Analyzing circulating tumor cells and epithelial-mesenchymal transition status of papillary thyroid carcinoma patients following thyroidectomy: a prospective cohort study.

BACKGROUND: This study investigated the prevalence and subtype distribution of circulating tumor cells (CTCs) in patients with papillary thyroid cancer (PTC) before and after thyroidectomy to determine the potential of CTC count as a noninvasive marker of the efficacy of surgical treatment in PTC. MATERIALS AND METHODS: Between January 2021 and January 2022, 62 PTC patients who underwent thyroidectomy at Seoul National University Bundang Hospital were prospectively evaluated. Peripheral blood samples (7.5 ml) were collected from each patient for CTC analysis before surgery and at 2 weeks and 3 months after surgery. CTC count and the distribution of CTC subtypes, including epithelial, epithelial-mesenchymal, and mesenchymal phenotypes, were analyzed using the negative selection method and immunofluorescence staining. The relationship between CTC count and clinicopathological characteristics was analyzed before and after surgery. RESULTS: Before surgery, CTCs were detected in 87% (54/62) of patients; the mean CTC count was 8.0 and the median was 5.0 in 7.5 ml of peripheral blood. The mesenchymal or epithelial-mesenchymal phenotypes were predominant. After thyroidectomy, the mean and median CTC count values decreased to 5.3 and 2.5, respectively, at 2 weeks and to 4.3 and 3.0, respectively, at 3 months. This postoperative reduction in CTCs was more pronounced in patients with lymphatic invasion, lymph node metastasis, or BRAF V600E mutation. CONCLUSION: CTCs were detected in patients with PTC with a predominance of cells undergoing epithelial-mesenchymal transition. The CTC count decreased postoperatively, suggesting that liquid biopsy with CTC detection could be a valuable noninvasive tool for monitoring the efficacy of surgery in PTC.

The Risk of Hypertension and Diabetes Mellitus According to Offspring's Birthweight in Women With Normal Body Mass Index: A Nationwide Population-Based Study.

BACKGROUND: Maladaptation to vascular, metabolic, and physiological changes during pregnancy can lead to fetal growth disorders. Moreover, adverse outcomes during pregnancy can further increase the risk of cardiovascular and metabolic diseases in mothers. Delivering a large-for-gestational-age (LGA) baby may indicate a pre-existing metabolic dysfunction, whereas delivering a small-for-gestational-age (SGA) baby may indicate a pre-existing vascular dysfunction. This study aims to assess the risk of hypertension (HTN) and diabetes mellitus (DM) in women with normal body mass index (BMI) scores who did not experience gestational DM or hypertensive disorders during pregnancy based on the offspring's birthweight. METHODS: This retrospective nationwide study included women with normal BMI scores who delivered a singleton baby after 37 weeks. Women with a history of DM or HTN before pregnancy and those with gestational DM or hypertensive disorders, were excluded from the study. We compared the risk of future maternal outcomes (HTN and DM) according to the offspring's birthweight. Multivariate analyses were performed to estimate the hazard ratio (HR) for the future risk of HTN or DM. RESULTS: A total of 64,037 women were included in the analysis. Of these, women who delivered very LGA babies (birthweight > 97th percentile) were at a higher risk of developing DM than those who delivered appropriate-for-gestational-age (AGA) babies (adjusted HR = 1.358 [1.068-1.727]), and women who delivered very SGA babies (birthweight < 3rd percentile) were at a higher risk of developing HTN than those who delivered AGA babies (adjusted HR = 1.431 [1.181-1.734]), even after adjusting for age, parity, gestational age at delivery, fetal sex, maternal BMI score, and a history of smoking. CONCLUSION: These findings provide a novel support for the use of the offspring's birthweight as a predictor of future maternal diseases such as HTN and DM.

The Role of the Aryl Hydrocarbon Receptor in Vascular Factors Related to Preeclampsia in a Smoking Mouse Model.

