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- Quality of life and therapeutic regimen management in onychomycosis patients and in vitro study of antiseptic solutionsPublication . Silva-Neves, Vasco; Hugo, Vitor; Alves, Paulo; Amado, João Costa; Pais-Vieira, Carla; Sousa, Fátima; Cerqueira, Fátima; Pinto, Eugénia; Pais-Vieira, MiguelOnychomycosis or tinea unguium (EE12.1) and Onychomycosis due to non-dermatophyte moulds (1F2D.5) (OM) is a fungal infection of the nail plates with a high prevalence that often afects vulnerable people with co-existing health problems. Gold standard pharmacological treatments for onychomycosis have been associated with low success rates and increasing antifungal resistance, suggesting that treatment outcome is dependent on multiple variables. Here, the prevalence of OM and quality of life were characterized in two vulnerable populations—Hospital patients and Homeless people. Comparing both groups, the most prevalent fungal species were identifed in Hospital patients. Then, the in vitro fungicidal properties of the antiseptics povidone-iodine, polyhexamethylene biguanide-betaine, octenidine dihydrochloride, and a super-oxidized solution against two ATCC strains (Candida albicans and Aspergillus niger) and three clinical fungal isolates from Hospital patients (Candida parapsilosis, Trichophyton interdigitale, and Trichophyton rubrum) were tested. OM prevalence was high in both patient groups studied, who also reported a reduction in quality of life and concerns about the state of their feet. In addition, Hospital patients had a nonnegligent therapeutic regimen management style. Antiseptics tested in vitro revealed antifungal properties. As antiseptics are low-cost and easy to apply and have few iatrogenic efects, the demonstration of fungicidal properties of these solutions suggests that they may constitute potential supportive therapeutics for OM.
- 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.
- Estudo preliminar da actividade antimicrobiana das folhas de cydonia oblonga millerPublication . Filipe, Catarina; Silva, Ricardo; Miranda, Ana; Oliveira, Andreia P.; Silva, Branca M.; Sousa, João Carlos; Cerqueira, FátimaO marmelo é reconhecido como uma importante fonte de compostos promotores da saúde sendo que a actividade antimicrobiana dos extractos da sua polpa, casca e sementes foi já avaliada. Não existem porém estudos da actividade antimicrobiana das folhas de marmeleiro. Este estudo preliminar teve como objectivo determinar a actividade dos seus extractos metanólicos. Concluiu-se que os extractos testados não apresentam actividade em E. coli, S. aureus, C. albicans, C. glabrata, A. niger, A. fumigatus, Mucor spp e Absídia spp pelo que novos extractos devem ser preparados sendo posteriormente avaliados. Quince fruit is recognized an important source of health promoting compounds being the antimicrobial activities of the quince pulp, peel grape and seed extracts already evaluated. No results are known for quince leaves antimicrobial activity. This preliminary work intended to determine the activity of quince leaves methanolic extracts. These had no antimicrobial activity either against E. coli, S. aureus, C. albicans, C. glabrata, A. niger, A. fumigatus, Mucor spp e Absídia spp and new extracts must be prepared and evaluated.
- 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.
- Modulation of human lymphocyte proliferation by antibacterial drugsPublication . Gomes, Ema; Esteves, Alexandra; Silva, Ricardo; Sousa, João Carlos; Cerqueira, FátimaThe aim of this work was to perform a systematic study of the interference of the different antibiotics with phytohaemaglutinin (PHA) stimulated human lymphocytes proliferation. Twelve antibiotics from different therapeutic classes were chosen: b-lactams (amoxicillin; ceftriaxone; imipenem), glycopeptides (vancomycin), aminoglycosides (gentamicin), macrolides (erythromycin), tetracyclines (tetracycline), rifampicin, quinolones (ciprofloxacin; nalidixic acid), sulfonamides (sulfamethoxazole) and nitrofuran (nitrofurantoin). Nitrofurantoin showed the strongest antiproliferative effect while tetracycline and rifampicin showed only moderate activities. All the other antibiotics were inactive even at the maximum concentration tested (100mg/ml). O objectivo do trabalho foi o estudo sistemático da interferência dos diferentes antibióticos com a proliferação de linfócitos humanos estimulados com fitohemaglutinina (PHA). Foram seleccionados doze antibióticos pertencentes a diferentes grupos terapêuticos: b-lactâmicos (amoxicilina; ceftriaxona; imipenemo), glicopéptidos (vancomicina), aminoglicosídeos (gentamicina), macrólidos (eritromicina), tetraciclinas (tetraciclina), rifampicina, quinolonas (ciprofloxacina; ácido nalidíxico), sulfonamidas (sulfametoxazole) e nitrofuranos (nitrofurantoína). A nitrofurantoína mostrou ser um potente inibidor da proliferação dos linfócitos enquanto a tetraciclina e a rifampicina apenas exibiram actividades moderadas. Nenhum dos outros antibióticos foi activo mesmo na concentração máxima testada (100 mg/ml).
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