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  • Metabolic dysfunction biomarkers as predictors of early diabetes
    Publication . Luís, Carla; Baylina, Pilar; Soares, Raquel; Fernandes, Rúben
    During the pathophysiological course of type 2 diabetes (T2D), several metabolic imbalances occur. There is increasing evidence that metabolic dysfunction far precedes clinical manifestations. Thus, knowing and understanding metabolic imbalances is crucial to unraveling new strategies and molecules (biomarkers) for the early-stage prediction of the disease’s non-clinical phase. Lifestyle interventions must be made with considerable involvement of clinicians, and it should be considered that not all patients will respond in the same manner. Individuals with a high risk of diabetic progression will present compensatory metabolic mechanisms, translated into metabolic biomarkers that will therefore show potential predictive value to differentiate between progressors/non-progressors in T2D. Specific novel biomarkers are being proposed to entrap prediabetes and target progressors to achieve better outcomes. This study provides a review of the latest relevant biomarkers in prediabetes. A search for articles published between 2011 and 2021 was conducted; duplicates were removed, and inclusion criteria were applied. From the 29 studies considered, a survey of the most cited (relevant) biomarkers was conducted and further discussed in the two main identified fields: metabolomics, and miRNA studies.
  • The impact of metabolic syndrome and type 2 diabetes Mellitus on prostate cancer
    Publication . Sousa, André P.; Costa, Raquel; Alves, Marco G.; Soares, Raquel; Baylina, Pilar; Fernandes, Rúben
    Prostate cancer (PCa) remains the second most common type of cancer in men worldwide in 2020. Despite its low death rate, the need for new therapies or prevention strategies is critical. The prostate carcinogenesis process is complex and multifactorial. PCa is caused by a variety of mutations and carcinogenic events that constitutes the disease’s multifactorial focus, capable of not only remodeling cellular activity, but also modeling metabolic pathways to allow adaptation to the nutritional requirements of the tumor, creating a propitious microenvironment. Some risk factors have been linked to the development of PCa, including Metabolic Syndrome (MetS) and Type 2 Diabetes Mellitus (T2DM). MetS is intrinsically related to PCa carcinogenic development, increasing its aggressiveness. On the other hand, T2DM has the opposite impact, although in other carcinomas its effect is similar to the MetS. Although these two metabolic disorders may share some developmental processes, such as obesity, insulin resistance, and dyslipidemia, their influence on PCa prognosis appears to have an inverse effect, which makes this a paradox. Understanding the phenomena behind this paradoxical behavior may lead to new concepts into the comprehension of the diseases, as well as to evaluate new therapeutical targets. Thus, this review aimed to evaluate the impact of metabolic disorders in PCa’s aggressiveness state and metabolism
  • Which role plays 2-Hydroxybutyric acid on Insulin resistance?
    Publication . Sousa, André P.; Cunha, Diogo M.; Franco, Carolina; Teixeira, Catarina; Gojon, Frantz; Baylina, Pilar; Fernandes, Rúben
    Type 2 Diabetes Mellitus (T2D) is defined as a chronic condition caused by beta cell loss and/or dysfunction and insulin resistance (IR). The discovering of novel biomarkers capable of identifying T2D and other metabolic disorders associated with IR in a timely and accurate way is critical. In this review, 2-hydroxybutyric acid (2HB) is presented as that upheaval biomarker with an unexplored potential ahead. Due to the activation of other metabolic pathways during IR, 2HB is synthesized as a coproduct of protein metabolism, being the progression of IR intrinsically related to the increasing of 2HB levels. Hence, the focus of this review will be on the 2HB metabolite and its involvement in glucose homeostasis. A literature review was conducted, which comprised an examination of publications from different databases that had been published over the previous ten years. A total of 19 articles fulfilled the intended set of criteria. The use of 2HB as an early indicator of IR was separated into subjects based on the number of analytes examined simultaneously. In terms of the association between 2HB and IR, it has been established that increasing 2HB levels can predict the development of IR. Thus, 2HB has demonstrated considerable promise as a clinical monitoring molecule, not only as an IR biomarker, but also for disease follow-up throughout IR treatment.
  • Polymorphisms and haplotypes of TOLLIP and MUC5B are associated with susceptibility and survival in patients with fibrotic hypersensitivity pneumonitis
    Publication . Mota, P.C.; Soares, M.L.; Ferreira, A.C.; F. Santos, Rita; Cavaleiro Rufo, J; Vasconcelos, D.; Carvalho, A.; Guimarães, S.; Vasques-Novo, F.; Cardoso, C.; Melo, N.; Alexandre, A.T.; Coelho, D.; Novais-Bastos, H.; Morais, A.
