Hypoxia and its possible relationship with endometrial receptivity in adenomyosis: a preliminary study.

BACKGROUND: Adenomyosis (AM) is an important cause of female infertility. However, the underlying mechanism remains unclear. This report describes a preliminary study of hypoxia and its possible association with endometrial receptivity in AM. METHODS: The study was divided into in vitro and in vivo experiments. In vitro, expression levels of the endometrial receptivity markers HOXA10 and HOXA11 in the implantation period were examined using real-time PCR and western blotting. Endometrial expression of hypoxia-inducible factor (HIF)-1α, HIF-2α, and HIF-3α was determined using immunohistochemistry. In vivo, using an AM mouse model established by oral administration of tamoxifen, we inhibited expression of HIF-2α using an HIF-2α antagonist (PT2399; 30 mg/kg body weight, twice daily by oral gavage for 2 days) and then examined expression levels of Hoxa10 and Hoxa11 using real-time PCR and western blotting. RESULTS: Endometrial mRNA and protein expression levels of HOXA10 and HOXA11 were significantly lower in patients with AM than in control patients. Expression of HIF-2α was significantly higher in the AM group than in the control group, whereas that of HIF-1α and HIF-3α was equivalent in both groups. In vivo analysis showed that administration of the HIF-2α antagonist resulted in increased expression of Hoxa10 and Hoxa11 at both the mRNA and protein levels in AM model mice. CONCLUSIONS: HIF-2α overexpression may be one reason for decreased endometrial receptivity in AM. The current findings provide insight into HIF-2α-mediated AM-related infertility and suggest that PT2399 has potential as a treatment for AM. TRIAL REGISTRATION: This trial was retrospectively registered.

Adjustable uniaxial zero thermal expansion and zero linear compressibility in unique hybrid semiconductors: the role of the organic chain.

Zero thermal expansion (ZTE) and zero linear compressibility (ZLC) are unique and rare properties. Materials combining ZTE and ZLC will have promising prospects. A novel route is proposed in this work to design the coexistence of uniaxial-ZTE and ZLC based on layered hybrid semiconductors [ZnTe(L)0.5] [L = N2H4, ethylenediamine (en), propyldiamine (pda)]. In the framework of [ZnTe(L)0.5], the organic chain contains the attractive and repulsive interactions that arise from the different organic components. It is demonstrated that changing the length of the organic chain can effectively regulate the interaction between different organic components and then achieve the uniaxial-ZTE and ZLC or the desired thermal expansion and compression behaviors. The origin of the coexistence of abnormal axial responses has been traced from thermodynamic formalisms, model Grüneisen parameters and specific vibration modes. It is found that low-energy phonons play an important internal role in realizing the multi-peculiar properties.

Expression of Liver Receptor Homolog-1 (LRH-1) in Villi and Decidua of Patients with Unexplained Recurrent Spontaneous Abortion.

BACKGROUND In view of the important function of nuclear receptor liver receptor homolog 1 (LRH 1) in various biological processes and the physiological changes accompanying unexplained recurrent spontaneous abortion (USRA), our study was carried out to investigate the potential roles of LRH-1 in USRA. MATERIAL AND METHODS Thirty patients with URSA at early the early state of pregnancy were selected, and 30 patients with normal early pregnancy were also selected from Aug 2015 to Sep 2016 as a control group. The expression of LRH-1 protein in decidua and villi were detected by immunohistochemistry and Western blot analysis, and the expression of LRH-1 mRNA was detected by RT-PCR. The expression levels of CYP19 and P450scc were detected by RT-PCR and Western blot analysis at mRNA and protein levels, respectively. RESULTS The levels of LRH-1, CYP19, and P450scc mRNA and protein in villi of the patients in the URSA group were significantly lower than in the control group. There were no significant differences between the URSA group and control group in the levels of LRH-1, CYP19, and P450scc mRNA and protein in villi in decidua. CONCLUSIONS URSA was related to the reduced expression level of LRH-1 in villous tissues but not in decidua, and expression of LRH-1 may be related to the expression of CYP19 and P450scc. We believe that the expression level of LRH-1 can be used as a marker in the early diagnosis of URSA, and the regulation of LRH-1 expression many lead to new URSA treatments.

The role of peptidylarginine deiminase 4 in ovarian cancer cell tumorigenesis and invasion.

Peptidylarginine deiminase 4 (PADI4) is an enzyme that converts both histone arginine and mono-methyl arginine residues to citrulline, and it has been detected in various subtypes of ovarian cancer. However, the mechanism of action of PADI4 in ovarian carcinogenesis remains unknown. To examine the function of PADI4, we transfected two ovarian cancer cell lines, wild-type p53 A2780 and p53-null SKOV3, with PADI4-siRNA and negative control siRNA. The proliferation of both A2780 and SKOV3 cells decreased significantly following PADI4-siRNA treatment (P A2780 < 0.01; P SKOV3 < 0.001). The invasion and migration ability of A2780 cells also significantly decreased in response to PADI4-siRNA treatment (P < 0.001), but SKOV3 cells showed no such decrease. The apoptotic rate of A2780 cells increased in the presence of PADI4-siRNA, but there was no such increase in SKOV3 cells (P > 0.05). PCR arrays of A2780 cells treated with PADI4-siRNA revealed the up-regulated expression of six genes, including cell death-inducing DFFA-like effector a (CIDEA) and tumor necrosis factor receptor superfamily member 9 (TNFRSF9), and the down-regulation of seven genes, including integrin beta 3 (ITGB3) and BCL2-antagonist/killer 1 (BAK1). These results suggest an important role for PADI4 in the p53 pathway and the regulation of the proliferation, apoptosis, invasion and migration of ovarian cancer cells. Our study also demonstrated that PADI4 contributes to tumor metastasis by regulating the gene expression of insulin-like growth factor 1 (IGF1) and WAS/WASL-interacting protein family member 1 (WIPF1).

Overexpression of GOLPH3 protein is associated with worse prognosis in patients with epithelial ovarian cancer.

Golgi phosphoprotein 3 (GOLPH3) has important roles in the pathogenesis of cancer, and overexpression of GOLPH3 has been found in several kinds of cancers. However, the relationship between GOLPH3 overexpression and prognosis in patients with epithelial ovarian cancer remains unknown. This study aimed to investigate the relationship between GOLPH3 overexpression and overall survival in patients with epithelial ovarian cancer. The expression of GOLPH3 protein in tumor tissue was evaluated using immunohistochemistry. Seventy-five patients with epithelial ovarian cancer with the data of GOLPH3 expression and follow-up were included. GOLPH3 overexpression was significantly associated with advanced stage, histology, high grade, and lymph node metastases (P < 0.05). Kaplan-Meier analysis showed that patients with GOLPH3 overexpression had significantly poorer overall survival than those with low expression of GOLPH3 (log-rank P < 0.001). In the multivariate Cox proportional hazards analysis, GOLPH3 overexpression was independently associated with poorer overall survival (hazard ratio [HR] = 3.60; 95 % confidence interval (CI0 1.14-11.33, P = 0.03). Therefore, overexpression of GOLPH3 protein is closely related to poorer prognosis in patients with epithelial ovarian cancer.