• Journal of Pharmacopuncture
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• v.27 no.2
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• pp.131-141
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• 2024

Objectives: Polycystic ovary syndrome (PCOS) is one of the most common disorders and it shows up to 20% prevalence in reproductive-aged women populations, but no cures are available to date. We aimed to investigate the protective effects of Changbudodam-tang (CBD) on cell death signaling pathways, inflammation, and oxidative stress observed in Bone-Marrow derived human mesenchymal stem cell (BM-hMSC) by means of PCOS therapeutics in the future. Methods: BM-hMSCs were applied with cell deaths and injuries. Apoptosis and pyroptosis signals were quenched with their related signaling pathways using quantitative PCR, Western blot, and fluorescence image analysis. Results: Our data clearly displayed hydrogen peroxide- and nigericin-treated cell death signaling pathways via regulations of mitochondrial integrity and interleukin (IL)-1β at the cellular levels (p < 0.01 or 0.001). We further observed that pre-treatment with CBD showed protective effects against oxidative stress by enhancement of antioxidant components at the cellular level, with respect to both protein and mRNA expression levels (p < 0.05, 0.01 or 0.001). The mechanisms of CBD were examined by Western blot analysis, and it showed anti-cell death, anti-inflammatory, and antioxidant effects via normalizations of the Jun N-terminal kinase/mitogen-activated protein kinase kinase 7/c-Jun signaling pathways. Conclusion: This study confirmed the pharmacological properties of CBD by regulation of cellular oxidation and the inflammation-provoked cell death condition of BM-hMSCs, which is mediated by the MKK7/JNK/c-Jun signaling pathway.

• Journal of Physiology & Pathology in Korean Medicine
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• v.32 no.4
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• pp.217-225
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• 2018

This study was to investigate the relationship between ultrasonographic examination and pattern identification classification on cinical studies in chinese medicine. We searched clinical studies related correlation between ultrasonographic examination and pattern identification classification in chinese medicine, that published from 2013 to 2016 in China National Knowledge Infrastructure (CNKI) databases by keywords, 'ultrasound(超?)', 'chinese medicine(中?)', 'syndrome differentiation (辨?)'. Seventeen studies were found. There were 7 studies of gynecological diseases including polycystic ovary syndrome and uterine myoma, 5 studies of fatty liver, 3 studies of arthritis, and 1 studie of thyroid nodule and lymphadenopathy respectively. As a result, ii is thought that there was a certain degree of correlation between the change of the ultrasonographic image and the pathological types according to traditional chinese medicine (TCM) syndrome differentiation and ultrasonographic examination could be used as secondary means for the TCM syndrome differentiation classification. In conclusion, by using ultrasonograph device in a medicinal way of TCM and traditional korean medicine (TKM), it is thought that more detailed and accurate diagnosis and treatment are possible and the evidence for reasonableness of syndrome differentiation in TCM and TKM its validity can be secured.

• Clinical and Experimental Reproductive Medicine
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• v.28 no.2
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• pp.141-145
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• 2001

Objective: We inversigated Small Heterodimer Partner (SHP) gene mutation in Korean Polycystic Ovarian Syndrome (PCOS) patients. SHP protein regulates the activity of nuclear receptors which regulate the cellular development and differentiation. Recently, the mutation of SHP gene was found in the obesity and diabetes patients in Japanese group, and suggested that its mutation may involved in pathogenic mechanism of PCOS. Methods: This study was performed in 20 PCOS patients and 20 normal women. The DNAs were extracted from the peripheral bloods, and amplified at each exon (1 and 2) of SHP gene by PCR method. Subsequently, each PCR product was digested with the restriction enzyme indicated below for studying restriction fragment length polymorphism (RFLP). After enzyme digestion, the results of RFLP were compared PCOS patients with control women to find any sequence variation. Results: We examined 9 regions of exon 1 with Msp I, Pvu II, Dde I and 3 regions of exon 2 with Pst I, Dde I. There is no heterozygous or homozygous mutation in patients and control women at these restriction sites. Conclusion: The genetic analysis at our restriction sites in the SHP gene did not show any genetic variation in Korean PCOS patients. Our PCR-RFLP analysis was not covered the entire SHP gene (68 bp/1,006 bp), we need to further analysis of the entire SHP gene.

