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Find video protocols related to scientific articles indexed in Pubmed.
Nuclear translocation of hARD1 contributes to proper cell cycle progression.
PLoS ONE
PUBLISHED: 08-18-2014
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Arrest defective 1 (ARD1) is an acetyltransferase that is highly conserved across organisms, from yeasts to humans. The high homology and widespread expression of ARD1 across multiple species and tissues signify that it serves a fundamental role in cells. Human ARD1 (hARD1) has been suggested to be involved in diverse biological processes, and its role in cell proliferation and cancer development has been recently drawing attention. However, the subcellular localization of ARD1 and its relevance to cellular function remain largely unknown. Here, we have demonstrated that hARD1 is imported to the nuclei of proliferating cells, especially during S phase. Nuclear localization signal (NLS)-deleted hARD1 (hARD1?N), which can no longer access the nucleus, resulted in cell morphology changes and cellular growth impairment. Notably, hARD1?N-expressing cells showed alterations in the cell cycle and the expression levels of cell cycle regulators compared to hARD1 wild-type cells. Furthermore, these effects were rescued when the nuclear import of hARD1 was restored by exogenous NLS. Our results show that hARD1 nuclear translocation mediated by NLS is required for cell cycle progression, thereby contributing to proper cell proliferation.
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Prompt meningeal reconstruction mediated by oxygen-sensitive AKAP12 scaffolding protein after central nervous system injury.
Nat Commun
PUBLISHED: 08-11-2014
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The meninges forms a critical epithelial barrier, which protects the central nervous system (CNS), and therefore its prompt reconstruction after CNS injury is essential for reducing neuronal damage. Meningeal cells migrate into the lesion site after undergoing an epithelial-mesenchymal transition (EMT) and repair the impaired meninges. However, the molecular mechanisms of meningeal EMT remain largely undefined. Here we show that TGF-?1 and retinoic acid (RA) released from the meninges, together with oxygen tension, could constitute the mechanism for rapid meningeal reconstruction. AKAP12 is an effector of this mechanism, and its expression in meningeal cells is regulated by integrated upstream signals composed of TGF-?1, RA and oxygen tension. Functionally, AKAP12 modulates meningeal EMT by regulating the TGF-?1-non-Smad-SNAI1 signalling pathway. Collectively, TGF-?1, RA and oxygen tension can modulate the dynamic change in AKAP12 expression, causing prompt meningeal reconstruction after CNS injury by regulating the transition between the epithelial and mesenchymal states of meningeal cells.
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Ninjurin1 enhances the basal motility and transendothelial migration of immune cells by inducing protrusive membrane dynamics.
J. Biol. Chem.
PUBLISHED: 06-10-2014
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Ninjurin1 is involved in the pathogenesis of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, by mediating leukocyte extravasation, a process that depends on homotypic binding. However, the precise regulatory mechanisms of Ninjurin1 during inflammation are largely undefined. We therefore examined the pro-migratory function of Ninjurin1 and its regulatory mechanisms in macrophages. Interestingly, Ninjurin1-deficient bone marrow-derived macrophages exhibited reduced membrane protrusion formation and dynamics, resulting in the impairment of cell motility. Furthermore, exogenous Ninjurin1 was distributed at the membrane of filopodial structures in Raw264.7 macrophage cells. In Raw264.7 cells, RNA interference of Ninjurin1 reduced the number of filopodial projections, whereas overexpression of Ninjurin1 facilitated their formation and thus promoted cell motility. Ninjurin1-induced filopodial protrusion formation required the activation of Rac1. In Raw264.7 cells penetrating an MBEC4 endothelial cell monolayer, Ninjurin1 was localized to the membrane of protrusions and promoted their formation, suggesting that Ninjurin1-induced protrusive activity contributed to transendothelial migration. Taking these data together, we conclude that Ninjurin1 enhances macrophage motility and consequent extravasation of immune cells through the regulation of protrusive membrane dynamics. We expect these findings to provide insight into the understanding of immune responses mediated by Ninjurin1.
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Autoacetylation regulates differentially the roles of ARD1 variants in tumorigenesis.
Int. J. Oncol.
PUBLISHED: 05-06-2014
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ARD1 is an acetyltransferase with several variants derived from alternative splicing. Among ARD1 variants, mouse ARD1225 (mARD1225), mouse ARD1235 (mARD1235), and human ARD1235 (hARD1235) have been the most extensively characterized and are known to have different biological functions. In the present study, we demonstrated that mARD1225, mARD1235, and hARD1235 have conserved autoacetylation activities, and that they selectively regulate distinct roles of ARD1 variants in tumorigenesis. Using purified recombinants for ARD1 variants, we found that mARD1225, mARD1235, and hARD1235 undergo similar autoacetylation with the target site conserved at the Lys136 residue. Moreover, functional investigations revealed that the role of mARD1225 autoacetylation is completely distinguishable from that of mARD1235 and hARD1235. Under hypoxic conditions, mARD1225 autoacetylation inhibited tumor angiogenesis by decreasing the stability of hypoxia-inducible factor-1? (HIF-1?). Autoacetylation stimulated the catalytic activity of mARD1225 to acetylate Lys532 of the oxygen-dependent degradation (ODD) domain of HIF-1?, leading to the proteosomal degradation of HIF-1?. In contrast, autoacetylation of mARD1235 and hARD1235 contributed to cellular growth under normoxic conditions by increasing the expression of cyclin D1. Taken together, these data suggest that autoacetylation of ARD1 variants differentially regulates angiogenesis and cell proliferation in an isoform-specific manner.
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Nocardia brain abscess in an immunocompetent patient.
Infect Chemother
PUBLISHED: 03-21-2014
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Nocardia cerebral abscess is rare, constituting approximately 1-2% of all cerebral abscesses. Mortality for a cerebral abscess of Nocardia is three times higher than that of other bacterial cerebral abscesses, therefore, early diagnosis and therapy is important. Nocardia cerebral abscess is generally occur among immunocompromised patients, and critical infection in immunocompetent patients is extremely rare. We report on a case of a brain abscess by Nocardia farcinica in an immunocompetent patient who received treatment with surgery and antibiotics. This is the second case of a brain abscess caused by N. farcinica in an immunocompetent patient in Korea.
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Suppression of cpn10 increases mitochondrial fission and dysfunction in neuroblastoma cells.
