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- Prevalence of Neisseria gonorrhoeae and Trichomonas vaginalis in portuguese women of childbearing agePublication . Silva, Jani; Cerqueira, Fátima; Teixeira, Ana Luísa; Campainha, Rui; Amorim, José; Medeiros, R.
- 1,2-dihydroxyxanthone: effect on A375-C5 melanoma cell growth associated with interference with THP-1 human macrophage activityPublication . Silva, Viviana; Cerqueira, Fátima; Nazareth, Nair; Medeiros, R.; Sarmento, Amélia; Sousa, Emília; Pinto, MadalenaXanthones have been suggested as prospective candidates for cancer treatment. 1,2- dihydroxyxanthone (1,2-DHX) is known to interfere with the growth of several cancer cell lines. We investigated the effects of 1,2-DHX on the growth of the A375-C5 melanoma cell line and THP-1 human macrophage activity. 1,2-DHX showed a moderate growth inhibition of A375-C5 melanoma cells (concentration that causes a 50% inhibition of cell growth (GI50) = 55.0 ±2.3 µM), but strongly interfered with THP-1 human macrophage activity. Supernatants from lipopolysaccharide (LPS)-stimulated THP-1 macrophage cultures exposed to 1,2-DHX significantly increased growth inhibition of A375-C5 cells, when compared to supernatants from untreated LPS-stimulated macrophages or to direct treatment with 1,2-DHX only. 1,2-DHX decreased THP-1 secretion of interleukin-1β (IL-1β) and interleukin-10 (IL-10), but stimulated tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) production. This xanthone also inhibited nitric oxide (NO) production by RAW 264.7 murine macrophages, possibly through inhibition of inducible NO synthase production. In conclusion, these findings suggest a potential impact of 1,2-DHX in melanoma treatment, not only due to a direct effect on cancer cells but also by modulation of macrophage activity.
- Plasmatic microRNAs and treatment outcomes of patients with metastatic castration-resistant prostate cancer: a hospital-based cohort study and in silico analysisPublication . Silva, Jani; Tavares, Valéria; Afonso, Ana; Garcia, Juliana; Cerqueira, Fátima; Medeiros, RuiProstate cancer (PCa) is one of the most common malignancies among men worldwide. Inevitably, all advanced PCa patients develop metastatic castration-resistant prostate cancer (mCRPC), an aggressive phase of the disease. Treating mCRPC is challenging, and prognostic tools are needed for disease management. MicroRNA (miRNA) deregulation has been reported in PCa, constituting potential non-invasive prognostic biomarkers. As such, this study aimed to evaluate the prognostic potential of nine miRNAs in the liquid biopsies (plasma) of mCRPC patients treated with second-generation androgen receptor axis-targeted (ARAT) agents, abiraterone acetate (AbA) and enzalutamide (ENZ). Low expression levels of miR-16-5p and miR-145-5p in mCRPC patients treated with AbA were significantly associated with lower progression-free survival (PFS). The two miRNAs were the only predictors of the risk of disease progression in AbA-stratified analyses. Low miR-20a-5p levels in mCRPC patients with Gleason scores of <8 were associated with worse overall survival (OS). The transcript seems to predict the risk of death regardless of the ARAT agent. According to the in silico analyses, miR-16-5p, miR-145-5p, and miR-20a-5p seem to be implicated in several processes, namely, cell cycle, proliferation, migration, survival, metabolism, and angiogenesis, suggesting an epigenetic mechanism related to treatment outcome. These miRNAs may represent attractive prognostic tools to be used in mCRPC management, as well as a step further in the identification of new potential therapeutic targets, to use in combination with ARAT for an improved treatment outcome. Despite the promising results, real-world validation is necessary.
