Objective: Recently, microRNA (miRNA) has been identified both as a powerful regulator involved in various biological processes through the regulation of numerous genes and as an effective biomarker for the prediction and diagnosis of various disease states. The objective of this study was to identify and validate miRNAs and their target genes involved in inflammation in placental tissue. Methods: Microarrays were utilized to obtain miRNA and gene expression profiles from placentas with or without inflammation obtained from nine normal pregnant women and 10 preterm labor patients. Quantitative real-time polymerase chain reaction and Western blots were performed to validate the miRNAs and differentially-expressed genes in the placentas with inflammation. Correlations between miRNA and target gene expression were confirmed by luciferase assays in HTR-8/SVneo cells. Results: We identified and validated miRNAs and their target genes that were differentially expressed in placentas with inflammation. We also demonstrated that several miRNAs (miR-371a-5p, miR-3065-3p, miR-519b-3p, and miR-373-3p) directly targeted their target genes (LEF1, LOX, ITGB4, and CD44). However, some miRNAs and their direct target genes showed no correlation in tissue samples. Interestingly, miR-373-3p and miR-3065-3p were markedly regulated by lipopolysaccharide (LPS) treatment, although the expression of their direct targets CD44 and LOX was not altered by LPS treatment. Conclusion These results provide candidate miRNAs and their target genes that could be used as placental biomarkers of inflammation. These candidates may be useful for further miRNA-based biomarker development.

PURPOSE: We investigated the changes in serum 25-hydroxyvitamin D (25[OH]D) levels before and after neoadjuvant chemotherapy (NCT) and the associations with pathologic complete response (pCR) and survival in patients with breast cancer. METHODS: Serum 25(OH)D concentrations were measured pre- and post-NCT in 374 patients between 2010 and 2013. Based on a cutoff of 20 ng/mL, patients were categorized into “either sufficient” or “both deficient” groups. The associations with clinicopathological data, including pCR and survival, were analyzed using multivariable analyses. RESULTS: Patients with either pre- or post-NCT sufficient 25(OH)D levels accounted for 23.8%, and the overall pCR rate was 25.9%. Most patients showed 25(OH)D deficiency at diagnosis and 65.8% showed decreased serum levels after NCT. Changes in 25(OH)D status were associated with postmenopause status, rural residence, baseline summer examination, and molecular phenotype, but not pCR. No association between survival and 25(OH)D status was found, including in the subgroup analyses based on molecular phenotypes. CONCLUSION: Most Korean patients with breast cancer showed vitamin D deficiency at diagnosis and a significant decrease in the serum concentration after NCT. No association with oncologic outcomes was found. Therefore, although optimal management for vitamin D deficiency is urgent for skeletal health, further research is warranted to clearly determine the prognostic role of vitamin D in patients with breast cancer who are candidates for NCT.
Breast Neoplasms* ; Breast* ; Diagnosis ; Drug Therapy* ; Humans ; Neoadjuvant Therapy ; Phenotype ; Polymerase Chain Reaction ; Postmenopause ; Treatment Outcome ; Vitamin D ; Vitamin D Deficiency

PURPOSE: The present study aimed to examine the clinical implications of CD4, CD8, and FOXP3 expression on the prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer using a web-based database, and to compare the immunohistochemical expression of T-lymphocyte markers using primary and metastatic HER2-positive tumor tissues before and after HER2-targeted therapy. METHODS: Using the cBioPortal for Cancer Genomics and Kaplan-Meier plotter, the mRNA expression, association between T-lymphocyte markers, and survival in HER2-positive cancers were investigated according to various cutoff levels. Immunohistochemistry analysis was performed using paired primary and metastatic tissues of 29 HER2-positive tumors treated with systemic chemotherapy and HER2-directed therapy. RESULTS: HER2 mRNA was mutually exclusive of T-lymphocyte markers, and a significant correlation between T-cell markers was observed in the cBioPortal for Cancer Genomics. According to analysis of the Kaplan-Meier plotter, the impact of T-lymphocyte marker expression on survival was statistically insignificant in clinical HER2-positive tumors, irrespective of the cutoff levels. However, in the intrinsic HER2-positive subtype, the individual analyses of T-cell markers except for FOXP3 and combined analysis showed significantly favorable survival irrespective of cutoff points. Although the small clinical sample size made it difficult to show the statistical relevance of immunohistochemistry findings, good responses to neoadjuvant treatments might be associated with positive expression of combined T-lymphocyte markers, and approximately half of the samples showed discordance of combined markers between baseline and resistant tumors. CONCLUSION: T-lymphocyte markers could be favorable prognostic factors in HER2-positive breast cancers; however, a consensus on patient section criteria, detection methods, and cutoff value could not be reached. The resistance to HER2-directed therapy might involve different and personalized mechanisms, and further research is required to understand the association between immune function and HER2 expression and to overcome the resistance mechanisms to HER2-targeted therapies.
Biomarkers ; Breast ; Breast Neoplasms ; Consensus ; Drug Resistance ; Drug Therapy ; Epidermal Growth Factor* ; Genomics ; Humans* ; Immunohistochemistry ; Neoadjuvant Therapy ; Prognosis ; Receptor, Epidermal Growth Factor* ; RNA, Messenger ; Sample Size ; T-Lymphocytes*

