Suppression of miR-181a attenuates H ₂ O ₂ -induced death of mesenchymal stem cells by maintaining hexokinase II expression

Lee, Seahyoung,Yun, Ina,Ham, Onju,Lee, Se-Yeon,Lee, Chang Yeon,Park, Jun-Hee,Lee, Jiyun,Seo, Hyang-Hee,Choi, Eunhyun,Hwang, Ki-Chul BioMed Central 2015 BIOLOGICAL RESEARCH Vol.48 No.1

<P><B>Background</B></P><P>Low survival rate of transplanted cells compromises the efficacy of cell therapy. Hexokinase II (HKII) is known to have anti-apoptotic activity through its interaction with mitochondria. The objective was to identify miRNAs targeting HKII and investigate whether miRNA-mediated modulation of HKII could improve the survival of mesenchymal stem cells (MSCs) exposed to H<SUB>2</SUB>O<SUB>2</SUB>. The expression of HKII in MSCs exposed to H<SUB>2</SUB>O<SUB>2</SUB> was evaluated, and HKII-targeting miRNA was screened based on miRNA-target prediction databases. The effect of H<SUB>2</SUB>O<SUB>2</SUB> on the expression of the selected HKII-targeting miRNA was examined and the effect of modulation of the selected HKII-targeting miRNA using anti-miRNA on H<SUB>2</SUB>O<SUB>2</SUB>-induced apoptosis of MSC was evaluated.</P><P><B>Results</B></P><P>H<SUB>2</SUB>O<SUB>2</SUB> (600 μM) induced cell death of MSCs and decreased mitochondrial HKII expression. We have identified miR-181a as a HKII-targeting miRNA and H<SUB>2</SUB>O<SUB>2</SUB> increased the expression of miR-181a in MSCs. Delivery of anti-miR-181a, which neutralizes endogenous miR-181a, significantly attenuated H<SUB>2</SUB>O<SUB>2</SUB>-induced decrease of HKII expression and disruption of mitochondrial membrane potential, improving the survival of MSCs exposed to H<SUB>2</SUB>O<SUB>2</SUB>.</P><P><B>Conclusions</B></P><P>These findings suggest that H<SUB>2</SUB>O<SUB>2</SUB>-induced up-regulation of miR-181a contributes to the cell death of MSCs by down-regulating HKII. Neutralizing miR-181a can be an effective way to prime MSCs for transplantation into ischemic tissues.</P>

Uterocutaneous fistula after High-Intensity Focused Ultrasound : a case report

( Eunhyun Lee ),( Ji Hyun Keum ),( Jeong Min Eom ),( Jaeman Bae ),( Won Moo Lee ),( Joong Sub Choi ),( Eunsaem Choi ) 대한산부인과학회 2018 대한산부인과학회 학술대회 Vol.104 No.-

We report a case of uterocutaneous fistula in a 46-year-old woman who underwent High-Intensity Focused Ultrasound(HIFU). She is a Korean who lives in Kazakhstan. She had heavy menstrual bleeding and suspected of adenomyosis and myoma. She had been recommended for hysterectomy, but she never wanted to undergo hysterectomy, just treated with hormone therapy and received blood transfusions every few months. The patient finally received HIFU in Korea and returned to Kazakhstan shortly after. She felt fever and pain in the abdominal wall at the time of the procedure, and subsequently relived the pain but sustained discharge in that area and took antibiotics. Because of persistent heavy menstrual bleeding and pelvic pain, she recommended to receive hysterectomy in Kazakhstan. But she refused and underwent wound debridement and primary closure of abdominal wall injury at the hospital that performed HIFU in South Korea, and strongly rejected further surgery. Five months after the procedure, blood was drawn from the wounds of the abdomen at the time of menstruation and referred to our hospital. At the midline of abdominal ASIS level, a discharge was observed through the abdominal wall skin opening and there was extensive redness in the lower abdomen around that. The abdomen MRI showed a heterogenous myoma on the right side of the uterus and adenomyosis with a non-enhancing cavitary portion on the left side and fundus of the uterus, which appeared to be necrosis inside. The cavitary portion of the adenomyosis was suspected to be connected to the uterine cavity and formed fistulous tract through anterior abdominal wall. Peritoneal and fat infiltration around the tract was seen. So, she underwent total abdominal hysterectomy with bilateral salpingectomy in gynecology and abdominoplasty in plastic surgery. This is the first report of uterocutaneous fistula after HIFU procedure and it is important to keep in mind that this type of complication may occur when performing HIFU.

