Center for Innovative Biomedicine and Biotechnology

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Publications

Cold atmospheric plasma, a novel approach against bladder cancer, with higher sensitivity for the high-grade cell line

Publication . Tavares-da-Silva, Edgar; Pereira, Eurico; Pires, Ana S.; Neves, Ana R.; Braz-Guilherme, Catarina; Marques, Inês A.; Abrantes, Ana M; Gonçalves, Ana C.; Caramelo, Francisco; Silva-Teixeira, Rafael; Mendes, Fernando; Figueiredo, Arnaldo; Botelho, Maria Filomena

Antitumor therapies based on Cold Atmospheric Plasma (CAP) are an emerging medical field. In this work, we evaluated CAP effects on bladder cancer. Two bladder cancer cell lines were used, HT-1376 (stage III) and TCCSUP (stage IV). Cell proliferation assays were performed evaluating metabolic activity (MTT assay) and protein content (SRB assay). Cell viability, cell cycle, and mitochondrial membrane potential (Δψm) were assessed using flow cytometry. Reactive oxygen and nitrogen species (RONS) and reduced glutathione (GSH) were evaluated by fluorescence. The assays were carried out with different CAP exposure times. For both cell lines, we obtained a significant reduction in metabolic activity and protein content. There was a decrease in cell viability, as well as a cell cycle arrest in S phase. The Δψm was significantly reduced. There was an increase in superoxide and nitric oxide and a decrease in peroxide contents, while GSH content did not change. These results were dependent on the exposure time, with small differences for both cell lines, but overall, they were more pronounced in the TCCSUP cell line. CAP showed to have a promising antitumor effect on bladder cancer, with higher sensitivity for the high-grade cell line.

2021-01-09Journal article

Open access

Crescent-like lesions as an early signature of nephropathy in a rat model of prediabetes induced by a hypercaloric diet

Publication . Nunes, Sara; Alves, André; Preguiça, Inês; Barbosa, Adelaide; Vieira, Pedro; Mendes, Fernando; Martins, Diana; Viana, Sofia; Reis, Flávio

Diabetic nephropathy (DN) is a major microvascular complication of diabetes. Obesity and hyperlipidemia, fueled by unhealthy food habits, are risk factors to glomerular filtration rate (GFR) decline and DN progression. Several studies recommend that diabetic patients should be screened early (in prediabetes) for kidney disease, in order to prevent advanced stages, for whom the current interventions are clearly inefficient. This ambition greatly depends on the existence of accurate early biomarkers and novel molecular targets, which only may arise with a more thorough knowledge of disease pathophysiology. We used a rat model of prediabetes induced by 23 weeks of high-sugar/high-fat (HSuHF) diet to characterize the phenotype of early renal dysfunction and injury. When compared with the control animals, HSuHF-treated rats displayed a metabolic phenotype compatible with obese prediabetes, displaying impaired glucose tolerance and insulin sensitivity, along with hypertriglyceridemia, and lipid peroxidation. Despite unchanged creatinine levels, the prediabetic animals presented glomerular crescent-like lesions, accompanied by increased kidney Oil-Red-O staining, triglycerides content and mRNA expression of IL-6 and iNOS. This model of HSuHF-induced prediabetes can be a useful tool to study early features of DN, namely crescent-like lesions, an early signature that deserves in-depth elucidation.

2020-03-25Journal article

Open access

The role of immune checkpoint blockade in acute myeloid leukemia

Publication . Silva, Margarida; Martins, Diana; Mendes, Fernando

Immune checkpoint inhibition (ICI) has emerged as a therapeutic option for acute myeloid leukemia (AML) for patients that suffer from relapsed or high-risk disease, or patients ineligible for standard therapy. We aimed to study ICI as monotherapy and/or combined therapy (with chemotherapy (QT), for AML patients. The PRISMA statement was used. The literature used comprised clinical trials, randomized controlled trials, and systematic reviews published within the last 7 years. The blockade of CTLA-4 presented a 42% of complete remission within AML. Nivolumab in high-risk AML showed a median recurrence-free survival (RFS) of 8.48 months. The same drug on relapsed hematologic malignancies after allogenic transplantation shows a 1-year OS of 56%. The use of prophylaxis post allogenic transplantation cyclophosphamide (PTCy), following checkpoint inhibition, demonstrated different baseline disease and transplantation characteristics when compared to no-PCTy patients, being 32% and 10%, respectively. CTLA-4 blockage was a worthy therapeutic approach in relapsed hematologic malignancies, presenting long-lasting responses. The approach to AML and myelodysplastic syndrome patients with ICI before allogenic hematopoietic stem cell transplantation and the use of a graft-versus-host disease prophylaxis have shown improvement in the transplantation outcomes, and therefore AML treatment.

2022-07-11Journal article

Open access

Impact of dietary sugars on gut microbiota and metabolic health

Publication . Garcia, Karina; Ferreira, Gonçalo; Reis, Flávio; Viana, Sofia

Excessive sugar consumption is a risk factor for the development of several disorders, including metabolic, cardiovascular, neurological conditions and even some cancers, and has been linked to increased morbidity and mortality. The popularization of the typical Western diet, featured by an excessive intake of saturated fats and added sugars and a low consumption of unprocessed fruits, vegetables and fiber, may directly affect the composition and functionality of the gut microbiota, staggering the balance of the intestinal microbiome that ultimately culminates into gut dysbiosis. Although added sugars in the form of nutritive and non-nutritive sweeteners are generally considered as safe, a growing body of evidence correlate their consumption with adverse effects on gut microbial ecosystem; namely an abnormal synthesis of short-chain fatty acids, altered intestinal barrier integrity and chronic inflammation that often fuel a panoply of metabolic conditions. Accordingly, this work revisited the available preclinical evidence concerning the impact of different types of dietary sugars—nutritive and non-nutritive sweeteners—on gut microbiota and metabolic health. Future research should consider gender and species vulnerability when the impact of such substances on GM community and metabolic health is scrutinized in order to guide their adequate use at doses relevant to human use.

2022Journal article

Open access