Added-Value Compounds in Cork By-Products: Methods for Extraction, Identification, and Quantification of Compounds with Pharmaceutical and Cosmetic Interest.

The growing threat of climatic crisis and fossil fuel extinction has caused a boom in sustainability trends. Consumer demand for so-called eco-friendly products has been steadily increasing, built upon the foundation of environmental protection and safeguarding for future generations. A natural product that has been used for centuries is cork, resulting from the outer bark of Quercus suber L. Currently, its major application is the production of cork stoppers for the wine industry, a process that, although considered sustainable, generates by-products in the form of cork powder, cork granulates, or waste such as black condensate, among others. These residues possess constituents of interest for the cosmetic and pharmaceutical industries, as they exhibit relevant bioactivities, such as anti-inflammatory, antimicrobial, and antioxidant. This interesting potential brings forth the need to develop methods for their extraction, isolation, identification, and quantification. The aim of this work is to describe the potential of cork by-products for the cosmetic and pharmaceutical industry and to assemble the available extraction, isolation, and analytical methods applied to cork by-products, as well the biological assays. To our knowledge, this compilation has never been done, and it opens new avenues for the development of new applications for cork by-products.

A Hydrophilic Sulfated Resveratrol Derivative for Topical Application: Sensitization and Anti-Allergic Potential.

Resveratrol (RSV), a naturally occurring metabolite, is widely used in skincare products, but its hydrophobicity impairs its own incorporation into cosmetic formulations. RSV-GS is a synthetic hydrophilic sulfated glycosylated derivative inspired by marine natural products that present a lower cytotoxicity than RSV while exhibiting similar levels of bioactivity. Herein, we predict the skin sensitization potential of this new compound using an in vitro approach based on the OECD 442E guideline. Furthermore, the anti-allergic potential of RSV-GS was also disclosed. The monocyte THP-1 cell line was stimulated with RSV and RSV-GS in the presence or absence of the extreme skin allergen 1-fluoro-2,4-dinitrobenzene (DNFB). The results demonstrated that RSV-GS alone (500 µM) evoked a relative fluorescence index (RFI) lower than the thresholds established by the OECD guideline for CD54 (200%) and CD86 (150%), indicating the absence of a skin sensitization potential. Interestingly, in the presence of the skin allergen DNFB, RSV-GS exhibited the ability to rescue the DNFB-induced maturation of THP-1 cells, with RFI values lower than those for RSV, suggesting the potential of RSV-GS to mitigate skin sensitization evoked by allergens and, consequently, allergic contact dermatitis. These results open new avenues for the use of RSV-GS as a safe and anti-allergic active cosmetic ingredient.

Quality of life in Female Users of Antiageing Cosmetic Products/Aesthetic Treatments.

BACKGROUND: Ageing is accompanied by physical changes, both at the physiological and appearance levels. The way people perceive these changes have important consequences on general health and quality of life (QoL). This study analysed the relationship between sociodemographic variables, psychological variables, use of antiageing cosmetic products/aesthetic treatments, and QoL. METHODS: This cross-sectional study included a sample of 271 women, aged between 25 and 70 years, users of antiageing cosmetic products and/or aesthetic services. Participants were assessed on psychological morbidity (Hospital Anxiety and Depression Scale), appearance schemes (Appearance Schemas Inventory - Revised), self-esteem (Rosenberg Self-Esteem Scale), perfectionism (Frost Multidimensional Perfectionism Scale), self-perceptions of ageing (Brief Aging Perceptions Questionnaire), and QoL (SF-12v2). RESULTS: Being older and having a higher household income was associated with better QoL. The use of facial firming products, hair colouring products, and sunscreen was also associated with better QoL. Psychological morbidity and perfectionism contributed negatively to QoL, while household income contributed positively. Ageing perceptions moderated the relationship between self-esteem and QoL. CONCLUSION: According to the findings, intervention programs to reduce psychological morbidity, increase self-esteem, promote more adaptive patterns of perfectionism, and recognize the role of age perception are needed to improve women's QoL. The perceived influence of the usage of cosmetic products to prevent/minimize aging signs should be further explored.

