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Find video protocols related to scientific articles indexed in Pubmed.
Evidence of non-pancreatic beta cell-dependent roles of Tcf7l2 in the regulation of glucose metabolism in mice.
Hum. Mol. Genet.
PUBLISHED: 11-16-2014
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Noncoding variation within TCF7L2 remains the strongest genetic determinant of type 2 diabetes risk in humans. A considerable effort has been placed in understanding the functional roles of TCF7L2 in pancreatic beta cells, despite evidence of TCF7L2 expression in various peripheral tissues important in glucose homeostasis. Here, we use a humanized mouse model overexpressing Tcf7l2, resulting in glucose intolerance, to infer the contribution of Tcf7l2 overexpression in beta cells and in other tissues to the metabolic phenotypes displayed by these mice. Restoring Tcf7l2 expression specifically in beta cells to endogenous levels, in face of its overexpression elsewhere, results in impaired insulin secretion, reduced beta cell number and islet area, corroborating data obtained in humans showing similar phenotypes as a result of manipulations leading to Tcf7l2 loss of function. Interestingly, the persistent overexpression of Tcf7l2 in non-pancreatic tissues results in a significant worsening in glucose tolerance in vivo, indicating that Tcf7l2 overexpression in beta cells does not account for the glucose intolerance in the Tcf7l2 overexpression mouse model. Collectively, these data posit that Tcf7l2 plays key roles in glucose metabolism through actions beyond pancreatic beta cells, and further points to functionally opposing cell-type specific effects for Tcf7l2 on the maintenance of balanced glucose metabolism, thereby urging a careful examination of its role in non-pancreatic tissues as well as its composite metabolic effects across distinct tissues. Uncovering these roles may lead to new therapeutic targets for type 2 diabetes.
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[Bone Mineral Density, Biochemical Bone Turnover Markers and Factors associated with Bone Health in Young Korean Women].
J Korean Acad Nurs
PUBLISHED: 11-11-2014
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This study was done to assess the bone mineral density (BMD), biochemical bone turnover markers (BTMs), and factors associated with bone health in young Korean women.
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Shape-responsive actuator from a single layer of a liquid-crystal polymer.
ACS Appl Mater Interfaces
PUBLISHED: 10-06-2014
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Actuation of various shape changes, including bending, helical twisting, and reversible hinging, has been achieved from a single-layer sheet of poly(1,4-di(4-(3-acryloyloxypropyloxy)benzoyloxy)-2-methylbenzene) [poly(RM257)]. This actuator was developed through photopolymerization of a reactive liquid-crystal (LC) monomer (RM257) mixed with 4-pentyl-4'-cyanobiphenyl (5CB, nematic LC at room temperature) in a planar polyimide-coated LC cell. The UV beam perpendicular to one side of the LC cell produced an asymmetric phase separation between the poly(RM257) network and 5CB that resulted in an asymmetric porous structure along the thickness direction when the 5CB was extracted, in which the UV-exposed surface was pore-free and compact while the opposite surface was highly porous. As a result of this structure, the dry and curled poly(RM257) film exhibits actuation behavior when placed in acetone because of a difference in swelling between the two morphologically different sides, the film UV-exposed and nonexposed sides. The actuation of a three-dimensional tetrahedron (pyramidal) structure is also demonstrated for the first time by using a simple photopatterning technique to selectively control its asymmetric morphology at specific locations.
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A monolithic and flexible fluoropolymer film microreactor for organic synthesis applications.
Lab Chip
PUBLISHED: 09-16-2014
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A photocurable and viscous fluoropolymer with chemical stability is a highly desirable material for fabrication of microchemical devices. Lack of a reliable fabrication method, however, limits actual applications for organic reactions. Herein, we report fabrication of a monolithic and flexible fluoropolymer film microreactor and its use as a new microfluidic platform. The fabrication involves facile soft lithography techniques that enable partial curing of thin laminates, which can be readily bonded by conformal contact without any external forces. We demonstrate fabrication of various functional channels (~300 ?m thick) such as those embedded with either a herringbone micromixer pattern or a droplet generator. Organic reactions under strongly acidic and basic conditions can be carried out in this film microreactor even at elevated temperature with excellent reproducibility. In particular, the transparent film microreactor with good deformability could be wrapped around a light-emitting lamp for close contact with the light source for efficient photochemical reactions with visible light, which demonstrates easy integration with optical components for functional miniaturized systems.
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Subclinical hypothyroidism in addition to common risk scores for prediction of cardiovascular disease: a 10-year community-based cohort study.
Eur. J. Endocrinol.
PUBLISHED: 09-02-2014
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This study was carried out to determine whether serum TSH levels improve the prediction of cardiovascular risk in addition to common clinical risk scores, given the association between subclinical hypothyroidism (SCH) and cardiovascular disease (CVD).
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Etanercept for steroid-refractory acute graft versus host disease following allogeneic hematopoietic stem cell transplantation.
Korean J. Intern. Med.
PUBLISHED: 08-28-2014
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The treatment for steroid-refractory acute graft versus host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT) needs to be standardized. We report our clinical experience with etanercept for steroid-refractory acute GVHD.
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Secular trends in the prognostic factors for papillary thyroid cancer.
Eur. J. Endocrinol.
PUBLISHED: 08-27-2014
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With the recent increasing rates of screening for thyroid cancer, the cancers now tend to be smaller and less aggressive than those that are diagnosed when presented with symptoms, suggesting changes in the clinical validity of conventional prognostic factors for outcomes. We performed the retrospective study to identify the secular trends in the prognostic factors of thyroid cancer.
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Serum thyroglobulin level after radioiodine therapy (Day 3) to predict successful ablation of thyroid remnant in postoperative thyroid cancer.
Ann Nucl Med
PUBLISHED: 08-20-2014
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The utility of serum thyroglobulin (Tg) level, 3 days after radioactive iodine (RAI) therapy, was assessed as a means of predicting successful ablation of thyroid remnant in patients with postoperative thyroid cancer.
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The risk of second primary malignancy is increased in differentiated thyroid cancer patients with a cumulative (131) I dose over 37 GBq.
Clin. Endocrinol. (Oxf)
PUBLISHED: 08-13-2014
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The aim of this study was to investigate the risk factors for second primary malignancy (SPM) diagnosed after differentiated thyroid cancer (DTC).
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The effect of long-term thyroid-stimulating hormone suppressive therapy on the cognitive function of elderly patients with differentiated thyroid carcinoma.
J. Clin. Endocrinol. Metab.
PUBLISHED: 07-16-2014
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Several studies have evidenced the association between subclinical hyperthyroidism and cognitive impairment in the elderly. However, the effect of long-term TSH suppressive therapy on the cognitive function in elderly patients with differentiated thyroid carcinoma (DTC) is still unclear.
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Identification of novel autoantibodies in type 1 diabetic patients using a high-density protein microarray.
Diabetes
PUBLISHED: 06-19-2014
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Autoantibodies can facilitate diagnostic and therapeutic means for type 1 diabetes (T1DM). We profiled autoantibodies from serum samples of 16 T1DM patients, 16 type 2 diabetic (T2DM) patients, and 27 healthy control subjects with normal glucose tolerance (NGT) by using protein microarrays containing 9,480 proteins. Two novel autoantibodies, anti-EEF1A1 and anti-UBE2L3, were selected from microarrays followed by immunofluorescence staining of pancreas. We then tested the validity of the candidates by ELISA in two independent test cohorts: 1) 95 adults with T1DM, 49 with T2DM, 11 with latent autoimmune diabetes in adults (LADA), 20 with Graves disease, and 66 with NGT and 2) 33 children with T1DM and 34 healthy children. Concentrations of these autoantibodies were significantly higher in T1DM patients than in NGT and T2DM subjects (P < 0.01), which was also confirmed in the test cohort of children (P < 0.05). Prevalence of anti-EEF1A1 and anti-UBE2L3 antibodies was 29.5% and 35.8% in T1DM, respectively. Of note, 40.9% of T1DM patients who lack anti-GAD antibodies (GADA) had anti-EEF1A1 and/or anti-UBE2L3 antibodies. These were also detected in patients with fulminant T1DM but not LADA. Our approach identified autoantibodies that can provide a new dimension of information indicative of T1DM independent of GADA and new insights into diagnosis and classification of T1DM.
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Therapeutic potential of Dickkopf-1 in wild-type BRAF papillary thyroid cancer via regulation of ?-catenin/E-cadherin signaling.
J. Clin. Endocrinol. Metab.
PUBLISHED: 05-21-2014
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Aberrant activation of the Wnt/?-catenin pathway is a common pathogenesis of various human cancers. We investigated the role of the Wnt inhibitor, Dkk-1, in papillary thyroid cancer (PTC).
