Cytotoxic Potential of the Marine Diatom Thalassiosira rotula: Insights into Bioactivity of 24-Methylene Cholesterol

Marine microalgae are receiving great interest as sustainable sources of bioactive metabolites for health, nutrition and personal care. In the present study, a bioassay-guided screening allowed identifying an enriched fraction from SPE separation of the methanolic extract of the marine diatom Thalassiosira rotula with a chemically heterogeneous composition of cytotoxic molecules, including PUFAs, the terpene phytol, the carotenoid fucoxanthin and the phytosterol 24-methylene cholesterol (24-MChol). In particular, this latter was the object of deep investigation aimed to gain insight into the mechanisms of action activated in two tumour cell models recognised as resistant to chemical treatments, the breast MCF7 and the lung A549 cell lines. The results of our studies revealed that 24-MChol, in line with the most studied β-sitosterol (β-SIT), showed cytotoxic activity in a 3-30 µM range of concentration involving the induction of apoptosis and cell cycle arrest, although differences emerged between the two sterols and the two cancer systems when specific targets were investigated (caspase-3, caspase-9, FAS and TRAIL)

RNA stabilizes transcription-Dependent Chromatin Loops Induced By Nuclear Hormones

We show that transcription induced by nuclear receptors for estrogen (e2) or retinoic acid (RA) is associated with formation of chromatin loops that juxtapose the 5’ end (containing the promoter) with the enhancer and the 3′ polyA addition site of the target gene. We nd three loop con gurations which change as a function of time after induction: 1. RA or E2-induced loops which connect the 5′ end, the enhancer and the 3′ end of the gene, and are stabilized by RNA early after induction; 2. E2-independent loops whose stability does not require RNA; 3. Loops detected only by treatment of chromatin with RNAse H1 prior to hormonal induction. RNAse H1 digests RNA that occludes the relevant restriction sites, thus preventing detection of these loops. R-loops at the 5′ and 3′ ends of the RA or e2-target genes were demonstrated by immunoprecipitation with anti-DNA-RNA hybrid antibodies as well as by sensitivity to RNAse H1. The cohesin RAD21 subunit is preferentially recruited to the target sites upon RA or e2 induction of transcription. R21 binding to chromatin is eliminated by RNAse H1. We identi ed e2-induced and RNase H1-sensitive antisense RNAs located at the 5′ and 3′ ends of the e2-induced transcription unit which stabilize the loops and RAD21 binding to chromatin. This is the rst report of chromatin loops that form after gene induction that are maintained by RNA:DNA hybrids

Akt Regulates Drug-Induced Cell Death through Bcl-w Downregulation

Akt is a serine threonine kinase with a major role in transducing survival signals and regulating proteins involved in apoptosis. To find new interactors of Akt involved in cell survival, we performed a two-hybrid screening in yeast using human full-length Akt c-DNA as bait and a murine c-DNA library as prey. Among the 80 clones obtained, two were identified as Bcl-w. Bcl-w is a member of the Bcl-2 family that is essential for the regulation of cellular survival, and that is up-regulated in different human tumors, such as gastric and colorectal carcinomas. Direct interaction of Bcl-w with Akt was confirmed by immunoprecipitation assays. Subsequently, we addressed the function of this interaction: by interfering with the activity or amount of Akt, we have demonstrated that Akt modulates the amount of Bcl-w protein. We have found that inhibition of Akt activity may promote apoptosis through the downregulation of Bcl-w protein and the consequential reduction in interaction of Bcl-w with pro-apoptotic members of the Bcl-2 family. Our data provide evidence that Bcl-w is a new member of the Akt pathway and that Akt may induce anti-apoptotic signals at least in part through the regulation of the amount and activity of Bcl-w

