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  • Warfarin–Supplement Interactions: A Systematic Review
    Publication . Alves, Pedro; Carreira, Bruno; Nogueira, Gonçalo; Sousa, Mariana; Cruz, Agotinho; Cruz, Agostinho
    Food supplements, which are concentrated forms of nutrients, play a crucial role in maintaining a balanced diet by providing essential missing nutrients. However, their impact on drug interactions cannot be overlooked. One such drug is warfarin, which is an anticoagulant with a complex interplay involving various medications, foods, and supplements. Given the significant increase in the use of dietary supplements in reent years, there is a compelling rationale to investigate their interactions with warfarin. This systematic review aims to identify supplements that interact with warfarin, thereby providing insights into potential risks and implications. In order to address the research question “What potential drug in‑ teractions may arise when food supplements are taken concomitantly with warfarin?”, a PRISMA 2020 systematic review was conducted. To accomplish a comprehensive under‑ standing of the issue at hand, several databases were consulted. In order to fulfill the search platforms’ requirements, the terms “interactions”, “warfarin”, and “supplements” were combined in multiple ways. The inclusion criteria took into account original, ran‑ domized or non‑randomized studies and case studies that mention a supplement used concomitantly with warfarin. An artificial intelligence‑based tool was used to evaluate the studies’ quality. The obtained results were summarized in a table format, detailing the supplement used and the how the interaction occurs. A search of the literature yielded 968 articles, of which 14 were selected for review. These articles met the specified criteria, namely the use of a dietary supplement concomitantly with warfarin. Of these, 11 indicated a potential interaction, while three articles suggested that no interaction occurred. This work clarified the interactions between supplements and warfarin, emphasizing supplements such as dong quai, milk thistle, and American ginseng, which alter the mechanism of action of the drug. Furthermore, it is imperative for patients to seek counsel from healthcare professionals before modifying their dietary regimen.
  • Use of Medicinal Plants for Treatment and Prophylaxis of Canine Parasitic Infections: A Literature Review
    Publication . Santos, Patrícia; Sousa, Mariana; Cruz, Agostinho; Cruz, Agostinho
    Dogs have been perceived as providing companionship to all members of the family, yet they can act as a vector for the transmission of parasitic agents to humans, particularly those who own or care for them. Traditional medicine seem to demonstrate effects in the treatment of diseases in animals; however, it is necessary to prove their effectiveness using more recent scientific evidence.
  • Systematic review of clinical trials on the potential of probiotics for the treatment of COVID‑19
    Publication . Santos, Rita Natália Couto dos; Moreira, Fernando Xavier Ferreira; Cruz, Agostinho Luís Silva; Cruz, Agostinho; Moreira, Fernando
    In recent decades, new deadly coronaviruses causing highly infectious diseases have emerged in human society, resulting in threats to public health and the global economy. In December 2019, in the province of Wuhan, China, the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) emerged. This infection was classified as the coronavirus dis‑ ease 2019 (COVID‑19) pandemic. Probiotics are live microorganisms whose administra‑ tion in adequate quantities has been associated with health benefits for the host, contribut‑ ing to the treatment and prevention of multiple pathologies. The present study aims to review scientific evidence on the impact of probiotic treatment on the progression of mor‑ bidity due to SARS‑CoV‑2. The research was conducted in the Cochrane Library, Clinical Trials, EBSCO, Medline, Web of Science, and Science Direct databases. Inclusion criteria were as follows: study period between 2019 and 2023; language in English or Portuguese; methodology based on clinical trials; studies in humans with a confirmed diagnosis of SARS‑CoV‑2 and administration of probiotics in the treatment of the pathology. Five stud‑ ies were included in this review, recruiting a total of patients ranging from 23 to 300 in‑ dividuals. The main positive results of the probiotic intervention compared to the control group were nearly an improvement in digestive symptoms (65% vs. 88%, p‑value 0.06) and overall symptoms (88.6% vs. 70.8%; p‑value 0.03). Also, in the probiotic group, there was an increase in serum concentrations of immunoglobulin G (IgG) in the receptor‑binding domain/spike 1 (RBD/S1) (225.9 vs. 105.6 binding antibody units/mL, p‑value 0.05). The major limitation is related to the fact that in all five studies, patients were concomitantly treated with several other drugs whose action may have influenced the observed results. The conducted studies suggest that the use of probiotics enhances a decrease in morbidity in SARS‑CoV‑2, although more studies are needed to confirm their efficacy in the disease.
