Effects of Luteolin on Human Breast Cancer Using Gene Expression Array: Inferring Novel Genes.

Taraxacum officinale (dandelion) is often used in traditional Chinese medicine for the treatment of cancer; however, the downstream regulatory genes and signaling pathways mediating its effects on breast cancer remain unclear. The present study aimed to explore the effects of luteolin, the main biologically active compound of T. officinale, on gene expression profiles in MDA-MB-231 and MCF-7 breast cancer cells. The results revealed that luteolin effectively inhibited the proliferation and motility of the MDA-MB-231 and MCF-7 cells. The mRNA expression profiles were determined using gene expression array analysis and analyzed using a bioinformatics approach. A total of 41 differentially expressed genes (DEGs) were found in the luteolin-treated MDA-MB-231 and MCF-7 cells. A Gene Ontology analysis revealed that the DEGs, including AP2B1, APP, GPNMB and DLST, mainly functioned as oncogenes. The human protein atlas database also found that AP2B1, APP, GPNMB and DLST were highly expressed in breast cancer and that AP2B1 (cut-off value, 75%) was significantly associated with survival rate (p = 0.044). In addition, a Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the DEGs were involved in T-cell leukemia virus 1 infection and differentiation. On the whole, the findings of the present study provide a scientific basis that may be used to evaluate the potential benefits of luteolin in human breast cancer. Further studies are required, however, to fully elucidate the role of the related molecular pathways.

Changes in sexual function and vaginal topography using transperineal ultrasound after vaginal laser treatment for women with stress urinary incontinence.

We aim to assess the changes in sexual function and vaginal topography using 3-D transperineal ultrasound in stress-incontinent women treated with Er:YAG vaginal laser. Two hundred and twenty women with stress urinary incontinence (SUI) treated with Er:YAG laser were recruited. Assessment before and 6 months after the treatment included vaginal topography using 3-D transperineal ultrasound and sexual function using female sexual function index questionnaire (FSFI). A total of 50 women with complete data showed that the symptomatic improvement was noted in 37 (74%) women. After Er:YAG vaginal laser treatment, significantly decreased width and cross-sectional area in proximal, middle, and distal vagina were found in women with SUI. Nearly all of the domains of FSFI improved significantly after the vaginal laser treatment, except sexual desire. In conclusion, 3-D transperineal ultrasound can be used to conduct vaginal topography. After Er:YAG vaginal laser treatment, the anatomical changes of vaginal shrinkage and the improvement of female sexual function were both noted. The favorable outcome of sexual function partly related to the tightening of vagina, as evidenced by the measurements of the 3-D transperineal ultrasound.

Impact of COVID-19 on Pregnancy.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is an emerging disease. There has been a rapid increase in cases and deaths since it was identified in Wuhan, China, in early December 2019, with over 4,000,000 cases of COVID-19 including at least 250,000 deaths worldwide as of May 2020. However, limited data about the clinical characteristics of pregnant women with COVID-19 have been reported. Given the maternal physiologic and immune function changes during pregnancy, pregnant women may be at a higher risk of being infected with SARS-CoV-2 and developing more complicated clinical events. Information on severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) may provide insights into the effects of COVID-19's during pregnancy. Even though SARS and MERS have been associated with miscarriage, intrauterine death, fetal growth restriction and high case fatality rates, the clinical course of COVID-19 pneumonia in pregnant women has been reported to be similar to that in non-pregnant women. In addition, pregnant women do not appear to be at a higher risk of catching COVID-19 or suffering from more severe disease than other adults of similar age. Moreover, there is currently no evidence that the virus can be transmitted to the fetus during pregnancy or during childbirth. Babies and young children are also known to only experience mild forms of COVID-19. The aims of this systematic review were to summarize the possible symptoms, treatments, and pregnancy outcomes of women infected with COVID-19 during pregnancy.

The clinical and urodynamic outcomes of single-incision mesh surgery using the Uphold system for the treatment of pelvic organ prolapse.

