Internalization and induction of antioxidant messages by microvesicles contribute to the antiapoptotic effects on human endothelial cells

Microvesicles are plasma membrane-derived fragments released from various cell types during activation and/or apoptosis and posses the ability to deliver biological information between cells. Microvesicles generated from T lymphocytes undergoing activation and apoptosis bear the morphogen Sonic Hedgehog, and exert a beneficial potential effect on the cardiovascular system through their dual capacity to increase nitric oxide and reduce reactive oxygen species production. This study investigated the effect of microvesicles on the apoptosis of human umbilical vein endothelial cells triggered by actinomycin D. Microvesicles prevented apoptosis induced by actinomycin D by modulating reactive oxygen species production: during the early phase of apoptosis, microvesicles might act directly as reactive oxygen species scavengers, owing to their ability to carry active antioxidant enzymes, catalase, and isoforms of the superoxide dismutase. Furthermore, their effects were associated with the ability to increase the expression of manganese-superoxide dismutase in endothelial cells, through the internalization process. Interestingly, microvesicles bearing Sonic Hedgehog induced cytoprotection in endothelial cells through the activation of the Sonic Hedgehog pathway. These findings provide additional evidence that microvesicles from T lymphocytes exert their vasculoprotective effects by promoting internalization and induction of antioxidant messages to the endothelial monolayer

Curcumin as prospective anti-aging natural compound: Focus on brain

The nutrients and their potential benefits are a new field of study in modern medicine for their positive impact on health. Curcumin, the yellow polyphenolic compound extracted from Curcuma longa species, is widely used in traditional Ayurvedic medicine to prevent and contrast many diseases, considering its antioxidant, immunomodulatory, anti-inflammatory, anti-microbial, cardio-protective, nephron-protective, hepato-protective, anti-neoplastic, and anti-rheumatic proprieties. In recent years, the investigations of curcumin have been focused on its application to aging and age-associated diseases. Aging is a physiological process in which there is a decreasing of cellular function due to internal or external stimuli. Oxidative stress is one of the most important causes of aging and age-related diseases. Moreover, many age-related disorders such as cancer, neuroinflammation, and infections are due to a low-grade chronic systemic inflammation. Curcumin acting on different proteins is able to contrast both oxidative stress than inflammation. In the brain, curcumin is able to modulate inflammation induced by microglia. Finally in brain tumors curcumin is able to reduce tumor growth by inhibition of telomerase activity. This review emphasizes the anti-aging role of curcumin focusing on its mechanism to counteract aging in the brain. Moreover, new formulations to increase the bioavailability of curcumin are discussed

Transfer of antioxidant message by microvesicles mediates antiapoptotic effects on human endothelial cells

Microvesicles (MVs) are small membrane-derived fragments shed from various cell types during activation and/or apoptosis and represent a new class of biological information mediators. MVs generated from T lymphocytes undergoing activation and apoptosis exert a beneficial potential effect on the cardiovascular system through their dual capacity to increase nitric oxide and reduce reactive oxygen species production. This study investigated the effect of MVs on the apoptosis of human umbilical vein endothelial cells triggered by actinomycin D (Act D). The effect of Act D treatment on reactive oxygen species (ROS) production was biphasic. Indeed, ROS levels significantly increased during the early phase of apoptosis (2 h) and after 10 h of treatment, but not at 4, 8 and 24 h. MVs significantly attenuated the increase in ROS production induced by Act D at 2 h, but not at 10 h, indicating that they normalize ROS production during the early phase of apoptosis by acting directly as ROS scavengers, owing to their ability to carry active antioxidant enzymes such as catalase and the three isoforms of the superoxide dismutase. Furthermore, the effects of MVs on the late phases of apoptosis were associated with the ability of these vesicles to increase the expression of manganese-superoxide dismutase, probably by the transfer of its mRNA, in endothelial cells, through internalization process. These findings illustrate new mechanisms by which MVs from T lymphocytes exert their vasculo-protective effects by improving endothelial function under pathological conditions in which apoptosis and oxidative stress are enhanced

Microparticles from activated/apoptotic lymphocytes preserve endothelial cell integrity

Microparticles (MPs), small membrane-derived fragments shed from various cell types during activation and/or apoptosis, represent a new class of biological information mediators. MPs generated from T lymphocytes undergoing activation and apoptosis exert a beneficial potential effect on the cardiovascular system through their dual capacity to increase nitric oxide and reduce reactive oxygen species production. This study investigated the effect of MPs on both the angiogenesis and apoptosis of human umbilical vein endothelial cells. MPs induced the formation of capillary-like structures in an in vitro model, by regulating cell proliferation. Both cell adhesion and expression of proteins involved in this process, such as Rho A, and phosphorylation of focal-activated kinase were increased by MPs, via a ROCK inhibitor-sensitive pathway. MPs increased mRNA and protein levels of pro-angiogenic factors as measured by qRT-PCR and western blot. MPs significantly attenuated the increase in reactive oxygen species (ROS) associated with Act D-induced apoptosis at early phase of apoptosis (2 h), by acting directly as ROS scavengers, owing to their ability to carry active antioxidant enzymes such as catalase and the 3 isoforms of the superoxide dismutase. Furthermore, the effects of MPs on the late phases of apoptosis were associated with the ability of these vesicles to increase the expression of manganese-superoxide dismutase through internalisation process. Interestingly, the effects induced by MPs on the formation of capillary-like structures, expression of adhesion molecules and pro-angiogenic factors and on apoptosis were reversed when Sonic Hedgehog signalling was pharmacologically inhibited with cyclopamine. These findings illustrate new mechanisms by which MPs from T lymphocytes exert their vasculo-protective effects by improving endothelial function under pathological conditions in which cell integrity is impaired

Energy and time resolution for a LYSO matrix prototype of the Mu2e experiment

We have measured the performances of a LYSO crystal matrix prototype tested with electron and photon beams in the energy range 60$-$450 MeV. This study has been carried out to determine the achievable energy and time resolutions for the calorimeter of the Mu2e experiment.Comment: 2 pages, 3 figures, 13th Pisa Meeting on Advanced Detector

Measurement of time resolution of the Mu2e LYSO calorimeter prototype

In this paper we present the time resolution measurements of the Lutetium–Yttrium Oxyorthosilicate (LYSO) calorimeter prototype for the Mu2e experiment. The measurements have been performed using the e− beam of the Beam Test Facility (BTF) in Frascati, Italy in the energy range from 100 to 400 MeV. The calorimeter prototype consisted of twenty five 30 x 30 x 130 mm^3, LYSO crystals read out by 10 × 10 mm^2 Hamamatsu Avalanche Photodiodes (APDs). The energy dependence of the measured time resolution can be parametrized as σ_t(E)=a/√E/GeV⊕b, with the stochastic and constant terms a=(51 ± 1)ps and b=(10 ± 4)ps, respectively. This corresponds to the time resolution of (162 ±4 )ps at 100 MeV

Characterization of a prototype for the electromagnetic calorimeter of the Mu2e experiment

The Mu2e experiment at Fermilab searches the neutrinoless conversion of the muon into electron in the field of an Aluminum nucleus. The observation of this process would be a proof of the Charged Lepton Flavor Violation (CLFV). In case of no observation, the upper limit will be set to Rμe < 6×10−17 @ 90% CL, improving by a factor of 4 the previous best determination. The Mu2e detector apparatus consists of a straw tubes tracker that will measure the electrons momentum, and an electromagnetic calorimeter that provides a tracking-independent measurement of the electron energy, time and position. In this paper, we describe the baseline project of the EMC and present results in terms of performances and R&D