Comparison of vitamin D status and BMD scores between Russian and Korean women

( Eunhyun Lee ),( Jeong Eun Lee ),( Min-jeong Park ),( Sungwook Chun ),( Yong-il Ji ) 대한산부인과학회 2018 대한산부인과학회 학술대회 Vol.104 No.-

Objective: (1) To compare of vitamin D status and bone mineral density between Russian and Korean women aged 30 to 60 (2) to evaluate the factors that make the differences in vitamin D level and BMD score between women in the two countries. Methods: 480 Korean and 480 Russian women were randomly selected from health care center of one hospital from March 2013 to December 2016. The mineral density of lumbar vertebrae was measured using dual energy X-ray absorptiometry(DXA) and serum 25-hydroxyvitamin D levels were analyzed using radioimmunoassay kits. Diagnosis of osteoporosis was based on World Health Organization T-score criteria. Vitamin D deficiency was defined when serum level of 25(OH)D is lower than 20 nmol/L. Differences in the peak BMD among women in the two countries were determined by One-Sample t test. The cubic regression was performed on the means of BMD for two groups to establish the changing curves of BMD with age. After peak stage, the BMD values were calculated by the corresponding cubic equations for various sites. Results: The baseline indices were not significantly different between the two groups. But concentration changes of serum 25(OH)D according to age were significantly different between Korean and Russian women. In Korean women, the mean concentration of this decreased significantly from 20 to 60 years. On the other hand, there was a gradual decline in this concentration in Russian women and consistently high values for all ages. There was no significant difference between the two groups when BMD changes of the spine were analyzed for 4 years. There was no statistically significant interaction between BMD and 25 (OH) D for the 4-year annual change. Conclusion: Vitamin D levels were significantly higher in Russian women than in Korean women. Conversely, lumbar spine BMD was not correlated between the two groups. This result may be due to genetic factors, lifestyle such as eating habits and clothing, and BMD measured only in the lumbar spine.

Comparision of histological outcomes from pre-menopausal and post-menopausal women with report of cervical cytological abnormality

( Eunhyun Lee ),( Lee Jeong Eun ),( Min-jeong Park ),( Sungwook Chun ),( Yong-il Ji ) 대한산부인과학회 2018 대한산부인과학회 학술대회 Vol.104 No.-

Objective: The aim of this study is to compare and investigate the histological outcomes between premenopause and post-menopausal women with report of cervical cytological abnormality. Methods: A comparison of cervical cytological results of 501 pre-menopausal women and 135 post-menopausal women between 20-83 years from January 2010 to April 2018 was performed for presence of cytological abnormalities. Results: The prevalence of cytological abnormality was 92.3% ; ASCUS, LSIL, ASCH, and HSIL was 13.3%, 14.1%, 10.3% and 54.4%. Cytological abnormalities were similar in premenopausal women in comparision to postmenopausal women(92.6% vs. 91.3%). However, the incidence of histologically confirmed cervical cytological abnormality was significantly higher in premenopausal women(63%) than postmenopausal women(44.6%). Colposcopic biopsies were performed on 70 patients(premenopausal n=58 vs. postmenopausal n=12) who had a smear result of ASCUS; 6 patients(10.3%) had chronic cervicitis or atrophic changes, 5(8.6%) returned to LSIL, and 29(50%) returned to HSIL in the premenopausal group. In contrast, 5(41.6%) patients were diagnosed with chronic cervicitis or atrophic changes and 2(16.6%) patients with LSIL, and 3(25%) patients with HSIL in postmenopausal group. Biopsy results of 74 patients(premenopausal n=53 vs. postmenopausal n=21) with LSIL revealed chronic cervicitis in 13 patients(24.5%) and HSIL in 24 patient(45.2%) in premenopausal group. In contrast, 6(28.5%) patients were detected to be chronic cervicitis or atrophic changes and 6(28.5%) were detected as HSIL in postmenopausal group. Conclusion: This study showed significant difference in correlation of cytology and histology results from premenopausal groups and postmenopausal groups with cervical cytology abnormality. We think that since cytological results in postmenopausal women have low sensitivity, follow up pap smear with high risk HPV testing would be a more conservative management and appropriate than immediate colposcopic biopsy.

Short term outcome of laparoscopic hysteropexy for apical prolapse: single-center experience

( Youngjin Lee ),( Soojin Oh ),( Minseong Choi ),( Minjeong Park ),( Eunhyun Lee ),( Yong-il Ji ) 대한산부인과학회 2023 대한산부인과학회 학술대회 Vol.109 No.-

Frontal Dysfunction Underlies Depression in Mild Cognitive Impairment: A FDG-PET Study

HyeSook Lee,IlHan Choo,DongYoung Lee,JeeWook Kim,EunHyun Seo,ShinGyeom Kim,ShinYoung Park,JiHye Shin,KiWoong Kim,JongInn Woo 대한신경정신의학회 2010 PSYCHIATRY INVESTIGATION Vol.7 No.3

