HAL - RIIP
Not a member yet
17635 research outputs found
Sort by
Development of New Benzo[ b ]Thiophene‐2‐Carboxamide Derivatives as Advanced Glycation End‐Products Receptor (RAGE) Antagonists
No full textInternational audienceThe activation of the receptor for advanced glycation end‐products (RAGE) induces a chronic, low‐noise inflammation responsible for the aging process, known as inflammaging. Associated with numerous pathologies such as Alzheimer's, insulin‐resistant diabetes, cardiovascular diseases, and certain cancers, RAGE has become an interesting therapeutic target in the context of aging well. To this end, we identified new benzo[ b ]thiophene‐2‐carboxamide derivatives as potential RAGE ligands. Herein, we developed an alternative approach to easily synthesize benzo[ b ]thiophene‐2‐carboxamide analogs from 5‐arylidene‐2,4‐thiazolidinedione intermediates based on the Ullmann–Goldberg coupling conditions. In light of LCMS, NMR, X‐ray, and DFT studies, a mechanism for this reaction was proposed. This novel strategy enabled us to synthesize analogs whose best molecule 3t′ , with an IC 50 of 13.2 µM, shows similar interactions with RAGE as the reference molecule Azeliragon (13.0 µM)
Development of a 3D microfluidic model of pancreatic adenocarcinoma integrating the mechanical stimuli of the tumor microenvironment
No full textInternational audienc
Usages traditionnels et activités pharmacologiques de cinq plantes de Nouvelle-Calédonie
No full textInternational audienceRenowned for its exceptional biodiversity, New Caledonia is a place where traditional medicine plays a central role, with local populations using plants to treat various symptoms anddiseases for generations. This article focuses on five of these plants: Fagraea berteroana, Melochia odorata, Coleus forsteri, Melaleuca quinquenervia and Acronychia laevis and presents for each its botanical description, its traditional therapeutic uses in New Caledonia and the pharmacological properties of its extracts. By highlighting the importance of traditional medicinal practices in the culture and health of local communities, this review aims to promote ethnopharmacological knowledge in New Caledonia and encourage future research. The promotion of traditional pharmacopoeia can thus contribute to the preservation and respect of local knowledge, to a better understanding and sustainable use of these natural resources, as well as to participate in modern therapeutic innovation.Réputée pour sa biodiversité exceptionnelle, la Nouvelle-Calédonie est un lieu où la médecine traditionnelle occupe une place centrale car les populations locales utilisent les plantes pour traiter divers symptômes et maladies depuis des générations. Cet article s'intéresse à cinq de ces plantes : Fagraea berteroana, Melochia odorata, Coleus forsteri, Melaleuca quinquenervia et Acronychia laevis et présente pour chacune sa description botanique, ses usages thérapeutiques traditionnels en Nouvelle-Calédonie et les propriétés pharmacologiques de ses extraits. En mettant en lumière l'importance des pratiques médicinales traditionnelles dans la culture et la santé des communautés locales, cette revue vise à promouvoir le savoir ethnopharmacologique de Nouvelle-Calédonie et à encourager de futures recherches. La valorisation de la pharmacopée traditionnelle pourra ainsi contribuer à la préservation et au respect des savoirs locaux, à une meilleure compréhension et à une utilisation durable de ces ressources naturelles, ainsi qu'à participer à l'innovation thérapeutique moderne
Postoperative central ulceration of a dermis-fat graft in an anophthalmic socket.
