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Find video protocols related to scientific articles indexed in Pubmed.
Inhibition of PKC? attenuates methamphetamine-induced dopaminergic toxicity via up-regulation of phosphorylation of TH-Ser40 by modulations of PP2A and PKA.
Clin. Exp. Pharmacol. Physiol.
PUBLISHED: 11-18-2014
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Recently, we have proposed that inhibition of protein kinase C? (PKC?) may be a useful target for protection against methamphetamine (MA)-induced dopaminergic toxicity. We have demonstrated that treatment with MA resulted in a significant decrease in phosphorylation of tyrosine hydroxylase (TH) at Ser40 in the striatum, but not in the phosphorylation of TH at Ser31. Treatment with rottlerin, a PKC? inhibitor or PKC? antisense oligonucleotide (ASO) significantly attenuated MA-induced reductions in the phosphorylation of TH at Ser40 and in the expression of protein kinase A (PKA). This attenuation was significantly counteracted by H89, a PKA inhibitor. Treatment with rottlerin or ASO significantly attenuated the MA-induced increase in protein phosphatase (PP) 2A activity. FTY720, a PP2A activator, significantly reversed the PKC? inhibition-mediated recovery in phosphorylation of TH against MA insult. Consistently, H89 and FTY720 counteracted PKC? inhibition-mediated recovery against MA-induced behavioral impairments, respectively. The effects, mediated by rottlerin or ASO, in MA-treated wild-type-mice were comparable to those in MA-treated PKC?(-/-) -mice. However, neither inhibition of mitogen-activated protein kinase (MAPK) subfamily nor inhibition of calcium calmodulin kinase II significantly altered PKC? inhibition-mediated attenuation against MA-induced impaired phosphorylation of TH. Our results suggest that genetic or pharmacological inhibition of PKC? requires modulation of PKA expression and/or PP2A activity for attenuating impairments in the phosphorylation of TH at Ser40 and behavioral activity induced by MA. This article is protected by copyright. All rights reserved.
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1,3-Dimethyl Benzimidazolones Are Potent, Selective Inhibitors of the BRPF1 Bromodomain.
ACS Med Chem Lett
PUBLISHED: 11-13-2014
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The BRPF (bromodomain and PHD finger-containing) protein family are important scaffolding proteins for assembly of MYST histone acetyltransferase complexes. Here, we report the discovery, binding mode, and structure-activity relationship (SAR) of the first potent, selective series of inhibitors of the BRPF1 bromodomain.
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Do physiological scoring and a novel point of care metabolic screen predict 48-h outcome in admissions from the emergency department resuscitation area?
Eur J Emerg Med
PUBLISHED: 11-08-2014
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We aimed to compare the performance of a widely used physiological score [Modified Early Warning Score (MEWS)] and a novel metabolic score (derived from a blood gas) in predicting outcome in emergency department patients.
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Spatial pattern analysis for water quality in free-surface constructed wetland.
Water Sci. Technol.
PUBLISHED: 10-18-2014
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Free-surface constructed wetlands are known as a low-energy green technique to highly decrease a wide range of pollutants in wastewater and stormwater before discharge into natural water. In this study, two spatial analyses, principal factor analysis and hierarchical cluster analysis (HACA), were employed to interpret the effect of wetland on the water quality variables (WQVs) and to classify the wetland into groups with similar characteristics. Eleven WQVs were collected at the 17 sampling stations twice a month for 13 months. All sampling stations were classified by HACA into three clusters, with high, moderate, and low pollution areas. To improve the water quality, the performance of Cluster-III (micropool) is more significant than Cluster-I and Cluster-II. Implications of this study include potential savings of time and cost for long-term data monitoring purposes in the free-constructed wetland.
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Oxidized high-density lipoprotein impairs endothelial progenitor cells function by activation of CD36-MAPK-TSP-1 pathways.
Antioxid. Redox Signal.
PUBLISHED: 10-15-2014
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Aims: High density lipoprotein (HDL) levels inversely correlate with cardiovascular events due to the protective effects on vascular wall and stem cells, which is susceptible to oxidative modifications and then leads to potential pro-atherosclerotic effects. We proposed that oxidized high density lipoprotein (ox-HDL) might lead to endothelial progenitor cells (EPCs) dysfunction and investigated underlying mechanisms. Results: ox-HDL was shown to increase apoptosis and intracellular ROS levels, but reduce migration, angiogenesis and cholesterol efflux of EPCs in a dose dependent manner. p38 mitogen-activated protein kinase (MAPK) and NF-?B were activated after ox-HDL stimulation, which also upregulated thrombospondin-1 expression without affecting vascular endothelial growth factor. Effects caused by ox-HDL could be significantly attenuated by pretreatment with shRNA-mediated CD36 knockdown or probucol. Data of in vivo experiments and the inversely correlation of ox-HDL and circulating EPC numbers among patients with coronary artery diseases or CAD and type 2 diabetes also supported it. Meanwhile HDL separated from such patients could significantly increase cultured EPC's caspase 3 activity, furthermore supporting our proposal. Innovation: This is the most complete study to date of how ox-HDL would impair EPCs function, which was involved with activation of CD36-p38 MAPK-TSP-1 pathways and proved by not only the inverse relationship between ox-HDL and circulating EPCs in clinic, but also pro-apoptotic effects of HDL separated from patients' serum. Conclusion: Activation of CD36-p38 MAPK-TSP-1 pathways contributes to the pathological effects of ox-HDL on EPCs' dysfunction, which might be one of potential etiological factors responsible for the disturbed neovascularization in chronic ischemic disease.
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Structural Studies and Anticancer Activity of a Novel Class of ?-Peptides.
Chem Asian J
PUBLISHED: 10-11-2014
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Functionalized oligomeric organic compounds with well-defined ?-proline scaffold have been synthesized by a cycloadditive oligomerization approach in racemic and enantiopure forms. The structure of the novel ?-peptides was investigated by NMR spectroscopic and X-ray methods determining the conformational shapes of the ?-proline oligomers in solution and solid states. The main structural elements subject to conformational switches are ?-peptide bonds between 5-arylpyrrolidine-2-carboxylic acid units existing in Z/E configurations. The whole library of short ?-peptides and intermediate acrylamides has been tested on antiproliferative activity towards the hormone-refractory prostate cancer cell line PC-3 revealing several oligomeric compounds with low micromolar and submicromolar activities. Bromine-substituted dimeric and trimeric acrylamides induced caspase-dependent apoptosis of PC-3 cells through cell-cycle arrest and mitochondrial damage.
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Growth Hormone-Releaser Diet Attenuates Cognitive Dysfunction in Klotho Mutant Mice via Insulin-Like Growth Factor-1 Receptor Activation in a Genetic Aging Model.
Endocrinol Metab (Seoul)
PUBLISHED: 09-25-2014
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It has been recognized that a defect in klotho gene expression accelerates the degeneration of multiple age-sensitive traits. Accumulating evidence indicates that aging is associated with declines in cognitive function and the activity of growth hormone (GH)/insulin-like growth factor-1 (IGF-1).
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The Discovery of I-BET726 (GSK1324726A), a Potent Tetrahydroquinoline ApoA1 Up-Regulator and Selective BET Bromodomain Inhibitor.
J. Med. Chem.
PUBLISHED: 09-24-2014
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Through their function as epigenetic readers of the histone code, the BET family of bromodomain-containing proteins regulate expression of multiple genes of therapeutic relevance, including those involved in tumor cell growth and inflammation. BET bromodomain inhibitors have profound antiproliferative and anti-inflammatory effects which translate into efficacy in oncology and inflammation models, and the first compounds have now progressed into clinical trials. The exciting biology of the BETs has led to great interest in the discovery of novel inhibitor classes. Here we describe the identification of a novel tetrahydroquinoline series through up-regulation of apolipoprotein A1 and the optimization into potent compounds active in murine models of septic shock and neuroblastoma. At the molecular level, these effects are produced by inhibition of BET bromodomains. X-ray crystallography reveals the interactions explaining the structure-activity relationships of binding. The resulting lead molecule, I-BET726, represents a new, potent, and selective class of tetrahydroquinoline-based BET inhibitors.
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The application of flow cytometry for evaluating biological aggressiveness of intracranial meningiomas.
Cytometry B Clin Cytom
PUBLISHED: 09-23-2014
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Meningiomas have classically been considered to include benign and atypical/anaplastic tumors. Despite the availability of clinical and pathologic parameters for prognostic prediction prognosis, the behavior of each meningioma may be difficult to predict. Here, we used DNA flow-cytometric studies to predict biological tumor behaviors of intracranial meningiomas.
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Mining Tissue-specific Contigs from Peanut (Arachis hypogaea L.) for Promoter Cloning by Deep Transcriptome Sequencing.
Plant Cell Physiol.
