Biomedical subjects

Isabelle Fournier

Publications and source records attributed to Isabelle Fournier.

11 recordsLinked to original sources

PubMed2026

Epithelial-Mesenchymal Transition Shapes the Lipotoxic Response of Colon Cancer Cells to Palmitic Acid.

Saturated fatty acids such as palmitic acid (PA) can induce lipotoxic stress, whereas monounsaturated fatty acids like oleic acid (OA) often promote adaptive responses through lipid droplets (LDs) formation. Here, we reveal that epithelial-mesenchymal transition (EMT) profoundly influences the lipotoxic response of colorectal cancer cells. Using the epithelial-like HCT15 and mesenchymal-like HCT116 cell lines, we combined proteomic, metabolic, and imaging analyses to elucidate how EMT status determines lipid storage capacity and resistance to PA-induced toxicity. A basal proteomic profiling highlighted a striking divergence in metabolic changes: HCT15 cells displayed enhanced glycolysis and reduced expression of LDs biogenesis proteins, while HCT116 cells exhibited oxidative metabolism and a "lipid-rich" proteomic signature enriched in PLIN2, GPAT3, and DGAT1. Functionally, PA triggered massive cytotoxicity and failed to induce LDs in HCT15 cells, correlating with DGAT1/2 downregulation and suppressed triacylglycerol synthesis. In contrast, HCT116 cells showed modest LDs accumulation, preserved mitochondrial function, and strong resistance to lipotoxic stress. OA treatment restored LDs formation and cell viability in both models, underscoring the protective role of unsaturated fatty acids. Notably, forced EMT induction in HCT15 cells by PMA markedly enhanced LDs accumulation and reduced PA-induced death, confirming that EMT confers metabolic plasticity and lipid-buffering capacity. These findings demonstrate that EMT status modulates differential lipid handling and stress adaptation in colon cancer cells, linking mesenchymal transition to enhanced LDs biogenesis and survival under lipotoxic conditions. Data are available via ProteomeXchange with identifier PXD071641.

Humans↗

PubMed2026

Profiler: an open web platform for multi-omics analysis.

MOTIVATION: High-throughput multi-omics technologies produce increasingly large and heterogeneous datasets that are difficult to analyze without advanced computational expertise. Existing bioinformatics tools are often fragmented or limited to specific omics types, hindering reproducibility and accessibility. There is a critical need for an integrated, user-friendly, and scalable platform capable of supporting multi-omics analyses across different data modalities. RESULTS: We present Profiler, an open-source, modular platform that unifies data import, quality control, preprocessing, statistical testing, machine and deep learning, biomarker discovery, pathway and drug-target enrichment, and survival modeling within a single reproducible environment. Built in Python with Streamlit, Profiler is available as both a web-based platform deployed on high-performance computing and a desktop version for local execution, enabling flexible usage across computational infrastructures. Profiler supports diverse omics modalities, including proteomics, transcriptomics, lipidomics, and electroencephalogram data. Through applications to glioblastoma proteomic, pancancer, and multi-omics datasets, Profiler reproduced known molecular subtypes, revealed potential therapeutic targets, and generated fully traceable analysis reports within minutes. By integrating advanced analytics behind an intuitive interface, Profiler democratizes multi-omics analysis and provides a robust, scalable foundation for systems biology and precision medicine research. AVAILABILITY AND IMPLEMENTATION: Profiler is open-source and freely available via its web platform (https://prism-profiler.univ-lille.fr) and GitHub (web version: https://github.com/yanisZirem/Profiler_v1_requests_datatests, desktop version: https://github.com/yanisZirem/prism-profiler), and archived on Zenodo (DOI: https://doi.org/10.5281/zenodo.17478158).

Software↗

PubMed2025

NMFProfiler: a multi-omics integration method for samples stratified in groups.

MOTIVATION: The development of high-throughput sequencing enabled the massive production of "omics" data for various applications in biology. By analyzing simultaneously paired datasets collected on the same samples, integrative statistical approaches allow researchers to get a global picture of such systems and to highlight existing relationships between various molecular types and levels. Here, we introduce NMFProfiler, an integrative supervised NMF that accounts for the stratification of samples into groups of biological interest. RESULTS: NMFProfiler was shown to successfully extract signatures characterizing groups with performances comparable to or better than state-of-the-art approaches. In particular, NMFProfiler was used in a clinical study on atopic dermatitis (AD) and to analyze a multi-omic cancer dataset. In the first case, it successfully identified signatures combining known AD protein biomarkers and novel transcriptomic biomarkers. In addition, it was also able to extract signatures significantly associated to cancer survival. AVAILABILITY AND IMPLEMENTATION: NMFProfiler is released as a Python package, NMFProfiler (v0.3.0), available on PyPI.

Humans↗

PubMed2005

Lipopolysaccharide mediated regulation of neuroendocrine associated proprotein convertases and neuropeptide precursor processing in the rat spleen.

