Cell Plasticity in a Mouse Model of Benign Prostate Hyperplasia Drives Amplification of Androgen-Independent Epithelial Cell Populations Sensitive to Antioxidant Therapy.

Benign prostate hyperplasia (BPH) is caused by the nonmalignant enlargement of the transition zone of the prostate gland, leading to lower urinary tract symptoms. Although current medical treatments are unsatisfactory in many patients, the limited understanding of the mechanisms driving disease progression prevents the development of alternative therapeutic strategies. The probasin-prolactin (Pb-PRL) transgenic mouse recapitulates many histopathological features of human BPH. Herein, these alterations parallel urodynamic disturbance reminiscent of lower urinary tract symptoms. Single-cell RNA-sequencing analysis of Pb-PRL mouse prostates revealed that their epithelium mainly includes low-androgen signaling cell populations analogous to Club/Hillock cells enriched in the aged human prostate. These intermediate cells are predicted to result from the reprogramming of androgen-dependent luminal cells. Pb-PRL mouse prostates exhibited increased vulnerability to oxidative stress due to reduction of antioxidant enzyme expression. One-month treatment of Pb-PRL mice with anethole trithione (ATT), a specific inhibitor of mitochondrial ROS production, reduced prostate weight and voiding frequency. In human BPH-1 epithelial cells, ATT decreased mitochondrial metabolism, cell proliferation, and stemness features. ATT prevented the growth of organoids generated by sorted Pb-PRL basal and LSCmed cells, the two major BPH-associated, androgen-independent epithelial cell compartments. Taken together, these results support cell plasticity as a driver of BPH progression and therapeutic resistance to androgen signaling inhibition, and identify antioxidant therapy as a promising treatment of BPH.

Mid-range atmospheric dispersion modelling. Intercomparison of simple models in EMRAS-2 project.

An intercomparison of atmospheric dispersion models has been carried out for a hypothetical accident occurring in a nuclear power plant in the center of Spain. The accident consisted of a steam generator tube rupture, and two radionuclides have been considered for the exercise: 137-Cs and 131-I. Meteorological conditions and radionuclide release rates were supplied. Models provided deposition maps, timeintegrated concentrations in air and arrival times of the plumes to specific locations. The effect of the meteorological conditions used in the modelling was clear, with different behavior of the plume with neutral stability vs. stable conditions. The predicted arrival times of the plume at specific locations showed much less variability than deposition and air concentrations. This variability in part reflects the uncertainties inherent in atmospheric dispersion modelling and in the selection of parameter values, such as deposition velocities or diffusivities.