PLoS ONE
PUBLISHED: 01-01-2014
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To date, several regulatory proteins involved in mitochondrial dynamics have been identified. However, the precise mechanism coordinating these complex processes remains unclear. Mitochondrial chaperones regulate mitochondrial function and structure. Chaperonin 10 (Cpn10) interacts with heat shock protein 60 (HSP60) and functions as a co-chaperone. In this study, we found that down-regulation of Cpn10 highly promoted mitochondrial fragmentation in SK-N-MC and SH-SY5Y neuroblastoma cells. Both genetic and chemical inhibition of Drp1 suppressed the mitochondrial fragmentation induced by Cpn10 reduction. Reactive oxygen species (ROS) generation in 3-NP-treated cells was markedly enhanced by Cpn10 knock down. Depletion of Cpn10 synergistically increased cell death in response to 3-NP treatment. Furthermore, inhibition of Drp1 recovered Cpn10-mediated mitochondrial dysfunction in 3-NP-treated cells. Moreover, an ROS scavenger suppressed cell death mediated by Cpn10 knockdown in 3-NP-treated cells. Taken together, these results showed that down-regulation of Cpn10 increased mitochondrial fragmentation and potentiated 3-NP-mediated mitochondrial dysfunction in neuroblastoma cells.
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Oligodendrocyte precursor cells support blood-brain barrier integrity via TGF-? signaling.
PLoS ONE
PUBLISHED: 01-01-2014
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Trophic coupling between cerebral endothelium and their neighboring cells is required for the development and maintenance of blood-brain barrier (BBB) function. Here we report that oligodendrocyte precursor cells (OPCs) secrete soluble factor TGF-?1 to support BBB integrity. Firstly, we prepared conditioned media from OPC cultures and added them to cerebral endothelial cultures. Our pharmacological experiments showed that OPC-conditioned media increased expressions of tight-junction proteins and decreased in vitro BBB permeability by activating TGB-?-receptor-MEK/ERK signaling pathway. Secondly, our immuno-electron microscopic observation revealed that in neonatal mouse brains, OPCs attach to cerebral endothelial cells via basal lamina. And finally, we developed a novel transgenic mouse line that TGF-?1 is knocked down specifically in OPCs. Neonates of these OPC-specific TGF-?1 deficient mice (OPC-specific TGF-?1 partial KO mice: PdgfraCre/Tgfb1flox/wt mice or OPC-specific TGF-?1 total KO mice: PdgfraCre/Tgfb1flox/flox mice) exhibited cerebral hemorrhage and loss of BBB function. Taken together, our current study demonstrates that OPCs increase BBB tightness by upregulating tight junction proteins via TGF-? signaling. Although astrocytes and pericytes are well-known regulators of BBB maturation and maintenance, these findings indicate that OPCs also play a pivotal role in promoting BBB integrity.
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AKAP12 mediates barrier functions of fibrotic scars during CNS repair.
PLoS ONE
PUBLISHED: 01-01-2014
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The repair process after CNS injury shows a well-organized cascade of three distinct stages: inflammation, new tissue formation, and remodeling. In the new tissue formation stage, various cells migrate and form the fibrotic scar surrounding the lesion site. The fibrotic scar is known as an obstacle for axonal regeneration in the remodeling stage. However, the role of the fibrotic scar in the new tissue formation stage remains largely unknown. We found that the number of A-kinase anchoring protein 12 (AKAP12)-positive cells in the fibrotic scar was increased over time, and the cells formed a structure which traps various immune cells. Furthermore, the AKAP12-positive cells strongly express junction proteins which enable the structure to function as a physical barrier. In in vivo validation, AKAP12 knock-out (KO) mice showed leakage from a lesion, resulting from an impaired structure with the loss of the junction complex. Consistently, focal brain injury in the AKAP12 KO mice led to extended inflammation and more severe tissue damage compared to the wild type (WT) mice. Accordingly, our results suggest that AKAP12-positive cells in the fibrotic scar may restrict excessive inflammation, demonstrating certain mechanisms that could underlie the beneficial actions of the fibrotic scar in the new tissue formation stage during the CNS repair process.
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Ninjurin1 deficiency attenuates susceptibility of experimental autoimmune encephalomyelitis in mice.
J. Biol. Chem.
PUBLISHED: 12-17-2013
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Ninjurin1 is a homotypic adhesion molecule that contributes to leukocyte trafficking in experimental autoimmune encephalomyelitis (EAE), an animal model of Multiple sclerosis (MS). However, in vivo gene-deficiency animal studies have not yet been done. Here, we constructed Ninjurin1 knockout (KO) mice and investigated the role of Ninjurin1 on leukocyte trafficking under inflammation conditions such as EAE and endotoxin-induced uveitis (EIU). Ninjurin1 KO mice attenuated EAE susceptibility by reducing leukocyte recruitment into the injury regions of the spinal cord and showed less adhesion of leukocytes on inflamed retinal vessels in EIU mice. Moreover, the administration of a custom-made antibody (Ab26-37) targeting the Ninjurin1 binding domain ameliorated the EAE symptoms, showing the contribution of its adhesion activity to leukocyte trafficking. In addition, we addressed the transendothelial migration (TEM) activity of bone-marrow derived macrophages (BMDMs) and Raw264.7 cells according to the expression level of Ninjurin1. TEM activity was decreased in Ninjurin1 KO BMDMs and siNinj1 Raw264.7 cells. Consistent with this, GFP-tagged mNinj1 overexpressing Raw264.7 cells increased their TEM activity. Taken together, we have clarified the contribution of Ninjurin1 to leukocyte trafficking in vivo and delineated its direct functions to TEM, emphasizing Ninjurin1 as a beneficial therapeutic target against inflammatory diseases such as MS.
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Oxidative stress interferes with white matter renewal after prolonged cerebral hypoperfusion in mice.
Stroke
PUBLISHED: 09-26-2013
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White matter injury caused by cerebral hypoperfusion may contribute to the pathophysiology of vascular dementia and stroke, but the underlying mechanisms remain to be fully defined. Here, we test the hypothesis that oxidative stress interferes with endogenous white matter repair by disrupting renewal processes mediated by oligodendrocyte precursor cells (OPCs).
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Crosstalk between cerebral endothelium and oligodendrocyte.
Cell. Mol. Life Sci.
PUBLISHED: 07-31-2013
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It is now relatively well accepted that the cerebrovascular system does not merely provide inert pipes for blood delivery to the brain. Cerebral endothelial cells may compose an embedded bunker of trophic factors that contribute to brain homeostasis and function. Recent findings suggest that soluble factors from cerebral endothelial cells nourish neighboring cells, such as neurons and astrocytes. Although data are strongest in supporting mechanisms of endothelial-neuron and/or endothelial-astrocyte trophic coupling, it is likely that similar interactions also exist between cerebral endothelial cells and oligodendrocyte lineage cells. In this mini-review, we summarize current advances in the field of endothelial-oligodendrocyte trophic coupling. These endothelial-oligodendrocyte interactions may comprise the oligovascular niche to maintain their cellular functions and sustain ongoing angiogenesis/oligodendrogenesis. Importantly, it should be noted that the cell-cell interactions are not static-the trophic coupling is disturbed under acute phase after brain injury, but would be recovered in the chronic phase to promote brain remodeling and repair. Oligodendrocyte lineage cells play critical roles in white matter function, and under pathological conditions, oligodendrocyte dysfunction lead to white matter damage. Therefore, a deeper understanding of the mechanisms of endothelial-oligodendrocyte trophic coupling may lead to new therapeutic approaches for white matter-related diseases, such as stroke or vascular dementia.
