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Find video protocols related to scientific articles indexed in Pubmed.
Association between Reversal in the Expression of Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channel and Age-Related Atrial Fibrillation.
Med. Sci. Monit.
PUBLISHED: 11-19-2014
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Background We compared cardiac electrophysiological indicators and regional expression levels of cardiac hyperpolarization-activated cyclic nucleotide-gated (HCN) channels between adult and aged dogs to identify possible mechanisms of age-related atrial fibrillation. Material and Methods Corrected sinus node recovery time (SNRTc) and effective refractory period (ERP) of the atrium and pulmonary veins were measured in 10 adult (3-6 years old) and 10 aged dogs (>9 years old). Expression levels of HCN2 and HCN4 channel mRNAs and proteins were measured in the sinoatrial node, atrium, and pulmonary veins by real-time PCR and Western blotting. Results Aged dogs exhibited a higher induction rate of atrial fibrillation (AF) in response to electrical stimulation, longer AF duration after induction, longer SNRTc, longer right atrial effective refractory period (AERP), shorter left AERP, and increased AERP dispersion compared to adults. Expression levels of HCN2 and HCN4 channel mRNAs and proteins were lower in the sinoatrial node but higher in the atrium and pulmonary veins of aged dogs. Conclusions Changes in atrial electrophysiological indicators in aged dogs revealed sinoatrial node dysfunction. There was a reversal in the local tissue distribution of HCN2 and HCN4 channel mRNA and protein, a decrease in sinoatrial node expression, and increase in atrial and pulmonary vein expression with age. Changes in atrial electrophysiological characteristics and regional HCN channel expression patterns were associated with the onset and maintenance of age-related atrial fibrillation.
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Spontaneous calf hematoma in a patient with diabetic nephropathy receiving maintenance hemodialysis: A case report and review of the literature.
Hemodial Int
PUBLISHED: 11-19-2014
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We report the outcome of a 52-year-old patient with diabetic nephropathy and receiving maintenance hemodialysis (HD) using low molecular weight heparin (LMWH) as an anticoagulant for 2 years. He presented right lower limb pain accompanied with difficulty in walking for 2 months, and had no history of bleeding tendency or trauma. Physical examination revealed marked swelling and tenderness on his right lower limb. By ultrasound and magnetic resonance imaging (MRI) diagnoses, the calf hematoma was diagnosed and identified with venous thrombosis. Following treatment with heparin-free HD, the swelling regressed and pain subsided, and a follow-up MRI showed complete dissolution of hematoma. However, similar symptoms recurred in the right upper limb after 2 months without any predisposition, he was just placed on HD with LMWH, and symptoms regressed following the aforementioned therapy. This suggests that HD patients, especially with diabetic nephropathy having extremity hematoma, should be watched for the development of spontaneous hemorrhage that can be differentially diagnosed by imaging tests, such as MRI, and can be effectively treated with heparin-free HD.
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[A clinical trial of ultrasound-guided facet joint block in the lumbar spine to treat facet joint related low back pain].
Sichuan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 10-08-2014
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To determine the feasibility and clinical efficacy of ultrasound-guided facet joint injection and nerve block in lumbar facet joint for the treatment of facet-joint related low back pain.
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Disruption of Renal Tubular Mitochondrial Quality Control by Myo-Inositol Oxygenase in Diabetic Kidney Disease.
J. Am. Soc. Nephrol.
PUBLISHED: 10-02-2014
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Diabetic kidney disease (DKD) is associated with oxidative stress and mitochondrial injury. Myo-inositol oxygenase (MIOX), a tubular-specific enzyme, modulates redox imbalance and apoptosis in tubular cells in diabetes, but these mechanisms remain unclear. We investigated the role of MIOX in perturbation of mitochondrial quality control, including mitochondrial dynamics and autophagy/mitophagy, under high-glucose (HG) ambience or a diabetic state. HK-2 or LLC-PK1 cells subjected to HG exhibited an upregulation of MIOX accompanied by mitochondrial fragmentation and depolarization, inhibition of autophagy/mitophagy, and altered expression of mitochondrial dynamic and mitophagic proteins. Furthermore, dysfunctional mitochondria accumulated in the cytoplasm, which coincided with increased reactive oxygen species generation, Bax activation, cytochrome C release, and apoptosis. Overexpression of MIOX in LLC-PK1 cells enhanced the effects of HG, whereas MIOX siRNA or d-glucarate, an inhibitor of MIOX, partially reversed these perturbations. Moreover, decreasing the expression of MIOX under HG ambience increased PTEN-induced putative kinase 1 expression and the dependent mitofusin-2-Parkin interaction. In tubules of diabetic mice, increased MIOX expression and mitochondrial fragmentation and defective autophagy were observed. Dietary supplementation of d-glucarate in diabetic mice decreased MIOX expression, attenuated tubular damage, and improved renal functions. Notably, d-glucarate administration also partially attenuated mitochondrial fragmentation, oxidative stress, and apoptosis and restored autophagy/mitophagy in the tubular cells of these mice. These results suggest a novel mechanism linking MIOX to impaired mitochondrial quality control during tubular injury in the pathogenesis of DKD and suggest d-glucarate as a potential therapeutic agent for the amelioration of DKD.
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Nephrotic syndrome of minimal change disease following exposure to mercury-containing skin-lightening cream.
Ann Saudi Med
PUBLISHED: 10-01-2014
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A 28-year-old female suffered from nephrotic syndrome after a long-term use of mercury-containing, skin-lightening cream. The blood and urinary mercury content of this patient increased with use. Renal biopsy showed minimal change disease. Her symptoms were relieved 6 months after discontinuing use of the cream and receiving sodium dimercaptosulfonate and glucocorticosteroid treatments. Proteinuria disappeared, and blood and urinary mercury levels returned to normal. Previous reports of nephrotic syndrome caused by mercury-containing, skin-lightening creams have mostly been identified as be.ing due to membranous nephropathy. Minimal change disease has been reported in a few case reports published in the English language. Here we report a case of nephrotic syndrome with minimal change disease following exposure to a mercury-containing, skin-lightening cream. We also reviewed relevant published reports to summarize clinical features and treatments and to explore the possible mechanisms involved.
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High glucose-induced Galectin-1 in human podocytes implicates the involvement of Galectin-1 in diabetic nephropathy.
Cell Biol. Int.
PUBLISHED: 09-02-2014
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The diabetic milieu is believed to change the activity, or result in damage of podocytes-a key component of the glomerular filtration barrier and known to secrete matrix for glomerular basement membrane. This in turn contributes to diabetic nephropathy. However, how podocyte dysfunction is triggered in diabetic nephropathy remains ambiguous. Galectin-1 belongs to Galectin family that bind to ?-galactoside residues of glycosylated proteins. We explored whether Galectin-1 is dysregulated in diabetic nephropathy using three different techniques, namely real-time polymerase chain reaction, western blotting, and immunofluorescent staining, to follow the expression of Galectin-1 under high glucose levels in podocytes. High glucose consistently induced Galectin-1 expression. Immunohistochemistry using a Galectin-1-specific antibody also showed elevated Galectin-1 in renal tissues of diabetic patients with manifestation of nephropathy, indicating a correlation of Galectin-1 overexpression with diabetic nephropathy. Upregulation of Galectin-1 is associated with loss of podocin, which is important for the physiological function of podocytes and decreases in the renal tissues of diabetic nephropathy. Increased Galectin-1 is a causal event for the high glucose-induced loss of podocin, since silencing Galectin-1 in podocytes increased podocin expression in the presence of 25?mM glucose. Thus expression of Galectin-1 in diabetic nephropathy may serve as a marker and contribute to disease progression by interfering with podocin expression.
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Significance of serum procalcitonin as biomarker for detection of bacterial peritonitis: a systematic review and meta-analysis.
BMC Infect. Dis.
PUBLISHED: 08-22-2014
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Bacterial peritonitis is serious disease and remains a diagnostic challenge for clinicians. Many studies have highlighted the potential usefulness of procalcitonin (PCT) for identification of bacterial peritonitis, however, the overall diagnostic value of PCT remains unclear. Therefore, we performed a meta-analysis to assess the accuracy of PCT for detection of bacterial peritonitis.
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Bio-mimetic Nanostructure Self-assembled from Au@Ag Heterogeneous Nanorods and Phage Fusion Proteins for Targeted Tumor Optical Detection and Photothermal Therapy.
Sci Rep
PUBLISHED: 08-20-2014
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Nanomaterials with near-infrared (NIR) absorption have been widely studied in cancer detection and photothermal therapy (PTT), while it remains a great challenge in targeting tumor efficiently with minimal side effects. Herein we report a novel multifunctional phage-mimetic nanostructure, which was prepared by layer-by-layer self-assembly of Au@Ag heterogenous nanorods (NRs) with rhodamine 6G, and specific pVIII fusion proteins. Au@Ag NRs, first being applied for PTT, exhibited excellent stability, cost-effectivity, biocompatibility and tunable NIR absorption. The fusion proteins were isolated from phage DDAGNRQP specifically selected from f8/8 landscape phage library against colorectal cancer cells in a high-throughput way. Considering the definite charge distribution and low molecular weight, phage fusion proteins were assembled on the negatively charged NR core by electrostatic interactions, exposing the N-terminus fused with DDAGNRQP peptide on the surface. The fluorescent images showed that assembled phage fusion proteins can direct the nanostructure into cancer cells. The nanostructure was more efficient than gold nanorods and silver nanotriangle-based photothermal agents and was capable of specifically ablating SW620 cells after 10?min illumination with an 808?nm laser in the light intensity of 4?W/cm(2). The prepared nanostructure would become an ideal reagent for simutaneously targeted optical imaging and PTT of tumor.
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Star-shaped poly(L-lactide)-b-poly(lactobionamidoethyl methacrylate) with porphyrin core: synthesis, self-assembly, singlet oxygen research and recognition properties.
J Biomater Sci Polym Ed
PUBLISHED: 08-20-2014
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Star-shaped porphyrin-cored poly(L-lactide)-b-poly(lactobionamidoethyl methacrylate) block copolymers (SPPLA-b-PLAMA) were synthesized via RAFT of unprotected Lactobionamidoethyl methacrylate (LAMA) in 1-methyl-2-pyrrolidinone (NMP) solution at 70 °C. The structure of this as-synthesized SPPLA-b-PLAMA block copolymer was thoroughly studied by nuclear magnetic resonance spectroscopy, gel permeation chromatography (GPC), and Fourier transforms infrared. Moreover, under the irradiation, such SPPLA-b-PGAMA copolymer exhibits efficient singlet oxygen generation (0.17) and indicates high fluorescence quantum yields (0.20). Notably, with UV-vis investigation, SPPLA-b-PLAMA showed a very specific recognition with RCA120 lectin. This will not only provide potentially prophyrin-cored star-shaped SPPLA-b-PLAMA block copolymers for targeted photodynamic therapy, but also improve the physical, biodegradation, biocompatibility properties of PLA-based biomaterials.