Comparison of Content in Phenolic Compounds and Antioxidant Capacity in Grains of White, Red, and Black Sorghum Varieties Grown in the Mediterranean Area

orghum (Sorghum bicolor L.) is a gluten-free cereal with many varieties containing greater amounts of bioactive compounds than other grains. In this work, the phenolic composition and antioxidant capacity were compared in three sorghum varieties grown in the Mediterranean, consisting of different pericarp colors: white, red, and black. The qualitative and quantitative profiles of acidified aqueous methanol extracts of whole grain sorghum flours were elucidated through ultrahigh performance liquid chromatography (UHPLC) coupled to photodiode array (PDA) and ion trap time-of-flight (IT-TOF) mass spectrometry. The investigated sorghum varieties contained polyamines, such as spermidines, and polyphenolic compounds belonging to different classes: hydroxycinnamic acids, flavanols, flavones, and flavanones. Pyrano-flavanone-flavanols were detected only in the black sorghum. Precolumn and postcolumn 2,2′-diphenyl-1-picrylhydrazyl (DPPH)· radical scavenging assays to determine the main antioxidant compounds isolated from sorghum were developed. These results will further help develop sorghum varieties containing polyphenols relevant to the potential prevention of human diseases

Nutritional composition of a selected white food-grade waxy sorghum variety grown in Mediterranean environment

A white food-grade waxy sorghum Tw variety, grown in two Mediterranean sites (named Tw1M and Tw1S) was evaluated for nutrient composition and fatty acid- and mineral concentrations in order to determine the suitability of producing waxy sorghum for human uses in southern Italy. The nutritional values of the grains of the Tw inbred line grown in the two trial fields were substantially the same, except for slight differences in ash level and accordingly slight variation in mineral composition. In samples from both locations, a higher percentage of K was observed among the nutritionally essential macro-elements, and higher percentages of Zn, Fe, Mn, Cu, Al among the nutritionally essential micro-element along with a strong difference in Cd content was among trace elements. Across both sites linoleic, oleic and palmitic were the most abundant fatty acids, while very slight variations in the content of minerals were found among the two samples examined. These results demonstrate the importance of developing agronomically productive waxy sorghum varieties suitable for growth in non-traditional sorghum producing regions both as a food and feed crop (i.e. with good nutritional quality) and for utilization in new products at the industrial level

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

MINDFULNESS IN UNIVERSITY EDUCATION: A PILOT STUDY

Abstract Background: Among professional psychologists distress and burnout are commonly reported and have implications for the quality of patient care. Already in the course of university studies, psychology students relate to mental distress and lower life satisfaction. The clinical efficacy of mindfulness has consistently been proved over the last two decades. A lot of studies, however, have been undertaken on its possible use in the adults training in a formal learning context. Methods: This pilot study aims to describe, through self-assessment tests with an assessment before and after the educational experience, the path of a group of young university Psychology Students, at University of Naples “Federico II”. The workshop was an inspired by the ACT structured program, and consisted of 6 sessions of two-hour as part of the course in the pedagogy of learning processes of the degree course in Psychology: among 50 students who participated in the workshops, 31 students completed the assessment, both the pre-test and post-test. Conclusions: The analysis of self-assessment questionnaires shows an improvement in all surveyed areas. The possible implications of the findings of this study regard the ability to use and promote the use of the techniques of mindfulness beyond the clinical setting as valuable tools for growth and development and above all within learning contexts. Particularly, the proposal to include a mindfulness protocol reflective practice in training programs in psychology is designed to provide skills to deal with the stressors of training, and through this experience of structured effective self-care, also improve longterm clinical skills of the future psychologists

Pharmacokinetic and pharmacodynamic considerations for the clinical efficacy of perampanel in focal onset seizures

Introduction: Medical therapy is the mainstay of management of epilepsy. Despite the increasing number of available antiepileptic drugs (AEDs), approximately one-third of epileptic patients do not have adequate control of seizures. There is still a need for the development of new AEDs with enhanced effectiveness and tolerability. Areas covered: The present manuscript is based on an Internet and PubMed search (January 2005 to August 2018). It is focused on pharmacokinetic and clinical data of perampanel (PER) for the treatment of epilepsy. Expert opinion: PER has a novel mechanism of action, which opens up new options for a rational combination therapy. Phase III trials have demonstrated the efficacy and safety of PER as adjunctive therapy for the treatment of partial-onset seizures (POS) and primary generalized tonic\u2013clonic seizures in patients aged 6512 years. PER is also approved by FDA as monotherapy for the treatment of POS. A clinical trial is ongoing to verify the efficacy and safety of PER monotherapy in untreated patients with POS. In the future, head-to-head comparisons are needed to determine the exact position of PER relative to other AEDs. Moreover, further studies are needed to evaluate the efficacy and safety of PER in patients aged <12 years