Novel cuproptosis-related prognostic gene profiles in preeclampsia.

BACKGROUND: Preeclampsia (PE) is a pregnancy-specific disorder with complex pathogenesis. Cuproptosis is a novel identified form of programmed cell death, however, the link between cuproptosis and clinical outcomes in PE is still not fully understood. In this study, we searched for cuproptosis-related genes (CRGs) in the placental tissues of normal and PE patients to clarify the importance of cuproptosis in the development of PE and provide potential predictive indicators for the occurrence of PE. METHODS: Using RNA sequencing data in the GEO database, we conducted functional enrichment analysis of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA), supported by linear regression model and operating characteristic curve (ROC) curve analysis, and summarized the role of CRGs in preeclampsia. RESULTS: A total of 2831 differentially expressed genes related to PE were screened through multiple database analyses. After further intersection with 19 reported CRGs, 5 CRGs have been closely associated with the pathogenesis of PE, including NFE2L2, PDHA1, PDHB, DLD and GLS. NFE2L2 was identified as a key central gene. Pearson correlation analysis showed that CRGs could be related to several maternal and fetal outcome factors, including the highest pregnancy blood pressure, placenta weight, umbilical blood flow pulsatility index (PI), and neonatal weight. Linear regression equation revealed that the expression of NFE2L2 is negatively correlated with the highest pregnancy blood pressure and umbilical blood flow PI but positively correlated with placental weight and neonatal weight. QRT-PCR showed that the expression of these CRGs was significantly lower in placental tissues. CONCLUSIONS: This cuproptosis pattern may be a potential prognostic factor in patients with PE and could provide new insights into disease progression.

IGF2BP2 enhances LincRNA01116 stability via m6 A: A potential biomarker and therapeutic target for patients with pre-eclampsia.

Pre-eclampsia (PE) is a serious complication in pregnant women characterized by failure of placental remodeling and is one of the primary causes of changes in the placental structure and function. The aberrant expression of long noncoding RNA is associated with the occurrence and progression of PE. This study found that linc01116 expression was significantly downregulated in PE patients and was related to poor uterine spiral artery remodeling. Knockdown of linc01116 remarkably decreased the angiogenesis of trophoblast cells in vitro and in vivo. Mechanistically, IGF2BP2 regulated linc01116 RNA stability via m6 A methylation. Bioinformatics and other experiments further revealed that linc01116 upregulates AAMP expression by adsorbing miR-210-3p in trophoblast cells. In conclusion, this study revealed the critical role of linc01116 in regulating trophoblast angiogenesis. Furthermore, the study provides new clues for detecting placental pathology in PE.

Downregulated DUXAP8 lncRNA impedes trophoblast cell proliferation and migration by epigenetically upregulating TFPI2 expression.

BACKGROUND: Preeclampsia (PE), a pregnancy complication characterized by new-onset hypertension and proteinuria during the second trimester, is the leading cause of neonatal and maternal morbidity and mortality. In the etiology of PE, failure of uterine spiral artery remodeling may be related to functioning abnormally of trophoblast cells, leading to the occurrence and progression of PE. Recently, long noncoding RNAs (lncRNAs) have been reported to play critical roles in PE nowadays. This study aimed to investigate the expression and functions of the TFPI2 pathway-related lncRNA DUXAP8. METHODS: DUXAP8 expression in the placenta from pregnancies was examined using qPCR. Then, the in vitro functions of DUXAP8 were investigated through MTT, EdU, colony, transwell, and flow cytometry experiments. The downstream gene expression profiles were assessed using RNA transcriptome sequencing analysis and verified using qPCR and western blot. Furthermore, Immunoprecipitation (RIP), chromatin immunoprecipitation (CHIP) and fluorescence in situ hybridization (FISH) were used to detect the interaction between lncDUXAP8/EZH2/TFPI2. RESULTS: The expression of lncRNA DUXAP8 in placenta of patients with eclampsia was significantly decreased. After knockout of DUXAP8, the proliferation and migration of trophoblasts were significantly decreased, and the percentage of apoptosis was increased. Flow cytometry showed that low expression of DUXAP8 increased the accumulation of cells in G2/M phase, while overexpression of DUXAP8 had the opposite effect. We also proved that DUXAP8 epigenetically inhibited TFPI2 expression by recruiting EZH2 and mediating H3K27me3 modification. CONCLUSION: Together, these resulting data clarify that aberrant expression of DUXAP8 is involved in the potential PE development and progress. Unraveling the role of DUXAP8 will provide novel insights into the pathogenesis of PE.