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[Effect of high-mobility group box 1 on the proliferation of primary neural stem cells in vitro].
Sheng Li Xue Bao
PUBLISHED: 08-19-2014
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The cell counting kit-8 (CCK-8) proliferation assay and diameter measure of neurospheres were used to investigate the effect of high-mobility group box 1 (HMGB1) on proliferation of primary rat neural stem cells (NSCs) in vitro, and c-Jun N-terminal protein kinase (JNK) potent inhibitor SP600125 was used to study the mechanism. The results demonstrated that HMGB1 significantly increased CCK-8 absorbance values and neurosphere diameters at concentrations of 1 and 10 ng/mL at 48 h and 72 h (P < 0.05), and the other HMGB1 concentration groups (0.01, 0.1, 100 ng/mL) showed no significant difference, compared with control group (P > 0.05). HMGB1 at 10 ng/mL significantly increased the NSCs proliferation accompanied by the rising of phosphorylated JNK levels (P < 0.01), and 10 ?mol/L SP600125 prevented these effects in HMGB1-cultured NSCs (P < 0.01). In conclusion, low concentration of HMGB1 (1-10 ng/mL) can increase NSCs proliferation, which may play a role by promoting JNK phosphorylation.
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Rapid diagnosis of childhood pulmonary tuberculosis by Xpert MTB/RIF assay using bronchoalveolar lavage fluid.
Biomed Res Int
PUBLISHED: 08-06-2014
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In order to evaluate the diagnostic accuracy of the Xpert MTB/RIF assay on childhood pulmonary tuberculosis (PTB) using bronchoalveolar lavage fluid (BALF), we evaluated the sensitivity, specificity, positive predictive value, and negative predictive value of Xpert MTB/RIF assay using BALF in comparison with acid-fast bacilli (AFB) microscopy and Mycobacterium tuberculosis (MTB) culture for diagnosing childhood PTB using Chinese "composite clinical reference standard" (CCRS) as reference standard. Two hundred fifty-five children with suspected PTB were enrolled at Beijing Children's Hospital from September 2010 to July 2013. Compared with Chinese CCRS, the sensitivity of AFB microscopy, MTB culture, and Xpert MTB/RIF assay was 8.4%, 28.9%, and 53.0%, respectively. The specificity of three assays was all 100%. Xpert MTB/RIF assay could detect 33.9% of cases with negative MTB culture, and 48.7% of cases with negative AFB microscopy. Younger age (<3 years), absence of BCG scar, and contact with TB patient were found significantly associated with a positive result of Xpert MTB/RIF assay. In conclusion, Xpert MTB/RIF assay using BALF can assist in diagnosing childhood PTB much faster when fiberoptic bronchoscopy is necessary according to the chest radiograph.
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Oxygen free radicals and mitochondrial signaling in oligospermia and asthenospermia.
Mol Med Rep
PUBLISHED: 07-29-2014
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The aim of this study was to investigate the roles of oxygen free radicals and mitochondrial signaling in semen disorders, in particular, how this induces low concentrations and reduced motility of sperm. Ejaculate samples were obtained from 120 young adult males (mean age, 28.7±5.3 years) with normal semen (n=30), oligospermia (n=30), asthenospermia (n=30) and oligoasthenozoospermia (n=30). The malondialdehyde (MDA) content, total superoxide dismutase (T?SOD) activity and glutathione peroxidase (GSH?Px) activity of the sperm samples were determined by enzymatic assays. Mitochondrial membrane potential (MMP) was determined by flow cytometric detection of accumulated membrane?permeable JC?1 fluorescent dye. The mRNA and protein expression levels of apoptosis-associated genes [Bcl?2, Bax, cytochrome c (Cyt C) and caspase-3] were measured by quantitative polymerase chain reaction and western blotting. Intergroup differences were evaluated by Student's t?test. The sperm samples from all semen disorder groups exhibited significantly lower T?SOD content and GSH?Px activity (all P<0.05 versus normal sperm), and the extent of reduction revealed a disorder-associated trend (asthenospermia < oligospermia ? oligoasthenozoospermia). By contrast, the semen disorder groups had significantly higher MDA content (all P<0.05 versus normal sperm); the extent of this increase also revealed a disorder-associated trend (asthenospermia > oligospermia ? oligoasthenozoospermia). The sperm from patients with semen disorders also exhibited significantly lower MMP than normal sperm, as evidenced by lower mean ratios of JC?1+ sperm per group. The semen disorder groups had significantly higher Bax, Cyt C and caspase-3 mRNA and protein expression levels in the sperm samples, but significantly lower levels of Bcl?2 (all P<0.05 versus normal sperm). However, only the extent of increases in Cyt C and caspase-3 exhibited a disorder-associated trend (oligospermia > asthenospermia). In conclusion, oxygen free radicals may be involved in reduced sperm concentration and motility, possibly through effects on the mitochondrial apoptotic signaling pathway. Perturbed mitochondrial release of Cyt C may be the distinguishing molecular feature between oligospermia and asthenospermia.
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Decomposition and extraction: a new framework for visual classification.
IEEE Trans Image Process
PUBLISHED: 06-12-2014
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In this paper, we present a novel framework for visual classification based on hierarchical image decomposition and hybrid midlevel feature extraction. Unlike most midlevel feature learning methods, which focus on the process of coding or pooling, we emphasize that the mechanism of image composition also strongly influences the feature extraction. To effectively explore the image content for the feature extraction, we model a multiplicity feature representation mechanism through meaningful hierarchical image decomposition followed by a fusion step. In particularly, we first propose a new hierarchical image decomposition approach in which each image is decomposed into a series of hierarchical semantical components, i.e, the structure and texture images. Then, different feature extraction schemes can be adopted to match the decomposed structure and texture processes in a dissociative manner. Here, two schemes are explored to produce property related feature representations. One is based on a single-stage network over hand-crafted features and the other is based on a multistage network, which can learn features from raw pixels automatically. Finally, those multiple midlevel features are incorporated by solving a multiple kernel learning task. Extensive experiments are conducted on several challenging data sets for visual classification, and experimental results demonstrate the effectiveness of the proposed method.
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LIMK1 is involved in the protective effects of bone morphogenetic protein 6 against amyloid-?-induced neurotoxicity in rat hippocampal neurons.
J. Alzheimers Dis.
PUBLISHED: 06-07-2014
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Bone morphogenetic protein 6 (BMP6) has neuroprotective effects against various neuronal injuries, but its effect on amyloid-? (A?)-induced neurotoxicity remains unclear. We exposed rat hippocampal neurons to different concentrations of A?25-35 to induce neurotoxicity, and then treated cells with BMP6 to assess the neuroprotective effects. In vivo, we bilaterally injected A?1-40 into basal forebrain to simulate the neuropathological process of Alzheimer's disease (AD), and explored changes in the expression of BMP6 and LIMK1. Our data demonstrated that BMP6 prevented apoptosis induced by a high dose of A?25-35, and inhibited rod formation induced by low dose of A?25-35 in hippocampal neurons. Forebrain injection of A?1-40 led to a significant downregulation of BMP6, and inactivation of LIMK1 pathway in basal forebrain, whereas the opposite changes were observed in hippocampus. Our results suggest that BMP6 has neuroprotective effects against A?25-35. The BMP6 and LIMK1 pathways may have different expression patterns at different stages of AD, and be self-regulating via a negative feedback mechanism between different brain regions.
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High-resolution genome-wide analysis identified recurrent genetic alterations in NK/T-cell lymphoma, nasal type, which are associated with disease progression.
Med. Oncol.
PUBLISHED: 06-06-2014
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Extranodal NK/T-cell lymphoma, nasal type, is an aggressive mature NK-cell/T-cell lymphoma. Using array-based comparative genomic hybridization (array CGH) assays, we screened genomic alterations and potential candidate genes implicated in pathogenesis, progression, and prognosis. Our array CGH analysis detected an average of 83 chromosomal aberrations in 13 cases, ranging from 0 to 387. There were 177 recurrent chromosomal gains and 35 recurrent losses. Eleven gains and 14 losses were detected in more than 30 % of the cases, including gains of 3q26.1, 7q34, and 8q24.3 and losses of 15q24.2, 19q13.32, 5p13.2, and 14q21.1. The most common losses were observed in the 15q24.2 and 19q13.32 regions (9 cases, 69.2 %, respectively). Loss of 8p11.23 was associated with significant poor survival (P = 0.024). Five out of six patients with the loss of 8p11.23 died within 8 months after initial diagnosis with a median survival of 6 months. Several candidate genes were identified in the regions with frequent chromosomal aberrations, including ADAM3A (8p11.23) and GSTT1 (22q11.23). In summary, our studies detected recurrent genetic alterations in NK/T-cell lymphoma, some of which are associated with adverse prognosis. Some candidate genes in these regions may be involved in the pathogenesis and disease progression.
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Cholesteryl-modification of a glucomannan from Bletilla striata and its hydrogel properties.
Molecules
PUBLISHED: 05-25-2014
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A glucomannan-type polysaccharide, named BSP, was obtained from the tubers of Bletilla striata by ultrasonic-assisted extraction, ethanol precipitation, deproteination and gel-permeation chromatography. HPLC analysis revealed that BSP contained mannose and glucose in the molar ratio of 3.5:1. Its molecular weight (Mw) was estimated to be 20 kDa. Methylation analysis, FT-IR and NMR analyses indicated that BSP consisted of (1?4)-linked ?-D-glucopyranosyl residues and (1?4)-linked ?-D-mannopyranosyl residues. Cholesteryl succinate was linked to BSP to make it more amphiphilic and the degree of substitution of cholesteryl succinate-BSP was 3.2%. The critical micelle concentration of modified BSP was 0.001 mg/mL, suggesting it could self-assemble into nanoparticles in aqueous solution.
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Polyketide and benzopyran compounds of an endophytic fungus isolated from Cinnamomum mollissimum: biological activity and structure.
Asian Pac J Trop Biomed
PUBLISHED: 05-22-2014
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To study bioactivity and compounds produced by an endophytic Phoma sp. fungus isolated from the medicinal plant Cinnamomum mollissimum.
