Circulating miRNAs as a Tool for Early Diagnosis of Endometrial Cancer-Implications for the Fertility-Sparing Process: Clinical, Biological, and Legal Aspects

This review article explores the possibility of developing an integrated approach to the management of the different needs of endometrial cancer (EC) patients seeking to become pregnant. Life preservation of the woman, health preservation of the baby, a precocious and-as much as possible-minimally invasive characterization of the health and fertility parameters of the patient, together with the concerns regarding the obstetric, neonatal, and adult health risks of the children conceived via assisted reproductive techniques (ART) are all essential aspects of the problem to be taken into consideration, yet the possibility to harmonize such needs through a concerted and integrated approach is still very challenging. This review aims to illustrate the main features of EC and how it affects the normal physiology of pre-menopausal women. We also focus on the prospect of a miR-based, molecular evaluation of patient health status, including both EC early diagnosis and staging and, similarly, the receptivity of the woman, discussing the possible evaluation of both aspects using a single specific panel of circulating miRs in the patient, thus allowing a relatively fast, non-invasive testing with a significantly reduced margin of error. Finally, the ethical and legal/regulatory aspects of such innovative techniques require not only a risk-benefit analysis; respect for patient autonomy and equitable health care access allocation are fundamental issues as well

Circulating miRNAs as a Tool for Early Diagnosis of Endometrial Cancer—Implications for the Fertility-Sparing Process: Clinical, Biological, and Legal Aspects

This review article explores the possibility of developing an integrated approach to the management of the different needs of endometrial cancer (EC) patients seeking to become pregnant. Life preservation of the woman, health preservation of the baby, a precocious and—as much as possible—minimally invasive characterization of the health and fertility parameters of the patient, together with the concerns regarding the obstetric, neonatal, and adult health risks of the children conceived via assisted reproductive techniques (ART) are all essential aspects of the problem to be taken into consideration, yet the possibility to harmonize such needs through a concerted and integrated approach is still very challenging. This review aims to illustrate the main features of EC and how it affects the normal physiology of pre-menopausal women. We also focus on the prospect of a miR-based, molecular evaluation of patient health status, including both EC early diagnosis and staging and, similarly, the receptivity of the woman, discussing the possible evaluation of both aspects using a single specific panel of circulating miRs in the patient, thus allowing a relatively fast, non-invasive testing with a significantly reduced margin of error. Finally, the ethical and legal/regulatory aspects of such innovative techniques require not only a risk-benefit analysis; respect for patient autonomy and equitable health care access allocation are fundamental issues as well

The role of number of copies, structure, behavior and copy number variations (CNV) of the Y chromosome in male infertility

The World Health Organization (WHO) defines infertility as the inability of a sexually active, non-contracepting couple to achieve spontaneous pregnancy within one year. Statistics show that the two sexes are equally at risk. Several causes may be responsible for male infertility; however, in 30–40% of cases a diagnosis of idiopathic male infertility is made in men with normal urogenital anatomy, no history of familial fertility-related diseases and a normal panel of values as for endocrine, genetic and biochemical markers. Idiopathic male infertility may be the result of gene/environment interactions, genetic and epigenetic abnormalities. Numerical and structural anomalies of the Y chromosome represent a minor yet significant proportion and are the topic discussed in this review. We searched the PubMed database and major search engines for reports about Y-linked male infertility. We present cases of Y-linked male infertility in terms of (i) anomalies of the Y chromosome structure/number; (ii) Y chromosome misbehavior in a normal genetic background; (iii) Y chromosome copy number variations (CNVs). We discuss possible explanations of male infertility caused by mutations, lower or higher number of copies of otherwise wild type, Y-linked sequences. Despite Y chromosome structural anomalies are not a major cause of male infertility, in case of negative results and of normal DNA sequencing of the ascertained genes causing infertility and mapping on this chromosome, we recommend an analysis of the karyotype integrity in all cases of idiopathic fertility impairment, with an emphasis on the structure and number of this chromosome

Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration.

