• 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.

• Molecules and Cells
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• v.44 no.3
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• pp.146-159
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• 2021

DNA methylation, and consequent down-regulation, of tumour suppressor genes occurs in response to epigenetic stimuli during cancer development. Similarly, human oncoviruses, including human papillomavirus (HPV), up-regulate and augment DNA methyltransferase (DNMT) and histone deacetylase (HDAC) activities, thereby decreasing tumour suppressor genes (TSGs) expression. Ubiquitin-like containing PHD and RING finger domain 1 (UHRF1), an epigenetic regulator of DNA methylation, is overexpressed in HPV-induced cervical cancers. Here, we investigated the role of UHRF1 in cervical cancer by knocking down its expression in HeLa cells using lentiviral-encoded short hairpin (sh)RNA and performing cDNA microarrays. We detected significantly elevated expression of thioredoxin-interacting protein (TXNIP), a known TSG, in UHRF1-knockdown cells, and this gene is hypermethylated in cervical cancer tissue and cell lines, as indicated by whole-genome methylation analysis. Up-regulation of UHRF1 and decreased TXNIP were further detected in cervical cancer by western blot and immunohistochemistry and confirmed by Oncomine database analysis. Using chromatin immunoprecipitation, we identified the inverted CCAAT domain-containing UHRF1-binding site in the TXNIP promoter and demonstrated UHRF1 knockdown decreases UHRF1 promoter binding and enhances TXNIP expression through demethylation of this region. TXNIP promoter CpG methylation was further confirmed in cervical cancer tissue by pyrosequencing and methylation-specific polymerase chain reaction. Critically, down-regulation of UHRF1 by siRNA or UHRF1 antagonist (thymoquinone) induces cell cycle arrest and apoptosis, and ubiquitin-specific protease 7 (USP7), which stabilises and promotes UHRF1 function, is increased by HPV viral protein E6/E7 overexpression. These results indicate HPV might induce carcinogenesis through UHRF1-mediated TXNIP promoter methylation, thus suggesting a possible link between CpG methylation and cervical cancer.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.2
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• pp.89-98
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• 2010

Sex and its tropic hormones influence the lacrimal system, corneal anatomy and disease, aqueous humor dynamics and glaucoma, crystalline lens and cataract, and retinal disease. Dry eye occurs especially frequently during pregnancy, oral contraceptive use, and after menopause, during which androgen levels decrease. Androgen control development, differentiation, and lipid production of sebaceous glands throughout the body, and androgen deficiency also leads to meibomian gland dysfunction and evaporative dry eye. On the other hand, estrogen causes a reduction in size, activity, and lipid production of sebaceous glands. Sex and its tropic hormones also influence the corneal anatomy and disease, and corneal thickening occurred on the second day of the menstrual cycle and around the time of ovulation and appeared to be related to estrogen levels. Fuchs' dystrophy is more commonly seen in postmenopausal women than men and may be linked to hormonal changes that occur with aging. In addition, overexpression of estrogen and progesterone receptors in the conjunctiva of vernal keratoconjunctivitis patients. Serum progesterone levels also may be associated with intraocular pressure especially in pregnant women, and for the women. For women with cataracts, hormone levels were typical of menopause, and there was a significant negative correlation between estradiol and follicular stimulating hormone levels. In addition, serum testosterone levels are associated with the development of diabetic retinopathy. Although the role of sex hormones on the eye is largely unknown, and the results should be interpreted with caution until replicated, the functions of sex hormones in ocular disease remains to be investigated, because they may be involved in structure and function of the ocular components, which are important in the pathogenesis of ocular disease.