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The inhibitory effect of PIK-75 on inflammatory mediator response induced by hydrogen peroxide in feline esophageal epithelial cells.
Mediators Inflamm.
PUBLISHED: 05-16-2014
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Isoform-selective inhibitors of phosphoinositide 3-kinase (PI3K) activation have an anti-inflammatory effect by reducing proinflammatory cytokines. Cultured feline esophageal epithelial cells (EEC) of passages 3~4 were treated with hydrogen peroxide and PIK-75. The cell viability was measured by a MTT incorporation assay. The distribution of PI3K isoforms, p-Akt, IL-1?, and IL-8 was inferred from Western blots. The release of IL-6 was determined by ELISA. The cell morphology was not considerably different from nontreated cells if the cells were pretreated with PIK-75 and treated with 300 ?M hydrogen peroxide. The density of p110? of PI3K was increased, but that of other types was not affected after the treatment with hydrogen peroxide. The density of p-Akt, when the cells were exposed to PIK-75 and hydrogen peroxide, was diminished dose dependently more than that of hydrogen peroxide treatment only. The decrease of p-Akt showed an inhibition of PI3K by PIK-75. PIK-75 dose dependently reduced the expression of IL-1?, IL-8, and the level of IL-6 compared with hydrogen peroxide treatment only. These results suggest evidence that p110? mediates esophageal inflammation and that PIK-75 has an anti-inflammatory effect by reducing proinflammatory cytokines on feline esophageal epithelial cultured cells.
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The Frequency and Clinical Implications of the BRAF(V600E) Mutation in Papillary Thyroid Cancer Patients in Korea over the Past Two Decades.
Endocrinol Metab (Seoul)
PUBLISHED: 05-12-2014
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Over the past several decades, there has been a rapid worldwide increase in the prevalence of papillary thyroid cancer (PTC) as well as a number of changes in the clinicopathological characteristics of this disease. BRAF(V600E), which is a mutation of the proto-oncogene BRAF, has become the most frequent genetic mutation associated with PTC, particularly in Korea. Thus, the present study investigated whether the prevalence of the BRAF(V600E) mutation has increased over the past two decades in the Korean population and whether various PTC-related clinicopathological characteristics have changed.
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Follicular and Hurthle cell carcinoma of the thyroid in iodine-sufficient area: retrospective analysis of Korean multicenter data.
Korean J. Intern. Med.
PUBLISHED: 04-29-2014
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Follicular thyroid carcinoma (FTC) and Hurthle cell carcinoma (HCC) of the thyroid are relatively uncommon thyroid malignancies in iodine-sufficient areas. In this study we evaluated the clinical behavior, prognostic factors and treatment outcomes of FTC and HCC in Korea.
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The effect of education on decreasing the prevalence and severity of neck and shoulder pain: a longitudinal study in Korean male adolescents.
Korean J Anesthesiol
PUBLISHED: 04-21-2014
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Neck and shoulder pain is fairly common among adolescents in Korea and results in significant health problem. The aims of this prospective study was to identify the effects of education, in terms of recognition of this issue and posture correction, on prevalence and severity of neck and shoulder pain in Korean adolescents.
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Expression of indoleamine 2,3-dioxygenase and infiltration of FOXP3+ regulatory T cells are associated with aggressive features of papillary thyroid microcarcinoma.
Thyroid
PUBLISHED: 04-19-2014
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Indoleamine 2,3-dioxygenase (IDO) is overexpressed in many different types of tumor and is associated with activation of FOXP3+ regulatory T cells (Treg cells) and downregulation of cytotoxic cellular immunity in the tumor microenvironment. It has been suggested that IDO inhibitors can be utilized as an effective therapeutic agent against human cancers. However, the expression of IDO and its association with tumor-infiltrating lymphocytes (TILs) remain unclear in papillary thyroid microcarcinoma (PTMC).
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Prevalence and risk factors of subclinical thyroid disease.
Endocrinol Metab (Seoul)
PUBLISHED: 04-18-2014
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Subclinical thyroid disease is defined biochemically by an abnormal thyrotropin (TSH) level and normal serum-free thyroxine level. The prevalence of this condition varies according to the reference range for TSH and geographic or demographic factors. Recently, several studies, including our community-based cohort studies, have reported on the incidence of subclinical thyroid disease in Korea. Using these studies, we reviewed the prevalence and risk factors of subclinical thyroid disease, focusing on subclinical hypothyroidism.
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A genome-wide association study on thyroid function and anti-thyroid peroxidase antibodies in Koreans.
Hum. Mol. Genet.
PUBLISHED: 04-09-2014
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Genetic factors are thought to be an important determinant of thyroid function and autoimmunity. However, there are limited data on genetic variants in Asians. In this study, we performed a genome-wide association study on plasma thyroid-stimulating hormone (TSH) and free thyroxine (fT4) concentration and anti-thyroid peroxidase (anti-TPO) antibody positivity in 4238 Korean subjects. In the Stage 1 genome scan, 3396 participants from the Ansung cohort were investigated using 1.42 million genotyped or imputed markers. In the Stage 2 follow-up, 10 markers were genotyped in 842 participants from the Korean Longitudinal Study on Health and Aging cohort. An intronic variant in VAV3, rs12126655, which has been reported in Europeans, was significantly associated with plasma TSH concentration in the joint Stages 1 and 2 analyses (P = 2.2 × 10(-8)). We observed that a novel variant, rs2071403, located 75 bp proximal to the translational start site of TPO was significantly associated with plasma anti-TPO antibody positivity in the joint Stages 1 and 2 analyses (P = 1.3 × 10(-10)). This variant had a marginal sex-specific effect, and its association was more significant in females. Subjects possessing the rs2071403A allele, associated with an absence of the anti-TPO antibody, had decreased TPO mRNA expression in their thyroid tissue. Another intronic variant of HLA-DPB2, rs733208, had a suggestive association with anti-TPO antibody positivity (P = 4.2 × 10(-7)). In conclusion, we have identified genetic variants that are strongly associated with TSH level and anti-TPO antibody positivity in Koreans. Further replications and meta-analysis are required to confirm these findings.
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Knot impingement after rotator cuff repair: is it real?
Arthroscopy
PUBLISHED: 04-07-2014
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The purpose of this study was to compare morphologic features of the acromion after 2 different repair methods (single-row [SR] repair with a minimum of 4 knots and suture-bridge [SB] repair with minimal knots) in medium to large rotator cuff tears.
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Involvement of heme oxygenase-1 in neuroprotection by sanguinarine against glutamate-triggered apoptosis in HT22 neuronal cells.
Environ. Toxicol. Pharmacol.
PUBLISHED: 04-03-2014
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Sanguinarine is a natural compound isolated from the roots of Macleaya cordata and M. microcarpa, has been reported to possess several biological activities such as anti-inflammatory and anti-oxidant effects. In the present study, we demonstrated that sanguinarine markedly induces the expression of HO-1 which leads to a neuroprotective response in mouse hippocampus-derived neuronal HT22 cells from apoptotic cell death induced by glutamate. Sanguinarine significantly attenuated the loss of mitochondrial function and membrane integrity associated with glutamate-induced neurotoxicity. Sanguinarine protected against glutamate-induced neurotoxicity through inhibition of HT22 cell apoptosis. JC-1 staining, which is a well-established measure of mitochondrial damage, was decreased after treatment with sanguinarine in glutamate-challenged HT22cells. In addition, sanguinarine diminished the intracellular accumulation of ROS and Ca(2+). Sanguinarine also induced HO-1, NQO-1 expression via activation of Nrf2. Additionally, we found that si RNA mediated knock-down of Nrf2 or HO-1 significantly inhibited sanguinarine-induced neuroprotective response. These findings revealed the therapeutic potential of sanguinarine in preventing the neurodegenerative diseases.
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Comparison of the efficacy and safety profiles of a pelubiprofen versus celecoxib in patients with rheumatoid arthritis: a 6-week, multicenter, randomized, double-blind, phase III, non-inferiority clinical trial.
BMC Musculoskelet Disord
PUBLISHED: 03-31-2014
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Pelubiprofen is a prodrug of 2-arylpropionic acid with relatively selective effects on cyclooxygenase-2 activity. The aim of this study was to compare the efficacy and safety profiles of pelubiprofen with those of celecoxib in patients with rheumatoid arthritis.
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Effect of immobilization without passive exercise after rotator cuff repair: randomized clinical trial comparing four and eight weeks of immobilization.