CONTEXTE: Le vieillissement s'accompagne de changements physiques, tant au niveau physiologique qu'au niveau de l'apparence. La façon dont les gens perçoivent ces changements a des conséquences importantes sur la santé générale et la qualité de vie (QdV). Cette étude a analysé la relation entre les variables sociodémographiques, les variables psychologiques, l'utilisation de produits cosmétiques anti-âge/soins esthétiques et la QdV. MÉTHODES: Cette étude transversale a inclus un échantillon de 271 femmes, âgées de 25 à 70 ans, utilisatrices de produits cosmétiques anti-âge et/ou de soins esthétiques. Les participants ont été évalués sur la morbidité psychologique (Hospit Anxiety and Depression Scale), les schémas d'apparence (Appearance Schemas Inventory - Revised), l'estime de soi (Roenberg Self-Esteem Scale), le perfectionnisme (Frost Multidimensional Perfectionism Scale), l'auto-perception du vieillissement (Brief Questionnaire sur les perceptions du vieillissement) et QdV (SF-12v2). RÉSULTATS: Être plus âgé et avoir un revenu du ménage plus élevé était associé à une meilleure qualité de vie. L'utilisation de produits raffermissants pour le visage, de produits de coloration capillaire et de soins solaires était également associée à une meilleure qualité de vie. La morbidité psychologique et le perfectionnisme ont contribué négativement à la qualité de vie, tandis que le revenu du ménage a contribué positivement. Les perceptions du vieillissement ont modéré la relation entre l'estime de soi et la qualité de vie. CONCLUSION: Selon les résultats, des programmes d'intervention visant à réduire la morbidité psychologique, à augmenter l'estime de soi, à promouvoir des schémas de perfectionnisme plus adaptatifs et à reconnaître le rôle de la perception de l'âge sont nécessaires pour améliorer la qualité de vie des femmes. L'influence de l'utilisation de produits cosmétiques pour prévenir/minimiser les signes du vieillissement doit être davantage perçue.

Sensitive skin: Active ingredients on the spotlight.

OBJECTIVE: Sensitive skin is characterized by self-reported sensory perceptions in response to stimuli that should not provoke unpleasant sensations. Cosmetic products for sensitive skin are designed to minimize these symptoms. This study aimed to unveil the most used active ingredients for sensitive skin in facial care products from the pharmacy and parapharmacy channel. METHODS: A pool of products from the pharmacy and parapharmacy channel whose label included the expressions 'sensitive skin', 'reactive skin' or 'intolerant skin' were analysed. The active ingredients were identified from product compositions and ranked in descending order of occurrence. The scientific evidence regarding the mechanism of action and efficacy of each ingredient was also compiled. RESULTS: Eighty-eight products from 19 multinational brands were included. Niacinamide leads the top, followed by Avena sativa, allantoin, glycyrrhetinic acid and derivatives and Laminaria ochroleuca. Ingredients that can reduce skin inflammation and act on the skin barrier were used in more than half of the products analysed. The clinical studies regarding the active ingredients used in these products remain sparse and lack methodological quality. Among the top ingredients, niacinamide, panthenol and acetyl dipeptide-1 cetyl ester were the only ones studied on volunteers having sensitive skin, while acetyl dipeptide-1 cetyl ester and palmitoyl tripeptide-8 were designed to act on the molecular targets involved in this condition. CONCLUSION: This study reveals the most used active ingredients in cosmetic products for sensitive skin, as well as the scientific evidence supporting their efficacy and the mechanisms of action. This insight is meaningful for dermatologists and other health professionals to provide customized advice based on the symptomatology of individuals with sensitive skin, and for the formulation of cosmetic products and design of new active ingredients.

