Characterization of microRNA in the follicular fluid of patients undergoing assisted reproductive technology.

Female fertility plays a decisive role in the reproduction of mammals, with related issues that include oocyte or embryo quality, establishment of pregnancy, and the physiology of the tissues that contribute to reproduction and metabolic disorders associated with reproductive failure. Although reproductive failure may be attributed to various factors in different species, female infertility is largely controlled by a number of molecular signals that can be regulated in a cycle- and tissue-dependent manner.

Silencing of GSTP1, a prostate cancer prognostic gene, by the estrogen receptor-ß and endothelial nitric oxide synthase complex.

We recently identified in prostate tumors (PCa) a transcriptional prognostic signature comprising a significant number of genes differentially regulated in patients with worse clinical outcome. Induction of up-regulated genes was due to chromatin remodeling by a combinatorial complex between estrogen receptor (ER)-ß and endothelial nitric oxide synthase (eNOS). Here we show that this complex can also repress transcription of prognostic genes that are down-regulated in PCa, such as the glutathione transferase gene GSTP1. Silencing of GSTP1 is a common early event in prostate carcinogenesis, frequently caused by promoter hypermethylation. We validated loss of glutathione transferase (GST) P1-1 expression in vivo, in tissue microarrays from a retrospective cohort of patients, and correlated it with decreased disease-specific survival. Furthermore, we show that in PCa cultured cells ERß/eNOS causes GSTP1 repression by being recruited at estrogen responsive elements in the gene promoter with consequential remodeling of local chromatin. Treatment with ERß antagonist or its natural ligand 5α-androstane-3ß,17ß-diol, eNOS inhibitors or ERß small interference RNA abrogated the binding and reversed GSTP1 silencing, demonstrating the direct involvement of the complex. In vitro, GSTP1 silencing by ERß/eNOS was specific for cells from patients with worse clinical outcome where it appeared the sole mechanism regulating GSTP1 expression because no promoter hypermethylation was present. However, in vivo chromatin immunoprecipitation assays on fresh PCa tissues demonstrated that silencing by ERß/eNOS can coexist with promoter hypermethylation. Our findings reveal that the ERß/eNOS complex can exert transcriptional repression and suggest that this may represent an epigenetic event favoring inactivation of the GSTP1 locus by methylation. Moreover, abrogation of ERß/eNOS function by 3ß-adiol emphasizes the significance of circulating or locally produced sex steroid hormones or their metabolites in PCa biology with relevant clinical/therapeutic implications.

[Clinical value of hemorrheology in peripheral arterial occlusive diseases]. / Valore clinico dell'emoreologia nelle arteriopatie ostruttive periferiche.

The authors report their study on the red blood cell deformability of 30 patients with isolated and combined obstructive lesions in both aorto-iliac and femoral trunk, performed before and after the exercise test. Such a test does not significantly change the deformability in normal patients while, on the contrary, the exercise test significantly changes the deformability in patients affected by atherosclerotic disease. Furthermore, in the experience of the authors the decrease of the deformability is directly related to the degree of the circulatory impairment.

[Erythrocyte filterability in Raynaud's disease]. / La filtrabilità eritrocitaria nel fenomeno di Raynaud.

Hemorheological changes were more recently believed to be responsible for the pathogenesis of the Raynaud's phenomenon. In order to verify such changes, the authors report the data on red blood cell deformability obtained from a study performed in 8 patients with cold-induced Raynaud's phenomenon. From the evaluation of these data it seems likely that hemorheological changes observed during the phenomenon are the consequence of the ischemia and not vice versa.