- Inhibitory effect of 5-aminoimidazole-4-carbohydrazonamides derivatives against Candida spp. biofilm on nanohydroxyapatite substratePublication . Gabriel, C.; Grenho, L.; Cerqueira, Fátima; Medeiros, R.; Dias, A. M.; Ribeiro, A. I.; Proença, M. F.; Fernandes, M. H.; Sousa, J. C.; Monteiro, F. J.; Ferraz, M. P.Candida can adhere and form biofilm on biomaterials commonly used in medical devices which is a key attribute that enhances its ability to cause infections in humans. Furthermore, biomaterial-related infections represent a major therapeutic challenge since Candida biofilms are implicated in antifungal therapies failure. The goals of the present work were to investigate the effect of three 5-aminoimidazole-4-carbohydrazonamides, namely (Z)-5-amino-1-methyl-N'-aryl-1H-imidazole-4-carbohydrazonamides [aryl = phenyl (1a), 4-fluorophenyl (1b), 3-fluorophenyl (1c)], on Candida albicans and Candida krusei biofilm on nanohydroxyapatite substrate, a well-known bioactive ceramic material. To address these goals, both quantitative methods (by cultivable cell numbers) and qualitative evaluation (by scanning electron microscopy) were used. Compounds cytocompatibility towards osteoblast-like cells was also evaluated after 24 h of exposure, through resazurin assay. The three tested compounds displayed a strong inhibitory effect on biofilm development of both Candida species as potent in vitro activity against C. albicans sessile cells. Regarding cytocompatibility, a concentration-dependent effect was observed. Together, these findings indicated that the potent activity of imidazole derivatives on Candida spp. biofilms on nanohydroxyapatite substrate, in particular compound 1c, is worth further investigating.
- Cervical cancer outcome and tumor-associated macrophages: research evidencePublication . Horta, Bruno; Pereira, Tomé; Medeiros, R.; Cerqueira, FátimaInflammation is a key factor in cancer promotion. Tumor-associated macrophages (TAMs), as part of the tumor microenvironment, are often associated with the progression of tumors and a worse prognosis in many cancers, namely on cervical cancer. This work exhaustively summarizes the conclusions of the different studies published concerning TAMs function in cervical cancer, from in vitro studies using cancer cell lines to the clinical perspective (histological samples-based studies). Most studies have led to the conclusion that TAMs increased density is directly related to increased severity of a malignant cervical lesion. Additionally, TAMs are normally polarized into an M2 phenotype, benefiting and promoting tumor progression, resulting in a worse disease outcome. The tumor microenvironment is also a highly critical contributor that not only influences tumor natural history but also modulates the specific immune response.
- Effect of heptaphylline and two related secondary metabolites on cervical (HeLa) and prostate (LNCaP and PC-3) cancer cell linesPublication . Horta, Bruno; Cerqueira, Fátima; Pinto, Madalena; Sousa, Emília; Puthongking, Ploenthip; Pereira, António; Medeiros, R.
- Effect of 1-carbaldehyde-3,4-dimethoxyxanthone on prostate and HPV-18 positive cervical cancer cell lines and on human THP-1 macrophagesPublication . Medeiros, R.; Horta, Bruno; Freitas-Silva, Joana; Silva, Jani; Dias, Francisca; Sousa, Emília; Pinto, Madalena; Cerqueira, FátimaXanthone derivatives have shown promising antitumor properties, and 1-carbaldehyde-3,4- dimethoxyxanthone (1) has recently emerged as a potent tumor cell growth inhibitor. In this study, its effect was evaluated (MTT viability assay) against a new panel of cancer cells, namely cervical cancer (HeLa), androgen-sensitive (LNCaP) and androgen-independent (PC-3) prostate cancer, and nonsolid tumor derived cancer (Jurkat) cell lines. The effect of xanthone 1 on macrophage functions was also evaluated. The effect of xanthone 1-conditioned THP-1 human macrophage supernatants on the metabolic viability of cervical and prostate cancer cell lines was determined along with its interference with cytokine expression characteristic of M1 profile (IL-1 ≤ β; TNF-α) or M2 profile (IL-10; TGF-β) (PCR and ELISA). Nitric oxide (NO) production by murine RAW264.7 macrophages was quantified by Griess reaction. Xanthone 1 (20 µM) strongly inhibited the metabolic activity of the cell lines and was significantly more active against prostate cell lines compared to HeLa (p < 0.05). Jurkat was the cell most sensitive to the effect of xanthone 1. Compound 1-conditioned IL-4-stimulated THP-1 macrophage supernatants significantly (p < 0.05) inhibited the metabolic activity of HeLa, LNCaP, and PC-3. Xanthone 1 did not significantly affect the expression of cytokines by THP-1 macrophages. The inhibiting effect of compound 1 observed on the production of NO by RAW 264.7 macrophages was moderate. In conclusion, 1-carbaldehyde-3,4-dimethoxyxanthone (1) decreases the metabolic activity of cancer cells and seems to be able to modulate macrophage functions.
