Bisphenol M inhibits mouse oocyte maturation in vitro by disrupting cytoskeleton architecture and cell cycle processes.

Bisphenol M (BPM), an alternative to bisphenol A (BPA), is commonly utilized in various industrial applications. However, BPM does not represent a safe substitute for BPA due to its detrimental effects on living beings. This research aimed to assess the influence of BPM exposure on the in vitro maturation of mouse oocytes. The findings revealed that BPM exposure had a notable impact on the germinal vesicle breakdown (GVBD) rate and polar body extrusion (PBE) rate throughout the meiotic progression of mouse oocytes, ultimately resulting in meiotic arrest. Investigations demonstrated that oocytes exposure to BPM led to continued activation of spindle assembly checkpoint. Further studies revealed that securin and cyclin B1 could not be degraded in BPM-exposed oocytes, and meiosis could not realize the transition from the MI to the AI stage. Mechanistically, BPM exposure resulted in abnormal spindle assembly and disrupted chromosome alignment of oocytes. Additionally, abnormal positioning of microtubule organizing center-associated proteins implied that MTOC may be dysfunctional. Furthermore, an elevation in the acetylation level of α-tubulin in oocytes was observed after BPM treatment, leading to decreased microtubule stability. In addition to its impact on microtubules, BPM exposure led to a reduction in the expression of the actin, signifying the disruption of actin assembly. Further research indicated a heightened incidence of DNA damage in oocytes following BPM exposure. Besides, BPM exposure induced alterations in histone modifications. The outcomes of this experiment demonstrate that BPM exposure impairs oocyte quality and inhibits meiotic maturation of mouse oocytes.

Scale or effectiveness? The nonlinear impact of talent agglomeration on high-quality economic development in China.

Talent agglomeration serves as a vital pathway for achieving high-quality economic development. This paper, based on provincial panel data from China spanning 2011-2020, first analyses the impact of talent agglomeration on high-quality economic development from two dimensions: the talent agglomeration scale and effectiveness. Second, with innovation activity as a threshold variable, this paper explores the nonlinear impact of the talent agglomeration scale and effectiveness on economic efficiency improvement and economic structure optimization. This study finds that (1) the main driving force for high-quality economic development within the sample period comes from the talent agglomeration scale, while the promoting role of talent agglomeration effectiveness has not yet passed significant tests. (2) Under different levels of innovation activity, the talent agglomeration scale has a diminishing marginal utility impact on economic efficiency improvement and economic structure optimization; talent agglomeration effectiveness also has different nonlinear effects on economic efficiency improvement and economic structure optimization.

Aberrant expression of UBE2C in endometrial cancer and its correlation to epithelial mesenchymal transition.

Ubiquitin-conjugating enzyme E2C (UBE2C), its overexpression promotes tumor progression, is a key component of the ubiquitin conjugating proteasome complex. Epithelial-mesenchymal transition, which is lost epithelial features and gained mesenchymal features in some epithelial cancers, is involved in epithelial cancers' invasiveness and metastasis. The aim of this study is to detect the expression of UBE2C, WNT5α, and E-cad in endometrial cancer (EC) and their clinical significance. The expression of UBE2C, WNT5α, and ZEB1 in 125 cases EC tissues were detected by immunohistochemistry. Patients clinicopathological, demography, and follow-up data were also collected. Positive rates of expression of UBE2C and ZEB1 were significantly higher in EC tissues when compared with the control tissues. The positive expression of UBE2C and ZEB1 were positively associated with tumor stages, local lymph node metastasis, and International Federation of Gynecology and Obstetrics (FIGO) stages. The positive rate of expression of WNT5a was significantly lower in EC tissues when compared with the control tissues. And positive expression of E-cad was inversely related to tumor stages, lymph node metastasis stages, and FIGO stages. Kaplan-Meier analyses demonstrated that positive expression of UBE2C or ZEB1 for EC patients had unfavorably overall survival time when compared with patients with negative expression of UBE2C or ZEB1. And EC patients with positive expression of WNT5a had favorably overall survival time when compared with EC patients with negative expression of WNT5a. Multivariate analysis demonstrated that positive expression UBE2C, WNT5α, and ZEB1, as well as FIGO stages were independent prognostic factors for EC patients. UBE2C, ZEB1, and WNT5a should be considered promising biomarkers for EC patients' prognosis.

