Korean red ginseng induces extrinsic and intrinsic apoptotic pathways in MCF-7 breast cancer cells and MCF-10A non-malignant breast cells.

BACKGROUND: Among non-hormonal treatments, herbal products are frequently used by women. Korean red ginseng (KRG) is one of the popular herbal medicines. KRG could be one option for relieving menopausal symptoms. However, there are still concerns about the safety for long-term use. In order to be used for alleviating menopausal symptoms, the safety of KRG on breast must be ensured. The purpose of this study was to investigate the effects of KRG on breast cells. METHODS: MCF-7 and MCF-10A cells were treated with different concentrations of KRG extracts for 48 h. Cell viability was evaluated by MTT assay, and apoptosis by flow cytometry. The expression of apoptosis-related proteins was determined by western blot analysis and estrogen receptor (ER) affinity by ER binding assay. RESULTS: KRG extract inhibited growth and induced apoptosis of both MCF-7 and MCF-10A cells in dose-dependent manner. KRG extract increased the expression of pro-apoptotic proteins BAX, BAK, and BAD and decreased the expression of anti-apoptotic proteins Bcl-2 and Bcl-XL in both cells. The expressions of Fas and FasL were increased in lower doses, but decreased in higher doses in both cells. Activities of caspase-3, -8 and -9 increased in MCF-10A, while caspase-8 and -9 showed increase in MCF-7. Competition of KRG to E2 was significant in MCF-7 as KRG dose increased, whereas ER binding was hardly shown in MCF-10. CONCLUSION: KRG induced apoptosis via extrinsic and intrinsic pathway in MCF-7 breast cancer cells and MCF-10A non-malignant cells. KRG may be safely used with regard to breast cancer risk in postmenopausal women to reduce the vasomotor symptoms.

Scheduled injection of ramosetron for prevention of nausea and vomiting following single-port access total laparoscopic hysterectomy: a prospective randomized study.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of scheduled ramosetron injections for controlling postoperative nausea and vomiting (PONV) after single-port access total laparoscopic hysterectomy (SPA-TLH). METHODS: Ninety patients who underwent SPA-TLH at the Korean National Health Insurance Service Ilsan Hospital between June 2013 and July 2014 were enrolled in this prospective, randomized, double-blinded, placebo-controlled study. The patients were divided into 2 groups as follows: the ramosetron group (0.3 mg intravenously [IV]; n=45) and the placebo group (normal saline IV; n=45). Both groups received their respective injections 12 and 24 hours post surgery. The incidence and severity of PONV (numerical rating scale, 0-10), and the use of rescue antiemetics post surgery were evaluated. RESULTS: Demographic and perioperative statistically significant differences were not observed between the 2 groups. The incidence of PONV in the ramosetron and placebo groups was 46.7% and 51.1%, respectively (P=0.51). We found significant differences in the severity of PONV between the 24- to 48-hour postoperative periods in both groups (ramosetron group, P=0.04 and placebo group, P=0.03). The use of rescue antiemetics was significantly lower in the ramosetron group than in the placebo group (P=0.02). CONCLUSION: After general anesthesia, scheduled injections of ramosetron 12 and 24 hours after SPA-TLH reduced the severity of PONV and the use of rescue antiemetics. Administration of ramosetron can be considered not only immediately after SPA-TLH but also during the first 24-hour recovery period. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02011659.

Comparison of the clinical outcome of frozen-thawed embryo transfer with and without pretreatment with a gonadotropin-releasing hormone agonist.

OBJECTIVE: To describe the clinical outcomes of frozen-thawed embryo transfer (FET) with artificial preparation of the endometrium, using a combination of estrogen (E2) and progesterone (P4) with or without a gonadotropin-releasing hormone agonist (GnRHa), and the modified natural cycle (MNC) with human chorionic gonadotropin (hCG) trigger. METHODS: In this retrospective study, we evaluated 187 patients during 3 years (February 2012-April 2015). The patients were allocated to the following treatment groups: group A, comprising 113 patients (181 cycles) who received GnRHa+E2+P4; group B, comprising 49 patients (88 cycles) who received E2+P4; and group C, comprising 25 patients (42 cycles) who received hCG+P4. The inclusion criteria were regular menstrual cycles (length 24-35 days) and age 21-45 years. RESULTS: The primary outcome of the study - implantation rate (IR) per embryo transferred - was not statistically different among the 3 groups. Similar results were found for the IRs with fetal heartbeat per embryo transferred (68/181 [37.6%] in group A vs. 22/88 [25.0%] in group B vs. 14/42 [33.3%] in group C) and for the live birth rates (LBRs) per embryo transferred (56/181 [30.9%] in group A vs. 18/88 [20.5%] in group B vs. 11/42 [26.2%] in group C). CONCLUSION: Although the pregnancy outcomes were better in the hormone therapy with GnRHa group, hormone therapy FET with GnRHa for pituitary suppression did not result in significantly improved IRs and LBRs when compared with hormone therapy FET without GnRHa or MNC FET.