- Prostate cancer: antitumor effect of chalcones on androgen dependent and androgen-independent prostate cancer cell linesPublication . Horta, Bruno; Cerqueira, Fátima; Pinto, Madalena; Cidade, Honorina; Silva, Jani; Pereira, António; Medeiros, R.
- Genomic profile in association with sport-type, sex, ethnicity, psychological traits and sport injuries of elite athletes: review and future perspectivesPublication . Silva, Hugo-Henrique; Silva, Maria Raquel; Cerqueira, Fátima; Tavares, Valéria; medeiros, rmIn the last few years, some inherited determinants have been associated with elite athletic performance, but its polygenic trait character has limited the correct definition of elite athlete's genomic profile. This qualitative descriptive study aims to summarise the current understanding about genetic and epigenetic factors in elite athletes, as well as their genomic profile in association with sport-type, sex, ethnicity, psychological traits and sport injuries. A narrative review of the literature across a broad cross-section of the elite athletes' genomic profile was undertaken. Elite performance relies on rare gene variants within a great interface between molecular, cellular and behavioural sport-related phenotypes and the environment, which is still poorly understood. ACTN3 rs1815739 and ACE I/D polymorphisms appear to be associated to specific sprint phenotypes and influence the athletic status, i.e., the rs1815739 variant is more influential to 200-m performance and the ACE ID polymorphism is more involved in the longer, 400-m sprint performance. Generally, athletes show endurance-based sports characteristics or power-based sports characteristics, but some studies have reported some genes associations to both sports-based characteristics. Furthermore, genetic studies with larger cohorts of single-sport athletes might be preferable than studies combining athletes of different sports, given the existence of distinct athlete profiles and sport demands. Athletic performance may be influenced by the serotonergic pathway and the potential injury risk (namely stress fracture) might be associated to a genetic predisposition associated to the mechanical loading from the intense physical exercise. The study of gene variants associated to sex and ethnicity-related to athletic performance needs further investigation. The combination of genome-wide association studies addressing the genetic architecture of athletes and the subsequent replication and validation studies might for additional genetic data is mandatory.
- Potential of portuguese viticulture by-products as natural resources of bioactive compounds—antioxidant and antimicrobial activitiesPublication . Ferreira da Vinha, Ana; Silva, Carla Sousa e; Vilela, Andreia; Ferreira, Joana; Medeiros, R.; Cerqueira, FátimaVitis vinifera is the grape variety used in the production of wine and other products. In the wine production process, many of the vine’s by-products are wasted, namely seeds and stems. Given the proportion of wine production worldwide, the quantity of by-products is beginning to be an environmental problem, making it urgent to take measures for their use to obtain bioactive compounds with health benefits. The aim of this work was to study the antioxidant and antimicrobial activities of extracts from the seeds and stems of four Portuguese grape varieties: Touriga Franca, Touriga Nacional, Viosinho, and Tinta Roriz. Total phenolic (TPC) and total flavonoids (TFC) contents present in the different extracts were evaluated, as well as the antioxidant activity, by DPPH and FRAP methods. TPC and TFC values of the stem’s extracts are much higher than those of the seeds of the same grape variety in the same solvent. The antioxidant activity of aqueous and ethanolic stem extracts is higher than that obtained for the seeds, showing that antioxidant activity is related to the content of polyphenols. The antimicrobial activity of different stem and seed extracts was determined against yeasts and Gram-positive and Gram-negative bacteria, and the effect was determined based on the minimal inhibitory concentrations calculated (MIC). In general, the ethanol:water (1:1) extract of the seeds from the different varieties tested inhibited C. albicans ATCC10231 and C. krusei ATCC6258 growth even at 200 μg/mL, and the effect was fungicidal at 200 μg/mL. The same type of extract showed selective antimicrobial activity, inhibiting S. aureus ATCC29213 growth but having no effect against E. coli ATCC25922 even at 200 μg/mL. The effect against S. aureus was bactericidal (at 200 μg/mL) for Touriga Franca, Touriga Nacional, and Viosinho. Taking all these results into account, it can be concluded that the by-products of the grape varieties tested are important sources of bioactive products, particularly as antioxidants and antimicrobials.