J Bone Joint Surg Am
PUBLISHED: 03-21-2014
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While animal studies have shown better healing with a longer duration of protection without motion exercise after rotator cuff repair, supporting clinical studies are rare. The purpose of this study was to assess the effect of immobilization following rotator cuff repair and to determine whether there was any difference in clinical outcome related to the duration of immobilization.
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The neuroprotective effects of ?-iso-cubebene on dopaminergic cell death: involvement of CREB/Nrf2 signaling.
Neurochem. Res.
PUBLISHED: 03-20-2014
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As a part of ongoing studies to elucidate pharmacologically active components of Schisandra chinensis, we isolated and studied ?-iso-cubebene. The neuroprotective mechanisms of ?-iso-cubebene in human neuroblastoma SH-SY5Y cells were investigated. ?-Iso-cubebene significantly inhibited cytotoxicity and apoptosis due to 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in dopaminergic SH-SY5Y cells. Pretreatment of cells with ?-iso-cubebene reduced intracellular accumulation of ROS and calcium in response to 6-OHDA. The neuroprotective effects of ?-iso-cubebene were found to result from protecting the mitochondrial membrane potential. Notably, ?-iso-cubebene inhibited the release of apoptosis-inducing factor from the mitochondria into the cytosol and nucleus after 6-OHDA treatment. ?-Iso-cubebene also induced the activation of PKA/PKB/CREB/Nrf2 and suppressed 6-OHDA-induced neurotoxicity. ?-Iso-cubebene was found to induce phosphorylation of PKA and PKB and activate Nrf2 and CREB signaling pathways in a dose-dependent manner. Additionally, ?-iso-cubebene stimulated the expression of the antioxidant response genes NQO1 and HO-1. Finally, ?-iso-cubebene-mediated neuroprotective effects were found to be reversible after transfection with CREB and Nrf2 small interfering RNAs.
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Pain and satisfaction during rigid cystoscopic ureteral stent removal: a preliminary study.
BMC Urol
PUBLISHED: 03-16-2014
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Cystoscopy evokes discomfort and pain, especially in males. The cystoscopic retrograde approach is standard in the removal of ureteral stents. However the satisfaction and degree of pain during the procedure according to the use of several pain controlling methods are unclear.
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Medullary thyroid carcinoma with ectopic adrenocorticotropic hormone syndrome.
Endocrinol Metab (Seoul)
PUBLISHED: 03-14-2014
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Ectopic adrenocorticotropic hormone (ACTH) syndrome is caused most frequently by a bronchial carcinoid tumor or by small cell lung cancer. Medullary thyroid carcinoma (MTC) is a rare etiology of ectopic ACTH syndrome. We describe a case of Cushing syndrome due to ectopic ACTH production from MTC in a 48-year-old male. He was diagnosed with MTC 14 years ago and underwent total thyroidectomy, cervical lymph node dissection and a series of metastasectomies. MTC was confirmed by the pathological examination of the thyroid and metastatic mediastinal lymph node tissues. Two years after his last surgery, he developed Cushingoid features, such as moon face and central obesity, accompanied by uncontrolled hypertension and new-onset diabetes. The laboratory results were compatible with ectopic ACTH syndrome. A bilateral adrenalectomy improved the clinical and laboratory findings that were associated with Cushing syndrome. This is the first confirmed case of ectopic ACTH syndrome caused by MTC in Korea.
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Involvement of activation of the Nrf2/ARE pathway in protection against 6-OHDA-induced SH-SY5Y cell death by ?-iso-cubebenol.
Neurotoxicology
PUBLISHED: 03-12-2014
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Free radical-mediated neurodegeneration is one of the many causes of Parkinson's disease (PD). As part of our ongoing studies on the identification of biologically active Schisandra chinensis components, we have isolated and structurally elucidated ?-iso-cubebenol. This study was carried out in an attempt to clarify the neuroprotective effect of ?-iso-cubebenol on toxin-insulted dopaminergic neuronal death using 6-hydroxy-dopamine (6-OHDA)-induced dopaminergic SH-SY5Y cells. ?-iso-cubebenol significantly attenuated the loss of mitochondrial function (MTT assay) and membrane integrity (lactate dehydrogenase assay) associated with 6-OHDA-induced neurotoxicity. Pretreatment of the cells with ?-iso-cubebenol diminished the intracellular accumulation of reactive oxygen species (ROS) and calcium in response to 6-OHDA. Moreover, ?-iso-cubebenol protected against 6-OHDA-induced neurotoxicity through inhibition of SH-SY5Y cell apoptosis. In addition, JC-1 staining, which is a well-established measure of mitochondrial damage, was decreased after treatment with ?-iso-cubebenol. Notably, ?-iso-cubebenol inhibited the release of mitochondrial flavoprotein apoptosis inducing factor (AIF) from the mitochondria to the cytosol and nucleus following 6-OHDA treatment. In addition, ?-iso-cubebenol reduced the 6-OHDA-induced phosphorylation of ERK and induced the phosphorylation of PKA, PKB, and CREB in a dose-dependent manner. Moreover, ?-iso-cubebenol stimulated the activation of Nrf2, a downstream target of CREB. Furthermore, ?-iso-cubebenol stimulated the expression of multiple antioxidant response genes (NQO-1 and HO-1). Finally, CREB and Nrf2 siRNA transfection diminished ?-iso-cubebenol-mediated neuroprotection.
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Intra-articular injection of hyaluronate versus corticosteroid in adhesive capsulitis.
Orthopedics
PUBLISHED: 02-20-2014
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The goal of this study was to prospectively compare the early clinical results of intra-articular injection of hyaluronate or corticosteroid in patients with idiopathic adhesive capsulitis. The authors' hypothesis was that there would be no difference between groups. Sixty-eight patients with idiopathic adhesive capsulitis were equally randomized to receive either corticosteroid or hyaluronate injection. All patients underwent standard physical examination and magnetic resonance imaging. Intra-articular injection was performed through an anterior approach by the same orthopedic surgeon without image guidance. Patients were followed up 2 and 12 weeks after completion of the injection. The primary outcome was the Constant score at week 12. Secondary outcomes included the visual analog scale (VAS) pain score, the American Shoulder and Elbow Surgeons (ASES) score, and range of motion at each time point. No significant differences were noted in preoperative demographic features or baseline shoulder function between groups. After treatment, no significant differences were noted in early clinical outcomes (at weeks 2 and 12) with VAS, ASES, and Constant scores between groups (all P>.05). Evaluation of range of motion showed no difference in forward elevation or external rotation at each time point. Internal rotation was significantly lower at week 2 in the hyaluronate group compared with the corticosteroid group (P=.015). Internal rotation improved at week 12, with no significant difference between groups. Patients treated with intra-articular injection of hyaluronate and corticosteroid for idiopathic adhesive capsulitis showed significant improvement in early clinical scores and range of motion without significant differences between groups.
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Crocin suppresses LPS-stimulated expression of inducible nitric oxide synthase by upregulation of heme oxygenase-1 via calcium/calmodulin-dependent protein kinase 4.
Mediators Inflamm.
PUBLISHED: 02-11-2014
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Crocin is a water-soluble carotenoid pigment that is primarily used in various cuisines as a seasoning and coloring agent, as well as in traditional medicines for the treatment of edema, fever, and hepatic disorder. In this study, we demonstrated that crocin markedly induces the expression of heme oxygenase-1 (HO-1) which leads to an anti-inflammatory response. Crocin inhibited inducible nitric oxide synthase (iNOS) expression and nitric oxide production via downregulation of nuclear factor kappa B activity in lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. These effects were abrogated by blocking of HO-1 expression or activity. Crocin also induced Ca(2+) mobilization from intracellular pools and phosphorylation of Ca(2+)/calmodulin-dependent protein kinase 4 (CAMK4). CAMK4 knockdown and kinase-dead mutant inhibited crocin-mediated HO-1 expression, Nrf2 activation, and phosphorylation of Akt, indicating that HO-1 expression is mediated by CAMK4 and that Akt is a downstream mediator of CAMK4 in crocin signaling. Moreover, crocin-mediated suppression of iNOS expression was blocked by CAMK4 inhibition. Overall, these results suggest that crocin suppresses LPS-stimulated expression of iNOS by inducing HO-1 expression via Ca(2+)/calmodulin-CAMK4-PI3K/Akt-Nrf2 signaling cascades. Our findings provide a novel molecular mechanism for the inhibitory effects of crocin against endotoxin-mediated inflammation.
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Loss of ER? expression in papillary thyroid carcinoma is associated with recurrence in young female.
