Effect of 1\u3b1,25(OH)2 vitamin D3 in mutant P53 glioblastoma cells: Involvement of neutral sphingomyelinase1

Glioblastoma is one the most aggressive primary brain tumors in adults, and, despite the fact that radiation and chemotherapy after surgical approaches have been the treatments increasing the survival rates, the prognosis of patients remains poor. Today, the attention is focused on highlighting complementary treatments that can be helpful in improving the classic therapeutic approaches. It is known that 1\u3b1,25(OH)2 vitamin D3, a molecule involved in bone metabolism, has many serendipidy effects in cells. It targets normal and cancer cells via genomic pathway by vitamin D3 receptor or via non-genomic pathways. To interrogate possible functions of 1\u3b1,25(OH)2 vitamin D3 in multiforme glioblastoma, we used three cell lines, wild-type p53 GL15 and mutant p53 U251 and LN18 cells. We demonstrated that 1\u3b1,25(OH)2 vitamin D3 acts via vitamin D receptor in GL15 cells and via neutral sphingomyelinase1, with an enrichment of ceramide pool, in U251 and LN18 cells. Changes in sphingomyelin/ceramide content were considered to be possibly responsible for the differentiating and antiproliferative effect of 1\u3b1,25(OH)2 vitamin D in U251 and LN18 cells, as shown, respectively, in vitro by immunofluorescence and in vivo by experiments of xenotransplantation in eggs. This is the first time 1\u3b1,25(OH)2 vitamin D3 is interrogated for the response of multiforme glioblastoma cells in dependence on the p53 mutation, and the results define neutral sphingomyelinase1 as a signaling effector

Effects of Goji berries supplementation on the productive performance of rabbit

Abstract Recognized by the traditional medicine and recent scientific research studies, Lycium barbarum berries (Goji berries) have beneficial effects on human and animal health. The aim of our study was to evaluate the effects of Goji berries on the productive performance of rabbits. One month before insemination, 60 New Zealand White does were randomly assigned to one of the following 3 dietary treatments: commercial standard diet (C); C supplemented with 1% Goji berries (LG); and C supplemented with 3% Goji berries (HG). After weaning up to 91 days of age, 15 randomly selected rabbits/group were fed the same diet as the mothers (C, LG, and HG). Non-pregnant and lactating does of C group showed the highest feed intake (P < 0.01), although no significant differences in body weight (BW) were observed between groups. Nutritional treatment did not affect the offspring's feed intake. However, the rabbits fed with Goji supplementation showed not only higher mean BW both during growth (P < 0.001) and at slaughter (P < 0.01), but also better feed conversion ratio (FCR; P < 0.01) than the control group. Rabbits of LG group showed the best performances in the pre-weaning period which was probably related to the highest milk production of the LG does (P < 0.001). Indeed, LG group showed lower pre-weaning mortality (P < 0.05), higher litter size (P < 0.05), and higher litter weight (P < 0.05) at day 18 as well as higher litter size at weaning (P = 0.05) compared to C group. In conclusion, the present study demonstrates that a low percentage of dietary supplementation with Goji berry improves both reproductive and productive traits of rabbits. Although further studies are needed, our study paves the way for the use of Goji berries in the rabbit nutrition

Relationship between fatty acids composition/antioxidant potential of breast milk and maternal diet: Comparison with infant formulas

The fatty acid composition of human breast milk is relevant for the energy, immunity and eicosanoid production in infants. Additionally, the antioxidant properties of foods are essential for human health. Therefore, in the present study we aimed to investigate the relationship between maternal diet and fatty acids composition as well as the antioxidant potential of breast milk from donors to human milk bank of Perugia\u2019s hospital, Italy. Results were compared with infant formulas. We observed increased levels of total fatty acids and, in particular, saturated and monounsaturated fatty acids in milk from mothers fed on a vegetable and fruit-rich diet compared with a Mediterranean diet. In the same milk, a reduced antioxidant potential was found. All infant formulas resulted in richer total fatty acid content than human breast milk. Only some formulas were qualitatively similar to breast milk. Of note, the antioxidant potential of the formulas was higher or lower than the human milk with the exception of one sample. The antioxidant potential of four formulas was very high. Dietary supplementation with antioxidants has been shown to have a teratogenic effect and to increase the formation of metastases in adult. There are no data on the effects of excess antioxidants in the infants, but the possibility that they can be harmful cannot be excluded

Acid and neutral sphingomyelinase behavior in radiation-induced liver pyroptosis and in the protective/preventive role of rMnSOD

