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61.
Ilaria Patruno Dr. Dawn Thompson Dr. Sergio Dall'Angelo Prof. Albert D. Windhorst Dr. Danielle J. Vugts Dr. Alex J. Poot Dr. Nimesh Mody Prof. Matteo Zanda 《ChemMedChem》2020,15(16):1579-1590
Fenretinide (4-HPR) is a synthetic derivative of all-trans-retinoic acid (ATRA) characterised by improved therapeutic properties and toxicological profile relative to ATRA. 4-HPR has been mostly investigated as an anti-cancer agent, but recent studies showed its promising therapeutic potential for preventing metabolic syndrome. Several biological targets are involved in 4-HPR's activity, leading to the potential use of this molecule for treating different pathologies. However, although 4-HPR displays quite well-understood multitarget promiscuity with regards to pharmacology, interpreting its precise physiological role remains challenging. In addition, despite promising results in vitro, the clinical efficacy of 4-HPR as a chemotherapeutic agent has not been satisfactory so far. Herein, we describe the preparation of a library of 4-HPR analogues, followed by the biological evaluation of their anti-cancer and anti-obesity/diabetic properties. The click-type analogue 3 b showed good capacity to reduce the amount of lipid accumulation in 3T3-L1 adipocytes during differentiation. Furthermore, it showed an IC50 of 0.53±0.8 μM in cell viability tests on breast cancer cell line MCF-7, together with a good selectivity (SI=121) over noncancerous HEK293 cells. Thus, 3 b was selected as a potential PET tracer to study retinoids in vivo, and the radiosynthesis of [18F] 3b was successfully developed. Unfortunately, the stability of [18F] 3b turned out to be insufficient to pursue imaging studies. 相似文献
62.
Immacolata Ruggiero Monica Terracciano Nicola M Martucci Luca De Stefano Nunzia Migliaccio Rosarita Tatè Ivo Rendina Paolo Arcari Annalisa Lamberti Ilaria Rea 《Nanoscale research letters》2014,9(1):329
Diatomite is a natural fossil material of sedimentary origin, constituted by fragments of diatom siliceous skeletons. In this preliminary work, the properties of diatomite nanoparticles as potential system for the delivery of drugs in cancer cells were exploited. A purification procedure, based on thermal treatments in strong acid solutions, was used to remove inorganic and organic impurities from diatomite and to make them a safe material for medical applications. The micrometric diatomite powder was reduced in nanoparticles by mechanical crushing, sonication, and filtering. Morphological analysis performed by dynamic light scattering and transmission electron microscopy reveals a particles size included between 100 and 300 nm. Diatomite nanoparticles were functionalized by 3-aminopropyltriethoxysilane and labeled by tetramethylrhodamine isothiocyanate. Different concentrations of chemically modified nanoparticles were incubated with cancer cells and confocal microscopy was performed. Imaging analysis showed an efficient cellular uptake and homogeneous distribution of nanoparticles in cytoplasm and nucleus, thus suggesting their potentiality as nanocarriers for drug delivery.
PACS
87.85.J81.05.Rm; 61.46. + w 相似文献63.
Camille Jacques Ilaria Floris Batrice Lejeune 《International journal of molecular sciences》2021,22(13)
Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) are two cytokines involved in the perpetuation of the chronic inflammation state characterizing rheumatoid arthritis (RA). Significant advances in the treatment of this pathology have been made over the past ten years, partially through the development of anti-TNF and anti-IL-1 therapies. However, major side effects still persist and new alternative therapies should be considered. The formulation of the micro-immunotherapy medicine (MIM) 2LARTH® uses ultra-low doses (ULD) of TNF-α, IL-1β, and IL-2, in association with other immune factors, to gently restore the body’s homeostasis. The first part of this review aims at delineating the pivotal roles played by IL-1β and TNF-α in RA physiopathology, leading to the development of anti-TNF and anti-IL-1 therapeutic agents. In a second part, an emphasis will be made on explaining the rationale of using multiple therapeutic targets, including both IL-1β and TNF-α in 2LARTH® medicine. Particular attention will be paid to the ULD of those two main pro-inflammatory factors in order to counteract their overexpression through the lens of their molecular implication in RA pathogenesis. 相似文献
64.