PUBLISHED: 09-16-2014
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Peanut (Arachis hypogaea L.), one of the most important oil legumes in the world, is heavily damaged by white grubs. Tissue-specific promoters are needed to incorporate insect resistance genes into peanut by genetic transformation to control the subterranean pests. Transcriptome sequencing is the most effective way to analyze differential gene expression in this non-model species and contribute to promoter cloning. The transcriptomes of the roots, seeds and leaves of peanut were sequenced using Illumina technology. A simple digital expression profile was established based on number of transcripts per million clean tags (TPM) from different tissues. Subsequently, 584 root-specific candidate transcript assembly contigs (TACs) and 316 seed-specific candidate TACs were identified. Among these candidate TACs, 55.3% were root-specific and 64.6% were seed-specific by semi-quantitative RT-PCR analysis. Moreover, the consistency of semi-quantitative RT-PCR with the simple digital expression profile was correlated with the length and TPM value of TACs. The results of gene ontology showed that some root-specific TACs are involved in stress resistance and respond to auxin stimulus, whereas, seed-specific candidate TACs are involved in embryo development, lipid storage and long-chain fatty acid biosynthesis. One root-specific promoter was cloned and characterized. We developed a high-yield screening system in peanut by establishing a simple digital expression profile based on Illumina sequencing. The feasible and rapid method presented by this study can be used for other non-model crops to explore tissue-specific or spatially specific promoters.
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Immunization with advanced glycation end products modified low density lipoprotein inhibits atherosclerosis progression in diabetic apoE and LDLR null mice.
Cardiovasc Diabetol
PUBLISHED: 09-15-2014
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BackgroundDiabetes propitiates atherosclerosis through undefined molecular mechanisms. Hyperglycemia induces formation of advanced glycation end product (AGE)-modified low-density lipoprotein (LDL). Anti-AGE-LDL autoantibodies favor atherosclerosis (AS) progression in humans, while anti oxidized LDL immunization inhibits AS in hypercholesterolemic, non-diabetic mice. We here investigated if AGE-LDL immunization protects against AS in diabetic mice.MethodsAfter diabetes induction with streptozotocin and high fat diet, both low density lipoprotein receptor (LDLR)¿/¿ and apoE female mice were randomized to: AGE-LDL immunization with aluminum hydroxide (Alum) adjuvant; Alum alone; or PBS.ResultsAGE-LDL immunization: significantly reduced AS; induced specific plasma IgM and IgG antibodies; upregulated splenic Th2, Treg and IL-10 levels, without altering Th1 or Th17 cells; and increased serum high density lipoprotein(HDL) while numerically lowering HbA1c levels.ConclusionsSubcutaneous immunization with AGE-LDL significantly inhibits atherosclerosis progression in hyperlipidemic diabetic mice possibly through activation of specific humoral and cell mediated immune responses and metabolic control improvement.
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Substance P exacerbates dopaminergic neurodegeneration through neurokinin-1 receptor-independent activation of microglial NADPH oxidase.
J. Neurosci.
PUBLISHED: 09-12-2014
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Although dysregulated substance P (SP) has been implicated in the pathophysiology of Parkinson's disease (PD), how SP affects the survival of dopaminergic neurons remains unclear. Here, we found that mice lacking endogenous SP (TAC1(-/-)), but not those deficient in the SP receptor (neurokinin-1 receptor, NK1R), were more resistant to lipopolysaccharide (LPS)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigral dopaminergic neurodegeneration than wild-type controls, suggesting a NK1R-independent toxic action of SP. In vitro dose-response studies revealed that exogenous SP enhanced LPS- and 1-methyl-4-phenylpyridinium (MPP(+))-induced dopaminergic neurodegeneration in a bimodal manner, peaking at submicromolar and subpicomolar concentrations, but was substantially less effective at intermediate concentrations. Mechanistically, the actions of submicromolar levels of SP were NK1R-dependent, whereas subpicomolar SP-elicited actions required microglial NADPH oxidase (NOX2), the key superoxide-producing enzyme, but not NK1R. Subpicomolar concentrations of SP activated NOX2 by binding to the catalytic subunit gp91(phox) and inducing membrane translocation of the cytosolic subunits p47(phox) and p67(phox). The importance of NOX2 was further corroborated by showing that inhibition or disruption of NOX2 blocked subpicomolar SP-exacerbated neurotoxicity. Together, our findings revealed a critical role of microglial NOX2 in mediating the neuroinflammatory and dopaminergic neurodegenerative effects of SP, which may provide new insights into the pathogenesis of PD.
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Protective effects of Hericium erinaceus mycelium and its isolated erinacine A against ischemia-injury-induced neuronal cell death via the inhibition of iNOS/p38 MAPK and nitrotyrosine.
Int J Mol Sci
PUBLISHED: 08-27-2014
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Hericium erinaceus, an edible mushroom, has been demonstrated to potentiate the effects of numerous biological activities. The aim of this study was to investigate whether H. erinaceus mycelium could act as an anti-inflammatory agent to bring about neuroprotection using a model of global ischemic stroke and the mechanisms involved. Rats were treated with H. erinaceus mycelium and its isolated diterpenoid derivative, erinacine A, after ischemia reperfusion brain injuries caused by the occlusion of the two common carotid arteries. The production of inflammatory cytokines in serum and the infracted volume of the brain were measured. The proteins from the stroke animal model (SAM) were evaluated to determine the effect of H. erinaceus mycelium. H. erinaceus mycelium reduced the total infarcted volumes by 22% and 44% at a concentration of 50 and 300 mg/kg, respectively, compared to the SAM group. The levels of acute inflammatory cytokines, including interleukin-1?, interleukin-6 and tumor necrosis factor á, were all reduced by erinacine A. Levels of nitrotyrosine-containing proteins, phosphorylation of p38 MAPK and CCAAT enhancer-binding protein (C/EBP) and homologous protein (CHOP) expression were attenuated by erinacine A. Moreover, the modulation of ischemia injury factors present in the SAM model by erinacine A seemed to result in the suppression of reactive nitrogen species and the downregulation of inducible NO synthase (iNOS), p38 MAPK and CHOP. These findings confirm the nerve-growth properties of Hericium erinaceus mycelium, which include the prevention of ischemic injury to neurons; this protective effect seems to be involved in the in vivo activity of iNOS, p38 MAPK and CHOP.
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Terfenadine induces anti-proliferative and apoptotic activities in human hormone-refractory prostate cancer through histamine receptor-independent Mcl-1 cleavage and Bak up-regulation.
Naunyn Schmiedebergs Arch. Pharmacol.
PUBLISHED: 08-26-2014
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Although the results of several studies have underscored the regulatory effect of H1-histamine receptors in cell proliferation of some cancer cell types, its effect in prostate cancers remains unclear. We have therefore studied the effect of terfenadine (an H1-histamine receptor antagonist) in prostate cancer cell lines. Our data demonstrate that terfenadine was effective against PC-3 and DU-145 cells (two prostate cancer cell lines). In contrast, based on the sulforhodamine B assay, loratadine had less potency while fexofenadine and diphenhydramine had little effect. Terfenadine induced the cleavage of Mcl-1 cleavage into a pro-apoptotic 28-kDa fragment and up-regulation of Bak, resulting in the loss of mitochondrial membrane potential (??m) and the release of cytochrome c and apoptosis-inducing factor into the cytosol. The activation of caspase cascades was detected to be linked to terfenadine action. Bak up-regulation was also examined at both the transcriptional and translational levels, and Bak activation was validated based on conformational change to expose the N terminus. Terfenadine also induced an indirect-but not direct-DNA damage response through the cleavage and activation of caspase-2, phosphorylation and activation of Chk1 and Chk2 kinases, phosphorylation of RPA32 and acetylation of Histone H3; these processes were highly correlated to severe mitochondrial dysfunction and the activation of caspase cascades. In conclusion, terfenadine induced apoptotic signaling cascades against HRPCs in a sequential manner. The exposure of cells to terfenadine caused the up-regulation and activation of Bak and the cleavage of Mcl-1, leading to the loss of ??m and activation of caspase cascades which further resulted in DNA damage response and cell apoptosis.
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Liposomal melatonin rescues methamphetamine-elicited mitochondrial burdens, proapoptosis, and dopaminergic degeneration through the inhibition PKC? gene.