Sphingomyelins (SMs) are a class of relevant bioactive molecules that act as key modulators of different cellular processes, such as growth arrest, exosome formation, and the inflammatory response influenced by many environmental conditions, leading to pyroptosis, a form of programmed cell death due to Caspase-1 involvement. To study liver pyroptosis and hepatic SM metabolism via both lysosomal acid SMase (aSMase) and endoplasmic reticulum/nucleus neutral SMase (nSMase) during the exposure of mice to radiation and to ascertain if this process can be modulated by protective molecules, we used an experimental design (previously used by us) to evaluate the effects of both ionizing radiation and a specific protective molecule (rMnSOD) in the brain in collaboration with the Joint Institute for Nuclear Research, Dubna (Russia). As shown by the Caspase-1 immunostaining of the liver sections, the radiation resulted in the loss of the normal cell structure alongside a progressive and dose-dependent increase of the labelling, treatment, and pretreatment with rMnSOD, which had a significant protective effect on the livers. SM metabolic analyses, performed on aSMase and nSMase gene expression, as well as protein content and activity, proved that rMnSOD was able to significantly reduce radiation-induced damage by playing both a protective role via aSMase and a preventive role via nSMase

Neutral sphingomyelinase modulation in the protective/preventive role of rMnSOD from radiation-induced damage in the brain

17Studies on the relationship between reactive oxygen species (ROS)/manganese superoxide dismutase (MnSOD) and sphingomyelinase (SMase) are controversial. It has been demonstrated that SMase increases the intracellular ROS level and induces gene expression for MnSOD protein. On the other hand, some authors showed that ROS modulate the activation of SMase. The human recombinant manganese superoxide dismutase (rMnSOD) exerting a radioprotective effect on normal cells, qualifies as a possible pharmaceutical tool to prevent and/or cure damages derived from accidental exposure to ionizing radiation. This study aimed to identify neutral SMase (nSMase) as novel molecule connecting rMnSOD to its radiation protective effects. We used a new, and to this date, unique, experimental model to assess the effect of both radiation and rMnSOD in the brain of mice, within a collaborative project among Italian research groups and the Joint Institute for Nuclear Research, Dubna (Russia). Mice were exposed to a set of minor γ radiation and neutrons and a spectrum of neutrons, simulating the radiation levels to which cosmonauts will be exposed during deep-space, long-term missions. Groups of mice were treated or not-treated (controls) with daily subcutaneous injections of rMnSOD during a period of 10 days. An additional group of mice was also pretreated with rMnSOD for three days before irradiation, as a model for preventive measures. We demonstrate that rMnSOD significantly protects the midbrain cells from radiation-induced damage, inducing a strong upregulation of nSMase gene and protein expression. Pretreatment with rMnSOD before irradiation protects the brain with a value of very high nSMase activity, indicating that high levels of activity might be sufficient to exert the rMnSOD preventive role. In conclusion, the protective effect of rMnSOD from radiation-induced brain damage may require nSMase enzyme.openopenCataldi S.; Borrelli A.; Ceccarini M.R.; Nakashidze I.; Codini M.; Belov O.; Ivanov A.; Krasavin E.; Ferri I.; Conte C.; Patria F.F.; Traina G.; Beccari T.; Mancini A.; Curcio F.; Ambesi-Impiombato F.S.; Albi E.Cataldi, S.; Borrelli, A.; Ceccarini, M. R.; Nakashidze, I.; Codini, M.; Belov, O.; Ivanov, A.; Krasavin, E.; Ferri, I.; Conte, C.; Patria, F. F.; Traina, G.; Beccari, T.; Mancini, A.; Curcio, F.; Ambesi-Impiombato, F. S.; Albi, E

Citizen to Stay or Citizen to Go? Naturalization, Security, and Mobility of Migrants in Italy

https://doi.org/10.1080/15562948.2016.1208316We analyze the relation between naturalization, mobility, and security through 50 in-depth interviews with migrants of different origins living in two Italian regions. We show how migrants pursue naturalization both to protect themselves against bureaucracy and deportation and to move to a third country. The second migration is motivated by improving one's conditions, forced by the economic crisis, or completes the original migratory project once a strong passport is obtained. We argue that citizenship is not essentially linked to either stability or mobility and that mobility should be understood as neither exceptional nor always chosen

Risultati preliminari delle indagini archeologiche ed etnografiche presso il sito di Togolok 1

Modern Turkmenistan is mainly constituted by a desert landscape, yet despite its harsh climate, cultures have been able to construct networks of water channels since the Bronze Age. This has resulted in a man-made landscape that integrates towns and villages. Extensive surveys and recent archaeological excavations have highlighted that between 2400 and 2100 BC (Namazga V period), the region of the Murghab alluvial fan was characterised by the development of complex urban societies. However, starting from the Late Bronze Age, a new group of mobile pastoralists appeared in the Murghab region and settled along the edges of the sedentary sites. Although their presence is well-attested both by survey and excavation data, their degree of interaction with the sedentary farmers is still debated. In modern Turkmenistan, semi-mobile shepherds continue to drive their cattle across the Murghab, using mobile camps for different months. This paper presents the preliminary results of the excavation of the sedentary site of Togolok 1, as well as the first ethnographic study of the mobile communities of the Murghab region