Long non-coding RNA forkhead box D3 antisense RNA 1 (FOXD3-AS1) functions as an oncogenic regulator in several types of cancer, including breast cancer, glioma and cervical cancer. However, the effects and mechanisms underlying FOXD3-AS1 in cervical cancer (CC) are not completely understood. The present study aimed to investigate the biological functions and potential molecular mechanisms underlying FOXD3-AS1 in CC progression. Reverse transcription-quantitative PCR was performed to detect FOXD3-AS1, microRNA (miR)-128-3p and LIM domain kinase 1 (LIMK1) expression levels in CC tissues and cells. Immunohistochemical staining and western blotting were conducted to assess LIMK1 protein expression levels in CC tissues and cells, respectively. Cell Counting Kit-8 and BrdU assays were used to determine the role of FOXD3-AS1 in regulating cell proliferation. CC cell migration and invasion were assessed by performing Transwell assays. Dual-luciferase reporter assays were conducted to verify the binding between miR-128-3p and FOXD3-AS1. FOXD3-AS1 expression was significantly increased in CC tissues and cell lines compared with adjacent healthy tissues and normal cervical epithelial cells, respectively. High FOXD3-AS1 expression was significantly associated with poor differentiation of tumor tissues, increased tumor size and positive lymph node metastasis. FOXD3-AS1 overexpression significantly increased CC cell proliferation, migration and invasion compared with the negative control (NC) group, whereas FOXD3-AS1 knockdown resulted in the opposite effects compared with the small interfering RNA-NC group. Moreover, the results demonstrated that FOXD3-AS1 targeted and negatively regulated miR-128-3p, which indirectly upregulated LIMK1 expression. Therefore, the present study demonstrated that FOXD3-AS1 upregulated LIMK1 expression via competitively sponging miR-128-3p in CC cells, promoting CC progression.

Vascular endothelial growth factor receptor-2 (VEGFR-2) regulates the mitogen-activated protein kinase (MAPK) signaling pathway and plays an important role in angiogenesis. Bu Shen Zhu Yun decoction (BSZYD) can improve endometrial receptivity and embryo implantation rates in patients undergoing in vitro fertilization. However, whether BSZYD improves endometrial receptivity via angiogenesis remains unclear. Here, we investigated the effects of BSZYD on the proliferation, migration, and angiogenesis of human endometrial microvascular endothelial cells (HEMECs) and found that BSZYD upregulated the expression of cyclin D1, matrix metalloproteinase 9 (MMP9), and proliferating cell nuclear antigen (PCNA) in HEMECs. Cell Counting Kit 8 assay, scratch-wound assay, and Tube Formation Assay results showed that BSZYD promoted the proliferation, migration, and angiogenesis of HEMECs. Western blot analysis results revealed the activation of the MAPK signaling pathway by BSZYD through the upregulation of VEGF and VEGFR-2 expression. Together, these findings highlight the novel mechanism underlying BSZYD-mediated improvement in endometrial receptivity through the MAPK signaling pathway.

Cold coagulation and blood stasis (CCBS) syndrome is one of the common traditional Chinese medicine (TCM) syndromes of gynecological diseases. However, the molecular mechanism of CCBS syndrome is still unclear. Thus, there is a need to reveal the occurrence and regulation mechanism of CCBS syndrome, in order to provide a theoretical basis for the treatment of CCBS syndrome in gynecological diseases. The plasma proteins in primary dysmenorrhea (PD) patients with CCBS syndrome, endometriosis (EMS) patients with CCBS syndrome, and healthy women were screened using Label‐free quantitative proteomics. Based on the TCM theory of “same TCM syndrome in different diseases,” the differentially expressed proteins (DEPs) identified in each group were subjected to intersection mapping to obtain common DEPs in CCBS syndrome. The DEPs of gynecological CCBS syndrome in the intersection part were again cross‐mapped with the DEPs of gynecological CCBS syndrome obtained by the research group according to the TCM theory of “different TCM syndromes in same disease” theory in the early stage, so as to obtain the DEPs of gynecological CCBS syndrome that were shared by the two parts. The common DEPs were subjected to bioinformatics analysis, and were verified by enzyme‐linked immunosorbent assay (ELISA). A total of 67 common DEPs were identified in CCBS syndrome, of which 33 DEPs were upregulated and 34 DEPs were downregulated. The functional classification of DEPs involved in metabolic process, energy production and conversion, immune system process, antioxidant activity, response to stimulus, and biological adhesion. The subcellular location mainly located in the cytoplasm, nucleus, and extracellular. Gene ontology (GO) enrichment analysis showed that the upregulated DEPs mainly concentrated in lipid transport, cell migration, and inflammatory reaction, and the downregulated DEPs mostly related to cell junction, metabolism, and energy response. Protein domain enrichment analysis and clustering analysis revealed that the DEPs mainly related to cell proliferation and differentiation, cell morphology, metabolism, and immunity. The Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis clustering analysis showed that the upregulated DEPs were involved in inflammation and oxidative damage, while the downregulated DEPs were involved in inflammation, cell adhesion, cell apoptosis, and metabolism. The results of ELISA showed significantly increased levels of Cell surface glycoprotein MUC18 (MCAM) and Apolipoprotein C1 (APOC1), and significantly decreased levels of Vasodilator‐stimulated phosphoprotein (VASP), Fatty acid‐binding protein 5 (FABP5), and Vinculin (VCL) in patients with CCBS syndrome compared with healthy women. We speculated that cold evil may affect the immune process, inflammatory response, metabolic process, energy production and conversion, oxidative damage, endothelial cell dysfunction, and other differential proteins expression to cause CCBS syndrome in gynecological diseases.

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Background Morroniside is the main ingredient of Cornus officinalis, which has an antioxidant effect. Ovarian granulosa cells (GCs) are responsible for regulating the development and atresia of follicles, which are susceptible to oxidative stress. In this study, we investigated whether morroniside could inhibit oxidative stress of GCs induced by hydrogen peroxide (H2O2), thus leading to improve oocyte quality. Methods The study was divided into 5 groups: control group, H2O2 group, morroniside (5 µM) + H2O2, morroniside (10 µM) + H2O2, Morroniside (20 µM) + H2O2. Cell survival rate was determined by CCK-8, ROS fluorescence level was determined by DCFH-DA probe, MDA, 8-OHdG, T-AOC, SOD, NQO1 and caspase-3 were determined by ELISA, SOD, NQO1, Bax, Bcl-2, caspase-3, caspase-9, Nrf2 and MAPKs protein expression were determined by Western blot, and Nrf2 nuclear translocation level was determined by immunofluorescence method. SPSS21.0 was used for statistical data analysis. Results After pretreatment with morroniside, the levels of ROS, MDA and 8-OHdG in ovarian GCs were significantly decreased. Morroniside significantly upregulated the level of p-Nrf2 and promoted the nuclear translocation level of Nrf2, which transcriptionally activated antioxidase SOD and NQO1. In addition, the levels of apoptosis-related proteins Bax, Bcl-2, caspase-3 and caspase-9 were significantly regulated via p38 and JNK pathway by morroniside. Conclusions These results suggested that morroniside could reduce oxidative damage and apoptosis of ovarian GCs induced by H2O2 in multiple ways, which provided a new idea for clinical improvement of oxidative stress in female reproductive system.