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  • 1
    Language: English
    In: BBA - Proteins and Proteomics, 2010, Vol.1804(7), pp.1516-1525
    Description: We performed a proteomic study to understand how adapts its metabolism during the exponential growth on three different concentrations of glucose; this information will be necessary to understand yeast carbon metabolism in different environments. We induced a natural diauxic shift by growing yeast cells in glucose restriction thus having a fast and complete glucose exhaustion. We noticed differential expressions of groups of proteins. Cells in high glucose have a decreased growth rate during the initial phase of fermentation; in glucose restriction and in high glucose we found an over-expression of a protein (Peroxiredoxin) involved in protection against oxidative stress insult. The information obtained in our study validates the application of a proteomic approach for the identification of the molecular bases of environmental variations such as fermentation in high glucose and during a naturally induced diauxic shift.
    Keywords: Yeast Fermentation ; Proteomics ; Diauxic Shift ; Glucose Metabolism ; Chemistry ; Anatomy & Physiology
    ISSN: 1570-9639
    E-ISSN: 1878-1454
    E-ISSN: 00063002
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  • 2
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States, March 19, 2013, Vol.110(12), p.4804(6)
    Description: Epigenetic mechanisms are involved in the pathophysiology of depressive disorders and are unique potential targets for therapeutic intervention. The acetylating agent L-acetylcarnitine (LAC), a well-tolerated drug, behaves as an antidepressant by the epigenetic regulation of type 2 metabotropic glutamate (mGlu2) receptors. It caused a rapid and long-lasting antidepressant effect in Flinders Sensitive Line rats and in mice exposed to chronic unpredictable stress, which, respectively, model genetic and environmentally induced depression. In both models, LAC increased levels of acetylated H3K27 bound to the Grm2 promoter and also increased acetylation of NF-KB-p65 subunit, thereby enhancing the transcription of Grm2 gene encoding for the mGlu2 receptor in hippocampus and prefrontal cortex. Importantly, LAC reduced the immobility time in the forced swim test and increased sucrose preference as early as 3 d of treatment, whereas 14 d of treatment were needed for the antidepressant effect of chlorimipramine. Moreover, there was no tolerance to the action of LAC, and the antidepressant effect was still seen 2 wk after drug withdrawal. Conversely, NF-kB inhibition prevented the increase in mGlu2 expression induced by LAC, whereas the use of a histone deacetylase inhibitor supported the epigenetic control of mGlu2 expression. Finally, LAC had no effect on mGlu2 knockout mice exposed to chronic unpredictable stress, and a single injection of the mGlu2/3 receptor antagonist LY341495 partially blocked LAC action. The rapid and long-lasting antidepressant action of LAC strongly suggests a unique approach to examine the epigenetic hypothesis of depressive disorders in humans, paving the way for more efficient antidepressants with faster onset of action. doi/10.1073/pnas.1216100110
    Keywords: Antidepressants -- Research ; Antidepressants -- Analysis ; Depression (Mood disorder) -- Research ; Depression (Mood disorder) -- Analysis
    ISSN: 0027-8424
    Source: Cengage Learning, Inc.
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  • 3
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 19 March 2013, Vol.110(12), pp.4804-4809
    Description: Epigenetic mechanisms are involved in the pathophysiology of depressive disorders and are unique potential targets for therapeutic intervention. The acetylating agent L-acetylcarnitine (LAC), a welltolerated drug, behaves as an antidepressant by the epigenetic regulation of type 2 metabotropic glutamate (mGlu2) receptors. It caused a rapid and long-lasting antidepressant effect in Flinders Sensitive Line rats and in mice exposed to chronic unpredictable stress, which, respectively, model genetic and environmentally induced depression. In both models, LAC increased levels of acetylated H3K27 bound to the Grm2 promoter and also increased acetylation of NF-KB-p65 subunit, thereby enhancing the transcription of Grm2 gene encoding for the mGlu2 receptor in hippocampus and prefrontal cortex. Importantly, LAC reduced the immobility time in the forced swim test and increased sucrose preference as early as 3 d of treatment, whereas 14 d of treatment were needed for the antidepressant effect of chlorimipramine. Moreover, there was no tolerance to the action of LAC, and the antidepressant effect was still seen 2 wk after drug withdrawal. Conversely, NF-κB inhibition prevented the increase in mGlu2 expression induced by LAC, whereas the use of a histone deacetylase inhibitor supported the epigenetic control of mGlu2 expression. Finally, LAC had no effect on mGlu2 knockout mice exposed to chronic unpredictable stress, and a single injection of the mGlu2/3 receptor antagonist LY341495 partially blocked LAC action. The rapid and long-lasting antidepressant action of LAC strongly suggests a unique approach to examine the epigenetic hypothesis of depressive disorders in humans, paving the way for more efficient antidepressants with faster onset of action.
