Adaptive β-Cell Neogenesis in the Adult Mouse in Response to Glucocorticoid-Induced Insulin Resistance

International audienceBoth type 1 and type 2 diabetes are characterized by deficient insulin secretion and decreased β-cell mass. Thus, regenerative strategies to increase β-cell mass need to be developed. To characterize mechanisms of β-cell plasticity, we studied a model of severe insulin resistance in the adult mouse and defined how β-cells adapt. Chronic corticosterone (CORT) treatment was given to adult mice and led to rapid insulin resistance and adaptive increased insulin secretion. Adaptive and massive increase of β-cell mass was observed during treatment up to 8 weeks. β-Cell mass increase was partially reversible upon treatment cessation and reinduced upon subsequent treatment. β-Cell neogenesis was suggested by an increased number of islets, mainly close to ducts, and increased Sox9 and Ngn3 mRNA levels in islets, but lineage-tracing experiments revealed that neoformed β-cells did not derive from Sox9- or Ngn3-expressing cells. CORT treatment after β-cell depletion partially restored β-cells. Finally, β-cell neogenesis was shown to be indirectly stimulated by CORT because serum from CORT-treated mice increased β-cell differentiation in in vitro cultures of pancreatic buds. Altogether, the results present a novel model of β-cell neogenesis in the adult mouse and identify the presence of neogenic factors in the serum of CORT-treated mice

Does crystallographic anisotropy prevent the conventional treatment of aqueous mineral reactivity? A case study based on K-feldspar dissolution kinetics

International audienceWhich conceptual framework should be preferred to develop mineral dissolution rate laws, and how the aqueous mineral reactivity should be measured? For over 30 years, the classical strategy to model solid dissolution over large space and time scales has relied on so-called kinetic rate laws derived from powder dissolution experiments. In the present study, we provide detailed investigations of the dissolution kinetics of K-feldspar as a function of surface orientation and chemical affinity which question the commonplace belief that elementary mechanisms and resulting rate laws can be retrieved from conventional powder dissolution experiments. Nanometer-scale surface measurements evidenced that K-feldspar dissolution is an anisotropic process, where the face-specific dissolution rate satisfactorily agrees with the periodic bond chain (PBC) theory. The chemical affinity of the reaction was shown to impact differently the various faces of a single crystal, controlling the spontaneous nucleation of etch pits which, in turn, drive the dissolution process. These results were used to develop a simple numerical model which revealed that single crystal dissolution rates vary with reaction progress. Overall, these results cast doubt on the conventional protocol which is used to measure mineral dissolution rates and develop kinetic rate laws, because mineral reactivity is intimately related to the morphology of dissolving crystals, which remains totally uncontrolled in powder dissolution experiments. Beyond offering an interpretive framework to understand the large discrepancies consistently reported between sources and across space scales, the recognition of the anisotropy of crystal reactivity challenges the classical approach for modeling dissolution and weathering, and may be drawn upon to develop alternative treatments of aqueous mineral reactivity

Ru(II)-based antineoplastic: A "wingtip" N-heterocyclic carbene facilitates access to a new class of organometallics that are cytotoxic to common cancer cell lines

The syntheses, structures, and chemotherapeutic activities of Ag(I)-, Au(I)-, and Ru(II)-complexes ligated to a novel N-heterocyclic carbene ligand, 2-(4-nitrophenyl)imidazo[1,5-a]pyridin-2-ylidene (1), are described. The corresponding complexes, [Ag(1)(2)][PF6], [Au(1)(2)][PF6] (3), and [Ru(1)(p-cymene)Cl][PF6] (4), were prepared using convenient transmetallation chemistry and characterized using a range of spectroscopic and analytical techniques. X-ray crystallography revealed that complexes 2 and 3 adopted linear structures whereas 4 exhibited a prototypical "piano-stool"-like geometry; the structural assignments were further supported by DFT calculations. A series of in vitro studies revealed that while the aforementioned Ag(I), Au(I) and Ru(II) complexes exhibited significant cytotoxicities against the human colon adenocarcinoma (HCT 116), lung cancer (A549), and breast cancer (MCF7) cell lines, the Ru derivative was most prominent

Sex disparities in COVID-19 outcomes of inpatients with diabetes: insights from the CORONADO study

