The response of the algae Fucus virsoides (Fucales, Ochrophyta) to Roundup® solution exposure: A metabolomics approach

8noGlyphosate, as a broad-spectrum herbicide, is frequently detected in water and several studies have investigated its effects on several freshwater aquatic organisms. Yet, only few investigations have been performed on marine macroalgae. Here, we studied both the metabolomics responses and the effect on primary production in the endemic brown algae Fucus virsoides exposed to different concentration (0, 0.5, 1.5 and 2.5 mg L−1) of a commercial glyphosate-based herbicide, namely Roundup®. Our results show that Roundup® significantly reduced quantum yield of photosynthesis (Fv/Fm) and caused alteration in the metabolomic profiles of exposed thalli compared to controls. Together with the decrease in the aromatic amino acids (phenylalanine and tyrosine), an increase in shikimate content was detected. The branched-amino acids differently varied according to levels of herbicide exposure, as well as observed for the content of choline, formate, glucose, malonate and fumarate. Our results suggest that marine primary producers could be largely affected by the agricultural land use, this asking for further studies addressing the ecosystem-level effects of glyphosate-based herbicides in coastal waters.partially_openopenFelline, Serena; Del Coco, Laura; Kaleb, Sara; Guarnieri, Giuseppe; Fraschetti, Simonetta; Terlizzi, Antonio; Fanizzi, Francesco Paolo; Falace, AnnalisaFelline, Serena; Del Coco, Laura; Kaleb, Sara; Guarnieri, Giuseppe; Fraschetti, Simonetta; Terlizzi, Antonio; Fanizzi, Francesco Paolo; Falace, Annalis

Chronic oleoylethanolamide treatment decreases hepatic triacylglycerol level in rat liver by a pparγ/srebp-mediated suppression of fatty acid and triacylglycerol synthesis

none11noOleoylethanolamide (OEA) is a naturally occurring bioactive lipid belonging to the family of N-acylethanolamides. A variety of beneficial effects have been attributed to OEA, although the greater interest is due to its potential role in the treatment of obesity, fatty liver, and eating-related disorders. To better clarify the mechanism of the antiadipogenic effect of OEA in the liver, using a lipidomic study performed by1H-NMR, LC-MS/MS and thin-layer chromatography analyses we evaluated the whole lipid composition of rat liver, following a two-week daily treatment of OEA (10 mg kg−1 i.p.). We found that OEA induced a significant reduction in hepatic triacylglycerol (TAG) content and significant changes in sphingolipid composition and ceramidase activity. We associated the antiadipogenic effect of OEA to decreased activity and expression of key enzymes involved in fatty acid and TAG syntheses, such as acetyl-CoA carboxylase, fatty acid synthase, diacylglycerol acyltransferase, and stearoyl-CoA desaturase 1. Moreover, we found that both SREBP-1 and PPARγ protein expression were significantly reduced in the liver of OEA-treated rats. Our findings add significant and important insights into the molecular mechanism of OEA on hepatic adipogenesis, and suggest a possible link between the OEA-induced changes in sphingolipid metabolism and suppression of hepatic TAG level.openRomano A.; Friuli M.; Del Coco L.; Longo S.; Vergara D.; Del Boccio P.; Valentinuzzi S.; Cicalini I.; Fanizzi F.P.; Gaetani S.; Giudetti A.M.Romano, A.; Friuli, M.; Del Coco, L.; Longo, S.; Vergara, D.; Del Boccio, P.; Valentinuzzi, S.; Cicalini, I.; Fanizzi, F. P.; Gaetani, S.; Giudetti, A. M

Treated Unconventional Waters Combined with Different Irrigation Strategies Affect 1 H NMR Metabolic Profile of a Monovarietal Extra Virgin Olive Oil

none8noThe agricultural sector is facing a decrease in water supply and water quality at a global level and this is a problem that strictly affects all the Mediterranean olive growing areas. The aim of this work was to evaluate, for the first time, by NMR Spectroscopy and multivariate data analysis the metabolic profiling of the oils produced under different irrigation schemes. Arbosana olive oils were obtained from the use of saline reclaimed water (RW) and treated municipal wastewater (DW), combined with: full irrigation (FI) and regulated deficit irrigation (RDI). The results show a higher relative content of saturated fatty acids in EVOOs obtained from RDI strategy, regardless of the water source. Moreover, an increase in unsaturated fatty acids, a ω6/ω3 ratio content was observed in EVOOs obtained from RW when compared with DW water. Furthermore, the RW–RDI showed an increase in secoiridoid derivatives and hydroperoxides with respect to DW–RDI. A sustainable irrigation management, by combining a deficit irrigation strategy and saline reclaimed water source, could be crucial in order to overcome the problem of water scarcity and to guarantee the olive oil nutraceutical properties. The1 H NMR-based metabolomic approach proved a powerful and versatile tool for this specific investigation.openAngile F.; Vivaldi G.A.; Girelli C.R.; Del Coco L.; Caponio G.; Lopriore G.; Fanizzi F.P.; Camposeo S.Angile, F.; Vivaldi, G. A.; Girelli, C. R.; Del Coco, L.; Caponio, G.; Lopriore, G.; Fanizzi, F. P.; Camposeo, S

The addition of rituximab to fludarabine improves clinical outcome in untreated patients with ZAP-70-negative chronic lymphocytic leukemia.

