Changes in the Expression of TBP-2 in Response to Histone Deacetylase Inhibitor Treatment in Human Endometrial Cells

Histone deacetylase inhibitors (HDACi) induce apoptosis preferentially in cancer cells by caspase pathway activation and reactive oxygen species (ROS) accumulation. Suberoylanilide hydroxamic acid (SAHA), a HDACi, increases apoptosis via altering intracellular oxidative stress through thioredoxin (TRX) and TRX binding protein-2 (TBP-2). Because ROS accumulation, as well as the redox status determined by TBP-2 and TRX, are suggested as possible mechanisms for endometriosis, we queried whether SAHA induces apoptosis of human endometrial cells via the TRX-TBP-2 system in endometriosis. Eutopic endometrium from participants without endometriosis, and ectopic endometrium from patients with endometriosis, was obtained surgically. Human endometrial stromal cells (HESCs) and Ishikawa cells were treated with SAHA and cell proliferation was assessed using the CCK-8 assay. Real-time PCR and Western blotting were used to quantify TRX and TBP-2 mRNA and protein expression. After inducing oxidative stress, SAHA was applied. Short-interfering TRX (SiTRX) transfection was performed to see the changes after TRX inhibition. The mRNA and protein expression of TBP-2 was increased with SAHA concentrations in HESCs significantly. The mRNA TBP-2 expression was decreased after oxidative stress, upregulated by adding 2.5 μM of SAHA. The TRX/TBP-2 ratio decreased, apoptosis increased significantly, and SiTRX transfection decreased with SAHA. In conclusion, SAHA induces apoptosis by modulating the TRX/TBP-2 system, suggesting its potential as a therapeutic agent for endometriosis.ope

Decreased Renal Function Is a Risk Factor for Subclinical Coronary Atherosclerosis in Korean Postmenopausal Women

Objectives : Decreased renal function is associated with increased cardiovascular risk. Our study was planned to verify the association of decreased renal function and subclinical coronary atherosclerosis in postmenopausal women. Methods : We performed a retrospective review of 251 Korean postmenopausal women who visited the health promotion center for a routine health checkup. Estimated glomerular filtration rate (eGFR) was used to show renal function, which was estimated by calculated using the Cockcroft-Gault (CG) and the modification of diet in renal disease (MDRD) formulas. Coronary atherosclerosis was assessed by 64-row multidetector computed tomography. Results : Women with reduced eGFR (< 60 mL/minute/1.73 m2) had significantly higher brachial-ankle pulse wave velocity (baPWV) than women with normal eGFR (≥ 60 mL/minute/1.73 m2). The eGFR was negatively correlated with baPWV (r = -0.352, P < 0.001), significantly. The eGFR was lower in women with coronary atherosclerosis than in normal control women, markedly. Reduced eGFR was significantly associated with the presence of coronary atherosclerosis (odds ratio [OR] = 7.528, 95% confidence interval [CI] = 2.728-20.772, P < 0.001). Conclusions : Decreased eGFR was closely associated with increased arterial stiffness and coronary atherosclerosis in postmenopausal women. Evaluating subclinical atherosclerosis by screening the renal function in postmenopausal women may be helpful screening high risk group and considering starting menopausal hormone therapy before atherosclerosis development.ope

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.ope

Association between levels of serum ferritin and bone mineral density in Korean premenopausal and postmenopausal women: KNHANES 2008-2010.

BACKGROUND: As women go through menopause, serum estrogen decreases and ferritin increases. Decreased serum estrogen is well known to cause detrimental effects on bone health; however, data on the associations of serum ferritin with BMD before and after menopause are still lacking. Therefore, this study aimed to investigate the association between serum ferritin levels and BMD in premenopausal and postmenopausal Korean women. METHODS: This study was performed using data from the 2008-2010 Korean National Health and Nutrition Examination Survey, including 7300 women (4229 premenopausal and 3071 postmenopausal). BMD was measured using dual X-ray absorptiometry at the femur and the lumbar spine, and serum ferritin levels were measured by chemiluminescent immunoassay. RESULTS: Median serum ferritin levels in postmenopausal women were higher than those in premenopausal women despite the same age ranges. Serum ferritin levels were only significantly correlated with BMD on the lumbar spine (β = -0.189, p-value = 0.005) in premenopausal women after adjusting confounding factors. Additionally, BMD on the lumbar spine had tended to decrease as serum ferritin quartiles increase (P for trend = 0.035) in premenopausal women after adjusting confounding factors. On the other hand, there were no significant associations between serum ferritin levels and BMD on the total femur and, femur neck in premenopausal women, and BMD on the total femur, femur neck, and lumbar spine in postmenopausal women. CONCLUSION: Increased serum ferritin levels were significantly associated with BMD in premenopausal women, particularly on the lumbar spine, but not in postmenopausal women.ope

