Maria Luisa Balestrieri

Professor of Biochemistry

Name Maria Luisa
Surname Balestrieri
Institution Università degli Studi della Campania Luigi Vanvitelli
Address Department of Biochemistry, Biophysics and General Pathology, University of Campania "L. Vanvitelli", Via L. De Crecchio 7, 80138 Naples, Italy
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Maria Luisa Balestrieri


  • Correction to: Thrombus aspiration in hyperglycemic ST-elevation myocardial infarction (STEMI) patients: clinical outcomes at 1-year follow-up.

    Publication Date: 27/12/2018 on Cardiovascular diabetology
    by Sardu C, Barbieri M, Balestrieri ML, Siniscalchi M, Paolisso P, Calabrò P, Minicucci F, Signoriello G, Portoghese M, Mone P, D'Andrea D, Gragnano F, Bellis A, Mauro C, Paolisso G, Rizzo MR, Marfella R
    DOI: 10.1186/s12933-018-0804-y

    Following publication of the original article [1], the authors reported an error in Acknowledgment section. The last sentence should read as "All authors have read and approval the submission to Cardiovascular Diabetology.

  • Thrombus aspiration in hyperglycemic ST-elevation myocardial infarction (STEMI) patients: clinical outcomes at 1-year follow-up.

    Publication Date: 29/11/2018 on Cardiovascular diabetology
    by Sardu C, Barbieri M, Balestrieri ML, Siniscalchi M, Paolisso P, Calabrò P, Minicucci F, Signoriello G, Portoghese M, Mone P, D'Andrea D, Gragnano F, Bellis A, Mauro C, Paolisso G, Rizzo MR, Marfella R
    DOI: 10.1186/s12933-018-0795-8

    We evaluate whether the thrombus aspiration (TA) before primary percutaneous coronary intervention (PPCI) may improve STEMI outcomes in hyperglycemic patients.

  • Ruminant meat and milk contain δ-valerobetaine, another precursor of trimethylamine N-oxide (TMAO) like γ-butyrobetaine.

    Publication Date: 15/09/2018 on Food chemistry
    by Servillo L, D'Onofrio N, Giovane A, Casale R, Cautela D, Castaldo D, Iannaccone F, Neglia G, Campanile G, Balestrieri ML
    DOI: 10.1016/j.foodchem.2018.03.114

    Quaternary ammonium compounds containing N-trimethylamino moiety, such as choline derivatives and carnitine, abundant in meat and dairy products, are metabolic precursors of trimethylamine (TMA). A similar fate is reported for N-trimethyllysine and γ-butyrobetaine. With the aim at investigating the metabolic profile of such metabolites in most employed animal dietary sources, HPLC-ESI-MS/MS analyses on ruminant and non-ruminant milk and meat were performed. Results demonstrate, for the first time, the presence of δ-valerobetaine, occurring at levels higher than γ-butyrobetaine in all ruminant samples compared to non-ruminants. Demonstration of δ-valerobetaine metabolic origin, surprisingly, showed that it originates from rumen through the transformation of dietary N-trimethyllysine. These results highlight our previous findings showing the ubiquity of free N-trimethyllysine in vegetable kingdom. Furthermore, δ-valerobetaine, similarly to γ-butyrobetaine, can be degraded by host gut microbiota producing TMA, precursor of the proatherogenic trimethylamine N-oxide (TMAO), unveiling its possible role in the biosynthetic route of TMAO.

  • Inflammatory Cytokines and SIRT1 Levels in Subcutaneous Abdominal Fat: Relationship With Cardiac Performance in Overweight Pre-diabetics Patients.

    Publication Date: 21/08/2018 on Frontiers in physiology
    by Sardu C, Pieretti G, D'Onofrio N, Ciccarelli F, Paolisso P, Passavanti MB, Marfella R, Cioffi M, Mone P, Dalise AM, Ferraraccio F, Panarese I, Gambardella A, Passariello N, Rizzo MR, Balestrieri ML, Nicoletti G, Barbieri M
    DOI: 10.3389/fphys.2018.01030