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Age-related decline in oligodendrogenesis retards white matter repair in mice.
Stroke
PUBLISHED: 07-23-2013
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Aging is one of the major risk factors for white matter injury in cerebrovascular disease. However, the effects of age on the mechanisms of injury/repair in white matter remain to be fully elucidated. Here, we ask whether, compared with young brains, white matter regions in older brains may be more vulnerable in part because of decreased rates of compensatory oligodendrogenesis after injury.
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Clinical availability of nonalcoholic fatty liver disease as an early predictor of type 2 diabetes mellitus in Korean men: 5-year prospective cohort study.
Hepatology
PUBLISHED: 07-06-2013
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There have been several reports about the clinical association between type 2 diabetes mellitus (DM) and nonalcoholic fatty liver disease (NAFLD). However, most of the studies were about the unilateral effects of type 2 DM on NAFLD, and studies on the reverse relation are rare. Thus, this study was designed to investigate the effect of NAFLD on type 2 DM. We conducted a prospective cohort study on 25,232 Korean men without type 2 DM for 5 years. We serially checked the various metabolic factors including fasting glucose and hemoglobin A1c (HbA1c), and monitored the development of type 2 DM. The incidence rate of type 2 DM was compared according to the degree of NAFLD (normal, mild, and moderate to severe), and a Cox proportional hazards model was used to measure the hazard ratios (HRs) of NAFLD on type 2 DM. The incidence rate of type 2 DM increased according to the degree of NAFLD (normal: 7.0%, mild: 9.8%, moderate to severe: 17.8%, P < 0.001). Even after adjusting for other multiple covariates, the HRs (95% confidence interval [CI]) for type 2 DM development was higher in the mild group (1.09; 0.81-1.48) and moderate to severe group (1.73; 1.00-3.01) compared to the normal group, respectively (P for trend <0.001).
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The effect of bevacizumab versus ranibizumab in the treatment of corneal neovascularization: a preliminary study.
Korean J Ophthalmol
PUBLISHED: 07-05-2013
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To compare the short term effects of bevacizumab and ranibizumab injections on the regression of corneal neovascularization (NV).
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The association between daily calcium intake and sarcopenia in older, non-obese Korean adults: the fourth Korea National Health and Nutrition Examination Survey (KNHANES IV) 2009.
Endocr. J.
PUBLISHED: 01-26-2013
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Recent data suggest that variations in calcium intake may influence body weight and composition; however, the relationship between daily calcium intake and muscle mass has not been well established. The objective of this study was to assess the relationship between daily calcium intake and sarcopenia. We analyzed data for older adults (over 60 years) from the fourth Korea National Health and Nutrition Examination Survey (KNHANES) conducted in 2009. A total of 1339 Non-Obese (BMI between 18.5 and 25 kg/m²), older adults (592 men and 707 women) were enrolled. Dietary variables were assessed using a nutrition survey that used a 24-hour recall method. Daily calcium intake based on the consumption of each food item was calculated. Sarcopenia was defined as an appendicular skeletal muscle mass divided by body weight less than 2 SD below the sex-specific mean for young adults. We found that daily calcium intake was negatively correlated with total body fat percentage and positively correlated with appendicular skeletal mass (p<0.001). Participants with sarcopenia appear to have significantly lower daily calcium intakes than participants without sarcopenia (p<0.001). The unadjusted prevalence of sarcopenia according to daily calcium intake tertiles were 6.3%, 4.3%, and 2.7% in tertiles 1, 2, and 3, respectively. After adjustment for age, sex, BMI, total energy intake, and lifestyle factors, compared with those in the lowest tertile of daily calcium intake, participants in the highest tertile had an odds ratio for sarcopenia of 0.295 (95% confidence interval, 0.087-0.768; p for trend = 0.014). We found that daily calcium intake, corrected for total energy intake and serum 25(OH)D status, was significantly lower in subjects with sarcopenia than in those without. Our results suggest a strong inverse association between daily calcium intake and sarcopenia in non-obese, older Korean adults.
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Fingolimod reduces hemorrhagic transformation associated with delayed tissue plasminogen activator treatment in a mouse thromboembolic model.
Stroke
PUBLISHED: 01-03-2013
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The sphingosine 1-phosphate receptor agonist fingolimod reduces infarct size in rodent models of stroke and enhances blood-brain barrier integrity. Based on these observations, we hypothesized that combination of fingolimod with tissue plasminogen activator (tPA) would reduce the risk of hemorrhagic transformation associated with delayed administration of tPA.
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Oligodendrocyte precursors induce early blood-brain barrier opening after white matter injury.
J. Clin. Invest.
PUBLISHED: 01-02-2013
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Oligodendrocyte precursor cells (OPCs) are thought to maintain homeostasis and contribute to long-term repair in adult white matter; however, their roles in the acute phase after brain injury remain unclear. Mice that were subjected to prolonged cerebral hypoperfusion stress developed white matter demyelination over time. Prior to demyelination, we detected increased MMP9 expression, blood-brain barrier (BBB) leakage, and neutrophil infiltration in damaged white matter. Notably, at this early stage, OPCs made up the majority of MMP9-expressing cells. The standard MMP inhibitor GM6001 reduced the early BBB leakage and neutrophil infiltration, indicating that OPC-derived MMP9 induced early BBB disruption after white matter injury. Cell-culture experiments confirmed that OPCs secreted MMP9 under pathological conditions, and conditioned medium prepared from the stressed OPCs weakened endothelial barrier tightness in vitro. Our study reveals that OPCs can rapidly respond to white matter injury and produce MMP9 that disrupts the BBB, indicating that OPCs may mediate injury in white matter under disease conditions.
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Metabolic health is more closely associated with coronary artery calcification than obesity.
PLoS ONE
PUBLISHED: 01-01-2013
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Recent studies have suggested that metabolic health may contribute more to the atherosclerosis than obesity. The aim of this study is to compare coronary artery calcium scores (CACS) among patients with different metabolic health and obesity status.
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Elevated fasting insulin predicts the future incidence of metabolic syndrome: a 5-year follow-up study.
