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- Lower melanoma pulmonary metastatic burden in obese mice: role of FGF-21Publication . Fonseca, Magda; Soares, Raquel; Coelho, PedroObesity is a risk factor for malignant melanoma. The lungs are main target organs for metastization and their immune response is a key modulator of this mechanism. The concept that the metastatic potential of some types of cancer is reduced or inhibited by obesity, known as the obesity paradox, drives major concerns on the prognosis of metastasized patients. The aim of this study was to investigate how high-fat diet (HFD)-induced obesity affects melanoma metastization. C57Bl6/J mice were fed with HFD or standard diet for 180 days and inoculated intravenously with B16F10 melanoma cells. Upon 21 days of inoculation, lung tissue of overweight and lean mice was assessed for histology and immunohistochemistry assays. Adipokine antibody arrays were performed in mice serum. In vitro RAW 264.7 macrophage cultures were established and incubated with FGF-21 and/or lipopolysaccharide (LPS). Conditioned media was added to B16F10 cells for viability quantification. HFD-fed mice presented a reduced number of metastases with lower proliferative rates. The high content of inflammatory foci observed in noninoculated obese mice was significantly decreased upon B16F10 inoculation, concurrent with a slight fibrosis reduction. Plasma levels of fibroblast growth factor-21 (FGF-21), an endocrine regulator, were elevated in noninoculated HFD mice and the expression of FGF receptor 1 (FGFR-1) was significantly upregulated after inoculation. FGF-21 reduced melanoma viability in LPS-stimulated macrophages. Altogether, these findings suggest that higher amounts of FGF-21 are able to counterbalance the proinflammatory effects associated with obesity, protecting the lungs from melanoma metastization.
- Evaluation of the probiotic potential of a strain of Saccharomyces cerevisiaePublication . Areal-Hermida, Lara; Pichardo-Gallardo, Ángeles; Coelho, Pedro; Prudêncio, Cristina; Sieiro, CarmenAccording to the World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations (FAO), probiotics are living microorganisms that, when administered in appropriate quantities, can confer a beneficial effect on the health of the host. Probiotic potential has been demonstrated especially for many strains of different species of bacteria. However, there are fewer strains of yeast for which their probiotic properties have been studied, despite their advantages, which include the fact that they are not affected by antibacterial antibiotics or their inability to disperse antibiotic resistance genes. As a result, there is a growing interest in characterizing new yeasts as probiotics. The aim of this study was to evaluate in our laboratories the probiotic potential of a strain of Saccharomyces cerevisiae var. boulardii (the main species marketed as a probiotic so far), to compare it with that of other yeasts. Strain identification was carried out by analyzing the ITS and D1/D2 regions of the rDNA. Regarding the ability of the strain to survive at 37ºC and resist gastrointestinal conditions, the strain showed 100 % viability at 37ºC and between 95-100 % in synthetic gastric and duodenal juices (pH 2-7.5, 0.3-10 % bile salts, 0.3 % pepsin and 0.1 % pancreatin). In addition, the selfaggregation and hydrophobicity properties shown by the strain allowed inferring the ability to adhere to the intestine, which was confirmed in Caco-2 cells. Additionally, the strain presented other properties of interest for probiotics, including a high anti-oxidant capacity and pathogen coaggregation, as well as a variable cytotoxic activity against different tumor cell lines.
- 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.
