Biphasic Effects of Ingenol 3,20-Dibenzoate on the Erythropoietin Receptor: Synergism at Low Doses and Antagonism at High Doses.

Although ingenol 3,20-dibenzoate (IDB) is known as a selective novel protein kinase C (PKC) agonist, its biologic actions and underlying mechanisms remain incompletely understood. In this study, we identified IDB as a proliferative agent for an erythropoietin (EPO)-dependent cell line, UT-7/EPO, through the screening of a natural compound library. To clarify the underlying mechanism of IDB's EPO-like activities, we thoroughly analyzed the mutual relation between EPO and IDB in terms of in vitro and in vivo activities, signaling molecules, and a cellular receptor.

Deregulation of Retinaldehyde Dehydrogenase 2 Leads to Defective Angiogenic Function of Endothelial Colony-Forming Cells in Pediatric Moyamoya Disease.

Objective--: Moyamoya disease (MMD) is a common cause of childhood stroke, in which the abnormal function of the endothelial colony-forming cell (ECFC) plays a key role in the pathogenesis of the disease. This study was designed to identify genes involved in MMD pathogenesis using gene expression profiling and to understand the defective function of MMD ECFCs.

Approach And Results--: We compared gene expression profiles of ECFCs isolated from patients with MMD and normal controls.

Tuberculous Tracheobronchial Strictures Treated with Balloon Dilation: A Single-Center Experience in 113 Patients during a 17-year Period.

Purpose: To evaluate the safety and effectiveness of balloon dilation in the treatment of tuberculous tracheobronchial strictures (TTBSs) in a series of 113 patients at a single institution.

Materials And Methods: The institutional review board approved the study and waived the requirement to obtain informed consent. Between 1997 and 2014, under bronchoscopic and fluoroscopic guidance, a total of 167 balloon dilation sessions were performed in 113 consecutive patients (14 male and 99 female patients; mean age, 37 years [age range, 17-73 years]), with a range of one to eight sessions per patient (mean, 1.

The Role of Core Needle Biopsy and Its Impact on Surgical Management in Patients with Medullary Thyroid Cancer: Clinical Experience at 3 Medical Institutions.

Background And Purpose: Medullary thyroid carcinoma is an uncommon malignancy that is challenging to diagnose. Our aim was to present our experience using core needle biopsy for the diagnosis of medullary thyroid carcinoma compared with fine-needle aspiration.

Materials And Methods: Between January 2000 and March 2012, 202 thyroid nodules in 191 patients were diagnosed as medullary thyroid cancer by using sonography-guided fine-needle aspiration, core needle biopsy, or surgery.

Thyroid Nodules: Nondiagnostic Cytologic Results according to Thyroid Imaging Reporting and Data System before and after Application of the Bethesda System.

Purpose: To compare the malignancy rates and the effectiveness of the Thyroid Imaging Reporting and Data System (TIRADS) for risk stratification of nodules with nondiagnostic results classified before and after application of the Bethesda System for Reporting Thyroid Cytopathology.

Materials And Methods: This retrospective study was approved by an institutional review board, with waiver of informed consent. A total of 763 patients with 790 thyroid nodules and nondiagnostic cytologic results were included (mean age ± standard deviation, 52.

Irisin, a Novel Myokine, Regulates Glucose Uptake in Skeletal Muscle Cells via AMPK.

Irisin is a novel myokine produced by skeletal muscle. However, its metabolic role is poorly understood. In the present study, irisin induced glucose uptake in differentiated skeletal muscle cells.

Negative Susceptibility Vessel Sign and Underlying Intracranial Atherosclerotic Stenosis in Acute Middle Cerebral Artery Occlusion.

Background And Purpose: The role of MR imaging in predicting underlying intracranial atherosclerotic stenosis before endovascular stroke therapy has not been studied. Our aim was to determine the diagnostic value of the negative susceptibility vessel sign on T2*-weighted gradient-echo MR imaging for predicting underlying intracranial atherosclerotic stenosis in patients with acute MCA occlusion.

Materials And Methods: Ninety-one consecutive patients with acute stroke because of MCA occlusion underwent gradient-echo MR imaging and MRA before endovascular therapy.

The effect of cyclosporine A in hemorrhagic shock model of rats.

Background: The inhibition of mitochondrial permeability transition pore opening during ischemia-reperfusion can ameliorate injuries. This study aimed to investigate the effects of cyclosporine A (CsA) in rats after hemorrhagic shock.

Methods: Male Sprague-Dawley rats were subjected to pressure-controlled hemorrhagic shock (mean arterial pressure, 38 ± 1 mm Hg) for 90 minutes.

