Nutrigenetics, nutrigenomics and phenotypic outcomes of dietary low-dose alcohol consumption in the suppression and induction of cancer development: evidence from in vitro studies

It is known that the intake of alcoholic beverages may impair genetic and epigenetic regulatory events with consequent crucial effects on cell phenotypes and that its association with selected genotypes can lead to a different risk of cancer in the population. The aim of this review is to pick up selected studies on this topic and recapitulate some of the biochemical and nutrigenetic/nutrigenomic aspects involved in the impact of dietary low-dose alcohol consumption on the switching-on or -off of tumorigenic pathways. These include i) the existence of predisposing or protective human genotypes and the relationship between dietary compounds and alcohol in the promotion or inhibition of carci…

The early plastisphere of biodegradable and non-biodegradable plastic films in marine environment

Introduction Plastic items are the most common form of marine debris and plastic accumulation in marine ecosystems is a serious environmental issue. One possible solution to reduce the amount of synthetic polymers released in the environment is to substitute them with bio-based polymers. When released in marine environments, plastics are readily colonized by biofilm-forming microorganisms, the so called “plastisphere community”, which may include pathogenic, invasive and plastic-degrading species; the composition and influence of the plastisphere on the fate of plastic is largely unknown. The aim of this study is to investigate the early biofilm formation and the structure and diversity of …

Methylation of cytokines gene promoters in IL-1β-treated human intestinal epithelial cells

Objective and design: Epigenetic regulation is important in the activation of inflammatory cells. In the present study, we evaluated if DNA-methylation variations are involved in Interleukin-1β (IL-1β)-induced intestinal epithelial cells activation. Materials and methods: Differentiated Caco-2 cells were exposed to IL-1β or to 5-azadeoxycytidine (5-azadC) for 24 or 48 h. Genome-wide methylation status was evaluated, while DNA methylation status at the promoter region of the gene encoding interleukin-6, 8 and 10 (IL-6, 8 and 10) was estimated. The levels of the corresponding gene products as well as DNA methyltransferases (DNMTs) quantity were assessed. Results: IL-1β decreased genomic m…

Il progetto Mentori per la Didattica dell’Università degli Studi di Palermo: l’estensione del numero dei partecipanti, la figura del Mentore Senior e le esperienze di innovazione didattica

L’esperienza del Progetto Mentore (PM) nasce nel 2013 dalla percezione, da parte di diversi docenti dell’Ateneo di Palermo, che l’Accademia italiana stesse abbandonando a sé stessa la funzione didattica, confidando di fatto nelle capacità di ognuno di organizzarsi, aggiornarsi e valutarsi (Felisatti, Scialdone, Cannarozzo, & Pennisi, 2019; Caradonna, Morale, Pace, Scargiali, Scialdone, & Auteri, 2020). Tale impressione era tra le altre cose basata sul fatto che nessuno dei sistemi di valutazione dei docenti universitari (il processo di abilitazione scientifica nazionale, ma anche la stessa valutazione della qualità dei corsi di studio) mettesse enfasi sulla necessità da parte del do…

Jay Amin Hydroxamic Acid (JAHA), a histone deacetylase inhibitor with cytotoxic activity and the property to increase DNA repair of triple-negative MDA-MB231 breast cancer cells.

Jay Amin Hydroxamic Acid (JAHA; N8-ferrocenylN1-hydroxy-octanediamide) is a ferrocene-containing analogue of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA). JAHA’s cytotoxic activity on MDA-MB231 triple negative breast cancer (TNBC) cells at 72 h has been previously demonstrated with an IC50 of 8.45 M. JAHA’s lethal effect was found linked to perturbations of cell cycle, mitochondrial activity, signal transduction and autophagy mechanisms. In order to glean novel insights on how MDA-MB231 breast cancer cells respond to the cytotoxic effect induced by JAHA, and to compare the biological effect with the related compound SAHA, we have employed a combination o…

