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841.
Anna M. Schoepf Dr. Stefan Salcher Verena Hohn Florina Veider Prof. Dr. Petra Obexer Prof. Dr. Ronald Gust 《ChemMedChem》2020,15(12):1067-1077
New strategies to eradicate cancer stem cells in chronic myeloid leukemia (CML) include a combination of imatinib with peroxisome proliferator-activated receptor gamma (PPARγ) ligands. Recently, we identified the partial PPARγ agonist telmisartan as effective sensitizer of resistant K562 CML cells to imatinib treatment. Here, the importance of the heterocyclic core on the cell death-modulating effects of the telmisartan-derived lead 4′-((2-propyl-1H-benzo[d]imidazol-1-yl)methyl)-[1,1′-biphenyl]-2-carboxylic acid ( 3 b ) was investigated. Inspired by the pharmacodynamics of HYL-6d and the selective PPARγ ligand VSP-51, the benzimidazole was replaced by a carbazole or an indole core. The results indicate no correlation between PPARγ activation and sensitization of resistant CML cells to imatinib. The 2-COOH derivatives of the carbazoles or indoles achieved low activity at PPARγ, while the benzimidazoles showed 60-100 % activation. Among the 2-CO2CH3 derivatives, only the ester of the lead ( 2 b ) slightly activated PPARγ. Sensitizing effects were further observed for this non-cytotoxic 2 b (80 % cell death), and to a lesser extent for the lead 3 b or the 5-Br-substituted ester of the benzimidazoles ( 5 b ). 相似文献
842.
843.
Amnon Amit Edmond Sabo Anna Petruseva Leah Stroller Ari Reiss Geula Klorin 《Microscopy research and technique》2022,85(3):892-899
Serous ovarian tumors may originate in epithelial cells of the fallopian tubes. Computerized morphometry was able to find significant alterations in the fallopian tube epithelium of healthy BRCA carriers. The purpose of this study was to identify a subgroup of BRCA carriers that may be at risk of developing serous ovarian cancer by evaluation of the epithelial nuclear symmetry in the fallopian tubes. Four groups of patients were analyzed; healthy patients, ovarian cancer patients, BRCA carriers, and BRCA noncarriers. All fallopian tubes appeared normal by H&E examination. The ImageProPlus software was used to assess the nuclear symmetry of 65 fimbriae epithelium cells and an artificial neural network algorithm aided in detecting a subpopulation among fimbriae of healthy BRCA carriers at risk for ovarian cancer. Significant differences were found between healthy patients and ovarian cancer patients, and between BRCA carriers and noncarriers. The algorithm was able to accurately predict BRCA carriers with associated ovarian cancer based on fallopian tube nuclear symmetry characteristics. These results reinforce the hypothesis that fimbriae epithelial cells of BRCA carriers may undergo early-stage changes that could predict the risk of progression toward malignancy. 相似文献
844.
Maxime Rochette Jean-Philippe Déry Anna M. Ritcey 《International Journal of Optomechatronics》2018,12(1):20-30
The experimental results obtained with a ferrofluidic deformable mirror controlled by electro-magnet actuators are presented here. Using a step input through a single actuator, we obtained a steady-state settling time of 100?ms; however, different combinations of overdrive inputs can be used to decrease it to 25?ms. A new technique which consists of laying down an elastomer membrane, coated with an aluminum film, on the ferrofluid is also discussed. By adding the membrane on the ferrofluid, it further decreases the time response by a factor of 2. Furthermore, the thin aluminum layer improves the reflectivity of the mirror. Finally, using the membrane and the overdrive techniques combined, the time response is improved by a factor of 20. Numerical simulations show that ferrofluidic mirrors using membranes and improved electronics should reach settling times of the order of a millisecond. Presumably, even lower settling times could be possible. 相似文献
845.
Máté Szabados Zsófia Csákó Bohumil Kotlík Helena Kazmarová Anna Kozajda Anja Jutraz Andreja Kukec Peter Otorepec Arianna Dongiovanni Andrea Di Maggio Stefano Fraire Tamás Szigeti 《Indoor air》2021,31(4):989-1003
The indoor air quality (IAQ) was investigated in sixty-four primary school buildings in five Central European countries (Czech Republic, Hungary, Italy, Poland, and Slovenia). The concentration of volatile organic compounds, aldehydes, PM2.5 mass, carbon dioxide, radon, as well as physical parameters were investigated during the heating period of 2017/2018. Significant differences were identified for the majority of the investigated IAQ parameters across the countries. The median indoor/outdoor ratios varied considerably. A comprehensive evaluation of IAQ in terms of potential health effects and comfort perception was performed. Hazard quotient values were below the threshold value of 1 with one exception. In contrast, 31% of the school buildings were characterized by hazard index values higher than 1. The maximum cumulative ratio approach highlighted that the concern for non-carcinogenic health effects was either low or the health risk was driven by more substances. The median excess lifetime cancer risk values exceeded the acceptable value of 1 × 10−6 in the case of radon and formaldehyde. PM2.5 mass concentration values exceeded the 24 h and annual guideline values set by the World Health Organization in 56 and 85% of the cases, respectively. About 80% of the schools could not manage to comply with the recommended concentration value for carbon dioxide (1000 ppm). 相似文献
846.