Cilostazol induces vasodilation through the activation of Ca(2+)-activated K(+) channels in aortic smooth muscle.

We investigated the vasorelaxant effect of cilostazol and related signaling pathways in phenylephrine (Phe)-induced pre-contracted aortic rings. Cilostazol induced vasorelaxation in a concentration-dependent manner when aortic rings were pre-contracted with Phe. Application of the voltage-dependent K(+) (Kv) channel inhibitor 4-AP, the ATP-sensitive K(+) (K(ATP)) channel inhibitor glibenclamide, and the inwardly rectifying K(+) (Kir) channel inhibitor Ba(2+) did not alter the vasorelaxant effect of cilostazol; however, pre- and post-treatment with the big-conductance Ca(2+)-activated K(+) (BK(Ca)) channel inhibitor paxilline inhibited the vasorelaxant effect of cilostazol.

Nonhypervascular Hypointense Nodules at Gadoxetic Acid-enhanced MR Imaging in Chronic Liver Disease: Diffusion-weighted Imaging for Characterization.

Purpose: To compare the diagnostic performance of magnetic resonance (MR) imaging features, including those on diffusion-weighted (DW) and T2-weighted images, in differentiating between hypovascular hepatocellular carcinoma (HCC) and dysplastic nodules seen as hypointense nodules at hepatobiliary phase gadoxetic acid-enhanced MR imaging.

Materials And Methods: The institutional review board approved this retrospective study and waived the need to obtain informed patient consent. There were 53 patients (39 men and 14 women; age range, 32-75 years) with histologically proven hypovascular HCCs (n = 25) and/or dysplastic nodules (n = 31) who underwent gadoxetic acid-enhanced MR imaging at 3.

Identification of a key residue in Kv7.1 potassium channel essential for sensing external potassium ions.

Kv7.1 voltage-gated K(+) (Kv) channels are present in the apical membranes of marginal cells of the stria vascularis of the inner ear, where they mediate K(+) efflux into the scala media (cochlear duct) of the cochlea. As such, they are exposed to the K(+)-rich (∼ 150 mM of external K(+) (K(+) e)) environment of the endolymph.

Assessment of perioperative cardiac risk of patients undergoing noncardiac surgery using coronary computed tomographic angiography.

Background: The appropriate indication for coronary computed tomographic angiography (CTA) as a part of preoperative evaluation has not been defined yet. We investigated the value of coronary CTA in patients undergoing noncardiac surgery.

Methods And Results: We included 844 patients (median age, 67 years; male sex, 62%) who underwent coronary CTA for screening of coronary artery disease before noncardiac surgery.

N1-Acetyl-5-Methoxykynuramine (AMK) is produced in the human epidermis and shows antiproliferative effects.

Previously, we demonstrated that skin cells metabolize melatonin to 6-hydroxymelatonin, N1-acetyl-N2-formyl-5-methoxykynuramine and 5-methoxytryptamine. In this study, we determined that N1-acetyl-5-methoxykynuramine (AMK) is endogenously produced in the human epidermis from melatonin through the kynuric pathway. The epidermal content of AMK (average from 13 subjects) is 0.

Association of thyroid functional disease with mortality in a national cohort of incident hemodialysis patients.

Context: Hypothyroidism is a common condition that disproportionately affects hemodialysis patients. In the general population, hypothyroidism is associated with higher mortality, particularly in populations with underlying cardiovascular risk. Despite their heightened cardiovascular mortality, the impact of hypothyroidism on the survival of hemodialysis patients remains uncertain.

Optical coherence tomographic observation of in-stent neoatherosclerosis in lesions with more than 50% neointimal area stenosis after second-generation drug-eluting stent implantation.

Background: Despite the enhanced properties of the second-generation drug-eluting stent (DES), its association with neoatherosclerosis has not been sufficiently evaluated. Therefore, we sought to evaluate and compare neoatherosclerosis in second-generation DESs to first-generation DESs.

Methods And Results: A total of 212 DES-treated patients with >50% percent neointimal cross-sectional area stenosis were retrospectively enrolled from the Korean multicenter optical coherence tomography (OCT) registry.

Deficiency of endothelium-specific transcription factor Sox17 induces intracranial aneurysm.

Background: Intracranial aneurysm (IA) is a common vascular disorder that frequently leads to fatal vascular rupture. Although various acquired risk factors associated with IA have been identified, the hereditary basis of IA remains poorly understood. As a result, genetically modified animals accurately modeling IA and related pathogenesis have been lacking, and subsequent drug development has been delayed.

