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Additionally, AZM caused an increase in MMP-1 expression in hGFs, whereas it did not affect the expression of any of the analyzed genes in hPLFs. Our findings indicate that AZM does not affect hPLFs and acts specifically on hGFs. Thus, AZM may increase the expression of IL-6 and IL-8 under LPS stimulation to modify the inflammatory response and increase the expression of MMP-1 to promote connective tissue remodeling.In this work, spectroscopic properties of europium and erbium ions in heavy metal oxide glasses have been studied. The phonon energy of the glass host was determined based on Eu3+ excitation spectra measurements. Near-IR emission spectra at 1550 nm related to 4I13/2 → 4I15/2 transition of erbium in heavy metal glasses were examined with special regards to luminescence bandwidth and measured lifetime. In particular, correlation between phonon energy and the measured lifetime 4I13/2 (Er3+) was proposed. The luminescence lifetime for the 4I13/2 upper laser state of erbium decreases with increasing phonon energy in glass matrices. Completely different results were obtained glass samples with europium ions, where the 5D0 lifetime increases with increasing phonon energy. Our investigations suggest that the values of measured 5D0 lifetime equal to radiative lifetimes for all heavy metal oxide glasses.Mutations in the pantothenate kinase 2 gene (PANK2) are the cause of pantothenate kinase-associated neurodegeneration (PKAN), the most common form of neurodegeneration with brain iron accumulation. Although different disease models have been created to investigate the pathogenic mechanism of PKAN, the cascade of molecular events resulting from CoA synthesis impairment is not completely understood. Moreover, for PKAN disease, only symptomatic treatments are available. Despite the lack of a neural system, Saccharomyces cerevisiae has been successfully used to decipher molecular mechanisms of many human disorders including neurodegenerative diseases as well as iron-related disorders. To gain insights into the molecular basis of PKAN, a yeast model of this disease was developed a yeast strain with the unique gene encoding pantothenate kinase CAB1 deleted, and expressing a pathological variant of this enzyme. A detailed functional characterization demonstrated that this model recapitulates the main phenotypes associated with human disease mitochondrial dysfunction, altered lipid metabolism, iron overload, and oxidative damage suggesting that the yeast model could represent a tool to provide information on pathophysiology of PKAN. Taking advantage of the impaired oxidative growth of this mutant strain, a screening for molecules able to rescue this phenotype was performed. Two molecules in particular were able to restore the multiple defects associated with PKAN deficiency and the rescue was not allele-specific. Furthermore, the construction and characterization of a set of mutant alleles, allowing a quick evaluation of the biochemical consequences of pantothenate kinase (PANK) protein variants could be a tool to predict genotype/phenotype correlation.Nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor which plays a critical role in maintenance of cellular redox, has been identified as a therapeutic target in a number of human diseases. Several reports have demonstrated beneficial effects of NRF2 manipulation in animal models of disease, and one NRF2-activating drug, dimethyl fumarate, is already approved for the treatment of multiple sclerosis. However, drug discovery is slowed due to a dearth of biomarkers which can inform target engagement and magnitude and duration of action. Peripheral blood mononuclear cells (PBMCs) are an accessible, minimally-invasive source of biomarkers which can be readily assayed and objectively monitored as a surrogate endpoint of NRF2 activation in clinical trials. We undertook a review of the literature on PBMC NRF2 measurements in human studies to explore its role as a suitable biomarker in various contexts of health and disease. It is clear that NRF2 and its target genes can be readily assayed from PBMCs in multiple disease contexts and may track with disease progression. Further work needs to be undertaken to evaluate its stability but should be considered as an exploratory marker in clinical trials targeting NRF2 activation.Body size in animals commonly shows geographic and temporal variations that may depend upon several environmental drivers, including climatic conditions, productivity, geography and species interactions. The topic of body size trends across time has gained momentum in recent years since this has been proposed as a third universal response to climate change along with changes in distribution and phenology. However, disentangling the genuine effects of climate change from those of other environmental factors is often far from trivial. A-485 In this study, we tested a set of hypotheses concerning body size variation across time and space in Italian populations of a rhinolophid bat, the lesser horseshoe bat Rhinolophus hipposideros. We examined forearm length (FAL) and cranial linear traits in a unique historical collection of this species covering years from 1869 to 2016, representing, to the best of our knowledge, the longest time series ever considered in a morphological assessment of a bat species. No temporal changes occurred, rejecting the hypotheses that body size varied in response to climate change or urbanization (light pollution). We found that FAL increased with latitude following a Bergmann's rule trend, whereas the width of upper incisors, likely a diet-related trait, showed an opposite pattern which awaits explanation. We also confirmed that FAL is sexually dimorphic in this species and ruled out that insularity has any detectable effect on the linear traits we considered. This suggests that positive responses of body size to latitude do not mean per se that concurring temporal responses to climate change are also expected. Further investigations should explore the occurrence of these patterns over larger spatial scales and more species in order to detect the existence of general patterns across time and space.