OBJECTIF: La peau sensible se caractérise par des perceptions sensorielles autorapportées en réponse à des stimuli qui ne devraient pas provoquer de sensations désagréables. Les produits cosmétiques pour peaux sensibles sont conçus pour minimiser ces symptômes. Cette étude visait à dévoiler les principes actifs les plus utilisés pour les peaux sensibles dans les produits de soins du visage de la pharmacie et de la chaîne de parapharmacie. MÉTHODES: Un ensemble de produits de la chaîne pharmacie et parapharmacie, dont l'étiquette comportait les expressions « peau sensible ¼, « peau réactive ¼ ou « peau intolérante ¼ ont été analysés. Les principes actifs ont été identifiés à partir des compositions du produit et classés par ordre décroissant d'occurrence. Les preuves scientifiques concernant le mécanisme d'action et l'efficacité de chaque ingrédient ont également été compilées. RÉSULTATS: Quatre-vingt-huit produits provenant de 19 marques multinationales ont été inclus. Le niacinamide est en tête, suivi de l'Avena sativa, de l'allantoïne, de l'acide glycyrrhétinique et de ses dérivés et de Laminaria ochroleuca. Des ingrédients pouvant réduire l'inflammation cutanée et agir sur la barrière cutanée ont été utilisés dans plus de la moitié des produits analysés. Les études cliniques concernant les principes actifs utilisés dans ces produits restent rares et manquent de qualité méthodologique. Parmi les principaux ingrédients, le niacinamide, le panthénol et l'ester de dipeptide acétyl-1 ont été les seuls étudiés sur des volontaires ayant une peau sensible, tandis que l'ester de dipeptide acétyl-1 et le tripeptide palmitoyl-8 ont été conçus pour agir sur les cibles moléculaires qui interviennent dans cette affection. CONCLUSION: Cette étude révèle les principes actifs les plus utilisés dans les produits cosmétiques pour les peaux sensibles, ainsi que les preuves scientifiques étayant leur efficacité et les mécanismes d'action. Cet éclairage est important pour les dermatologues et autres professionnels de la santé pour apporter des conseils personnalisés basés sur la symptomatologie des personnes ayant la peau sensible, et pour la formulation de produits cosmétiques et la conception de nouveaux principes actifs.

Analysis of indicators of surface water pollution in Atlantic Forest preservation areas.

Managing water resources in regions with scarce data, like most developing countries, is still one of the major challenges around the world. Analysis of water quality parameters can provide important information for understanding the current status of water resources and their surroundings, including the changes that have occurred over time. This study aims to evaluate the influence of preservation areas on surface water quality in the Atlantic Forest biome. For this purpose, water quality monitoring sites with a greater number of parameters and longer monitoring time, located in six basins in the Atlantic Forest region of Brazil near preservation areas, were selected. This study employs seven statistical methods, such as cluster and principal component analysis (PCA), and promotes a robust analysis of the pollution of water resources in the Atlantic Forest. The most preserved basins, with more than 87% preservation area, have lower levels of pollution. The second most degraded basin, with 56% preservation area, presents intermediate pollution levels. The most degraded basin has the highest level of pollution. The basin with the lowest area of native vegetation is considered a degraded basin. Finally, non-point sources of pollution from agricultural activities were identified as the main sources of pollution in the region. The cophenetic correlation of 0.97 indicates a good performance of the cluster analysis. In addition, the pre-tests of PCA showed the suitability of the data for performing the test (Bartlett test, < 2.2e-16 and KMO, P= 0.7). The first principal component in the PCA, which accounts for 31.4% of the total variation, is associated with strong ammonia nitrogen and total Kjeldahl nitrogen loads, and moderate biological oxygen demand and nitrite loads. The second component, representing 13.6% of the total variation, indicates periods of self-cleaning of water resources after contamination. The results indicate the importance of maintaining preservation areas in the watershed contribution areas for the improvement of surface water quality in the Atlantic Forest.

Reduced free asparagine in wheat grain resulting from a natural deletion of TaASN-B2: investigating and exploiting diversity in the asparagine synthetase gene family to improve wheat quality.