  • Apple fermentation: Valorization of surpluses from the fruit industry
    Publication . Ribeiro, Tatiana; Leitão, Mariana; García, Pablo; Barreiros, Luísa; Correia, Patrícia; Correia, Patrícia Carla dos Santos Correia
    Fermentation is an anaerobic process in which sugars are converted into alcohol by bacterial enzymes or into lactic acid by yeasts. Apple is rich in vitamins and phytochemicals, mainly flavonoids, and it is responsible for antioxidant action. Apples that are unsuitable for fresh use or of inappropriate commercial size are not valued in the market, as they often do not have the physical characteristics the consumer appreciates and are therefore rejected. Furthermore, in industries and fruit processing, high amounts of waste are generated. Study possibilities for valorizing apple waste through fermentation, combining the circular and sustainable economy concepts. Local producers, processing industries, and commercial areas were contacted to establish collaborations and test different apple fermentation conditions, varying the part of the fruit used. Flasks with apple and water were placed in the oven at 30 ◦C, samples were collected every 24 h, and the pH was measured. The fermented products were analyzed to evaluate their antimicrobial activity, measuring the inhibition halo for Escherichia coli, Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Candida albicans. The most promising was the test with only apple pulp, since it was under these conditions that a greater inhibition halo was recorded compared to tests with combinations of pulp, peel, seed, and stem. Fermented apple pulp demonstrated greater activity in the sensitivity test for Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Staphylococcus epidermidis. Fermented apple appears to have antimicrobial activity against several species. It is necessary to repeat the tests and analyze the intermediate fermentation times. It would be interesting to vary the state of division of the fruit as well as to carry out biostimulation tests and bioinoculation. As a future project, in addition to analyzing antimicrobial activity, it is intended to identify fermented products, using UV/VIS spectrophotometry and HPLC.
  • Fermented Papaya: Available formulations from online markets
    Publication . Leitão, Mariana; Ribeiro, Tatiana; García, Pablo; Barreiros, Luísa; Correia, Patrícia; Barreiros, Luisa; Correia, Patrícia Carla dos Santos Correia
    Fermentation is a process of central metabolism in which an organism converts a carbohydrate, such as starch or sugar, into an alcohol or an acid. Carica papaya, also known as papaya or pawpaw, belongs to the Caricaceae family and has four genera in the world. Due to papaya’s health benefits, this fruit is considered a valuable nutraceutical with an exceptionally diverse composition, encompassing vitamins and enzymes. Fermented papaya preparations, produced by the fermentation of Carica papaya, are a wellknown food supplement that exhibit anti‑inflammatory, antioxidant, and immunostimulatory action. A descriptive study was carried out to find out which commercial fermented papaya formulations are available in the market. Data were gathered during 2021 from February to March. The main available commercial fermented papaya formulations were searched for on international online shopping sites, such as Amazon®, Naturitas®, Ebay®, Nutribio®, Life Natura®, and Fruugo®. A search was conducted by using the following keywords: “fermented papaya”, “FPP®—Fermented Papaya Preparation” “Fermented papaya extracts”. Fermented papaya is available from several brands and in different dosage forms. Its nutritional composition differs between brands not only in the dose of fermented papaya but also in the presence of other constituents. Many products are available in the online market, making it difficult to choose a suitable supplement because little is known about their labeling and contents to evaluate their appropriateness. Even if the “fermented papaya” composition is included on labels, this does not guarantee that the products have the same fermented papaya composition related to scientific studies with one specific brand (Immun’Âge‑FPP®). Consumers may often interpret anything stated on the label to be authentic merely because it is in print. There are already many commercial fermented papaya formulations available on the market. However, a deep investigation based on its pharmacokinetic properties is mandatory, as is more regulation.