J. Pineal Res.
PUBLISHED: 08-24-2014
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We have demonstrated that mitochondrial oxidative damage and PKC? overexpression contribute to methamphetamine-induced dopaminergic degeneration. Although it is recognized that antioxidant melatonin is effective in preventing neurotoxicity induced by methamphetamine, its precise mechanism remains elusive. C57BL/6J wild type mice exhibited a similar degree of dopaminergic deficit when methamphetamine was administered during light and dark phases. Furthermore, dopaminergic neuroprotection by genetic inhibition of PKC? during the light phase was comparable to that during the dark phase. Thus, we have focused on the light phase in order to examine whether melatonin modulates PKC?-mediated neurotoxic signaling after multiple high doses of methamphetamine. To enhance the bioavailability of melatonin, we applied liposomal melatonin. Treatment with methamphetamine resulted in hyperthermia, mitochondrial translocation of PKC?, oxidative damage (mitochondria > cytosol), mitochondrial dysfunction, pro-apoptotic changes, ultrastructural mitochondrial degeneration, dopaminergic degeneration, and behavioral impairment in wild type mice. Treatment with liposomal melatonin resulted in a dose-dependent attenuation against degenerative changes induced by methamphetamine in wild type mice. Attenuation by liposomal melatonin might be comparable to that by genetic inhibition (using PKC?((-/-)) mice or PKC? antisense oligonucleotide). However, liposomal melatonin did not show any additional protective effects on the attenuation by genetic inhibition of PKC?. Our results suggest that the circadian cycle cannot be a key factor in modulating methamphetamine toxicity under the current experimental condition, and that PKC? is one of the critical target genes for melatonin-mediated protective effects against mitochondrial burdens (dysfunction), oxidative stress, pro-apoptosis, and dopaminergic degeneration induced by methamphetamine. This article is protected by copyright. All rights reserved.
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[Effect of advanced glycation end products on the function and angiogenesis of adipose tissue-derived stem cells and the protective effect of danhong injection: an experimental study].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 08-21-2014
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OBJECTIVE To investigate the effect of Nepsilon-(carboxymethyl) lysine albumin (CMLs), a primary advanced glycation end products (AGEPs) isoform in diabetic body, on the function and angiogenesis of adipose tissue-derived stem cells (ADSCs) and the protective effect of Danhong Injection (DH). METHODS Human ADSCs were cultured and separated from human subcutaneous fatty tissue using enzymatic digestion and centrifugation. The morphology was observed using optical microscope and differentiation capacities assessed. Cells were exposed to 5 different interventions respectively for 24 h, i.e., PBS, 60 1 microg/mL BSA, 60 microg/mL CML-BSA, 100 microL/mL DH, and 60 micro./mL CML-BSA +100 microL/mL DH. Their effect on the proliferation, migration, apoptosis, and secretion were observed using WST-1 assay, Transwell assay, Annexin V-FITC/PI flow meter test reagent kit, human VEGF reagent kit, ELISA reagent kit, respectively. The effect on ADSCs angiogenesis was observed by in vitro angiogenesis test.
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Extremely low-frequency electromagnetic fields cause G1 phase arrest through the activation of the ATM-Chk2-p21 pathway.
PLoS ONE
PUBLISHED: 08-11-2014
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In daily life, humans are exposed to the extremely low-frequency electromagnetic fields (ELF-EMFs) generated by electric appliances, and public concern is increasing regarding the biological effects of such exposure. Numerous studies have yielded inconsistent results regarding the biological effects of ELF-EMF exposure. Here we show that ELF-EMFs activate the ATM-Chk2-p21 pathway in HaCaT cells, inhibiting cell proliferation. To present well-founded results, we comprehensively evaluated the biological effects of ELF-EMFs at the transcriptional, protein, and cellular levels. Human HaCaT cells from an immortalized epidermal keratinocyte cell line were exposed to a 1.5 mT, 60 Hz ELF-EMF for 144 h. The ELF-EMF could cause G1 arrest and decrease colony formation. Protein expression experiments revealed that ELF-EMFs induced the activation of the ATM/Chk2 signaling cascades. In addition, the p21 protein, a regulator of cell cycle progression at G1 and G2/M, exhibited a higher level of expression in exposed HaCaT cells compared with the expression of sham-exposed cells. The ELF-EMF-induced G1 arrest was diminished when the CHK2 gene expression (which encodes checkpoint kinase 2; Chk2) was suppressed by specific small interfering RNA (siRNA). These findings indicate that ELF-EMFs activate the ATM-Chk2-p21 pathway in HaCaT cells, resulting in cell cycle arrest at the G1 phase. Based on the precise control of the ELF-EMF exposure and rigorous sham-exposure experiments, all transcriptional, protein, and cellular level experiments consistently supported the conclusion. This is the first study to confirm that a specific pathway is triggered by ELF-EMF exposure.
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Comparative analyses between retained introns and constitutively spliced introns in Arabidopsis thaliana using random forest and support vector machine.
PLoS ONE
PUBLISHED: 08-11-2014
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One of the important modes of pre-mRNA post-transcriptional modification is alternative splicing. Alternative splicing allows creation of many distinct mature mRNA transcripts from a single gene by utilizing different splice sites. In plants like Arabidopsis thaliana, the most common type of alternative splicing is intron retention. Many studies in the past focus on positional distribution of retained introns (RIs) among different genic regions and their expression regulations, while little systematic classification of RIs from constitutively spliced introns (CSIs) has been conducted using machine learning approaches. We used random forest and support vector machine (SVM) with radial basis kernel function (RBF) to differentiate these two types of introns in Arabidopsis. By comparing coordinates of introns of all annotated mRNAs from TAIR10, we obtained our high-quality experimental data. To distinguish RIs from CSIs, We investigated the unique characteristics of RIs in comparison with CSIs and finally extracted 37 quantitative features: local and global nucleotide sequence features of introns, frequent motifs, the signal strength of splice sites, and the similarity between sequences of introns and their flanking regions. We demonstrated that our proposed feature extraction approach was more accurate in effectively classifying RIs from CSIs in comparison with other four approaches. The optimal penalty parameter C and the RBF kernel parameter [Formula: see text] in SVM were set based on particle swarm optimization algorithm (PSOSVM). Our classification performance showed F-Measure of 80.8% (random forest) and 77.4% (PSOSVM). Not only the basic sequence features and positional distribution characteristics of RIs were obtained, but also putative regulatory motifs in intron splicing were predicted based on our feature extraction approach. Clearly, our study will facilitate a better understanding of underlying mechanisms involved in intron retention.
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Sleep Apnea and the Risk of Chronic Kidney Disease: A Nationwide Population-Based Cohort Study.
Sleep
PUBLISHED: 08-06-2014
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Sleep apnea (SA) is characterized by apnea during sleep and is associated with cardiovascular diseases and an increase in all-cause mortality. Chronic kidney disease (CKD) is a global health problem that has placed a substantial burden on healthcare resources. However, the relationship between SA and the incidence of CKD is not clear. This study aimed to determine whether SA is an independent risk factor for the development of CKD.
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MicroRNA-26a/b Regulate DNA Replication Licensing, Tumorigenesis, and Prognosis by Targeting CDC6 in Lung Cancer.
Mol. Cancer Res.
PUBLISHED: 08-06-2014
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Cancer is characterized by mutations, genome rearrangements, epigenetic changes, and altered gene expression that enhance cell proliferation, invasion, and metastasis. To accommodate deregulated cellular proliferation, many DNA replication-initiation proteins are overexpressed in human cancers. However, the mechanism that represses the expression of these proteins in normal cells and the cellular changes that result in their overexpression are largely unknown. One possible mechanism is through miRNA expression differences. Here, it is demonstrated that miR26a and miR26b inhibit replication licensing and the proliferation, migration, and invasion of lung cancer cells by targeting CDC6. Importantly, miR26a/b expression is significantly decreased in human lung cancer tissue specimens compared with the paired adjacent normal tissues, and miR26a/b downregulation and the consequential upregulation of CDC6 are associated with poorer prognosis of patients with lung cancer. These results indicate that miR26a/b repress replication licensing and tumorigenesis by targeting CDC6.
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Impact of age on the prognostic value of left ventricular function in relation to procedural outcomes following percutaneous coronary intervention; insights from the British Cardiovascular Intervention Society.
Catheter Cardiovasc Interv
PUBLISHED: 08-04-2014
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Background Around one third of patients undergoing percutaneous coronary intervention (PCI) have left ventricular (LV) dysfunction. Whilst the prevalence of LV dysfunction is known to increase with age, the prevalence of LV dysfunction in different age groups in the PCI setting is not known and the effect of age on the prognostic value of LV function in the PCI setting has not been examined. Methods The relationship between LV function and 30-day mortality in patients undergoing PCI in different age groups (<60 years, 60 to <70 years, 70 to <80 years and ?80 years) was studied in 246,840 patients in the UK between 2006-2011. Results Prevalent LV dysfunction in patients undergoing PCI increased with age; 25,106 / 83161 (30.2 %: <60 years), 24,114 / 76,895 (31.4%: 60 to <70 years), 23,580 / 64,711 36.4% (70 to <80 years) and 9851 / 22,073 (44.6%) in patients aged 80 or over (P<0.0001). Poor LV function was independently associated with increased risk of 30-day mortality outcomes in all age groups (OR 5.65:95% CI 4.21-7.58, age <60 years; OR 5.07: 95% CI 3.91-6.57, age 60 to <70 years; OR 4.50: 95% CI 3.64-5.57, 70 to <80 years and OR 4.83:95% CI 3.79-6.15, age ?80 years). Conclusions Our analysis suggests that worsening LV function is an important independent predictor of worse 30-day mortality outcomes across all age groups and underscores the need for a measure of LV function in all patients for accurate risk stratification prior to PCI. © 2014 Wiley Periodicals, Inc.