Clinical trials of monoclonal antibodies in combination with chemotherapy have reported previously unattained response rates in patients with B-cell chronic lymphocytic leukemia (B-CLL); however, the analysis of ZAP-70 protein and/or CD38 may explain better the discordant outcomes independent of treatment

DNA Damage Response Protein CHK2 Regulates Metabolism in Liver Cancer

Defective mitosis with chromosome missegregation can have a dramatic effect on genome integrity by causing DNA damage, activation of the DNA damage response (DDR), and chromosomal instability. Although this is an energy-dependent process, mechanisms linking DDR to cellular metabolism are unknown. Here we show that checkpoint kinase 2 (CHK2), a central effector of DDR, regulates cellular energy production by affecting glycolysis and mitochondrial functions. Patients with hepatocellular carcinoma (HCC) had increased CHK2 mRNA in blood, which was associated with elevated tricarboxylic acid cycle (TCA) metabolites. CHK2 controlled expression of succinate dehydrogenase (SDH) and intervened with mitochondrial functions. DNA damage and CHK2 promoted SDH activity marked by increased succinate oxidation through the TCA cycle; this was confirmed in a transgenic model of HCC with elevated DNA damage. Mitochondrial analysis identified CHK2-controlled expression of SDH as key in sustaining reactive oxygen species production. Cells with DNA damage and elevated CHK2 relied significantly on glycolysis for ATP production due to dysfunctional mitochondria, which was abolished by CHK2 knockdown. This represents a vulnerability created by the DNA damage response that could be exploited for development of new therapies

Toward optimization of postremission therapy for residual disease-positive patients with acute myeloid leukemia

Purpose:Despite the identification of several baseline prognostic indicators, the outcome of patients with acute myeloid leukemia (AML) is generally heterogeneous. The effects of autologous (AuSCT) or allogeneic stem-cell transplantation (SCT) are still under evaluation. Minimal residual disease (MRD) states may be essential for assigning patients to therapy-dependent risk categories. Patients and Methods: By multiparametric flow cytometry, we assessed the levels of MRD in 142 patients with AML who achieved complete remission after intensive chemotherapy. Results: A level of 3.5 x 10(-4) residual leukemia cells (RLCs) after consolidation therapy was established to identify MRD-negative and MRD-positive cases, with 5-year relapse-free survival (RFS) rates of 60% and 16%, respectively (P <.0001) and overall survival (OS) rates of 62% and 23%, respectively (P=.0001). Of patients (n = 77) who underwent a transplantation procedure (56 AuSCT and 21 SCT procedures); 42 patients (55%) were MRD positive (28 patients who underwent AuSCT and 14 patients who underwent SCT) and 35 patients (45%) were MRD negative (28 patients who underwent AuSCT and seven who underwent SCT). MRD-negative patients had a favorable prognosis, with only eight (22%) of 35 patients experiencing relapse, whereas 29 (69%) of 42 MRD-positive patients experienced relapse (P <.0001). In this high-risk group of 42 patients, we observed that 23 (82%) of 28 of those who underwent AuSCT experienced relapse, whereas six (43%) of 14 who underwent SCT experienced relapse (P=.014). Patients who underwent SCT also had a higher likelihood of RFS (47% v 14%). Conclusion A threshold of 3.5 x 10(-4) RLCs postconsolidation is critical for predicting disease outcome. MRD-negative patients have a good outcome regardless of the type of transplant they receive. In the MRD-positive group, AuSCT does not improve prognosis and SCT represents the primary option

Effects of a diet based on foods from symbiotic agriculture on the gut microbiota of subjects at risk for metabolic syndrome

none18noDiet is a major driver of gut microbiota variation and plays a role in metabolic disorders, including metabolic syndrome (MS). Mycorrhized foods from symbiotic agriculture (SA) exhibit improved nutritional properties, but potential benefits have never been investigated in humans. We conducted a pilot interventional study on 60 adults with ≥ 1 risk factors for MS, of whom 33 consumed SA‐derived fresh foods and 27 received probiotics over 30 days, with a 15‐day follow‐up. Stool, urine and blood were collected over time to explore changes in gut microbiota, metabolome, and biochemical, inflammatory and immunologic parameters; previous dietary habits were investigated through a validated food‐frequency questionnaire. The baseline microbiota showed alterations typical of metabolic disorders, mainly an increase in Coriobacteriaceae and a decrease in health-associated taxa, which were partly reversed after the SA‐based diet. Improvements were observed in metabolome, MS presence (two out of six subjects no longer had MS) or components. Changes were more pronounced with less healthy baseline diets. Probiotics had a marginal, not entirely fa-vorable, effect, although one out of three subjects no longer suffered from MS. These findings sug-gest that improved dietary patterns can modulate the host microbiota and metabolome, counteract-ing the risk of developing MS.openTurroni S.; Petracci E.; Edefonti V.; Giudetti A.M.; D'amico F.; Paganelli L.; Giovannetti G.; Del Coco L.; Fanizzi F.P.; Rampelli S.; Guerra D.; Rengucci C.; Bulgarelli J.; Tazzari M.; Pellegrini N.; Ferraroni M.; Nanni O.; Serra P.Turroni, S.; Petracci, E.; Edefonti, V.; Giudetti, A. M.; D'Amico, F.; Paganelli, L.; Giovannetti, G.; Del Coco, L.; Fanizzi, F. P.; Rampelli, S.; Guerra, D.; Rengucci, C.; Bulgarelli, J.; Tazzari, M.; Pellegrini, N.; Ferraroni, M.; Nanni, O.; Serra, P

