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  • Dual-action peptides as potential novel topical agents for treatment of skin and soft tissue infections
    Publication . Gomes, Ana; Bessa, Lucinda; Ferraz, Ricardo; Prudêncio, Cristina; Gameiro, Paula; Teixeira, Cátia; Gomes, Paula
    Chronic skin and soft-tissue infections (SSTI) such as diabetic foot ulcers (DFU) exhibit signs and symptoms that are consistent with localized bacterial biofilms that contribute to tissue destruction, delayed woundhealing and other serious complications. As such, most current approaches for advanced wound care aim at providing antimicrobial protection to the open wound together with a matrix scaffold (often collagenbased) to boost reestablishment of the skin tissue. While efficient production of recombinant human collagen remains an unmet goal, an alternative sensible option may be the design of formulations containing collagen-boosting instead of collagen-like components. Actually, collagen-boosting peptides, e.g., Matrikines®, are already used in cosmetics to promote extracellular matrix production, rebuilding structure and restoring all functions of healthy skin. Additionally, many antimicrobial peptides (AMP) can also act as wound-healing peptides, thus displaying the dual antimicrobial and tissue-regenerating properties highly desired in novel topical agents for treatment of SSTI. With the increasing prevalence of multi-drug resistant bacteria, and considering the burden that DFU alone represents to human health and healthcare facilities, the development of novel topical agents for effective treatment for this and other severe SSTI is an urgent need.
  • Wound-Healing Peptides for Treatment of Chronic Diabetic Foot Ulcers and Other Infected Skin Injuries
    Publication . Gomes, Ana; Teixeira, Cátia; Ferraz, Ricardo; Prudêncio, Cristina; Gomes, Paula
    As the incidence of diabetes continues to increase in the western world, the prevalence of chronic wounds related to this condition continues to be a major focus of wound care research. Additionally, over 50% of chronic wounds exhibit signs and symptoms that are consistent with localized bacterial biofilms underlying severe infections that contribute to tissue destruction, delayed wound-healing and other serious complications. Most current biomedical approaches for advanced wound care aim at providing antimicrobial protection to the open wound together with a matrix scaffold (often collagen-based) to boost reestablishment of the skin tissue. Therefore, the present review is focused on the efforts that have been made over the past years to find peptides possessing wound-healing properties, towards the development of new and effective wound care treatments for diabetic foot ulcers and other skin and soft tissue infections.
  • Chronic toxicity of valproic acid in daphnia magna
    Publication . Machado, Beatriz; Prudêncio, Cristina; Ferraz, Ricardo; Barros, Piedade
    Environmental exposure to pharmaceuticals, have negative effects on the health of ecosystems and humans and numerous pharmaceuticals have been identified on surface watersall around the world. After administration, medicines are absorbed, metabolized,and excreted to the sewer system, but many are refractory to the traditional wastewater treatment and become widely distributed in freshwater riversand lakes. Valproic acid is a short-chain fatty acid,clinically used as a broad-spectrum antiepileptic drug, in neurological diseases, whose adverse effects in aquatic organisms are not fully studied. Daphnia magnaisa planktonic crustacean found in lakes and ponds and is one of the most used organisms in aquatic toxicology studies. The adverse effects of pharmaceuticals in Daphni ahave consequences in all the ecosystem. The aim of this study is to evaluate the influence of valproic acid in the reproduction of Daphnia magna. The chronic toxicity study had a duration of 21 days. It was evaluated the effect of five different concentrations of valproic acid(0,4 mg/L, 0,6 mg/L, 0,8 mg/L, 1,0 mg/L and 1,2 mg/L). The parameters evaluated were age at first, second and third posture; the number and mortality of juveniles of each posture. Valproic acid affected the age of the first posture in all the concentrations, it is notice able a delay comparatively to the control. In relation to the juveniles, all concentrations of valproic acid induced aborted eggs, and this number was higher at the highest concentrations (1,0 mg/L and 1,2 mg/L). The control didn’t have any aborted eggs. At the highest concentrations, juvenile mortality was higher,and postures were smaller than the control. Valproic acid interfere with the reproduction of Daphnia magna, causing a delay in reproduction and affecting the number and viability of the offspring.
  • Bridging cyanobacteria to neurodegenerative diseases: a new potential source of bioactive compounds against Alzheimer’s disease
    Publication . Castaneda, Andrea; Ferraz, Ricardo; Vieira, Mónica; Cardoso, Isabel; Vasconcelos, Vítor; Martins, Rosário
    Neurodegenerative diseases (NDs) represent a drawback in society given the ageing population. Dementias are the most prevalent NDs, with Alzheimer’s disease (AD) representing around 70% of all cases. The current pharmaceuticals for AD are symptomatic and with no effects on the progression of the disease. Thus, research on molecules with therapeutic relevance has become a major focus for the scientific community. Cyanobacteria are a group of photosynthetic prokaryotes rich in biomolecules with confirmed activity in pathologies such as cancer, and with feasible potential in NDs such as AD. In this review, we aimed to compile the research works focused in the anti-AD potential of cyanobacteria, namely regarding the inhibition of the enzyme β-secretase (BACE1) as a fundamental enzyme in the generation of β-amyloid (Aβ), the inhibition of the enzyme acetylcholinesterase (AChE) lead to an increase in the availability of the neurotransmitter acetylcholine in the synaptic cleft and the antioxidant and anti-inflammatory effects, as phenomena associated with neurodegeneration mechanisms.