BACKGROUND: Understanding the determinants of free asparagine concentration in wheat grain is necessary to reduce levels of the processing contaminant acrylamide in baked and toasted wheat products. Although crop management strategies can help reduce asparagine concentrations, breeders have limited options to select for genetic variation underlying this trait. Asparagine synthetase enzymes catalyse a critical step in asparagine biosynthesis in plants and, in wheat, are encoded by five homeologous gene triads that exhibit distinct expression profiles. Within this family, TaASN2 genes are highly expressed during grain development but TaASN-B2 is absent in some varieties. RESULTS: Natural genetic diversity in the asparagine synthetase gene family was assessed in different wheat varieties revealing instances of presence/absence variation and other polymorphisms, including some predicted to affect the function of the encoded protein. The presence and absence of TaASN-B2 was determined across a range of UK and global common wheat varieties and related species, showing that the deletion encompassing this gene was already present in some wild emmer wheat genotypes. Expression profiling confirmed that TaASN2 transcripts were only detectable in the grain, while TaASN3.1 genes were highly expressed during the early stages of grain development. TaASN-A2 was the most highly expressed TaASN2 homeologue in most assayed wheat varieties. TaASN-B2 and TaASN-D2 were expressed at similar, lower levels in varieties possessing TaASN-B2. Expression of TaASN-A2 and TaASN-D2 did not increase to compensate for the absence of TaASN-B2, so total TaASN2 expression was lower in varieties lacking TaASN-B2. Consequently, free asparagine concentrations in field-produced grain were, on average, lower in varieties lacking TaASN-B2, although the effect was lost when free asparagine accumulated to very high concentrations as a result of sulphur deficiency. CONCLUSIONS: Selecting wheat genotypes lacking the TaASN-B2 gene may be a simple and rapid way for breeders to reduce free asparagine concentrations in commercial wheat grain.

FDG-PET Patterns Predict Amyloid Deposition and Clinical Profile in Corticobasal Syndrome.

BACKGROUND: Corticobasal syndrome (CBS) is an atypical parkinsonian syndrome related to multiple underlying pathologies. OBJECTIVE: To investigate if individual brain [18 F]fluorodeoxyglucose-positron emission tomography (FDG-PET) patterns could distinguish CBS due to Alzheimer's disease (AD) from other pathologies based on [11 C]Pittsburgh Compound-B (PIB)-PET. METHODS: Forty-five patients with probable CBS were prospectively evaluated regarding cognitive and movement disorders profile. They underwent FDG-PET and were distributed into groups: likely related to AD (CBS FDG-AD) or likely non-AD (CBS FDG-nonAD) pathology. Thirty patients underwent PIB-PET on a hybrid PET-magnetic resonance imaging equipment to assess their amyloid status. FDG and PIB-PET images were classified individually based on visual and semi-quantitative analysis, blinded to each other. Quantitative group analyses were also performed. RESULTS: CBS FDG-AD group demonstrated worse cognitive performances, mostly concerning attention, memory, visuospatial domains, and displayed more myoclonus and hallucinations. The non-AD metabolic group presented more often limb dystonia, ocular motor dysfunction, motor perseveration, and dysarthria. All patients classified as CBS FDG-AD tested positive at PIB-PET compared to 3 of 20 in the non-AD group. The individual FDG-PET classification demonstrated 76.92% of sensitivity, 100% of specificity and positive predictive value and 88.5% of balanced accuracy to detect positive PIB-PET scans. Individuals with positive and negative PIB-PET showed hypometabolism in posterior temporoparietal areas and in thalamus and brainstem, respectively, mainly contralateral to most affected side, disclosing possible metabolic signatures of CBS variants. CONCLUSION: FDG-PET was useful to predict AD and non-AD CBS variants depicting their specific degeneration patterns, different clinical features, and brain amyloid deposition. © 2020 International Parkinson and Movement Disorder Society.

Analytical tools for urocanic acid determination in human samples: A review.