This retrospective cohort study aims to assess the clinical and urodynamic outcomes of single-incision mesh surgery with the Uphold system. The medical records of 140 women with anterior and/or apical compartment prolapse stage 2 or greater who underwent Uphold mesh surgeries were reviewed. The clinical evaluation included a pelvic examination, a urodynamic study (UDS), and a personal interview to evaluate lower urinary tract symptoms (LUTS). After a follow-up time of 12-30 months, the anatomical reduction rates were 100% and 96.4% for the apical and anterior compartments, respectively, and these rates were similar across women with or without hysterectomy. All of the LUTS and several UDS parameters improved significantly. The continence rate in women with stress urinary incontinence (SUI) was improved if they also underwent a mid-urethral sling (MUS) operation. However, the continence rate did not differ between women with and without occult urodynamic stress incontinence who did not undergo a concomitant MUS operation. The rate of vaginal mesh extrusion was 2.8%, and this complication rarely occurred beyond the learning curve. In conclusion, the anatomic correction of the Uphold system was satisfactory with a low rate of mesh extrusion. Women with SUI would benefit from a concomitant MUS operation.

Predictors for de novo stress urinary incontinence following pelvic reconstruction surgery with transvaginal single-incisional mesh.

The study aims to identify predictors for de novo stress urinary incontinence (SUI) following Elevate mesh surgery. A total of 164 women who underwent Elevate mesh surgeries between November 2011 and February 2014 in a single center were included. Seventy-three women were excluded due to preoperative incontinence or concomitant mid-urethral sling surgery. Fourteen others were excluded due to incomplete medical records. Fisher's exact test and χ2 test were applied. The univariate logistic regression was used for odds ratios. Of the 77 continent women, 24 (31.2%) experienced de novo SUI after the operation. Significantly more women with de novo SUI were over the age of 64 years (75.0% vs. 47.2%, p = 0.023, OR 3.36, 95% CI 1.15-9.79). Preoperative occult urodynamic stress incontinence (29.2% vs. 3.8%, p = 0.003, OR 10.0, 95% CI 2.0-50.0) and previous SUI history (41.7% vs. 7.6%, p = 0.001, OR 9.1, 95% CI 2.38-33.3) were 2 other predictors of de novo SUI postoperatively. In conclusion, age over 64 years old, occult urodynamic stress incontinence, and previous history of SUI are 3 significant predictors for de novo SUI following the single-incision mesh surgeries.

CD47 promotes cell growth and motility in epithelial ovarian cancer.

Endometriosis is considered a high risk factor for the development of ovarian carcinoma, including clear cell and endometrioid malignancies. The mechanism by which endometriosis-associated ovarian cancer (EAOC) avoids anti-tumor immune surveillance by macrophages remains unclear, but CD47 is a very important immune checkpoint for macrophage phagocytosis. Therefore, we collected 36 clinical ovarian samples and detected the protein profile of CD47 by immunohistochemistry and analyzed the correlation with clinical pathological features using statistical software. We found that CD47 expression was relatively higher in patients with EAOC compared with the normal group. High CD47 expression was positively and significantly correlated with histology (P = 0.007) and tumor grade (P = 0.002). We also found that CD47 overexpression promotes cancer cell growth and motility in the TOV-112D and TOV-21G cell lines. Silencing CD47 and anti-CD47 mAb inhibit cancer cell growth and motility in cancer cell lines. Together, these results demonstrate that CD47 in EAOC may be a useful surface marker and offer a novel therapeutic option by targeting CD47 in ovarian cancer.

Estradiol induces cell proliferation in MCF­7 mammospheres through HER2/COX­2.

