Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: KBBE.2011.2.2-02 | Award Amount: 7.84M | Year: 2012
NutriTech will build on the foundations of traditional human nutrition research using cutting-edge analytical technologies and methods to comprehensively evaluate the diet-health relationship and critically assess their usefulness for the future of nutrition research and human well-being. Technologies include genomics, transcriptomics, proteomics, metabolomics, laser scanning cytometry, NMR based lipoprotein profiling and advanced imaging by MRI/MRS. All methods will be applied in an integrated manner to quantify the effect of diet on phenotypic flexibility, based on metabolic flexibility (the capacity for the organism to adapt fuel oxidation to fuel availability). However, NutriTech will move beyond the state-of-the-art by applying these integrated methods to assess the underlying and related cell biological and genetic mechanisms and multiple physiological processes of adaptation when homeostasis is challenged. Methods will in the first instance be evaluated within a human intervention study, and the resulting optimal methods will be validated in a number of existing cohorts against established endpoints. NutriTech will disseminate the harmonised and integrated technologies on a global scale by a large academic network including 6 non-EU partners and by providing an integrated and standardised data storage and evaluation platform. The impact of NutriTech will be multifold and exploitation is crucial as major breakthroughs from our technology and research are expected. This will be achieved by collaboration with a consortium of 8 major food industries and by exploitation of specific technologies by our 6 SME partners. Overall, NutriTech will lay the foundations for successful integration of emerging technologies intro nutrition research.
Omodei D.,University of Washington |
Licastro D.,CBM Scrl Genomics |
Salvatore F.,CEINGE Biotecnologie Avanzate scarl |
Crosby S.D.,University of Washington |
And 2 more authors.
Aging | Year: 2013
Calorie restriction (CR) without malnutrition is the most robust intervention to slow aging and extend healthy lifespan in experimental model organisms. Several metabolic and molecular adaptations have been hypothesized to play a role in mediating the anti-aging effects of CR, including enhanced stress resistance, reduced oxidative stress and several neuroendocrine modifications. However, little is known about the independent effect of circulating factors in modulating key molecular pathways. In this study, we used sera collected from individuals practicing long-term CR and from age- and sex-matched individuals on a typical US diet to culture human primary fibroblasts and assess the effects on gene expression and stress resistance. We show that treatment of cultured cells with CR sera caused increased expression of stress-response genes and enhanced tolerance to oxidants. Cells cultured in serum from CR individuals showed a 30% increase in resistance to H2O2 damage. Consistently, SOD2 and GPX1 mRNA, two key endogenous antioxidant enzymes, were increased by 2 and 2.5 folds respectively in cells cultured with CR sera. These cellular and molecular adaptations mirror some of the key effects of CR in animals, and further suggest that circulating factors contribute to the CR-mediated protection against oxidative stress and stress-response in humans as well. © Omodei et al.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.1.2-5 | Award Amount: 3.42M | Year: 2009
This project aims to elucidate the molecular coding of meso-diencephalic dopaminergic (mdDA) neurons forming the complex meso-limbic and nigro-striatal dopaminergic system in the vertebrate central nervous system. Recent advances in molecular and developmental biology have shown that this system harbors u multitude of functional units that are defined by spatial and temporal cues and are represented by specific molecular codes. These codes are essential to understand specific mdDA neuronal pathology as Parkinsons diseases and schizophrenia. In this collaborative project we gather the expertise on early and late development, cross species molecular-coding conservation, migration and axonal pathfinding to capture the significance of the understanding of mdDA neuronal development to generate a real advance in clinical understanding and treatment of mdDA pathology.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.1.4-1;HEALTH.2012.2.3.2-1 | Award Amount: 7.81M | Year: 2013
Worldwide, 200 million people are infected with the hepatitis C virus (HCV). An estimated 15 million individuals are living with HCV infection within the EU. The economic, health and societal costs of chronic HCV infection are significant. HCV is the principal cause of death from liver disease and the leading indication for liver transplantation. The only treatment for end-stage liver disease is a liver transplant, yet the transplanted liver becomes rapidly re-infected and is frequently destroyed within 5 years after transplantation. In this cohort of patients current antiviral treatments are too toxic - there is an urgent need to develop safe and effective treatments for use in this setting. Human monoclonal antibodies (MAbs) that target virus entry, are as yet an underutilised and potentially highly effective and safe weapon in the armoury against HCV infection. The consortium has identified MAb leads which, in pre-clinical analyses, potently block HCV infection. HCV exhibits a high degree of genetic and antigenic variability, which enables the virus to escape protective immune responses. Crucially, the lead antibodies identified by the consortium are capable of preventing infection by a wide range of genetically distinct isolates because they target highly conserved epitopes on the virus or host receptor molecules. This limits the chances of virus resistance. Also, each lead antibody targets a unique component of the viral entry pathway, thereby paving the way for powerful combinatorial approaches which maximises clinical potency. HepaMAb harnesses leading expertise in MAb technology, preclinical efficacy and safety testing, biomanufacture and clinical trial to progress at least one anti-viral and one anti-receptor human MAb to phase I/IIa proof of concept clinical trial in the liver transplant setting for the prevention of graft reinfection. We will establish a much-needed therapeutic MAb pipeline for use in this solid organ transplant setting.
