Brazilian Green Propolis Inhibits Inflammatory Angiogenesis in a Murine Sponge Model

Angiogenesis and inflammation are persistent features of several pathological conditions. Propolis, a sticky material that honeybees collect from living plants, has been reported to have multiple biological effects including anti-inflammatory and anti-neoplasic activities. Here, we investigated the effects of water extract of green propolis (WEP) on angiogenesis, inflammatory cell accumulation and endogenous production of cytokines in sponge implants of mice over a 14-day period. Blood vessel formation as assessed by hemoglobin content and by morphometric analysis of the implants was reduced by WEP (500 mg kg−1 orally) compared to the untreated group. The levels of vascular endothelial growth factor (VEGF) increased progressively in the treated group but decreased after Day 10 in the control group. Accumulation of neutrophils and macrophages was determined by measuring myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAG) activities, respectively. Neutrophil accumulation was unaffected by propolis, but NAG activity was reduced by the treatment at Day 14. The levels TGF-β1 intra-implant increased progressively in both groups but were higher (40%) at Day 14 in the control implants. The pro-inflammatory levels of TNF-α peaked at Day 7 in the control implants, and at Day 14 in the propolis-treated group. Our results indicate that the anti-inflammatory/anti-angiogenic effects of propolis are associated with cytokine modulation

Histone Deacetylase 4 is crucial for proper skeletal muscle development and disease

Epigenetics plays a pivotal role in modulating gene response to physiological or pathological stimuli. Histone Deacetylase inhibitors (HDACi) have been used in the treatment of various cancers1, are effective in several animal models of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), and are currently in clinical trial to promote muscle repair in muscular dystrophies2. However, long-term use of pan-HDAC inhibitors is not tolerated3. The assignment of distinct biological functions to individual HDACs in skeletal muscle is a prerequisite to improve the efficacy of pharmacological treatments based on HDACi. HDAC4 is a member of class II HDACs that mediates many cellular responses. Clinical reports suggest that inhibition of HDAC4 can be beneficial to cancer cachexia, dystrophic or ALS patients. All the above conditions are characterized by progressive muscle wasting and up-regulation of HDAC4 expression in skeletal muscle, suggesting a potential role for this protein in regulating these diseases. To study the role of HDAC4 with a genetic approach, we generated several models of muscle disease in mice lacking HDAC4 in skeletal muscle: cancer cachexia, by implanting Lewis lung carcinoma (LLC), muscular dystrophy, by using mdx mice, or ALS, by using SODG93A mice. Lack of HDAC4 worsens skeletal muscle atrophy induced by both LLC and ALS, demonstrated by a reduction in muscle mass and myofibers size. Conversely, dystrophic mice lacking HDAC4 in skeletal muscle show an increased number of necrotic myofibers and run less efficiently than mdx mice. The aggravation of the dystrophic phenotype may be partially due to the impairment in skeletal muscle regeneration observed in mice lacking HDAC4 in skeletal muscle. Our results indicate that HDAC4 is necessary for maintaining skeletal muscle homeostasis and function. Current studies aim to investigate the molecular mechanisms underlying the role of HDAC4 in skeletal muscle maintenance in response to cancer cachexia, ALS or muscular dystrophy

HDAC4 is necessary for satellite cell differentiation and muscle regeneration

In response to injury, skeletal muscle exhibits high capacity to regenerate and epigenetics controls multiple steps of this process (Giordani et al., 2013). It has been demonstrated in vitro that completion of muscle differentiation requires shuttling of histone deacetylase 4 (HDAC4), a member of class IIa HDACs, from the nucleus to the cytoplasm and consequent activation of MEF2-dependent differentiation genes (McKinsey et al., 2000). In vivo, HDAC4 expression is up-regulated in skeletal muscle upon injury, suggesting a role for this protein in muscle regeneration. With the aim to elucidate the role of HDAC4 in skeletal muscle regeneration, we generate mice lacking HDAC4 in the satellite cells (HDAC4fl/fl;Pax7CE Cre). Lack of HDAC4 inhibits satellite cell differentiation. Despite having similar amount of sorted cells, HDAC4 KO satellite cells proliferate less and have less pax7 than controls. Importantly, muscle regeneration in vivo is impaired in HDAC4fl/fl;Pax7CE Cre mice. These results are confirmed by molecular analyses of the expression of myogenic markers. All together, these data delineate the importance of HDAC4 in muscle regeneration and suggest a protective role in response to muscle damage

PRISM (Polarized Radiation Imaging and Spectroscopy Mission): A White Paper on the Ultimate Polarimetric Spectro-Imaging of the Microwave and Far-Infrared Sky

