Upregulation of IFNE in cervical biopsies of patients with high-risk human papillomavirus infections.

PROBLEM: Interferon epsilon (IFN-ε) is constitutively expressed in the epithelium of female reproductive tract and confers vital protection against sexually transmitted pathogens in mouse models. However, there is limited insight into the role of IFN-ε in human sexually transmitted infections such as human papillomavirus (HPV). METHOD OF STUDY: Cervical biopsies were obtained from high-risk (HR) HPV positive (n = 28) and HR-HPV negative (n = 10) women. mRNA expression of IFN-ε in cervical tissues was measured by qPCR. Expression of the IFN-ε protein was determined by Western blot analysis, immunohistochemistry and immunofluorescence staining. RESULTS: mRNA expression of IFN-ε was higher in the ectocervix than that of other IFNs, and was further upregulated in HR-HPV positive women compared with HR-HPV negative women. Expression of the IFN-ε protein was comparable between HR-HPV infected patients and healthy controls. CONCLUSIONS: These results reveal differential expression of IFN-ε mRNA between individuals with or without HR-HPV infection, and imply direct or indirect regulatory mechanisms for IFN-ε transcription by HPV. Expression of IFN-ε protein in HPV infections would require further validation.

Lichong decoction inhibits micro-angiogenesis by reducing the expressions of hypoxia inducible factor-1α and vascular endothelial growth factor in hysteromyoma mouse model.

OBJECTIVE: To investigate the efficacy of Lichong decoction (LD) from Traditional Chinese Medicine, on micro-angiogenesis in a mouse model of hysteromyoma. METHODS: A mouse model of hysteromyoma was developed by orthotopic intrauterine injection of primary human myoma cells isolated from patients from the Beijing Obstetrics and Gynecology Hospital into CB-17 Scid mice. Mice were administered high-dose LD, low-dose LD, mifepristone or water (control) daily by gavage for 4 weeks. Uterine diameter and coefficient (uterine weight/body weight) were measured. Uterine morphology was assessed by light microscopy (hematoxylin and eosin) and transmission electron microscopy. Serum levels of estradiol, progesterone, follicle-stimulating hormone and luteinizing hormone (LH) were measured by enzyme-linked immunosorbent assay. Uterine protein expression of hypoxia inducible factor (HIF)-1α, CD31 and proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry. VEGF and HIF-1α mRNAs were quantified by RT-PCR. RESULTS: High-dose LD, low-dose LD and mifepristone reduced uterine diameter and coefficient, and attenuated the morphologic abnormalities associated with hysteromyoma. High-dose LD, low-dose LD and mifepristone inhibited hysteromyoma-induced micro-angiogenesis, as evidenced by a decrease in the number of new microvessels co-immunostaining for CD31 and PCNA (P < 0.01). High-dose LD and mifepristone lowered serum levels of estradiol, progesterone and LH (P < 0.05). High-dose LD, low-dose LD and mifepristone down-regulated HIF-1α mRNA and protein expressions and VEGF mRNA expression (P < 0.01). CONCLUSION: The inhibition of hysteromyoma by LD may involve reductions in HIF-1α and VEGF expression and suppression of micro-angiogenesis.

MiR-199a-5p Targets ZEB1 to Inhibit the Epithelial-Mesenchymal Transition of Ovarian Ectopic Endometrial Stromal Cells Via PI3K/Akt/mTOR Signal Pathway In Vitro and In Vivo.

Endometriosis (Ems) is a common gynecological disease with the characteristics of infertility, pelvic pain, and sexual intercourse difficulty. Our present study aimed to investigate the effect of miR-199a-5p on cell mobility and epithelial-mesenchymal transition (EMT) in Ems. Ectopic endometrial stromal cells (EcSCs) and control endometrial stromal cells (CSCs) were isolated in our in vitro experiments. The level of miR-199a-5p in EcSCs was found much lower than that in CSCs. Besides, miR-199a-5p mimic suppressed the invasion and migration ability of EcSCs. At the same time, EMT was also found to be suppressed by miR-199a-5p mimic in EcSCs. Our further bioinformatics analysis and luciferase reporter assay revealed that ZEB1, a marker of EMT, was a direct target of miR-199a-5p. In addition, the combination of pcDNA3.1-ZEB1 weakened the inhibiting effect of miR-199a-5p mimic on the mobility and EMT of EcSCs. What is more, the PI3K/Akt/mTOR signal pathway was demonstrated to be inactivated by miR-199a-5p mimic. And then, the inducer of PI3K/Akt/mTOR signal pathway, IGF-1, abolished the effect of miR-199a-5p mimic on Ems progression. At last, an Ems rat model was established, and we found that miR-199a-5p agomir effectively suppressed the expression of vascular endothelial growth factor (VEGF) and EMT in vivo. The PI3K/Akt/mTOR signal pathway was also inactivated by miR-199a-5p agomir in our Ems rat model. Taken together, we concluded that miR-199a-5p targeted ZEB1 to inhibit the EMT of ovarian ectopic endometrial stromal cells via PI3K/Akt/mTOR signal pathway in vitro and in vivo, advancing our understanding of miR-199a-5p as regulators of Ems progression and making contribution to the treatment of Ems.