Effects of Nonsteroidal Anti-Inflammatory Drugs as Patient Controlled Analgesia on Early Bowel Function Recovery after Radical Cystectomy.

This study aimed to evaluate the effects of ketorolac, a commonly used non-steroidal anti-inflammatory drug (NSAID) as patient controlled intravenous infusion analgesia (PCIA) for the patients underwent radical cystectomy (RC) due to bladder cancer regarding post-operational indices of recovery. Total seventy patients who underwent radical cystectomy for the treatment of bladder cancer were included in the study. 35 patients received ketorolac as PCIA (NSAIDS group) and 35 patients had morphine infusion as PCIA (morphine group). Pain intensity, bowel function recovery and length of hospital stay were evaluated. Early postoperative complications were analyzed according to surgical types (robot RC vs. open RC). Demographics were similar between two groups. NSAIDS group showed a significant reduction in postoperative vomiting (p = 0.001), time to flatus (p = 0.028), time to first bowel movement (p = 0.001) and time to first clear liquid diet (p = 0.002) compared with morphine group. No statistically significant differences were observed between two groups regarding length of hospitalization, and postoperative complications. For 48 hours after RC, pain relief was slightly better in morphine group (p < 0.001). Both open RC and robot RC cases showed significantly better bowel function recovery with NSAIDS groups. Ketorolac as PCIA is relatively effective in pain management with better gastrointestinal recovery after RC.

Common Causes of Postmenopausal Bleeding in Korean Women: 10-Year Outcomes from a Single Medical Center.

The common causes of postmenopausal bleeding (PMB), according to the data from the western world, are atrophy, hormone replacement therapy (HRT), endometrial cancer, etc. We conducted a retrospective study to assess whether the causes of PMB in Korean postmenopausal women are similar to those already known. This retrospective study used 10-year medical records (March 2005 to December 2014) of 792 PMB women in the Yonsei University Health System. The data were divided into 2 categories by 5-year intervals to compare the differences between the 2 periods. The most common cause of PMB in Korean women was atrophy (51.1%). Polyps and HRT were the second, followed by anticoagulant medications, cervical cancer, and endometrial cancer. The proportion of patients with cervical cancer significantly decreased during the second half of the decade (8.7% vs. 5.2%; P = 0.048). Although no significant change was noted for HRT, its rank was higher during the latter 5-year period. Only the most common cause of PMB was the same as the conventional data. Interestingly, the proportion of patients with cervical cancer decreased during the latter half of the decade, reflecting the changes in the nation's cancer prevalence rate, while the use of HRT increased.

Correction: The Relationship between Serum Ferritin Levels and Insulin Resistance in Pre- and Postmenopausal Korean Women: KNHANES 2007-2010.

[This corrects the article DOI: 10.1371/journal.pone.0157934.].

The Relationship between Serum Ferritin Levels and Insulin Resistance in Pre- and Postmenopausal Korean Women: KNHANES 2007-2010.

BACKGROUND: Serum ferritin levels increase in postmenopausal women, and they are reported to be linked to major health problems. Here, we investigated the association between serum ferritin levels and insulin resistance (IR) in postmenopausal women. METHODS: A total of 6632 healthy Korean women (4357 premenopausal and 2275 postmenopausal) who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) in 2007-2010 were enrolled in the study. Serum ferritin values were divided into six groups for the premenopausal and postmenopausal groups. IR and obesity indices were evaluated according to the six serum ferritin groups. Statistical analysis was carried out using SAS software, version 9.2 (SAS Institute Inc., Cary, NC, USA). RESULTS: The association between the IR indices and ferritin groups had a higher level of statistical significance in the postmenopausal group than in the premenopausal group. In addition, for the postmenopausal group, the estimates increased significantly in the sixth ferritin group compared to those in the first ferritin group. However, the association between the obesity indices and ferritin levels was not significantly different between the premenopausal and postmenopausal groups. CONCLUSION: Elevated serum ferritin levels were associated with an increased risk of insulin resistance in postmenopausal women.

Serum Thyroid Stimulating Hormone Levels Are Associated with the Presence of Coronary Atherosclerosis in Healthy Postmenopausal Women.