Cluster of differentiation (CD)44+/CD24- breast cancer cells have stem cell­like characteristics and are potent initiators of tumorigenesis. Mammosphere cells can partially initiate breast tumorigenesis by inducing estradiol (E2)­dependent breast cancer cells. However, the mechanisms by which E2 mediates cancer formation in MCF­7 mammosphere (MS) cells have remained elusive. In the present study, MS cells were isolated by sphere culture. It was possible to maintain these MS cells in culture for long periods of time, while retaining the CD44+/CD24- stem cell marker status. The CD44+/CD24- status was confirmed by flow cytometry. Furthermore, the stem­cell markers Musashi­1, cytokeratin (CK)7 and CK19 were identified by immunofluorescence microscopy. It was revealed that treatment of MS cells with E2 increased the expression of CD44, whereas decreased the expression of CD24 on MS cells. In addition, treatment with E2 increased colony formation by MS cells. E2 also induced cyclooxygenase­2 (COX­2) expression in MS cells, which promoted their proliferation through the estrogen receptor/human epidermal growth factor receptor 2 (HER2)/mitogen­activated protein kinase/phosphoinositide­3 kinase signaling pathway. The results suggested a tumorigenic mechanism by which E2 promotes tumor cell proliferation via HER2/COX­2 signaling. The present study provided evidence for the molecular impact of E2 on breast tumorigenesis, and suggested possible strategies for preventing and treating human breast cancer.

Comparison of clinical outcomes using "elevate anterior" versus "Perigee" system devices for the treatment of pelvic organ prolapse.

OBJECTIVE: This study aims to compare clinical outcomes using the Perigee versus Elevate anterior devices for the treatment of pelvic organ prolapse (POP). STUDY DESIGN: One hundred and forty-one women with POP stages II to IV were scheduled for either Perigee (n = 91) or Elevate anterior device (n = 50). Preoperative and postoperative assessments included pelvic examination, urodynamic study, and a personal interview about quality of life and urinary symptoms. RESULTS: Despite postoperative point C of Elevate group being significantly deeper than the Perigee group (median: -7.5 versus -6; P < 0.01), the 1-year success rates for two groups were comparable (P > 0.05). Apart from urgency incontinence, women with advanced POP experienced significant resolution of irritating and obstructive symptoms after both procedures (P < 0.05), generating the improvement in postoperative scores of Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7) (P < 0.01). On urodynamics, only the residual urine decreased significantly following these two procedures (P < 0.05). Women undergoing Perigee mesh experienced significantly higher visual analogue scale (VAS) scores and vaginal extrusion rates compared with the Elevate anterior procedure (P < 0.05). CONCLUSIONS: With comparable success rates, the Elevate procedure has advantages over the Perigee surgery with lower extrusion rate and postoperative day 1 VAS scores.

HDAC inhibitors target HDAC5, upregulate microRNA-125a-5p, and induce apoptosis in breast cancer cells.

Histone deacetylase inhibitors (HDACi) are novel clinical anticancer drugs that inhibit HDAC gene expression and induce cell apoptosis in human cancers. Nevertheless, the detailed mechanism or the downstream HDAC targets by which HDACi mediates apoptosis in human breast cancer cells remains unclear. Here, we show that HDACi reduce tumorigenesis and induce intrinsic apoptosis of human breast cancer cells through the microRNA miR-125a-5p in vivo and in vitro. Intrinsic apoptosis was activated by the caspase 9/3 signaling pathway. In addition, HDACi mediated the expression of miR-125a-5p by activating RUNX3/p300/HDAC5 complex. Subsequently, miR-125a-5p silenced HDAC5 post-transcriptionally in the cells treated with HDACi. Thus, a regulatory loop may exist in human breast cancer cells involving miR-125a-5p and HDAC5 that is controlled by RUNX3 signaling. Silencing of miR-125a-5p and RUNX3 inhibited cancer progression and activated apoptosis, but silencing of HDAC5 had a converse effect. In conclusion, we demonstrate a possible new mechanism by which HDACi influence tumorigenesis and apoptosis via downregulation of miR-125a-5p expression. This study provides clinical implications in cancer chemotherapy using HDACi.

Comparison of low urinary tract symptoms during pregnancy between primiparous and multiparous women.

