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)

Translational approach to address therapy in myotonia permanens due to a new SCN4A mutation

Objective: We performed a clinical, functional, and pharmacologic characterization of the novel p.P1158L Nav1.4 mutation identified in a young girl presenting a severe myotonic phenotype. Methods: Wild-type hNav1.4 channel and P1158L mutant were expressed in tsA201 cells for functional and pharmacologic studies using patch-clamp. Results: The patient shows pronounced myotonia, slowness of movements, and generalized muscle hypertrophy. Because of general discomfort with mexiletine, she was given flecainide with satisfactory response. In vitro, mutant channels show a slower current decay and a rightward shift of the voltage dependence of fast inactivation. The voltage dependence of activation and slow inactivation were not altered. Mutant channels were less sensitive to mexiletine, whereas sensitivity to flecainide was not altered. The reduced inhibition of mutant channels by mexiletine was also observed using clinically relevant drug concentrations in a myotonic-like condition. Conclusions: Clinical phenotype and functional alterations of P1158L support the diagnosis of myotonia permanens. Impairment of fast inactivation is consistent with the possible role of the channel domain III S4-S5 loop in the inactivation gate docking site. The reduced sensitivity of P1158L to mexiletine may have contributed to the unsatisfactory response of the patient. The success of flecainide therapy underscores the usefulness of in vitro functional studies to help in the choice of the best drug for each individual

Cerebral Small Vessel Disease Burden and Longitudinal Cognitive Decline from age 73 to 82: the Lothian Birth Cohort 1936

Slowed processing speed is considered a hallmark feature of cognitive decline in cerebral small vessel disease (SVD); however, it is unclear whether SVD’s association with slowed processing might be due to its association with overall declining general cognitive ability. We quantified the total MRI-visible SVD burden of 540 members of the Lothian Birth Cohort 1936 (age: 72.6 ± 0.7 years; 47% female). Using latent growth curve modelling, we tested associations between total SVD burden at mean age 73 and changes in general cognitive ability, processing speed, verbal memory and visuospatial ability, measured at age 73, 76, 79 and 82. Covariates included age, sex, vascular risk and childhood cognitive ability. In the fully adjusted models, greater SVD burden was associated with greater declines in general cognitive ability (standardised β: −0.201; 95% CI: [−0.36, −0.04]; pFDR = 0.022) and processing speed (−0.222; [−0.40, −0.04]; pFDR = 0.022). SVD burden accounted for between 4 and 5% of variance in declines of general cognitive ability and processing speed. After accounting for the covariance between tests of processing speed and general cognitive ability, only SVD’s association with greater decline in general cognitive ability remained significant, prior to FDR correction (−0.222; [−0.39, −0.06]; p = 0.008; pFDR = 0.085). Our findings do not support the notion that SVD has a specific association with declining processing speed, independent of decline in general cognitive ability (which captures the variance shared across domains of cognitive ability). The association between SVD burden and declining general cognitive ability supports the notion of SVD as a diffuse, whole-brain disease and suggests that trials monitoring SVD-related cognitive changes should consider domain-specific changes in the context of overall, general cognitive decline

Cognitive change before old age (11 to 70) predicts cognitive change during old age (70 to 82)

Identifying predictors of cognitive decline in old age helps us understand its mechanisms and identify those at greater risk. Here, we examined how cognitive change from ages 11 to 70 is associated with cognitive change at older ages (70 to 82 years) in the Lothian Birth Cohort 1936 longitudinal study (N = 1,091 at recruitment). Using latent-growth-curve models, we estimated rates of change from ages 70 to 82 in general cognitive ability (g) and in three cognitive domains: visuospatial, memory, and processing speed. We found that g accounted for 71.3% of interindividual change variance. Greater cognitive gain from ages 11 to 70 predicted slower decline in g over 12 subsequent years (β = 0.163, p = .001), independently of cognitive level in childhood and at age 70, and domain-specific change beyond g. These results contribute to the goal of identifying people at higher risk of age-related cognitive decline

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

The second life of food by-products: Consumers’ intention to purchase and willingness to pay for an upcycled pizza

