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101.
Juan Pablo Rigalli Nadia Ciriaci Agostina Arias María Paula Ceballos Silvina Stella Maris Villanueva Marcelo Gabriel Luquita Aldo Domingo Mottino Carolina Inés Ghanem Viviana Alicia Catania María Laura Ruiz 《PloS one》2015,10(3)
Hepatocellular carcinoma (HCC) is the fifth most frequent cancer worldwide. Sorafenib is the only drug available that improves the overall survival of HCC patients. P-glycoprotein (P-gp), Multidrug resistance-associated proteins 2 and 3 (MRP2 and 3) and Breast cancer resistance protein (BCRP) are efflux pumps that play a key role in cancer chemoresistance. Their modulation by dietary compounds may affect the intracellular accumulation and therapeutic efficacy of drugs that are substrates of these transporters. Genistein (GNT) is a phytoestrogen abundant in soybean that exerts its genomic effects through Estrogen-Receptors and Pregnane-X-Receptor (PXR), which are involved in the regulation of the above-mentioned transporters. We evaluated the effect of GNT on the expression and activity of P-gp, MRP2, MRP3 and BCRP in HCC-derived HepG2 cells. GNT (at 1.0 and 10 μM) increased P-gp and MRP2 protein expression and activity, correlating well with an increased resistance to sorafenib cytotoxicity as detected by the methylthiazole tetrazolium (MTT) assay. GNT induced P-gp and MRP2 mRNA expression at 10 but not at 1.0 μM concentration suggesting a different pattern of regulation depending on the concentration. Induction of both transporters by 1.0 μM GNT was prevented by cycloheximide, suggesting translational regulation. Downregulation of expression of the miR-379 by GNT could be associated with translational regulation of MRP2. Silencing of PXR abolished P-gp induction by GNT (at 1.0 and 10 μM) and MRP2 induction by GNT (only at 10 μM), suggesting partial mediation of GNT effects by PXR. Taken together, the data suggest the possibility of nutrient-drug interactions leading to enhanced chemoresistance in HCC when GNT is ingested with soy rich diets or dietary supplements. 相似文献
102.
Deciphering preferential interactions within supramolecular protein complexes: the proteasome case
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Bertrand Fabre Thomas Lambour Luc Garrigues François Amalric Nathalie Vigneron Thomas Menneteau Alexandre Stella Bernard Monsarrat Benoît Van den Eynde Odile Burlet‐Schiltz Marie‐Pierre Bousquet‐Dubouch 《Molecular systems biology》2015,11(1)
In eukaryotic cells, intracellular protein breakdown is mainly performed by the ubiquitin–proteasome system. Proteasomes are supramolecular protein complexes formed by the association of multiple sub-complexes and interacting proteins. Therefore, they exhibit a very high heterogeneity whose function is still not well understood. Here, using a newly developed method based on the combination of affinity purification and protein correlation profiling associated with high-resolution mass spectrometry, we comprehensively characterized proteasome heterogeneity and identified previously unknown preferential associations within proteasome sub-complexes. In particular, we showed for the first time that the two main proteasome subtypes, standard proteasome and immunoproteasome, interact with a different subset of important regulators. This trend was observed in very diverse human cell types and was confirmed by changing the relative proportions of both 20S proteasome forms using interferon-γ. The new method developed here constitutes an innovative and powerful strategy that could be broadly applied for unraveling the dynamic and heterogeneous nature of other biologically relevant supramolecular protein complexes. 相似文献
103.
Association of the fat mass and obesity‐associated gene risk allele,rs9939609A,and reward‐related brain structures
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104.
