Neuroprotective potential of isothiocyanates in an in vitro model of neuroinflammation

Isothiocyanates (ITCs), present as glucosinolate precursors in cruciferous vegetables, have shown anti-inflammatory, antioxidant and anticarcinogenic activities. Here, we compared the effects of three different ITCs on ROS production and on the expression of matrix metalloproteinase (MMP)-2 and -9, which represent important pathogenetic factors of various neurological diseases. Primary cultures of rat astrocytes were activated by LPS and simultaneously treated with different doses of Allyl isothiocyanate (AITC), 2-Phenethyl isothiocyanate (PEITC) and 2-Sulforaphane (SFN). Results showed that SFN and PEITC were able to counteract ROS production induced by H2O2. The zymographic analysis of cell culture supernatants evidenced that PEITC and SFN were the most effective inhibitors of MMP-9, whereas, only SFN significantly inhibited MMP-2 activity. PCR analysis showed that all the ITCs used significantly inhibited both MMP-2 and MMP-9 expression. The investigation on the mitogen-activated protein kinase (MAPK) signaling pathway demonstrated that ITCs modulate MMP transcription by inhibition of extracellular-regulated protein kinase (ERK) activity. Results of this study suggest that ITCs could be promising nutraceutical agents for the prevention and complementary treatment of neurological diseases associated with MMP involvement

Sex-differences in the longitudinal recovery of neuromuscular function in COVID-19 associated acute respiratory distress syndrome survivors

Introduction: Patients admitted to the intensive care unit (ICU) following severe acute respiratory syndrome 2 (SARS-CoV-2) infection may have muscle weakness up to 1 year or more following ICU discharge. However, females show greater muscle weakness than males, indicating greater neuromuscular impairment. The objective of this work was to assess sex differences in longitudinal physical functioning following ICU discharge for SARS-CoV-2 infection. Methods: We performed longitudinal assessment of physical functioning in two groups: 14 participants (7 males, 7 females) in the 3-to-6 month and 28 participants (14 males, 14 females) in the 6-to-12 month group following ICU discharge and assessed differences between the sexes. We examined self-reported fatigue, physical functioning, compound muscle action potential (CMAP) amplitude, maximal strength, and the neural drive to the tibialis anterior muscle. Results: We found no sex differences in the assessed parameters in the 3-to-6-month follow-up, indicating significant weakness in both sexes. Sex differences emerged in the 6-to-12-month follow-up. Specifically, females exhibited greater impairments in physical functioning, including lower strength, walking lower distances, and high neural input even 1 year following ICU-discharge. Discussion: Females infected by SARS-CoV-2 display significant impairments in functional recovery up to 1 year following ICU discharge. The effects of sex should be considered in post-COVID neurorehabilitation

High surface area mesoporous silica nanoparticles with tunable size in the sub-micrometer regime: Insights on the size and porosity control mechanisms

Mesoporous silica nanostructures (MSNs) attract high interest due to their unique and tunable physical chemical features, including high specific surface area and large pore volume, that hold a great potential in a variety of fields, i.e., adsorption, catalysis, and biomedicine. An essential feature for biomedical application of MSNs is limiting MSN size in the sub-micrometer regime to control uptake and cell viability. However, careful size tuning in such a regime remains still chal-lenging. We aim to tackling this issue by developing two synthetic procedures for MSN size mod-ulation, performed in homogenous aqueous/ethanol solution or two-phase aqueous/ethyl acetate system. Both approaches make use of tetraethyl orthosilicate as precursor, in the presence of cetyltri-methylammonium bromide, as structure-directing agent, and NaOH, as base-catalyst. NaOH catalyzed syntheses usually require high temperature (>80 °C) and large reaction medium volume to trigger MSN formation and limit aggregation. Here, a successful modulation of MSNs size from 40 up to 150 nm is demonstrated to be achieved by purposely balancing synthesis conditions, being able, in addition, to keep reaction temperature not higher than 50 °C (30 °C and 50 °C, respectively) and reaction mixture volume low. Through a comprehensive and in-depth systematic morphologi-cal and structural investigation, the mechanism and kinetics that sustain the control of MSNs size in such low dimensional regime are defined, highlighting that modulation of size and pores of the structures are mainly mediated by base concentration, reaction time and temperature and ageing, for the homogenous phase approach, and by temperature for the two-phase synthesis. Finally, an in vitro study is performed on bEnd.3 cells to investigate on the cytotoxicity of the MNSs

COVID-19 affects serum brain-derived neurotrophic factor and neurofilament light chain in aged men. Implications for morbidity and mortality

Background and Methods: Severe COVID-19 is known to induce neurological damage (NeuroCOVID), mostly in aged individuals, by affecting brain-derived neurotrophic factor (BDNF), matrix metalloproteinases (MMP) 2 and 9 and the neurofilament light chain (NFL) pathways. Thus, the aim of this pilot study was to investigate BDNF, MMP-2, MMP-9, and NFL in the serum of aged men affected by COVID-19 at the beginning of the hospitalization period and characterized by different outcomes, i.e., attending a hospital ward or an intensive care unit (ICU) or with a fatal outcome. As a control group, we used a novelty of the study, unexposed age-matched men. We also correlated these findings with the routine blood parameters of the recruited individuals. Results: We found in COVID-19 individuals with severe or lethal outcomes disrupted serum BDNF, NFL, and MMP-2 presence and gross changes in ALT, GGT, LDH, IL-6, ferritin, and CRP. We also confirmed and extended previous data, using ROC analyses, showing that the ratio MMPs (2 and 9) versus BDNF and NFL might be a useful tool to predict a fatal COVID-19 outcome. Conclusions: Serum BDNF and NFL and/or their ratios with MMP-2 and MMP-9 could represent early predictors of NeuroCOVID in aged men

