Search

Hydroalcoholic extracts from Malbec and Torrontés wine pomaces (Vitis vinifera L.) originating from the high-altitude vineyards of Argentina’s Calchaquí Valleys were characterized. Total phenolics, hydroxycinnamic acids, orthodiphenols, anthocyanins, non-flavonoid phenolics, total flavonoids, flavones/flavonols, flavanones/dihydroflavonols, and tannins were quantified through spectrophotometric methods, with the Malbec extract exhibiting higher concentrations in most of phytochemical groups when compared to Torrontés. HPLC-DAD identified more than 30 phenolic compounds in both extracts. Malbec displayed superior antiradical activity (ABTS cation, nitric oxide, and superoxide anion radicals), reduction power (iron, copper, and phosphomolybdenum), hypochlorite scavenging, and iron chelating ability compared to Torrontés. The cytotoxicity assessments revealed that Torrontés affected the viability of HT29-MTX and Caco-2 colon cancer cells by 70% and 50%, respectively, at the highest tested concentration (1 mg/mL). At the same time, both extracts did not demonstrate acute toxicity in Artemia salina or in red blood cell assays at 500 µg/mL. Both extracts inhibited the lipoxygenase enzyme (IC50: 154.7 and 784.7 µg/mL for Malbec and Torrontés), with Malbec also reducing the tyrosinase activity (IC50: 89.9 µg/mL), and neither inhibited the xanthine oxidase. The substantial phenolic content and diverse biological activities in the Calchaquí Valleys’ pomaces underline their potentialities to be valorized for pharmaceutical, cosmetic, and food industries.

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.

Addressing pressing health concerns, modern medical research seeks to identify new antimicrobials to combat drug resistance, novel molecules for cancer treatment, and antioxidants for inflammation-related diseases. Pisolithus (Basidiomycota) is a ubiquitous and widely distributed fungal genus in forest ecosystems, known for establishing ectomycorrhizal associations with a range of host plants, enhancing their growth, and conferring protection against biotic and abiotic stresses. Beyond ecological applications, Pisolithus yields bioactive compounds with medicinal potential. This comprehensive review explores the transversal biological activity of Pisolithus fungi, aiming to provide a thorough overview of their antimicrobial, anticancer, and antioxidant potential. The focus is on elucidating bioactive compounds within Pisolithus to trigger further research for innovative applications. Compounds from Pisolithus displayed antimicrobial activity against a broad spectrum of microorganisms, including antibiotic-resistant bacteria. The efficacy of Pisolithus-derived compounds matched established medications, emphasizing their therapeutic potential. In anticancer research, the triterpene pisosterol stood out with documented cytotoxicity against various cancer cell lines, showcasing promise for novel anticancer therapies. Pisolithus was also recognized as a potential source of antioxidants, with basidiocarps exhibiting high antioxidant activity. In vivo validation and comprehensive studies on a broader range of compounds, together with mechanistic insights into the mode of action of Pisolithus-derived compounds, are compelling areas for future research.

Environmental sustainability is an increasing challenge in the pharmaceutical field, leading to the search for eco-friendly active ingredients. Among natural ingredients, propolis arises as an excellent alternative, being a complex substance with pharmacological properties. This work aims to explore the potential of propolis as a new pharmaceutical ingredient for the replacement of conventional vulvovaginal antifungals. Propolis extracts were obtained by Ultrasound-Assisted Extraction using different solvents (water, water/ethanol (50:50, v/v), and ethanol). Afterwards, the extracts were characterized regarding total phenolic content (TPC), antioxidant/antiradical activities, radical scavenging capacity, antifungal activity against strains of Candida species, and viability effect on two female genital cell lines. The aqueous extract achieved the best TPC result as well as the highest antioxidant/antiradical activities and ability to capture reactive oxygen species. A total of 38 phenolic compounds were identified and quantified by HPLC, among which ferulic acid, phloridzin and myricetin predominated. Regarding the anti-Candida spp. activity, the aqueous and the hydroalcoholic extracts achieved the best outcomes (with MIC values ranging between 128 and 512 μg/mL). The cell viability assays confirmed that the aqueous extract presented mild selectivity, while the hydroalcoholic and alcoholic extracts showed higher toxicities. These results attest that propolis has a deep potential for vulvovaginal candidiasis management, supporting its economic valorization.

Glioblastoma (GBM) is the most common and deadly primary malignant brain tumor. Current therapies are insufficient, and survival for individuals diagnosed with GBM is limited to a few months. New GBM treatments are urgent. Polymeric nanoparticles (PNs) can increase the circulation time of a drug in the brain capillaries. Polymersomes (PMs) are PNs that have been described as having attractive characteristics, mainly due to their stability, prolonged circulation period, biodegradability, their ability to sustain the release of drugs, and the possibility of surface functionalization. In this work, a poly(ethylene glycol)-ε-caprolactone (PEG-PCL) copolymer was synthesized and PMs were prepared and loaded with an hydrolytic instable compound, previously synthesized by our research team, the 3,6-bis(2,3,4,6-tetra-O-acetyl-β-glucopyranosyl)xanthone (XGAc), with promising cytotoxicity on glioblastoma cells (U-373 MG) but also on healthy cerebral endothelial cells (hCMEC/D3). The prepared PMs were spherical particles with uniform morphology and similar sizes (mean diameter of 200 nm) and were stable in aqueous suspension. The encapsulation of XGAc in PMs (80% encapsulation efficacy) protected the healthy endothelial cells from the cytotoxic effects of this compound, while maintaining cytotoxicity for the glioblastoma cell line U-373 MG. Our studies also showed that the prepared PMs can efficiently release XGAc at intratumoral pHs.

