Voltammetric responses at modified electrodes and aggregation effects of two anticancer molecules: irinotecan and sunitinib

Voltammetric analyses of two anticancer molecules at modified electrodes and influence of aggregate formation on their differential pulse voltammetry (DPV) responses

Transient Receptor Potential Vanilloid 1 Expression and Functionality in MCF-7 Cells: A Preliminary Investigation

PURPOSE: Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel belonging to the transient receptor potential family, and it is expressed in different neoplastic tissues. Its activation is associated with regulation of cancer growth and progression. The aim of this research was to study the expression and pharmacological characteristics of TRPV1 in cells derived from human breast cancer MCF-7 cells. METHODS: TRPV1 presence was assessed by binding studies and Western blotting. Receptor binding characteristics were evaluated through competition assays, while 3-(4,5-dimethylthiazol-2-yl)-2,5,-dipheyltetrazolium bromide reduction assays were performed to confirm an early hypothesis regarding the modulation of cancer cell proliferation. The functionality of TRPV1 was evaluated by measuring Ca(2+) uptake in the presence of increasing concentrations of TRPV1 agonists and antagonists. RESULTS: Binding studies identified a single class of TRPV1 (B(max) 1,492±192 fmol/mg protein), and Western blot showed a signal at 100 kDa corresponding to the molecular weight of human TRPV1. Among the different tested agonists and antagonists, anandamide (Ki: 2.8×10(-11) M) and 5-iodoresiniferatoxin (5-I-RTX) (Ki: 5.6×10(-11) M) showed the highest degrees of affinity for TRPV1, respectively. All tested TRPV1 agonists and antagonists caused a significant (p<0.05) decrease in cell growth rate in MCF-7 cells. For agonists and antagonists, the efficacy of tested compounds displayed the following rank order: resiniferatoxin>anandamide>capsaicin and 5-I-RTX=capsazepine, respectively. CONCLUSION: These data indicate that both TRPV1 agonists and antagonists induce significant inhibition of MCF-7 cell growth. Even though the mechanisms involved in the antiproliferative effects of TRPV1 agonists and antagonists should be further investigated, it has been suggested that agonists cause desensitization of the receptor, leading to alteration in Ca(2+)-influx regulation. By contrast, antagonists cause a functional block of the receptor with consequent fatal dysregulation of cell homeostasis

Equine-Assisted Interventions (EAIs) for Children with Autism Spectrum Disorders (ASD): Behavioural and Physiological Indices of Stress in Domestic Horses (Equus caballus) during Riding Sessions

Equine-assisted interventions (EAIs) are well-known complementary practices combining physical activity with emotional/cognitive stimulation. They are especially suited for children with autism spectrum disorders (ASD) who need a high degree of physical and psychological enrichment. Even though EAIs have become a common practice, stress responses in horses interacting with individuals that can manifest inappropriate behaviours, such as ASD children, have not been thoroughly investigated. Our multicentre study aimed to investigate behavioural and physiological indices of stress in horses involved in EAI standardised sessions with children with ASD compared to typically developing (TD) children. A controlled within-subject design with repeated measurements involving 19 horses and 38 children was adopted. Stress-related behaviours, heart rate, heart rate variability, and eye temperature were recorded during the riding sessions. Moreover, blood samples were collected from horses before and after each session to monitor changes in blood adrenocorticotropic hormone (ACTH), cortisol, and catecholamines. Results indicate that, in general, stress responses in horses involved in EAIs did not differ as a function of the horse being ridden by children with ASD or TD. A lower sympathetic tone in horses involved in ASD sessions was found, while in the mounting and dismounting phases, horses displayed behavioural signs of stress, independently from children’s behaviour. We conclude that professionals working in EAI should increase their awareness of animal welfare and refine riding practices, taking into account horse’s needs

PNRR Orienta. Kit per le scuole

L'Università di Torino propone agli/alle insegnati questo kit di orientamento alla scelta del percorso formativo successivo alla scuola secondaria superiore. Si tratta di uno dispositivo, sviluppato nell’ambito del progetto “PNRR orienta”, che offre una serie di strumenti, percorsi e proposte didattiche utili per articolare una vera e propria attività di formazione alla scelta. Il kit è articolato nelle seguenti sezioni: materiale per l’insegnante; schede per gli studenti; approfondimenti per l’insegnante realizzabili in classe; approfondimento dei percorsi di studio; sezione gestita dal consulente; spunti per una didattica orientativa

Cholesterol-loaded nanoparticles ameliorate synaptic and cognitive function in Huntington's disease mice