Postpartum adverse effects and sexual satisfaction following cesarean delivery in Beijing.

OBJECTIVE: To investigate short- and long-term postpartum complications of different delivery methods in terms of sexual satisfaction, stress urinary incontinence (SUI), and pelvic-floor dysfunction in the Beijing region. METHODS: A questionnaire-based study was conducted between June 30, 2013 and July 1, 2014. Female residents of Beijing aged 20-65 years, who were attending routine physical examinations, were enrolled and completed a face-to-face survey including questions on short- and long-term complications related to sexual satisfaction, SUI, and pelvic-floor dysfunction postpartum. RESULTS: In total, 2649 individuals were enrolled. In comparison with patients that underwent vaginal delivery, patients that had undergone cesarean delivery experienced a greater length of time before resuming intercourse (2.70±2.0 9months vs 4.32±4.10 months; P<0.001) and higher incidences of decreased libido (93 [6.1%] vs 234 [20.7%]; P<0.001), vaginal dryness (39 [2.6%] vs 177 [15.7%]; P<0.001), sexual dissatisfaction (117 [7.7%] vs 234 [20.7%]; P<0.001), and painful intercourse (48 [3.2%] vs 252 [22.3%]; P<0.001) after delivery. Cesarean delivery did not demonstrate any long-term protective effects against future SUI in comparison with vaginal delivery. CONCLUSION: Cesarean delivery resulted in a greater incidence of adverse effects on postpartum sexual function and cesarean delivery provides no long-term protective effects against postpartum SUI.

Lichong decoction reduces Matrix Metalloproteinases-2 expression but increases Tissue Inhibitors of Matrix Metalloproteinases-2 expression in a rat model of uterine leiomyoma.

OBJECTIVE: To study the effect of Lichong decoction (LD) on expression of matrix metalloproteinase- 2 (MMP-2) and metalloproteinase-2 (TIMP-2) in a rat model of uterine leiomyoma (UL). METHODS: UL was induced in rats using exogenous estrogen and progesterone. LD was administered (p.o.) for 4 weeks, and mifepristone (RU-486) used as a control. To observe the effect of LD on the uterine coefficient and uterine transverse diameter, a radioimmunoassay method was used to detect serum levels of sex hormones. Light microscopic analyses of pathologic changes in the tissues of UL rats were evaluated. Expression of the proteins of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in uterine tissues was assessed by immunohistochemical staining and western blotting. RESULTS: A UL model in rats was established successfully. LD reduced uterine weight, uterine coefficient, and uterine transverse diameter compared with untreated controls. LD reduced levels of estradiol, progesterone, follicle-stimulating hormone, and luteinizing hormone in our UL models. LD improved the pathologic condition of uterine muscle. Expression of MMP-2 protein decreased to varying extents in LD-treated groups, but TIMP-2 levels were enhanced. LD appears to reduce MMP-2 expression and increase TIMP-2 expression in UL tissue. CONCLUSION: These data suggest that the mechanism of action of LD on ULs may involve reduction of MMP-2 expression and increase in TIMP-2 expression in rats.

Effect of Lichong decoction on expression of Bcl-2 and Bcl-2-associated X protein mRNAs in hysteromyoma model rat.

OBJECTIVE: To study on effects of Lichong decoction on expression of apoptosis-controlling genes, Bcl-2 and Bcl-2-associated X protein (Bax) mRNAs in hysteromyoma tissue of the hysteromyoma model rat. METHODS: Fifty Wistar female rats were randomly divided into a normal group, a model group, a Lichong decoction group, a Guizifuling capsule group and a Mifepristone group. The hysteromyoma rat model was established by intraperitoneal injection of exogenous estrin and progestogens. Pathological examination of uterine tissue, uterine coefficient and uterine transverse diameter were made under optic microscope and expressions of Bcl-2 and Bax mRNAs in uterine tissue in the groups were detected with real-time fluorescent quantitative polymerase chain reaction (PCR) technique. RESULTS: After treatment, under microscope it was found that in the Lichong decoction group myometrium thinned, muscle fiber slightly overgrowth or long and thin, regular arrangement, inserting phenomenon of inner circular muscle and external longitudinal muscle was occasionally or not seen in the Lichong decoction group. The uterine coefficient and the uterine transverse diameter significantly decreased (P < 0.01), and Bcl-2 mRNA expression significantly decreased (P < 0.01) and Bax mRNA expression significantly increased in hysteromyoma tissue (P < 0.01) in the Lichong decoction group as compared with the model group. CONCLUSION: Therapeutic effects of Lichong decoction on hysteromyoma is related with decrease of Bcl-2 mRNA expression and increase of Bax mRNA expression.