Establishment of a novel glycolysis-immune-related diagnosis gene signature for endometriosis by machine learning.

PURPOSE: The objective of this study was to investigate the key glycolysis-related genes linked to immune cell infiltration in endometriosis and to develop a new endometriosis (EMS) predictive model. METHODS: A training set and a test set were created from the Gene Expression Omnibus (GEO) public database. We identified five glycolysis-related genes using least absolute shrinkage and selection operator (LASSO) regression and the random forest method. Then, we developed and tested a prediction model for EMS diagnosis. The CIBERSORT method was used to compare the infiltration of 22 different immune cells. We examined the relationship between key glycolysis-related genes and immune factors in the eutopic endometrium of women with endometriosis. In addition, Gene Ontology (GO)-based semantic similarity and logistic regression model analyses were used to investigate core genes. Reverse real-time quantitative PCR (RT-qPCR) of 5 target genes was analysed. RESULTS: The five glycolysis-related hub genes (CHPF, CITED2, GPC3, PDK3, ADH6) were used to establish a predictive model for EMS. In the training and test sets, the area under the curve (AUC) of the receiver operating characteristic curve (ROC) prediction model was 0.777, 0.824, and 0.774. Additionally, there was a remarkable difference in the immune environment between the EMS and control groups. Eventually, the five target genes were verified by RT-qPCR. CONCLUSION: The glycolysis-immune-based predictive model was established to forecast EMS patients' diagnosis, and a detailed comprehension of the interactions between endometriosis, glycolysis, and the immune system may be vital for the recognition of potential novel therapeutic approaches and targets for EMS patients.

Simvastatin attenuates diabetes mellitus erectile dysfunction in rats by miR-9-5p-regulated PDCD4.

DMED is a common complication of diabetes, for which new treatment methods are urgently required. Focused on DMED, the pharmacological mechanism of simvastatin (Sim) was probed. A model of DMED was made in rats with streptozotocin and orally medicated with Sim. Lentiviral vectors that interfere with miR-9-5p or PDCD4 were injected, and the erectile function, histopathology of cavernous tissue, and α-SMA expression were evaluated. Cavernous smooth muscle cells (CMSCs) obtained from DMED rats were treated with Sim and transfected with the plasmid vector that interferes with miR-9-5p or PDCD4 to observe cell viability and apoptosis. The binding relationship between miR-9-5p and PDCD4 was checked. After 8-week treatment with Sim, erectile function was improved and the corpus cavernosum injury was alleviated. Upregulating miR-9-5p or downregulating PDCD4 further improved erectile function and cavernous injury in rats. miR-9-5p targeted regulation of PDCD4. In vitro cell experiment results showed that Sim induced proliferation and reduced apoptosis of CSMCs by enhancing miR-9-5p-targeted regulating PDCD4 in vitro. Sim attenuates DMED in rats via miR-9-5p/PDCD4.

Expression and Clinical Significance of HIF-1α in Follicular Fluid and Granulosa Cells in Infertile PCOS Patients.

The present study aimed to determine the clinical predictive significance of HIF-1α in follicular development and assisted reproductive technology (ART). We collected follicular fluid (FF) and granulosa cells (GCs) from PCOS (polycystic ovary syndrome) patients (experimental group) and other patients who were infertile due to tubal factors or male factors (control group) with IVF/ICSI-ET. The localization and expression of HIF-1α in GCs were determined by immunofluorescence staining. HIF-1α protein and mRNA expression were detected by enzyme-linked immunosorbent assay and quantitative real-time PCR, respectively. To clarify the regulation of HIF-1α by TGF-ß1, we added the HIF-1α-specific blocker YC-1 to GCs. The serum AMH, LH, LH/FSH, testosterone, BMI and the number of oocytes retrieved in the PCOS group were significantly higher, while the cleavage rate was significantly lower, than those in the control group. HIF-1α protein was expressed in the cytoplasm of GCs. The expression of HIF-1α protein in the FF of the PCOS group was significantly lower than that in the control group. However, the expression of HIF-1α protein in GCs between the two groups was not significantly different. HIF-1α protein was highly expressed in large FF (follicular diameter ≥ 14 mm). Compared with the control group, the expression of HIF-1α mRNA in GCs of the PCOS group was significantly lower. The results showed a significant positive correlation between HIF-1α and TGF-ß1 expression. We found that both HIF-1α and TGF-ß1 were involved in the development of PCOS follicular development. The mutual regulation of HIF-1α and TGF-ß1 may be one of the important mechanisms of the occurrence and development of PCOS.