Istradefylline protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin antitumor effects

Cisplatin is a potent chemotherapeutic drug that is widely used in the treatment of various solid cancers. However, its clinical effectiveness is strongly limited by frequent severe adverse effects, in particular nephrotoxicity and chemotherapy-induced peripheral neuropathy. Thus, there is an urgent medical need to identify novel strategies that limit cisplatin-induced toxicity. In the present study, we show that the FDA-approved adenosine A2A receptor antagonist istradefylline (KW6002) protected from cisplatin-induced nephrotoxicity and neuropathic pain in mice with or without tumors. Moreover, we also demonstrate that the antitumoral properties of cisplatin were not altered by istradefylline in tumor-bearing mice and could even be potentiated. Altogether, our results support the use of istradefylline as a valuable preventive approach for the clinical management of patients undergoing cisplatin treatment

A Double-Negative Feedback Interaction between miR-21 and PPAR-α in Clear Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is the main histotype of kidney cancer, which is typically highly resistant to conventional therapies and known for abnormal lipid accumulation. In this context, we focused our attention on miR-21, an oncogenic miRNA overexpressed in ccRCC, and peroxysome proliferator-activated receptor-α (PPAR- α), one master regulator of lipid metabolism targeted by miR-21. First, in a cohort of 52 primary ccRCC samples, using RT-qPCR and immunohistochemistry, we showed that miR-21 overexpression was correlated with PPAR-α downregulation. Then, in ACHN and 786-O cells, using RT-qPCR, the luciferase reporter gene, chromatin immunoprecipitation, and Western blotting, we showed that PPAR-α overexpression (i) decreased miR-21 expression, AP-1 and NF-κB transcriptional activity, and the binding of AP-1 and NF-κB to the miR-21 promoter and (ii) increased PTEN and PDCD4 expressions. In contrast, using pre-miR-21 transfection, miR-21 overexpression decreased PPAR-α expression and transcriptional activity mediated by PPAR-α, whereas the anti-miR-21 (LNA-21) strategy increased PPAR-α expression, but also the expression of its targets involved in fatty acid oxidation. In this study, we showed a double-negative feedback interaction between miR-21 and PPAR-α. In ccRCC, miR-21 silencing could be therapeutically exploited to restore PPAR-α expression and consequently inhibit the oncogenic events mediated by the aberrant lipid metabolism of ccRCC

Recording breathing volumes with magnetic motion sensors, dedicated to COPD during the CPT session

International audienceCOPD is the third leading cause of death worldwide. Such pathologies require airway clearance methods implemented during CPT sessions. Monitoring breathing volumes during a session could provide better understanding these techniques, as well as the time tracking of obstructions. Spirometry and thoracic movement measurements are performed on healthy subjects thanks to a dedicated innovative device, in order to calculate FEV1/FVC% index. We compare the results obtained with the motion sensors with those of the spirometer using the Bland-Altman plot method. This measuring system will allow to monitor the evolution of the respiratory volumes during a CPT session

SYBILLE : UN OUTIL D'ETUDE DE L'ENCOMBREMENT BRONCHIQUE DE PATIENTS BPCO DANS LE CADRE DE LEUR PRISE EN CHARGE EN KINESITHERAPIE RESPIRATOIRE

National audienceLes pathologies respiratoires chroniques, comme la bronchopneumopathie chronique obstructive (BPCO), représentent un défi de santé publique : en 2020 la BPCO est la troisième cause de mortalité dans le monde. Ces pathologies respiratoires sécrétantes nécessitent une prise en charge en kinésithérapie respiratoire (KR), notamment pour désencombrer les voies respiratoires inférieures. Lors d'une séance de KR, le praticien réalise une évaluation de l'état d'encombrement du patient. Celle-ci se base sur un recueil d'informations sonores et haptiques, ce qui nécessite une forte expertise du praticien. De plus, les pratiques actuelles en KR ne donnant pas toujours lieu à des consensus, une objectivation des pratiques est nécessaire. Le laboratoire SYMME a conçu dans cet objectif le gilet instrumenté Sybille, capable de réaliser des enregistrements de bruits respiratoires et de volumes thoraciques avant, pendant et après les manoeuvres de toilettes bronchiques pour chercher à caractériser de manière objective l'état d'encombrement du patient. Ce dispositif pourrait en outre permettre la localisation et le suivi temporel de l'évolution des obstructions ainsi que l'obtention d'informations quantifiées menant à l'analyse de la pratique professionnelle, dans le cadre de l'étude clinique MUKROBS

The interferon inducible isoform of NCOA7 inhibits endosome-mediated viral entry

International audienceInterferons (IFNs) mediate cellular defence against viral pathogens by upregulation of IFN-stimulated genes whose products interact with viral components or alter cellular physiology to suppress viral replication1-3. Among the IFN-stimulated genes that can inhibit influenza A virus (IAV)4 are the myxovirus resistance 1 GTPase5 and IFN-induced transmembrane protein 3 (refs 6,7). Here, we use ectopic expression and gene knockout to demonstrate that the IFN-inducible 219-amino acid short isoform of human nuclear receptor coactivator 7 (NCOA7) is an inhibitor of IAV as well as other viruses that enter the cell by endocytosis, including hepatitis C virus. NCOA7 interacts with the vacuolar H+-ATPase (V-ATPase) and its expression promotes cytoplasmic vesicle acidification, lysosomal protease activity and the degradation of endocytosed antigen. Step-wise dissection of the IAV entry pathway demonstrates that NCOA7 inhibits fusion of the viral and endosomal membranes and subsequent nuclear translocation of viral ribonucleoproteins. Therefore, NCOA7 provides a mechanism for immune regulation of endolysosomal physiology that not only suppresses viral entry into the cytosol from this compartment but may also regulate other V-ATPase-associated cellular processes, such as physiological adjustments to nutritional status, or the maturation and function of antigen-presenting cells

Argelia. Mapas generales (1844). 1:1700000

Presenta además 1 carta de Africa con escala 1:60000000 y 3 mapas de detalle de Orán, Argel y ConstantineEscalas gráficas de "10 Myriametres" [= 12 cm], "30 lieues de 25 au degré" [= 10,5 cm], "20 lieues de 20 au degré" [= 10 cm]. Proyec. cónica. Coordenadas referidas, al parecer, al meridiano de París (O 3°20'-E 8°25'/N 37°20'- 32°50'). Red geográfica de 1 en 1 gradoRelieve representado por normalesTabla de signos convencionales para indicar, núcleos de población de distinta categoráa, estaciones, caminos y puertosTabla explicativa de algunos nombres árabes traducidos al francésEntelado en 15 cuarterone

SARS-CoV-2 Triggers an MDA-5-Dependent Interferon Response Which Is Unable To Control Replication in Lung Epithelial Cells

International audienc