Cardiovasc Diabetol
PUBLISHED: 09-19-2011
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There is controversy about the specific pathophysiology of metabolic syndrome (MS) but several authors have argued that hyperinsulinemia is a key feature of the cluster. We aimed to assess whether the baseline insulin levels could predict the development of MS in a well characterised cohort of otherwise healthy adults who were followed over a five year period.
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Management of blood pressure in patients with type 2 diabetes mellitus: a nationwide survey in korean.
Diabetes Metab J
PUBLISHED: 07-11-2011
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Hypertension is common in patients with type 2 diabetes, affecting up to 60% of patients. The Korean Diabetes Association performed a nationwide survey about prevalence, awareness and control of hypertension among diabetic Koreans.
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Impact of gestational hypertension on left ventricular function and geometric pattern.
Circ. J.
PUBLISHED: 03-07-2011
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The effect of gestational hypertension on left ventricular (LV) function in previously normotensive young women has not been evaluated.
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Clusterin protects H9c2 cardiomyocytes from oxidative stress-induced apoptosis via Akt/GSK-3? signaling pathway.
Exp. Mol. Med.
PUBLISHED: 01-29-2011
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Clusterin is a secretory glycoprotein, which is highly up-regulated in a variety of normal and injury tissues undergoing apoptosis including infarct region of the myocardium. Here, we report that clusterin protects H9c2 cardiomyocytes from H2O2-induced apoptosis by triggering the activation of Akt and GSK-3?. Treatment with H2O2 induces apoptosis of H9c2 cells by promoting caspase cleavage and cytochrome c release from mitochondria. However, co-treatment with clusterin reverses the induction of apoptotic signaling by H2O2, thereby recovers cell viability. The protective effect of clusterin on H2O2-induced apoptosis is impaired by PI3K inhibitor LY294002, which effectively suppresses clusterin-induced activation of Akt and GSK-3?. In addition, the protective effect of clusterin is independent on its receptor megalin, because inhibition of megalin has no effect on clusterin-mediated Akt/GSK-3? phosphoylation and H9c2 cell viability. Collectively, these results suggest that clusterin has a role protecting cardiomyocytes from oxidative stress and the Akt/GSK-3? signaling mediates anti-apoptotic effect of clusterin.
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Asian dust and titanium dioxide particles-induced inflammation and oxidative DNA damage in C57BL/6 mice.
Inhal Toxicol
PUBLISHED: 11-13-2010
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Inhaled particulate matter (PM) might influence many adverse health effects in human body, including increased exacerbations of pulmonary and cardiovascular diseases. In this study, we examined the associations between PM and pulmonary adverse effects. Two types of particles, Asian dust (AD) and titanium dioxide (TiO(2)), were administered intratracheally to C57BL/6 mice. The mice were exposed to saline and saline suspensions of 20 mg/kg of AD, TiO(2) particles twice a week for 12 weeks. Following exposure with these particles, the lungs were analyzed histopathologically by hematoxylin and eosin (H&E) and Massons trichrome (MT) staining. Oxidative injuries were determined by immunohistochemistry (IHC) for 8-oxoguanine in the lungs and Comet assays in peripheral blood mononuclear cells (PBMCs) of C57BL/6 mice. Mice exposed to AD and TiO(2) showed significant inflammatory changes and oxidative damages in the lungs as compared with the control group. DNA damage in PBMCs was also increased significantly in AD and TiO(2)-exposed mice. However, lung fibrosis was minimal and there was no significant difference between PM exposed and control mice. Exposure to AD and TiO(2) particles-induced similar inflammatory damages in the lungs and elicited oxidative DNA damage in the PBMCs.
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A case of metachronous metastasis to the breast from non-small cell lung carcinoma.
Cancer Res Treat
PUBLISHED: 09-30-2010
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Breast metastases from an extramammary primary tumor are very rare and the prognosis for such patients is generally poor. We report here on a case of a 42-year-old female with metastasis of non-small cell lung cancer to the breast, and she is now being followed up on an outpatient basis. In 2004, she presented with a solitary pulmonary nodule in the left lung, and this lesion had been noted to have gradually increased in size over time. The final pathological diagnosis was adenocarcinoma, and the diagnosis was made by performing percutaneous needle aspiration and lobectomy of the left upper lobe. Adjuvant chemotherapy and radiotherapy were given. Unfortunately, a nodule in the left breast was noted three years later, and metastatic non-small-cell lung cancer to the breast was diagnosed by excisional biopsy. Making the correct diagnosis to distinguish a primary breast carcinoma from a metastatic one is important, because the therapeutic plan and outcome for these two types of cancer are quite different.
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Training-free, generic object detection using locally adaptive regression kernels.
IEEE Trans Pattern Anal Mach Intell
PUBLISHED: 07-17-2010
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We present a generic detection/localization algorithm capable of searching for a visual object of interest without training. The proposed method operates using a single example of an object of interest to find similar matches, does not require prior knowledge (learning) about objects being sought, and does not require any preprocessing step or segmentation of a target image. Our method is based on the computation of local regression kernels as descriptors from a query, which measure the likeness of a pixel to its surroundings. Salient features are extracted from said descriptors and compared against analogous features from the target image. This comparison is done using a matrix generalization of the cosine similarity measure. We illustrate optimality properties of the algorithm using a naive-Bayes framework. The algorithm yields a scalar resemblance map, indicating the likelihood of similarity between the query and all patches in the target image. By employing nonparametric significance tests and nonmaxima suppression, we detect the presence and location of objects similar to the given query. The approach is extended to account for large variations in scale and rotation. High performance is demonstrated on several challenging data sets, indicating successful detection of objects in diverse contexts and under different imaging conditions.
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Inhibition of endothelial cell migration through the down?regulation of MMP-9 by A-kinase anchoring protein 12.
Mol Med Rep
PUBLISHED: 07-01-2010
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Matrix metalloproteinases (MMPs) play an important role in the degradation of extracellular matrix (ECM) molecules. ECM degradation is associated with tumor metastasis and angiogenesis. Therefore, the regulation of MMPs is of potential benefit in the treatment of various diseases, including cancer. A-kinase anchoring protein 12 (AKAP12) has been identified as a potential tumor suppressor. However, the function of AKAP12 as a tumor suppressor is not well understood. Herein, to determine the relationship between AKAP12 and MMP-9 in cancer, we first investigated the expression of MMP-9 under normoxic and hypoxic conditions in human fibrosarcoma cells. The expression of MMP-9 was not detected under normoxic conditions.; however, it was markedly increased under hypoxia in HT1080 cells. The effect of AKAP12 on the expression of MMP-9 was subsequently investigated. Hypoxia-induced MMP-9 mRNA expression was significantly reduced by overexpression of AKAP12, as was MMP-9 protein expression. In addition, when the AKAP12 transfectant-conditioned media (CM) were transferred into human endothelial cells, cell migration was significantly inhibited compared to the control group. Notably, the inhibition of AKAP12 expression by siRNA targeting AKAP12 resulted in an increase in the expression of active MMP-2 under normoxia, as well as of MMP-9. Endothelial cell migration was also strongly increased by treatment with CM of siRNA against AKAP12, as compared to the control group. Taken together, the results indicate that AKAP12 is involved in the regulation of endothelial cell migration through the inhibitory regulation of MMP-9 expression in tumor cells.
