Biologie Aujourd''hui最新文献

The latest IPBES report clearly showed that pollution and proliferation of invasive alien species constituted two of the five major factors responsible for the biodiversity decline. Faced with this situation, we present here the development of nature-based solutions in response to these two challenges. This approach has firstly made it possible to progress in understanding the adaptation strategies of plants and associated micro-organisms to respond to attacks such as pollution. Thus, relevant studies showed that certain plant species are able to grow in environments contaminated with metallic elements, or even to sequester toxic pollutants in their leaves or their roots. This research has made it possible to provide original solutions for the ecological restoration of soils and the decontamination of aquatic systems using dead invasive exotic plant species. The promotion of these solutions through the concept of ecocatalysis, at the interface of ecology and chemistry, contributed to make them sustainable and economically viable.

ANCA-associated vasculitis brings together three diseases, granulomatosis with polyangiitis, microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. This group of diseases has benefited over the last 3 decades from major therapeutic advances both in terms of therapeutic strategies and availability of new drugs, mainly for targeted therapies. Treatments, whether conventional or not, include an induction phase followed by a maintenance phase. Induction treatment today poses few problems. It is essentially based on the combination of corticosteroids and rituximab or cyclophosphamide. Remission is achieved in less than 6 months and maintenance treatment, preventing relapses, is then started. We showed that the best maintenance treatment was rituximab, surpassing the efficacy of methotrexate or azathioprine. During this phase, corticosteroid therapy is stopped or given at a very small dose. In Eosinophilic Granulomatosis with Polyangiitis (GEPA), the strategy is slightly different and there is a lack of prospective trials to demonstrate the benefits of rituximab or mepolizumab (anti-IL5) in inducing remission. Regarding maintenance treatment, prolonged corticosteroid therapy (orally and/or inhaled) is often necessary to control asthmatic disease. Only mepolizumab has shown its ability to prevent relapses and reduce the dose of corticosteroids controlling asthma. The current questions posed by maintenance treatment are its duration which could be variable and adapted to the risk of relapse and the risks induced by prolonged immunosuppression, particularly infectious.

The health effects of air pollution have been recognized for many years. However, this area of research continues to receive increasing attention from both the scientific community and civil society. The aim of this article is to review the main epidemiological findings on the effects of outdoor air pollution. First, we will define outdoor air pollution, then describe how the exposure to different pollutants is estimated in epidemiology. Finally, we will present three examples of epidemiological studies on the effects of air pollution.

The review is focused on recent drug discovery advances based on targeted protein degradation strategies. This new area of research has exploded leading to the development of potential drugs useful in a large variety of human diseases. They first target disease relevant proteins difficult to counteract with other classical strategies and extend now to aggregates, organelles, nucleic acids or lipidic droplets. These degraders engaged either the ubiquitin-proteasome system for PROTACs and molecular glues (first generation), or the lysosomal system via endosome-lysosome degradation (LYTACs) and autophagy-lysosome degradation (ATTEC, AUTAC, AUTOTAC) (following generations of degraders). PROTACs have expanded from the orthodox heterobifunctional ones to new derivatives such as homo-PROTACs, pro-PROTACs, CLIPTACs, HaloPROTACs, PHOTOTACs, Bac-PROTACs, AbTACs, ARN-PROTACs. The small molecular-weight molecular glues induce the formation of new ternary complexes which implicate the targeted protein and an ubiquitin ligase E3 allowing the protein ubiquinitation followed by its proteasomal degradation. Lysosomal degraders (LYTAC, ATTEC, AUTAC, AUTOTAC) specifically recognize extracellular and membrane proteins or dysfunctional organelles and transport them into lysosomes where they are degraded. They overcome the limitations observed with proteasomal degradations induced by PROTAC and molecular glues and demonstrate their potential to treat human diseases, especially neurodegenerative ones. Pharmaceutical companies are engaged at the world level to develop these new potential drugs targeting cancers, immuno-inflammatory and neurodegenerative diseases as well as a variety of other ones. Efficiency and risks for these novel therapeutic strategies are discussed.

