1H-NMR metabolomic profile of healthy and osteoarthritic canine synovial fluid before and after UC-II supplementation

The aim of the study was to compare the metabolomic synovial fluid (SF) profile of dogs affected by spontaneous osteoarthritis (OA) and supplemented with undenatured type II collagen (UC-II), with that of healthy control dogs. Client-owned dogs were enrolled in the study and randomized in two different groups, based on the presence/absence of OA (OA group and OA-free group). All dogs were clinically evaluated and underwent SF sampling for 1H-Nuclear Magnetic Resonance spectroscopy (1H-NMR) analysis at time of presentation. All dogs included in OA group were supplemented with UC-II orally administered for 30 days. After this period, they were reassessed (OA-T30). The differences in the 1H-NMR metabolic SFs profiles between groups (OA-free, OA-T0 and OA-T30) were studied. The multivariate statistical analysis performed on SFs under different conditions (OA-T0 vs OA-T30 SFs; OA-T0 vs OA-free SFs and OA-T30 vs OA-free SFs) gave models with excellent goodness of fit and predictive parameters, revealed by a marked separation between groups. β-Hydroxybutyrate was identified as a characteristic compound of osteoarthritic joints, showing the important role of fat metabolism during OA. The absence of β-hydroxybutyrate after UC-II supplementation suggests the supplement’s effectiveness in rebalancing the metabolism inside the joint. The unexpectedly high level of lactate in the OA-free group suggests that lactate could not be considered a good marker for OA. These results prove that 1H-NMR-based metabolomic analysis is a valid tool to study and monitor OA and that UC-II improves clinical symptoms and the SF metabolic profile in OA dog

Harvest year effects on Apulian EVOOs evaluated by (1)H NMR based metabolomics

none5noNine hundred extra virgin olive oils (EVOO) were extracted from individual olive trees of four olive cultivars (Coratina, Cima di Mola, Ogliarola, Peranzana), originating from the provinces of Bari and Foggia (Apulia region, Southern Italy) and collected during two consecutive harvesting seasons (2013/14 and 2014/15). Following genetic identification of individual olive trees, a detailed Apulian EVOO NMR database was built using 900 oils samples obtained from 900 cultivar certified single trees. A study on the olive oil lipid profile was carried out by statistical multivariate analysis (Principal Component Analysis, PCA, Partial Least-Squares Discriminant Analysis, PLS-DA, Orthogonal Partial Least-Squares Discriminant Analysis, OPLS-DA). Influence of cultivar and weather conditions, such as the summer rainfall, on the oil metabolic profile have been evaluated. Mahalanobis distances and J2 criterion have been measured to assess the quality of resulting scores clusters for each cultivar in the two harvesting campaigns. The four studied cultivars showed non homogeneous behavior. Notwithstanding the geographical spread and the wide number of samples, Coratina showed a consistent behavior of its metabolic profile in the two considered harvests. Among the other three Peranzana showed the second more consistent behavior, while Cima di Mola and Ogliarola having the biggest change over the two years.Girelli, Chiara R; Del Coco, Laura; Papadia, Paride; De Pascali, Sandra A; Fanizzi, Francesco PGirelli, CHIARA ROBERTA; DEL COCO, Laura; Papadia, Paride; DE PASCALI, SANDRA ANGELICA; Fanizzi, Francesco Paol

Metabolomic NMR analysis and organoleptic perceptions of pomegranate wines: Influence of cultivar and yeast on the product characteristics

