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Find video protocols related to scientific articles indexed in Pubmed.
Effect of ulinastatin on liver function of patients after bilateral total knee arthroplasty.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao
PUBLISHED: 11-01-2014
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Objective To investigate the effect of ulinastatin,a urinary trypsin inhibitor,on the postoperative liver function in patients who have received bilateral total knee arthroplasty(TKA)under pneumatic tourniquet. Methods Totally 40 patients who were scheduled to receive bilateral TKA under thigh tourniquet were randomly assigned into trial group(U group,receiving intravenous ulinastatin)and control group(C group,receiving natural saline). All patients received the same general anesthesia and postoperative analgesia. The plasma concentrations of alanine transaminase(ALT),total bilirubin(TBil),and direct bilirubin(DBil)were recorded and compared preoperatively and 4,24,48,and 72 hours after the surgery. Results The demographic data were not significantly different between these two groups(P>0.05). The ALT was not significantly changed after the surgery in the C group(P>0.05)but was significantly decreased 48 hours(P=0.002)and 72 hours(P=0.001)after the surgery in the U group. TBil and DBil were significantly increased 48 hours(P=0.012,P=0.000)and 72 hours(P=0.000,P=0.000)after the surgery in C group,while only that at 48 hours(P=0.010,P=0.038)was significantly increased in the U group. ALT 4 hours(P=0.026),48 hours(P=0.013),72 hours(P=0.004)after the surgery were significantly lower in the U group than those in C group. TBil at the 72 hours postoperatively in U group was significantly lower than that in C group(P=0.036). DBil was not significantly different between C group and U group at all time points(all P>0.05). Conclusion The application of ulinastatin in bilateral TKA can protect postoperative liver function.
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Association between the XRCC3 Thr241Met polymorphism and breast cancer risk: an updated meta-analysis of 36 case-control studies.
Asian Pac. J. Cancer Prev.
PUBLISHED: 08-30-2014
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The X-ray repair cross-complementing group 3 (XRCC3) is a highly suspected candidate gene for cancer susceptibility. Attention has been drawn upon associations of the XRCC3 Thr241Met polymorphism with breast cancer risk. However, the previous published findings remain controversial. Hence, we performed a meta-analysis to accurately evaluate any association between breast cancer and XRCC3 T241M (23, 812 cases and 25, 349 controls) in different inheritance models.
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Mono-anionic phosphopeptides produced by unexpected histidine alkylation exhibit high plk1 polo-box domain-binding affinities and enhanced antiproliferative effects in hela cells.
Biopolymers
PUBLISHED: 08-25-2014
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Binding of polo-like kinase 1 (Plk1) polo-box domains (PBDs) to phosphothreonine (pThr)/phosphoserine (pSer)-containing sequences is critical for the proper function of Plk1. Although high-affinity synthetic pThr-containing peptides provide starting points for developing PBD-directed inhibitors, to date the efficacy of such peptides in whole cell assays has been poor. This potentially reflects limited cell membrane permeability arising, in part, from the di-anionic nature of the phosphoryl group or its mimetics. In our current article we report the unanticipated on-resin N(?)-alkylation of histidine residues already bearing a N(?)- alkyl group. This resulted in cationic imidazolium-containing pThr peptides, several of which exhibit single-digit nanomolar PBD-binding affinities in extracellular assays and improved antimitotic efficacies in intact cells. We enhanced the cellular efficacies of these peptides further by applying bio-reversible pivaloyloxymethyl (POM) phosphoryl protection. New structural insights presented in our current study, including the potential utility of intramolecular charge masking, may be useful for the further development of PBD-binding peptides and peptide mimetics. © 2014 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 102: 444-455, 2014.
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[Effect of different bonding procedure and root region on bond strength of fiber posts to root canal].
Shanghai Kou Qiang Yi Xue
PUBLISHED: 08-09-2014
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To evaluate the effect of different bonding procedure and different root region on the bond strength of fiber posts to root canal.
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[Detection of slight bruises on apples based on hyperspectral imaging and MNF transform].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 08-07-2014
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Bruising is one of the major defects occurring on apple surface inevitably during postharvest handling and processing stage. To detect slight bruises on apples fast and efficiently, a novel bruises detection algorithm based on hyperspectral imaging and minimum noise fraction transform is proposed. First, the hyperspectral images in the visible and near-infrared (400 approximately 1 000 nm) ranges are acquired, and MNF transform based on full ranges could obtain better detection performance compared to PCA transform; Second, five wavebands (560, 660, 720, 820 and 960 nm) are selected as the effective wavebands based on the coefficient curve of I-RELIEF method conducted on spectra extracted from intact and bruise surface; Third, the bruises detection algorithm is developed based on the effective wavebands and MNF transform method. For the investigated 40 sound samples and 40 different time stage bruise samples, the results with a 97. 1% overall detection rate are got. The recognition results indicate that the proposed methods and the effective wavelengths selected in this paper are feasible and efficient. This research lays a foundation for the development of multispectral imaging system based on MNF transform for slight bruises detection on apples.
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[Near-infrared hyperspectral imaging combined with CARS algorithm to quantitatively determine soluble solids content in "Ya" pear].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 08-07-2014
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The present study proposed competitive adaptive reweighted sampling (CARS) algorithm to be used to select the key variables from near-infrared hyperspectral imaging data of "Ya" pear. The performance of the developed model was evaluated in terms of the coefficient of determination(r2), and the root mean square error of prediction (RMSEP) and the ratio (RPD) of standard deviation of the validation set to standard error of prediction were used to evaluate the performance of proposed model in the prediction process. The selected key variables were used to build the PLS model, called CARS-PLS model. Comparing results obtained from CARS-PLS model and results obtained from full spectra PLS, it was found that the better results (r(2)pre = 0. 908 2, RMSEP=0. 312 0 and RPD=3. 300 5) were obtained by CARS-PLS model based on only 15. 6% information of full spectra. Moreover, performance of CARS-PLS model was also compared with PLS models built by using variables got by Monte Carlo-uninformative variable elimination (MC-UVE) and genetic algorithms (GA) method. The result found that CARS variable selection algorithm not only can remove the uninformative variables in spectra, but also can reduce the collinear variables from informative variables. Therefore, this method can be used to select the key variables of near-infrared hyperspectral imaging data. This study showed that near-infrared hyperspectral imaging technology combined with CARS-PLS model can quantitatively predict the soluble solids content (SSC) in "Ya" pear. The results presented from this study can provide a reference for predicting other fruits quality by using the near-infrared hyperspectral imaging.
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Kinetic models and pathways of ronidazole degradation by chlorination, UV irradiation and UV/chlorine processes.
Water Res.
PUBLISHED: 08-06-2014
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Degradation kinetics and pathways of ronidazole (RNZ) by chlorination (Cl2), UV irradiation and combined UV/chlorine processes were investigated in this paper. The degradation kinetics of RNZ chlorination followed a second-order behavior with the rate constants calculated as (2.13 ± 0.15) × 10(2) M(-2) s(-1), (0.82 ± 0.52) × 10(-2) M(-1) s(-1) and (2.06 ± 0.09) × 10(-1) M(-1) s(-1) for the acid-catalyzed reaction, as well as the reactions of RNZ with HOCl and OCl(-), respectively. Although UV irradiation degraded RNZ more effectively than chlorination did, very low quantum yield of RNZ at 254 nm was obtained as 1.02 × 10(-3) mol E(-1). RNZ could be efficiently degraded and mineralized in the UV/chlorine process due to the generation of hydroxyl radicals. The second-order rate constant between RNZ and hydroxyl radical was determined as (2.92 ± 0.05) × 10(9) M(-1) s(-1). The degradation intermediates of RNZ during the three processes were identified with Ultra Performance Liquid Chromatography - Electrospray Ionization - mass spectrometry and the degradation pathways were then proposed. Moreover, the variation of chloropicrin (TCNM) and chloroform (CF) formation after the three processes were further evaluated. Enhanced formation of CF and TCNM precursors during UV/chlorine process deserves extensive attention in drinking water treatment.
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[Research on treatment of high salt wastewater by the graphite and activated carbon fiber composite electrodes].
