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Find video protocols related to scientific articles indexed in Pubmed.
The complete mitochondrial genome of the Epinephelus akaara (Perciformes: Serranidae).
Mitochondrial DNA
PUBLISHED: 11-19-2014
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Abstract The complete mitochondrial genome of the Epinephelus akaara was presented in this study. The mitochondrial genome is 16,743?bp long and consists of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a control region. The gene order and composition of Epinephelus akaara mitochondrial genome was similar to that of most other vertebrates. The nucleotide compositions of the light strand are 27.31% of A, 16.20% of C, 28.68% of T and 27.81% of G. With the exception of the NADH dehydrogenase subunit 6 (ND6) and eight tRNA genes, all other mitochondrial genes are encoded on the heavy strand.
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Protective Effects of Sesaminol on BEAS-2B Cells Impaired by Cigarette Smoke Extract.
Cell Biochem. Biophys.
PUBLISHED: 11-19-2014
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The aim of this study is to investigate protective effects of sesaminol on the human bronchial epithelial (BEAS-2B) cell line against oxidative damage of cigarette smoke extract (CSE). BEAS-2B cells were pre-incubated with sesaminol for 12 h and then treated with various concentrations of CSE for 24 h. After that proliferation ability, levels of reactive oxygen species (ROS) and lactate dehydrogenase (LDH), cell apoptosis, activities of catalase (CAT) and superoxide dismutase (SOD), and mRNA levels of IL-8 and IL-6 were measured. The results showed that sesaminol significantly improved BEAS-2B cell viability, reduced the production of ROS and LDH of cells, inhibited cell apoptosis and increased CAT and SOD activities in CSE-treated cells. Sesaminol also inhibited the expression of IL-8 and IL-6 mRNA following CSE exposure. In conclusion, sesaminol may protect BEAS-2B cells against CSE-induced oxidative damage.
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Matrix metalloproteinase 1, 3, and 9 polymorphisms and esophageal squamous cell carcinoma risk.
Med. Sci. Monit.
PUBLISHED: 11-14-2014
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Background Matrix metalloproteinases (MMPs) are multifunctional zinc-dependent proteinases that play a fundamental role in the pathogenesis of tumors. We have analyzed the association between 3 single-nucleotide polymorphisms (SNPs; MMP1 -1607 1G/2G, MMP3 -1612 5A/6A, and MMP9 -1562 C/T) and the risk of esophageal squamous cell carcinoma (ESCC). Material and Methods We investigated these 3 SNPs in 132 patients and 132 controls using polymerase chain reaction-restriction fragment length polymorphism methods. The MMP1 and MMP3 genes are located on the same chromosome. Haplotype analysis was performed to study the combined effect of the linked MMP polymorphisms on ESCC risk. Results The MMP1 and MMP9 promoter polymorphisms were not associated with ESCC risk, while the MMP3 -1612 5A/6A polymorphism was significantly associated with susceptibility to ESCC. Patients carrying the 5A allele had a significantly higher risk for developing ESCC compared with individuals carrying the 6A allele (OR=1.93; 95% CI 1.34-2.77; p<0.01). The 2G-5A and 1G-5A haplotypes were associated with a significantly increased risk of ESCC as compared with the 2G-6A haplotype (OR=2.04, 95% CI 1.37-3.04 and OR=3.65, 95% CI 1.26-10.55, respectively). Conclusions These findings implicate this MMP3 polymorphism as a contributor to ESCC susceptibility.
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Learning Multiple Relative Attributes with Humans in The Loop.
IEEE Trans Image Process
PUBLISHED: 11-06-2014
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Semantic attributes have been recognized as a more spontaneous manner to describe and annotate image content. It is widely accepted that image annotation using semantic attributes is a significant improvement to the traditional binary or multi-class annotation due to its naturally continuous and relative properties. Though useful, existing approaches rely on an abundant supervision and high quality training data, which limit their applicability. Two standard methods to overcome small amounts of guidance and low quality training data are transfer and active learning. In the context of relative attributes this would entail learning multiple relative attributes simultaneously and actively querying a human for additional information. This work addresses the two main limitations in existing work: i) it actively adds humans to the learning loop so that minimal additional guidance can be given, and ii) it learns multiple relative attributes simultaneously and thereby leverages dependence amongst them. In this paper, we formulate a joint active learning to rank framework with pairwise supervision to achieve these two aims which also has other benefits such as the ability to be kernelized. The proposed framework optimizes over a set of ranking functions (measuring the strength of the presence of attributes) simultaneously and dependently on each other. The proposed pairwise queries take the form of "which one of these two pictures is more natural?", and can be easily answered by humans. Extensive empirical study on real image datasets shows that our proposed method, compared to several state-of-the-art methods, achieves superior retrieval performance while requires significantly less human inputs.
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[Expression of nucleotide-binding oligomerization domain 1, nuclear factor-kappa B and human beta-defensins in candidal albicans leukoplakia].
Zhonghua Kou Qiang Yi Xue Za Zhi
PUBLISHED: 10-30-2014
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To examine the expression of nucleotide-binding oligomerization domain 1 (NOD1), nuclear factor-kappa B (NF-?B) and human beta-defensins in candidal albicans leukoplakia and to investigate the effect of candida albicans infection on key proteins in NOD1 signaling pathway and the expression of human beta-defensin.
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[Chemical constituents from Punica granatum flowers].
Zhong Yao Cai
PUBLISHED: 10-23-2014
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To investigate the chemical constituents in the flowers of Punica granatum.
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Development of Substrate-Selective Probes for Affinity Pulldown of Histone Demethylases.
ACS Chem. Biol.
PUBLISHED: 10-22-2014
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JmjC-domain containing histone demethylases (JHDMs) play critical roles in many key cellular processes and have been implicated in multiple disease conditions. Each enzyme within this family is known to have a strict substrate scope, specifically the position of the lysine within the histone and its degree of methylation. While much progress has been made in determining the substrates of each enzyme, new methods with which to systematically profile each histone mark are greatly needed. Novel chemical tools have the potential to fill this role and, furthermore, can be used as probes to answer fundamental questions about these enzymes and serve as potential therapeutic leads. In this work, we first investigated three small-molecule probes differing in the degree of "methylation state" and their differential bindings to JHDM1A (an H3K36me1/2 demethylase) using a fluorescence polarization-based competition assay. We then applied this specificity toward the "methylation state" and combined it with specificity toward lysine position in the design and synthesis of a peptidic probe targeting H3K36me2 JHDMs. The probe is further functionalized with a benzophenone cross-linking moiety and a biotin for affinity purification. Results showed binding of the peptidic probe to JHDM1A and specific enrichment of this protein in the presence of its native histone substrates. Affinity purification pulldown experiments from nuclear lysate coupled with mass spectrometry revealed the capability of the probe to pull out and enrich JHDMs along with other epigenetic proteins and transcriptional regulators.
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[Effects of exhaustive exercise-induced oxidative stress on red blood cell deformability].
Zhongguo Ying Yong Sheng Li Xue Za Zhi
PUBLISHED: 10-22-2014
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The aim of the present study is to explore the effects of exhaustive exercise-induced oxidative stress on the antioxidant capacity and diformability of rat red blood cells.
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Simultaneous targeting of PI3K? and a PI3K?-dependent MEK1/2-Erk1/2 pathway for therapy in pediatric B-cell acute lymphoblastic leukemia.
Oncotarget
PUBLISHED: 10-15-2014
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B cell acute lymphoblastic leukemia (B-ALL) is the most common hematological malignancy diagnosed in children, and blockade of the abnormally activated PI3K? displayed promising outcomes in B cell acute or chronic leukemias, but the mechanisms are not well understood. Here we report a novel PI3K? selective inhibitor X-370, which displays distinct binding mode with p110? and blocks constitutively active or stimulus-induced PI3K? signaling. X-370 significantly inhibited survival of human B cell leukemia cells in vitro, with associated induction of G1 phase arrest and apoptosis. X-370 abrogated both Akt and Erk1/2 signaling via blockade of PDK1 binding to and/or phosphorylation of MEK1/2. Forced expression of a constitutively active MEK1 attenuated the antiproliferative activity of X-370. X-370 preferentially inhibited the survival of primary pediatric B-ALL cells displaying PI3K?-dependent Erk1/2 phosphorylation, while combined inhibition of PI3K? and MEK1/2 displayed enhanced activity. We conclude that PI3K? inhibition led to abrogation of both Akt and Erk1/2 signaling via a novel PI3K-PDK1/MEK1/2-Erk1/2 signaling cascade, which contributed to its efficacy against B-ALL. These findings support the rationale for clinical testing of PI3K? inhibitors in pediatric B-ALL and provide insights needed to optimize the therapeutic strategy.
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Ezetimibe prevents the development of non?alcoholic fatty liver disease induced by high?fat diet in C57BL/6J mice.