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Vegetarian diet, Seventh Day Adventists and risk of cardiovascular mortality: A systematic review and meta-analysis.
Int. J. Cardiol.
PUBLISHED: 08-04-2014
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Dietary interventions are an important component of cardiovascular risk factor management although their impact on cardiovascular risk and mortality remains uncertain. We have studied influence of a vegetarian diet on cardiovascular risk and mortality.
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Antitumor effects of dammarane-type saponins from steamed Notoginseng.
Pharmacogn Mag
PUBLISHED: 07-24-2014
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Six dammarane-type saponins were extracted from steamed Panax notoginseng. Their chemical structures were identified spectroscopically as ginsenosides Rh1 (1), Rg1 (2), 20 (S)-Rg3 (3), 20 (R)-Rg3 (4), Rb3 (5), and Rb1 (6). Compounds (0.1-10 ?M) were tested for inhibition of tumor necrosis factor-? (TNF)-induced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) luciferase reporter activity using a human kidney 293T cell-based assay. Ginsenoside Rb3 (5) showed the most significant activity with an IC50 of 8.2 ?M. This compound also inhibited the induction of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) messenger Ribonucleic acid (mRNA) in a dose-dependent manner after HepG2 cells had been treated with TNF-? (10 ng/mL).
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Prediction of water quality index in constructed wetlands using support vector machine.
Environ Sci Pollut Res Int
PUBLISHED: 07-08-2014
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Poor water quality is a serious problem in the world which threatens human health, ecosystems, and plant/animal life. Prediction of surface water quality is a main concern in water resource and environmental systems. In this research, the support vector machine and two methods of artificial neural networks (ANNs), namely feed forward back propagation (FFBP) and radial basis function (RBF), were used to predict the water quality index (WQI) in a free constructed wetland. Seventeen points of the wetland were monitored twice a month over a period of 14 months, and an extensive dataset was collected for 11 water quality variables. A detailed comparison of the overall performance showed that prediction of the support vector machine (SVM) model with coefficient of correlation (R (2))?=?0.9984 and mean absolute error (MAE)?=?0.0052 was either better or comparable with neural networks. This research highlights that the SVM and FFBP can be successfully employed for the prediction of water quality in a free surface constructed wetland environment. These methods simplify the calculation of the WQI and reduce substantial efforts and time by optimizing the computations.
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Prognostic value of troponins in acute coronary syndrome depends upon patient age.
Heart
PUBLISHED: 06-28-2014
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This study aims to determine whether the prognostic significance of troponins in acute coronary syndrome in predicting mortality varies by age, and if so, to what extent when other prognostic indicators are considered.
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Body fat percentage, body mass index and waist-to-hip ratio as predictors of mortality and cardiovascular disease.
Heart
PUBLISHED: 06-27-2014
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To study the utility of body fat percentage in predicting health outcomes when other obesity indices are considered.
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Similarity of patient characteristics and outcomes in consecutive data collection on stroke admissions over one month compared to longer periods.
BMC Res Notes
PUBLISHED: 06-06-2014
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The usefulness of time-limited consecutive data collection compared to continuous consecutive data collection in conditions which show seasonal variations is unclear. The objective of this study is to assess whether one month of admission data can be representative of data collected over two years in the same hospitals.
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Interleukin-17 induces CC chemokine receptor 6 expression and cell migration in colorectal cancer cells.
J. Cell. Physiol.
PUBLISHED: 05-21-2014
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The CC chemokine receptor 6 (CCR6) and its ligand CCL20 are involved in human colorectal cancer (CRC) carcinogenesis and can promote the progression of CRC. In addition, interleukin-17 (IL-17), produced by a T cell subset named "Th17," has been identified as an important player in inflammatory responses, and has emerged as a mediator in inflammation-associated cancer. However, the relevance of IL-17 in the development and progression of CRC still remains to be explored. This study aimed to investigate the effect of IL-17 on the cell migration of CRC cells. Human CRC HCT-116 cells were used to study the effect of IL-17 on CCR6 expression and cell migration in CRC cells. IL-17 treatment induced migration of HCT-116 cells across the Boyden chamber membrane and increased the expression level of the CCR6. Inhibition of CCR6 by small interfering RNA (siRNA) and neutralizing antibody inhibited IL-17-induced cell migration. By using specific inhibitors and short hairpin RNA (shRNA), we demonstrated that the activation of ERK and p38 pathways are critical for IL-17-induced CCR6 expression and cell migration. Promoter activity and transcription factor ELISA assays showed that IL-17 increased NF-?B-DNA binding activity in HCT-116 cells. Inhibition of NF-?B activation by specific inhibitors and siRNA blocked the IL-17-induced CCR6 expression. Our findings support the hypothesis that CCR6 up-regulation stimulated by IL-17 may play an active role in CRC cell migration. J. Cell. Physiol. © 2014 Wiley Periodicals, Inc.
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Single-Dose, Randomized, Open-Label, 2-Way Crossover Study of the Pharmacokinetics of Amitriptyline Hydrochloride 10- and 25-mg Tablet in Healthy Male Korean Volunteers.
Clin Ther
PUBLISHED: 05-08-2014
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Amitriptyline is the most widely used tricyclic antidepressant (TCA). Although amitriptyline hydrochloride 10 and 25 mg has been marketed in Korea, no data on the dose proportionality of amitriptyline in Korean subjects are available. This clinical trial was designed to evaluate and compare the relative bioavailability with regard to dose proportionality between the two marketed strengths of amitriptyline hydrochloride tablets after a single-dose, oral administration under fasting conditions in healthy, male, Korean volunteers.
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Addressing the unmet need for visualizing conditional random fields in biological data.
BMC Bioinformatics
PUBLISHED: 04-24-2014
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The biological world is replete with phenomena that appear to be ideally modeled and analyzed by one archetypal statistical framework - the Graphical Probabilistic Model (GPM). The structure of GPMs is a uniquely good match for biological problems that range from aligning sequences to modeling the genome-to-phenome relationship. The fundamental questions that GPMs address involve making decisions based on a complex web of interacting factors. Unfortunately, while GPMs ideally fit many questions in biology, they are not an easy solution to apply. Building a GPM is not a simple task for an end user. Moreover, applying GPMs is also impeded by the insidious fact that the "complex web of interacting factors" inherent to a problem might be easy to define and also intractable to compute upon.
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Guibitang, a traditional herbal medicine, induces apoptotic death in A431 cells by regulating the activities of mitogen-activated protein kinases.
BMC Complement Altern Med
PUBLISHED: 04-22-2014
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Guibi-tang (GBT), a traditional herbal formula, mainly has been shown to possess immune regulation, antioxidant and protective effect of the gastric mucosa. Constituent herbs of GBT are frequently used to treat various diseases; however, their pharmacological effects, especially on cancer cells, differ from those of GBT. Furthermore, the molecular mechanisms behind effects of GBT remain unclear. In the present study, we explored the mechanism of chemopreventive/chemotherapeutic efficacy of GBT against human squamous cell carcinoma without cytotoxicity in normal cells and proved the efficacy of GBT through performing in vivo xenograft assay.
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Ginseng gintonin activates the human cardiac delayed rectifier K+ channel: involvement of Ca2+/calmodulin binding sites.
Mol. Cells
PUBLISHED: 04-11-2014
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Gintonin, a novel, ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand, elicits [Ca(2+)]i transients in neuronal and non-neuronal cells via pertussis toxin-sensitive and pertussis toxin-insensitive G proteins. The slowly activating delayed rectifier K(+) (I(Ks)) channel is a cardiac K(+) channel composed of KCNQ1 and KCNE1 subunits. The C terminus of the KCNQ1 channel protein has two calmodulin-binding sites that are involved in regulating I(Ks) channels. In this study, we investigated the molecular mechanisms of gintonin-mediated activation of human I(Ks) channel activity by expressing human I(Ks) channels in Xenopus oocytes. We found that gintonin enhances IKs channel currents in concentration- and voltage-dependent manners. The EC50 for the I(Ks) channel was 0.05 ± 0.01 ?g/ml. Gintonin-mediated activation of the I(Ks) channels was blocked by an LPA1/3 receptor antagonist, an active phospholipase C inhibitor, an IP3 receptor antagonist, and the calcium chelator BAPTA. Gintonin-mediated activation of both the I(Ks) channel was also blocked by the calmodulin (CaM) blocker calmidazolium. Mutations in the KCNQ1 [Ca(2+)]i/CaM-binding IQ motif sites (S373P, W392R, or R539W)blocked the action of gintonin on I(Ks) channel. However, gintonin had no effect on hERG K(+) channel activity. These results show that gintonin-mediated enhancement of I(Ks) channel currents is achieved through binding of the [Ca(2+)]i/CaM complex to the C terminus of KCNQ1 subunit.