Abstract Recovery of bioactive compounds from biowaste is gaining more and more interest in circular economy models. The oilseed cakes are usually insufficiently exploited by most technologies since they represent valuable matrices abundant in proteins, minerals, and phytochemicals, but their use is mostly limited to feed ingredients, fertilizers or biofuel production. This study was thus focused on the exploration of new valorization pathways of oilseed cakes by subcritical water, representing a safe and economic alternative in the creation of value chains. Pumpkin, hemp, and flax seed cakes were treated with subcritical water in nitrogen and carbon-dioxide atmospheres, as well as in nitrogen atmosphere with the addition of acid catalyst. The degradation of carbohydrate fraction was studied by quantifying sugars and sugar degradation products in the obtained extracts. The extracts obtained under different conditions were further compared chemically with respect to total phenols and flavonoids, as well as to the content of individual phenolic compounds. Furthermore, the effects of subcritical water treatment conditions on antioxidant, antiradical and cytotoxic properties of thus obtained extracts were defined and discussed. Graphical Abstract

Neurodegenerative diseases (NDs) are characterized by progressive and irreversible neuronal loss, accompanied by a range of pathological pathways, including aberrant protein aggregation, altered energy metabolism, excitotoxicity, inflammation, and oxidative stress. Some of the most common NDs include Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and Huntington’s Disease (HD). There are currently no available cures; there are only therapeutic approaches that ameliorate the progression of symptoms, which makes the search for new drugs and therapeutic targets a constant battle. Cyanobacteria are ancient prokaryotic oxygenic phototrophs whose long evolutionary history has resulted in the production of a plethora of biomedically relevant compounds with anti-inflammatory, antioxidant, immunomodulatory, and neuroprotective properties, that can be valuable in this field. This review summarizes the major NDs and their pathophysiology, with a focus on the anti-neurodegenerative properties of cyanobacterial compounds and their main effects.

Actinidia arguta leaves have gained notoriety over the past years due to their rich bioactive composition with human pro-healthy effects, particularly in relation to antioxidants. Nevertheless, antioxidants are well known for their chemical instability, making it necessary to develop suitable delivery systems, such as microparticles, to provide protection and ensure a controlled release. The aim of this work was to produce polymeric particles of A. arguta leaves extract by spray-drying that may improve the oral mucositis condition. Microparticles were characterized by size, shape, antioxidant/antiradical activities, swelling capacity, moisture content, and effect on oral cells (TR146 and HSC-3) viability, with the aim to assess their potential application in this oral condition. The results attested the microparticles’ spherical morphology and production yields of 41.43% and 36.40%, respectively, for empty and A. arguta leaves extract microparticles. The A. arguta leaves extract microparticles obtained the highest phenolic content (19.29 mg GAE/g) and antioxidant/antiradical activities (FRAP = 81.72 µmol FSE/g; DPPH = 4.90 mg TE/g), being perceived as an increase in moisture content and swelling capacity. No differences were observed between empty and loaded microparticles through FTIR analysis. Furthermore, the exposure to HSC-3 and TR146 did not lead to a viability decrease, attesting their safety for oral administration. Overall, these results highlight the significant potential of A. arguta leaves extract microparticles for applications in the pharmaceutical and nutraceutical industries.

Alzheimer’s disease (AD) is well-known among neurodegenerative diseases for the decline of cognitive functions, making overall daily tasks difficult or impossible. The disease prevails as the most common form of dementia and remains without a well-defined etiology. Being considered a disease of multifactorial origin, current targeted treatments have only managed to reduce or control symptoms, and to date, only two drugs are close to being able to halt its progression. For decades, natural compounds produced by living organisms have been at the forefront of research for new therapies. Mushrooms, which are well-known for their nutritional and medicinal properties, have also been studied for their potential use in the treatment of AD. Natural products derived from mushrooms have shown to be beneficial in several AD-related mechanisms, including the inhibition of acetylcholinesterase (AChE) and β-secretase (BACE 1); the prevention of amyloid beta (Aβ) aggregation and neurotoxicity; and the prevention of Tau expression and aggregation, as well as antioxidant and anti-inflammatory potential. Several studies in the literature relate mushrooms to neurodegenerative diseases. However, to the best of our knowledge, there is no publication that summarizes only AD data. In this context, this review aims to link the therapeutic potential of mushrooms to AD by compiling the anti-AD potential of different mushroom extracts or isolated compounds, targeting known AD-related mechanisms.

Chestnut shells (CSs) are an appealing source of bioactive molecules, and constitute a popular research topic. This study explores the effects of in vitro gastrointestinal digestion and intestinal permeability on the bioaccessibility and bioactivity of polyphenols from CS extract prepared by subcritical water extraction (SWE). The results unveiled higher phenolic concentrations retained after gastric and intestinal digestion. The bioaccessibility and antioxidant/antiradical properties were enhanced in the following order: oral < gastric ≤ intestinal digests, attaining 40% of the maximum bioaccessibility. Ellagic acid was the main polyphenol in the digested and undigested extract, while pyrogallol–protocatechuic acid derivative was only quantified in the digests. The CS extract revealed potential mild hypoglycemic (

(1) Background: In recent years, numerous studies have highlighted the beneficial effects of extra virgin olive oil (EVOO) as an active ingredient against chronic diseases. The properties of EVOO are due to its peculiar composition, mainly to its rich content of polyphenols. In fact, polyphenols may contribute to counteract oxidative stress, which often accompanies chronic diseases. In this work, the antioxidant effects of high-value polyphenol oleocanthal (OC) and its main metabolites, tyrosol (Tyr) and oleocanthalic acid (OA), respectively, have been investigated along with their impact on cell viability. (2) Methods: OC, Tyr, and OA have been evaluated regarding antiradical properties in term of scavenging capacity towards biologically relevant reactive species, including O2●−, HOCl, and ROO●, as well as their antioxidant/antiradical capacity (FRAP, DPPH●, ABTS●+). Moreover, the ability to permeate the intestinal membrane was assessed by an intestinal co-culture model composed by Caco-2 and HT29-MTX cell lines. (3) Results: The capacity of OC and Tyr as radical oxygen species (ROS) scavengers, particularly regarding HOCl and O2●−, was clearly demonstrated. Furthermore, the ability to permeate the intestinal co-culture model was plainly proved by the good permeations (>50%) achieved by all compounds. (4) Conclusions: OC, OA, and Tyr revealed promising properties against oxidative diseases.

