Inhibition of nitric oxide biosynthesis by anthocyanin fraction of blackberry extract.

Anthocyanins are natural colorant belonging to the flavonoid family, widely distributed among flowers, fruits, and vegetables. Some flavonoids have been found to possess anticarcinogenic, cytotoxic, cytostatic, antioxidant, and anti-inflammatory properties. Since increased nitric oxide (NO) plays a role in inflammation, we have investigated whether the pharmacological activity of the anthocyanin fraction of a blackberry extract (cyanidin-3-O-glucoside representing about 88% of the total anthocyanin content) was due to the suppression of NO synthesis. The markedly increased production of nitrites by stimulation of J774 cells with lipopolysaccharide (LPS) for 24 h was concentration-dependently inhibited by the anthocyanin fraction (11, 22, 45, and 90 μg/ml) of the extract. Moreover, this inhibition was dependent on a dual mechanism, since the extract attenuated iNOS protein expression and decreased the iNOS activity in lungs from LPS-stimulated rats. Inhibition of iNOS protein expression appeared to be at the transcriptional level, since the extract and similarly cyanidin-3-O-glucoside (10, 20, 40, and 80 μg/ml, amounts corresponding to the concentrations present in the extract) decreased LPS-induced NF-κB activation, through inhibition of IκBα degradation, and reduced ERK-1/2 phosphorylation in a concentration-dependent manner. In conclusion, our study demonstrates that at least some part of the anti-inflammatory activity of blackberry extract is due to the suppression of NO production by cyanidin-3-O-glucoside, which is the main anthocyanin present in the extract. The mechanism of this inhibition seems to be due to an action on the expression/activity of the enzyme. In particular, the protein expression was inhibited through the attenuation of NF-κB and/or MAPK activatio

The local order of supercooled water in solution with LiCl studied by NMR proton chemical shift

We study by means of Nuclear Magnetic Resonance (NMR) spectroscopy the local order of water molecules in solution with lithium chloride at eutectic concentration. In particular, by measuring the proton chemical shift as a function of the temperature in the interval 203K < T < 320K, we observe a net change at about 235 K. We ascribe this result to the increase of the hydrogen bond interaction that on decreasing the temperature favors the formation of the network that characterizes the low density liquid phase of water. Furthermore, the Gaussian deconvolution of the NMR peak allows the investigation of the mutual difference between the chemical shift of water solvating lithium and chlorine individually. The thermal behavior of this quantity confirms previous results about the role of the temperature in the solvation mechanisms down to about 225 K. This temperature coincides with that of the so-called Widom line for water supporting the liquid-liquid transition hypothesis

Preface: Earth Observation for Integrated Water and Basin Management: Challenges for adaptation to a changing environment

Integrated river basin management involves a sound knowledge of water and land interactions, and impacts from and feedbacks to human activity. Remote sensing has been an efficient and increasingly promising means of gathering direct information of the Earth surface, as well as information on water and energy fluxes. The recent generation of high-resolution sensors offers a huge potential for monitoring, assessing, and modelling our changing environment in a context of uncertainty about how future climate conditions will affect the current water resource and basin management framework. Moreover, large amounts of data are now available posing a challenging opportunity to the scientific community for both exploring and transforming these data into readily usable information products for different end-users in our societies

Green Extraction Approaches for Carotenoids and Esters: Characterization of Native Composition from Orange Peel