Within the secretory pathway, the family of proprotein convertases cleave inactive precursors at paired basic residues to generate a myriad of biologically active peptides. Within the PC family, PC1/3 and PC2 are well known for their preferential expression within neuroendocrine cells. However, various data now indicate their potential expression in immune cells. The aim of our study was two fold: (1) survey PC expression in immune tissues, with emphasis on PC1/3 and PC2 and (2) examine PC expression under conditions that mimic an infectious state using lipopolysaccharide, known to activate immune cells via toll-like receptors. Spatial and temporal analyses of tissues from control and lipopolysaccharide treated rats were carried out using in situ hybridization histochemistry, Northern blot, mass spectrometry and antibacterial assays. Our tissue survey showed the basal expression of all PCs in the lymph nodes, thymus and spleen including PC1/3 and PC2. Focusing on the spleen, basal expression of PC1/3 was seen in the red pulp/marginal zone areas, suggesting expression within macrophages. Lipopolysaccharide treatment produced significant changes in PC1/3 expression and notably an induction in B lymphocytes within germinal centers. Similarly, PC2, which was undetectable in control spleens, was induced in germinal centers following lipopolysaccharide treatment. The PC1/3 and PC2 substrate proenkephalin was also induced following lipopolysaccharide treatment in the marginal zone, where PC1/3 expression was also found. Mass spectrometry analysis of spleen extracts demonstrated the presence of the antibacterial peptide enkelytin. Our studies confirmed that PC1/3 and PC2 expression was not restricted to neurons and endocrine cells, but was also found under basal conditions in both macrophage and lymphocytes. Additionally, plasticity of PC expression in immune cells was observed under conditions that mimic pathogen-like infections, suggesting a mechanistic link through Toll-like receptors. Collectively, these data clearly implicate PCs in immune responses, both innate and acquired.

Animals↗

PubMed2005

Structured treatment interruptions in primary HIV-1 infection: the ANRS 100 PRIMSTOP trial.

BACKGROUND: Whether structured treatment interruptions (STIs) can induce anti-HIV immune response and control HIV replication following discontinuation of highly active antiretroviral therapy (HAART) in patients with primary HIV infection is controversial. METHODS: In this multicenter, prospective trial, patients with early symptomatic primary HIV infection were given HAART continuously for 34 weeks. Afterward, patients with plasma viral load (PVL) <50 copies/mL entered the STI phase, which consisted of 3 consecutive periods of 2, 4, and 8 weeks off HAART, each separated by 12 weeks on HAART. HAART was permanently stopped at week 84 and patients were followed up for 24 weeks. The primary endpoint for definition of virologic success was a PVL <50 copies/mL during the 6 months following HAART discontinuation. RESULTS: Of the 29 patients enrolled, 26 completed the trial. Six months after HAART discontinuation, only 1 patient (3.8%, 95% CI: 0.1% to 19.6%) had PVL <50 copies/mL, whereas 6 of 26 (23.1%, 95% CI: 9.0% to 43.7%) had PVL <1000 copies/mL. Female gender was the only parameter significantly associated with a PVL <1000 copies/mL. No other parameter, either at baseline or before HAART discontinuation, predicted virologic success at week 108. A major protease inhibitor resistance mutation (L90M) developed in 3 patients. CONCLUSIONS: This trial failed to confirm that a significant proportion of patients with primary HIV infection can maintain suppression of viremia after a sequence of HAART/STIs followed by HAART discontinuation.

Adult↗

PubMed2005

Health-related quality of life and health locus of control beliefs among HIV-infected treated patients.

OBJECTIVE: This study examined the relations between health locus of control (HLOC) beliefs and health-related quality of life (HRQL) in 302 HIV-infected patients enrolled in a French cohort, 44 months (M44) after they began highly active antiretroviral therapy (HAART). METHODS: HLOC beliefs were measured with the Multidimensional Health Locus of Control (MHLOC) scale and HRQL, with the Medical Outcome Study Short-Form Health Survey (MOS-SF-36). RESULTS: Internal HLOC beliefs at the initiation of treatment were associated with both physical HRQL in multivariate analysis, while chance HLOC beliefs on beginning HAART were associated with mental HRQL at M44. CONCLUSION: These findings suggest the importance of considering the psychological characteristics and psychosocial beliefs of patients at the initiation of ARV treatment to optimise the long-term HRQL of HIV-infected patient and to develop adaptive intervention on coping strategies.

Adult↗

PubMed2004

Silencing of SPC2 expression using an engineered delta ribozyme in the mouse betaTC-3 endocrine cell line.

Endoproteolytic processing is carried out by subtilase-like pro-protein convertases in mammalian cells. In order to understand the distinct roles of a member of this family (SPC2), gene silencing in cultured cells is an ideal approach. Previous studies showed limited success in either the degree of inhibition obtained or the stability of the cell lines. Here we demonstrate the high potential of delta ribozyme as a post-transcriptional gene silencing tool in cultured cells. We used an expression vector based on the RNA polymerase III promoter to establish betaTC-3 stable cell lines expressing the chimeric tRNA(Val)-delta ribozyme transcript targeting SPC2 mRNA. Northern and Western blot hybridizations showed a specific reduction of SPC2 mRNA and protein. Validation of processing effects was tested by measuring the levels of dynorphin A-(1-8), which are present in betaTC-3 cells as a result of the unique cleavage of dynorphin A-(1-17) by SPC2. Moreover, a differential proteomic analysis confirmed these results and allowed identification of secretogranin II as a potential substrate of SPC2. The development of efficient, specific, and durable silencing tools, such as described in the present work, will be of great importance in elucidating the functions of the subtilase-like pro-protein convertases in regard to peptide processing and derived cellular events.

