- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Long-Term Effects of COVID-19
- Blood Coagulation and Thrombosis Mechanisms
- COVID-19 Clinical Research Studies
- Pneumonia and Respiratory Infections
- Respiratory Support and Mechanisms
- Immune Response and Inflammation
- Pancreatic and Hepatic Oncology Research
- Pulmonary Hypertension Research and Treatments
- Neonatal Respiratory Health Research
- Intensive Care Unit Cognitive Disorders
- Medical Imaging and Pathology Studies
- Chronic Kidney Disease and Diabetes
- Thermal Regulation in Medicine
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Inhalation and Respiratory Drug Delivery
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Inflammasome and immune disorders
- Sarcoidosis and Beryllium Toxicity Research
- Cancer-related Molecular Pathways
- IL-33, ST2, and ILC Pathways
- SARS-CoV-2 and COVID-19 Research
- Asthma and respiratory diseases
Amsterdam University Medical Centers
2019-2025
University of Amsterdam
2014-2025
Amsterdam UMC Location University of Amsterdam
2012-2023
University Medical Center
2020
Université Paris Cité
2017-2018
Inserm
2017-2018
Délégation Paris 7
2017-2018
Sorbonne Paris Cité
2017-2018
Physiopathologie et Epidémiologie des Maladies Respiratoires
2017-2018
Laboratoire Excell
2017-2018
The mechanisms underlying the initiation of puberty in fish are poorly understood, and whether Kiss1 receptor (Kiss1r; previously designated G protein-coupled 54; GPR54) its ligands, kisspeptins, play a significant role, as has been established mammals, is not yet known. We determined (via real-time PCR) temporal patterns expression brain kiss1r, gnrh2, gnrh3 suite related genes hypothalamo-pituitary-gonadal (HPG) axis analyzed them against timing gonadal germ cell development male female...
Knowledge of the pathophysiology COVID-19 is almost exclusively derived from studies that examined immune response in blood. We here aimed to analyse pulmonary during severe and compare this with blood responses.This was an observational study patients admitted intensive care unit (ICU). Mononuclear cells were purified bronchoalveolar lavage fluid (BALF) blood, analysed by spectral flow cytometry; inflammatory mediators measured BALF plasma.Paired samples obtained 17 patients, four whom died...
Rationale: Bacterial lung microbiota are correlated with inflammation and acute respiratory distress syndrome (ARDS) altered in severe coronavirus disease (COVID-19). However, the association between (including fungi) resolution of ARDS COVID-19 remains unclear. We hypothesized that increased bacterial fungal burdens related to nonresolving mortality COVID-19. Objectives: To determine relation clinical outcomes COVID-19–related ARDS. Methods: This observational cohort study enrolled...
Patients with COVID-19-related acute respiratory distress syndrome (ARDS) show limited systemic hyperinflammation, but immunomodulatory treatments are effective. Little is known about the inflammatory response in lungs and if this could be targeted using high-dose steroids (HDS). We aimed to characterise alveolar immune patients ARDS, determine its association mortality, explore between HDS treatment response.In observational cohort study, a comprehensive panel of 63 biomarkers was measured...
Abstract Autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) are found in the blood of at least 15% unvaccinated patients with life-threatening COVID-19 pneumonia. We report here presence auto-Abs IFNs bronchoalveolar lavage (BAL) 54 415 (13%) pneumonia tested. The individuals BAL included 45 (11%) against IFN-α2, 37 (9%) IFN-ω, IFN-α2 and/or ω, and five (1%) IFN-β, including three (0.7%) two (0.5%) IFN-β. Auto-Abs also neutralize other 12 subtypes IFN-α. Paired plasma samples...
Human herpesviruses, particularly cytomegalovirus (CMV) and herpes simplex virus (HSV), frequently reactivate in critically ill patients, including those with acute respiratory distress syndrome (ARDS) related to coronavirus disease 2019 (COVID-19). The clinical interpretation of pulmonary herpesvirus reactivation is challenging there ongoing debate about its association mortality benefit antiviral medication. We aimed quantify the incidence pathogenicity CMV HSV reactivations COVID-19 patients.
Protease activated receptor (PAR)-1 expression in tumor cells is associated with disease progression and overall survival a variety of cancers epithelial origin; however, the importance PAR-1 microenvironment remains unexplored. Utilizing an orthotopic pancreatic cancer model which are positive whereas stromal negative, we show that drives induces chemoresistance cancer. enhances monocyte recruitment into by regulating migration fibroblast dependent chemokine production thereby inducing...
Background Imatinib reduced 90-day mortality in hospitalised coronavirus disease 2019 (COVID-19) patients a recent clinical trial, but the biological effects that cause improved outcomes are unknown. We aimed to determine changes elicited by imatinib with COVID-19 and what baseline profile moderates effect of imatinib. Methods undertook secondary analysis randomised, double-blind, placebo-controlled trial oral hospitalised, hypoxaemic patients. Mediating plasma concentration 25 host response...