The advent of high-throughput omics data and the generation of new algorithms provide the biologists with the opportunity to explore living processes in the context of systems biology aiming at revealing the gene interactions, the networks underlying complex cellular functions. In this article, we discuss two methods for gene network reconstruction, WGCNA (Weighted Gene Correlation Network Analysis) developed by Steve Horvath and collaborators in 2008, and MIIC (Multivariate Information-based Inductive Causation) developed by Hervé Isambert and his team in 2017 and 2024. These two methods are complementary, WGCNA generating undirected networks in which most gene-to-gene interactions are indirect, while MIIC reveals direct interactions and some causal links. We illustrate these aspects according to our own work aiming at identifying the gene interactions underlying the hematopoietic stem cell supportive activity of mesenchymal stromal cells at an early developmental stage.

In the animal kingdom, metamorphosis is a well-known developmental transition within various taxa (Cnidarians, Echinoderms, Molluscs, Arthropods, Vertebrates, etc.), which is characterized by the switching from a larval stage to an adult form through the induction of morpho-anatomical, physiological, behavioral, and/or ecological changes. Over the last decades, numerous studies have focused on the hormonal control of cellular processes underlying metamorphosis. Recently, another regulatory network has emerged trough the discovery of microRNAs, non-coding RNAs of 19 to 25 nucleotides that are highly conserved among taxa and act by modulating gene expression at the post-transcriptional level. Experiments carried out on model insects highlighted the relevance of microRNAs in several developmental processes during metamorphosis. This review aims to give an overview of the regulatory actions of microRNAs in the programming of cellular and molecular events associated with the metamorphosis of insects and also to provide new insights into the evolutionary history of this taxon.

Interleukin (IL)-17A and then IL-17F have been discovered through their roles in chronic inflammatory diseases. These cytokines share 50% of sequence homology and bind to the same receptor made of the IL-17RA et IL-17RC chains. While they have rather similar pro-inflammatory effects, slight differences exist depending on the cell type considered or whether there is TNF or not. Indeed, there is a synergistic effect of TNF and IL-17A or IL-17F on many cell types. In addition, the interactions between immune and stromal cells also modulate their effects which vary according to stromal cell subtype. The identification of IL-17A and IL-17F roles in inflammatory diseases, as psoriasis, has led to the development of inhibitors of those cytokines. Anti-IL-17A, then anti-IL-17A/F and now anti-IL-17RA have been approved for different diseases and are particularly efficient in psoriasis. Their use is expending to other diseases like psoriatic arthritis and spondyloarthritis. Last, the recent understanding of the importance of stromal cells during chronic inflammation explains the relative inefficacy of such inhibitors in some other diseases.

Systemic lupus erythematosus (SLE) presents a complex clinical landscape with diverse manifestations, suggesting a multifactorial etiology. However, the identification of rare monogenic forms of the disease has shed light on specific genetic defects underlying SLE pathogenesis, offering valuable insights into its underlying mechanisms and clinical heterogeneity. By categorizing these monogenic forms based on the implicated signaling pathways, such as apoptotic body clearance, type I interferon signaling, JAK-STAT pathway dysregulation, innate immune receptor dysfunction and lymphocytic abnormalities, a more nuanced understanding of SLE's molecular basis emerges. Particularly in pediatric populations, where monogenic forms are more prevalent, routine genetic testing becomes increasingly important, with a diagnostic yield of approximately 10% depending on the demographic and methodological factors involved. This approach not only enhances diagnostic accuracy but also informs personalized treatment strategies tailored to the specific molecular defects driving the disease phenotype.

Sjögren's disease (SjD) is a systemic autoimmune disorder characterized by a triad of key symptoms affecting almost all patients (salivary and lacrimal dryness, pain and fatigue) and extra-glandular systemic involvement affecting one to two-thirds of patients. Over the past decade, knowledge of the epidemiology, classification criteria, assessment of systemic activity and symptoms presented by patients has grown. In addition, advances in understanding the pathophysiology of SjD have enabled a more targeted therapeutic approach. Current management of SjD is based on EULAR treatment guidelines. But since these recommendations, new drugs targeting specific pathophysiological pathways of the disease, and essentially B lymphocyte activation, have shown efficacy in phase 2 trials. In this review, we will summarize the available evidence on systemic therapies, including: 1. advances in outcome assessment, 2. current evidence on targeted disease-modifying therapies and biologic drugs targeting primarily B lymphocytes, 3. an overview of promising drugs being tested in ongoing trials.