Mol Med Rep
PUBLISHED: 10-10-2014
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There is currently no established treatment for non?alcoholic fatty liver disease (NAFLD), including its most extreme form, non?alcoholic steatohepatitis (NASH). Ezetimibe, an inhibitor of Niemann?Pick C1 Like 1?dependent cholesterol absorption, improves diet?induced hyperlipidemia and attenuates liver steatosis and insulin resistance. The aim of the present study was to determine whether ezetimibe treatment is able to inhibit the development of NAFLD, and to elucidate the underlying mechanism, using C57BL/6J (B6) mice maintained on a high?fat diet. Male B6 mice (20 weeks of age) were divided into the following two groups (n=7 in each group): Mice fed a high?fat diet for four weeks and mice fed a high?fat diet with 0.0064% (wt/wt) ezetimibe (5 mg/kg/day) for four weeks. Administration of ezetimibe significantly reduced liver steatosis and fibrosis. Ezetimibe reduced serum cholesterol, hepatic fat accumulation and insulin resistance in the liver of mice fed the high?fat diet. Furthermore, ezetimibe significantly reduced hepatic mRNA expression of Acc1 and Scd1, which are involved in hepatic fatty acid synthesis. Ezetimibe significantly reduced hepatic Cd36 gene expression, upregulation of which is significantly associated with insulin resistance, hyperinsulinemia and increased steatosis. The protein expression of SKP2, a viable therapeutic target in human cancer, was also reduced by ezetimibe. These findings suggest that ezetimibe may be an effective therapy for high fat?induced NAFLD, including NASH.
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The complete mitochondrial genome of the Epinephelus lanceolatus (Perciformes: Serranidae).
Mitochondrial DNA
PUBLISHED: 10-07-2014
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Abstract The complete mitochondrial genome of the Epinephelus lanceolatus was presented in this study. The mitochondrial genome is 16,743?bp long and consists of 13 protein-coding genes, two rRNA genes, 22 tRNA genes and a control region. The gene order and composition of E. lanceolatus mitochondrial genome was similar to that of most other vertebrates. The nucleotide compositions of the light strand are 26.55% of A, 15.02% of C, 29.67% of T and 28.76% of G. With the exception of the NADH dehydrogenase subunit 6 (ND6) and eight tRNA genes, all other mitochondrial genes are encoded on the heavy strand.
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Interference in autophagosome fusion by rare Earth nanoparticles disrupts autophagic flux and regulation of an interleukin-1? producing inflammasome.
ACS Nano
PUBLISHED: 10-01-2014
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Engineered nanomaterials (ENMs) including multiwall carbon nanotubes (MWCNTs) and rare earth oxide (REO) nanoparticles, which are capable of activating the NLRP3 inflammasome and inducing IL-1? production, have the potential to cause chronic lung toxicity. Although it is known that lysosome damage is an upstream trigger in initiating this pro-inflammatory response, the same organelle is also an important homeostatic regulator of activated NLRP3 inflammasome complexes, which are engulfed by autophagosomes and then destroyed in lysosomes after fusion. Although a number of ENMs have been shown to induce autophagy, no definitive research has been done on the homeostatic regulation of the NLRP3 inflammasome during autophagic flux. We used a myeloid cell line (THP-1) and bone marrow derived macrophages (BMDM) to compare the role of autophagy in regulating inflammasome activation and IL-1? production by MWCNTs and REO nanoparticles. THP-1 cells express a constitutively active autophagy pathway and are also known to mimic NLRP3 activation in pulmonary macrophages. We demonstrate that, while activated NLRP3 complexes could be effectively removed by autophagosome fusion in cells exposed to MWCNTs, REO nanoparticles interfered in autophagosome fusion with lysosomes. This leads to the accumulation of the REO-activated inflammasomes, resulting in robust and sustained IL-1? production. The mechanism of REO nanoparticle interference in autophagic flux was clarified by showing that they disrupt lysosomal phosphoprotein function and interfere in the acidification that is necessary for lysosome fusion with autophagosomes. Binding of LaPO4 to the REO nanoparticle surfaces leads to urchin-shaped nanoparticles collecting in the lysosomes. All considered, these data demonstrate that in contradistinction to autophagy induction by some ENMs, specific materials such as REOs interfere in autophagic flux, thereby disrupting homeostatic regulation of activated NLRP3 complexes.
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Activation of Glycogen Synthase Kinase-3 Mediates the Olfactory Deficit-Induced Hippocampal Impairments.
Mol. Neurobiol.
PUBLISHED: 09-13-2014
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The populations with olfactory dysfunction show an increased chance for hippocampus-dependent episodic memory deficit. Although it is known that the olfactory information projects to the hippocampus through entorhinal cortex layer II, the molecular mechanisms linking olfactory deficit to the hippocampus is not understood. Using bilateral olfactory bulbectomy (OBX) as a model, we found that OBX induced memory deficits with activation of several memory-related protein kinases in the hippocampal extracts, including glycogen synthase kinase-3? (GSK-3?), protein kinase A (PKA), extracellular-signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), phosphatidylinositol-3-kinase (PI3K), and protein kinase B (PKB). The OBX rats also show suppression of long-term potentiation (LTP); reduction of synapsin I, synaptophysin, NR2A/B, and PSD95; thinner presynaptic active zone and postsynaptic density with enlarged synaptic space; decreased spine numbers and mushroom-type spines; and tau hyperphosphorylation. After injection of SB216763 for several weeks by vena caudalis, selective inhibition of GSK-3? ameliorated the OBX-induced memory deficits with recovery of the synaptic components and tau phosphorylation. Furthermore, genetic ablation of GSK-3? by lentivirus-packed shRNA effectively rescued the memory deficits, synaptic disorder, and tauopathy. Our data indicate that GSK-3 activation mediates the olfactory deficits to the hippocampus, and targeting GSK-3 blocks the pathological connection.
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Mn(III)-mediated reactions of 2-isocyanobiaryl with 1,3-dicarbonyl compounds: efficient synthesis of 6-alkylated and 6-monofluoro-alkylated phenanthridines.
Chem. Commun. (Camb.)
PUBLISHED: 09-13-2014
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Mn(III)-mediated reactions of 2-isocyanobiaryls with 1,3-dicarbonyl compounds were described for the construction of 6-alkylated and 6-monofluoro-alkylated phenanthridines in moderate to good yields. The reaction involves formation of two new C-C bonds and one C-C bond cleavage.
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The complete mitochondrial genome of the Rhabdosargus sarba (Perciformes: Sparidae).
Mitochondrial DNA
PUBLISHED: 09-11-2014
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Abstract The complete mitochondrial genome of the Rhabdosargus sarba was presented in our study. The mitochondrial genome is 16,644?bp long and consists of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a control region. The gene order and composition of R. sarba mitochondrial genome was similar to that of most other vertebrates. The nucleotide compositions of the light strand are 27.01% of A, 17.96% of C, 26.02% of T and 29.01% of G. With the exception of the NADH dehydrogenase subunit 6 (ND6) and eight tRNA genes, all other mitochondrial genes are encoded on the heavy strand.
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Distinct Roles of Ape1 Protein, an Enzyme Involved in DNA Repair, in High or Low Linear Energy Transfer Ionizing Radiation-induced Cell Killing.
J. Biol. Chem.
PUBLISHED: 09-10-2014
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High linear energy transfer (LET) radiation from space heavy charged particles or a heavier ion radiotherapy machine kills more cells than low LET radiation, mainly because high LET radiation-induced DNA damage is more difficult to repair. Relative biological effectiveness (RBE) is the ratio of the effects generated by high LET radiation to low LET radiation. Previously, our group and others demonstrated that the cell-killing RBE is involved in the interference of high LET radiation with non-homologous end joining but not homologous recombination repair. This effect is attributable, in part, to the small DNA fragments (?40 bp) directly produced by high LET radiation, the size of which prevents Ku protein from efficiently binding to the two ends of one fragment at the same time, thereby reducing non-homologous end joining efficiency. Here we demonstrate that Ape1, an enzyme required for processing apurinic/apyrimidinic (known as abasic) sites, is also involved in the generation of small DNA fragments during the repair of high LET radiation-induced base damage, which contributes to the higher RBE of high LET radiation-induced cell killing. This discovery opens a new direction to develop approaches for either protecting astronauts from exposure to space radiation or benefiting cancer patients by sensitizing tumor cells to high LET radiotherapy.
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Profiles of the auditory epithelia related microRNA expression in neonatal and adult rats.
Eur. J. Med. Res.
PUBLISHED: 09-06-2014
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BackgroundThe impact of miRNA differential expression on the auditory epithelium stem cell development in postnatal rats is not clear. The present study was designed to analyze miRNA expression in the organ of Corti of neonatal and adult rats.MethodsThe cochleae of newborn (P0) and adult (P30) Sprague-Dawley rats were dissected in cold PBS to collect the sensory epithelia. Small RNAs were extracted using the mirVana RNA Isolation kit. Then, miRNA expression profiling was performed with RNAs from three newborns and three adult rats utilizing the TaqMan Array Rodent MicroRNA Panel.ResultsEighteen miRNAs were found be differentially expressed, 16 were unregulated in mature cochleae with the fold changes ranging from 17 to 600 folds. The expression levels of two miRNAs were reduced in the mature rat cochleae. GO analysis and signaling pathway analysis revealed the potential involvement of the miRNAs in the regulation of Wnt and TGF-ß signaling pathways in hair cell development.ConclusionsOur results provided novel insights into the functional significance of miRNAs in the basilar membrane cells development, and revealed the potential importance of miRNAs in the hair cell by regulation of Wnt and TGF-ß signaling.
