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- Repurposing antiplasmodial leads for cancer: Exploring the antiproliferative effects of N-cinnamoyl-aminoacridinesPublication . Fonte, Mélanie; Rôla, Catarina; Santana, Sofia; Ferraz, Ricardo; Prudêncio, Miguel; Almeida, Joana; Ferraz, Ricardo; Prudêncio, Cristina; Teixeira, Cátia; Gomes, PaulaDrug repurposing and rescuing have been widely explored as cost-effective approaches to expand the portfolio of chemotherapeutic agents. Based on the reported antitumor properties of both trans-cinnamic acids and quinacrine, an antimalarial aminoacridine, we explored the antiproliferative properties of two series of N-cinnamoyl-aminoacridines recently identified as multi-stage antiplasmodial leads. The compounds were evaluated in vitro against three cancer cell lines (MKN-28, Huh-7, and HepG2), and human primary dermal fibroblasts. One of the series displayed highly selective antiproliferative activity in the micromolar range against the three cancer cell lines tested, without any toxicity to non-carcinogenic cells.
- Quinoxaline, its derivatives and applications: A state of the art reviewPublication . Almeida, Joana; Pessoa, Ana M.; Cordeiro, M. Natália D. S.; Fernandes, Rúben; Prudêncio, Cristina; Noronha, João Paulo; Vieira, MónicaQuinoxaline derivatives are an important class of heterocycle compounds, where N replaces some carbon atoms in the ring of naphthalene. Its molecular formula is C8H6N2, formed by the fusion of two aromatic rings, benzene and pyrazine. It is rare in natural state, but their synthesis is easy to perform. In this review the State of the Art will be presented, which includes a summary of the progress made over the past years in the knowledge of the structure and mechanism of the quinoxaline and quinoxaline derivatives, associated medical and biomedical value as well as industrial value. Modifying quinoxaline structure it is possible to obtain a wide variety of biomedical applications, namely antimicrobial activities and chronic and metabolic diseases treatment.
- Potentional radiosensitizer effect of TUDCA in a obesity model of brain tumor cellsPublication . Silva, Liliana; Almeida, Joana; Coelho, Pedro; Faria, Isabel; Monteiro, Armanda; Soares, Raquel; Vieira, Mónica; Prudêncio, Cristina; Fernandes, RúbenObesity may play an important role in the biology of seve ral types of cancer, but the correlation with glioma Is still not very well defined. Former studies indicated that obesity may be related with an decreased resistance to radiation and increased redox status in brain tumors. Since radiothetapy is the most commonly treatment modality used in this type of tumor, we creale a new model of experiments to determinate the influence of obesity in glioma cells [n the presence of radiation with an imbalance of redox status, BC3H1 glioma cells were treated with t-BOOH (150~M), TUDCA (25~M) and a mix of t-BOOH and TUOCA{150~M and 25~M respectively) in serum-free OMEM or conditioned media (CM) from differentiated 3T3-L 1 adj pocytes. Afterwards the cells were irradiated with a total dose of 2 Gy. Subsequently BC3H1 viability was evaluated, by MTT assay, after 4 and 12 hours. We observed an increase in viability In all cells treated solely with 3T3-L 1 eM. Interestingly, in the presence of CM plus TUDCA or t-BOOH, the viability of 6C3H1 was inferior of TUOCA or t~BOOH treatments alone, this effect was independent of irradia tion. After 12 hours the I/iability of the glioma cells was significantly higher on irradiated ceUs treated only with eM, this effect was not yet observed at the 4 hours time point But, in the presence of mix of t~BOOH and TUDCA, with eM and irradiation the cells viability decrea se significanUy. The 3T3-L 1 Me increase (he cell viabrlity in the presence of radiation or not, after 12 hours expose" But in the presence of oxidatIve inducer and, In specially, with the antioxidant TUDCA, the BC3Hi viability significantly decrease. So, we observed a potential radiosensitfzer effect of TUDCA in BC3H1 in the presence of 3T3-L1 adipocytes.