No full textInternational audienceDermis-fat graft is a surgical technique that can be utilized for orbital reconstruction in anophthalmic patients. Initially described in maxillofacial surgery for rehabilitation after major facial fractures, it was first employed in 1978 by Smith and Petrelli for augmentation of orbital volume [1]. It can be considered as a primary option, particularly in situations where a lack of material or laxity of orbital soft tissues is anticipated (e.g., radiation therapy, phthisis). More commonly, it is also the preferred choice as a secondary intervention after failed intraorbital implantation and in cases of postoperative infectious complications or implant exposure [2]. This surgical technique appears to be reliable, avoiding the disadvantages associated with the implantation of foreign material, with good long-term esthetic results [3], [4]. While infrequent, postoperative complications include conjunctival granulomas, central ulcerations, and enophthalmos [5].Herein, we present a case of a 27-year-old patient who developed central ulceration in the early postoperative period following dermis-fat graft, as well as its management
Développement d'un modèle 3D in vitro d'adénocarcinome canalaire pancréatique dans un système microfluidique pour l'étude des interactions tumeur-stroma et de la sensibilité aux chimiothérapies
No full textIn 2023, around 80% of the 15,991 new cases of pancreatic cancer were diagnosed at a locally advanced or metastatic stage. Pancreatic cancer incidence and mortality have been rising since 1990, and could become the second leading cause of cancer deaths by 2040. The only curative treatment is surgery, which is possible in 20% of cases, mainly because of the late diagnosis of this cancer and the time allowed for the tumour stroma to take hold. For the majority of patients, the treatments available are not very effective, and research into new therapies fails in the clinical phase due to insufficiently predictive study models. Study models (2D monolayer culture, human cell xenografts in mice, 3D organoids) only imperfectly represent the reality of human biological tissues, making it difficult to predict the action of molecules used for therapeutic purposes. The microenvironment of tumours, in particular the fibroblasts associated with cancer, considerably modulates the interaction of these molecules with their target, which means that it must be considered in the models. Nowadays, models using microfluidic technology are being developed, making it possible to increase the relevance of models by considering the dynamic nature of living organisms. These new models also have the capacity to represent the physical properties characteristic of pancreatic cancer. In this context, the aim of my thesis project was to develop a 3D coculture model of pancreatic ductal adenocarcinoma cells and pancreatic stellate cells in a synthetic matrix. The use of a synthetic matrix makes it possible to modify its biochemistry and mechanical properties. This makes it possible to develop a model that complies with the 3R rule. The second objective of my thesis was to integrate the cellular heterogeneity present in cancer patients, by introducing tumoroids, in order to be even more relevant. This model should enable the study of tumour-stroma interactions and their behaviour following treatment with FOLFIRINOX. Finally, the final objective of my thesis was to integrate this 3D coculture model into a microfluidic culture chamber in order to study the effects of dynamic culture and particularly those of shear stresses.En 2023, environ 80% des 15 991 nouveaux cas de cancer du pancréas étaient diagnostiqués à un stade localement avancé ou métastatique. Ce cancer, dont l'incidence et la mortalité augmentent depuis 1990, pourrait devenir la deuxième cause de décès par cancer d'ici 2040. Le seul traitement curatif est la chirurgie, possible dans 20% des cas, notamment à cause du diagnostic tardif de ce cancer et du temps laissé au stroma tumoral pour s’installer. Pour la majorité des patients, les traitements disponibles sont peu efficaces et les recherches de nouvelles thérapies échouent en phase clinique en raison de modèles d’étude insuffisamment prédictifs. Les modèles d’étude (i.e. : culture en monocouche 2D, xénogreffes de cellules humaines chez la souris, organoïdes 3D) ne représentent que de manière imparfaite la réalité des tissus biologiques humains, rendant difficile la prédiction de l’action de molécules à visée thérapeutique. Le microenvironnement des tumeurs, notamment composé de fibroblastes associés au cancer, module considérablement l’interaction de ces molécules avec leur cible, ce qui nécessite de le prendre en compte dans les modèles. De nos jours, des modèles utilisant la technologie microfluidique sont développés, permettant d’augmenter la pertinence des modèles en prenant en compte la nature dynamique du vivant. Ces nouveaux modèles ont également la capacité de représenter les propriétés physiques caractéristiques du cancer du pancréas. Dans ce contexte, l’objectif de mon projet de thèse a été de développer un modèle de coculture 3D de cellules d’adénocarcinome canalaire pancréatique et de cellules stellaires pancréatiques dans une matrice synthétique. L’usage d’une matrice synthétique rend possible sa modification biochimique, ainsi que ses propriétés mécaniques. Cela permet de développer un modèle respectant la règle des 3R. Le second objectif de ma thèse a été d’intégrer l’hétérogénéité cellulaire présente chez les patients atteints de cancer, par l’introduction de tumoroïdes, afin d’être encore plus pertinent. Ce modèle devra permettre l’étude des interactions tumeur-stroma et leur comportement suite au traitement par le FOLFIRINOX. Enfin, l’objectif final de ma thèse a été d’intégrer ce modèle de coculture 3D dans une chambre de culture microfluidique pour étudier les effets de la culture dynamique et notamment ceux des contraintes de cisaillement
Impact of Islet Transplantation on Diabetes Complications and Mortality in Patients Living With Type 1 Diabetes.