- Effect of umbilical cord mesenchymal stem cells secretome in melanomaPublication . Accioly, Gustavo; Aguiar, Gonçalo; Areal, Lara; Costa, Pedro; Coelho, Pedro; Gomes, AndreiaMelanoma of the skin is one of the most prominent and fastest growing malignancies. More than 300 thousand diagnosed cases and 57 thousand deaths in 2020 worldwide and roughly 517 thousand cases of were registered during the 2015-2020 period. Melanoma is generally regarded as an aggressive and unpredictable cancer whose conventional therapies, such as local excision, chemotherapy and immunotherapy, have encountered difficulties to prevent larger scale-tumours and metastasis, as well as overcome recurrence and development of drug resistance. Stem cellbased therapies have been studied as interesting therapeutical approaches for cancer whenever conventional therapy fails to impede its progression. That is owing to the anti-proliferative and immunomodulatory capacity of some SC, being one of the major examples, Mesenchymal Stem Cells. Due to its high abundance, well defined extraction and expansion protocols as well as documented anti-tumorigenic characteristics, Umbilical Cord derived Mesenchymal Stem Cells (UC-MSC) have been observed as a promising candidate for Melanoma treatment, specially through acellular therapy using its secretome. MSC secretome is defined as the set of MSCs-derived bioactive factors available extracellularly and is responsible for the major therapeutic effects of MSCs, namely in oncological pathologies. In this study we hypothesize the ability of UC-MSC’s secretome to inhibit Melanoma growth in vitro. UC-MSC secretome, in the form of conditioned medium (CM), was obtained by extraction from selected umbilical cords and expansion of while murine melanoma cell line B16-F10 culture was established. After treating melanoma cells with different concentrations of CM (100%, 50% and 25%), common cancer hallmarks such as cell viability, motility, colony formation and cell interactions were assessed through MTT, Wound Healing and Colony formation and Hanging-Drop assays, respectively. General analysis of viability and motility showed no statistically significant difference between treated and control groups as well as no concentration-dependent effect whereas formation of cellular aggregates follows an inhibition trend on the treated groups. These results put into perspective the effect of secretome of UC-MSCs. Moreover, further larger scale studies are needed for deeper understanding of MSC secretome mechanisms of action, therefore enabling their use in acellular therapies against melanoma in the future.
- Secretome of umbilical cord mesenchymal stem cells: Potential effects on melanomaPublication . Fernandes, Pablo ; Gomes, Andreia ; Coelho, PedroMelanoma, a tumor resulting from the malignant transformation of melanocytes, is characterized by its aggressive nature and propensity to metastasize. Current treatment options for advanced melanoma are limited and mostly ineffective, highlighting the need for novel therapeutic approaches. Mesenchymal stem cells (MSCs) have increased considerable attention due to their anti-cancer and immunomodulatory properties. In particular, human umbilical cord MSCs (hUCMSCs) have shown promise in various therapeutic applications.
- Potential probiotic and functional properties of Brettanomyces strains isolated from kombucha teaPublication . Areal-Hermida, Lara; Coelho, Pedro; Pichardo-Gallardo, Ángeles; Prudêncio, Cristina; Sieiro, CarmenKombucha, a beverage traditionally obtained through the fermentation of tea, is believed to have beneficial health properties. Therefore, characterizing the microorganisms responsible for this fermentation is essential to demonstrate its potential health benefits and to identify candidates for new probiotics. In this study, four probiotic yeast strains isolated from kombucha tea were identified, by the PCR-RFLP analysis of the ribosomal ITS region and the sequence of the D1/D2 domain of the 26S rDNA, as Brettanomyces bruxellensis (UVI55 and UVI56) and B. anomalus (UVI57 and UVI58). Properties relevant to probiotics were also studied in these strains. All of them showed excellent survival in simulated gastric (99%–100%) and duodenal (95%–100%) juices. The ability to self-aggregate (38%–100%), adhesion to xylene (15%–50%) and, above all, adhesion to Caco-2 cells (4%–21%), revealed its potential capacity to adhere to the intestinal epithelium. In addition, the tested strains showed excellent antioxidant capacity (82%–94%), antimicrobial activity against different pathogens (Escherichia coli, Staphylococcus aureus, Salmonella enterica, Listeria monocytogenes, and Bacillus cereus), as well as remarkable cytotoxic activity against colon, melanoma and ovarian tumor cell lines. Finally, using Caenorhabditis elegans as a model, strain UVI56 exhibited ability to both extend the lifespan of the nematode and protect it against infection by S. enterica. These results support the probiotic and functional properties of the analyzed strains. In conclusion, the study revealed that kombucha tea could be a source of potential probiotics that contribute to its health-promoting properties and that the characterized Brettanomyces strains could be exploited directly as probiotics or for the development of new functional foods.
- 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.
