Golgi α-mannosidase: opposing structures of Drosophila melanogaster and novel human model using molecular dynamics simulations and docking at different pHs.

The search for Golgi α-mannosidase II (GMII) potent and specific inhibitors has been a focus of many studies for the past three decades since this enzyme is a key target for cancer treatment. α-Mannosidases, such as those from Drosophila melanogaster or Jack bean, have been used as functional models of the human Golgi α-mannosidase II (hGMII) because mammalian mannosidases are difficult to purify and characterize experimentally. Meanwhile, computational studies have been seen as privileged tools able to explore assertive solutions to specific enzymes, providing molecular details of these macromolecules, their protonation states and their interactions. Thus, modelling techniques can successfully predict hGMII 3D structure with high confidence, speeding up the development of new hits. In this study, Drosophila melanogaster Golgi mannosidase II (dGMII) and a novel human model, developed in silico and equilibrated via molecular dynamics simulations, were both opposed for docking. Our findings highlight that the design of novel inhibitors should be carried out considering the human model's characteristics and the enzyme operating pH. A reliable model is evidenced, showing a good correlation between Ki/IC50 experimental data and theoretical ΔGbinding estimations in GMII, opening the possibility of optimizing the rational drug design of new derivatives.Communicated by Ramaswamy H. Sarma.

Detection of serum biomarkers of HPV-16 driven oropharynx and oral cavity cancer in Brazil.

BACKGROUND: HPV-16 driven oropharynx/oral cavity squamous cell carcinomas prevalence varies globally. We evaluated the presence of HPV-16 ctDNA and HPV-16 E6 antibodies in samples obtained from participants treated at the Instituto do Cancer do Estado de Sao Paulo, ICESP, and from whom tumoral HPV DNA, HPV-16 E6*I mRNA, and p16INK4a status was also accessed. METHODS: HPV was genotyped by PCR-hybridization. All HPV DNA positive and ∼10 % HPV DNA negative cases underwent p16INK4a immunohistochemistry and E6*I RNA testing using a multiplex bead based protocol. HPV-16 ctDNA and anti-E6 antibodies were assessed by ddPCR (digital droplet PCR) and multiplex serology, respectively. RESULTS: The prevalence of HPV-16 in oropharynx carcinoma (OPC) cases was low (8.7 %) when considering solely HPV-16 DNA detection, and even lower (5.2 %) when taken into consideration the concomitant detection of HPV-16 E6*I RNA and/or p16INK4 (HPV-16 attributable fraction - AF). None of the oral cavity cancer (OCC) cases were detected with HPV-16 DNA. HPV-16 ctDNA was more commonly detected than HPV-16 E6 antibodies (29.8 % versus 10.6 %). Both serum biomarkers attained 100 % sensitivity of detecting HPV-16 AF OPC, however the specificity of the HPV-16 anti-E6 biomarker was higher compared to ctDNA (93.2 % versus 75.0 %). Finally, when both HPV-16 ctDNA and anti-E6 biomarkers were considered together, the sensitivity and specificity for HPV-16 OPC detection was 100 % and about 70 %, respectively, independently of analyzing HPV-16 DNA positive or HPV-16 AF tumors. CONCLUSIONS: Our findings corroborate that serum biomarkers are highly sensitive and specific biomarkers for detection of HPV-associated OPC.

Betacyanins obtained from alternative novel sources as natural food colorant additives: incorporated in savory and sweet food products.

The aim of this study was to assess the performance and stability of betacyanin compounds present in enriched extracts of red-fleshed pitaya peels (Hylocereus costaricensis) and the flowers of Amaranthus caudatus; they were evaluated as natural food colorants in tagliatelle pasta and meringue cookies. The recovered natural extracts showed promising stability, maintaining a deep pink color over a storage time of 14 days, without deeply changing the chemical composition. A number of factors were assessed, including the microbial load, texture, color, nutritional value, and contents of organic acids, fatty acids, and even free sugars of the products. Some significant interactions between the type of colorant and storage time contributed to the changes in some analyzed parameters, as can be observed from the results for organic and fatty acids in the tagliatelle pasta and meringue cookies. Another significant achievement was the reduction in the microbial load during the storage time, which strengthens the antibacterial power of these natural extracts.

