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De novo human angiotensin - converting enzyme 2 Decoy NL-CVX1 protects mice fro...

Rebelo, Maria; Tang, Cong; Coelho, Ana R.; Labão-Almeida, Carlos; Schneider, Matthias M.; Tatalick, Laurie; Ruivo, Pedro; de Miranda, Marta Pires

The emergence of novel variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need to investigate alternative approaches to prevent infection and treat patients with coronavirus disease 2019. Here, we report the preclinical efficacy of NL-CVX1, a de novo decoy that blocks virus entry into cells by binding with nanomolar affinity and high specificity to the receptor-binding doma...


Maternal γδ T cells shape offspring pulmonary type 2 immunity in a microbiota-d...

Papotto, Pedro H.; Yilmaz, Bahtiyar; Pimenta, Gonçalo; Mensurado, Sofia; Cunha, Carolina; Fiala, Gina; Gomes Da Costa, Daniel; Gonçalves-Sousa, Natacha

Immune development is profoundly influenced by vertically transferred cues. However, little is known about how maternal innate-like lymphocytes regulate offspring immunity. Here, we show that mice born from γδ T cell-deficient (TCRδ-/-) dams display an increase in first-breath-induced inflammation, with a pulmonary milieu selectively enriched in type 2 cytokines and type 2-polarized immune cells, when compared ...


Are We Ready for the Day After?

Albuquerque, Carolina; Carvalho, Tânia

The manuscript does not include an abstract


De novo human angiotensin-converting enzyme 2 decoy NL-CVX1 protects mice from ...

Rebelo, Maria; Tang, Cong; Coelho, Ana R; Labão-Almeida, Carlos; Schneider, Matthias M.; Tatalick, Laurie; Ruivo, Pedro; Pires de Miranda, Marta

The emergence of novel variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need to investigate alternative approaches to prevent infection and treat patients with coronavirus disease 2019. Here, we report the preclinical efficacy of NL-CVX1, a de novo decoy that blocks virus entry into cells by binding with nanomolar affinity and high specificity to the receptor-binding doma...


Interplay between liver and blood stages of Plasmodium infection dictates malar...

Chora, Ângelo Ferreira; Marques, Sofia; Lisboa Gonçalves, Joana; Lima, Priscila; Gomes Da Costa, Daniel; Fernandez-Ruiz, Daniel; Marreiros, Maria Inês

Plasmodium replicates within the liver prior to reaching the bloodstream and infecting red blood cells. Because clinical manifestations of malaria only arise during the blood stage of infection, a perception exists that liver infection does not impact disease pathology. By developing a murine model where the liver and blood stages of infection are uncoupled, we showed that the integration of signals from both s...


Spillover events of rabbit haemorrhagic disease virus 2 (recombinant GI.4P-GI.2...

Abade dos Santos, F.A.; Pinto, Andreia; Burgoyne, Thomas; Dalton, Kevin P.; Carvalho, Carina L.; Ramilo, David; Carneiro, Carla; Carvalho, Tânia

Rabbit haemorrhagic disease (RHD) is a major threat to domestic and wild European rabbits. Presently, in Europe, the disease is caused mainly by Rabbit haemorrhagic disease virus 2 (RHDV2/b or Lagovirus europaeus GI.2), the origin of which is still unclear, as no RHDV2 reservoir hosts were identified. After the RHDV2 emergence in 2010, viral RNA was detected in a few rodent species. Furthermore, RHDV2 was found...


Trypanosoma brucei triggers a broad immune response in the adipose tissue

Machado, Henrique; Rebelo, Tiago; Sequeira, Mariana; Trindade, Sandra; Carvalho, Tânia; Rijo-Ferreira, Filipa; Rentroia-Pacheco, Barbara; Serre, Karine

Adipose tissue is one of the major reservoirs of Trypanosoma brucei parasites, the causative agent of sleeping sickness, a fatal disease in humans. In mice, the gonadal adipose tissue (AT) typically harbors 2-5 million parasites, while most solid organs show 10 to 100-fold fewer parasites. In this study, we tested whether the AT environment responds immunologically to the presence of the parasite. Transcriptome...


Type 2 diabetes progression differently affects endothelial function and vascul...

Melo, Bernardete F.; Prieto-Lloret, Jesus; Cabral, Marlene D.; Martins, Fatima O.; Martins, Inês B.; Sacramento, Joana F.; Ruivo, Pedro; Carvalho, Tânia

Type 2 diabetes (T2D) is associated with cardiovascular and pulmonary disease. How T2D affects pulmonary endothelial function is not well characterized. We investigated the effects of T2D progression on contractility machinery and endothelial function in the pulmonary and systemic circulation and the mechanisms promoting the dysfunction, using pulmonary artery (PA) and aorta. A high-fat (HF, 3 weeks 60% lipid-r...


Celastrol efficacy by oral administration in the adjuvant-induced arthritis model

Cascao, Rita; Vidal, Bruno; Carvalho, Tânia; Lopes, Inês; Romão, Vasco C.; Goncalves, Joao; Moita, Luis; Fonseca, João Eurico

Background: We previously demonstrated that celastrol has significant anti-inflammatory and bone protective effects when administered via the intraperitoneal route. For further preclinical evaluation, an effective oral administration of celastrol is crucial. Here we aimed to study the therapeutic dose range for its oral administration. Methods: Celastrol (1-25 μg/g/day, N = 5/group) was administrated orally to ...


Vulnerability of progeroid smooth muscle cells to biomechanical forces is media...

Pitrez, Patricia R.; Estronca, Luís; Monteiro, Luís Miguel; Colell, Guillem; Vazão, Helena; Santinha, Deolinda; Harhouri, Karim; Thornton, Daniel

Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disease in children that leads to early death. Smooth muscle cells (SMCs) are the most affected cells in HGPS individuals, although the reason for such vulnerability remains poorly understood. In this work, we develop a microfluidic chip formed by HGPS-SMCs generated from induced pluripotent stem cells (iPSCs), to study their vulnerability to flow...


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