Browsing by Author "Martins-Mendes, Daniela"
Now showing 1 - 7 of 7
Results Per Page
Sort Options
- Cutibacterium acnes dysbiosis: Alternative therapeutics for clinical applicationPublication . Sá, Sara; Fernandes, Ruben; Gestoso, Álvaro; Macedo, José Mário; Martins-Mendes, Daniela; Pereira, Ana Cláudia; Baylina, PilarCutibacterium acnes (C. acnes) is a Gram-positive anaerobic facultative bacterium that is part of the human skin commensal microbiome. It colonizes various regions of the body, including the face, back, and chest. While typically a harmless commensal, under certain conditions, C. acnes can become pathogenic, leading to or promoting conditions such as acne vulgaris (AV), post-surgical infections, prostate cancer, and sarcoidosis. Current treatments for C. acnes infections often involve antibiotics, but the rise of antibiotic resistance has raised concerns. This review presents the virulence factors, clinical relevance, and current treatments of C. acnes, highlighting its association with AV, postsurgical infections, and other diseases. It also explores alternative innovative therapies such as phage therapy in development/research that are gaining prominence, with a growing focus on personalized medical approaches. To enhance C. acnes treatment while minimizing side effects and antibiotic prescription concerns, numerous clinical studies have been undertaken. These investigations span various pathological profiles and employ diverse strategies, such as utilizing bacterial extracts and compounds to restore healthy skin flora. The limitations and challenges of current and innovative treatments are also addressed, emphasizing the need for multidisciplinary strategies to combat C. acnes infections effectively.
- Enhanced 3T3-L1 differentiation into adipocytes by pioglitazone pharmacological activation of peroxisome proliferator activated receptor-gamma (PPAR-gamma)Publication . Teixeira, Catarina; Sousa, André P.; Santos, Inês; Rocha, Ana Catarina; Alencastre, Inês; Pereira, Ana Cláudia; Martins-Mendes, Daniela; Barata, Pedro; Baylina, Pilar; Fernandes, RúbenDespite the primary function of pioglitazone in antidiabetic treatment, this drug is a potent inducer of PPAR-γ, a crucial receptor that is involved in adipocyte differentiation. In this work, we propose an optimized methodology to enhance the differentiation of 3T3-L1 fibroblasts into adipocytes. This process is crucial for adipocyte secretome release, which is fundamental for understanding the molecular mechanisms that are involved in obesity for in vitro studies. To achieve this, a pioglitazone dose-response assay was determined over a range varying from 0 to 10 µM. Lipid accumulation was evaluated using Oil-Red-O. The results showed that 10 µM pioglitazone enhanced differentiation and increased secretome production. This secretome was then added into two cell lines: PC3 and RAW264.7. In the PC3 cells, an increase of aggressiveness was observed in terms of viability and proliferation, with the increase of anti-inflammatory cytokines. Conversely, in RAW264.7 cells, a reduction of viability and proliferation was observed, with a decrease in the overexpression of pro-inflammatory cytokines. Overall, the present work constitutes an improved method for adipocyte secretome production that is suitable for experimental biology studies and that could help with our understanding of the molecular mechanisms underlying adiposity influence in other cells.