A Novel Approach to Assess Balneotherapy Effects on Musculoskeletal Diseases-An Open Interventional Trial Combining Physiological Indicators, Biomarkers, and Patients' Health Perception.

The present study aimed to evaluate whether a 14-day period of balneotherapy influences the inflammatory status, health-related quality of life (QoL) and quality of sleep, underlying overall health state, and clinically relevant benefits of patients with musculoskeletal diseases (MD). The health-related QoL was evaluated using the following instruments: 5Q-5D-5L, EQ-VAS, EUROHIS-QOL, B-IPQ, and HAQ-DI. The quality of sleep was evaluated by a BaSIQS instrument. Circulating levels of IL-6 and C-reactive protein (CRP) were measured by ELISA and chemiluminescent microparticle immunoassay, respectively. The smartband, Xiaomi MI Band 4, was used for real-time sensing of physical activity and sleep quality. MD patients improved the health-related QoL measured by 5Q-5D-5L (p < 0.001), EQ-VAS (p < 0.001), EUROHIS-QOL (p = 0.017), B-IPQ (p < 0.001), and HAQ-DI (p = 0.019) after balneotherapy; the sleep quality was also improved (BaSIQS, p = 0.019). Serum concentrations of IL-6 were markedly decreased after the 14-day balneotherapy (p < 0.001). No statistically significant differences were observed regarding the physical activity and sleep quality data recorded by the smartband. Balneotherapy may be an effective alternative treatment in managing the health status of MD patients, with a decrease in inflammatory states, along with positive effects on pain reduction, patient's functionality, QoL, quality of sleep, and disability perception status.

Insights into the Chemical Composition and In Vitro Bioactive Properties of Mangosteen (Garcinia mangostana L.) Pericarp.

The industrial processing of mangosteen (Garcinia mangostana L.) generates high amounts of waste, as ~60% of the fruit is formed by an inedible pericarp. However, its pericarp has been explored as a source of xanthones; nevertheless, studies addressing the recovery of other chemical compounds from such biomass are still scarce. Hence, this study intended to elucidate the chemical composition of the mangosteen pericarp, including fat-soluble (tocopherols and fatty acids) and water-soluble (organic acids and phenolic compound non-xanthones) compounds present in the following extracts: hydroethanolic (MT80), ethanolic (MTE), and aqueous (MTW). In addition, the antioxidant, anti-inflammatory, antiproliferative and antibacterial potentials of the extracts were assessed. The mangosteen pericarp showed a composition with seven organic acids, three tocopherol isomers, four fatty acids and fifteen phenolic compounds. Regarding the extraction of phenolics, the MT80 was the most efficient (54 mg/g extract), followed by MTE (19.79 mg/g extract) and MTW (4.011 mg/g extract). All extracts showed antioxidant and antibacterial activities; however, MT80 and MTE extracts were more efficient than MTW. Only MTW did not show anti-inflammatory properties, whereas MTE and MT80 showed inhibitory activities towards tumor cell lines. Notwithstanding, MTE showed cytotoxicity towards normal cells. Our findings support the idea that the ripe mangosteen pericarp is a source of bioactive compounds, although their recovery is dependent on the extraction solvent.

Outcomes in Pregnant Women with Valvular Heart Disease from Portuguese-Speaking African Countries Treated in Portugal through an International Agreement of Health Cooperation.