Lycium barbarum L. is a species widely used in dietary supplements and natural healthcare products. The berries, also known as goji or wolfberries, mostly grow in China, but recent reports on their outstanding bioactive properties have increased their popularity and cultivation around the world. Goji berries are a remarkable source of phenolic compounds (such as phenolic acids and flavonoids), carotenoids, organic acids, carbohydrates (fructose and glucose), and vitamins (ascorbic acid). Several biological activities, such as antioxidant, antimicrobial, anti-inflammatory, prebiotic, and anticancer activities, have been associated with its consumption. Hence, goji berries were highlighted as an excellent source of functional ingredients with promising applications in food and nutraceutical fields. This review aims to summarize the phytochemical composition and biological activities, along with various industrial applications, of L. barbarum berries. Simultaneously, the valorization of goji berries by-products, with its associated economic advantages, will be emphasized and explored.

ABSTRACT Staphylococcus epidermidis is a major nosocomial pathogen with a remarkable ability to persist on indwelling medical devices through biofilm formation. Nevertheless, it remains intriguing how this process is efficiently achieved under the host’s harsh conditions, where the availability of nutrients, such as essential metals, is scarce. Following our previous identification of two iron-regulated loci putatively involved in iron transport, hts and fhuC, we assessed here their individual contribution to both bacterial physiology and interaction with host immune cells. Single deletions of the hts and fhuC loci led to marked changes in the cell iron content, which were partly detrimental for planktonic growth and strongly affected biofilm formation under iron-restricted conditions. Deletion of each of these two loci did not lead to major changes in S. epidermidis survival within human macrophages or in an ex vivo human blood model of bloodstream infection. However, the lack of either hts or fhuC loci significantly impaired bacterial survival in vivo in a murine model of bacteremia. Collectively, this study establishes, for the first time, the pivotal role of the iron-regulated loci hts and fhuC in S. epidermidis biofilm formation and survival within the host, providing relevant information for the development of new targeted therapeutics against this pathogen. IMPORTANCE Staphylococcus epidermidis is one of the most important nosocomial pathogens and a major cause of central line-associated bloodstream infections. Once in the bloodstream, this bacterium must surpass severe iron restriction in order to survive and establish infection. Surprisingly, very little is known about the iron acquisition mechanisms in this species. This study represents the first report on the involvement of the S. epidermidis iron-regulated loci hts and fhuC in biofilm formation under host relevant conditions and, most importantly, in survival within the host. Ultimately, these findings highlight iron acquisition and these loci in particular, as potential targets for future therapeutic strategies against biofilm-associated S. epidermidis infections.

Iron acquisition through siderophores, a class of small, potent iron-chelating organic molecules, is a widely spread strategy among pathogens to survive in the iron-restricted environment found in the host. Although these molecules have been implicated in the pathogenesis of several species, there is currently no comprehensive study addressing siderophore production in Staphylococcus epidermidis. Staphylococcus epidermidis is an innocuous skin commensal bacterium. The species, though, has emerged as a leading cause of implant-associated infections, significantly supported by an inherent ability to form biofilms. The process of adaptation from skin niche environments to the hostile conditions during invasion is yet not fully understood. Herein, we addressed the possible role of siderophore production in S. epidermidis virulence. We first identified and deleted a siderophore homolog locus, sfaABCD, and provided evidence for its involvement in iron acquisition. Our findings further suggested the involvement of siderophores in the protection against oxidative stress-induced damage and demonstrated the in vivo relevance of a siderophore-mediated iron acquisition during S. epidermidis infections. Conclusively, this study addressed, for the first time in this species, the underlying mechanisms of siderophore production, highlighting the importance of a siderophore-mediated iron acquisition under host relevant conditions and, most importantly, its contribution to survival within the host.

This study aims to validate a new cosmetic ingredient from Salicornia ramosissima S J. Woods through in vitro and ex vivo assays. The halophyte extracts were obtained by subcritical water extraction (SWE) at different temperatures (110, 120, 140, 160 and 180 °C). The antioxidant/radical scavenging activities and the phenolic profile were screened for all extracts. The optimal extract was assessed in keratinocytes and fibroblasts, while permeation assays were performed in Franz cells. The inhibitory activity of hyaluronidase and elastase was also evaluated. The sample extracted at 180 °C presented the highest phenolic content (1739.28 mg/100 g of dry weight (dw)). Despite not being efficient in the sequestration of ABTS•+, this extract scavenged the DPPH• (IC50 = 824.57 µg/mL). The scavenging capacity of superoxide (O2•−) and hypochlorous acid (HOCl) was also considerable (respectively, IC50 = 158.87 µg/mL and IC50 = 5.80 µg/mL). The cell viability assays confirmed the absence of negative effects on keratinocytes, while the fibroblasts’ viability slightly decreased. The ex vivo permeation of rutin, quercetin and syringic acid after 24 h was, respectively, 11, 20 and 11%. Additionally, the extract showed a good elastase and hyaluronidase inhibitory activity. The results obtained support the S. ramosissima bioactivity as a cosmetic ingredient.