Saturated fatty acid promotes calcification via suppressing SIRT6 expression in vascular smooth muscle cells.

BACKGROUND: This study aims to investigate the effects of saturated free fatty acid on calcification and SIRT6 expression in vascular smooth muscle cells (VSMCs) and the role of SIRT6 in regulating VSMC calcification. METHODS: Sprague-Dawley rats were randomly allocated to two groups: rats with normal diet (ND) and high-fat diet (HFD) from 4 to 12 weeks. At 12 weeks, part rats randomly selected from ND and HFD were administrated with vitamin D3 and nicotine to establish a model of vascular calcification. Thoracic aortas were collected from treatment rats at 16 weeks for assaying vascular calcification and related protein expression. Primary VSMCs isolated from Sprague-Dawley rats were used for investigating the effects of palmitic acid on VSMCs' calcification, apoptosis and target protein expression. RESULTS: HFD-facilitated calcification in medial aorta, with decreased SIRT6 expression in VSMCs of aortas. Palmitic acid decreased SIRT6 expression while increased calcification, apoptosis and protein expression of BMP2 and RUNX2 in primary VSMCs. Overexpression of SIRT6 could, partially or completely, rescue the palmitic acid-induced elevation of calcification, apoptosis and expression of BMP2 and RUNX2. CONCLUSION: This study demonstrated that vascular calcification induced by HFD was linked to the palmitic acid-induced downregulation of SIRT6. Overexpression of SIRT6 could decrease palmitic acid-induced calcification and apoptosis in VSMCs.

Hypoxia regulates fibrosis-related genes via histone lactylation in the placentas of patients with preeclampsia.

BACKGROUND: Histone lactylation, a novel epigenetic modification induced by hypoxia and lactate, plays an important role in regulating gene expression. However, the role of histone lactylation in the pathogenesis of preeclampsia remains unknown. METHODS: Placentas from preeclamptic patients and control pregnant women were collected for protein immunoassay to detect the expression level of histone lactylation, and two trophoblast cell lines were used to simulate the effect of histone lactylation on genes. RESULTS: We found that lactate and histone lactylation levels were increased in preeclamptic placentas. In vitro, hypoxia was demonstrated to induce histone lactylation by promoting the production of lactate in human-trophoblast-derived cell line (HTR-8/SVneo) and human first-trimester extravillous trophoblast cell line (TEV-1) cells. In addition, 152 genes were found to be upregulated by both hypoxia exposure and sodium l-lactate treatment in HTR-8/SVneo cells. These genes were mainly enriched in the pathways including the response to hypoxia, cell migration and focal adhesion. Among the 152 genes, nine were upregulated in preeclamptic placentas. Most noteworthy, two upregulated fibrosis-related genes, FN1 and SERPINE1, were promoted by hypoxia through histone lactylation mediated by the production of lactate. CONCLUSIONS: The present study demonstrated the elevated levels of histone lactylation in preeclamptic placentas and identified fibrosis-related genes that were promoted by histone lactylation induced by hypoxia in trophoblast cells, which provides novel insights into the mechanism of placental dysfunction in preeclampsia.

Expression profiles and functions of ferroptosis-related genes in the placental tissue samples of early- and late-onset preeclampsia patients.