    ISSN: 00278424
    Source: Archival Journals (JSTOR)
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  • 4
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 19 March 2013, Vol.110(12), pp.4804-9
    Description: Epigenetic mechanisms are involved in the pathophysiology of depressive disorders and are unique potential targets for therapeutic intervention. The acetylating agent L-acetylcarnitine (LAC), a well-tolerated drug, behaves as an antidepressant by the epigenetic regulation of type 2 metabotropic glutamate (mGlu2) receptors. It caused a rapid and long-lasting antidepressant effect in Flinders Sensitive Line rats and in mice exposed to chronic unpredictable stress, which, respectively, model genetic and environmentally induced depression. In both models, LAC increased levels of acetylated H3K27 bound to the Grm2 promoter and also increased acetylation of NF-ĸB-p65 subunit, thereby enhancing the transcription of Grm2 gene encoding for the mGlu2 receptor in hippocampus and prefrontal cortex. Importantly, LAC reduced the immobility time in the forced swim test and increased sucrose preference as early as 3 d of treatment, whereas 14 d of treatment were needed for the antidepressant effect of chlorimipramine. Moreover, there was no tolerance to the action of LAC, and the antidepressant effect was still seen 2 wk after drug withdrawal. Conversely, NF-ĸB inhibition prevented the increase in mGlu2 expression induced by LAC, whereas the use of a histone deacetylase inhibitor supported the epigenetic control of mGlu2 expression. Finally, LAC had no effect on mGlu2 knockout mice exposed to chronic unpredictable stress, and a single injection of the mGlu2/3 receptor antagonist LY341495 partially blocked LAC action. The rapid and long-lasting antidepressant action of LAC strongly suggests a unique approach to examine the epigenetic hypothesis of depressive disorders in humans, paving the way for more efficient antidepressants with faster onset of action.
    Keywords: Acetylcarnitine -- Pharmacology ; Antidepressive Agents -- Pharmacology ; Epigenesis, Genetic -- Drug Effects ; Hippocampus -- Metabolism ; Nerve Tissue Proteins -- Biosynthesis ; Prefrontal Cortex -- Metabolism ; Receptors, Metabotropic Glutamate -- Biosynthesis
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 5
    In: Journal of Paediatrics and Child Health, December 2015, Vol.51(12), pp.1214-1220
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/jpc.12927/abstract Byline: Mario Barreto, Melania Evangelisti, Luigi Principessa, Maurizio Simmaco, Valentina Negro, Luana Lionetto, Martina Campisano, Maria Pia Villa Keywords: asthma; child; functional gastrointestinal disorder; inflammation; intestinal permeability; recurrent respiratory symptom Aim Increased intestinal permeability has been reported in asthmatic subjects as well as in patients with gastrointestinal disease, thus suggesting the involvement of all the mucosal immune system. We aimed to assess intestinal permeability according to recurrent respiratory and gastrointestinal symptoms in children with asthma and children with functional gastrointestinal disorders (FGIDs). Methods In 108 outpatients aged 3-14 years (45 asthmatic, 63 with FGIDs), we measured the urinary lactulose/mannitol (L/M) ratio, performed allergy skin prick tests and administered questionnaires for recurrent respiratory and gastrointestinal symptoms starting from at least 2 months which persisted over the previous 4 weeks. L/M ratios were compared with previously reported normal values yielded by our chromatographic method (liquid chromatography-mass spectrometry). Results High L/M ratios (〉0.030) were less frequent in asthmatic children than in children with FGIDs (9/45: 20% vs. 41/63: 65%, P 〈 0.001). High L/M ratios were associated with gastrointestinal symptoms in 8/9 asthmatic (P 〈 0.05) and 39/41 subjects with FGIDs (P 〈 0.005). L/M ratios were not associated with respiratory symptoms or atopy. In a regression model, a high L/M was predicted by low height, absence of asthma and presence of gastrointestinal symptoms (r = 0.72, P 〈 0.001). Conclusions Increased intestinal permeability is associated with recurrent gastrointestinal symptoms rather than with recurrent respiratory symptoms in both asthmatic children and those with FGIDs. Our findings do not support the hypothesis of mucosal intestinal damage following an inflammatory stimulus in the respiratory mucosa. Article Note: Conflict of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
    Keywords: Asthma ; Child ; Functional Gastrointestinal Disorder ; Inflammation ; Intestinal Permeability ; Recurrent Respiratory Symptom
    ISSN: 1034-4810
    E-ISSN: 1440-1754
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  • 6
    Language: English
    In: PLoS ONE, 01 January 2013, Vol.8(8), p.e67301
    Description: BACKGROUND:Recent clinical studies have shown that the presence of CC genotype in the rs12979860 region of IL28B gene is associated with an increase in the probability of spontaneous clearance of hepatitis C virus (HCV). Moreover, IL28B polymorphism seems to influence the probability of developing...