Aims: We performed a clinical audit of maternal and fetal outcomes in pregnant women with valvular heart disease (VHD) from Portuguese-speaking African countries who were transferred for their care, during a twenty-year period, through a memorandum of agreement of international cooperation. Methods and results: A retrospective analysis of 81 pregnancies in 45 patients with VHD (median age 24, interquartile range 22-29 years) from 2000 to 2020 was performed. The main outcome measures were maternal cardiovascular and fetal outcomes. History of rheumatic heart disease was present in 60 (74.1%) pregnancies. Most were in New York Heart Association (NYHA) functional class I or II; at the first evaluation, 35 (43.2%) were on cardiac medication and 49 (60.5%) were anticoagulated. Forty-eight pregnancies had at least one valvular prosthesis, including 38 mechanical heart valves. During pregnancy, deterioration in NYHA functional class occurred in 35 (42.0%), and eight (9.9%) patients required initiation or intensified cardiac medication. Mechanical valve thrombosis complicated four (4.9%) pregnancies, all cases on heparin, and resulted in one maternal death. Haemorrhagic complications happened in 7 (8.6%) anticoagulated patients, in the immediate postpartum or puerperal period. The 81 pregnancies resulted in 56 (69.1%) live births, while miscarriage and fetal malformations occurred in 19 (23.5%) and 12 (14.8%) pregnancies, respectively. In multivariate analysis, vitamin K antagonist therapy was the only independent predictor of an unsuccessful pregnancy (p = 0.048). Conclusion: In a high-income country, successful pregnancy was possible with low rate of maternal events in women with VHD transferred from five low-middle income countries in Africa. The use of anticoagulation with a vitamin K antagonist was associated with an unsuccessful pregnancy.

[Hereditary Spherocytosis and Pregnancy: A Case Report]. / Esferocitose Hereditária e Gravidez: A Propósito de um Caso Clínico.

Even though it is a rare condition, hereditary spherocytosis (EH) is the main inherited cause of haemolytic anaemia and presents with a broad spectrum of symptoms. In the few reported cases of pregnancy and EH, maternal and foetal outcomes are controversial. Particularly, reports of pregnancies with EH associated with thrombosis or portal hypertension are scarce. We present a case of a woman who underwent splenectomy with EH and non-cirrhotic portal hypertension. Our patient presented polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) and plasminogen activator inhibit-1 that have a controversial impact on thrombotic risk. During pregnancy, the woman showed no signs of haemodynamical or cirrhosis deterioration. Concerning the foetus, late-onset foetal growth restriction was diagnosed but did not determine preterm delivery. Five weeks post-partum after an episode of acute abdominal pain, mesenteric venous thrombosis was diagnosed. In this case report, we describe our experience in managing pregnancy, labour and post-partum of a woman with EH, highlighting potential complications of this condition.

A esferocitose hereditária (EH), embora rara, constitui a principal causa de anemia hemolítica hereditária, tendo uma apresentação clínica muito diversa. Raros casos de grávidas com EH estão publicados, tendo um impacto incerto nos desfechos maternos e fetais. Os relatos de gestações complicadas por EH e de complicações trombóticas ou hipertensão portal são particularmente escassos. Apresentamos o caso de uma grávida esplenectomizada, com EH e hipertensão portal não cirrótica. A utente apresentava polimorfismos da metiltetrahidrofolato redutase e fator inibidor do ativador do plasminogénio, mutações com impacto controverso no risco trombótico. Durante a gestação não ocorreu deterioração hemodinâmica ou hepática, diagnosticando-se restrição de crescimento fetal tardia que não condicionou término precoce da gravidez. Cinco semanas após o parto, surgiu um quadro de dor abdominal, tendo-se diagnosticado trombose de veia mesentérica. Descrevemos a nossa experiência de vigilância da gravidez, parto e puerpério de uma mulher com EH grave, com destaque para potenciais complicações associadas à EH.

Primary biliary cholangitis: a rare diagnosis during pregnancy.

Primary biliary cholangitis is an autoimmune disease that mostly affects women. It is uncommon in women of childbearing age and the diagnosis during pregnancy is rare and can be challenging. Described here is a case of primary biliary cholangitis first manifesting during pregnancy, with the onset of pruritus, jaundice, biochemical liver abnormalities and positive antimitochondrial antibodies. Although treatment with ursodeoxycholic acid was started at the time of diagnosis, there was a progressive worsening of cholestatic biochemical markers throughout pregnancy. In addition, fasting hyperglycemia with polyhydramnios was diagnosed, consistent with gestational diabetes. She had a spontaneous preterm delivery at 31 weeks of gestation, of a newborn who was admitted to the neonatal intensive care unit but who subsequently had no long-term sequelae of preterm delivery. A maternal postpartum flare occurred. Treatment with ursodeoxycholic acid was well tolerated during pregnancy and lactation.

