Biology subjects

Felix, C.

Publications and source records attributed to Felix, C..

3 recordsLinked to original sources

bioRxiv2026

Patient-Derived Synovium-on-a-Chip Recapitulates Disease and Treatment Response and Permits Study of Resistance

Rheumatoid arthritis (RA) is a chronic inflammatory disease with substantial interpatient heterogeneity in synovial pathology and therapeutic response. Reliable methods to predict drug efficacy for a given patients remain a critical unmet need. We developed a vascularized, immunocompetent synovium-on-a-chip platform that integrates patient-derived fibroblast-like synoviocytes (FLS) with matched peripheral blood leukocytes to provide a physiological human model of RA. The platform reconstructed the lining-sublining synovial architecture, recapitulated key features of RA inflammation, and exhibited transcriptional profiles resembling those of patient synovial tissue. Across patients spanning low, mixed, and high inflammatory endotypes, stromal-vascular organization was associated with distinct immune cell positioning and activation patterns, and on-chip immune phenotypes correlated with histological joint inflammation scores. We then tested infliximab, tocilizumab, and tofacitinib in parallel and integrated cytokine secretion, extracellular matrix remodeling, immune cell survival and immune cell recruitment into a composite treatment response score. On-chip scores for clinically matched treatments correlated with clinical improvement measured by {Delta}DAS28-ESR (Pearson r = 0.844). To investigate the cellular basis of heterogeneous drug responses, single-cell RNA sequencing identified SFRP1 remodeling FLS that persisted under treatment and exhibited high inflammatory programs in poorly responding chips. Cell-cell communication analysis linked reduced FN1-CD44 signaling toward SFRP1 remodeling FLS to higher NF-{kappa}B activity and drug resistance. We tested the functional relevance of this finding in chips derived from an independent TNFi-nonresponsive patient, where fibronectin supplementation reduced IL-6 secretion and restored the composite treatment response. Together, these findings support patient-derived synovium-on-a-chip as a platform for individualized drug evaluation and identify ECM-mediated niche signaling as a potential therapeutic target for overcoming drug resistance in RA.

bioengineering↗

bioRxiv2026

Integrating coastal microbiome observations for human, oyster and environmental protection

The Reseau dObservatoires de Microbiologie Environnementale integree (ROME) was a pilot study conducted in France from September 2020 to August 2023 aiming to establish a network of eDNA-based observatories across four estuarine ecosystems associated with oyster farming: the Bay of Veys (Normandy), the Bay of Brest (Brittany), Marennes-Oleron (Nouvelle-Aquitaine), and the Thau Lagoon (Occitania). Within a One Health framework, the study assessed the influence of river inputs on estuarine microbiome structuring and the emergence of microbiological hazards affecting human, aquaculture, and ecosystem health. Over 2,000 samples were collected during the study, including biweekly surface water and monthly adult oyster samples. Environmental nucleic acids were analysed using metabarcoding (bacterial and protist communities) and metagenomics (human RNA viruses). The coastal microbiome, including pathogenic and harmful taxa relevant to humans and aquatic invertebrates, was characterized. River influence on microbial community composition was examined through spatial comparisons of stations exposed to varying levels of freshwater runoff, while oysters acted as bio-integrators of local microbial diversity. Results revealed coherent coastal-to-offshore microbiome structuring across all ecosystems, with local variations linked to riverine inputs. eDNA metabarcoding allowed to detect a wide range of prokaryotic and eukaryotic pathogens, as well as harmful algal bloom (HAB) genera, several not captured by conventional monitoring. These findings demonstrate the potential of the ROME eDNA observatory network for high-resolution, integrative surveillance of microbial biodiversity and early detection of biological risks in estuarine environments.

genomics↗

bioRxiv2025

Diclofenac stress responses and biotransformation pathways in the marine diatom Phaeodactylum tricornutum

Effects of organic contaminants (OCs) on phytoplankton physiology were extensively studied in the last years while a knowledge gap exists regarding the ability of phytoplankton to transform OCs. Knowledge about biotransformation pathways in these organisms lag far behind that of other microorganisms. A better understanding of biotransformation pathways would help identify biomarkers of contaminants exposure, improve microalgae-based water remediation strategies and help better assess contaminants persistence and trophic transfer in natural aquatic environments. The present study investigated diclofenac (DCF) physiological effects, transcriptional responses and metabolism in the marine diatom Phaeodactylum tricornutum with the aim of getting an insight on detoxifications pathways. P. tricornutum did not result in significant removal capacity of DCF from the exposure medium. Bioconcentration factors varied depending on the exposure concentration (3.9 and 2.7 for 1.5 mg L-1 and 10 mg L-1 DCF respectively) but remained relatively low. DCF resulted in mild physiological effects on P. tricornutum but gene expression analysis indicated that multiple molecular functions and biological processes were altered by DCF exposure. Transcriptomic analysis suggested increased nutrients and energy requirements possibly associated with the contaminant stress and detoxification metabolism. CYP gene expression was not significantly regulated upon DCF exposure but 4-Hydroxy Diclofenac (OH-DCF), a metabolite generally associated with CYP enzymatic activity, was detected. However, CYP gene expression was not significantly regulated upon DCF exposure. Five additional DCF metabolites with high molecular weight were detected. These metabolites were not previously described in the literature and were suggested to be generated via amino acid (or peptides) conjugation. Gene ontology analysis indicated that amino acid and peptide biosynthetic pathways were regulated upon DCF exposure supporting a possible correlation between organic contaminants detoxification responses and amino acid and protein content in phytoplankton cells. Our findings contribute to highlighting the diversity of biotransformation pathways in phytoplankton and provide mechanistic information about contaminants detoxification.

microbiology↗