PRISM (Polarized Radiation Imaging and Spectroscopy Mission) was proposed to ESA in response to the Call for White Papers for the definition of the L2 and L3 Missions in the ESA Science Programme. PRISM would have two instruments: (1) an imager with a 3.5m mirror (cooled to 4K for high performance in the far-infrared---that is, in the Wien part of the CMB blackbody spectrum), and (2) an Fourier Transform Spectrometer (FTS) somewhat like the COBE FIRAS instrument but over three orders of magnitude more sensitive. Highlights of the new science (beyond the obvious target of B-modes from gravity waves generated during inflation) made possible by these two instruments working in tandem include: (1) the ultimate galaxy cluster survey gathering 10e6 clusters extending to large redshift and measuring their peculiar velocities and temperatures (through the kSZ effect and relativistic corrections to the classic y-distortion spectrum, respectively) (2) a detailed investigation into the nature of the cosmic infrared background (CIB) consisting of at present unresolved dusty high-z galaxies, where most of the star formation in the universe took place, (3) searching for distortions from the perfect CMB blackbody spectrum, which will probe a large number of otherwise inaccessible effects (e.g., energy release through decaying dark matter, the primordial power spectrum on very small scales where measurements today are impossible due to erasure from Silk damping and contamination from non-linear cascading of power from larger length scales). These are but a few of the highlights of the new science that will be made possible with PRISM.Comment: 20 pages Late

Planck intermediate results XIV : Dust emission at millimetre wavelengths in the Galactic plane

Peer reviewe

Antibacterial and Antibiofilm Properties of Three Resin-Based Dental Composites against <i>Streptococcus mutans</i>

Antibacterial and antibiofilm properties of restorative dental materials may improve restorative treatment outcomes. The aim of this in vitro study was to evaluate Streptococcus mutans capability to adhere and form biofilm on the surface of three commercially available composite resins (CRs) with different chemical compositions: GrandioSO (VOCO), Venus Diamond (VD), and Clearfil Majesty (ES-2). Disk-shaped specimens were manufactured by light-curing the CRs through two glass slides to maintain a perfectly standardized surface topography. Specimens were subjected to Planktonic OD600nm, Planktonic CFU count, Planktonic MTT, Planktonic live/dead, Adherent Bacteria CFU count, Biomass Quantification OD570nm, Adherent Bacteria MTT, Concanavalin A, and Scanning Electron Microscope analysis. In presence of VOCO, VD, and ES2, both Planktonic CFU count and Planktonic OD600nm were significantly reduced compared to that of control. The amount of Adherent CFUs, biofilm Biomass, metabolic activity, and extracellular polymeric substances were significantly reduced in VOCO, compared to those of ES2 and VD. Results demonstrated that in presence of the same surface properties, chemical composition might significantly influence the in vitro bacterial adhesion/proliferation on resin composites. Additional studies seem necessary to confirm the present results

Flogosis and heart involvement in large vessel vasculitis

Flogosis and Heart involvement in Large Vessel Vasculiti

Esophageal impedance baseline in infants with bronchopulmonary dysplasia: A pilot study

Background: Bronchopulmonary dysplasia (BPD) may induce gastroesophageal reflux (GER). Esophageal impedance baseline values (BI) reflect mucosal inflammation. Our aim was to evaluate BI levels in preterm infants with BPD compared with those without BPD and to identify BI predictors. Methods: This is a retrospective pilot study including infants born &lt;32 weeks' gestational age (GA) who underwent esophageal multichannel intraluminal impedance (MII)-pH. Univariate/multivariate analysis were performed to compare data between BPD and non-BPD infants and to identify BI predictors. A subgroup analysis was performed in infants born &lt;29 weeks' GA, at highest risk for BPD. Results: Ninety-seven patients (median GA 285/7 weeks, mean postnatal age 49 days, 29 with BPD), were studied. BPD infants had significantly lower birth weight compared with non-BPD infants (750 vs. 1275 g), were more immature (274/7 vs. 290/7 weeks GA), were older at MII-pH (79 vs. 38 days) and received less fluids during MII-pH (147 vs. 161 ml/kg/day). The same findings were found in the group of 53 infants born &lt;29 weeks. BPD versus non-BPD infants had significantly lower BI (2050 vs. 2574 ohm, p = 0.007) (&lt;1000 ohm in five BPD infants vs. one non-BPD) whereas the other MII-pH parameters were not significantly different. Multiple regression analysis found that increasing chronological age was positively associated with BI (B = 9.3, p = 0.013) whereas BPD was associated with lower BI (B = −793.4, p &lt; 0.001). Conclusions: BPD versus non-BPD infants had significantly lower BI despite similar MII-pH data. BPD and chronological age predicted BI, whereas only BPD predicted BI in the most immature infants