AEROBIC 1,2-DICHLOROETHANE DEGRADERS IN CONTAMINATED GROUNDWATER

Two immortalized rat astrocyte cell lines as in vitro model for specific cell proliferation studies: cytogenetic and epigenomic characterization and diversification

Here we report differences between: 1) a heterogeneous population of primary rat brain astrocytes (Primary), in culture since several years ago, and 2) a cloned cell line (Clone), obtained from the Primary cells. Both populations maintain astrocyte morphology but, according to cytogenetic and epigenomic characterization, differ for the chromosomal asset from rat normal cells (42 chromosomes): Primary cells show mostly a bimodal karyotype with 41 or 43 chromosomes, and Clone has a unique-modal karyotype of 43 chromosomes. Interestingly, we also found that both cell lines show genome-wide DNA hypomethylation, with Clone showing even more pronounced demethylation respect to Primary cells. Thes…

Integrated production of biopolymers with industrial wastewater treatment: Effects of OLR on process yields, biopolymers characteristics and mixed microbial community enrichment

The production of polyhydroxyalkanoates (PHA) using industrial wastewaters as feedstocks is a current and challenging topic. This study investigated the production of biopolymers by a mixed microbial culture under different OLRs equal to 1 kgCOD m-3d-1 (Period 1), 2 kgCOD m-3d-1 (Period 2) and 3 kgCOD m-3d-1 (Period 3). The maximum PHA content was achieved in Period 2 (0.38 gPHA gTSS-1), whereas lower values were obtained in Period 1 (0.13 gPHA gTSS-1) and Period 3 (0.26 gPHA gTSS-1). Overall, the maximum PHA productivity resulted equal to 0.08 gPHA L-1h-1 (P2), 0.05 gPHA L-1h-1 (P1) and 0.04 gPHA L-1h-1 (P3), respectively. The molecular weight of the PHA increased from Period 1 (250 kDa) t…

Cytotoxic activity of the histone deacetylase 3-Selective inhibitor Pojamide on MDA-MB-231 triple-negative breast cancer cells

We examined the effects of the ferrocene-based histone deacetylase-3 inhibitor Pojamide (N1-(2-aminophenyl)-N8-ferrocenyloctanediamide) and its two derivatives N1-(2-aminophenyl)-N6-ferrocenyladipamide and N1-(2-aminophenyl)-N8-ferroceniumoctanediamide tetrafluoroborate on triple-negative MDA-MB-231 breast cancer cells. Viability/growth assays indicated that only the first two compounds at 70 &mu

An In Vitro Model of Glioma Development

Gliomas are the prevalent forms of brain cancer and derive from glial cells. Among them, astrocytomas are the most frequent. Astrocytes are fundamental for most brain functions, as they contribute to neuronal metabolism and neurotransmission. When they acquire cancer properties, their functions are altered, and, in addition, they start invading the brain parenchyma. Thus, a better knowledge of transformed astrocyte molecular properties is essential. With this aim, we previously developed rat astrocyte clones with increasing cancer properties. In this study, we used proteomic analysis to compare the most transformed clone (A-FC6) with normal primary astrocytes. We found that 154 proteins are…

Genotoxicity and Epigenotoxicity of Carbazole-Derived Molecules on MCF-7 Breast Cancer Cells

The carbazole compounds PK9320 (1-(9-ethyl-7-(furan-2-yl)-9H-carbazol-3-yl)-N-methylmethanamine) and PK9323 (1-(9-ethyl-7-(thiazol-4-yl)-9H-carbazol-3-yl)-N-methylmethanamine), second-generation analogues of PK083 (1-(9-ethyl-9H-carbazol-3-yl)-N-methylmethanamine), restore p53 signaling in Y220C p53-mutated cancer cells by binding to a mutation-induced surface crevice and acting as molecular chaperones. In the present paper, these three molecules have been tested for mutant p53-independent genotoxic and epigenomic effects on wild-type p53 MCF-7 breast adenocarcinoma cells, employing a combination of Western blot for phospho-γH2AX histone, Comet assay and methylation-sensitive arbitrarily pr…