- Harvesting the power of green synthesis: gold nanoparticles tailored for prostate cancer therapyPublication . Oliveira, Marco; Sousa, André; Sá, Sara; Soares, Sílvia; Pereira, Ana Cláudia; Rocha, Ana Catarina; Pais, Patrick; Ferreira, Diogo; Almeida, Cátia; Luís, Carla; Lima, Cláudio; Almeida, Fábio; Gestoso, Álvaro; Duarte, Miguel-Correa; Barata, Pedro; Martins-Mendes, Daniela; Baylina, Pilar; Pereira, Carla F.; Fernandes, RúbenBiosynthetic gold nanoparticles (bAuNPs) present a promising avenue for enhancing biocompatibility and offering an economically and environmentally responsible alternative to traditional production methods, achieved through a reduction in the use of hazardous chemicals. While the potential of bAuNPs as anticancer agents has been explored, there is a limited body of research focusing on the crucial physicochemical conditions influencing bAuNP production. In this study, we aim to identify the optimal growth phase of Pseudomonas aeruginosa cultures that maximizes the redox potential and coordinates the formation of bAuNPs with increased efficiency. The investigation employs 2,6-dichlorophenolindophenol (DCIP) as a redox indicator. Simultaneously, we explore the impact of temperature, pH, and incubation duration on the biosynthesis of bAuNPs, with a specific emphasis on their potential application as antitumor agents. Characterization of the resulting bAuNPs is conducted using ATR-FT-IR, TEM, and UV-Vis spectroscopy. To gain insights into the anticancer potential of bAuNPs, an experimental model is employed, utilizing both non-neoplastic (HPEpiC) and neoplastic (PC3) epithelial cell lines. Notably, P. aeruginosa cultures at 9 h/OD600 = 1, combined with biosynthesis at pH 9.0 for 24 h at 58 ◦C, produce bAuNPs that exhibit smaller, more spherical, and less aggregated characteristics. Crucially, these nanoparticles demonstrate negligible effects on HPEpiC cells while significantly impacting PC3 cells, resulting in reduced viability, migration, and lower IL-6 levels. This research lays the groundwork for the development of more specialized, economical, and ecologically friendly treatment modalities.
- Low skeletal muscle function, but not mass, is associated with the presence of type 2 DiabetesPublication . Rigor, Joana; Barbosa, João Portugal; Luís, Carla; Fernandes, Rúben; Barata, Pedro; Martins-Mendes, DanielaThe pathophysiology of type 2 Diabetes mellitus (T2DM) is intimately connected to the skeletal muscle (SkM). SkM affects insulin resistance and is, in turn, affected by the metainflammation, microvascular disease and ectopic fat deposition of T2DM. SkM mass can be inferred by the waist-to-calf ratio (WCR) and its function by the Short Physical Performance Battery (SPPB). The aim of this study was to determine the association between SkM mass and function with T2DM in patients with Metabolic Syndrome (MetS). Patients with MetS, aged 18 to 75 years-old, attending an outpatient clinic from April 15th to September 30th 2019, were consecutively included. Exclusion criteria comprised type 1 Diabetes, secondary hypertension, active neoplasia, autoimmune disease, HIV or hepatitis virus B or C infection and end-stage renal disease and/or liver disease. History and anthropometric data were collected, including weight, height, waist circumference (WC) and WCR; the SPPB was applied. A total of 81 patients were included, of which 58.0% had T2DM; most patients were female (55.6%) and the median age was 65 (interquartile range 16.5) years. Patients with T2DM were older (64.1 vs. 56.5 years, p=0.001) and more likely to have concurrent hypertension (96% vs. 65%, p<0.001) and dyslipidemia (96% vs. 56%, p<0.001). In univariate analysis, WC [odds ratio (OR) 1.1, 95% confidence interval (CI) 1.0-1.1), WCR (OR 146.2, 95% CI 9.9-2159.0) and SPPB (0.6, 95% CI 0.4-0.8) were associated with T2DM. In multivariate analysis, only SPPB maintained its association (OR 0.65, 95% CI 0.44-0.97). Poorer muscle function, as determined by the SPPB, was associated with the presence of T2DM, even when considering body composition, per WCR. Longitudinal and mechanistic studies are warranted to best characterize this relationship.
- Moving towards personalized medicine—The broad use of aptamers for targeted theranosticPublication . Sousa, André P.; Rocha, Ana C.; Almeida, Cátia; Carneiro, Mariana C. C. G.; Pais, Patrick P.; Viana, Rejane; Fernandes, Rúben; Barata, Pedro; Gestoso, Álvaro; Ramalho, Susana; Martins-Mendes, Daniela; Baylina, Pilar; Pereira, Ana CláudiaAptamers are short, single-stranded oligonucleotides synthesized in vitro from a randomized oligonucleotide library against a specific target. These molecules are capable of binding to a wide range of biological targets with high specificity and affinity. They present great advantages over antibodies with potential applications in research, diagnosis, and therapeutics. Specifically for tumors with late-stage identification and poor prognosis, like pancreatic cancer, the study of novel aptamers holds tremendous potential for cancer diagnosis and treatment. Along with cancer treatment, aptamers have also shown high potential in regulating the immune response and modulating several critical steps of signaling cascades, such as in immune checkpoints. In the context of microbiota and infection, aptamers are being studied to identify microbes and their metabolites. This assessment has the potential to improve the detection and management of infectious diseases while assisting us in better understanding health risks and treatment outcomes by tracking changes in the microbiota. In this review, the potential of aptamers is explored regarding their applications in cancer, immune, and microbiota therapy.