    In obese patients the superficial adipose tissue expresses cytokines, and sirtuins, that may affect myocardial function. In this study, we investigated the effect of metformin therapy added to a hypocaloric diet on the inflammatory pattern and cardiac performance (MPI) in obese patients with pre-diabetic condition. Fifty-eight obese patients that were enrolled for abdominoplastic surgery were divided into patients with pre-diabetic condition (n 40) and normo-glycemic patients (n18). Patients with pre-diabetic condition were randomly assigned to metformin therapy added to a hypocaloric diet (group 1, n 20) or to a hypocaloric diet therapy alone (group 2, n20). Patients with normo-glycemic condition were assigned to a hypocaloric diet therapy. During enrollment, obese patients with a pre-diabetic condition (group 1 and 2) presented higher glucose values, lower values of insulin, and higher values of the homeostasis model for the assessment of insulin resistance (HOMA-IR) than obese patients with normo-glycemic condition(group 3). In addition, they had higher values of C Reactive protein (CRP), interleukin 6 (IL6), and lower values of sirtuin 1(SIRT1). In the 12th month of the follow-up, metformin therapy induced in patients with pre-diabetic condition (group 1) a significant reduction of glucose values, HOMA-IR, and inflammatory markers such as CRP (1.04 ± 0.48 vs. 0.49 ± 0.02 mmol/L, < 0.05), IL6 (4.22 ± 0.45 vs. 3.33 ± 0.34 pg/ml, < 0.05), TNFα (6.95 ± 0.59 vs. 5.15 ± 0.44 pg/ml, < 0.05), and Nitrotyrosine (5,214 ± 0,702 vs. 2,151 ± 0,351 nmol/l, < 0.05). This was associated with a significant reduction of Intima-media thickness (1.01 ± 0.15 vs. 0.86 ± 0.15 mm, < 0.05), Septum (14 ± 2.5 vs. 10.5 ± 2 mm, < 0.05), Posterior wall (11 ± 1.5 vs. 8 ± 1 mm, < 0.05), LV mass (192.5 ± 49.5 vs. 133.2 ± 37.6 g, < 0.05) and of MPI (0.58 ± 0.03 vs. 0.38 ± 0.02, < 0.05). At 12 months of follow-up, group 2 experienced only a reduction of cholesterol (4.15 ± 0.94 vs. 4.51 ± 0.88 mmol/L, < 0.05) and triglycerides (1.71 ± 1.18 vs. 1.83 ± 0.54 mmol/L, < 0.05). At 12 months of follow-up, group 3 experienced a significant reduction of inflammatory markers, and also of echographic parameters, associated with amelioration of myocardial performance. To date, IL6 expression was related to higher values of left ventricle mass (-value 0.272, -value 0.039), and to higher IMT (-value 0.272, -value 0.039), such as those observed for CRP (-value 0.308, -value 0.021), for glucose blood values (-value 0.449, -value 0.001), and for HOMA-IR (-value 0.366, -value 0.005). An inverse correlation was found between subcutaneous fat expression of SIRT1 and myocardial performance index (-value-0.236, -value 0.002). In obese patients with pre-diabetic condition a metformin therapy may reduce inflammation and oxidative stress, and this may be associated with the amelioration of the cardiac performance. Clinical research trial number: NCT03439592.

  • Carnitine Precursors and Short-Chain Acylcarnitines in Water Buffalo Milk.

    Publication Date: 24/07/2018 on Journal of agricultural and food chemistry
    by Servillo L, D'Onofrio N, Neglia G, Casale R, Cautela D, Marrelli M, Limone A, Campanile G, Balestrieri ML
    DOI: 10.1021/acs.jafc.8b02963

    Ruminants' milk contains δ-valerobetaine originating from rumen through the transformation of dietary N-trimethyllysine. Among ruminant's milk, the occurrence of δ-valerobetaine, along with carnitine precursors and metabolites, has not been investigated in buffalo milk, the second most worldwide consumed milk, well-known for its nutritional value. HPLC-ESI-MS/MS analyses of bulk milk revealed that the Italian Mediterranean buffalo milk contains δ-valerobetaine at levels higher than those in bovine milk. Importantly, we detected also γ-butyrobetaine, the l-carnitine precursor, never described so far in any milk. Of interest, buffalo milk shows higher levels of acetylcarnitine, propionylcarnitine, butyrylcarnitine, isobutyrylcarnitine, and 3-methylbutyrylcarnitine (isovalerylcarnitine) than cow milk. Moreover, buffalo milk shows isobutyrylcarnitine and butyrylcarnitine at a 1-to-1 molar ratio, while in cow's milk this ratio is 5 to 1. Results indicate a peculiar short-chain acylcarnitine profile characterizing buffalo milk, widening the current knowledge about its composition and nutritional value.

  • Ophthalmic acid is a marker of oxidative stress in plants as in animals.

    Publication Date: 01/04/2018 on Biochimica et biophysica acta
    by Servillo L, Castaldo D, Giovane A, Casale R, D'Onofrio N, Cautela D, Balestrieri ML
    DOI: 10.1016/j.bbagen.2018.01.015

    Ophthalmic acid (OPH), γ-glutamyl-L-2-aminobutyryl-glycine, a tripeptide analogue of glutathione (GSH), has recently captured considerable attention as a biomarker of oxidative stress in animals. The OPH and GSH biosynthesis, as well as some biochemical behaviors, are very similar. Here, we sought to investigate the presence of OPH in plants and its possible relationship with GSH, known to possess multiple functions in the plant development, growth and response to environmental changes.

  • The betaine profile of cereal flours unveils new and uncommon betaines.

    Publication Date: 15/01/2018 on Food chemistry
    by Servillo L, D'Onofrio N, Giovane A, Casale R, Cautela D, Ferrari G, Castaldo D, Balestrieri ML
    DOI: 10.1016/j.foodchem.2017.06.111

    We report the LC-ESI-MS/MS determination of betaines in commercial flours of cereals and pseudocereals most utilized in human nutrition. Results showed that glycine betaine, trigonelline, proline betaine, Nε-trimethyllysine were metabolites common to all examined flours, whereas an uncommon betaine, valine betaine, and glutamine betaine were present only in flours of barley, rye, oat, durum wheat, winter wheat, Triticum dicoccum and Triticum monococcum. Valine betaine and glutamine betaine, the latter never reported before in plants and animals, are not evenly distributed in the Poaceae family, but their presence or absence in flours depends on the subfamily to which the plant belongs. Interestingly, we also report for the first time the occurrence of pipecolic acid betaine (homostachydrine) and its precursor 1,2-N-methylpipecolic acid in rye flour. These two metabolites were not detected in any other cereal or pseudocereal flour, suggesting their potential role as markers of rye flour occurrence in cereal-based foods.