Oil in Northeast Brazil: mapping conflicts and impacts of the largest disaster on the country's coast.

The crude oil spill on the Brazilian coast in 2019 is considered the largest environmental disaster of this nature in the country. It had important repercussions on the environment and on the living and health conditions of the population, particularly artisanal fishermen, intensifying the vulnerability process, causing situations of injustice and environmental conflicts with negative repercussions on the territories. Aiming to analyze this environmental conflict and its impacts on environment and health of the affected population, the study applied the method proposed by the Global Atlas of Environmental Justice. It analyzed open-access documents made available by governmental and non-governmental organizations, and publications in newspapers of wide circulation. The data obtained allowed to characterize the oil spill and the identification of the socioeconomic, health, and environmental impacts published in the Atlas. There was a deepening of the vulnerability of the people of the waters, influencing the social determination of the health-disease process. The lack of sustainability of the current development model pushes for building environmental and health diagnoses in order to take remedial measures in disasters such as oil spills. EJAtlas is a way to debate situations of environmental injustice and give voice to historically oppressed communities.

Biochemical Approaches on Commercial Strains of Agaricus subrufescens Growing under Two Environmental Cultivation Conditions.

In the present work, the effect of the cultivation process, in the field and under a controlled environment, on biochemical parameters by using commercial strains of A. subrufescens were evaluated. The results obtained revealed that the strains cultivated in the field presented higher levels for most of the parameters evaluated (organic acids (20.5-48.0 g/100 g dw), tocopherols (107.0-198.6 µg/100 g dw), and phenolic acids and related compounds (245.2-359.0 µg/100 g dw and 10.6-23.7 µg/100 g dw, respectively)), except for the carbohydrates (53.4-72.6 g/100 g dw), energetic value (373-380 Kcal/100 g dw), and total free sugars (28.8-43.1 g/100 g dw), parameters in which the strains grown in a controlled environment present better results. For both cultivation systems, similar results were obtained regarding saturated, monounsaturated, and polyunsaturated fatty acids, as well as antioxidant and antimicrobial activities. These data contribute to the knowledge and highlight the characterized strains and the cultivation process, which can be used to obtain ingredients with potential applicability as a source of functional compounds.

Correction: Silva et al. Chemical Profile and Bioactivities of Extracts from Edible Plants Readily Available in Portugal. Foods 2021, 10, 673.

The authors found a mistake in the original paper [...].

One Year of COVID-19 in Pregnancy: A National Wide Collaborative Study.

INTRODUCTION: Even though the risk of COVID-19 in pregnancy may be increased, large-scale studies are needed to better understand the impact of the infection in this population. The aim of this study is to describe obstetric complications and the rate of vertical transmission in pregnant women with SARS-CoV-2 infection. MATERIAL AND METHODS: Detected cases of SARS-CoV-2 infection in pregnancy were registered in Portuguese hospitals by obstetricians. Epidemiological, pregnancy and childbirth data were collected. RESULTS: There were 630 positive cases in 23 Portuguese maternity hospitals, most at term (87.9%) and asymptomatic (62.9%). The most frequent maternal comorbidity was obesity. The rates of preterm birth and small-to-gestational-age were 12.1% and 9.9%, respectively. In the third trimester, 2.9% of pregnant women required respiratory support. There were eight cases (1.5%) of fetal death, including two cases of vertical transmission. There were five cases of postpartum respiratory degradation, but no maternal deaths were recorded. The caesarean section rate was higher in the first than in the second wave (68.5% vs 31.5%). RT-PCR SARS-CoV-2 positivity among newborns was 1.3%. CONCLUSION: SARS-Cov-2 infection in pregnancy may carry increased risks for both pregnant women and the fetuses. Individualized surveillance and the prophylaxis of this population with vaccination. is recommended in these cases.