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A novel small molecule hybrid of vorinostat and DACA displays anticancer activity against human hormone-refractory metastatic prostate cancer through dual inhibition of histone deacetylase and topoisomerase I.
Biochem. Pharmacol.
PUBLISHED: 04-06-2014
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Vorinostat, which is an extensively studied inhibitor against histone deacetylase (HDAC), shows limited clinical activity to solid tumors. WJ35435, a new hybrid of vorinostat and DACA (a topoisomerase inhibitor) potently inhibited HDAC activity (in particular HDAC1 and HDAC6) in kinase assay and cell-based examination. The anti-HDAC effect was confirmed by the induction of histone H3 acetylation and phosphorylation, ?-tubulin acetylation and ?-H2AX formation. WJ35435 showed better potency than vorinostat and DACA against PC-3 and DU-145, two human hormone-refractory metastatic prostate cancer (HRMPC) cell lines, but not benign prostate cells. WJ35435 at differential concentrations induced G1- or G2-phase arrest of the cell cycle in HRMPCs but not in benign prostate cells. WJ35435 induced the formation of topoisomerase I-DNA cleavable complexes but not type-II? or -II?. Topoisomerase activity assay confirmed the selective inhibition of topoisomerase I. WJ35435 induced profound DNA damage using comet tailing assay. WJ35435 was less effective than camptothecin and etoposide in inducing the phosphorylation and activation of Chk1, Chk2 and RPA32 which were crucial coordinators in DNA repair pathway, indicating a low DNA repair activity to WJ35435 action. Furthermore, WJ35435 showed an in vivo antitumor activity. A synergistic apoptosis (combination index=0.55) was obtained in combination between WJ35435 and MG-132 (a proteasome inhibitor). In summary, WJ35435 is a dual-targeted anticancer hybrid induces anti-HDAC and anti-topoisomerase I activities that cause DNA damage associated with a low DNA repair capability, and induce cell cycle arrest at G1- and G2-phase. Ultimately, WJ35435 inhibits cell proliferation and induces apoptosis of HRMPCs.
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Visual gene-network analysis reveals the cancer gene co-expression in human endometrial cancer.
BMC Genomics
PUBLISHED: 04-04-2014
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Endometrial cancers (ECs) are the most common form of gynecologic malignancy. Recent studies have reported that ECs reveal distinct markers for molecular pathogenesis, which in turn is linked to the various histological types of ECs. To understand further the molecular events contributing to ECs and endometrial tumorigenesis in general, a more precise identification of cancer-associated molecules and signaling networks would be useful for the detection and monitoring of malignancy, improving clinical cancer therapy, and personalization of treatments.
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Cystatin C as a Predictor for Outcomes in Patients with Negligible Renal Function.
Blood Purif.
PUBLISHED: 04-03-2014
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Background: High serum cystatin C (CysC) has been associated with clinical risks independently of the glomerular filtration rate (GFR). This study aims to investigate the predictive power of CysC in patients with a negligible GFR. Methods: Patients on chronic hemodialysis or peritoneal dialysis were enrolled for measurement of CysC levels and were followed up for one year. A daily urine amount <100 ml was considered negligible residual renal function (RRF). Results: CysC results were available in 183 dialysis patients. Of these, 131 patients had a negligible RRF. The multivariate Cox proportional hazards model showed that CysC was an independent predictor of fatal and nonfatal cardiovascular and infection events in all dialysis patients and in dialysis patients with a negligible RRF. Conclusion: CysC maintained its predictive power for adverse outcomes in patients with no meaningful GFR, indicating that the prognostic value of CysC is independent of the GFR. © 2014 S. Karger AG, Basel.
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Deafness induced by Connexin 26 (GJB2) deficiency is not determined by endocochlear potential (EP) reduction but is associated with cochlear developmental disorders.
Biochem. Biophys. Res. Commun.
PUBLISHED: 03-31-2014
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Connexin 26 (Cx26, GJB2) mutations are the major cause of hereditary deafness and are responsible for >50% of nonsyndromic hearing loss. Mouse models show that Cx26 deficiency can cause congenital deafness with cochlear developmental disorders, hair cell degeneration, and the reduction of endocochlear potential (EP) and active cochlear amplification. However, the underlying deafness mechanism still remains undetermined. Our previous studies revealed that hair cell degeneration is not a primary cause of hearing loss. In this study we investigated the role of EP reduction in Cx26 deficiency-induced deafness. We found that the EP reduction is not associated with congenital deafness in Cx26 knockout (KO) mice. The threshold of auditory brainstem response (ABR) in Cx26 KO mice was even greater than 110 dB SPL, demonstrating complete hearing loss. However, the EP in Cx26 KO mice varied and not completely abolished. In some cases, the EP could still remain at higher levels (>70 mV). We further found that the deafness in Cx26 KO mice is associated with cochlear developmental disorders. Deletion of Cx26 in the cochlea before postnatal day 5 (P5) could cause congenital deafness. The cochlea had developmental disorders and the cochlear tunnel was not open. However, no congenital deafness was found when Cx26 was deleted after P5. The cochlea also displayed normal development and the cochlear tunnel was open normally. These data suggest that congenital deafness induced by Cx26 deficiency is not determined by EP reduction and may result from cochlear developmental disorders.
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Effect of serum interleukin 21 on the development of coronary artery disease.
APMIS
PUBLISHED: 03-28-2014
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There has been more and more evidence to confirm the essential role of inflammatory processes in the development of coronary artery disease (CAD). Interleukin-21 (IL-21), the most recently discovered CD132-dependent cytokine, plays a key role in regulating inflammation. The aim of the study was to understand the effect of peripheral IL-21 on the pathogenesis and progression of CAD. Serum level of IL-21 in 92 CAD patients and 73 controls was measured by the enzyme-linked immunosorbent assay. Data showed that IL-21 expression was significantly increased in CAD than in controls (p < 0.001). Interestingly, when comparing IL-21 level with different genders, male subjects revealed higher IL-21 than female subjects (p = 0.024). Also, we observed that patients with hypertension had upregulated level of serum IL-21 (p = 0.002). Moreover, serum level of IL-21 was positively correlated with total cholesterol level (p = 0.015) or low-density lipoprotein cholesterol (p = 0.0009) of CAD cases. In addition, we analyzed IL-21 level with the severity of CAD, and identified that cases with 3-vessel affected had significantly elevated level of IL-21 than those with 1-vessel or 2-vessel affected. These data suggested that serum level of IL-21 may be closely associated with the development and progression of CAD.
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Activation of neutral-sphingomyelinase, MAPKs, and p75 NTR-mediating caffeic acid phenethyl ester-induced apoptosis in C6 glioma cells.
J. Biomed. Sci.
PUBLISHED: 03-25-2014
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Caffeic acid phenethyl ester (CAPE), a component of propolis, is reported to possess anti-inflammatory, anti-bacterial, anti-viral, and anti-tumor activities. Previously, our laboratory demonstrated the in vitro and in vivo bioactivity of CAPE and addressed the role of p53 and the p38 mitogen-activated protein kinase (MAPK) pathway in regulating CAPE-induced apoptosis in C6 glioma cells.
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Magnolol protects neurons against ischemia injury via the downregulation of p38/MAPK, CHOP and nitrotyrosine.
Toxicol. Appl. Pharmacol.
PUBLISHED: 03-20-2014
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Magnolol is isolated from the herb Magnolia officinalis, which has been demonstrated to exert pharmacological effects. Our aim was to investigate whether magnolol is able to act as an anti-inflammatory agent that brings about neuroprotection using a global ischemic stroke model and to determine the mechanisms involved. Rats were treated with and without magnolol after ischemia reperfusion brain injury by occlusion of the two common carotid arteries. The inflammatory cytokine production in serum and the volume of infarction in the brain were measured. The proteins present in the brains obtained from the stroke animal model (SAM) and control animal groups with and without magnolol treatment were compared. Magnolol reduces the total infarcted volume by 15% and 30% at dosages of 10 and 30mg/kg, respectively, compared to the untreated SAM group. The levels of acute inflammatory cytokines, including interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6 were attenuated by magnolol. Magnolol was also able to suppress the production of nitrotyrosine, 4-hydroxy-2-nonenal (4-HNE), inducible NO synthase (iNOS), various phosphorylated p38 mitogen-activated protein kinases and various C/EBP homologues. Furthermore, this modulation of ischemia injury factors in the SAM model group treated with magnolol seems to result from a suppression of reactive oxygen species production and the upregulation of p-Akt and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B). These findings confirm the anti-oxidative properties of magnolol, including the inhibition of ischemic injury to neurons; this protective effect seems to involve changes in the in vivo activity of Akt, GSK3? and NF-?B.