  • Phytosome-based nanocarriers enhanced with seaweed extracts: Overcoming the blood–brain barrier
    Publication . Portela, Mariana; Silva, Aurora; Carpena, Maria; Grosso, Clara; Barroso, Maria Fátima; Oliveira, Ana Isabel; Martins, Claudia; Ribeiro, Cristina; Prieto, Miguel A.; Oliveira, Ana Isabel
    Neurodegenerative diseases impact millions of people globally and are emerging as an imminent challenge due to the rapid aging of the population. The current treatments only focus on relieving their symptoms, so it is necessary to adopt innovative strategies. However, delivering pharmacological agents directly into the brain is difficult because of the presence of the Blood–Brain Barrier (BBB). To overcome this obstacle, nanotransporters such as phytosomes have been developed. This study reports the preparation and characterization of phosphatidylcholine (PC) phytosomes based on hydroethanolic extracts of three macroalgae: Ascophyllum nodosum (L.) Le Jolis (AN), Bifurcaria bifurcata R.Ross (BB), and Fucus spiralis L. (FS). Additionally, some phytosomes were functionalized with polyethylene glycol (PEG) and apolipoprotein E (ApoE). Phytosome characterization was carried out in terms of encapsulation rate, size, polydispersity index (PDI), zeta potential, and stability, and the efficacy of passage through the BBB was tested using an in vitro transwell model based on hCMEC/D3 cells. The results showed a high percentage of extract bound to PC (from 74.9 to 80.3%), and tests conducted over three weeks showed the stability of the phytosomes developed. There was a notable distinction between the functionalized and non-functionalized phytosomes, reflected in the values of their sizes (from 117.71 to 167.73 nm for non-functionalized and from 277.07 to 361.44 nm for PEG-ApoE phytosomes), PDIs (0.286–0.411 for non-functionalized and 0.389-0.539 for functionalized phytosomes), and zeta potentials (1.91–2.22 and −3.31–−0.68 mV for non-functionalized and functionalized phytosomes), respectively. Regarding their ability to cross the BBB, the functionalization of phytosomes with ApoE did not prove to be a crucial step, perhaps due to the low amount of ApoE used (1%), as all of the nanotransporters always passed through the hCMEC/D3 cell monolayer, regardless of their formulation.
  • Influence of dispersant and surfactant on nZVI characterization by dynamic light scattering
    Publication . Fernandes, Filipe Jorge; Oliveira, Ana Isabel; Delerue-Matos, Cristina; Grosso, Clara; Oliveira, Ana Isabel
    The agrifood industries generate tremendous amounts of waste. The valorisation of these wastes is of the utmost importance. Here, spent coffee ground (SCG) and Cistus ladanifer L. leaf (CLL) post-distillation residues were used to prepare 50:50 (v/v) hydromethanolic extracts for green zero-valent iron nanoparticle (nZVI) production. Then, the nZVIs’ size, polydispersity index (PDI) and zeta potential (ZP) were determined through dynamic light scattering (DLS). Since nZVIs are known to be heavily reactive and display a tendency to agglomerate, dispersant influence (water or methanol) and surfactant addition (Tween® 20) were studied. SCG NPs dispersed in water displayed a size of 565.6 ± 80.84 nm, with a PDI of ± 0.084, and a ZP of −19.57 ± 0.95 mV. Adding Tween®-20 resulted in much lower sizes for these NPs (14.64 ± 0.76 nm with a PDI of 0.238 ± 0.066) and an increase in ZP (−5.99 ± 1.71 mV). CLL nZVIs dispersed in water displayed similar results, with lower size and higher ZP after surfactant addition (766.43 ± 129.49 nm, 0.684 ± 0.151 PDI vs. 13.4 ± 4.26 nm, 0.31 ± 0.042 PDI, −5.51 ± 0.86 mV). Using methanol as the dispersant for nZVIs displayed far worse results, which shows that nZVIs are better dispersed in water, and the addition of Tween® 20 highly reduced agglomeration, increasing the zeta potential. These results allow for better understanding of the importance of dispersant and surfactant usage for an accurate characterization by DLS.
  • Innovative pedagogical tools for parasitology based on interactive learning
    Publication . Sequeira, Susie; Sousa, Mariana; Fernandes, Sara; Barreiros, Luísa; Cunha, Agostinho; Cruz, Agostinho; Fernandes, Sara; Barreiros, Luisa
    Parasitic infections in children, in particular ectoparasitoses, remain a public health challenge within the school context in Portugal. As part of the curricular unit “Agentes e Vectores de Doença I” included in the first year of the Bachelor of Pharmacy, pedagogical tools have been developed to raise awareness on this issue among the various stakeholders involved in primary education. The developed activities, in addition to enable the consolidation of technical and scientific knowledge, promote the development of transversal competences, namely soft skills, essential for the training of future health professionals. The created instruments have been successfully applied in teacher training activities and in awareness-raising sessions for children. The adoption of interactive learning approaches has contributed to higher student engagement and better learning outcomes, while simultaneously promoting a culture of education and health promotion supported by innovative and collaborative pedagogical practices.
