Adhesion force spectroscopy with nanostructured colloidal probes reveals nanotopography-dependent early mechanotransductive interactions at the cell membrane level.

Mechanosensing, the ability of cells to perceive and interpret the microenvironmental biophysical cues (such as the nanotopography), impacts strongly cellular behaviour through mechanotransductive processes and signalling. These events are predominantly mediated by integrins, the principal cellular adhesion receptors located at the cell/extracellular matrix (ECM) interface. Because of the typical piconewton force range and nanometre length scale of mechanotransductive interactions, achieving a detailed understanding of the spatiotemporal dynamics occurring at the cell/microenvironment interface is challenging; sophisticated interdisciplinary methodologies are required. Moreover, an accurate control over the nanotopographical features of the microenvironment is essential, in order to systematically investigate and precisely assess the influence of the different nanotopographical motifs on the mechanotransductive process. In this framework, we were able to study and quantify the impact of microenvironmental nanotopography on early cellular adhesion events by means of adhesion force spectroscopy based on innovative colloidal probes mimicking the nanotopography of natural ECMs. These probes provided the opportunity to detect nanotopography-specific modulations of the molecular clutch force loading dynamics and integrin clustering at the level of single binding events, in the critical time window of nascent adhesion formation. Following this approach, we found that the nanotopographical features are responsible for an excessive force loading in single adhesion sites after 20-60 s of interaction, causing a drop in the number of adhesion sites. However, by manganese treatment we demonstrated that the availability of activated integrins is a critical regulatory factor for these nanotopography-dependent dynamics.

Endocrinological features and endometrial morphology in climacteric women receiving hormone replacement therapy.

Prolactin (PRL), follicle stimulating hormone (FSH), luteinizing hormone (LH), oestrone (E1), and oestradiol (E2) levels were determined in 204 women who were receiving hormone replacement therapy for their climacteric symptoms. The changes in these hormone levels and the endometrial morphology were studied in order to determine the effects of the replacement therapy. The women were divided into two groups: the first group of 120 women was treated with conjugated oestrogens administered cyclically, plus norethisterone acetate. The second group of 84 women received oral oestriol succinate, also administered cyclically but without additional progestogens. The oestrogen-progestogen therapy resulted in a disappearance of the climacteric symptoms and a significant decrease of FSH and LH levels. Oestriol therapy was less effective than the conjugated oestrogens as a replacement therapy. Oestriol therapy also resulted in a less remarkable decrease of gonadotrophin levels. There were no significant changes in prolactin levels in either group of women. The endometrial histology did not change significantly after either of the two hormone replacement therapies.