Abstract: Orange peel is a by-product produced in large amounts that acts as a source of natural pigments such as carotenoids. Xanthophylls, the main carotenoid class found in citrus fruit, can be present in its free form or esterified with fatty acids, forming esters. This esterification modifies the compound’s chemical properties, affecting their bioavailability in the human body, and making it important to characterize the native carotenoid composition of food matrices. We aimed to evaluate the non-saponified carotenoid extracts of orange peel (cv. Pera) obtained using alternative green approaches: extraction with ionic liquid (IL), analyzed by high performance liquid chromatography coupled to a diode array detector with atmospheric pressure chemical ionization and mass spectrometry HPLC-DAD-APCI-MS, and supercritical fluid extraction (SFE), followed by supercritical fluid chromatography with atmospheric pressure chemical ionization and triple quadrupole mass spectrometry detection (SFC-APCI/QqQ/MS) in an online system. Both alternative green methods were successfully applied, allowing the total identification of five free carotenoids, one apocarotenoid, seven monoesters, and 11 diesters in the extract obtained with IL and analyzed by HPLC-DAD-APCI-MS, and nine free carotenoids, six carotenoids esters, 19 apocarotenoids, and eight apo-esters with the SFE-SFC-APCI/QqQ/MS approach, including several free apocarotenoids and apocarotenoid esters identified for the first time in oranges, and particularly in the Pera variety, which could be used as a fruit authenticity parameter.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Bioscience Department, Universidade Federal de São Paulo, Rua Silva Jardin 136, 11015-020 Santos, BrazilDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Polo Annunziata, Viale Annunziata, 98168 Messina, ItalyDepartment of Mathematical and Computer Science, Physical Sciences and Earth Sciences, University of Messina, 98168 Messina, ItalyFederal Institute of São Paulo, Av. Clara Gianotti de Souza 5180, 11900-000 Registro, BrazilChemistry Department, Federal University of São Carlos, Rodovia Washington Luíz, Km 235, 13565-905 São Carlos, BrazilChromaleont s.r.l., c/o Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyBeSep s.r.l., c/o Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, ItalyUnit of Food Science and Nutrition, Department of Medicine, University Campus Bio-Medico of Rome, 00128 Rome, ItalyDepartment of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, Via Consolare Valeria, 98125 Messina, ItalyBioscience Department, Universidade Federal de São Paulo, Rua Silva Jardin 136, 11015-020 Santos, BrazilFAPESP: 2015/26789-5FAPESP: 2016/18910-1FAPESP: 2017/20861-1FAPESP: 2019/25303-

Insulin Reduces Cerebral Ischemia/Reperfusion Injury in the Hippocampus of Diabetic Rats: A Role for Glycogen Synthase Kinase-3β

OBJECTIVE—There is evidence that insulin reduces brain injury evoked by ischemia/reperfusion (I/R). However, the molecular mechanisms underlying the protective effects of insulin remain unknown. Insulin is a well-known inhibitor of glycogen synthase kinase-3β (GSK-3β). Here, we investigate the role of GSK-3β inhibition on I/R-induced cerebral injury in a rat model of insulinopenic diabetes

Genetic dissection of agronomic and quality traits based on association mapping and genomic selection approaches in durum wheat grown in Southern Spain

Climatic conditions affect the growth, development and final crop production. As wheat is of paramount importance as a staple crop in the human diet, there is a growing need to study its abiotic stress adaptation through the performance of key breeding traits. New and complementary approaches, such as genome-wide association studies (GWAS) and genomic selection (GS), are used for the dissection of different agronomic traits. The present study focused on the dissection of agronomic and quality traits of interest (initial agronomic score, yield, gluten index, sedimentation index, specific weight, whole grain protein and yellow colour) assessed in a panel of 179 durum wheat lines (Triticum durum Desf.), grown under rainfed conditions in different Mediterranean environments in Southern Spain (Andalusia). The findings show a total of 37 marker-trait associations (MTAs) which affect phenotype expression for three quality traits (specific weight, gluten and sedimentation indexes). MTAs could be mapped on the A and B durum wheat subgenomes (on chromosomes 1A, 1B, 2A, 2B and 3A) through the recently available bread wheat reference assembly (IWGSC RefSeqv1). Two of the MTAs found for quality traits (gluten index and SDS) corresponded to the known Glu-B1 and Glu-A1 loci, for which candidate genes corresponding to high molecular weight glutenin subunits could be located. The GS prediction ability values obtained from the breeding materials analyzed showed promising results for traits as grain protein content, sedimentation and gluten indexes, which can be used in plant breeding programs.Junta de Andalucía (Andalusian Regional Government) P12- AGR-0482FEDER P12- AGR-0482MINECO (Spanish Ministry of Economy, Industry and Competitiveness) AGL2016-77149-C2-1-

SPARC regulation of PMN clearance protects from pristane-induced lupus and rheumatoid arthritis

The secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein with unexpected immunosuppressive function in myeloid cells. We investigated the role of SPARC in autoimmunity using the pristane-induced model of lupus that, in mice, mimics human systemic lupus erythematosus (SLE). Sparc−/− mice developed earlier and more severe renal disease, multi-organ parenchymal damage, and arthritis than the wild-type counterpart. Sparc+/- heterozygous mice showed an intermediate phenotype suggesting Sparc gene dosage in autoimmune-related events. Mechanistically, reduced Sparc expression in neutrophils blocks their clearance by macrophages, through defective delivery of don't-eat-me signals. Dying Sparc−/− neutrophils that escape macrophage scavenging become source of autoantigens for dendritic cell presentation and are a direct stimulation for γδT cells. Gene profile analysis of knee synovial biopsies from SLE-associated arthritis showed an inverse correlation between SPARC and key autoimmune genes. These results point to SPARC down-regulation as a leading event characterizing SLE and rheumatoid arthritis pathogenesis