Eight isoflavonoid compounds were isolated from the EtOAc fraction of Maackia amurensis which had shown the highest anti-Helicobacter pylori activity among the fractions, using medium pressure liquid chromatography and recrystallization. Based on the spectroscopic data including 1H-NMR, 13C-NMR, HMBC and MS data, the chemical structures of the isolates were determined to be (-)-medicarpin (1), afromosin (2), formononetin (3), tectorigenin (4), prunetin (5), wistin (6), tectoridin (7) and ononin (8). Anti-H. pylori activity of each compound was evaluated with broth dilution assay. As a result, (-)-medicarpin (1), tectorigenin (4) and wistin (6) showed anti-H. pylori activity. (-)-Medicarpin (1) exhibited the most potent growth inhibitory activity against H. pylori with the minimal inhibitory concentration (MIC)90 of 25 microM, and tectorigenin (4) with MIC90 of 100 microM ranked the second. This is the first study to show the anti-H. pylori activity of M. amurensis, and it is suggested that the stem bark of M. amurensis or the EtOAc fraction or the isolated compounds can be a new natural source for the treatment of H. pylori infection.
Chromatography, Liquid ; Maackia*

To overcome the difficulty of controlling stem cell fate and function in applications to regenerative medicine, a number of alternative approaches have been made. Recent reports demonstrate that a non-cellular niche modulating the biophysical microenvironment with chemical factors can support stem cell self-renewal. In our previous studies, early establishment was executed to optimize biophysical factors and it was subsequently found that the microgeometry of the extracellular matrix made huge differences in stem cell behavior and phenotype. We review here a three-dimensional, non-cellular niche designed to support stem cell self-renewal. The characteristics of stem cells under the designed system are further discussed.
Extracellular Matrix ; Phenotype ; Regenerative Medicine ; Stem Cells

Plasma pH can be altered during pregnancy and at labor. Membrane excitability of smooth muscle including uterine muscle is suppressed by the activation of K+ channels. Because contractility of uterine muscle is regulated by extracellular pH and humoral factors, K+ conductance could be connected to factors regulating uterine contractility during pregnancy. Here, we showed that TASK-2 inhibitors such as quinidine, lidocaine, and extracellular acidosis produced contraction in uterine circular muscle of mouse. Furthermore, contractility was significantly increased in pregnant uterine circular muscle than that of non-pregnant muscle. These patterns were not changed even in the presence of tetraetylammonium (TEA) and 4-aminopyridine (4-AP). Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretchactivated channels in myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed increased immunohistochemical expression of TASK-2. Therefore, TASK-2, seems to play a key role during regulation of myometrial contractility in the pregnancy and provides new insight into preventing preterm delivery.
4-Aminopyridine ; Acidosis ; Animals ; Contracts ; Female ; Hydrogen-Ion Concentration ; Lidocaine ; Membranes ; Methionine ; Mice ; Muscle, Smooth ; Muscles ; Myometrium ; Plasma ; Pregnancy ; Quinidine ; Relaxation ; Uterine Contraction ; Uterus

PURPOSE: To determine methods tried in clinical trials to reduce the progression of myopia in children, and spectacle prescribing patterns of hospital ophthalmologists. METHODS: A multi-sectioned survey composed of Likert items relating to the methods of reducing myopia progression (orthokeratology lenses [O-K lenses], undercorrected glasses, and topical atropine) and the patterns of prescribing spectacles for children (including two cases involving a 5-year-old girl and an 8-year-old boy) were distributed to members of the Korean Ophthalmological Society, and the collected data was statistically analyzed. RESULTS: A total of 78 out of 130 ophthalmologists returned the survey. On a scale of 1 to 5, the mean rates of whether the ophthalmologists think O-K lenses arrest myopia progression, and whether they recommend their patients to wear O-K lenses if indicative, were 3.06 and 2.75, respectively. Moreover, the mean rates of whether they consider that wearing glasses which are undercorrected would slow down the progression of the myopia, or if they think topical atropine helps in arresting myopia progression in children, were 2.34 and 1.27, respectively. In response to the case studies, the majority of practitioners preferred to prescribe the full amount found in cycloplegic refraction to pediatric patients with myopia. CONCLUSIONS: Ophthalmologists in clinical practice encouraged children to wear O-K lenses more than undercorrected glasses as a way to retard myopia progression. However, the application of atropine is rarely tried in clinical trials. In managing pediatric patients with myopia (case specific), the majority of the practitioners chose to prescribe glasses with full cycloplegic correction.
Atropine/administration & dosage ; Child ; Child, Preschool ; Data Collection ; Disease Progression ; Eyeglasses/classification/*utilization ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Myopia/physiopathology/*prevention & control ; Physician's Practice Patterns ; Prescriptions/*statistics & numerical data ; Republic of Korea

