Publications by authors named "Giovanni N Berta"

10 Publications

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Macro and trace elements signature of periodontitis in saliva: A systematic review with quality assessment of ionomics studies.

J Periodontal Res 2022 Jan 27;57(1):30-40. Epub 2021 Nov 27.

Department of Surgical Sciences, C.I.R. Dental School, University of Turin, Turin, Italy.

Objectives: The present systematic review examined the available evidence on distinctive salivary ion profile in periodontitis compared to periodontal health and provided a qualitative assessment of the literature.

Background: Macro and trace elements are essential for cellular physiology, and their changes in biological fluids can be revelatory of an underlying pathological status.

Methods: Data from relevant studies identified from PubMed, Embase, and Scopus databases were retrieved to answer the following PECO question: "In systemically healthy individuals, are there any differences in any salivary macro or trace element concentration between periodontally healthy subjects (H) and patients with periodontitis (P)?" Quality of included studies was rated using a modified version of the QUADOMICS tool. A consistency analysis was performed to identify significantly discriminant chemical elements.

Results: After the screening of 873 titles, 13 studies were included reporting data on 22 different elements. Among them, levels of sodium and potassium were consistently and significantly higher in P compared to H. Conflicting results were found for all the other elements, despite concentration of calcium, copper, and manganese mostly increased in saliva of P. Levels of magnesium were found higher in P than in H in 2 studies but lower in 3. Zinc resulted significantly increased in saliva from H compared to P individuals in 2 studies, but one study reported opposite results. Four studies were considered as high quality, while reporting of operative protocols and statistical analysis was a major limitation for the others. Due to high methodologic heterogeneity, meta-analysis was not performed.

Conclusions: Levels of macro or trace elements were differentially identified in saliva across diverse periodontal conditions, having a major potential for investigation of oral homeostasis and for high-resolution periodontal diagnosis. Products of inflammatory physiologic cellular impairment, such as sodium and potassium, were the most consistently associated with periodontitis (PROSPERO CRD42021235744).
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http://dx.doi.org/10.1111/jre.12956DOI Listing
January 2022

Salivary metabolomics for the diagnosis of periodontal diseases: a systematic review with methodological quality assessment.

Metabolomics 2021 01 1;17(1). Epub 2021 Jan 1.

Department of Surgical Sciences, C.I.R. Dental School, University of Turin, Turin, Italy.

Introduction: Early diagnosis of periodontitis by means of a rapid, accurate and non-invasive method is highly desirable to reduce the individual and epidemiological burden of this largely prevalent disease.

Objectives: The aims of the present systematic review were to examine potential salivary metabolic biomarkers and pathways associated to periodontitis, and to assess the accuracy of salivary untargeted metabolomics for the diagnosis of periodontal diseases.

Methods: Relevant studies identified from MEDLINE (PubMed), Embase and Scopus databases were systematically examined for analytical protocols, metabolic biomarkers and results from the multivariate analysis (MVA). Pathway analysis was performed using the MetaboAnalyst online software and quality assessment by means of a modified version of the QUADOMICS tool.

Results: Twelve studies met the inclusion criteria, with sample sizes ranging from 19 to 130 subjects. Compared to periodontally healthy individuals, valine, phenylalanine, isoleucine, tyrosine and butyrate were found upregulated in periodontitis patients in most studies; while lactate, pyruvate and N-acetyl groups were the most significantly expressed in healthy individuals. Metabolic pathways that resulted dysregulated are mainly implicated in inflammation, oxidative stress, immune activation and bacterial energetic metabolism. The findings from MVA revealed that periodontitis is characterized by a specific metabolic signature in saliva, with coefficients of determination ranging from 0.52 to 0.99.

Conclusions: This systematic review summarizes candidate metabolic biomarkers and pathways related to periodontitis, which may provide opportunities for the validation of diagnostic or predictive models and the discovery of novel targets for monitoring and treating such a disease (PROSPERO CRD42020188482).
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http://dx.doi.org/10.1007/s11306-020-01754-3DOI Listing
January 2021

Childhood acute poisoning in the Italian North-West area: a six-year retrospective study.

Ital J Pediatr 2020 Jun 11;46(1):83. Epub 2020 Jun 11.