Clin. Endocrinol. (Oxf)
PUBLISHED: 02-04-2014
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We investigated the expression of oestrogen receptors (ERs) in papillary thyroid cancers (PTCs) and evaluated their prognostic role.
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Preoperative factors affecting footprint coverage in rotator cuff repair.
Am J Sports Med
PUBLISHED: 02-04-2014
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One of the goals of rotator cuff repair is to restore the torn tendon to its original insertion anatomically. However, it is sometimes difficult to restore the entire footprint.
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The neuroprotective effects of cordycepin inhibit glutamate-induced oxidative and ER stress-associated apoptosis in hippocampal HT22 cells.
Neurotoxicology
PUBLISHED: 01-21-2014
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Glutamate toxicity increases the formation of reactive oxygen species (ROS) and intracellular calcium levels, resulting in neuronal dysfunction, neurodegenerative disorders, and death. Cordycepin is a derivative of the nucleoside adenosine, and is believed to exert neuroprotective effects against glutamate-induced oxidative toxicity in HT22 neuronal cells. Excessive glutamate induces oxidative and endoplasmic reticulum (ER) stress, gradually increasing ER-related pro-apoptotic transcription factor C/EBP homologous protein (CHOP) expression, and eventually up-regulating expression of the pro-apoptotic factor Bax. Cordycepin inhibits CHOP and Bax expressions, as well as p-ERK, p-JNK, and p-p38, all of which are involved in oxidative or ER stress-induced apoptosis. In addition, the increased production of ROS from excessive glutamate leads to elevation of mitochondrial membrane potential (MMP), a hallmark of mitochondrial dysfunction. Cordycepin retains MMP and reduces the elevated levels of ROS and Ca(2+) induced by glutamate. Caspases are crucial mediators involved in mitochondrial apoptosis, and while glutamate disrupts mitochondrial function, it does not change expression levels of caspase 3 and caspase 9. Similarly, cordycepin has no effect on caspase 3 and caspase 9 expressions; however, it decreases the expression of ER stress-specific caspase 12, which plays a key role in the initiation of ER stress-induced apoptosis. Finally, we found that the anti-apoptotic effects of cordycepin are partially dependent on activation of the adenosine A1 receptor, whereas an antagonist selectively attenuated the neuroprotective effects of cordycepin. Collectively, these results suggest that cordycepin could be a potential future therapeutic agent for neuronal disorders.
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Incidental thyroid cancer detected by (18)F-FDG PET: does it have different clinicopathological features?
Nucl Med Commun
PUBLISHED: 01-15-2014
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The prevalence and risk of malignancy in thyroid incidentalomas has been investigated in previous studies; however, these studies have not looked at the characteristics of incidental thyroid cancer (ITC) detected by fluorine-18 fluorodeoxyglucose PET. Therefore, we aimed to assess the clinicopathologic features of ITC.
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Ethyl linoleate from garlic attenuates lipopolysaccharide-induced pro-inflammatory cytokine production by inducing heme oxygenase-1 in RAW264.7 cells.
Int. Immunopharmacol.
PUBLISHED: 01-14-2014
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In the present study, an essential fatty acid, ethyl linoleate (ELA), was isolated from the cloves of Allium sativum, and its structure was elucidated by NMR and GC-MS analyses. In vitro systems were used to evaluate the anti-inflammatory activity of ELA. Our results indicate that ELA down-regulates inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and thereby reduces nitric oxide (NO) and prostaglandin E2 production in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Immunofluorescent microscopy and western blot analyses revealed that these effects were mediated by impaired translocation of nuclear factor (NF)-?B and inhibition of phosphorylation of mitogen activated protein kinases. Furthermore, ELA exerted its anti-inflammatory activity by inducing heme oxygenase-1 (HO-1) expression, as determined by HO-1 small interfering (Si) RNA system. Si RNA-mediated knock-down of HO-1 abrogated the inhibitory effects of ELA on the production of NO, TNF-?, IL-1?, and IL-6 in LPS-induced macrophages. These findings indicate the potential therapeutic use of ELA as an anti-inflammatory agent.
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Therapeutic potential of metformin in papillary thyroid cancer in vitro and in vivo.
Mol. Cell. Endocrinol.
PUBLISHED: 01-10-2014
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Metformin, an anti-diabetic drug used in type 2 diabetes treatment, is reported to have oncopreventive or therapeutic roles in several human cancers. The present study investigated the therapeutic potential of physiologic dose of metformin in PTC. Metformin inhibited PTC cell viability and increased cell apoptosis in various doses (0.5-20mM) in BCPAP and BHP10-3SC cells. Western blot analysis demonstrated that the p-AMPK/AMPK ratio increased with increased metformin treatment. The ectopic tumor experiment was performed using BHP10-3SC cells and athymic nude mice. Oral metformin treatment via drinking water significantly delayed tumor growth in both tumor development model and established tumor models. Necrotic area in tumors significantly increased with metformin treatment. Western blot analysis revealed an increase in p-AMPK/AMPK ratio and suppressions of mTOR and Akt expressions in metformin-treated mice compared to the results in mock-treated control mice. Our results indicate that a physiologic dose of metformin has anti-tumorigenic effects that result from activation of AMPK signaling and inhibition of Akt signaling.
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Diabetes mellitus and risk of thyroid cancer: a meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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Diabetes mellitus (DM) is an important risk factor for endocrine cancers; however, the association with thyroid cancer is not clear. We performed a systematic review and meta-analysis to clarify the association between thyroid cancer and DM.
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Lower-but-normal serum TSH level is associated with the development or progression of cognitive impairment including mild cognitive impairment and dementia in elderly: A result from Korean Longitudinal Study on Health and Aging (KLoSHA).
J. Clin. Endocrinol. Metab.
PUBLISHED: 11-27-2013
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Context:The association between subclinical hyperthyroidism and the risk of dementia has been validated in several studies. However, the effect of thyroid function within reference range on the risk of cognitive dysfunction including mild cognitive impairment (MCI) and dementia is still unclear.Objective:Our aim was to investigate the association between thyroid function and the risk of MCI and dementia in euthyroid elderly subjects.Design, setting, and participants:We conducted a population-based prospective study as a part of the Korean Longitudinal Study on Health and Aging (KLoSHA). 313 participants who were euthyroid and non-demented at baseline and completed cognitive function tests at 5-year-follow-up evaluation (mean age, 72.5 ± 6.9 yrs) were analyzed in the present study.Main outcome measure:Baseline thyroid function was compared according to the development of MCI or dementia during the study period. Binary logistic regression analysis was performed to investigate the independent association between thyroid function and cognitive impairment.Results:At baseline evaluation, 237 subjects were cognitively normal, and 76 subjects were MCI. Diagnoses of cognitive function in 259 subjects remained unchanged or improved during the study period (non-progression group), whereas 54 subjects showed progression of cognitive impairment to MCI or dementia (progression group). In the progression group, baseline serum TSH levels were lower than those in non-progression group. Baseline serum free-T4 levels were not significantly different between these two groups. The association between lower baseline serum TSH levels and the development of MCI or dementia was maintained after adjustment for conventional baseline risk factors.Conclusions:Lower serum TSH level within reference range was independently associated with the risk of cognitive impairment including MCI and dementia in elderly subjects.
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Coexistence of expanding abdominal aortic aneurysm and aggravated intervertebral disc extrusion -a case report-.
Korean J Anesthesiol
PUBLISHED: 10-24-2013
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Abdominal aortic aneurysm is included in the differential diagnosis of lower back pain. Although rare, this important disease can cause potentially lethal complications. In this case, expanding abdominal aortic aneurysm coexisted with intervertebral disc extrusion. The diagnosis of abdominal aortic aneurysm was delayed, putting the patient at risk of aneurysmal rupture. In the management of patients with degenerative spinal diseases, we should not overlook the possibility of comorbidities such as an abdominal aortic aneurysm. We also suggest the importance of interpreting images more carefully, especially for elderly male patients.
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Sanguinarine inhibits invasiveness and the MMP?9 and COX?2 expression in TPA-induced breast cancer cells by inducing HO-1 expression.
Oncol. Rep.
