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Molecular maps of synovial cells in inflammatory arthritis using an optimized s...

Edalat, Sam G.; Gerber, Reto; Houtman, Miranda; Lückgen, Janine; Teixeira, Rui Lourenço; Palacios Cisneros, Maria del Pilar; Pfanner, Tamara

In this study, we optimized the dissociation of synovial tissue biopsies for single-cell omics studies and created a single-cell atlas of human synovium in inflammatory arthritis. The optimized protocol allowed consistent isolation of highly viable cells from tiny fresh synovial biopsies, minimizing the synovial biopsy drop-out rate. The synovium scRNA-seq atlas contained over 100,000 unsorted synovial cells fr...


Bone phenotyping approaches in human, mice and zebrafish : expert overview of t...

Foessl, Ines; Bassett, J. H. Duncan; Bjørnerem, Åshild; Busse, Björn; Calado, Ângelo; Chavassieux, Pascale; Christou, Maria; Douni, Eleni

A synoptic overview of scientific methods applied in bone and associated research fields across species has yet to be published. Experts from the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal Traits translational Network") Working Group 2 present an overview of the routine techniques as well as clinical and research approaches employed to characterize bone phenotypes in humans and selected animal models...


Effects of diabetes on microcirculation and leukostasis in retinal and non-ocul...

Silva-Herdade, Ana S.; Mota-Silva, Iara; Calado, Ângelo; Saldanha, Carlota; Nguyen, Ngan-Ha; Hou, Isabella; Castanho, Miguel A. R. B.; Roy, Sayon

Changes in retinal microcirculation are associated with the development of diabetic retinopathy (DR). However, it is unclear whether such changes also develop in capillary beds of other non-retinal tissues. Here, we investigated microcirculatory changes involving velocity of rolling neutrophils, adherence of neutrophils, and leukostasis during development of retinal vascular lesions in diabetes in other non-ret...


Increased monohexosylceramide levels in the serum of established rheumatoid art...

Miltenberger-Miltenyi, Gabriel; Machado, Ana Rita; Saville, Jennifer; Conceição, Vasco A.; Calado, Ângelo; Lopes, Inês; Fuller, Maria

Objectives: To identify serum sphingolipids that could act as candidate biomarkers in RA. Methods: We performed lipidomic analyses in the serum of 82 participants: 19 established RA patients, 18 untreated early RA patients, 13 untreated early arthritis patients not fulfilling the classification criteria for RA, 12 established SpA patients and 20 controls. We compared the lipid levels from the different patient ...


Diet, microbiota, and gut permeability : the unknown triad in rheumatoid arthritis

Guerreiro, Catarina Sousa; Calado, Ângelo; Sousa, Joana; Fonseca, João Eurico

Growing experimental and clinical evidence suggests that a chronic inflammatory response induced by gut dysbiosis can critically contribute to the development of rheumatic diseases, including rheumatoid arthritis (RA). Of interest, an adherence to a Mediterranean diet has been linked to a reduction in mortality and morbidity in patients with inflammatory diseases. Diet and intestinal microbiota are modifying fa...


Hydrodynamics of a free-flowing leukocyte toward the endothelial wall

Herdade, Ana Santos Silva; Sequeira, Adélia; Calado, Ângelo; Saldanha, Carlota; Kafi, Oualid

Leukocyte recruitment is an essential stage of the inflammatory response and although the molecular mechanisms of this process are relatively well known, the influence of the hydrodynamic effects that govern the inflammatory response are still under study. In this paper we made use of the images and experimental parameters obtained by intravital microscopy in an in vivo animal model of inflammation to track the...


Erythrocyte deformability : a partner of the inflammatory response

Herdade, Ana Santos Silva; Andolina, Giulia; Faggio, Caterina; Calado, Ângelo; Saldanha, Carlota

We aim to establish an in vivo animal model of acute inflammation using PAF (platelet activating factor) as inflammatory agent and to study the erythrocyte deformability changes induced by the inflammatory response. Counting the number of rolling and adherent neutrophils to endothelium after 2, 4 and 6 h of intrascrotal injection of PAF we showed the induction of an inflammatory state. Blood samples are collect...


Cxcl8-l1 and Cxcl8-l2 are required in the zebrafish defense against Salmonella ...

De Oliveira, Sofia; Lopez-Muñoz, Azucena; Martínez-Navarro, Francisco J.; Galindo-Villegas, Jorge; Mulero, Victoriano; Calado, Ângelo

In recent years zebrafish has emerged as an excellent model for studying the Cxcl8 signaling pathway in inflammation elicited upon tissue damage or infection. Zebrafish has two true homologs of mammalian CXCL8, named Cxcl8-l1 and Cxcl8-l2. Previously, we have shown that in wound-associated inflammation, these chemokines are up-regulated and are relevant for neutrophil recruitment. In infections, no such knowled...


ATP modulates acute inflammation In Vivo through Dual Oxidase 1–derived H2O2 pr...

De Oliveira, Sofia; López-Muñoz, Azucena; Candel, Sergio; Pelegrín, Pablo; Calado, Ângelo; Mulero, Victoriano

Dual oxidase 1 (Duox1) is the NADPH oxidase responsible for the H2O2 gradient formed in tissues after injury to trigger the early recruitment of leukocytes. Little is known about the signals that modulate H2O2 release from DUOX1 and whether the H2O2 gradient can orchestrate the inflammatory response in vivo. In this study, we report on a dominant-negative form of zebrafish Duox1 that is able to inhibit endogeno...


Cxcl8 (IL-8) mediates neutrophil recruitment and behavior in the zebrafish infl...

De Oliveira, Sofia; Reyes-Aldasoro, Constantino C.; Candel, Sergio; Renshaw, Stephen A.; Mulero, Victoriano; Calado, Ângelo

Neutrophils play a pivotal role in the innate immune response. The small cytokine CXCL8 (also known as IL-8) is known to be one of the most potent chemoattractant molecules that, among several other functions, is responsible for guiding neutrophils through the tissue matrix until they reach sites of injury. Unlike mice and rats that lack a CXCL8 homolog, zebrafish has two distinct CXCL8 homologs: Cxcl8-l1 and C...


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