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111.
Gene delivery: A single nuclear localization signal peptide is sufficient to carry DNA to the cell nucleus 总被引:20,自引:0,他引:20
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Maria Antonietta Zanta Pascale Belguise-Valladier Jean-Paul Behr 《Proceedings of the National Academy of Sciences of the United States of America》1999,96(1):91-96
Translocation of exogenous DNA through the nuclear membrane is a major concern of gene delivery technologies. To take advantage of the cellular import machinery, we have synthesized a capped 3.3-kbp CMVLuciferase-NLS gene containing a single nuclear localization signal peptide (PKKKRKVEDPYC). Transfection of cells with the tagged gene remained effective down to nanogram amounts of DNA. Transfection enhancement (10- to 1,000-fold) as a result of the signal peptide was observed irrespective of the cationic vector or the cell type used. A lysine to threonine mutation of the third NLS amino acid completely abolished these remarkable features, suggesting importin-mediated translocation. Our hypothesis is that the 3-nm-wide DNA present in the cytoplasm is initially docked to and translocated through a nuclear pore by the nuclear import machinery. As DNA enters the nucleus, it is quickly condensed into a chromatin-like structure, which provides a mechanism for threading the remaining worm-like molecule through the pore. A single NLS signal is thus sufficient, whereas many signals on a gene would actually inhibit entry, the same DNA molecule being threaded through adjacent pores. 相似文献
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Histone deacetylase inhibitors as a new weapon in the arsenal of differentiation therapies of cancer 总被引:1,自引:0,他引:1
Absent or altered differentiation is one of the major features of cancer cells. Histone deacetylases (HDACs) play a central role in the epigenetic regulation of gene expression. Aberrant activity of HDACs has been documented in several types of cancers, leading to the development of HDAC inhibitors (HDACi) as anti-tumor drugs. In vitro and in vivo experimental evidences show that HDACi are able to resume the process of maturation in undifferentiated cancer cells, justifying their introduction as differentiating agents in several clinical trials. Modulation of cell fate by HDACi is observed at several levels, including the stem cell compartment: HDACi can act both on cancer stem cells, and with the rest of the tumor cell mass, leading to complex biological outputs. As a note of caution, when used as single agent, HDACi show only a moderate and limited biological response, which is augmented in combinatorial therapies with drugs designed against other epigenetic targets. The optimal employment of these molecules may be therefore in combination with other epigenetic drugs acting against the set of enzymes responsible for the set-up and maintenance of epigenetic information. 相似文献
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Gianluca Trifirò MD MSc Antoine Pariente MD PhD Preciosa M. Coloma MD Jan A. Kors PhD Giovanni Polimeni PharmD PhD Ghada Miremont‐Salamé MD Maria Antonietta Catania MD Francesco Salvo MD Anaelle David MD Nicholas Moore MD PhD Achille Patrizio Caputi MD Miriam Sturkenboom PharmD PhD Mariam Molokhia PhD Julia Hippisley‐Cox MD Carlos Diaz Acedo Johan van der Lei MD PhD Annie Fourrier‐Reglat PharmD PhD 《Pharmacoepidemiology and drug safety》2009,18(12):1176-1184
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Jean-François Desaphy Sabata Pierno Antonella Liantonio Viviana Giannuzzi Claudio Digennaro Maria Maddalena Dinardo Giulia M. Camerino Patrizia Ricciuti Lorenza Brocca Maria Antonietta Pellegrino Roberto Bottinelli Diana Conte Camerino 《Pharmacological research》2010,61(6):553-563
Oxidative stress was proposed as a trigger of muscle impairment in various muscle diseases. The hindlimb-unloaded (HU) rodent is a model of disuse inducing atrophy and slow-to-fast transition of postural muscles. Here, mice unloaded for 14 days were chronically treated with the selective antioxidant trolox. After HU, atrophy was more pronounced in the slow-twitch soleus muscle (Sol) than in the fast-twitch gastrocnemius and tibialis anterior muscles, and was absent in extensor digitorum longus muscle. In accord with the phenotype transition, HU Sol showed a reduced expression of myosin heavy chain type 2A (MHC-2A) and increase in MHC-2X and MHC-2B isoforms. In parallel, HU Sol displayed an increased sarcolemma chloride conductance related to an increased expression of ClC-1 channels, changes in excitability parameters, a positive shift of the mechanical threshold, and a decrease of the resting cytosolic calcium concentration. Moreover, the level of lipoperoxidation increased proportionally to the degree of atrophy of each muscle type. As expected, trolox treatment fully prevented oxidative stress in HU mice. Atrophy was not prevented but the drug significantly attenuated Sol phenotypic transition and excitability changes. Trolox treatment had no effect on control mice. These results suggest possible benefits of antioxidants in protecting muscle against disuse. 相似文献
116.
Valeria Crivaro Anna Di Popolo Alessandro Caprio Antonietta Lambiase Mario Di Resta Tonia Borriello Alda Scarcella Maria Triassi Raffaele Zarrilli 《BMC infectious diseases》2009,9(1):70
Background
Pseudomonas aeruginosa, a non-fermentative, gram-negative rod, is responsible for a wide variety of clinical syndromes in NICU patients, including sepsis, pneumonia, meningitis, diarrhea, conjunctivitis and skin infections. An increased number of infections and colonisations by P. aeruginosa has been observed in the neonatal intensive care unit (NICU) of our university hospital between 2005 and 2007. 相似文献117.
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Eugenia Bruzzese Valeria Raia Eliana Ruberto Riccardo Scotto Antonietta Giannattasio Dario Bruzzese Maria Cristina Cavicchi Michela Francalanci Carla Colombo Nadia Faelli Valeria Daccò Giuseppe Magazzù Stefano Costa Vincenzina Lucidi Fabio Majo Alfredo Guarino 《Journal of cystic fibrosis》2018,17(3):375-382