Introdução: Apesar do risco da COVID-19 na gravidez poder ser acrescido, são necessários estudos em larga escala para o melhor conhecimento do impacto desta infeção nesta população. O objetivo deste estudo é descrever as complicações obstétricas e a taxa de transmissão vertical em grávidas com infeção a SARS-CoV-2. Material e Métodos: Os casos conhecidos de infeção por SARS-CoV-2 na gravidez foram registados nos hospitais portugueses por obstetras. Foram recolhidos dados epidemiológicos, da gravidez e do parto. Resultados: Registaram-se 630 casos positivos em 23 maternidades portuguesas, a maioria no termo (87,9%) e assintomática (62,9%). A comorbilidade materna mais frequente foi a obesidade. A taxa de parto pré-termo e de leves para a idade gestacional foi de 12,1% e 9,9%, respectivamente. No terceiro trimestre, 2,9% das grávidas necessitaram de suporte respiratório. Verificou-se uma taxa de 1,5% de morte fetal, incluindo dois casos de transmissão vertical. Houve cinco casos de degradação respiratória no pós-parto, mas sem mortes maternas registadas. A taxa de cesarianas foi mais elevada na primeira do que na segunda vaga (68,5% vs 31,5%). A positividade do RT-PCR SARS-CoV-2 entre os recém-nascidos foi de 1,3%. Conclusão: A infeção pelo SARS-Cov-2 na gravidez pode acarretar riscos aumentados para as grávidas e fetos. Recomenda-se uma vigilância individualizada nestes casos e a profilaxia desta população com a vacinação.

Red pitaya (Hylocereus costaricensis) peel as a source of valuable molecules: Extraction optimization to recover natural colouring agents.

Hylocereus costaricensis peel contains large amounts of betacyanins and can be exploited as a source of natural colorants. This work aimed the chemical characterization and evaluation of bioactive properties of this by-product and the optimization of the ultrasound-assisted extraction (UAE) of betacyanins using the response surface methodology (RSM). Oxalic and malic acids and traces of fumaric acid were detected, as well as the four tocopherol isoforms, predominantly γ-tocopherol. Four betacyanins were identified and used as response criteria for UAE optimization, namely phyllocactin, isobetanin, isophyllocactin, and betanin. Sample processing at 487 W for 38 min result in the maximum betacyanin content (36 ± 1 mg/g dw). The peel extract inhibit the oxidative haemolysis, with IC50 values of 255 and 381 µg/mL for Δt of 60 and 120 min, respectively, and the growth of pathogenic bacteria, with minimum inhibitory concentrations ranging from 5 to 20 mg/mL. Furthermore, no toxicity was observed for normal cells.

Sobre gestar e parir uma criança com a Síndrome Congênita do Zika Vírus: um estudo de caso / On gestating and giving birth to a child with congenital zika virus syndrome: a case study

Resumo Este artigo busca analisar o contexto de gestação, pré-natal e parto de uma criança com Síndrome Congênita do Zika (SCZ). É um estudo exploratório qualitativo, tipo estudo de caso único, delineado a partir de entrevista em profundidade realizada com uma mãe de criança diagnosticada com SCZ em Pernambuco. A análise dos dados ocorreu mediante a categorização do conteúdo da entrevista em quatro núcleos temáticos: contexto da descoberta da gestação; condições da assistência ao pré-natal e ao parto; condições de diagnóstico e assistência à criança; e sentimentos envolvidos na descoberta da gestação e do diagnóstico da síndrome. Esse caso sinaliza falhas no planejamento reprodutivo e na assistência ao pré-natal e parto; despreparo dos profissionais de saúde; e mudanças significativas na rotina da família, que implicam escolhas difíceis num contexto de deficitária assistência pública à saúde. A epidemia da SCZ revelou problemas que vão além do controle vetorial do mosquito. O panorama atual escancara vulnerabilidades dessas famílias, intensificadas com o surgimento e as consequências da covid-19, o que tem exposto ainda mais as fragilidades da atenção integral à saúde da mulher e a necessidade de manter uma rede articulada e resolutiva na assistência e vigilância em saúde.