BackgroundPost-acute sequela of SARS-CoV-2 infection (PASC) encompass fatigue, post-exertional malaise and cognitive problems. The abundant expression the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase-2 (IDO2) in fatal/severe COVID-19, led us to determine, an exploratory observational study, whether IDO2 is expressed active PASC, may correlate with pathophysiology.MethodsPlasma or serum, peripheral blood mononuclear cells (PBMC) were obtained from well-characterized PASC...
Rationale Systemic activation of procoagulant and inflammatory mechanisms has been implicated in the pathogenesis COVID-19. Knowledge these host response pathways lung compartment COVID-19 patients is limited. Objectives To evaluate local systemic coagulation interconnected responses critically ill with persistent acute respiratory distress syndrome. Methods Paired bronchoalveolar lavage fluid plasma samples were obtained from 17 related syndrome (mechanical ventilation > 7 days) 1 2...
COVID-19 is a pandemic with high morbidity and mortality. In an autopsy cohort of patients, we found extensive accumulation the tryptophan degradation products 3-hydroxy-anthranilic acid quinolinic in lungs, heart, brain. This was not related to expression tryptophan-catabolizing indoleamine 2,3-dioxygenase (IDO)-1, but rather that its isoform IDO-2, which otherwise expressed rarely. Bioavailability absolute requirement for proper cell functioning synthesis hormones, whereas can cause death....
Idiopathic pulmonary fibrosis (IPF) is a devastating disease that remains refractory to current therapies.To characterize the expression and activity of membrane-anchored serine protease matriptase in IPF humans unravel its potential role human experimental fibrogenesis.Matriptase was assessed tissue specimens from patients with versus control subjects using quantitative reverse transcriptase-polymerase chain reaction, immunohistochemistry, Western blotting, while monitored by fluorogenic...
<h3>Background</h3> Idiopathic pulmonary fibrosis is the most devastating fibrotic diffuse parenchymal lung disease which remains refractory to pharmacological therapies. Therefore, novel treatments are urgently required. Protease-activated receptor (PAR)-1 a G-protein-coupled that mediates critical signalling pathways in pathology and physiology. Bleomycin-induced has been shown be diminished PAR-1-deficient mice. The purpose of this study investigate whether PAR-1 inhibition potential...
Bacterial pneumonia remains associated with high morbidity and mortality. The gram-positive pathogen Streptococcus pneumoniae is the most common cause of community-acquired pneumonia. Lipoteichoic acid (LTA) an important proinflammatory component bacterial cell wall. R-roscovitine, a purine analog, potent cyclin-dependent kinase (CDK)-1, -2, -5 -7 inhibitor that has ability to inhibit cycle induce polymorphonuclear (PMN) apoptosis. We sought investigate effect R-roscovitine on LTA-induced...
Endogenously administered activated protein C ameliorates diabetic nephropathy (DN) in a protease-activated receptor-1 (PAR-1)-dependent manner, suggesting that PAR-1 activation limits the progression of DN. Activation fibroblast-like cells, however, induces proliferation and extracellular matrix production, thereby driving fibrotic disease. Considering key role mesangial production during DN, may fact potentiate diabetes-induced kidney injury. To determine net effect streptozotocin-induced...
Abstract End‐stage renal disease, the final stage of all chronic kidney disorders, is associated with fibrosis and inevitably leads to failure death. Transition tubular epithelial cells (TECs) into mesenchymal fibroblasts constitutes a proposed mechanism underlying progression here we assessed whether protease‐activated receptor (PAR)‐1, which recently emerged as an inducer epithelial‐to‐mesenchymal transition (EMT), aggravates fibrosis. We show that PAR‐1 activation on TECs reduces...
CCAAT/enhancer-binding protein delta (C/EBPδ) has been shown to promote tumour growth, drug resistance and metastasis formation in some cancers, whereas we have that its re-expression limits the features of progression pancreatic ductal adenocarcinoma (PDAC). The pharmacological targeting-either activation or inhibition-of C/EBPδ may therefore harbour clinical relevance is desirable for preclinical studies on different contexts. Regrettably, date, only few molecules identified modify C/EBPδ....
Childhood asthma has been linked to distinct metabolomic profiles. To identify phenotypes (metabotypes) in children with moderate-to-severe through integrative fecal and serum metabolome analysis. Children from the Systems Pharmacology Approach Uncontrolled Pediatric Asthma cohort Global Initiative for treatment step ≥3 were recruited. control was defined by Control Test annual exacerbation history. Targeted metabolomics profiling of feces performed using liquid chromatography flow injection...