HAL - RIIP
Not a member yet
17635 research outputs found
Sort by
Siltuximab as a salvage therapy in multi-refractory adult-onset Still's disease: A case series
No full textInternational audienceIntroductionAdult-onset Still's disease (AOSD) is a systemic auto-inflammatory disorder characterized by a cytokine storm. Four major cytokines can be specifically targeted in severe, refractory or corticosteroid-dependent forms: interleukin 1 (IL-1), interleukin 6 (IL-6), interleukin 18 (IL-18), and Tumor necrosis factor alpha (TNFa). According to the French national protocol for adult-onset Still's disease, anti-IL-6 agents are the second-line of treatment after corticosteroids. We report here on the efficacy and safety of siltuximab prescribed off-label in patients with multi-refractory forms.Observations/resultsThese 4 patients, aged 24 to 74 years old, had polycyclic and inflammatory AOSD. The introduction of siltuximab was proposed after failure or poor tolerance of several lines of treatment. A partial or complete clinico-biological response was observed in all 4 patients.ConclusionSiltuximab is a possible salvage treatment for multi-refractory AOSD.IntroductionLa maladie de Still de l’adulte est une maladie auto-inflammatoire systémique dans laquelle 4 cytokines jouant un rôle majeur peuvent faire l’objet d’un ciblage spécifique dans les formes sévères, réfractaires ou corticodépendantes : interleukine 1 (IL-1), interleukine 6 (IL-6), interleukine 18 (IL-18), et le Tumor necrosis factor alpha (TNFa). Selon le PNDS de la maladie de Still de l’adulte, les anti-IL-6 se positionnent en 2e ligne après les corticoïdes. Nous rapportons ici l’efficacité et la tolérance du siltuximab prescrit hors AMM chez les patients avec des formes multiréfractaires.Observations/résultatsQuatre patients âgés de 24 à 74 ans ayant une maladie de Still polycyclique et inflammatoire étaient en échec ou avaient une mauvaise tolérance de plusieurs lignes de traitements. Une réponse clinico-biologique partielle ou complète sous siltuximab était observée chez les 4 patients.ConclusionLe siltuximab est un traitement de rattrapage possible des maladies de Still multiréfractaires
Sepsis Induces Long‐Term Muscle and Mitochondrial Dysfunction due to Autophagy Disruption Amenable by Urolithin A
No full textInternational audienceBackground Sepsis survivors often experience sustained muscle weakness, leading to physical disability, with no pharmacological treatments available. Despite these well‐documented long‐term clinical consequences, research exploring the cellular and molecular mechanisms is sorely lacking. Methods Bioinformatic analysis was performed in the vastus lateralis transcriptome of human ICU survivors 7 days after ICU discharge (D7), 6 months (M6) and age‐ and sex‐matched controls. Enrichment analysis using Gene Ontology (GO) terms and Mitocarta3.0 was performed at D7 and M6 on differentially expressed genes (DEGs) and modules identified by weighted gene co‐expression network analysis (WGCNA). Using a murine model of resuscitated sepsis induced by caecal slurry injection, pathways identified by the bioinformatics analysis were explored in 18‐ to 24‐week‐old sepsis‐surviving (SS) mice at Day 10. Autophagy flux was investigated both in vivo and in vitro with chloroquine, a lysosomal inhibitor and urolithin A (UA), an autophagy inducer. Systemic metabolism was evaluated with indirect calorimetry, muscle phenotype with in situ and ex vivo contractility, muscle mass, myofibre cross‐sectional area and typing and mitochondrial population with transmission electron microscopy (TEM), as well as mitochondrial function with high‐resolution respirometry. Autophagic vacuole (AV) level was monitored using LC3B‐II and P62 protein expression and TEM. Results Pathways related to ‘mitochondrion’ were the only ones whose deregulation persisted between D7 and M6 ( p < 0.05) and characterized WGCNA modules correlated with muscle mass, strength and physical function. Shared mitochondrial DEGs between D7 and M6 encoded matrix mitochondrial proteins related to ‘metabolism’ and ‘mitochondrial dynamics’. SS mice exhibited reduced complex I‐driven oxygen consumption (CI‐J O2 ) (−45%), increased S‐nitrosylation of complex I, damaged (+35%) and oxidized (+51%) mitochondria and AV accumulation (5 vs. 50 AVs/mm 2 ) compared with sham pair‐fed mice ( p < 0.05) despite no differences in mitochondrial size or number. Autophagy flux was reduced in SS mice due to decreased AV degradation ratio ( p < 0.05). UA restored a balanced autophagy flux (turnover ratio 0.96 vs. −0.17) by increasing AVs formation and degradation ratio ( p < 0.05). UA also improved CI‐J O2 (81 vs. 106 pmol/s/mg), tetanic force (215 vs. 244 mN/mm 2 ) and hindlimb muscle weight in SS mice ( p < 0.05). Conclusion Mitochondrial and autophagy disruption contributes to long‐term muscle dysfunction in human and mouse sepsis survivors. We demonstrate for the first time that sepsis induces an autophagy flux blockade. Urolithin A prevents mitochondrial and muscle impairments both in vivo and in vitro by improving autophagy flux
Absence of Macrolide-Resistant Mutations in Bordetella pertussis in Antananarivo (Madagascar) and Cambodia During the Last Pertussis Cycle Before the COVID-19 Pandemic
No full textInternational audienceAbstract Macrolides are the first-line treatment against pertussis. The high prevalence of macrolide-resistant Bordetella pertussis (MRBP) strains reported in China is concerning. MBRP might be underestimated in other countries. Looking for the mutation causative for MRBP in retrospective studies conducted in Madagascar and Cambodia, we found no MRBP
Proceedings of the annual meeting of the European Consortium of Lipodystrophies (ECLip) Paris, France, 20-21 May 2025.
