Fabric phase sorptive extraction of selected steroid hormone residues in commercial raw milk followed by ultra-high-performance liquid chromatography–tandem mass spectrometry

Hormones in edible matrices, such as milk, are a subject of concern because of their adverse effects on the endocrine system and cell signaling and the consequent disruption of homeostasis in human consumers. Therefore, the assessment of the presence of hormones in milk as potential endocrine-disrupting compounds is warranted. However, the complexity of milk as a sample matrix and the ultra-low concentration of hormones pose significant analytical challenges. Fabric phase sorptive extraction (FPSE) has emerged as a powerful analytical technique for the extraction of emerging pollutants from complex aqueous matrices. FPSE allows for substantially simplified sample handling and short extraction and desorption times, as well as the decreased use of organic solvents. It is considered a green alternative to traditional extraction methodologies. In this work, the FPSE technique was evaluated to perform the simultaneous extraction of 15 steroid hormones from raw milk without employing any sample pretreatment steps. Clean and preconcentrated hormone solutions obtained from FPSE of raw milk were analyzed using ultra-high-performance liquid chromatography–tandem mass spectrometry to achieve low detection limits, which ranged from 0.047 to 1.242 ng·mL−1. Because of the presence of many interferents in milk, such as proteins, lipids, and sugar, the effect of fat content on the extraction procedure was also thoroughly studied. Additionally, for the first time, the effect of lactose on the extraction of steroid hormones was evaluated, and the results showed that the extraction efficiencies were enhanced in lactose-free samples. Finally, the optimized methodology was applied to commercial samples of cow and goat milk, and no measurable concentrations of the studied hormones were detected in these samples

CD38/cADPR Signaling Pathway in Airway Disease: Regulatory Mechanisms

Asthma is an inflammatory disease in which proinflammatory cytokines have a role in inducing abnormalities of airway smooth muscle function and in the development of airway hyperresponsiveness. Inflammatory cytokines alter calcium (Ca2+) signaling and contractility of airway smooth muscle, which results in nonspecific airway hyperresponsiveness to agonists. In this context, Ca2+ regulatory mechanisms in airway smooth muscle and changes in these regulatory mechanisms encompass a major component of airway hyperresponsiveness. Although dynamic Ca2+ regulation is complex, phospholipase C/inositol tris-phosphate (PLC/IP3) and CD38-cyclic ADP-ribose (CD38/cADPR) are two major pathways mediating agonist-induced Ca2+ regulation in airway smooth muscle. Altered CD38 expression or enhanced cyclic ADP-ribosyl cyclase activity associated with CD38 contributes to human pathologies such as asthma, neoplasia, and neuroimmune diseases. This review is focused on investigations on the role of CD38-cyclic ADP-ribose signaling in airway smooth muscle in the context of transcriptional and posttranscriptional regulation of CD38 expression. The specific roles of transcription factors NF-kB and AP-1 in the transcriptional regulation of CD38 expression and of miRNAs miR-140-3p and miR-708 in the posttranscriptional regulation and the underlying mechanisms of such regulation are discussed

Spitz nevus: a case report and the use of dermoscopy

O nevo de Spitz é uma lesão melanocítica benigna com características clínicas e histopatológicas semelhantes às do melanoma. Foi descrito em 1948, mas até hoje, ainda, existe grande controvérsia no seu diagnóstico e conduta. A utilização da dermatoscopia pode aumentar a sua acurácia diagnóstica. As características dermatoscópicas do nevo de Spitz incluem um padrão estelar (starburst), que é o mais frequente, seguido do padrão globular e do padrão atípico. O diagnóstico deve ser confirmado por exame histopatológico, principalmente, nos casos atípicos.The Spitz nevus is a benign melanocytic lesion with clinical and histopathological features similar to those of melanoma. It was first described in 1948 but great controversy still remains today with respect to its diagnosis and management. The use of dermoscopy may increase diagnostic accuracy. In Spitz nevus, the most common dermoscopic finding is a starburst-like pattern, followed by globular and atypical patterns. Diagnosis must be confirmed by histopathology, particularly in atypical cases

AVALIAÇÃO DA ATIVIDADE ANTIOXIDANTE E DE COMPOSTOS FENÓLICOS TOTAIS NA BIOMASSA DO NONI (MORINDA CITRIFOLIA LINN) EM CINCO ESTÁDIOS DE MATURAÇÃO