Bianco A.,University of Molise |
Mazzarella G.,The Second University of Naples |
Turchiarelli V.,University of Molise |
Nigro E.,CEINGE Biotecnologie Avanzate Scarl |
And 5 more authors.
Nutrients | Year: 2013
Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory lung disease which may be complicated by development of co-morbidities including metabolic disorders. Metabolic disorders commonly associated with this disease contribute to lung function impairment and mortality. Systemic inflammation appears to be a major factor linking COPD to metabolic alterations. Adipose tissue seems to interfere with systemic inflammation in COPD patients by producing a large number of proteins, known as "adipokines", involved in various processes such as metabolism, immunity and inflammation. There is evidence that adiponectin is an important modulator of inflammatory processes implicated in airway pathophysiology. Increased serum levels of adiponectin and expression of its receptors on lung tissues of COPD patients have recently highlighted the importance of the adiponectin pathway in this disease. Further, in vitro studies have demonstrated an anti-inflammatory activity for this adipokine at the level of lung epithelium. This review focuses on mechanisms by which adiponectin is implicated in linking COPD with metabolic disorders. © 2013 by the authors; licensee MDPI, Basel, Switzerland.
Ferone G.,Netherlands Cancer Institute |
Mollo M.R.,CEINGE Biotecnologie Avanzate SCarl |
Mollo M.R.,University of Naples Federico II |
Missero C.,University of Naples Federico II
Cell and Tissue Research | Year: 2015
As the outermost tissue of the body, the epidermis is the first physical barrier for any pressure, stress or trauma. Several specialized cell–matrix and cell–cell adhesion structures, together with an intracellular network of dedicated intermediate filaments, are required to confer critical resilience to mechanical stress. The transcription factor p63 is a master regulator of gene expression in the epidermis and in other stratified epithelia. It has been extensively demonstrated that p63 positively controls a large number of tissue-specific genes, including those encoding a large fraction of tissue-restricted cell adhesion molecules. Consistent with p63 functions in cell adhesion and in epidermal differentiation, heterozygous mutations clustered mainly in the p63 C-terminus are causative of AEC syndrome, an autosomal dominant disorder characterized by cleft palate, ankyloblepharon and ectodermal dysplasia associated with severe skin erosions, bleeding and infections. The molecular basis of skin erosions in AEC patients is not fully understood, although defects in desmosomes and in other cell junctions are likely to be involved. Here, we provide an extensive review of the different epidermal cell junctions that cooperate to withstand mechanical stress and on the mechanisms by which p63 regulates gene expression of their components in healthy skin and in AEC syndrome. Collectively, advancement in understanding the molecular mechanisms by which epidermal cell junctions precisely exert their functions and how p63 orchestrates their coordinated expression, will ultimately lead to insight into developing future strategies for the treatment of AEC syndrome and more in generally for diseases that share an overlapping phenotype. © 2015, Springer-Verlag Berlin Heidelberg.
Nigro E.,CEINGE Biotecnologie Avanzate Scarl |
Scudiero O.,CEINGE Biotecnologie Avanzate Scarl |
Scudiero O.,University of Naples Federico II |
Sarnataro D.,CEINGE Biotecnologie Avanzate Scarl |
And 5 more authors.
International Journal of Biochemistry and Cell Biology | Year: 2013
Adiponectin (Acrp30) exerts protective functions on metabolic and cellular processes as energy metabolism, cell proliferation and differentiation by two widely expressed receptors, AdipoR1 and AdipoR2. To date, the biological role of Acrp30 in lung has not been completely assessed but altered levels of Acrp30 and modulated expression of both AdipoRs have been related to establishment and progression of chronic obstructive pulmonary disease (COPD) and lung cancer. Here, we investigated the effects of Acrp30 on A549, a human alveolar epithelial cell line, showing how, in a time and dose-dependent manner, it decreases cell viability and increases apoptosis through ERK1/2 and AKT. Furthermore, we examined the effects of Acrp30 on A549 cells exposed to TNFa and/or IL-1ß, two potent lung inflammatory cytokines. We showed that Acrp30, in dose- and time-dependent manner, reduces cytotoxic effects of TNFa and/or IL-1ß improving cell viability and decreasing apoptosis. In addition, Acrp30 inhibits NF-?B nuclear trans-activation and induces the expression of the anti-inflammatory IL-10 cytokine without modifying that of pro-inflammatory IL-6, IL-8, and MCP-1 molecules via ERK1/2 and AKT. Finally, specifically silencing AdipoR1 or AdipoR2, we observed that NF-?B inhibition is mainly mediated by AdipoR1. Taken together, our data provides novel evidence for a direct effect of Acrp30 on the proliferation and inflammation status of A549 cells strongly supporting the hypothesis for a protective role of Acrp30 in lung. Further studies are needed to fully elucidate the Acrp30 lung effects in vivo but our results confirm this adipokine as a promising therapeutic target in lung diseases. © 2013 Elsevier Ltd.