Department of Pediatric Emergency, Regina Margherita Children's Hospital, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy.

Background: Data about acute poisoning in Italian pediatric patients are obsolete or absent. This study would partially fill this exiting gap and compare the scene with others around the world.

Methods: A retrospective evaluation was performed on a 2012-2017 data registry of the Children's Emergency Department at the Regina Margherita Hospital of Turin, where 1030 children under age 14 were accepted with a diagnosis of acute intoxication.

Results: The median age of the patients was 2.2 years (IQR 2.3) and 55% were male. Events occurred mostly in children aged 1-4 years (n = 751, 72.9%). Six hundred and eight patients (59%) were exposed to Nonpharmaceutical agents, the household cleaning products being the more frequent (n = 298, 49%). Exposure to Pharmaceuticals were 422 (41%); the most common Pharmaceuticals were analgesics (n = 88, 20.8%), psychotropics (n = 77, 18.2%) and cardiovascular (n = 53, 12.6%) drugs. The 85% of the intoxications occurred accidentally, the 10.6% as therapeutic error, the 2.3% as suicide attempts and the 1.5% for recreational purposes. No patient died.

Conclusions: Despite acute poisoning being a relevant problem in pediatric emergency, our results would seem to paint a less worrying picture if compared to other countries, mainly when considering the children hospitalized in the pediatric intensive care unit and the number of deaths. Nevertheless, our study might represent a tool for public health authorities to program incisive interventions.
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http://dx.doi.org/10.1186/s13052-020-00845-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291716PMC
June 2020

Patient-Specific iPSC-Derived Endothelial Cells Provide Long-Term Phenotypic Correction of Hemophilia A.

Stem Cell Reports 2018 12 8;11(6):1391-1406. Epub 2018 Nov 8.

Department of Health Sciences, Università del Piemonte Orientale "A. Avogadro", 28100 Novara, Italy. Electronic address:

We generated patient-specific disease-free induced pluripotent stem cells (iPSCs) from peripheral blood CD34+ cells and differentiated them into functional endothelial cells (ECs) secreting factor VIII (FVIII) for gene and cell therapy approaches to cure hemophilia A (HA), an X-linked bleeding disorder caused by F8 mutations. iPSCs were transduced with a lentiviral vector carrying FVIII transgene driven by an endothelial-specific promoter (VEC) and differentiated into bona fide ECs using an optimized protocol. FVIII-expressing ECs were intraportally transplanted in monocrotaline-conditioned non-obese diabetic (NOD) severe combined immune-deficient (scid)-IL2rγ null HA mice generating a chimeric liver with functional human ECs. Transplanted cells engrafted and proliferated in the liver along sinusoids, in the long term showed stable therapeutic FVIII activity (6%). These results demonstrate that the hemophilic phenotype can be rescued by transplantation of ECs derived from HA FVIII-corrected iPSCs, confirming the feasibility of cell-reprogramming strategy in patient-derived cells as an approach for HA gene and cell therapy.
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http://dx.doi.org/10.1016/j.stemcr.2018.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294075PMC
December 2018

Benefits and drawbacks of open partial horizontal laryngectomies, Part B: Intermediate and selected advanced stage laryngeal carcinoma.

Head Neck 2016 04 15;38 Suppl 1:E649-57. Epub 2015 Jun 15.

Otorhinolaryngology Service, Vittorio Veneto Hospital, Vittorio Veneto, Treviso, Italy.

Background: Cancer of the larynx in the intermediate/advanced stage still presents a major challenge in terms of controlling the disease and preserving the organ. Among therapeutic options, open partial horizontal laryngectomy is proposed as a function-sparing surgical technique.

Methods: We analyzed the clinical outcomes of 555 patients with laryngeal cancer staged pT3 to pT4a who underwent open partial horizontal laryngectomy.

Results: Five-year overall survival (OS), disease-free survival (DFS), locoregional control, local control, laryngectomy-free survival, and laryngeal function preservation rates were 84.6%, 84.2%, 86.3%, 90.6%, 93.3%, and 91.2%, respectively. DFS, locoregional control, and laryngeal function preservation rates were significantly affected by pT4a staging (68.1%, 71.7%, and 78.0%, respectively), whereas pN+ influenced only DFS (≤72.6%) and locoregional control (≤79.6%).