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[Estimation of water clarity in offshore marine areas based on modified semi-analysis spectra model].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 05-15-2014
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The main objectives of the research described in the present paper are to develop a semi-analysis model of water clarity for case 2 waters without inputting the absorption and scattering coefficient, which are not easy to be obtained for offshore marine areas so far. Based on the Zsd (Secchi depth)inversion theory, a simple semi-analysis spectra model was established for offshore seawater clarity by analyzing the relationship between vertical diffuse attenuation coefficient K(d) (490) and the beam attenuation coefficient c(490) with remote sensing reflectance. This semi-analysis spectra model needed two band reflectance ratios on- ly, while tidal correction was produced for this model to improve the precision of the retrieving results. The semi-analysis spectra model was applied to ASD hyperspectral reflectance data measured in the Pearl River Estuary Ecological Zone (October 21, 23, 2012, November 2, 2012; N=20) and the Xuwen Coral Reef Protection Zone (January 13, 14, 2013, N=25) which covered different water body of tidal times and different pollution sources. The results indicated that the changing tendency of predicted values was consistent with the synchronous measurement values after comparing them. However, water clarity calculated by the ASD hyperspectral reflectance measured in spring tidal time, generated 0. 4 m deviation compared with in-situ water clarity, while water clarity calculated by the ASD hyperspectral reflectance measured in neap tidal time is close to the in-situ water clarity. So the tidal correction coefficient of 0.4 was further applied for the model. After modification, the coefficient of determination between the inversed and measured water clarity was 0. 663, the average absolute error was 0. 14 m and the average relative error was 19.5%. Research demonstrated that this semi-analysis inversion algorithm just needs two band reflectance ratio to complete the inversion of water clarity, which is simple and works relatively well for lower clarity (less than 2 meters) waters compared to He' (2004) and Doron' (2011) algorithms.
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PKC? Promotes High Glucose Induced Renal Tubular Oxidative Damage via Regulating Activation and Translocation of p66Shc.
Oxid Med Cell Longev
PUBLISHED: 05-11-2014
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Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). Renal tubular injury by overproduction of ROS in mitochondria plays a critical role in the pathogenesis of DKD. Evidences have shown that p66Shc was involved in renal tubular injury via mitochondrial-dependent ROS production pathway, but little is known about the upstream signaling of p66Shc that leads to tubular oxidative damage under high glucose conditions. In this study, an increased PKC? and p66Shc activation and ROS production in renal tissues of patients with diabetic nephropathy were seen and further analysis revealed a positive correlation between the tubulointerstitial damage and p-PKC?, p-p66Shc, and ROS production. In vitro, we investigated the phosphorylation and activation of p66Shc and PKC? during treatment of HK-2 cells with high glucose (HG). Results showed that the activation of p66Shc and PKC? was increased in a dose- and time-dependent manner, and this effect was suppressed by Rottlerin, a pharmacologic inhibitor of PKC?. Moreover, PKC? siRNA partially blocked HG-induced p66Shc phosphorylation, translocation, and ROS production in HK-2 cells. Taken together, these data suggest that activation of PKC? promotes tubular cell injury through regulating p66Shc phosphorylation and mitochondrial translocation in HG ambient.
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Brain metabolite alterations demonstrated by proton magnetic resonance spectroscopy in diabetic patients with retinopathy.
Magn Reson Imaging
PUBLISHED: 04-25-2014
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Due to the homology between retinal and cerebral microvasculatures, retinopathy is a putative indicator of cerebrovascular dysfunction. This study aimed to detect metabolite changes of brain tissue in type 2 diabetes mellitus (T2DM) patients with diabetic retinopathy (DR) using proton magnetic resonance spectroscopy ((1)H-MRS). Twenty-nine T2DM patients with DR (DR group), thirty T2DM patients without DR (DM group) and thirty normal controls (NC group) were involved in this study. Single-voxel (1)H-MRS (TR: 2000ms, TE: 30ms) was performed at 3.0T MRI/MRS imager in cerebral left frontal white matter, left lenticular nucleus, and left optic radiation. Our data showed that NAA/Cr ratios of the DR group were significantly lower than those of the DM group in the frontal white matter and optic radiation. In the lenticular nucleus, MI/Cr ratios were significantly higher in the DM group than those in the NC group, while MI/Cr ratios were significantly lower in the DR group than those in the DM group. In the frontal white matter, NAA/Cho ratios were found to be decreased in the DR group as compared to the NC group. Additionally, our finding indicated that NAA/Cr ratios were negatively associated with DR severity in both the frontal white matter and optic radiation. A decrease in NAA indicated neuronal loss and the likely explanation for a decrease in MI was glial loss. In conclusion, we inferred that cerebral neurons and glia cells were damaged in patients with DR. Our data support that DR is associated with brain tissue damage.
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[Tubulointerstitial nephritis antigen expression in chronic kidney disease and its clinical significance].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 04-16-2014
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To explore tubulointerstitial nephritis antigen (TIN-ag) expression of chronic kidney disease (CKD) patients' renal tissue and the correlation to clinical phenotype.
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Relationship between c-reactive protein and the asymmetric dimethylarginine-induced endothelial dysfunction pathway in vasospastic angina.
Pharmazie
PUBLISHED: 04-11-2014
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Vasospastic angina (VSA) is a special form of atherosclerotic disease. There is some evidence suggesting a relationship between inflammation and VSA. We sought to demonstrate the relationship between high-sensitivity c-reactive protein (hs-CRP), a sensitive marker of inflammation, and the asymmetric dimethylarginine (ADMA)-induced endothelial dysfunction pathway in patients with VSA. We studied 68 patients who were diagnosed with VSA with typical symptoms and had a positive hyperventilation test. We determined plasma levels of hs-CRP, ADMA, brachial flow-mediated dilation (FMD), and other biochemical parameters in these 68 VSA patients and 68 age-matched non-VSA subjects. Multivariate logistic regression indicated that hs-CRP (OR, 3.81 P < 0.001) and a history of smoking (OR, 3.06 P = 0.008) were independently associated with the incidence of VSA. Moreover, we found that CRP was directly related to ADMA (r = 0.69, P < 0.001) but inversely related to brachial FMD (r = -0.66, P < 0.001) in patients with VSA. Additionally, ADMA was inversely related to brachial FMD (r = -0.75, P < 0.001) in patients with VSA. These results indicate that there is a relationship between CRP and the ADMA-induced endothelial dysfunction pathway in patients with VSA. Anti-inflammatory agents may be a potential strategy for the treatment of endothelial dysfunction in VSA.
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Prognostic significance of heart rate turbulence parameters in patients with chronic heart failure.
BMC Cardiovasc Disord
PUBLISHED: 04-03-2014
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This study is aimed to evaluate the clinical significance of heart rate turbulence (HRT) parameters in predicting the prognosis in patients with chronic heart failure (CHF).
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Two new natural products from Croton kongensis Gagnep.
Nat. Prod. Res.
PUBLISHED: 04-02-2014
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A new diterpenoid, 14?-hydroxy-3-oxo-ent-kaur-16-ene (1), and a new nor-lignan, 8S-( - )-8-(4-hydroxy-3-methoxybenzoyl)-dihydrofuran-8(8'H)-one (4), along with five known compounds were isolated from the twigs and leaves of Croton kongensis Gagnep. Their isolations were clarified and structures were elucidated by the extensive spectroscopic analyses, especially 2D NMR experiments.
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MAPK phosphotase 5 deficiency contributes to protection against blood-stage Plasmodium yoelii 17XL infection in mice.
J. Immunol.
PUBLISHED: 03-14-2014
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Cell-mediated immunity plays a crucial role in the development of host resistance to asexual blood-stage malaria infection. However, little is known of the regulatory factors involved in this process. In this study, we investigated the impact of MAPK phosphotase 5 (MKP5) on protective immunity against a lethal Plasmodium yoelii 17XL blood-stage infection using MKP5 knockout C57BL/6 mice. Compared with wild-type control mice, MKP5 knockout mice developed significantly lower parasite burdens with prolonged survival times. We found that this phenomenon correlated with a rapid and strong IFN-?-dependent cellular immune response during the acute phase of infection. Inactivation of IFN-? by the administration of a neutralizing Ab significantly reduced the protective effects in MKP5 knockout mice. By analyzing IFN-? production in innate and adaptive lymphocyte subsets, we observed that MKP5 deficiency specifically enhanced the IFN-? response mediated by CD4+ T cells, which was attributable to the increased stimulatory capacity of splenic CD11c+ dendritic cells. Furthermore, following vaccination with whole blood-stage soluble plasmodial Ag, MKP5 knockout mice acquired strongly enhanced Ag-specific immune responses and a higher level of protection against subsequent P. yoelii 17XL challenge. Finally, we found the enhanced response mediated by MKP5 deficiency resulted in a lethal consequence in mice when infected with nonlethal P. yoelii 17XNL. Thus, our data indicate that MKP5 is a potential regulator of immune resistance against Plasmodium infection in mice, and that an understanding of the role of MKP5 in manipulating anti-malaria immunity may provide valuable information on the development of better control strategies for human malaria.
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Small interfering RNA targeting ILK inhibits EMT in human peritoneal mesothelial cells through phosphorylation of GSK?3?.
Mol Med Rep
PUBLISHED: 03-11-2014
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Emerging evidence has suggested that human peritoneal mesothelial cells (HPMCs) undergo epithelial?mesenchymal transition (EMT) in peritoneal fibrosis. The molecular mechanisms underlying peritoneal fibrosis and the key molecules involved are not yet fully elucidated. In order to enhance the understanding of peritoneal fibrosis, the present study investigated the roles of integrin?linked kinase (ILK) and glycogen synthase kinase 3? (GSK?3?) in high glucose?induced phenotypic alterations of HPMCs. It was observed that HPMCs exhibited a cobblestone morphology under normal glucose conditions, whereas under high glucose conditions they had a spindle morphology. Additionally, under high glucose conditions it was found that E?cadherin expression was decreased and vimentin expression was increased in HPMCs, suggesting HPMCs underwent EMT. ILK expression in high glucose conditions was also increased in a dose? and time?dependent manner. The role of ILK in the induction of EMT in HPMCs was further investigated using small interfering RNA (siRNA). Following knockdown of ILK gene expression by siRNA, low vimentin expression as well as high E?cadherin expression were observed, suggesting that EMT was inhibited. ILK?knockdown also inhibited phosphorylation of GSK?3?. These results indicate that ILK?knockdown inhibits EMT of HPMCs through inhibition of GSK?3? phosphorylation. These findings suggest that ILK may be used as a novel diagnostic and therapeutic target for HPMC fibrosis in the future.