Postoperative simultaneous integrated boost-intensity modulated radiation therapy for patients with locoregionally advanced papillary thyroid carcinoma: preliminary results of a phase II trial and propensity score analysis.

Context: With recent technical advances in radiotherapy (RT) planning, simultaneous integrated boost intensity modulated radiotherapy (SIB-IMRT) has made possible the delivery of high radiation dose to the tumor, minimizing surrounding normal tissues.

Objective: This study aimed to evaluate the clinical effectiveness and safety of postoperative SIB-IMRT in patients with locoregionally advanced papillary thyroid cancer (PTC).

Design And Setting: This was a propensity score-matched case control study conducted at a tertiary referring center.

Thyroid dysfunction associated with follicular cell steatosis in obese male mice and humans.

Adult thyroid dysfunction is a common endocrine disorder associated with an increased risk of cardiovascular disease and mortality. A recent epidemiologic study revealed a link between obesity and increased prevalence of hypothyroidism. It is conceivable that excessive adiposity in obesity might lead to expansion of the interfollicular adipose (IFA) depot or steatosis in thyroid follicular cells (thyroid steatosis, TS).

Comparison of surface roughness and bacterial adhesion between cosmetic contact lenses and conventional contact lenses.

Objective: To compare physical characteristics of cosmetic contact lenses (Cos-CLs) and conventional contact lenses (Con-CLs) that might affect susceptibility to bacterial adhesion on the contact lens (CL) surface.

Methods: Surface characteristics of Cos-CLs and Con-CLs made from the same material by the same manufacturer were measured by atomic force microscopy (AFM) and scanning electron microscopy. To determine the extent and rate of bacterial adhesion, Cos-CL and Con-CL were immersed in serum-free Roswell Park Memorial Institute media containing Staphylococcus aureus or Pseudomonas aeruginosa.

Human Connexin43E42K mutation from a sudden infant death victim leads to impaired ventricular activation and neonatal death in mice.

Background: Sudden infant death syndrome (SIDS) describes the sudden, unexplained death of a baby during its first year of age and is the third leading cause of infant mortality. It is assumed that ≤20% of all SIDS cases are because of cardiac arrhythmias resulting from mutations in ion channel proteins. Besides ion channels also cardiac gap junction channels are important for proper conduction of cardiac electric activation.

Ground-state energy of the q-state Potts model: The minimum modularity.

A wide range of interacting systems can be described by complex networks. A common feature of such networks is that they consist of several communities or modules, the degree of which may quantified as the modularity. However, even a random uncorrelated network, which has no obvious modular structure, has a finite modularity due to the quenched disorder.

The risk of incident type 2 diabetes in a Korean metabolically healthy obese population: the role of systemic inflammation.

Objective: This study sought to investigate whether the metabolically healthy obese (MHO) phenotype is associated with an increased risk of incident type 2 diabetes in a Korean population and, if so, whether systemic inflammation affects this risk in MHO individuals.

Design And Methods: The study population comprised 36 135 Koreans without type 2 diabetes. Participants were stratified by body mass index (cutoff value, 25.

Descending control of itch transmission by the serotonergic system via 5-HT1A-facilitated GRP-GRPR signaling.

Central serotonin (5-hydroxytryptophan, 5-HT) modulates somatosensory transduction, but how it achieves sensory modality-specific modulation remains unclear. Here we report that enhancing serotonergic tone via administration of 5-HT potentiates itch sensation, whereas mice lacking 5-HT or serotonergic neurons in the brainstem exhibit markedly reduced scratching behavior. Through pharmacological and behavioral screening, we identified 5-HT1A as a key receptor in facilitating gastrin-releasing peptide (GRP)-dependent scratching behavior.

Functional role of serotonin in insulin secretion in a diet-induced insulin-resistant state.

The physiological role of serotonin, or 5-hydroxytryptamine (5-HT), in pancreatic β-cell function was previously elucidated using a pregnant mouse model. During pregnancy, 5-HT increases β-cell proliferation and glucose-stimulated insulin secretion (GSIS) through the Gαq-coupled 5-HT2b receptor (Htr2b) and the 5-HT3 receptor (Htr3), a ligand-gated cation channel, respectively. However, the role of 5-HT in β-cell function in an insulin-resistant state has yet to be elucidated.

Grading and interpretation of white matter hyperintensities using statistical maps.

Background And Purpose: We aimed to generate rigorous graphical and statistical reference data based on volumetric measurements for assessing the relative severity of white matter hyperintensities (WMHs) in patients with stroke.

Methods: We prospectively mapped WMHs from 2699 patients with first-ever ischemic stroke (mean age=66.8±13.