Ilardi G.,University of Naples Federico II |
Zambrano N.,CEINGE Biotecnologie Avanzate SCaRL |
Merolla F.,University of Naples Federico II |
Siano M.,University of Naples Federico II |
And 5 more authors.
Current Medicinal Chemistry | Year: 2014
Intrinsic and acquired drug resistance of tumor cells still causes the failure of treatment regimens in advanced human cancers. It may be driven by intrinsic tumor cells features, or may also arise from micro environmental influences. Hypoxia is a microenvironment feature associated with the aggressiveness and metastasizing ability of human solid cancers. Hypoxic cancer cells overexpress Carbonic Anhydrase IX (CA IX). CA IX ensures a favorable tumor intracellular pH, while contributing to stromal acidosis, which facilitates tumor invasion and metastasis. The overexpression of CA IX is considered an epiphenomenon of the presence of hypoxic, aggressive tumor cells. Recently, a relationship between CA IX overexpression and the cancer stem cells (CSCs) population has been hypothesized. CSCs are strictly regulated by tumor hypoxia and drive a major non-mutational mechanism of cancer drug-resistance. We reviewed the current data concerning the role of CA IX overexpression in human malignancies, extending such information to the expression of the stem cells markers CD44 and nestin in solid cancers, to explore their relationship with the biological behavior of tumors. CA IX is heavily expressed in advanced tumors. A positive trend of correlation between CA IX overexpression, tumor stage/grade and poor outcome emerged. Moreover, stromal CA IX expression was associated with adverse events occurrence, maybe signaling the direct action of CA IX in directing the mesenchymal changes that favor tumor invasion; in addition, membranous/cytoplasmic co-overexpression of CA IX and stem cells markers were found in several aggressive tumors. This suggests that CA IX targeting could indirectly deplete CSCs and counteract resistance of solid cancers in the clinical setting. © 2014 Bentham Science Publishers.
Gemei M.,CEINGE Biotecnologie Avanzate s.c.a.r.l |
Corbo C.,CEINGE Biotecnologie Avanzate s.c.a.r.l |
D'Alessio F.,CEINGE Biotecnologie Avanzate s.c.a.r.l |
Di Noto R.,CEINGE Biotecnologie Avanzate s.c.a.r.l |
And 4 more authors.
Proteomics | Year: 2013
Cancer stem cell characterization represents a breakthrough in cancer research. Despite evidence showing the existence and the role of cancer stem cells in osteosarcoma (OS) onset and progression, little is known about their specific surface phenotype. To address this issue, we carried out a cytometric analysis with an antibody-array comprising 245 membrane proteins comparing the stem and differentiated OS cells. As experimental model, we chose the stem-like cell line 3aminobenzamide-OS and its parental, differentiated, cell line MG63. We identified 50 differentially expressed, 23 homogeneously expressed, and 172 not expressed proteins in the two cell line models, thus defining a surface protein signature specific for each of them. Furthermore, we selected ERK1/2 (p44/42 mitogen-activated protein kinases) as a potential pathway correlated with processes that characterize tumorigenic potential and stemness of 3aminobenzamide-OS cells. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PubMed | CEINGE Biotecnologie Avanzate Scarl, The Second University of Naples and University of Naples Federico II
Type: | Journal: Pulmonary pharmacology & therapeutics | Year: 2017
The influence of obesity on development, severity and prognosis of both asthma and COPD is attracting growing interest. The impact of obesity on the respiratory system ranges from structural modifications (decline of total lung capacity) to humoral alterations. Adipose tissue strongly contributes to the establishment of an inflammatory state being an important source of adipokines. Amongst adipokines, adiponectin is an important component of organ cross talk with adipose tissue exerting protective effects on a variety of pathophysiological processes. Adiponectin is secreted in serum where it abundantly circulates as complexes of different molecular weight. Adiponectin properties are mediated by specific receptors that are widely expressed with AdipoR1, AdipoR2, and T-cadherin being present on epithelial and endothelial pulmonary cells indicating a functional role on lung physiology. In COPD, mild to moderate obesity has been shown to have protective effects on patients survival, while a higher mortality rate has been observed in patients with low BMI. A specific cluster of obese patients has been identified; in this group, asthma features are particularly severe and difficult to treat. Better understanding of the molecular mechanisms at the base of cross talk among different tissues and organs will lead to identification of new targets for both diagnosis and treatment of asthma and COPD.