No full textInternational audienceOBJECTIVEThis study aimed to evaluate the impact of islet transplantation (IT) on diabetes complications, death, and cancer incidence.RESEARCH DESIGN AND METHODSThis retrospective, multicenter, cohort study included patients from three IT clinical trials (intervention group) and from the French health insurance claims database Système National des Données de Santé (SNDS) (control group). Two cohorts of IT recipients were analyzed: IT recipients after kidney transplantation (IAK) and IT recipients alone (ITA). They were matched with patients living with type 1 diabetes (T1D) from the SNDS using a propensity score. The primary outcome was a composite criterion including death, dialysis, amputation, nonfatal stroke, nonfatal myocardial infarction, and transient ischemic attack. The secondary outcome was cancer. Hazard ratio (HRs) and P values were obtained using Cox proportional hazards analysis and log-rank test, respectively.RESULTSThe study included 61 ITA recipients matched to 610 T1D control patients and 45 IAK recipients matched to 45 T1D control patients over a median follow-up period >10 years. Compared with T1D control patients, ITA and IAK recipients had a lower composite outcome risk (HR 0.39 [95% CI 0.21–0.71; P = 0.002] and 0.52 [0.30–0.88; P = 0.014], respectively) that seemed driven by reduced mortality (0.22 [0.09–0.54]; P < 0.001) for ITA and reduced dialysis (0.19 [0.07–0.50]; P < 0.001) for IAK. Both groups showed no significant changes in cancer risk.CONCLUSIONSThis study suggests long-term benefits of IT on diabetes-related outcomes. Furthermore, despite the use of immunosuppressive drugs following IT, we observed no significant increase in the risk of cancer. Altogether, these findings highlight a favorable risk-benefit ratio of IT in treating patients with unstable T1D
Genetic characterization of Haemophilus ducreyi from non-genital skin lesions in Cameroon
No full textInternational audienceBackgroundHaemophilus ducreyi, traditionally recognized as the etiological agent of chancroid, a genital ulcer disease, is increasingly being identified as a significant cause of cutaneous ulcers in yaws-endemic regions across the South Pacific, Southeast Asia, and Sub-Saharan Africa. Despite its clinical relevance, this pathogen remains poorly characterized, and comprehensive genetic tools for analyzing isolate relationships are still lacking.MethodsIn this study, we present a follow-up of our previous research and developed a multilocus sequence typing (MLST) approach based on six of the seven loci from the Haemophilus influenzae MLST scheme and applied it to 82 primary clinical samples, previously confirmed to contain H. ducreyi, without culture. We also performed whole-genome sequencing (WGS) and antibiotic susceptibility testing on four cultured isolates obtained from cutaneous ulcers in yaws endemic health districts of Cameroon.ResultsAntibiotic susceptibility testing of H. ducreyi cultured isolates revealed sensitivity to all tested antibiotics, including ceftriaxone, azithromycin, and ciprofloxacin. MLST analysis, using data extracted from WGS and directly from clinical samples, identified 38 complete profiles across the six loci (34 from direct samples and four from cultured isolates), identifying 14 distinct sequence types (STs). BURST analysis of the six MLST genes grouped the STs into two distinct clonal complexes. An additional, polymorphism was observed in the ftsI gene, which encodes the penicillin-binding protein 3.ConclusionsThis study highlights the need for genetic typing of H. ducreyi strains circulating in the yaws-endemic regions of Cameroon. The developed MLST scheme offered effective strain discrimination and provided valuable insights into their genetic relationships in these areas
Interaction between breastfeeding duration and an obesity genetic risk score to predict body fat composition in European adolescents: The HELENA study.
No full textInternational audienceBackgroundAlthough the genetic interplay with the environment has a major impact on obesity development, little is known on whether breastfeeding could modulate the genetic predisposition to obesity.ObjectivesTo investigate whether breastfeeding attenuates the effect of an obesity genetic risk score (GRS) on adiposity in European adolescents.MethodsTotally 751 adolescents from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study were included, divided according to breastfeeding status into never breastfed, 1–3 months and ≥4 months. Adjusting by socioeconomic status and lifestyle factors multiple linear regression models were used to assess (1) the main effect of breastfeeding duration and (2) its interaction effect with an obesity GRS, to predict different adiposity measures.ResultsA significant negative association between ≥4 months of breastfeeding and waist circumference (WC) z-score was observed [β (95% confidence interval), p-value] = [β = −0.189 (−0.37, −0.00), p = 0.044]. Also, significant interaction effects were observed for 1–3 and ≥4 months of breastfeeding and obesity GRS regarding body mass index (BMI) z-score [β = 0.155 (0.06, 0.24), p = 0.001] and [β = 0.108 (0.01, 0.18), p = 0.020, respectively] and fat mass index (FMI) z-score [β = 0.134 (0.04, 0.22), p = 0.003] and [β = 0.100 (0.01, 0.18), p = 0.026, respectively].ConclusionsBreastfeeding modulates the association between the obesity GRS and body composition in adolescents
