In epithelial tissues, the lineage relationship between normal progenitor cells and cell type(s) of origin for cancer has been poorly understood. Here we show that a known regulator of prostate epithelial differentiation, the homeobox gene Nkx3.1, marks a stem cell population that functions during prostate regeneration. Genetic lineage-marking demonstrates that rare luminal cells which express Nkx3.1 in the absence of testicular androgens (castration-resistant Nkx3.1-expressing cells, CARNs) are bipotential and can self-renew in vivo, while single-cell transplantation assays show that CARNs can reconstitute prostate ducts in renal grafts. Functional assays of Nkx3.1 mutant mice in serial prostate regeneration assays suggest that Nkx3.1 is required for stem cell maintenance. Finally, targeted deletion of the Pten tumor suppressor gene in CARNs results in rapid formation of carcinoma following androgen-mediated regeneration. These observations indicate that CARNs represent a novel luminal stem cell population that is an efficient target for oncogenic transformation in prostate cancer.

Nanotechnology is an enable technology that has the potential to revolutionize agriculture and food systems. Driven by increasing consumer demand for healthy food products, researchers have been applying tools and knowledge in nanotechnology to address the issues relevant to food and nutrition. This concise review is mainly focused on nanoemulsions and polymer micelles-based delivery systems which have shown enhanced oral bioavailability and biological efficacies (that is, antiinflammation, anti-cancer, and so on) of different phytochemicals. Nanoemulsions are a class of extremely small droplets that appear to be transparent or translucent with a bluish coloration. They are usually in the range 50 to 200 nm but much smaller than the range (from 1 to 100 μm) for conventional emulsions. Nanoemulsion preparation, characterization, and bioavailability have been discussed. Curcumin nanoemulsions show 85% inhibition of TPA-induced mouse ear inflammation as well as the inhibition of cyclin D1 expression, while dibenzoylmethane (DBM) nanoemulsion shows about 3-fold increase in oral bioavailability compared to the conventional DBM emulsion. Biopolymer micelles show significantly improved water solubility/dispersibility and in vitro anti-cancer activity of phytochemicals. More research efforts are still needed for the understanding of the potential impacts of nanoencapsulated phytochemicals on the human body and environment to address the public concerns.

Curcumin is a natural bioactive compound with many health-promoting benefits. Its low oral bioavailability limits its application in functional foods. In the present study, novel organogel-based nanoemulsions have been developed for oral delivery of curcumin and improvement of its bioavailability. Recently developed curcumin organogel was used as the oil phase in the curcumin nanoemulsion formulation. Tween 20 was selected as the emulsifier on the basis of maximum in vitro bioaccessibility of curcumin in the nanoemulsion. In vitro lipolysis profile revealed that the digestion of nanoemulsion was significantly faster and more complete than the organogel. Permeation experiments on Caco-2 cell monolayers suggested that digestion-diffusion was the major absorption mechanism for curcumin in the nanoemulsion. Furthermore, in vivo pharmacokinetics analysis on mice confirmed that the oral bioavailability of curcumin in the nanoemulsion was increased by 9-fold compared with unformulated curcumin. This novel formulation approach may also be used for oral delivery of other poorly soluble nutraceuticals with high loading capacity, which has significant impact in functional foods, dietary supplements and pharmaceutical industries.

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