A5066115409- Respiratory Support and Mechanisms
- Mesenchymal stem cell research
- Neonatal Respiratory Health Research
- Macrophage Migration Inhibitory Factor
- Asthma and respiratory diseases
- IL-33, ST2, and ILC Pathways
- Fatty Acid Research and Health
- Immune cells in cancer
- Immune Cell Function and Interaction
- Gastroesophageal reflux and treatments
- Cancer, Hypoxia, and Metabolism
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Child Nutrition and Feeding Issues
- Tissue Engineering and Regenerative Medicine
- Epigenetics and DNA Methylation
- Malaria Research and Control
- Mosquito-borne diseases and control
- Occupational and environmental lung diseases
- Virus-based gene therapy research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Viral Infections and Vectors
- Inhalation and Respiratory Drug Delivery
- Tryptophan and brain disorders
- Hemoglobinopathies and Related Disorders
Instituto Gulbenkian de Ciência
2023-2025
Universidade Federal do Rio de Janeiro
2016-2023
New York University
2021
Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
2016-2017
Fundação Oswaldo Cruz
2014
Asthma is a chronic inflammatory disease that can be difficult to treat due its complex pathophysiology. Most current drugs focus on controlling the process, but are unable revert changes of tissue remodeling. Human mesenchymal stromal cells (MSCs) effective at reducing inflammation and remodeling; nevertheless, no study has evaluated therapeutic effects extracellular vesicles (EVs) obtained from human adipose tissue-derived MSCs (AD-MSC) established airway remodeling in experimental...
Abstract Mesenchymal stromal cells (MSCs) from different sources have differential effects on lung injury. To compare the of murine MSCs bone marrow (BM), adipose tissue (AD), and (LUNG) inflammatory remodeling processes in experimental allergic asthma, female C57BL/6 mice were sensitized challenged with ovalbumin (OVA) or saline (C). Twenty-four hours after last challenge, received either (50 µl, SAL), BM-MSCs, AD-MSCs, LUNG-MSCs (105 per mouse 50 µl total volume) intratracheally. At 1...
Protective adaptive immunity to Zika virus (ZIKV) has been mainly attributed cytotoxic CD8+ T cells and neutralizing antibodies, while the participation of CD4+ in resistance remained largely uncharacterized. Here, we show a antibody response, dependent on IFNγ signaling, which detected during first week infection is associated with reduced viral load brain, prevention rapid disease onset survival. We demonstrate these components ZIKV primary murine adoptive transfer models heterologous...
Abstract Regulatory T (TREG) cells develop via a program orchestrated by the transcription factor forkhead box protein P3 (FOXP3). Maintenance of TREG cell lineage relies on sustained FOXP3 mechanism involving demethylation cytosine-phosphate-guanine (CpG)-rich elements at conserved non-coding sequences (CNS) in locus. This cytosine is catalyzed ten–eleven translocation (TET) family dioxygenases, and it involves redox reaction that uses iron (Fe) as an essential cofactor. Here, we establish...
Silicosis is an occupational lung disease for which no effective therapy exists. We hypothesized that bosutinib, a tyrosine kinase inhibitor, might ameliorate inflammatory responses, attenuate pulmonary fibrosis, and thus improve function in experimental silicosis. For this purpose, we investigated the potential efficacy of bosutinib treatment silicosis induced C57BL/6 mice by intratracheal administration silica particles. After 15 days, once was established, animals were randomly assigned...
Macrophages are an essential part of tissue development and physiology. Perivascular macrophages have been described in tissues appear to play a role disease processes, although it remains unclear what the key features these cells are. Here, we identify subpopulation perivascular several organs, characterized by their dependence on transcription factor c-MAF displaying nonconventional macrophage markers including LYVE1, folate receptor 2, CD38. Conditional deletion lineages caused ablation...
Abstract Eosinophils play a crucial role as effector cells in asthma pathogenesis, with their differentiation being tightly regulated by metabolic mechanisms. While the involvement of iron various cellular processes is well known, its specific eosinophil has largely remained unexplored. This study demonstrates that levels are increased during process from progenitors to mature and activated eosinophils context allergic airway inflammation. Through experiments involving chelators,...
Whether jaundice, a common presentation of Plasmodium ( P .) falciparum malaria (1-3) arising from the accumulation circulating bilirubin, represents an adaptive or maladaptive response to spp. infection is not understood (1-3). We found that asymptomatic P. was associated with >10-fold higher ratio unconjugated bilirubin over parasite burden, compared symptomatic malaria. Genetic suppression synthesis by biliverdin reductase A (BVRA) (4) increased virulence and mortality in mice....
Disease tolerance is a defensive strategy that limits tissue damage during infection. Macrophage migration inhibitory factor (MIF)-deficient mice ( Mif-/- ) are protected in different models of infection and intestinal inflammation due to unclear disease mechanisms, whereas low disease-tolerant Il10-/- develop microbiota-dependent spontaneous gut inflammation. Here, we examined whether IL-10 required for the phenotype seen and, conversely, contribution MIF deficiency. While breeding...
Abstract Asthma is a chronic inflammatory disease characterized by airway inflammation and remodeling, which can lead to progressive decline of lung function. Although mesenchymal stromal cells (MSCs) have shown beneficial immunomodulatory properties in preclinical models allergic asthma, effects on remodeling been limited. Mounting evidence suggests that prior exposure MSCs specific stimuli or environments enhance their properties. Therefore, we investigated whether stimulating with...
