CYTOCHROME P450 3A13 AND ENDOTHELIN JOINTLY MEDIATE DUCTUS ARTERIOSUS CONSTRICTION TO OXYGEN IN MICE

The fetal ductus arteriosus (DA) contracts to oxygen, and this feature, maturing through gestation, is considered important for its closure at birth. We have previously obtained evidence of the involvement of cytochrome P-450, possibly of the 3A subfamily (CYP3A), in oxygen sensing and have also identified endothelin (ET)-1 as the attendant effector for the contraction. Here, we examined comparatively wild-type (WT) and CYP3Anull (Cyp3a(-/-)) mice for direct validation of this concept. We found that the CYP3A subfamily is represented only by CYP3A13 in the WT DA. CYP3A13 was also detected in the DA by immunofluorescence microscopy, being primarily colocalized with the endoplasmic reticulum in both endothelial and muscle cells. However, a distinct signal was also evident in the plasma membrane. Isolated DAs from term WT animals developed a sustained contraction to oxygen with transient contractions superimposed. Conversely, no tonic response occurred in Cyp3a(-/-) DAs, whereas the phasic response persisted unabated. Oxygen did not contract the preterm WT DA but caused a full-fledged contraction after retinoic acid (RA) treatment. RA also promoted an oxygen contraction in the Cyp3a(-/-) DA. However, responses of RA-treated WT and Cyp3a(-/-) mice differed in that only the former abated with ET-1 suppression. This implies the existence of an alternative target for RA responsible for the oxygen-induced contraction in the absence of CYP3A13. In vivo, the DA was constricted in WT and Cyp3a(-/-) newborns, although with a tendency to be less narrowed in the mutant. We conclude that oxygen acts primarily through the complex CYP3A13 (sensor)/ET-1 (effector) and, in an accessory way, directly onto ET-1. However, even in the absence of CYP3A13, the DA may close postnatally thanks to the contribution of ET-1 and the likely involvement of compensating mechanism(s) identifiable with an alternative oxygen-sensing system and/or the withdrawal of relaxing influence(s) operating prenatally

Increasing cell culture density during a developmental window prevents fated rod precursors derailment toward hybrid rod-glia cells

: In proliferating multipotent retinal progenitors, transcription factors dynamics set the fate of postmitotic daughter cells, but postmitotic cell fate plasticity driven by extrinsic factors remains controversial. Transcriptome analysis reveals the concurrent expression by postmitotic rod precursors of genes critical for the Müller glia cell fate, which are rarely generated from terminally-dividing progenitors as a pair with rod precursors. By combining gene expression and functional characterisation in single cultured rod precursors, we identified a time-restricted window where increasing cell culture density switches off the expression of genes critical for Müller glial cells. Intriguingly, rod precursors in low cell culture density maintain the expression of genes of rod and glial cell fate and develop a mixed rod/Muller glial cells electrophysiological fingerprint, revealing rods derailment toward a hybrid rod-glial phenotype. The notion of cell culture density as an extrinsic factor critical for preventing rod-fated cells diversion toward a hybrid cell state may explain the occurrence of hybrid rod/MG cells in the adult retina and provide a strategy to improve engraftment yield in regenerative approaches to retinal degenerative disease by stabilising the fate of grafted rod precursors

Update of Laparoscopic Surgery in Borderline Ovarian Tumor: Systematic Review

Background: Borderline ovarian tumor (BOT) predominantly affects young women and is often diagnosed at an early stage. BOT accounts for 15% of all epithelial tumors. In this regard, a minimally invasive surgical approach and the ability to preserve fertility, without increasing the incidence of recurrences or worsening the prognosis, are crucial. This review aims to provide an update on the role and indications of laparoscopic surgery in BOTs. Methods: The electronic research was performed on Pubmed, Medline, and Embase. Articles published in the last 20 years (2004–2023) were included, and the following keywords were used: ‘borderline ovarian tumor’ and ‘laparoscopic surgery’, ‘borderline ovarian tumor’ and ‘minimally invasive surgery’, ‘borderline ovarian tumor’ and ‘fertility sparing’, ‘borderline ovarian tumor’ and ‘recurrence’ and ‘Borderline ovarian tumor’ and ‘relapse’. The agreement about potential relevance was reached by consensus of the researchers and according to PRISMA statement guidelines. We thoroughly reviewed all bibliographies to assess the inclusion of any further eligible studies. We excluded studies that did not align with the study’s objectives. Results: The electronic database search yielded 767 total studies. Of whom, 188 were published before 2004, 84 were case reports, and 45 were not in the English language. Of the remaining 450 studies, 148 were considered eligible for the study. We included 20 studies in this review. Conclusions: Despite the latest guidelines recommending an open approach for the treatment of BOT, the laparoscopic approach has gained popularity as a feasible and safe alternative. The use of an endo-bag, along with advanced laparoscopic skills, has made the minimally invasive approach increasingly safe, with oncological outcomes almost comparable to those of reference. Moreover, in the context of fertility-sparing surgery (FSS), laparoscopy seems to be associated with improved obstetrical outcomes, without detrimental effects on overall survival and disease-free survival. Therefore, the laparoscopic approach in the treatment of BOT appears to be a safe and effective option, especially in the case of FSS

A comprehensive molecular and morphological study of the effects of space flight on human capillary endothelial cells: sample quality assessment and preliminary results.

ESA (ESA ILSRA-2009-1026); ASI (contract no. 5681); Regione Toscana (POR FSE 2007-2013-FORTEC); Kayser Italia; Lions Club International, District 108LA, Toscana, Italy

Microgravity and space radiation inhibit autophagy in human capillary endothelial cells, through either opposite or synergistic effects on specific molecular pathways

Availability of data and materials: All transcriptome analysis raw data were deposited in GEO as GSE157937.Code availability: Not applicable.Microgravity and space radiation (SR) are two highly influential factors affecting humans in space flight (SF). Many health problems reported by astronauts derive from endothelial dysfunction and impaired homeostasis. Here, we describe the adaptive response of human, capillary endothelial cells to SF. Reference samples on the ground and at 1g onboard permitted discrimination between the contribution of microgravity and SR within the combined responses to SF. Cell softening and reduced motility occurred in SF cells, with a loss of actin stress fibers and a broader distribution of microtubules and intermediate filaments within the cytoplasm than in control cells. Furthermore, in space the number of primary cilia per cell increased and DNA repair mechanisms were found to be activated. Transcriptomics revealed the opposing effects of microgravity from SR for specific molecular pathways: SR, unlike microgravity, stimulated pathways for endothelial activation, such as hypoxia and inflammation, DNA repair and apoptosis, inhibiting autophagic flux and promoting an aged-like phenotype. Conversely, microgravity, unlike SR, activated pathways for metabolism and a pro-proliferative phenotype. Therefore, we suggest microgravity and SR should be considered separately to tailor effective countermeasures to protect astronauts’ health.European Space Agency (ESA ILSRA-2009-1026), Agenzia Spaziale Italiana (contract number 5681)

Platform based design of technical aids for independent living

Assistive technology (AT) market is soaring. Substantial outlay of small and medium enterprises to develop new products is often unbearable because of low recurrent costs return due to lack of scale economies. Most of assistive devices answer to a rather general architectural scheme and use standard consumer electronics. This suggested the design and implementation of a development platform for assistive devices, which makes possible to automate and speed up some steps of the project flow and obtain a cost effective final product complete emulator