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C-Myc-activated long noncoding RNA CCAT1 promotes colon cancer cell proliferation and invasion.
Tumour Biol.
PUBLISHED: 09-04-2014
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Recently, more and more evidence are rapidly accumulating that long noncoding RNAs (lncRNAs) are involved in human tumorigenesis and misregulated in many cancers, including colon cancer. LncRNA could regulate essential pathways that contribute to tumor initiation and progression with their tissue specificity, which indicates that lncRNA would be valuable biomarkers and therapeutic targets. Colon cancer-associated transcript 1 (CCAT1) is a 2628 nucleotide-lncRNA and located in the vicinity of a well-known transcription factor c-Myc. CCAT1 has been found to be upregulated in many cancers, including gastric carcinoma and colonic adenoma-carcinoma. However, its roles in colon cancer are still not well documented and need to be investigated. In this study, we aim to investigate the prognostic value and biological function of CCAT1 and discover which factors may contribute to the deregulation of CCAT1 in colon cancer. Our results revealed that CCAT1 was significantly overexpressed in colon cancer tissues when compared with normal tissues, and its increased expression was correlated with patients' clinical stage, lymph nodes metastasis, and survival time after surgery. Moreover, c-Myc could promote CCAT1 transcription by directly binding to its promoter region, and upregulation of CCAT1 expression in colon cancer cells promoted cell proliferation and invasion. These data suggest that c-Myc-activated lncRNA CCAT1 expression contribute to colon cancer tumorigenesis and the metastatic process and could predict the clinical outcome of colon cancer and be a potential target for lncRNA direct therapy.
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Chemoselective synthesis of polycyclic spiroindolines and polysubstituted pyrroles via the domino reaction of 2-isocyanoethylindoles.
J. Org. Chem.
PUBLISHED: 09-03-2014
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Chemoselective 2-isocyanoethylindole-based domino reactions for the construction of polycyclic spiroindoline derivatives and polysubstituted pyrroles have been developed. The reaction of 2-isocyanoethylindoles and gem-diactivated olefins lead to the polycyclic spiroindoline derivatives (up to 92% yields) in EtOH under reflux conditions. Furthermore, the three-component reaction of 2-isocyanoethylindoles with gem-diactivated olefins and secondary amines afford polysubstituted pyrroles (in moderate yields) in CH3CN under reflux conditions.
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[Determination of 24 metal elements and their compounds in air of workplace by ICP-AES].
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi
PUBLISHED: 08-30-2014
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To establish a method for determination of the levels of 24 metal elements and their compounds in the air of workplace by inductively coupled plasma-atomic emission spectroscopy (ICP- AES).
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Ribosomal protein S27-like is a physiological regulator of p53 that suppresses genomic instability and tumorigenesis.
Elife
PUBLISHED: 08-21-2014
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Cell-based studies showed that several Mdm2-binding ribosomal proteins, upon overexpression, stabilize and activate p53. In contrast, here we show in a mouse knockout study that Mdm2-binding ribosomal protein S27-like (Rps27l), upon disruption, activates p53. Germline inactivation of Rps27l triggers ribosomal stress to stabilize Mdm2, which degrades Mdm4 to reduce Mdm2-Mdm4 E3 ligase towards p53, leading to p53-dependent apoptotic depletion of hematopoietic stem cells and postnatal death, which is rescued by Trp53 deletion. Paradoxically, while increased p53 is expected to inhibit tumorigenesis, Rps27l?/?;Trp53?/? mice develop lymphomas at higher incidence with p53 loss-of-heterozygosity and severe genome aneuploidy, suggesting that Rps27l disruption impose a selection pressure against p53. Thus, Rps27l has dual functions in p53 regulation: under Trp53?/? background, Rps27l disruption triggers ribosomal stress to induce p53 and apoptosis, whereas under Trp53?/? background, Rps27l disruption triggers genomic instability and Trp53 deletion to promote tumorigenesis. Our study provides a new paradigm of p53 regulation.
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Interaction of ERK1/2 and Smad2/3 signaling pathways in TGF-?1-induced TIMP-3 expression in rat chondrocytes.
Arch. Biochem. Biophys.
PUBLISHED: 08-15-2014
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Tissue inhibitor of metalloproteinase-3 (TIMP-3) is an important natural inhibitor of matrix metalloproteinases (MMPs) and of a disintegrin and metalloproteinase with thrombospondin motif (ADAMTs), which can cleave cartilage extracellular matrix components to cause cartilage degradation. In this study, our data suggest TGF-?1 induces TIMP-3 expression through activations of both the ERK1/2 and Smad2/3 signaling pathways. TGF-?1-stimulated TIMP-3 expression was significantly inhibited by SB525334 (TGF-? receptor I kinase inhibitor), accompanied by a reduction in ERK1/2 and Smad3 phosphorylation. We used PD98059 (MEK inhibitor) and SIS3 (inhibitor of Smad3 phosphorylation) to investigate the respective roles of ERK1/2 and Smad2/3 signaling pathways in TGF-?1-induced TIMP-3 expression. The results show PD98059 treatment significantly suppressed TGF-?1-induced ERK1/2 phosphorylation and TIMP-3 expression. Under these conditions, the degree of Smad3 phosphorylation correlated with ERK1/2 activation, which suggests that ERK1/2 may activate Smad3 phosphorylation. SIS3 significantly inhibited TGF-?1-induced Smad3 phosphorylation and TIMP-3 expression. ERK1/2 phosphorylation alone had no effect on TGF-?1-induced TIMP-3 expression, which suggests ERK1/2 via Smad3 phosphorylation regulates TGF-?1-induced TIMP-3 expression. Here, we demonstrate that ERK1/2 may be capable of activating the Smad2/3 signaling pathway to result in TGF-?1-induced TIMP-3 up-regulation.
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The safety parameters of the study on intraductal cytotoxic agent delivery to the breast before mastectomy.
Chin. J. Cancer Res.
PUBLISHED: 08-13-2014
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Intraductal administration of cytotoxic agents has been shown to inhibit the development of breast cancer in animal models. The object of this study was to demonstrate the safety of intraductal delivery cytotoxic agents in patients prior to mastectomy. This method is hopeful to be developed as a chemoprevention approach in patients with pre-malignant or non-invasive ductal lesions to prevent breast cancer which will be further developed.
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Farnesoid X receptor inhibits LNcaP cell proliferation via the upregulation of PTEN.
Exp Ther Med
PUBLISHED: 08-11-2014
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Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. In the present study, the activation of the farnesoid X receptor (FXR), a member of the nuclear receptor superfamily, was demonstrated to inhibit cell proliferation in LNcaP cells. Using clinical samples, mRNA and protein levels of FXR were found to be significantly decreased by quantitative PCR and western blot analysis in prostate cancer tissues. In vitro studies identified further that activation or overexpression of FXR suppressed prostate cancer cell proliferation as measured by BrdU incorporation assays. At the molecular level, the results further revealed that the expression of the tumor suppressor gene, PTEN, was upregulated by FXR activation. Therefore, the observations indicated that FXR functions as a tumor suppressor in prostate cancer, which may provide a novel method for molecular targeting cancer treatment.
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Isolation and characterization of a Sca-1+/CD31- progenitor cell lineage derived from mouse heart tissue.
BMC Biotechnol.
PUBLISHED: 08-09-2014
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Myocardial infarction remains the leading cause of mortality in developed countries despite recent advances in its prevention and treatment. Regenerative therapies based on resident cardiac progenitor cells (CPCs) are a promising alternative to conventional treatments. However, CPCs resident in the heart are quite rare. It is unclear how these CPCs can be isolated and cultured efficiently and what the effects of long-term culture in vitro are on their 'stemness' and differentiation potential, but this is critical knowledge for CPCs' clinical application.
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Antisense knockdown of pyruvate dehydrogenase kinase promotes the neutral lipid accumulation in the diatom Phaeodactylum tricornutum.
Microb. Cell Fact.
PUBLISHED: 08-09-2014
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Microalgae have been an emerging biofuel resource; however, the germplasm improvement has been slow due to the lack of molecular tools. Pyruvate dehydrogenase kinase (PDK) deactivates the pyruvate dehydrogenase complex (PDC) which catalyzes the oxidative decarboxylation of pyruvate. Acetyl-CoA production via PDC is important in plant tissues that are active in fatty acid synthesis.
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Impact of constitutional isomerism on phosphorescence and anion-sensing properties of donor-acceptor organoboron Pt(II) complexes.
