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101.
Dr. Daniela Carbone Dr. Barbara Parrino Dr. Stella Cascioferro Camilla Pecoraro Prof. Elisa Giovannetti Dr. Veronica Di Sarno Dr. Simona Musella Dr. Giulia Auriemma Prof. Girolamo Cirrincione Prof. Patrizia Diana 《ChemMedChem》2021,16(3):537-554
A new series of topsentin analogs, in which the central imidazole ring of the natural lead was replaced by a 1,2,4-oxadiazole moiety, was efficiently synthesized. All derivatives were pre-screened for antiproliferative activity against the National Cancer Institute (NCI-60) cell lines panel. The five most potent compounds were further investigated in various pancreatic ductal adenocarcinoma (PDAC) cell lines, including SUIT-2, Capan-1, and Panc-1 cells, eliciting EC50 values in the micromolar and sub-micromolar range, associated with significant reduction of cell migration. These remarkable results might be explained by the effects of these new topsentin analogues on epithelial-to-mesenchymal transition markers, including SNAIL-1/2 and metalloproteinase-9. Moreover, flow cytometric analysis after Annexin V-FITC and propidium iodide staining demonstrated that these derivatives enhanced apoptosis of PDAC cells. Keeping with these data, the PathScan intracellular signaling and ELISA array revealed cleavage of caspase-3 and PARP and a significant inhibition of GSK3β phosphorylation, suggesting this kinase as a potential downstream target of our novel compounds. This was further supported by a specific assay for the evaluation of GSK3β activity, showing IC50 values for the most active compounds against this enzyme in the micromolar range. 相似文献
102.
103.
Jayasheelan Vaithilingam Paola Sanjuan‐Alberte Simona Campora Graham A. Rance Long Jiang Jordan Thorpe Laurence Burroughs Christopher J. Tuck Chris Denning Ricky D. Wildman Richard J. M. Hague Morgan R. Alexander Frankie J. Rawson 《Advanced functional materials》2019,29(38)
Biological structures control cell behavior via physical, chemical, electrical, and mechanical cues. Approaches that allow us to build devices that mimic these cues in a combinatorial way are lacking due to there being no suitable instructive materials and limited manufacturing procedures. This challenge is addressed by developing a new conductive composite material, allowing for the fabrication of 3D biomimetic structures in a single manufacturing method based on two‐photon polymerization. The approach induces a combinatorial biostimulative input that can be tailored to a specific application. Development of the 3D architecture is performed with a chemically actuating photocurable acrylate previously identified for cardiomyocyte attachment. The material is made conductive by impregnation with multiwalled carbon nanotubes. The bioinstructive effect of 3D nano‐ and microtopography is combined with electrical stimulation, incorporating biochemical, and electromechanical cues to stimulate cells in serum‐free media. The manufactured architecture is combined with cardiomyocytes derived from human pluripotent stem cells. It is demonstrated that by mimicking biological occurring cues, cardiomyocyte behavior can be modulated. This represents a step change in the ability to manufacture 3D multifunctional biomimetic modulatory architectures. This platform technology has implications in areas spanning regenerative medicine, tissue engineering to biosensing, and may lead to more accurate models for predicting toxicity. 相似文献
104.
Simona Dimchevska Nikola Geskovski Gjorgji Petruševski Marina Chacorovska Riste Popeski-Dimovski Sonja Ugarkovic 《Drug development and industrial pharmacy》2017,43(3):502-510
One of the most important problems in nanoencapsulation of extremely hydrophobic drugs is poor drug loading due to rapid drug crystallization outside the polymer core. The effort to use nanoprecipitation, as a simple one-step procedure with good reproducibility and FDA approved polymers like Poly(lactic-co-glycolic acid) (PLGA) and Polycaprolactone (PCL), will only potentiate this issue. Considering that drug loading is one of the key defining characteristics, in this study we attempted to examine whether the nanoparticle (NP) core composed of two hydrophobic polymers will provide increased drug loading for 7-Ethyl-10-hydroxy-camptothecin (SN-38), relative to NPs prepared using individual polymers. D-optimal design was applied to optimize PLGA/PCL ratio in the polymer blend and the mode of addition of the amphiphilic copolymer Lutrol®F127 in order to maximize SN-38 loading and obtain NPs with acceptable size for passive tumor targeting. Drug/polymer and polymer/polymer interaction analysis pointed to high degree of compatibility and miscibility among both hydrophobic polymers, providing core configuration with higher drug loading capacity. Toxicity studies outlined the biocompatibility of the blank NPs. Increased in vitro efficacy of drug-loaded NPs compared to the free drug was confirmed by growth inhibition studies using SW-480 cell line. Additionally, the optimized NP formulation showed very promising blood circulation profile with elimination half-time of 7.4?h. 相似文献
105.
106.
Davide Tedeschi Elena Blundo Marco Felici Giorgio Pettinari Boqing Liu Tanju Yildrim Elisa Petroni Chris Zhang Yi Zhu Simona Sennato Yuerui Lu Antonio Polimeni 《Advanced materials (Deerfield Beach, Fla.)》2019,31(44)
At the few‐atom‐thick limit, transition‐metal dichalcogenides (TMDs) exhibit strongly interconnected structural and optoelectronic properties. The possibility to tailor the latter by controlling the former is expected to have a great impact on applied and fundamental research. As shown here, proton irradiation deeply affects the surface morphology of bulk TMD crystals. Protons penetrate the top layer, resulting in the production and progressive accumulation of molecular hydrogen in the first interlayer region. This leads to the blistering of one‐monolayer thick domes, which stud the crystal surface and locally turn the dark bulk material into an efficient light emitter. The domes are stable (>2‐year lifetime) and robust, and host strong, complex strain fields. Lithographic techniques provide a means to engineer the formation process so that the domes can be produced with well‐ordered positions and sizes tunable from the nanometer to the micrometer scale, with important prospects for so far unattainable applications. 相似文献
107.
