Recent progress in the design of nanocarriers for the codelivery of a drug/drug, drug/gene, and gene/gene for synergistic cancer therapeutic effects.

Apoptosis of hypothalamic neurons is believed to play an important role in the development and perpetuation of obesity. Similar to the hippocampus, the hypothalamus presents constitutive and stimulated neurogenesis, suggesting that obesity-associated hypothalamic dysfunction can be repaired. Here, we explored the hypothesis that n-3 polyunsaturated fatty acids (PUFAs) induce hypothalamic neurogenesis. Both in the diet and injected directly into the hypothalamus, PUFAs were capable of increasing hypothalamic neurogenesis to levels similar or superior to the effect of brain-derived neurotrophic factor (BDNF). Most of the neurogenic activity induced by PUFAs resulted in increased numbers of proopiomelanocortin but not NPY neurons and was accompanied by increased expression of BDNF and G-protein–coupled receptor 40 (GPR40). The inhibition of GPR40 was capable of reducing the neurogenic effect of a PUFA, while the inhibition of BDNF resulted in the reduction of global hypothalamic cell. Thus, PUFAs emerge as a potential dietary approach to correct obesity-associated hypothalamic neuronal loss.

Morphological and stereological analyses were used to characterize the growth kinetics of the Wistar rat ventral prostate (VP). Volume density and absolute volume of the epithelium, lumen, smooth muscle cells (SMCs), and nonmuscular stroma were determined by stereology and paired with plasma testosterone levels and different morphometric measurements. The VP shows an initial growth within the first 3 weeks, a resting phase, and the puberal growth. The puberal growth was coincident with the raise in plasma testosterone. Lumen formation occurred within the 3 postnatal weeks. After an expected increase during puberty, the lumen showed a further increase at the 12th week. The volume density of the nonmuscular stroma and of the SMCs decreased slowly postnatally. Absolute volume of the luminal compartment showed three phases of growth (weeks 1–3, 6–9, and 11–12). On the other hand, the increase in the absolute volume of the epithelium was steady up to the 8th week and then showed a marked increase up the 10th week. The increase in epithelial volume was characterized morphologically by the presence of epithelial infoldings and sprouts. The growth of the epithelium showed a 2‐week delay as compared to the lumen and occurred only until the 10th week. The epithelial height was variable but could be related to the synthetic activity of the epithelium. In conclusion, the postnatal growth of the VP results from a combination of epithelial proliferation/differentiation and synthesis/accumulation of the secretory products in the lumen. Anat Rec Part A, 288A:885–892, 2006.

This review focuses on the mechanisms of DNA methylation, DNA methylation pattern formation and their involvement in gene regulation. Association of DNA methylation with imprinting, embryonic development and human diseases is discussed. Furthermore, besides considering changes in DNA methylation as mechanisms of disease, the role of epigenetics in general and DNA methylation in particular in transgenerational carcinogenesis, in memory formation and behavior establishment are brought about as mechanisms based on the cellular memory of gene expression patterns.

Smooth muscle cells (SMC) play roles in prostatic development and function. The cells also respond to tissue injury and hormonal variations, alternating between a fully differentiated and contractile phenotype and a dedifferentiated synthetic or secretory phenotype. However, the phenotypic changes in SMC after androgen deprivation have not yet been described. The ventral prostate of control and castrated rats was processed for routine histology, immunocytochemistry, reverse transcriptase polymerase chain reaction (RT‐PCR), and scanning electron microscopy (SEM). The maintenance of SMC phenotype was confirmed by immunocytochemistry and by RT‐PCR. Stereological analyses were done to define the relative and absolute volume of the SMC. SMC were elongated and flattened against the epithelium. After castration, the cells shortened concomitantly with pleating of the cell surface, leading to a spinous aspect. SEM showed that the smooth surface of SMC became progressively folded. Immunocytochemistry demonstrated both smooth muscle myosin heavy chain and smooth muscle α‐actin in the prostatic SMC 21 days after castration, whereas RT‐PCR amplified the message for smoothelin. Stereological analysis showed an increase in the relative volume of SMC in relation to the whole gland and the stroma. A decrease in the absolute volume of SMC occurred only within the first 7 days after castration and remained unchanged thereafter. The prostatic SMC are affected by the absence of androgens and there is a critical transition point during the first week in which the total volume occupied by SMC diminished. The remaining SMC showed a marked phenotypical change. These findings indicate that ventral prostate SMC maintain their differentiated phenotype after castration. The alterations in SMC behavior correlate with general stromal modifications taking place after castration.