Dalton Trans
PUBLISHED: 08-08-2014
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A new dimesitylboryl-functionalized molecule (NBppy) and its corresponding N^C chelate platinum(II) complex (Pt-NBppy) have been synthesized and fully characterized. The photophysical and electronic properties of NBppy and Pt-NBppy were examined and compared to their constitutional isomers, BNppy and Pt-BNppy, respectively. Due to the presence of the electron-donating diphenylamino group, the NBppy and BNppy compounds exhibit intense donor–acceptor charge transfer (CT) and bright blue fluorescence. Pt-NBppy displays weak phosphorescence, originating from a mixture of MLCT/???* and CT transitions while Pt-BNppy displays bright phosphorescence originating from a CT transition. The Lewis acidity of the isomers was examined by fluoride titration experiments, which established that BNppy exhibits much higher affinity towards fluoride ions than NBppy. In addition, while the phosphorescence of Pt-BNppy is quenched by fluoride addition, Pt-NBppy demonstrates an unusual turn-on phosphorescent response towards fluoride ions, which illustrate the distinct impact of constitutional isomers on phosphorescence and anion sensing.
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[Microsurgical management of male infertility in china: 15-year development and prospects].
Zhonghua Nan Ke Xue
PUBLISHED: 08-07-2014
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Male infertility is a common and complex disease in urology and andrology, and for many years there has been no effective surgical treatment. With the emergence of microsurgery and assisted reproductive medicine (IVF/ICSI), rapid development has been achieved in the treatment of male infertility. The Center for Male Reproductive Medicine and Microsurgery at Weill Cornell Medical College of Cornell University has been playing an important leading role in developing microsurgical techniques for the management of male infertility. The development of microsurgical treatment of male infertility in China has experienced the 3 periods of emerging, making, and boosting ever since its systematic introduction from Weill Cornell Medical College 15 years ago. At present, many Chinese hospitals have adopted microsurgery in the management of male infertility, which has contributed to the initial establishment of a microsurgical treatment system for male infertility in China. However, some deficiencies do exist concerning microsurgical treatment of male infertility, as in normalized technical training programs for competent surgeons, unified criteria for evaluation of surgical outcomes, and detailed postoperative follow-up data. This article presents an overview on the 15-year development of microsurgical management of male infertility in China, points out the existing deficiencies, and offers some propositions for the promotion of its development.
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Survivin-targeting Artificial MicroRNAs Mediated by Adenovirus Suppress Tumor Activity in Cancer Cells and Xenograft Models.
Mol Ther Nucleic Acids
PUBLISHED: 07-24-2014
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Survivin is highly expressed in most human tumors and fetal tissue, and absent in terminally differentiated cells. It promotes tumor cell proliferation by negatively regulating cell apoptosis and facilitating cell division. Survivin's selective expression pattern suggests that it might be a suitable target for cancer therapy, which would promote death of transformed but not normal cells. This was tested using artificial microRNAs (amiRNAs) targeting survivin. After screening, two effective amiRNAs, which knocked down survivin expression, were identified and cloned into a replication-defective adenoviral vector. Tumor cells infected with the recombinant vector downregulated expression of survivin and underwent apoptotic cell death. Further studies showed that apoptosis was associated with increases in caspase 3 and cleaved Poly (ADP-ribose) polymerase, and activation of the p53 signaling pathway. Furthermore, amiRNA treatment caused blockade of mitosis and cell cycle arrest at the G2/M phase. In vivo, survivin-targeting amiRNAs expressed by adenoviral vectors effectively delayed growth of hepatocellular and cervical carcinomas in mouse xenograft models. These results indicate that silencing of survivin by amiRNA has potential for treatment of cancer.
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TRPV1 Activation Attenuates High-Salt Diet-Induced Cardiac Hypertrophy and Fibrosis through PPAR-? Upregulation.
PPAR Res
PUBLISHED: 07-24-2014
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High-salt diet-induced cardiac hypertrophy and fibrosis are associated with increased reactive oxygen species production. Transient receptor potential vanilloid type 1 (TRPV1), a specific receptor for capsaicin, exerts a protective role in cardiac remodeling that resulted from myocardial infarction, and peroxisome proliferation-activated receptors ? (PPAR-?) play an important role in metabolic myocardium remodeling. However, it remains unknown whether activation of TRPV1 could alleviate cardiac hypertrophy and fibrosis and the effect of cross-talk between TRPV1 and PPAR-? on suppressing high-salt diet-generated oxidative stress. In this study, high-salt diet-induced cardiac hypertrophy and fibrosis are characterized by significant enhancement of HW/BW%, LVEDD, and LVESD, decreased FS and EF, and increased collagen deposition. These alterations were associated with downregulation of PPAR-?, UCP2 expression, upregulation of iNOS production, and increased oxidative/nitrotyrosine stress. These adverse effects of long-term high-salt diet were attenuated by chronic treatment with capsaicin. However, this effect of capsaicin was absent in TRPV1(-/-) mice on a high-salt diet. Our finding suggests that chronic dietary capsaicin consumption attenuates long-term high-salt diet-induced cardiac hypertrophy and fibrosis. This benefit effect is likely to be caused by TRPV1 mediated upregulation of PPAR-? expression.
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Optimization of chemical fungicide combinations targeting the maize fungal pathogen, Bipolaris maydis: a systematic quantitative approach.
IEEE Trans Biomed Eng
PUBLISHED: 07-24-2014
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To control the southern corn leaf blight (SCLB), a severe disease of maize around the world, a combination of fungicides is often more potent than using individual fungicides. However, the number of possible combinations increases exponentially with the increase of the number of fungicides combined and their concentrations. It is thus extremely challenging to identify effective fungicide combinations by trial and error from all possible combinations. In this paper, a systematic approach based on a support vector machine, a machine learning algorithm, is proposed to searching for the optimal combinations using only a limited number of measurements. The constructed model also incorporates information related to the inhibition rate and the cost of each composing fungicide into the optimization process. With this method, we show that only around 130 measurements on a coarse grid of concentrations out of thousands of possible experiments are sufficient to reconstruct the response model and to obtain the optimal fungicide combinations. Experimental results demonstrate that the optimized combinations can achieve an inhibition rate greater than 90% while the required concentrations and the cost of individual fungicides are dramatically reduced. We anticipate that this method should be equally effective in the search for optimal combinations of multiple compounds in other diseases.
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Conjugated Bile Acid Activated S1P Receptor 2 Is a Key Regulator of Sphingosine Kinase 2 and Hepatic Gene Expression.
Hepatology
PUBLISHED: 07-23-2014
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Bile acids have been shown to be important hormones during the feed/fast cycle, allowing the liver to coordinately regulate nutrient metabolism. How they accomplish this has not been fully elucidated. Conjugated bile acids have been shown to activate both the ERK1/2 and AKT signaling pathways via S1PR2 in rodent hepatocytes and in vivo. Here, we report that feeding mice a high fat diet, infusion of taurocholate into the chronic bile fistula rat, or overexpression of the gene encoding S1PR2 in mouse hepatocytes significantly up-regulated hepatic SphK2, but not SphK1. Key genes encoding nuclear receptors/enzymes involved in nutrient metabolism were significantly down-regulated in livers of S1PR2(-/-) and SphK2(-/-) mice. In contrast, overexpression of the gene encoding S1PR2 in primary mouse hepatocytes differentially increased SphK2, but not SphK1, and mRNA levels of key genes involved in nutrient metabolism. Nuclear levels of S1P, an endogenous inhibitor of HDAC 1/2, as well as the acetylation of H3K9, H4K5 and H2BK12, were significantly decreased in hepatocytes prepared from S1PR2(-/-) and SphK2(-/-) mice. Both S1PR2(-/-) and SphK2(-/-) mice rapidly developed fatty livers on a high fat diet suggesting the importance of conjugated bile acids, S1PR2 and SphK2 in regulating hepatic lipid metabolism. (Hepatology 2014;).
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microRNA-181 promotes prostate cancer cell proliferation by regulating DAX-1 expression.
Exp Ther Med
PUBLISHED: 07-16-2014
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microRNAs (miRNAs) are a class of short noncoding RNA molecules that have a critical role in the initiation and progression of types of human cancer, including prostate cancer. In the present study, the expression of miR-181 in prostate cancer tissues was evaluated and was demonstrated to be significantly upregulated in prostate cancer tissues compared with that in adjacent normal tissues. The results of in vitro MTT and BrdU incorporation assays, as well as cell-cycle analysis, indicated that miR-181 overexpression markedly promoted the proliferation of LNCaP cells. Furthermore, miR-181 overexpression was found to promote the progression of LNCaP tumor growth in nude mice. Mechanistic studies demonstrated that dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (DAX-1), a negative regulator of androgen receptor in prostate cancer, was inhibited by miR-181 overexpression. Therefore, the results from the present study suggest that miR-181 functions as a growth-suppressive miRNA during prostate cancer development.
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[Expression of Ki67 and clinicopathological features in breast cancer].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 07-04-2014
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To analyze the relationship between the expression level of Ki67 and clinicopathological features in breast cancer.
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Optimal treatment determination on the basis of haematoma volume and intra-cerebral haemorrhage score in patients with hypertensive putaminal haemorrhages: a retrospective analysis of 310 patients.