Huan Jing Ke Xue
PUBLISHED: 07-25-2014
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High salinity wastewater is one of the difficulties in the field of wastewater treatment. As a new desalination technology, electrosorption technology has many advantages. This paper studied a new type of carbon-based electrodes, the graphite and activated carbon fiber composite electrodes. And the influencing factors of electrosorption and its desalination effect were investigated. The electrosorption device had optimal desalination effect when the voltage was 1. 6 V, the retention time was 60 min and the plate spacing was 1 cm. The graphite and activated carbon fiber composite electrodes were used to treat the black liquor of refined cotton and sodium copper chlorophyll wastewater to investigate its desalination effect. When the electrodes were used to treat the black liquor of refined cotton after acid treatment, the removal rate of conductivity and COD reached 58. 8% and 75. 6% respectively when 8 pairs of electrodes were used. And when the electrode was used to treat the sodium copper chlorophyll wastewater, the removal rate of conductivity and COD reached higher than 50. 0% and 13. 5% respectively when 6-8 pairs of electrodes were used.
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The effect of HNS on the reinforcement of TNT crystal: a molecular simulation study.
J Mol Model
PUBLISHED: 06-29-2014
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The effect of crystal modifier 2,2',4,4',6,6'-hexanitrostillbene(HNS) on the reinforcement of crystalline 1,3,5-trinitrotoluene (TNT) was investigated by molecular simulation. The intermolecular interactions between HNS and TNT were revealed by quantum chemistry calculations in detail, strong attractive forces were found between HNS and TNT. The solid interface models of TNT/HNS along three crystalline directions were studied, the distance between HNS molecule and TNT system was narrowed after optimization; the mechanical properties were calculated, showing the mechanism of the reinforcement.
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NBS1 Glu185Gln polymorphism and susceptibility to urinary system cancer: a meta-analysis.
Tumour Biol.
PUBLISHED: 06-04-2014
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A number of studies have investigated the association between the NBS1 Glu185Gln (rs1805794, 8360 G?>?C) polymorphism and risk for urinary system cancer including bladder cancer, prostate cancer, and renal cell cancer; however, the findings are conflicting. We conducted a meta-analysis focusing on eight published studies with 3,542 cases and 4,210 controls to derive a more precise evaluation of the relationship between the NBS1 Glu185Gln polymorphism and urinary system cancer susceptibility. Overall, the NBS1 Glu185Gln polymorphism was significantly related to increased risk for urinary system cancer (homozygous model: odds ratio (OR)?=?1.23, 95 % confidence interval (95 % CI)?=?1.05-1.44, p?=?0.011; heterozygous model: OR?=?1.14, 95 % CI?=?1.04-1.26, p?=?0.008; dominant model: OR?=?1.16, 95 % CI?=?1.05-1.27, p?=?0.002; and Gln vs. Glu: OR?=?1.12, 95 % CI?=?1.04-1.20, p?=?0.002) and further stratification analysis indicated an increased risk for bladder cancer (heterozygous model: OR?=?1.13, 95 % CI?=?1.02-1.26, p?=?0.022; dominant model: OR?=?1.14, 95 % CI?=?1.03-1.26, p?=?0.014; and Gln vs. Glu: OR?=?1.09, 95 % CI?=?1.01-1.18, p?=?0.023) and Caucasian populations (homozygous model: OR?=?1.33, 95 % CI?=?1.11-1.59, p?=?0.002; heterozygous model: OR?=?1.16, 95 % CI?=?1.04-1.30, p?=?0.009; dominant model: OR?=?1.19, 95 % CI?=?1.07-1.32, p?=?0.001; and Gln vs. Glu: OR?=?1.15, 95 % CI?=?1.06-1.25, p?
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Effect of Freezing Plasma at -20°C for 2 Weeks on Prothrombin Time, Activated Partial Thromboplastin Time, Dilute Russell Viper Venom Time, Activated Protein C Resistance, and d-Dimer Levels.
Clin. Appl. Thromb. Hemost.
PUBLISHED: 05-21-2014
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To assess the impact of preanalytical variables of time and temperature on prothrombin time (PT), activated partial thromboplastin time (aPTT), dilute Russell viper venom time (DRVVT), activated protein C resistance (APCR), and d-dimer, samples from 23 healthy individuals and 18 patients having coagulopathy with known abnormal PT and aPTT were collected. Plasma from each individual was separately pooled and aliquoted; the first 2 aliquots were stored at room temperature then analyzed at 2 hours (baseline) and 4 hours postcollection. The remaining aliquots were stored at -20°C and thawed for analysis at 48 hours, 1, and 2 weeks. In both healthy participants and participants with coagulopathy, PT, aPTT, APCR, DRVVT, and D-dimer had no significant changes at 4 and 48 hours, and 1 and 2 weeks postcollection compared to baseline, or the changes were less than 10%. The results indicate PT, aPTT, DRVVT, APCR, and d-dimer can be stored for 2 weeks at -20°C without compromising clinical interpretation in both healthy individuals and individuals with coagulopathy. Increasing storage time will facilitate sample processing from off-site clinics.
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Design and synthesis of Fmoc-Thr[PO(OH)(OPOM)] for the preparation of peptide prodrugs containing phosphothreonine in fully protected form.
Chem. Biodivers.
PUBLISHED: 05-16-2014
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The design and efficient synthesis of N-Fmoc-phosphothreonine protected by a mono-(pivaloyloxy)methyl (POM) moiety at its phosphoryl group (Fmoc-Thr[PO(OH)(OPOM)]-OH, 1, is reported. This reagent is suitable for solid-phase syntheses employing acid-labile resins and Fmoc-based protocols. It allows the preparation of phosphothreonine (pThr)-containing peptides bearing bis-POM-phosphoryl protection. The methodology allows the first reported synthesis of pThr-containing polypeptides having bioreversible prodrug protection, and as such it should be useful in a variety of biological applications.
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Gold nanoparticle supported phospholipid membranes as a biomimetic biosensor platform for phosphoinositide signaling detection.
Biosens Bioelectron
PUBLISHED: 05-06-2014
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Enzyme mediated phosphoinositide signaling plays important regulatory roles in diverse cellular processes and has close implication in human diseases. However, detection of phosphoinositide enzymes remains a challenge because of the difficulty in discriminating the phosphorylation patterns of phosphoinositide. Here we develop a novel enzyme-activated gold nanoparticles (AuNPs) assembly strategy as a homogeneous colorimetric biosensor for activity detection of phosphoinositide kinases and phosphatases. This strategy utilizes a biomimetic mechanism of phosphoinositide signaling, in which AuNP supported phospholipid membranes are constructed to mimic the cellular membrane substrate, and AuNPs modified with the pleckstrin homology (PH) domain of cytosolic proteins are designed for specific, multivalent recognition of phosphorylated phosphoinositides. This biomimetic strategy enables efficient enzymatic reactions of the substrate and highly selective detection of target enzyme. The biosensor is demonstrated for the detection of phosphoinositide 3-kinase (PI3K) and phosphatase with tensin homology (PTEN). The results revealed that it allows sensitive, rapid visual detection of the enzymes with pM detection limits and four-decade wide dynamic ranges, and is capable of detecting enzyme activities in complex cell lysate samples. This biosensor might provide a general biosensor platform for high-throughput detection of phosphoinositide enzymes with high sensitivity and selectivity in biomedical research and clinical diagnostics.
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Pro-osteogenic effects of fibrin glue in treatment of avascular necrosis of the femoral head in vivo by hepatocyte growth factor-transgenic mesenchymal stem cells.
J Transl Med
PUBLISHED: 04-28-2014
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Autologous transplantation of modified mesenchymal stem cells (MSCs) is a promising candidate for the treatment of the refractory clinical disease, avascular necrosis of the femoral head (ANFH). Our previous attempts by compounding MSCs with medical fibrin glue to treat ANFH in animal model have achieved excellent effects. However, the underlying molecular mechanism is unclear, especially on the transgenic gene expression.
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[Role of CD8(+)T cells and their secreted cytokines in the pathogenesis of aplastic anemia].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 04-26-2014
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Aplastic anemia(AA) is mostly considered as an immune-mediated bone marrow failure syndrome, characterized by pancytopenia and bone marrow hypoplasia. The pathogenesis of AA is complicated, until now it is not fully understood. Further study on the pathological mechanism will be helpful for the diagnosis and treatment of AA. CD8(+) T cells and their secreted cytokines play important roles in the abnormal immunity during the process of AA. Thus, this review focuses on the role of CD8(+) T cells and their secreted cytokines in the pathogenesis of AA.
