The Neuroprotective Effect of Isotetrandrine on Parkinson's Disease via Anti-Inflammation and Antiapoptosis In Vitro and In Vivo.

Parkinson's disease (PD) is one of the most influential diseases in the world, and the current medication only can relieve the clinical symptoms but not slow the progression of PD. Therefore, we intend to examine the neuroprotective activity of plant-derived compound isotetrandrine (ITD) in vitro and in vivo. In vitro, cells were cotreated with ITD and LPS to detect the inflammatory-related protein and mRNA. In vivo, zebrafish were pretreated with ITD and inhibitors prior to 6-OHDA treatment. Then, the behavior was monitored at 5 dpf. Our result showed ITD inhibited LPS-induced upregulation of iNOS, COX-2 protein expression, and iL-6, inos, cox-2, and cd11b mRNA expression in BV2 cells. The data in zebrafish also demonstrated a significant improvement of ITD on the 6-OHDA-induced locomotor deficiency. ITD also improved 6-OHDA-induced apoptosis in zebrafish PD. We also pharmacologically validated the mechanism with three inhibitors, including LY294002, PI3K inhibitor; LY32141996, ERK inhibitor, SnPP, and HO-1 inhibitors. All of these inhibitors could abolish the neuroprotective effect of ITD partially in locomotor activity. Besides, the molecular level also showed the same trend. Treatment of these inhibitors could significantly abolish ITD-induced antineuroinflammatory and antioxidative stress effects in zebrafish PD. Our study showed ITD possessed a neuroprotective activity in zebrafish PD. The mRNA level also supported our arguments. The neuroprotection of ITD might be through antineuroinflammation and antiapoptosis pathways via PI3K, ERK, and HO-1.

Fumarate hydratase functions as a tumor suppressor in endometrial cancer by inactivating EGFR signaling.

Fumarase hydratase (FH) is an enzyme that catalyzes the reversible hydration and dehydration of fumarate to malate in the tricarboxylic acid cycle. The present study addressed the role of FH in endometrial cancer and clinically observed that the expression of FH was significantly lower in endometrial cancer tissues compared with normal endometrial tissues and, furthermore, that the decreased FH expression in endometrial cancer tissues was significantly associated with increased tumor size and lymph node metastasis. Further analysis in in vitro study showed that cell proliferation, migration and invasion abilities were increased when the expression of FH in the endometrial cancer cells was knocked down, but, by contrast, overexpression of FH in endometrial cancer cells decreased cell proliferative, migratory and invasive abilities. Mechanistic studies showed that the expression of vimentin and twist, being two well-studied mesenchymal markers in endometrial cancer cells, were upregulated in fumarate hydratase-knockdowned cells. In addition, phosphokinase array analysis demonstrated that the expression of phospho-EGFR (Y1086), which promotes carcinogenesis in cancers, was increased in endometrial cancer cells when FH was knocked down. In conclusion, the present study suggested that FH is a tumor suppressor and inhibits endometrial cancer cell proliferation and metastasis by inactivation of EGFR. Further studies are required to clarify its role as a prognostic biomarker and therapeutic target for endometrial cancer.

Relationship between Q-Tip Test and Urethral Hypermobility on Perineal Ultrasound.

BACKGROUND: The aim of this study was to assess the correlation between the overall rest-stress distance measured by transperineal ultrasound (TPUS) and Q-tip test angle in women with urodynamic stress incontinence (USI), and determine a cut-off value of rest-stress distance for predicting urethral hypermobility (UH). METHODS: Women with USI scheduled for mid-urethral sling surgery were retrospectively recruited. UH was defined as a Q-tip angle more than or equal to 30 degrees. Ultrasonic measurement of the overall rest-stress distance was defined as the linear distance of bladder-neck position change from resting status to maximal strain. RESULTS: Among the 132 enrolled women, the Pearson correlation coefficient between the overall rest-stress distance in TPUS and Q-tip test angle was 0.9104 (95% CI, 0.8758-0.9357, p < 0.001). In receiver-operating-characteristic-curve analysis, a rest-stress distance of more than 13.3 mm was an optimal cut-off value to predict UH (sensitivity = 76.47%, specificity = 93.3%; area = 0.937, 95% confidence interval: 0.881-0.972). CONCLUSIONS: The overall rest-stress distance in TPUS correlated well with the Q-tip test angle, indicating that it can be an alternative method for the assessment of USI. A rest-stress distance of more than 13.3 mm was an optimal cut-off value to predict UH in women with USI.