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Effectiveness of a national transitional care program in reducing acute care use.
J Am Geriatr Soc
PUBLISHED: 03-17-2014
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This study evaluated the effectiveness of a national transitional care program for elderly adults with complex care needs and limited social support. The Aged Care Transition (ACTION) Program was designed to improve coordination and continuity of care and reduce rehospitalizations and visits to emergency departments (EDs). Dedicated care coordinators provided coaching to help individuals and families understand the individuals' conditions, effectively articulate their preferences, and enable self-management and care planning. Participants were individuals aged 65 and older hospitalized and enrolled from five public general hospitals in Singapore between February 2009 and July 2010 (N = 4,132). The coordinators worked with participants during hospitalization and followed up with telephone calls and home visits for 1 to 2 months after discharge and coordinated placements with appropriate community service providers. Unplanned rehospitalization and ED visit (up to 6 months after discharge) rates were compared with those of a comparator group of individuals who did not receive care coordination using propensity score-based weighting. Participant and caregiver surveys on quality of life and self-rated health were also administered. Recipients of the ACTION program had fewer unplanned rehospitalizations and ED visits after discharge. Propensity score-adjusted odds ratios of participants versus control for number of unplanned rehospitalization and ED visits were 0.5 (95% confidence interval (CI) = 0.5-0.6) and 0.81 (95% CI = 0.72-0.90) 30 days after discharge and 0.6 (95% CI = 0.6-0.7) and 0.90 (95% CI = 0.82-0.99) 180 days after discharge. Quality of life and self-rated health were better 4 to 6 weeks after discharge than 1 week after discharge. These findings confirm the effectiveness of the ACTION program in improving the transition of vulnerable older adults from hospital to community. Such transitional care should be considered as an integral part of care integration.
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Bioinformatics analysis of alternative polyadenylation in green alga Chlamydomonas reinhardtii using transcriptome sequences from three different sequencing platforms.
G3 (Bethesda)
PUBLISHED: 03-15-2014
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Messenger RNA 3'-end formation is an essential posttranscriptional processing step for most eukaryotic genes. Different from plants and animals where AAUAAA and its variants routinely are found as the main poly(A) signal, Chlamydomonas reinhardtii uses UGUAA as the major poly(A) signal. The advance of sequencing technology provides an enormous amount of sequencing data for us to explore the variations of poly(A) signals, alternative polyadenylation (APA), and its relationship with splicing in this algal species. Through genome-wide analysis of poly(A) sites in C. reinhardtii, we identified a large number of poly(A) sites: 21,041 from Sanger expressed sequence tags, 88,184 from 454, and 195,266 from Illumina sequence reads. In comparison with previous collections, more new poly(A) sites are found in coding sequences and intron and intergenic regions by deep-sequencing. Interestingly, G-rich signals are particularly abundant in intron and intergenic regions. The prevalence of different poly(A) signals between coding sequences and a 3'-untranslated region implies potentially different polyadenylation mechanisms. Our data suggest that the APA occurs in about 68% of C. reinhardtii genes. Using Gene Ontolgy analysis, we found most of the APA genes are involved in RNA regulation and metabolic process, protein synthesis, hydrolase, and ligase activities. Moreover, intronic poly(A) sites are more abundant in constitutively spliced introns than retained introns, suggesting an interplay between polyadenylation and splicing. Our results support that APA, as in higher eukaryotes, may play significant roles in increasing transcriptome diversity and gene expression regulation in this algal species. Our datasets also provide useful information for accurate annotation of transcript ends in C. reinhardtii.
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Resistin-induced stromal cell-derived factor-1 expression through Toll-like receptor 4 and activation of p38 MAPK/ NF?B signaling pathway in gastric cancer cells.
J. Biomed. Sci.
PUBLISHED: 03-04-2014
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Stromal cell-derived factor-1 (SDF-1) (CXC chemokine ligand-12)/CXC chemokine receptor 4 (CXCR4) is involved in the carcinogenesis of human gastric cancer, where it stimulates angiogenesis and favors metastasis of tumor cells to distant organs. In addition, resistin is suggested to be an important link between obesity and the development of gastric cancer. Resistin has identified as an important player in inflammatory responses, and emerged as a mediator in inflammation-associated cancer. A limited number of studies have investigated the association of resistin and SDF-1 with gastric cancer. Herein, we investigated the molecular mechanisms by which resistin influences the expression of SDF-1 in gastric carcinoma cells.
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The commonly used PI3-kinase probe LY294002 is an inhibitor of BET bromodomains.
ACS Chem. Biol.
PUBLISHED: 02-19-2014
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A commonly used small-molecule probe in cell-signaling research is the phosphoinositide 3-kinase inhibitor LY294002. Quantitative chemoproteomic profiling shows that LY294002 and LY303511, a close analogue devoid of PI3K activity, inhibit the BET bromodomain proteins BRD2, BRD3, and BRD4 that comprise a family of targets structurally unrelated to PI3K. Both compounds competitively inhibit acetyl-lysine binding of the first but not the second bromodomain of BET proteins in cell extracts. X-ray crystallography shows that the chromen-4-one scaffold represents a new bromodomain pharmacophore and establishes LY294002 as a dual kinase and BET-bromodomain inhibitor, whereas LY303511 exhibits anti-inflammatory and antiproliferative effects similar to the recently discovered BET inhibitors.
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Shorter daily dwelling time in peritoneal dialysis attenuates the epithelial-to-mesenchymal transition of mesothelial cells.
BMC Nephrol
PUBLISHED: 02-14-2014
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Peritoneal dialysis (PD) therapy is known to induce morphological and functional changes in the peritoneal membrane. Long-term exposure to conventional bio-incompatible dialysate and peritonitis is the main etiology of inflammation. Consequently, the peritoneal membrane undergoes structural changes, including angiogenesis, fibrosis, and hyalinizing vasculopathy, which ultimately results in technique failure. The epithelial-to-mesenchymal transition (EMT) of mesothelial cells (MCs) plays an important role during the above process; however, the clinical parameters associated with the EMT process of MCs remain to be explored.
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Risk factors of sensitization to human leukocyte antigen in end-stage renal disease patients.
Hum. Immunol.
PUBLISHED: 02-04-2014
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Pre-sensitization to human leukocyte antigen (HLA) is closely related to the prognosis of renal transplantation. Concerning the risk factors for HLA sensitization, most studies focused only on selected transplant candidates.
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Plate versus nail for distal tibial fractures: a systematic review and meta-analysis.
J Orthop Trauma
PUBLISHED: 01-28-2014
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To undertake a systematic review to determine whether there are advantages in using plate or nail fixation for distal meta-diaphyseal tibial fractures with or without articular involvement.
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Bariatric surgery and its impact on cardiovascular disease and mortality: a systematic review and meta-analysis.
Int. J. Cardiol.
PUBLISHED: 01-19-2014
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Bariatric surgery has been shown to improve cardiovascular risk factors but long term benefits for survival and cardiovascular events are still uncertain.
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Comparative coronary risks of apixaban, rivaroxaban and dabigatran: a meta-analysis and adjusted indirect comparison.
Br J Clin Pharmacol
PUBLISHED: 01-16-2014
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There are concerns regarding increased risk of acute coronary syndrome with dabigatran. We aimed to assess whether alternative treatment options such as rivaroxaban or apixaban carry a similar risk as compared with dabigatran.
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SCOPE++: sequence classification of homoPolymer emissions.
Genomics
PUBLISHED: 01-09-2014
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mRNA polyadenylation, the addition of a poly(A) tail to the 3'-end of pre-mRNA, is a process critical to gene expression and regulation in eukaryotes. To understand the molecular mechanisms governing polyadenylation and other relevant biological processes, it is important to identify these poly(A) tails accurately in transcriptome sequencing data and differentiate them from artificial adapter sequences added in the sequencing process. But the annotation of these tails is complicated by the presence of sequencing errors and post-transcriptional modifications. While determining that a tail is present in a given transcript fragment is straight-forward, these obfuscations make the problem of boundary identification a challenge; conventional seed-and-extend algorithms struggle to accurately identify these poly(A) tail end-points. Further, all existing tools that we are aware of focus exclusively on the trimming of poly(A) tails, failing to provide the detailed information needed for studying the polyadenylation process.
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Bone mineral density and incidence of stroke: European prospective investigation into cancer-norfolk population-based study, systematic review, and meta-analysis.
Stroke
PUBLISHED: 01-07-2014
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The prospective link between osteoporosis and future risk of stroke requires evidence from large-scale population-based long-term studies.
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Haemolytic uremic syndrome following fire ant bites.