Effects of a diet based on foods from symbiotic agriculture on the gut microbiota of subjects at risk for metabolic syndrome

Diet is a major driver of gut microbiota variation and plays a role in metabolic disorders, including metabolic syndrome (MS). Mycorrhized foods from symbiotic agriculture (SA) exhibit improved nutritional properties, but potential benefits have never been investigated in humans. We conducted a pilot interventional study on 60 adults with 65 1 risk factors for MS, of whom 33 consumed SA\u2010derived fresh foods and 27 received probiotics over 30 days, with a 15\u2010day follow\u2010up. Stool, urine and blood were collected over time to explore changes in gut microbiota, metabolome, and biochemical, inflammatory and immunologic parameters; previous dietary habits were investigated through a validated food\u2010frequency questionnaire. The baseline microbiota showed alterations typical of metabolic disorders, mainly an increase in Coriobacteriaceae and a decrease in health-associated taxa, which were partly reversed after the SA\u2010based diet. Improvements were observed in metabolome, MS presence (two out of six subjects no longer had MS) or components. Changes were more pronounced with less healthy baseline diets. Probiotics had a marginal, not entirely fa-vorable, effect, although one out of three subjects no longer suffered from MS. These findings sug-gest that improved dietary patterns can modulate the host microbiota and metabolome, counteract-ing the risk of developing MS

Progress towards sustainable control of xylella fastidiosa subsp. Pauca in olive groves of salento (apulia, italy)

Xylella fastidiosa subsp. pauca is the causal agent of “olive quick decline syndrome” in Salento (Apulia, Italy). On April 2015, we started interdisciplinary studies to provide a sustainable control strategy for this pathogen that threatens the multi-millennial olive agroecosystem of Salento. Confocal laser scanning microscopy and fluorescence quantification showed that a zinc-copper-citric acid biocomplex—Dentamet® —reached the olive xylem tissue either after the spraying of the canopy or injection into the trunk, demonstrating its effective systemicity. The biocomplex showed in vitro bactericidal activity towards all X. fastidiosa subspecies. A mid-term evaluation of the control strategy performed in some olive groves of Salento indicated that this biocomplex significantly reduced both the symptoms and X. f. subsp. pauca cell concentration within the leaves of the local cultivars Ogliarola salentina and Cellina di Nardò. The treated trees started again to yield. A1 H-NMR metabolomic approach revealed, upon the treatments, a consistent increase in malic acid and γ-aminobutyrate for Ogliarola salentina and Cellina di Nardò trees, respectively. A novel endotherapy technique allowed injection of Dentamet® at low pressure directly into the vascular system of the tree and is currently under study for the promotion of resprouting in severely attacked trees. There are currently more than 700 ha of olive groves in Salento where this strategy is being applied to control X. f. subsp. pauca. These results collectively demonstrate an efficient, simple, low-cost, and environmentally sustainable strategy to control this pathogen in Salento

Comité Institucional para el Cuidado y Uso de Animales de Laboratorio (CICUAL) de la Facultad de Ciencias Médicas UNLP

En base a la gran cantidad de grupos de trabajo que utilizan animales de laboratorio dentro del ámbito de la Facultad, y teniendo en cuenta la necesidad de realizar un buen control del uso y cuidado de los mismos, en Julio de 2012 se crea el CICUAL de la Fac. de Cs. Médicas (CICUAL-FCM) mediante Resolución 230/12 del HCD. Depende de la Secretaría de Ciencia y Técnica de la FCM y entre sus integrantes se incluyen Médicos Veterinarios, Investigadores con experiencia en experimentación con animales y Personal de la Comisión de Bioterio de la Facultad. Tiene por objetivos: Revisar, aprobar y registrar los protocolos de uso experimental y cuidado de los animales de laboratorio; supervisar el cumplimiento de las normativas para el cuidado y uso de animales de laboratorio, asesorar a los investigadores y docentes sobre los principios 3R (refinamiento, reducción y reemplazo), capacitar al personal e informar lo actuado.Facultad de Ciencias Médica