Urocanic acid is a chromophore found in the skin that has been identified as an important immunosuppressant and carcinogenesis mediator through its photoisomerization from trans to cis form induced by ultraviolet radiation. Research on analytical methods that explore urocanic acid isomerization is indispensable to fully understand the deleterious effects mediated by this biomarker. In this context, the current relevant analytical methods for determination of these isomers in human samples are summarized in this review. The methods presented here are applicable to human samples collected by noninvasive methods (or minimally invasive), encompassing an array of analytical techniques, including high-performance capillary electrophoresis, confocal Raman spectroscopy, gas chromatography, high-performance liquid chromatography, and mass spectrometry, among others. Developed high-performance liquid chromatography methods have proven to be advantageous, allowing noninvasive collections for in vivo analysis and the confocal Raman, specially, for real-time analysis. Among all these methods, high-performance liquid chromatography is the most investigated one with mass spectrometry or ultraviolet detector, and the mass spectrometry detector being the most studied in the last years, demonstrating high sensitivity, very low detection limits, and accurate identification, especially for clinical investigations.

Marine Ingredients for Sensitive Skin: Market Overview.

Marine ingredients are a source of new chemical entities with biological action, which is the reason why they have gained relevance in the cosmetic industry. The facial care category is the most relevant in this industry, and within it, the sensitive skin segment occupies a prominent position. This work analyzed the use of marine ingredients in 88 facial cosmetics for sensitive skin from multinational brands, as well as their composition and the scientific evidence that supports their efficacy. Marine ingredients were used in 27% of the cosmetic products for sensitive skin and included the species Laminaria ochroleuca, Ascophyllum nodosum (brown macroalgae), Asparagopsis armata (red macroalgae), and Chlorella vulgaris (microalgae). Carotenoids, polysaccharides, and lipids are the chemical classes highlighted in these preparations. Two ingredients, namely the Ascophyllum nodosum extract and Asparagopsis armata extracts, present clinical evidence supporting their use for sensitive skin. Overall, marine ingredients used in cosmetics for sensitive skin are proposed to reduce skin inflammation and improve the barrier function. Marine-derived preparations constitute promising active ingredients for sensitive skin cosmetic products. Their in-depth study, focusing on the extracted metabolites, randomized placebo-controlled studies including volunteers with sensitive skin, and the use of extraction methods that are more profitable may provide a great opportunity for the cosmetic industry.

Trends in the Use of Botanicals in Anti-Aging Cosmetics.

Botanical ingredients have been used for thousands of years in skincare for their convenience as well as the diversity and abundance in compounds with biological activity. Among these, polyphenols and especially flavonoids have gained increasing prominence due to their antioxidant and anti-inflammatory properties. In this study, the most used botanical preparations in anti-aging products marketed in 2011 were determined. The analysis was repeated in 2018 for new and reformulated products. The scientific evidence for their application as active ingredients in anti-aging cosmetics and their flavonoid content was also compiled by searching in online scientific databases. Overall, in 2018, there was a noticeable increase in the use of botanical preparations in anti-aging cosmetics. However, the top three botanical species in both years were Vitis vinifera, Butyrospermum parkii, and Glycine soja, which is consistent with the greater amount of scientific evidence supporting their efficacy. Regarding the function of botanical preparations, there is a clear preference for DNA-protecting ingredients. The most prevalent flavonoids were flavan-3-ols, proanthocyanidins, and anthocyanins. This study provided an updated overview of the market trends regarding the use of botanicals in anti-aging products and documented the state of the art of scientific evidence for the most used plants.

In Vitro Evaluation of the Photoreactivity and Phototoxicity of Natural Polyphenol Antioxidants.

Polyphenols are a large family of natural compounds widely used in cosmetic products due to their antioxidant and anti-inflammatory beneficial properties and their ability to prevent UV radiation-induced oxidative stress. Since these compounds present chromophores and are applied directly to the skin, they can react with sunlight and exert phototoxic effects. The available scientific information on the phototoxic potential of these natural compounds is scarce, and thus the aim of this study was to evaluate the photoreactivity and phototoxicity of five phenolic antioxidants with documented use in cosmetic products. A standard ROS assay was validated and applied to screen the photoreactivity of the natural phenolic antioxidants caffeic acid, ferulic acid, p-coumaric acid, 3,4-dihydroxyphenylacetic acid (DOPAC), and rutin. The phototoxicity potential was determined by using a human keratinocyte cell line (HaCaT), based on the 3T3 Neutral Red Uptake phototoxicity test. Although all studied phenolic antioxidants absorbed UV/Vis radiation in the range of 290 to 700 nm, only DOPAC was able to generate singlet oxygen. The generation of reactive oxygen species is an early-stage chemical reaction as part of the phototoxicity mechanism. Yet, none of the studied compounds decreased the viability of keratinocytes after irradiation, leading to the conclusion that they do not have phototoxic potential. The data obtained with this work suggests that these compounds are safe when incorporated in cosmetic products.

