1,721,003 research outputs found
Multiple parameters are involved in the effects of cadmium on prenatal hepatocytes
No full textCadmium, a toxic heavy metal, expresses its toxicity by affecting several cellular functions such as, enzyme activities, DNA repair systems, redox state of the cell and signal transduction. Although the liver is a known target organ, the mechanisms involved in cadmium toxicity are not yet clarified, especially during prenatal development. Here we consider the effects of cadmium on viability, proliferation. adhesion and defence mechanisms in primary adult and fetal rat hepatocytes. Fetal hepatocytes are less sensitive to cadmium toxicity, they appear to be unaffected or even stimulated by treatments that strongly inhibit DNA synthesis in adult cells. The behaviour of proteins involved in cell cycle regulation also differs from adult cells, according to the proliferative state. In addition, following Cd exposure, E-cadherin/betacatenin complex disassembles in both cell types, with fetal cells being influenced at higher doses. The beta-catenin is not found in the nucleus, ruling out a direct role on DNA synthesis stimulation Finally., metallothionein is more easily inducible in fetal hepatocytes, while Cd intracellular concentrations and HSP protein levels are not differentially affected. In conclusion, multiple cellular targets are affected by Cd in primary hepatocytes and the adverse effects of the metal are always better counteracted by fetal cells. (C) 2009 Elsevier Ltd. All rights reserved
Morphological and Genetic Characterization of Lignicolous Macrofungi in Extreme Environments of Abruzzo
No full textThe Abruzzo region is characterized by its diverse ecological landscapes and hosts a remarkable assemblage of lignicolous macrofungi (polypores). This study focuses on the morphological and genetic characterization of selected polypores collected from two distinct and extreme environments (within the project PRIN Prot. P20228KSTN): Fonte Gelata and Monte Sirente, areas recognized for their harsh environmental conditions, including low temperatures, high altitudes, landslide and nutrient-poor substrates. The survey identified several fungal species, including Trametes hirsuta, Phellinus lundellii, Fomitopsis pinicola, and Fomes fomentarius. Morphological analyses emphasized macro- and microscopic features, such as basidiocarp texture, pore size, and spore morphology, while genetic characterization employed ITS (Internal Transcribed Spacer) sequencing to confirm species identification and analyze phylogenetic relationships. This combined approach provided insights into their ecological roles and adaptive strategies. The results highlighted the high biodiversity of polypores in these regions, with species like Fomitopsis pinicola and Fomes fomentarius exhibiting strong adaptations to lignin degradation in extreme climatic conditions. Genetic analysis revealed population-level divergences, suggesting local adaptations to substrate and environmental stressors. Additionally, Phellinus lundellii and Trametes hirsuta demonstrated habitat specificity, contributing to the ecological stability of these forest ecosystems. These findings underscore the importance of preserving fungal biodiversity in Abruzzo’s extreme environments as a critical component of ecosystem resilience and nutrient cycling. Conservation strategies, including habitat protection and in situ monitoring and changes in forest management, are essential to safeguard these fungi as bioindicators and reservoirs of genetic and functional diversity that can be exploited for human well-being. In fact, these species are know to produce a vast repertory of bioactive metabolites that are under study in the current project
Adhesion to the extracellular matrix is positively regulated by retinoic acid in HepG2 cells
No full textAims: In this work, we aimed to investigate the possible modulation of cell–matrix interactions by retinoic acid (RA), in view of the well-known role of the extracellular matrix (ECM) and integrins in hepatocyte differentiation and proliferation. For this purpose, we analysed the adhesion ability of HepG2 cells on different substrates in the presence and absence of RA evaluating both the expression and cellular localisation of major proteins involved in focal contacts, using Western blot and confocal microscopy. Results: A positive and substratedependent effect of RA on cell–matrix adhesion was observed after long-term culture. The increased adhesiveness in the treated cells was accompanied by an enhanced expression of b1 and a3 integrin subunits, together with a redistribution of b1 receptors clustered at the basal surface. In contrast, the levels of focal adhesion kinase (FAK), paxillin and a-actinin were unchanged, as was the phosphorylation state of FAK. Nonetheless, a stronger association between b1 integrin and intracytoplasmatic proteins of focal contacts was observed in coimmunoprecipitation experiments after RA treatment, suggesting improved connection with the actin cytoskeleton.These results are consistent with previously described antiproliferative and differentiative effects of RA on transformed hepatocytes, and confirm the hypothesis of a direct influence of RA on specific adhesion molecules
Chitosan-coated PLGA nanoparticles: A sustained drug release strategy for cell cultures