Oral mucositis (OM), a common side effect of oncological treatment, is an oral mucosal disorder characterized by painful ulcerations and increased risk of infection. The use of natural antioxidants to suppress the redox imbalance responsible for the OM condition has emerged as an interesting approach to prevent/treat OM. This study aims to explore the chestnut (Castana sativa) shells as potential active ingredient against OM. Therefore, chestnut shells were extracted at different temperatures (110–180 °C) by Subcritical Water Extraction (SWE), aiming to recover antioxidants. The extracts were also evaluated against microorganisms present in the oral cavity as well as on human oral cell lines (TR146 and HSC3). The highest phenolic content was obtained with the extraction temperature of 110 °C, exhibiting the best antioxidant/antiradical activities and scavenging efficiencies against HOCl (IC50 = 4.47 μg/mL) and ROO• (0.73 μmol TE/mg DW). High concentrations of phenolic acids (e.g., gallic and protocatechuic acids) and flavanoids (catechin, epicatechin and rutin) characterized the phenolic profile. The antimicrobial activity against several oral microorganisms present in the oral cavity during OM, such as Streptococcus, Staphylococcus, Enterococcus, and Escherichia, was demonstrated. Finally, the effects on HSC3 and TR146 cell lines revealed that the extract prepared at 110 °C had the lowest IC50 (1325.03 and 468.15 µg/mL, respectively). This study highlights the potential effects of chestnut shells on OM.

Actinidia arguta (Siebold & Zucc.) Planch. ex Miq. (kiwiberry) leaves are a source of phenolic compounds with pro-health biological effects, such as antioxidant and anti-inflammatory activities. Despite the huge number of studies reporting the composition of A. arguta leaves, no in vitro or in vivo studies explore its potential use as nutraceutical ingredient based on these activities. Therefore, this study aims to characterize the safety profile of kiwiberry leaf extracts using in vitro and in vivo approaches through the assessment of intestinal cell viability (Caco-2 and HT29-MTX), 3D intestinal permeation, and, most important, the redox markers, biochemical profile and liver and kidney function effects after the animal assays. Briefly, wistar rats were orally treated for 7 days with kiwiberry leaf extracts (50 and 75 mg/kg bw), water (negative control), or vitamin C (positive control). The cell viability was above 90% at 1000 μg/mL for both cells. Coumaroyl quinic acid and rutin achieved a permeation higher than 25% in the 3D intestinal model. The animal studies confirmed the extracts’ ability to increase superoxide dismutase, glutathione peroxidase, and catalase content in animals’ livers and kidneys while simultaneously decreasing the triglycerides content. This study highlighted the antioxidant capacity of kiwiberry leaf extracts, ensuring their efficacy and safety as a nutraceutical ingredient.

This study aims to evaluate the optimal ultrasound-assisted extraction (UAE) conditions of antioxidants polyphenols from Actinidia arguta (Siebold & Zucc.) Planch. Ex Miq. (kiwiberry) leaves using a response surface methodology (RSM). The effects of solid:liquid ratio (2.5–10.0% w/v), time (20–60 min), and intensity (30–70 W/m2) on the total phenolic content (TPC) and antioxidant/antiradical activities were investigated. The optimal UAE conditions were achieved using a solid:liquid ratio of 10% (w/v) and an ultrasonic intensity of 30 W/m2 for 31.11 min. The results demonstrated that the optimal extract showed a high TPC (97.50 mg of gallic acid equivalents (GAE)/g dw) and antioxidant/antiradical activity (IC50 = 249.46 µg/mL for ABTS assay; IC50 = 547.34 µg/mL for DPPH assay; 1440.13 µmol of ferrous sulfate equivalents (FSE)/g dw for ferric reducing antioxidant power (FRAP)) as well as a good capacity to scavenge superoxide and hypochlorous acid (respectively, IC50 = 220.13 μg/mL and IC50 =10.26 μg/mL), which may be related with the 28 phenolic compounds quantified. The in vitro cell assay demonstrated that the optimal extract did not decrease the keratinocytes’ (HaCaT) viability, while the fibroblasts’ (HFF-1) viability was greater than 70.63% (1000 µg/mL). This study emphasizes the great potential of kiwiberry leaves extracted by UAE for skin application.

Cancer, a major world public health problem, is associated with chemotherapy treatments whose administration leads to secondary concerns, such as oral mucositis (OM). The OM disorder is characterized by the presence of ulcers in the oral mucosa that cause pain, bleeding, and difficulty in ingesting fluids and solids, or speaking. Bioactive compounds from natural sources have arisen as an effective approach for OM. This review aims to summarize the new potential application of different natural products in the prevention and treatment of OM in comparison to conventional ones, also providing a deep insight into the most recent clinical studies. Natural products, such as Aloe vera, Glycyrrhiza glabra, Camellia sinensis, Calendula officinalis, or honeybee crops, constitute examples of sources of bioactive compounds with pharmacological interest due to their well-reported activities (e.g., antimicrobial, antiviral, anti-inflammatory, analgesic, or wound healing). These activities are associated with the bioactive compounds present in their matrix (such as flavonoids), which are associated with in vivo biological activities and minimal or absent toxicity. Finally, encapsulation has arisen as a future opportunity to preserve the chemical stability and the drug bioa vailability of bioactive compounds and, most importantly, to improve the buccal retention period and the therapeutic effects.