OBJECTIVES: Menopause is a natural aging process causing estrogen deficiency, accelerating atherogenic processes including dyslipidemia. Prevalence of thyroid dysfunction is also high in postmenopausal women, and it is known to elevate the risk of cardiovascular disease (CVD). Therefore, we are to study on the associations in between serum thyroid stimulating hormone (TSH) and prevalence of CVD in postmenopausal women who have normal thyroid function. METHODS: We performed a retrospective review of 247 Korean postmenopausal women who visited the health promotion center from January, 2007 to December, 2009. Postmenopausal women with normal serum TSH were included in the study. Coronary atherosclerosis was assessed by 64-row multidetector computed tomography. RESULTS: In multiple linear regression analysis, serum TSH was associated with serum triglyceride (TG) (ß = 0.146, P = 0.023). In multiple logistic regression analysis, increasing age and serum TSH were associated with an increased risk of coronary atherosclerosis in euthyroid postmenopausal women (odds ratio [OR] = 1.107 [1.024-1.197], P = 0.011 and OR = 1.303 [1.024-1.658], P = 0.031, respectively). CONCLUSIONS: It revealed that significant predictor of serum TSH was serum TG, and increasing age and TSH were found to have associations with an increased risk of coronary atherosclerosis in euthyroid postmenopausal women. Screening and assessing risks for CVD in healthy postmenopausal women would be helpful before atherosclerosis develops.

Anti-Proliferative and Apoptotic Activities of Müllerian Inhibiting Substance Combined with Calcitriol in Ovarian Cancer Cell Lines.

PURPOSE: This study aimed to investigate whether Müllerian inhibiting substance (MIS) in combination with calcitriol modulates proliferation and apoptosis of human ovarian cancer (OCa) cell lines (SKOV3, OVCAR3, and OVCA433) and identify the signaling pathway by which MIS mediates apoptosis. MATERIALS AND METHODS: OCa cell lines were treated with MIS in the absence or presence of calcitriol. Cell viability and proliferation were evaluated using the Cell Counting Kit-8 assay and apoptosis was evaluated by DNA fragmentation assay. Western blot and enzyme-linked immunosorbent assay were used to determine the signaling pathway. RESULTS: The cells showed specific staining for the MIS type II receptor. Treatment of OCa cells with MIS and calcitriol led to dose- and time-dependent inhibition of cell growth and survival. The combination treatment significantly suppressed cell growth, down-regulated the expression of B-cell lymphoma 2 (Bcl-2), and up-regulated the expressions of Bcl-2 associated X protein, caspase-3, and caspase-9 through the extracellular signal-regulated kinase signaling pathway. CONCLUSION: These results, coupled with a much-needed decrease in the toxic side effects of currently employed therapeutic agents, provide a strong rationale for testing the therapeutic potential of MIS, alone or in combination with calcitriol, in the treatment of OCa.

Effects of levonorgestrel-releasing intrauterine system on lymphangiogenesis of adenomyosis.

OBJECTIVES: Lymphangiogenesis may be involved in the pathogenesis of adenomyosis. We investigated the lymphatic vessels of patients with adenomyosis, including those treated with levonorgestrel-releasing intrauterine system (LNG-IUS). METHODS: Full-thickness uterine samples were obtained from patients who received hysterectomies. Twenty-one patients with adenomyosis and 17 patients with adenomyosis who were treated with LNG-IUS were included. Eighteen patients with cervical intraepithelial neoplasia served as controls. Immunohistochemical staining was performed with antibodies against podoplanin and lymphatic vessel endothelial hyaluronan receptor 1. The lymphovascular density (LVD) was analyzed in each sample by the "hot spot" method. RESULTS: The LVDs were significantly higher in the endometrial and myometrial tissues of patients with adenomyosis compared with those of patients treated with the LNG-IUS or controls. No significant differences were noted between the LNG-IUS-treated group and controls. Evaluation of the LVDs according to the menstrual cycle showed that the differences in the endometrial tissues of the adenomyosis group and those of the LNG-IUS-treated group or the controls were more prominent during the secretory phase. CONCLUSIONS: Treatment with the LNG-IUS resulted in reduced lymphangiogenesis and LVD in the endometrial and myometrial tissues of patients with adenomyosis. Reduced lymphangiogenesis may be one mechanism by which the LNG-IUS reduces adenomyosis-related symptoms.

Renal function is associated with bone mineral density and arterial stiffness in healthy postmenopausal women.