Brain cholesterol biosynthesis and cholesterol levels are reduced in mouse models of Huntington's disease (HD), suggesting that locally synthesized, newly formed cholesterol is less available to neurons. This may be detrimental for neuronal function, especially given that locally synthesized cholesterol is implicated in synapse integrity and remodeling. Here, we used biodegradable and biocompatible polymeric nanoparticles (NPs) modified with glycopeptides (g7) and loaded with cholesterol (g7-NPs-Chol), which per se is not blood-brain barrier (BBB) permeable, to obtain high-rate cholesterol delivery into the brain after intraperitoneal injection in HD mice. We report that g7-NPs, in contrast to unmodified NPs, efficiently crossed the BBB and localized in glial and neuronal cells in different brain regions. We also found that repeated systemic delivery of g7-NPs-Chol rescued synaptic and cognitive dysfunction and partially improved global activity in HD mice. These results demonstrate that cholesterol supplementation to the HD brain reverses functional alterations associated with HD and highlight the potential of this new drug-administration route to the diseased brain

Distribution of Exonic Variants in Glycogen Synthesis and Catabolism Genes in Late Onset Pompe Disease (LOPD)

Pompe disease (PD) is a monogenic autosomal recessive disorder caused by biallelic pathogenic variants of the GAA gene encoding lysosomal alpha-glucosidase; its loss causes glycogen storage in lysosomes, mainly in the muscular tissue. The genotype-phenotype correlation has been extensively discussed, and caution is recommended when interpreting the clinical significance of any mutation in a single patient. As there is no evidence that environmental factors can modulate the phenotype, the observed clinical variability in PD suggests that genetic variants other than pathogenic GAA mutations influence the mechanisms of muscle damage/repair and the overall clinical picture. Genes encoding proteins involved in glycogen synthesis and catabolism may represent excellent candidates as phenotypic modifiers of PD. The genes analyzed for glycogen synthesis included UGP2, glycogenin (GYG1-muscle, GYG2, and other tissues), glycogen synthase (GYS1-muscle and GYS2-liver), GBE1, EPM2A, NHLRC1, GSK3A, and GSK3B. The only enzyme involved in glycogen catabolism in lysosomes is alpha-glucosidase, which is encoded by GAA, while two cytoplasmic enzymes, phosphorylase (PYGB-brain, PGL-liver, and PYGM-muscle) and glycogen debranching (AGL) are needed to obtain glucose 1-phosphate or free glucose. Here, we report the potentially relevant variants in genes related to glycogen synthesis and catabolism, identified by whole exome sequencing in a group of 30 patients with late-onset Pompe disease (LOPD). In our exploratory analysis, we observed a reduced number of variants in the genes expressed in muscles versus the genes expressed in other tissues, but we did not find a single variant that strongly affected the phenotype. From our work, it also appears that the current clinical scores used in LOPD do not describe muscle impairment with enough qualitative/quantitative details to correlate it with genes that, even with a slightly reduced function due to genetic variants, impact the phenotype

Modulation of Antioxidant Defense in Farmed Rainbow Trout (Oncorhynchus mykiss) Fed with a Diet Supplemented by the Waste Derived from the Supercritical Fluid Extraction of Basil (Ocimum basilicum)

Phytotherapy is based on the use of plants to prevent or treat human and animal diseases. Recently, the use of essential oils and polyphenol-enriched extracts is also rapidly increasing in the aquaculture sector as a means of greater industrial and environmental sustainability. Previous studies assessed the antibacterial and antiparasitic effects of these bioactive compounds on fish. However, studies on the modulation of oxidative stress biomarkers are still scant to date. Thus, in this study, the modulation of antioxidant defense against oxidative stress exerted by fish diets supplemented with a basil supercritical extract (F1-BEO) was assessed in rainbow trout Oncorhynchus mykiss. The F1-BEO extracted with supercritical fluid extraction was added to the commercial feed flour (0.5, 1, 2, 3% w/w) and mixed with fish oil to obtain a suitable compound for pellet preparation. Fish were fed for 30 days. The levels of stress biomarkers such as superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase, glyoxalase I, glyoxalase II, lactate dehydrogenase, glutathione and malondialdehyde showed a boost in the antioxidant pathway in fish fed with a 0.5% F1-BEO-supplemented diet. Higher F1-BEO supplementation led to a failure of activity of several enzymes and the depletion of glutathione levels. Malondialdehyde concentration suggests a sufficient oxidative stress defense against lipid peroxidation in all experimental groups, except for a 3% F1-BEO-supplemented diet (liver 168.87 ± 38.79 nmol/mg prot; kidney 146.86 ± 23.28 nmol/mg prot), compared to control (liver 127.76 ± 18.15 nmol/mg prot; kidney 98.68 ± 15.65 nmol/mg prot). Our results suggest supplementing F1-BEO in fish diets up to 0.5% to avoid potential oxidative pressure in farmed trout.This research was funded by Italian Ministry of Health, Ricerca Finalizzata, grant number GR-2013-02355796.Peer reviewe