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Suv39h1 mediates AP-2?-dependent inhibition of C/EBP? expression during adipogenesis.
Mol. Cell. Biol.
PUBLISHED: 04-14-2014
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Previous studies have shown that CCAAT/enhancer-binding protein ? (C/EBP?) plays a very important role during adipocyte terminal differentiation and that AP-2? (activator protein 2?) acts as a repressor to delay the expression of C/EBP?. However, the mechanisms by which AP-2? prevents the expression of C/EBP? are not fully understood. Here, we present evidence that Suv39h1, a histone H3 lysine 9 (H3K9)-specific trimethyltransferase, and G9a, a euchromatic methyltransferase, both interact with AP-2? and enhance AP-2?-mediated transcriptional repression of C/EBP?. Interestingly, we discovered that G9a mediates dimethylation of H3K9, thus providing the substrate, which is methylated by Suv39h1, to H3K9me3 on the C/EBP? promoter. The expression level of AP-2? was consistent with enrichment of H3K9me2 and H3K9me3 on the C/EBP? promoter in 3T3-L1 preadipocytes. Knockdown of Suv39h markedly increased C/EBP? expression and promoted adipogenesis. Conversely, ectopic expression of Suv39h1 delayed C/EBP? expression and impaired the accumulation of triglyceride, while simultaneous knockdown of AP-2? or G9a partially rescued this process. These findings indicate that Suv39h1 enhances AP-2?-mediated transcriptional repression of C/EBP? in an epigenetic manner and further inhibits adipocyte differentiation.
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Dose dependent cytotoxicity of pranoprofen in cultured human corneal endothelial cells by inducing apoptosis.
Drug Chem Toxicol
PUBLISHED: 03-20-2014
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Abstract Pranoprofen (PPF), a non-steroidal anti-inflammatory drugs (NSAIDs), is often used in keratitis treatment in clinic. Several studies have assessed in vitro the cytotoxicity of topical NSAIDs to corneal epithelial cells due to its importance for predicting human corneal toxicity. Damage by cytotoxic drugs can result in excessive loss of human corneal endothelial (HCE) cells which lead to decompensation of the endothelium and eventual loss of visual acuity. However, the endothelial cytotoxicity of PPF has not yet been reported using an in vitro model of HCE cells. This study assessed the cytotoxicity of PPF to HCE cells and its underlying mechanism. Cellular viability was determined using inverted phase contrast light microscopy, and plasma membrane permeability, genomic DNA fragmentation, and ultrastructure were detected by acridine orange/ethidium bromide staining, DNA agarose gel electrophoresis, and transmission electron microscopy (TEM), respectively. The results on cellular viability showed that PPF at concentrations ranging from 0.0625 to 1.0?g/l had poignant cytotoxicity to HCE cells, and the extent of its cytotoxicity was dose- and time-dependent. Further characterization indicated that PPF induced plasma membrane permeability elevation, DNA fragmentation, and apoptotic body formation, proving its apoptosis inducing effect on HCE cells. In conclusion, PPF above 0.0625?g/l has poignant cytotoxicity on HCE cells in vitro by inducing cell apoptosis, and should be carefully employed in eye clinic.
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HMGB1 mediates hyperglycaemia-induced cardiomyocyte apoptosis via ERK/Ets-1 signalling pathway.
J. Cell. Mol. Med.
PUBLISHED: 02-22-2014
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Apoptosis is a key event involved in diabetic cardiomyopathy. The expression of high mobility group box 1 protein (HMGB1) is up-regulated in diabetic mice. However, the molecular mechanism of high glucose (HG)-induced cardiomyocyte apoptosis remains obscure. We aimed to determine the role of HMGB1 in HG-induced apoptosis of cardiomyocytes. Treating neonatal primary cardiomyocytes with HG increased cell apoptosis, which was accompanied by elevated levels of HMGB1. Inhibition of HMGB1 by short-hairpin RNA significantly decreased HG-induced cell apoptosis by reducing caspase-3 activation and ratio of Bcl2-associated X protein to B-cell lymphoma/leukemia-2 (bax/bcl-2). Furthermore, HG activated E26 transformation-specific sequence-1 (Ets-1), and HMGB1 inhibition attenuated HG-induced activation of Ets-1 via extracellular signal-regulated kinase 1/2 (ERK1/2) signalling. In addition, inhibition of Ets-1 significantly decreased HG-induced cardiomyocyte apoptosis. Similar results were observed in streptozotocin-treated diabetic mice. Inhibition of HMGB1 by short-hairpin RNA markedly decreased myocardial cell apoptosis and activation of ERK and Ets-1 in diabetic mice. In conclusion, inhibition of HMGB1 may protect against hyperglycaemia-induced cardiomyocyte apoptosis by down-regulating ERK-dependent activation of Ets-1.
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Prevention of contrast-induced nephropathy with prostaglandin E1 in high-risk patients undergoing percutaneous coronary intervention.
Int Urol Nephrol
PUBLISHED: 02-13-2014
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Contrast-induced nephropathy (CIN) is an important complication in the use of iodinated contrast media. The present study aimed to assess the safety and efficacy of prostaglandin E1 (PGE1) in prevention of CIN in patients with high-risk factors undergoing percutaneous coronary intervention (PCI).
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Dyserythropoiesis in a child with pyruvate kinase deficiency and coexistent unilateral multicystic dysplastic kidney.
Pediatr Blood Cancer
PUBLISHED: 01-30-2014
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Pyruvate kinase (PK) deficiency is the commonest enzyme deficiency in the glycolytic pathway leading to hemolytic anemia secondary to decreased Adenosine Triphosphate (ATP) synthesis in the red cells. synthesis. PK deficiency due to mutations in the PKLR (1q21) gene leads to highly variable clinical presentation ranging from severe fetal anemia to well compensated anemia in adults. We describe dyserythropoiesis in the bone marrow of a child with transfusion dependent anemia and unilateral multicystic dysplastic kidney (MCDK) mimicking Congenital Dyserythropoietic Anemia type I (CDA type I). Persistently low erythrocyte PK levels and double heterozygous mutations present in the PKLR gene confirmed the diagnosis of PK deficiency.
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A randomized phase 2 trial of erlotinib versus pemetrexed as second-line therapy in the treatment of patients with advanced EGFR wild-type and EGFR FISH-positive lung adenocarcinoma.
Cancer
PUBLISHED: 01-30-2014
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The current study was undertaken to investigate the efficacy and safety of erlotinib versus pemetrexed as second-line therapy for patients with advanced epidermal growth factor receptor (EGFR) wild-type and EGFR fluorescence in situ hybridization (FISH)-positive lung adenocarcinoma.
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The influence of demographics, psychological factors and self-efficacy on symptom distress in colorectal cancer patients undergoing post-surgical adjuvant chemotherapy.
Eur J Oncol Nurs
PUBLISHED: 01-28-2014
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To explore the influence of self-efficacy and demographic, disease-related, and psychological factors on symptom distress among Chinese colorectal cancer patients receiving postoperative adjuvant chemotherapy.
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Structure of the unique SEFIR domain from human interleukin 17 receptor A reveals a composite ligand-binding site containing a conserved ?-helix for Act1 binding and IL-17 signaling.
Acta Crystallogr. D Biol. Crystallogr.
PUBLISHED: 01-20-2014
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Interleukin 17 (IL-17) cytokines play a crucial role in mediating inflammatory and autoimmune diseases. A unique intracellular signaling domain termed SEFIR is found within all IL-17 receptors (IL-17Rs) as well as the key adaptor protein Act1. SEFIR-mediated protein-protein interaction is a crucial step in IL-17 cytokine signaling. Here, the 2.3 Å resolution crystal structure of the SEFIR domain of IL-17RA, the most commonly shared receptor for IL-17 cytokine signaling, is reported. The structure includes the complete SEFIR domain and an additional ?-helical C-terminal extension, which pack tightly together to form a compact unit. Structural comparison between the SEFIR domains of IL-17RA and IL-17RB reveals substantial differences in protein topology and folding. The uniquely long insertion between strand ?C and helix ?C in IL-17RA SEFIR is mostly well ordered, displaying a helix (?CC'ins) and a flexible loop (CC'). The DD' loop in the IL-17RA SEFIR structure is much shorter; it rotates nearly 90° with respect to the counterpart in the IL-17RB SEFIR structure and shifts about 12?Å to accommodate the ?CC'ins helix without forming any knots. Helix ?C was identified as critical for its interaction with Act1 and IL-17-stimulated gene expression. The data suggest that the heterotypic SEFIR-SEFIR association via helix ?C is a conserved and signature mechanism specific for IL-17 signaling. The structure also suggests that the downstream motif of IL-17RA SEFIR together with helix ?C could provide a composite ligand-binding surface for recruiting Act1 during IL-17 signaling.