Smoking cigarettes is known to lower the risk of preeclampsia. The objective of this study is to evaluate the effect of smoking on the expression of soluble FMS-like tyrosine kinase-1 (sFlt-1), vascular endothelial growth factor (VEGF), and endoglin (sEng)-1 and the role of the aryl hydrocarbon receptor (AhR) in pregnant mice. We developed a smoking mouse model using a gas-filling system. One or two cigarettes per day were exposed to each of the five pregnant mice for five days a week throughout pregnancy. AhR agonist and antagonist were injected. Serum levels and expression in the placenta of sFlt-1, VEGF, and sEng-1 were analyzed and compared among the cigarette smoke and no-exposure groups after delivery. Compared to the no-smoke exposure group, the serum level of sFlt-1 was significantly decreased in the two-cigarette-exposed group (p < 0.001). When the AhR antagonist was added to the two-cigarette-exposed group, sFlt-1 levels were significantly increased compared to the two-cigarette group (p = 0.002). The levels of sFlt-1 in the AhR antagonist group did not change regardless of two-cigarette exposure (p = 0.064). With the AhR agonist, sFlt-1 decreased significantly compared to the control (p = 0.001) and AhR antagonist group (p = 0.002). The sFlt-1 level was significantly decreased after the injection of the AhR agonist compared to the control group (p = 0.001). Serum levels of VEGF were significantly decreased in the one-cigarette-exposed group compared to the control group; however, there was no difference between the control and the two-cigarette-exposed groups. The placental expression of sFlt-1, VEGF, and sEng were inconsistent. This study offers insights into the potential role of AhR on antiangiogenic sFlt-1 associated with preeclampsia. It may support the invention of a new treatment strategy for preeclampsia using AhR activation.

An Exosome-Rich Conditioned Medium from Human Amniotic Membrane Stem Cells Facilitates Wound Healing via Increased Reepithelization, Collagen Synthesis, and Angiogenesis.

Tissue regeneration is an essential requirement for wound healing and recovery of organs' function. It has been demonstrated that wound healing can be facilitated by activating paracrine signaling mediated by exosomes secreted from stem cells, since exosomes deliver many functional molecules including growth factors (GFs) and neurotrophic factors (NFs) effective for tissue regeneration. In this study, an exosome-rich conditioned medium (ERCM) was collected from human amniotic membrane stem cells (AMSCs) by cultivating the cells under a low oxygen tension (2% O2 and 5% CO2). The contents of GFs and NFs including keratinocyte growth factor, epidermal growth factor, fibroblast growth factor 1, transforming growth factor-ß, and vascular endothelial growth factor responsible for skin regeneration were much higher (10-30 folds) in the ERCM than in normal conditioned medium (NCM). In was found that CM-DiI-labeled exosomes readily entered keratinocytes and fibroblasts, and that ERCM not only facilitated the proliferation of keratinocytes in normal condition, but also protected against H2O2 cytotoxicity. In cell-migration assay, the scratch wound in keratinocyte culture dish was rapidly closed by treatment with ERCM. Such wound-healing effects of ERCM were confirmed in a rat whole skin-excision model: i.e., the wound closure was significantly accelerated, remaining minimal crusts, by topical application of ERCM solution (4 × 109 exosome particles/100 µL) at 4-day intervals. In the wounded skin, the deposition of collagens was enhanced by treatment with ERCM, which was supported by the increased production of collagen-1 and collagen-3. In addition, enhanced angiogenesis in ERCM-treated wounds was confirmed by increased von Willebrand factor (vWF)-positive endothelial cells. The results indicate that ERCM from AMSCs with high concentrations of GFs and NFs improves wound healing through tissue regeneration not only by facilitating keratinocyte proliferation for skin repair, but also activating fibroblasts for extracellular matrix production, in addition to the regulation of angiogenesis and scar tissue formation.

Repeated Intravenous Administration of Human Neural Stem Cells Producing Choline Acetyltransferase Exerts Anti-Aging Effects in Male F344 Rats.