International audienceObjective - Male sex is one of the determinants of severe coronavirus diseas-e-2019 (COVID-19). We aimed to characterize sex differences in severe outcomes in adults with diabetes hospitalized for COVID-19. Methods - We performed a sex-stratified analysis of clinical and biological features and outcomes (i.e. invasive mechanical ventilation (IMV), death, intensive care unit (ICU) admission and home discharge at day 7 (D7) or day 28 (D28)) in 2380 patients with diabetes hospitalized for COVID-19 and included in the nationwide CORONADO observational study (NCT04324736). Results - The study population was predominantly male (63.5%). After multiple adjustments, female sex was negatively associated with the primary outcome (IMV and/or death, OR: 0.66 (0.49-0.88)), death (OR: 0.49 (0.30-0.79)) and ICU admission (OR: 0.57 (0.43-0.77)) at D7 but only with ICU admission (OR: 0.58 (0.43-0.77)) at D28. Older age and a history of microvascular complications were predictors of death at D28 in both sexes, while chronic obstructive pulmonary disease (COPD) was predictive of death in women only. At admission, C-reactive protein (CRP), aspartate amino transferase (AST) and estimated glomerular filtration rate (eGFR), according to the CKD-EPI formula predicted death in both sexes. Lymphocytopenia was an independent predictor of death in women only, while thrombocytopenia and elevated plasma glucose concentration were predictors of death in men only. Conclusions - In patients with diabetes admitted for COVID-19, female sex was associated with lower incidence of early severe outcomes, but did not influence the overall in-hospital mortality, suggesting that diabetes mitigates the female protection from COVID-19 severity. Sex-associated biological determinants may be useful to optimize COVID-19 prevention and management in women and men

sj-docx-1-wso-10.1177_17474930231205213 – Supplemental material for Evaluation of mechanical thrombectomy in acute ischemic stroke related to a distal arterial occlusion: A randomized controlled trial

Supplemental material, sj-docx-1-wso-10.1177_17474930231205213 for Evaluation of mechanical thrombectomy in acute ischemic stroke related to a distal arterial occlusion: A randomized controlled trial by Frédéric Clarençon, Isabelle Durand-Zaleski, Kévin Premat, Amandine Baptiste, Emmanuel Chabert, Anna Ferrier, Marc-Antoine Labeyrie, Peggy Reiner, Laurent Spelle, Christian Denier, Titien Tuilier, Hassan Hosseini, Christine Rodriguez-Régent, Guillaume Turc, Cédric Fauché, Matthias Lamy, Bertrand Lapergue, Arturo Consoli, Charlotte Barbier, Marion Boulanger, Nicolas Bricout, Hilde Henon, Benjamin Gory, Sébastien Richard, Aymeric Rouchaud, Francisco Macian-Montoro, Omer Eker, Tae-Hee Cho, Sébastien Soize, Solène Moulin, Jean-Christophe Gentric, Serge Timsit, Jean Darcourt, Jean-François Albucher, Kévin Janot, Mariam Annan, Fernando Pico, Vincent Costalat, Caroline Arquizan, Gautier Marnat, Igor Sibon, Raoul Pop, Valérie Wolff, Eimad Shotar, Stéphanie Lenck, Nader-Antoine Sourour, Anne Radenne, Sonia Alamowitch and Agnès Dechartres in International Journal of Stroke</p

sj-docx-8-wso-10.1177_17474930231205213 – Supplemental material for Evaluation of mechanical thrombectomy in acute ischemic stroke related to a distal arterial occlusion: A randomized controlled trial

Supplemental material, sj-docx-8-wso-10.1177_17474930231205213 for Evaluation of mechanical thrombectomy in acute ischemic stroke related to a distal arterial occlusion: A randomized controlled trial by Frédéric Clarençon, Isabelle Durand-Zaleski, Kévin Premat, Amandine Baptiste, Emmanuel Chabert, Anna Ferrier, Marc-Antoine Labeyrie, Peggy Reiner, Laurent Spelle, Christian Denier, Titien Tuilier, Hassan Hosseini, Christine Rodriguez-Régent, Guillaume Turc, Cédric Fauché, Matthias Lamy, Bertrand Lapergue, Arturo Consoli, Charlotte Barbier, Marion Boulanger, Nicolas Bricout, Hilde Henon, Benjamin Gory, Sébastien Richard, Aymeric Rouchaud, Francisco Macian-Montoro, Omer Eker, Tae-Hee Cho, Sébastien Soize, Solène Moulin, Jean-Christophe Gentric, Serge Timsit, Jean Darcourt, Jean-François Albucher, Kévin Janot, Mariam Annan, Fernando Pico, Vincent Costalat, Caroline Arquizan, Gautier Marnat, Igor Sibon, Raoul Pop, Valérie Wolff, Eimad Shotar, Stéphanie Lenck, Nader-Antoine Sourour, Anne Radenne, Sonia Alamowitch and Agnès Dechartres in International Journal of Stroke</p

sj-docx-2-wso-10.1177_17474930231205213 – Supplemental material for Evaluation of mechanical thrombectomy in acute ischemic stroke related to a distal arterial occlusion: A randomized controlled trial