: Pomegranate (Punica granatum L.) fruits are a historical agricultural product of the Mediterranean basin that became increasingly popular in the latest years for being rich in antioxidants and other micronutrients, and are extensively commercialized as fruits, juice, jams and, in some Eastern countries, as a fermented alcoholic beverage. In this work, four different pomegranate wines specifically designed using combinations of two cultivars (Jolly Red and Smith) and two yeast starters with markedly different characteristics (Saccharomyces cerevisiae Clos and Saccharomyces cerevisiae ex-bayanus EC1118) were analyzed. The chemical characterization of the wines together with the originating unfermented juices was performed by 1H NMR spectroscopy metabolomic analysis. The full spectra were used for unsupervised and supervised statistical multivariate analysis (MVA), namely Principal Component Analysis (PCA), Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA), and sparse PCA (SPCA). The MVA of the wines showed a clear discrimination between the cultivars, and a smaller, yet significant, discrimination between the yeasts used. In particular, a higher content of citrate and gallate was observed for the Smith cv. and, on the contrary, a statistically significant higher content of fructose, malate, glycerol, 2,3 butanediol, trigonelline, aromatic amino acids and 4-hydrophenylacetate was observed in Jolly Red pomegranate wines samples. Significant interaction among the pomegranate cultivar and the fermenting yeast was also observed. Sensorial analysis was performed by a panel of testing experts. MVA of tasting data showed that the cultivar significantly affected the organoleptic parameters considered, while the yeast had a minor impact. Correlation analysis between NMR-detected metabolites and organoleptic descriptors identified several potential sensorially-active molecules as those significantly impacting the characteristics of the pomegranate wines

1H-NMR Metabolomics Study after Foliar and Endo-Therapy Treatments of Xylella fastidiosa subsp. pauca Infected Olive Trees: Medium Time Monitoring of Field Experiments

Here we report the medium-term effects of foliar spray and endo-therapy treatments with different doses of a Cu/Zn citric acid biocomplex (Dentamet®) in Xylella fastidiosa infected olive trees of Salento, Apulia region (South-east Italy). Leaf extract samples from field-treated 150 years old olive trees cvs Ogliarola salentina and Cellina di Nardò were studied by 1H NMR-based metabolomics. The result of different applications of Dentamet® endo-therapy after 60, 120 and 180 days in comparison with traditional foliar spray treatment and water injection as a control have been investigated. The metabolic profile analyses, performed by 1H NMR-based metabolomic approach, indicated plant metabolites variations connected to the disease progression such as mannitol, quinic acid, and oleuropein related compounds. The best results, in terms of discrimination of the metabolic profiles with respect to water injection, were found for monthly endo-therapy treatments. Dentamet® foliar application demonstrated more specific time related progressive effectiveness with respect to intravascular treatments. Therefore, besides a possible more effective performance of endo-therapy with respect to foliar treatments, the need of further doses/frequencies trimming to obtain longterm results was also assessed. The present field studies confirmed the indication of Dentamet® effectiveness in metabolic variation induction, potentially linked with reducing the X. fastidiosa subspecies pauca related Olive Quick Decline Syndrome (OQDS) symptoms development

1H-NMR metabolomics reveals a multitarget action of Crithmum maritimum ethyl acetate extract in inhibiting hepatocellular carcinoma cell growth

Hepatocellular carcinoma (HCC) is nowadays the sixth cause of tumour-related deceases worldwide, estimated to become the third in Western countries by 2030. New drugs for HCC treatment still have many adverse effects. Several lines of evidence indicate that plant metabolites offer concrete opportunities for developing new therapeutic strategies for many diseases, including cancer. We previously reported that ethyl acetate extract of a spontaneous edible plant harvested in Apulia, Crithmum maritimum, significantly inhibited cell growth in HCC cells. By 1H-NMR spectroscopy, here we show that Crithmum maritimum ethyl acetate extract counteracts the Warburg effect, by reducing intracellular lactate, inhibits protein anabolism, by decreasing amino acid level, and affects membrane biosynthesis by lowering choline and phosphocholine. Also, we observed an effect on lipid homeostasis, with a reduction in triglycerides, cholesterol, monounsaturated fatty acids (MUFA), and diunsaturated fatty acids (DUFA), and an increase in polyunsaturated fatty acids (PUFA). Taken together, these data demonstrate that Crithmum maritimum-induced cytostasis is exerted through a multi-effect action, targeting key metabolic processes in HCC cells. Overall, our findings highlight the role of Crithmum maritimum as a promising tool for the prevention and the improvement of the therapeutic options for HCC and other types of tumours