Effect of the water stress on gross primary production modeling of a Mediterranean oak savanna ecosystem

Dehesa ecosystem consists of widely-spaced oak trees combined with crops, pasture and Mediterranean shrubs. It is located in the southwest of the Iberian Peninsula, where water scarcity is recurrent, severely affecting the multiple productions and services of the ecosystem. Upscaling in situ Gross Primary Production (GPP) estimates in these areas is challenging for regional and global studies, given the significant spatial variability of plant functional types and the vegetation stresses usually present. The estimation of GPP is often addressed using light use efficiency models (LUE-models). Under soil water deficit conditions, biomass production is reduced below its potential rate. This work investigates the effect of different parameterizations to account for water stress on GPP estimates and their agreement with observations. Ground measurements of GPP are obtained using an Eddy Covariance (EC) system installed over an experimental site located in Córdoba, Spain. GPP is estimated with a LUE-model in the footprint of the EC tower using several approaches: a fixed value taken from previous literature; a fixed value modified by daily weather conditions; and both formulations modified by an additional coefficient to explicitly consider the vegetation water stress. The preliminary results obtained during two hydrological years (2015/2016 and 2016/2017) are compared, focusing on specific wet and dry periods.</p

Perfusion of isolated rat kidney with Mesenchymal Stromal Cells/Extracellular Vesicles prevents ischaemic injury

Kidney donation after circulatory death (DCD) is a less than ideal option to meet organ shortages. Hypothermic machine perfusion (HMP) with Belzer solution (BS) improves the viability of DCD kidneys, although the graft clinical course remains critical. Mesenchymal stromal cells (MSC) promote tissue repair by releasing extracellular vesicles (EV). We evaluated whether delivering MSC-/MSC-derived EV during HMP protects rat DCD kidneys from ischaemic injury and investigated the underlying pathogenic mechanisms. Warm ischaemic isolated kidneys were cold-perfused (4 hrs) with BS, BS supplemented with MSC or EV. Renal damage was evaluated by histology and renal gene expression by microarray analysis, RT-PCR. Malondialdehyde, lactate, LDH, glucose and pyruvate were measured in the effluent fluid. MSC-/EV-treated kidneys showed significantly less global ischaemic damage. In the MSC/EV groups, there was up-regulation of three genes encoding enzymes known to improve cell energy metabolism and three genes encoding proteins involved in ion membrane transport. In the effluent fluid, lactate, LDH, MDA and glucose were significantly lower and pyruvate higher in MSC/EV kidneys as compared with BS, suggesting the larger use of energy substrates by MSC/EV kidneys. The addition of MSC/EV to BS during HMP protects the kidney from ischaemic injury by preserving the enzymatic machinery essential for cell viability and protects the kidney from reperfusion damage

Integrative analysis of the genomic and transcriptomic landscape of double-refractory multiple myeloma

In multiple myeloma, novel treatments with proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs) have prolonged survival but the disease remains incurable. At relapse, next-generation sequencing has shown occasional mutations of drug targets but has failed to identify unifying features that underlie chemotherapy resistance. We studied 42 patients refractory to both PIs and IMiDs. Whole-exome sequencing was performed in 40 patients, and RNA sequencing (RNA-seq) was performed in 27. We found more mutations than were reported at diagnosis and more subclonal mutations, which implies ongoing evolution of the genome of myeloma cells during treatment. The mutational landscape was different from that described in published studies on samples taken at diagnosis. The TP53 pathway was the most frequently inactivated (in 45% of patients). Conversely, point mutations of genes associated with resistance to IMiDs were rare and were always subclonal. Refractory patients were uniquely characterized by having a mutational signature linked to exposure to alkylating agents, whose role in chemotherapy resistance and disease progression remains to be elucidated. RNA-seq analysis showed that treatment or mutations had no influence on clustering, which was instead influenced by karyotypic events. We describe a cluster with both amp(1q) and del(13) characterized by CCND2 upregulation and also overexpression of MCL1, which represents a novel target for experimental treatments. Overall, high-risk features were found in 65% of patients. However, only amp(1q) predicted survival. Gene mutations of IMiD and PI targets are not a preferred mode of drug resistance in myeloma. Chemotherapy resistance of the bulk tumor population is likely attained through differential, yet converging evolution of subclones that are overall variable from patient to patient and within the same patient