Editorial: Sirtuinome Rewiring to Hijack Cancer Cell Behavior and Hamper Resistance to Anticancer Intervention

In this Research Topic we collected original studies (mini)review and perspective articles that were focused on the SIRT-dependent mechanisms that underlie various tumor- and cancer-related processes, both at cellular and tissue level

Regular and moderate exercise initiated in middle age prevents age-related amyloidogenesis and preserves synaptic and neuroprotective signaling in mouse brain cortex

Abstract Although the beneficial responses induced in the central nervous system by early-initiated exercise have been broadly investigated, the effects of a chronic and moderate lately-initiated exercise on biochemical hallmarks of very early brain senescence have not been extensively studied. We previously reported that a midlife-initiated regimen of moderate running was able not only to prevent the age-related decay of antioxidative and detoxification functions in mouse brain cortex, but also to preserve neurotrophic support and molecular integrity. On this basis, this work investigated whether and how a 2-mo or 4-mo midlife-initiated running protocol could affect the activity of those systems involved in maintaining neuronal function and in preventing the onset of neurodegeneration within the brain cortex of middle-aged CD-1 mice. In particular, we analyzed the production of the peptide amyloid-β and the expression of synapsin Ia, which is known to play a key role in neurotransmission and synaptic plasticity. In addition, we studied the expression of sirtuin 3, as a protein marker of neuroprotection against age-dependent mitochondrial dysfunction, as well as the pro-death pathway induced by proBDNF through the interaction with p75NTR and the co-receptor sortilin. The midlife-initiated 4-mo running program triggered multiple responses within the mouse brain cortex, through the activation of anti-amyloidogenic, pro-survival, synaptogenic and neuroprotective pathways. However, most of the beneficial actions of the exercise regimen appeared only after 4 months, since 2-mo-exercised mice showed marked impairments of the endpoints we considered. This could imply that a midlife-initiated regimen of moderate treadmill running may require an adequate time lag to activate beneficial compensative mechanisms within the mouse brain cortex

Amphibian transition to the oxidant terrestrial environment affects the expression of glutathione S-transferases isoenzymatic pattern

AbstractIt has been postulated that glutathione S-transferases (GST; EC 2.5.1.18) may play a role in protecting against oxidative stress.In previous studies, we have purified and characterised from Bufo bufo embryos a GST isoenzyme (BbGSTP1-1), which falls at very low level in the adult liver, where a novel isoform (BbGSTP2-2), starts to be highly expressed. During transition to adult life, B. bufo leaves the aquatic environment to live predominantly in the terrestrial environment, characterised by higher oxygen concentration.It has been found that BbGSTP2-2 is more efficient in scavenging from organic hydroperoxides.Therefore, the appearance of BbGSTP2-2 may respond to the necessity of providing the adult toad with a more suitable protection against oxygen toxic by-products. In this work, we performed experiments aimed at verifying if oxidative stress (hyperoxic and H2O2 treatments) could act as a modulator of BbGSTP2-2 expression. Results show that: (a) BbGSTP2 mRNA starts to be expressed in the late embryonic period, while protein appears during metamorphosis; (b) oxidative stress induces anticipation of BbGSTP2 gene expression at both transcriptional and translational levels.These findings seem to indicate that the appearance of BbGSTP2-2 is aimed at endowing the adult toad with more efficient antioxidant defence in the terrestrial atmosphere

Proposal for the reuse of the ELI-NP GBS pre injector for a radioactive beams facility

In the framework of the ELI-NP GBS program a full pre-injector was delivered in the Magurele premises (Romania). This article develops the scenario of the re-use of the pre injector components to integrate a radioactive beams facility in the ELI site, considering the possible interest of the local nuclear physics community

Design, realization, and high power test of high gradient, high repetition rate brazing-free S -band photogun