Conclusions: Open partial horizontal laryngectomy with a modular approach can be considered effective in terms of prognostic and functional results in intermediate-stage and selected advanced-stage laryngeal cancers, even with subglottic extension. © 2015 Wiley Periodicals, Inc. Head Neck 38: E649-E657, 2016.
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http://dx.doi.org/10.1002/hed.24064DOI Listing
April 2016

ErbB2 receptor over-expression improves post-traumatic peripheral nerve regeneration in adult mice.

PLoS One 2013 21;8(2):e56282. Epub 2013 Feb 21.

Department of Clinical and Biological Sciences, University of Turin, Orbassano (TO), Italy.

In a transgenic mice (BALB-neuT) over-expressing ErbB2 receptor, we investigated the adult mouse median nerve in physiological and pathological conditions. Results showed that, in physiological conditions, the grip function controlled by the median nerve in BALB-neuT mice was similar to wild-type (BALB/c). Stereological assessment of ErbB2-overexpressing intact nerves revealed no difference in number and size of myelinated fibers compared to wild-type mice. By contrast, after a nerve crush injury, the motor recovery was significantly faster in BALB-neuT compared to BALB/c mice. Moreover, stereological assessment revealed a significant higher number of regenerated myelinated fibers with a thinner axon and fiber diameter and myelin thickness in BALB-neuT mice. At day-2 post-injury, the level of the mRNAs coding for all the ErbB receptors and for the transmembrane (type III) Neuregulin 1 (NRG1) isoforms significantly decreased in both BALB/c and BALB-neuT mice, as shown by quantitative real time PCR. On the other hand, the level of the mRNAs coding for soluble NRG1 isoforms (type I/II, alpha and beta) increased at the same post-traumatic time point though, intriguingly, this response was significantly higher in BALB-neuT mice with respect to BALB/c mice. Altogether, these results suggest that constitutive ErbB2 receptor over-expression does not influence the physiological development of peripheral nerves, while it improves nerve regeneration following traumatic injury, possibly through the up-regulation of soluble NRG1 isoforms.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0056282PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3578860PMC
August 2013

Self-renewal and multipotency coexist in a long-term cultured adult rat dental pulp stem cell line: an exception to the rule?

Stem Cells Dev 2012 Dec 25;21(18):3278-88. Epub 2012 Jun 25.

Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.

The stemness state is characterized by self-renewal and differentiation properties. However, stem cells are not able to preserve these characteristics in long-term culture because of the intrinsic fragility of their phenotype easily undergoing senescence or neoplastic transformation. Furthermore, although isolated from the same original tissue using similar protocols, adult stem cells can display dissimilar phenotypes and important cell clone/species contamination. Finally, the lack of a clear standardization contributes to complicate the comprehension about the stemness condition. In this context, cell lines displaying a particularly stable phenotype must be identified to define one or multiple benchmarks against which other stem cell lines could be reliably assessed. The present paper demonstrates that it is possible to isolate from the rat dental pulp a stem cell line (MUR-1) that does not display neoplastic transformation in long-term culture. MUR-1 cells stably express a broad range of stemness markers and are able to differentiate into adipogenic, osteogenic, chondrogenic, neurogenic, and cardiomyogenic lineages independently of the culture passages. Moreover, serial in vitro passages have not changed their immunophenotype, proliferation capacity, or differentiation potential. The uniqueness of these characteristics candidates MUR-1 as a model to reliably improve the understanding of the mechanisms governing the stem cell fate in the same as well as in other stem cell populations.
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http://dx.doi.org/10.1089/scd.2012.0141DOI Listing
December 2012

A DNA vaccine against ERBB2 impairs chemical carcinogenesis in random-bred hamsters.

Cancer Prev Res (Phila) 2011 Jul;4(7):994-1001

Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.