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[Clinical characteristics and prognosis analysis of patients with LMP-1 positive Hodgkin's lymphoma after EBV infection].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 03-07-2014
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This study was purposed to investigate the expression of latent membrane protein 1 (LMP-1) and CD68 in Hodgkin's lymphoma (HL) patients with EB virus infection and to analyze the relation of LMP-1 expression and CD68(+) tumor-associated macrophage count with clinical features and prognosis of HL patients. The expression of LMP1 and count of CD68(+) TAM were detected by immunohistochemical staining in tissue specimens of 72 HL patients; their correlation with clinical features and prognosis of HL patients was analyzed by using statistical method. The results showed that among tissue specimens of 72 HL patients, the positive rate of LMP-1 expression was 18.1% (13/72), the CD68(+) TAM count was more higher in LMP-1 positive expression [250 of CD68(+) TAM/high power field (hpf) is used as demarcation point] (P = 0.003). The statistical analysis showed that the LMP-1 positive expression was more observed in mixed type HL patients (P = 0.000); the positive rate of LMP-1 expression was much high in HL patients with albumin <40 g/L and age ? 45 years (P < 0.05). There was no relation of LMP-1 expression and CD68(+) TAM count with the short term therapeutic efficacy of HL patients, but the overall survival time of LMP-1 positive patients among patients followed-up for ? 5 years was short (P < 0.05). Moveover, no correlation of CD68(+) TAM count with the overall survival time of HL patients was found. It is concluded that the high count of CD68(+) TAM is more observed in LMP-1 positive expression of HL tissue, the LMP-1 expression states relates both with the pathological types, age and albumin level of patient with HL. The HL patients with LMP-1 positive expression have poor prognosis, suggesting that LMP-1 may be a new prognostic marker for HL patients.
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High-mobility group box 1 released from astrocytes promotes the proliferation of cultured neural stem/progenitor cells.
Int. J. Mol. Med.
PUBLISHED: 03-04-2014
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Astrocytes are major components of the adult neurogenic niche and play a crucial role in regulating neural stem cell proliferation and differentiation. Following brain injury, astrocytes become reactive and release high-mobility group box 1 (HMGB1), which plays a crucial role in the inflammatory process. However, although it has been reported that HMGB1 promotes neural stem/progenitor cell (NS/PC) proliferation in the developing brain, whether HMGB1 released by reactive astrocytes regulates NS/PC proliferation remains unknown. In this study, we aimed to investigate whether HMGB1 released from reactive astrocytes enhances NS/PC proliferation and to elucidate the possible mechanisms involved in this process. To evaluate the effects of HMGB1 on NS/PC proliferation, NS/PCs were cultured in HMGB1 culture medium and astrocyte-conditioned medium with or without reactive astrocyte-derived HMGB1 by RNA interference (RNAi). To explore the possible mechanisms, the HMGB1 receptor for advanced glycation endproducts (RAGE) in the NS/PCs was blocked with anti-RAGE antibody, and c-Jun N-terminal protein kinase (JNK) in the NS/PCs was inhibited using the potent JNK inhibitor, SP600125. Our results suggested that HMGB1 released from reactive astrocytes promoted NS/PC proliferation in vitro, and the blockade of RAGE or the inhibition of the JNK signaling pathway in the NS/PCs prevented the HMGB1-induced NS/PC proliferation. Our findings demonstrated that HMGB1 released by reactive astrocytes promoted NS/PC proliferation by binding RAGE and enhancing the phosphorylation of the JNK signaling pathway. These findings support a previously described mechanism of a crosstalk between astrocytes and NS/PCs, and suggest that reactive astrocyte-derived HMGB1 plays an important role in the repair of the central nervous system following brain injury.
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Effects of vitamin E-coated dialyzer on oxidative stress and inflammation status in hemodialysis patients: a systematic review and meta-analysis.
Ren Fail
PUBLISHED: 02-27-2014
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Vitamin E-coated dialyzer may have an effect on oxidative stress and inflammation status in hemodialysis (HD) patients. Therefore, we performed a systematic review to assess the anti-oxidation and anti-inflammatory effects of vitamin E-coated dialyzer in HD patients.
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Modulation of angiotensin II-induced inflammatory cytokines by the Epac1-Rap1A-NHE3 pathway: implications in renal tubular pathobiology.
Am. J. Physiol. Renal Physiol.
PUBLISHED: 02-19-2014
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Besides the glomerulus, the tubulointerstitium is often concomitantly affected in certain diseases, e.g., diabetic nephropathy, and activation of the renin-angiotensin system, to a certain extent, worsens its outcome because of perturbations in hemodynamics and possibly tubuloglomerular feedback. Certain studies suggest that pathobiology of the tubulointerstitium is influenced by small GTPases, e.g., Rap1. We investigated the effect of ANG II on inflammatory cytokines, while at the same time focusing on upstream effector of Rap1, i.e., Epac1, and some of the downstream tubular transport molecules, i.e., Na/H exchanger 3 (NHE3). ANG II treatment of LLC-PK1 cells decreased Rap1a GTPase activity in a time- and dose-dependent manner. ANG II treatment led to an increased membrane translocation of NHE3, which was reduced with Epac1 and PKA activators. ANG II-induced NHE3 translocation was notably reduced with the transfection of Rap1a dominant positive mutants, i.e., Rap1a-G12V or Rap1a-T35A. Transfection of cells with dominant negative Rap1a mutants, i.e., Rap1a-S17A, or Epac1 mutant, i.e., EPAC-?cAMP, normalized ANG II-induced translocation of NHE3. In addition, ANG II treatment led to an increased expression of inflammatory cytokines, i.e., IL-1?, IL-6, IL-8, and TNF-?, which was reduced with Rap1a-G12V or Rap1a-T35A transfection, while it reverted to previous comparable levels following transfection of Rap1a-S17A or EPAC-?cAMP. ANG II-induced expression of cytokines was reduced with the treatment with NHE3 inhibitor S3226 or with Epac1 and PKA activators. These data suggest that this novel Epac1-Rap1a-NHE3 pathway conceivably modulates ANG II-induced expression of inflammatory cytokines, and this information may yield the impetus for developing strategies to reduce tubulointertstitial inflammation in various renal diseases.
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Effect of L-carnitine therapy on patients in maintenance hemodialysis: a systematic review and meta-analysis.
J. Nephrol.
PUBLISHED: 02-19-2014
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L-Carnitine has been used as adjuvant therapy in hemodialysis (HD) patients for many years. However, there is controversy whether L-carnitine supplementation is beneficial. Therefore we performed a meta-analysis of randomized controlled trials (RCTs) to assess the effect of L-carnitine on HD patients.
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One family cluster of avian influenza A(H7N9) virus infection in Shandong, China.
BMC Infect. Dis.
PUBLISHED: 02-12-2014
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The first case of human infection with avian influenza A (H7N9) virus was identified in March, 2013 and the new H7N9 virus infected 134 patients and killed 45 people in China as of September 30, 2013. Family clusters with confirmed or suspected the new H7N9 virus infection were previously reported, but the family cluster of H7N9 virus infection in Shandong Province was first reported.
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Self-renewal of hepatoblasts under chemically defined conditions by reiterative growth factor and chemical screening.
Hepatology
PUBLISHED: 02-11-2014
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Tissue-specific stem/progenitor cells are essential to mediate organogenesis and tissue homeostasis. In addition, these cells have attracted significant interests for their therapeutic potentials. However, it remains challenging to expand most types of these cells in vitro. In this study, we devised a screening strategy aimed at identifying growth factors and small molecules that can sustain self-renewal of mouse hepatoblasts. This approach began with a defined basal condition, on top of which collections of growth factors and bioactive small molecules were screened for maintaining self-renewal of primary hepatoblasts. The initially identified proteins and small molecules were then combined in the basal media for subsequent screening to identify additional molecules that can synergistically promote hepatoblast self-renewal. This strategy was performed reiteratively to eventually define a small molecule and growth factor cocktail, including epidermal growth factor, glycogen synthase kinase 3 inhibitor, transforming growth factor ? receptor inhibitor, lysophosphatidic acid and sphingosine 1-phosphate, that was sufficient to sustain long-term self-renewal of the murine hepatoblasts under chemically defined condition. These expanded hepatoblasts retain the ability to respond to liver developmental cues and produce functional hepatocytes and form bile duct-like structures. Conclusion: Our work established a chemically defined condition that allows long-term expansion of hepatoblasts, improved our understanding of hepatoblast self-renewal, and highlights the power of phenotypic screening to enable self-renewal of somatic stem/progenitor cells. (Hepatology 2014;).
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Oxygen glucose deprivation/reperfusion astrocytes promotes primary neural stem/progenitor cell proliferation by releasing high-mobility group box 1.
Neurochem. Res.
PUBLISHED: 02-05-2014
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Cerebral ischemia/reperfusion is known to activate endogenous neural stem/progenitor cell (NS/PC) proliferation, but the mechanisms leading to NS/PC proliferation remain unknown. Astrocytes are vital components of the neurogenic niche and play a crucial role in regulating NS/PC proliferation and differentiation. After focal cerebral ischemia/reperfusion (I/R), astrocytes release a damage-associated molecular-pattern molecule called high-mobility group box 1 (HMGB1). Since HMGB1 is critical for NS/PC proliferation during brain development, we modeled I/R using glucose deprivation/reperfusion (OGD/R) in vitro and examined the effect of HMGB1 released by astrocytes on NS/PC proliferation. Further, we determined the role of the PI3K/Akt signaling pathway in this process. Using conditioned media from OGD/R astrocytes with or without RNA interference for HMGB1, as well as with anti-HMGB1 antibodies, we evaluated the effect of astrocyte-derived HMGB1 on NS/PC proliferation. Using the potent PI3K/Akt inhibitor, LY294002, we explored the likely mechanism of HMGB1-induced NS/PC proliferation. OGD/R astrocyte-conditioned media (ACM) increased NS/PC proliferation, and HMGB1 RNA interference prevented this effect. Using an HMGB1 neutralizing antibody in OGD/R ACM also abrogated NS/PC proliferation. LY294002 effectively reduced phospho-Akt levels and reduced NS/PC proliferation induced by HMGB1 in vitro. Our data demonstrate that HMGB1 released by OGD/R astrocytes promotes NS/PC proliferation through activation of the PI3K/Akt signaling pathway. Local HMGB1 release may induce endogenous NS/PC to proliferate following cerebral I/R and suggests that HMGB1 may play a pivotal role in brain tissue repair after an ischemic event.
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Scaffold structure and fabrication method affect proinflammatory milieu in three-dimensional-cultured chondrocytes.