BMC Neurol
PUBLISHED: 06-30-2014
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Hypertensive putaminal haemorrhage comprises major part of intra-cerebral haemorrhages, with particularly high morbidity and mortality. However, the optimal treatments for these individuals remain controversial.
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The complete mitochondrial genome of the Pampus nozawae (Perciformes: Stromateidae).
Mitochondrial DNA
PUBLISHED: 06-25-2014
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Abstract The complete mitochondrial genome of the Pampus nozawae was presented in this study. The mitochondrial genome is 16,556?bp long and consists of 13 protein-coding genes, two rRNA genes, 22 tRNA genes and a control region. The gene order and composition of Pampus nozawae mitochondrial genome was similar to that of most other vertebrates. The nucleotide compositions of the light strand are 30.01% of A, 27.51% of C, 27.29% of T and 15.18% of G. With the exception of the NADH dehydrogenase subunit 6 (ND6) and seven tRNA genes, all other mitochondrial genes are encoded on the heavy strand.
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Characterization and subcellular localization of two 14-3-3 genes and their response to abiotic stress in wheat.
Sheng Wu Gong Cheng Xue Bao
PUBLISHED: 06-20-2014
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In order to investigate biological functions of the 14-3-3 genes and their response to abiotic stress, two cDNAs (designated as Ta14R1 and Ta14R2) encoding putative 14-3-3 proteins were isolated from wheat by PCR and rapid amplification of cDNA end (RACE) technique. The cDNA of Ta14R1 is 999bp and encodes a protein of 262 amino acids, while the cDNA of Ta14R2 is 897bp in length and encodes a protein of 261 amino acids. Transient expression assays using Ta14R1/Ta14R2-GFP fusion constructs indicated that Ta14R1 and Ta14R2 were located in cytoplasm and cell membrane but not in chloroplasts. Real-time quantitative (RT-PCR) analysis revealed that Ta14R1 and Ta14R2 were differentially expressed in wheat tissues and significantly up-regulated in roots and shoots 1d after germination, indicating they may play a role in process of seed germination. The expression of the two genes in roots and leaves were significantly induced by plant hormone ABA, as well as heat, cold and drought treatments, suggesting that the two 14-3-3 genes in wheat may be involved in ABA dependent stress-responding pathway and response to heat, cold and drought stress.
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[Array comparative genomic hybridization analysis of early-stage arrested human embryos].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
PUBLISHED: 06-15-2014
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To investigate chromosomal euploidies in early-stage arrested human embryos.
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Temporal Changes in Microbial Metabolic Characteristics in Field-Scale Biopiles Composed of Aged Oil Sludge.
Environ. Eng. Sci.
PUBLISHED: 05-18-2014
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Disposal of oil sludge, a hazardous waste, is currently a prevalent environmental issue. In this study, two field-scale biopiles were constructed to explore the temporal changes of microbial metabolic characteristics during the biotreatment of aged oil sludge. Bulking agent was mixed thoroughly with oily sludge to form a treated pile. The BIOLOG™ system was used to analyze the community level physiological parameters, including microbial metabolic activity, diversity, and variance. In comparison with the control, the community level physiological parameters of the treated pile were dramatically improved. Microbial metabolic activity of the treated pile was improved by 25.06% calculated from the maximums during the treatment. Microbial diversity index (Shannon index) ranges were improved from 1.64-3.02 (control pile) to 2.34-3.14 (treated pile). The numbers of petroleum-degrading bacteria and the total heterotrophic bacteria were correlated with the environmental temperature, and microbial metabolic characteristics in the treated pile revealed the distinctive carbon resources selection with the addition of cotton stalk. Temporal microbial metabolic characteristics, which have important effect on bioremediation, were revealed in this study.
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Asymmetric dimethylarginine triggers macrophage apoptosis via the endoplasmic reticulum stress pathway.
Mol. Cell. Biochem.
PUBLISHED: 05-16-2014
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Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), is emerging as a key contributing factor in atherogenesis, a process in turn known to involve macrophage apoptosis. The aim of this study was to determine the effect of ADMA on macrophage apoptosis, with specific reference to the endoplasmic reticulum (ER) stress pathway. Macrophage apoptosis was evaluated by Annexin V- Propidium iodide (PI) and Hoechst 33258 staining assays. Levels of the ER stress marker glucose regulated protein 78 (GRP78) were characterized by western blot. Levels of the proapoptotic C/EBP-homologous protein (CHOP) were evaluated by western blot and reverse transcription polymerase chain reaction (RT-PCR), and caspase-4 activity was measured using a colorimetric protease assay kit. We observed ADMA dose- and time-dependent increases in macrophage levels of GRP78. Similar ADMA dose- and time-dependent increases were detected in intracellular caspase-4 activity and macrophage apoptosis, all of which were sensitive to treatment with siRNAs for protein kinase RNA-like ER kinase and inositol-requiring protein-1 (IRE1), the ADMA antagonist L-arginine, as well as inhibitors of eukaryotic translation initiation factor-2 (salubrinal), IRE1 (irestatin 9389), and c-Jun N-terminal kinase (SP600125). Our results indicate that ADMA triggers macrophage apoptosis via the ER stress pathway.
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Satellite fault diagnosis using support vector machines based on a hybrid voting mechanism.
ScientificWorldJournal
PUBLISHED: 05-06-2014
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The satellite fault diagnosis has an important role in enhancing the safety, reliability, and availability of the satellite system. However, the problem of enormous parameters and multiple faults makes a challenge to the satellite fault diagnosis. The interactions between parameters and misclassifications from multiple faults will increase the false alarm rate and the false negative rate. On the other hand, for each satellite fault, there is not enough fault data for training. To most of the classification algorithms, it will degrade the performance of model. In this paper, we proposed an improving SVM based on a hybrid voting mechanism (HVM-SVM) to deal with the problem of enormous parameters, multiple faults, and small samples. Many experimental results show that the accuracy of fault diagnosis using HVM-SVM is improved.
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PKM2: the thread linking energy metabolism reprogramming with epigenetics in cancer.
Int J Mol Sci
PUBLISHED: 04-23-2014
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Cancer metabolism reprogramming or alterations in epigenetics are linked to an incidence of cancer. It is apparent that epigenetic changes have been found in tumors, therefore, the complete epigenome and entire pathways relevant to cell metabolism are subject to epigenetic dysregulation. Here, we review the pyruvate kinase M2 (PKM2) isoform, a glycolytic enzyme involved in ATP generation and pyruvate production, which plays an essential role in tumor metabolism and growth, and also functions as a protein kinase that phosphorylates histones during genes transcription and chromatin remodeling. We also discuss the potential role of PKM2 in the dynamic integration between metabolic reprogramming and alterations in epigenetics during carcinogenesis and cancer progression.
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The beneficial effects of intracoronary autologous bone marrow stem cell transfer as an adjunct to percutaneous coronary intervention in patients with acute myocardial infarction.
Biotechnol. Lett.
PUBLISHED: 04-16-2014
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The efficacy of post-percutaneous coronary intervention (PCI) intracoronary injection with bone marrow mesenchymal stem cells (BMSCs) in patients with acute myocardial infarction (AMI) remains controversial. Here, 58 patients with AMI undergoing PCI were randomly divided into two groups: BMSC and control groups. Autologous BSMCs were then generated in vitro from the BMSC patients. After transplantation, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimensions (LVDd), and infarct size (IS) were evaluated in both groups. LVEF, LVDd, and IS improved after BMSC transplantation but the changes were not significantly different from those in the controls. The number of adverse events and rehospitalization rates after 1 month were significantly higher in the control group than in the BMSC group. BMSC transplantation thus benefits patients by decreasing the number of adverse events and reducing the rehospitalization rate in the early stages following PCI.
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Relationship between intracranial pressure and aneurysmal subarachnoid hemorrhage grades.
J. Neurol. Sci.
PUBLISHED: 04-08-2014
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Intracranial pressure (ICP) is frequently elevated following aneurysmal subarachnoid hemorrhage (aSAH). In this prospective study, the factors associated with increased ICP and the relationship between ICP and the aSAH grade were evaluated.
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Alteration Young's moduli by protein 4.1 phosphorylation play a potential role in the deformability development of vertebrate erythrocytes.
J Biomech
PUBLISHED: 04-01-2014
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The mechanical properties of vertebrate erythrocytes depend on their cytoskeletal protein networks. Membrane skeleton proteins spectrin and protein 4.1 (4.1R) cross-link with actin to maintain membrane stability under mechanical stress. Phosphorylation of 4.1R alters the affinity of 4.1R for spectrin-actin binding and this modulates the mechanical properties of human erythrocytes. In this study, phorbol 12-myristate-13-acetate (PMA)-induced phosphorylation of 4.1R was tested, erythrocyte deformability was determined and the erythrocyte elastic modulus was detected in human, chick, frog and fish. Furthermore, amino acid sequences of the functionally important domains of 4.1R were analyzed. Results showed that PMA-induced phosphorylation of 4.1R decreased erythrocyte deformability and this property was stable after 1h. The values of Young's modulus alteration gradually decreased from human to fish (0.388 ± 0.035 kPa, 0.219 ± 0.022 kPa, 0.191 ± 0.036 kPa and 0.141 ± 0.007 kPa). Ser-312 and Ser-331 are located within the consensus sequence recognized by protein kinase C (PKC); however, Ser-331 in zebrafish was replaced by Ala-331. The sequence of the 8 aa motif from vertebrate 4.1R showed only one amino acid mutation in frog and numerous substitutions in fish. Analyses of Young's modulus suggested that the interaction between 4.1R with the spectrin-actin binding domain may have a special relationship with the development of erythrocyte deformability. In addition, amino acid mutations in 4.1R further supported this relationship. Thus, we hypothesize that alteration of membrane skeleton protein binding affinity may play a potential role in the development of erythrocyte deformability, and alteration of Young's modulus values may provide a method for determining the deformability development of vertebrate erythrocytes.