The epicardium and its derivatives provide trophic and structural support for the developing and adult heart. Here we tested the ability of human embryonic stem cell (hESC)-derived epicardium to augment the structure and function of engineered heart tissue in vitro and to improve efficacy of hESC-cardiomyocyte grafts in infarcted athymic rat hearts. Epicardial cells markedly enhanced the contractility, myofibril structure and calcium handling of human engineered heart tissues, while reducing passive stiffness compared with mesenchymal stromal cells. Transplanted epicardial cells formed persistent fibroblast grafts in infarcted hearts. Cotransplantation of hESC-derived epicardial cells and cardiomyocytes doubled graft cardiomyocyte proliferation rates in vivo, resulting in 2.6-fold greater cardiac graft size and simultaneously augmenting graft and host vascularization. Notably, cotransplantation improved systolic function compared with hearts receiving either cardiomyocytes alone, epicardial cells alone or vehicle. The ability of epicardial cells to enhance cardiac graft size and function makes them a promising adjuvant therapeutic for cardiac repair.: This work was supported by the British Heart Foundation (BHF; Grants NH/11/1/28922, G1000847, FS/13/29/30024 and FS/18/46/33663), Oxford-Cambridge Centre for Regenerative Medicine (RM/13/3/30159), the UK Medical Research Council (MRC) and the Cambridge Hospitals National Institute for Health Research Biomedical Research Centre funding (SS), as well as National Institutes of Health Grants P01HL094374, P01GM081619, R01HL12836 and a grant from the Fondation Leducq Transatlantic Network of Excellence (CEM). J.B. was supported by a Cambridge National Institute for Health Research Biomedical Research Centre Cardiovascular Clinical Research Fellowship and subsequently, by a BHF Studentship (Grant FS/13/65/30441). DI received a University of Cambridge Commonwealth Scholarship. LG is supported by BHF Award RM/l3/3/30159 and LPO is funded by a Wellcome Trust Fellowship (203568/Z/16/Z). NF was supported by BHF grants RG/13/14/30314. NL was supported by the Biotechnology and Biological Sciences Research Council (Institute Strategic Programmes BBS/E/B/000C0419 and BBS/E/B/000C0434). SS and MB were supported by the British Heart Foundation Centre for Cardiovascular Research Excellence. Core support was provided by the Wellcome-MRC Cambridge Stem Cell Institute (203151/Z/16/Z), The authors thank Osiris for provision of the primary mesenchymal stem cells (59

Intrinsically disordered proteins and structured proteins with intrinsically disordered regions have different functional roles in the cell

Many studies about classification and the functional annotation of intrinsically disordered proteins (IDPs) are based on either the occurrence of long disordered regions or the fraction of disordered residues in the sequence. Taking into account both criteria we separate the human proteome, taken as a case study, into three variants of proteins: i) ordered proteins (ORDPs), ii) structured proteins with intrinsically disordered regions (IDPRs), and iii) intrinsi- cally disordered proteins (IDPs). The focus of this work is on the different functional roles of IDPs and IDPRs, which up until now have been generally considered as a whole. Previous studies assigned a large set of functional roles to the general category of IDPs. We show here that IDPs and IDPRs have non-overlapping functional spectra, play different roles in human diseases, and deserve to be treated as distinct categories of proteins. IDPs enrich only a few classes, functions, and processes: nucleic acid binding proteins, chromatin bind- ing proteins, transcription factors, and developmental processes. In contrast, IDPRs are spread over several functional protein classes and GO annotations which they partly share with ORDPs. As regards to diseases, we observe that IDPs enrich only cancer-related pro- teins, at variance with previous results reporting that IDPs are widespread also in cardiovas- cular and neurodegenerative pathologies. Overall, the operational separation of IDPRs from IDPs is relevant towards correct estimates of the occurrence of intrinsically disordered pro- teins in genome-wide studies and in the understanding of the functional spectra associated to different flavors of protein disorder