J Biomed Mater Res A
PUBLISHED: 01-23-2014
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Cartilage tissue engineering has emerged as an attractive therapeutic option for repairing damaged cartilage tissue in the arthritic joint. High levels of proinflammatory cytokines present at arthritic joints can cause cartilage destruction and instability of the engineered cartilage tissue, and thus it is critical to engineer strong and stable cartilage that is resistant to the inflammatory environment. In this study, we demonstrate that scaffolding materials with different pore sizes and fabrication methods influence the microenvironment of chondrocytes and the response of these cells to proinflammatory cytokines, interleukin-1beta, and tumor necrosis factor alpha. Silk scaffolds prepared using the organic solvent hexafluoroisopropanol as compared to an aqueous-based method, as well as those with larger pore sizes, supported the deposition of higher cartilage matrix levels and lower expression of cartilage matrix degradation-related genes, as well as lower expression of endogenous proinflammatory cytokines IL-1? in articular chondrocytes. These biochemical properties could be related to the physical properties of the scaffolds such as the water uptake and the tendency to leach or adsorb proinflammatory cytokines. Thus, scaffold structure may influence the behavior of chondrocytes by influencing the microenvironment under inflammatory conditions, and should be considered as an important component for bioengineering stable cartilage tissues. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2014.
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A 3'UTR polymorphism of IL-6R is associated with Chinese pediatric tuberculosis.
Biomed Res Int
PUBLISHED: 01-21-2014
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IL-6 is a proinflammatory cytokine that plays a critical role in host defense against tuberculosis (TB). Genetic polymorphisms of IL-6 and its receptor IL-6R had been discussed in adult TB recently. However, their role in pediatric TB is still unclear. Due to the obvious differences in TB pathophysiology in children, which may also reflect differences in genetic background, further association studies in pediatric populations are needed.
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Proteasome inhibitors activate autophagy involving inhibition of PI3K-Akt-mTOR pathway as an anti-oxidation defense in human RPE cells.
PLoS ONE
PUBLISHED: 01-01-2014
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The two major intracellular protein degradation systems, the ubiquitin-proteasome system (UPS) and autophagy, work collaboratively in many biological processes including development, apoptosis, aging, and countering oxidative injuries. We report here that, in human retinal pigment epithelial cells (RPE), ARPE-19 cells, proteasome inhibitors, clasto-lactacystin?-lactone (LA) or epoxomicin (Epo), at non-lethal doses, increased the protein levels of autophagy-specific genes Atg5 and Atg7 and enhanced the conversion of microtubule-associated protein light chain (LC3) from LC3-I to its lipidative form, LC3-II, which was enhanced by co-addition of the saturated concentration of Bafilomycin A1 (Baf). Detection of co-localization for LC3 staining and labeled-lysosome further confirmed autophagic flux induced by LA or Epo. LA or Epo reduced the phosphorylation of the protein kinase B (Akt), a downstream target of phosphatidylinositol-3-kinases (PI3K), and mammalian target of rapamycin (mTOR) in ARPE-19 cells; by contrast, the induced changes of autophagy substrate, p62, showed biphasic pattern. The autophagy inhibitor, Baf, attenuated the reduction in oxidative injury conferred by treatment with low doses of LA and Epo in ARPE-19 cells exposed to menadione (VK3) or 4-hydroxynonenal (4-HNE). Knockdown of Atg7 with siRNA in ARPE-19 cells reduced the protective effects of LA or Epo against VK3. Overall, our results suggest that treatment with low levels of proteasome inhibitors confers resistance to oxidative injury by a pathway involving inhibition of the PI3K-Akt-mTOR pathway and activation of autophagy.
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Syphilis and its correlates among heterosexual males attending sexually transmitted infection clinics - observation from a multicity cohort in Jiangsu Province, China.
PLoS ONE
PUBLISHED: 01-01-2014
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To estimate the prevalence of HIV and syphilis, incidence of syphilis and to identify the correlates of syphilis infection among heterosexual male attendees of sexually transmitted infection (STI) clinics (MSC).
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Genetic contribution of CISH promoter polymorphisms to susceptibility to tuberculosis in Chinese children.
PLoS ONE
PUBLISHED: 01-01-2014
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Tuberculosis (TB) is the leading cause of death due to an infectious disease worldwide, particularly in developing countries. A series of candidate genes have been suggested to be associated with development of TB disease. Among them, the human Cytokine-inducible Src homology 2(SH2) domain protein (CISH) gene has been very recently reported to be involved in T cell activation and differentiation in response to Mycobacterium tuberculosis infection. Here, we studied the association between CISH promoter polymorphisms and pediatric TB. A case-control study enrolled 352 TB patients and 527 healthy controls, who were of Han Chinese ethnicity and aged from 0.2 to 18 years. CISH gene promoter SNPs rs414171, rs622502 and rs809451 were genotyped in all subjects and transcriptional activity, mRNA level, and plasma cytokine level of subjects with different genotypes were further examined. Carriers with rs414171TT homozygotes and rs809451GC heterozygotes had a 1.78-fold (95% CI,1.16-2.74) and 1.86-fold (95% CI, 1.26-2.74) excess risk of developing TB compared to those with wild-type genotypes. A greater risk of TB disease was observed in population carrying C(-809451)-T(-414171)-C(-622502) haplotype (OR 3.66, 95% CI:2.12-6.32). The G(-809451)-A(-414171)-C(-622502)-containing CISH promoter drove a 5.43-fold increased reporter expression compared to the C(-809451)-T(-414171)-C(-622502)-containing counterpart in Hela cell lines (P = 0.0009). PBMCs carrying rs414171TT homozygotes and rs809451GC heterozygotes showed a reduced CISH mRNA level compared to cells carrying wild type genotypes. Individuals with the rs414171TT genotype had significantly increased IL-12p40 and IL-10 production. In conclusion, CISH promoter rs414171 and rs809451 polymorphisms may play a vital role in mediating individual susceptibility to tuberculosis.
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[RIFLE and AKIN criteria for mortality and risk factors of acute kidney injury in hospitalized patients.]
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 12-31-2013
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Objective: To evaluate the mortality and risk factors for acute kidney injury (AKI) in hospitalized patients by the risk, injury, failure, loss, end stage kidney disease (RIFLE) and acute kidney injury network (AKIN). Methods: We constructed a retrospective study of all AKI patients in the Second Xiangya Hospital of Central South University between February 2006 and January 2011. The diagnosis and classification of AKI were reconfirmed and categorized by RIFLE and AKIN criteria. To compare the clinical characteristics, mortality and associated risk factors in AKI patients by the RIFLE and AKIN stage, univariate analysis and multivariate logistic regression analysis were performed. Results: The patients were diagnosed as AKI by AKIN (n=1027) or by RIFLE criteria (n=1020). There was no significant difference in the hospital mortality, hospital length stay (days), or the proportion of complete recovery in each stage of AKI patients by RIFLE and AKIN (P>0.05). In the univariate analysis, age, pre-renal causes, proportion of hospital acquired AKI, mechanical ventilation, hypotension, the number of failed organs, acute tubular necrosis-index severity score (ATN-ISS), and the peak of serum potassium ion concentration were significantly higher in the non-survivors than in the survivors (P<0.05). Logistic regression analysis revealed that age older than 65, hospital acquired AKI, hypotension, number of failed organs, ATN-ISS scores, and the peak of serum potassium ion concentration were independent risk factors for hospital mortality. Conclusion: Both RIFLE and AKIN criteria have similar scientific value in assessing hospital mortality. AKI stage is associated with the recent prognosis of AKI patients.
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[Role and mechanism of tranilast preventing the progression of tubulointerstilial fibrosis in diabetic kidney diseases.]
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 12-31-2013
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Objective: To determine the role and mechanism of tranilast preventing the progression of tubulointerstilial fibrosis in diabetic kidney disease (DKD). Methods: Sprague-Dawley rats were randomly divided into a control group (n=6), DKD model group (n=8), low dose tranilast group [200 mg/(kg.d), n=8], and high dose tranilast group [400 mg/(kg.d), n=8]. Tranilast was administered daily after the model was built. Rats were sacrificed at day 56, 24 hour urine was collected to measure 24-hour urine albumin excretion, and blood was collected to determine the renal function and serum albumin. Then the kidneys were harvested and subjected to studies. The expression of C3aR, E-cadherin, ?-SMA, fibronectin(FN), collagen I (Col I), stem cell factor (SCF) and c-kit were detected by immunohistochemical staining respectively. The expression of E-cadherin, ?-SMA, FN, Col I, SCF and c-kit protein was analyzed by Western blot, and the expression of FN, Col I, SCF and c-kit mRNA was examined by RT-PCR. Results: Tranilast can inhibit the infiltration of mast cells in the kidneys of DKD rats. The expression of ?-SMA in the kidneys of DKD rats inereased significantly (P<0.05), while the expression of E-cadherin decreased (P<0.05). Tranilast increased the expression of E-cadherin and decreased the expression of ?-SMA in the prophase of DKD dose dependently. The expressions of FN and Col I were increased in the tubulointerstitial fields in DKD model rats (P<0.05). After the tranilast treatment, these changes were relieved to a certein degree (P<0.05). The expression of SCF and c-kit in the tubular and interstitial tissue was slight. The increased expressions of SCF and c-kit protein and mRNA in DKD model rats were downregulated by tranilat (P<0.05). The expressions of SCF and c-kit were positively correlated with the infiltration degree of mast cells and the expressions of FN, Col I. Conclusion: Mast cells participate in and aggravate the renal tubulointerstitial fibrosis in DKD rats. Tranilast can reverse the EMT of renal tubular cells and inhibit the tubulointersitial fibrosis of DKD by blocking the infiltration of mast cells induced by SCF/c-kit pathway.
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Rap1 ameliorates renal tubular injury in diabetic nephropathy.
Diabetes
PUBLISHED: 12-18-2013
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Rap1b ameliorates high glucose (HG)-induced mitochondrial dysfunction in tubular cells. However, its role and precise mechanism in diabetic nephropathy (DN) in vivo remains unclear. We hypothesize that Rap1 plays a protective role in tubular damage of DN by modulating primarily the mitochondria-derived oxidative stress.The role and precise mechanisms of Rap1b on mitochondrial dysfunction and of tubular cells in DN was examined in rats with Streptozotocin (STZ)-induced diabetes that have Rap1b gene transfer using an ultrasound microbubble-mediated technique as well as in renal proximal epithelial tubular cell line (HK-2) exposed to HG ambiance. The results showed that Rap1b expression decreased significantly in tubules of renal biopsies from patients with DN. Over-expression of a constitutively active Rap1b G12V notably ameliorated renal tubular mitochondrial dysfunction, oxidative stress, apoptosis in the kidneys of STZ-induced rats, which was accompanied with increased expression of transcription factor C/EBP-? and PGC-1?. Furthermore, Rap1b G12V also decreased phosphorylation of Drp1, a key mitochondrial fission protein, while boosting the expression of genes related to mitochondrial biogenesis and antioxidants in HK-2 cells induced treated with HG. These effects were imitated by transfection with C/EBP-? or PGC-1? siRNA. In addition, Rap1b could modulate C/EBP-? binding to the endogenous PGC-1? promoter and the interaction between PGC-1? and Catalase or mitochondrial superoxide dismutase. Indicating that Rap1b ameliorates tubular injury and slows the progression of DN by modulation of mitochondrial dysfunction via C/EBP-?:PGC-1? signaling.
