Objectives: The purpose of this study was to explore the effects of Erzhi Tiangui Granule (ETG) on DNA methyltransferases (DNMT) 1 protein expression in endometrium of infertile women with Kidney-yin Deficiency syndrome. Methods: A randomized, double-blinded, placebo-controlled clinical trial was conducted. Sixty-six (66) infertile patients who had Kidney-yin Deficiency syndrome and who were to undergo in vitro fertilization-embryo transfer (IVF-ET) were randomly assigned to either a treatment group or a control group according to a random table. Besides gonadotropin (Gn) therapy in both groups, the treatment group received ETG for 3 menstrual cycles before IVF, and the control group received placebo granules. The ETG and the placebo granules were made with similar color and shape, as well as in the same packaging. The scores of the Kidney-yin Deficiency syndrome were assessed. Other outcome measures included the dosage and duration of Gn, the number of retrieved oocytes, the rate of high-quality oocytes, the rate of high-quality embryos, the fertilization rate, and the clinical pregnancy rate. DNMT1 protein expression in the endometrium was measured in the midluteal phase. Results: The difference in the syndrome score change before and after treatment between the two groups was statistically significant ( p < 0.05). The dosage and duration of Gn were significantly lower in the treatment group than those in the control group ( p < 0.05). The high-quality oocyte and embryo rates, and clinical pregnancy rate were all higher in the treatment group than those in the control group ( p < 0.05). The fertilization rate was not significant when compared to the placebo group. No difference was found in the number of retrieved oocytes between the two groups. The DNMT1 protein expression in the endometrium was much more abundant in the treatment group than that in the control group ( p < 0.05). Conclusions: For the infertile patients undergoing IVF, the Chinese recipe for tonifying the Kidney as an adjunct treatment could reduce Gn dosage and treatment duration, alleviate clinical symptoms, and improve the clinical pregnancy rate. The increased level of DNMT1 protein expression after treatment may lead to enhanced endometrial receptivity. This finding may explain the improvement in clinical pregnancy rate.
QJR could markedly improve the symptoms of menorrhagia and menstrual disorder, and its mechanism might be related with the lowering of eutopic endometrial VEGF expression. VEGF and Ki-67 show a high expression in eutopic endometrium of patients with EM.
The present study aimed to identify altered genes and pathways associated with four histotypes of ovarian cancer, according to the systematic tracking of dysregulated modules of reweighted protein-protein interaction (PPI) networks. Firstly, the PPI network and gene expression data were initially integrated to infer and reweight normal ovarian and four types of ovarian cancer (endometrioid, serous, mucinous and clear cell carcinoma) PPI networks based on Spearman's correlation coefficient. Secondly, modules in the PPI network were mined using a clique-merging algorithm and the differential modules were identified through maximum weight bipartite matching. Finally, the gene compositions in the altered modules were analyzed, and pathway functional enrichment analyses for disrupted module genes were performed. In five conditional-specific networks, universal alterations in gene correlations were revealed, which leads to the differential correlation density among disrupted module pairs. The analyses revealed 28, 133, 139 and 33 altered modules in endometrioid, serous, mucinous and clear cell carcinoma, respectively. Gene composition analyses of the disrupted modules revealed five common genes (mitogen-activated protein kinase 1, phosphoinositide 3-kinase-encoding catalytic 110-KDα, AKT serine/threonine kinase 1, cyclin D1 and tumor protein P53) across the four subtypes of ovarian cancer. In addition, pathway enrichment analysis confirmed one common pathway (pathways in cancer), in the four histotypes. This systematic module approach successfully identified altered genes and pathways in the four types of ovarian cancer. The extensive differences of gene correlations result in dysfunctional modules, and the coordinated disruption of these modules contributes to the development and progression of ovarian cancer.
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