PUBLISHED: 09-23-2013
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Most complications of breast cancer are attributed to metastasis to distant organs, including lymph nodes, bone, lung and liver. Metastasis is considered the leading cause of mortality in patients with breast cancer. The emergence of anti-metastatic properties in breast cancer is an important clinical phenomenon affecting long-term survival. In the present study, we investigated the anti-invasive mechanism of sanguinarine by focusing on its role in inducing HO-1 in breast cancer cells. The results showed that sanguinarine inhibited TPA-induced MMP-9 and COX?2 mRNA and protein expression in a dose-dependent manner at non-cytotoxic concentrations. Similarly, the MMP-9 enzymatic activity and the PGE2 levels significantly decreased in MCF-7 breast cancer cells. TIMP?1 and TIMP-2, specific endogenous inhibitors of MMP-9, were slightly induced by sanguinarine. Subsequent studies revealed that sanguinarine suppressed TPA-induced NF-?B and AP-1 activation, as well as the phosphorylation of Akt and ERK. Furthermore, sanguinarine significantly inhibited TPA-induced invasion and migration in breast cancer cells. We also demonstrated that sanguinarine induced HO-1 expression, and that the inhibition of MMP-9 and COX-2 expression and the enzymatic activity of sanguinarine were abrogated by siRNA-mediated knockdown of HO-1 expression. Thus, knockdown of endogenous HO-1 decreased TPA-induced cell invasion. Overall, the results of the present study demonstrate that HO-1 plays a pivotal role in the anti-invasive response of sanguinarine in TPA-stimulated breast cancer cells.
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Long-Term Prognosis of Differentiated Thyroid Cancer with Lung Metastasis in Korea and Its Prognostic Factors.
Thyroid
PUBLISHED: 09-11-2013
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Background: Distant metastasis, generally to lung and bone, is rare in differentiated thyroid carcinoma (DTC) and the prognosis is still elusive. We investigated long-term outcomes of lung metastasis in DTC patients and its prognostic factors. Methods: A retrospective review was performed of 4572 patients who underwent surgery for DTC from 1962 to 2009 at Seoul National University Hospital. Among them, 164 patients were identified with lung metastasis and 152 patients were enrolled in the final analysis. Poor prognosis was defined as progressive disease or death. Results: Of these 152 patients, 10- and 20-year survival rates were 85.0% and 71.0%, respectively. No evidence of disease, stable disease, progressive disease, and death was identified in 22.4%, 28.3%, 35.5%, and 13.8%, respectively, after 11 years of median follow-up (range 2-41 years). Older age at diagnosis (?45 years), primary tumor size ?2?cm, follicular thyroid cancer, metastasis diagnosed after initial evaluation or (131)I remnant ablation (late metastasis), multiple metastases other than lung, (131)I nonavidity, and the presence of macronodules (?1?cm) were more frequent in poor prognoses. Cox proportional hazard ratio for progression-free survival showed that (131)I nonavidity was the only independent predictive factor for poor prognosis. Conclusions: The prognosis of lung metastasis from DTC in Korea within this study was favorable. (131)I nonavidity, observed more frequently in late metastasis, was the only independent factor predicting poor prognosis.
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Effect of ECQ on Iodoacetamide-Induced Chronic Gastritis in Rats.
Korean J. Physiol. Pharmacol.
PUBLISHED: 09-06-2013
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This study investigated effect of extract containing quercetin-3-O-?-D-glucuronopyranoside from Rumex Aquaticus Herba (ECQ) against chronic gastritis in rats. To produce chronic gastritis, the animals received a daily intra-gastric administration of 0.1 ml of 0.15% iodoacetamide (IA) solution for 7 days. Daily exposure of the gastric mucosa to IA induced both gastric lesions and significant reductions of body weight and food and water intake. These reductions recovered with treatment with ECQ for 7 days. ECQ significantly inhibited the elevation of the malondialdehyde levels and myeloperoxidase activity, which were used as indices of lipid peroxidation and neutrophil infiltration. ECQ recovered the level of glutathione, activity of superoxide dismutase (SOD), and expression of SOD-2. The increased levels of total NO concentration and iNOS expression in the IA-induced chronic gastritis were significantly reduced by treatment with ECQ. These results suggest that the ECQ has a therapeutic effect on chronic gastritis in rats by inhibitory actions on neutrophil infiltration, lipid peroxidation and various steps of reactive oxygen species (ROS) generation.
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Halofuginone induces the apoptosis of breast cancer cells and inhibits migration via downregulation of matrix metalloproteinase-9.
Int. J. Oncol.
PUBLISHED: 09-02-2013
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Halofuginone (HF) is extracted from Dichroa febrifuga, a plant used in traditional medicine. We report that the HF extract inhibits the growth of breast cancer cells and induces the generation of reactive oxygen species (ROS) and apoptosis, an important feature of potential anticancer agents. In addition, HF significantly reduces the migration and invasion of MCF-7 and MDA-MB-231 human breast cancer cells after 12-O-tetraecanoylphorbol-13-acetate (TPA) stimulation. As matrix metalloproteinase-9 plays a critical role in tumor metastasis, we analyzed its expression with the HF extract treatment. Western blot analysis and gelatin zymography showed that HF suppresses MMP-9 expression and activity concentration-dependently. HF also decreases the nuclear protein levels of nuclear factor kappa B (NF-?B) and c-fos (AP-1), critical transcription factors regulating MMP-9 expression through binding the MMP-9 promoter region. Luciferase assays showed that HF decreases TPA-induced MMP-9 promoter binding activities of NF-?B and AP-1. Taken together, these are the first results indicating that halofuginone may represent a promising new agent for breast cancer chemotherapy.
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Decreased expression of hepatic low-density lipoprotein receptor-related protein 1 in hypothyroidism: a novel mechanism of atherogenic dyslipidemia in hypothyroidism.
Thyroid
PUBLISHED: 08-28-2013
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The atherogenic effects of hypothyroidism on lipid metabolism could result, in part, from the reduced clearance of remnant lipoproteins. In this study, we investigated the expression of hepatic low-density lipoprotein receptor-related protein 1 (LRP1), a receptor for remnant lipoproteins, in hypothyroidism and the effect of 3,3,5-triiodo-L-thyronine (T3) treatment on hepatic LRP1 expression.
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Elevated FGF21 secretion, PGC-1? and ketogenic enzyme expression are hallmarks of iron-sulfur cluster depletion in human skeletal muscle.
Hum. Mol. Genet.
PUBLISHED: 08-13-2013
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Iron-sulfur (Fe-S) clusters are ancient enzyme cofactors found in virtually all life forms. We evaluated the physiological effects of chronic Fe-S cluster deficiency in human skeletal muscle, a tissue that relies heavily on Fe-S cluster-mediated aerobic energy metabolism. Despite greatly decreased oxidative capacity, muscle tissue from patients deficient in the Fe-S cluster scaffold protein ISCU showed a predominance of type I oxidative muscle fibers and higher capillary density, enhanced expression of transcriptional co-activator PGC-1? and increased mitochondrial fatty acid oxidation genes. These Fe-S cluster-deficient muscles showed a dramatic up-regulation of the ketogenic enzyme HMGCS2 and the secreted protein FGF21 (fibroblast growth factor 21). Enhanced muscle FGF21 expression was reflected by elevated circulating FGF21 levels in the patients, and robust FGF21 secretion could be recapitulated by respiratory chain inhibition in cultured myotubes. Our findings reveal that mitochondrial energy starvation elicits a coordinated response in Fe-S-deficient skeletal muscle that is reflected systemically by increased plasma FGF21 levels.
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Loss of small heterodimer partner protects against atherosclerosis in apolipoprotein E-deficient mice.
Endocr. J.
PUBLISHED: 08-03-2013
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Small heterodimer partner (SHP) is involved in bile, lipid, and glucose metabolism. The aim of this study was to investigate the effect of SHP on the development of atherosclerosis. Apolipoprotein E knockout (ApoE-/-) mice were crossed with SHP knockout (SHP-/-) mice to generate double knockout (ApoE-/-SHP-/-) mice. ApoE-/- and ApoE-/-SHP-/- male mice were fed a western diet for 20 weeks. Body weight in ApoE-/-SHP-/) mice was significantly lower than that in ApoE-/- mice (37±1 g vs. 42±1 g, p<0.01). Loss of SHP in ApoE-/- mice decreased the size of adipocytes in white adipose tissue and reduced lipid accumulation in the liver. Glucose intolerance was improved in ApoE-/-SHP-/- mice as compared with ApoE-/- mice (p<0.01). There was no statistical difference in non-high density lipoprotein cholesterol levels between ApoE-/-SHP-/- mice and ApoE-/- mice despite an increase of cholesterol 7?-hydroxylase expression in the liver. The proportion of atherosclerotic lesions in the aorta was significantly lower in ApoE-/-SHP-/- mice than in ApoE-/- mice (2.8±2.0% vs. 9.1±1.9%, p<0.01). In conclusion, loss of SHP function can prevent atherosclerosis, and resistance to diet-induced obesity is the primary factor contributing to this protective effect.