BACKGROUND AND PURPOSE: Low urinary tract symptoms (LUTS) are a common problem during pregnancy. This study aimed to compare changes in the prevalence of LUTS during pregnancy between primiparous and multiparous women. METHODS: A chart review of consecutive pregnant women who attended our antenatal clinic from March 2002 to January 2006 was performed. All of the women were asked to respond to a LUTS questionnaire in either of the three trimesters. RESULTS: Of the 270 women included, 164 were nullipara and 106 were multipara. The most common LUTS during pregnancy were frequency (77%), followed by nocturia (75.6%), stress urinary incontinence (SUI) (51.1%), incomplete emptying (43.7%), dysuria (17.8%), and urgency incontinence (10.4%). There was a significantly higher prevalence of SUI (P<0.001) and urgency incontinence (P=0.005) in the multiparous compared to the nulliparous women. Increasing prevalence rates of frequency, nocturia, SUI, and incomplete emptying were reported with gestational age in both the nulliparous and multiparous women. CONCLUSIONS: Frequency and nocturia were the two most common LUTS during pregnancy. The prevalence rates of all LUTS increased with increasing gestational age except for frequency in the nulliparous women during the second trimester. In addition, multipara was a predictor of SUI during pregnancy.

Clinical and urodynamic effects of tolterodine in women with an overactive bladder.

OBJECTIVE: The aim of this study was to compare the changes in urinary symptoms and urodynamic parameters after administration of tolterodine in women with an overactive bladder (OAB). MATERIALS AND METHODS: Thirty-eight women diagnosed with OAB and treated with tolterodine were reviewed. Urinalysis, pelvic examination, 3-day bladder diary, urodynamic study, and a personal interview to identify urinary symptoms prior to and 3 months after treatment were recorded and interpreted. RESULTS: Most of our patients were menopausal (76.3%; mean age 55.7 years) and multiparous (mean parity 3.3) women. Urinary symptoms such as urinary frequency, urgency, urge incontinence, and nocturia were decreased significantly (p < 0.05). All urodynamic parameters did not change significantly except for the maximum cystometric capacity (p < 0.05), showing a significant increase after 3 months of medication. CONCLUSIONS: Tolterodine, at a recommended dose, improves the symptoms of OAB syndrome without causing urine retention, as proved by the changes of urodynamic parameters.

Risk factors of surgical failure following transvaginal mesh repair for the treatment of pelvic organ prolapse.

OBJECTIVE: To identify the factors associated with pelvic organ prolapse (POP) recurrence after transvaginal mesh (TVM) repair. STUDY DESIGN: One hundred and thirteen women with symptomatic POP stage II to IV were scheduled for TVM procedures. All subjects underwent urinalyses and pelvic examination using the POP quantification (POP-Q) staging system before and after surgery. RESULTS: Seven (6.2%) of 113 women reported POP recurrence after a mean follow-up time of 30 months. We performed a univariate analysis of patients' characteristics to identify the predictors of surgical failure after TVM. There was no difference between two groups as to body mass index, POP stage, mesh type, and preoperative urinary symptoms and urodynamic parameters (P>0.05). However, we found that uterine prolapse (P=0.016) and surgical experience (P=0.043) were two significant predictors of surgical failure. Multivariate logistic regression showed similar results. CONCLUSION: Advanced uterine prolapse and lack of surgical experience were two significant predictors of failure following TVM. POP recurrence after mesh repair appears to be unlikely beyond the learning curve.

Three-year outcome of transvaginal mesh repair for the treatment of pelvic organ prolapse.

OBJECTIVE: To evaluate the clinical and urodynamic outcomes of transvaginal mesh repair (TVM) for the treatment of pelvic organ prolapse (POP). STUDY DESIGN: One hundred and twenty-four women with POP stage II to IV were scheduled for a TVM procedure. Preoperative and postoperative assessments included pelvic examination, urodynamic testing, and a personal interview about urinary symptoms using a standard questionnaire. RESULTS: We found a significant improvement at points Aa, Ba, C, Ap, and Bp (P<0.001) except for total vaginal length (P=0.08), and the overall success rate was 93.5% (116/124). Various urinary symptoms improved significantly following TVM (P<0.01). In addition, residual urine, functional urethral length, and the rate of detrusor overactivity, improved significantly after surgery (P<0.05). Apart from vaginal erosion (14/124; 11.3%), the rates of other surgical complications were acceptably low. CONCLUSION: TVM is an effective procedure for the treatment of POP and urinary symptoms, this being possibly related to postoperative release of urethral obstruction. Vaginal erosion is less likely to occur beyond the learning curve.