No full textA recently patented one-step methodology was used for the formulation of chitosan (CS) coated polylactic-co-glycolic acid (PLGA) nanoparticles containing dexamethasone (DXM) as a model drug. SEM investigations showed that nanoparticles (NPs) were spherical in shape with smooth surface. CS coating switched NPs zeta-potential from negative to positive, without modifying particle size distribution. Moreover, CS coating allowed a significant modulation of in vitro drug release, providing a sustained drug delivery in cultured cells. The uptake of fluorescent CS-coated PLGA NPs by hepatocytes (C3A) and fibroblasts (3T6) as well as the fate of internalized NPs were investigated by confocal microscopy. 3T6 and C3A cells were treated with DXM-loaded NPs and experiments were addressed to analyze the specific cell response to DXM, in order to evaluate its functional efficiency in comparison with conventional addition to culture medium. CS-coating of DXM loaded PLGA NPs allowed their uptake by cultured cells without inducing cytotoxicity. (c) 2012 Elsevier B.V. All rights reserved
Targeting Cyclic AMP Signalling in Hepatocellular Carcinoma
Get PDFHepatocellular carcinoma (HCC) is a major healthcare problem worldwide, representing one of the leading causes of cancer mortality. Since there are currently no predictive biomarkers for early stage diagnosis, HCC is detected only in advanced stages and most patients die within one year, as radical tumour resection is generally performed late during the disease. The development of alternative therapeutic approaches to HCC remains one of the most challenging areas of cancer. This review focuses on the relevance of cAMP signalling in the development of hepatocellular carcinoma and identifies the modulation of this second messenger as a new strategy for the control of tumour growth. In addition, because the cAMP pathway is controlled by phosphodiesterases (PDEs), targeting these enzymes using PDE inhibitors is becoming an attractive and promising tool for the control of HCC. Among them, based on current preclinical and clinical findings, PDE4- specific inhibitors remarkably demonstrate therapeutic potential in the management of cancer outcomes, especially as adjuvants to standard therapies. However, more preclinical studies are warranted to ascertain their effica
Hypertonic stress regulates amino acid transport and cell cycle proteins in chick embryo hepatocytes
No full textHyperosmotic stress affects cell growth, decreasing cell volume and increasing the uptake of organic osmolytes. However, the sensitivity of embryonic cells to osmotic treatment remains to be established. We have analysed some aspects of cell-cycle control and amino-acid transport in hypertonic conditions during prenatal life. The effects of hyperosmotic stress on amino-acid uptake mediated by system A, H-3-thymidine incorporation, and regulation of cell-cycle proteins were analysed in chick embryo hepatocytes. Hypertonic stress increased system A activity and caused cell-cycle delay. Effects on amino-acid transport involved p38 kinase activation and new carrier synthesis. Cyclin D1, cdk4 (cyclin-dependent kinase 4) and PCNA (proliferating-cell nuclear antigen) levels decreased, whereas cyclin E, p21 and p53 levels were unchanged. Incorporation of H-3-leucine indicated decreased synthesis of cyclin D1 In contrast, analysis of mRNA by qRT-PCR (quantitative real-time FOR) showed a net increase of cyclin D1 transcripts, suggesting post-transcriptional regulation. The data show that chick embryo hepatocytes respond to hyperosmotic conditions by arresting cell growth to prevent DNA damage and increasing osmolyte uptake to regulate cell volume, indicating that the adaptive response to environmental stress exists during prenatal life
Effects of resveratrol on HepG2 cells as revealed by 1H-NMR based metabolic profiling
No full textBackground: Resveratrol, a polyphenol found in plant products, has been shown to regulate many cellular processes and to display multiple protective and therapeutic effects. Several in vitro and in vivo studies have demonstrated the influence of resveratrol on multiple intracellular targets that may regulate metabolic homeostasis. Methods: We analysed the metabolic modifications induced by resveratrol treatment in a human hepatoblastoma line, HepG2 cells, using a H-1-NMR spectroscopy-based metabolomics approach that allows the simultaneous screening of multiple metabolic pathways. Results: Results demonstrated that cells cultured in the presence or absence of resveratrol displayed different metabolic profiles: the treatment induced a decreased utilisation of glucose and amino acids for purposes of energy production and synthesis associated to a decreased release of lactate in the culture medium and an increase in succinate utilisation. At the same time, resveratrol treatment slowed the cell cycle in the S phase without inducing apoptosis, and increased Sirt1 expression, also affecting its intracellular localisation. Conclusions: Our results show that the metabolomic analysis of the exometabolome of resveratrol-treated HepG2 cells indicates a metabolic switch from glucose and amino acid utilisation to fat utilisation for the production of energy, and seem in agreement with an effect mediated via AMPK- and Sirt1-activation. General significance: NMR-based metabolomics has been applied in a hepatocyte cell culture model in relation to resveratrol treatment; such an approach could be transferred to evaluate the effects of nutritional compounds with health impact. (C) 2011 Elsevier B.V. All rights reserved
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
ETHANOL EXTRACTS OF Ganoderma Pfeifferi, Laetiporus Sulphureus AND Fomes Inzengae EXERT ANTI TUMORAL EFFECTS ON HEPATOCARCINOMA CELLS
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