Choosing an appropriate water quality model-a review.

Water quality models are quite complex to use even for scientists, requiring knowledge in different areas such as biology, chemistry, physics, and engineering. Hence, the use of these models by a non-specialist is quite complicated, demanding considerable time and research, particularly to choose which model is the most appropriate for a given situation. In this study, a comparative guide is suggested, which can help users select the appropriate water quality model for certain systems and variables. Five models were considered as follows: AQUATOX, CE-QUAL-W2, Spatially Referenced Regression Model on Watershed Attributes (SPARROW), Soil and Water Assessment Tool (SWAT), and Water Quality Analysis Simulation Program 7 (WASP7), which have been widely used during the last 5 years. All of these selected models are free and easily available. It was verified that each model has its particularities and applications; however, the AQUATOX model has several advantages compared with the other models analyzed. In addition, to illustrate the availability of the proposed comparative guide, a case study was carried out to demonstrating the selection process of the selected models.

Multivariate analysis of factors influencing the peak flow and runoff volume in the Cerrado and Atlantic Forest biomes in Brazil.

This study evaluates the influence of physiographic characteristics on the peak flow to runoff volume ratio in watersheds belonging to the Cerrado and Atlantic Forest biomes, in the Center-South region of Brazil. Specifically, the peak flow and runoff volume values obtained in the outlet section are related to the physiographic characteristics of the watersheds. Using a geographic information system tool, 13 watersheds are delimited, and 38 variables are selected from each watershed. A recursive digital filter is used to separate the direct (surface) flow from base (groundwater) flow. Data are analyzed using multivariate statistics, which allows interpretation of the structure of a data set from the respective correlation matrices. The results indicate that the peak flow and runoff volume are strongly correlated with the physical characteristics of the watersheds and the types of anthropogenic activity in both biomes. Furthermore, the presence of woods and forests reduces the peak flow and runoff volume.

Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients.

OBJECTIVES: The analysis of annotated transcripts from genome-wide expression studies may help to understand the pathogenesis of complex diseases, such as systemic sclerosis (SSc). We performed a whole blood (WB) transcriptome analysis on RNA collected in the context of the European PRECISESADS project, aiming at characterising the pathways that differentiate SSc from controls and that are reproducible in geographically diverse populations. METHODS: Samples from 162 patients and 252 controls were collected in RNA stabilisers. Cases and controls were divided into a discovery (n=79+163; Southern Europe) and validation cohort (n=83+89; Central-Western Europe). RNA sequencing was performed by an Illumina assay. Functional annotations of Reactome pathways were performed with the Functional Analysis of Individual Microarray Expression (FAIME) algorithm. In parallel, immunophenotyping of 28 circulating cell populations was performed. We tested the presence of differentially expressed genes/pathways and the correlation between absolute cell counts and RNA transcripts/FAIME scores in regression models. Results significant in both populations were considered as replicated. RESULTS: Overall, 15 224 genes and 1277 functional pathways were available; of these, 99 and 225 were significant in both sets. Among replicated pathways, we found a deregulation in type-I interferon, Toll-like receptor cascade, tumour suppressor p53 protein function, platelet degranulation and activation. RNA transcripts or FAIME scores were jointly correlated with cell subtypes with strong geographical differences; neutrophils were the major determinant of gene expression in SSc-WB samples. CONCLUSIONS: We discovered a set of differentially expressed genes/pathways validated in two independent sets of patients with SSc, highlighting a number of deregulated processes that have relevance for the pathogenesis of autoimmunity and SSc.

Management of skin adverse reactions in oncology.