  • Influence of temperature on the subcritical water extraction of Actinidia arguta leaves: A screening of pro-healthy compounds
    Publication . Silva, Ana Margarida; Luís, Ana Sofia; Moreira, Manuela M.; Ferraz, Ricardo; Brezo-Borjan, Tanja; Svarc-Gajic, Jaroslava; Costa, Paulo C.; Delerue-Matos, Cristina; Rodrigues, Francisca
    Actinidia arguta is a species disseminated in Europe and classified by the Chinese Herbal Medicine as a medicinal plant. The fruit (kiwiberry) has been extensively exploited for multiple purposes, while leaves where discarded. The objective of this study was to evaluate the optimal Subcritical Water Extraction (SWE) temperature (110 °C - 160 °C) of antioxidants and polyphenols from A. arguta leaves. The optimal temperature of extraction was 123 °C, revealing the highest phenolic and flavonoid contents and good scavenging efficiencies against HOCl (IC50 = 17.06 μg/mL) and O2●- (IC50 = 335.2 μg/mL), without toxicity on intestinal cells. The phenolic profile was characterized by high amounts of phenolic acids (e.g., gallic acids), flavanols (catechin) and flavonols (e.g., quercetin-3-O-galactoside). This work allows to conclude that SWE can be a useful extraction technique for the recovery of polyphenolics from A. arguta leaves.
  • Bioactivity of ionic liquids based on valproate in the human osteoclastogenesis
    Publication . Correia, Joana; Ferraz, Ricardo; Costa-Rodrigues, João; Fernandes, Maria Helena; Branco, Luís C.; Noronha, João Paulo; Petrovski, eljko; Prudêncio, Cristina
    Ionic Liquids (ILs) are salts (with at least one organic cation), that have a melting point lower than 100º C. The interest in these compounds has been increasing as well as the number of applications where they can be used. Their first applications were on batteries and in organic synthesis and soon they started to be applied on health sciences. With this work we intend to study the biological properties of ILs based on valproate, and evaluate their modulation potential on human osteoclastogenesis.
  • Insights into the bioactive composition, antioxidant properties and In vitro cell effects of disphyma crassifolium
    Publication . Silva, Ana Margarida; Moreira, Manuela M.; Teixeira, Filipa; Delerue-Matos, Cristina; Rodrigues, Francisca; Ferraz, Ricardo; Salazar, Miguel
    Disphyma crassifolium, commonly known as sea fingers, is a halophyte plant recently introduced in gourmet cuisine. The present study aims to extract the bioactive compounds of D. crassifolium using ultrasound-assisted extraction and employing green solvents (water and ethanol). The antioxidant/antiradical activities, scavenging capacity against reactive species, phenolic profile, and intestinal effects were evaluated. The highest total phenolic (53.13 mg of gallic acid equivalent (GAE)/g on dry weight (dw)) and flavonoid contents (18.98 mg of catechin equivalent (CE)/g dw) as well as antioxidant (149.69 µmol of ferrous sulphate equivalent (FSE)/g dw) and antiradical capacities (9.37 mg of ascorbic acid equivalent (AAE)/g dw) were achieved for the alcoholic extract. Moreover, the alcoholic extract exhibited an efficient uptake of HOCl (IC50 = 1.97 µg/mL) and ROO• (0.34 µmol of Trolox equivalent (TE)/mg dw). A total of 34 phenolic compounds were identified in the extracts, with flavonols (isorhamnetin-3-O-rutinoside, quercetin-3-O-galactoside, and myricetin), flavanols (catechin), and phenolic acids (gallic and ellagic acids) being the principal classes. The intestinal cell viability assays attested that the alcoholic extract presented the lowest IC50 values (289.82 and 35.77 µg/mL for HT29-MTX and Caco-2), showing probable anticancer activity. These results emphasize the potential of D. crassifolium as a nutraceutical ingredient.
  • The Impact of [C16Pyr][Amp] on the Aggressiveness in Breast and Prostate Cancer Cell Lines
    Publication . Quintela Vieira, Ana Filipa; Marques-Magalhães, Ângela; Miranda-Gonçalves, Vera; Ferraz, Ricardo; Vieira, Mónica; Prudêncio, Cristina; Jerónimo, Carmen; Silva, Regina
    Breast (BrCa) and prostate (PCa) cancers are the most common malignancies in women and men, respectively. The available therapeutic options for these tumors are still not curative and have severe side e↵ects. Therefore, there is an urgent need for more e↵ective antineoplastic agents. Herein, BrCa, PCa, and benign cell lines were treated with two ionic liquids and two quinoxalines and functional experiments were performed—namely cell viability, apoptosis, cytotoxicity, and colony formation assays.
  • 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.
  • Molecular impact of [C16Pyr][Amp] treatment on breast and prostate cancer cell lines
    Publication . Quintela Vieira, Ana Filipa; Marques-Magalhães, Ângela; Miranda-Gonçalves, Vera; Ferraz, Ricardo; Prudêncio, Cristina; Jerónimo, Carmen; Silva, Regina
    Prostate Cancer (PCa) and Breast Cancer (BCa) are the leading causes of cancer morbidity and mortality, worldwide, when diagnosed in advanced stages of the disease. Currently available therapies have limited curative effect, leading to the progression to highly aggressive hormone-resistant phenotypes. Thus, the development of new anti-tumor agents becomes imperative. Ionic liquids are organic salts with anti-neoplastic activity and have been studied in the pharmaceutical industry. Previous work of our team demonstrated that the ionic liquid [C16Pyr][Amp] has significant anti-tumor properties in PCa and BCa cell lines. However, the main cellular pathways affected were not characterized. Therefore, the aim of this work was to explore the molecular impact of [C16Pyr][Amp] treatment in order to identify relevant genes that have altered expression upon treatment and that can justify the anti-cancer effect observed in the in vitro assays.