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  1. Article ; Online: Knockdown of NANOG Reduces Cell Proliferation and Induces G0/G1 Cell Cycle Arrest in Human Adipose Stem Cells

    Maria Pitrone / Giuseppe Pizzolanti / Antonina Coppola / Laura Tomasello / Stefania Martorana / Gianni Pantuso / Carla Giordano

    International Journal of Molecular Sciences, Vol 20, Iss 10, p

    2019  Volume 2580

    Abstract: The core components of regenerative medicine are stem cells with high self-renewal and tissue regeneration potentials. Adult stem cells can be obtained from many organs and tissues. NANOG , SOX2 and OCT4 represent the core regulatory network that ... ...

    Abstract The core components of regenerative medicine are stem cells with high self-renewal and tissue regeneration potentials. Adult stem cells can be obtained from many organs and tissues. NANOG , SOX2 and OCT4 represent the core regulatory network that suppresses differentiation-associated genes, maintaining the pluripotency of mesenchymal stem cells. The roles of NANOG in maintaining self-renewal and undifferentiated status of adult stem cells are still not perfectly established. In this study we define the effects of downregulation of NANOG in maintaining self-renewal and undifferentiated state in mesenchymal stem cells (MSCs) derived from subcutaneous adipose tissue (hASCs). hASCs were expanded and transfected in vitro with short hairpin Lentivirus targeting NANOG . Gene suppressions were achieved at both transcript and proteome levels. The effect of NANOG knockdown on proliferation after 10 passages and on the cell cycle was evaluated by proliferation assay, colony forming unit (CFU), qRT-PCR and cell cycle analysis by flow-cytometry. Moreover, NANOG involvement in differentiation ability was evaluated. We report that downregulation of NANOG revealed a decrease in the proliferation and differentiation rate, inducing cell cycle arrest by increasing p27 / CDKN1B (Cyclin-dependent kinase inhibitor 1B) and p21 / CDKN1A (Cyclin-dependent kinase inhibitor 1A) through p53 and regulate DLK1 / PREF1 . Furthermore, NANOG induced downregulation of DNMT1 , a major DNA methyltransferase responsible for maintaining methylation status during DNA replication probably involved in cell cycle regulation. Our study confirms that NANOG regulates the complex transcription network of plasticity of the cells, inducing cell cycle arrest and reducing differentiation potential.
    Keywords human adipose stem cell ; NANOG ; cell cycle regulation ; DNMT1 ; lentiviral transduction ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 571
    Language English
    Publishing date 2019-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: The Prevalence of NAFLD and Fibrosis in Bariatric Surgery Patients and the Reliability of Noninvasive Diagnostic Methods

    Maurizio Soresi / Daniela Cabibi / Rosaria V. Giglio / Stefania Martorana / Giuseppina Guercio / Rossana Porcasi / Antonino Terranova / Luigi A. Lazzaro / Maria R. Emma / Giuseppa Augello / Melchiorre Cervello / Gianni Pantuso / Giuseppe Montalto / Lydia Giannitrapani

    BioMed Research International, Vol

    2020  Volume 2020

    Abstract: Background. Bariatric surgery patients have a higher prevalence of nonalcoholic fatty liver (NAFL) than the general population; however, its assessment and the accurate staging of fibrosis are often complicated because noninvasive tests are not very ... ...

    Abstract Background. Bariatric surgery patients have a higher prevalence of nonalcoholic fatty liver (NAFL) than the general population; however, its assessment and the accurate staging of fibrosis are often complicated because noninvasive tests are not very accurate in patients with morbid obesity, and liver biopsy cannot be performed as a routine exam. The aim of this study was to evaluate (A) the histological prevalence of NAFL, nonalcoholic steatohepatitis (NASH), and fibrosis in patients undergoing bariatric surgery; (B) the reliability of ultrasound (US) in diagnosing NAFL; and (C) the reliability of various fibrosis scoring systems for defining fibrosis. Methods. US and intraoperative liver biopsy results were reviewed in 57 bariatric surgery patients. NAFL, NASH, and fibrosis were diagnosed according to the Kleiner scoring system. US diagnosis of liver steatosis was based on the bright liver. Fibrosis scores used were (i) the BMI, AST/ALT Ratio, Diabetes (BARD) scoring system; (ii) the nonalcoholic fatty liver disease (NAFLD) fibrosis score; and (iii) the fibrosis-4 (FIB-4) index. Results. The prevalence of NAFL was 81%, NASH 61.4%, and fibrosis 94% (F3 5.7%, cirrhosis 2.8%). The sensitivity of US was 95%, specificity 50%, and likelihood ratio (LR+, LR-) 1.91 and 0.1. The reliability of fibrosis scores for F≥2 were as follows: BARD score: sensitivity 46%, specificity 54%, and area under the receiver-operating characteristics (AUROC) curve 0.5; NAFLD score: sensitivity 30%, specificity 89%, and AUROC 0.5; and FIB-4: sensitivity 68%, specificity 67%, and AUROC 0.7. Conclusions. In bariatric surgery patients, the prevalence of NAFL was 81%, NASH 61.4%, and fibrosis 94%. US is able to rule out the presence of NAFL, while the commonly used scores may be inaccurate in defining fibrosis in patients with morbid obesity.
    Keywords Medicine ; R
    Subject code 610
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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