• Journal of Ginseng Research
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• v.33 no.2
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• pp.115-126
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• 2009

To evaluate the efficacy and safety of red ginseng on women's health-related quality of life (QOL) and sexual function. A randomized, double-blind, placebo-controlled, crossover clinical study was performed. The main efficacy was measured using the Female Sexual Function Index (FSFl) and the 36-Item Short-Form Health Survey (SF-36). Twenty-four healthy, married women aged 30-45 years with FSFl scores below 25 were randomly divided into two groups: the red-ginseng group (N=12) and the placebo group (N=12). During the first six-week period (Study 1), each group was given red ginseng or placebo twice a day. Before the start of the second six-week period (Study 2), a crossover design was chosen with a two-week break (washout period). Interchanging the two groups after the washout period, red ginseng and placebo were given to each group. The outcomes were measured before and after each six-week period. Overall, 23 participants completed the study. In Study 1, the changes relative to the baseline in the FSFl total score were 22.50% and 22.99% for red ginseng and placebo, respectively. In Study 2, the relative changes were 8.14% for red ginseng and 6.29% for placebo. The results showed a greater improving trend in Study 1 with respect to all of the participants' sexual functions, but no significant difference was found between the groups (P=0.9567). After taking red ginseng, all the participants exhibited an improving trend in the desire domain of FSFl, but no significant difference was shown. In the measurement of SF-36, no significant difference was likewise shown. After taking red ginseng, though, all the participants exhibited an improving trend in the physical functioning (PF) domain of SF-36, with no significant difference. Moreover, there was no significant adverse event related to red ginseng. The QOL and sexual function of the study participants in the red-ginseng group were mostly improved, but no statistically significant effect of red ginseng was shown. It is supposed that this result was partly due to the affirmative impression of red ginseng in Korea. Thus, it is anticipated that a long-term clinical trial will show a significant effect of red ginseng on the QOL and sexual function.

• Journal of Genetic Medicine
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• v.7 no.2
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• pp.160-164
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• 2010

Structural abnormalities of the Y chromosome affect normal testicular differentiation and spermatogenesis. The present case showed a rare monocentric derivative Y chromosome with partial duplication of Yp including the SRY gene and deletion of Yq12 heterochromatin. The karyotype was 46,X,der(Y)(pter${\rightarrow}$q11.23::p11.2${\rightarrow}$pter).ish der(Y)(DYZ3+,DYZ1-,SRY++), confirmed through a FISH study. Even though the patient possessed an abnormal Y chromosome, testicular biopsy showed normal testicular volumes in the proband, with gonadal hormonal levels in the normal range but bilateral varicocele and hypospermatogenesis. We speculate that the abnormal Y chromosome arose from sister chromatids during Y chromosome recombination or intra chromosomal NAHR (non-allelic homologous recombination) during meiosis in the patient's father or in the very early stages of embryogenesis. The derivative Y chromosome might interfere in the meiotic stage of spermatogenesis, leading to the developmental arrest of germ cells. The present case illustrates that the infertility phenotype can have various causes. Also, it emphasizes the importance of accurate and various genetic analyses and could aid in male infertility treatment.

• Radiation Oncology Journal
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• v.11 no.1
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• pp.149-158
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• 1993