Nowadays there is a growing demand for nutraceuticals to prevent diseases related to redox imbalances, such as atherosclerosis and diabetes, being crucial to search for new matrixes rich in bioactive compounds. This work aims to characterize the value-added compounds extracted from Curcubita pepo seeds using green methodologies, namely microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE), employing water as an extracting solvent for two ratios (condition 1: 1 mg/20 mL; condition 2: 2.5 mg/20 mL). The extract with the best antioxidant/antiradical activity in FRAP (71.09 μmol FSE/g DW) and DPPH (5.08 mg TE/g DW) assays was MAE condition 1, while MAE condition 2 exhibited the highest activity in the ABTS assay (13.29 mg AAE/g DW) and TPC (16.89 mg GAE/g DW). A remarkable scavenging capacity was observed, particularly for HOCl, with IC50 values ranging from 1.88–13.50 μg/mL. A total of 21 phenolic compounds were identified, being catechin (4.567–7.354 mg/g DW), caffeine (1.147–2.401 mg/g DW) and gallic acid (0.945–1.337 mg/g DW) predominant. No adverse effects were observed on Caco-2 viability after exposure to MAE extracts, while the other conditions led to a slight viability decrease in NSC-34. These results highlighted that the extract from MAE condition 2 is the most promising as a potential nutraceutical ingredient.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a very poor prognosis. Its treatment is hindered by a lack of new therapeutic alternatives and the existence of the blood–brain barrier (BBB), which restricts the access of drugs commonly used in ALS, such as riluzole, to the brain. To overcome these limitations and increase brain targeting, riluzole-loaded nanostructured lipid carriers (NLC) were prepared and functionalized with lactoferrin (Lf), facilitating transport across the BBB by interacting with Lf receptors expressed in the brain endothelium. NLC were characterized with respect to their physicochemical properties (size, zeta potential, polydispersity index) as well as their stability, encapsulation efficiency, morphology, in vitro release profile, and biocompatibility. Moreover, crystallinity and melting behavior were assessed by DSC and PXRD. Nanoparticles exhibited initial mean diameters between 180 and 220 nm and a polydispersity index below 0.3, indicating a narrow size distribution. NLC remained stable over at least 3 months. Riluzole encapsulation efficiency was very high, around 94–98%. FTIR and protein quantification studies confirmed the conjugation of Lf on the surface of the nanocarriers, with TEM images showing that the functionalized NLC presented a smooth surface and uniform spherical shape. An MTT assay revealed that the nanocarriers developed in this study did not cause a substantial reduction in the viability of NSC-34 and hCMEC/D3 cells at a riluzole concentration up to 10 μM, being therefore biocompatible. The results suggest that Lf-functionalized NLC are a suitable and promising delivery system to target riluzole to the brain.

Introdução: O resveratrol é uma fitoalexina natural cujos principais benefícios devem-se às suas propriedades antiinflamatórias e antioxidantes. Os seus efeitos sugerem que este é um suplemento útil para a redução da inflamação, podendo desempenhar um papel fundamental na prevenção das doenças cardiovasculares. Este promove a vasodilatação pela indução da síntese de óxido nítrico (NO), possui atividade antitrombótica e evita a agregação plaquetária. O fator de crescimento endotelial vascular (VEGF) é responsável pela angiogénese, sendo a sua expressão influenciada pelo resveratrol. Objetivos: Avaliar o efeito do resveratrol no perfil vascular pela determinação da pressão arterial e dos biomarcadores interleucina-6 (IL-6), proteína C reativa (PCR), VEGF e NO. Material e Métodos: 27 alunos com idades compreendidas entre os 18 e os 22 anos foram divididos em grupo controlo (GC) e grupo de intervenção (GI), que consumiram placebo e 100 mg de resveratrol por dia, respetivamente, durante 1 mês. A pressão arterial foi medida com aparelho automático validado. Os níveis de PCR foram obtidos por imunoturbidimetria, os de IL-6 e VEGF por slot blot e a quantificação de NO por espectrofotometria. Resultados: Entre os grupos observou-se uma diminuição da pressão arterial braquial e central (??0.05). A variação negativa no NO apresentou-se superior no GC apesar das diferenças não serem significativas (p>0,05). Nos restantes marcadores avaliados não se observaram diferenças significativas. Conclusões: A ingestão regular de resveratrol parece ser uma abordagem preventiva a nível vascular, dado que modula positivamente o perfil vascular, reduzindo a pressão arterial. A variação nos níveis de NO poderá ajudar a explicar os benefícios verificados.

Halophytes are salinity-sensitive plants that tolerate extremely high salt concentrations, and are mainly found in saltmarshes and coastal areas worldwide, including Portugal [1]. Halophytes, such as Salicornia spp., are used by humans for commercial, ecological and gastronomic purposes [2]. Inside this genus, Salicornia ramosissima is of particular interest, being considered an alternative to salt [3]. The valorization of S. ramosissima may be a sustainable and environmentally friendly way to obtain extracts, which may be of interest for the nutraceutical industry. Nevertheless, extraction is a key step in acquiring bioactive compounds from plants, with emphasis on the extraction technique and solvent employed, which should maximize the extraction yield [4]. The aim of this study was to recover bioactive compounds from S. ramosissima by conventional extraction (CE) and Microwave-assisted extraction (MAE) techniques using water as an extractor solvent. In this study, the total phenolic and flavonoid contents (TPC and TFC, respectively) and antioxidant/antiradical activities (through FRAP and ABTS assays), as well as the phenolic profile and the in vitro effects on intestinal cells, were screened. Briefly, CE was performed as a decoction preparation while MAE was executed at selected temperatures (72–94 °C) for 1 to 5 min, with constant medium stirring. After the extraction, samples were filtrated and lyophilized for further assays. The values of TPC ranged between 8.34 and 15.02 mg of gallic acid equivalents (GAE)/g for CE and MAE extracts, respectively. Similarly, CE extract exhibited the highest TFC value (8.44 mg of catechin equivalents (CAE)/g). Regarding the ABTS and FRAP assays, the MAE extract showed the highest values (60.61 μmol FSE/g dw and 16.06% inhibition for FRAP and ABTS assays, respectively). On the other hand, the total amounts of phenolic compounds identified and quantified in both extracts were similar, the phenolic acids and flavonols being the principal constituents. For both extracts, myricetin was the compound present in the highest amounts (0.4250 and 0.4655 mg myricetin/g dw for CE and MAE extracts, respectively), and gallic acid was the major phenolic acid present in the extracts (0.2105 and 0.1553 mg gallic acid/g dw for CE and MAE extracts, respectively). The cell effects demonstrated that neither extract led to a decrease in HT29-MTX viability. In the Caco-2 cell line, only the highest concentration of MAE (1000 µg/mL) led to a decrease in viability (86.55%). In this sense, S. ramosissima extracted by CE or MAE can be classified as non-toxic and rich in bioactive compounds. However further studies, such as in vitro intestinal permeation assays and in vivo studies, are needed to underline this potential.

