Small plastic debris (0.1 μm to 5 mm) or microplastics (MPs) have become major pollutants of aquatic ecosystems worldwide and studies suggest that MPs exposure can pose serious threats to human and wildlife health. However, to date the potential biological impacts of MPs accumulating in low amount in tissues during early life remains unclear. Here, for a more realistic assessment, we have used environmentally representative, mildly weathered, polyethylene terephthalate microplastics (PET MPs), cryomilled (2-100 μm) and fluorescently labeled. We leveraged the amphibian Xenopus laevis tadpoles as an animal model to define the biodistribution of PET MPs and determine whether exposure to PET MPs induce perturbations of antiviral immunity. Exposure to PET MPs for 1 to 14 days resulted in detectable PET MPs biodistribution in intestine, gills, liver, and kidney as determined by fluorescence microscopy on whole mount tissues. PET MPs accumulation rate in tissues was further evaluated via a novel in situ enzymatic digestion and subsequent filtration using silicon nanomembranes, which shows that PET MPs rapidly accumulate in tadpole intestine, liver and kidneys and persist over a week. Longer exposure (1 month) of tadpoles to relatively low concentration of PET MPs (25 μg/ml) significantly increased susceptibility to viral infection and altered innate antiviral immunity without inducing overt inflammation. This study provides evidence that exposure to MPs negatively impact immune defenses of aquatic vertebrates.
Despite decades of research into the molecular mechanisms of cancer and the development of new treatments, drug resistance persists as a major problem. This is in part due to the heterogeneity of cancer, including the diversity of tumor cell lineage and cell plasticity, the spectrum of somatic mutations, the complexity of microenvironments, and immunosuppressive characteristic, then necessitating the use of many different therapeutic approaches. We summarize here the biological causes of resistance, thus offering new perspectives for tackle drug resistance.
Mycobacterium abscessus (Mab) is an emerging human pathogen that has a high rate of incidence in immunocompromised individuals. We have found a putative secondary metabolite pathway within Mab, which may be a key factor in its pathogenesis. This novel pathway is encoded in a gene cluster spanning MAB_0284c to 0305 and is related to Streptomyces pathways, producing the secondary metabolites streptonigrin and nybomycin. We constructed an in-frame deletion of the MAB_0295 (phzC) gene and tested it in our Xenopus laevis animal model. We have previously shown that X. laevis tadpoles, which have functional lungs and T cells, can serve as a reliable comparative model for persistent Mab infection and pathogenesis. Here, we report that tadpoles intraperitoneally infected with the ∆phzC mutant exhibit early decreased bacterial loads and significantly increased survival compared with those infected with WT Mab. ∆phzC mutant Mab also induced lower transcript levels of several pro-inflammatory cytokines (IL-1β, TNF-α, iNOS, IFN-γ) than those of WT Mab in the liver and lungs. In addition, there was impaired macrophage recruitment and decreased macrophage infection in tadpoles infected with the ∆phzC mutant, by tail wound inoculation, compared to those infected with the WT bacteria, as assayed by intravital confocal microscopy. These data underline the relevance and usefulness of X. laevis tadpoles as a novel comparative animal model to identify genetic determinants of Mab immunopathogenesis, suggesting a role for this novel and uncharacterized pathway in Mab pathogenesis and macrophage recruitment.
Recently, an article by Seneff et al. entitled “Innate immunosuppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs” was published in Food and Chemical Toxicology (FCT). Here, we describe why this article, which contains unsubstantiated claims and misunderstandings such as “billions of lives are potentially at risk” with COVID-19 mRNA vaccines, is problematic and should be retracted. We report here our request to the editor of FCT to have our rebuttal published, unfortunately rejected after three rounds of reviewing. Fighting the spread of false information requires enormous effort while receiving little or no credit for this necessary work, which often even ends up being threatened. This need for more scientific integrity is at the heart of our advocacy, and we call for large support, especially from editors and publishers, to fight more effectively against deadly disinformation.
Le lupus érythémateux systémique (LES) est une maladie auto-immune rare ayant un impact significatif sur la morbi-mortalité et la qualité de vie. À ce jour, peu d’études ont évalué l’épidémiologie du LES à l’échelle nationale. L’objectif de cette étude était d’actualiser les données de prévalence et d’incidence du LES en France, à partir des données médico-administratives du Système national des données de santé (SNDS). Cette étude a utilisé le SNDS, qui contient les données pseudonymisées de plus de 66 millions de personnes. Les patients inclus dans l’étude étaient atteints d’un LES, identifiés par le code CIM-10 M32 (LES) documenté dans le cadre d’une affection de longue durée (ALD) et/ou au cours d’une hospitalisation. Deux sous-populations ont été considérées : la population prévalente constituée des patients vivants au 01/01/2020 et une population incidente constituée des patients nouvellement diagnostiqués en 2017 et 2018. Au 01/01/2020, un total de 31 852 cas prévalents de LES a été identifié, soit un taux de prévalence brut de 47,4 cas pour 100 000. La majorité des patients étaient des femmes (86,3 %). L’âge moyen était de 49,2 (±15,8) ans chez les femmes et de 52,5 (±15,9) ans chez les hommes. L’ancienneté moyenne de la maladie était de 7,2 (±6,3) ans chez les femmes et de 6,3 (±5,6) ans chez les hommes. La prévalence maximale était observée chez les femmes âgées de 40 à 49 ans (142,3/100 000) et chez les hommes âgés de 60 à 69 ans (23,7/100 000) (Tableau 1). Les taux de prévalence bruts par région en France métropolitaine étaient compris entre 32,4/100 000 en Pays de la Loire et 75,8/100 000 en Corse. Ces taux étaient plus élevés en Martinique (108,4/100 000) et en Guadeloupe (104,9/100 000). Parmi l’ensemble des cas prévalents, 10,2 % et 0,3 % bénéficiaient de la CMUc et de l’AME, respectivement. Un total de 2971 et 2695 cas incidents de SLE ont été identifiés respectivement en 2017 et 2018, soit des taux d’incidence bruts de 4,4/100 000 en 2017 et 4,0/100 000 en 2018. Parmi les patients incidents en 2018, la majorité était des femmes (83,9 %). Le pic d’incidence en 2018 a été observé chez les femmes âgées de 30 à 39 ans (11,6/100 000) et chez les hommes âgés de 50 à 59 ans (2,5/100 000). Les taux d’incidence bruts par région en France métropolitaine en 2018 étaient compris entre 2,6/100 000 en Pays de la Loire et 5,6/100 000 en Corse. Ces taux étaient plus élevés en Guadeloupe (8,5/100 000) et Martinique (8,4/100 000). Parmi l’ensemble des cas incidents en 2018, un total de 12,7 % et 0,5 % bénéficiaient de la CMUc et de l’AME, respectivement (Tableau 1). La prévalence a été estimée à 47,4 cas/100 000 et l’incidence annuelle à 4,0/100 000 en 2018, le LES reste donc considéré comme une maladie auto-immune rare en France.