Lingping Kong Jue Gong Qingyang Hu Francesco Capitani Anna Celeste Takanori Hattori Asami Sano-Furukawa Nana Li Wenge Yang Gang Liu Ho-kwang Mao 《Advanced functional materials》2021,31(9):2009131
The soft nature of organic–inorganic halide perovskites renders their lattice particularly tunable to external stimuli such as pressure, undoubtedly offering an effective way to modify their structure for extraordinary optoelectronic properties. Here, using the methylammonium lead iodide as a representative exploratory platform, it is observed that the pressure-driven lattice disorder can be significantly suppressed via hydrogen isotope effect, which is crucial for better optical and mechanical properties previously unattainable. By a comprehensive in situ neutron/synchrotron-based analysis and optical characterizations, a remarkable photoluminescence (PL) enhancement by threefold is convinced in deuterated CD3ND3PbI3, which also shows much greater structural robustness with retainable PL after high peak-pressure compression–decompression cycle. With the first-principles calculations, an atomic level understanding of the strong correlation among the organic sublattice and lead iodide octahedral framework and structural photonics is proposed, where the less dynamic CD3ND3+ cations are vital to maintain the long-range crystalline order through steric and Coulombic interactions. These results also show that CD3ND3PbI3-based solar cell has comparable photovoltaic performance as CH3NH3PbI3-based device but exhibits considerably slower degradation behavior, thus representing a paradigm by suggesting isotope-functionalized perovskite materials for better materials-by-design and more stable photovoltaic application. 相似文献
847.
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
848.
Rossella Gratton Paola Maura Tricarico Adamo Pio dAdamo Anna Monica Bianco Ronald Moura Almerinda Agrelli Lucas Brando Luisa Zupin Sergio Crovella 《International journal of molecular sciences》2020,21(22)
Notch pathway is a highly conserved intracellular signaling route that modulates a vast variety of cellular processes including proliferation, differentiation, migration, cell fate and death. Recently, the presence of a strict crosstalk between Notch signaling and inflammation has been described, although the precise molecular mechanisms underlying this interplay have not yet been fully unravelled. Disruptions in Notch cascade, due both to direct mutations and/or to an altered regulation in the core components of Notch signaling, might lead to hypo- or hyperactivation of Notch target genes and signaling molecules, ultimately contributing to the onset of autoinflammatory diseases. To date, alterations in Notch signaling have been reported as associated with three autoinflammatory disorders, therefore, suggesting a possible role of Notch in the pathogenesis of the following diseases: hidradenitis suppurativa (HS), Behçet disease (BD), and giant cell arteritis (GCA). In this review, we aim at better characterizing the interplay between Notch and autoinflammatory diseases, trying to identify the role of this signaling route in the context of these disorders. 相似文献
849.
Monika K. Nisiewicz Agata Kowalczyk Anna Sobiepanek Agata Jagielska Barbara Wagner Julita Nowakowska Marianna Gniadek Ireneusz P. Grudzinski Tomasz Kobiela Anna M. Nowicka 《International journal of molecular sciences》2021,22(1)
Nearly half of patients with advanced and metastatic melanomas harbor a BRAF mutation. Vemurafenib (VEM), a BRAF inhibitor, is used to treat such patients, however, responses to VEM are very short-lived due to intrinsic, adaptive and/or acquired resistance. In this context, we present the action of the B-Raf serine-threonine protein kinase inhibitor (vemurafenib) on the glycans structure and metallomics profiles in melanoma cells without (MeWo) and with (G-361) BRAF mutations. The studies were performed using α1-acid glycoprotein (AGP), a well-known acute-phase protein, and concanavalin A (Con A), which served as the model receptor. The detection of changes in the structure of glycans can be successfully carried out based on the frequency shifts and the charge transfer resistance after interaction of AGP with Con A in different VEM treatments using QCM-D and EIS measurements. These changes were also proved based on the cell ultrastructure examined by TEM and SEM. The LA-ICP-MS studies provided details on the metallomics profile in melanoma cells treated with and without VEM. The studies evidence that vemurafenib modifies the glycans structures and metallomics profile in melanoma cells harboring BRAF mutation that can be further implied in the resistance phenomenon. Therefore, our data opens a new avenue for further studies in the short-term addressing novel targets that hopefully can be used to improve the therapeutic regiment in advanced melanoma patients. The innovating potential of this study is fully credible and has a real impact on the global patient society suffering from advanced and metastatic melanomas. 相似文献
850.
Heinz Bässler Daniel Kroh Franz Schauer Vojtech Nádaždy Anna Köhler 《Advanced functional materials》2021,31(9):2007738
Although the density of states (DOS) distribution of charge transporting states in an organic semiconductor is vital for device operation, its experimental assessment is not at all straightforward. In this work, the technique of energy resolved–electrochemical impedance spectroscopy (ER-EIS) is employed to determine the DOS distributions of valence (highest occupied molecular orbital (HOMO)) as well as electron (lowest unoccupied molecular orbital (LUMO)) states in several organic semiconductors in the form of neat and blended films. In all cases, the core of the inferred DOS distributions are Gaussians that sometimes carry low energy tails. A comparison of the HOMO and LUMO DOS of P3HT inferred from ER-EIS and photoemission (PE) or inverse PE (IPE) spectroscopy indicates that the PE/IPE spectra are by a factor of 2–3 broader than the ER-EIS spectra, implying that they overestimate the width of the distributions. A comparison of neat films of MeLPPP and SF-PDI2 or PC(61)BM with corresponding blends reveals an increased width of the DOS in the blends. The results demonstrate that this technique does not only allow mapping the DOS distributions over five orders of magnitude and over a wide energy window of 7 eV, but can also delineate changes that occur upon blending. 相似文献