Is fetal gender associated with adverse perinatal outcome in intrauterine growth restriction (IUGR)?

OBJECTIVE: The purpose of this study was to determine if there is a difference in perinatal outcome by gender among growth-restricted fetuses. STUDY DESIGN: This was a retrospective cohort study of intrauterine growth restriction (IUGR) singleton pregnancies over a 5-year period. Clinical outcomes compared by gender included preterm delivery, perinatal mortality (PNM), respiratory distress syndrome (RDS), grade 3 or 4 intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and periventricular leukomalacia (PVL). Statistical analysis included bivariate and multivariable techniques. RESULTS: Seven hundred and twenty-seven singleton pregnancies with IUGR were identified. Three hundred and forty-six (47.6%) were males. Birth weight was similar between the groups. After adjusting for maternal demographics, medical history, gestational age, mode of delivery, and antenatal corticosteroids, adverse perinatal outcomes were similar between the groups. Severity of outcomes was also similar between males and females (P = .66). CONCLUSION: Male fetuses with IUGR have similar outcomes when compared with female IUGR fetuses. Gender does not play a role in perinatal outcome in the setting of fetal growth restriction

The emergence of new psychoactive substance (NPS) benzodiazepines: a review

The market for new psychoactive substances has increased markedly in recent years and there is now a steady stream of compounds appearing every year. Benzodiazepines consist of only a fraction of the total number of these compounds but their use and misuse has rapidly increased. Some of these benzodiazepines have only been patented, some of them have not been previously synthesised and the majority have never undergone clinical trials or tests. Despite their structural and chemical similarity, large differences exist between the benzodiazepines in their pharmacokinetic parameters and metabolic pathways and so they are not easily comparable. As benzodiazepines have been clinically used since the 1960s many analytical methods exist to quantify them in a variety of biological matrices and it is expected that these methods would also be suitable for the detection of benzodiazepines that are new psychoactive substances. Illicitly obtained benzodiazepines have been found to contain a wide range of compounds such as opiates which presents a problem since the use of them in conjunction with each other can lead to respiratory depression and death. The aim of this review is to collate the available information on these benzodiazepines and to provide a starting point for the further investigation of their pharmacokinetics which is clearly required

Le complexe de remodelage de la chromatine CHD4/NuRD associe régulation épigénétique, flux glycolytique et prolifération dans les cellules de mélanome et d’autres cancers

The Nucleosome Remodelling and Deacetylation (NuRD) complex is an epigenetic regulator of gene expression that includes two mutually exclusive ATPase subunits CHD3 and CHD4. Our results show that NuRD associates with essential melanoma cell transcription factors namely MITF and SOX10. However, despite their physical association and genomic co-localization, CHD4-NuRD does not appear to act as a cofactor for MITF or SOX10 regulated gene expression. Nevertheless, CHD4 silencing leads to a slow growth phenotype and de-represses the expression of PADI1 (Protein Arginine DeIminase 1) and PADI3, two enzymes involved in converting arginines to citrullines in melanoma and multiple types of cancer cells. Increased expression of PADI1 and PADI3 enhances citrullination of arginines within the key glycolytic regulatory enzyme PKM2 then promoting excessive glycolysis, lowering ATP levels and slowing down proliferation. PKM2 citrullination lowers its sensitivity to allosteric inhibitors thus shifting equilibrium towards allosteric activators thereby bypassing the normal physiological regulation of glycolysis. Overall, our results lead to describe a novel pathway linking, epigenetic regulation of PADI1 and PADI3 expression by CHD4/NuRD and reprogramming of PKM2 allosteric regulation through arginines citrullination, to glycolytic flux and cancer cell proliferation.Le complexe de remodelage de la chromatine NuRD, composé des sous-unités catalytiques CHD3 et CHD4, est un régulateur épigénétique de l’expression génique. Nos résultats montrent que NuRD s’associe avec les facteurs de transcription essentiels du mélanome que sont MITF et SOX10. Cependant, malgré une association physique et une co-localisation génomique, CHD4/NuRD ne semble pas agir comme un cofacteur important pour MITF ou SOX10. Néanmoins, la répression de CHD4 conduit à un ralentissement de la prolifération et déréprime l’expression des enzymes PADI1 et PADI3 dans les cellules de mélanome ainsi que dans de nombreux types de cellules cancéreuses. Ainsi, l’induction de ces enzymes, responsables de la conversion des arginines en citrullines, entraîne la citrullination spécifique de PKM2, une enzyme glycolytique essentielle, diminuant ainsi sa sensibilité aux inhibiteurs allostériques, et donc altérant l’équilibre physiologique entre activateurs et inhibiteurs de l’enzyme. L’ensemble de ce travail de thèse a permis de mettre en évidence une nouvelle voie reliant, d’une part la régulation épigénétique de l’expression de PADI1 et PADI3 par CHD4/NuRD ainsi que la reprogrammation de la régulation allostérique de PKM2 via la citrullination d’arginines, au flux glycolytique et au contrôle de la prolifération des cellules cancéreuses d’autre part

Regulation of glycolysis and cancer cell proliferation by PKM2 citrullination

International audienceConversion of peptidyl-arginine to peptidyl citrulline, known as citrullination, is a posttranslational protein modification catalysed by the PADI (Protein Arginine Deiminase) family of enzymes. PADI1 and PADI3 catalyse citrullination of arginine 106 in the glycolytic enzyme pyruvate kinase M2 modulating its allosteric regulation, glycolysis and cancer cell proliferation

Peptide library purity by mass spectrometry (Coassolo et al., 2023)

The library was produced as crude peptides at a quantity of 1-4mg with a C-terminal amidation as the only modification for comparative studies between peptides. Identity and purity of the peptides used in vivo were verified by LC-MS using an Agilent Q-TOF LC–MS instrument. The raw mass spectrometry (MS1 spectra) data are deposited as Agilent .d file for the six synthesized peptides used in the in vivo screen (BRINP2_peptide 5.d, EDIL3_peptide 5.d, FGF3_peptide 4.d, FGF5_peptide 5.d, FSTL4_peptide 3.d and SCG1_peptide 9.d).THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Régulation épigénétique de l’expression génique dans le mélanome malin

Le mélanome malin est un cancer très agressif capable de générer des métastases à des stades précoces de son développement. La transformation oncogénique des mélanocytes résulte principalement de mutations dans BRAF, NRAS ou NF1 qui activent de façon constitutive la voie de signalisation des MAP kinases et la prolifération cellulaire. D’autres mutations inactivant CDKN2A ou PTEN, des mutations activatrices dans la voie béta-caténine ainsi que des altérations de l’épigénome permettent aux cellules d’échapper à la sénescence induite par les oncogènes. Quelle que soit la nature des mutations activatrices, la physiologie des cellules de mélanome est régulée par des facteurs de transcription et des mécanismes épigénétiques. MITF (Microphthalmia-associated Transcription Factor) et SOX10 sont deux facteurs de transcription jouant également un rôle essentiel dans la physiologie des mélanocytes normaux. Par une combinaison d’approches incluant la génétique de la souris, la biochimie et la génomique à haut débit, nous avons identifié des protéines partenaires de MITF et analysé les mécanismes de régulation de la transcription par MITF, SOX10 et leurs partenaires