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An Elevated Peripheral Blood Lymphocyte-to-Monocyte Ratio Predicts Favorable Response and Prognosis in Locally Advanced Breast Cancer following Neoadjuvant Chemotherapy.
PLoS ONE
PUBLISHED: 01-01-2014
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Neoadjuvant chemotherapy (NCT) is a standard treatment option for locally advanced breast cancer. However, the lack of an efficient method to predict treatment response and patient prognosis hampers the clinical evaluation of patient eligibility for NCT. An elevated lymphocyte-to-monocyte ratio (LMR) has been reported to be associated with a favorable prognosis for certain hematologic malignancies and for nasopharyngeal carcinoma; however, this association has not been investigated in breast cancer. The purpose of this study was to evaluate whether pre-NCT LMR analysis could predict the prognosis of patients with locally advanced breast cancer.
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Screening of RB1 gene mutations in Chinese patients with retinoblastoma and preliminary exploration of genotype-phenotype correlations.
Mol. Vis.
PUBLISHED: 01-01-2014
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Retinoblastoma (RB) sets the paradigm for hereditary cancer syndromes, for which medical care can change depending on the results of genetic testing. In this study, we screened constitutional mutations in the RB1 gene via a method combining DNA sequencing and multiplex ligation-dependent probe amplification (MLPA), and performed a preliminary exploration of genotype-phenotype correlations.
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Cytotoxic effects of betaxolol on healthy corneal endothelial cells both in vitro and in vivo.
Int J Ophthalmol
PUBLISHED: 01-01-2014
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To demonstrate the cytotoxic effect of betaxolol and its underlying mechanism on human corneal endothelial cells (HCE cells) in vitro and cat corneal endothelial cells (CCE cells) in vivo, providing experimental basis for safety anti-glaucoma drug usage in clinic of ophthalmology.
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Diffuse large B-cell lymphoma arising in a composite lymphoma with biclonality by flow cytometry and one monoclonal band by PCR.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Composite lymphoma (CL) refers to the presence of two or more distinct types of lymphomas in a single organ or tissue. CL is an infrequent finding and may be due to the existence of two genetically related neoplasms, i.e. transformation of a single lymphoma into another lymphoma, or be due to the presence of two clonally unrelated lymphomas. CL composed of more than two lymphomas is even rare. Herein we describe a case of diffuse large B-cell lymphoma (DLBCL) arising in a CL of follicular lymphoma (FL) and small lymphocytic lymphoma (SLL) in an inguinal lymph node of an 85 year old woman. The three lymphomas were morphologically and immunophenotypically distinct while flow cytometry detected two monoclonal B-cell populations. Karyotyping and Polymerase Chain Reaction (PCR) for B-cell clonality each detected a single monoclonal B-cell population. The morphology findings may suggest DLBCL being transformed from FL while Richter transformation from SLL appears to be less likely in our case. Due to the single clone by chromosome study and PCR study, the precise relationships of the three lymphomas are unknown.
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[Heavy metal speciation and stability in the sediment of Lihu Lake].
Huan Jing Ke Xue
PUBLISHED: 12-03-2013
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The spatial occurrence characteristics of the speciation of Cr, Ni, Cu, Zn, As, Cd, Hg and Pb in sediments of the lake body and river mouths of Lihu Lake were studied. Meanwhile, combined with the spatial distribution of metals in interstitial water, the stability and bio-availability of various forms of studied metals were discussed. The results showed that metals in interstitial water and extractable metals in surface sediments both had obvious spatial heterogeneity, and the metal contents in retreated fishery district were lower. High value areas of Cr, Cu and Zn distributed in belt along Baojie Bridge and Lihu Lake Bridge, and the high value areas of Ni, As, Cd, Hg distributed in sector extending from river mouths to the lake body. Most metals mainly existed in residue state except for Cd, Cu and Ni, the extractable content of which respectively accounted for 71.02%, 54.79% and 50.62% of the total content. The stability of eight studied metals was in the order of Cr > Pb > Hg > As > Cu > Ni > Zn > Cd. Cd and Zn were unstable in most studied sites, so there was higher risk of quick desorption and release. Toxicity assessment of interstitial water showed that the tested metals would not pose acute toxicity for aquatic ecosystem, but Hg and Pb in some districts, especially in the river mouths, might pose chronic toxicity for the benthonic organisms.
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Peptide-Templated Gold Nanocluster Beacon as a Sensitive, Label-Free Sensor for Protein Post-translational Modification Enzymes.
Anal. Chem.
PUBLISHED: 11-26-2013
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Protein post-translational modifications (PTMs), which are chemical modifications and most often regulated by enzymes, play key roles in functional proteomics. Detection of PTM enzymes, thus, is critical in the study of cell functioning and development of diagnostic and therapeutic tools. Herein, we develop a simple peptide-templated method to direct rapid synthesis of highly fluorescent gold nanoclusters (AuNCs) and interrogate the effect of enzymatic modifications on their luminescence. A new finding is that enzymes are able to exert chemical modifications on the peptide-templated AuNCs and quench their fluorescence, which furnishes the development of a real-time and label-free sensing strategy for PTM enzymes. Two PTM enzymes, histone deacetylase 1 and protein kinase A, have been employed to demonstrate the feasibility of this enzyme-responsive fluorescent nanocluster beacon. The results reveal that the AuNCs fluorescence can be dynamically decreased with increasing concentration of the enzymes, and subpicomolar detection limits are readily achieved for both enzymes. The developed strategy can thus offer a useful, label-free biosensor platform for the detection of protein-modifying enzymes and their inhibitors in biomedical applications.
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p300-Dependent Acetylation of ATF5 Enhances C/EBP? Transactivation of C/EBP? During 3T3-L1 Differentiation.
Mol. Cell. Biol.
PUBLISHED: 11-11-2013
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Adipogenesis is a multistep process by which 3T3-L1 preadipocytes differentiate into mature adipocytes through mitotic clonal expansion (MCE) and terminal differentiation. The CCAAT/enhancer-binding protein (C/EBP) ? is an important transcription factor that takes part in both of these processes. C/EBP? not only transactivates C/EBP? and the peroxisome proliferator-activated receptor (PPAR) ?, which cause 3T3-L1 preadipocytes to enter terminal adipocyte differentiation, but is also required to activate cell cycle genes necessary for MCE. The identification of potential cofactors of C/EBP? will help to explain how C/EBP? undertakes these specialized roles during the different stages of adipogenesis. In this study, we found that activating transcription factor 5 (ATF5) can bind to the promoter of C/EBP? via its direct interaction with C/EBP? (which is mediated via the p300-dependent acetylation of ATF5) leading to enhanced C/EBP? transactivation of C/EBP?. We also show that p300 is important for the interaction of ATF5 with C/EBP? as well as the binding activity of this complex on the C/EBP? promoter. Consistent with these findings, overexpression of ATF5 and an acetylated ATF5 mimic both promoted 3T3-L1 adipocyte differentiation, whereas siRNA-mediated ATF5 down-regulation inhibited this process. Furthermore, we show that the elevated expression of ATF5 is correlated with an obese phenotype in both mice and humans. In summary, we have identified ATF5 as a new cofactor of C/EBP? and examined how C/EBP? and ATF5 (acetylated by a p300-dependent mechanism) regulate the transcription of C/EBP?.
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[Efficacy and safety of the HAA regimen as induction chemotherapy in 236 de novo acute myeloid leukemia].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 11-01-2013
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To evaluate the efficacy and safety of the HAA regimen (homoharringtonine, cytarabine and aclarubicin) as induction chemotherapy in de novo acute myeloid leukemia (AML).