Hazard characterization of the mycotoxins enniatins and beauvericin to identify data gaps and improve risk assessment for human health
No full textInternational audienceEnniatins (ENNs) and beauvericin (BEA) are cyclic hexadepsipeptide fungal metabolites which have demonstrated antibiotic, antimycotic, and insecticidal activities. The substantial toxic potentials of these mycotoxins are associated with their ionophoric molecular properties and relatively high lipophilicities. ENNs occur extensively in grain and grain-derived products and are considered a food safety issue by the European Food Safety Authority (EFSA). The tolerable daily intake and maximum levels for ENNs in humans and animals remain unestablished due to key toxicological and toxicokinetic data gaps, preventing full risk assessment. Aiming to find critical data gaps impeding hazard characterization and risk evaluation, this review presents a comprehensive summary of the existing information from in vitro and in vivo studies on toxicokinetic characteristics and cytotoxic, genotoxic, immunotoxic, endocrine, reproductive and developmental effects of the most prevalent ENN analogues (ENN A, A1, B, B1) and BEA. The missing information identified showed that additional studies on ENNs and BEA have to be performed before sufficient data for an in-depth hazard characterisation of these mycotoxins become available
Surgery for the treatment of arterial hypertension in patients with unilateral adrenal incidentalomas and mild autonomous cortisol secretion (CHIRACIC): a multicentre, open-label, superiority randomised controlled trial
No full textInternational audienceBackgroundAdrenal incidentalomas are found in 3–10% of adults undergoing abdominal imaging. Of these, 30–50% are responsible for mild autonomous cortisol secretion (MACS), which is frequently associated with hypertension. The impact of adrenalectomy on hypertension in patients with unilateral incidentalomas and MACS remains uncertain. The aim of the CHIRACIC study was to prospectively assess the impact of surgical excision of the incidentaloma on blood pressure with a randomised trial combining accurate blood pressure measurement and standardisation of antihypertensive treatment.MethodsCHIRACIC was a multicentre, superiority, open-label, parallel, randomised controlled trial performed at 17 university hospitals in France, Italy, and Germany. Adults with hypertension with MACS entered a run-in phase to confirm hypertension with multiple home blood pressure measurements (HBPM) before blood pressure was normalised with standardised stepped-care antihypertensive treatment. Eligible participants were then randomly assigned (1:1) to adrenalectomy or conservative management. Randomisation was blocked (random block size of 4 and 6) and stratified by intensity of antihypertensive treatment. Participants were followed up for 13 months and systematic attempts were made to gradually reduce antihypertensive treatment. The primary endpoint was the proportion of normotensive participants using HBPM who reduced their antihypertensive treatment in the intention-to-treat population at study completion. Key secondary endpoints included 24 h ambulatory blood pressure measurement (ABPM), mean change in antihypertensive treatment, and the proportion of participants with antihypertensive treatment at study completion. This study was registered with ClinicalTrials.gov, NCT02364089, and is completed.FindingsBetween April 9, 2015 and Nov 23, 2022, 78 patients were enrolled, and 52 eligible participants were randomly assigned to adrenalectomy (n=26, 23 underwent adrenalectomy and completed the study) or conservative management (n=26, 25 completed the study). The median age of participants was 63·3 years (IQR 57·4–68·2) and 36 (69%) were female. At study completion, a reduction in antihypertensive treatment with normal HBPM was observed in 12 (46%) of 26 participants treated with adrenalectomy and in four (15%) of 26 treated conservatively (adjusted risk difference [RD] 0·34 [95% CI 0·11 to 0·58]; p=0·0038). Similar results of smaller magnitude were observed for systolic blood pressure during 24 h ABPM. There were ten (43%) of 23 participants still needing antihypertensive treatment in the adrenalectomy group and 24 (96%) of 25 in the conservative management group (adjusted RD –0·58 [95% CI –0·78 to –0·38]; p<0·0001). Mean antihypertensive treatment step was 0·8 (SD 1·1) in the adrenalectomy group and 3·0 (1·4) in the conservative management groups (adjusted difference –2·05 [95% CI –2·61 to –1·50]; p<0·0001]. The number of patients with normal systolic HBPM and no hypertensive treatment was 12 (52%) of 23 in the adrenalectomy group and none in the conservative management group. Serious adverse events occurred in eight (35%) of 23 participants in the adrenalectomy group and eight (31%) of 26 participants in the conservative management group. Three serious adverse events for three (13%) participants were related to the surgery (post-surgical wall pain and hypotension).InterpretationMACS associated with unilateral adrenal incidentalomas is responsible for secondary hypertension that can be safely improved by minimally-invasive adrenalectomy