Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-related liver disorder and may cause adverse perinatal outcomes. This large cross-sectional retrospective study aimed to eva...

Intrahepatic cholestasis of pregnancy (ICP) is a rare liver disease occurring during pregnancy that is characterized by disordered bile acid (BA) metabolism. It is related to adverse clinical outcomes in both the mother and fetus. Our aim was to evaluate the BA metabolism profiles in different types of ICP and investigate the association between specific BAs and perinatal complications in ICP patients. We consecutively evaluated 95 patients with ICP, in which 53 patients were diagnosed with early-onset ICP (EICP) and 42 patients were diagnosed with late-onset ICP (LICP). Concentrations of 15 BA components were detected using high-performance liquid chromatography tandem mass spectrometry. Clinical information was abstracted from the medical records. The percentage of conjugated bile acids increased in ICP patients. Specifically, taurocholic acid (TCA) accumulated in LICP patients, and glycocholic acid (GCA) predominated in EICP patients. A higher preterm birth incidence was observed among ICP patients. Albumin, total bile acids, total bilirubin and GCA percentage values at ICP diagnosis predicts 83.5% of preterm birth in EICP, and the percentage of TCA in total bile acids at ICP diagnosis predicts 93.2% of preterm birth in LICP. This analysis showed that the BA metabolism profiles of EICP and LICP were distinct. Increased hepatic load was positively correlated with preterm birth in EICP. An elevated TCA percentage in total bile acids provides a biomarker to predict preterm birth in LICP.

Ferroptosis induction through the suppression of glutathione peroxidase 4 (GPX4) and apoptosis-inducing factor mitochondria-associated 2 (AIFM2) has proven to be an effective approach in eliminating chemotherapy-resistant cells of various types. However, a comprehensive understanding of the roles of GPX4 and AIFM2 in acute myeloid leukemia (AML) has not yet been achieved. Using cBioPortal, DepMap, GEPIA, Metascape, and ONCOMINE, we compared the transcriptional expression, survival data, gene mutation, methylation, and network analyses of GPX4- and AIFM2-associated signaling pathways in AML. The results revealed that high expression levels of GPX4 and AIFM2 are associated with an adverse prognosis for AML patients. Overexpression of AIFM2 correlated with elevated mutation frequencies in NPM1 and DNMT3A. GPX4 upregulation modulated the following pathways: GO:0045333, cellular respiration; R-HSA-5389840, mitochondrial translation elongation; GO:0009060, aerobic respiration; R-HSA-9609507, protein localization; and R-HSA-8953854, metabolism of RNA. On the other hand, the overexpression of AIFM2 influenced the following processes: GO:0048704, embryonic skeletal system morphogenesis; GO:0021546, rhombomere development; GO:0009954, proximal/distal pattern formation; and GO:0048732, gland development. This study identifies the high expression of GPX4 and AIFM2 as novel biomarkers predicting a poor prognosis for AML patients. Furthermore, ferroptosis induction may improve the stratified treatment of AML.