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[Osteoclasts and early bone remodeling after orthodontic micro-implant placement].
Shanghai Kou Qiang Yi Xue
PUBLISHED: 10-09-2013
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To observe the incidence of osteoclasts during early bone remodeling after orthodontic micro-implant placement.
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Arginase I enhances atherosclerotic plaque stabilization by inhibiting inflammation and promoting smooth muscle cell proliferation.
Eur. Heart J.
PUBLISHED: 09-01-2013
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The aim of this study was to investigate the effect of Arginase I (ArgI) on plaque stabilization in unruptured atherosclerotic plaque and explore its mechanism.
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[Homoharringtonine combined arsenic trioxide induced apoptosis in human multiple myeloma cell line RPMI 8226: an experimental research].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 08-29-2013
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To clarify the effects and mechanisms of homoharringtonine (HHT) monomer therapy or combination therapy with arsenic trioxide (ATO) on human multiple myeloma (MM) cell line RPMI 8226 in in vitro researches.
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[The microbiology and antimicrobial susceptibility of the infected knee arthroplasty].
Zhonghua Wai Ke Za Zhi
PUBLISHED: 08-21-2013
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To describe the microbiology, antimicrobial susceptibility of patients proven prosthetic joint infection (PJI) after primary total knee arthroplasty (TKA)and to provide reference for the diagnosis and treatment of this complication.
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[Assessing the benthic ecological status in Yangtze River Estuary using AMBI and M-AMBI].
Huan Jing Ke Xue
PUBLISHED: 08-07-2013
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Both AMBI and M-AMBI could effectively assess the benthic ecological status of estuaries and coastal systems with soft sediments, and show the response of benthic communities to human pressures and natural changes. To monitor the ecological status of Yangtze River Estuary, macroinvertebrate samples and environmental data were collected in April 2009. Results showed that the benthic habit of Yangtze River Estuary was disturbed to various degrees, especially in the watersheds of Hangzhou Bay, coastal areas of Zhoushan islands and in the inner part of Yangtze River Estuary, which was related to land resourced discharges, eutrophication and large amounts of coastal projects. No significant difference was found between the calculation results of AMBI and M-AMBI based on density and biomass, as indicated by one-way Analysis of Variance (ANOVA). Compared with AMBI, M-AMBI could be more effective to assess the ecological status of Yangtze River Estuary because M-AMBI matched the community structure and environmental variables better. Moreover, according to results of Pearson correlation and linear regression analysis, significant negative relationships were found between the eutrophication index both in the surface and bottom water layers and M-AMBI, but no significant relationship was found between the eutrophication index and AMBI. Therefore, M-AMBI could be more suitable in indicating the eutrophication stress of Yangtze River Estuary.
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[Expression of IL-27 in multiple myeloma and its cell lines].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 08-03-2013
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To study the expression and significance of IL-27 in patients with multiple myeloma (MM) and in the supernatant of MM cell lines U266 and RPMI8226 cells culture medium.
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Epithelial-mesenchymal transition is necessary for acquired resistance to cisplatin and increases the metastatic potential of nasopharyngeal carcinoma cells.
Int. J. Mol. Med.
PUBLISHED: 08-02-2013
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Radiotherapy and adjuvant cisplatin (DDP) chemotherapy are standard approaches used in the treatment of nasopharyngeal carcinoma (NPC). However, resistance to chemotherapy has recently become more common, resulting in the failure of this combination therapy for NPC. The aim of the present study was to assess the cellular morphology, motility and molecular changes in DDP-resistant NPC cells in relation to epithelial-mesenchymal transition (EMT). CNE2 cells were continuously exposed to increasing doses of DDP to establish a stable cell line resistant to DDP (CNE2/DDP cells). The human NPC cell lines, HNE1, CNE2, HNE1/DDP and CNE2/DDP, were used to examine the association between chemoresistance and the acquisition of an EMT-like phenotype of cancer cells. The DDP-resistant cells were less sensitive than the HNE1 cells to treatment with DDP, and were shown by a cell viability assay, western blot analysis and qRT-PCR to have acquired chemoresistance. The HNE1/DDP cells examined by wound healing and Transwell Boyden chamber assays exhibited an increased migration and invasion potential. The DDP-resistant cells exhibited morphological and molecular changes consistent with EMT, as observed by western blot analysis and qRT-PCR. These changes included becoming more spindle-like in shape, a loss of polarity and formation of pseudopodia, the downregulation of E-cadherin and ?-catenin and the upregulation of vimentin, ?bronectin and matrix metalloproteinase (MMP)-9. Moreover, the levels of the EMT-related transcription factors, Snail, Slug, Twist and zinc finger E-box binding homeobox 1 (ZEB1), were higher in the DDP?resistant NPC cells. These data suggest that the development of DDP resistance of NPC cells is accompanied by inducible EMT-like changes with an increased metastatic potential in vitro. Further elucidation of the association between resistance to DDP and EMT may facilitate the future development of novel therapeutic approaches for the treatment of chemoresistant tumors.
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Therapeutic effects of electroacupuncture at ST36 acupoint on sodium-taurocholate-induced severe acute pancreatitis.
Chin J Integr Med
PUBLISHED: 07-27-2013
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To explore the protective effects and mechanisms of electroacupuncture (EA) at Zusanli (ST36) acupoint in rats with severe acute pancreatitis (SAP).
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Clinical outcome of childhood lymphoblastic lymphoma in Shanghai China 2001-2010.
Pediatr Blood Cancer
PUBLISHED: 06-28-2013
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This retrospective cohort study analysed the clinical characteristics and outcomes of patients with childhood lymphoblastic lymphoma (LBL) treated in Shanghai, China.
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HuR is required for IL-17-induced Act1-mediated CXCL1 and CXCL5 mRNA stabilization.
J. Immunol.
PUBLISHED: 06-14-2013
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IL-17, a major inflammatory cytokine plays a critical role in the pathogenesis of many autoimmune inflammatory diseases. In this study, we report a new function of RNA-binding protein HuR in IL-17-induced Act1-mediated chemokine mRNA stabilization. HuR deficiency markedly reduced IL-17-induced chemokine expression due to increased mRNA decay. Act1-mediated HuR polyubiquitination was required for the binding of HuR to CXCL1 mRNA, leading to mRNA stabilization. Although IL-17 induced the coshift of Act1 and HuR to the polysomal fractions in a sucrose gradient, HuR deficiency reduced the ratio of translation-active/translation-inactive IL-17-induced chemokine mRNAs. Furthermore, HuR deletion in distal lung epithelium attenuated IL-17-induced neutrophilia. In summary, HuR functions to couple receptor-proximal signaling to posttranscriptional machinery, contributing to IL-17-induced inflammation.
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Transactivation of Atg4b by C/EBP? promotes autophagy to facilitate adipogenesis.
Mol. Cell. Biol.
PUBLISHED: 06-10-2013
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Autophagy is a highly conserved self-digestion pathway involved in various physiological and pathophysiological processes. Recent studies have implicated a pivotal role of autophagy in adipocyte differentiation, but the molecular mechanism for its role and how it is regulated during this process are not clear. Here, we show that CCAAT /enhancer-binding protein ? (C/EBP?), an important adipogenic factor, is required for the activation of autophagy during 3T3-L1 adipocyte differentiation. An autophagy-related gene, Atg4b, is identified as a de novo target gene of C/EBP? and is shown to play an important role in 3T3-L1 adipocyte differentiation. Furthermore, autophagy is required for the degradation of Klf2 and Klf3, two negative regulators of adipocyte differentiation, which is mediated by the adaptor protein p62/SQSTM1. Importantly, the regulation of autophagy by C/EBP? and the role of autophagy in Klf2/3 degradation and in adipogenesis are further confirmed in mouse models. Our data describe a novel function of C/EBP? in regulating autophagy and reveal the mechanism of autophagy during adipocyte differentiation. These new insights into the molecular mechanism of adipose tissue development provide a functional pathway with therapeutic potential against obesity and its related metabolic disorders.
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Design and synthesis of a reagent for solid-phase incorporation of the phosphothreonine mimetic (2S,3R)-2-amino-3-methyl-4-phosphonobutyric acid (Pmab) into peptides in a bio-reversible phosphonyl-bis-pivaloyloxymethyl (POM) prodrug form.