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Treatment outcome and mortality among patients with multidrug-resistant tuberculosis in tuberculosis hospitals of the public sector.
J. Korean Med. Sci.
PUBLISHED: 05-25-2010
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This study was conducted to evaluate treatment outcome, mortality, and predictors of both in patients with multidrug-resistant tuberculosis (MDR-TB) at 3 TB referral hospitals in the public sector of Korea. We included MDR-TB patients treated at 3 TB referral hospitals in 2004 and reviewed retrospectively their medical records and mortality data. Of 202 MDR-TB patients, 75 (37.1%) had treatment success and 127 (62.9%) poor outcomes. Default rate was high (37.1%, 75/202), comprising 59.1% of poor outcomes. Male sex (adjusted odds ratio [aOR], 2.91; 95% confidence interval [CI], 1.13-7.49), positive smear at treatment initiation (aOR, 5.50; 95% CI, 1.22-24.90), and extensively drug-resistant TB (aOR, 10.72; 95% CI, 1.23-93.64) were independent predictors of poor outcome. The all-cause mortality rate was 31.2% (63/202) during the 3-4 yr after treatment initiation. In conclusion, the treatment outcomes of patients with MDR-TB at the 3 TB hospitals are poor, which may reflect the current status of MDR-TB in the public sector of Korea. A more comprehensive program against MDR-TB needs to be integrated into the National Tuberculosis Program of Korea.
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Arrest defective 1 autoacetylation is a critical step in its ability to stimulate cancer cell proliferation.
Cancer Res.
PUBLISHED: 05-25-2010
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The N-acetyltransferase arrest defective 1 (ARD1) is an important regulator of cell growth and differentiation that has emerged recently as a critical molecule in cancer progression. However, the regulation of the enzymatic and biological activities of human ARD1 (hARD1) in cancer is presently poorly understood. Here, we report that hARD1 undergoes autoacetylation and that this modification is essential for its functional activation. Using liquid chromatography-tandem mass spectrometry and site-directed mutational analyses, we identified K136 residue as an autoacetylation target site. K136R mutation abolished the ability of hARD1 to promote cancer cell growth in vitro and tumor xenograft growth in vivo. Mechanistic investigations revealed that hARD1 autoacetylation stimulated cyclin D1 expression through activation of the transcription factors beta-catenin and activator protein-1. Our results show that hARD1 autoacetylation is critical for its activation and its ability to stimulate cancer cell proliferation and tumorigenesis.
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The development of the conditionally replication-competent adenovirus: replacement of E4 orf1-4 region by exogenous gene.
J Gene Med
PUBLISHED: 05-05-2010
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Tumor or tissue specific replicative adenovirus armed with a therapeutic gene has shown a promising anti-cancer therapeutic modality. However, because the genomic packaging capacity is constrained, only a few places inside it are available for transgene insertion. In the present study, we introduce a novel strategy utilizing the early E4 region for the insertion of therapeutic gene(s).
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Roles of arrest-defective protein 1(225) and hypoxia-inducible factor 1alpha in tumor growth and metastasis.
J. Natl. Cancer Inst.
PUBLISHED: 03-01-2010
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Vascular endothelial growth factor A (VEGFA), a critical mediator of tumor angiogenesis, is a well-characterized target of hypoxia-inducible factor 1 (HIF-1). Murine arrest-defective protein 1A (mARD1A(225)) acetylates HIF-1alpha, triggering its degradation, and thus may play a role in decreased expression of VEGFA.
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Identification of Bacillus cereus in a chungkukjang that showed high anticancer effects against AGS human gastric adenocarcinoma cells.
J Med Food
PUBLISHED: 12-23-2009
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Anticancer effects of chungkukjang (a Korean short-term fermented soy paste) were studied in human gastric adenocarcinoma cells, and Bacillus strains from chungkukjang were isolated and identified. Before the experiments, six different chungkukjang products (K-, M-, Mn-, O-, Os-, and H-chungkukjangs) were purchased from a folk village in the Sunchang region, Jeonbuk, Republic of Korea. Based on sensory evaluation tests and general chemical and quality studies, K-, H-, and M-chungkukjangs were selected for the experiments. All chungkukjang samples exhibited in vitro anticancer activities; however, K-chungkukjang revealed the highest anticancer activity in the previous studies. In this experiment, K-chungkukjang again showed the highest anticancer effect in the AGS cells. At the concentration of 1 mg/mL, K-chungkukjang (87%) showed the highest growth inhibitory effect, followed by H-chungkukjang (85%) and MC-chungkukjang (69%) (P < .05). K-chungkukjang induced apoptosis as determined by 4,6-diamidino-2-phenylindole staining and exhibited increased bax and decreased bcl-2 mRNA expression. Three representative Bacillus strains from K-chungkukjang were isolated and identified by recA gene sequencing as Bacillus cereus, Bacillus amyloliquefaciens, and Bacillus subtilis. Identifying B. cereus in the chungkukjang means that when chungkukjang is prepared by the traditional method, B. cereus, which is a common cause of foodborne disease, can grow during the natural fermentation process. All B. cereus strains, of course, are not pathogens, but its presence causes food safety concerns. Therefore, using a starter culture is safer than the traditional natural fermentation for the industrialization of chungkukjang in Korea.
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Dactylosporangium darangshiense sp. nov., isolated from rock soil.
Int. J. Syst. Evol. Microbiol.