Major features of aging might be progressive decreases in cognitive function and physical activity, in addition to withered appearance. Previously, we reported that the intracerebroventricular injection of human neural stem cells (NSCs named F3) encoded the choline acetyltransferase gene (F3.ChAT). The cells secreted acetylcholine and growth factors (GFs) and neurotrophic factors (NFs), thereby improving learning and memory function as well as the physical activity of aged animals. In this study, F344 rats (10 months old) were intravenously transplanted with F3 or F3.ChAT NSCs (1 × 106 cells) once a month to the 21st month of age. Their physical activity and cognitive function were investigated, and brain acetylcholine (ACh) and cholinergic and dopaminergic system markers were analyzed. Neuroprotective and neuroregenerative activities of stem cells were also confirmed by analyzing oxidative damages, neuronal skeletal protein, angiogenesis, brain and muscle weights, and proliferating host stem cells. Stem cells markedly improved both cognitive and physical functions, in parallel with the elevation in ACh levels in cerebrospinal fluid and muscles, in which F3.ChAT cells were more effective than F3 parental cells. Stem cell transplantation downregulated CCL11 and recovered GFs and NFs in the brain, leading to restoration of microtubule-associated protein 2 as well as functional markers of cholinergic and dopaminergic systems, along with neovascularization. Stem cells also restored muscular GFs and NFs, resulting in increased angiogenesis and muscle mass. In addition, stem cells enhanced antioxidative capacity, attenuating oxidative damage to the brain and muscles. The results indicate that NSCs encoding ChAT improve cognitive function and physical activity of aging animals by protecting and recovering functions of multiple organs, including cholinergic and dopaminergic systems, as well as muscles from oxidative injuries through secretion of ACh and GFs/NFs, increased antioxidant elements, and enhanced blood flow.

A Randomized, Multicenter, Double-Blind, Parallel, Non-Inferiority Clinical Study to Compare the Efficacy and Safety of Unicenta and Melsmon for Menopausal Symptom Improvement.

This study was conducted to evaluate the efficacy and safety of Unicenta in female subjects with menopausal symptoms by analyzing the changes in the Kupperman index (primary endpoint) and hormonal changes (secondary endpoint). It was a randomized, multi-center, double-blind, parallel, non-inferiority clinical study conducted at two different tertiary medical centers. A Unicenta injection was shown to be non-inferior to Melsmon based on the Kupperman index in both the intent-to-treat and per-protocol populations (p = 0.789 and p = 0.826, respectively). Additionally, there were no statistically significant differences in hormone levels (estradiol, follicular-stimulating hormone) or in the evaluation of facial flushes. There was no statistically significant difference in the incidence rate of adverse events between the two groups (p = 0.505). The study demonstrated that Unicenta is not inferior to Melsmon in terms of the change in the Kupperman index after 12 days of injection. The efficacy and safety of Unicenta were shown, resulting in the improvement of menopausal symptoms.

Investigating the regenerative effects of folic acid on human amniotic epithelial stem cells and amniotic pore culture technique (APCT) model in vitro using an integrated pharmacological-bioinformatic approach.

INTRODUCTION: Disruption of fetal membranes before the onset of labor is referred to as premature rupture of membranes (PROM). Lack of maternal folic acid (FA) supplementation reportedly leads to PROM. However, there is a lack of information on the location of FA receptors in the amniotic tissue. Additionally, the regulatory role and potential molecular targets of FA in PROM in vitro have rarely been investigated. METHODS: The three FA receptors (folate receptor α isoform [FRα], transporter of reduced folate [RFC], and proton-coupled folate transporter [PCFT]) in human amniotic epithelial stem cells (hAESCs) and amniotic tissue were localized using immunohistochemistry and immunocytochemistry staining. Effect and mechanism analyses of FA were performed in hAESCs and amniotic pore culture technique (APCT) models. An integrated pharmacological-bioinformatics approach was utilized to explore the potential targets of FA for the treatment of PROM. RESULTS: The three FA receptors were widely expressed in human amniotic tissue, especially in the hAESC cytoplasm. FA stimulated the amnion regeneration in the in vitro APCT model. This mimics the PROM status, in which cystathionine-ß-synthase, an FA metabolite enzyme, may play an important role. The top ten hub targets (STAT1, mTOR, PIK3R1, PTPN11, PDGFRB, ABL1, CXCR4, NFKB1, HDAC1, and HDAC2) of FA for preventing PROM were identified using an integrated pharmacological-bioinformatic approach. DISCUSSION: FRα, RFC, and PCFT are widely expressed in human amniotic tissue and hAESCs. FA aids the healing of ruptured membrane.