Amino Acids
PUBLISHED: 06-07-2013
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Reported herein are the synthesis and solid-phase peptide incorporation of N-Fmoc-(2S,3R)-2-amino-3-methyl-4-phosphonobutyric acid bis-pivaloyloxymethyl phosphoryl ester [Fmoc-Pmab(POM)2-OH, 2] as a phosphatase-stable phosphothreonine (pThr) mimetic bearing orthogonal protection suitable for the synthesis of Pmab-containing peptides having bio-reversible protection of the phosphonic acid moiety. This represents the first report of a bio-reversibly protected pThr mimetic in a form suitable for facile solid-phase peptide synthesis.
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Peptide-based inhibitors of Plk1 polo-box domain containing mono-anionic phosphothreonine esters and their pivaloyloxymethyl prodrugs.
Chem. Biol.
PUBLISHED: 06-04-2013
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Binding of polo-like kinase 1 (Plk1) polo-box domains (PBDs) to phosphothreonine (pThr)/phosphoserine (pSer)-containing sequences is critical for the proper function of Plk1. Although high-affinity synthetic pThr-containing peptides may be used to disrupt PBD function, the efficacy of such peptides in whole cell assays has been poor. This potentially reflects limited cell membrane permeability arising in part from the di-anionic nature of the phosphoryl group. We report five-mer peptides containing mono-anionic pThr phosphoryl esters that exhibit single-digit nanomolar PBD binding affinities in extracellular assays and improved antimitotic efficacies in whole cell assays. The cellular efficacies of these peptides have been further enhanced by the application of bio-reversible pivaloyloxymethyl (POM) phosphoryl protection to a pThr-containing polypeptide. Our findings may redefine structural parameters for the development of PBD-binding peptides and peptide mimetics.
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Antibody-directed Double Suicide Gene Therapy Targeting of MUC1- Positive Leukemia Cells In Vitro and In Vivo.
Curr Gene Ther
PUBLISHED: 05-17-2013
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Our aim was to specifically transfer the cytosine deaminase (CD) and thymidine kinase (TK) genes into mucin 1 (MUC1)-positive leukemia cells by anti-MUC1 antibody directed infection of replication-defective lentivirus and to evaluate the targeted cytotoxicity of double suicide genes to leukemia. The target gene vector (containing CD and TK) and envelope (containing GFP and anti-MUC1) and packaging plasmids were cotransfected into 293T cells to produce the recombinant lentivirus. Suicide genes in virus-infected leukemia cells (U937, Jurkat, and K562) were detected by western blot. The cytotoxicity and bystander effect in vitro and the therapeutic effect in vivo were detected after treatment with the prodrugs. The results revealed that combined treatment with prodrug 5-fluorocytosine (5-FC) and ganciclovir (GCV) inhibited leukemia cell growth and caused significant bystander effect than treatment with either prodrug alone. TK/GCV treatment alone induced degeneration and cell death while the effect of CD/5-FC alone mainly caused vacuolar degeneration and necrosis. The addictive effects of combinatorial use of GCV and 5-FC mainly induced swelling of the mitochondria followed by necrosis of the leukemia cells. In vivo experiments revealed that both single and combinatorial prodrug treatments could prolong the survival time of leukemic mice. In summary, anti-MUC1 antibody directed lentiviral vector successfully transduced dual suicide genes and exerted targeted cytotoxicity against MUC1 positive leukemia cells. This targeted lentiviral dual suicide gene delivering system provides a promising approach for clinical treatment of leukemia in future.
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Clinical effects and complications of TIPS for portal hypertension due to cirrhosis: A single center.
World J. Gastroenterol.
PUBLISHED: 05-07-2013
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To determine the clinical effects and complications of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension due to cirrhosis.
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A case of Philadelphia chromosome positive myeloproliferative neoplasm in a pregnant woman with unusual primary myelofibrosis features.
Case Rep Hematol
PUBLISHED: 04-18-2013
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Myeloproliferative neoplasms (MPNs) are traditionally separated into BCR-ABL-positive chronic myeloid leukemia (CML), and BCR-ABL-negative MPNs including primary myelofibrosis (PMF), essential thrombocythemia (ET), and so forth. One of the diagnostic requirements for PMF and ET is the absence of the Philadelphia chromosome, while its presence is almost universally indicative of CML. However, a diagnostic dilemma arises when Philadelphia chromosome-positive MPNs lack the majority of the typical features seen in CML. Some of these classic CML features include basophilIa, marked leukocytosis, neutrophils left-shift with myelocytes bulge, and "dwarf" megakaryocytes. Presented here is a case of a 32-year-old pregnant patient who did not have typical morphologic findings for CML, and yet the Philadelphia chromosome was positive. The patient demonstrated some pathologic features that are commonly presented in PMF that included bone marrow reticulin fibrosis, leukoerythroblastosis, splenomegaly, and increased serum lactate dehydrogenase.
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[A cone-beam computed tomography study of changes in canal isthmus of maxillary first premolars before and after instrumentation].
Shanghai Kou Qiang Yi Xue
PUBLISHED: 04-05-2013
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To analyze the difference of the incidence and type of root canal isthmus in maxillary first premolars with single root and two canals before and after instrumentation using cone-beam computed tomography(CBCT), and investigate the application and effect of CBCT in analysis of root canal isthmus.
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G9a is transactivated by C/EBP? to facilitate mitotic clonal expansion during 3T3-L1 preadipocyte differentiation.
Am. J. Physiol. Endocrinol. Metab.
PUBLISHED: 03-19-2013
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In 3T3-L1 preadipocyte differentiation, the CCAAT/enhancer-binding protein-? (C/EBP?) is an important early transcription factor that activates cell cycle genes during mitotic clonal expansion (MCE), sequentially activating peroxisome proliferator-activated receptor-? (PPAR?) and C/EBP? during terminal differentiation. Although C/EBP? acquires its DNA binding activity via dual phosphorylation at about 12-16 h postinduction, the expression of PPAR? and C/EBP? is not induced until 36-72 h. The delayed expression of PPAR? and C/EBP? ensures the progression of MCE, but the mechanism responsible for the delay remains elusive. We provide evidence that G9a, a major euchromatic methyltransferase, is transactivated by C/EBP? and represses PPAR? and C/EBP? through H3K9 dimethylation of their promoters during MCE. Inhibitor- or siRNA-mediated G9a downregulation modestly enhances PPAR? and C/EBP? expression and adipogenesis in 3T3-L1 preadipocytes. Conversely, forced expression of G9a impairs the accumulation of triglycerides. Thus, this study elucidates an epigenetic mechanism for the delayed expression of PPAR? and C/EBP?.
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Optical visualization of individual ultralong carbon nanotubes by chemical vapour deposition of titanium dioxide nanoparticles.
Nat Commun
PUBLISHED: 03-14-2013
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Direct visualization and manipulation of individual carbon nanotubes in ambient conditions is of great significance for their characterizations and applications. However, the observation of individual carbon nanotubes usually requires electron microscopes under high vacuum. Optical microscopes are much more convenient to be used, yet their resolution is low. Here we realize the visualization and manipulation of individual ultralong carbon nanotubes under optical microscopes by deposition of TiO2 nanoparticles on them. The strong scattering of TiO2 nanoparticles to visible light renders them visible by optical microscopes. Micro-Raman-spectroscopy measurement of individual carbon nanotubes is greatly facilitated by their optical visualization. With the assistance of TiO2 nanoparticles, individual carbon nanotubes can be easily manipulated under an optical microscope at macroscopic scale and in ambient conditions. Based on our approach, various manipulation of ultralong carbon nanotubes, including cutting, transfer, fabrication of structures/devices and pulling out inner shells of multiwalled carbon nanotubes, are demonstrated.
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Transplantation of tissue-engineered human corneal endothelium in cat models.
Mol. Vis.
PUBLISHED: 02-15-2013
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To evaluate the performance of reconstructed tissue-engineered human corneal endothelium (TE-HCE) by corneal transplantation in cat models.
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MicroRNA-140 promotes adipocyte lineage commitment of C3H10T1/2 pluripotent stem cells via targeting osteopetrosis-associated transmembrane protein 1.