Red Blood Cell Morphologic Abnormalities in Patients Hospitalized for COVID-19

Peripheral blood smear is a simple laboratory tool, which remains of invaluable help for diagnosing primary and secondary abnormalities of blood cells despite advances in automated and molecular techniques. Red blood cells (RBCs) abnormalities are known to occur in many viral infections, typically in the form of mild normo-microcytic anemia. While several hematological alterations at automated complete blood count (including neutrophilia, lymphopenia, and increased red cell distribution width—RDW) have been consistently associated with severity of COVID-19, there is scarce information on RBCs morphological abnormalities, mainly as case-reports or small series of patients, which are hardly comparable due to heterogeneity in sampling times and definition of illness severity. We report here a systematic evaluation of RBCs morphology at peripheral blood smear in COVID-19 patients within the first 72 h from hospital admission. One hundred and fifteen patients were included, with detailed collection of other clinical variables and follow-up. A certain degree of abnormalities in RBCs morphology was observed in 75 (65%) patients. Heterogenous alterations were noted, with spiculated cells being the more frequent morphology. The group with >10% RBCs abnormalities had more consistent lymphopenia and thrombocytopenia compared to those without abnormalities or <10% RBCs abnormalities (p < 0.018, and p < 0.021, respectively), thus underpinning a possible association with an overall more sustained immune-inflammatory “stress” hematopoiesis. Follow-up analysis showed a different mortality rate across groups, with the highest rate in those with more frequent RBCs morphological alterations compared to those with <10% or no abnormalities (41.9%, vs. 20.5%, vs. 12.5%, respectively, p = 0.012). Despite the inherent limitations of such simple association, our results point out towards further studies on erythropoiesis alterations in the pathophysiology of COVID-19

A generalization of the Virasoro algebra to arbitrary dimensions

Colored tensor models generalize matrix models in higher dimensions. They admit a 1/N expansion dominated by spherical topologies and exhibit a critical behavior strongly reminiscent of matrix models. In this paper we generalize the colored tensor models to colored models with generic interaction, derive the Schwinger Dyson equations in the large N limit and analyze the associated algebra of constraints satisfied at leading order by the partition function. We show that the constraints form a Lie algebra (indexed by trees) yielding a generalization of the Virasoro algebra in arbitrary dimensions

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. A 1H-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

Bubbles and jackets: new scaling bounds in topological group field theories

We use a reformulation of topological group field theories in 3 and 4 dimensions in terms of variables associated to vertices, in 3d, and edges, in 4d, to obtain new scaling bounds for their Feynman amplitudes. In both 3 and 4 dimensions, we obtain a bubble bound proving the suppression of singular topologies with respect to the first terms in the perturbative expansion (in the cut-off). We also prove a new, stronger jacket bound than the one currently available in the literature. We expect these results to be relevant for other tensorial field theories of this type, as well as for group field theory models for 4d quantum gravity.Comment: v2: Minor modifications to match published versio

Adalimumab and ABP 501 in the Treatment of a Large Cohort of Patients with Inflammatory Arthritis: A Real Life Retrospective Analysis

The recent introduction of ABP 501, an adalimumab biosimilar, in the treatment of rheumatic diseases was supported by a comprehensive comparability exercise with its originator. On the other hand, observational studies comparing adalimumab and ABP 501 in inflammatory arthritis are still lacking. The main aim of this study is to compare the clinical outcomes of the treatment with adalimumab, both the originator and ABP 501, in a large cohort of patients affected by autoimmune arthritis in a real life setting. We retrospectively analysed the baseline characteristics and the retention rate in a cohort of patients who received at least a course of adalimumab (originator or ABP 501) from January 2003 to December 2020. We stratified the study population according to adalimumab use: naive to original (oADA), naive to ABP 501 (bADA) and switched from original to ABP 501 (sADA). The oADA, bADA and sADA groups included, respectively, 724, 129 and 193 patients. In each group, the majority of patients had a diagnosis of rheumatoid arthritis. The total observation period was 9805.6 patient-months. The 18-month retentions rate in oADA, bADA and sADA was, respectively, 81.5%, 84.0% and 88.0% (p > 0.05). The factors influencing the adalimumab retention rate were an axial spondylarthritis diagnosis (Hazard Ratio (HR) 0.70; p = 0.04), switch from oADA to ABP 501 (HR 0.53; p = 0.02) and year of prescription (HR 1.04; p = 0.04). In this retrospective study, patients naive to the adalimumab originator and its biosimilar ABP 501 showed the same retention rate. Patients switching from the originator to biosimilar had a higher retention rate, even though not statistically significant, when compared to naive