Effect of Human Amniotic Epithelial Stem Cell Transplantation on Preterm Premature Rupture of Fetal Membrane Using the Amniotic Pore Culture Technique in vitro.

OBJECTIVES: The objective of this study was to evaluate the efficacy of cell therapy using human amniotic epithelial stem cells (hAESCs) for the treatment of premature rupture of membranes (PROM) in vitro. DESIGN: Using the amniotic pore culture technique (APCT), we mimicked the environment of PROM in vitro, thus enabling the observation of the healing process of hAESC-treated amniotic membranes. MATERIALS: Amniotic membrane samples were collected from placentas of pregnant women who underwent elective cesarean sections. APCT model and isolated hAESCs were used in this study. All patients who participated in this study provided their written informed consent prior to the commencement of the study. SETTINGS: To create the APCT model in vitro, isolated amniotic membranes were punched to create 5 mm diameter circles and re-punched to form a 1-mm pore at the center. Membranes were cultured in α-minimal essential medium, and the hAESCs were collected and cultured as well. Subsequently, the APCT models were divided into two groups: hAESC treated and control. METHODS: Within the culture period, pore sizes were calculated to evaluate the degree of tissue regeneration in both groups. We then evaluated the histology, cell density, and epithelial thickness of the regenerated tissues. Statistical analyses were performed using SPSS software ver. 20.0 (IBM, Armonk, NY, USA) with repeated-measures one-way analysis of variance or paired samples t test. The significance level was set at p < 0.05. RESULTS: As per the evaluation of the APCT model in vitro, the pore size in the hAESC-treated group reduced by 62.2% on day 6 (62.2 ± 0.19, n = 24), whereas in the control group, it shrank by only 36.8% (p < 0.05) (36.8 ± 0.19, n = 24). Furthermore, the epithelial thickness in the amniotic epithelial stem cell-treated group (10.08 ± 1.26 µm, n = 8) was significantly higher than that in the control group (5.87 ± 0.94 µm, n = 8). Cell density in the regenerated tissue in the amniotic epithelial stem cell-treated group (57 ± 2.77, n = 8) was significantly higher than that in the control group (49 ± 2.23, n = 8). LIMITATIONS: In this study, we did not explore the molecular mechanisms by which hAESCs participate in membrane healing in the APCT model. Although our results showed a significant difference, this difference was not too obvious. Therefore, further research on the mechanisms of hAESCs is needed, with more amniotic tissues and APCT samples being tested. CONCLUSIONS: We developed an APCT model to investigate the PROM conditions in vitro. By implanting donor hAESCs in the pores of the APCT model, we observed that hAESCs seeding accelerated pore healing in vitro. Thus, hAESCs may be a valuable source of cells for cell therapies in regenerative medicine.

Women with multiple gestations have an increased risk of development of hypertension in the future.