BMC Nephrol
PUBLISHED: 01-06-2014
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Haemolytic-uremic syndrome (HUS) is a severe, life-threatening disease with symptoms such as haemolytic anaemia, renal failure, and a low platelet count. Possible aetiology includes bacterial infections, medication, post-hematopoietic cell transplantation, pregnancy, autoimmune disease, and acquired immunodeficiency syndrome.
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Exploring the effects of tert-butylhydroperoxide induced liver injury using proteomic approach.
Toxicology
PUBLISHED: 01-03-2014
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Tert-butyl hydroperoxide (t-BHP), an organic lipid hydroperoxide analog, has been demonstrated to exert pro-oxidant effects to evaluate mechanisms involving oxidative stress in hepatocyte cells and rat liver. Herein, we present an investigation of the event of molecular mechanism of t-BHP related acute liver injury. A proteomic approach was used to identify proteins which are differentially expressed in liver cells following t-BHP treatment and the mechanism of its action in apoptotic and endoplasmic reticulum stress pathways. Our results demonstrate that the t-BHP treatment of liver cells increased cell cytoxicity and apoptosis. t-BHP dose-dependent induction of cell apoptosis and stained liver sections relieved the acute rat liver injury were accompanied by sustained phosphorylation of JNK1/2 and p65. In addition, there were 13 differentially displayed proteins between the t-BHP-induced and untreated were assayed and validated in vivo. Furthermore, we demonstrated that t-BHP induced human Chang liver cell viability and apoptosis properties by up-regulating the levels of ETFA (electron transfer flavoprotein subunit alpha). This study demonstrated that there was an increase in the cellular levels of ETFA in the t-BHP induction in viability and apoptosis via the activation of JNK1/2 and NF?B signaling modules. NAC administration and shRNA ETFA conferred resistance to t-BHP-increased ETFA and CHOP expression via IRE1-alpha/TRAF2 complex formation, activation of JNK1/2 and p50. We concluded that the mechanism of t-BHP-induced an apoptosis cascade and endoplasmic reticulum stress in hepatocyte cells by up-regulation of ETFA, providing a new mechanism for liver injury.
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Distinct Epidermal Keratinocytes Respond to Extremely Low-Frequency Electromagnetic Fields Differently.
PLoS ONE
PUBLISHED: 01-01-2014
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Following an increase in the use of electric appliances that can generate 50 or 60 Hz electromagnetic fields, concerns have intensified regarding the biological effects of extremely low-frequency electromagnetic fields (ELF-EMFs) on human health. Previous epidemiological studies have suggested the carcinogenic potential of environmental exposure to ELF-EMFs, specifically at 50 or 60 Hz. However, the biological mechanism facilitating the effects of ELF-EMFs remains unclear. Cellular studies have yielded inconsistent results regarding the biological effects of ELF-EMFs. The inconsistent results might have been due to diverse cell types. In our previous study, we indicated that 1.5 mT, 60 Hz ELF-EMFs will cause G1 arrest through the activation of the ATM-Chk2-p21 pathway in human keratinocyte HaCaT cells. The aim of the current study was to investigate whether ELF-EMFs cause similar effects in a distinct epidermal keratinocyte, primary normal human epidermal keratinocytes (NHEK), by using the same ELF-EMF exposure system and experimental design. We observed that ELF-EMFs exerted no effects on cell growth, cell proliferation, cell cycle distribution, and the activation of ATM signaling pathway in NHEK cells. We demonstrated that the 2 epidermal keratinocytes responded to ELF-EMFs differently. To further validate this finding, we simultaneously exposed the NHEK and HaCaT cells to ELF-EMFs in the same incubator for 168 h and observed the cell growths. The simultaneous exposure of the two cell types results showed that the NHEK and HaCaT cells exhibited distinct responses to ELF-EMFs. Thus, we confirmed that the biological effects of ELF-EMFs in epidermal keratinocytes are cell type specific. Our findings may partially explain the inconsistent results of previous studies when comparing results across various experimental models.
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Differential Regulation of Human Aortic Smooth Muscle Cell Proliferation by Monocyte-Derived Macrophages from Diabetic Patients.
PLoS ONE
PUBLISHED: 01-01-2014
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Macrophage accumulation in the arterial wall and smooth muscle cell (SMC) proliferation are features of type 2 diabetes mellitus (DM) and its vascular complications. However, the effects of diabetic monocyte-derived macrophages on vascular SMC proliferation are not clearly understood. In the present study, we investigated the pro-proliferative effect of macrophages isolated from DM patients on vascular SMCs. Macrophage-conditioned media (MCM) were prepared from macrophages isolated from DM patients. DM-MCM treatment induced HASMC proliferation, decreased p21Cip1 and p27Kip1 expressions, and increased microRNA (miR)-17-5p and miR-221 expressions. Inhibition of either miR-17-5p or miR-221 inhibited DM-MCM-induced cell proliferation. Inhibition of miR-17-5p abolished DM-MCM-induced p21Cip1 down-regulation; and inhibition of miR-221 attenuated the DM-MCM-induced p27Kip1 down-regulation. Furthermore, blocking assays demonstrated that PDGF-CC in DM-MCM is the major mediators of cell proliferation in SMCs. In conclusion, our present data support the hypothesis that SMC proliferation stimulated by macrophages may play critical roles in vascular complications in DM patients and suggest a new mechanism by which arterial disease is accelerated in diabetes.
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detectIR: A Novel Program for Detecting Perfect and Imperfect Inverted Repeats Using Complex Numbers and Vector Calculation.
PLoS ONE
PUBLISHED: 01-01-2014
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Inverted repeats are present in abundance in both prokaryotic and eukaryotic genomes and can form DNA secondary structures - hairpins and cruciforms that are involved in many important biological processes. Bioinformatics tools for efficient and accurate detection of inverted repeats are desirable, because existing tools are often less accurate and time consuming, sometimes incapable of dealing with genome-scale input data. Here, we present a MATLAB-based program called detectIR for the perfect and imperfect inverted repeat detection that utilizes complex numbers and vector calculation and allows genome-scale data inputs. A novel algorithm is adopted in detectIR to convert the conventional sequence string comparison in inverted repeat detection into vector calculation of complex numbers, allowing non-complementary pairs (mismatches) in the pairing stem and a non-palindromic spacer (loop or gaps) in the middle of inverted repeats. Compared with existing popular tools, our program performs with significantly higher accuracy and efficiency. Using genome sequence data from HIV-1, Arabidopsis thaliana, Homo sapiens and Zea mays for comparison, detectIR can find lots of inverted repeats missed by existing tools whose outputs often contain many invalid cases. detectIR is open source and its source code is freely available at: https://sourceforge.net/projects/detectir.
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Renal denervation and blood pressure reduction in resistant hypertension: a systematic review and meta-analysis.
Open Heart
PUBLISHED: 01-01-2014
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The objective of this study is to evaluate the efficacy and safety of renal denervation in patients with resistant hypertension.
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Major bleeding after percutaneous coronary intervention and risk of subsequent mortality: a systematic review and meta-analysis.
Open Heart
PUBLISHED: 01-01-2014
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To examine the relationship between periprocedural bleeding complications and major adverse cardiovascular events (MACEs) and mortality outcomes following percutaneous coronary intervention (PCI) and study differences in the prognostic impact of different bleeding definitions.
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Visualized gene network reveals the novel target transcripts Sox2 and Pax6 of neuronal development in trans-placental exposure to bisphenol A.
PLoS ONE
PUBLISHED: 01-01-2014
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Bisphenol A (BPA) is a ubiquitous endocrine disrupting chemical in our daily life, and its health effect in response to prenatal exposure is still controversial. Early-life BPA exposure may impact brain development and contribute to childhood neurological disorders. The aim of the present study was to investigate molecular target genes of neuronal development in trans-placental exposure to BPA.
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YouGenMap: a web platform for dynamic multi-comparative mapping and visualization of genetic maps.
Front Genet
PUBLISHED: 01-01-2014
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Comparative genetic maps are used in examination of genome organization, detection of conserved gene order, and exploration of marker order variations. YouGenMap is an open-source web tool that offers dynamic comparative mapping capability of users' own genetic mapping between 2 or more map sets. Users' genetic map data and optional gene annotations are uploaded, either publically or privately, as long as they follow our template which is available in several standard file formats. Data is parsed and loaded into MySQL relational database to be displayed and compared against users' genetic maps or other public data available on YouGenMap. With the highly interactive GUIs, all public data on YouGenMap are maps available for visualization, comparison, search, filtration and download. YouGenMap web tool is available on the website (http://conifergdb.miamioh.edu/yougenmap) with the source-code repository at (http://sourceforge.net/projects/yougenmap/?source=directory).
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Benefits and harms of extending the duration of dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stents: a meta-analysis.
ScientificWorldJournal
PUBLISHED: 01-01-2014
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The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) is unclear.
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Maternal arsenic exposure and DNA damage biomarkers, and the associations with birth outcomes in a general population from Taiwan.
