Biology subjects

Bourdon, C.

Publications and source records attributed to Bourdon, C..

6 recordsLinked to original sources

bioRxiv2025

Feeding a low-protein diet exacerbates the susceptibility to Citrobacter rodentium and Dextran Sulfate Sodium-induced intestinal injury in mice.

Globally, almost half of all early childhood deaths are linked to severe undernutrition, herein referred to as severe malnutrition. Mortality in severely malnourished children is often attributed to common infectious diseases, including enteric infections. It has been proposed that impaired intestinal barrier function contributes to mortality, but direct evidence is limited and thus there exists a need to develop improved preclinical models to test these and other mechanistic hypotheses. In this study, we aimed to describe differences in response to enteric inflammation and infection in the colon of malnourished mice compared to well-nourished littermates. C57Bl/6 male weanlings were fed isocaloric diets, either a low 1% protein diet (LPD) or a control 18% protein diet (CPD) for 2-weeks either in combination with oral administration of dextran sodium sulfate (DSS), or Citrobacter rodentium (C. rodentium). LPD-fed mice were more susceptible to DSS or C. rodentium as evidenced by increased clinical severity scores, and reaching their humane endpoints. LPD-fed mice also showed more signs of colonic dysfunction with reduced levels of tight junction proteins, higher colonic pathogen load, and increased systemic inflammation and bacterial spread. Taken together, these observations show that malnourished animals have increased susceptibility to intestinal dysfunction caused by either chemical exposure or infection. These novel preclinical models can be used to further elucidate the processes involved in enteric dysfunction in malnutrition and to test therapies to improve intestinal repair and outcomes.

microbiology↗

bioRxiv2024

Depletion of all platelet integrins impacts hemostasis, thrombosis and tumor metastasis

Platelet integrins, in addition to other platelet receptors, are known to control hemostasis, thrombosis but also metastatic progression. Yet, their exclusive but combined deficiency has never been tested in these processes. Taking advantage of PF4Cre-{beta}1-/-/{beta}3-/- mouse strain, we show that platelets are exclusively depleted for all integrins. While they displayed impaired binding to fibrinogen and annexin-V, P-selectin exposure was normal. Platelet adhesion was abrogated on immobilized fibrinogen and fibrillar fibronectin under shear flow. PF4Cre-{beta}1-/- /{beta}3-/- mice presented an increased bleeding time and a profound defect in experimental models of arterial thrombosis. Platelet adhesion to tumor cells was also reduced, with a profound impact on tumor growth and metastatic burden in a model of triple negative breast cancer. Overall, these results confirm the central role of platelet integrins in hemostasis and thrombosis, and define their role in tumor growth and metastasis formation. 40-word summary: Depletion of all platelet integrins in PF4Cre-{beta}1-/-/{beta}3-/- mice leads to increased bleeding time and inhibits in vivo arterial thrombosis. Integrin-null platelets reduce tumor growth and metastatic burden in orthotopic and experimental metastasis models. Platelet integrins control hemostasis, thrombosis and metastasis.

cancer biology↗

bioRxiv2023

Characterization of the bioaccumulation and toxicity of copper pyrithione, an antifouling compound, on juveniles of rainbow trout