PUBLISHED: 08-07-2009
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A novel actinomycete was isolated from soil of a rock surface collected from the peak of Darangshi Oreum (Small Mountain) in Jeju, Republic of Korea. Phylogenetic analyses based on 16S rRNA gene sequences demonstrated that strain DLS-44(T) belonged to the genus Dactylosporangium, with the type strains of Dactylosporangium roseum (99.1 % sequence similarity) and Dactylosporangium fulvum (99.0 %) as the nearest phylogenetic relatives. Substrate mycelium was abundant, irregularly branched, twisted and vivid orange-yellow in colour. Aerial mycelium was not produced on most media tested. Finger-shaped sporangia and globose bodies were formed directly from the vegetative mycelium. The combination of morphological and chemotaxonomic characteristics supported assignment of the actinomycete to the genus Dactylosporangium. Strain DLS-44(T) could be distinguished clearly from all type strains of the genus based on its physiological properties (utilization of methyl alpha-d-mannoside and glycerol, nitrate reduction and growth at 20 degrees C and pH 9.1) and some chemotaxonomic characteristics (absence of unsaturated fatty acids). DNA-DNA relatedness values between strain DLS-44(T) and its closest phylogenetic relatives were 12.2-14.8 % with D. roseum DSM 43916(T) and 2.5-3.6 % with D. fulvum IMSNU 22055(T). On the basis of phenotypic, phylogenetic and DNA-DNA hybridization data, strain DLS-44(T) represents a novel species of the genus Dactylosporangium, for which the name Dactylosporangium darangshiense sp. nov. is proposed. The type strain is strain DLS-44(T) (=KCTC 19560(T) =DSM 45260(T)).
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Loktanella pyoseonensis sp. nov., isolated from beach sand, and emended description of the genus Loktanella.
Int. J. Syst. Evol. Microbiol.
PUBLISHED: 08-05-2009
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A novel Gram-stain-negative, aerobic, heterotrophic, obligately halophilic bacterium, designated strain JJM85(T), was isolated from beach sand in Jeju, Republic of Korea. Cells were rod-shaped and motile by means of flagella; colonies were pink, convex and smooth with an entire edge. The organism grew at pH 5.0-10.0 and 4-30 degrees C. Phylogenetic analysis based on 16S rRNA gene sequences showed that the organism belonged to the genus Loktanella of the class Alphaproteobacteria and formed a tight cluster with the type strain of Loktanella hongkongensis (96.0 % sequence similarity). The DNA G+C content and fatty acid profile of the novel strain supported affiliation with the genus Loktanella. However, the novel strain could be differentiated clearly from members of this genus by cell motility, some physiological properties and low 16S rRNA gene sequence similarity (93.1-96.0 %). On the basis of the polyphasic data presented here, strain JJM85(T) is considered to represent a novel species of the genus Loktanella, for which the name Loktanella pyoseonensis sp. nov. is proposed; the type strain is JJM85(T) (=KCTC 22372(T) =DSM 21424(T)).
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Altererythrobacter marensis sp. nov., isolated from seawater.
Int. J. Syst. Evol. Microbiol.
PUBLISHED: 08-03-2009
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A novel Gram-negative bacterium, designated MSW-14(T), was isolated from seawater collected around Mara Island, Jeju, Republic of Korea. The organism was motile by means of a flagellum and showed optimum growth at 0-4 % NaCl, 30 degrees C and pH 7.1. Phylogenetic analyses based on 16S rRNA gene sequences showed that the isolate belonged to the family Erythrobacteraceae. The strains closest phylogenetic neighbours were Altererythrobacter epoxidivorans JCS350(T) (97.7 % sequence similarity), Altererythrobacter luteolus SW-109(T) (97.3 %) and Altererythrobacter indicus MSSRF26(T) (95.0 %). The dominant cellular fatty acid was C(18 : 1) (summed feature 7, 52.8 %). The major ubiquinone was UQ-10. The DNA G+C content was 63.1 mol%. DNA-DNA hybridization values between strain MSW-14(T) and A. epoxidivorans KCCM 42314(T) and A. luteolus KCTC 12311(T) were 26.0-27.3 % and 9.8-15.2 %, respectively. On the basis of the data from the polyphasic characterization, strain MSW-14(T) represents a novel species, for which the name Altererythrobacter marensis sp. nov. is proposed. The type strain is MSW-14(T) (=KCTC 22370(T)=DSM 21428(T)).
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Actinocatenispora rupis sp. nov., isolated from cliff soil, and emended description of the genus Actinocatenispora.
Int. J. Syst. Evol. Microbiol.
PUBLISHED: 07-30-2009
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A novel actinomycete, designated strain CS5-AC17(T), was isolated from cliff soil in the Republic of Korea. Cells of the organism were aerobic and catalase- and oxidase-negative. Substrate mycelium was well developed and was pale to strong yellow. Spore chains were borne on rudimentary aerial mycelium. The spores (0.4-0.5x0.9-1.6 microm) were smooth surfaced and cylindrical. Growth occurred at 25-42 degrees C, at pH 5.1-12.1 and in the presence of up to 4 % NaCl. Phylogenetic analyses based on 16S rRNA gene sequences indicated that the isolate was closely related to members of the genus Actinocatenispora in the family Micromonosporaceae. The phylogenetic neighbours were Actinocatenispora thailandica TT2-10(T) (97.7 % 16S rRNA gene sequence similarity) and Actinocatenispora sera KV-744(T) (97.6 %). The diagnostic diamino acid in the cell-wall peptidoglycan was meso-diaminopimelic acid. The major respiratory quinones were MK-9(H(4)), MK-9(H(6)) and MK-9(H(8)). The polar lipids contained phosphatidylethanolamine and phosphatidylinositol with a small amount of phosphatidylglycerol. The DNA G+C content was 74.3 mol%. DNA-DNA relatedness values between strain CS5-AC17(T) and its phylogenetically closest relatives were 6.1-7.1 % (A. thailandica DSM 44816(T)) and 21.5-27.6 % (A. sera NRRL B-24477(T)). On the basis of the phenotypic features and the DNA-DNA hybridization data, strain CS5-AC17(T) (=DSM 45178(T)=NRRL B-24660(T)) represents a novel species of the genus Actinocatenispora, for which the name Actinocatenispora rupis sp. nov. is proposed.
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Static and space-time visual saliency detection by self-resemblance.
J Vis
PUBLISHED: 05-13-2009
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We present a novel unified framework for both static and space-time saliency detection. Our method is a bottom-up approach and computes so-called local regression kernels (i.e., local descriptors) from the given image (or a video), which measure the likeness of a pixel (or voxel) to its surroundings. Visual saliency is then computed using the said "self-resemblance" measure. The framework results in a saliency map where each pixel (or voxel) indicates the statistical likelihood of saliency of a feature matrix given its surrounding feature matrices. As a similarity measure, matrix cosine similarity (a generalization of cosine similarity) is employed. State of the art performance is demonstrated on commonly used human eye fixation data (static scenes (N. Bruce & J. Tsotsos, 2006) and dynamic scenes (L. Itti & P. Baldi, 2006)) and some psychological patterns.
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A case of primary infective endocarditis caused by community-associated methicillin-resistant Staphylococcus aureus in a healthy individual and colonization in the family.