Gianmauro Numico Antonella Cristofano Alessandro Mozzicafreddo Olga Elisabetta Cursio Pierfrancesco Franco Giulia Courthod Antonio Trogu Alessandra Malossi Mariella Cucchi Zuzana Sirotovà Maria Rosa Alvaro Anna Stella Fulvia Grasso Silvia Spinazzé Nicola Silvestris 《PloS one》2015,10(3)
Background
Cancer patients are frequently admitted to hospital due to acute conditions or refractory symptoms. This occurs through the emergency departments and requires medical oncologists to take an active role. The use of acute-care hospital increases in the last months of life.Patients and methods
We aimed to describe the admissions to a medical oncology inpatient service within a 16-month period with respect to patients and tumor characteristics, and the outcome of the hospital stay.Results
672 admissions of 454 patients were analysed. The majority of admissions were urgent (74.1%), and were due to uncontrolled symptoms (79.6%). Among the chief complaints, dyspnoea occurred in 15.7%, pain in 15.2%, and neurological symptoms in 14.5%. The majority of the hospitalizations resulted in discharge to home (60.6%); in 26.5% the patient died and in 11.0% was transferred to a hospice. Admissions due to symptoms correlated with a longer hospital stay and a higher incidence of in-hospital death.Conclusion
We suggest that hospital use is not necessarily a sign of inappropriately aggressive care: inpatient care is probably an unavoidable step in the cancer trajectory. Optimization of inpatient supportive procedures should be a specific task of modern medical oncology. 相似文献105.
Athina Dimopoulou Stella Manta Vanessa Parmenopoulou Petros Gkizis Evdoxia Coutouli-Argyropoulou Dominique Schols 《Nucleosides, nucleotides & nucleic acids》2015,34(4):289-308
We report the synthesis of novel thiopurine pyranonucleosides. Direct coupling of silylated 6-mercaptopurine and 6-thioguanine with the appropriate pyranoses 1a–e via Vorbrüggen nucleosidation, gave the N-9 linked mercaptopurine 2a–e and thioguanine 4a–e nucleosides, while their N-7 substituted congeners 10a–e and 7a–e, were obtained through condensation of the same acetates with 6-chloro and 2-amino-6-chloropurines, followed by subsequent thionation. Nucleosides 3a–e, 5a–e, 8a–e, and 11a–e were evaluated for their cytostatic activity in three different tumor cell proliferative assays. 相似文献
106.
Eldin Talundzic Stella M. Chenet Ira F. Goldman Dhruviben S. Patel Julia A. Nelson Mateusz M. Plucinski John W. Barnwell Venkatachalam Udhayakumar 《PloS one》2015,10(8)
Plasmodium falciparum resistance to artemisinin has emerged in the Greater Mekong Subregion and now poses a threat to malaria control and prevention. Recent work has identified mutations in the kelch propeller domain of the P. falciparum K13 gene to be associated artemisinin resistance as defined by delayed parasite clearance and ex vivo ring stage survival assays. Species specific primers for the two most prevalent human malaria species, P. falciparum and P. vivax, were designed and tested on multiple parasite isolates including human, rodent, and non- humans primate Plasmodium species. The new protocol described here using the species specific primers only amplified their respective species, P. falciparum and P. vivax, and did not cross react with any of the other human malaria Plasmodium species. We provide an improved species specific PCR and sequencing protocol that could be effectively used in areas where both P. falciparum and P. vivax are circulating. To design this improved protocol, the kelch gene was analyzed and compared among different species of Plasmodium. The kelch propeller domain was found to be highly conserved across the mammalian Plasmodium species. 相似文献
107.
