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Bortezomib is a novel proteasome inhibitor, which has been successfully used to treat mantle cell lymphoma and multiple myeloma. However, the direct effects of bortezomib on acute promyelocytic leukaemia (APL) have not been fully investigated. In the present study, the WST-8 assay, western blotting, flow cytometry, monodansylcadaverine staining and transmission electron microscopy were performed. It was demonstrated that bortezomib treatment induced a time- and dose-dependent decrease in the viability of NB4 cells. Bortezomib treatment induced cell apoptosis in NB4 cells, as assessed by Annexin V/propidium iodide analysis, and the detection of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase, Bax and Bcl-2 expression. Furthermore, bortezomib treatment induced autophagy in NB4 cells, as indicated by autophagosome formation, p62 degradation, LC3-I to LC3-II conversion and formation of acidic autophagic vacuoles. Notably, autophagy induced by bortezomib was initiated prior to apoptosis. Inhibition of autophagy by knocking down Beclin-1 expression increased bortezomib-induced apoptosis in NB4 cells. Therefore, the present study revealed that the combination of bortezomib and autophagy inhibition may be a potential treatment strategy for APL. 相似文献
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Maria Gonzalez-Cao Cristina Carrera Juan Francisco Rodriguez Moreno Pedro Rodríguez-Jiménez Mónica Antoñanzas Basa Rosa Feltes Ochoa Teresa Puertolas Eva Muñoz-Couselo José Luis Manzano Ivan Marquez-Rodas Juan Martín-Liberal Ainara Soria Pilar Lopez Criado Almudena Garcia-Castaño Aram Boada Pablo Ayala de Miguel Susana Puig Guillermo Crespo Alfonso Berrocal 《Journal of the American Academy of Dermatology》2021,84(5):1412-1415
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Ana M. Gómez Angelica Imitola Diana Henao Maira García-Jaramillo Marga Giménez Clara Viñals Bruno Grassi Mariana Torres Isabella Zuluaga Oscar Mauricio Muñoz Martin Rondón Fabián León-Vargas Ignacio Conget 《Diabetes & Metabolic Syndrome: Clinical Research & Reviews》2021,15(1):267-272
Background and aimsDespite using sensor-augmented pump therapy (SAPT) with predictive low-glucose management (PLGM), hypoglycemia is still an issue in patients with type 1 Diabetes (T1D). Our aim was to determine factors associated with clinically significant hypoglycemia (<54 mg/dl) in persons with T1D treated with PLGM-SAPT.Methodology: This is a multicentric prospective real-life study performed in Colombia, Chile and Spain. Patients with T1D treated with PLGM-SAPT, using sensor ≥70% of time, were included. Data regarding pump and sensor use patterns and carbohydrate intake from 28 consecutive days were collected. A bivariate and multivariate Poisson regression analysis was carried out, to evaluate the association between the number of events of <54 mg/dl with the clinical variables and patterns of sensor and pump use.Results188 subjects were included (41 ± 13.8 years-old, 23 ± 12 years disease duration, A1c 7.2% ± 0.9). The median of events <54 mg/dl was four events/patient/month (IQR 1–10), 77% of these events occurred during day time. Multivariate analysis showed that the number of events of hypoglycemia were higher in patients with previous severe hypoglycemia (IRR1.38; 95% CI 1.19–1.61; p < 0.001), high glycemic variability defined as Coefficient of Variation (CV%) > 36% (IRR 2.09; 95%CI 1.79–2.45; p < 0.001) and hypoglycemia unawareness. A protector effect was identified for adequate sensor calibration (IRR 0.77; 95%CI 0.66–0.90; p:0.001), and the use of bolus wizard >60% (IRR 0.74; 95%CI 0.58–0.95; p:0.017).ConclusionIn spite of using advanced SAPT, clinically significant hypoglycemia is still a non-negligible risk. Only the identification and intervention of modifiable factors could help to prevent and reduce hypoglycemia in clinical practice. 相似文献
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José A. Lorente Pablo Cardinal-Fernández Diego Muñoz Fernando Frutos-Vivar Arnaud W. Thille Carlos Jaramillo Aida Ballén-Barragán José M. Rodríguez Oscar Peñuelas Guillermo Ortiz José Blanco Bruno Valle Pinheiro Nicolás Nin María del Carmen Marin Andrés Esteban Taylor B. Thompson 《Intensive care medicine》2015,41(11):1921-1930
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María Cabrerizo Gloria Trallero María José Pena Amaia Cilla Gregoria Megias Carmen Mu?oz-Almagro Eva Del Amo Diana Roda Ana Isabel Mensalvas Antonio Moreno-Docón Juan García-Costa Nuria Rabella Manuel Ome?aca María Pilar Romero Sara Sanbonmatsu-Gámez Mercedes Pérez-Ruiz María José Santos-Mu?oz Cristina Calvo And the study group of “Enterovirus parechovirus infections in children under ?years-old Spain” PI- 《European journal of pediatrics》2015,174(11):1511-1516