Silvio Borrelli Luca De Nicola Ilaria De Gregorio Lucio Polese Luigi Pennino Claudia Elefante Alessandro Carbone Tiziana Rappa Roberto Minutolo Carlo Garofalo 《International journal of molecular sciences》2021,22(23)
Sodium overload is common in end-stage kidney disease (ESKD) and is associated with increased cardiovascular mortality that is traditionally considered a result of extracellular volume expansion. Recently, sodium storage was detected by Na23 magnetic resonance imaging in the interstitial tissue of the skin and other tissues. This amount of sodium is osmotically active, regulated by immune cells and the lymphatic system, escapes renal control, and, more importantly, is associated with salt-sensitive hypertension. In chronic kidney disease, the interstitial sodium storage increases as the glomerular filtration rate declines and is related to cardiovascular damage, regardless of the fluid overload. This sodium accumulation in the interstitial tissues becomes more significant in ESKD, especially in older and African American patients. The possible negative effects of interstitial sodium are still under study, though a higher sodium intake might induce abnormal structural and functional changes in the peritoneal wall. Interestingly, sodium stored in the interstial tissue is not unmodifiable, since it is removable by dialysis. Nevertheless, the sodium removal by peritoneal dialysis (PD) remains challenging, and new PD solutions are desirable. In this narrative review, we carried out an update on the pathophysiological mechanisms of volume-independent sodium toxicity and possible future strategies to improve sodium removal by PD. 相似文献
65.
Serena Montalbano Francesca Degola Jennifer Bartoli Franco Bisceglie Annamaria Buschini Mauro Carcelli Donatella Feretti Serena Galati Laura Marchi Nicol Orsoni Giorgio Pelosi Marianna Pioli Francesco M. Restivo Dominga Rogolino Mirco Scaccaglia Olga Serra Giorgio Spadola Gaia C. V. Viola Ilaria Zerbini Claudia Zani 《International journal of molecular sciences》2021,22(9)
The control of the fungal contamination on crops is considered a priority by the sanitary authorities of an increasing number of countries, and this is also due to the fact that the geographic areas interested in mycotoxin outbreaks are widening. Among the different pre- and post-harvest strategies that may be applied to prevent fungal and/or aflatoxin contamination, fungicides still play a prominent role; however, despite of countless efforts, to date the problem of food and feed contamination remains unsolved, since the essential factors that affect aflatoxins production are various and hardly to handle as a whole. In this scenario, the exploitation of bioactive natural sources to obtain new agents presenting novel mechanisms of action may represent a successful strategy to minimize, at the same time, aflatoxin contamination and the use of toxic pesticides. The Aflatox® Project was aimed at the development of new-generation inhibitors of aflatoxigenic Aspergillus spp. proliferation and toxin production, through the modification of naturally occurring molecules: a panel of 177 compounds, belonging to the thiosemicarbazones class, have been synthesized and screened for their antifungal and anti-aflatoxigenic potential. The most effective compounds, selected as the best candidates as aflatoxin containment agents, were also evaluated in terms of cytotoxicity, genotoxicity and epi-genotoxicity to exclude potential harmful effect on the human health, the plants on which fungi grow and the whole ecosystem. 相似文献
66.
Quinone‐Fused Pyrazoles through 1,3‐Dipolar Cycloadditions: Synthesis of Tricyclic Scaffolds and in vitro Cytotoxic Activity Evaluation on Glioblastoma Cancer Cells 下载免费PDF全文
Giulio Bertuzzi Simone Crotti Pierpaolo Calandro Bianca Flavia Bonini Ilaria Monaco Erica Locatelli Mariafrancesca Fochi Paolo Zani Elena Strocchi Prof. Andrea Mazzanti Dr. Mario Chiariello Prof. Mauro Comes Franchini 《ChemMedChem》2018,13(17):1744-1750
A novel and straightforward synthesis of highly substituted isoquinoline‐5,8‐dione fused tricyclic pyrazoles is reported. The key step of the synthetic sequence is a regioselective, Ag2CO3 promoted, 1,3‐dipolar cycloaddition of C‐heteroaryl‐N‐aryl nitrilimines and substituted isoquinoline‐5,8‐diones. The broad functional group tolerability and mild reaction conditions were found to be suitable for the preparation of a small library of compounds. These scaffolds were designed to interact with multiple biological residues, and two of them, after brief synthetic elaborations, were analyzed by molecular docking studies as potential anticancer drugs. In vitro studies confirmed the potent anticancer effects, showing promising IC50 values as low as 2.5 μm against three different glioblastoma cell lines. Their cytotoxic activity was finally positively correlated to their ability to inhibit PI3K/mTOR kinases, which are responsible for the regulation of diverse cellular processes in human cancer cells. 相似文献
67.