Due diverse esperienze di lezioni sperimentali condotte secondo il metodo di co-teaching

Nell’ambito del progetto “Mentori per la didattica”, nato nel 2013 da un ristretto gruppo di docenti dell’Università di Palermo e che comprende oggi 120 docenti, oltre alle attività di mentoring fra pari, sono state promosse diverse attività formative. Fra queste, tre workshop in tre anni consecutivi sono stati dedicati alla formazione sull’active learning e su metodi e tecniche di didattica innovativa ed in particolare nell’ultimo anno è stata importante la partecipazione di alcuni componenti del progetto al congresso “Faculty development“ e al pre-workshop del convegno di Genova di maggio 2019. A partire da tutte queste esperienze, diversi docenti hanno iniziato a sperimentare nuove modal…

Mid-region parathyroid hormone-related protein is a genome-wide chromatin-binding factor that promotes growth and differentiation of HB2 epithelial cells from the human breast

Human parathyroid hormone-related protein (PTHrP) is a polyhormone that undergoes proteolytic cleavage producing smaller peptides which exert diversified biological effects. PTHrP signalization is prominently involved in breast development and physiology, but the studies have been focused onto either N-terminal species or full-length protein introduced by gene transfer techniques. Our present work investigates for the first time the effect of the mid-region PTHrP secretory form, that is, the fragment [38-94], on HB2 non-tumoral breast epithelial cells. We examined viability/proliferation of cells grown in PTHrP-containing media supplemented with different serum concentration and on differen…

Molecular Signatures Associated with Treatment of Triple-Negative MDA-MB231 Breast Cancer Cells with Histone Deacetylase Inhibitors JAHA and SAHA

Jay Amin Hydroxamic Acid (JAHA; N8-ferrocenylN1-hydroxy-octanediamide) is a ferrocene-containing analogue of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA). JAHA’s cytotoxic activity on MDA-MB231 triple negative breast cancer (TNBC) cells at 72 h has been previously demonstrated with an IC50 of 8.45 M. JAHA’s lethal effect was found linked to perturbations of cell cycle, mitochondrial activity, signal transduction and autophagy mechanisms. In order to glean novel insights on how MDA-MB231 breast cancer cells respond to the cytotoxic effect induced by JAHA, and to compare the biological effect with the related compound SAHA, we have employed a combination of…

Protective effects of melatonin in inflamed intestinal epithelium are associated with reduced NF-κB activation and changes in DNA methylation status

Melatonin is the main product of the pineal gland but is also released in the gastrointestinal tract (GIT). Production of melatonin at GIT is independent of the photoperiod and contributes almost completely to plasma melatonin concentration during daylight hours. The physiological role of melatonin at GIT is poorly characterized but recently anti-inflammatory effects have been reported. In this study, we evaluated the effect of Melatonin in intestinal epithelial cells (IEC) stimulated by Interleukin-1β. Our results clearly show that melatonin at micromolar concentrations inhibits the inflammatory response in IEC. The protective effect is expressed through a marked decrease in release and ex…

CHARACTERIZATION OF TRANSFORMED CELL LINES OBTAINED FROM PRIMARY RAT CORTICAL ASTROCYTES

Brain cancers are complex and heterogeneous; most of them derive from glial cells[1], and are called gliomas, further subdivided into astrocytomas, oligodendrogliomas, ependymomas and glioastrocytomas[2]. The malignant cells undergo modifications of their metabolism and behaviour, and acquire the ability to migrate along the blood vessels in small groups (model of the guerrilla war)[3], thus invading the surrounding brain parenchyma. Most important, they have the capacity to affect the surrounding microenvironment, by altering both the extracellular matrix and the properties of the normal cells present in the brain, including glial-, endothelial-, and immune-cells, further promoting cancer …

