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A mathematical model of fibrinogen-mediated erythrocyte–erythrocyte adhesion

Lopes, Catarina S.; Curty, Juliana; Carvalho, Filomena Almeida; Hernández-Machado, A.; Kinoshita, Koji; Santos, Nuno C.; Travasso, Rui D. M.

Erythrocytes are deformable cells that undergo progressive biophysical and biochemical changes affecting the normal blood flow. Fibrinogen, one of the most abundant plasma proteins, is a primary determinant for changes in haemorheological properties, and a major independent risk factor for cardiovascular diseases. In this study, the adhesion between human erythrocytes is measured by atomic force microscopy (AFM...


Synthetic red blood cell-specific glycolytic intermediate 2,3-diphosphoglycerat...

Morais, Inês; Medeiros, Márcia M.; Carvalho, Maria; Morello, Judit; Teixeira, Sara M.; Maciel, Suelma; Nhantumbo, Janice; Balau, Ana

Mechanisms of malaria parasite interaction with its host red blood cell may provide potential targets for new antimalarial approaches. Pyruvate kinase deficiency has been associated with resistance to malaria in both experimental models and population studies. Two of the major pyruvate kinase deficient-cell disorders are the decrease in ATP and the increase in 2,3-biphosphoglycerate (2,3-BPG) concentration. Hig...


Fighting S. aureus catheter-related infections with sophorolipids: electing an ...

Mendes, Rita M.; Francisco, Ana P.; Carvalho, Filomena Almeida; Dardouri, Maissa; Costa, Bruna; Bettencourt, Ana F.; Costa, Judite; Gonçalves, Lidia

Staphylococcus aureus medical devices related-infections, such as blood stream catheter are of major concern. Their prevention is compulsory and strategies, not prone to the development of resistance, to prevent S. aureus biofilms on catheter surfaces (e.g. silicone) are needed. In this work two different approaches using sophorolipids were studied to prevent S. aureus biofilm formation on medical grade silicon...


Increased therapeutic efficacy of SLN containing Etofenamate and Ibuprofen in t...

Mancini, Giuliana; Gonçalves, Lídia; Marto, Joana; Carvalho, Filomena Almeida; Simões, Sandra; Ribeiro, Helena; Almeida, António José

Innovative formulations, including solid lipid nanoparticles (SLNs), have been sought to improve skin permeation of non-steroidal anti-inflammatory drugs (NSAIDs). The present study explores the use of SLNs, prepared using a fusion-emulsification method, to increase skin permeation and in vivo activity of two relevant NSAIDs: A liquid molecule (etofenamate) and a solid one (ibuprofen), formulated in a 2% hydrox...


Non-canonical Wnt signaling regulates junctional mechanocoupling during angioge...

Carvalho, Joana R.; Fortunato, Isabela C.; Fonseca, Catarina; Pezzarossa, Anna; Barbacena, Pedro; Dominguez-Cejudo, Maria Angeles

Morphogenesis of hierarchical vascular networks depends on the integration of multiple biomechanical signals by endothelial cells, the cells lining the interior of blood vessels. Expansion of vascular networks arises through sprouting angiogenesis, a process involving extensive cell rearrangements and collective cell migration. Yet, the mechanisms controlling angiogenic collective behavior remain poorly underst...


Fibrinogen–erythrocyte binding and hemorheology measurements in the assessment ...

Guedes, Ana Filipa; Moreira, Carlos; Nogueira, José B.; Santos, Nuno C.; Carvalho, Filomena Almeida

Some studies have reported a positive association between plasma fibrinogen levels, erythrocyte aggregation and essential arterial hypertension (EAH). The aim of this study was to understand how the interaction between fibrinogen and its erythrocyte membrane receptor is altered in EAH. EAH patients (n = 31) and healthy blood donors (n = 65) were enrolled in the study. EAH patients were therapeutically controlle...


West Nile virus capsid protein interacts with biologically relevant host lipid ...

Martins, Ana S.; Carvalho, Filomena Almeida; Faustino, André F.; Martins, Ivo C.; Santos, Nuno C.

West Nile and dengue viruses are closely related flaviviruses, originating mosquito-borne viral infections for which there are no effective and specific treatments. Their capsid proteins sequence and structure are particularly similar, forming highly superimposable α-helical homodimers. Measuring protein-ligand interactions at the single-molecule level yields detailed information of biological and biomedical re...


SRC inhibition prevents P-cadherin mediated signaling and function in basallike...

Ribeiro, Ana Sofia; Nobre, Ana Rita; Mendes, Nuno; Almeida, João; Vieira, André Filipe; Sousa, Bárbara; Carvalho, Filomena Almeida; Monteiro, Joana

BACKGROUND: Basal-like breast cancer (BLBC) is a poor prognosis subgroup of triple-negative carcinomas that still lack specific target therapies and accurate biomarkers for treatment selection. P-cadherin is frequently overexpressed in these tumors, promoting cell invasion, stem cell activity and tumorigenesis by the activation of Src-Family kinase (SRC) signaling. Therefore, our aim was to evaluate if the trea...


AFM imaging-force spectroscopy combination for molecular recognition at the sin...

Carvalho, Filomena Almeida; Santos, Nuno

Molecular recognition at the single-cell level is an increasingly important issue in Biomedical Sciences. With atomic force microscopy, cell surface receptors may be recognized through the interaction with their ligands, inclusively for the identification of cell-cell adhesion proteins. The spatial location of a specific interaction can be determined by adhesion force mapping, which combines topographic images ...


Impact of γ’γ’ fibrinogen interaction with red blood cells on fibrin clots

Guedes, Ana Filipa; Carvalho, Filomena Almeida; Domingues, Marco; Macrae, Fraser L.; McPherson, Helen R.; Sabban, Aliaa; Martins, Ivo C.; Duval, Cédric

AIM: γ' fibrinogen has been associated with thrombosis. Here the interactions between γ'γ' or γAγA fibrinogen and red blood cells (RBCs), and their role on fibrin clot properties were studied. MATERIALS & METHODS: Atomic Force microscopy (AFM)-based force spectroscopy, rheological, electron and confocal microscopy, and computational approaches were conducted for both fibrinogen variants. RESULTS & CONCLUSION: A...


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