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?-Iso-cubebene exerts neuroprotective effects in amyloid beta stimulated microglia activation.
Neurosci. Lett.
PUBLISHED: 07-24-2013
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Schisandra chinensis is commonly used for food and as a traditional remedy for the treatment of neuronal disorders. However, it is unclear which component of S. chinensis is responsible for its neuropharmacological effects. To answer this question, we isolated ?-iso-cubebene, a dibenzocyclooctadiene lignin, from S. chinensis and determined if it has any anti-neuroinflammatory and neuroprotective properties against amyloid ?-induced neuroinflammation in microglia. Microglia that are stimulated by amyloid ? increased their production of pro-inflammatory cytokines and chemokines, prostaglandin E2 (PGE2), nitric oxide (NO) and reactive oxygen species (ROS) and the enzymatic activity of matrix metalloproteinase 9 (MMP-9). We found this was all inhibited by ?-iso-cubebene. Consistent with these results, ?-iso-cubebene inhibited the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) and MMP-9 in amyloid ?-stimulated microglia. Subsequent mechanistic studies revealed that ?-iso-cubebene inhibited the phosphorylation and degradation of I?B-?, the phosphorylation and transactivity of NF-?B, and the phosphorylation of MAPK in amyloid ?-stimulated microglia. These results suggest that ?-iso-cubebene impairs the amyloid ?-induced neuroinflammatory response of microglia by inhibiting the NF-?B and MAPK signaling pathways. Importantly, ?-iso-cubebene can provide critical neuroprotection for primary cortical neurons against amyloid ?-stimulated microglia-mediated neurotoxicity. To the best of our knowledge, this is the first report showing that ?-iso-cubebene can provide neuroprotection against, and influence neuroinflammation triggered by, amyloid ? activation of microglia.
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Proangiogenic TIE2(+)/CD31 (+) macrophages are the predominant population of tumor-associated macrophages infiltrating metastatic lymph nodes.
Mol. Cells
PUBLISHED: 07-03-2013
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Tumor-associated macrophages (TAMs) accumulate in various cancers and promote tumor angiogenesis and metastasis, and thus may be ideal targets for the clinical diagnosis of tumor metastasis with high specificity. However, there are few specific markers to distinguish between TAMs and normal or inflammatory macrophages. Here, we show that TAMs localize in green fluorescent protein-labeled tumors of metastatic lymph nodes (MLNs) from B16F1 melanoma cells but not in necrotic tumor regions, suggesting that TAMs may promote the growth of tumor cells and the progression of tumor metastasis. Furthermore, we isolated pure populations of TAMs from MLNs and characterized their gene expression signatures compared to peritoneal macrophages (PMs), and found that TAMs significantly overexpress immunosuppressive cytokines such as IL-4, IL-10, and TGF-? as well as proangiogenic factors such as VEGF, TIE2, and CD31. Notably, immunological analysis revealed that TIE2(+)/CD31(+) macrophages constitute the predominant population of TAMs that infiltrate MLNs, distinct from tissue or inflammatory macrophages. Importantly, these TIE2(+)/CD31(+) macrophages also heavily infiltrated MLNs from human breast cancer biopsies but not reactive hyperplastic LNs. Thus, TIE2(+)/ CD31(+) macrophages may be a unique histopathological biomarker for detecting metastasis in clinical diagnosis, and a novel and promising target for TAM-specific cancer therapy.
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The Role of Ultrasound Findings in the Management of Thyroid Nodules with Atypia or Follicular Lesions of Undetermined Significance.
Clin. Endocrinol. (Oxf)
PUBLISHED: 07-02-2013
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Atypia or follicular lesions of undetermined significance (AUS/FLUS) is a broad cytologic category in the Bethesda system for classifying thyroid cytology. This study investigated the diagnostic accuracy of ultrasound (US) analysis of thyroid nodules with AUS/FLUS.
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Comparison of anti-inflammatory potential of four different dibenzocyclooctadiene lignans in microglia; action via activation of PKA and Nrf-2 signaling and inhibition of MAPK/STAT/NF-?B pathways.
Mol Nutr Food Res
PUBLISHED: 06-25-2013
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The aim of our study was to determine the signaling pathways associated with the antineuroinflammatory and neuroprotective responses induced by dibenzocyclooctadiene lignans in microglia.
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Opioid sparing effect of low dose ketamine in patients with intravenous patient-controlled analgesia using fentanyl after lumbar spinal fusion surgery.
Korean J Anesthesiol
PUBLISHED: 06-24-2013
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The opioid sparing effect of low dose ketamine is influenced by bolus dose, infusion rate, duration of infusion, and differences in the intensity of postoperative pain. In this study, we investigated the opioid sparing effect of low dose ketamine in patients with intravenous patient-controlled analgesia (PCA) using fentanyl after lumbar spinal fusion surgery, which can cause severe postoperative pain.
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Changes in the clinicopathological characteristics and outcomes of thyroid cancer in Korea over the past four decades.
Thyroid
PUBLISHED: 06-21-2013
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Thyroid cancer has increased globally, with a prominent increase in small, papillary thyroid cancers (PTC). The Korean population has a high iodine intake, high prevalence of BRAF V600E mutations, and family histories of thyroid cancer. We examined the clinicopathological characteristics and outcomes of thyroid cancers in Korean patients over four decades.
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Effect of seasonal changes on the transition between subclinical hypothyroid and euthyroid status.
J. Clin. Endocrinol. Metab.
PUBLISHED: 06-14-2013
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The widespread use of thyroid tests in asymptomatic individuals identifies many patients with transient subclinical hypothyroidism.
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Plasma FGF21 levels are increased in patients with hypothyroidism independently of lipid profile.
Endocr. J.
PUBLISHED: 06-12-2013
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Thyroid hormone is a potent regulator of metabolic and energy homeostasis implicated in various metabolic diseases. Fibroblast growth factor 21(FGF21) is a systemic metabolic regulator known to modulate various biological functions similar to the actions of thyroid hormone. We investigated the differences in plasma FGF21 concentrations in patients with varying thyroid function. Ninety drug-naïve subjects who underwent thyroid evaluation at Seoul National University Bundang Hospital were enrolled and classified into euthyroid, subclinical hypothyroid, and overtly hypothyroid groups. Biochemical markers and plasma FGF21 levels were measured and analyzed. The mean age of the subjects was 42.6 ± 9.1 years. The mean body mass index (BMI), waist circumference, and fasting glucose concentrations were similar between groups. Overtly hypothyroid subjects exhibited significantly higher concentrations of total cholesterol, triglyceride, and LDL-cholesterol than the other groups (p<0.01). Mean plasma FGF21 concentrations in euthyroid, subclinical hypothyroid and overtly hypothyroid groups were 43.2 ± 39.2 pg/mL, 63.6 ± 73.6 pg/mL, and 101.5 ± 74.9 pg/mL, respectively (p<0.01 between groups). Plasma FGF21 concentrations remained significantly higher in overtly hypothyroid subjects after adjusting for serum triglyceride concentrations (p<0.005). Multivariate analysis revealed a significant positive linear relationship between serum TSH concentrations and plasma FGF21 concentrations (? = 0.192, p = 0.002) and a significant negative linear relationship between free T4 and plasma FGF21 concentrations (? = -0.382, p = 0.037) after adjusting for gender, BMI and serum concentrations of triglycerides and glucose. Plasma FGF21 levels were significantly increased in patients with hypothyroidism independently of BMI, or lipid or glucose metabolism.
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?-Iso-cubebenol inhibits inflammation-mediated neurotoxicity and amyloid beta 1-42 fibril-induced microglial activation.
J. Pharm. Pharmacol.
PUBLISHED: 06-03-2013
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To examine the antineuroinflammatory and neuroprotective activity of ?-iso-cubebenol and its molecular mechanism of action in amyloid ? (A?) 1-42 fibril-stimulated microglia.
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Gastroprotective effect of the three glucuronopyranoside flavonoids in rats.
Korean J. Physiol. Pharmacol.
PUBLISHED: 05-28-2013
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In this study, we investigated the protective action of glucuronopyranoside flavonoids (QGC, AGC, LGC) on gastritis in rats. QGC, AGC and omeprazole decreased the gastric volume significantly, and each ID50 was 0.75, 0.54 and 8.5 mg/kg, respectively, thus the order of potency was AGC, QGC and omeprazole. They also decreased acid output, and each ID50 was 7.81, 0.58 and 6.71 mg/kg, respectively, thus the order of potency was AGC, omeprazole and QGC. They inhibited gastritis induced by indomethacin, and it recovered significantly by increasing the GSH levels in gastritis. The gastric MPO activity in the gastritis group increased more than in the normal group. QGC, LGC, or AGC administration reduced moderately the MPO activity in a dose-dependent manner. This study demonstrated that AGC, QGC, or LGC showed potent efficacy on the gastritis, by preventing oxidative stress. These results suggest that QGC, AGC, or LGC have gastroprotective effect in rats.