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[Effect of high glucose peritoneal dialysis solution on PGC-1? expression and mitochondria related oxidative injury in human peritoneal mesothelial cells].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 12-10-2013
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Objective: To investigate the mechanism of mitochondrial oxidative injury induced by high glucose peritoneal dialysis solution (PDS) and the protective effect of peroxisome proliferatoractivated receptor gamma coactivator 1-alpha (PGC-1?) in the mitochondria of human peritoneal mesothelial cells (HPMC) in the high glucose ambience. Methods: HPMC was cultured in a PDS containing 1.5%, 2.5% and 4.25% glucose for 24 hours. Western blot analysis was used to detect PGC-1? expression. MitoSOX? Red staining, respiratory chain complexes and antioxidant enzyme activities were determined. Results: The activities of respiratory chain complex III and antioxidant enzymes decreased significantly in a concentration- and time-dependent manner, along with the increased production of mitochondrial reactive oxygen species (ROS) and cellular apoptosis. In addition, protein expression of PGC-1? was also decreased in the high glucose PDS ambience. Conclusion: High glucose PDS might inhibit PGC-1? expression, resulting in the inhibition of mitochondrial function and increase of mitochondrial ROS and cellular apoptosis.
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Brain metabolite changes in patients with type 2 diabetes and cerebral infarction using proton magnetic resonance spectroscopy.
Int. J. Neurosci.
PUBLISHED: 11-19-2013
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The aim of this study was to investigate the possible brain metabolic alterations in patients with type 2 diabetes mellitus (T2DM) and cerebral infarction (DMCI) using proton magnetic resonance spectroscopy (MRS). Thirty-four patients with T2DM and DMCI were scanned together with 33 patients with nondiabetic cerebral infarction (NDCI) on a 1.5-T MRI/MRS imager. Voxels were placed in the infarcted area and the contralateral normal area in the basal ganglia. N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, and lactate (Lac)/Cr ratios were calculated. Cerebral NAA/Cr ratios in the infarcted area were lower than those in the contralateral normal area of the NDCI group. There was a significant decrease in NAA/Cr in the infarcted area of the DMCI group as compared with the infarcted area of the NDCI group. NAA/Cr ratios in the contralateral normal area of DMCI group were lower than those of the NDCI group. Lac/Cr ratios were increased in the infarcted area of both the DMCI group and NDCI group, and Lac/Cr ratios tended to be higher in the infarcted area of the DMCI group than those of the NDCI group. Glycosylated hemoglobin (HbA1c) levels were negatively correlated with NAA/Cr ratios. The study suggested that the metabolite changes were different between DMCI patients and NDCI patients, which may provide important information in the treatment of DMCI.
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Oxidative stress, a common molecular pathway for kidney disease: Role of the redox enzyme p66Shc.
Ren Fail
PUBLISHED: 11-04-2013
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Abstract Accumulation of oxidative stress is considered to be a causative mediator of kidney disease, and oxidative stress can affect some key regulators of kidney homeostasis and control a number of signaling pathways that are relevant to kidney disease. The p66Shc adaptor protein was discovered more than two decades ago as a pivotal regulator of oxidative stress. Given the importance of oxidative stress in kidney homeostasis, several molecular and cellular studies using a p66Shc antagonist have depicted a role for p66Shc in renal pathophysiology. The specificity of p66Shc functions may depend upon their intracellular localization and expression in the kidney. This review focuses on the biochemical functions of the p66Shc adaptor protein, as well as its potential implications in the pathophysiology of kidney disease. In addition, the concept that pharmacologic modulation of p66Shc expression and activity may serve as a novel and effective target for the treatment of kidney disease is discussed.
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The Inhibitory Effects of a Rhamnogalacturonan I (RG-I) Domain from Ginseng Pectin on Galectin-3 and Its Structure-Activity Relationship.
J. Biol. Chem.
PUBLISHED: 10-07-2013
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Pectin has been shown to inhibit the actions of galectin-3, a ?-galactoside-binding protein associated with cancer progression. The structural features of pectin involved in this activity remain unclear. We investigated the effects of different ginseng pectins on galectin-3 action. The rhamnogalacturonan I-rich pectin fragment, RG-I-4, potently inhibited galectin-3-mediated hemagglutination, cancer cell adhesion and homotypic aggregation, and binding of galectin-3 to T-cells. RG-I-4 specifically bound to the carbohydrate recognition domain of galectin-3 with a dissociation constant of 22.2 nm, which was determined by surface plasmon resonance analysis. The structure-activity relationship of RG-I-4 was investigated by modifying the structure through various enzymatic and chemical methods followed by activity tests. The results showed that (a) galactan side chains were essential to the activity of RG-I-4, whereas arabinan side chains positively or negatively regulated the activity depending on their location within the RG-I-4 molecule. (b) The activity of galactan chain was proportional to its length up to 4 Gal residues and largely unchanged thereafter. (c) The majority of galactan side chains in RG-I-4 were short with low activities. (d) The high activity of RG-I-4 resulted from the cooperative action of these side chains. (e) The backbone of the molecule was very important to RG-I-4 activity, possibly by maintaining a structural conformation of the whole molecule. (f) The isolated backbone could bind galectin-3, which was insensitive to lactose treatment. The novel discovery that the side chains and backbone play distinct roles in regulating RG-I-4 activity is valuable for producing highly active pectin-based galectin-3 inhibitors.
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Greater omentum folding in the open surgical placement of peritoneal dialysis catheters: a randomized controlled study and systemic review.
Nephrol. Dial. Transplant.
PUBLISHED: 09-30-2013
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Mechanical catheter dysfunction caused by omentum entrapment remains a major complication of peritoneal dialysis (PD) therapy. The purpose of this study was to determine the outcomes of omentum folding at the time of primary open catheter insertion.
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EBV associated lymphomas in 2008 WHO classification.
Pathol. Res. Pract.
PUBLISHED: 09-26-2013
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Epstein-Barr virus (EBV) is a ubiquitous ?-herpes virus that asymptomatically infects more than 90% of the worlds population. The exact mechanism of EBV in oncogenesis is an area of active debate. However, EBV has been implicated in the pathogenesis of several kinds of lymphomas and lymphoproliferative disorders, including B-, T- and NK-cell derived. Subsequent studies have proven that the EBV gene expression product plays an activating and/or promoting role on lymphomagenesis, and paves the way for novel cellular therapies of EBV-associated lymphomas. This review concentrates on the pathology, morphology, treatment and prognosis of EBV-associated lymphomas in the 2008 WHO classification of tumors of hematopoietic and lymphoma tissues.
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Differential effect of aneuploidy on the X chromosome and genes with sex-biased expression in Drosophila.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 09-23-2013
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Global analysis of gene expression via RNA sequencing was conducted for trisomics for the left arm of chromosome 2 (2L) and compared with the normal genotype. The predominant response of genes on 2L was dosage compensation in that similar expression occurred in the trisomic compared with the diploid control. However, the male and female trisomic/normal expression ratio distributions for 2L genes differed in that females also showed a strong peak of genes with increased expression and males showed a peak of reduced expression relative to the opposite sex. For genes in other autosomal regions, the predominant response to trisomy was reduced expression to the inverse of the altered chromosomal dosage (2/3), but a minor peak of increased expression in females and further reduced expression in males were also found, illustrating a sexual dimorphism for the response to aneuploidy. Moreover, genes with sex-biased expression as revealed by comparing amounts in normal males and females showed responses of greater magnitude to trisomy 2L, suggesting that the genes involved in dosage-sensitive aneuploid effects also influence sex-biased expression. Each autosomal chromosome arm responded to 2L trisomy similarly, but the ratio distributions for X-linked genes were distinct in both sexes, illustrating an X chromosome-specific response to aneuploidy.
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Predicting enhancer transcription and activity from chromatin modifications.
Nucleic Acids Res.
PUBLISHED: 09-12-2013
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Enhancers play a pivotal role in regulating the transcription of distal genes. Although certain chromatin features, such as the histone acetyltransferase P300 and the histone modification H3K4me1, indicate the presence of enhancers, only a fraction of enhancers are functionally active. Individual chromatin marks, such as H3K27ac and H3K27me3, have been identified to distinguish active from inactive enhancers. However, the systematic identification of the most informative single modification, or combination thereof, is still lacking. Furthermore, the discovery of enhancer RNAs (eRNAs) provides an alternative approach to directly predicting enhancer activity. However, it remains challenging to link chromatin modifications to eRNA transcription. Herein, we develop a logistic regression model to unravel the relationship between chromatin modifications and eRNA synthesis. We perform a systematic assessment of 24 chromatin modifications in fetal lung fibroblast and demonstrate that a combination of four modifications is sufficient to accurately predict eRNA transcription. Furthermore, we compare the ability of eRNAs and H3K27ac to discriminate enhancer activity. We demonstrate that eRNA is more indicative of enhancer activity. Finally, we apply our fibroblast trained model to six other cell-types and successfully predict eRNA synthesis. Thus, we demonstrate the learned relationships are general and independent of cell-type. We provided a powerful tool to identify active enhancers and reveal the relationship between chromatin modifications, eRNA production and enhancer activity.
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Holographic plasmonic lenses for surface plasmons with complex wavefront profile.
Opt Express
PUBLISHED: 08-14-2013
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We present a direct-method solution toward the general problem of plasmonic wavefront manipulation and shaping to realize pre-designated functionalities based on the surface-wave holography (SWH) method. We demonstrate theoretically and experimentally the design and fabrication of holographic plasmonic lenses over surface plasmons with complex wavefront profiles. We show that visible light at 632.8 nm transmitting through a high-aspect-ratio slit or a micro-rectangle hole in a silver film can be focused to a preset three-dimensional point spot in free space via appropriately manipulating the interaction of excited surface plasmons with the nanoscale groove pattern of the holographic lens. The experiment results of scanning near-field optical microscopy for measuring the three-dimensional optical field distribution agree well both with designs and with numerical simulations, and this strongly supports the effectiveness and efficiency of the SWH method in the design of plasmonic devices that can fulfill manipulation and transformation of complicated-profile surface plasmons.
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Production of marker-free and RSV-resistant transgenic rice using a twin T-DNA system and RNAi.
