Preclinical research

  • Article |

    Hydroxychloroquine did not confer protection against SARS-CoV-2 infection or reduce the viral load after infection in macaques; these findings do not support the use of hydroxychloroquine as an antiviral drug treatment of COVID-19 in humans.

    • Pauline Maisonnasse
    • , Jérémie Guedj
    •  & Roger Le Grand
  • Article |

    An artificial intelligence (AI) system performs as well as or better than radiologists at detecting breast cancer from mammograms, and using a combination of AI and human inputs could help to improve screening efficiency.

    • Scott Mayer McKinney
    • , Marcin Sieniek
    •  & Shravya Shetty
  • Letter |

    α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and human thrombomodulin require non-ischaemic preservation with continuous perfusion and post-transplantation growth control to ensure long-term orthotopic function of the xenograft in baboons.

    • Matthias Längin
    • , Tanja Mayr
    •  & Jan-Michael Abicht
  • Letter |

    The HIF-2 antagonist PT2399 is tested in mice bearing tumourgrafts derived from human renal cell cancers to demonstrate its efficacy, identify markers of sensitivity and characterize its effects.

    • Wenfang Chen
    • , Haley Hill
    •  & James Brugarolas
  • Letter |

    The authors report a new biomimetic nanodelivery platform in which polymeric nanoparticles enclosed in the plasma membrane of human platelets are used for disease-relevant targeting, and the therapeutic potential of the concept is demonstrated in animal models of coronary restenosis and systemic bacterial infection.

    • Che-Ming J. Hu
    • , Ronnie H. Fang
    •  & Liangfang Zhang
  • Article |

    Mutations that dysregulate Notch1 and Ras/PI3K signalling are common in T-cell acute lymphoblastic leukaemia; here, treatment with a PI3K inhibitor is shown to induce drug resistance that is associated with downregulation of activated Notch1 signalling, suggesting that inhibition of both Notch1 and PI3K could promote drug resistance.

    • Monique Dail
    • , Jason Wong
    •  & Kevin Shannon
  • Letter |

    Regeneration of the heart muscle after myocardial infarction with cardiomyocytes derived from human embryonic stem cells is demonstrated in non-human primates, with the grafts showing evidence of electromechanical coupling, although they were also associated with non-fatal arrhythmias.

    • James J. H. Chong
    • , Xiulan Yang
    •  & Charles E. Murry
  • Letter |

    PLX4032 is a selective inhibitor of the B-RAF protein that has shown promising results in an early clinical trial in melanoma patients with an activating mutation in B-RAF. Now the structure and function of this inhibitor are described. Translational data from a phase I trial show that clinical efficacy requires a substantial degree of inhibition of the ERK pathway downstream of B-RAF. The data also show that BRAF-mutant melanomas are highly dependent on B-RAF activity.

    • Gideon Bollag
    • , Peter Hirth
    •  & Keith Nolop
  • Article |

    African sleeping sickness, caused by Trypanosoma brucei species, is responsible for some 30,000 human deaths each year. Available treatments are limited by poor efficacy and safety profiles. However, a new molecular target for potential treatments has now been identified. The protein target is T. brucei N-myristoyltransferase. In further experiments, lead compounds have been discovered that inhibit this protein, kill trypanosomes in vitro and in vivo, and can cure trypanosomiasis in mice.

    • Julie A. Frearson
    • , Stephen Brand
    •  & Paul G. Wyatt