Supplemental material, sj-docx-2-wso-10.1177_17474930231205213 for Evaluation of mechanical thrombectomy in acute ischemic stroke related to a distal arterial occlusion: A randomized controlled trial by Frédéric Clarençon, Isabelle Durand-Zaleski, Kévin Premat, Amandine Baptiste, Emmanuel Chabert, Anna Ferrier, Marc-Antoine Labeyrie, Peggy Reiner, Laurent Spelle, Christian Denier, Titien Tuilier, Hassan Hosseini, Christine Rodriguez-Régent, Guillaume Turc, Cédric Fauché, Matthias Lamy, Bertrand Lapergue, Arturo Consoli, Charlotte Barbier, Marion Boulanger, Nicolas Bricout, Hilde Henon, Benjamin Gory, Sébastien Richard, Aymeric Rouchaud, Francisco Macian-Montoro, Omer Eker, Tae-Hee Cho, Sébastien Soize, Solène Moulin, Jean-Christophe Gentric, Serge Timsit, Jean Darcourt, Jean-François Albucher, Kévin Janot, Mariam Annan, Fernando Pico, Vincent Costalat, Caroline Arquizan, Gautier Marnat, Igor Sibon, Raoul Pop, Valérie Wolff, Eimad Shotar, Stéphanie Lenck, Nader-Antoine Sourour, Anne Radenne, Sonia Alamowitch and Agnès Dechartres in International Journal of Stroke</p

sj-docx-5-wso-10.1177_17474930231205213 – Supplemental material for Evaluation of mechanical thrombectomy in acute ischemic stroke related to a distal arterial occlusion: A randomized controlled trial

Supplemental material, sj-docx-5-wso-10.1177_17474930231205213 for Evaluation of mechanical thrombectomy in acute ischemic stroke related to a distal arterial occlusion: A randomized controlled trial by Frédéric Clarençon, Isabelle Durand-Zaleski, Kévin Premat, Amandine Baptiste, Emmanuel Chabert, Anna Ferrier, Marc-Antoine Labeyrie, Peggy Reiner, Laurent Spelle, Christian Denier, Titien Tuilier, Hassan Hosseini, Christine Rodriguez-Régent, Guillaume Turc, Cédric Fauché, Matthias Lamy, Bertrand Lapergue, Arturo Consoli, Charlotte Barbier, Marion Boulanger, Nicolas Bricout, Hilde Henon, Benjamin Gory, Sébastien Richard, Aymeric Rouchaud, Francisco Macian-Montoro, Omer Eker, Tae-Hee Cho, Sébastien Soize, Solène Moulin, Jean-Christophe Gentric, Serge Timsit, Jean Darcourt, Jean-François Albucher, Kévin Janot, Mariam Annan, Fernando Pico, Vincent Costalat, Caroline Arquizan, Gautier Marnat, Igor Sibon, Raoul Pop, Valérie Wolff, Eimad Shotar, Stéphanie Lenck, Nader-Antoine Sourour, Anne Radenne, Sonia Alamowitch and Agnès Dechartres in International Journal of Stroke</p

sj-docx-4-wso-10.1177_17474930231205213 – Supplemental material for Evaluation of mechanical thrombectomy in acute ischemic stroke related to a distal arterial occlusion: A randomized controlled trial

Supplemental material, sj-docx-4-wso-10.1177_17474930231205213 for Evaluation of mechanical thrombectomy in acute ischemic stroke related to a distal arterial occlusion: A randomized controlled trial by Frédéric Clarençon, Isabelle Durand-Zaleski, Kévin Premat, Amandine Baptiste, Emmanuel Chabert, Anna Ferrier, Marc-Antoine Labeyrie, Peggy Reiner, Laurent Spelle, Christian Denier, Titien Tuilier, Hassan Hosseini, Christine Rodriguez-Régent, Guillaume Turc, Cédric Fauché, Matthias Lamy, Bertrand Lapergue, Arturo Consoli, Charlotte Barbier, Marion Boulanger, Nicolas Bricout, Hilde Henon, Benjamin Gory, Sébastien Richard, Aymeric Rouchaud, Francisco Macian-Montoro, Omer Eker, Tae-Hee Cho, Sébastien Soize, Solène Moulin, Jean-Christophe Gentric, Serge Timsit, Jean Darcourt, Jean-François Albucher, Kévin Janot, Mariam Annan, Fernando Pico, Vincent Costalat, Caroline Arquizan, Gautier Marnat, Igor Sibon, Raoul Pop, Valérie Wolff, Eimad Shotar, Stéphanie Lenck, Nader-Antoine Sourour, Anne Radenne, Sonia Alamowitch and Agnès Dechartres in International Journal of Stroke</p