J. Biosci.
PUBLISHED: 08-14-2013
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A twin T-DNA system is a convenient strategy for creating selectable marker-free transgenic plants. The standard transformation plasmid, pCAMBIA 1300, was modified into a binary vector consisting of two separate T-DNAs, one of which contained the hygromycin phosphotransferase (hpt) marker gene. Using this binary vector, we constructed two vectors that expressed inverted-repeat (IR) structures targeting the rice stripe virus (RSV) coat protein (CP) gene and the special-disease protein (SP) gene. Transgenic rice lines were obtained via Agrobacterium-mediated transformation. Seven independent clones harbouring both the hpt marker gene and the target genes (RSV CP or SP) were obtained in the primary transformants of pDTRSVCP and pDTRSVSP, respectively. The segregation frequencies of the target gene and the marker gene in the T1 plants were 8.72 percent for pDTRSVCP and 12.33 percent for pDTRSVSP. Two of the pDTRSVCP lines and three pDTRSVSP lines harbouring the homozygous target gene, but not the hpt gene, were strongly resistant to RSV. A molecular analysis of the resistant transgenic plants confirmed the stable integration and expression of the target genes. The resistant transgenic plants displayed lower levels of the transgene transcripts and specific small interfering RNAs, suggesting that RNAi induced the viral resistance.
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One-stage posterior surgical treatment for lumbosacral tuberculosis with major vertebral body loss and kyphosis.
Orthopedics
PUBLISHED: 08-14-2013
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The treatment goals of tuberculous spondylitis are to eradicate infection and to prevent or treat instability, deformity, and neurologic deficit. The purpose of this study was to evaluate the clinical outcomes following chemotherapy with 1-stage posterior debridement, correction, and instrumentation and fusion for the treatment of lumbosacral tuberculosis with major vertebral body loss and kyphosis. Fourteen patients with lumbosacral tuberculosis with major vertebral body loss and kyphosis underwent 1-stage posterior surgery. Clinical assessments included low back ache, Oswestry Disability Index, Scoliosis Research Society-22 scores, neurologic deficit, erythrocyte sedimentation rate, and C-reactive protein level. Radiographic parameters included kyphosis angle, anteroposterior translation, local scoliosis, lumbar lordosis, pelvic parameters, sagittal offset, and fusion. Thorough debridement was performed. Patients were followed for an average of 39.3 months. Constitutional symptoms, low back ache, and functional outcome improved in all patients postoperatively. At final follow-up, Frankel Grade improved by 0 to 2 grades, mean kyphosis angle improvement was 44.3°, and satisfactory spinopelvic and sagittal balance were achieved. Spinal posterolateral fusion was obtained in all patients and no fixation loosening was found at 2-year follow-up. Differences existed between the pre- and postoperative radiographic parameters (P<.05). Correction loss at last follow-up was not statistically significant (P>.05). No surgical complications or infection recurrence occurred. Tuberculosis can be cured and effective correction of kyphosis can be achieved for lumbosacral tuberculosis with major vertebral body loss and kyphosis by performing 1-stage posterior surgery and chemotherapy.
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[Monolithic molecularly imprinted column-high performance liquid chromatography for enrichment and determination of trace cytokinins in plant samples].
Se Pu
PUBLISHED: 08-01-2013
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A method based on monolithic molecularly imprinted polymer enrichment combining with high performance liquid chromatography (mMIP-HPLC) detection was developed for the selective determination of trace cytokinins (CTKs) in plant samples. Monolithic molecularly imprinted polymer (mMIP) column was prepared in stainless steel tube by using kinetin as the template, methacrylic acid (MAA) as the functional monomer, ethylene glycol dimethacrylate (EGDMA) as the cross-linker, and toluene-dodecanol as the porogenic solvents. Compared with non-imprinted polymer (NIP) monolith, the prepared mMIP exhibited selective separation ability, good reproducibility and reusability, and high extraction efficiency in the separation and enrichment of the four CTKs. Under the optimized experimental conditions, mean recoveries were 91.9%, 80.0%, 87.5% and 50.2% for kinetin (K), kinetin glucoside (KR) , trans-zeatin (tZ) and meta-topolin (mT), respectively, with the corresponding RSDs less than 11.8%. The proposed mMIP-HPLC method was successfully applied in the separation and determination of the four cytokinins in different plant samples
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[Resveratrol reduces inflammatory cytokines via inhibiting nuclear factor-?B and mitogen-activated protein kinase signal pathway in a rabbit atherosclerosis model].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 07-15-2013
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Inflammation serves as the initial pathologic step of cardiovascular diseases including atherosclerosis. Resveratrol possesses many pharmacological properties including antioxidant, cardioprotective and anti-cancer effects. In this study, we investigate the anti-inflammatory effect and mechanisms of resveratrol in an atherosclerotic rabbit model.
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[Expression of Galectins in umbilical cord mesenchymal stem cells].
Beijing Da Xue Xue Bao
PUBLISHED: 06-19-2013
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To investigate the expression of Galectins in umbilical cord mesenchymal stem cells (UC-MSCs) from Whartons jelly.
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Identification of Salmonella enterica serovar Pullorum antigenic determinants expressed in vivo.
Infect. Immun.
PUBLISHED: 06-17-2013
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Salmonella enterica serovar Pullorum affecting poultry causes pullorum disease and results in severe economic loss in the poultry industry. Currently, it remains a major threat in countries with poor poultry surveillance and no efficient control measures. As S. Pullorum could induce strong humoral immune responses, we applied an immunoscreening technique, the in vivo-induced antigen technology (IVIAT), to identify immunogenic bacterial proteins expressed or upregulated during S. Pullorum infection. Convalescent-phase sera from chickens infected with S. Pullorum were pooled, adsorbed against antigens expressed in vitro, and used to screen an S. Pullorum genomic expression library. Forty-five proteins were screened out, and their functions were implicated in molecular biosynthesis and degradation, transport, metabolism, regulation, cell wall synthesis and antibiotic resistance, environmental adaptation, or putative functions. In addition, 11 of these 45 genes were assessed for their differential expression by quantitative real-time reverse transcription-PCR (RT-PCR), revealing that 9 of 11 genes were upregulated to different degrees under in vivo conditions, especially the regulator of virulence determinants, phoQ. Then, four in vivo-induced proteins (ShdA, PhoQ, Cse3, and PbpC) were tested for their immunoreactivity in 28 clinical serum samples from chickens infected with S. Pullorum. The rate of detection of antibodies against ShdA reached 82% and was the highest among these proteins. ShdA is a host colonization factor known to be upregulated in vivo and related to the persistence of S. Typhimurium in the intestine. Furthermore, these antigens identified by IVIAT warrant further evaluation for their contributions to pathogenesis, and more potential roles, such as diagnostic, therapeutic, and preventive uses, need to be developed in future studies.
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[Feasibility and accuracy of ultrasound-guided methodology in the examination of lumbar spine facet joints].
Sichuan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 06-11-2013
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To investigate the feasibility, accuracy of B ultrasound in the examination of joint space of lumbar spine facet joints compared with CT scan.
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IFNG polymorphisms are associated with tuberculosis in Han Chinese pediatric female population.
Mol. Biol. Rep.
PUBLISHED: 06-05-2013
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Host genetic factors play a major role in determining differential susceptibility to human tuberculosis (TB), a re-emerging infectious disease throughout the world. Genetic variations in the IFNG gene coding for interferon gamma (IFN-?), have been identified in TB patients. To investigate the association of the IFNG polymorphisms with TB susceptibility in Chinese pediatric population. A case-control study of 189 TB patients and 164 controls was performed using single-nucleotide polymorphism (SNP) analysis. Genomic DNA was extracted from leukocytes in peripheral blood. Three SNPs of IFNG, including -1616C/T (rs2069705), +874A/T (rs2430561), and +3234C/T (rs2069718), were selected for genotyping and analysis. The +874A and +3234C alleles were more frequent among TB patients (P = 0.108 and P = 0.088), especially in females (both P = 0.029), although this difference was not significant since Bonferroni corrected significance threshold was 0.025 (two of three SNPs were found to be in linkage disequilibrium). More pronounced differences for the +874 and +3234 polymorphisms were found under the genotype comparison between TB cases and controls in the total population [P = 0.026 (borderline non-significance) and P = 0.020, respectively], and in the female subgroup (P = 0.020 and P = 0.020). The dominant model of inheritance was shown to be significant for +874A and +3234C alleles (both P = 0.019) in the female subgroup. The +874A and +3234C alleles were more frequently found in extrapulmonary TB patients than in controls (P = 0.039). Haplotype analysis carried out on these three SNPs showed the TTT haplotype to be more frequent in controls than in TB cases, and this difference showed a strong significance (P = 0.005). The +874A and +3234C alleles may be related to TB susceptibility in the female subgroup in the Chinese pediatric population of North China. The higher rate of +874A (known to correlate with lower IFN-? expression) in the extrapulmonary TB subgroup suggests a sufficient IFN-? expression to be not only an important factor for the onset of TB disease but also for limiting its dissemination to lungs.
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Bilateral apical vertebral derotation technique by vertebral column manipulation compared with vertebral coplanar alignment technique in the correction of lenke type 1 idiopathic scoliosis.
BMC Musculoskelet Disord
PUBLISHED: 05-29-2013
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BACKGROUND: Widely used rod rotation and translation techniques for idiopathic scoliosis (IS) are effective in correcting spinal coronal deformity. Bilateral apical vertebral derotation technique by vertebral column manipulation (VCM) and vertebral coplanar alignment (VCA) technique are two strategies for three-dimensional (3D) correction for IS. The purpose of this study is to compare the post-surgical results and technical features of the bilateral apical vertebral derotation technique by VCM against the VCA technique in patients with Lenke type 1 IS. METHODS: Forty-eight patients with Lenke type 1 IS were enrolled in the present prospective clinical assay. They were divided into groups A (bilateral apical vertebral derotation technique by VCM, n=24) and B (VCA technique, n=24). Radiographic parameters measured before and after surgery included the Cobb angle, thoracic kyphosis, and apical vertebral rotation. Scoliosis Research Society (SRS)-22 scores were evaluated during the final follow-up. The differences in the demographics, surgical details, and radiographic measurements between the two groups were determined using a T test. The Mann--Whitney U test was used to evaluate the differences in the SRS-22 scores. A value of P<0.05 was considered statistically significant. RESULTS: In the coronal plane, a significant difference was found in the correction rate of the major curve (group A: 84.8%, group B: 78.4%; P=0.045) and in the Cincinnati Correction Index between two groups (group A: 2.21, group B: 1.98; P=0.047). In the sagittal plane, no difference was found in the postoperative thoracic kyphosis between the two groups (P=0.328). In the transverse plane, no difference was found between the two groups in the correction rates of the rotation angle sagittal (P=0.298), rib hump (P=0.934), apical vertebral body-to-rib ratio (P=0.988), or apical rib spread difference (P=0.184). Patients underwent follow up for an average of 21.9 and 22.2 months in groups A and B, respectively. Results obtained at the final follow-up indicated no significant loss of correction. No differences were found in the SRS-22 scores between the two groups. No aortic or neurological complications were observed. CONCLUSIONS: The 3D deformity of the spine was effectively corrected using the bilateral apical vertebral derotation technique by VCM and the VCA technique, and encouraging post-surgical results were obtained for patients with Lenke type 1 IS. The two techniques were effective in allowing 3D correctional force that was applied in different ways.