  • Effects of incretin treatment on cardiovascular outcomes in diabetic STEMI-patients with culprit obstructive and multivessel non obstructive-coronary-stenosis.

    Publication Date: 03/01/2018 on Diabetology & metabolic syndrome
    by Marfella R, Sardu C, Balestrieri ML, Siniscalchi M, Minicucci F, Signoriello G, Calabrò P, Mauro C, Pieretti G, Coppola A, Nicoletti G, Rizzo MR, Paolisso G, Barbieri M
    DOI: 10.1186/s13098-017-0304-3

    No proper data on prognosis and management of type-2 diabetic ST elevation myocardial infarction (STEMI) patients with culprit obstructive lesion and multivessel non obstructive coronary stenosis (Mv-NOCS) exist. We evaluated the 12-months prognosis of Mv-NOCS-diabetics with first STEMI non-diabetics, and then Mv-NOCS-diabetics previously treated with incretin based therapy vs. a matched cohort of STEMI-Mv-NOCS never treated with such therapy.

  • Non-ST-elevation myocardial infarction outcomes in patients with type 2 diabetes with non-obstructive coronary artery stenosis: Effects of incretin treatment.

    Publication Date: 26/09/2017 on Diabetes, obesity & metabolism
    by Marfella R, Sardu C, Calabrò P, Siniscalchi M, Minicucci F, Signoriello G, Balestrieri ML, Mauro C, Rizzo MR, Paolisso G, Barbieri M
    DOI: 10.1111/dom.13122

    There are insufficient data on the prognosis and management of people with type 2 diabetes who experience a non-obstructive coronary artery stenosis (NOCS)-non-ST-elevation myocardial infarction (NSTEMI) event. We evaluated the 12-month prognosis of patients with diabetes and NOCS (20%-49% luminal stenosis) who experience a first NSTEMI as compared with patients without diabetes. In addition, we investigated the 12-month prognosis in patients with diabetes and NSTEMI-NOCS previously treated with incretin-based therapy compared with a matched cohort of patients with NSTEMI-NOCS never treated with such therapy. We categorized the patients with diabetes as current incretin users (6 months' treatment with glucagon-like peptide-1 agonists or dipeptidyl peptidase-4 inhibitors) and non-users of incretins. The endpoint was all-cause mortality, cardiac death, recurrent acute coronary syndrome (ACS), and heart failure. The unadjusted Kaplan-Meier analysis, and a risk-adjusted hazard analysis showed that, all-cause mortality, cardiac death, readmission for ACS and heart failure rates during the 12-month follow-up were higher in patients with diabetes and NOCS-NSTEMI than in those with NOCS-NSTEMI without diabetes. Among the patients with diabetes, the current incretin users had a significantly lower rate of all-cause mortality, cardiac death and readmission for ACS at 12 months. In patients with type 2 diabetes and NOCS-NSTEMI, we observed a higher incidence of 1-year mortality and adverse cardiovascular outcomes, as compared with patients without diabetes with NOCS-NSTEMI. In people with diabetes, non-users of incretins had a worse prognosis than current incretin users.

  • p27<sup>Kip1</sup> and human cancers: A reappraisal of a still enigmatic protein.

    Publication Date: 10/09/2017 on Cancer letters
    by Bencivenga D, Caldarelli I, Stampone E, Mancini FP, Balestrieri ML, Della Ragione F, Borriello A
    DOI: 10.1016/j.canlet.2017.06.031

    p27Kip1 is a cell cycle regulator firstly identified as a cyclin-dependent kinase inhibitor. For a long time, its function has been associated to cell cycle progression inhibition at G1/S boundary in response to antiproliferative stimuli. The picture resulted complicated by the discovery that p27Kip1 is an intrinsically unstructured protein, with numerous CDK-dependent and -independent functions and involvement in many cellular processes, such as cytoskeleton dynamics and cell motility control, apoptosis and autophagy activation. Depending on the cell context, these activities might turn to be oncogenic and stimulate cancer progression and metastatization. Nevertheless, p27Kip1 role in cancer biology suppression was underscored by myriad data reporting its down-regulation and/or cytoplasmic relocalization in different tumors, while usually no genetic alterations were found in human cancers, making the protein a non-canonical oncosuppressor. Recently, mostly due to advances in genomic analyses, CDKN1B, p27Kip1 encoding gene, has been found mutated in several cancers, thus leading to a profound reappraisal of CDKN1B role in tumorigenesis. This review summarizes the main p27Kip1 features, with major emphasis to its role in cancer biology and to the importance of CDKN1B mutations in tumor development.