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451.
Sant'Anna C Parussini F Lourenço D de Souza W Cazzulo JJ Cunha-e-Silva NL 《Histochemistry and cell biology》2008,130(6):1187-1198
Trypanosoma cruzi epimastigote forms concentrate their major protease, cruzipain, in the same compartment where these parasites store macromolecules
obtained from medium and for this ability these organelles were named as reservosomes. Intracellular digestion occurs mainly
inside reservosomes and seems to be modulated by cruzipain and its natural inhibitor chagasin that also concentrates in reservosomes.
T. cruzi mammalian forms, trypomastigotes and amastigotes, are unable to capture macromolecules by endocytosis, but also express cruzipain
and chagasin, whose role in infectivity has been described. In this paper, we demonstrate that trypomastigotes and amastigotes
also concentrate cruzipain, chagasin as well as serine carboxypeptidase in hydrolase-rich compartments of acidic nature. The
presence of P-type proton ATPase indicates that this compartment is acidified by the same enzyme as epimastigote endocytic
compartments. Electron microscopy analyzes showed that these organelles are placed at the posterior region of the parasite
body, are single membrane bound and possess an electron-dense matrix with electronlucent inclusions. Three-dimensional reconstruction
showed that these compartments have different size and shape in trypomastigotes and amastigotes. Based on these evidences,
we suggest that all T. cruzi developmental stages present lysosome-related organelles that in epimastigotes have the additional and unique ability of
storing cargo. 相似文献
452.
Rossella Luc Maria Rita Assenza Fabio Maiullari Luisa Pieroni Silvia Maiullari Giulia Federici Federica Marini Roberto Rizzi Andrea Urbani Silvia Soddu Fabiola Moretti 《Cell death & disease》2021,12(6)
Epithelial ovarian cancer (EOC) is a highly heterogeneous disease with a high death rate mainly due to the metastatic spread. The expression of MDM4, a well-known p53-inhibitor, is positively associated with chemotherapy response and overall survival (OS) in EOC. However, the basis of this association remains elusive. We show that in vivo MDM4 reduces intraperitoneal dissemination of EOC cells, independently of p53 and an immune-competent background. By 2D and 3D assays, MDM4 impairs the early steps of the metastatic process. A 3D-bioprinting system, ad hoc developed by co-culturing EOC spheroids and endothelial cells, showed reduced dissemination and intravasation into vessel-like structures of MDM4-expressing cells. Consistent with these data, high MDM4 levels protect mice from ovarian cancer-related death and, importantly, correlate with increased 15 y OS probability in large data set analysis of 1656 patients. Proteomic analysis of EOC 3D-spheroids revealed decreased protein synthesis and mTOR signaling, upon MDM4 expression. Accordingly, MDM4 does not further inhibit cell migration when its activity towards mTOR is blocked by genetic or pharmacological approaches. Importantly, high levels of MDM4 reduced the efficacy of mTOR inhibitors in constraining cell migration. Overall, these data demonstrate that MDM4 impairs EOC metastatic process by inhibiting mTOR activity and suggest the usefulness of MDM4 assessment for the tailored application of mTOR-targeted therapy.Subject terms: Metastasis, Mechanisms of disease 相似文献
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456.
Structural basis for selective inhibition of COX-2 by nimesulide 总被引:2,自引:0,他引:2
Gabriel F. Fabiola Vasantha Pattabhi Kuppuswamy Nagarajan 《Bioorganic & medicinal chemistry》1998,6(12):2337-2344
Nimesulide 1 is a novel nonsteroidal antiinflammatory drug which inhibits the enzyme cyclooxygenase 2 (COX-2) more selectively than cyclooxygenase 1 (COX-1). Molecular modelling studies have been carried out on complexes of 1 with COX-1 and with mutants of COX-1 simulating COX-2. These indicate that the mutations I523V and S516A largely contribute to the selectivity. A comparative study with SC-558 2 has also been performed. 相似文献
457.
Maria Rivera-Ch Alfredo Gamboa Fabiola Léon-Velarde Jose-Antonio Palacios David F O'Connor Peter A Robbins 《Journal of applied physiology》2003,94(3):1263-8; discussion 1253-4
Sea-level (SL) natives acclimatizing to high altitude (HA) increase their acute ventilatory response to hypoxia (AHVR), but HA natives have values for AHVR below those for SL natives at SL (blunting). HA natives who live at SL retain some blunting of AHVR and have more marked blunting to sustained (20-min) hypoxia. This study addressed the question of what happens when HA natives resident at SL return to HA: do they acclimatize like SL natives or revert to the characteristics of HA natives? Fifteen HA natives resident at SL were studied, together with 15 SL natives as controls. Air-breathing end-tidal Pco(2) and AHVR were determined at SL. Subjects were then transported to 4,300 m, where these measurements were repeated on each of the following 5 days. There were no significant differences in the magnitude or time course of the changes in end-tidal Pco(2) and AHVR between the two groups. We conclude that HA natives normally resident at SL undergo ventilatory acclimatization to HA in the same manner as SL natives. 相似文献
458.
Bas Brouwers Edson Mendes de Oliveira Maria Marti-Solano Fabiola B.F. Monteiro Suli-Anne Laurin Julia M. Keogh Elana Henning Rebecca Bounds Carole A. Daly Shane Houston Vikram Ayinampudi Natalia Wasiluk David Clarke Bianca Plouffe Michel Bouvier M. Madan Babu I. Sadaf Farooqi Jacek Mokrosiński 《Cell reports》2021,34(12):108862
459.
Nayely Garibay-Nieto Brianda Areli Hernández-Morán Eréndira Villanueva-Ortega María José Garcés-Hernández Karen Pedraza-Escudero América Arroyo-Valerio César Pedraza-Helvert Arturo Herrera-Rosas Estibalitz Laresgoiti-Servitje Mireya León-Hernández Neyla Baltazar-López Joselin Hernández-Ruíz Fabiola Serratos-Canales Gloria Queipo-García Sarah Elizabeth Messiah Srinivas Mummidi Juan Carlos López-Alvarenga 《Endocrine practice》2022,28(3):315-320
ObjectiveTo describe a third-degree polynomial function (hysteresis) of the effect size of age, obesity, and insulin sensitivity over the carotid intima-media thickness (c-IMT), in the pediatric and adult groups.MethodsA quasi-experimental study with fixed factor analysis of age (children aged 8-12 years, n = 73; adults aged 21-45 years, n = 82) and obesity (yes, n = 76; no, n = 79) was conducted to analyze the effect on the c-IMT and Matsuda insulin sensitivity index values. This quasi-experimental design was analyzed with robust regression modeling.ResultsThe additive effect of obesity, independent of age, was evident in the case of the c-IMT values. There was no interaction effect, but a significant difference between participants with normal weight and those with obesity was found (P < .0001). The difference between adults and children was also significant, but the effect size was smaller. A model was created based on age, Tanner stage, and obesity using the c-IMT and Matsuda insulin sensitivity index values. A linear function fit as R2, and the cubic function estimated parameters like a polynomial model.ConclusionThis practical study design showed that children with obesity displayed the same levels of carotid intima-media abnormalities as adults with obesity. The polynomial shape of the model suggests potentially poor outcomes that resemble the hysteresis process and may predict chronic cardiometabolic events during early adulthood. 相似文献