Poly(vinyl alcohol) (PVA) hydrogels were prepared in the presence/absence of Laponite RD (LRD) by using glutaraldehyde (GL) as chemical crosslinker. The effect of GL concentration (CHO/OH ratio between 0.02 and 0.38) and of clay addition on the PVA hydrogel properties was investigated. The swollen hydrogels showed good transparency and flexibility. LRD incorporation into the PVA hydrogel, revealed by Fourier transform infrared spectroscopy, led to a significant increase of the roughness of the dried hydrogel surface (about two times), as established by atomic force microscopy. The swelling ability was affected in a small extent by the clay addition. The elastic modulus decreased from 4680 to 3340 Pa and from 2195 to 1603 Pa by addition of 0.5% LRD into PVA hydrogels obtained with CHO/OH ratio of 0.02 and 0.06, respectively. The LRD addition reduced the gelation time determined by in situ rheological monitoring of PVA crosslinking reaction. The experimental investigations showed that there is an optimum CHO/OH ratio of 0.02 for which the PVA/LRD hybrid hydrogel presents the properties required by a targeted application, as for example support material for wound dressings. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46661. 相似文献
108.
Russo A Maccaferri S Djakovac T Precali R Degobbis D Deserti M Paschini E Lyons DM 《The Science of the total environment》2005,353(1-3):24-38
Mucilage events (formation of very large organic aggregates and gelatinous surface layers) have been documented several times during the past two centuries in the northern Adriatic Sea (NA), while their frequency has significantly increased since 1988. In this work, meteorological and oceanographic conditions in the NA during the period June 1999-July 2002 are described and their relation to the outbreak and fate of the mucilage phenomenon was investigated. Salinity and temperature data were collected during approximately monthly cruises along three transects in the NA. Relevant meteorological situations (air temperature, rainfall, wind) were selected from large-scale ECMWF analyses and from the Local Analysis and Prediction System (LAPS; Emilia Romagna Meteorological Service), while sea conditions (waves) were analysed by means of the Wave Adriatic Model (WAM). Data for air temperature, rainfall, and wind from several meteorological stations in the region were used. Average seasonal cycles of sea temperature and salinity simulated with statistical models, based on historical data collected in the NA since 1972, were used to determine thermal and haline anomalies. The monthly anomaly variability of maximum and minimum air temperatures, rainfall amount and number of rainy days did not appear to be relevant for the mucilage phenomenon outbreak. In contrast, both vertical and horizontal thermohaline gradients in the region were more developed during late spring and summer of 2000 and particularly of 2002, when the mucilage events were of greatest extent in space and time, compared to 2001 (short-lived event) and 1999 (no event). These more pronounced gradients were due to a combination of several unusual conditions: sharp heating of the sea surface in May-June, domination of eastwards transport of freshened waters formed in the Po Delta area, and intrusion of very high salinity intermediate waters originating in the eastern Mediterranean. Moreover, in winter of both 2000 and 2002 very dense and cold water formed and remained in the bottom layer until spring, contributing to increase the stratification degree of the water column. The duration of the mucilage events and their spatial distribution in the region depend strongly on meteorological changes. Recurrent anticyclonic conditions, characterized by low wind and calm sea, favour extended events in time (up 2 months in 2002). In contrast, highly perturbed weather, particularly due to strong "bora" wind, can be determined in sharp decay of the event (e.g. in July 2000). 相似文献
109.
Gottardini E Cristofori A Cristofolini F Maccherini S Ferretti M 《The Science of the total environment》2008,402(2-3):299-305
A fully randomized sampling design was adopted to test whether pollen viability of Austrian pine (Pinus nigra Arnold) was impacted by NO(2) pollution. Spatial strata (500500 m each) with high (41.9-44.6 microg m(-3)) and low (15.4-21.0 microg m(-3)) NO(2) were selected from a defined population in a small area (236.5 km(2), <200 m range in elevation) in Northern Italy. Pollen viability was measured by means of the Tetrazolium (TTC) test. Analysis of variance by means of a generalised linear model showed that NO(2) was a significant factor (P=0.0425) affecting pollen viability. Within the treatment, no significant differences were detected among replicates. Within each replicate, sampling unit data were significantly different (P=0.000) and this suggested some improvement in the applied sampling design was needed. Pollen viability was significantly related to pollen germination (P<0.01) and tube length (P<0.01). This suggested a possible impact of NO(2) on the regeneration of Austrian pine in polluted environments. 相似文献
110.
The purpose of this study was to investigate the photocatalytic oxidation of a reactive azo dye. The photocatalytic activity of the TiO2 was studied using a reactor equipped with UV-A sources, with maximum emission at 365 nm. The photocatalytic activity of the TiO2 powder (99.9% anatase) and thin films has been measured through the decomposition of methyl orange solutions. The thin film was prepared by doctor blade and spray pyrolysis deposition (SPD). The TiO2 suspensions were prepared at 1 g/L concentration, and the initial methyl orange concentration was fixed at 7.8125 mg/L. The influence of the TiO2 (powder or thin films) and/or O2 and H2O2 on the photobleaching rate, was tested under different experiments, at pH = 5. Thin films (doctor blade) of TiO2 formed of mezo-sized aggregates formed of nanosized anatase crystallites show better photobleaching efficiency than thin film (SPD) due to their large internal surface. The rate is even higher in H2O2 compared to oxygen environment. 相似文献