A novel regulatory mechanism network mediated by lncRNA TUG1 that induces the impairment of spiral artery remodeling in preeclampsia.

Preeclampsia (PE) is associated with maternal and fetal perinatal morbidity and mortality, which brings tremendous suffering and imposes an economic burden worldwide. The failure of uterine spiral artery remodeling may be related to the abnormal function of trophoblasts and lead to the occurrence and progression of PE. Aberrant expression of long non-coding RNAs (lncRNAs) is involved in the failure of uterine spiral artery remodeling. However, the regulation of lncRNA expression in PE is poorly characterized. Here, we reported that hypoxia-induced microRNA (miR)-218 inhibited the expression of lncRNA TUG1 by targeting FOXP1. Further RNA sequencing and mechanism analysis revealed that silencing of TUG1 increased the expression of DNA demethylase TET3 and proliferation-related DUSP family, including DUSP2, DUSP4, and DUSP5, via binding to SUV39H1 in the nucleus. Moreover, TUG1 modulated the DUSP family in vitro through a TET3-mediated epigenetic mechanism. Taken together, our results unmask a new regulatory network mediated by TUG1 as an essential determinant of the pathogenesis of PE, which regulates cell growth and possibly the occurrence and development of other diseases.

Silencing of AFAP1-AS1 lncRNA impairs cell proliferation and migration by epigenetically promoting DUSP5 expression in pre-eclampsia.

As a unique and common obstetric complication of pregnant women, pre-eclampsia (PE) has been the first leading cause of maternal and perinatal morbidity and mortality in the world. Mounting studies have demonstrated that an abnormality of long noncoding RNA (lncRNA) expression was related to the pathological process of PE. Here, we showed that lncRNA AFAP1-AS1 was markedly downregulated in pre-eclamptic placentas. We further investigated the mechanism underlying the regulatory role of AFAP1-AS1 in PE using human trophoblast cells. In vitro functional assays revealed that AFAP1-AS1 knockdown inhibited trophoblast proliferation, migration, and invasion. Moreover, AFAP1-AS1 interacts with EZH2 and inhibits DUSP5 expression through modulating H3K27m3 in the DUSP5 promoter of trophoblast cells, thus being involved in PE pathogenesis. Overall, these findings suggest that AFAP1-AS1 could potentially become a prognostic biomarker as well as a new therapeutic target for PE.

Liver X receptor ß regulates the development of the dentate gyrus and autistic-like behavior in the mouse.

The dentate gyrus (DG) of the hippocampus is a laminated brain region in which neurogenesis begins during early embryonic development and continues until adulthood. Recent studies have implicated that defects in the neurogenesis of the DG seem to be involved in the genesis of autism spectrum disorders (ASD)-like behaviors. Liver X receptor ß (LXRß) has recently emerged as an important transcription factor involved in the development of laminated CNS structures, but little is known about its role in the development of the DG. Here, we show that deletion of the LXRß in mice causes hypoplasia in the DG, including abnormalities in the formation of progenitor cells and granule cell differentiation. We also found that expression of Notch1, a central mediator of progenitor cell self-renewal, is reduced in LXRß-null mice. In addition, LXRß deletion in mice results in autistic-like behaviors, including abnormal social interaction and repetitive behavior. These data reveal a central role for LXRß in orchestrating the timely differentiation of neural progenitor cells within the DG, thereby providing a likely explanation for its association with the genesis of autism-related behaviors in LXRß-deficient mice.

Electrospinning Preparation of La-Doped SnO2 Hollow Nanofibers: An Improvement of Their Gas Sensing Properties.

SnO2 hollow nanofibers with different amount of La-doped were prepared by electrostatic spinning method. Their composition, morphology and structure were characterized by XRD, SEM, BET and XPS respectively and their gas sensing properties were also investigated. The results showed that the hollow nanofibers with the molar ratio of tin to La of 7% had the best sensitivity to ammonia of 500 ppm at the temperature of 300 °C, and the sensitivity value reached 480, which was 10 times that of pure SnO2. And its response time was also significantly shortened.