One of the challenges that Europe has undertaken is the transition from a linear economic system to a circular economy, where waste and resources are recovered and regenerated. The practice of upcycling in the agri-food sector represents one of the most promising solutions to the enormous problem of food waste. However, the information available to consumers about foods made with upcycled ingredients is still scarce, limiting their acceptance and creating a critical barrier to their success in the market. The objective of this study is to determine the factors that affect Italian consumers’ intention to purchase and willingness to pay for a specific upcycled food enriched with a high-value vegetable by-product by applying a logit model, an interval regression, and a contingent valuation. Results show that knowledge about upcycling and the circular economy is still limited. Innovative consumers who are already aware of upcycling, who are not food neophobic, and who have a positive opinion of recycling are more willing to purchase upcycled products. At the same time, women who are already aware that the food industry produces considerable quantities of waste and who have a positive image of recycling are more willing to pay for a specific upcycled food. Finally, our sample proved to be willing to pay a premium price for an upcycled frozen margherita pizza. An informed consumer, aware of the environmental and health benefits of upcycled products, may become more willing to purchase them and to pay more compared to the same conventional products

Distribution and Level of Bioactive Monoacylglycerols in 12 Marine Microalgal Species

Microalgae are currently considered an attractive source of highly valuable metabolites potentially exploitable as anticancer agents, nutraceuticals and cosmeceuticals and for bioenergy purposes. Their ease of culturing and their high growth rates further promote their use as raw material for the production of specialty products. In the present paper, we focused our attention on specific glycerol-based lipid compounds, monoacylglycerols (MAGs), which displayed in our previous studies a selective cytotoxic activity against the haematological U-937 and the colon HCT-116 cancer cell lines. Here, we performed a quali/quantitative analysis of MAGs and total fatty acids (FAs) along with a profiling of the main lipid classes in a panel of 12 microalgal species, including diatoms and dinoflagellates. Our results highlight an inter- and intraspecific variability of MAG profile in the selected strains. Among them, Skeletonema marinoi (strain FE7) has emerged as the most promising source for possible biotechnological production of MAGs

A prokaryotic superoxide dismutase paralog lacking two Cu ligands: From largely unstructured in solution to ordered in the crystal

Little is known about prokaryotic homologs of Cu,Zn superoxide dismutase (SOD), an enzyme highly conserved among eukaryotic species. In 138 Archaea and Bacteria genomes, 57 of these putative homologs were found, 11 of which lack at least one of the metal ligands. Both the solution and the crystal structures of the SOD-like protein from Bacillus subtilis, lacking two Cu ligands and found to be enzymatically inactive, were determined. In solution, the protein is monomeric. The available nuclear Overhauser effects, together with chemical-shift index values, allowed us to define and to recognize the typical Cu,Zn SOD Greek β-barrel but with largely unstructured loops (which, therefore, sample a wide range of conformations). On the contrary, in the crystal structure (obtained in the presence of slight excess of Zn), the protein is well structured and organized in covalent dimers held by a symmetric bridge consisting of a Zn ion bound to an Asp–His dyad in a tetrahedral geometry. Couples of dimers held by hydrophobic interactions and H bonds are further organized in long chains. The order/disorder transition is discussed in terms of metal binding and physical state

Cognitive change before old age (11 to 70) predicts cognitive change after old age (70 to 82)

Identifying predictors of cognitive decline within older age helps to understand its mechanisms and to identify those at greater risk. Here we examine how cognitive change from 11 to 70 years is associated with cognitive change within older age (70 to 82 years) in the Lothian Birth Cohort 1936 longitudinal study (N=1091 at recruitment). Using latent growth curve models, we estimate rates of change from age 70 to 82 in general cognitive ability (g) and in three cognitive domains: visuospatial, memory and processing speed. g accounted for 71.3% of interindividual change variance. Greater 11-70 cognitive gain predicted slower decline in g over 12 subsequent years (β = .163, p = .001), independently of cognitive level at age 70, and domain-specific change beyond g. These results contribute toward identifying people at higher risk of age-related cognitive decline. Age-related cognitive decline is a significant threat to the quality of life in older age. Its economic and social impact on society will increase together with the steadily rising life expectancy. How can we preserve cognitive health in older age? Researchers have made significant advances in identifying protective and risk factors. However, most studies focus on a limited age range, and cognitive change mechanisms are not yet completely understood. This work takes advantage of almost life-spanning longitudinal data to test if cognitive trajectory across childhood and adulthood can predict cognitive trajectories in older age. Our findings show that earlier change is associated with later change. Some factors related to individual differences in cognitive change might thus operate over much of the adult life course, and certainly before older age. This knowledge can help identify individuals at higher risk of decline and understand the mechanisms and factors responsible