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The intracellular Ca(2+) channel MCOLN1 is required for sarcolemma repair to prevent muscular dystrophy.
Nat. Med.
PUBLISHED: 03-05-2014
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The integrity of the plasma membrane is maintained through an active repair process, especially in skeletal and cardiac muscle cells, in which contraction-induced mechanical damage frequently occurs in vivo. Muscular dystrophies (MDs) are a group of muscle diseases characterized by skeletal muscle wasting and weakness. An important cause of these group of diseases is defective repair of sarcolemmal injuries, which normally requires Ca(2+) sensor proteins and Ca(2+)-dependent delivery of intracellular vesicles to the sites of injury. MCOLN1 (also known as TRPML1, ML1) is an endosomal and lysosomal Ca(2+) channel whose human mutations cause mucolipidosis IV (ML4), a neurodegenerative disease with motor disabilities. Here we report that ML1-null mice develop a primary, early-onset MD independent of neural degeneration. Although the dystrophin-glycoprotein complex and the known membrane repair proteins are expressed normally, membrane resealing was defective in ML1-null muscle fibers and also upon acute and pharmacological inhibition of ML1 channel activity or vesicular Ca(2+) release. Injury facilitated the trafficking and exocytosis of vesicles by upmodulating ML1 channel activity. In the dystrophic mdx mouse model, overexpression of ML1 decreased muscle pathology. Collectively, our data have identified an intracellular Ca(2+) channel that regulates membrane repair in skeletal muscle via Ca(2+)-dependent vesicle exocytosis.
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Histone H3K4 methyltransferase Mll1 regulates protein glycosylation and tunicamycin-induced apoptosis through transcriptional regulation.
Biochim. Biophys. Acta
PUBLISHED: 02-24-2014
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Disrupting protein glycosylation induces ER (endoplasmic reticulum) stress, resulting in the activation of UPR (unfolded protein response) pathways. A key function of the UPR is to restore ER homeostasis, but prolonged or unsolved ER stress can lead to apoptosis. MLL1 (Mixed Lineage Leukemia 1, also named ALL-1 or HRX), a histone H3K4 methyltransferase in mammals, plays important roles in leukemogenesis, transcriptional regulation, cell cycle and development. Here, we find that Mll1 deficiency enhances UPR and apoptosis induced by the glycosylation inhibitor TM (tunicamycin). The abnormal regulation of the UPR appears to be caused by a defect in protein glycosylation. Furthermore, Mll1 directly binds to the promoters of H6pd, Galnt12 and Ugp2, which regulates H3K4 trimethylation and the subsequent expression of these genes. The knockdown of H6pd, Galnt12 or Ugp2 enhances TM-induced apoptosis in Mll1(+/+)MEF cells, whereas the ectopic expression of these proteins inhibits TM-induced apoptosis in Mll1(-/-) MEF cells. Together, our data suggest that the maturation of glycoproteins in the ER is subject to regulation at the epigenetic level by a histone methyltransferase whose abnormality can lead to cancer and developmental defects.
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Crystal Structures of PI3K? Complexed with PI103 and Its Derivatives: New Directions for Inhibitors Design.
ACS Med Chem Lett
PUBLISHED: 02-13-2014
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The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays important roles in cell proliferation, growth, and survival. Hyperactivated PI3K is frequently found in a wide variety of human cancers, validating it as a promising target for cancer therapy. We determined the crystal structure of the human PI3K?-PI103 complex to unravel molecular interactions. Based on the structure, substitution at the R1 position of the phenol portion of PI103 was demonstrated to improve binding affinity via forming a new H-bond with Lys802 at the bottom of the ATP catalytic site. Interestingly, the crystal structure of the PI3K?-9d complex revealed that the flexibility of Lys802 can also induce additional space at the catalytic site for further modification. Thus, these crystal structures provide a molecular basis for the strong and specific interactions and demonstrate the important role of Lys802 in the design of novel PI3K? inhibitors.
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Health-related quality of life and preferred health-seeking institutions among rural elderly individuals with and without chronic conditions: a population-based study in Guangdong Province, China.
Biomed Res Int
PUBLISHED: 02-07-2014
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The aim of this study was to examine health-related quality of life (HRQL) as measured by SF-36 and to identify these factors and the preferred health-seeking institutions of 12,800 persons aged 60 and older with and without chronic conditions in rural areas of Guangdong Province by multistage stratified cluster sampling method. HRQL among rural elderly subjects with chronic conditions was lower than that of elderly subjects with no chronic conditions. Multiple linear regression showed that marital status, living with children, cardiovascular disease, osteoporosis, cataract disease, and mental disease were the main affecting factors of HRQL. The main preferred health-seeking institutions selected by the rural elderly were community/town health service institutions, district hospitals, or secondary hospitals. Our findings indicate that the elderly in rural areas of Guangdong Province have a poor HRQL and incorrect health-seeking pathway. The healthcare policymakers should emphasize the need of developing effective and targeted community services strategies to improve the elderly individuals' HRQL in rural areas of China.
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Microbubbles coupled to methotrexate-loaded liposomes for ultrasound-mediated delivery of methotrexate across the blood-brain barrier.
Int J Nanomedicine
PUBLISHED: 01-01-2014
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Methotrexate (MTX) is the single most effective agent for the treatment of primary central nervous system lymphoma. Currently, the delivery of MTX to the brain is achieved by high systemic doses, which cause severe long-term neurotoxicity, or intrathecal administration, which is highly invasive and may lead to infections or hemorrhagic complications. Acoustically active microbubbles have been developed as drug carriers for the noninvasive and brain-targeted delivery of therapeutics. However, their application is limited by their low drug-loading capacity. To overcome this limitation, we prepared microbubbles coupled to MTX-loaded liposomes using ZHIFUXIAN, a novel type of microbubbles with a superior safety profile and long circulation time. MTX-liposome-coupled microbubbles had a high drug-loading capacity of 8.91%± 0.86%, and their size (2.64 ± 0.93 ?m in diameter) was suitable for intravenous injection. When used with ultrasound, they showed more potent in vitro cytotoxicity against Walker-256 cancer cells than MTX alone or MTX-loaded liposomes. When Sprague-Dawley rats were exposed to sonication, administration of these MTX-liposome-coupled microbubbles via the tail vein led to targeted disruption of the blood-brain barrier without noticeable tissue or capillary damage. High-performance liquid chromatography analysis of the brain MTX concentration showed that MTX delivery to the brain followed the order of MTX-liposome-coupled microbubbles + ultrasound (25.3 ± 2.4 ?g/g) > unmodified ZHIFUXIAN + MTX + ultrasound (18.6 ± 2.2 ?g/g) > MTX alone (6.97 ± 0.75 ?g/g) > MTX-liposome-coupled microbubbles (2.92 ± 0.39 ?g/g). Therefore, treatment with MTX-liposome-coupled microbubbles and ultrasound resulted in a significantly higher brain MTX concentration than all other treatments (P<0.01). These results suggest that MTX-liposome-coupled microbubbles may hold great promise as new and effective therapies for primary central nervous system lymphoma and other central nervous system malignancies.
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Meta-analysis of peritumoural rCBV values derived from dynamic susceptibility contrast imaging in differentiating high-grade gliomas from intracranial metastases.
Int J Clin Exp Med
PUBLISHED: 01-01-2014
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In the preoperative period, it is very important to accurately differentiate high-grade gliomas from intracranial metastases, as treatment strategies vary. Hence we performed a meta-analysis to evaluate the sensitivity and specificity of peritumoural relative cerebral blood volume (rCBV) values derived from dynamic susceptibility contrast imaging (DSCI) in differentiating high-grade gliomas from intracranial metastases.
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Protective effects of carbon monoxide-releasing molecule-2 on the barrier function of intestinal epithelial cells.
PLoS ONE
PUBLISHED: 01-01-2014
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To investigate the protective effects and mechanisms of carbon monoxide-releasing molecule-2 (CORM-2) on barrier function of intestinal epithelial cells.
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Genome-wide analysis of the NADK gene family in plants.
PLoS ONE
PUBLISHED: 01-01-2014
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NAD(H) kinase (NADK) is the key enzyme that catalyzes de novo synthesis of NADP(H) from NAD(H) for NADP(H)-based metabolic pathways. In plants, NADKs form functional subfamilies. Studies of these families in Arabidopsis thaliana indicate that they have undergone considerable evolutionary selection; however, the detailed evolutionary history and functions of the various NADKs in plants are not clearly understood.