This is a retrospective analysis of 135 patients with invasive carcinoma of the uterine cervix treated with curative radiotherapy from March 1983 through October 1989 at the Department of Therapeutic Radiology, Kang-Nam 51. Mary's Hospital. Among them, 78 patients received radiotherapy alone and 42 patients treated with neoadjuvant chemotherapy followed by radiotherapy and 15 patients were lost to follow up. All patients had follow up from 2 to 106 months (median; 62 months). Age of the patients ranged from 32 to 79 years at presentation (median; 59 years). According to FIGO classification, there were 20 ($16.7{\%}$) in stage IB, 19 ($15.8{\%}$) in stage IIA,49 ($40.8{\%}$) in stage IIB, 5 ($4.2{\%}$) in stage IIIA, 13 ($10.8{\%}$,) in stage IIIB,14 ($11.7{\%}$) in stage IVA. The pathological classification showed 96 ($80.0{\%}$) squamous cell carcinomas, 5 ($4.2{\%}$) adenocarcinomas and 19 ($15.8{\%}$) proven by cytology. The overall 5-year survival rates was $50.8{\%}$, and the 5-year survival rates by stage IB, IIA, IIB, IIIA, IIIB, IVA was $47.7{\%},\;70.2{\%},\;64.1{\%},\;40.0{\%},\;23.1{\%},\;14.3{\%}$, respectively. The 5-year survival rates was noted $51.2{\%}$ of radiotherapy alone and $50.4{\%}$of neoadjuvant chemotherapy followed by radiotherapy. The overall failure rate was $18.3{\%}$(22/120) including $11.7{\%}$ (14/120) locoregional failure, $5.8{\%}$ (7/120) distant metastasis and $0.8{\%}$(1/120) locoregional failure with distant metastasis. Treatment failure rates by the stages were $15{\%}$ (3/20) in stage IB. $10.5{\%}$ (2/19) in stage IIA, $10.2{\%}$, (5/49) in stage IIB, $20{\%}$ (1/5) in stage IIIA, $61.5{\%}$(8/13) in stage IIB, and $28.6{\%}$ (4/14) in stage IVA. The overall complication rate was $34.2{\%}$(41/120) including wet desquamation $7.5{\%}$, (9/120), diarrhea $6.7{\%}(8/120), radiation proctitis $5.8{\%}$(7/120) in decreasing order. A multivariate analysis of factors influencing the survival showed patient age (p < 0.0291), FIGO stage (p<0.0001), Karnofsky performance status (p<0.0043), initial hemoglobin level (p<0.0001), and intracavitary radiation (p<0.0004), but, no significancy in histology (p<0.29) and treatment method (p < 0.87).

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.6
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• pp.1008-1013
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• 2011

Osteoporosis is the leading underlying cause of fractures, particularly in postmenopausal women, due to the loss of estrogen-mediated suppression of bone resorption. More than 50% of adults 50 years of age or older are estimated to have osteoporosis. Osteoclast which is main target for treatment of osteoporosis is originated from hematopoietic cell line. Aloe has been widely used in worldwide country as a coadjuvant medicine. Extracts of the leaves of Aloe have been used in condition to improve dermatologic problem such as seborrheic dermatitis, aphthous stomatitis, xerosis, lichen planus and has been known to exert anti-inflammatory, anti-oxidant and anti-tumor effects. However, despite the popularity of aloe as a plant food supplements, the evaluation of its efficacy as a possible therapeutic option for osteoporosis remains scarce. Thus, we evaluated the effect of Aloe on receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation. Here we found that Aloe significantly inhibited osteoclast differentiation induced by RANKL. Aloe suppressed the activation of p38 pathway and $NF{\kappa}B$ in bone marrow macrophages (BMMs) treated with RANKL. Also, Aloe significantly inhibited the mRNA expression of c-Fos, tartrate-resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), nuclear factor of activated T cells (NFAT)c1 and cathepsin K in BMMs treated with RANKL. Particularly, Aloe greatly inhibited the protein expression of c-fos and NFATc1. Taken together, our results suggested that Aloe may be useful tool for treatment of osteoporosis by inhibition of osteoclast differentiation.

• IMMUNE NETWORK
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• v.1 no.2
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• pp.143-150
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• 2001

Background : Many investigators have found transforming growth factor-${\beta}1$ (TGF-${\beta}1$) to be elevated in tumors. Changes in responsiveness to TGF-${\beta}1$ have been linked to malignant transformation, tumor progression and tumor regression. Many malignant cell lines of epithelial or hematopoietic origin are refractory to the antiproliferative effects of TGF-${\beta}1$. However, a little is known about the association of TGF-${\beta}1$ with progression of malignant tumor. Methods : In this study, we measured the plasma level of TGF-${\beta}1$ in various cancer patients and evaluated the utility of plasma TGF-${\beta}1$ as a possible tumor marker. Plasma TGF-${\beta}1$ levels were measured using enzyme-linked immunosorbent assay in cancer patients and normal controls. Carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) as tumor marker were compared with TGF-${\beta}1$ in the aspects of sensitivity and specificity. Results : The mean of plasma TGF-${\beta}1$ levels was $1.219{\pm}0.834ng/ml$ in normal controls, $5.491{\pm}3.598ng/ml$ in breast cancer, $12.670{\pm}10.386ng/ml$ in lung cancer, $5.747{\pm}3.228ng/ml$ in hepatocellular carcinoma and $10.854{\pm}7.996ng/ml$ in cervical cancer. In comparison with CEA and AFP, TGF-${\beta}1$ is more sensitive. Conclusion : We conclude that the high levels of TGF-${\beta}1$ are common in the plasma of cancer patients. These results suggest that the plasma TGF-${\beta}1$ level can be a potent tumor marker in various cancer patients.