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[Expression of interleukin-6 and its clinicopathological significance in Castlemans disease].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 05-22-2013
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To evaluate the expression of interleukin-6 (IL-6) and its clinicopathological significance in Castlemans disease (CD).
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Changes in expression of four molecular marker proteins and one microRNA in mesothelial cells of the peritoneal dialysate effluent fluid of peritoneal dialysis patients.
Exp Ther Med
PUBLISHED: 04-27-2013
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The aim of this study was to detect the expression of microRNA-200c and epithelial-mesenchymal transition (EMT) in the mesothelial cells of the peritoneal dialysate effluent fluid of peritoneal dialysis (PD) patients, and to investigate the association between microRNA-200c and peritoneal mesothelial cell EMT. Twelve patients who had recently started continuous ambulatory peritoneal dialysis (PD start group) and 16 patients who had been undergoing peritoneal dialysis for >6 months (PD >6 months group) were randomly chosen for the isolation, culture and identification of effluent cells. qPCR and western blot analysis were used to detect the expression levels of microRNA-200c and the levels of four cellular marker proteins, E-cadherin, vimentin, fibronectin (FN) and COL-1, in effluent cells. The results showed that the effluent cells in peritoneal dialysis were peritoneal mesothelial cells. The level of E-cadherin protein expression was significantly lower in the PD >6 months group than in the PD start group, while vimentin, FN and COL-1 protein expression levels were significantly increased in the PD >6 months group. microRNA-200c in the PD >6 months group was significantly downregulated. The E-cadherin protein expression level was significantly decreased and vimentin, FN and COL-1 protein expression levels were significantly increased in the PD >6 months group. The level of microRNA-200c was significantly reduced in the PD > 6 months group, suggesting that microRNA-200c may be associated with EMT.
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Intrachromosomal looping is required for activation of endogenous pluripotency genes during reprogramming.
Cell Stem Cell
PUBLISHED: 04-19-2013
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Generation of induced pluripotent stem cells (iPSCs) by defined factors is an extremely inefficient process, because there is a strong epigenetic block preventing cells from achieving pluripotency. Here we report that virally expressed factors bound to the promoters of their target genes to the same extent in both iPSCs and unreprogrammed cells (URCs). However, expression of endogenous pluripotentcy genes was observed only in iPSCs. Comparison of local chromatin structure of the OCT4 locus revealed that there was a cohesin-complex-mediated intrachromosomal loop that juxtaposes a downstream enhancer to the genes promoter, enabling activation of endogenous stemness genes. None of these long-range interactions were observed in URCs. Knockdown of the cohesin-complex gene SMC1 by RNAi abolished the intrachromosomal interaction and affected pluripotency. These findings highlight the importance of the SMC1-orchestrated intrachromosomal loop as a critical epigenetic barrier to the induction of pluripotency.
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Urine miRNAs: potential biomarkers for monitoring progression of early stages of diabetic nephropathy.
Med. Hypotheses
PUBLISHED: 03-19-2013
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With a steep increase in the incidence of type 1 and 2 diabetes globally, diabetic nephropathy (DN) has now become the leading cause of renal failure in the world. There are no suitable biomarkers for the diagnosis of early stages of DN. In recent years, tremendous efforts are being made worldwide to delineate the role of micro RNAs in the pathogenesis of DN. Circulating miRNAs in serum, plasma, urine and other body fluids, which reflect a response to various pathophysiological stresses, are being investigated in the context of diabetic nephropathy. Delineation of the changes in miRNA levels in patients with DN may lead to a better understanding of the progression of the disease. We present here an exhaustive survey of the miRNA literature, highlighting various studies performed over the last decade. The aim is to assess if changes in various miRNAs could correlate with the progression of diabetic nephropathy. Based on the survey, we found that miRNA-377, miRNA-192, miRNA-216/217 and miRNA-144 are increased in body fluids of patients with DN, while miRNA-21 and miRNA-375 are decreased. Overall, there are a very few miRNAs that are kidney specific, and although significant differences were observed in the urinary excretion of certain miRNAs, they were not correlative to their levels in the blood or plasma. Thus, it is completely plausible that urine-specific miRNAs could serve as novel biomarkers for the diagnosis of early stages of diabetic nephropathy.
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Easily misdiagnosed delayed metastatic intraspinal extradural melanoma of the lumbar spine: A case report and review of the literature.
Oncol Lett
PUBLISHED: 03-14-2013
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Metastatic melanoma of the spine usually occurs as vertebral metastatic melanoma or intramedullary spinal cord metastatic melanoma. The present study reports a case of easily misdiagnosed delayed metastatic intraspinal extradural melanoma of the lumbar spine. A 67-year-old female patient presented with lower back pain accompanied by progressive intermittent claudication. Magnetic resonance imaging (MRI) suggested compression of the lumbar spinal cord caused by an extradural mass. The mass showed T2-hypointensity, T1-hypointensity and slight enhancement following a gadolinium-contrast injection. The patient had been diagnosed with a vulvar melanoma 13 years previously and had also undergone a resection of this tumor. A current diagnosis of a lumbar stenosis resulting from hypertrophy of the ligamentum flavum was suspected. However during corrective surgery, a dark gray solid mass was observed. An L3 laminectomy and removal of the tumor was performed. The tumor was confirmed to be a malignant melanoma by histopathological investigation. The patient was treated with radiotherapy and immunotherapy. At the final 13-month follow-up, the patient showed no signs of recurrence. It may be concluded that an early diagnosis of metastatic melanoma was prevented by delayed metastasis, the location of the mass and its unusual appearance in MRI scans. In such cases, early surgical removal and an appropriate comprehensive treatment are critical for patient survival. These observations suggest that caution should be used in the diagnosis of similar cases.
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Enhanced preservation of the rat heart after prolonged hypothermic ischemia with erythropoietin-supplemented Celsior solution.
J. Heart Lung Transplant.
PUBLISHED: 01-04-2013
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The cardioprotective efficacy of erythropoietin (EPO) has been widely documented in rodent models of acute coronary syndrome. We sought to evaluate its cardioprotective potential as an adjunct to Celsior cardioplegia in a rodent model of prolonged hypothermic global ischemia-reperfusion injury.
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Development of a Fluorescence Polarization Based High-Throughput Assay to Identify Casitas B-Lineage Lymphoma RING Domain Regulators.
PLoS ONE
PUBLISHED: 01-01-2013
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The E3 ubiquitin protein ligase Casitas B-lineage Lymphoma (Cbl) proteins and their binding partners play an important role in regulating signal transduction pathways. It is important to utilize regulators to study the protein-protein interactions (PPIs) between these proteins. However, finding specific small-molecule regulators of PPIs remains a significant challenge due to the fact that the interfaces involved in PPIs are not well suited for effective small molecule binding. We report the development of a competitive, homogeneous, high-throughput fluorescence polarization (FP) assay to identify small molecule regulators of Cbl (RING) domain. The FP assay was used to measure binding affinities and inhibition constants of UbCH7 peptides and small molecule regulators of Cbl (RING) domains, respectively. In order to rule out promiscuous, aggregation-based inhibition, two assay conditions were developed and compared side by side. Under optimized conditions, we screened a 10,000 natural compound library in detergent-free and detergent-present (0.01% Triton X-100) systems. The results indicate that the detergent-present system is more suitable for high-throughput screens. Three potential compounds, methylprotodioscin, leonuride and catalpol, have been identified that bind to Cbl (RING) domain and interfere with the Cbl (RING)-UbCH7 protein-protein interaction.
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Oncogenic Features of PHF8 Histone Demethylase in Esophageal Squamous Cell Carcinoma.
PLoS ONE
PUBLISHED: 01-01-2013
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Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. It has been reported that histone demethylases are involved in the carcinogenesis of certain types of tumors. Here, we studied the role of one of the histone lysine demethylases, plant homeodomain finger protein 8 (PHF8), in the carcinogenesis of esophageal squamous cell carcinoma (ESCC). Using short hairpin RNA via lentiviral infection, we established stable ESCC cell lines with constitutive downregulation of PHF8 expression. Knockdown of PHF8 in ESCC cells resulted in inhibition of cell proliferation and an increase of apoptosis. Moreover, there were reductions of both anchorage-dependent and -independent colony formation. In vitro migration and invasion assays showed that knockdown of PHF8 led to a reduction in the number of migratory and invasive cells. Furthermore, downregulation of PHF8 attenuated the tumorigenicity of ESCC cells in vivo. Taken together, our study revealed the oncogenic features of PHF8 in ESCC, suggesting that PHF8 may be a potential diagnostic marker and therapeutic target for ESCC.
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A novel application of furazolidone: anti-leukemic activity in acute myeloid leukemia.
PLoS ONE
PUBLISHED: 01-01-2013
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Acute myeloid leukemia (AML) is the most common malignant myeloid disorder of progenitor cells in myeloid hematopoiesis and exemplifies a genetically heterogeneous disease. The patients with AML also show a heterogeneous response to therapy. Although all-trans retinoic acid (ATRA) has been successfully introduced to treat acute promyelocytic leukemia (APL), it is rather ineffective in non-APL AML. In our present study, 1200 off-patent marketed drugs and natural compounds that have been approved by the Food and Drug Administration (FDA) were screened for anti-leukemia activity using the retrovirus transduction/transformation assay (RTTA). Furazolidone (FZD) was shown to inhibit bone marrow transformation mediated by several leukemia fusion proteins, including AML1-ETO. Furazolidone has been used in the treatment of certain bacterial and protozoan infections in human and animals for more than sixty years. We investigated the anti-leukemic activity of FZD in a series of AML cells. FZD displayed potent antiproliferative properties at submicromolar concentrations and induced apoptosis in AML cell lines. Importantly, FZD treatment of certain AML cells induced myeloid cell differentiation by morphology and flow cytometry for CD11b expression. Furthermore, FZD treatment resulted in increased stability of tumor suppressor p53 protein in AML cells. Our in vitro results suggest furazolidone as a novel therapeutic strategy in AML patients.
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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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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.