BACKGROUND: Multiple gestations are associated with an increased incidence of preeclampsia. However, there exists no evidence for an association between multiple gestations and development of hypertension(HTN) later in life. This study aimed to determine whether multiple gestations are associated with HTN beyond the peripartum period. METHODS: In this retrospective nationwide population-based study, women who delivered a baby between January 1, 2007, and December 31, 2008, and underwent a national health screening examination within one year prior to their pregnancy were included. Subsequently, we tracked the occurrence of HTN during follow-up until December 31, 2015, using International Classification of Diseases-10th Revision codes. RESULTS: Among 362,821 women who gave birth during the study period, 4,944 (1.36%) women had multiple gestations. The cumulative incidence of HTN was higher in multiple gestations group compared with singleton group (5.95% vs. 3.78%, p < 0.01, respectively). On the Cox proportional hazards models, the risk of HTN was increased in women with multiple gestations (HR 1.35, 95% CI 1.19, 1.54) compared with those with singleton after adjustment for age, primiparity, preeclampsia, atrial fibrillation, body mass index, blood pressure, diabetes mellitus, high total cholesterol, abnormal liver function test, regular exercise, and smoking status. CONCLUSIONS: Multiple gestations are associated with an increased risk of HTN later in life. Therefore, guidelines for the management of high-risk patients after delivery should be established.

Association of Preterm Birth with Depression and Particulate Matter: Machine Learning Analysis Using National Health Insurance Data.

This study uses machine learning and population data to analyze major determinants of preterm birth including depression and particulate matter. Retrospective cohort data came from Korea National Health Insurance Service claims data for 405,586 women who were aged 25-40 years and gave births for the first time after a singleton pregnancy during 2015-2017. The dependent variable was preterm birth during 2015-2017 and 90 independent variables were included (demographic/socioeconomic information, particulate matter, disease information, medication history, obstetric information). Random forest variable importance was used to identify major determinants of preterm birth including depression and particulate matter. Based on random forest variable importance, the top 40 determinants of preterm birth during 2015-2017 included socioeconomic status, age, proton pump inhibitor, benzodiazepine, tricyclic antidepressant, sleeping pills, progesterone, gastroesophageal reflux disease (GERD) for the years 2002-2014, particulate matter for the months January-December 2014, region, myoma uteri, diabetes for the years 2013-2014 and depression for the years 2011-2014. In conclusion, preterm birth has strong associations with depression and particulate matter. What is really needed for effective prenatal care is strong intervention for particulate matters together with active counseling and medication for common depressive symptoms (neglected by pregnant women).

Role of sex hormones in cervical changes in a cervical excision-related preterm delivery mouse model.

Progesterone and oestrogen play important roles during parturition; however, their roles in the uterine cervix during preterm labour and delivery are unknown. We evaluated the serum progesterone and oestrogen levels and changes in their receptors (PR and ER) in the cervix in a cervical excision-associated preterm delivery mouse model. Adult female C57BL/6 mice were divided into four groups: sham, cervical excision (Ex), lipopolysaccharide (LPS) and Ex + LPS. Mating was permitted at 3 weeks post-Ex. On gestation day 16, mice were administered LPS intrauterine (100 µg/100 µL/mouse) or physiological saline (100 µL) via laparotomy. Uterine cervices and blood were sampled immediately postpartum. As a result, epithelial PR and muscular ERα were down- and upregulated, respectively, in the proximal cervix in Ex + LPS group compared to in the sham group. These results indicate that unique sex hormone effects are exerted on the uterine cervix during cervical excision-associated spontaneous preterm labour and delivery.Impact statementWhat is already known on this subject? Preterm and term parturition require the withdrawal of progesterone and the activation of oestrogen in the uterine body and systemic levels. However, we have little understanding of the role of the sex hormones in the uterine cervix.What do the results of this study add? Increased ERα-to-PR expression ratio in the proximal cervix was associated with preterm labour and delivery. ERα expression in the smooth muscle layer of the proximal cervix was higher and PR expression in the proximal cervix epithelium was lower during preterm labour and delivery.What are the implications of these findings for clinical practice and/or further research? This study revealed the differences between the roles of sex hormones and their receptors in epithelial and muscle layers of proximal and distal cervices in preterm labour and delivery.

Serum sFlt-1, cystatin C and cathepsin B are potential severity markers in preeclampsia: a pilot study.

