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Antimicrobial peptide-loaded hyaluronic acid-based formulations, method of prod...

Gama, F. M.; Silva, João Pedro; Appelberg, Rui; Pedrosa, Jorge; Castro, António G.

The present disclosure relates to a novel formulation for the delivery of an antimicrobial peptide (AMP) for the treatment of infections, particularly in the lungs and/or airways. More particularly, it relates to a peptide loaded in hyaluronic acid polymer, preferably antimicrobial peptide encapsulated in hyaluronic acid nanoparticles. This solution may be used in medicine or as a medicament.


Innate IFN-γ-Producing Cells Developing in the Absence of IL-2 Receptor Common ...

Resende, Mariana; Cardoso, Marcos S.; Ribeiro, Ana R.; Flórido, Manuela; Borges, Margarida; Castro, António G.; Alves, Nuno L.; Cooper, Andrea M.

IFN-gamma is known to be predominantly produced by lymphoid cells such as certain subsets of T cells, NK cells, and other group 1 innate lymphoid cells. In this study, we used IFN-gamma reporter mouse models to search for additional cells capable of secreting this cytokine. We identified a novel and rare population of nonconventional IFN-gamma-producing cells of hematopoietic origin that were characterized by t...


Delivery of nanogel formulations with antimicrobial peptides for the treatment ...

Silva-Carvalho, Ricardo; Cristelo, C.; Silva, João Pedro; Coutinho, Olga; Castro, António G.; Pedrosa, Jorge; Appelberg, Rui; Gama, F. M.

[Excerpt] Mycobacterium tuberculosis is the human pathogen that causes Tuberculosis (TB). In 2015, 10.4 million TB cases and 1.8 million deaths were reported, placing this disease alongside HIV/AIDS as the deadliest infectious diseases. Current treatments rely in the administration of a cocktail of four first-line antibiotics during 6 months and, in the worst case scenario, a long-lasting treatment (24 months) ...


Antimicrobial peptides as novel anti-tuberculosis therapeutics

Silva, João Pedro Martins Soares Castro; Appelberg, Rui; Gama, F. M.

Tuberculosis (TB), a disease caused by the human pathogen Mycobacterium tuberculosis, has recently joined HIV/AIDS as the world's deadliest infectious disease, affecting around 9.6 million people worldwide in 2014. Of those, about 1.2 million died from the disease. Resistance acquisition to existing antibiotics, with the subsequent emergence of Multi-Drug Resistant mycobacteria strains, together with an increas...


Delivery of LLKKK18 loaded into self-assembling hyaluronic acid nanogel for tub...

Silva, João P.; Gonçalves, Carine; Costa, C.; Sousa, Jeremy; Silva-Gomes, Rita; Castro, António G.; Pedrosa, Jorge; Appelberg, Rui; Gama, F. M.

uberculosis (TB), a disease caused by the human pathogen Mycobacterium tuberculosis, recently joined HIV/AIDS on the top rank of deadliest infectious diseases. Low patient compliance due to the expensive, long-lasting and multi-drug standard therapies often results in treatment failure and emergence of multi-drug resistant strains. In this scope, antimicrobial peptides (AMPs) arise as promising candidates for T...


Type I IFN inhibits alternative macrophage activation during mycobacterium tube...

Moreira-Teixeira, Lúcia; Sousa, Jeremy Nicolas Carvalho; McNab, Finlay W.; Torrado, Egídio; Cardoso, Filipa; Machado, Henrique; Castro, Flávia

Tuberculosis causes ∼1.5 million deaths every year, thus remaining a leading cause of death from infectious diseases in the world. A growing body of evidence demonstrates that type I IFN plays a detrimental role in tuberculosis pathogenesis, likely by interfering with IFN-γ–dependent immunity. In this article, we reveal a novel mechanism by which type I IFN may confer protection against Mycobacterium tuberculos...


The Warburg effect in mycobacterial granulomas is dependent on the recruitment ...

Appelberg, Rui; Moreira, Diana; Silva, Palmira Conceição Araújo Barreira; Borges, Margarida; Silva, Letícia; Dinis-Oliveira, Ricardo Jorge

Granulomas are the hallmark of mycobacterial disease. Here, we demonstrate that both the cell recruitment and the increased glucose consumption in granulomatous infiltrates during Mycobacterium avium infection are highly dependent on interferon-y (IFN-y). Mycobacterium avium-infected mice lacking IFN-y signalling failed to developed significant inflammatory infiltrations and lacked the characteristic uptake of ...


Biomedical applications of human cathelicidin

Gama, F. M.; Silva, João P.; Martins-Green, Manuela; Castro, Gil; Pedrosa, Jorge; Appelberg, Rui

[Excerpt] Antimicrobial peptides (AMPs) are good candidates to treat burn wounds, a major cause of morbidity, impaired life quality and resources consumption in developed countries. Tuberculosis (TB), a disease caused by the human pathogen Mycobacterium tuberculosis, represents the second world’s deadliest infectious disease, affecting around 9 million people worldwide in 2013. Of those, about 1.1 million died ...


IL-17A promotes intracellular growth of Mycobacterium by inhibiting apoptosis o...

Cruz, Andrea; Ludovico, Paula; Torrado, Egídio; Gama, José B.; Sousa, Jeremy Nicolas Carvalho; Gaifem, Joana; Appelberg, Rui

The fate of infected macrophages is a critical aspect of immunity to mycobacteria. By depriving the pathogen of its intracellular niche, apoptotic death of the infected macrophage has been shown to be an important mechanism to control bacterial growth. Here, we show that IL-17 inhibits apoptosis of Mycobacterium bovis BCG- or Mycobacterium tuberculosis-infected macrophages thus hampering their ability to contro...


Studies in the mouse model identify strain variability as a major determinant o...

Marques, Filipe; Vale-Costa, Sílvia; Cruz, Tânia; Marques, Joana Moreira; Silva, Tânia; Neves, João Vilares; Cortes, Sofia; Fernandes, Ana

Visceral leishmaniasis is a severe and potentially fatal disease caused by protozoa of the genus Leishmania, transmitted by phlebotomine sandflies. In Europe and the Mediterranean region, L. infantum is the commonest agent of visceral leishmaniasis, causing a wide spectrum of clinical manifestations, including asymptomatic carriage, cutaneous lesions and severe visceral disease. Visceral leishmaniasis is more f...


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