The objective of this work was to optimize subcritical water extraction (SWE) conditions of phenolic compounds and antioxidant activity from vineyard pruning residues. For that, a central composite design (CCD) was conducted to investigate the influence of temperature (123–307 °C) and time (14–56 min). The optimal extraction conditions were 33 min and 280 °C, revealing a high TPC (229 ± 23 mgGAE/g dw) and antioxidant activity by FRAP and ABTS assays (228 ± 20 and 236 ± 11 mgAAE/g dw). The phenolic composition revealed high amounts of catechin, gallic acid and quercetin. SWE demonstrated to be a powerful extraction technique for polyphenols recovery from vine-canes.

Kiwiberry is a nutritive fruit produced by Actinidia arguta vine [1]. During its production and harvesting, different by-products, such as leaves, are generated [2]. These by-products are enriched in bioactive compounds, enabling its recovery and reuse [1]. The objective of this study was to evaluate the antioxidant, radical scavenging, and cell viability effects of A. arguta leaf extracts at different temperatures (110–160 °C), applying subcritical water extraction (SWE), a sustainable extractive methodology. The total phenolic content (TPC), total flavonoid content (TFC), and antiradical activity (DPPH and ABTS assays) were evaluated, as well as the scavenging activity against superoxide (O2•−), hypochlorous acid (HOCl), and peroxyl radical (ROO●). Additionally, cell viability assays on HT29-MTX and Caco-2 cell lines were performed. The extract obtained at 123 °C achieved the best results in all assays (TPC = 109.72 mg GAE/g dw; TFC = 53.11 mg CE/g dw; DPPH = 497.13 µg/mL; O2− = 335.23 µg/mL; HOCl = 17.06 µg/mL; Ssample/STrolox = 0.15), except in ABTS assay. TPC, TFC, and HOCl values were better than those obtained by different authors employing other extractive methods [2–4]. The cell viability assays allowed us to observe that the viability was not affected by the extracts at the highest tested concentration (1000 µg/mL) for HT29-MTX cells. Relative to Caco-2 cells, the extract at 160 °C displayed viabilities of 80.93% at concentrations of 10 µg/mL. Therefore, temperature probably influences the content of the extracted bioactive compounds, leading to the obtained results. These results highlight the potentialities of A. arguta leaves for pharmaceutical, food, or cosmetic applications.

Salicornia ramosissima J.Woods is an edible halophyte, widely distributed in the Portuguese salt marsh that has been under valorized. The aim of this study is to expand the knowledge regarding S. ramosissima bioactive composition and safety, highlighting its potential use as nutraceutical ingredient. Therefore, extracts obtained by conventional (CE) and microwave-assisted extraction (MAE) were characterized regarding phenolic profile, antioxidant activity, radical scavenging capacity and intestinal cell effects. Moreover, organic pesticides were screened to guarantee the consumers safety. The highest phenolic and flavonoid contents were observed for the CE, as well as the scavenging capacity of O2•− (IC50 = 979.36 µg/mL) and HOCl (IC50 = 90.28 µg/mL). In contrast, the best antioxidant and antiradical activities were achieved by MAE (65.56 µmol FSE/g dw and 17.74 µg AAE/g dw for FRAP and ABTS assays, respectively). The phenolic composition was similar for both extracts, being characterized by the presence of phenolic acids, flavonols, flavanols, flavones and flavanones. The predominant compound for both extracts was myricetin. None of the extracts were cytotoxic in intestinal cell lines. Vestigial levels of β-endosulfan and p,p’-DDE were identified in MAE. These results support that S. ramosissima could be a source of bioactive compounds for nutraceutic industry.

During kiwiberry production, different by-products are generated, including leaves that are removed to increase the fruit’s solar exposure. The aim of this work was to extract bioactive compounds from kiwiberry leaf by employing microwave-assisted extraction (MAE). Compatible food solvents (water and ethanol) were employed. The alcoholic extract contained the highest phenolic and flavonoid contents (629.48 mg of gallic acid equivalents (GAE) per gram of plant material on dry weight (dw) (GAE/g dw) and 136.81 mg of catechin equivalents per gram of plant material on dw (CAE/g dw), respectively). Oppositely, the hydroalcoholic extract achieved the highest antioxidant activity and scavenging activity against reactive oxygen and nitrogen species (IC50 = 29.10 μg/mL for O2•−, IC50 = 1.87 μg/mL for HOCl and IC50 = 1.18 μg/mL for •NO). The phenolic profile showed the presence of caffeoylquinic acids, proanthocyanidin, and quercetin in all samples. However, caffeoylquinic acids and quercetin were detected in higher amounts in the alcoholic extract, while proanthocyanidins were prevalent in the hydroalcoholic extract. No adverse effects were observed on Caco-2 viability, while the highest concentration (1000 µg/mL) of hydroalcoholic and alcoholic extracts conducted to a decrease of HT29-MTX viability. These results highlight the MAE potentialities to extract bioactive compounds from kiwiberry leaf.