The chemical composition of the aerial parts essential oil of Pulicaria odora (L.) Rchb. growing in Sicily (Italy)

The genus Pulicaria Gaertn. (Asteraceae) comprises more than ninety-two species as annual or perennial herbs or small shrubs, distributed in Africa, Europe, and Asia, and concentrated mainly in the Mediterranean region. Several species have been used in the traditional medicine of many countries. In the present study the chemical composition of the essential oil from aerial parts of Pulicaria odora (L.) Rchb., present in the Mediterranean region and collected in Sicily, was analysed by GC-MS. No papers have been previously published on the essential oil of the aerial part of this species. The result showed the presence of large quantity of carbonyl compounds (25.29%), oxygenated sesquiterpenes (23.28%) and thymol derivatives (16.76%). Chemical considerations with respect of other oils of Pulicaria taxa were carried out

The chemical composition of the aerial parts' essential oil of Nepeta apuleji Ucria (Lamiaceae) growing in Sicily (Italy)

The genus Nepeta L. (Lamiaceae) comprises about 300 species as annual or perennial herbs or small shrubs, spread in central and southern Europe, the Near East, central and southern Asia, and some areas of Africa. Several species have been used in the traditional medicine. In the present study, the chemical composition of the essential oils from aerial parts of two populations of Nepeta apuleji Ucria collected in Sicily, a rare species, growing also in South Spain and NW Africa, were analysed by GC-MS. No one has been previously worked and published on the essential oil of this species. Main constituents of the two oils of the two populations were the monoterpenes beta-pinene (11.6-6.3%) and gamma-terpinene (9.4-5.0%), and the sesquiterpenes beta-caryophyllene (11.9-9.8%) and germacrene D (1.8-13.0%). The chemical profile of the two essential oils presented herein and they compared with previously investigated Nepeta taxa oils, reported in the article

Chemical composition of the essential oils of three taxa of Cytisus growing wild in Sicily, Italy

The genus Cytisus is native Canary Islands, Europe to Mediterranean, Morocco, Algeria and Tunisia and several species of the genus are used in folk medicine of different countries. In this work the chemical composition of the essential oils from the aerial parts of three taxa of this genus growing wild in Sicily, Cytisus scoparius (L.) Link, C. villosus Pourr. and C. aeolicus Guss., has been investigated. No one report has been published on the Sicilian accession of the former two species, and, at the best of our knowledge, C. aeolicus is devoid of any chemical investigation. Cytisus scoparius and C. aeolicus essential oils have similar composition characterised by the occurrence of almost the same amount of compounds belonging to "other" class (59.5-52.0%) and carbonyl compounds (22.2-19.6%). Cytisus villosus showed a different composition with hydrocarbons as the main class (52.0%), totally absent in the other two species

The chemical composition of the aerial parts' essential oil of Cynoglossum clandestinum Desf. growing in Sicily, Italy

Cynoglossum L. is a taxonomically difficult genus belonging to the Boraginaceae family, distributed in Asia, Europe, mainly in Turkey, and in the Mediterranean region. Plants of this genus are used against various diseases in the ethnomedicine of several countries. In the present study, the chemical composition of the essential oil was obtained from the hydrodistillation of aerial parts of the Sicilian accession of Cynoglossum clandestinum Desf. was analysed by GC and GC-MS. The main constituents of the essential oil were aldehydes and ketones (69.9%) with nonanal (18.9%), 4-sec-butoxy-2-butanone (18.1%), and 3-methyl-butanal (13.1%) as main metabolites. No one paper has been previously published on the essential oil of this species, and there is a lack of studies also in the near related genera. The aim of this work is in fact, to study a species that has never been investigated, and through this, try to help place it within the Boraginaceae family