Objective-Depression is a very common symptom in people with mild cognitive impairment (MCI), a preclinical stage of Alzheimer’s disease (AD), and in those with clinically evident AD. Moreover, MCI individuals with depression show a higher conversion rate to clinical AD than those without depression. This study aimed to elucidate the functional neuroanatomical substrate of depression in MCI. Methods-Thirty-six patients were recruited from a University Hospital-based cohort; 18 of these subjects had MCI with depression (MCI_D); the remaining 18 subjects were age- and gender-matched, and had MCI with no depression (MCI_ND). For comparison, 16 cognitively normal (CN) elderly individuals were also included. All subjects underwent Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) scanning and regional cerebral glucose metabolism was compared among the three groups by a voxel-based method. The relationship between severity of depression, as measured by Hamilton Rating Scale for Depression (HRSD) scores, and glucose metabolism was also investigated. Results-MCI_D showed lower glucose metabolism in the right superior frontal gyrus than MCI_ND. There was a significant negative correlation between HRSD score and glucose metabolism at the same frontal region for overall MCI subjects. When compared with CN, both MCI_D and MCI_ND showed decreased glucose metabolism in the precuneus, while MCI_D had, in addition, reduced metabolism in other diffuse brain regions. Conclusion-Given previous observations on depression in AD, our results suggest that functional disruption of the frontal region, known to be associated with primary or other secondary depression, underlies depression in preclinical AD as well as clinically evident AD.

Property-Based Optimization of Hydroxamate-Based γ-Lactam HDAC Inhibitors to Improve Their Metabolic Stability and Pharmacokinetic Profiles

Choi, Eunhyun,Lee, Chulho,Cho, Misun,Seo, Jeong Jea,Yang, Jee Sun,Oh, Soo Jin,Lee, Kiho,Park, Song-Kyu,Kim, Hwan Mook,Kwon, Ho Jeong,Han, Gyoonhee American Chemical Society 2012 Journal of medicinal chemistry Vol.55 No.23

<P>Hydroxamate-based HDAC inhibitors have promising anticancer activities but metabolic instability and poor pharmacokinetics leading to poor in vivo results. QSAR and PK studies of HDAC inhibitors showed that a γ-lactam core and a modified cap group, including halo, alkyl, and alkoxy groups with various carbon chain linkers, improved HDAC inhibition and metabolic stability. The biological properties of the γ-lactam HDAC inhibitors were evaluated; the compound designated <B>8f</B> had potent anticancer activity and high oral bioavailability.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jmcmar/2012/jmcmar.2012.55.issue-23/jm3009376/production/images/medium/jm-2012-009376_0004.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jm3009376'>ACS Electronic Supporting Info</A></P>

Prognostic factors in early endometrial cancer: A cohort study of postmenopausal women

( Jisoo Lee ),( Minjeong Park ),( Yong-il Ji ),( Eunhyun Lee ),( Minseong Park ) 대한산부인과학회 2023 대한산부인과학회 학술대회 Vol.109 No.-

Modulation of Fas-Fas Ligand Interaction Rehabilitates Hypoxia-Induced Apoptosis of Mesenchymal Stem Cells in Ischemic Myocardium Niche

Ham, Onju,Lee, Se-Yeon,Song, Byeong-Wook,Cha, Min-Ji,Lee, Chang Youn,Park, Jun-Hee,Kim, Il-Kwon,Lee, Jiyun,Seo, Hyang-Hee,Seung, Min-Ji,Choi, Eunhyun,Jang, Yangsoo,Hwang, Ki-Chul SAGE Publications 2015 CELL TRANSPLANTATION Vol.24 No.7

Effect of gynecological cancer and its treatment on bone mineral density and the risk of osteoporosis and osteoporotic fracture

( Jeong Eun Lee ),( Che Yon Park ),( Eunhyun Lee ),( Yong Il Ji¸ ) 대한산부인과학회 2020 Obstetrics & Gynecology Science Vol.63 No.4

Objective The purpose of this study was to evaluate the risk of osteopenia and osteoporosis by examining the bone mineral density (BMD) of the lumbar spine and femur in patients with gynecological cancer without bone metastasis and to evaluate the impact of treatment for different cancers on BMD. Methods This study retrospectively reviewed the medical records of 243 women with gynecological cancer and 240 controls between March 2010 and December 2016. Patients with cervical cancer (n=105), endometrial cancer (n=63), and ovarian cancer (n=75) were treated with total hysterectomy including bilateral salpingo-oophorectomy and/or chemotherapy and/or radiotherapy. For the control group, healthy post-menopausal women without gynecologic cancer were selected. Results Before anticancer treatment, the BMD of patients with cervical cancer and ovarian cancer was significantly lower than that of the controls, and the BMD of patients with endometrial cancer was not significantly different from that of the controls. However, the BMD of endometrial cancer significantly decreased after treatment. According to the treatment methods, there were significant differences in the BMD of L3, L4, and the femur neck. Changes in the BMD were lowest in patients who underwent surgical treatment only, and the highest bone loss was found in patients who underwent postoperative concurrent chemoradiotherapy. Conclusion Patients with cervical and ovarian cancer had lower BMD than those in the control group before treatment, and patients with endometrial cancer had decreased bone density after treatment. Therefore, during the treatment of gynecological cancer, strategies should be implemented to mitigate these risks.