Radioresistance stands as a fundamental barrier that limits the effectiveness of radiotherapy in cancer treatment. Recent evidences suggest that radioresistance is due to tumour repopulation and involves several signalling pathways, including p53/MDM2 interaction. Ionizing radiation induces p53-dependent MDM2 gene transcription that, in turn, inhibits p53 transcriptional activity, favouring its nuclear export and stimulating its degradation. In light of the observation that in many human tumours the inadequate function of p53 is the result of MDM2 over-expression, several authors have considered as an attractive therapeutic strategy to activate p53 signalling in tumours by inhibiting MDM2 activities or p53/MDM2 interaction. We retain that, by preventing the interaction p53/MDM2 with Nutlin, a small molecule that bind at the interface between these two proteins, the effectiveness of ionizing radiation treatment could be improved. Promising results have recently emerged from in vitro studies performed on laryngeal, prostate and lung cancer cell lines treated with Nutlin in combination with ionizing radiation. Based on these findings, we believe that the combined approach Nutlin/ionizing radiation should be further investigated for efficacy on both solid tumours and lymphoproliferative disorders as well as for side effects on normal cells and tissues. Therefore, the purpose of this review is to report the first results obtained by using Nutlins alone or in combination with other therapeutic agents on primary tumour cells, in vitro cell lines or tumour xenografts and to present the most recent advances in the understanding of the molecular mechanisms underlining ionizing radiation cytotoxicity and resistance.

Heart valve diseases are usually treated by surgical intervention addressed for the replacement of the damaged valve with a biosynthetic or mechanical prosthesis. Although this approach guarantees a good quality of life for patients, it is not free from drawbacks (structural deterioration, nonstructural dysfunction, and reintervention). To overcome these limitations, the heart valve tissue engineering (HVTE) is developing new strategies to synthesize novel types of valve substitutes, by identifying efficient sources of both ideal scaffolds and cells. In particular, a natural matrix, able to interact with cellular components, appears to be a suitable solution. On the other hand, the well-known Wharton's jelly mesenchymal stem cells (WJ-MSCs) plasticity, regenerative abilities, and their immunomodulatory capacities make them highly promising for HVTE applications. In the present study, we investigated the possibility to use porcine valve matrix to regenerate in vitro the valve endothelium by WJ-MSCs differentiated along the endothelial lineage, paralleled with human umbilical vein endothelial cells (HUVECs), used as positive control. Here, we were able to successfully decellularize porcine heart valves, which were then recellularized with both differentiated-WJ-MSCs and HUVECs. Data demonstrated that both cell types were able to reconstitute a cellular monolayer. Cells were able to positively interact with the natural matrix and demonstrated the surface expression of typical endothelial markers. Altogether, these data suggest that the interaction between a biological scaffold and WJ-MSCs allows the regeneration of a morphologically well-structured endothelium, opening new perspectives in the field of HVTE.

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Gonadotropin-releasing hormone antagonists (GnRH-ant) are routinely used to prevent premature luteinizing hormone (LH) surges in women undergoing in vitro fertilization (IVF) programs. GnRH-ant act by competitively binding GnRH receptors (GnRHr), leading to rapid pituitary suppression. GnRH-ant can also block extrapituitary GnRHr, including those present in ovary, placenta, and endometrium. A full understanding of the functional roles played by extrapitutary GnRHr, along with a better characterization of the possible reproductive consequences of their blockage may aid the refinement of controlled ovarian stimulation (COS) protocols using GnRHant. This review summarizes current research in the area, especially focusing on the possible impact of GnRH-ant on steroidogenesis, folliculogenesis and endometrial receptivity.

It is still undefined whether all the couples entering an assisted reproduction program should undergo to karyotype analysis. The present study was conducted to determine the prevalence of chromosomal abnormalities in a non-selected sample of 1,146 couples referred to assisted reproduction technologies (ART), and to analyze the outcome of pregnancies from couples in whom cytogenetic anomalies were detected. Irrespective of the infertility factor, fertilization was achieved by intracytoplasmic sperm injection (ICSI). A total number of 35 karyotype anomalies were diagnosed, corresponding to an abnormality frequency of 1.52% (1.83% for men and 1.22% for women). As could be expected, the majority of men presenting karyotype anomalies had a low sperm count. Among women, the majority of cytogenetic anomalies were detected in individual not presenting risk factors for aberrant karyotype. Around 41% of pregnancies achieved in couples presenting chromosomal anomalies ended in spontaneous abortion. Information on fetal karyotype was limited. No major malformations were observed among newborns from parents with abnormal karyotype. In consideration of the elevated frequency of pregnancy loss, it seems advisable to recommend that chromosomal analysis be performed in all couples undergoing ART. This with the aim of identifying patients that would possibly benefit from pre-implantation genetic diagnosis.