Effects of vitamin D deficiency and daily calcium intake on bone mineral density and osteoporosis in Korean postmenopausal woman

OBJECTIVE: We evaluated the combined effects of vitamin D and daily calcium intake on bone mineral density (BMD) and osteoporosis in Korean postmenopausal women. METHODS: This study is a cross-sectional study consisting of 1,921 Korean postmenopausal women aged 45 to 70 years without thyroid dysfunction, from the 2008-2011 Korean National Health and Nutrition Examination Survey. Participants were classified into six groups according to serum 25-hydroxyvitamin D (25(OH)D) levels and daily calcium intake. BMD was measured using dual-energy X-ray absorptiometry at femur and at lumbar spine, and the serum vitamin D levels were measured by radioimmunoassay. RESULTS: The BMD divided according to serum 25(OH)D and daily calcium intakes were not statistically different among the groups. However, when both daily calcium intake and serum 25(OH)D were not sufficient, risk of osteopenia and osteoporosis showed significant increase in both femur neck and lumbar spine (odds ratio [OR] 2.242, P=0.006; OR 3.044, P=0.001; respectively). Although daily calcium intake was sufficient, risks of osteopenia and osteoporosis significantly increased in lumbar spine group if serum 25(OH)D is <20 ng/mL (OR 2.993, P=0.006). CONCLUSION: The combined effects of insufficient daily calcium intake and vitamin D deficiency may cause low BMD and increase in prevalence of osteopenia and osteoporosis in Korean postmenopausal women aged 45 to 70 years.ope

Minimal stimulation using gonadotropin combined with clomiphene citrate or letrozole for intrauterine insemination

PURPOSE: To evaluate the efficacy of minimal stimulation using discretely administered gonadotropin combined with clomiphene citrate (CC) or letrozole (LTZ) for intrauterine insemination (IUI) cycles. MATERIALS AND METHODS: Total 257 IUI cycles from 158 infertile couples were assessed. A CC dose of 100 mg/day (n=126 cycles) or a LTZ dose of 5 mg/day (n=131 cycles) was administered on days 3-5 of the menstrual cycle for 5 days. Each group received human menopausal gonadotropin at a dose of 150 IU by two or three alternative day: CC combined with alternate-day regimen for 2 or 3 days (CC+300, n=37; CC+450, n=89) and LTZ combined with alternate-day regimen for 2 or 3 days (LTZ+300, n=36; LTZ+450, n=95). RESULTS: The clinical pregnancy rate was comparable between the CC and LTZ groups (18.3% vs. 13.0%, p=0.243). The clinical pregnancy rate also showed no significant difference among the 4 groups (21.6% vs. 16.9% vs. 11.1% vs. 12.6%, p=0.507). The multiple pregnancy rate was significantly higher in LTZ compared to CC group (37.5% vs. 8.7%, p=0.028) and in the LTZ+450 compared to CC+450 group (50% vs. 13.3%, p=0.038). Overall, there were 15 cases of ovarian hyperstimulation syndrome (OHSS), with the prevalence being significantly lower in the LTZ compared to CC group (1.5% vs. 10.3%, p=0.003). OHSS was more prevalent in the CC+450 compared to the LTZ+450 group (12.4% vs. 1.1%, p=0.002). CONCLUSION: Our findings suggest that minimal stimulation using two alternate-day gonadotropin with LTZ decreases the development of OHSS and multiple pregnancies, while maintaining comparable pregnancy rates in IUI cycles.ope

A study on the Korean literary criticism in the 1950`s

학위논문(박사)--서울대학교 대학원 :국어국문학과 현대문학전공,2002.Docto

Association of metabolic syndrome with coronary atherosclerosis in non-diabetic postmenopausal women

