FiorGen Foundation

Sesto Fiorentino, Italy

FiorGen Foundation

Sesto Fiorentino, Italy
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Aimetti M.,University of Turin | Cacciatore S.,University of Florence | Cacciatore S.,FiorGen Foundation | Graziano A.,University of Turin | And 2 more authors.
Metabolomics | Year: 2012

The diagnoses of periodontal diseases (PD) are primarily based on clinical examination and radiographic parameters. In this pilot exploration we want to supply some evidence whether metabonomic profiling of saliva samples can provide a signature of the disease. Saliva samples were analyzed by Nuclear Magnetic Resonance (NMR) metabonomics from 22 healthy subjects (HS) and 32 patients with clinic and radiographic diagnosis of different PD: Gingivitis (G), Localized Chronic Periodontitis (LCP), Generalized Chronic Periodontitis (GCP), Localized Aggressive Periodontitis (LAP), and Generalized Aggressive Periodontitis (GAP). Pattern recognition analysis of NMR profiles can discriminate GCP patients (n = 21) from HS (n = 22) with an accuracy of 84.1%. Metabolic profiles of GCP patients exhibited higher concentrations of acetate, γ-aminobutyrate, n-butyrate, succinate, trimethylamine, propionate, phenylalanine and valine, and decreased concentrations of pyruvate and N-acetyl groups compared with controls. Our results can provide a contribution to the understanding of the biochemical network and pathway in the GCP and other PD, however at this stage the method can not be extended to the general population as a ready-to-use clinical tool, due to the limited cohort recruited and the exploratory nature of this work. Anyway, a further validation of the statistical model on a larger cohort is in progress with the aim to demonstrate the potential impact in clinical practice of our findings. © 2011 Springer Science+Business Media, LLC.

Bertini I.,University of Florence | Bertini I.,FiorGen Foundation | Cacciatore S.,University of Florence | Cacciatore S.,FiorGen Foundation | And 8 more authors.
Cancer Research | Year: 2012

Earlier detection of patients with metastatic colorectal cancer (mCRC) might improve their treatment and survival outcomes. In this study, we used proton nuclear magnetic resonance ( 1H-NMR) to profile the serum metabolome in patients withmCRC and determine whether a disease signature may exist that is strong enough to predict overall survival (OS). In 153 patients with mCRC and 139 healthy subjects from three Danish hospitals, we profiled two independent sets of serum samples in a prospective phase II study. In the training set, 1H-NMR metabolomic profiling could discriminate patients with mCRC from healthy subjects with a cross-validated accuracy of 100%. In the validation set, 96.7% of subjects were correctly classified. Patients from the training set with maximally divergent OS were chosen to construct an OS predictor. After validation, patients predicted to have short OS had significantly reduced survival (HR, 3.4; 95% confidence interval, 2.06-5.50; P = 1.33 × 10 -6). A number of metabolites concurred with the 1H-NMR fingerprint of mCRC, offering insights into mCRC metabolic pathways. Our findings establish that 1H-NMR profiling of patient serum can provide a strong metabolomic signature of mCRC and that analysis of this signature may offer an independent tool to predict OS. ©2011 AACR.

Oakman C.,Hospital of Prato | Tenori L.,University of Florence | Tenori L.,FiorGen Foundation | Biganzoli L.,Hospital of Prato | And 4 more authors.
International Journal of Biochemistry and Cell Biology | Year: 2011

Metabolomics, the study of metabolites and small intermediate molecules, may play a key role in further elucidation of breast cancer. This dynamic, simultaneous assessment of thousands of metabolites allows identification of the presence, concentration and fluxes of specific metabolites, and recognition of the critical metabolic pathways recruited in carcinogenesis. Studies of tumour cell and tissue allow focused analysis on the tumour, whilst studies of biofluids have the appeal of concurrent assessment of tumour and host. Elucidation of these metabolites and pathways may provide essential insights into both the intercellular environment and host/tumour interaction, allowing recognition of new biomarkers for diagnosis and prediction of outcome, new therapy targets and novel approaches for monitoring response and toxicity. Certainly, the field of metabolomics may evolve as a valuable, complementary clinical tool. In this review, current metabolomic data in breast cancer will be presented. The dominant metabolic pathways and metabolite disturbances associated with malignant transformation of breast cells will be outlined, leading to an overview of potential clinical implications for individuals with breast cancer. © 2009 Elsevier Ltd. All rights reserved.

Tarocchi M.,University of Florence | Polvani S.,University of Florence | Marroncini G.,University of Florence | Marroncini G.,FiorGen Foundation | And 2 more authors.
World Journal of Gastroenterology | Year: 2014

Hepatitis B virus (HBV) infection is a global public health problem with approximately 2 billion people that have been exposed to the virus. HBV is a member of a family of small, enveloped DNA viruses called hepadnaviruses, and has a preferential tropism for hepatocytes of mammals and birds. Epidemiological studies have proved a strong correlation between chronic hepatitis B virus infection and the development of hepatocellular carcinoma (HCC). HCC is the fifth most common malignancy with about 700000 new cases each year, and more than 50% of them arise in HBV carriers. A large number of studies describe the way in which HBV can contribute to HCC development. Multiple mechanisms have been proposed, including the accumulation of genetic damage due to immune-mediated hepatic inflammation and the induction of oxidative stress. There is evidence of the direct effects of the viral proteins HBx and HBs on the cell biology. Integration of HBV-DNA into the human genome is considered an early event in the carcinogenic process and can induce, through insertional mutagenesis, the alteration of gene expression and chromosomal instability. HBV has also epigenetic effects through the modification of the genomic methylation status. Furthermore, the virus plays an important role in the regulation of microRNA expression. This review will summarize the many mechanisms involved in HBV-related liver carcinogenesis. © 2014 Baishideng Publishing Group Inc. All rights reserved.

Bernini P.,University of Florence | Bernini P.,FiorGen Foundation | Bertini I.,University of Florence | Bertini I.,FiorGen Foundation | And 3 more authors.
Journal of Proteome Research | Year: 2011

The identification and the present wide acceptance of cardiovascular risk factors such as age, sex, hypertension, hyperlipidemia, smoking, obesity, diabetes, and physical inactivity have led to dramatic reductions in cardiovascular morbidity and mortality. However, novel risk predictors present opportunities to identify more patients at risk and to more accurately define the biochemical signature of that risk. In this paper, we present a comprehensive metabonomic analysis of 864 plasma samples from healthy volunteers, through Nuclear Magnetic Resonance (NMR) and multivariate statistical analysis (regression and classification). We have found that subjects that are classified as at high or at low risk using the common clinical markers can also be discriminated using NMR metabonomics. This discrimination is not only due to common markers (such as total cholesterol, triglycerides, LDL, HDL), but also to (p < 0.05 after Bonferroni correction) other metabolites (e.g., 3-hydroxybutyrate, α-ketoglutarate, threonine, dimethylglycine) previously not associated with cardiovascular diseases. © 2011 American Chemical Society.

Bernini P.,University of Florence | Bernini P.,FiorGen Foundation | Bertini I.,University of Florence | Luchinat C.,University of Florence | And 3 more authors.
Journal of Biomolecular NMR | Year: 2011

1H NMR metabolic profiling of urine, serum and plasma has been used to monitor the impact of the pre-analytical steps on the sample quality and stability in order to propose standard operating procedures (SOPs) for deposition in biobanks. We analyzed the quality of serum and plasma samples as a function of the elapsed time (t = 0-4 h) between blood collection and processing and of the time from processing to freezing (up to 24 h). The stability of the urine metabolic profile over time (up to 24 h) at various storage temperatures was monitored as a function of the different pre-analytical treatments like pre-storage centrifugation, filtration, and addition of the bacteriostatic preservative sodium azide. Appreciable changes in the profiles, reflecting changes in the concentration of a number of metabolites, were detected and discussed in terms of chemical and enzymatic reactions for both blood and urine samples. Appropriate procedures for blood derivatives collection and urine preservation/storage that allow maintaining as much as possible the original metabolic profile of the fresh samples emerge, and are proposed as SOPs for biobanking. © 2011 Springer Science+Business Media B.V.

Ceni E.,University of Florence | Mello T.,University of Florence | Galli A.,University of Florence | Galli A.,FiorGen Foundation
World Journal of Gastroenterology | Year: 2014

Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases, resulting in fatty liver, alcoholic hepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma (HCC). Although the pathogenesis of alcoholic liver disease (ALD) involves complex and still unclear biological processes, the oxidative metabolites of ethanol such as acetaldehyde and reactive oxygen species (ROS) play a preeminent role in the clinical and pathological spectrum of ALD. Ethanol oxidative metabolism influences intracellular signaling pathways and deranges the transcriptional control of several genes, leading to fat accumulation, fibrogenesis and activation of innate and adaptive immunity. Acetaldehyde is known to be toxic to the liver and alters lipid homeostasis, decreasing peroxisome proliferator-activated receptors and increasing sterol regulatory element binding protein activity via an AMP-activated protein kinase (AMPK)-dependent mechanism. AMPK activation by ROS modulates autophagy, which has an important role in removing lipid droplets. Acetaldehyde and aldehydes generated from lipid peroxidation induce collagen synthesis by their ability to form protein adducts that activate transforming-growth-factor-β-dependent and independent profibrogenic pathways in activated hepatic stellate cells (HSCs). Furthermore, activation of innate and adaptive immunity in response to ethanol metabolism plays a key role in the development and progression of ALD. Acetaldehyde alters the intestinal barrier and promote lipopolysaccharide (LPS) translocation by disrupting tight and adherent junctions in human colonic mucosa. Acetaldehyde and LPS induce Kupffer cells to release ROS and proinflammatory cytokines and chemokines that contribute to neutrophils infiltration. In addition, alcohol consumption inhibits natural killer cells that are cytotoxic to HSCs and thus have an important antifibrotic function in the liver. Ethanol metabolism may also interfere with cell-mediated adaptive immunity by impairing proteasome function in macrophages and dendritic cells, and consequently alters allogenic antigen presentation. Finally, acetaldehyde and ROS have a role in alcohol-related carcinogenesis because they can form DNA adducts that are prone to mutagenesis, and they interfere with methylation, synthesis and repair of DNA, thereby increasing HCC susceptibility. © 2014 Baishideng Publishing Group Inc. All rights reserved.

Bertini I.,University of Florence | Hu X.,University of Florence | Hu X.,FiorGen Foundation | Luchinat C.,University of Florence
Metabolomics | Year: 2014

Pre-analytical treatments of bacteria are crucial steps in bacterial metabolomics studies. In order to achieve reliable samples that can best represent the global metabolic profile in vivo both qualitatively and quantitatively, many sample treatment procedures have been developed. The use of different methods makes it difficult to compare the results among different groups. In this work, E. coli samples were tested by using NMR spectroscopy. Both liquid N2 and cold methanol quenching procedures reduce the cell membrane integrity and cause metabolites leakage. However, liquid N2 quenching affected the cell viability and the NMR metabolites’ profile less than cold methanol procedure. Samples obtained by metabolite extraction were significantly superior over cell suspensions and cell lysates, with a higher number of detectable metabolites. Methanol/chloroform extraction proved most efficient at extraction of intracellular metabolites from both qualitative and quantitative points of view. Finally, standard operating procedures of bacterial sample treatments for NMR metabolomics study are presented. © 2013, Springer Science+Business Media New York.

Bertini I.,University of Florence | Luchinat C.,University of Florence | Miniati M.,University of Florence | Monti S.,National Research Council Italy | And 2 more authors.
Metabolomics | Year: 2014

Spirometry is used to establish the diagnosis of chronic obstructive pulmonary disease (COPD) and to assess disease progression, but it seems inadequate to characterize COPD phenotypes. Metabolomics has been introduced for molecular fingerprinting of biosamples in a variety of clinical disorders. The aim of the study was to establish whether exhaled breath condensate (EBC) in COPD features a distinct metabolic fingerprint, and to identify the metabolites that characterize the EBC profile in COPD. EBC was collected using a home-made glass condenser in 37 stable COPD patients, and 25 non-obstructed controls. Samples were analyzed using proton nuclear magnetic resonance spectroscopy (1H NMR). Random forest was applied for both supervised and unsupervised learning, using spectral buckets as input variables. Metabolomics of EBC discriminated COPD patients from controls with an overall accuracy of 86 %. As compared to controls, EBC from COPD featured significantly lower (p < 0.05) levels of acetone, valine and lysine, and significantly higher (p < 0.05) levels of lactate, acetate, propionate, serine, proline, and tyrosine. Based on unsupervised analysis of NMR spectra, the COPD sample was split in three clusters, one of which had the highest prevalence of radiologic emphysema. NMR spectroscopy of EBC holds promise in COPD fingerprinting. It may prove valuable in outcome studies, and in assessing the efficacy of therapeutic interventions. © 2013, Springer Science+Business Media New York.

Cacciatore S.,Dana-Farber Cancer Institute | Cacciatore S.,Rovira i Virgili University | Tenori L.,FiorGen Foundation
Medical Hypotheses | Year: 2013

Wilson disease (WD) is an autosomal recessive inherited disorder of copper (Cu) metabolism, resulting in pathological accumulation of Cu in many organs and tissues, predominantly in the liver and brain. There clearly is a close and complex relationship between Cu and the cholesterol's metabolic pathway; therefore any theory about the cholesterol metabolism in the brain of patients with WD must take it into account. The hypothesis presented in this paper is that the imbalance in cerebral copper homeostasis caused by WD may plays a key role in the derangement of the cholesterol homeostasis in the brain, and thus promoting the observed WD related neurological disorders. © 2013.

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