1,171 research outputs found
N-acetyl-L-cysteine ethyl ester (NACET) as a potential therapeutic strategy for the prevention and treatment of Age-related Macular Degeneration
No full textAge-related macular degeneration (AMD) is a multifactorial progressive chronic ocular disease. Genetics, environmental insults, and age-related issues are risk factors for the development of the disease. Dysfunction of retinal pigment epithelium (RPE) is involved in AMD and oxidative stress in RPE is one of the major causes of the etiopathogenesis of AMD. Therefore, the introduction of antioxidants may represent one of the most effective ways to delay the onset of AMD. Glutathione (GSH) is a key player in the detoxification of xenobiotics, their metabolites and of reactive oxygen species (ROS) and consequently many drugs are currently in use as GSH enhancers. N-acetyl-L-cysteine ethyl ester (NACET) is a lipophilic and cell permeable GSH prodrug that has been proposed to delay AMD progression. Here, we reported an RNA-seq transcriptome analysis of human Retinal Pigment Epithelial cells (ARPE-19) and described for the first time that NACET induces transcriptional activation of nuclear factor erythroid 2-related factor 2 (NRF2) target genes. NRF2 is a transcription factor that allows the maintenance of redox homeostasis by binding to the antioxidant responsive elements (ARE) in the upstream promoter region of many antioxidative genes and thereby inducing their transcription. By means of HPLC analysis, RT-qPCR, Western blot analysis, CRISPR-Cas9 gene editing and luciferase assay, we validated the transcriptome analysis and demonstrated that NACET increases the intracellular level of free cysteine and promotes transcriptional activation of NRF2 target genes through inhibition of NRF2 degradation. Moreover, using transcriptional profiling of retina of young and old mice orally treated with NACET, we showed that NACET rescued 57 genes impaired by aging, many of which have been correlated with retinal dysfunctions. Our study suggests that NACET, as cysteine and GSH precursor and as NRF2 activator, may be a useful tool for the treatment of oxidative stress-related retinal diseases. Although we tested NACET focusing on AMD, we also verified that NACET-induced NRF2 activation is not cell-context dependent, suggesting that NACET may be a promising agent for prevention/treatment of any pathology where oxidative stress is involved
Role of endocannabinoids in regulating drug dependence
No full textDaniela Parolaro, Daniela Vigano’, Natalia Realini, Tiziana RubinoNeuroscience Center, DBSF, University of Insubria, Busto Arsizio, ItalyAbstract: This review will discuss the latest knowledge of how the endocannabinoid system might be involved in treating addiction to the most common illicit drugs. Experimental models are providing increasing evidence for the pharmacological management of endocannabinoid signaling not only to block the direct reinforcing effects of cannabis, opioids, nicotine and ethanol, but also for preventing relapse to the various drugs of abuse, including opioids, cocaine, nicotine, alcohol and metamphetamine. Preclinical and clinical studies suggest that the endocannabinoid system can be manipulated by the CB1 receptor antagonist SR141716A, that might constitute a new generation of compounds for treating addiction across different classes of abused drugs.Keywords: Endocannabinoids, drug dependence, opioids, nicotine, alcohol, psychostimulant
Workers’ buyout: the Italian experience, 1986-2016
No full textWorkers’ buyout (WBOs) are emerging during the present economic crisis as an alternative tool to maintain employment and production. In Italy, in the last thirty years, 258 cases have been recorded. What are their general characteristics? Why do WBOs develop and who are the main sponsors and financing tools? The present analysis aims at defining the phenomenon and the enabling environment. Moreover, primary sources collected from different actors will explain how WBOs have developed and thrived across Italy saving jobs and productive capacity
Giulia Veronica Varisco
No full textThe headword explains the biography and the contribution of the author Giulia Varisco to the children's literatur
Involvement of the endocannabinoid system in phencyclidine-induced cognitive deficits modelling schizophrenia.
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Chronic URB597 treatment at adulthood reverted most depressive-like symptoms induced by adolescent exposure to THC in female rats.
No full textComplete Acid Ceramidase ablation prevents cancer-initiating cell formation in melanoma cells
No full textAcid ceramidase (AC) is a lysosomal cysteine hydrolase that catalyzes the conversion of ceramide into fatty acid and sphingosine. This reaction lowers intracellular ceramide levels and concomitantly generates sphingosine used for sphingosine-1-phosphate (S1P) production. Since increases in ceramide and consequent decreases of S1P reduce proliferation of various cancers, AC might offer a new target for anti-tumor therapy. Here we used CrispR-Cas9-mediated gene editing to delete the gene encoding for AC, ASAH1, in human A375 melanoma cells. ASAH1-null clones show significantly greater accumulation of long-chain saturated ceramides that are substrate for AC. As seen with administration of exogenous ceramide, AC ablation blocks cell cycle progression and accelerates senescence. Importantly, ASAH1-null cells also lose the ability to form cancer-initiating cells and to undergo self-renewal, which is suggestive of a key role for AC in maintaining malignancy and self-renewal of invasive melanoma cells. The results suggest that AC inhibitors might find therapeutic use as adjuvant therapy for advanced melanoma
Ytterbium Disilicate/Monosilicate Multilayer Environmental Barrier Coatings: Influence of Atmospheric Plasma Spray Parameters on Composition and Microstructure
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Ytterbium Disilicate/Monosilicate Multilayer Environmental Barrier Coatings: Influence of Atmospheric Plasma Spray Parameters on Composition and Microstructure
by Giulia Di Iorio,Laura Paglia *ORCID,Giulia PedrizzettiORCID,Virgilio GenovaORCID,Francesco MarraORCID,Cecilia BartuliORCID andGiovanni PulciORCID
INSTM Reference Laboratory for Materials and Surface Engineering, Sapienza University of Rome, Eudossiana 18, 00184 Rome, Italy
*
Author to whom correspondence should be addressed.
Coatings 2023, 13(9), 1602; https://doi.org/10.3390/coatings13091602
Original submission received: 10 August 2023 / Revised: 31 August 2023 / Accepted: 11 September 2023 / Published: 13 September 2023
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Abstract
SiC/SiC ceramic matrix composites (SiCf/SiC CMCs) are regarded as the new materials for the hot-section components of aircraft gas turbine engines, since they have one-third of the density of metallic superalloys, a higher temperature capability, good mechanical strength, and excellent thermal shock resistance. However, high-temperature water-vapor-rich combustion gases can induce severe surface recession phenomena in SiC/SiC leading to component failure. For this reason, it is necessary to design protective coatings, i.e., environmental barrier coatings (EBCs), able to protect the SiC/SiC surface in combustion environments. In the present work, ytterbium monosilicate (Yb2SiO5), stable when exposed to water vapor at high temperatures, and ytterbium disilicate (Yb2Si2O7), characterized by a thermal expansion coefficient closer to that of the substrate, were selected for a multilayer EBC system. EBCs were processed using the atmospheric plasma spray (APS) technique. A set of deposition parameters were tested, varying the power of the torch, and the composition and microstructure of the deposited coatings were studied in terms of porosity, crack density, and post-deposition phase retention by performing SEM, EDS, and XRD analysis. The results allow for the definition of the influence of deposition parameters on the final properties of multilayer EBC coatings
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