Preto, Marco; Oliveira, Rui S.; Martins, Rosário
    Cancer is one of the most important causes of death and morbidity worldwide. According to the World Health Organization 8.2 million people have died from cancer in 2012. The treatment of this fast growing disease is regarded as a major challenge in health for the XXI century. Conventional anti-cancer therapy is usually aggressive to the patients due to systemic toxicity caused by lack of specificity of the chemotherapy drugs (Kidd, 2000). This has triggered the interest of the scientific community to search for new and more effective therapies, less aggressive than conventional treatments. Used since antiquity in oriental civilizations, fungi, in particular mushrooms have been shown to limit or reverse tumor growth (Kidd, 2000). Pisolithustinctorius (Basidiomycota) is a soil fungus with world-wide distribution that it known to form ectomycorrhizal symbioses in forest ecosystems (Kope & Fortin, 1990). The sporocarps of this fungus contain Pisosterol, a triterpene that has been shown to have antitumor activity against some cancer cell lines (Montenegro et al., 2004). Nevertheless, no studies have focused on the anticancer potential of other structures such as spores and thus the anticancer potential of P. tinctorius , remains largely unknown.
  • Construction and optimization of an electrochemical genosensor for the detection of BDNF gene Val66Met polymorphism
    Publication . Caldevilla, Renato; Santos, Marlene; Barroso, M. Fátima
    Major depression disorder (MDD) is the most prevalent psychiatric condition worldwide. Currently, antidepressants constitute the main pharmacological treatment for this condition. Despite the growing arsenal of antidepressant medications, almost half of MDD patients have insufficient remission rates during their treatments. A growing body of scientific evidence points to genetic factors as having a crucial role in patients’ response to antidepressant treatments. One of these genetic components is the BDNF gene, that codes for the BDNF neurotrophin, an important player in neuroplasticity and neurogenesis.
  • Is it possible to prevent Harmful Algal Blooms? An electrochemical genosensor that detects dinoflagellates could be the answer
    Publication . Pereira, Eduarda; Silva, Aurora; Morais, Stephanie L.; Costa-Rama, Estefanía; Moreira, Patrícia R.; Fraga-Corral, M.; Torrado, Ana M.; Rodríguez, Francisco; Barros, Piedade; Cruz, Agostinho; Delerue-Matos, Cristina; Prieto, M. A.; Simal-Gandara, J.; Silva, Nádia F. D.; Santos, Marlene; Barroso, M. Fátima
    Harmful Algal Blooms (HABs) are a very common phenomenon in the last few years that results from the accumulation of microalgae, such as dinoflagellates of the Dinophysis genus. Hence, the development of analytical technologies capable of detecting these microorganisms and thereby avoiding environmental and public health crisis, has become a major priority. Biosensors have been gaining recognition lately given their notable assets: they are fast, sensitive and allow in situ analysis.
  • Elucidating the mechanisms Involved in the cytotoxicity induced by marine cyanobacteria strains against the RKO colon carcinoma cell line
    Publication . Freitas, S.; Urbatzka, R.; Osório, H.; Costa, M.; Barros, Piedade; Vasconcelos, V.; Martins, Rosário
    Cyanobacteria are known to synthesize secondary metabolites that may have potential as drugs for the treatment of human diseases such as cancer. Previous studies on marine cyanobacteria isolated from the Portuguese coast revealed strains of the picoplanktonic genera Cyanobium and Synechocystis as potential sources of anticancer compounds. The ethyl acetate fraction of the strains Cyanobium sp. LEGE06113 and the Synechocystis salina LEGE06155 was found to reduce cell viability of cancer cell lines. This work aimed to elucidate the mechanisms involved in the cytotoxicity of this strains in the colon adenocarcinoma cell line RKO by employing real-time PCR (RT-PCR) for genes involved in cell cycle and apoptosis, by flow cytometry for cell cycle and by two-dimensional gel electrophoresis for protein expression. RT-PCR results revealed differences in mRNA expression of genes CCNB1 (cell cycle) and BCL-2 (apoptosis). Flow cytometry results revealed a decrease in the G0/G1 and S phase and increased its number in the G2/M phase, which is in accordance with the lower expression of CCNB1. The proteomic results demonstrated different protein patterns comparing treatment groups with control. Proteins differentially regulated in exposed RKO cells were involved in cell cycle regulation, apoptosis, cell structure, protein regulation and cell metabolism. Although several of these proteins were identified in cells exposed to both cyanobacterial extracts, the data provides an indication that the cytotoxicity is induced by different toxic mechanisms in LEGE06113 and LEGE06155 fractions.
  • Effect of the pharmaceuticals metformin, escitalopram and furosemide in cyanobacteria growth
    Publication . Oliveira, L.; Pereira, R.; Costa, J.; Barros, Piedade
    Worldwide one of the most prevalent water problems is eutrophication, a result of high nutrient concentration, mainly phosphorus and nitrogen. In freshwater environments, anthropogenic inputs of nutrients and other substances are a major contributing to eutrophication and consequent formation of cyanobacteria and algal blooms. The formation of cyanobacteria blooms can result in toxin production and have ecological and human health impacts. Another emerging water quality concern is the impact of personal care products and pharmaceuticals in the environment. In eutrophic waters the increased availability of pharmaceuticals can interfere with cyanobacteria cells and disrupt or enhance cyanobacteria growth. This study describes the effect of metformine, escitalopram and furosemide in the cyanobacteria Microcystis aeruginosa. Cyanobacteria tests were conducted following the European Guideline (OECD 201) for algal and cyanobacteria growth inhibition test. Cyanobacteria were incubated in microplate with pharmaceuticals solutions prepared in Z8 medium under continuous light and shaking at 22ºC. Results were quantified in terms of average growth rates calculated from cell numbers based on OD determination at 24h period until 120h. Pharmaceuticals used were metformin an anti-diabetic, escitalopram an antidepressive and furosemide a diuretic in ten concentrations. At 120h exposure and at the higher concentration tested the three pharmaceuticals (metformin-10mg/mL; 100% inhibition; escitalopram- 0.1mg/ml; 100% inhibition and furosemide-0.4 mg/mL; 50% inhibition) inhibited Microcystis growth rate. Escitalopram response showed hormesis but at higher concentrations it was more toxic than metformin and furosemide. Time related response was different between pharmaceuticals. The three pharmaceuticals interfere with Microcystis growth rate in different ways.
  • Virtual reality cognitive-behavioral therapy biofeedback system for glossophobia
    Publication . Correia, António; Gomes, Paulo Veloso; Donga, João; Marques, António; Pereira, Javier
    The fear of public speaking is one of the most common social phobias causing anxiety problems in many people. In this context, this project focuses on developing a tool capable of helping mental health professionals using virtual reality as a controlled environment in expository therapies, in this case applied to Glossophobia. To enhance the creation of self-control mechanisms in these patients, the use of virtual reality is explored with the aid of Neuro and Biofeedback, allowing the visualization in real time of the physiological response to the stimuli of the virtual environment.