30 research outputs found
Targeting A3 and A2A adenosine receptors in the fight against cancer
No full textIntroduction: There is a vicious cycle of tumor hypoxia, high adenosine levels, immune suppression and cancer growth that involves the use of adenosine receptor ligands in tumors. After several years of research, the candidates emerging as promising new anticancer drugs are A3 adenosine receptor agonists and A2A receptor antagonists. Areas covered: The authors give an updated overview of the field related to A3 receptor agonists and A2A receptor antagonists in cancer and propose their perspectives on the status of these compounds in oncology. The rationale for the modulation of adenosine receptors in cancer is addressed, starting from the first in vitro evidence of their efficacy up to the animal and clinical studies. Expert opinion: A3 and A2A receptors are attractive targets in oncologic therapy due to their involvement in cancer progression and immune-resistance. Of relevance, the A3 subtype is also a tumor marker to be used in a personalized drug treatment program while the A2A receptor, playing a non-redundant role in immunomodulation, may be blocked in combination with checkpoint inhibitors to improve their efficacy. The future will reveal how successful this approach is in the fight against cancer
Per una ricostruzione dell’Apostolado del Duca d’Alcalá
No full textL'articolo ricostruisce per la prima volta la celebre serie dell'Apostolato che il Duca d'Alcalà commissionò ai tredici pittori "più insigni" che si trovavano in Italia nel 1625. La ricerca ha permesso di collegare alla serie, per la prima volta, tele di Artemisia Gentileschi, Guido Reni, Giovanni Baglione, Battistello Caracciolo e Jusepe de Ribera
A1 Adenosine Receptor Partial Agonists and Allosteric Modulators: Advancing Toward the Clinic?
No full textThis opinion article discusses the most interesting results obtained in preclinical and clinical studies using A1AR partial agonists and positive allosteric modulators
Le strategie per affrontare la carenza di infermieri in 11 aziende sanitarie: una analisi descrittiva
No full textIdentification and characterization of a new reversible MAGL inhibitor
No full textMonoacylglycerol lipase is a serine hydrolase that play a major role in the degradation of 2-arachidonoylglycerol, an endocannabinoid neurotransmitter implicated in several physiological processes. Recent studies have shown the possible role of MAGL inhibitors as antiinflammatory, anti-nociceptive and anti-cancer agents. The use of irreversible MAGL inhibitors determined an unwanted chronic MAGL inactivation, which acquires a functional antagonism function of the endocannabinoid system. However, the application of reversible MAGL inhibitors has not yet been explored, mainly due to the scarcity of known compounds possessing efficient reversible inhibitory activities. In this study we reported the first virtual screening analysis for the identification of reversible MAGL inhibitors. Among the screened compounds, the (4-(4-chlorobenzoyl)piperidin-1-yl)(4-methoxyphenyl)methanone (CL6a) is a promising reversible MAGL inhibitor lead (Ki = 8.6 μM), which may be used for the future development of a new class of MAGL inhibitors. Furthermore, the results demonstrate the validity of the methodologies that we followed, encouraging additional screenings of other commercial databases
Pulsed electromagnetic field and relief of hypoxia-induced neuronal cell death: The signaling pathway
No full textLow-energy low-frequency pulsed electromagnetic fields (PEMFs) exert several protective effects, such as the regulation of kinases, transcription factors as well as cell viability in both central and peripheral biological systems. However, it is not clear on which bases they affect neuroprotection and the mechanism responsible is yet unknown. In this study, we have characterized in nerve growth factor-differentiated pheochromocytoma PC12 cells injured with hypoxia: (i) the effects of PEMF exposure on cell vitality; (ii) the protective pathways activated by PEMFs to relief neuronal cell death, including adenylyl cyclase, phospholipase C, protein kinase C epsilon and delta, p38, ERK1/2, JNK1/2 mitogen-activated protein kinases, Akt and caspase-3; (iii) the regulation by PEMFs of prosurvival heat-shock proteins of 70 (HSP70), cAMP response element-binding protein (CREB), brain-derived neurotrophic factor (BDNF), and Bcl-2 family proteins. The results obtained in this study show a protective effect of PEMFs that are able to reduce neuronal cell death induced by hypoxia by modulating p38, HSP70, CREB, BDNF, and Bcl-2 family proteins. Specifically, we found a rapid activation (30 min) of p38 kinase cascade, which in turns enrolles HSP70 survival chaperone molecule, resulting in a significant CREB phosphorylation increase (24 hr). In this cascade, later (48 hr), BDNF and the antiapoptotic pathway regulated by the Bcl-2 family of proteins are recruited by PEMFs to enhance neuronal survival. This study paves the way to elucidate the mechanisms triggered by PEMFs to act as a new neuroprotective approach to treat cerebral ischemia by reducing neuronal cell death