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[Analysis of influencing factors to metastasis in sentinel lymph nodes and non-sentinel lymph nodes in breast cancer].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 12-30-2013
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To explore the relevant factors influencing sentinel and non-sentinel lymph node (SLNM, NSLNM) metastases in breast cancer.
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DW09849, a selective PI3K inhibitor, Prevents PI3K signaling and preferentially inhibits proliferation of cells containing the oncogenic mutation p110? (H1047R).
J. Pharmacol. Exp. Ther.
PUBLISHED: 12-20-2013
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PI3K? (phosphatidylinositol-3-kinase, ? isoform) plays essential roles in cell metabolism, growth and proliferation and has been validated as a promising anti-cancer target. In an effort to search for new PI3K? selective inhibitors, DW series compounds were designed and synthesized aiming to reduce the off-target effects of their parent compound PIK-75, which was reported to selectively target PI3K?. DW series compounds potently inhibited the kinase activity of PI3K? with little activity against PI3K-related protein kinases (PIKKs) and a panel of 15 tyrosine kinases. Similar to PIK-75, DW series compounds were more potent to inhibit PI3K? among four class I PI3K isoforms, while a representative compound DW09849 displayed distinct binding mode compared to PIK75. Although DW series compounds inhibited proliferation of rhabdomyosarcoma RH30 cells at elevated 50% inhibitory concentrations (IC50s) in comparison with PIK-75, they were more selective than PIK-75 to inhibit PI3K signaling in the cellular context. Particularly, DW09849 significantly and persistently blocked PI3K/Akt signaling in RH30 cells, which consequently arrested RH30 cells in G1 phase. Moreover, DW09849 selectively suppressed the proliferation and clonogenesis of transformed RK3E/HR cells harboring oncogenic mutation of p110? H1047R, as well as a panel of human breast cancer cells containing mutated PI3K?, which is consistent with the result that DW09849 demonstrated preference against H1047R mutated PI3K? in molecular docking stimulation. These results suggest that DW series compounds, especially DW09849, selectively targeting PI3K? with less off-target effects than PIK-75, provide new clues for the design and discovery of new specific PI3K? inhibitors for cancer therapy.
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Probing the Location of Hot Spots by Surface-Enhanced Raman Spectroscopy: Toward Uniform Substrates.
ACS Nano
PUBLISHED: 12-19-2013
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Wide applications of surface plasmon resonance rely on the in-depth understanding of the near-field distribution over a metallic nanostructure. However, precisely locating the strongest electric field in a metallic nanostructure still remains a great challenge in experiments because the field strength decays exponentially from the surface. Here, we demonstrate that the hot spot position for gold nanoparticles over a metal film can be precisely located using surface-enhanced Raman spectroscopy (SERS) by rationally choosing the probe molecules and excitation wavelengths. The finite difference time domain simulation verifies the experimental results and further reveals that the enhancement for the above system is sensitive to the distance between nanoparticles and the metal film but insensitive to the distance of nanoparticles. On the basis of this finding, we propose and demonstrate an approach of using a nanoparticles-on-metal film substrate as a uniform SERS substrate. This work provides a convenient way to probe the location of strong near-field enhancement with SERS and will have important implications in both surface analysis and surface plasmonics.
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Alterations of high endothelial venules in primary and metastatic tumors are correlated with lymph node metastasis of oral and pharyngeal carcinoma.
Cancer Biol. Ther.
PUBLISHED: 12-18-2013
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High endothelial venules (HEVs) are special blood vessels in the paracortical region of lymph nodes (LNs) and govern lymphocyte recruitment. LN metastasis has similarity to circulating lymphocytes homing to LNs, but the role of HEVs in the progression of oral and pharyngeal squamous cell carcinoma (OPSCC) is unclear. In this study, we found that HEVs experienced a series of morphological and functional changes during OPSCC progression and were correlated with LN metastasis. In 9 cases of 73 metastatic LNs, tumor emboli were located adjacent to HEVs or just out of the vessels but not lymphatic channels. Gap junctions of tumor cells close to HEVs decreased or disappeared, and gaps were left at contact points where tumor cells attached to the HEVs. Moreover, the proliferation rate of endothelial cells of HEVs was the highest in metastatic LNs. Finally, L-selectin was detected in both primary and metastatic tumors, and it facilitated tumor cells adhering to LNs. In conclusion, our findings suggest that remodeled HEVs are correlated with LN metastasis of OPSCC and play important role in this process by preparing premetastatic soil for cancer cell metastasis.
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Genetically encoded fluorescent probe to visualize intracellular phosphatidylinositol 3,5-bisphosphate localization and dynamics.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 12-09-2013
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Phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] is a low-abundance phosphoinositide presumed to be localized to endosomes and lysosomes, where it recruits cytoplasmic peripheral proteins and regulates endolysosome-localized membrane channel activity. Cells lacking PI(3,5)P2 exhibit lysosomal trafficking defects, and human mutations in the PI(3,5)P2-metabolizing enzymes cause lysosome-related diseases. The spatial and temporal dynamics of PI(3,5)P2, however, remain unclear due to the lack of a reliable detection method. Of the seven known phosphoinositides, only PI(3,5)P2 binds, in the low nanomolar range, to a cytoplasmic phosphoinositide-interacting domain (ML1N) to activate late endosome and lysosome (LEL)-localized transient receptor potential Mucolipin 1 (TRPML1) channels. Here, we report the generation and characterization of a PI(3,5)P2-specific probe, generated by the fusion of fluorescence tags to the tandem repeats of ML1N. The probe was mainly localized to the membranes of Lamp1-positive compartments, and the localization pattern was dynamically altered by either mutations in the probe, or by genetically or pharmacologically manipulating the cellular levels of PI(3,5)P2. Through the use of time-lapse live-cell imaging, we found that the localization of the PI(3,5)P2 probe was regulated by serum withdrawal/addition, undergoing rapid changes immediately before membrane fusion of two LELs. Our development of a PI(3,5)P2-specific probe may facilitate studies of both intracellular signal transduction and membrane trafficking in the endosomes and lysosomes.
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Anhedonia and Pain Avoidance in the Suicidal Mind: Behavioral Evidence for Motivational Manifestations of Suicidal Ideation in Patients With Major Depressive Disorder.
J Clin Psychol
PUBLISHED: 12-04-2013
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Psychological pain may be helpful in conceptualizing suicidal behavior, in that high motivation to avoid pain combined with painful feelings may contribute to an increased risk of suicide. However, no experimental study has tested this hypothesis. The aim of the present study is to provide empirical evidence for the relationship between anhedonia, pain avoidance motivation, and suicidal ideation.
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Optical-fiber frequency domain interferometer with nanometer resolution and centimeter measuring range.
Rev Sci Instrum
PUBLISHED: 12-03-2013
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A new optical-fiber frequency domain interferometer (OFDI) device for accurate measurement of the absolute distance between two stationary objects, with centimeter measuring range and nanometer resolution, has been developed. Its working principle and on-line data processing method were elaborated. The new OFDI instrument was constructed all with currently available commercial communication products. It adopted the wide-spectrum amplified spontaneous emission light as the light source and optical-fiber tip as the test probe. Since this device consists of only fibers or fiber coupled components, it is very compact, convenient to operate, and easy to carry. By measuring the single-step length of a translation stage and the thickness of standard gauge blocks, its ability in implementing nanometer resolution and centimeter measuring range on-line measurements was validated.
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[Comparison of soil fertility among open-pit mine reclaimed lands in Antaibao regenerated with different vegetation types].
Huan Jing Ke Xue
PUBLISHED: 12-03-2013
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Re-vegetation is mainly applied into regeneration in opencast mine to improve the soil quality. It is very important to choose feasible vegetation types for soil restoration. In this study, three typical forest restoration types were studied at Antaibao mine, namely, Medicago sativa, mixed forests Pinus taebelaefolius-Robinia pseudoacacia-Caragana korshinskii and Elaeagnus angustifolia-Robinia pseudoacacia-Caragana korshinskii-Hipophae rhamnoides, to determine the nutrient contents and enzyme activities in different soil layers. The results showed that re-vegetation markedly increased soil nutrient contents and the enzyme activities during the restoration process. The nutrient content of soil in the P. taebelaefolius-R. pseudoacacia-C. korshinskii mixed forest field was significantly higher than those in other plots. It was found that the soil of the P. taebelaefolius-R. pseudoacacia-C. korshinskii mixed forest had the highest integrated fertility index values. In conclusion, the restoration effects of the P. zaebelaefolius-R. pseudoacacia-C. Korshinskii mixed forest was better than that of E. angustifolia-R. pseudoacacia-C. korshinskii-H. rhamnoides, while M. sativa grassland had the least effect.
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Engineering an effective immune adjuvant by designed control of shape and crystallinity of aluminum oxyhydroxide nanoparticles.