Human populations and natural ecosystems are bound to be exposed to ionizing radiation from the deposition of artificial radionuclides resulting from nuclear accidents, nuclear devices or radiological dispersive devices (“dirty bombs”). On the other hand, Naturally Occurring Radioactive Material industries such as phosphate production or uranium mining, contribute to the on site storage of residuals with enhanced concentrations of natural radionuclides. Therefore, in the context of the European agreements concerning nuclear energy, namely the European Atomic Energy Community Treaty, monitoring is an essential feature of the environmental radiological surveillance. In this work, we obtain 3D maps from outdoor scenarios, and complete such maps with measured radiation levels and with its radionuclide signature. In such scenarios, we face challenges such as unknown and rough terrain, limited number of sampled locations and the need for different sensors and therefore different tasks. We propose a radiological solution for scouting, monitoring and inspecting an area of interest, using a fleet of drones and a controlling ground station. First, we scout an area with a Light Detection and Ranging sensor onboard a drone to accurately 3D-map the area. Then, we monitor that area with a Geiger–Müller Counter at a low-vertical distance from the ground to produce a radiological (heat)map that is overlaid on the 3D map of the scenario. Next, we identify the hotspots of radiation, and inspect them in detail using a drone by landing on them, to reveal its radionuclide signature using a Cadmium–Zinc–Telluride detector. We present the algorithms used to implement such tasks both at the ground station and on the drones. The three mission phases were validated using actual experiments in three different outdoor scenarios. We conclude that drones can not only perform the mission efficiently, but in general they are faster and as reliable as personnel on the ground.

This paper attempts to address the origins of the Hospital and Asylum of the Venerable Third Order of Coimbra, Portugal: how and why it was founded (in 1851 and 1884), the adaptation of spaces to assistance functions and its regulations, seeking, whenever possible, giving standard and exceptional examples in order to illustrate the behavior of the Hospital and the Asylum between 1851 and 1910. Since early times their ministers and other members of the Definitory had a founding dream of the implementation of an hospital dedicated exclusively to the secular Franciscan brothers. It was only possible in 1845 with the donation of the Carmo building, localized in Sofia street.

Foodborne outbreaks due to the consumption of ready-to-eat vegetables have increased worldwide, with Escherichia coli (E. coli) being one of the main sources responsible. Viable but nonculturable bacteria (VBNC) retain virulence even after some disinfection procedures and constitute a huge problem to public health due to their non-detectability through conventional microbiological techniques. Flow cytometry (FCM) is a promising tool in food microbiology as it enables the distinction of the different physiological states of bacteria after disinfection procedures within a short time. In this study, samples of lettuce inoculated with E. coli were subject to disinfection with sodium hypochlorite at free chlorine concentrations of 5, 10, 25, 50, and 100 mg·L−1 or with 35% peracetic acid at concentrations of 5, 10, 25, and 50 mg·L−1. The efficiency of these disinfectants on the viability of E. coli in lettuce was evaluated by flow cytometry with LIVE/DEAD stains. Results from this study suggest that FCM can effectively monitor cell viability. However, peracetic acid is more effective than sodium hypochlorite as, at half the concentration, it is enough to kill 100% of bacteria and always induces a lower percentage of VBNC. Finally, we can conclude that the recommended levels of chemical disinfectants for fresh fruit and vegetables are adequate when applied in lettuce. More importantly, it is possible to ensure that all cells of E. coli are dead and that there are no VBNC cells even with lower concentrations of those chemicals. These results can serve as guidance for lettuce disinfection, improving quality and the safety of consumption.