A Morinda citrifolia Linn, popularmente conhecida como noni, possui compostos anticancerígenos, anti-inflamatórios e antioxidantes. Entretanto, o seu uso alimentício, ainda é pouco explorado, abrindo espaço para uma importante vertente de pesquisa. Diante disso, esse estudo teve como objetivo avaliar o teor de compostos fenólicos, bem como a atividade antioxidante da biomassa de frutos do Noni em diferentes estádios de maturação. Para tanto a biomassa foi desidratada e submetida a diferentes condições de extração, a fim de obter extratos etanólicos, metanólicos, etéreos e acetônicos. As condições usadas nas extrações variaram conforme planejamento fatorial completo 22, onde as variáveis foram pH e tempo de extração. O tempo foi a variável que mais influenciou o processo de extração, e as melhores condições de tempo e pH variaram conforme o solvente, com maiores teores de fenólicos para o etanol e os menores com acetona. A atividade antioxidante mais elevada foi obtida no extrato metanólico, com resultado mais elevado para o estádio de maturação 1 (81,63%).  Assim, o Noni apresenta considerável potencial antioxidante, o que possibilita seu emprego como fonte natural de compostos bioativos na indústria alimentícia. Abstract Morinda citrifolia Linn, popularly known as noni, has anti-cancer, anti-inflammatory and antioxidant compounds However, its food use is still little known and exploited, opening space for an important research strand. Therefore, this study aimed to evaluate the phenolic content and antioxidant activity of the fruit biomass of Noni in different maturation stages. For this purpose, the biomass was dried and subjected to different conditions of extraction, to obtain ethanolic, methanolic, ether and acetonic extracts. The conditions used in the extractions varied according to complete factorial design 22, where the variables were pH and extraction time. The time was the variable that most influenced the extraction processes, being that the best conditions of time and pH varied according to the solvent, with higher phenolic contents for ethanol and smaller ones with acetone. The highest antioxidant activity was obtained in methanolic extracts, with a higher result for stage 1 (81.63%). Thus, Noni has a considerable antioxidant potential, which allows its use as a natural source of bioactive compounds in the food industry

Mast Cells Induce Blood Brain Barrier Damage in SCD by Causing Endoplasmic Reticulum Stress in the Endothelium

Endothelial dysfunction underlies the pathobiology of cerebrovascular disease. Mast cells are located in close proximity to the vasculature, and vasoactive mediators released upon their activation can promote endothelial activation leading to blood brain barrier (BBB) dysfunction. We examined the mechanism of mast cell-induced endothelial activation via endoplasmic reticulum (ER) stress mediated P-selectin expression in a transgenic mouse model of sickle cell disease (SCD), which shows BBB dysfunction. We used mouse brain endothelial cells (mBECs) and mast cells-derived from skin of control and sickle mice to examine the mechanisms involved. Compared to control mouse mast cell conditioned medium (MCCM), mBECs incubated with sickle mouse MCCM showed increased, structural disorganization and swelling of the ER and Golgi, aggregation of ribosomes, ER stress marker proteins, accumulation of galactose-1-phosphate uridyl transferase, mitochondrial dysfunction, reactive oxygen species (ROS) production, P-selectin expression and mBEC permeability. These effects of sickle-MCCM on mBEC were inhibited by Salubrinal, a reducer of ER stress. Histamine levels in the plasma, skin releasate and in mast cells of sickle mice were higher compared to control mice. Compared to control BBB permeability was increased in sickle mice. Treatment of mice with imatinib, Salubrinal, or P-selectin blocking antibody reduced BBB permeability in sickle mice. Mast cells induce endothelial dysfunction via ER stress-mediated P-selectin expression. Mast cell activation contributes to ER stress mediated endothelial P-selectin expression leading to increased endothelial permeability and impairment of BBB. Targeting mast cells and/or ER stress has the potential to ameliorate endothelial dysfunction in SCD and other pathobiologies

Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles

Several classification systems have been proposed to address genomic heterogeneity of glioblastoma multiforme, but they either showed limited prognostic value and/or are difficult to implement in routine diagnostics. Here we propose a prognostic stratification model for these primary tumors based on tumor gene amplification profiles, that might be easily implemented in routine diagnostics, and potentially improve the patients management. Gene amplification profiles were prospectively evaluated in 80 primary glioblastoma multiforme tumors using single-nucleotide polymorphism arrays and the results obtained validated in publicly available data from 267/347 cases. Gene amplification was detected in 45% of patients, and chromosome 7p11.2 including the EGFR gene, was the most frequently amplified chromosomal region – either alone (18%) or in combination with amplification of DNA sequences in other chromosomal regions (10% of cases). Other frequently amplified DNA sequences included regions in chromosomes 12q(10%), 4q12(7%) and 1q32.1(4%). Based on their gene amplification profiles, glioblastomas were subdivided into: i) tumors with no gene amplification (55%); ii) tumors with chromosome 7p/EGFR gene amplification (with or without amplification of other chromosomal regions) (38%); and iii) glioblastoma multiforme with a single (11%) or multiple (6%) amplified DNA sequences in chromosomal regions other than chromosome 7p. From the prognostic point of view, these amplification profiles showed a significant impact on overall survival of glioblastoma multiforme patients (p>0.001). Based on these gene amplification profiles, a risk-stratification scoring system was built for prognostic stratification of glioblastoma which might be easily implemented in routine diagnostics, and potentially contribute to improved patient management.This work was supported by RETICC RD06/0020/0035, RD06/0020/0059 and RD12/0036/0048 grants from Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, (Madrid, Spain and FONDOS FEDER), AES PI16/000476 (Instituto de Salud Carlos III, Madrid, Spain and FONDOS FEDER), GRS909A14 (JCYL) and CB16/12/00400 grant (CIBERONC, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and FONDOS FEDER)

Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles

[EN]everal classification systems have been proposed to address genomic heterogeneity of glioblastoma multiforme, but they either showed limited prognostic value and/or are difficult to implement in routine diagnostics. Here we propose a prognostic stratification model for these primary tumors based on tumor gene amplification profiles, that might be easily implemented in routine diagnostics, and potentially improve the patients management. Gene amplification profiles were prospectively evaluated in 80 primary glioblastoma multiforme tumors using singlenucleotide polymorphism arrays and the results obtained validated in publicly available data from 267/347 cases. Gene amplification was detected in 45% of patients, and chromosome 7p11.2 including the EGFR gene, was the most frequently amplified chromosomal region - either alone (18%) or in combination with amplification of DNA sequences in other chromosomal regions (10% of cases). Other frequently amplified DNA sequences included regions in chromosomes 12q(10%), 4q12(7%) and 1q32.1(4%). Based on their gene amplification profiles, glioblastomas were subdivided into: i) tumors with no gene amplification (55%); ii) tumors with chromosome 7p/EGFR gene amplification (with or without amplification of other chromosomal regions) (38%); and iii) glioblastoma multiforme with a single (11%) or multiple (6%) amplified DNA sequences in chromosomal regions other than chromosome 7p

Extensive Sheep and Goat Production: The Role of Novel Technologies towards Sustainability and Animal Welfare

[EN] Sheep and goat extensive production systems are very important in the context of global food security and the use of rangelands that have no alternative agricultural use. In such systems, there are enormous challenges to address. These include, for instance, classical production issues, such as nutrition or reproduction, as well as carbon-efficient systems within the climate-change context. An adequate response to these issues is determinant to economic and environmental sustainability. The answers to such problems need to combine efficiently not only the classical production aspects, but also the increasingly important health, welfare, and environmental aspects in an integrated fashion. The purpose of the study was to review the application of technological developments, in addition to remote-sensing in tandem with other state-of-the-art techniques that could be used within the framework of extensive production systems of sheep and goats and their impact on nutrition, production, and ultimately, the welfare of these species. In addition to precision livestock farming (PLF), these include other relevant technologies, namely omics and other areas of relevance in small-ruminant extensive production: heat stress, colostrum intake, passive immunity, newborn survival, biomarkers of metabolic disease diagnosis, and parasite resistance breeding. This work shows the substantial, dynamic nature of the scientific community to contribute to solutions that make extensive production systems of sheep and goats more sustainable, efficient, and aligned with current concerns with the environment and welfareSIThe CECAV authors acknowledge financial support of the research unit, which was financed by the National Funds from FCT, the Portuguese Foundation for Science and Technology (FCT), project number UIDB/CVT/00772/2020. Financial support from FCT (Fundação para a Ciência e a Tecnologia, Lisboa, Portugal) in the form of infrastructural funding to LEAF (UID/AGR/04129) and PhD grants SFRH/BD/143992/2019 (DM Ribeiro) and 2021.07638.BD (L Sacarrão-Birrento). Author L.E.H.C. acknowledges funding from the Agencia Estatal de Investigación (Spain) (RYC2019- 027064-I/AEI/10.13039/501100011033

Stellar populations of bulges at low redshift

This chapter summarizes our current understanding of the stellar population properties of bulges and outlines important future research directions.Comment: Review article to appear in "Galactic Bulges", Editors: Laurikainen E., Peletier R., Gadotti D., Springer Publishing. 34 pages, 12 figure