Abiraterone acetate (AA) is an inhibitor of androgen biosynthesis, though this cannot fully explain its efficacy against androgen-independent prostate cancer. Here, we demonstrate that androgen deprivation therapy depletes androgen-utilizing Corynebacterium spp. in prostate cancer patients and that oral AA further enriches for the health-associated commensal, Akkermansia muciniphila. Functional inferencing elucidates a coinciding increase in bacterial biosynthesis of vitamin K2 (an inhibitor of androgen dependent and independent tumor growth). These results are highly reproducible in a host-free gut model, excluding the possibility of immune involvement. Further investigation reveals that AA is metabolized by bacteria in vitro and that breakdown components selectively impact growth. We conclude that A. muciniphila is a key regulator of AA-mediated restructuring of microbial communities, and that this species may affect treatment response in castrate-resistant cohorts. Ongoing initiatives aimed at modulating the colonic microbiota of cancer patients may consider targeted delivery of poorly absorbed selective bacterial growth agents.

The procedure was easily mastered and technically simple, and represents savings in cost, time and human resources in our setting.

No abstract

No abstract

No abstract

No abstract

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20410-x

suggests that there may be a potential opportunity to bias the host response towards repair and replacement of tissue defects. This may be achieved by maneuvering host stem and progenitor cells using target specific scaffolds. In this study, we aimed to regenerate muscle functionality following volumetric muscle loss through the use of a targetspecific scaffolding system. The objectives of this study were to evaluate the functionalized decellularized tissue scaffolds on the host muscle cell migration and muscle function recovery in vivo.METHODS: Decellularized porcine scaffolds were implanted into a created defect site in the tibialis anterior muscle of rats. Three experimental groups were tested (along with two control groups); those with empty scaffolds, scaffolds seeded with muscle progenitor cells, and scaffolds injected with IGF-1 prior to implantation. To evaluate the effect of the scaffolds, a force transducer was utilized to measure isometric force produced by the tibialis anterior muscle at either 2 or 4 weeks post-implantation. To evaluate the cell infiltration of the scaffolds, the muscle and scaffold were removed and characterized by H&E and Masson 0 s Trichrome.RESULTS: Functional testing showed an increase in muscle functionality in all groups by 4 weeks relative to the defect only group. Scaffolds seeded with primary muscle cells recovered 53% of functionality by week 4, a 21% increase over the defect only group. The retrieved implants showed progressive cell infiltration of the scaffolds over time. The IGF-1 and seeded progenitor cell scaffolds yielded the greatest cell count. Fiber-like orientation of infiltrated cells within the scaffold could be seen as early as week 2.CONCLUSIONS: Our data suggest an ability of host stem cells to recruit into the scaffolds with the capability of differentiating to muscle cells, which resulted in accelerating muscle regeneration in situ. This study hopes to provide a platform for the development of tissue engineering and regenerative medicine in regards to volumetric muscle loss.