PURPOSE: Preeclampsia is associated with abnormal invasion of the trophoblast through decidua and subsequently altered remodeling of the maternal spiral arteries and endothelial dysfunction. This phenomenon is explained by the dysregulation of various kinds of vascular factors and proteases. The purpose of this study was to compare the circulating levels of sFlt-1, cathepsin B, and cystatin C in preeclamptic and normotensive pregnancies. STUDY DESIGN: Sixty-two pregnant women were enrolled in this prospective study. Twenty women were preeclamptic and 42 were normotensive. Serum levels of sFlt-1, cathepsin B, and cystatin C were measured using an enzyme-linked immunosorbent assay kit. RESULTS: Circulating levels of sFlt-1, cathepsin B, and cystatin C were significantly higher in preeclamptic than in normotensive pregnant women (p < 0.001; p = 0.017; p = 0.003). Preeclamptic women with severe features demonstrated significantly higher levels of cathepsin B (p = 0.05). Serum sFlt-1 and cystatin C levels were positively correlated with elevated systolic and diastolic blood pressure. The levels of cathepsin B were positively correlated with alanine and aspartate aminotransferase. The amount of 24 h proteinuria was positively, but non-significantly correlated with sFlt-1 and cystatin C. CONCLUSIONS: In addition to sFlt-1 levels, the serum levels of cathepsin B and cystatin C significantly change when preeclampsia develops. These markers are associated with severity markers of elevated blood pressure and liver injury in preeclampsia.

CXCR2 Ligands and mTOR Activation Enhance Reprogramming of Human Somatic Cells to Pluripotent Stem Cells.

Induced pluripotent stem cell (iPSC) technology has great promise in regenerative medicine and disease modeling. In this study, we show that human placenta-derived cell conditioned medium stimulates chemokine (C-X-C motif) receptor 2 (CXCR2) in human somatic cells ectopically expressing the pluripotency-associated transcription factors Oct4, Sox2, Klf4, and cMyc (OSKM), leading to mechanistic target of rapamycin (mTOR) activation. This causes an increase in endogenous cMYC levels and a decrease in autophagy, thereby enhancing the reprogramming efficiency of human somatic cells into iPSCs. These findings were reproduced when human somatic cells after OSKM transduction were cultured in a widely used reprogramming medium (mTeSR) supplemented with CXCR2 ligands interleukin-8 and growth-related oncogene α or an mTOR activator (MHY1485). To our knowledge, this is the first report demonstrating that mTOR activation in human somatic cells with ectopic OSKM expression significantly enhances the production of iPSCs. Our results support the development of convenient protocols for iPSC generation and further our understanding of somatic cell reprogramming.

Predicting peripartum blood transfusion: focusing on pre-pregnancy characteristics.

BACKGROUND: Obstetric hemorrhage is one of the most common causes of obstetrical morbidity and mortality, and transfusion is the most important management for hemorrhage. The aim of our study was to investigate the pre-pregnancy and pregnancy risk factors for peripartum transfusion. METHODS: Women who delivered a baby from 2010 to 2014 in Korea and participated in the Korean National Health Screening Program for Infants and Children were included. To analyze pre-pregnant risk factors for peripartum transfusion, an additional analysis was done for women who underwent a National Health Screening Examination within 1 year before pregnancy, including maternal waist circumference, body mass index, blood pressure, laboratory tests and history of smoking. Multivariable logistic regression analysis was used to estimate the risk factors for peripartum transfusion. RESULTS: Of the total 1,980,126 women who met the inclusion criteria, 36,868 (1.86%) were transfused at peripartum. In a multivariable regression model, the pregnancy risk factors for peripartum transfusion included maternal age above 35 years [odds ratio (OR): 1.41; 95% confidence interval (CI): 1.32-1.50], preterm birth (OR: 2.39; 95% CI: 2.15-2.65), and maternal hypertension (OR: 2.49; 95% CI: 2.24-2.77). Pre-pregnancy risk factors including fasting glucose level of more than 126 mg/dL (OR: 1.11; 95% CI: 1.02-1.20), current-smoker status (OR: 1.20; 95% CI: 1.06-1.37), and waist-circumference less than 80 cm (OR: 1.18; 95% CI: 1.06-1.30) were independently associated with peripartum blood transfusion. CONCLUSIONS: Several pre-pregnancy and pregnancy risk factors were associated with peripartum blood transfusion. Some identified factors are modifiable before conception, and our study validated peripartum blood transfusion as a form of triage.