Yonsei Med. J.
PUBLISHED: 02-24-2009
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Primary community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) endocarditis has rarely been reported in healthy individuals without risk factors, such as skin and soft tissue infections, and intravenous drug abuse. We describe a case of infective endocarditis by CA-MRSA (ST72-PVL negative-SCCmec IVA) in previously healthy individuals with no underlying medical condition and CA-MRSA colonization in the family.
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High-mobility group box 1 from reactive astrocytes enhances the accumulation of endothelial progenitor cells in damaged white matter.
J. Neurochem.
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High-mobility group box 1 (HMGB1) was initially described as a damage-associated-molecular-pattern (DAMP) mediator that worsens acute brain injury after stroke. But, recent findings suggest that HMGB1 can play a surprisingly beneficial role during stroke recovery by promoting endothelial progenitor cell (EPC) function and vascular remodeling in cortical gray matter. Here, we ask whether HMGB1 may also influence EPC responses in white matter injury. The standard lysophosphatidylcholine (LPC) injection model was used to induce focal demyelination in the corpus callosum of mice. Immunostaining showed that within the focal white matter lesions, HMGB1 was up-regulated in GFAP-positive reactive astrocytes, along with the accumulation of Flk1/CD34-double-positive EPCs that expressed pro-recovery mediators such as brain-derived neurotrophic factor and basic fibroblast growth factor. Astrocyte-EPC signaling required the HMGB1 receptor RAGE as treatment with RAGE-neutralizing antibody significantly decreased EPC accumulation. Moreover, suppression of HMGB1 with siRNA in vivo significantly decreased EPC numbers in damaged white matter as well as proliferated endothelial cell numbers. Finally, in vitro cell culture systems confirmed that HMGB1 directly affected EPC function such as migration and tube formation. Taken together, our findings suggest that HMGB1 from reactive astrocytes may attract EPCs to promote recovery after white matter injury.
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The N-terminal ectodomain of Ninjurin1 liberated by MMP9 has chemotactic activity.
Biochem. Biophys. Res. Commun.
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Ninjurin1 is known as an adhesion molecule promoting leukocyte trafficking under inflammatory conditions. However, the posttranslational modifications of Ninjurin1 are poorly understood. Herein, we defined the proteolytic cleavage of Ninjurin1 and its functions. HEK293T cells overexpressing the C- or N-terminus tagging mouse Ninjurin1 plasmid produced additional cleaved forms of Ninjurin1 in the lysates or conditioned media (CM). Two custom-made anti-Ninjurin1 antibodies, Ab(1-15) or Ab(139-152), specific to the N- or C-terminal regions of Ninjurin1 revealed the presence of its shedding fragments in the mouse liver and kidney lysates. Furthermore, Matrix Metalloproteinase (MMP) 9 was responsible for Ninjurin1 cleavage between Leu(56) and Leu(57). Interestingly, the soluble N-terminal Ninjurin1 fragment has structural similarity with well-known chemokines. Indeed, the CM from HEK293T cells overexpressing the GFP-mNinj1 plasmid was able to attract Raw264.7 cells in trans-well assay. Collectively, we suggest that the N-terminal ectodomain of mouse Ninjurin1, which may act as a chemoattractant, is cleaved by MMP9.
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The association of baseline adipocytokine levels with glycemic progression in nondiabetic Korean adults in 4 years of follow-up.
Diabetes Res. Clin. Pract.
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Low-grade inflammation and lipotoxicity contribute to insulin resistance and islet secretory dysfunction that lead to insulin deficiency. We analyzed the associations of several adipocytokines measured at baseline with glycemic progression in non-diabetic Korean subjects after a 4-year follow-up.
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Neuregulin-1 effects on endothelial and blood-brain-barrier permeability after experimental injury.
Transl Stroke Res
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Blood-brain-barrier disruption occurs with a high incidence after traumatic brain injury, and is an important contributor to many pathological processes, including brain edema, inflammation, and neuronal cell death. Therefore, blood-brain-barrier integrity is an important potential therapeutic target in the treatment of the acute phase of brain trauma. In this short communication, we report our data showing that neuregulin-1 (NRG1), a growth factor with diverse functions in the CNS, ameliorates pathological increases in endothelial permeability and in BBB permeability in experimental models of injury. For in-vitro studies, rat brain endothelial cells were incubated with the inflammatory cytokine IL-1?, which caused an increase in permeability of the cell layer. Co-incubation with NRG1 ameliorated this permeability increase. For in-vivo studies, C57Bl mice were subjected to controlled cortical impact (CCI) under anesthesia, and BBB permeability was assessed by measuring the amount of Evans blue dye extravasation at 2h. NRG1 administered by tail-vein injection 10 minutes after CCI resulted in a decrease in Evans blue dye extravasation by 35%. Since Evans blue extravasation may result from an increase in BBB permeability or from bleeding due to trauma, hemoglobin ELISA was also performed at the same time point. There was a trend towards lower levels of hemoglobin extravasation in the NRG1 group, but the results did not reach statistical significance. MMP-9 activity was not different between groups at 2h. These data suggest that NRG1 has beneficial effects on endothelial permeability and BBB permeability following experimental trauma, and may have neuroprotective potential during CNS injury.
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Delayed inhibition of c-Jun N-terminal kinase worsens outcomes after focal cerebral ischemia.
J. Neurosci.
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The stress-activated protein kinase c-Jun N-terminal kinase (JNK) is a central regulator in neuronal death cascades. In animal models of cerebral ischemia, acute inhibition of JNK reduces infarction and improves outcomes. Recently however, emerging data suggest that many neuronal death mediators may have biphasic properties-deleterious in the acute stage but potentially beneficial in the delayed stage. Here, we hypothesized that JNK may also have biphasic actions, so some caution may be required in the development of JNK inhibitors for stroke. Sprague Dawley rats underwent 90 min transient occlusions of the middle cerebral artery. Acute treatment (10 min poststroke) with the JNK inhibitor SP600125 reduced infarction volumes. In contrast, delayed treatment (7 d poststroke) worsened infarction volumes and neurological outcomes. Immunostaining of peri-infarct cortex showed that JNK inhibition suppressed surrogate markers of neurovascular remodeling, including matrix metalloproteinase-9 in GFAP-positive astrocytes and microvascular density. Consistent with these in vivo data, SP600125 significantly suppressed in vitro angiogenesis in rat brain endothelial cultures. Our data provide initial proof-of-concept that the neuronal death target JNK may also participate in endogenous processes of neurovascular remodeling and recovery after cerebral ischemia.
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Neurovascular matrix metalloproteinases and the blood-brain barrier.