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Surfactin exhibits neuroprotective effects by inhibiting amyloid ?-mediated microglial activation.
Neurotoxicology
PUBLISHED: 05-28-2013
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Microglial-mediated neuroinflammation and neurotoxicity contribute to the pathogenesis of neurodegenerative diseases including Alzheimers disease; therefore, control of microglial activation and subsequent suppression of neurotoxic pro-inflammatory molecules could provide a potential therapeutic approach for the treatment of such diseases. In this study, we investigated the effects of surfactin, a surfactant from Bacillus subtilis, on oligomeric amyloid ? (A?)-induced microglial activation and neurotoxicity. Surfactin significantly suppressed expression of MMP-9, iNOS and COX-2, as well as production of ROS, NO, PGE2, TNF-?, IL-1?, IL-6 and MCP-1 in A?-stimulated BV-2 microglial cells. Moreover, surfactin markedly inhibited A?-induced nuclear translocation and activation of NF-?B as well as phosphorylation of JNK and p38 MAPK. Furthermore, surfactin protected hippocampal HT22 cells from indirect neuronal toxicity mediated by A?-treated microglial cells, but had no effect on A?-induced direct toxicity to HT22 cells. These results suggest that surfactin impairs the A?-induced inflammatory response of microglial cells and confers protection against indirect neurotoxicity to hippocampal cells. Our findings indicate that surfactin may have therapeutic potential for ameliorating Alzheimers disease as well as other neurodegenerative disorders which involve neuroinflammation.
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Caspase-cleaved fragments of cytokeratin-18 as a marker of inflammatory activity in chronic hepatitis B virus infection.
J. Clin. Virol.
PUBLISHED: 05-21-2013
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The differential diagnosis between inactive carrier and active hepatitis is important in patients with chronic hepatitis B (CHB) virus infection. Serum cytokeratin (CK)-18 fragments (M30-antigen) are proposed as biomarkers of apoptosis.
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Serum FGF21 concentration is associated with hypertriglyceridaemia, hyperinsulinaemia and pericardial fat accumulation, independently of obesity, but not with current coronary artery status.
Clin. Endocrinol. (Oxf)
PUBLISHED: 05-06-2013
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Fibroblast growth factor 21 (FGF21) is an emerging metabolic regulator associated with glucose and lipid metabolism. However, previous studies of FGF21 have been largely confounded by obesity, and data are limited for advanced outcomes such as coronary artery disease (CAD) and ectopic fat accumulation. We investigated the associations between serum FGF21 concentrations and glucose/lipid metabolism, CAD, and pericardial fat deposition in subjects strictly matched for obesity parameters.
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Schizandrin C exerts anti-neuroinflammatory effects by upregulating phase II detoxifying/antioxidant enzymes in microglia.
Int. Immunopharmacol.
PUBLISHED: 05-03-2013
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We investigated the anti-neuroinflammatory properties of schizandrin C by focusing on its roles in the induction of phase II detoxifying/antioxidant enzymes and in the modulation of upstream signaling pathways. Schizandrin C induced expression of phase II detoxifying/antioxidant enzymes including heme oxygenase-1 (HO-1) and NADPH dehydrogenase quinone-1 (NQO-1). Activation of upstream signaling pathways, such as the cAMP/protein kinase A/cAMP response element-binding protein (cAMP/PKA/CREB) and erythroid-specific nuclear factor-regulated factor 2 (Nrf-2) pathways, significantly increased following treatment with schizandrin C. In addition, expressions of schizandrin C-mediated phase II detoxifying/antioxidant enzymes were completely attenuated by adenylyl cyclase inhibitor (ddAdo) and protein kinase A (PKA) inhibitor (H-89). In microglia, schizandrin C significantly inhibited lipoteichoic acid (LTA)-stimulated pro-inflammatory cytokines and chemokines, prostaglandin E2 (PGE2), nitric oxide (NO), and reactive oxygen species (ROS) production, and inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and matrix metallopeptidase-9 (MMP-9) protein expressions. Moreover, schizandrin C suppressed LTA-induced nuclear factor-kappa B (NF-?B), activator protein-1 (AP-1), janus-kinase/signal transducer and activator of transcription (JAK-STATs), and mitogen-activated protein kinase (MAPK) activation. Schizandrin C also effectively suppressed ROS generation and NO production, as well as iNOS promoter activity in LTA-stimulated microglia. This suppressive effect was reversed by transfection with Nrf-2 and HO-1 siRNA and co-treatment with inhibitors ddAdo and H-89. Our results indicate that schizandrin C isolated from Schisandra chinensis could be used as a natural anti-neuroinflammatory agent, inducing phase II detoxifying/antioxidant enzymes via cAMP/PKA/CREB and Nrf-2 signaling.
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Arthroscopic suture anchor tenodesis: loop-suture technique.
Arthrosc Tech
PUBLISHED: 05-01-2013
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With advancements in arthroscopic surgery, arthroscopic biceps tenodesis with suture anchor recently has been reported to be a reasonable option for the treatment of biceps pathologies, especially for those that are symptomatic or accompanied by a rotator cuff tear. We introduce our technique of arthroscopic biceps tenodesis with suture anchor that we call the loop-suture technique, which is constructed with 1 loop strand and another sutured strand. This technique can help to improve biceps grip and simultaneously minimize longitudinal splitting of the tendon. In addition, it is relatively simple and can be performed with the use of conventional devices and arthroscopic portals used for rotator cuff repair, without the formation of additional portals or a separate incision for the tenodesis.
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A case of mediastinal ectopic thyroid presenting with a paratracheal mass.
Korean J. Intern. Med.
PUBLISHED: 05-01-2013
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Mediastinal ectopic thyroid is a very rare condition, with few reported cases in the literature and no reported cases in Korea. This report describes an asymptomatic 65-year-old man with a right paratracheal mass compressing the superior vena. Additionally, the epidemiology, clinical manifestation, diagnosis, and management of mediastinal ectopic thyroids are discussed. A mediastinal ectopic thyroid should be considered in the differential diagnosis of all mediastinal masses. Surgical excision is recommended for both the diagnosis and treatment of this condition, because of its potential for malignancy and compression of mediastinal structures. This case demonstrates the clinical importance of mediastinal etopic thyroid.
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F-box only protein 9 is required for adipocyte differentiation.
Biochem. Biophys. Res. Commun.
PUBLISHED: 04-12-2013
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The objective of this study is to investigate whether F-box only protein 9 (FBXO9), an ubiquitination E3 ligase, has a functional role in adipocyte differentiation. Expression of FBXO9 was compared between obese mice and control lean mice using real-time PCR. Also, expression pattern of FBXO9 was monitored during 3T3-L1 adipocyte differentiation. FBXO9 was highly expressed in obese mice, and increased in the early stages of adipogenesis. To verify a functional role of FBXO9 in adipogenesis, FBXO9 was knocked down using transfection of siRNAs against FBXO9 into 3T3-L1 cells during the induction of adipogenesis. Knockdown of FBXO9 in early stage of adipogenesis almost completely inhibited adipogenesis, and CCAAT/enhancer binding protein ? (C/EBP?) levels were significantly reduced. However, the cells stably expressing C/EBP? were fairly differentiated into adipocytes in the FBXO9 knockdown condition. These results suggest that FBXO9 is required for adipocyte differentiation, and C/EBP? plays a role in the effect of FBXO9 on adipogenesis.
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Transcriptional regulation of glutathione biosynthesis genes, ?-glutamyl-cysteine ligase and glutathione synthetase in response to cadmium and nonylphenol in Chironomus riparius.
Environ. Toxicol. Pharmacol.