    Hypersensitivity pneumonitis (HP) is an interstitial lung disease with diverse clinical features that can present a fibrotic phenotype similar to idiopathic pulmonary fibrosis (IPF) in genetically predisposed individuals. While several single nucleotide polymorphisms (SNPs) have been associated with IPF, the genetic factors contributing to fibrotic HP (fHP) remain poorly understood. This study investigated the association of MUC5B and TOLLIP variants with susceptibility, clinical presentation and survival in Portuguese patients with fH. A case-control study was undertaken with 97 fHP patients and 112 controls. Six SNPs residing in the MUC5B and TOLLIP genes and their haplotypes were analyzed. Associations with risk, survival, and clinical, radiographic, and pathological features of fHP were probed through comparisons among patients and controls. MUC5B rs35705950 and three neighboring TOLLIP variants (rs3750920, rs111521887, and rs5743894) were associated with increased susceptibility to fHP. Minor allele frequencies were greater among fHP patients than in controls (40.7% vs 12.1%, P<0.0001; 52.6% vs 40.2%, P = 0.011; 22.7% vs 13.4%, P = 0.013; and 23.2% vs 12.9%, P = 0.006, respectively). Haplotypes formed by these variants were also linked to fHP susceptibility. Moreover, carriers of a specific haplotype (G-T-G-C) had a significant decrease in survival (adjusted hazard ratio 6.92, 95% CI 1.73–27.64, P = 0.006). Additional associations were found between TOLLIP rs111521887 and rs5743894 variants and decreased lung function at baseline, and the MUC5B SNP and radiographic features, further highlighting the influence of genetic factors in fHP. These findings suggest that TOLLIP and MUC5B variants and haplotypes may serve as valuable tools for risk assessment and prognosis in fibrotic hypersensitivity pneumonitis, potentially contributing to its patient stratification, and offer insights into the genetic factors influencing the clinical course of the condition.
  • The neuroprotective role of cyanobacteria with focus on the anti-inflammatory and antioxidant potential: Current status and perspectives
    Publication . Rodrigues, Flávia; Reis, Mariana; Ferreira, Leonor; Grosso, Clara; Ferraz, Ricardo; Vieira, Mónica; Vasconcelos, Vítor; Martins, Rosário
    Neurodegenerative diseases are linked to the process of neurodegeneration. This can be caused by several mechanisms, including inflammation and accumulation of reactive oxygen species. Despite their high incidence, there is still no effective treatment or cure for these diseases. Cyanobacteria have been seen as a possible source for new compounds with anti-inflammatory and antioxidant potential, such as polysaccharides (sacran), phycobiliproteins (phycocyanin) and lipopeptides (honaucins and malyngamides), which can be interesting to combat neurodegeneration. As a promising case of success, Arthrospira (formerly Spirulina) has revealed a high potential for preventing neurodegeneration. Additionally, advantageous culture conditions and sustainable production of cyanobacteria, which are allied to the development of genetic, metabolic, and biochemical engineering, are promising. The aim of this review is to compile and highlight research on the anti-inflammatory and antioxidant potential of cyanobacteria with focus on the application as neuroprotective agents. Also, a major goal is to address essential features that brand cyanobacteria as an ecoefficient and economically viable option, linking health to sustainability.
  • Repurposing antiplasmodial leads for cancer: Exploring the antiproliferative effects of N-cinnamoyl-aminoacridines
    Publication . Fonte, Mélanie; Rôla, Catarina; Santana, Sofia; Ferraz, Ricardo; Prudêncio, Miguel; Almeida, Joana; Ferraz, Ricardo; Prudêncio, Cristina; Teixeira, Cátia; Gomes, Paula
    Drug repurposing and rescuing have been widely explored as cost-effective approaches to expand the portfolio of chemotherapeutic agents. Based on the reported antitumor properties of both trans-cinnamic acids and quinacrine, an antimalarial aminoacridine, we explored the antiproliferative properties of two series of N-cinnamoyl-aminoacridines recently identified as multi-stage antiplasmodial leads. The compounds were evaluated in vitro against three cancer cell lines (MKN-28, Huh-7, and HepG2), and human primary dermal fibroblasts. One of the series displayed highly selective antiproliferative activity in the micromolar range against the three cancer cell lines tested, without any toxicity to non-carcinogenic cells.