Curr. Pharm. Des.
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Blood-brain barrier (BBB) leakage and brain edema is a critical part of stroke pathophysiology. In this mini-review, we briefly survey the potential role of matrix metalloproteinases (MMPs) in BBB dysfunction. A large body of data in both experimental models as well as clinical patient populations suggests that MMPs may disrupt BBB permeability and interfere with cell-cell signaling in the neurovascular unit. Hence, ongoing efforts are underway to validate MMPs as potential biomarkers in stroke as well as pursue MMP blockers as therapeutic opportunities. Because BBB perturbations may also occur in neurodegeneration, MMPs and associated neurovascular unit mechanisms may also be potential targets in a broader range of CNS disorders.
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Positive conversion of negative signaling of CTLA4 potentiates antitumor efficacy of adoptive T-cell therapy in murine tumor models.
Blood
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Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) has been known to be a strong tolerance-inducing inhibitory receptor on T-cell surface. Systemic blocking of CTLA4 function with blocking antibodies has been regarded as an attractive strategy to enhance antitumor immunity. However, this strategy accompanies systemic autoimmune side effects that are sometimes problematic. Therefore, we developed a novel CTLA4 mutant that could be expressed in tumor antigen-specific T cells to enhance antitumor effect without systemic autoimmunity. This mutant, named CTLA4-CD28 chimera, consists of extracellular and transmembrane domains of CTLA4, linked with cytoplasmic CD28 domain. Overexpression of CTLA4-CD28 chimera in T cells delivered stimulatory signals rather than inhibitory signals of CTLA4 and significantly enhanced T-cell reactivity. Although this effect was observed in both CD4 and CD8 T cells, the effect on CD4 T cells was predominant. CTLA4-CD28 chimera gene modification of CD4 T cells significantly enhanced antitumor effect of unmodified CD8 T cells. Nonetheless, the gene modification of CD8 T cells along with CD4 T cells further maximized antitumor effect of T cells in 2 different murine tumor models. Thus, CTLA4-CD28 chimera gene modification of both tumor antigen-specific CD4 and CD8 T cells would be an ideal way of modulating CTLA4 function to enhance tumor-specific T-cell reactivity.
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Crosstalk between oligodendrocytes and cerebral endothelium contributes to vascular remodeling after white matter injury.
Glia
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After stroke and brain injury, cortical gray matter recovery involves mechanisms of neurovascular matrix remodeling. In white matter, however, the mechanisms of recovery remain unclear. In this study, we demonstrate that oligodendrocytes secrete matrix metalloproteinase-9 (MMP-9), which accelerates the angiogenic response after white matter injury. In primary oligodendrocyte cultures, treatment with the proinflammatory cytokine interleukin-1? (IL-1?) induced an upregulation and secretion of MMP-9. Conditioned media from IL-1?-stimulated oligodendrocytes significantly amplified matrigel tube formation in brain endothelial cells, indicating that MMP-9 from oligodendrocytes can promote angiogenesis in vitro. Next, we asked whether similar signals and substrates operate after white matter injury in vivo. Focal white matter injury and demyelination was induced in mice via stereotactic injection of lysophosphatidylcholine into corpus callosum. Western blot analysis showed that IL-1? expression was increased in damaged white matter. Immunostaining demonstrated MMP-9 signals in myelin-associated oligodendrocytic basic protein-positive oligodendrocytes. Treatment with an IL-1?-neutralizing antibody suppressed the MMP-9 response in oligodendrocytes. Finally, we confirmed that the broad spectrum MMP inhibitor GM6001 inhibited angiogenesis around the injury area in this white matter injury model. In gray matter, a neurovascular niche promotes cortical recovery after brain injury. Our study suggests that an analogous oligovascular niche may mediate recovery in white matter.
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Cerebral endothelial derived vascular endothelial growth factor promotes the migration but not the proliferation of oligodendrocyte precursor cells in vitro.
Neurosci. Lett.
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In gray matter, cerebral endothelium is known to provide trophic support for neighboring cells such as neurons. However, signaling from cerebral endothelium to white matter cells remains to be elucidated. Here, we show that vascular endothelial growth factor (VEGF-A) secreted from cerebral endothelial cells promotes the migration but not the proliferation of oligodendrocyte precursor cells (OPCs). Cultured OPCs were obtained from newborn rat cortex, and treatment with conditioned culture media of cerebral endothelial cells increased the OPC proliferation and migration. Importantly, co-treatment with anti-neutralizing antibody for Flk-1 (VEGF-receptor2) inhibited OPC movement but did not affect OPC propagation. Western blot and flow cytometry analyses confirmed that our cultured cerebral endothelial cells produced VEGF-A and our cultured OPCs expressed Flk-1. Taken together, our current data suggest that cerebral endothelium is supportive for oligodendrocyte lineage cells and VEGF-A may participate in the endothelium-OPC cell-cell signaling. This phenomenon may be important for white matter homeostasis.
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Validation of the Energy Conservation Strategies Inventory (ECSI).
J Pain Symptom Manage
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In applying good energy conservation strategies to relieve cancer-related fatigue, it is critical to first identify cancer patients who are at a high risk for poor energy conservation. However, instruments have not been developed to evaluate energy conservation strategies in an oncology setting.
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Pro-angiogenic effects of resveratrol in brain endothelial cells: nitric oxide-mediated regulation of vascular endothelial growth factor and metalloproteinases.
J. Cereb. Blood Flow Metab.
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Resveratrol may be a powerful way of protecting the brain against a wide variety of stress and injury. Recently, it has been proposed that resveratrol not only reduces brain injury but also promotes recovery after stroke. But the underlying mechanisms are unclear. Here, we tested the hypothesis that resveratrol promotes angiogenesis in cerebral endothelial cells and dissected the signaling pathways involved. Treatment of cerebral endothelial cells with resveratrol promoted proliferation, migration, and tube formation in Matrigel assays. Consistent with these pro-angiogenic responses, resveratrol altered endothelial morphology resulting in cytoskeletal rearrangements of ?-catenin and VE-cadherin. These effects of resveratrol were accompanied by activation of phosphoinositide 3 kinase (PI3-K)/Akt and Mitogen-Activated Protein Kinase (MAPK)/ERK signaling pathways that led to endothelial nitric oxide synthase upregulation and increased nitric oxide (NO) levels. Subsequently, elevated NO signaling increased vascular endothelial growth factor and matrix metalloproteinase levels. Sequential blockade of these signaling steps prevented resveratrol-induced angiogenesis in cerebral endothelial cells. These findings provide a mechanistic basis for the potential use of resveratrol as a candidate therapy to promote angiogenesis and neurovascular recovery after stroke.
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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.