The impact of simulated birth trauma and ovariectomy on the gene expression of detrusor muscarinic receptors in female rats.

INTRODUCTION AND HYPOTHESIS: This study aims to investigate the effects of simulated birth trauma and ovariectomy on detrusor muscarinic receptors (M2 and M3), urethral neuronal nitric oxide synthase (nNOS), and estrogen receptor beta (ER beta). METHODS: Forty primiparous rats were equally divided into five groups: group A--delivery, group B--delivery plus ovariectomy, group C--delivery plus balloon dilatation for 2 h, group D--delivery plus balloon dilatation for 4 h, and group E--delivery plus balloon dilatation for 2 h plus ovariectomy. The gene expression of M2, M3, nNOS, and ER beta were assessed by reverse transcription polymerase chain reaction. RESULTS: Significant decreases in mRNA expression of M2 receptors and nNOS (P < 0.05), and a significant increase in M3 mRNA expression (P < 0.05) were observed in groups D and E when compared with group A. CONCLUSIONS: Ovariectomy following birth trauma may synergistically impact the function of urinary tract, this being possibly related to the modification of the gene expression of muscarinic receptors.

Effect of laparoscopic hysterectomy on the vascularization of the lower urinary tract.

INTRODUCTION: The aim of this prospective study was to evaluate the changes in the vascularization of the lower urinary tract following laparoscopic hysterectomy (LH). METHODS: Seventy women undergoing LH not under the indication of a uterine myoma were included. All subjects underwent urinalysis, pelvic examination, and introital color Doppler ultrasonography and completed a urinary questionnaire before and 6 months after LH. One-hour pad tests and urodynamic studies were performed in clinically incontinent women pre- and postoperatively. RESULTS: Evaluation of the Doppler velocimetric parameters of bladder neck and periurethral vessels before and after LH, including number of vessels, pulsatility index, systolic peak, and minimum diastole, revealed no statistically significant differences (p > 0.05). In addition, the prevalence of stress urinary incontinence (SUI) decreased significantly from 37.1% (n = 26) preoperatively to 17.1% (n = 12) postoperatively (p < 0.01). A total of 19 patients reported no further SUI following LH. Their urinary leakages on the pad tests had all <10 g before surgery. When we analyzed the data of the women reporting no further SUI (n = 19) and de novo SUI (n = 5) following LH, the changes in the pulsatility index also showed no significant difference from the pre-LH values (p > 0.05). CONCLUSIONS: The results of our study suggest that LH has little impact on the blood flow of bladder neck and urethra. Although some women experienced relief of the symptoms of mild or de novo SUI after LH, this being unrelated to changes in the vascularization of the lower urinary tract.

Incidental finding of a benign bladder tumor during the tension-free vaginal tape procedure.

As use of the tension-free vaginal tape (TVT) grows, more unexpected findings during this procedure are likely to be encountered. However, concomitant resection of a bladder tumor during the TVT procedure is rare. A TVT operation was carried out in a 56-year-old woman with urodynamic stress incontinence. A bladder tumor located in the trigone was found incidentally during cystoscopy. Concomitant resection of the bladder tumor was performed following the TVT procedure. The surgical result of our patient suggests that concomitant resection of a benign intravesical pathology with TVT procedure is safe and effective. Moreover, it does not compromise overall improvement of stress incontinence. The value of cystoscopy during the TVT procedure is emphasized.

A randomized comparative study of the effects of oral and topical estrogen therapy on the vaginal vascularization and sexual function in hysterectomized postmenopausal women.