Prepregnancy liver enzyme levels and risk of preeclampsia in a subsequent pregnancy: A population-based cohort study.

BACKGROUND & AIMS: Preeclampsia is a serious multisystemic disorder leading to maternal and neonatal adverse outcomes. However, little is known about the early markers of this disease. The aim of this study was to investigate the association between prepregnancy liver function and the development of preeclampsia. METHODS: We enrolled 192 571 Korean women who had their first delivery between January 1, 2008, and December 31, 2014, and had undergone a national health screening examination through the National Health Insurance Corporation during 1-2 years before delivery. RESULTS: Preeclampsia developed in 3973 (2.0%) women. The rate of development of preeclampsia was higher in women with abnormal prepregnancy liver enzyme levels than in those with normal liver enzyme levels before pregnancy. On multivariate analysis, women with abnormal alanine aminotransferase level before pregnancy had a 1.21-fold increased risk of developing preeclampsia than those with normal alanine aminotransferase level before pregnancy, after adjusting for age, family history of hypertension, hepatitis B virus carrier status, smoking, alcohol status, prepregnancy body mass index and blood pressure. Prepregnancy γ-glutamyltransferase and aspartate aminotransferase levels were not associated with the risk of preeclampsia development. CONCLUSION: Abnormal prepregnancy alanine aminotransferase level was associated with the development of preeclampsia in a subsequent pregnancy. Further studies are needed to evaluate whether early intervention for liver function before pregnancy can decrease the risk of preeclampsia.

Previous uterine artery embolization increases the rate of repeat embolization in a subsequent pregnancy.

This study aimed to determine the rate of repeat uterine artery embolization (UAE) in women with a previous UAE. Study data were collected from the Korea National Health Insurance Claims Database of the Health Insurance Review and Assessment Service for 2009-2013. We enrolled women who had a first delivery in 2009 and a second delivery between 2010 and 2013. Among 226,408 women who had a first delivery in 2009, 296 underwent UAE. A total of 127,506 women had a second delivery between 2010 and 2013. Of 296 women who underwent UAE after the first delivery, 94 had a second delivery between 2010 and 2013. Women with a previous UAE had a higher rate of UAE at the second delivery than women without a previous UAE. Multivariate adjusted analysis showed that a UAE at the first delivery increased the rate of UAE at the second delivery (odds ratio 25.56, 95% confidence interval 9.86-66.23). Women with a previous UAE should be appropriately counseled and monitored for the need for a repeat UAE.

Structural diversity of marine cyclic peptides and their molecular mechanisms for anticancer, antibacterial, antifungal, and other clinical applications.

Many cyclic peptides and analogues derived from marine sources are known to possess biological properties, including anticancer, antitumor, antibacterial, antifungal, antiparasitic, anti-inflammation, anti-proliferative, anti-hypertensive, cytotoxic, and antibiotic properties. These compounds demonstrate different activities and modes of action according to their structure such as cyclic oligopeptide, cyclic lipopeptide, cyclic glycopeptide and cyclic depsipeptide. The recent advances in application of the above-mentioned cyclic peptides were reported in dolastatins, soblidotin, didemnin B, aplidine, salinosporamide A, kahalalide F and bryostatin 1 and they are currently in clinical trials. These cyclic peptides are possible novel drugs discovered and developed from marine origin. Literature data concerning the potential properties of marine cyclic peptides were reviewed here, and the structural diversity and biological activities of marine cyclic peptides are discussed in relation to the molecular mechanisms of these marine cyclic peptides.