Jean Yves Le Reste Patrice Nabbe Charles Rivet Charilaos Lygidakis Christa Doerr Slawomir Czachowski Heidrun Lingner Stella Argyriadou Djurdjica Lazic Radost Assenova Melida Hasaganic Miquel Angel Munoz Hans Thulesius Bernard Le Floch Jeremy Derriennic Agnieska Sowinska Harm Van Marwijk Claire Lietard Paul Van Royen 《PloS one》2015,10(1)
Background
Multimorbidity, according to the World Health Organization, exists when there are two or more chronic conditions in one patient. This definition seems inaccurate for the holistic approach to Family Medicine (FM) and long-term care. To avoid this pitfall the European General Practitioners Research Network (EGPRN) designed a comprehensive definition of multimorbidity using a systematic literature review.Objective
To translate that English definition into European languages and to validate the semantic, conceptual and cultural homogeneity of the translations for further research.Method
Forward translation of the EGPRN’s definition of multimorbidity followed by a Delphi consensus procedure assessment, a backward translation and a cultural check with all teams to ensure the homogeneity of the translations in their national context. Consensus was defined as 70% of the scores being higher than 6. Delphi rounds were repeated in each country until a consensus was reachedResults
229 European medical expert FPs participated in the study. Ten consensual translations of the EGPRN comprehensive definition of multimorbidity were achieved.Conclusion
A comprehensive definition of multimorbidity is now available in English and ten European languages for further collaborative research in FM and long-term care. 相似文献108.
Andrew Wu Philip J. Budge John Williams Marie R. Griffin Kathryn M. Edwards Monika Johnson Yuwei Zhu Stella Hartinger Hector Verastegui Ana I. Gil Claudio F. Lanata Carlos G. Grijalva 《PloS one》2015,10(6)
Introduction
The disease burden and risk factors for respiratory syncytial virus (RSV) and human metapneumovirus (MPV) infections among children living in remote, rural areas remain unclear.Materials and Methods
We conducted a prospective, household-based cohort study of children aged <3 years living in remote rural highland communities in San Marcos, Cajamarca, Peru. Acute respiratory illnesses (ARI), including lower respiratory tract infection (LRTI), were monitored through weekly household visits from March 2009 through September 2011. Nasal swabs collected during ARI/LRTI were tested for RSV, MPV, and other respiratory viruses using real-time RT-PCR. Incidence rates and rate ratios were calculated using mixed effects Poisson regression.Results
Among 892 enrolled children, incidence rates of RSV and MPV ARI were 30 and 17 episodes per 100 child-years, respectively. The proportions of RSV and MPV ARI that presented as LRTI were 12.5% and 8.9%, respectively. Clinic visits for ARI and hospitalizations were significantly more frequent (all p values <0.05) among children with RSV (clinic 41% and hospital 5.3%) and MPV ARI (38% and 3.5%) when compared with other viral infections (23% and 0.7%) and infections without virus detected (24% and 0.6%). In multivariable analysis, risk factors for RSV detection included younger age (RR 1.02, 95% CI: 1.00-1.03), the presence of a smoker in the house (RR 1.63, 95% CI: 1.12-2.38), residing at higher altitudes (RR 1.93, 95% CI: 1.25-3.00 for 2nd compared to 1st quartile residents; RR 1.98, 95% CI: 1.26-3.13 for 3rd compared to 1st quartile residents). Having an unemployed household head was significantly associated with MPV risk (RR 2.11, 95% CI: 1.12-4.01).Conclusion
In rural high altitude communities in Peru, childhood ARI due to RSV or MPV were common and associated with higher morbidity than ARI due to other viruses or with no viral detections. The risk factors identified in this study may be considered for interventional studies to control infections by these viruses among young children from developing countries. 相似文献109.
Maggy Jennings David B. Morton Emmanuelle Charton Jane Cooper Coenraad Hendriksen Stella Martin Michael C. Pearce Scott Price Keith Redhead Nick Reed Hugh Simmons Stephen Spencer Hilary Willingale 《Biologicals》2010,38(6):684-695
This report aims to facilitate the implementation of the Three Rs (reduction, refinement and replacement) in the testing of vaccines for regulatory and other purposes. The focus is predominantly on identification of reduction and refinement opportunities in batch potency testing but the principles described are widely applicable to other situations that involve experimental infections of animals. The report should also help to interpret the requirements of the European Pharmacopoeia with regard to the use of alternative tests, humane endpoints and other refinements. Two specific worked examples, for batch potency testing of Clostridium chauvoei and canine leptospira, with recommendations for harmonisation of international test requirements for these and other vaccines, are provided as appendices online. 相似文献
110.