No full textInternational audienceLipodystrophy syndromes are rare diseases characterized by anatomical and functional defects of adipose tissue, frequently leading to severe insulin resistance-associated metabolic complications. Subtypes of lipodystrophy syndromes differ in: their clinical presentation, with generalized or partial loss of adipose tissue; in their origin, either genetic or acquired; and in their comorbidities, forming a heterogeneous group of disorders of different severity. The European Consortium of Lipodystrophies (ECLip) was founded in 2014 as a non-profit network of health professionals, scientists and patient associations. ECLip aims to promote international collaborations to increase pathophysiological and clinical knowledge, and improve the management of lipodystrophy syndromes. ECLip now comprises 59 groups from 30 countries from Europe and beyond. The consortium developed in parallel to the increased awareness of clinical diagnosis, the growing scientific interest for these diseases at the crossroads between adipose tissue biology, whole body metabolism, genetics and immunity, and to the emergence of new pharmacological approaches. The ECLip congress, held every 18 months, aims to discuss the recent achievements and projects in the field of lipodystrophies, to consolidate ECLip activities and to promote future collaborations, highlighting clinical and fundamental aspects as well as patients' perspectives. Oral communications presented during the meeting in Paris, France, in 2025 are summarized in these minutes
Eating behavior changes with an online cognitive behavioral therapy program for weight loss in individuals with overweight or obesity: A pilot study
No full textInternational audienceSupporting individuals with overweight or obesity cannot rely on simplistic and directive recommendations aimed at energy restriction. Cognitive-behavioural approaches must be implemented. This pilot study analyses the effects of an online cognitive behavioral therapy program incorporating mindful eating and therapeutic education over a treatment duration of 6 to 9 months. Seventy patients (BMI 32.7 ± 3.1 kg/m2) were included in this program. Fifty-four subjects completed the study and were subject to statistical analysis. Weight, waist circumference, and energy intake significantly decreased (P < 0.02 for all three elements). Improved listening to internal hunger (P < 0.0001) and satiety signals (P < 0.03), as well as a decrease in emotional eating (P < 0.003) and external eating (P < 0.0001), were observed. The level of program adherence is positively associated with better outcomes for these two aspects. However, there were no changes in cognitive restriction, food pleasure, mood, and anxiety. Overall, these data highlight that this type of program can be useful in the management of overweight and obesity.L’accompagnement des personnes souffrant de surpoids ou d’obésité ne peut pas reposer sur des recommandations simplistes et autoritaires visant à obtenir une restriction énergétique. Des approches cognitivo-comportementales doivent être mises en œuvre. Cette étude pilote vise à observer les effets d’un programme de thérapie cognitivo-comportementale en ligne qui inclut également des outils d’éducation thérapeutique et de pleine conscience centrée sur l’alimentation. 70 patients (IMC 32,7 ± 3,1 kg/m2) ont été inclus dans ce programme de 6 à 9 mois. Cinquante-quatre sujets ont terminé l’étude et ont fait l’objet de l’analyse statistique. Le poids (p < 0,02), le tour de taille (p < 0,02), et les apports énergétiques (p < 0,02) ont diminué de façon significative. Le respect des signaux alimentaires internes de faim (p < 0,0001) et de satiété (p < 0,03) ont été améliorés, ainsi que l’alimentation émotionnelle (p < 0,003) et l’externalité alimentaire (p < 0,0001). Le niveau d’adhésion au programme est associé à de meilleurs résultats pour ces deux items. Il n’y a pas eu de changement en ce qui concerne la restriction cognitive, le plaisir alimentaire, l’humeur et l’anxiété. Les résultats de cette étude pilote mettent en évidence que ce programme peut être utile dans la prise en charge du surpoids ou de l'obésité
Screening Methods for NMD Inhibitors or Readthrough Activators
No full textInternational audienceNonsense mutations cause approximately 10% of genetic disease cases. Certain molecules can rescue the expression of genes carrying a nonsense mutation, either by activating readthrough of the premature termination codon or by inhibiting the mRNA surveillance mechanism called nonsensemediated mRNA decay (NMD). In the first approach, a full-length protein will be synthesized, differing by at most one amino acid from the wild-type protein. In the second approach, a truncated protein will be synthesized, which sometimes retains partially or completely the function of the wildtype protein. Here we describe methods for identifying, by screening, molecules having the capacity either to inhibit NMD or to activate readthrough.</div
Associations between air pollution and biomarkers of oxidative stress and lung damage in a large population-based sample of non-smoking adults in northern France.