Animals↗

PubMed2003

TACE/ADAM-17 maturation and activation of sheddase activity require proprotein convertase activity.

Proprotein convertases (PCs) have been proposed to play a role in tumor necrosis factor-alpha converting enzyme (TACE) processing/activation. Using the furin-deficient LoVo cells, as well as the furin-proficient synoviocytes and HT1080 cells expressing the furin inhibitor alpha(1)-PDX, we demonstrate that furin activity alone is not sufficient for effective maturation and activation of the TACE enzyme. Data from in vitro and in vivo cleavage assays indicate that PACE-4, PC5/PC6, PC1 and PC2 can directly cleave the TACE protein and/or peptide. PC inhibition in macrophages reduced the release of soluble TNF-alpha from transmembrane pro-TNF-alpha. We therefore conclude that furin, in addition to other candidate PCs, is involved in TACE maturation and activation.

ADAM Proteins↗

PubMed2002

The effects of amphotericin B on pure and ergosterol- or cholesterol-containing dipalmitoylphosphatidylcholine bilayers as viewed by 2H NMR.

Amphotericin B (AmB) is a widely used polyene antibiotic to treat systemic fungal infections. This drug is known to be lethal to fungal cells but it has also side effect toxicity on mammalian cells. The mechanism of action of AmB is thought to be related to the difference of the main sterol present in the mammalian and the fungal cells, namely cholesterol and ergosterol, respectively. The effect of AmB has been investigated on pure dipalmitoylphosphatidylcholine (DPPC) and on cholesterol- and ergosterol-containing DPPC bilayers by 2H NMR spectroscopy. The 2H NMR results first confirm that AmB forms a complex with sterol-free DPPC bilayers, the interaction causing the structurization of the lipids and the increase of the gel-to-lamellar fluid DPPC phase transition temperature with increasing concentration of the antibiotic. The results also show that the effects of AmB on cholesterol- and ergosterol-containing DPPC bilayers are remarkably different. On one hand, the drug causes an increase of the orientational order of the lipid acyl chains in cholesterol-containing membranes, mostly in high cholesterol content membranes. On the other hand, the addition of AmB disorders the DPPC acyl chains when ergosterol is present. This is thought to be due to the direct complexation of the ergosterol by AmB, causing the sterol ordering effect to be weaker on the lipids.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2002

Folate deficiency alters melatonin secretion in rats.

The final step of melatonin (MLT) synthesis is methylation of N-acetyl-serotonin, with S-adenosylmethionine as a methyl donor provided by a metabolic pathway involving sulfur-containing amino acids (homocysteine and methionine). Remethylation of homocysteine to methionine requires folate. The present study was undertaken to test the influence of folate deficiency on MLT secretion. Severe folate deficiency was induced in rats by feeding them a synthetic diet containing (per kg diet) 0 mg folate and 10 g succinylsulfathiazole. Control rats were fed the same diet containing 8 mg folate/kg. After 4 wk, erythrocyte folate concentrations were significantly lower and plasma homocysteine levels were greater in folate-deficient rats than in controls. Pineal MLT concentration and urinary excretions of MLT, 6 sulfatoxymelatonin (the main hepatic MLT metabolite) and methoxylated catechol compounds were lower in the folate-deficient group than in the controls, whereas plasma catecholamine concentrations did not differ. Decreases generally were more marked at wk 2 than at wk 4 for the urinary metabolite excretions. These findings indicate that folate deficiency dramatically alters MLT secretion in rats.

Animals↗

PubMedDate not supplied

Direct analysis of neuropeptides by in situ MALDI-TOF mass spectrometry in the rat brain.

The measure of neuropeptides is an important tool in biology to better define endocrine and neuroendocrine function. Traditionally most methods have relied on the development of specific antibodies. Newer molecular methodologies have used measures of gene expression of neuropeptide precursors, such as Northern blot, PCR or in situ hybridization analysis. Matrix-assisted laser desorption/ionization (MALDI) mass analysis is a novel powerful technique for investigation of neuropeptides. Multiple peptides and peptide forms can be detected simultaneously and with great sensitivity in tissue extracts or partially purified samples. We have now adapted a MALDI methodology for the direct measurement of neuropeptides on fresh tissue sections of rat brains. We have validated the method by examining peptidergic mass profiles of the supraoptic nucleus (SON) and caudate putamen hypothalamic regions. Interestingly, mass profiles showed that vasopressin, which is specifically present in the SON, is modulated when animals are treated with lipopolysaccharides. MALDI-MS on brain slides is a novel complementary technique for neurobiologists and endocrinologists in order to investigate the dynamic and regional distribution of neuropeptides during physiological events.

Animals↗