Zinc Finger Protein 90 Knockdown Promotes Cisplatin Sensitivity via Nrf2/HO-1 Pathway in Ovarian Cancer Cell.

Our study discussed the role of Zfp90 in ovarian cancer (OC) cell lines' sensitivity to cisplatin. We used two OC cell lines, SK-OV-3 and ES-2, to evaluate their role in cisplatin sensitization. The protein levels of p-Akt, ERK, caspase 3, Bcl-2, Bax, E-cadherin, MMP-2, MMP-9 and other drug resistance-related molecules, including Nrf2/HO-1, were discovered in the SK-OV-3 and ES-2 cells. We also used a human ovarian surface epithelial cell to compare the effect of Zfp90. Our outcomes indicated that cisplatin treatment generates reactive oxygen species (ROS) that modulate apoptotic protein expression. The anti-oxidative signal was also stimulated, which could hinder cell migration. The intervention of Zfp90 could greatly improve the apoptosis pathway and block the migrative pathway to regulate the cisplatin sensitivity in the OC cells. This study implies that the loss of function of Zfp90 might promote cisplatin sensitization in OC cells via regulating the Nrf2/HO-1 pathway to enhance cell apoptosis and inhibit the migrative effect in both SK-OV-3 and ES-2 cells.

Impact of management on the prognosis of pure uterine papillary serous cancer - a Taiwanese Gynecologic Oncology Group (TGOG) study.

OBJECTIVE: To investigate the clinical and pathological characteristics and the management of uterine papillary serous carcinoma (UPSC) in relation to patients' outcomes. METHODS: Clinicopathological data and the management of patients treated between 1991 and 2010 at 11 member hospitals of the Taiwanese Gynecologic Oncology Group (TGOG) were retrospectively reviewed. The Kaplan-Meier method was used to generate survival curves, and factors predictive of outcome were compared using the log-rank test and Cox regression analysis. RESULTS: A total of 119 pure UPSC patients were recruited. Stages I, II, III, and IV were identified in 34.5%, 2.5%, 36.1%, and 26.9% of the patients, respectively. The recurrence rate was 20.5% in FIGO stage I/II disease and 55.2% in FIGO stage III/IV disease. The 5-year overall survival rates for the patients with stage I, II, III, and IV disease were 92.0%, 66.7%, 34.2%, and 17.3%, respectively. Multivariate analysis showed that tumor stage (stage III/IV hazard ratio [HR] 8.65, 95% confidence interval [CI] 3.00-24.9) and optimal cytoreduction (HR 0.40, 95% CI 0.22-0.73) independently influenced the overall survival rate of UPSC patients. In addition, optimal cytoreduction (HR 0.36, 95% CI 0.17-0.78) and the combination of chemotherapy and radiation (HR 0.11, 95% CI 0.04-0.37) improved the overall survival of the advanced stage (FIGO stage III/IV) UPSC patients. CONCLUSIONS: UPSC represents an aggressive subtype of endometrial cancer commonly accompanied by extra-uterine disease. Comprehensive surgical staging with cytoreductive surgery is mandatory and beneficial for UPSC patients. Systemic chemotherapy combined with radiation should be considered as an adjuvant therapy for advanced stage UPSC patients.

Increased concentrations of serum inhibin B among male workers with long-term moderate lead exposure.