OBJECTIVE: To compare the effects of oral and vaginal estrogen therapy (ET) on the vaginal blood flow and sexual function in postmenopausal women with previous hysterectomy. DESIGN: Fifty-seven women were randomized to receive either oral (0.625 mg of conjugated equine estrogens per tablet; n = 27) or topical (0.625 mg conjugated equine estrogens per 1 g vaginal cream; n = 30) estrogen administered once daily. All women underwent estradiol measurements, urinalysis, pelvic examination, introital color Doppler ultrasonographies, and personal interviews for sexual symptoms using a validated questionnaire before and 3 months after ET. RESULTS: A higher serum level of estradiol was noted in the oral group compared with the topical group after 3 months of ET. There were significant increases in the number of vaginal vessels and the minimum diastole (P < 0.01), and marked decreases of pulsatility index values (P < 0.01) in both groups after ET. Regarding the systolic peak, we found a significant decrease only in the topical group (P < 0.05). Although the post-ET prevalence of anorgasmia decreased significantly in both groups (P < 0.05), changes in other domains, including the rates of low libido and coital frequency, were not statistically significant (P > 0.05). In the topical group, ET improved sexual function on the vaginal dryness and dyspareunia domains in a statistically significant manner (P < 0.05), but this was not the case in the oral group (P > 0.05). However, the efficacy of oral ET for vaginal dryness and dyspareunia reached 80% and 70.6%, respectively. The corresponding figures of the topical ET were 79.2% and 75%. CONCLUSIONS: The results of our study suggest that ET alone in hysterectomized postmenopausal women increases the vaginal blood flow and improves some domains of sexual function, but it may not have an impact on diminished sexual desire or activity. Compared with systemic therapy, topical vaginal preparations are found to correlate with better symptom relief despite the lower serum level of estradiol.

A randomized comparative study of the effects of oral and topical estrogen therapy on the lower urinary tract of hysterectomized postmenopausal women.

OBJECTIVE: To compare the effects of oral and vaginal estrogen therapy (ET) on the lower urinary tract in postmenopausal women with prior hysterectomy. DESIGN: Randomized, prospective study. SETTING: Tertiary teaching hospital. PATIENT(S): Fifty-seven hysterectomized, postmenopausal women. INTERVENTION(S): Patients were randomized to receive either oral (0.625 mg of conjugated equine E per tablet; n = 27) or topical (0.625 mg conjugated equine E per 1 g vaginal cream; n = 30) E, administered once daily. MAIN OUTCOME MEASURE(S): All subjects had E2 measurements, urinalysis, pelvic examination, introital color Doppler ultrasonographies, and personal interviews with the Bristol Female Lower Urinary Tract Symptoms Questionnaires before and 3 months after ET. RESULT(S): A higher serum level of E2 was noted in the oral group compared with the topical group after ET. The post-ET pulsatility index of periurethral vessels and bladder neck revealed statistically significant decreases in both groups. The incidences of urinary frequency and nocturia were significantly decreased after 3 months of ET in both groups. Changes in the incidence of other symptoms, including stress incontinence and urge incontinence, were not statistically significant. However, subjective improvement of stress incontinence was found in 72.7% of the oral group and 60% of the topical group. CONCLUSION(S): The results suggest that ET alone, by an oral or vaginal route, could increase the blood flow around the bladder neck and mid-urethra and relieve the symptoms of overactive bladder and stress incontinence in postmenopausal women with prior hysterectomy. In addition, vaginal preparations are as effective as systemic therapy at the lower serum level of E2.

Concomitant resection of congenital vaginal septum during the tension-free vaginal tape procedure.

This case report illustrates how the tension-free vaginal tape (TVT) procedure can be successfully combined with another gynecological intervention. A 38-year-old patient had been diagnosed with didelphys uterus during cesarean section. She came to us for treatment of confirmed genuine stress incontinence. In conjunction with the TVT procedure, we resected the congenital vaginal septum. The patient has remained continent for over 1 year.