👤 Nadia A Lanman

IntroductionAging and metabolic disease enhance inhaled particulate toxicity. Nanoparticles (NPs) are rapidly coated with biomolecules forming a biocorona (BC), upon entering the body and may contribute to the susceptibility. Aging and metabolic syndrome (MetS) are progressive conditions resulting in biomolecule alterations over time potentially influencing susceptibility. We hypothesize NP-biomolecule interactions are altered during aging and throughout MetS progression.MethodsC57BL/6J mice at 6 weeks of age were fed a healthy diet or a high-fat western diet. BALF was collected after 2, 4, 8, 12, 16, 20 or 24 weeks on diets. NP-biomolecules interactions were compared between healthy and MetS to determine age- and disease progression-related BC variations (proteins and lipids).ResultsUnique BCs were determined to form at each time point indicative of aging for the healthy and aging and disease progression for the MetS. Comparisons between healthy and MetS BCs at each time demonstrated distinct biomolecule interactions attributable to disease. Comparisons determined both unique protein and lipid content as well as quantitative differences. Proteins such as apolipoprotein A-IV, complement C3 and lipids such as PE (37:5), PE (O-38:5), PE (P-38:4), PC(40:7), PC(39:0), and PC(O-40:0) were identified on the MetS BC suggesting disease progression modifications. Proteins such as pulmonary surfactant protein A, fibrinogen alpha-chain and lipids such as CE (19:0)-NH4, DG (36:7), and DG (35:0)_C18:0 were increasingly present in the healthy BC over time, suggesting age-related interactions.DiscussionOverall, unique BCs were identified demonstrating the impact of age and disease progression on BC formation which will aid in understanding initial pulmonary NP-biomolecular interactions potentially contributing to susceptibility. Show less

The reactivation of developmental genes and pathways during adulthood may contribute to pathogenesis of diseases such as prostate cancer. Analysis of the mechanistic links between development and disease could be exploited to identify signalling pathways leading to disease in the prostate. However, the mechanisms underpinning prostate development require further characterisation to interrogate fully the link between development and disease. Previously, our group developed methods to produce prostate organoids using induced pluripotent stem cells (iPSCs). Here, we show that human iPSCs can be differentiated into prostate organoids using neonatal rat seminal vesicle mesenchyme in vitro. The organoids can be used to study prostate development or modified to study prostate cancer. We also elucidated molecular drivers of prostate induction through RNA-sequencing analyses of the rat urogenital sinus and neonatal seminal vesicles. We identified candidate drivers of prostate development evident in the inductive mesenchyme and epithelium involved with prostate specification. Our top candidates included Spx, Trib3, Snai1, Snai2, Nrg2 and Lrp4. This work lays the foundations for further interrogation of the reactivation of developmental genes in adulthood, leading to prostate disease. Show less