  • Affinity coefficient for clustering autoregressive moving average models
    Publication . Nascimento, Ana Paula; Oliveira, Alexandra; Faria, Brígida Mónica; Pimenta, Rui; Vieira, Mónica; Prudêncio, Cristina; Nicolau, Helena Bacelar
    In various fields, such as economics, finance, bioinformatics, geology, and medicine, namely, in the cases of electroencephalogram, electrocardiogram, and biotechnology, cluster analysis of time series is necessary. The first step in cluster applications is to establish a similarity/dissimilarity coefficient between time series. This article introduces an extension of the affinity coefficient for the autoregressive expansions of the invertible autoregressive moving average models to measure their similarity between them. An application of the affinity coefficient between time series was developed and implemented in R. Cluster analysis is performed with the corresponding distance for the estimated simulated autoregressive moving average of order one. The primary findings indicate that processes with similar forecast functions are grouped (in the same cluster) as expected concerning the affinity coefficient. It was also possible to conclude that this affinity coefficient is very sensitive to the behavior changes of the forecast functions: processes with small different forecast functions appear to be well separated in different clusters. Moreover, if the two processes have at least an infinite number of π- weights with a symmetric signal, the affinity value is also symmetric.
  • From the gut to the brain: Is microbiota a new paradigm in Parkinson’s disease treatment?
    Publication . Vilela, Cristiana; Araújo, Bruna; Guedes, Carla; Silva, Rita Caridade; Macedo, Joana Martins; Teixeira, Catarina; Gomes, Eduardo; Prudêncio, Cristina; Vieira, Mónica; Teixeira, Fábio G.
    Parkinson’s disease (PD) is recognized as the second most prevalent primary chronic neurodegenerative disorder of the central nervous system. Clinically, PD is characterized as a movement disorder, exhibiting an incidence and mortality rate that is increasing faster than any other neurological condition. In recent years, there has been a growing interest concerning the role of the gut microbiota in the etiology and pathophysiology of PD. The establishment of a brain–gut microbiota axis is now real, with evidence denoting a bidirectional communication between the brain and the gut microbiota through metabolic, immune, neuronal, and endocrine mechanisms and pathways. Among these, the vagus nerve represents the most direct form of communication between the brain and the gut. Given the potential interactions between bacteria and drugs, it has been observed that the therapies for PD can have an impact on the composition of the microbiota. Therefore, in the scope of the present review, we will discuss the current understanding of gut microbiota on PD and whether this may be a new paradigm for treating this devastating disease.
  • Potential probiotic and functional properties of Brettanomyces strains isolated from kombucha tea
    Publication . Areal-Hermida, Lara; Coelho, Pedro; Pichardo-Gallardo, Ángeles; Prudêncio, Cristina; Sieiro, Carmen
    Kombucha, 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.
  • The influence of adipocyte secretome on selected metabolic fingerprints of breast cancer cell lines representing the four major breast cancer subtypes
    Publication . Luís, Carla; Guerra-Carvalho, Bárbara; Braga, Patrícia C.; Guedes, Carla; Patrício, Emília; Alves, Marco G.; Fernandes, Ruben; Soares, Raquel
    Molecular subtype (MS) is one of the most used classifications of breast cancer (BC). Four MSs are widely accepted according to receptor expression of estrogen, progesterone, and HER2. The impact of adipose tissue on BC MS metabolic impairment is still unclear. The present work aims to elucidate the metabolic alterations in breast cancer cell lines representing different MSs subjected to adipocyte associated factors. Preadipocytes isolated from human subcutaneous adipose tissue were differentiated into mature adipocytes. MS representative cell lines were exposed to mature adipocyte secretome. Extracellular medium was collected for metabolomics and RNA was extracted to evaluate enzymatic expression by RT-PCR. Adipocyte secretome exposure resulted in a decrease in the Warburg effect rate and an increase in cholesterol release. HER2+ cell lines (BT-474 and SK-BR-3) exhibited a similar metabolic pattern, in contrast to luminal A (MCF-7) and triple negative (TN) (MDA-MB-231), both presenting identical metabolisms. Anaplerosis was found in luminal A and TN representative cells, whereas cataplerotic reactions were likely to occur in HER2+ cell lines. Our results indicate that adipocyte secretome affects the central metabolism distinctly in each BC MS representative cell line.