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Abstract: Diabetes-induced metabolic derangements promote endothelial malfunction, contributing to erectile dysfunction (ED). However, it remains unclear which angiogenic molecular mechanisms are deregulated in diabetic corpus cavernosum (CC). We investigated early and late alterations in cavernosal angiogenic gene expression associated to diabetes. Angiogenic changes were assessed in penile tissue of streptozotocin-induced Wistar rats, in an early (2-week) and established stage (8-week) of diabetes. Differentially expressed genes were identified by microarrays and expression data validated by quantitative real-time PCR (qrt-PCR). At protein level, quantitative immunohistochemistry confirmed the arrays data and dual immunofluorescence for selected alterations and α-smooth muscle actin (α-SMA) identified the cellular location of target proteins. The selected differentially expressed genes were also evaluated in human non-diabetic and diabetic CC by quantitative immunolabeling. At 2-week diabetes there was no differential gene expression between non-diabetic and diabetic CC. At 8-week, 10 genes were found down-regulated in diabetics. The results were validated by qrt-PCR for the insulin-like growth factor-1 (Igf1) and the natriuretic peptide receptor-1 (Npr1) genes. Dual immunofluorescence for IGF-1/ α-SMA showed predominant localization of IGF-1 in SM. NPR-1 expression was diffuse and mostly present in trabecular fibroblasts and SM. Quantitative immunostaining confirmed the decreased expression of both proteins in diabetic tissues. Concordantly, we detected a significant reduction in IGF-1 and NPR-1 protein expressions in human diabetic samples. Microarray analysis identified 10 angiogenic-related molecules deregulated in CC of established diabetes. Among them, IGF-1 and NPR-1 were significantly down-regulated and might result in preventive/therapeutic targets for ED management. [Copyright &y& Elsevier]

Abstract: We have previously identified the expression of an estradiol (E2)-related molecule by Schistosoma haematobium total antigen (Sh). We now show that this molecule has an antagonistic effect of estradiol in vitro. Our results are consistent with the existence of an estrogenic molecule that antagonizes the activity of estradiol. We found evidence for this molecule as we identified and characterized by mass spectrometry new estrogenic molecules previously unknown, present in schistosome worm extracts and sera of Schistosoma-infected individuals. We also show that Sh is able to interact in vitro with estrogen receptor (ER), explaining how host endocrine system can favor the establishment of schistosomes. These findings highlight the exploitation of the host endocrine system by schistosomes and represent an additional regulatory component of schistosome development that defines a novel paradigm enabling host–parasite interactions. The identification of these molecules opens new ways for the development of alternative drugs to treat schistosomiasis. [ABSTRACT FROM AUTHOR]

Hydroxyurea (HU), or hydroxycarbamide, is used for the treatment of some myeloproliferative and neoplastic diseases, and is currently the only drug approved by the FDA for use in sickle cell disease (SCD). Despite the relative success of HU therapy for SCD, a genetic disorder of the hemoglobin γ03b2; chain that results in red-cell sickling, hemolysis, vascular inflammation and recurrent vasoocclusion, the exact mechanisms by which HU actuates remain unclear. We hypothesized that HU may modulate endothelial angiogenic processes, with important consequences for vascular inflammation. The effects of HU (50-200μM; 17-24h) on endothelial cell functions associated with key steps of angiogenesis were evaluated using human umbilical vein endothelial cell (HUVEC) cultures. Expression profiles of the HIF1A gene and the miRNAs 221 and 222, involved in endothelial function, were also determined in HUVECs following HU administration and the direct in vivo antiangiogenic effects of HU were assessed using a mouse Matrigel-plug neovascularization assay. Following incubation with HU, HUVECs exhibited high cell viability, but displayed a significant 75% inhibition in the rate of capillary-like-structure formation, and significant decreases in proliferative and invasive capacities. Furthermore, HU significantly decreased HIF1A expression, and induced the expression of miRNA 221, while downregulating miRNA 222. In vivo, HU reduced vascular endothelial growth factor (VEGF)-induced vascular development in Matrigel implants over 7days. Findings indicate that HU is able to inhibit vessel assembly, a crucial angiogenic process, both in vitro and in vivo, and suggest that some of HU's therapeutic effects may occur through novel vascular mechanisms. [ABSTRACT FROM AUTHOR]

Abstract: Anti-VEGF therapy proved to be useful against several ocular pathological situations, including choroidal neovascularization and proliferative retinopathies. Ranibizumab (Ran), Pegaptanib (Peg) and Bevacizumab (Bev) are the pharmacological agents more frequently used in clinical practice by intravitreal injection. However, their exact effects on the angiogenic process have not been accurately established in a comparative study. The aim of the present study was to elucidate the precise effects of Ran, Peg and Bev on the multiple steps of the angiogenic process. Human umbilical vein endothelial cells (HUVEC) were incubated with each agent within the clinically established concentration range, or identical amounts of the excipients; cell cytotoxicity, proliferation, apoptosis, migration and vessel assembly were assessed. No cytotoxic effects were found for any of the agents studied at any concentration tested. At the clinical dose, cell proliferation was significantly reduced by Bev and Ran, whereas no difference was observed after Peg treatment. In addition, HUVEC apoptosis was effectively increased by Bev and Ran. Cell migration was reduced after incubation with every agent analyzed, though only reaching statistical significance upon Ran intravitreal dose. At clinical doses, capillary assembly was only affected by Bev. In agreement with these data, the active form of VEGF receptor-2 expression was decreased after incubation with Bev (to 66% of control values), Ran (78%) and Peg (86%) relative to controls. These findings indicate that these three agents display distinct effects on endothelial cells. [Copyright &y& Elsevier]

Visual pH-sensing cellulose acetate (CA)-based films was incorporated with different concentrations of red cabbage extract (RCE). The films were characterized by color, barrier and thermal properties, microscopic and topographic characteristics, mechanical performance, detection capacity of volatile ammonia, and time-dependent color stability and lighting. The RCE incorporation into CA-based films promoted a color-changing capacity with an increased light barrier and exhibited a plasticizer effect on the mechanical properties of the films. Moreover, the surface patterns of films were heterogeneous and irregular due to the presence of RCE aggregates, which increased as the extract concentration enhanced. The intelligent films showed excellent performance to detect volatile ammonia after 15 min of contact time, despite lower thermal stability and oxygen barrier. The detection of volatile ammonia was fitted well to a statistical model (p < 0.05; R2 = 0.89) as a function of contact time and RCE concentration. The storage time and incidence of lighting influenced the color and the colorimetric transition of films after 30 days. Regarding biodegradability, sensitivity, simplicity, and low cost, these results suggested that CA intelligent films added with RCE have a great potential application as a volatile base sensor to monitor food degradation. • Visual pH-sensing cellulose acetate-based films were prepared and characterized. • The films showed heterogeneous surface patterns and excellent UV-light barrier property. • The extract incorporation promoted a plasticizer effect on the film mechanical properties. • The intelligent films exhibited an excellent performance to detect volatile ammonia. • Storage time and lighting affected the color transition of the films. [ABSTRACT FROM AUTHOR]