Since the global ban on tributyltin in antifouling paints in 2008 by the International Maritime Organization, new products have been developed and brought to the market. Among them, copper pyrithione (CuPT) is used, but its mechanisms of toxicity remain little known. This project aimed to identify and measure the impacts of aqueous exposure to CuPT, an organic compound, and compare it to ionic Cu2+ added in the form of its inorganic salt CuSO4, in equivalent Cu2+ molar concentrations, on rainbow trout (Oncorhynchus mykiss) juveniles under controlled laboratory conditions. A 24-hour acute exposure was performed with nominal concentrations of 50 and 100 {micro}g/L Cu from either CuSO4 or CuPT (labelled CuSO4_50, CuSO4_100, CuPT_50 and CuPT_100, respectively). The CuPT_100 condition induced 85 % mortality in 15 hours and the CuPT_50 condition induced 5 % mortality in the same period. A chronic exposure was then performed with nominal concentrations of 1 and 10 {micro}g/L Cu from CuPT and 10 {micro}g/L Cu2+ from CuSO4 (labelled CuSO4_1, CuSO4_10, CuPT_1 and CuPT_10, respectively). Measured aqueous concentrations of Cu2+ were slightly higher than nominal concentrations for the lower concentrations, but lower for the CuPT_10 condition. The 8- and 16-day toxicokinetics showed a greater accumulation of copper in the gills of fish exposed to CuPT compared to fish exposed to Cu2+ from CuSO4. The CuPT_10 condition induced 35 and 38 % mortality after 8 and 16 days of exposure, while no mortality was observed in the CuSO4_10 condition. The growth of juveniles was not impacted during the 16 days of exposure for any condition. The activity of antioxidant enzymes (CAT, SOD, GPx) did not respond to exposure to either contaminant. The expression of genes involved in the antioxidant response (sod1, sod2, gpx), detoxification (cyp1a, mt1x, mt2x), Cu transport (ctr1, ctr2, slc11a2), energy metabolism (AcoAc, cox, 12S) and cell cycle regulation (bax) strongly decreased at Day 8 in the gills and at Day 16 in the liver of CuPT-exposed fish in comparison to controls at the same time point. This study clearly showed that the toxicity of Cu in the form of CuPT was much higher than that of ionic Cu from CuSO4 and provides new information on the compound that will be useful to develop regulations concerning its use and release in the aquatic environment. Credit author statementCharlotte Bourdon: Methodology, Validation, Investigation, Writing - Original Draft. Jerome Cachot: Conceptualization, Methodology, Validation, Investigation, Writing - Original Draft, Supervision. Patrice Gonzalez: Validation, Investigation, Writing - Original Draft, Supervision, Funding acquisition. Patrice Couture: Conceptualization, Methodology, Validation, Investigation, Writing - Original Draft, Supervision, Project administration, Funding acquisition.

pharmacology and toxicology↗

bioRxiv2022

Platelets favor the outgrowth of established metastases

Despite abundant evidence demonstrating that platelets foster metastasis, a therapeutic approach based on anti-platelet agents is not an option due to the risk of hemorrhages. In addition, whether platelets can regulate metastasis at the late stages of the disease remains unknown. In this study, we subjected syngeneic models of metastasis to various thrombocytopenic regimes to show that platelets provide a biphasic contribution to metastasis. While potent intravascular binding of platelets to tumor cells efficiently promotes metastasis, platelets further support the outgrowth of established metastases. Genetic depletion and pharmacological targeting of the platelet-specific receptor GPVI in humanized mouse models efficiently reduced the growth of established metastases, independently of active platelet binding to tumor cells in the bloodstream. Our study is the first to demonstrate therapeutic efficacy when targeting animals carrying growing metastases. It further identifies GPVI as the first molecular target whose inhibition can impair metastasis without inducing collateral hemostatic perturbations.

cancer biology↗

bioRxiv2021

Micronutrient supplements with iron promote disruptive protozoan and fungal communities in the developing infant gut

Supplementation with micronutrients, including vitamins, iron and zinc, is a key strategy to alleviate child malnutrition. However, adverse events resulting in gastrointestinal disorders, largely associated with iron, has resulted in ongoing debate over their administration. To better understand their impact on gut microbiota, we analysed the bacterial, protozoal, fungal and helminth communities of stool samples collected from children that had previously been recruited to a cluster randomized controlled trial of micronutrient supplementation in Pakistan. We show that while bacterial diversity was reduced in supplemented children, vitamins and iron may promote colonization with distinct protozoa and mucormycetes, whereas the addition of zinc ameliorates this effect. In addition to supplements, residence in a rural versus urban setting is an important determinant of eukaryotic composition. We suggest that the risks and benefits of such interventions may be mediated in part through eukaryotic communities, in a manner dependent on setting.

microbiology↗

bioRxiv2019

RumimiR: a detailed microRNA database focused on ruminant species

In recent years, the increasing use of Next Generation Sequencing technologies to explore the genome has generated large quantities of data. For microRNAs, more and more publications have described several thousand sequences, all species included. In order to obtain a detailed description of microRNAs from the literature for three ruminant species (bovine, caprine and ovine), a new database has been created: RumimiR. To date, 2,887, 2,733 and 5,095 unique microRNAs of bovine, caprine and ovine species, respectively, have been included. In addition to the most recent reference genomic position and sequence of each microRNA, this database contains details on the animals, tissue origins and experimental conditions available from the publications. Identity with human or mouse microRNA is mentioned. The RumimiR database enables data filtering, the selection of microRNAs being based on defined criteria such as animal status or tissue origin. For ruminant studies, RumimiR supplements the widely used miRBase database by browsing and filtering using complementary criteria, and the integration of all published sequences described as novel. The principal goal of this database is to provide easy access to all ruminant microRNAs described in the literature.

genomics↗