Stem-cell challenges in the treatment of Alzheimer's disease: a long way from bench to bedside.

Alzheimer's disease (AD) is the most prevalent type of dementia, and its neuropathology is characterized by deposition of insoluble ß-amyloid peptides, intracellular neurofibrillary tangles, and the loss of diverse neurons. Current pharmacological treatments for AD relieve symptoms without affecting the major pathological characteristics of the disease. Therefore, it is essential to develop new and effective therapies. Stem-cell types include tissue-specific stem cells, such as neural stem cells and mesenchymal stem cells, embryonic stem cells derived from blastocysts, and induced pluripotent stem cells (iPSCs) reprogrammed from somatic cells. Recent preclinical evidence suggests that stem cells can be used to treat or model AD. The mechanisms of stem cell based therapies for AD include stem cell mediated neuroprotection and trophic actions, antiamyloidogenesis, beneficial immune modulation, and the replacement of the lost neurons. iPSCs have been recently used to model AD, investigate sporadic and familial AD pathogenesis, and screen for anti-AD drugs. Although considerable progress has been achieved, a series of challenges must be overcome before stem cell based cell therapies are used clinically for AD patients. This review highlights the recent experimental and preclinical progress of stem-cell therapies for AD, and discusses the translational challenges of their clinical application.

Changing microbiome community structure and functional potential during permafrost thawing on the Tibetan Plateau.

Large amounts of carbon sequestered in permafrost on the Tibetan Plateau (TP) are becoming vulnerable to microbial decomposition in a warming world. However, knowledge about how the responsible microbial community responds to warming-induced permafrost thaw on the TP is still limited. This study aimed to conduct a comprehensive comparison of the microbial communities and their functional potential in the active layer of thawing permafrost on the TP. We found that the microbial communities were diverse and varied across soil profiles. The microbial diversity declined and the relative abundance of Chloroflexi, Bacteroidetes, Euryarchaeota, and Bathyarchaeota significantly increased with permafrost thawing. Moreover, warming reduced the similarity and stability of active layer microbial communities. The high-throughput qPCR results showed that the abundance of functional genes involved in liable carbon degradation and methanogenesis increased with permafrost thawing. Notably, the significantly increased mcrA gene abundance and the higher methanogens to methanotrophs ratio implied enhanced methanogenic activities during permafrost thawing. Overall, the composition and functional potentials of the active layer microbial community in the Tibetan permafrost region are susceptible to warming. These changes in the responsible microbial community may accelerate carbon degradation, particularly in the methane releases from alpine permafrost ecosystems on the TP.

Maternal and neonatal outcomes of repeated antepartum bleeding in 493 placenta previa cases: a retrospective study.

OBJECTIVE: To explore the effect of antepartum bleeding caused by PP on pregnancy outcomes. STUDY DESIGN: We retrospectively analyzed 493 pregnant women complicated with PP. Patients were divided into antepartum repeated bleeding and non-bleeding groups. Maternal characteristics and pregnancy outcomes were compared. RESULTS: The risk of antepartum hemorrhage was 2.038 times higher when gravidity was 5 (95% CI 1.104-3.760, p = .023). Pregnant women with a history of more than three intrauterine procedures had a 1.968 times higher risk of antepartum hemorrhage (95% CI 1.135-3,412, p = .016) compared to pregnant women without any intrauterine procedures. The risk of antepartum bleeding was found to be decreasing with the pregnancy advancing; When the placenta edge was noted to be over cervical os, the risk of antepartum bleeding was 4.385-fold than the low-lying plcaenta cases (95%CI2.454-8.372, p = .000). In the respect of maternal outcomes, the repeated bleeding group, the risk of emergency surgery was 7.213 times higher than elective surgery (95% CI 4.402-11.817, p = .000). As for the neonatal outcomes, the risk of asphyxia was 2.970 times and the risk of neonatal intensive care unit (NICU) admission was 2.542-fold higher in repeated bleeding group compared to non-bleeding group, respectively. CONCLUSIONS: Obstetricians should be aware of the increased risk of antepartum bleeding especially for ≤34 weeks and placenta edge over cervical os PP patients, they have a higher risk of antepartum bleeding. These women have higher possibility of emergency C-section and need preterm newborn resuscitation.