No full textInternational audienceAir pollution is an environmental risk factor associated with lung and cardiovascular disease that may be mediated by physiological pathways such as oxidative stress. Previous studies have identified associations between air pollution and biomarkers of oxidative stress (8-OHdG, 4-HNE, and fluorescent oxidation products (FOPs)), as well as lung health marker CC16, in younger and asthmatic populations. The objective of this study of a large population-based sample of non-smoking adults was to explore the relationship between long-term and short-term atmospheric pollution exposures and plasma or urine levels of these biomarkers. Our study was a post-hoc analysis of the cross-sectional ELISABET study from 2011 to 2013. We included non-smoking inhabitants of Lille, France from the ELISABET study. We assessed mean pluri-annual residential and short-term exposures to atmospheric pollution components (PM10, NO2, and O3) and collected several biomarkers (CC16, 8-OHdG, 4-HNE, and fluorescent oxidation products (FOPs)). We searched for associations between pollutants and biomarkers using log-linear robust multivariate regressions. Our work did not show any association between short- or long-term exposure to air pollution components and CC16, 8-OHdG, 4-HNE or FOP in a large (980 subjects) sample of Lille’s general population, despite having sufficient statistical power to replicate previous findings of associations between air pollution and these biomarkers found in younger or asthmatic populations
IL-34 is expressed in the pancreas and regulates local inflammation
No full textInternational audienceInterleukin-34, a ligand of CD115, controls Langerhans cells and microglia homeostasis and acts as regulatory cytokine. Here, we describe an unexpected role for IL-34 in metabolic homeostasis. We show that IL-34 is constitutively expressed by human β-cell and mouse islets of Langerhans. β-cell specific genetic invalidation of Il34 in mice (IL-34ΔPdx) impaired glucose tolerance associated with increased inflammation in islets of Langerhans during aging. This phenotype was exacerbated when IL-34ΔPdx mice were subjected to a high-fat diet, suggesting a role for IL-34 in controlling local inflammation. Accordingly, in the presence of pro-inflammatory cytokines, ex vivo murine islets of Langerhans exhibited a decreased insulin synthesis, which was restored in the presence of IL-34. Finally, we observed that the levels of Il-34 mRNA were elevated in islets of Langerhans from type 2 diabetic donors. Collectively, these results identify IL-34 as a major regulator of pancreas inflammation
A Soft Sensing Approach for Efficient Monitoring of Nanobody-Based Scorpion Antivenom Production
No full textInternational audienceBy eliciting immune activation in the digestive tract, intestinal pathogens may perturb gut homeostasis. Some gastrointestinal infections can indeed increase the risk of developing post-infectious irritable bowel syndrome (PI-IBS). Intriguingly, the prevalent foodborne parasite Toxoplasma gondii has not been linked to the development of PI-IBS and the impact of this infection on colon homeostasis remains ill-defined. We show in a mouse model that latent T. gondii decreases visceral nociceptive responses in an opioid signaling-dependent manner. Despite the accumulation of Th1 and cytotoxic T cells in the colon of latently infected mice, the selective invalidation of enkephalin gene in T cells ruled out the involvement of T cell-derived enkephalins in hypoalgesia. These findings provide clues about how this widespread infection durably shapes the gut immune landscape and modifies intestinal physiological parameters. They suggest that in contrast to other gut microbes, T. gondii infection could be negatively associated with abdominal pain
A Narrative Review of Heavy Metals and Sperm Quality: The Interplay with Antioxidant Imbalance and Reactive Oxygen Species
No full textInternational audienceReproductive infertility is characterized by the inability to achieve pregnancy after a year or more of unprotected sexual intercourse. This review highlights the significant impact of exposure to both types of heavy metals (essential and non-essential) on the reproductive performance of various species, particularly humans. Heavy metals present a high atomic density and weight, including lead, mercury, cadmium, nickel, chromium, and arsenic, and are delivered into the environment through natural and human activities, posing a threat to ecological systems and human reproductive health. These heavy metals have the potential for bioaccumulation and can adversely affect male fertility and sperm quality due to their role in disrupting endocrine functions, altering hormone levels responsible for sperm production, and inducing oxidative stress. The elevated production of reactive oxygen species (ROS) exceeds the capability of antioxidants and can lead to the alteration of sperm quality. Seminal fluid contains antioxidants like vitamin C, vitamin E, zinc, and selenium to counteract the impacts of ROS and also to preserve the sperm function. This review aims also to explore the impact of heavy metals on sperm quality and their relationship with antioxidant imbalance and ROS. The exposure to heavy metals whether through occupational or environmental means increases the production of ROS and therefore leads to an imbalance of antioxidants production. All these factors have no doubt an impact on male reproductive health