Abstract This study analyzes the context of pregnancy, prenatal care and birth of children with Congenital Zika Syndrome (CZS). A single case exploratory study was conducted with a mother of a child diagnosed with CZS in Pernambuco, Brazil. Data were collected by an in-depth interview and content was categorized into four themes: discovery of pregnancy; conditions of prenatal and childbirth care; conditions of diagnosis and childcare; and feelings involved in the pregnancy discovery and syndrome diagnosis. This case study highlights failures in reproductive planning and in prenatal and childbirth care; unpreparedness of health professionals; and significant changes in the family's routine, which imply difficult choices under a deficient public health care. CZS epidemic uncovered problems that go beyond mosquito vector control. The current scenario highlights the vulnerabilities of these families, intensified by the emergence and consequences of COVID-19, which has further exposed the weaknesses of women's comprehensive health care and the need to maintain an articulated and resolute network in health care and surveillance.

Índice de qualidade na manutenção do cateter venoso central num serviço de medicina intensiva / Quality index in central venous catheters maintenance in an intensive care unit / Índice de calidad en el mantenimiento del catéter venoso central en una unidad de cuidados intensivos

Resumo Enquadramento: As infeções associadas aos cuidados de saúde são consideradas como uma das principais ameaças à segurança do doente e à qualidade dos cuidados. O uso do cateter venoso central (CVC) com fins diagnósticos e terapêuticos é cada vez mais frequente, mas, simultaneamente são responsáveis por cerca de 90% das bacteriemias a nível hospitalar. Objetivos: Analisar o Índice de Qualidade de Manutenção (IQM) do CVC num serviço de medicina intensiva (SMI) de um centro hospitalar do norte de Portugal. Metodologia: Estudo transversal e analítico. A amostra foi de 35 enfermeiros e 170 observações de manutenção ao CVC, através da grelha de observação adaptada da Direção-Geral da Saúde para determinar o IQM. Resultados: Foi obtido um IQM do CVC de 89,2%. O sexo feminino e ser especialista influenciaram o IQM do CVC (p < 0,05). Conclusão: IQM do CVC dentro dos valores recomendados. A formação e a investigação em contexto de trabalho são fundamentais para a melhoria na prestação de cuidados de enfermagem.

Abstract Background: Healthcare-associated infections are one of the main threats to patient safety and quality of care. Although central venous catheters (CVCs) are increasingly used for diagnostic and therapeutic purposes, they are responsible for about 90% of bacteremia in hospitals. Objectives: To analyze the CVC Maintenance Quality Index (MQI) in an intensive care unit (ICU) of a hospital center in northern Portugal. Methodology: Cross-sectional and analytical study. The sample consisted of 35 nurses and 170 CVC maintenance observations using the observation grid adapted from the Directorate-General for Health to determine the MQI. Results: A CVC MQI of 89.2% was obtained. The female gender and being a specialist influenced the CVC MQI (p < 0.05). Conclusion: The CVC MQI was within the recommended values. In-service training and research are essential to improve nursing care.

Resumen Marco contextual: Las infecciones asociadas a la asistencia sanitaria se consideran una de las principales amenazas para la seguridad del paciente y la calidad de la atención. El uso del catéter venoso central (CVC) con fines diagnósticos y terapéuticos es cada vez más frecuente, pero, a la vez, es responsable de cerca del 90% de las bacteriemias a nivel hospitalario. Objetivos: Analizar el Índice de Calidad de Mantenimiento (ICM) del CVC en una unidad de cuidados intensivos (UCI) de un centro hospitalario del norte de Portugal. Metodología: Estudio transversal y analítico. La muestra estuvo compuesta por 35 enfermeros y 170 observaciones de mantenimiento del CVC, para lo cual se utilizó la parrilla de observación adaptada de la Dirección General de Salud para determinar el ICM. Resultados: Se obtuvo un ICM del CVC de 89,2%. El sexo femenino y ser especialista influyeron en el ICM del CVC (p < 0,05). Conclusión: ICM del CVC dentro de los valores recomendados. La formación y la investigación en el lugar de trabajo son fundamentales para mejorar la prestación de los cuidados de enfermería.