• Clinical and Experimental Reproductive Medicine
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• v.32 no.2
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• pp.155-164
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• 2005

Objective: This study was performed to investigate the effects of pioglitazone, an insulin sensitizing agent, on insulin resistance, ovarian function and intraovarian stromal blood flow in patients with polycystic ovarian syndrome (PCOS). Material and Methods: Thirty patients with PCOS, aged 18~34 years, were recruited. Criteria for diagnosis of PCOS were as defined in 2003 Rotterdam consensus. They were treated for 6 months with pioglitazone at a dose of 30 mg/day orally. The hormonal blood profile, fasting serum glucose levels, a glycemic response to 75 g oral glucose tolerance test (OGTT), and an ovarian stromal artery (OSA) blood flow were assessed at baseline and after 6 months of treatment. Results: Eighteen (60.0%) of 30 patients treated with pioglitazone demonstrated a spontaneous ovulation After pioglitazone treatment, fasting insulin concentrations, serum glucose levels after 75 g OGTT significantly decreased (p=0.001, p=0.04, respectively), and fasting glucose to insulin (G/I) ratio significantly increased (p<0.001). The pioglitazone treatment induced a significant reduction in serum LH, testosterone (T) and free T levels (p<0.001, p=0.02, p=0.002, respectively). The resistance index (RI) values of OSA significantly increased after treatment (p<0.001). In analyzing pioglitazone-treated patients according to their body mass index (BMI), nonobese group as well as obese group showed a significant improvement in fasting G/I ratio (p<0.01). The pioglitazone treatment induced a significant reduction in serum LH and free T levels in nonobese group (p<0.001, p<0.05, respectively) as well as obese group (p=0.001, p<0.05, respectively). The RI values of OSA significantly increased in both nonobese and obese groups after pioglitazone treatment (p<0.001, p=0.003, respectively). Conclusions: Pioglitazone could ameliorate the glycoinsulinemic metabolism, and this beneficial effects of this drug could improve the endocrine-reproductive condition associated with the decrease of ovarian stromal artery blood flow, in both nonobese and obese patients with PCOS.

• Clinical and Experimental Reproductive Medicine
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• v.40 no.3
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• pp.115-121
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• 2013

Objective: Letrozole and estradiol valerate are used to treat some hormonally-responsive symptoms and also in modeling of the polycystic ovary syndrome. However, the stereological analysis of the ovary has received less attention. Estimation of the whole ovary volume using the Cavalieri method can be applied in any orientation desired, but estimation of the mean volume of the oocytes requires isotropic uniform random sectioning. Here, a combined method was developed for estimating the parameters. To our knowledge, no comparison has been made of the effects of letrozole and estradiol on the ovary. Methods: Sixty rats were divided into 4 groups receiving estradiol (4 mg/kg), olive oil, letrozole (1 mg/kg), or normal saline. After 21 days, their ovaries were studied. Results: Relative to the control group, the total volume of the ovary and the cortex increased in the letrozole-treated and estradiol-treated rats. In addition, the number of the preantral, antral, and granulosa cells decreased by 43% to 56% in the letrozole- and estradiol-treated rats. On average, a 19% increase was observed in the atretic oocytes of the letrozole-treated and estradiol-treated rats, but the mean oocyte volume decreased by 29% to 44% in letrozole- and estradiol-treated rats. Furthermore, the letrozole-treated rats showed a 5-fold and 7-fold increase in the volume of the cysts and corpus luteum, respectively. A 3-fold increase was found in the volume of both the cysts and corpus luteum in the estradiol group. Conclusion: The structural changes of the ovary were most pronounced in the letrozole-treated animals.

• Clinical and Experimental Pediatrics
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• v.64 no.12
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• pp.619-627
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• 2021

Pediatric obesity has become a serious public health issue. The prevalence of obesity in children and adolescents has increased worldwide and in Korea over several decades. Obese children are more likely to be obese adults with an increased cardiovascular risk. Therefore, maintaining a healthy weight and preventing obesity during childhood are of critical importance. Moreover, obese children and adolescents often have endocrine comorbidities such as prediabetes, type 2 diabetes, dyslipidemia, metabolic syndrome, polycystic ovary syndrome, and central precocious puberty. Hence, the early implementation of obesity management using a multidisciplinary team approach and screening for these comorbidities in obese children and adolescents are required with the appropriate management of each comorbidity and/or specialist referral.

• The Journal of Korean Obstetrics and Gynecology
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• v.24 no.3
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• pp.28-47
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• 2011

Objectives: This study was performed to investigate the effects of Angelicae gigantis Radix (AGR) which is one of the most useful herbal-drug to treat patients with Polycystic Ovary Syndrome (PCOS) in Oriental medicine on gene expression of ovary tissue. Methods: The effects of AGR on gene expression of ovary tissue resected from PCOS induced rats using single injection of $\ss$-Estradiol 17-valerate (EV) was measured using microarray technique, and the functional analysis on these genes was conducted. Results: Total 2,812 genes were up-regulated or down-regulated, 1,421 genes were up-regulated, 1,391 genes were down-regulated by induction of PCOS. Up-regulated genes were mainly involved in biological function such as cell signalling pathways and inflammatory response. Expression levels of 1,442 genes were restored to those of naive animals by administration of AGR. 558 genes were restored to those of naive animals, which were lowered by induction of PCOS. 884 genes were lowered to naive levels, which were elevated by induction of PCOS. The functions of restored genes were partially involved in the restoration of expression levels, which were changed by induction of PCOS. Especially, up-regulated gene by induction of PCOS were mainly involved in these changes. These results mean restorative effects of AGR on damaged functions by induction of PCOS. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as IRS2, MCM10, ORC2L related in up-regulated genes, CTBP2, CD44, RHOA, related in down-regulated genes that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: Restored genes by AGR were thought to have common pathways related in regulation of gene expressions. Especially, genes in restored expression levels by AGR, which were up-regulated by induction of PCOS, were regulated by 9 of common transcription factors, genes in restored expression levels by AGR, which were down-regulated by induction of PCOS, were involved in 25 of common transcription factors.