J. Biol. Chem.
PUBLISHED: 02-06-2013
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BMP4 has been shown to induce C3H10T1/2 pluripotent stem cells to commit to adipocyte lineage. In addition to several proteins identified, microRNAs also play a critical role in the process. In this study, we identified microRNA-140 (miR-140) as a direct downstream component of the BMP4 signaling pathway during the commitment of C3H10T1/2 cells to adipocyte lineage. Overexpression of miR-140 in C3H10T1/2 cells promoted commitment, whereas knockdown of its expression led to impairment. Additional studies indicated that Ostm1 is a bona fide target of miR-140, which is significantly decreased during commitment, and Ostm1 was also demonstrated to function as an anti-adipogenic factor.
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BMP4-mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 02-06-2013
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Expression of bone morphogenetic protein 4 (BMP4) in adipocytes of white adipose tissue (WAT) produces "white adipocytes" with characteristics of brown fat and leads to a reduction of adiposity and its metabolic complications. Although BMP4 is known to induce commitment of pluripotent stem cells to the adipocyte lineage by producing cells that possess the characteristics of preadipocytes, its effects on the mature white adipocyte phenotype and function were unknown. Forced expression of a BMP4 transgene in white adipocytes of mice gives rise to reduced WAT mass and white adipocyte size along with an increased number of a white adipocyte cell types with brown adipocyte characteristics comparable to those of beige or brite adipocytes. These changes correlate closely with increased energy expenditure, improved insulin sensitivity, and protection against diet-induced obesity and diabetes. Conversely, BMP4-deficient mice exhibit enlarged white adipocyte morphology and impaired insulin sensitivity. We identify peroxisome proliferator-activated receptor gamma coactivator 1-? (PGC1?) as the target of BMP signaling required for these brown fat-like changes in WAT. This effect of BMP4 on WAT appears to extend to human adipose tissue, because the level of expression of BMP4 in WAT correlates inversely with body mass index. These findings provide a genetic and metabolic basis for BMP4s role in altering insulin sensitivity by affecting WAT development.
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HDA18 affects cell fate in Arabidopsis root epidermis via histone acetylation at four kinase genes.
Plant Cell
PUBLISHED: 01-29-2013
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The differentiation of hair (H) and non-hair (N) cells in the Arabidopsis thaliana root epidermis is dependent on positional relationships with underlying cortical cells. We previously found that histone acetylation relays positional information and that a mutant altered in the histone deacetylase gene family member HISTONE DEACETYLASE 18 (HDA18) exhibits altered H and N epidermal cell patterning. Here, we report that HDA18 has in vitro histone deacetylase activity and that both mutation and overexpression of HDA18 led to cells at the N position having H fate. The HDA18 protein physically interacted with histones related to a specific group of kinase genes, which are demonstrated in this study to be components of a positional information relay system. Both down- and upregulation of HDA18 increased transcription of the targeted kinase genes. Interestingly, the acetylation levels of histone 3 lysine 9 (H3K9), histone 3 lysine 14 (H3K14) and histone 3 lysine 18 (H3K18) at the kinase genes were differentially affected by down- or upregulation of HDA18, which explains why the transcription levels of the four HDA18-target kinase genes increased in all lines with altered HDA18 expression. Our results reveal the surprisingly complex mechanism by which HDA18 affects cellular patterning in Arabidopsis root epidermis.
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Crystal structure of IL-17 receptor B SEFIR domain.
J. Immunol.
PUBLISHED: 01-25-2013
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IL-17 cytokines play a crucial role in a variety of inflammatory and autoimmune diseases. They signal through heterodimeric receptor complexes consisting of members of IL-17R family. A unique intracellular signaling domain was identified within all IL-17Rs, termed similar expression to fibroblast growth factor genes and IL-17R (SEFIR). SEFIR is also found in NF-?B activator 1 (Act1), an E3 ubiquitin ligase, and mediates its recruitment to IL-17Rs. In this study, to our knowledge, we report the structure of the first SEFIR domain from IL-17RB at 1.8Å resolution. SEFIR displays a five-stranded parallel ?-sheet that is wrapped by six helices. Site-directed mutagenesis on IL-17RB identified helix ?C as being critical for its interaction with Act1 and IL-25 (IL-17E) signaling. Using the current SEFIR structure as a template, the key functional residues in Act1 are also mapped as part of helix ?C, which is conserved in IL-17RA and RC, suggesting this helix as a common structural signature for heterotypic SEFIR-SEFIR association. In contrast, helix ?B is important for homodimerization of Act1, implicating a dual ligand-binding model for SEFIR domain, with distinct structural motifs participating in either homotypic or heterotypic interactions. Furthermore, although the IL-17RB-SEFIR structure resembles closest to the Toll/IL-1R domain of TLR10 with low sequence homology, substantial differences were observed at helices ?C, ?D, and DD loop. To our knowledge, this study provides the first structural view of the IL-17R intracellular signaling, unraveling the mechanism for the specificity of SEFIR versus Toll/IL-1R domain in their respective signaling pathways.
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Occludin is required for TRPV1-modulated paracellular permeability in the submandibular gland.
J. Cell. Sci.
PUBLISHED: 01-23-2013
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Occludin plays an important role in maintaining tight junction barrier function in many types of epithelia. We previously reported that activation of transient receptor potential vanilloid subtype 1 (TRPV1) in rabbit submandibular gland promoted salivary secretion, partly by an increase in paracellular permeability. We have now explored the role of occludin in TRPV1-modulated paracellular permeability in a rat submandibular gland cell line SMG-C6. Both TRPV1 and occludin were expressed in SMG-C6 cells, and capsaicin induced redistribution of occludin, but not claudin-3, claudin-4 or E-cadherin, from the cell membrane into the cytoplasm. Capsaicin also decreased transepithelial electrical resistance (TER) and increased the Trypan Blue and FITC-dextran flux. Capsazepine (CPZ), a TRPV1 antagonist, inhibited the capsaicin-induced occludin redistribution and TER decrease. Moreover, occludin knockdown by shRNA suppressed, whereas occludin re-expression restored, the TER response to capsaicin. Mechanistically, TRPV1 activation increased ERK1/2 and MLC2 phosphorylation. PD98059, an ERK1/2 kinase inhibitor, abolished the capsaicin-induced MLC2 phosphorylation, whereas ML-7, an MLC2 kinase inhibitor, did not affect ERK1/2 phosphorylation, suggesting that ERK1/2 is the upstream signaling molecule of MLC2. Capsaicin also induced F-actin reorganization, which was abolished by CPZ, PD98059 and ML-7, indicating that TRPV1 activation altered F-actin organization in an ERK1/2- and MLC2-dependent manner. Furthermore, either PD98059 or ML-7 could abolish the capsaicin-induced TER response and occludin redistribution, whereas knockdown of ERK1/2 further confirmed that the TRPV1-modulated paracellular permeability was ERK1/2 dependent. Taken together, these results identified a crucial role of occludin in submandibular epithelial cells, and more importantly, demonstrated that occludin was required to mediate TRPV1-modulated paracellular permeability.
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Etiological and clinical analysis of osteonecrosis of the femoral head in Chinese patients.
Chin. Med. J.
PUBLISHED: 01-18-2013
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Many potential causative factors are related to the initiation and progression of osteonecrosis of the femoral head. The aim of this research was to investigate the etiology and clinical features of osteonecrosis of the femoral head in Chinese patients.
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Acrylamide biodegradation ability and plant growth-promoting properties of Variovorax boronicumulans CGMCC 4969.