Antibiofilm Potential of Medicinal Plants against Candida spp. Oral Biofilms: A Review.

The use of natural products to promote health is as old as human civilization. In recent years, the perception of natural products derived from plants as abundant sources of biologically active compounds has driven their exploitation towards the search for new chemical products that can lead to further pharmaceutical formulations. Candida fungi, being opportunistic pathogens, increase their virulence by acquiring resistance to conventional antimicrobials, triggering diseases, especially in immunosuppressed hosts. They are also pointed to as the main pathogens responsible for most fungal infections of the oral cavity. This increased resistance to conventional synthetic antimicrobials has driven the search for new molecules present in plant extracts, which have been widely explored as alternative agents in the prevention and treatment of infections. This review aims to provide a critical view and scope of the in vitro antimicrobial and antibiofilm activity of several medicinal plants, revealing species with inhibition/reduction effects on the biofilm formed by Candida spp. in the oral cavity. The most promising plant extracts in fighting oral biofilm, given their high capacity to reduce it to low concentrations were the essential oils extracted from Allium sativum L., Cinnamomum zeylanicum Blume. and Cymbopogon citratus (DC) Stapf.

Chemical and Bioactive Characterization of Spanish and Belgian Apple Pomace for Its Potential Use as a Novel Dermocosmetic Formulation.

Currently, there is a general trend towards reutilizing industrial by-products that would otherwise be discarded or considered as waste, aiming to explore them as alternative sources of valuable compounds. The apple pomace remaining from cider and apple juice industries represents a high-potential source of bioactive compounds with putative application in food or pharmaceutical-related products. Accordingly, the work reported herein was conducted to characterize the phenolic compounds in apple pomace from Belgium and Spain, as well as to evaluate its chemical composition and particular types of bioactivity. As a proof of concept, a new hydrogel was prepared, incorporated with the bioactive compounds and pectin extracted from apple pomace, aiming to obtain the most organic formulation possible. Independently of the extracting agent, it became evident that using lyophilization as the drying step is a better choice than thermal processes as it yielded a richer phenolic profile (fifteen individual compounds), with 5-O-caffeoylquinic acid as the major compound (66 to 114 mg/100 g dw) in Belgian samples. In general, the hydroethanolic extracts showed the strongest antioxidant and antimicrobial (particularly against Propionibacterium acnes: MIC = 2.5 mg/mL) activities. This result, together with the lipid nature of human skin, led it to be chosen as the extract type to be incorporated in the hydrogel. In general, apple pomace stood out as a valuable source of bioactive compounds, especially polyphenols and pectin, with good potential to be incorporated in dermal formulations.

Chemical Profile and Bioactivities of Extracts from Edible Plants Readily Available in Portugal.

Plant extracts have been proposed as alternative biocides and antioxidants to be included in a variety of food products. In this work, to assess the potential of rosemary, lemon balm, basil, tarragon, sage, and spearmint to be used as food additives, the chemical profiles and bioactivities of such plant extracts were studied. Furthermore, to evaluate the influence of extraction methods and solvents on the chemical characteristics and bioactivities of the plant extracts, two extraction methods (solid-liquid and Soxhlet extraction) and two solvents (water and ethanol 70% (v/v)) were tested for each plant. Groupwise summary statistics were calculated by plant, extraction method, and solvent, and linear models were built to assess the main effects of those terms and their interactions on the chemical characteristics and bioactivities of the extracts. The results revealed that all factors-type of plant, extraction method and solvent-have influence on the chemical profile and antioxidant activity of the resultant extracts. Interactions between factors were also observed. Hydroethanolic Soxhlet extracts presented the least potential as biopreservatives due to their low phenolic content and reduced antioxidant capacity. Oppositely, aqueous Soxhlet extracts and hydroethanolic solid-liquid extracts showed high contents in phenolic compounds and high antioxidant activities. In particular, the hydroethanolic solid-liquid extracts of lemon balm, spearmint, and sage presented the highest phenolic and flavonoid contents, accompanied by a high antioxidant activity, and they revealed antimicrobial activity against four pathogens (S. enterica ser. Typhimurium, E. coli, L. monocytogenes and S. aureus). These results demonstrate the potential of these natural resources to be incorporated as bioactive preservatives in foods or their packaging.