Chemo and targeted anticancer therapies present significant skin adverse reactions, which impair the patients' quality of life. Cutaneous toxicities lead to poor treatment adherence, drug cessation, and psychosocial distress. This review aims to summarize the current knowledge concerning the prevention and management of skin toxicity arising from these therapies. A systematic literature search on online databases was conducted. The categorization of the main preventive and treatment measures was performed according to the level of evidence. Management of skin adverse reactions of oncology treatments is very heterogeneous, which can be explained by the lack of sound evidence-based treatments. The most studied adverse effects are papulopustular eruption, xerosis, and hand-foot syndrome. Prevention of xerosis stands out as the strategy most supported by level II studies. With respect to treatment, the use of antibiotics in papulopustular eruption resulting from anti-epidermal growth factor receptor agents is the most evidence-based approach. In general, the number of studies published in the literature classified with a level II of evidence (52%) is similar to the ones classified as level IV (33%), making clear the need of more randomized controlled trials regarding the effectiveness of preventive and treatment measures of skin adverse reactions of chemo and targeted anticancer therapies.

Efficacy, Stability, and Safety Evaluation of New Polyphenolic Xanthones Towards Identification of Bioactive Compounds to Fight Skin Photoaging.

Antioxidants have long been used in the cosmetic industry to prevent skin photoaging, which is mediated by oxidative stress, making the search for new antioxidant compounds highly desirable in this field. Naturally occurring xanthones are polyphenolic compounds that can be found in microorganisms, fungi, lichens, and some higher plants. This class of polyphenols has a privileged scaffold that grants them several biological activities. We have previously identified simple oxygenated xanthones as promising antioxidants and disclosed as hit, 1,2-dihydroxyxanthone (1). Herein, we synthesized and studied the potential of xanthones with different polyoxygenated patterns as skin antiphotoaging ingredients. In the DPPH antioxidant assay, two newly synthesized derivatives showed IC50 values in the same range as ascorbic acid. The synthesized xanthones were discovered to be excellent tyrosinase inhibitors and weak to moderate collagenase and elastase inhibitors but no activity was revealed against hyaluronidase. Their metal-chelating effect (FeCl3 and CuCl2) as well as their stability at different pH values were characterized to understand their potential to be used as future cosmetic active agents. Among the synthesized polyoxygenated xanthones, 1,2-dihydroxyxanthone (1) was reinforced as the most promising, exhibiting a dual ability to protect the skin against UV damage by combining antioxidant/metal-chelating properties with UV-filter capacity and revealed to be more stable in the pH range that is close to the pH of the skin. Lastly, the phototoxicity of 1,2-dihydroxyxanthone (1) was evaluated in a human keratinocyte cell line and no phototoxicity was observed in the concentration range tested.

Follow-up of fatty acid ß-oxidation disorders in expanded newborn screening era.

Fatty acid ß-oxidation (FAO) disorders have a wide variety of symptoms, not usually evident between episodes of acute decompensations. Cardiac involvement is frequent, and severe ventricular arrhythmias are suspected of causing sudden death. Expanded newborn screening (ENS) for these disorders, hopefully, contribute to prevent potentially acute life-threatening events. In order to characterize acute decompensations observed in FAO-deficient cases identified by ENS, a retrospective analysis was performed, covering a period of 9 years. Demographic data, number/type of acute decompensations, treatment, and follow-up were considered. Eighty-three clinical charts, including 66 medium-chain acyl-CoA dehydrogenase deficiency (MCADD), 5 carnitine-uptake deficiency (CUD), 3 carnitine palmitoyltransferase I and II (CPT I/II) deficiency, 5 very long-chain acyl-CoA dehydrogenase deficiency (VLCADD), and 4 multiple acyl-CoA dehydrogenase deficiency (MADD) cases were reviewed. Nineteen patients had acute decompensations (1 CPT I, 1 CPT II, 3 MADD, 14 MCADD). Six patients developed symptoms previously to ENS diagnosis. Severe clinical manifestations included multiple organ failure, liver failure, heart failure, and sudden death. Long-chain FAO disorders had the highest number of decompensations per patient.Conclusion: Despite earlier diagnosis by ENS, sudden deaths were not avoided and acute decompensations with severe clinical manifestations still occur as well. What is Known: • Severe ventricular arrhythmias are suspected to cause unexpected death in FAO disorders. • Neonatal screening intends to reduce the incidence of severe metabolic crisis and death. What is New: • Acute severe decompensations occurred in FAO disorders diagnosed through neonatal screening. • Sudden deaths were not avoided by starting treatment precociously.