In this paper, we address the energy spread and slice energy spread of an externally injected electron beam in plasma wakefield accelerators operating in the linear or quasilinear regime. The energy spread is first derived taking into account the phase dependence of the wakefield along the finite-length bunch together with the dephasing during acceleration and found to be strongly dependent on the bunch length. This could be compensated by the beam loading effect, the energy spread from which is then derived and found to be nearly independent of the bunch length. However, the transverse dependence of the beam loading effect also makes the particles at the same longitudinal position experience different accelerating fields, introducing a significant slice energy spread. To estimate the slice energy spread, a theoretical analysis was conducted by taking the transverse betatron motion into account. As a study case, 3D simulations for the 5 GeV laser-plasma acceleration stage of the European Plasma Research Accelerator with eXcellence in Applications project have been performed. Careful optimization of the parameters allows one to obtain an energy spread of ≤1% and a slice energy spread of ≤0.1%, with good agreement between theories and simulations

The natural carotenoid crocetin and the synthetic tellurium compound as101 protect the ovary against cyclophosphamide by modulating sirt1 and mitochondrial markers

Cancer therapies are associated with increased infertility risk due to accelerated reproductive aging. Oxidative stress (OS) is a potential mechanism behind ovarian toxicity by cyclophosphamide (CPM), the most ovotoxic anticancer drug. An important sensor of OS is SIRT1, a NAD+-dependent deacetylase which regulates cellular defence and cell fate. This study investigated whether the natural carotenoid crocetin and the synthetic compound AS101 protect the ovary against CPM by modulating SIRT1 and mitochondrial markers. We found that the number of primordial follicles of female CD1 mice receiving crocetin plus CPM increased when compared with CPM alone and similar to AS101, whose protective effects are known. SIRT1 increased in CPM mouse ovaries revealing the occurrence of OS. Similarly, mitochondrial SIRT3 rose, whilst SOD2 and the mitochondrial biogenesis activator PGC1-α decreased, suggesting the occurrence of mitochondrial damage. Crocetin and AS101 administration prevented SIRT1 burst suggesting that preservation of redox balance can help the ovary to counteract ovarian damage by CPM. Decreased SIRT3 and increased SOD2 and PGC1-α in mice receiving crocetin or AS101 prior to CPM provide evidence for mitochondrial protection. Present results improve the knowledge of ovarian damage by CPM and may help to develop interventions for preserving fertility in cancer patients

Delivery status of the ELI-NP gamma beam system

International audienceThe ELI-NP GBS is a high intensity and monochromatic gamma source under construction in Magurele (Romania). The design and construction of the Gamma Beam System complex as well as the integration of the technical plants and the commissioning of the overall facility, was awarded to the Eurogammas Consortium in March 2014. The delivery of the facility has been planned in for 4 stages and the first one was fulfilled in October 31st 2015. The engineering aspects related to the delivery stage 1 are presented

Long Term Running Biphasically Improves Methylglyoxal-Related Metabolism, Redox Homeostasis and Neurotrophic Support within Adult Mouse Brain Cortex

Oxidative stress and neurotrophic support decline seem to be crucially involved in brain aging. Emerging evidences indicate the pro-oxidant methylglyoxal (MG) as a key player in the age-related dicarbonyl stress and molecular damage within the central nervous system. Although exercise promotes the overproduction of reactive oxygen species, habitual exercise may retard cellular aging and reduce the age-dependent cognitive decline through hormetic adaptations, yet molecular mechanisms underlying beneficial effects of exercise are still largely unclear. In particular, whereas adaptive responses induced by exercise initiated in youth have been broadly investigated, the effects of chronic and moderate exercise begun in adult age on biochemical hallmarks of very early senescence in mammal brains have not been extensively studied. This research investigated whether a long-term, forced and moderate running initiated in adult age may affect the interplay between the redox-related profile and the oxidative-/MG-dependent molecular damage patterns in CD1 female mice cortices; as well, we investigated possible exercise-induced effects on the activity of the brain derived neurotrophic factor (BDNF)-dependent pathway. Our findings suggested that after a transient imbalance in almost all parameters investigated, the lately-initiated exercise regimen strongly reduced molecular damage profiles in brains of adult mice, by enhancing activities of the main ROS- and MG-targeting scavenging systems, as well as by preserving the BDNF-dependent signaling through the transition from adult to middle age