Targeting dementias through cancer kinases inhibition

The failures in Alzheimer's disease (AD) therapy strongly suggest the importance of reconsidering the research strategies analyzing other mechanisms that may take place in AD as well as, in general, in other neurodegenerative dementias. Taking into account that in AD a variety of defects result in neurotransmitter activity and signaling efficiency imbalance, neuronal cell degeneration and defects in damage/repair systems, aberrant and abortive cell cycle, glial dysfunction, and neuroinflammation, a target may be represented by the intracellular signaling machinery provided by the kinome. In particular, based on the observations of a relationship between cancer and AD, we focused on cancer kinases for targeting neurodegeneration, highlighting the importance of targeting the intracellular pathways at the intersection between cell metabolism control/duplication, the inhibition of which may stop a progression in neurodegeneration

The molecular mechanism of the cholesterol-lowering effect of dill and kale: The influence of the food matrix components

open4noNome progetto: BASEFOOD (Sustainable exploitation of bioactive components from the Black Sea Area traditional foods)Foods are complex matrices containing many different compounds, all of which contribute to the overall effect of the food itself, although they have different mechanisms of action. While evaluating the effect of bioactive compounds, it is important to consider that the use of a single compound can hide the effects of the other molecules that can act synergistically or antagonistically in the same food. The aim of the present study was to evaluate the influence of food matrix components by comparing two edible plants (dill and kale) with cholesterol-lowering potential and similar contents of their most representative bioactive, quercetin. The molecular effects of the extracts were evaluated in HepG2 cells by measuring the expression of sterol-regulatory element-binding proteins (SREBPs), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and low density lipoprotein receptor (LDLR) at the mRNA and protein level. The results reported here show that both extracts reduced the cellular cholesterol level with a similar trend and magnitude. It is conceivable that the slightly different results are due to the diverse composition of minor bioactive compounds, indicating that only by considering food as a whole is it possible to understand the complex relationship between food, nutrition, and health in a foodomics vision.openDanesi, Francesca; Govoni, Marco; D'Antuono, Luigi Filippo; Bordoni, AlessandraDanesi, Francesca; Govoni, Marco; D'Antuono, Luigi Filippo; Bordoni, Alessandr

Priming adult stem cells by hypoxic pretreatments for applications in regenerative medicine

The efficiency of regenerative medicine can be ameliorated by improving the biological performances of stem cells before their transplantation. Several ex-vivo protocols of non-damaging cell hypoxia have been demonstrated to significantly increase survival, proliferation and post-engraftment differentiation potential of stem cells. The best results for priming cultured stem cells against a following, otherwise lethal, ischemic stress have been obtained with brief intermittent episodes of hypoxia, or anoxia, and reoxygenation in accordance with the extraordinary protection afforded by the conventional maneuver of ischemic preconditioning in severely ischemic organs. These protocols of hypoxic preconditioning can be rather easily reproduced in a laboratory; however, more suitable pharmacological interventions inducing stem cell responses similar to those activated in hypoxia are considered among the most promising solutions for future applications in cell therapy. Here we want to offer an up-to-date review of the molecular mechanisms translating hypoxia into beneficial events for regenerative medicine. To this aim the involvement of epigenetic modifications, microRNAs, and oxidative stress, mainly activated by hypoxia inducible factors, will be discussed. Stem cell adaptation to their natural hypoxic microenvironments (niche) in healthy and neoplastic tissues will be also considered

Optimizing Patient Care: A Systematic Review of Multidisciplinary Approaches for SLE Management

Systemic lupus erythematosus (SLE) is characterized by multisystemic clinical manifestations ranging from a relatively mild involvement to potentially life-threatening complications. Due to this complexity, a multidisciplinary (MD) approach is the best strategy for optimizing patients' care. The main aim of this systematic literature review (SLR) was to scrutinize the published data regarding the MD approach for the management of SLE patients. The secondary objective was to evaluate the outcomes of the MD approach in SLE patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were used. We performed an SLR to retrieve articles available in English or Italian listed in PubMed, Embase, Cinahl, and Cochrane Library concerning the MD approach used in observational studies and clinical trials. Four independent reviewers performed the study selection and data collection. Of 5451 abstracts evaluated, 19 studies were included in the SLR. The MD approach was most frequently described in the context of SLE pregnancy, reported in 10 papers. MD teams were composed of a rheumatologist, except for one cohort study; a gynecologist; a psychologist; a nurse; and other health professionals. MD approaches had a positive impact on pregnancy-related complications and disease flares and improved SLE psychological impact. Although international recommendations advise an MD approach for managing SLE, our review highlighted the paucity of data supporting this strategy, with most of the available evidence on the management of SLE during pregnancy

Strategies Affording Prevascularized Cell-Based Constructs for Myocardial Tissue Engineering