Signaling pathways involved in anti-inflammatory effects of Pulsed Electromagnetic Field in microglial cells
No full textLiterature studies suggest important protective effects of low-frequency, low-energy pulsed electromagnetic fields (PEMFs) on inflammatory pathways affecting joint and cerebral diseases. However, it is not clear on which bases they affect neuroprotection and the mechanism responsible is yet unknown. Therefore the aim of this study was to identify the molecular targets of PEMFs anti-neuroinflammatory action. The effects of PEMF exposure in cytokine production by lipopolysaccharide (LPS)-activated N9 microglial cells as well as the pathways involved, including adenylyl cyclase (AC), phospholipase C (PLC), protein kinase C epsilon (PKC-ε) and delta (PKC-δ), p38, ERK1/2, JNK1/2 mitogen activated protein kinases (MAPK), Akt and caspase 1, were investigated. In addition, the ability of PEMFs to modulate ROS generation, cell invasion and phagocytosis, was addressed. PEMFs reduced the LPS-increased production of TNF-α and IL-1β in N9 cells, through a pathway involving JNK1/2. Furthermore, they decreased the LPS-induced release of IL-6, by a mechanism not dependent on AC, PLC, PKC-ε, PKC-δ, p38, ERK1/2, JNK1/2, Akt and caspase 1. Importantly, a significant effect of PEMFs in the reduction of crucial cell functions specific of microglia like ROS generation, cell invasion and phagocytosis was found. PEMFs inhibit neuroinflammation in N9 cells through a mechanism involving, at least in part, the activation of JNK MAPK signalling pathway and may be relevant to treat a variety of diseases characterized by neuroinflammation
Upregulation of Cortical A2Aadenosine receptors is reflected in platelets of patients with Alzheimer's Disease
No full textBackground: Alzheimer's disease (AD) is a neurodegenerative pathology covering about 70%of all cases of dementia. Adenosine, a ubiquitous nucleoside, plays a key role in neurodegeneration, through interaction with four receptor subtypes. The A2A receptor is upregulated in peripheral blood cells of patients affected by Parkinson's and Huntington's diseases, reflecting the same alteration found in brain tissues. However, whether these changes are also present in AD pathology has not been determined. Objective: In this study we verified any significant difference between AD cases and controls in both brain and platelets and we evaluated whether peripheral A2A receptors may reflect the status of neuronal A2A receptors. Methods: We evaluated the expression of A2A receptors in frontal white matter, frontal gray matter, and hippocampus/entorhinal cortex, in postmortem AD patients and control subjects, through [3H]ZM 241385 binding experiments. The same analysis was performed in peripheral platelets from AD patients versus controls. Results: The expression of A2A receptors in frontal white matter, frontal gray matter, and hippocampus/entorhinal cortex, revealed a density (Bmax) of 174±29, 219±33, and 358±84 fmol/mg of proteins, respectively, in postmortem AD patients in comparison to 104±16, 103±19, and 121±20 fmol/mg of proteins in controls (p < 0.01). The same trend was observed in peripheral platelets from AD patients versus controls (Bmax of 214±17 versus 95±4 fmol/mg of proteins, respectively, p < 0.01). Conclusion: AD subjects show significantly higher A2A receptor density than controls. Values on platelets seem to correlate with those in the brain supporting a role for A2A receptor as a possible marker of AD pathology and drug target for novel therapies able to modify the progression of dementia
Antibacterial activity of biogenic silver nanoparticles and cytotoxicity in human hepatocarcinoma cells (Huh-7)
No full textopenAttualmente le nanoparticelle d’argento (AgNPs) vengono impiegate principalmente per le loro proprietà antimicrobiche; tuttavia, è possibile osservare il loro effetto inibitorio sulla crescita e sulla proliferazione di varie cellule tumorali. Questo studio intende analizzare l’attività antibatterica di nanoparticelle d’argento biogeniche e la loro citotossicità in cellule di epatocarcinoma umano (Huh-7). La sintesi biogenica di AgNPs è stata condotta utilizzando il secretoma acquoso del fungo Fusarium oxysporum f. sp. cubense (AgNP@Fo) e l'estratto di buccia d'arancia (AgNP@OR). Nonostante presentassero proprietà fisiche e morfologiche simili, evidenziate attraverso microscopia STEM (Scanning Transmission Electron Microscopy) e AFM (Atomic Force Microscopy), le nanoparticelle hanno dimostrato bioattività diverse. L’efficacia antimicrobica di entrambe le nanoparticelle è stata valutata rispetto diversi batteri, come S. Aureus ed E. Coli: AgNP@Fo è risultata circa dieci volte più potente di AgNP@OR. Gli effetti antitumorali sono stati dimostrati dal saggio MTT, confermati dal test della calceina-AM e dall'imaging a fluorescenza: AgNP@Fo ha mostrato una citotossicità 20 volte superiore rispetto ad AgNP@OR, con un valore IC50 di 0,545 μmol L−1. I risultati di questo lavoro stabiliscono, dunque, solide basi per la futura esplorazione delle interazioni molecolari delle nanoparticelle sintetizzate attraverso diverse vie biosintetiche, in particolare all'interno di ambienti cellulari batterici e tumorali
