http://elea.unisa.it/xmlui/handle/10556/89 2026-04-20T10:53:50Z 2026-04-20T10:53:50Z Cassiano, Chiara http://elea.unisa.it/xmlui/handle/10556/3880 2025-04-30T15:09:43Z 2014-04-24T00:00:00Z

In vitro and in cell functional proteomics on natural compounds Cassiano, Chiara Chemical proteomics has acquired a pivotal role in chemical biology because of its peculiar capability to deeply analyze the proteome from many points of view. Proteins identification, characterization and quantification provide a detailed portrait of a biological system. In particular, pharmaceutical research is looking with interest at chemical proteomics because the mechanism of action of bioactive molecules remains one of the main challenge. Particularly, the identification of target proteins and investigation of ligand-receptor interactions are today considered essential steps in the drug discovery and development process. Affinity purification-based mass spectrometry approaches (AP-MS) have emerged as a valuable mean to link bioactive compounds to their cellular targets. In recent years, the application of such techniques led to successful results in determining the macromolecular partners of many interesting bioactive molecules. These techniques require the chemical modifications of the molecule of interest onto a solid matrix, in order to allow the bioactive compound to “fish out” its specific interactors from a cell lysate or a tissue extract. Once eluted, these cellular targets are identified by MS and bioinformatics analysis. Later on, the biological profile of the selected compound toward its cellular interactors is investigated by in vitro and/or in vivo assays. 2012 - 2013

2014-04-24T00:00:00Z Di Cristo, Francesca http://elea.unisa.it/xmlui/handle/10556/2488 2025-04-30T14:29:45Z 2017-03-22T00:00:00Z

Design, synthesis, biological studies of new mitochondrial modulators improving neurological deficits in experimental models of Huntington's disease Di Cristo, Francesca 2014 - 2015

2017-03-22T00:00:00Z Esposito, Andrea http://elea.unisa.it/xmlui/handle/10556/2487 2025-04-30T14:32:04Z 2017-03-24T00:00:00Z

Techniques of proteomic analysis as tools for studies in biomedical field Esposito, Andrea It is known that prenatal exposure to pollutants and particularly heavy metals can have long term damaging consequences on infants, due to their accumulation in-body. Since the 1990s, ten million tonnes of waste have been illegally dumped in the area around Caserta and Naples. Thus, direct exposure to waste and heavy metals during the last two decades was very frequent in the so-called “Lands of fires”. The number of children suffering from cancer and of malformed fetuses in Italy's "Land of Fires", an area where toxic waste has been dumped by the mafia, is reported significantly higher than elsewhere in the country. In this thesis we examined the proteome of the umbilical cords from malformed fetuses obtained by therapeutic abortions, after mothers' being exposed to the pollution on “land of fire” during early pregnancy, and analyzed the differences between umbilical cords from malformed fetuses to healthy ones. The main goals were to understand the impact of the contamination by heavy metals on the fetus development, and to identify new putative biomarkers of exposure to metal contaminants. All umbilical cords were obtained in Campania region (Naples and Caserta, mainly in the “land of fires”). The collection of the biological samples was carried out in collaboration with the Caserta Hospital “Sant’Anna e San Sebastiano” and with the Avellino Hospital “San Giuseppe Moscati”. A proteomic approach based on Filter-Aided Sample Preparation (FASP) method was set up and performed. This bio-analytical strategy combines the advantages of in-gel and in-solution digestion for mass spectrometry–based proteomics, greatly reduces the time required for sample preparation and enables more flexibility in sample processing. Protein identification and quantification were performed by matching mass spectrometry data in on-line protein database, using the MaxQuant 1.5.2.8 software. Statistical analyses were employed to identify proteins whose levels were sensibly different in the umbilical cords from malformed fetuses. Gene Ontology (GO) classification was used in order to obtain functional information of the differentially expressed proteins and to correlate them to the embryonic development. Finally, Matrix Metalloproteinases (MMPs) have been shown to play significant roles in a number of physiological processes, including embryogenesis and angiogenesis, but they also contribute to the development of pathological processes. Thus, gelatin zymography technique was performed to detect MMPs enzymatic activity in the umbilical cords. Our results support a significant role of MMPs in the fetus development. [edited by author] 2014 - 2015

2017-03-24T00:00:00Z Fiore, Donatella http://elea.unisa.it/xmlui/handle/10556/2485 2026-02-05T11:56:41Z 2017-03-23T00:00:00Z

In vitro and in vivo study of cannabinoids as modulators of Wnt/β-catenin pathway in human colorectal cancer Fiore, Donatella Colorectal cancer (CRC) is the second most common cause of cancer death. Molecular events in CRC has been extensively studied and several data suggest that Wnt/β-catenin signaling deregulation play a pivotal role in colorectal carcinogenesis. Majority of both familial syndromes (FAP) and sporadic colon cancers, arise from APC or β-catenin genes alterations, leading to Wnt signaling hyperactivation. According to the cancer stem cells (CSCs) theory, some cancer-initiating cells, harboring stem-cell like properties, evade standard chemotherapies, resulting in recurrent and metastatic tumors. Wnt/β-catenin signaling and its deregulation is involved in the recurrence and maintenance of CSCs. In recent years, understanding of molecular mechanisms underlying CSCs biology, led to development of novel strategies to completely eradicate colorectal cancer. Some evidences suggest a potential crosstalk between the endocannabinoid system and the Wnt pathway, also in cancer stem cells, in several tumor types. This could represent a key mechanism in the control of the anti-cancer activity of cannabinoids, as well as a novel putative site for pharmacological intervention. Results from this work led to identification of Rimonabant, originally an inverse agonist of CB1 cannabinoids receptor, as modulator of Wnt/β-catenin pathway in CRC, able to control colon cancer stemness, without toxicity toward cells from healty tissue. Moreover, for the first time, we proposed a novel epigenetic mechanism Rimonabant-mediated. [edited by author] 2014 - 2015

2017-03-23T00:00:00Z