Vaccines against oncoantigens halt early neoplastic lesions in several cancer-prone, genetically engineered mouse models, whereas their ability to prevent chemical carcinogenesis has not been explored. This is a significant issue, as exposure to chemical mutagens is responsible for a substantial percentage of cancers worldwide. Here, we show that the archetypal oncoantigen ERBB2 is transiently overexpressed in Syrian hamsters during the early stages of 7,12-dimethylbenz[α]anthracene (DMBA)-induced oral carcinogenesis. Repeated DNA vaccinations against ERBB2 significantly reduce the number, size, and severity of oral lesions in a manner directly proportional to the anti-ERBB2 antibody response. These results support the prospects of vaccines as a fresh strategy in the management of individuals at risk for exposure to defined carcinogenic agents.
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http://dx.doi.org/10.1158/1940-6207.CAPR-10-0301DOI Listing
July 2011

Apelin-13 limits infarct size and improves cardiac postischemic mechanical recovery only if given after ischemia.

Am J Physiol Heart Circ Physiol 2011 Jun 4;300(6):H2308-15. Epub 2011 Mar 4.

Dipartimento di Scienze Cliniche e Biologiche, Facoltà di Medicina e Chirurgia "S. Luigi Gonzaga", Regione Gonzole 10, 10043 Orbassano (TO) Italy.

We studied whether apelin-13 is cardioprotective against ischemia/reperfusion injury if given as either a pre- or postconditioning mimetic and whether the improved postischemic mechanical recovery induced by apelin-13 depends only on the reduced infarct size or also on a recovery of function of the viable myocardium. We also studied whether nitric oxide (NO) is involved in apelin-induced protection and whether the reported ischemia-induced overexpression of the apelin receptor (APJ) plays a role in cardioprotection. Langendorff-perfused rat hearts underwent 30 min of global ischemia and 120 min of reperfusion. Left ventricular pressure was recorded. Infarct size and lactate dehydrogenase release were determined to evaluate the severity of myocardial injury. Apelin-13 was infused at 0.5 μM concentration for 20 min either before ischemia or in early reperfusion, without and with NO synthase inhibition by N(G)-nitro-l-arginine (l-NNA). In additional experiments, before ischemia also 1 μM apelin-13 was tested. APJ protein level was measured before and after ischemia. Whereas before ischemia apelin-13 (0.5 and 1.0 μM) was ineffective, after ischemia it reduced infarct size from 54 ± 2% to 26 ± 4% of risk area (P < 0.001) and limited the postischemic myocardial contracture (P < 0.001). l-NNA alone increased postischemic myocardial contracture. This increase was attenuated by apelin-13, which, however, was unable to reduce infarct size. Ischemia increased APJ protein level after 15-min perfusion, i.e., after most of reperfusion injury has occurred. Apelin-13 protects the heart only if given after ischemia. In this protection NO plays an important role. Apelin-13 efficiency as postconditioning mimetic cannot be explained by the increased APJ level.
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http://dx.doi.org/10.1152/ajpheart.01177.2010DOI Listing
June 2011

Salicylate inhibition of rat mammary carcinogenesis and angiogenesis in female rat compatible with misoprostol administration.

Int J Oncol 2005 Mar;26(3):697-702

Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, I-10043 Orbassano (TO), Italy.

Epidemiological data suggest that non-steroidal anti-inflammatory drugs prevent colon cancer. The evidence for other types of tumour is less conclusive, though animal and in vitro studies indicate that they may be effective against mammary cancer cells. We assessed the effect of dietary acetylsalicylic and salicylic acid against dimethylbenzanthracene-induced rat tumours. Tumour angiogenesis was also investigated to explore the mechanism responsible for salicylate effect. Mammary tumours were induced in female Sprague-Dawley rats fed with different amounts of acetylsalicylic and salicylic acid. Serum vascular endothelial growth factor concentrations were measured and vascularization of basement membrane proteins injected in vivo (Matrigel) was determined by evaluation of haemoglobin content to assess the extent to which angiogenesis was inhibited. Dimethylbenzanthracene-induced carcinogenesis was inhibited by both acids and there was a log-dose/response correlation between the tumour diameter and salicylate concentration. Salicylic acid seems more effective than acetylsalicylic acid. Vascular endothelial growth factor was less concentrated in treated animals than in the controls and so was Matrigel haemoglobin. The mechanism involved, however, is still uncertain, though concomitant inhibition of tumour angiogenesis may be an important component. The documented salicylate serum VEGF modulation is interesting also for presence of the flk-1 receptor in mammary tumour cells of our model. Although misoprostol is a prostaglandin analogous its concomitant administration did not compromise the salicylate anti-tumour effect.
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March 2005
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