The Contribution of Homocysteine Metabolism Disruption to Endothelial Dysfunction: State-of-the-Art.

Homocysteine (Hcy) is a sulfur-containing non-proteinogenic amino acid formed during the metabolism of the essential amino acid methionine. Hcy is considered a risk factor for atherosclerosis and cardiovascular disease (CVD), but the molecular basis of these associations remains elusive. The impairment of endothelial function, a key initial event in the setting of atherosclerosis and CVD, is recurrently observed in hyperhomocysteinemia (HHcy). Various observations may explain the vascular toxicity associated with HHcy. For instance, Hcy interferes with the production of nitric oxide (NO), a gaseous master regulator of endothelial homeostasis. Moreover, Hcy deregulates the signaling pathways associated with another essential endothelial gasotransmitter: hydrogen sulfide. Hcy also mediates the loss of critical endothelial antioxidant systems and increases the intracellular concentration of reactive oxygen species (ROS) yielding oxidative stress. ROS disturb lipoprotein metabolism, contributing to the growth of atherosclerotic vascular lesions. Moreover, excess Hcy maybe be indirectly incorporated into proteins, a process referred to as protein N-homocysteinylation, inducing vascular damage. Lastly, cellular hypomethylation caused by build-up of S-adenosylhomocysteine (AdoHcy) also contributes to the molecular basis of Hcy-induced vascular toxicity, a mechanism that has merited our attention in particular. AdoHcy is the metabolic precursor of Hcy, which accumulates in the setting of HHcy and is a negative regulator of most cell methyltransferases. In this review, we examine the biosynthesis and catabolism of Hcy and critically revise recent findings linking disruption of this metabolism and endothelial dysfunction, emphasizing the impact of HHcy on endothelial cell methylation status.

Measles outbreak in a tertiary level hospital, Porto, Portugal, 2018: challenges in the post-elimination era.

A measles outbreak has been occurring in a healthcare setting in Porto, Portugal, since early March 2018, posing public health challenges for a central hospital and the community. Up to 22 April, 96 cases were confirmed, 67 in vaccinated healthcare workers, mostly between 18-39 years old. Following identification of the first cases, control measures were rapidly implemented. Concomitantly, other measles cases were notified in the Northern Region of the country. No common epidemiological link was identified.

S-adenosylhomocysteine induces inflammation through NFkB: A possible role for EZH2 in endothelial cell activation.

S-adenosylhomocysteine (SAH) can induce endothelial dysfunction and activation, contributing to atherogenesis; however, its role in the activation of the inflammatory mediator NFkB has not been explored. Our aim was to determine the role of NFkB in SAH-induced activation of endothelial cells. Furthermore, we examined whether SAH, as a potent inhibitor of S-adenosylmethionine-dependent methyltransferases, suppresses the function of EZH2 methyltransferase to contribute to SAH-induced endothelial cell activation. We found that excess SAH increases the expression of adhesion molecules and cytokines in human coronary artery endothelial cells. Importantly, this up-regulation was suppressed in cells expressing a dominant negative form of the NFkB inhibitor, IkB. Moreover, SAH accumulation triggers the activation of both the canonical and non-canonical NFkB pathways, decreases EZH2, and reduces histone 3 lysine 27 trimethylation. EZH2 knockdown recapitulated the effects of excess SAH on endothelial activation, i.e., it induced NFkB activation and the subsequent up-regulation of adhesion molecules and cytokines. Our findings suggest that suppression of the epigenetic regulator EZH2 by excess SAH may contribute to NFkB activation and the consequent vascular inflammatory response. These studies unveil new targets of SAH regulation, demonstrating that EZH2 suppression and NFkB activation mediated by SAH accumulation may contribute to its adverse effects in the vasculature.