The production of a functional cardiac tissue to be transplanted in the injured area of the infarcted myocardium represents a challenge for regenerative medicine. Most cell-based grafts are unviable because of inadequate perfusion; therefore, prevascularization might be a suitable approach for myocardial tissue engineering. To this aim, cells with a differentiation potential towards vascular and cardiac muscle phenotypes have been cocultured in 2D or 3D appropriate scaffolds. In addition to these basic approaches, more sophisticated strategies have been followed employing mixed-cell sheets, microvascular modules, and inosculation from vascular explants. Technologies exerting spatial control of vascular cells, such as topographical surface roughening and ordered patterning, represent other ways to drive scaffold vascularization. Finally, microfluidic devices and bioreactors exerting mechanical stress have also been employed for high-throughput scaling-up production in order to accelerate muscle differentiation and speeding the endothelialization process. Future research should address issues such as how to optimize cells, biomaterials, and biochemical components to improve the vascular integration of the construct within the cardiac wall, satisfying the metabolic and functional needs of the myocardial tissue

Spectral Index of the Filaments in the Abell 523 Radio Halo

The galaxy cluster Abell 523 hosts a radio halo characterized by the presence of two filaments transversely located with respect to the cluster merger axis. In this paper, we present a spectral index image of these filaments between 1.410 and 1.782 GHz obtained with Jansky Very Large Array observations. We find a steepening of the spectral index of the filaments at frequencies 1.4 GHz and an indication that bright patches are characterized by flat spectral indices. Our results are consistent with a scenario of highly-efficient turbulence induced by merger phenomena

Puzzling large-scale polarization in the galaxy cluster Abell 523

Large-scale magnetic fields reveal themselves through diffuse synchrotron sources observed in galaxy clusters such as radio halos. Total intensity filaments of these sources have been observed in polarization as well, but only in three radio halos out of about one hundred currently known. In this paper we analyze new polarimetric Very Large Array data of the diffuse emission in the galaxy cluster Abell 523 in the frequency range 1-2 GHz. We find for the first time evidence of polarized emission on scales of ~ 2.5 Mpc. Total intensity emission is observed only in the central part of the source, likely due to observational limitations. To look for total intensity emission beyond the central region, we combine these data with single-dish observations from the Sardinia Radio Telescope and we compare them with multi-frequency total intensity observations obtained with different instruments, including the LOw Frequency ARray and the Murchison Widefield Array. By analysing the rotation measure properties of the system and utilizing numerical simulations, we infer that this polarized emission is associated with filaments of the radio halo located in the outskirts of the system, in the peripheral region closest to the observer.Comment: 14 pages, 12 figures, accepted for publication on MNRA

A new case of limb girdle muscular dystrophy 2g in a greek patient, founder effect and review of the literature

Limb girdle muscular dystrophy (LGMD) type 2G is a rare form of muscle disease, described only in a few patients worldwide, caused by mutations in TCAP gene, encoding the protein telethonin. It is characterised by proximal limb muscle weakness associated with distal involvement of lower limbs, starting in the first or second decade of life. We describe the case of a 37-year-old woman of Greek origin, affected by disto-proximal lower limb weakness. No cardiac or respiratory involvement was detected. Muscle biopsy showed myopathic changes with type I fibre hypotrophy, cytoplasmic vacuoles, lipid overload, multiple central nuclei and fibre splittings; ultrastructural examination showed metabolic abnormalities. Next generation sequencing analysis detected a homozygous frameshift mutation in the TCAP gene (c.90_91del), previously described in one Turkish family. Immunostaining and Western blot analysis showed complete absence of telethonin. Interestingly, Single Nucleotide Polymorphism analysis of the 10 Mb genomic region containing the TCAP gene showed a shared homozygous haplotype of both the Greek and the Turkish patients, thus suggesting a possible founder effect of TCAP gene c.90_91del mutation in this part of the Mediterranean area. (C) 2018 Elsevier B.V. All rights reserved.Peer reviewe

Spectro-polarimetric observations of the CIZA J2242.8+5301 northern radio relic: no evidence of high-frequency steepening

Observations of radio relics at very high frequency (>10 GHz) can help to understand how particles age and are (re-)accelerated in galaxy cluster outskirts and how magnetic fields are amplified in these environments. In this work, we present new single-dish 18.6 GHz Sardinia Radio Telescope and 14.25 GHz Effelsberg observations of the well known northern radio relic of CIZA J2242.8+5301. We detected the relic which shows a length of $\sim$1.8 Mpc and a flux density equal to $\rm S_{14.25\,GHz}=(9.5\pm3.9)\,mJy$ and $\rm S_{18.6\,GHz}=(7.67\pm0.90)\,mJy$ at 14.25 GHz and 18.6 GHz respectively. The resulting best-fit model of the relic spectrum from 145 MHz to 18.6 GHz is a power-law spectrum with spectral index $\alpha=1.12\pm0.03$: no evidence of steepening has been found in the new data presented in this work. For the first time, polarisation properties have been derived at 18.6 GHz, revealing an averaged polarisation fraction of $\sim40\%$ and a magnetic field aligned with the 'filaments' or 'sheets' of the relic.Comment: 10 pages, 8 figure

P39 Longitudinal changes of cerebral white matter tissue microstructure in early-onset systemic lupus erythematosus

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