Nutritional epigenomic and DNA-damage modulation effect of natural stilbenoids

The aim of the present work is the evaluation of biological effects of natural stilbenoids found in Vitis vinifera, with a focus on their activity as epigenetic modulators. In the present study, resveratrol, pterostilbene and for the first time their dimers (±)-trans-δ-viniferin, (±)-trans-pterostilbene dehydrodimer were evaluated in Caco-2 and HepG-2 cell lines as potential epigenetic modulators. Stilbenoids were added in a Caco-2 cell culture as a model of the intestinal epithelial barrier and in the HepG-2 as a model of hepatic environment, to verify their dose-dependent toxicity, ability to interact with DNA, and epigenomic action. Resveratrol, pterostilbene, and (±)-trans-pterostilbene…

Establishment and Preliminary Characterization of Three Astrocytic Cells Lines Obtained from Primary Rat Astrocytes by Sub-Cloning.

Gliomas are complex and heterogeneous tumors that originate from the glial cells of the brain. The malignant cells undergo deep modifications of their metabolism, and acquire the capacity to invade the brain parenchyma and to induce epigenetic modifications in the other brain cell types. In spite of the efforts made to define the pathology at the molecular level, and to set novel approaches to reach the infiltrating cells, gliomas are still fatal. In order to gain a better knowledge of the cellular events that accompany astrocyte transformation, we developed three increasingly transformed astrocyte cell lines, starting from primary rat cortical astrocytes, and analyzed them at the cytogenet…

1,2-DICHLOROETHANE CONTAMINATED AQUIFER: MICROBIAL COMMUNITY RESPONSE TO BIOSTIMULATION IN MICROCOSM

Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin‐1β

Melatonin is the main secretory product of the pineal gland, and it is involved in the regulation of periodic events. A melatonin production independent of the photoperiod is typical of the gut. However, the local physiological role of melatonin at the intestinal tract is poorly characterized. In this study, we evaluated the anti-inflammatory activities of melatonin in an in vitro model of inflamed intestinal epithelium. To this purpose, we assessed different parameters usually associated with intestinal inflammation using IL-1 beta-stimulated Caco-2 cells. Differentiated monolayers of Caco-2 cells were preincubated with melatonin (1 nmol/L-50 mu mol/L) and then exposed to IL-1 beta. After …

Plastica in mare: biodiversità della plastisfera

La plastica costituisce la componente più abbondante dei rifiuti in ambiente marino. Le plastiche in mare sono colonizzate da biofilm microbici, denominati plastisfera, che possono comprendere patogeni, specie algali tossiche e invasive e, potenzialmente, organismi in grado di biodeteriorare e degradare le plastiche (Zettler et al. 2013). Lo scopo di questo lavoro è studiare e confrontare le comunità microbiche che colonizzano plastiche biodegradabili e non biodegradabili in ambiente marino. Un esperimento di esposizione di film plastici in ambiente marino portuale è stato allestito per studiare la diversità della plastisfera di alcune plastiche biodegradabili (Mater Bi e PLA-acido polilatt…

ENHANCED BIOREMEDIATION E MONITORAGGIO MICROBIOLOGICO DI ACQUA CONTAMINATA DA SOLVENTI CLORURATI

I solventi clorurati sono composti organici di sintesi appartenenti alla classe degli idrocarburi alifatici clorurati, largamente impiegati in diversi settori industriali e, come conseguenza, ampiamente diffusi nell’ambiente come inquinanti e particolarmente pericolosi anche per la salute umana. Tra i metodi di bonifica di siti contaminati da solventi clorurati, quelli basati sul biorisanamento sfruttano uno dei peculiari metabolismi batterici coinvolti nella biodegradazione di tali composti: la declorurazione riduttiva anaerobia in cui il composto clorurato è utilizzato come accettore terminale di elettroni in un vero e proprio processo di respirazione anaerobia, detta dealorespirazione; i…