PLoS ONE
PUBLISHED: 01-01-2014
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Inorganic arsenic (iAs) is an established transplacental agent known to affect fetal development in animal studies. However, iAs has not been adequately studied in the general population with respect to iAs exposure during pregnancy and its impact on the health status of newborns. The aims of this study were to 1) elucidate the association between arsenic exposure and oxidative/methylated DNA damage in pregnant women, and 2) determine the association with birth outcomes. A birth cohort study of 299 pregnant mother-newborn pairs was recruited during 2001-2002 in Taiwan. We collected maternal urine samples during the 3(rd) trimester for measuring iAs and its metabolites. We used high-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC-ICP-MS) for quantifications of the arsenic species. Liquid chromatography/tandem mass spectrometer (LC-MS/MS) was used to measure the 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and N(7)-methylguanosine (N(7)-MeG) DNA damage biomarkers. Birth outcomes were collected to assess the associations with maternal arsenic exposure and the DNA damage biomarkers. Multiple regression analyses showed that maternal urinary iAs had positive associations with the methylated N(7)-MeG (beta?=?0.35, p<0.001) and oxidative 8-oxodG (beta?=?0.24, p<0.001) DNA damage biomarkers, and a decreased one-minute (1-min) Apgar score (beta?=?-0.23, p?=?0.041). Maternal N(7)-MeG was also associated with a decreased 1-min Apgar score (beta?=?-0.25, p?=?0.042). Mutual adjustment for iAs and N(7)-MeG showed an independent and significant prediction for a decreased 1-min Apgar score of iAs (beta?=?-0.28, p?=?0.036). Maternal iAs exposure was associated with both maternal DNA damage and adverse newborn health. Maternal N(7)-MeG levels might be a novel biomarker for monitoring fetal health related to iAs.
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Reevesioside A, a cardenolide glycoside, induces anticancer activity against human hormone-refractory prostate cancers through suppression of c-myc expression and induction of G1 arrest of the cell cycle.
PLoS ONE
PUBLISHED: 01-01-2014
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In the past decade, there has been a profound increase in the number of studies revealing that cardenolide glycosides display inhibitory activity on the growth of human cancer cells. The use of potential cardenolide glycosides may be a worthwhile approach in anticancer research. Reevesioside A, a cardenolide glycoside isolated from the root of Reevesia formosana, displayed potent anti-proliferative activity against human hormone-refractory prostate cancers. A good correlation (r²?=?0.98) between the expression of Na?/K?-ATPase ?? subunit and anti-proliferative activity suggested the critical role of the ?? subunit. Reevesioside A induced G1 arrest of the cell cycle and subsequent apoptosis in a thymidine block-mediated synchronization model. The data were supported by the down-regulation of several related cell cycle regulators, including cyclin D1, cyclin E and CDC25A. Reevesioside A also caused a profound decrease of RB phosphorylation, leading to an increased association between RB and E2F1 and the subsequent suppression of E2F1 activity. The protein and mRNA levels of c-myc, which can activate expression of many downstream cell cycle regulators, were dramatically inhibited by reevesioside A. Transient transfection of c-myc inhibited the down-regulation of both cyclin D1 and cyclin E protein expression to reevesioside A action, suggesting that c-myc functioned as an upstream regulator. Flow cytometric analysis of JC-1 staining demonstrated that reevesioside A also induced the significant loss of mitochondrial membrane potential. In summary, the data suggest that reevesioside A inhibits c-myc expression and down-regulates the expression of CDC25A, cyclin D1 and cyclin E, leading to a profound decrease of RB phosphorylation. G1 arrest is, therefore, induced through E2F1 suppression. Consequently, reevesioside A causes mitochondrial damage and an ultimate apoptosis in human hormone-refractory prostate cancer cells.
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A MATLAB-based tool for accurate detection of perfect overlapping and nested inverted repeats in DNA sequences.
Bioinformatics
PUBLISHED: 11-08-2013
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Palindromic sequences, or inverted repeats (IRs), in DNA sequences involve important biological processes such as DNA-protein binding, DNA replication and DNA transposition. Development of bioinformatics tools that are capable of accurately detecting perfect IRs can enable genome-wide studies of IR patterns in both prokaryotes and eukaryotes. Different from conventional string-comparison approaches, we propose a novel algorithm that uses a cumulative score system based on a prime number representation of nucleotide bases. We then implemented this algorithm as a MATLAB-based program for perfect IR detection. In comparison with other existing tools, our program demonstrates a high accuracy in detecting nested and overlapping IRs.Availability and implementation: The source code is freely available on (http://bioinfolab.miamioh.edu/bioinfolab/palindrome.php) CONTACT: liangc@miamioh.edu or karroje@miamioh.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Cystogram use and outcomes in colorectal surgery involving bladder repair: a clinical audit.
ANZ J Surg
PUBLISHED: 10-07-2013
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The role of routine cystograms after bladder repair during colorectal surgery is unclear so we aimed to evaluate this in our department.
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Discovery of epigenetic regulator I-BET762: lead optimization to afford a clinical candidate inhibitor of the BET bromodomains.
J. Med. Chem.
PUBLISHED: 09-25-2013
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The bromo and extra C-terminal domain (BET) family of bromodomains are involved in binding epigenetic marks on histone proteins, more specifically acetylated lysine residues. This paper describes the discovery and structure-activity relationships (SAR) of potent benzodiazepine inhibitors that disrupt the function of the BET family of bromodomains (BRD2, BRD3, and BRD4). This work has yielded a potent, selective compound I-BET762 that is now under evaluation in a phase I/II clinical trial for nuclear protein in testis (NUT) midline carcinoma and other cancers.
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Bioaerosols from a food waste composting plant affect human airway epithelial cell remodeling genes.
Int J Environ Res Public Health
PUBLISHED: 09-11-2013
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The composting procedure in food waste plants generates airborne bioaerosols that have the potential to damage human airway epithelial cells. Persistent inflammation and repair responses induce airway remodeling and damage to the respiratory system. This study elucidated the expression changes of airway remodeling genes in human lung mucoepidermoid NCI-H292 cells exposed to bioaerosols from a composting plant. Different types of microorganisms were detectable in the composting plant, using the agar culture method. Real-time polymerase chain reaction was used to quantify the level of Aspergillus fumigatus and the profile of remodeling genes. The real-time PCR results indicated that the amount of A. fumigatus in the composting hall was less than 102 conidia. The endotoxins in the field bioaerosols were determined using a limulus amebocyte lysate test. The endotoxin levels depended on the type of particulate matter (PM), with coarse particles (2.5-10 ?m) having higher endotoxin levels than did fine particles (0.5-2.5 ?m). After exposure to the conditioned medium of field bioaerosol samples, NCI-H292 cells showed increased pro-inflammatory interleukin (IL)-6 release and activated epidermal growth factor receptor (EGFR), transforming growth factor (TGF)-?1 and cyclin-dependent kinase inhibitor 1 (p21WAF1/CIP1) gene expression, but not of matrix metallopeptidase (MMP)-9. Airborne endotoxin levels were higher inside the composting hall than they were in other areas, and they were associated with PM. This suggested that airborne bioaerosols in the composting plant contained endotoxins and microorganisms besides A. fumigatus that cause the inflammatory cytokine secretion and augment the expression of remodeling genes in NCI-H292 cells. It is thus necessary to monitor potentially hazardous materials from bioaerosols in food composting plants, which could affect the health of workers.
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Demonstrating Enhanced Throughput of RapidFire Mass Spectrometry through Multiplexing Using the JmjD2d Demethylase as a Model System.
J Biomol Screen
PUBLISHED: 07-29-2013
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Using mass spectrometry to detect enzymatic activity offers several advantages over fluorescence-based methods. Automation of sample handling and analysis using platforms such as the RapidFire (Agilent Technologies, Lexington, MA) has made these assays amenable to medium-throughput screening (of the order of 100,000 wells). However, true high-throughput screens (HTS) of large compound collections (>1 million) are still considered too time-consuming to be feasible. Here we propose a simple multiplexing strategy that can be used to increase the throughput of RapidFire, making it viable for HTS. The method relies on the ability to analyze pooled samples from several reactions simultaneously and to deconvolute their origin using "mass-tagged" substrates. Using the JmjD2d H3K9me3 demethylase as a model system, we demonstrate the practicality of this method to achieve a 4-fold increase in throughput. This was achieved without any loss of assay quality. This multiplex strategy could easily be scaled to give even greater reductions in analysis time.
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A simple 8-point score strongly predicts early outcomes in acute stroke.
Int J Stroke
PUBLISHED: 07-09-2013
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Previous prognostic scoring systems in predicting stroke mortality are complex, require multiple measures that vary with time and failed to produce a simple scoring system.
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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.

How does it work?

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

Video X seems to be unrelated to Abstract Y...

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.