Resumo: Objetivos: Caracterizar a população de adolescentes e jovens adultos com cardiopatias congénitas (CC) ao nível do seu ajustamento psicossocial e morbilidade psiquiátrica, bem como avaliar a qualidade de vida (QV), para perceber quais são as variáveis com impacto na vida e na adaptação à doença. População e métodos: Participaram 74 pacientes com CC, sendo 41 do sexo masculino e 33 do sexo feminino, com idades entre 12-26 (média = 18,76 ± 3,86). Foram recolhidos os dados demográficos e clínicos mais relevantes dos pacientes e foi aplicado um conjunto de instrumentos, incluindo uma entrevista semiestruturada sobre tópicos de suporte social, estilo de educação na família, autoimagem e limitações físicas, uma entrevista psiquiátrica estandardizada e questionários para avaliar o ajustamento psicossocial na forma de autorrelato (YSR e ASR) e relato dos cuidadores (CBCL e ABCL), bem como um questionário de avaliação da qualidade de vida (WHOQOL-BREF). Resultados: O sexo feminino relatou mais ansiedade/depressão (u = 952,500; p = 0,003), alterações do pensamento (u = 929,500; p = 0,005) e comportamento agressivo (u = 999,000; p = 0,000). Pacientes com CC complexas relataram mais alterações de pensamento (u = 442,000; p = 0,027) e internalização (u = 429,000; p = 0,021). Comparativamente com a população portuguesa, os nossos participantes apresentaram melhor QV nos domínios relações sociais (t = 2,333; p = 0,022) e ambiente (t = 3,754; p = 0,000). Os pacientes que não foram submetidos a intervenções cirúrgicas revelaram melhor QV nos domínios físico (t = −1,989; p = 0,050), de relações sociais (t = −2,012; p = 0,048) e QV geral (u = 563,000; p = 0,037). A presença de um melhor suporte social está relacionada com uma melhor QV nos pacientes em todos os domínios avaliados, com destaque para o físico (t = 3,287; p = 0,002) e relações sociais (t = 3,669; p = 0,000). Um melhor desempenho académico encontrava-se também associado com uma melhor perceção de QV global (u = 457 000; p = 0,046), com menos tendência ao isolamento (u = 812.500; p = 0,031), menos sentimentos de ansiedade e de depressão (u = 854 000; p = 0,009), menos problemas de atenção (u = 903 500; p = 0,001), e valores mais baixos de internalização (u = 817 000; p = 0,029) e de externalização (u = 803 500; p = 0,042). As limitações físicas tinham um efeito nocivo no QV (u = 947 500; p = 0,001). Discussão: As participantes do sexo feminino evidenciaram pior ajustamento psicossocial e maior propensão à psicopatologia. As CC complexas exigem mais cuidados regulares, limitando o contacto social com pares, a integração escolar e de lazer, e dificultando a adaptação. A realização de cirurgias influencia a QV dos pacientes, pela exigência de mais cuidados médicos, induzindo maiores limitações na sua vida diária, o que dificulta a aquisição de uma rede de suporte social satisfatória. Conclusões: Os pacientes com CC evidenciaram uma maior tendência a apresentar psicopatologia, sendo o sexo feminino mais predisposto a sofrer com os efeitos do desajustamento psicossocial. O suporte social revelou um papel preponderante no ajustamento dos doentes. Abstract: Objectives: We aimed to study the psychosocial adjustment (PSA), psychiatric morbidity and quality of life of adolescents and young adults with congenital heart disease (CHD) to determine which demographic and clinical variables negatively affect adjustment and which increase resilience. Methods: The study included 74 patients with CHD, 41 male and 33 female, aged between 12 and 26 years (mean 18.76±3.86). Demographic information and a complete clinical history were obtained. The participants were interviewed regarding social support, family environment, self-image and physical limitations. A standardized psychiatric interview was conducted, and self-report questionnaires were administered for assessment of PSA (Youth Self Report and Adult Self Report) and quality of life (World Health Organization Quality of Life – Short Version). A caregiver completed an observational version of the PSA questionnaire (Child Behavior Checklist or Adult Behavior Checklist). Results: Female participants showed more feelings of anxiety and depression (U=952.500; p=0.003), thought problems (U=929.500; p=0.005) and aggressive behavior (U=999.000; p=0.000). They also showed a higher rate of psychopathology. Patients with complex forms of CHD reported more thought problems (U=442.000; p=0.027) and internalization (U=429.000; p=0.021). Compared to the Portuguese population as a whole, participants showed better quality of life in the domains of social relationships (t=2.333; p=0.022) and environment (t=3.754; p=0.000). Patients who had undergone surgery had worse quality of life in physical terms (t=-1.989; p=0.050), social relationships (t=-2.012; p=0.048) and general quality of life (U=563.000; p=0.037), compared to those who were not operated. Better social support was associated with better quality of life in physical terms (t=3.287; p=0.002) and social relationships (t=3.669; p=0.000). Better school performance was also associated with better overall quality of life (U=457.000; p=0.046), less withdrawn behavior (U=812.500; p=0.031), fewer feelings of anxiety and depression (U=854.000; p=0.009), fewer attention problems (U=903.500; p=0.001), and lower scores for internalization (U=817.000; p=0.029) and externalization (U=803.500; p=0.042). Physical limitations had a detrimental effect on quality of life (U=947.500; p=0.001). Discussion: Female participants were more prone to worse psychological adjustment and to psychopathology. Patients with complex forms of CHD showed worse PSA, as they need regular care, which restricts social contact with peers and family and integration in school and leisure activities. Patients who had undergone surgery showed worse quality of life as they often have long hospital stays, during which social activities are restricted, making it more difficult for them to develop a good social support network. They require close medical care, and the restrictions on their activities may be life-limiting. Their sense of survival may also be threatened. Conclusions: Patients with CHD appear to be more prone to psychopathology and female patients are more likely to show worse PSA. Social support was shown to play a crucial role in buffering stress and promoting patients’ adjustment. Palavras-chave: Ajustamento psicossocial, Cardiopatias congénitas, Morbilidade psiquiátrica, Qualidade de vida, Keywords: Psychosocial adjustment, Congenital heart disease, Psychiatric morbidity, Quality of life

OBJETIVOS: Avaliar a prevalência de doença respiratória em crianças em idade escolar e determinar o valor da espirometria de campo. MÉTODOS: Avaliaram-se 313 alunos do primeiro e quarto ano de quatro escolas de Lisboa. Aplicou-se questionário respiratório auto-preenchido, e efetuou-se espirometria. Realizou-se análise descritiva e bivariada seguida de análise de regressão logística múltipla. RESULTADOS: Trinta e cinco por cento das crianças tiveram pelo menos um episódio de sibilância (18% > 2 episódios), e 4% tiveram diagnóstico de asma. Sibilância foi mais frequente com história familiar de atopia (OR ajustado = 2,7, IC95% 1,4-5,1), tabagismo na gravidez, infecção respiratória baixa (IRB) (OR ajustado = 2,8; IC95% 1,2-6,2), bronquiolite (OR ajustado = 3,3; IC95% 1,3-8,2) e alergia a aeroalérgenos (OR ajustado = 3,2; IC95% 1,4-7,2). Asma foi mais frequente com história de IRB (OR ajustado = 14,6; IC95% 1,7-122,9) e alergia a aeroalérgenos (OR ajustado = 8,2; IC95% 2,0-34,2). Cento e sessenta e nove (54%) valores espirométricos preencheram critérios de aceitabilidade. O grupo com sibilância tinha em média valores de escore z inferiores para volume expiratório forçado no primeiro segundo (VEF1), razão entre VEF1 e capacidade vital forçada (CVF) (VEF1/CVF) e fluxo expiratório forçado entre 25 e 75% (FEF25-75) (p < 0,05), além de maior percentagem de crianças com valores anormais para VEF1, VEF1/CVF e FEF25-75 (FEF25-75, p < 0,05). CONCLUSÕES: Este estudo piloto revelou frequência elevada de sintomatologia respiratória obstrutiva em escolares em Lisboa. Verificou-se boa correlação entre o questionário e os valores espirométricos. A baixa prevalência de asma leva-nos a especular que este diagnóstico esteja subestimado nesta população.