- Adipocyte-released factors enhance melanocyte’s proliferation and motilityPublication . Fernandes, Rúben; Coelho, Pedro; Almeida, Joana; Prudêncio, Cristina; Soares, RaquelObesity, favored by the modern lifestyle, acquired epidemic proportions nowadays. Obesity has been associated with various major causes of death and morbidity including malignant neoplasms. Cutaneous melanoma incidence rates have also been increasing uring the last four decades in several countries. Obesity involvement in melanoma etiology has been recognized, but the implicated mechanisms remain unclear. We propose to address the above relationship and investigate the mechanism interplaying between obesity and an increased risk of melanoma onset.
- Neurogenic inflammation in allergen-challenged obese mice: a missing link in the obesity-asthma association?Publication . Ramalho, Renata; Almeida, Joana; Beltrão, Marília; Pirraco, Ana; Costa, Raquel; Sokhatska, Oksana; Guardão, Luísa; Palmares, Carmo; Guimarães, João Tiago; Delgado, Luís; Moreira, André; Soares, RaquelA number of studies have shown an association between obesity and asthma. Controversy remains on the mechanisms supporting this association. In this study we aimed to assess neurogenic inflammation in a model of diet-induced obesity and allergen-challenged mice. High fat diet-induced (HFD) obese Balb/c mice were sensitized and challenged with ovalbumin (OVA). Glucose, insulin, OVA-specific IgE and substance P (SP), and the main tachykinin involved in neurogenic inflammation, were quantified in sera. Cell counts were performed in bronchoalveolar lavage fluid (BALF). The extent of peribronchial infiltrates was estimated on lung tissue sections and inflammation was score based on inflammatory cell counts surrounding the bronchi. Obesity per se and allergen-sensitization per se increased serum SP (P = .027, P = .004, respectively). Further increased was observed in obese-sensitized mice (P = .007). Obese-sensitized mice also showed higher insulin (P = .0016), OVA-specific IgE (P = .016), peribronchial inflammatory score (P = .045), and tendency for higher glycemia. The interaction of obesity and asthma on SP levels was confirmed (P = .005, R2 = 0.710). SP was positively correlated with metabolic (glycemia, r = 0.539, P = .007) and allergic inflammation parameters (BALF eosinophils, r = 0.445, P = 0.033; BALF mast cells, r = 0.574, P = .004; peribronchial inflammation score, r = 0.661, P < .001; and OVA-specific IgE, r = 0.714, P < .001). Our findings provide support to the neurogenic inflammation link between obesity and asthma in mice. These two conditions independently increased SP and the presence of both pathologies further increased this level. Neurogenic inflammation may be a previously unrecognized mechanism beyond the obese-asthma phenotype. Further studies are need to confirm this role of SP in human obesity-asthma association.
- Substance P antagonist improves both obesity and asthma in a mouse modelPublication . Ramalho, R.; Almeida, Joana; Beltrão, M.; Pirraco, A.; Costa, R.; Sokhatska, O.; Guardão, L.; Palmares, C.; Guimarães, J. T.; Delgado, L.; Moreira, A.; Soares, R.Evidence suggests a causal relationship between obesity and asthma; however, the underlying mechanisms remain unknown. Substance P (SP), involved in neurogenic inflammation by acting through its receptor NK1-R, seems to participate in obese–asthma phenotype in mice. To evaluate the effect of a selective substance P receptor antagonist on a mouse model of diet-induced obesity and asthma. Diet-induced obese Balb/c mice were sensitized and challenged with ovalbumin (OVA) and treated with a selective NK1-R antagonist or placebo. Serum glucose, insulin, IL-6, resistin, and OVA-specific IgE levels were quantified. A score for peribronchial inflammation in lung histology was used. Cells were counted in bronchoalveolar lavage fluid. Adipocyte sizes were measured. Ovalbumin-obese mice treated with NK1-R antagonist had lower weight (P = 0.0002), reduced daily food intake (P = 0.0021), reduced daily energy intake (P = 0.0021), reduced surface adipocyte areas (P < 0.0001), lower serum glucose (P = 0.04), lower serum insulin (P = 0.03), lower serum IL-(P = 0.0022), lower serum resistin (P = 0.0043), lower serum OVA-specific IgE (P = 0.035), and lower peribronchial inflammation score (P < 0.0001) than nontreated OVA-obese mice. We observed an interaction between obesity, allergen sensitization, and treatment with NK1-R antagonist for metabolic and systemic biomarkers, and for allergen sensitization and bronchial inflammation, showing a synergy between these variables. In an experimental model of obesity and asthma in mice, NK1-R blockade improved metabolic and systemic biomarkers, as well as allergen sensitization and bronchial inflammation. These positive effects support a common pathway in the obese–asthma phenotype and highlight SP as a target with potential clinical interest in the obese–asthma epidemics.