• Clinical and Experimental Reproductive Medicine
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• v.44 no.2
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• pp.63-72
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• 2017

Objective: Hyperstimulation methods are broadly used for in vitro fertilization (IVF) in patients with infertility; however, the side effects associated with these therapies, such as ovarian hyperstimulation syndrome (OHSS), have not been well studied. N-glycoproteomes are subproteomes used for the remote sensing of ovarian stimulation in follicular growth. Glycoproteomic variation in human follicular fluid (hFF) has not been evaluated. In this study, we aimed to identify and quantify the glycoproteomes and N-glycoproteins (N-GPs) in natural and stimulated hFF using label-free nano-liquid chromatography/electrospray ionization-quad time-of-flight mass spectrometry. Methods: For profiling of the total proteome and glycoproteome, pooled protein samples from natural and stimulated hFF samples were selectively isolated using hydrazide chemistry to obtain the total proteomes and glycoproteomes. N-GPs were validated by the consensus sequence N-X-S/T (92.2% specificity for the N-glycomotif at p<0.05). All data were compared between natural versus hyperstimulated hFF samples. Results: We detected 41 and 44 N-GPs in the natural and stimulated hFF samples, respectively. Importantly, we identified 11 N-GPs with greater than two-fold upregulation in stimulated hFF samples compared to natural hFF samples. We also validated the novel N-GPs thyroxine-binding globulin, vitamin D-binding protein, and complement proteins C3 and C9. Conclusion: We identified and classified N-GPs in hFF to improve our understanding of follicular physiology in patients requiring assisted reproduction. Our results provided important insights into the prevention of hyperstimulation side effects, such as OHSS.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6935-6940
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• 2013

Background: This study aimed to develop a prognostic model in patients with early-stage cervical squamous cell carcinoma based on clinicopathological features, including invasive margin characteristics. Materials and Methods: Clinicopathological features and outcomes of 190 patients with FIGO stage IB-IIA cervical squamous cell carcinoma treated by surgery were collected and analyzed for factors associated with tumor recurrence. In addition to well-recognized pathological risk factors, the pathological characteristics of invasive margin (type of invasive pattern and degree of stromal desmoplasia and peritumoral inflammatory reaction) were also included in the analysis. Multiple scoring models were made by matching different clinicopathological variables and/or different weighting of the score for each variable. The model with the best performance in the prediction of recurrence and decreased survival was selected. Results: The model with the best performance was composed of a combined score of invasive pattern, lymphovascular space invasion (LVSI), and degree of inflammatory reaction and stromal desmoplasia (total score =10). Compared to those with score ${\leq}8$, the patients with score 9-10 had a significantly higher recurrence rate in the overall group (p<0.001) and the subgroup without adjuvant therapy (p<0.001), while the significance was marginal in the subgroup with adjuvant therapy (p=0.069). In addition, the patients with score 9-10 had a higher rate of tumor recurrence at distant sites (p=0.007). The disease-free survival was significantly lower in the patients with score 9-10 than those with score ${\leq}8$ among the overall patients (p<0.001), in the subgroup without adjuvant therapy (p<0.001), and the subgroup with adjuvant therapy (p=0.047). Conclusions: In this study, a prognostic model based on a combination of pathological characteristics of invasive margin and LVSI proved to be predictive of tumor recurrence and decreased disease-free survival in patients with early-stage cervical squamous cell carcinoma.