Isolated infective endocarditis in the native pulmonary valve is an unusual clinical entity in non-intravenous drug users. Intravenous drug abuse, alcoholism, sepsis, catheter related infections and congenital heart diseases account for the majority of predisposing factors. We report two cases of isolated pulmonary valve infective endocarditis complicating ventricular septal defect (VSD). A 43 year-old male was admitted because of mild fever, pansystolic murmur on the left lower sternal border. Transthoracic and transesophageal echocardiography revealed a large perimembranous ventricular septal defect and vegetations at the pulmonary valve. After the intravenous use of penicillin and gentamicin, patch closure of VSD with resection of vegetations, resection of anomalous muscle bundles on the right ventricle outlet tract and pulmonary valvuloplasty was performed. A 43 year-old female was admitted with spiking fever, dyspnea. Transthoracic and transesophageal echocardiography showed a small perimenbranous ventricular septal defect with pulmonary valve vegetations. Intravenous penicillin and gentamicin were continued for 4 weeks and she is doing well.
Adult ; Alcoholism ; Catheter-Related Infections ; Causality ; Drug Users ; Dyspnea ; Echocardiography, Transesophageal ; Endocarditis* ; Female ; Fever ; Gentamicins ; Heart Diseases ; Heart Septal Defects, Ventricular* ; Heart Ventricles ; Humans ; Male ; Penicillins ; Pulmonary Valve* ; Sepsis ; Substance Abuse, Intravenous

BACKGROUND/AIMS: Despite of increasing numbers of reports on intraductal papillary mucinous tumor (IPMT), there is still difficulty in its' diagnosis, treatment and prediction of prognosis. The purpose of this multicenter study was to evaluate the clinico-pathological features of IPMT in Korea and suggest the prediction criteria of malignancy in IPMT. METHODS: We retrospectively reviewed the clinico-pathological data of 208 patients who underwent operations with IPMT between 1993 and 2002 at 28 institutes in Korea. RESULTS: Of the 208 patients with a mean age of 60.5+/-9.7 years, 147 were men and 61 were women. 124 patients underwent pancreatoduodenectomy, 42 distal pancreatectomy, 17 total pancreatectomy, 25 limited pancreas resection. Benign cases were 128 (adenoma (n=62), borderline (n=66)) and malignant cases were 80 (non-invasive (n=29), invasive (n=51)). A significant difference in 5-year survival was observed between benign and malignant group (92.6% vs. 65.3%; p=0.006). Of the 6 factors (age, location, duct dilatation, tumor appearance, main duct type, and tumor size) that showed the statistical difference in univariate analysis between benign and malignant group, we found three significant factors (tumor appearance (p=0.009), tumor size (p=0.023), and dilated duct size (p=0.010)) by multivariate analysis. CONCLUSION: Although overall prognosis of IPMT is superior to ordinary pancreatic cancer, more curative surgery is recommended in malignant IPMT. Tumor appearance (papillary), tumor size (> or =30 mm) and dilated duct size (> or = 12 mm) can be used as preoperative indicators of malig-nancy in IPMT.
Academies and Institutes ; Diagnosis ; Dilatation ; Female ; Humans ; Korea* ; Male ; Mucins* ; Multivariate Analysis ; Pancreas* ; Pancreatectomy ; Pancreatic Neoplasms ; Pancreaticoduodenectomy ; Prognosis ; Retrospective Studies

A valvular perforation is a well-known, and common, complication of infective endocarditis that may adversely affect the clinical outcome. However, a 'windsock' deformity of the mitral valve, as a delayed presentation of infective endocarditis, affecting the mitral valve alone, is very rare. A 42-year-old man, who underwent a mitral valvuloplasty and annuloplasty six years previously, suddenly developed pulmonary edema. He had also had a previous history of infective endocarditis, dating back three years. A transthoracic echocardiogram revealed a 'windsock' deformity of the anterior mitral leaflet (AML), resulting in an acute severe mitral regurgitation. During the operation, the AML was found to have been damaged by the previous endocarditis, resulting in an aneurysmal change of the central scallop, and a rupture of the roof. A mitral valve replacement was successfully performed, and the patient recovered uneventfully. Here, we report a rare case of a 'windsock' deformity of the mitral valve, with two perforations as a delayed complication of a healed infective endocarditis.
Adult ; Aneurysm ; Congenital Abnormalities* ; Endocarditis* ; Humans ; Mitral Valve ; Mitral Valve Insufficiency* ; Pectinidae ; Pulmonary Edema ; Rupture