Protective effects of a SIRT1 inhibitor on primordial follicle activation and growth induced by cyclophosphamide: insights from a bovine in vitro folliculogenesis system

Purpose: Although oncological advances have improved survival rates of female cancer patients, they often suffer a reduced fertility due to treatment side effects. In the present study, we evaluated the potential fertoprotective effects of the specific inhibitor of SIRT1, EX-527, on the gonadotoxic action exerted by cyclophosphamide (CPM) on loss of primordial follicles (PFs). Methods: The effects of the CPM metabolite phosphoramide mustard (PM) on follicle activation, growth and viability and the protective action of EX-527 against PM effects were evaluated on bovine ovarian cortical strips in vitro cultured for 1 or 6 days. To understand whether PFs exposed to PM plus EX-527 were able to activate and grow to the secondary stage after suspension of the treatment, strips cultured for 3 days in PM plus EX-527 for 3 days were transferred to plain medium until day 6. Follicle growth and health were evaluated through histology and viability assay at a confocal microscope. In order to investigate the molecular pathways underlying the ovarian response to PM in the presence of EX-527, we analysed the protein level of SIRT1, HuR, PARP1 and SOD2 after 1 day of in vitro culture. Results: We found that (1) PM, the main CPM active metabolite, promotes PF activation; (2) the ovarian stress response induced by PM includes a SIRT1-dependent pathway; and (3) EX-527 reduces PF activation and growth induced by PM. Conclusion: SIRT1 can represent a candidate molecule to be targeted to protect ovarian follicles from alkylating agents and EX-527 could represent a potential fertoprotective agent for cancer patients

Social cognition in people with schizophrenia: A cluster-analytic approach

Background The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. Method A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. Results We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. Conclusions If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person

Social cognition in people with schizophrenia: A cluster-analytic approach

Background The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. Method A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. Results We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. Conclusions If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person

Crossing Conceptual Boundaries XI, Winter 2021

ISSN: 2041-9090 Crossing Conceptual Boundaries PhD Annual Yearbook New Series Volume XI A peer-reviewed graduate publication, School of Social Sciences, UEL, U

Cryopreservation and ossidative stress in reproductive cells

In spite of the optimisation of cryopreservation protocols, post-thawing trauma to mammalian gametes cannot be completely avoided. Based on recent literature, cellular cryodamage in reproductive cells has been extensively characterised in terms of changes in the cell structure, whereas biochemical alterations have been poorly investigated. The present paper reviews the current knowledge about the involvement of oxidative stress in frozen-thawed cells by considering the most relevant studies in sperm and oocytes. Recognising that spermatozoa are highly susceptible to oxidative damage induced by cryopreservation, the need for further research is highlighted in order to understand whether changes in the redox state have a role in the reduced developmental potential of cryopreserved human reproductive cells

XVII Congresso Nazionale AIBG, Associazione Italiana di Biologia e Genetica Generale e Molecolare Atti del Congresso, 30 settembre - 1 ottobre 2016 Cagliari

Chemotherapy regimens based on cyclophosphamide (CPM) severely impacts fertility in women. CPM activates a damage response that suggests the involvement of oxidative stress (OS). In the ovary, this drug stimulates activation and premature loss of follicle reserve by activating PI3K/PTEN/AKT pathway throughout phosphorylation and inhibition of FOXO3a (Roness et al., 2014). In female germ cells, FOXO3a is also a component of an OS adaptive response under SIRT1 control (Di Emidio et al., 2014). This work investigates whether oral administration of saffron­derived crocetin, a carotenoid with antioxidant and antitumor properties, affects ovarian early response to CPM and prevents gonadotoxicity in female mice. Eighteen CD1 female mice received a single intraperitoneal injection of PBS (CTRL), or CPM (100mg/kg) or crocetin (100mg/Kg) per os for fifteen days prior to CPM. We found that follicle loss in CPM­mice assessed at 7 days post­CPM was associated with an early increase of SIRT1 expression along with decrease of mitochondrial superoxide dismutase (SOD2) and mitochondrial biogenesis activator PGC1alpha at 24 hr post­CPM. Crocetin administration significantly decreased CPM­induced follicles loss and prevented early CPM­damage response. In crocetin+CPM mice, the pattern of expression of pFOXO3a, pAKT and SIRT1 were similar to control mice and increased levels of SOD2 and PGC1alpha were observed suggesting that modulation of redox balance may help the ovary counteracting ovarian damage by CPM. Our results increase the knowledge of mechanisms underlying ovarian damage by CPM and will be helpful to develop new therapeutic opportunities