  • Improving honey authentication: Electrochemical genosensors for the detection of Erica arborea in commercial honey
    Publication . Morais, Stephanie; Castanheira, Michelle; Santos, Marlene; Domingues, Valentina; Delerue-Matos, Cristina; Barroso, M. Fátima; Santos, Marlene
    Monofloral honeys, like heather honey, are a highly sought-after ingredient. However, food safety concerns have emerged due to the number of adulterated honeys found in the global market [1,2]. Thus, this work aimed to develop an electrochemical genosensor capable of detecting the residual DNA of Erica arborea (heather flower) in commercial honey samples. Analyzing public databases, a 98-mer E. arborea DNA-target probe and its complementary sequence were selected and designed. The developed genosensor was constructed on screen-printed gold electrodes. The electrochemical signal resulted from the sandwich-format hybridization reaction between the DNA-target and its complementary probe, previously cut into a 28-mer DNA-capture probe and a 70-mer DNA-signaling probe labeled with a fluorescein. Honeys samples were acquired from the local markets and their DNA extracted and amplified using DNA kits. Employing chronoamperometry, a linear correlation was obtained in a 0.03 to 2.00 nM concentration range. The DNA from the purchased honey samples were successfully extracted and applied to the genosensor. The developed electrochemical genosensor was able to detect the presence of E. arborea in the analyzed honey samples. This device is a promising analytical tool to combat honey fraud, facilitate honey authenticity and promote food safety.
  • Enantiomeric biodistribution and toxicity of 3-chloromethcathinone (3-CMC) in Wistar rats after acute exposure – preliminary data
    Publication . Langa, Ivan; Rocha-Pereira, Carolina; Milhazes, Nuno; Silva, Diana Dias da; Domingues, Susana; Silva, Paula; Barbosa, Joana; Faria, Juliana; Tiritan, Maria Elizabeth; Ribeiro, Cláudia; Dias da Silva, Diana Cristina
    There has been a surge in global attention to New Psychoactive Substances (NPS) [1]. Synthetic cathinones stand out as a widely consumed NPS class. Notably, 3-chloromethcathinone (3-CMC) accounted for over 34% of NPS seizures in 2021 [2], which underscores concerns regarding its consumption and health effects. Of note, 3-CMC is chiral and mostly sold as a racemate. As human me-tabolism and pharmacological effects can be enantioselective [3], determination of the impact of enanti-oselectivity in toxicokinetics/toxicodynamics is essential for the assessment of 3-CMC effects. This work aimed to evaluate in vivothe enantioselective biodistribution and toxicity of racemic 3-CMC, after an acute exposure to 3-CMC. Ten-week-old male Wistar rats were administered intraperitoneally with saline or 3-CMC (10 or 20 mg/kg; n=6). Twenty-four hours after, animals were deeply anesthetized and nine organs (brain, liver, kidneys, lungs, heart, spleen, gut, muscle, adipose tis-sue), blood and urine were collected. For evaluation of the enantiomeric biodistribution, a previous in houseestablished indirect method by gas chromatography [3], was adapted and validated. Some biochem-ical analysis was performed using an analyser, whereas TBARS, ATP, glutathione and total protein were determined by spectrophotometry. Organs were also processed for histological analysis. After 24 h, 3-CMC was not found in most organs. Both enantiomers were detected in urine with one dominant enantiomer, suggesting enantioselectivity in metabolism. The histopathological results showed possible central chromatolysis in the brain (20 mg/kg), liver inflammation, renal lesions, lungs’ haemoptysis, and alveolar haemorrhage, in most 3-CMC-exposed animals. No differences were observed inthe heart. Our findings show rapid 3-CMC renal elimination, with enantio selectivity in metabolism. Alt-hough biochemical evaluations are ongoing, the results are expected to give further insights on the 3-CMC toxicity and histological abnormalities found in the brain, kidneys, liver and lungs.