Zn in Athenian Black Gloss Ceramic Slips: A Trace Element Marker for Fabrication Technology 下载免费PDF全文
Marc Walton Karen Trentelman Ilaria Cianchetta Jeffrey Maish David Saunders Brendan Foran Apurva Mehta 《Journal of the American Ceramic Society》2015,98(2):430-436
The black‐colored pottery slips produced in Athens from the 6th to 4th centuries B.C., had a consistent composition achieved through processing and refinement of raw clay. Little direct evidence has been established as to what were these refinement methods. To better understand how the slip material was prepared, the major and trace elemental compositions of 19 slips from different ceramic vessels and their corresponding bodies of Athenian red‐figure and black‐figure vases were determined using laser ablation inductively coupled plasma mass spectrometry (LA‐ICPMS). Notably higher Zn concentrations were found in the slips (271–1959 ppm) than in their corresponding body ceramics (<361 ppm). The Zn concentrations in the slips were also found to be above the natural background for typical clay (between 10 and 300 ppm) suggesting an unintentional anthropogenic enrichment of this metal. Based on the abnormally high Zn content of the slip, it is speculated that the clay was treated using vitriol (concentrated acid mine runoff which is rich in Zn), to induce flocculation and remove carbonate mineral phases from the raw material that, if present, would prevent the slip from vitrifying. This same signature of elevated levels of Zn with a corresponding Ce anomaly is also observed for black glosses produced in Corinthian and Etrurian (Italy) workshops indicating that these trace element signatures were imparted to the material by means of shared methods of manufacturing instead of being indicative of a single unique source for this material. 相似文献
68.
Elisabetta Coppi Ilaria Dettori Federica Cherchi Irene Bulli Martina Venturini Daniele Lana Maria Grazia Giovannini Felicita Pedata Anna Maria Pugliese 《International journal of molecular sciences》2020,21(24)
Adenosine is a signaling molecule, which, by activating its receptors, acts as an important player after cerebral ischemia. Here, we review data in the literature describing A2BR-mediated effects in models of cerebral ischemia obtained in vivo by the occlusion of the middle cerebral artery (MCAo) or in vitro by oxygen-glucose deprivation (OGD) in hippocampal slices. Adenosine plays an apparently contradictory role in this receptor subtype depending on whether it is activated on neuro-glial cells or peripheral blood vessels and/or inflammatory cells after ischemia. Indeed, A2BRs participate in the early glutamate-mediated excitotoxicity responsible for neuronal and synaptic loss in the CA1 hippocampus. On the contrary, later after ischemia, the same receptors have a protective role in tissue damage and functional impairments, reducing inflammatory cell infiltration and neuroinflammation by central and/or peripheral mechanisms. Of note, demyelination following brain ischemia, or autoimmune neuroinflammatory reactions, are also profoundly affected by A2BRs since they are expressed by oligodendroglia where their activation inhibits cell maturation and expression of myelin-related proteins. In conclusion, data in the literature indicate the A2BRs as putative therapeutic targets for the still unmet treatment of stroke or demyelinating diseases. 相似文献
69.
According to the Linear Elastic Fracture Mechanics criteria, a numerical model is developed to simulate the failure evolution
of multi-cracked finite plates by means of an incremental loading procedure. A modified crack length control scheme is used
in order to analyse such problems depending on one or more independent parameters. The aim is to provide information about
a discontinuous response, such as the snap-back instability, which can be highlighted only by a deformation controlled process.
The load vs. displacement curve, included possible snap-back branches, is numerically traced by means of a procedure based
on the Displacement Discontinuity Boundary Element Method. With reference to finite plates with ordered crack distributions
in plane strain loading conditions, the model is applied in order to analyse the effects of the crack interaction on the fracture
evolution.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
70.
Complex Price Dynamics in a Financial Market with Imitation 总被引:1,自引:0,他引:1
In this work a simple financial model with fundamentalists and imitators is being considered. In order to describe the price dynamics of the heterogeneous stock market, a synergetic approach is used and some global bifurcations arising in the model are being studied. It is shown that the fundamental equilibrium point P* may be destabilized through a subcritical Neimark–Sacker bifurcation and that two invariant closed curves, one attracting and one repelling, appear when P* is still stable. This particular bifurcation scenario allows us to show some noticeable features of the market that emerge when the imitation effect is emphasized. Among these features are, for instance, the volatility clusters associated with the presence of multistability (i.e. coexistence of attractors) and the hysteresis phenomenon. 相似文献