BACKGROUND: The accumulation of reactive oxygen species (ROS) resulting from upregulated levels of oxidative stress is commonly implicated in preeclampsia (PE). Ferroptosis is a novel form of iron-dependent cell death instigated by lipid peroxidation that likely plays an important role in PE pathogenesis. This study aimed to investigate the expression profiles and functions of ferroptosis-related genes (FRGs) in early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE). METHODS: Gene expression data and clinical information were downloaded from the Gene Expression Omnibus (GEO) database. The "limma" R package was used to screen differentially expressed genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network analyses were conducted to investigate the bioinformatics functions and molecular interactions of significantly different FRGs. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to verify the expression of hub FRGs in PE. RESULTS: A total of 4215 differentially expressed genes (DEGs) were identified between EOPE and preterm cases while 556 DEGs were found between LOPE and term controls. Twenty significantly different FRGs were identified in EOPE subtypes, while only 3 FRGs were identified in LOPE subtypes. Functional enrichment analysis revealed that the differentially expressed FRGs were mainly involved in EOPE and enriched in hypoxia- and iron-related pathways, such as the response to hypoxia, iron homeostasis and iron ion binding process. PPI network analysis and verification by RT-qPCR resulted in the identification of the following five FRGs of interest: FTH1, HIF1A, FTL, MAPK8 and PLIN2. CONCLUSIONS: EOPE and LOPE have distinct underlying molecular mechanisms, and ferroptosis may be mainly implicated in the pathogenesis of EOPE. Further studies are necessary for deeper inquiry into placental ferroptosis and its role in the pathogenesis of EOPE.

Alteration of vaginal microbiota in patients with recurrent miscarriage.

The aim of this study was to characterise the structure of vaginal microbiota in unexplained recurrent miscarriage (RM). The vaginal bacterial communities of 16 patients with RM and 20 healthy volunteers were sampled. Then, the microbiomes of bacterial profiles of RM patients and healthy volunteers were compared by sequencing the V3-V4 regions of the bacterial 16S ribosomal RNA gene using the Illumina MiSeq platform (Illumina, San Diego, CA). Taxonomic analysis demonstrated that abundance of Lactobacillus and Gardnerella were significantly different between the RM and control groups. Furthermore, at the genus level, Lactobacillus was the most dominant genus in the two groups. Statistically significant differences were observed in three genera between RM and control groups. In the control group, two bacterial taxa were significantly more abundant (Lactobacillus and Gardnerella), while only one taxon was overrepresented in the RM group (Atopobium). These present findings provide experimental evidence supporting vaginal microbiota dysbiosis in women with RM.Impact statementWhat is already known on this subject? Currently, bacterial vaginosis is thought to be mainly due to the vaginal dysbacteriosis, which can induce unexplained recurrent miscarriage, premature rupture of membranes, low birth weight premature birth, premature birth, chorioamnionitis and series of diseases.What do the results of this study add? The current study demonstrated that Lactobacillus and Gardnerella were significantly decreased in RM patients compared to healthy control, while Atopobium was overrepresented in the RM group.What are the implications of these findings for clinical practice and/or further research? Clinically, women with RM might benefit from vaginal microbiota treatment, adjuvant therapy with Lactobacillus-based live biotherapeutics.

Fucoxanthin induces apoptosis in human cervical cancer cell line HeLa via PI3K/Akt pathway.

Cervical cancer (CC) is a malignant neoplasm arising from cells originating in the cervix uteri, among the top causes of death from cancer in women. In a gene expression profiling study of metabolic response to treatment, PI3K/Akt signaling pathway are associated with the development of CC. A common mechanism of Akt activation seen in cancer types is alterations in the upstream regulators of Akt such as phosphatidylinositol 3-kinase (PI3K), which is overexpressed in cervical cancer tissues, and leads to phosphorylation of Akt. Both PI3K and Akt inhibitors exist and may be therapeutically valuable. In the present study, we use MTT assay and western blot for the high-throughput screening to select specific inhibitors of PI3K/Akt signaling pathway, and then obtain fucoxanthin. Fucoxanthin is a water-soluble dietary fiber, taken from the unique slimy component of alginic cells. Various studies have pointed out that fucoxanthin is very effective for the treatment of cancer. Our results have shown that fucoxanthin induced a significant apoptosis of HeLa cells, compared with other candidates. After treatment with fucoxanthin for 24 h, the level of phosphorylation was inhibited in a dose-dependent manner, and the proteins of apoptotic markers were changed in HeLa cells. And fucoxanthin could suppress tumor growth in vivo. In addition, the mitochondrial signal transduction pathway maybe was involved in its mechanism and NF-κB activation was decreased after treatment with fucoxanthin. Therefore, fucoxanthin may be used as anti-cervical cancer drugs in the future.