- Book of abstracts 4th Meeting on Medicinal Biotechnology (4EBtM)Publication . Costa, Ana Rita; Dias, Ana Rita; Prudêncio, Cristina; Borges, Cristina; Teixeira, Dulce; Almeida, Joana; Vieira, Mónica; Coelho, Pedro; Ferraz, Ricardo; Cunha, SofiaThese meetings have been held once a year since 2015 and have played an important role as a point of contact among several professionals and students in Medicinal Biotechnology. Like the Medicinal Biotechnology field itself, these meetings have also been expanding, not only in the number of participants, but also in their geographical origin. Therefore, it is our goal to act as an interface between students and biotechnology companies/researchers, as well as to increasingly promote networking, projects and collaborations within this field for the upcoming years.
- The influence of phytochemicals on grade IV prostate adenocarcinomaPublication . Casal, Ana Carolina; Almeida, JoanaAdenocarcinoma is a worldwide concern, being one of the main causes of death in men. Bone metastases derived from this type of cancer, the fact that tumor cells are increasingly resistant to existing oncological drugs and the side effects caused by these are the main causes for the need to develop new therapies. Thus, silymarin and cinnamic acid (CINN) are examples of two phytochemicals that have been studied for the treatment of this pathology, since they have a fundamental role in chemoprevention, that is, they prevent stages of initiation, promotion and progression, associated with carcinogenesis, reducing cancer morbidity and mortality. The main objective of this project is to evaluate the effect of both phytochemicals on the PC3 cell line of grade IV prostatic adenocarcinoma. Thus, parameters such as viability (MTT) and cell motility (injury) were evaluated through the application of different concentrations of compounds in tumor cells. It was demonstrated, with the results obtained, that both silymarin and CINN have the ability to decrease the viability and motility of prostate cancer cells. In short, it is possible to state that the phytochemicals in question have an antitumor effect, proving their potential as treatments against the PC3 cell line, through the reduction of cell proliferation and induction of apoptosis.
- Biomolecules in the relationship of cancer and obesityPublication . Almeida, Joana; Coelho, Pedro; Prudêncio, Cristina; Vieira, Mónica; Fernandes, Rúben; Fonseca, Magda; Soares, Raquel; Silva, Liliana; Faria, Isabel; Monteiro, Armanda; Pinto, Gabriela; Cea, V.; Galesio, M.; Noronha, J. P.; Diniz, M. S.; Sala, C.Obesity has been associated with various major causes of death and morbidity including malignant neoplasms. This increased prevalence has been accompanied by a worldwide increase in cutaneous melanoma incidence rates during the last decades, as well as gliomas, the most common primary malignant brain tumors in adults (Almeida et al., 2019). Although obesity aetiology is established, the implicated mechanisms remain unclear (Coelho et al., 2016). Melanoma is refractory to conventional therapies, and radiotherapy usage as an adjuvant therapy in cutaneous melanoma patients is ineffective, so it is extremely important to understand the antioxidant modulation of melanoma under an environment of obesity (Coelho et al., 2017; Oliveira et al., 2016). Moreover, the metastatic potential of some types of cancer is reduced or inhibited by obesity, which drives major concerns on the prognosis of metastasized patients (Fonseca et al., 2021). All of the studies disclose interesting models for the study of these tumors’ biology under an obese environment, that can be explored for the search of biomarkers, prognostic markers and therapeutic approaches.
- Biotechnology and biochemistry laboratorial education through the SARS-CoV2 pandemic: challenges, truths and takeawaysPublication . Almeida, Joana; Pereira, Cassilda; Coelho, Pedro; Teixeira, Dulce; Louçano, Marta; Bento, C.; Cerqueira, Maria João; Prudêncio, Cristina; Ferraz, Ricardo; Vieira, MónicaIn early 2020, the COVID-19 pandemic forced the higher education institutions to adapt to a new form of teaching and learning, from presential to full remote, blended and hybrid environment.