- Impact of umbilical cord mesenchymal stem cells secretome in cancer progressionPublication . Cristóvão, André; Coelho, Pedro; Gomes, AndreiaOvarian cancer is a malignant neoplasm exclusive to females that develops in the ovaries, female sex organs and epithelial ovarian cancer. It has a high mortality rate and is the seventh leading cause of death in women diagnosed with cancer because it develops silently and diagnostic tests have a low predictive value. Thus, developing more accurate diagnostic tests combined with new anti-tumor therapies advance are needy measure to fight this disease. Mesenchymal stem cells (MSC) are multipotent cells, characterized by high proliferation rate and immunomodulatory, secretory, and paracrine properties. Theis cell type can be obtained from several sources in the human body such as marrow bone, adipose tissue and Umbilical cord (UC). UC stands out for being a source that is easily accessible and obtainable, non-invasive, and contains cells with high proliferation and differentiation rates. It has been verified that these cells may be involved in tumor regulatory processes, exerting their effects on metabolic processes such as cell proliferation, survival, angiogenesis, and in tumor-associated inflammatory and immunosuppressive processes [6]. The present work aimed to evaluate how the secretome of human UC-derived MSC (hUC-MSC) influences the tumor capacity of the epithelial ovarian cancer cell line SKOV-3. Conditioned medium (CM) was obtained from hUC-MSC culture and then tumor cells were incubated with different concentrations of conditioned medium, 100%, 50%, and 25%. Parameters such as viability, motility, and cell interactions were evaluated. From the results obtained it was found that CM decreases cell viability, proliferation, and cell-cell interactions, however it stimulated the motility of SKOV-3 cells. In summary, it is possible to conclude that MC from hUC-MSC presented an antitumor effect and can be used as a possible co-adjuvant therapy in the treatment of ovarian cancer.
- In vitro evaluation of peptides with potential antioxidant, anti-inflammatory and antihypertensive activitiesPublication . Borges, Thais; Ferraz, Ricardo; Coelho, Pedro; Prudêncio, Cristina; Gomes, Ana; Gomes, PaulaHypertension develops from genetic and environmental factors, and is exacerbated by disorders that increase systemic vascular resistance, like oxidative stress, inflammation and immune system dysfunction1,2. The search for natural compounds as an alternative or a complement to the drugs used to treat hypertension and other chronic diseases has gained momentum in recent years1 . One example is that of food-derived peptides as nutraceuticals3,4,5. In this context, we are exploring the antioxidant, anti-inflammatory, and antihypertensive potential of synthetic peptides derived from proteins found in milk (lactoferrins from different species of mammals) and in other food sources (e.g., jumbo squid - Dosidicus gigas). Antioxidant activity in vitro was determined by both the DPPH radical scavenging activity and the Ferric Reducing Antioxidant Power (FRAP) assays. While none of the squid peptides was active, lactoferrin (LF) ones showed antioxidant potential: aLF-17-31, from donkey (Equus africanus asinus) LF, displayed the stronger radical scavenging activity (IC50 3.53 mol/mol DPPH), and nhLF268-284, from human (Homo sapiens) LF, showed the stronger reducing power (1.26 ± 0.86 mM Fe2+ equivalents). The ABTS radical scavenging activity of LF peptides was further assessed, with bLF-1-11 from bovine (Bos taurus) LF standing out with a Total Antioxidant Status (TAS) of 5.68 ± 9.23 mM. The peptides’ ability to inhibit the angiotensin converting enzyme 1 (ACE1) was also tested in vitro, as an indication of their antihypertensive potential; squid peptide RC7 inhibited ACE1 with an IC50 of 908.6 µM. Relevantly, none of the peptides was cytotoxic (MTT assay on macrophages), as only bLF1-11 showed some toxicity (IC50 417.6 µg/mL). In conclusion, new non-toxic food-derived peptides with ntioxidant/antihypertensive activity were found. Ongoing studies will assess their anti-inflammatory activity (Griess method) as well as their effect of on the TAS in macrophages (superoxide anion production).
- Book of Abstracts of 5th Meeting of Medicinal Biotechnology (5MBtM) and 2nd Iberian Congress on Medicinal BiotechnologyPublication . Sieiro, Carmen; Pereira, Cassilda; Prudêncio, Cristina; Oliveira, Daniela; Teixeira, Dulce; Barros, Eduarda; Almeida, Joana; Cerqueira, Maria João; Louçano, Marta; Vieira, Mónica; Coelho, Pedro; Ferraz, Ricardo