Asthma is characterized by chronic lung inflammation and airway hyperresponsiveness. Despite recent advances in the understanding of its pathophysiology, asthma remains a major public health problem and, at present, there are no effective interventions capable reversing remodeling. Mesenchymal stromal cell (MSC)-based therapy mitigates experimental allergic asthma; however, ability to reduce remodeling limited. We aimed investigate whether pre-treatment with eicosapentaenoic acid (EPA)...
Even though mesenchymal stromal cells (MSCs) mitigate lung and distal organ damage in experimental polymicrobial sepsis, mortality remains high. We investigated whether preconditioning with eicosapentaenoic acid (EPA) would potentiate MSC actions sepsis by further decreasing injury, thereby improving survival.In C57BL/6 mice, was induced cecal hligation puncture (CLP); sham-operated animals were used as control. Twenty-four hours after surgery, CLP mice randomized to receive saline, adipose...
Abstract In experimental house dust mite (HDM)-induced allergic asthma, therapeutic administration of a single dose adipose tissue-derived mesenchymal stromal cells (MSCs) ameliorates lung inflammation but is unable to reverse remodeling. We hypothesized that multiple doses MSCs might exert better effects by reducing and remodeling also result in immunosuppressive asthma. HDM was administered intranasally C57BL/6 mice. After the last challenge, mice received two or three (105 per day) saline...
Despite long-standing efforts to enhance care for chronic asthma, symptomatic treatments remain the only option manage this highly prevalent and debilitating disease. We demonstrate that key pathology of allergic asthma can be almost completely resolved in a therapeutic manner by inhaled gene therapy. After disease was fully stably established, we treated mice intratracheally with single dose thymulin-expressing plasmids delivered via nanoparticles engineered have unique ability penetrate...
Cutaneous leishmaniasis remains both a public health and therapeutic challenge. To date, no ideal therapy for cutaneous has been identified, universally accepted regimen approved vaccines are available. Due to the mesenchymal stromal cell (MSC) immunomodulatory capacity, they have applied in wide variety of disorders, including infectious, inflammatory allergic diseases. We evaluated potential effects bone marrow MSC murine model leishmaniasis. In vitro, co-culture infected macrophages with...
Summary Background Prophylactic administration of mesenchymal stromal cells ( MSC s) derived from adipose AD ‐ ) and bone marrow tissue BM in ovalbumin‐induced asthma hinders inflammation a Treg‐dependent manner. It is uncertain whether s act through Tregs when already established induced by clinically relevant allergen. Objective Evaluate the effect therapeutic on Treg house dust mite HDM )‐induced asthma. Methods were administered intratracheally to C57 BL /6 mice 1 day after last...
Iron recycling prevents the development of anemia under homeostatic conditions. Whether iron was co-opted as a defense strategy to prevent in response infection is unclear. We find that severe Plasmodium falciparum malaria, onset life-threatening associated with acute kidney injury (AKI), irrespective parasite load. Using well-established experimental rodent model malaria anemia, we identify transcriptional endows renal proximal tubule epithelial cells (RPTECs) capacity store and recycle...
A single administration of mesenchymal stromal cells (MSCs) has been shown to reduce lung inflammation in experimental elastase-induced emphysema; however, effects were limited terms lung-tissue repair and cardiac function improvement. We hypothesized that two doses MSCs could induce further cardiovascular by mitigating remodeling a model emphysema induced multiple elastase instillations. aimed comparatively investigate the one versus MSCs, administered 1 week apart, murine emphysema....
The innate immune response plays an important role in the pathophysiology of acute respiratory distress syndrome (ARDS). Glutamine (Gln) decreases lung inflammation experimental ARDS, but its impact on formation extracellular traps (ETs) is unknown. In a mouse model endotoxin-induced pulmonary effects Gln treatment leukocyte counts and ET content bronchoalveolar lavage fluid (BALF), inflammatory profile tissue, morphofunction were evaluated vivo. Furthermore, formation, reactive oxygen...
Although bone marrow-derived mesenchymal stromal cells (BM-MSCs) from patients with chronic obstructive pulmonary disease (COPD) appear to be phenotypically and functionally similar BM-MSCs healthy sources in vitro , the impact of COPD on MSC metabolism mitochondrial function has not been evaluated. In this study, we aimed comparatively characterize MSCs emphysematous donors (H-MSCs E-MSCs) assess therapeutic potential these their extracellular vesicles (H-EVs E-EVs) an vivo model severe...
Administration of bone marrow mononuclear cells (BMMCs) modulates lung inflammation and fibrosis in experimental silicosis. However, no studies have evaluated whether silicosis affects the efficacy autologous BMMCs treatment. We hypothesized that obtained from healthy or silicotic mice may improve function, but they might affect inflammatory fibrotic processes differently C57BL/6 were randomly divided into control (C) (SIL) groups. Mice SIL group instilled with silica particles...
Variable ventilation has been shown to improve pulmonary function and reduce lung damage in different models of acute respiratory distress syndrome. Nevertheless, variable not tested during pneumonia. Theoretically, periodic increases tidal volume (VT) airway pressures might worsen the impairment alveolar barrier usually seen pneumonia could increase bacterial translocation into bloodstream. We investigated impact on histologic damage, as well markers inflammation, epithelial endothelial...
Abstract Macrophage migration inhibitory factor (MIF) is present in high amounts the BALF and serum of asthmatic patients, contributing to pathogenesis experimental asthma induced by OVA mice. Whether MIF contributes physiopathology on a more complex relevant model has not been characterized. Mif ‐deficient ( −/− ) or WT mice treated with anti‐MIF antibody were challenged multiple times using house dust mite (HDM) extract intranasal route. HDM‐challenged presented decreased airway...