Bioactive and Nutritional Potential of Medicinal and Aromatic Plant (MAP) Seasoning Mixtures.

Medicinal and aromatic plants (MAPs), worldwide appreciated and used as condiments, dyes, and preservatives, possess several biological properties that justify their continuous application in the food industry. In the present study, the nutritional and chemical profiles, as well as the bioactive properties of four combinations of condiments, sold for seasoning poultry, meat, fish, and salads, were evaluated. Twenty-five phenolic compounds (HPLC-DAD-ESI/MS) were identified, with apigenin-O-malonyl-pentoside-hexoside as the major compound detected in all extracts. Oxalic and citric acids were identified in all mixtures (UFLC-PDA), as well as all the four tocopherol isoforms (HPLC-fluorescence). Regarding bioactivities, the mixtures for meat and salads (TBARS) and meat and poultry (OxHLIA) stood out for their antioxidant potential, whereas for the anti-inflammatory and antitumor properties, the mixtures revealing the greatest results were those for poultry and salad, respectively. In terms of antimicrobial activity, all the mixtures revealed the capacity to inhibit the growth of some bacterial strains. In brief, condiment mixtures showed to be a good source of bioactive compounds, as they confer health benefits, validating the importance of their inclusion in the human diet as a good dietary practice.

Glutaminolysis dynamics during astrocytoma progression correlates with tumor aggressiveness.

BACKGROUND: Glioblastoma is the most frequent and high-grade adult malignant central nervous system tumor. The prognosis is still poor despite the use of combined therapy involving maximal surgical resection, radiotherapy, and chemotherapy. Metabolic reprogramming currently is recognized as one of the hallmarks of cancer. Glutamine metabolism through glutaminolysis has been associated with tumor cell maintenance and survival, and with antioxidative stress through glutathione (GSH) synthesis. METHODS: In the present study, we analyzed the glutaminolysis-related gene expression levels in our cohort of 153 astrocytomas of different malignant grades and 22 non-neoplastic brain samples through qRT-PCR. Additionally, we investigated the protein expression profile of the key regulator of glutaminolysis (GLS), glutamate dehydrogenase (GLUD1), and glutamate pyruvate transaminase (GPT2) in these samples. We also investigated the glutathione synthase (GS) protein profile and the GSH levels in different grades of astrocytomas. The differential gene expressions were validated in silico on the TCGA database. RESULTS: We found an increase of glutaminase isoform 2 gene (GLSiso2) expression in all grades of astrocytoma compared to non-neoplastic brain tissue, with a gradual expression increment in parallel to malignancy. Genes coding for GLUD1 and GPT2 expression levels varied according to the grade of malignancy, being downregulated in glioblastoma, and upregulated in lower grades of astrocytoma (AGII-AGIII). Significant low GLUD1 and GPT2 protein levels were observed in the mesenchymal subtype of GBM. CONCLUSIONS: In glioblastoma, particularly in the mesenchymal subtype, the downregulation of both genes and proteins (GLUD1 and GPT2) increases the source of glutamate for GSH synthesis and enhances tumor cell fitness due to increased antioxidative capacity. In contrast, in lower-grade astrocytoma, mainly in those harboring the IDH1 mutation, the gene expression profile indicates that tumor cells might be sensitized to oxidative stress due to reduced GSH synthesis. The measurement of GLUD1 and GPT2 metabolic substrates, ammonia, and alanine, by noninvasive MR spectroscopy, may potentially allow the identification of IDH1mut AGII and AGIII progression towards secondary GBM.