Caveolin-1 is suggested to act as a tumor suppressor. We tested the hypothesis that caveolin-1 does so by repression of survivin, an Inhibitor of apoptosis protein that regulates cell-cycle progression as well as apoptosis and is commonly overexpressed in human cancers. Ectopic expression of caveolin-1 in HEK293T and ZR75 cells or siRNA-mediated silencing of caveolin-1 in NIH3T3 cells caused downregulation or upregulation of survivin mRNA and protein, respectively. Survivin downregulation in HEK293T cells was paralleled by reduced cell proliferation, increases in G0-G1 and decreases in G2-M phase of the cell cycle. In addition, apoptosis was evident, as judged by several criteria. Importantly, expression of green fluorescent protein-survivin in caveolin-1-transfected HEK293T cells restored cell proliferation and viability. In addition, expression of caveolin-1 inhibited transcriptional activity of a survivin promoter construct in a β-catenin-Tcf/Lef-dependent manner. Furthermore, in HEK293T cells caveolin-1 associated with β-catenin and inhibited Tcf/Lef-dependent transcription. Similar results were obtained upon caveolin-1 expression in DLD1 cells, where APC mutation leads to constitutive activation of β-catenin-Tcf/Lef-mediated transcription of survivin. Taken together, these results suggest that anti-proliferative and pro-apoptotic properties of caveolin-1 may be attributed to reduced survivin expression via a mechanism involving diminished β-catenin-Tcf/Lef-dependent transcription.

Among the different DNA anomalies that can be present in the male gamete, DNA fragmentation is the most frequent, particularly in infertile subjects. There is now consistent evidence that a sperm containing fragmented DNA can be alive, motile, morphologically normal and able to fertilize an oocyte. There is also evidence that the oocyte is able to repair DNA damage; however, the extent of this repair depends on the type of DNA damage present in the sperm, as well as on the quality of the oocyte. Thus, it is important to understand the possible consequences of sperm DNA fragmentation (SDF) for embryo development, implantation, pregnancy outcome and the health of progeny conceived, both naturally and by assisted reproductive technology (ART). At present, data on the consequences of SDF for reproduction are scarce and, in many ways, inconsistent. The differences in study conclusions might result from the different methods used to detect SDF, the study design and the inclusion criteria. Consequently, it is difficult to decide whether SDF testing should be carried out in fertility assessment and ART. It is clear that there is an urgent need for the standardisation of the methods and for additional clinical studies on the impact of SDF on ART outcomes.

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It was synthesized nine polyoxygenated chalcones with a potential and safe use as antioxidant, antimicrobial and anti-inflammatory therapies. Chalcones obtained by Claisen-Schmidt condensation were studied as antioxidant, inhibitors of human 5-lipoxygenase, antifungal, antibacterial and antibiotic resistance modifiers. Two chalcones with catecholic moieties were able to strongly decrease the minimum inhibitory concentration (MIC) of methicillin against methicillin-resistant Staphylococcus aureus, increase the antiradical activity and significantly inhibit the human 5-lipoxygenase. Only one of these chalcones was active synergistically with methicillin. Chalcones with methoxyl substituents at different positions displayed the best activities against Cryptococcus neoformans. Only one chalcone showed good activity against the plant pathogenic bacteria Pseudomonas syringae whose half maximal inhibitory concentration (IC 50) value (2.5 µg mL-1) was similar to that observed with the antibiotic streptomycin (2.9 µg mL-1). These simple chalcones have safe potential uses in antioxidant, antimicrobial and anti-inflammatory therapies.