- Unveiling the path to resilience: prioritizing mental health, sleep, and nutrition in the Post-COVID EraPublication . Ramalho, Susana; Martins-Mendes, Daniela; Macedo, José Mário; Barros, Carla; Luís, Carla; Sá, Sara; Gestoso, Álvaro; Pereira, Ana Cláudia; Baylina, Pilar; Fernandes, RúbenThe COVID-19 pandemic has disrupted daily life, impacting relationships, work, and education. This has led to increased stress, anxiety, and depression, along with altered sleep patterns and eating behaviors. Quarantine and isolation have worsened mental health, especially in children and the elderly, due to the loss of activities and physical contact. Sleep disorders and negative dreams perpetuate poor sleep quality, increasing the risk of health issues. Sedentary lifestyles and emotional effects contribute to unhealthy eating patterns and obesity, exacerbated by disrupted routines and limited outdoor activities. Addressing these challenges requires prioritizing mental health, promoting healthy sleep habits, and addressing obesity factors. The pandemic has profoundly affected human well-being, but resilience, mental health, sleep, and nutrition can enhance overall well-being and adaptability in the post-COVID era. This comprehensive opinion aims to raise awareness of the wide-ranging impacts of this pandemic on various aspects of human well-being and to emphasize the importance of implementing strategies that prioritize mental health, improve sleep habits, address eating behaviors, and foster resilience to navigate and thrive in the face of future challenges.
- Virulence-linked mutations in rubredoxin reductase and glutaredoxin: impact on antibiotic susceptibility and phage therapy in Pseudomonas aeruginosaPublication . Sá, Sara; Silva, Carina; Dias, Maria Clara; Veiga, Marlene; Lopes, Sofia; Fernandes, Ruben; Rocha, Ana Catarina; Pais, Patrick J.; Oliveira, Marco; Mendes, João; Novais, Gonçalo; Luís, Carla; Gestoso, Álvaro; Macedo, José Mário; Martins-Mendes, Daniela; Pereira, Ana Cláudia; Baylina, PilarPseudomonas aeruginosa (PAO1) is an opportunistic pathogen, lethal in immunocompromised individuals. The clinical management of PAO1 infections still depends deeply on antibiotic therapy. However, this therapy has been alarmingly overpowered by growing bacterial resistance mechanisms over the years. One of these bacterial mechanisms is quorum sensing (QS). QS is involved in the production of biofilm, rhamnolipids and pyocyanin, among other factors. The present study aimed to study the effect of the mutations in the genes of rubredoxin (Rub A1 and Rub A2) and glutaredoxin (GLRx) in the production of virulence traits and susceptibility of PAO1 to the antibiotic ciprofloxacin (CIP) and to infection by a phage cocktail. Rub A1, Rub A2, and GLRx showed a decrease in the expression of genes lasI, lasR, mvfR, and rpsL when compared to the wild type, PAO1. Rub A1 and Rub A2 also showed a decrease in the expression of the gene pqsA, while the mutant GLRx showed an increase of over 200% in expression compared to PAO1. The biofilm produced by the mutants Rub A1, Rub A2, and GLRx increased more than 1.5 times in comparison to PAO1, with statistical significance (p < 0.0001). In the viability assay, the mutant strain Rub A2 was the most susceptible to ciprofloxacin in both concentrations tested (p < 0.0001). The production of proteases increased in the mutant strains when compared to PAO1 (p < 0.05). However, there was a decrease in the production of rhamnolipids and pyocyanins in the mutant strains. In the phage assay, we could perceive a reduction in the growth of the mutant strains when compared to PAO1. Additionally, after the addition of the phages, all the strains showed susceptibility to the phage assay (p < 0.0001), observed in the decrease in the absorbance values. These results may highlight the relevance of the genes Rub A1, Rub A2, and GLRX in the proliferation and treatment of infections with PAO1. Overall, this study gives preliminary insights into how gene expression may be helpful in strategies to overcome antibiotic resistance.