BACKGROUND/AIMS: This study aimed to investigate the effect of renal function on bone mineral density (BMD) and arterial stiffness in postmenopausal women. METHODS: This is a retrospective cross-sectional study. We studied 252 postmenopausal women who visited a health promotion center for a medical checkup. The estimated glomerular filtration rate (eGFR) was calculated using the Cockcroft-Gault (CG) formula and the modification of diet in renal disease (MDRD) formula. Areal BMD measurements were performed using dual-energy X-ray absorptiometry, and arterial stiffness was measured using the brachial-ankle pulse wave velocity (baPWV). RESULTS: The eGFR according to the CG formula was significantly correlated with age, BMI, follicle-stimulating hormone, thyroid-stimulating hormone, high-density lipoprotein cholesterol, baPWV, and BMD at the lumbar spine, femoral neck, and total hip sites. However, the eGFR according to the MDRD formula was significantly correlated with age and baPWV but not with BMD at the lumbar spine, femoral neck, and total hip sites. Decreased renal function (eGFR <60 ml/min/1.73 m(2) according to the CG formula) was independently associated with decreased BMD at the femoral neck site and with increased baPWV (>1,500 cm/s) after adjusting for confounding variables. CONCLUSION: Postmenopausal women with decreased renal function are more likely to have a decreased BMD and greater arterial stiffness.

Antioxidative effects of Korean red ginseng in postmenopausal women: a double-blind randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Red ginseng (RG) has been widely used to treat various diseases in East Asian countries. Previous studies have shown the anti-oxidative and anti-diabetic effects of RG. This study aimed to investigate the effects of RG on oxidative stress and insulin resistance in postmenopausal women. MATERIALS AND METHODS: We performed a randomized, double-blind, placebo-controlled trial in 82 postmenopausal women aged 45-60 years. Participants were randomized to receive 3g red ginseng daily or placebo for 12 weeks. Antioxidant enzymes activity (superoxide dismutase, glutathione peroxidase) and oxidative stress markers (malondialdehyde, 8-hydroxydeoxyguanosine) were assessed, and the homeostatic model assessment of insulin resistance index was calculated at the baseline and at the end of the trial. RESULTS: A total of 71 postmenopausal women completed the study. Serum superoxide dismutase activity was significantly increased after the 12-week RG supplementation (P<0.001), and these changes were statistically significant compared with the placebo group (P=0.004). Serum malondialdehyde levels showed a tendency to decrease after the 12-week RG supplementation (P=0.001), but these changes were not statistically significant compared with the placebo group (P=0.064). No statistically significant changes in serum glutathione peroxidase and 8-hydroxydeoxyguanosine were noted. Further, RG supplementation showed no effects on fasting glucose, fasting insulin, and insulin resistance. CONCLUSIONS: The results suggest that RG may reduce oxidative stress by increasing antioxidant enzyme activity in postmenopausal women.

Association between vitamin D status and risk of metabolic syndrome among Korean postmenopausal women.

This study aimed to investigate the association between serum levels of 25-hydroxyvitamin D [25(OH)D] and metabolic syndrome along with its associated risk factors in Korean postmenopausal women. This study was performed using data from the KNHANES 2008-2010 study and included 4,364 postmenopausal Korean women. Clinical and other objective characteristics, seasonality, and presence of metabolic syndrome with its five components were evaluated and correlated with the serum levels of 25(OH)D. Although no statistically significant associations were observed between the levels of serum 25(OH)D and the prevalence of metabolic syndrome, the adjusted OR for elevated blood pressure, elevated triglycerides (TGs), and reduced high-density lipoprotein cholesterol (HDL-C) showed tendency to decrease sequentially as tertiles of serum 25(OH)D levels increased (p for trends  = 0.066, 0.043, and 0.010, respectively). Women in the highest tertile of serum 25(OH)D showed a significant decrease in the prevalence of elevated blood pressure, elevated TGs, and reduced HDL-C as compared with those in the lowest tertile of serum 25(OH)D (p = 0.020, 0.014, and 0.002, respectively). Based on these results, we consider that adequate serum levels of 25(OH)D in Korean postmenopausal women may not entirely indicate a lower risk of developing metabolic syndrome. However, adequate serum levels of 25(OH)D are significantly associated with a decrease in elevated blood pressure, elevated TGs, and reduced HDL-C levels in postmenopausal women.

Evaluation of elevated urinary enolase I levels in patients with endometriosis.

OBJECTIVE: The aim of this study is to validate and investigate the clinical value of urinary enolase I in patients with endometriosis. METHODS: Urine samples of 39 patients with histologically confirmed endometriosis and 20 patients without endometriosis were collected. Western blot analysis and enzyme-linked immunosorbent assay were used to detect the increase of enolase I in patients' urine. RESULTS: Urinary enolase I expression corrected for creatinine ratio (non neuronal enolase (NNE)-Cr) was significantly greater in patients with endometriosis (p = 0.026). When the diagnostic performance of NNE-Cr was evaluated with serum CA-125 combination, the area under the curve was 0.821 (95% confidence interval 0.713-0.928) with sensitivity and specificity of 76.9% and 85.0%, respectively. CONCLUSION: Elevated urinary enolase I, in conjunction with serum CA-125, may be used as a potential biomarker for endometriosis.