PUBLISHED: 04-02-2013
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We characterized Chironomus riparius glutathione (GSH) biosynthesis genes, ?-glutamyl-cysteine ligase catalytic subunit (cr-gcl) and glutathione synthetase (cr-gs) and studied their expression after cadmium (Cd) and nonylphenol (NP) exposure. The full length cDNA of the Cr-GCL catalytic subunit was 2185 base pair (bp) in length containing an open reading frame of 1905bp, a 13bp 5 and 267bp 3 untranslated regions. The theoretical molecular mass of the deduced amino acid sequence (633) was 72.65kDa with an estimated pI of 5.42. The partial cDNA of Cr-GS was 739bp in length consisting 221 amino acids. The deduced amino acid sequence of Cr-GCL and Cr-GS cDNAs showed high conservation with homologs from other species. In phylogenetic analysis Cr-GCL and Cr-GS were grouped with equivalent genes from insects belonging to the dipteran order. The expression of cr-gcl and cr-gs was measured using quantitative real-time PCR after exposure to sub lethal concentrations of Cd (2, 10 and 20mg/L) and NP (10, 50 and 100?g/L) for 12, 24, 48 and 72h using real-time PCR methods. The mRNA expression of Cr-GCL and Cr-GS was significantly modulated after exposure to different concentrations of Cd and NP for different time periods. Total GSH levels showed a non-significant decrease after exposure to Cd for 24h. However, no change in GSH levels was observed after exposure to NP for 24h. These results suggest that Cr-GS and Cr-GCL expression is modulated by Cd and NP stress and may play an important role in detoxification of xenobiotics and antioxidant defense. We conclude that Cr-GS and Cr-GCL could be used as biomarkers of Cd and NP stress in aquatic environment for the studied species.
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Positive regulation of osteogenesis by bile acid through FXR.
J. Bone Miner. Res.
PUBLISHED: 03-11-2013
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Farnesoid X receptor (FXR) is a nuclear receptor that functions as a bile acid sensor controlling bile acid homeostasis. We investigated the role of FXR in regulating bone metabolism. We identified the expression of FXR in calvaria and bone marrow cells, which gradually increased during osteoblastic differentiation in vitro. In male mice, deletion of FXR (FXR(-/-) ) in vivo resulted in a significant reduction in bone mineral density by 4.3% to 6.6% in mice 8 to 20 weeks of age compared with FXR(+/+) mice. Histological analysis of the lumbar spine showed that FXR deficiency reduced the bone formation rate as well as the trabecular bone volume and thickness. Moreover, tartrate-resistant acid phosphatase (TRACP) staining of the femurs revealed that both the osteoclast number and osteoclast surface were significantly increased in FXR(-/-) mice compared with FXR(+/+) mice. At the cellular level, induction of alkaline phosphatase (ALP) activities was blunted in primary calvarial cells in FXR(-/-) mice compared with FXR(+/+) mice in concert with a significant reduction in type I collagen a1(Col1a1), ALP, and runt-related transcription factor 2 (Runx2) gene expressions. Cultures of bone marrow-derived macrophages from FXR(-/-) mice exhibited an increased number of osteoclast formations and protein expression of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1). In female FXR(-/-) mice, although bone mineral density (BMD) was not significantly different from that in FXR(+/+) mice, bone loss was accelerated after an ovariectomy compared with FXR(+/+) mice. In vitro, activation of FXR by bile acids (chenodeoxycholic acid [CDCA] or 6-ECDCA) or FXR agonists (GW4064 or Fexaramine) significantly enhanced osteoblastic differentiation through the upregulation of Runx2 and enhanced extracellular signal-regulated kinase (ERK) and ?-catenin signaling. FXR agonists also suppressed osteoclast differentiation from bone marrow macrophages. Finally, administration of a farnesol (FOH 1%) diet marginally prevented ovariectomy (OVX)-induced bone loss and enhanced bone mass gain in growing C57BL/6J mice. Taken together, these results suggest that FXR positively regulates bone metabolism through both arms of the bone remodeling pathways; ie, bone formation and resorption.
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Characterization and expression of cytochrome p450 cDNA (CYP9AT2) in Chironomus riparius fourth instar larvae exposed to multiple xenobiotics.
Environ. Toxicol. Pharmacol.
PUBLISHED: 03-03-2013
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We identified and characterized a CYP9 family gene, CrCYP9AT2, from Chironomus riparius, an eco-toxicologically important model organism. The 1978 base pair (bp) length CrCYP9AT2 cDNA has an open reading frame of 1587bp encoding a putative 528 amino acid protein. There was 267bp 5 and 123bp 3 untranslated region with a polyadenylation signal site (AATAAA). The putative heme-binding cysteine at position 471 and the typical p450 signature sequence of 463-FGIGPRNCIG-473 were also present. The CrCYP9AT2 transcript was present in all life stages with the highest expression in larvae. The modulation of CrCYP9AT2 was studied using real-time polymerase chain reaction after 24h exposure to cadmium chloride, benzo(a)pyrene; bisphenol A; nonylphenol; chlorpyrifos and ethinylestradiol. Significant up-regulation of CrCYP9AT2 gene was observed after exposure to Cd, B(a)P and CP. However, CrCYP9AT2 was significantly down-regulated after exposure to BPA, NP and EE.
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Evaluation of the effect of silver nanoparticles and silver ions using stress responsive gene expression in Chironomus riparius.
Chemosphere
PUBLISHED: 02-25-2013
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Silver nanoparticles (AgNPs) are extensively used in many commercial products because of their antimicrobial properties and they are therefore released into the environment from various products. A number of genes, especially those representing antioxidant and detoxification pathways, have potential application for studying mechanism of action of environmental pollutants at molecular level. In the present study, the stress responsive transcription of antioxidant and detoxification genes in response to AgNPs and Ag(+) ions exposure is studied in the ecotoxicologically important model species Chironomus riparius. The selected genes were superoxide dismutases (CuZnSOD and MnSOD), catalase (CAT), phospholipid hydroperoxide glutathione peroxidase 1 (PHGPx1), thioredoxin reductase 1 (TrxR1), and delta-3, sigma-4 and epsilon-1 classes of glutathione S-transferases (GSTs). The mRNA expression levels of each gene were determined after exposure of animals for 24h to three different AgNP and Ag(+) ion concentrations using Real-Time PCR method. Significant up-regulation of CuZnSOD and MnSOD was found after exposure to Ag(+) ions and AgNPs, respectively. The transcript levels of CAT, PHGPx1 and TrxR1 were significantly up-regulated only after exposure to AgNPs and no significant change was observed after exposure to Ag(+) ions. The expression levels of all the GSTs were more pronounced after exposure to AgNPs as compared to Ag(+) ions. The overall results suggest that AgNPs led to pronounced induction of genes related to oxidative stress and detoxification than Ag(+) ions.
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Factors related to decreased bone mineral density in childhood cancer survivors.
J. Korean Med. Sci.
PUBLISHED: 02-24-2013
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The risk of osteoporosis or osteopenia is known to increase after childhood cancer treatment. The purpose of this study was to evaluate patterns of bone mineral density (BMD) and to identify factors related to the decreased BMD in childhood cancer survivors. We studied 78 patients (34 boys, 44 girls) treated for childhood cancer. Twenty (25.7%) patients had lumbar BMD (LBMD) standard deviation score (SDS) lower than -2. Nineteen (24.4%) patients had femur neck BMD (FNBMD) SDS lower than -2. The patients treated with hematopoietic stem cell transplantation had lower LBMD SDS (-1.17 ± 1.39 vs -0.43 ± 1.33, P = 0.025). The risk of having LBMD SDS < -2 was higher in the patients treated with glucocorticoid (GC) for graft-versus-host disease (GVHD) (36.6% vs 13.5%; odds ratio [OR], 3.7; P = 0.020). In multivariate logistic regression analysis, longer duration of GC treatment for GVHD (OR, 1.12; 95% confidence interval [CI], 1.05-1.20) and lower body mass index (BMI) SDS (OR, 0.59; 95% CI, 0.36-0.95) were associated with decreased LBMD SDS. These findings suggest that prolonged GC use and reduction in BMI are risk factors for decreased BMD in childhood cancer survivors. Anticipatory follow-up and appropriate treatment are necessary, especially for the patients with risk factors.
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Differential significance of plasma visfatin concentrations according to adiposity in children and adolescents.
Horm Res Paediatr
PUBLISHED: 02-11-2013
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Visfatin is an adipocytokine predominantly expressed in visceral adipose tissue. We examined the relationship between plasma visfatin concentrations and anthropometric and metabolic parameters in children and adolescents, who are relatively less influenced by the effects of accompanying disease.
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Thyroglobulin in washout fluid from lymph node fine-needle aspiration biopsy in papillary thyroid cancer: large-scale validation of the cutoff value to determine malignancy and evaluation of discrepant results.
J. Clin. Endocrinol. Metab.
PUBLISHED: 02-07-2013
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There are still some controversies regarding the cutoff value and the influential factors of thyroglobulin (Tg) concentration in washout fluid from fine-needle aspiration (FNA) biopsy (FNA-Tg) on cervical lymph nodes (LNs) in patients with papillary thyroid cancer (PTC).
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.