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 7
    Language: English
    In: PLoS ONE, 01 January 2016, Vol.11(9), p.e0163105
    Description: BACKGROUND:5-FU based chemotherapy is the most common first line regimen used for metastatic colorectal cancer (mCRC). Identification of predictive markers of response to chemotherapy is a challenging approach for drug selection. The present study analyzes the predictive role of 5-FU degradation...
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 8
    Language: English
    In: European Child & Adolescent Psychiatry, 2017, Vol.26(12), pp.1433-1441
    Description: This study aims at determining serum levels of tryptophan and other metabolites of the kynurenine pathway in children with attention deficit hyperactivity disorder (ADHD) compared to healthy controls. Such metabolites interact with glutamate receptors in the central nervous system, potentially modulating mechanisms that are pivotal in ADHD and thus potentially representing peripheral biomarkers of the disorder. We measured serum levels of tryptophan and some metabolites of the kynurenine pathway in 102 children with ADHD and 62 healthy controls by liquid chromatography–tandem mass spectrometry (LC–MS/MS). As compared to healthy controls, children with ADHD showed a reduction in serum levels of anthranilic acid (−60%), kynurenic acid (−11.2%), and xanthurenic acid (−12.5%). In contrast, serum levels of tryptophan (+11.0%) and kynurenine (+48.6%) were significantly enhanced, and levels of quinolinic acid were unchanged in children with ADHD. In a logistic regression model, the presence of ADHD was predicted by low anthranilic acid and high tryptophan levels. These findings support the involvement of the kynurenine pathway in the pathophysiology of ADHD and suggest that anthranilic acid and tryptophan levels should be investigated as potential peripheral biomarker for ADHD.
    Keywords: ADHD ; Biomarker ; Kynurenines ; Children ; Neurobiology
    ISSN: 1018-8827
    E-ISSN: 1435-165X
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  • 9
    Language: English
    In: International Journal of Cardiology, 2011, Vol.153(3), pp.306-310
    Description: Cardiac resynchronization therapy (CRT) promotes left ventricular (LV) reverse remodelling and affects myocardial collagen turnover in heart failure (HF) patients. Osteopontin (OPN) is a matrix glycoprotein required for the activation of fibroblasts upon TGF-β1 stimulation. In humans, plasma OPN and OPN-expressing lymphocytes correlate with the severity of HF. We sought to evaluate whether plasma OPN and TGF-β1 reflect LV reverse remodelling following CRT. Eighteen patients (12 men, mean age 65 ± 11 years) undergoing CRT were studied. Patients underwent baseline clinical and echocardiographic evaluation, and assessment of plasma OPN and TGF-β1. The evaluation was repeated 8.5 ± 4 months after device implantation. Eight healthy age- and sex-matched subjects served as controls. In HF patients, baseline plasma OPN and TGF-β1 were higher as compared to control subjects (OPN: 99 ± 48 vs 59 ± 22 ng/ml; p 〈 0.05; TGF-β1: 15.9 ± 8.0 vs 9.3 ± 5.6 ng/ml; p 〈 0.05). At follow-up, 12 patients responded to CRT and showed LV reverse remodelling, whereas 6 did not. Plasma OPN decreased in CRT responders (108 ± 47 vs 84 ± 37 ng/ml; p = 0.03) and increased in non-responders (79 ± 58 vs 115 ± 63 ng/ml; p 〈 0.01). TGF-β1 showed a trend towards reduction in responders (17.5 ± 8.7 vs 10.2 ± 8.9 ng/ml; p = 0.08) and was unchanged in non-responders. A significant correlation (r = − 0.56; p = 0.01) was found between relative changes of LVESV and plasma OPN. CRT-induced LV reverse remodelling is reflected by changes in plasma OPN. Circulating OPN may represent a marker of LV dilation/impairment and an indicator of the response to HF therapies promoting LV reverse remodelling.
    Keywords: Osteopontin ; Tgf-Β1 ; Resynchronization ; Biventricular ; Reverse Remodelling ; Heart Failure ; Medicine
    ISSN: 0167-5273
    E-ISSN: 1874-1754
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  • 10
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