ACS Nano
PUBLISHED: 12-02-2013
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Adjuvants based on aluminum salts (Alum) are commonly used in vaccines to boost the immune response against infectious agents. However, the detailed mechanism of how Alum enhances adaptive immunity and exerts its adjuvant immune effect remains unclear. Other than being comprised of micrometer-sized aggregates that include nanoscale particulates, Alum lacks specific physicochemical properties to explain activation of the innate immune system, including the mechanism by which aluminum-based adjuvants engage the NLRP3 inflammasome and IL-1? production. This is putatively one of the major mechanisms required for an adjuvant effect. Because we know that long aspect ratio nanomaterials trigger the NLRP3 inflammasome, we synthesized a library of aluminum oxyhydroxide (AlOOH) nanorods to determine whether control of the material shape and crystalline properties could be used to quantitatively assess NLRP3 inflammasome activation and linkage of the cellular response to the materials adjuvant activities in vivo. Using comparison to commercial Alum, we demonstrate that the crystallinity and surface hydroxyl group display of AlOOH nanoparticles quantitatively impact the activation of the NLRP3 inflammasome in human THP-1 myeloid cells or murine bone marrow-derived dendritic cells (BMDCs). Moreover, these in vitro effects were correlated with the immunopotentiation capabilities of the AlOOH nanorods in a murine OVA immunization model. These results demonstrate that shape, crystallinity, and hydroxyl content play an important role in NLRP3 inflammasome activation and are therefore useful for quantitative boosting of antigen-specific immune responses. These results show that the engineered design of aluminum-based adjuvants in combination with dendritic cell property-activity analysis can be used to design more potent aluminum-based adjuvants.
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S100A14,a member of EF-hand Calcium-Binding Proteins, is overexpressed in breast cancer and acts as a modulator of HER2 signaling.
J. Biol. Chem.
PUBLISHED: 11-27-2013
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HER2 is overexpressed in 20-25% of breast cancers. Overexpression of HER2 is an adverse prognostic factor and correlates with decreased patient survival. HER2 stimulates breast tumorigenesis via a number of intracellular signaling molecules including PI3K/AKT and MAPK/ERK. S100A14, one member of the S100 protein family, is significantly associated with outcome of breast cancer patients. Here, for the first time, we show that S100A14 and HER2 are coexpressed in invasive breast cancer specimens, and there is a significant correlation between the expression levels of the two proteins by immunohistochemistry. S100A14 and HER2 are colocalized in plasma membrane of breast cancer tissue cells and breast cancer cell lines BT474 and SK-BR3. We demonstrate that S100A14 binds directly to HER2 by co-immunoprecipitation and pull down assays. Further study shows that residues 956-1154 of HER2 intracellular domain and the residue 83 of S100A14 are essential for the two proteins binding. Moreover, we observe a decrease of HER2 phosphorylation, downstream signaling, and HER2-stimulated cell proliferation in S100A14-silenced MCF-7, BT474 and SK-BR3 cells. Our findings suggest that S100A14 functions as a modulator of HER2 signaling and provide mechanistic evidence for its role in breast cancer progression.
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[Fingertip replantation with anastomosis of palm vein and retaining the nail].
Zhongguo Gu Shang
PUBLISHED: 11-26-2013
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To study the replantation methods and clinical results of amputated fingertip.
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Dynamic Wetting of Hydrophobic Polymers by Aqueous Surfactant and Superspreader Solutions.
Langmuir
PUBLISHED: 11-18-2013
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In this paper, we comparatively investigated the wetting performance of aqueous surfactant solutions in a wide range of concentrations, including conventional ionic surfactants (CTAB, SDS) and two nonionic polyether-modified trisiloxane surfactants (TSS6/3, TSS10/2), over hydrophobic polypropylene substrates. In all cases, scaling analysis of the experimental data of spreading drops showed that the early spreading stage was dominated by inertia and that the duration of this stage was not influenced by the addition of surfactant. For conventional surfactant solutions, we only observed the inertia-dominated spreading stage before the drops stopped wetting with a finite stable contact angle. For both trisiloxane surfactants, after the inertial stage we observed a second viscosity-dominated spreading stage. In this stage, TSS10/2 showed an enhanced wetting capability independent of its concentration, while TSS6/3 started to show a concentration-dependent spreading behavior that was fully developed in a third superspreading stage. Our findings suggest that the superspreading property of TSS6/3 began to take effect after a characteristic time, before which the superspreading TSS6/3 and the nonsuperspreading TSS10/2 behaved similarly. Power law fits to the superspreading regime are in agreement with an interpretation of Marangoni flows resulting from surface tension gradients.
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Kindlin-2 regulates renal tubular cell plasticity by activation of Ras and its downstream signaling.
Am. J. Physiol. Renal Physiol.
PUBLISHED: 11-13-2013
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Kindlin-2 is an adaptor protein that contributes to renal tubulointerstitial fibrosis (TIF). Epithelial-to-mesenchymal transition (EMT) in tubular epithelial cells was regarded as one of the key events in TIF. To determine whether Kindlin-2 is involved in the EMT process, we investigated its regulation on EMT in human kidney TECs and explored the underlying mechanism. In this study, we found that overexpression of Kindlin-2 suppressed epithelial marker E-cadherin and increased the expression of fibronectin and the myofibroblast marker ?-SMA. Kindlin-2 significantly activated ERK1/2 and AKT and inhibition of ERK1/2 or AKT reversed Kindlin-2-induced EMT in human kidney TECs. Mechanistically, Kindlin-2 interacted with Ras and Sos-1. Furthermore, overexpression of Kindlin-2 increased Ras activation through recruiting Sos-1. Treatment with a Ras inhibitor markedly repressed Kindlin-2-induced ERK1/2 and AKT activation, leading to restraint of EMT. We further demonstrated that knockdown of Kindlin-2 inhibited EGF-induced Ras-Sos-1 interaction, resulting in reduction of Ras activation and suppression of EMT stimulated by EGF. Importantly, we found that depletion of Kindlin-2 significantly inhibited activation of ERK1/2 and AKT signaling in UUO mice. We conclude that Kindlin-2, through activating Ras and the downstream ERK1/2 and AKT signaling pathways, plays an important role in regulating renal tubular EMT and could be a potential therapeutic target for the treatment of fibrotic kidney diseases.
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[Retroperitoneal laparoscopic decortication and adrenalectomy for the therapy of adrenal cysts].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 10-31-2013
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To summarize the clinical characteristics of adrenal cysts and compare the therapeutic results of two different laparoscopic surgical techniques.
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Fluviicola hefeinensis sp. nov., isolated from the waste water of a chemical factory.
Int. J. Syst. Evol. Microbiol.
PUBLISHED: 10-29-2013
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A Gram-negative, strictly aerobic, yellow-orange-pigmented, motile, short rod-shaped, catalase-positive, oxidase-negative bacterium, strain MYL-8T, was isolated from the waste water of the Jin Tai Chemical Factory in Hefei, China. Strain MYL-8T grew optimally at 30°C, in the absence of NaCl and at pH 7. Menaquinone-6 was the sole respiratory quinone and the major fatty acids were iso-C15:0 (36.96%), iso-C15:1 G (18.14%), iso-C17:0 3-OH (13.67%) and summed feature 3 (C16:1 ?7c/iso-C15:0 2-OH) (11.17%). The polar lipid profile was composed predominantly of polar lipids and aminolipids. Minor amounts of phosphatidylethanolamine and phospholipids were also detectable. The DNA G+C content of strain MYL-8T was 43.5 mol%. The 16S rRNA gene sequence of strain MYL-8T showed the highest similarity to that of Fluviicola taffensis RW262T (97.03%), followed by Wandonia haliotis Haldis-1-1T (92.05%), Lishizhenia caseinilytica UST040201-001T (91.43%) and Lishizhenia tianjinensis JCM 15141T (90.61%). DNA-DNA relatedness between strain MYL-8T and strain RW262T was 21.35 ± 0.90%. On the basis of phenotypic, chemotaxonomic, genomic and phylogenetic data, strain MYL-8T is considered to represent a novel species of the genus Fluviicola, for which the name Fluviicola hefeinensis sp. nov. is proposed. The type strain is MYL-8T (= KACC 16597T = CCTCC AB 2013168T).
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Newly developed techniques in andrology: endoscopy of the vas deference and a new imaging technique for in situ localization of vital spermatozoa.
Asian J. Androl.
PUBLISHED: 10-21-2013
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During the past decade, endourology represents the most advanced technology in urology which has provided minimal invasive diagnostic and therapeutic tool for patients with urology diseases. However, because of the much smaller lumen of genital tract, endoscopic andrology remained a dream for andrologists until the first clinical application of vesiculoscopy in laser lithotripsy of seminal vesicle stones in 2006. Lately, Dr Trottmann at Ludwig-Maximilians University, Germany, for the first time established vasoscopy in the seminal duct using a new prototype of a microendoscope and also applied a new imaging technique for in situ localization of vital spermatozoa. These newly developed techniques will greatly speed up the clinical practice of endoandrology.
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What is Visualize?

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

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

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