OBJECTIVE: We investigated the possible association of metabolic syndrome with arterial stiffness and coronary atherosclerosis in non-diabetic, postmenopausal women. METHODS: A total of 293 non-diabetic, postmenopausal women who visited the health promotion center for a routine health check-up were included in a cross-sectional study. Arterial stiffness was measured by brachial-ankle pulse wave velocity, and coronary atherosclerosis was detected using 64-row multi-detector computed tomography. RESULTS: Women with coronary atherosclerosis had a significantly higher proportion of metabolic syndrome than those without coronary atherosclerosis. The brachial-ankle pulse wave velocity was significantly higher in women who had metabolic syndrome compared to those who had no metabolic syndrome (1567.71 ± 211.81 vs. 1336.75 ± 159.62 cm/s, p < 0.001). In addition, the brachial-ankle pulse wave velocity was shown to increase with increasing number of metabolic syndrome components (p for trend < 0.001). Metabolic syndrome was associated with increased risk of coronary atherosclerosis (adjusted odds ratio 2.38; 95% confidence interval 1.01-5.06), after adjusting for confounding factors. CONCLUSIONS: Metabolic syndrome increases the risk of coronary atherosclerosis in postmenopausal women. Increased arterial stiffness may partly explain an increased risk of coronary atherosclerosis in postmenopausal women with metabolic syndrome.ope

Postoperative Levonorgestrel-Releasing Intrauterine System Insertion After Gonadotropin-Releasing Hormone Agonist Treatment for Preventing Endometriotic Cyst Recurrence: A Prospective Observational Study

OBJECTIVE: The aim of this study was to evaluate the effectiveness of postoperative levonorgestrel-releasing intrauterine system (LNG-IUS) insertion after gonadotropin-releasing hormone agonist (GnRH-a) treatment for preventing endometriotic cyst recurrence. STUDY DESIGN: The LNG-IUS was applied to 28 women who had undergone surgery for endometriosis followed by 6 cycles of GnRH-a treatment. Clinical characteristics, endometriosis recurrence, and adverse effects were analyzed. Student t test was performed for analysis. RESULTS: Before surgery, 20 (71.4%) patients had dysmenorrhea, and the mean pain score (visual analog scale [VAS]) was 4.26. The numbers of women diagnosed with stage III endometriosis and stage IV endometriosis were 15 (53.6%) and 13 (46.4%), respectively, according to the revised American Fertility Society scoring system. The mean cancer antigen 125 levels and VAS scores were significantly lower after treatment than before treatment (11.61 vs 75.66 U/mL, P < .0001 and 0.50 vs 4.26 U/mL, P < .0001, respectively). Of the 28 patients, 13 (46.4%) simultaneously had adenomyosis, and 2 (7.1%) underwent LNG-IUS removal because of unresolved vaginal bleeding and dysmenorrhea. Recurrence was noted in 2 (7.1%) women. CONCLUSION: Postoperative LNG-IUS insertion after GnRH-a treatment is an effective approach for preventing endometriotic cyst recurrence, especially in women who do not desire to conceive.restrictio

Trichostatin A Induces NAG-1 Expression and Apoptosis in Human Endometriotic Stromal Cells

To investigate the effects of trichostatin A (TSA) on nonsteroidal anti-inflammatory drug-activated gene 1 (NAG-1) expression and apoptosis in human endometriotic stromal cells (HESCs), ectopic endometrial tissues were obtained from 15 patients with endometriotic cysts who underwent cystectomy. Human endometriotic stromal cells were isolated and cultured with different concentrations of TSA. Nonsteroidal anti-inflammatory drug-activated gene-1 messenger RNA (mRNA) and protein levels were evaluated by real-time polymerase chain reaction and Western blotting, respectively, and apoptosis was assessed by flow cytometry. Viability of HESCs was reduced in a dose-dependent manner by treatment with TSA. The percentage of early and late apoptotic HESCs was increased upon treatment with TSA. Nonsteroidal anti-inflammatory drug-activated gene-1 mRNA and protein expression was induced in a dose-dependent manner by TSA treatment. Gene knockdown experiments using small-interfering RNA confirmed an association between NAG-1 expression and TSA-induced apoptosis. Whether effects of TSA on NAG-1 gene expression are enhanced in the presence of 5-aza-2'-deoxycytidine (5-aza-dC) are also investigated; however, TSA-induced apoptosis was unaffected by 5-aza-dC. In conclusion, TSA induced apoptosis in HESCs via induction of NAG-1 expression. These results suggest that upregulation of NAG-1 contributes to TSA-induced apoptosis in HESCs.restrictio