On possible interpretations of the high energy electron-positron spectrum measured by the Fermi Large Area Telescope

The Fermi-LAT experiment recently reported high precision measurements of the spectrum of cosmic-ray electrons-plus-positrons (CRE) between 20 GeV and 1 TeV. The spectrum shows no prominent spectral features, and is significantly harder than that inferred from several previous experiments. Here we discuss several interpretations of the Fermi results based either on a single large scale Galactic CRE component or by invoking additional electron-positron primary sources, e.g. nearby pulsars or particle Dark Matter annihilation. We show that while the reported Fermi-LAT data alone can be interpreted in terms of a single component scenario, when combined with other complementary experimental results, specifically the CRE spectrum measured by H.E.S.S. and especially the positron fraction reported by PAMELA between 1 and 100 GeV, that class of models fails to provide a consistent interpretation. Rather, we find that several combinations of parameters, involving both the pulsar and dark matter scenarios, allow a consistent description of those results. We also briefly discuss the possibility of discriminating between the pulsar and dark matter interpretations by looking for a possible anisotropy in the CRE flux.Comment: 29 pages, 12 figures. Final version accepted for publication in Astroparticle Physic

Fermi LAT Observations of the Supernova Remnant W28 (G6.4-0.1)

We present detailed analysis of the two gamma-ray sources,1FGL J1801.3-2322c and 1FGL J1800.5-2359c,that have been found toward the supernova remnant(SNR) W28 with the Large Area Telescope(LAT) on board the Fermi Gamma-ray Space Telescope.1FGL J1801.3-2322c is found to be an extended source within the boundary of SNR W28,and to extensively overlap with the TeV gamma-ray source HESS J1801-233,which is associated with a dense molecular cloud interacting with the supernova remnant.The gamma-ray spectrum measured with LAT from 0.2--100 GeV can be described by a broken power-law function with a break of ~1GeV,and photon indices of 2.09$\pm$0.08(stat)$\pm$0.28(sys) below the break and 2.74$\pm$0.06(stat)$\pm$0.09(sys) above the break.Given the clear association between HESS J1801-233 and the shocked molecular cloud and a smoothly connected spectrum in the GeV--TeV band,we consider the origin of the gamma-ray emission in both GeV and TeV ranges to be the interaction between particles accelerated in the SNR and the molecular cloud.The decay of neutral pions produced in interactions between accelerated hadrons and dense molecular gas provide a reasonable explanation for the broadband gamma-ray spectrum. 1FGL J1800.5-2359c, located outside the southern boundary of SNR W28, cannot be resolved.An upper limit on the size of the gamma-ray emission was estimated to be ~16$'$ using events above ~2GeV under the assumption of a circular shape with uniform surface brightness. It appears to coincide with the TeV source HESS J1800-240B,which is considered to be associated with a dense molecular cloud that contains the ultra compact HII region W28A2(G5.89-0.39).We found no significant gamma-ray emission in the LAT energy band at the positions of TeV sources HESS J1800-230A and HESS J1800-230C.The LAT data for HESS J1800-230A combined with the TeV data points indicate a spectral break between 10GeV and 100GeV.Comment: 23 pages, 6 figures. Accepted for publication in the Astrophysical Journal. Corresponding authors: H. Katagiri, H. Tajima, T. Tanaka, and Y. Uchiyam

GeV Gamma-ray Flux Upper Limits from Clusters of Galaxies

The detection of diffuse radio emission associated with clusters of galaxies indicates populations of relativistic leptons infusing the intracluster medium. Those electrons and positrons are either injected into and accelerated directly in the intracluster medium, or produced as secondary pairs by cosmic-ray ions scattering on ambient protons. Radiation mechanisms involving the energetic leptons together with decay of neutral pions produced by hadronic interactions have the potential to produce abundant GeV photons. Here, we report on the search for GeV emission from clusters of galaxies using data collected by the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope (Fermi) from August 2008 to February 2010. Thirty-three galaxy clusters have been selected according to their proximity and high mass, X-ray flux and temperature, and indications of non-thermal activity for this study. We report upper limits on the photon flux in the range 0.2-100 GeV towards a sample of observed clusters (typical values 1-5 x 10^-9 ph cm^-2 s^-1) considering both point-like and spatially resolved models for the high-energy emission, and discuss how these results constrain the characteristics of energetic leptons and hadrons, and magnetic fields in the intracluster medium. The volume-averaged relativistic-hadron-to-thermal energy density ratio is found to be < 5-10% in several clusters.Comment: 9 pages, 3 tables, 1 figure, accepted for publication in ApJ Letter

Fermi-LAT observations of the exceptional gamma-ray outbursts of 3C 273 in September 2009

We present the light curves and spectral data of two exceptionally luminous gamma-ray outburts observed by the Large Area Telescope (LAT) experiment on board Fermi Gamma-ray Space Telescope from 3C 273 in September 2009. During these flares, having a duration of a few days, the source reached its highest gamma-ray flux ever measured. This allowed us to study in some details their spectral and temporal structures. The rise and decay are asymmetric on timescales of 6 hours, and the spectral index was significantly harder during the flares than during the preceding 11 months. We also found that short, very intense flares put out the same time-integrated energy as long, less intense flares like that observed in August 2009.Comment: Corresponding authors: E. Massaro, [email protected]; G. Tosti, [email protected]. 15 pages, 4 figures, published in The Astrophysical Journal Letters, Volume 714, Issue 1, pp. L73-L78 (2010