Lead is known to have an adverse effect to human reproductive system. This study investigates the association between different lead indices (both current and cumulative) and serum inhibin B as well as hormone concentrations in a group of 181 male lead workers. We used data collected during annual health examinations, including measurements of blood lead levels, inhibin B, follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (TTE) as well as age, gender, height, weight, smoking and drinking habits. The cumulative lead index included index of cumulative blood lead (ICL) and time weighted index of cumulative blood lead (TWICL) which were calculated from the series blood lead concentrations by annual health examinations since 1991 to the time of the study. Data was analyzed by Pearson correlation and multiple regressions. We found the Pearson correlation coefficients of ICL and TWICL vs. inhibin B to be 0.220 (p=0.003) and 0.231 (p=0.008), respectively. After adjusting for age, smoking, drinking, LH, FSH, and TTE, our multiple regression models revealed that with each unit increase in ICL and TWICL, there was a 0.047 pg/mL (p=0.017) and 1.333 pg/mL (p=0.007) increase in inhibin B. We found an association between cumulative lead index and concentration of serum inhibin B in male workers exposed to lead over long period, possibly indirectly affecting spermatogenesis.

Primary T-cell lymphoma of the uterine corpus.

Malignant lymphoma involving the genital tract is rare, and primary lymphoma of the uterus is even rarer. Immunohistochemically, most of the reported cases have been diffuse large cell lymphomas with a B-cell nature. Herein, we report an unusual case of uterine T-cell lymphoma in a 68-year-old woman. She suffered from fever, vaginal bleeding, and a huge mass in the lower abdomen. The initial clinical and histologic studies failed to indicate a cell type. We provide the clinical details of the case and discuss the diagnostic pitfalls.

Association between quantitative high-risk human papillomavirus DNA load and cervical intraepithelial neoplasm risk.

Human papillomavirus (HPV) infection is a high-risk factor for cervical intraepithelial neoplasm (CIN) but the association between the quantitative HPV DNA load and the severity of CIN remains controversial. We conducted a community study to investigate the correlation between the two. Potential study subjects were selected through Pap smear screening in Kaohsiung County, Taiwan. Ninety-one subjects with either their first case of inflammation or > or =CIN1 by biopsy confirmation were assigned to a case group; 175 normal subjects with negative findings by Pap smears or biopsies were assigned to a control group. Cervical HPV load was detected with Hybrid Capture II assay for high-risk HPV infection, with nested PCR for high- and low-risk HPV infection, and with type-specific PCR for HPV type 16 (HPV-16). Individuals with positive high-risk HPV infection had an increased risk of developing CIN. Compared with HPV-negative subjects, the odds ratios were 32.2 [95% confidence interval (95% CI), 10.4-99.5] for subjects with CIN1, 37.2 (95% CI, 7.4-187.6) for subjects with CIN2, and 68.3 (95% CI, 14.1-328.5) for subjects with > or =CIN3 after adjusting for other confounding factors. The similar trend was also found among the HPV-16-negative individuals. In addition, high-risk HPV DNA load levels were highly correlated with the different grades of CINs in the overall population (Spearman's correlation coefficient r = 0.67, P < 0.0001, n = 266) and the HPV-16-negative population (Spearman's correlation coefficient r = 0.58, P < 0.0001, n = 234). We concluded that high-risk HPV infection, irrespective of HPV-16 infection, was highly and positively associated with the development of CIN.

Cyclooxygenase-2 expression in the endometrium at the end of 2 years' continuous combined hormone replacement therapy.

OBJECTIVE: To evaluate the change of endometrial histology and the expression of cyclooxygenase-2 (Cox-2) in the endometrium after continuous combined hormone replacement therapy (HRT). METHODS: Forty-five postmenopausal women were recruited. All participants received 0.625 mg conjugated equine estrogen (CEE) and 2.5 mg medroxyprogesterone (MPA) daily for 2 years. Endometrial biopsy was performed twice, before medication (baseline) and after 2 years of HRT, respectively. Immunohistochemistry was used to detect the presence of Cox-2 expression. RESULTS: More atrophic and weak secretory features of endometrium were noted after the 2-year HRT. Endometrial hyperplasia and carcinoma were not found and immunohistochemistry results revealed that Cox-2 was not expressed in the endometrium. CONCLUSION: Cox-2, known to play an important role in the tumorigenesis of cancer, was not stained in endometrium tissue after hormonal induction and more endometrium atrophy was noted after the 2-year HRT. From the results, it is noted that continuous combined HRT may be a relatively safe and appropriate regimen for long-term use in postmenopausal women.