Biodegradation
PUBLISHED: 01-16-2013
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Species of the genus Variovorax are often isolated from nitrile or amide-containing organic compound-contaminated soil. However, there have been few biological characterizations of Variovorax and their contaminant-degrading enzymes. Previously, we reported a new soil isolate, Variovorax boronicumulans CGMCC 4969, and its nitrile hydratase that transforms the neonicotinoid insecticide thiacloprid into an amide metabolite. In this study, we showed that CGMCC 4969 is able to degrade acrylamide, a neurotoxicant and carcinogen in animals, during cell growth in a mineral salt medium as well as in its resting state. Resting cells rapidly hydrolyzed 600 mg/L acrylamide to acrylic acid with a half-life of 2.5 min. In in vitro tests, CGMCC 4969 showed plant growth-promoting properties; it produced a siderophore, ammonia, hydrogen cyanide, and the phytohormone salicylic acid. Interestingly, in soil inoculated with this strain, 200 mg/L acrylamide was completely degraded in 4 days. Gene cloning and overexpression in the Escherichia coli strain Rosetta (DE3) pLysS resulted in the production of an aliphatic amidase of 345 amino acids that hydrolyzed acrylamide into acrylic acid. The amidase contained a conserved catalytic triad, Glu59, Lys 134, and Cys166, and an "MRHGDISSS" amino acid sequence at the N-terminal region. Variovorax boronicumulans CGMCC 4969, which is able to use acrylamide for cell growth and rapidly degrade acrylamide in soil, shows promising plant growth-promoting properties. As such, it has the potential to be developed into an effective Bioaugmentation strategy to promote growth of field crops in acrylamide-contaminated soil.
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Metabolic changes in the visual cortex of binocular blindness macaque monkeys: a proton magnetic resonance spectroscopy study.
PLoS ONE
PUBLISHED: 01-01-2013
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To evaluate proton magnetic resonance spectroscopy ((1)H-MRS) in a study of cross-modal plasticity in the visual cortex of binocular blindness macaque monkeys.
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Streptozotocin induced diabetic retinopathy in rat and the expression of vascular endothelial growth factor and its receptor.
Int J Ophthalmol
PUBLISHED: 01-01-2013
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To establish the rat model of streptozotocin (STZ)-induced diabetic retinopathy (DR), which is the most common cause of visual loss and blindness in patients with diabetes, and observe the gene expression of vascular endothelial growth factor (VEGF) and its receptors during the development of DR.
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Biotransformation of the neonicotinoid insecticide thiacloprid by the bacterium Variovorax boronicumulans strain J1 and mediation of the major metabolic pathway by nitrile hydratase.
J. Agric. Food Chem.
PUBLISHED: 12-23-2011
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A neonicotinoid insecticide thiacloprid-degrading bacterium strain J1 was isolated from soil and identified as Variovorax boronicumulans by 16S rRNA gene sequence analysis. Liquid chromatography-mass spectrometry and nuclear magnetic resonance analysis indicated the major pathway of thiacloprid (THI) metabolism by V. boronicumulans J1 involved hydrolysis of the N-cyanoimino group to form an N-carbamoylinino group containing metabolite, THI amide. Resting cells of V. boronicumulans J1 degraded 62.5% of the thiacloprid at a concentration of 200 mg/L in 60 h, and 98% of the reduced thiacloprid was converted to the final metabolite thiacloprid amide. A 2.6 kb gene cluster from V. boronicumulans J1 that includes the full length of the nitrile hydratase gene was cloned and investigated by degenerate primer polymerase chain reaction (PCR) and inverse PCR. The nitrile hydratase gene has a length of 1304 bp and codes a cobalt-type nitrile hydratase with an ?-subunit of 213 amino acids and a ?-subunit of 221 amino acids. The nitrile hydratase gene was recombined into plasmid pET28a and overexpressed in Escherichia coli BL21 (DE3). The resting cells of recombinant E. coli BL21 (DE3)-pET28a-NHase with overexpression of nitrile hydratase transformed thiacloprid to its amide metabolite, whereas resting cells of the control E. coli BL21 (DE3)-pET28a did not. Therefore, the major hydration pathway of thiacloprid is mediated by nitrile hydratase.
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[The immunocyte subsets and their clinical significance in the peripheral blood of 35 patients with immune thrombocytopenic purpura].
Zhonghua Nei Ke Za Zhi
PUBLISHED: 12-20-2011
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To explore the clinical significance of immunocyte subsets before and after immunosuppressive therapy in the peripheral blood of patients with immune thrombocytopenic purpura (ITP).
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Is there any relationship between dietary patterns and depression and anxiety in Chinese adolescents?
Public Health Nutr
PUBLISHED: 11-25-2011
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To determine the association between major dietary patterns characterized by factor analysis and risk of depression and anxiety symptoms among adolescents.
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A CC loop decoy peptide blocks the interaction between Act1 and IL-17RA to attenuate IL-17- and IL-25-induced inflammation.
Sci Signal
PUBLISHED: 11-03-2011
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Interleukin-17 (IL-17) and IL-25 signaling induce the expression of genes encoding inflammatory factors and are implicated in the pathology of various inflammatory diseases. Nuclear factor ?B (NF-?B) activator 1 (Act1) is an adaptor protein and E3 ubiquitin ligase that is critical for signaling by either IL-17 or IL-25, and it is recruited to their receptors (IL-17R and IL-25R) through heterotypic interactions between the SEFIR [SEF (similar expression to fibroblast growth factor genes) and IL-17R] domain of Act1 and that of the receptor. SEFIR domains have structural similarity with the Toll-IL-1 receptor (TIR) domains of Toll-like receptors and IL-1R. Whereas the BB loop of TIR is required for TIR-TIR interactions, we found that deletion of the BB loop from Act1 or IL-17RA (a common subunit of both IL-17R and IL-25R) did not affect Act1-IL-17RA interactions; rather, deletion of the CC loop from Act1 or IL-17RA abolished the interaction between both proteins. Surface plasmon resonance measurements showed that a peptide corresponding to the CC loop of Act1 bound directly to IL-17RA. A cell-permeable decoy peptide based on the CC loop sequence inhibited IL-17- or IL-25-mediated signaling in vitro, as well as IL-17- and IL-25-induced pulmonary inflammation in mice. Together, these findings provide the molecular basis for the specificity of SEFIR-SEFIR versus TIR-TIR domain interactions and consequent signaling. Moreover, we suggest that the CC loop motif of SEFIR domains is a promising target for therapeutic strategies against inflammatory diseases associated with IL-17 or IL-25 signaling.
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[Analysis of flavonoids in platycladi cacumen by UPLC-MS].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 10-20-2011
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To investigate the flavonoids in Platycladi Cacumen.
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The design, synthesis and in vitro immunosuppressive evaluation of novel isobenzofuran derivatives.
Bioorg. Med. Chem. Lett.
PUBLISHED: 09-13-2011
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The synthesis and biological evaluation of a series of novel isobenzofuran-based compounds are described. The compounds were evaluated for their immunosuppressive effects of T-cell proliferation and IMPDH type II inhibitor activity in vitro, as well as their structure-activity relationships were assessed. Several compounds demonstrated highly efficacious immunosuppressive properties, especially compounds 2d, 2e, 2h and 2j, which were superior to MPA, while compounds 2k, 2m, 2n, 4c and 5d exhibited an equipotent inhibitory activity compared to MPA. Generally, it was obviously demonstrated that ?,?-unsaturated amides proved more potent than the diamide and urea series. The present study provides a guide for further research on development of safe and effective immunosuppressive agents.
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Evaluation of magnetic resonance imaging criteria for Meckels cave lesion: logistic regression analysis and correlation with surgical findings.
Clin Imaging
PUBLISHED: 08-30-2011
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Our aim was to investigate the statistical preoperative diagnostic criteria of lesions of Meckels cave (MC) on MRI.
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[Clinical study of Philadelphia chromosome-positive adult acute lymphoblastic leukemia].
Zhonghua Xue Ye Xue Za Zhi
PUBLISHED: 08-21-2011
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To study the clinical characteristics, risk factors and therapeutic outcome of Philadelphia chromosome-positive adult acute lymphoblastic leukemia (Ph(+)aALL).
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Translocation (5; 11) in a conjunctival MALT lymphoma.
Int J Clin Exp Pathol
PUBLISHED: 08-15-2011
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Lymphoma is the most frequent malignant tumor of the ocular adnexa with the most common histologic type being extranodal marginal zone B-cell lymphoma (EMZL) of mucosa-associated lymphoid tissue (MALT lymphoma). Here we report a case of a 28 year-old male who presented with a left conjunctival mass of one year duration. A diagnosis of primary MALT lymphoma of the conjunctiva was made based on morphologic and immunopheno-typic studies. Chromosome analysis revealed a male karyotype with a translocation t (5;11) (q33;p11.2) as the primary chromosomal abnormality, which, to the best of our knowledge, is the first reported translocation in MALT lym-phomas and ocular MALT lymphomas as well.
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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.