• Clinical and Experimental Reproductive Medicine
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• v.40 no.3
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• pp.135-140
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• 2013

Objective: To evaluate correlations between serum anti-M${\ddot{u}}$llerian hormone (AMH) levels, phenotypes of polycystic ovary syndrome (PCOS), obesity, and metabolic parameters in patients with PCOS. Methods: A total of 175 patients with PCOS were diagnosed according to the Rotterdam Consensus were included. Exclusion criteria were age over 40, FSH>25 mIU/mL, and 17a-OHP>1.5 ng/mL. The Phenotypes of PCOS were divided into a severe form (oligo-anovulation, ANOV/hyperandrogenism/polycystic ovary morphology [PCOM]; n=59) and a mild form without HA (ANOV/PCOM, n=105). The serum AMH levels were classified into 3 groups (<5 vs. 5-10 vs. >10 ng/mL). Obesity was defined as body mass index (BMI) ${\geq}25kg/m^2$ (n=34). Results: The mean age was $25.9{\pm}5.7$ year and mean AMH level was $10.1{\pm}5.4$ ng/mL. The BMI ($kg/m^2$) was higher in group 1 ($24.2{\pm}6.3$) than in group 2 ($21.9{\pm}4.3$, p=0.046) or group 3 ($21.6{\pm}3.3$, p=0.019). There was no difference among the three groups in age, menstrual interval, antral follicle counts, androgens, or other metabolic parameters. The obesity group showed significantly lower AMH ($7.7{\pm}3.9$ ng/mL vs. $10.7{\pm}5.6$ ng/mL), p=0.004) and low-density lipoprotein levels ($93.1{\pm}21.2$ mg/dL vs. $107.5{\pm}39.3$ mg/dL, p=0.031), and showed higher total T ($0.74{\pm}0.59$ L vs. $0.47{\pm}0.36$ ng/mL, p=0.001), free T ($2.01{\pm}1.9$ vs. $1.04{\pm}0.8$ pg/mL, p=0.0001), and free androgen index ($6.2{\pm}7.9$ vs. $3.5{\pm}3.0$, p=0.003). After controlling for age factors and BMI, the serum AMH levles did not show any significant correlations with other hormonal or metabolic parmeters. Conclusion: For PCOS patients under the age 40, serum AMH is not negatively correlated with age. High serum AMH levels can not predict the phenotype of PCOS and metabolic disturbances in PCOS patients in the non-obese group. Further study might be needed to define the relation more clearly.

• Journal of Nutrition and Health
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• v.47 no.3
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• pp.176-185
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• 2014

Purpose: The purpose of this study was to investigate the relationship between dietary flavonoids intake and metabolic syndrome (MetS) in Korean women with polycystic ovary syndrome (PCOS). Methods: A total of 223 subjects (mean age; $27.3{\pm}4.2$ yrs, range; 17-38 yrs) were divided into the MetS group (n = 27) and non-MetS group (n = 196). Dietary intake data were assessed by 24-hour recall method for two non-consecutive days and the average of the two days was used to estimate the usual dietary intake. Dietary habits were assessed using the Mini Dietary Assessment (MDA) score. We analyzed the intakes of six flavonoid classes (anthocyanidins, flavan-3-ols, flavanones, flavones, flavonols, and iso-flavones) using a flavonoids database. Results: After adjustment for age, total energy intake, alcohol consumption, smoking, regular exercise, and oral contraceptive use, dietary flavonols intake was significantly lower in the MetS group ($5.1{\pm}2.4$ mg/d) than in the non-MetS group ($8.9{\pm}2.8$ mg/d) (p = 0.0472). Intakes of other flavonoids except for flavonols did not differ between the two groups. In MDA scores, significant differences were observed only for that related to daily consumption of fruit or fruit juice (p = 0.0180). A significant inverse relationship was observed between flavonols intake and the risk of MetS (4th vs. 1st quartile, OR = 0.11, 95% CI = 0.02-0.62, p for trend = 0.0131). Conclusion: These results suggest that higher intake of flavonols may be beneficial for MetS in PCOS women.

• 대한생식의학회:학술대회논문집
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• 2004.11a
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• pp.88.2-89
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• 2004