Mannose-modified hyaluronic acid nanocapsules for the targeting of tumor-associated macrophages

Tumor-associated macrophages (TAMs), a class of immune cells that play a key role in tumor immunosuppression, are recognized as important targets to improve cancer prognosis and treatment. Consequently, the engineering of drug delivery nanocarriers that can reach TAMs has acquired special relevance. This work describes the development and biological evaluation of a panel of hyaluronic acid (HA) nanocapsules (NCs), with different compositions and prepared by different techniques, designed to target macrophages. The results showed that plain HA NCs did not significantly influence the polarization of M0 and M2-like macrophages towards an M1-like pro-inflammatory phenotype; however, the chemical functionalization of HA with mannose (HA-Man) led to a significant increase of NCs uptake by M2 macrophages in vitro and to an improved biodistribution in a MN/MNCA1 fibrosarcoma mouse model with high infiltration of TAMs. These functionalized HA-Man NCs showed a higher accumulation in the tumor compared to non-modified HA NCs. Finally, the pre-administration of the liposomal liver occupying agent Nanoprimer™ further increased the accumulation of the HA-Man NCs in the tumor. This work highlights the promise shown by the HA-Man NCs to target TAMs and thus provides new options for the development of nanomedicine and immunotherapy-based cancer treatmentsOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by the 2^2-INTRATARGET project (A20/00028) funded by the ISCIII under the umbrella of the ERA NET EuroNanoMed GA N 723770 of the EU Horizon 2020 Research and Innovation Programme. This work was also supported by the Xunta de Galicia (ED431C 2018/30, and “Centro singular de investigación de Galicia” accreditation 2019 − 2022, ED431G2019/03), and the European Union (European Regional Development Fund-ERDF)S

Induction of regulatory T cells: A role for probiotics and prebiotics to suppress autoimmunity.

Regulatory T cells (Tregs) are comprised of a heterogeneous population of cells that play a vital role in suppressing inflammation and maintaining immune tolerance. Given the crucial role of Tregs in maintaining immune homeostasis, it is probably not surprising that many microbial species and their metabolites have the potential to induce Tregs. There is now great interest in the therapeutic potential of probiotics and prebiotics based strategies for a range of autoimmune disorders. This review will summarise recent findings concerning the role of probiotics and prebiotics in induction of Tregs to ameliorate the autoimmune conditions. In addition, the article is focused to explain the different mechanisms of Treg induction and function by these probiotics and prebiotics, based on the available studies till date. The article further proposes that induction of Tregs by probiotics and prebiotics could lead to the development of new therapeutic approach towards curbing the autoimmune response and as an alternative to detrimental immunosuppressive drugs

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

OXYDES ET HYDROXYACETATES LAMELLAIRES DE METAUX DE TRANSITION (ZINC, COBALT, NICKEL) (NOUVELLE VOIE DE SYNTHESE PAR HYDROLYSE EN MILIEU POLYOL, CARACTERISATION)

CETTE ETUDE PRESENTE LA SYNTHESE PAR HYDROLYSE EN MILIEU POLYOL D'OXYDES ET DES HYDROXYACETATES LAMELLAIRES DE ZINC DE COBALT ET DE NICKEL ET LEUR CARACTERISATION STRUCTURALE (DRX ET IR RESOLUS EN TEMPERATURE, XANES, EXAFS, UV-VISIBLE) ET MORPHOLOGIQUE (MEB, TEM). ON SAVAIT QUE LES POLYOLS SONT DES MILIEUX FAVORABLES A LA SYNTHESE DE METAUX PAR REDUCTION. ON MONTRE ICI QU'ILS PEUVENT AUSSI ETRE PROPICES A LA SYNTHESE D'AUTRES MATERIAUX INORGANIQUES (OXYDES, SELS D'HYDROXYDES) PAR HYDROLYSE. NOUS AVONS PU METTRE EN EVIDENCE LE ROLE DETERMINANT DE L'ANION ASSOCIE AU METAL DANS LE COMPOSE DE DEPART ET EN PARTICULIER CELUI DE L'ANION ACETATE (QUI DECOULE DE SES PROPRIETES ACIDO-BASIQUES ET A SON POUVOIR COMPLEXANT) DANS LES REACTIONS MISES EN JEU. DANS CES MILIEUX REDUCTEURS, C'EST LE TAUX D'HYDROLYSE QUI APPARAIT COMME LE FACTEUR DETERMINANT POUR ORIENTER LA REACTION VERS LA FORMATION D'OXYDE PLUTOT QUE VERS LA REDUCTION EN METAL. PAR AILLEURS, NOUS AVONS MONTRE QUE LE TAUX D'HYDROLYSE INFLUE AUSSI SUR LE MODE DE CROISSANCE DES PARTICULES D'OXYDE. SON AUGMENTATION EMPECHE EN EFFET LA CROISSANCE PAR AGGREGATION DES PARTICULES PRIMAIRES ET FAVORISE EN REVANCHE LEUR CROISSANCE PAR DIFFUSION. UN MODELE STRUCTURAL A ETE PROPOSE POUR CHAQUE HYDROXYACETATE. CEUX DES COMPOSES AU ZINC ET AU COBALT DERIVENT DU TYPE HYDROZINCITE, ALORS QUE CELUI AU NICKEL EST CONSTITUE D'EMPILEMENT DE FEUILLETS DE TYPE BRUCITE. L'ANION ACETATE Y EST COORDONNE AUX CATIONS METALLIQUES DANS LES PHASES AU COBALT ET AU NICKEL, ALORS QU'IL EST INSERE ENTRE LES FEUILLETS DANS CELLE DU ZINC. L'EAU, ELLE, EST INSEREE EN MONOCOUCHE ENTRE LES FEUILLETS DANS LE CAS DU COBALT ET DU NICKEL, ALORS QU'ELLE EST LIEE AU CATION DANS L'HYDROXYACETATE DE ZINC. ENFIN, L'ETUDE MAGNETIQUE DES HYDROXYACETATES DE NICKEL ET DE COBALT ET DES HYDROXYCARBONATES CORRESPONDANTS OBTENUS PAR ECHANGE, A MIS EN EVIDENCE UN COMPORTEMENT D'AIMANT A BASSE TEMPERATURE, CE QUELLES QUE SOIENT LA STRUCTURE DES FEUILLETS, LEUR ESPACEMENT ET LA NATURE DU CATION.PARIS-BIUSJ-Thèses (751052125) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF