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Find video protocols related to scientific articles indexed in Pubmed.
1,1-Alkenylboration of diarylphosphino-enynes: convenient synthetic entry to vicinal P/B Lewis pairs at extended conjugated ?-frameworks.
Org. Biomol. Chem.
PUBLISHED: 11-12-2014
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Alkenylboranes R-CH[double bond, length as m-dash]CH-B(C6F5)2 undergo carbon-carbon coupling by means of 1,1-alkenylboration with diarylphosphino-enynes to give substituted conjugated hexatriene derivatives that bear a vicinal pair of B(C6F5)2 Lewis acid and PAr2 Lewis base functionalities at their central carbon portions. A series of six examples was prepared and all compounds were characterized by X-ray diffraction. Consecutive reactions of two selected examples were carried out.
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Outcomes of adjuvant endocrine therapy and hormone receptor status change following neoadjuvant chemotherapy in breast cancer patients.
Int. J. Biol. Markers
PUBLISHED: 11-05-2014
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This retrospective study investigated the therapeutic benefit of adjuvant endocrine therapy (ET) in breast cancer patients with hormone receptor (HR) status change from positive to negative after neoadjuvant chemotherapy (NAC).
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Inhibition of mTORC1/2 Overcomes Resistance to MAPK Pathway Inhibitors Mediated by PGC1? and Oxidative Phosphorylation in Melanoma.
Cancer Res.
PUBLISHED: 10-08-2014
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Metabolic heterogeneity is a key factor in cancer pathogenesis. We found that a subset of BRAF- and NRAS-mutant human melanomas resistant to the MEK inhibitor selumetinib displayed increased oxidative phosphorylation (OxPhos) mediated by the transcriptional coactivator PGC1?. Notably, all selumetinib-resistant cells with elevated OxPhos could be resensitized by cotreatment with the mTORC1/2 inhibitor AZD8055, whereas this combination was ineffective in resistant cell lines with low OxPhos. In both BRAF- and NRAS-mutant melanoma cells, MEK inhibition increased MITF expression, which in turn elevated levels of PGC1?. In contrast, mTORC1/2 inhibition triggered cytoplasmic localization of MITF, decreasing PGC1? expression and inhibiting OxPhos. Analysis of tumor biopsies from patients with BRAF-mutant melanoma progressing on BRAF inhibitor ± MEK inhibitor revealed that PGC1? levels were elevated in approximately half of the resistant tumors. Overall, our findings highlight the significance of OxPhos in melanoma and suggest that combined targeting of the MAPK and mTORC pathways may offer an effective therapeutic strategy to treat melanomas with this metabolic phenotype. Cancer Res; 74(23); 1-11. ©2014 AACR.
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Oral targeted therapies in the treatment of pulmonary arterial hypertension: A meta-analysis of clinical trials.
Pulm Pharmacol Ther
PUBLISHED: 08-27-2014
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Oral targeted therapies have been widely used in the treatment of pulmonary arterial hypertension (PAH). Many new oral agents emerge for PAH in recent years. In this study, we performed a meta-analysis to evaluate the efficacy and safety of oral targeted therapies in PAH, focusing on overall survival improvement.
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Complete Loss of PTEN Protein Expression Correlates with Shorter Time to Brain Metastasis and Survival in Stage IIIB/C Melanoma Patients with BRAFV600 Mutations.
Clin. Cancer Res.
PUBLISHED: 08-27-2014
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Loss of function of PTEN is a frequent event in melanoma, particularly in tumors with BRAF(V600) mutations. The prevalence, pathologic features, and clinical outcomes associated with PTEN loss in patients with stage IIIB/C melanoma were interrogated to improve our understanding of the clinical significance of this molecular event.
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Nanocomposites of Sulfonic Polyaniline Nanoarrays on Graphene Nanosheets with an Improved Supercapacitor Performance.
Chemistry
PUBLISHED: 08-13-2014
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A new nanocomposite, poly(aniline-co-diphenylamine-4-sulfonic acid)/graphene (PANISP/rGO), was prepared by means of an in?situ oxidation copolymerization of aniline (ANI) with diphenylamine-4-sulfonic acid (SP) in the presence of graphene oxide, followed by the chemical reduction of graphene oxide using hydrazine hydrate as a reductant. The morphology and structure of PANISP/rGO were characterized by field-emission (FE) SEM, TEM, X-ray photoelectron spectroscopy (XPS), Raman, FTIR, and UV/Vis spectra. The electrochemical performance was evaluated by cyclic voltammetry, galvanostatic charge-discharge, and electrochemical impedance spectroscopy. The PANISP/rGO nanocomposite showed a nanosized structure, with sulfonic polyaniline nanoarrays coated homogeneously on the surface of graphene nanosheets. This special structure of the nanocomposite also facilitates the enhancement of the electrochemical performance of the electrodes. The PANISP/rGO nanocomposite exhibits a specific supercapacitance up to 1170?F?g(-1) at the current density of 0.5?A?g(-1) . The as-prepared electrodes show excellent supercapacitive performance because of the synergistic effects between graphene and the sulfonic polyaniline copolymer chains.
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Paired immunoglobulin-like receptor B regulates platelet activation.
Blood
PUBLISHED: 07-29-2014
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Murine paired immunoglobulin-like receptors B (PIRB), as the ortholog of human leukocyte immunoglobulin-like receptor B2 (LILRB2), is involved in a variety of biological functions. Here, we found that PIRB and LILRB2 were expressed in mouse and human platelets, respectively. PIRB intracellular domain deletion (PIRB-TM) mice had thrombocythemia and significantly higher proportions of megakaryocytes in bone marrow. Agonist-induced aggregation and spreading on immobilized fibrinogen were facilitated in PIRB-TM platelets. The rate of clot retraction in platelet-rich plasma containing PIRB-TM platelets was also increased. Characterization of signaling confirmed that PIRB associated with phosphatases Shp1/2 in platelets. The phosphorylation of Shp1/2 was significantly downregulated in PIRB-TM platelets stimulated with collagen-related peptide (CRP) or on spreading. The results further revealed that the phosphorylation levels of the linker for activation of T cells, SH2 domain-containing leukocyte protein of 76kDa, and phospholipase C were enhanced in PIRB-TM platelets stimulated with CRP. The phosphorylation levels of FAK Y397 and integrin ?3 Y759 were also enhanced in PIRB-TM platelet spread on fibrinogen. The PIRB/LILRB2 ligand angiopoietin-like-protein 2 (ANGPTL2) was expressed and stored in platelet ?-granules. ANGPTL2 inhibited agonist-induced platelet aggregation and spreading on fibrinogen. The data presented here reveal that PIRB and its ligand ANGPTL2 possess an antithrombotic function by suppressing collagen receptor glycoprotein VI and integrin ?IIb?3-mediated signaling.
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Plasma soluble ST2 levels correlate with disease severity and predict clinical worsening in patients with pulmonary arterial hypertension.
Clin Cardiol
PUBLISHED: 07-29-2014
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Soluble suppression of tumorigenicity (sST2) has been proposed to be a marker for biomechanical strain and a possible predictor of mortality in patients with chronic heart failure. The use of sST2 in pulmonary arterial hypertension (PAH) has not been well defined.
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Effects of cascaded vgb promoters on poly(hydroxybutyrate) (PHB) synthesis by recombinant Escherichia coli grown micro-aerobically.
Appl. Microbiol. Biotechnol.
PUBLISHED: 07-26-2014
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Micro-aeration is a situation that will be encountered in bacterial cell growth especially when the saturated dissolved oxygen level cannot match the demand from cells grown to a high density. Therefore, it is desirable to separate aerobic growth and micro-aerobic product formation into two stages using methods including anaerobic or micro-aerobic promoters that are inducible under low aeration intensity. Eleven potential low aeration-inducible promoters were cloned and studied for their induction strengths under micro-aerobic conditions. Of them, Vitreoscilla hemoglobin promoter (P vgb ) was found to be the strongest among all 11 promoters. At the same time, six E. coli hosts harboring poly(R-3-hydroxybutyrate) (PHB) synthesis operon phaCAB were compared for their ability to accumulate poly(hydroxyalkanoates) (PHA). E. coli S17-1 was demonstrated to be the best host achieving a 70 % (mass fraction) PHB in the cell dry weigh (CDW) after 48 h under micro-aerobic growth. Cascaded P vgb repeats (P nvgb ) were investigated for enhanced expression level under micro-aerobic growth. The highest PHA production was obtained when a promoter containing eight cascaded P vgb repeats (P 8vgb ) was used, 5.37 g/l CDW containing 90 % PHB was obtained from recombinant in E. coli S17-1. Cells grew further to 6.30 g/l CDW containing 91 % PHB when oxygen-responsive transcription factor ArcA (arcA) was deleted in the same recombinant E. coli S17-1. This study revealed that vgb promoter containing cascaded P vgb repeats (P 8vgb ) is useful for product formation under low aeration intensity.
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The BCL2L1 and PGAM5 axis defines hypoxia-induced receptor-mediated mitophagy.
Autophagy
PUBLISHED: 07-17-2014
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Receptor-mediated mitophagy is one of the major mechanisms of mitochondrial quality control essential for cell survival. We previously have identified FUNDC1 as a mitophagy receptor for selectively removing damaged mitochondria in mammalian systems. A critical unanswered question is how receptor-mediated mitophagy is regulated in response to cellular and environmental cues. Here, we report the striking finding that BCL2L1/Bcl-xL, but not BCL2, suppresses mitophagy mediated by FUNDC1 through its BH3 domain. Mechanistically, we demonstrate that BCL2L1, but not BCL2, interacts with and inhibits PGAM5, a mitochondrially localized phosphatase, to prevent the dephosphorylation of FUNDC1 at serine 13 (Ser13), which activates hypoxia-induced mitophagy. Our results showed that the BCL2L1-PGAM5-FUNDC1 axis is critical for receptor-mediated mitophagy in response to hypoxia and that BCL2L1 possesses unique functions distinct from BCL2.
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Acoustic rainbow trapping by coiling up space.
Sci Rep
PUBLISHED: 07-07-2014
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We numerically realize the acoustic rainbow trapping effect by tapping an air waveguide with space-coiling metamaterials. Due to the high refractive-index of the space-coiling metamaterials, our device is more compact compared to the reported trapped-rainbow devices. A numerical model utilizing effective parameters is also calculated, whose results are consistent well with the direct numerical simulation of space-coiling structure. Moreover, such device with the capability of dropping different frequency components of a broadband incident temporal acoustic signal into different channels can function as an acoustic wavelength division de-multiplexer. These results may have potential applications in acoustic device design such as an acoustic filter and an artificial cochlea.
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Rhodoligotrophos jinshengii sp. nov., isolated from activated sludge.
Int. J. Syst. Evol. Microbiol.
PUBLISHED: 07-07-2014
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A Gram-stain-negative, non-spore-forming, non-motile, ovoid, aerobic bacterial strain, designated BUT-3(T), was isolated from activated sludge from the wastewater treatment facility of a herbicide-manufacturing plant in Kunshan city, Jiangsu province, PR China. Strain BUT-3(T) grew between 15 and 40 °C, with optimum growth at 30 °C. The pH range for growth was between 5.0 and 10.0 (optimum pH 7.0). The range of NaCl concentrations for growth of strain BUT-3(T) was 0-7.0?% (w/v), with an optimum of 1.5-3.0?% (w/v). A phylogenetic tree based on 16S rRNA gene sequence analysis showed that strain BUT-3(T) clustered closely with Rhodoligotrophos appendicifer 120-1(T) (98.32?% similarity), with a bootstrap confidence level of 100?%. The major fatty acids (>5?% of total fatty acids) were C19?:?0 cyclo ?8c, C18?:?1?7c, C16?:?0, anteiso-C15?:?0 and iso-C15?:?0. Strain BUT-3(T) contained ubiquinone Q-10 as the predominant respiratory quinone. The polar lipid profile comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, three unidentified aminolipids (AL1-3), two unknown phospholipids (PL1, 5), four unidentified glycolipids (GL1-4) and two unknown lipids (L1, 2). The G+C content of the genomic DNA was 67.7 mol%. The DNA-DNA relatedness between BUT-3(T) and R. appendicifer 120-1(T) was 44.1±0.6?%. Based on the polyphasic taxonomic data, strain BUT-3(T) should be classified as a representative of a novel species of the genus Rhodoligotrophos, for which the name Rhodoligotrophos jinshengii sp. nov. is proposed. The type strain is BUT-3(T) (?=?CCTCC AB2013083(T)?=?KACC 17220(T)).
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Engineering Halomonas TD01 for the low-cost production of polyhydroxyalkanoates.
Metab. Eng.
PUBLISHED: 06-02-2014
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The halophile Halomonas TD01 and its derivatives have been successfully developed as a low-cost platform for the unsterile and continuous production of chemicals. Therefore, to increase the genetic engineering stability of this platform, the DNA restriction/methylation system of Halomonas TD01 was partially inhibited. In addition, a stable and conjugative plasmid pSEVA341 with a high-copy number was constructed to contain a LacI(q)-Ptrc system for the inducible expression of multiple pathway genes. The Halomonas TD01 platform, was further engineered with its 2-methylcitrate synthase and three PHA depolymerases deleted within the chromosome, resulting in the production of the Halomonas TD08 strain. The overexpression of the threonine synthesis pathway and threonine dehydrogenase made the recombinant Halomonas TD08 able to produce poly(3-hydroxybutyrate-co-3-hydroxyvalerate) or PHBV consisting of 4-6mol% 3-hydroxyvalerate or 3HV, from various carbohydrates as the sole carbon source. The overexpression of the cell division inhibitor MinCD during the cell growth stationary phase in Halomonas TD08 elongated its shape to become at least 1.4-fold longer than its original size, resulting in enhanced PHB accumulation from 69wt% to 82wt% in the elongated cells, further promoting gravity-induced cell precipitations that simplify the downstream processing of the biomass. The resulted Halomonas strains contributed to further reducing the PHA production cost.
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Development of an enhanced chromosomal expression system based on porin synthesis operon for halophile Halomonas sp.
Appl. Microbiol. Biotechnol.
PUBLISHED: 06-02-2014
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Since halophile Halomonas spp. can grow contamination free in seawater under unsterile and continuous conditions, it holds great promise for industrial biotechnology to produce low-cost chemicals in an economic way. Yet, metabolic engineering methods are urgently needed for Halomonas spp. It is commonly known that chromosomal expression is more stable yet weaker than plasmid one is. To overcome this challenge, a novel chromosomal expression method was developed for halophile Halomonas TD01 and its derivatives based on a strongly expressed porin gene as a site for external gene integration. The gene of interest was inserted downstream the porin gene, forming an artificial operon porin-inserted gene. This chromosome expression system was proven functional by some examples: First, chromosomal expression of heterologous polyhydroxybutyrate (PHB) synthase gene phaC Re from Ralstonia eutropha completely restored the PHB accumulation level in endogenous phaC knockout mutant of Halomonas TD01. The integrated phaC Re was expressed at the highest level when inserted at the locus of porin compared with insertions in other chromosome locations. Second, an inducible expression system was constructed in phaC-deleted Halomonas TD01 by integrating the lac repressor gene (lacI) into the porin site in the host chromosome. The native porin promoter was inserted with the key 21 bp DNA of lac operator (lacO) sequence to become an inducible promoter encoded in a plasmid. This inducible system allowed on-off switch of gene expression in Halomonas TD strains. Thus, the stable and strong chromosomal expression method in Halomonas TD spp. was established.
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Targeted therapy resistance mechanisms and therapeutic implications in melanoma.
Hematol. Oncol. Clin. North Am.
PUBLISHED: 06-02-2014
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Although selective mutant BRAF inhibitors have revolutionized the treatment of metastatic melanoma, the magnitude and duration of their clinical benefit are significantly undermined by de novo and acquired resistance. Functional studies, molecular characterization of clinical samples, and clinical trials are providing insights into the landscape of resistance mechanisms in this disease. These findings have implications for the development of rational therapeutic approaches, and have identified several challenges that remain to be overcome if outcomes are to be improved in patients with metastatic melanoma.
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[Fe(F20 TPP)Cl]-Catalyzed Amination with Arylamines and {[Fe(F20 TPP)(NAr)](PhI?NAr)}?+?. Intermediate Assessed by High-Resolution ESI-MS and DFT Calculations.
Chem Asian J
PUBLISHED: 05-29-2014
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Amination of C?H bonds catalyzed by transition metal complexes via nitrene/imide insertion is an appealing strategy for C?N bond formation, and the use of iminoiodinanes, or their in situ generated forms from 'PhI(OAc)2 +primary amides (such as sulfonamides, sulfamates, and carbamates)', as nitrogen sources for the amination reaction has been well documented. In this work, a 'metal catalyst+PhI(OAc)2 +primary arylamines' amination protocol has been developed using [Fe(F20 TPP)Cl] (H2 F20 TPP=meso-tetrakis(pentafluorophenyl)porphyrin) as a catalyst. This catalytic method is applicable for both intra- and intermolecular amination of sp(2) and sp(3) C?H bonds (>27 examples), affording the amination products, including natural products such as rutaecarpine, in moderate-to-good yields. ESI-MS analysis and DFT calculations lend support for the involvement of {[Fe(F20 TPP)(NC6 H4 -p-NO2 )](PhI=NC6 H4 -p-NO2 )}?+?. intermediate in the catalysis.
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Microbial synthesis of functional homo-, random, and block polyhydroxyalkanoates by ?-oxidation deleted Pseudomonas entomophila.
Biomacromolecules
PUBLISHED: 05-28-2014
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Functional polyhydroxyalkanoates (PHAs) allow chemical modifications to widen PHA diversity, promising to increase values of these biodegradable and biocompatible polyesters. Among functional PHAs, unsaturated PHA site chains can be easily grafted to add chemical groups, and to cross-link with other PHA polymer chains. However, it has been very difficult to obtain structurally controllable functional homo-, random, or block PHA. For the first time, a ?-oxidation deleted Pseudomonas entomophila was used to successfully synthesize random copolymers of 3-hydroxydodecanoate (3HDD) and 3-hydroxy-9-decenoate (3H9D). Compositions of the random copolymers P(3HDD-co-3H9D) can be adjusted by ratios of dodecanoic acid (DDA) to 9-decenol (9DEO) fed to the culture of P. entomophila. Homopolymer P3H9D was formed when only 9DEO was added to the culture. Diblock copolymers of P3HDD-b-P3H9D were produced by feeding DDA as the first precursor to form a P3HDD block followed by adding 9DEO as the second precursor to form a second P3H9D block. It was demonstrated that random copolymers P(3HDD-co-3H9D) could be crossed-linked under UV-radiation due to the presence of the unsaturated bonds. Thermal and mechanical characterizations of the above homo-, random, and diblock PHA polymers were conducted. It was found that the diblock polymer P3HDD-b-P3H9D increased at least 2-fold on Young's modulus compared with its random copolymers consisting of similar 3HDD/3H9D ratios. This study demonstrates that PHA functionality could be controlled to meet various requirements.
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Long-term outcomes following adjuvant endocrine therapy in breast cancer patients with a positive-to-negative change of hormone receptor status following neoadjuvant chemotherapy.
Mol Clin Oncol
PUBLISHED: 05-27-2014
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The aim of the present study was to investigate whether breast cancer patients with changes from positive to negative in the hormone receptor following neoadjuvant chemotherapy (NAC) could benefit from adjuvant endocrine therapy (ET). Between December 2000 and November 2010, 97 eligible patients with a positive-to-negative switch of the hormone receptor status following NAC were identified. All the patients were categorized into two groups on the basis of the administration of ET: 57 ET-administered and 40 ET-naïve patients. Survival analyses were performed to examine the prognostic value of ET administration, as well as other clinical and pathological variables. The administration of ET was associated with a significantly improved disease-free survival (DFS) (P=0.018) in patients with a positive-to-negative switch of the hormone receptor status. The 5-year DFS rates were 77.0 and 55.5% in ET-administered and ET-naïve patients, respectively. The 5-year overall survival (OS) rate for ET-administered was also higher than that of the ET-naïve patients (81.3 vs. 72.7%, P=0.053), but the difference between the two groups did not reach a statistical significance. The present study revealed that patients with the hormone receptor that was altered from positive to negative following NAC benefit from ET, and the hormone receptor status should be evaluated not only in specimens obtained during post-NAC surgery, but also in specimens biopsied prior to NAC.
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rs10505474 and rs7837328 at 8q24 cumulatively confer risk of prostate cancer in Northern Han Chinese.
Asian Pac. J. Cancer Prev.
PUBLISHED: 05-13-2014
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Genome-wide association studies (GWAS) have identified several risk variants for prostate cancer (pCa) mainly in Europeans, which need to be further verified in other racial groups. We selected six previously identified variants as candidates and to define the association with PCa in Northern Han Chinese.
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Molecular Profiling of Patient-Matched Brain and Extracranial Melanoma Metastases Implicates the PI3K Pathway as a Therapeutic Target.
Clin. Cancer Res.
PUBLISHED: 05-06-2014
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An improved understanding of the molecular pathogenesis of brain metastases, one of the most common and devastating complications of advanced melanoma, may identify and prioritize rational therapeutic approaches for this disease. In particular, the identification of molecular differences between brain and extracranial metastases would support the need for the development of organ-specific therapeutic approaches.
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Engineering Escherichia coli for enhanced production of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) in larger cellular space.
Metab. Eng.
PUBLISHED: 05-05-2014
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Polyhydroxyalkanoates (PHA) are intracellularly accumulated as inclusion bodies. Due to the limitation of the cell size, PHA accumulation is also limited. To solve this problem, Escherichia coli was enlarged by over-expression of sulA gene to inhibit the cell division FtsZ ring assembly, leading to the formation of filamentary E. coli that have larger internal space for PHA accumulation compared with rod shape E. coli. As a result, more than 100% increases on poly(3-hydroxybutyrate) (PHB) contents and cell dry weights (CDW) were achieved compared with its control strain under same conditions. The enlarged cell strategy was applied to the production of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) or P(3HB-co-4HB) by sad, gabD, essential genes ispH and folK knockout E. coli harboring two addictives and thus stable plasmids consisting of P(3HB-co-4HB) producing genes, including phaCAB operon, orfZ, 4hbD, sucD, essential genes ispH and folK as well as the sulA. The so constructed E. coli grew in glucose to form filamentary shapes with an improved P(3HB-co-4HB) accumulation around 10% more than its control strain without addition of 4HB precursor, reaching over 78% P(3HB-co-4HB) in CDW. Importantly, the shape changing E. coli was able to precipitate after 20min stillstand. Finally, the filamentary recombinant E. coli was not only able to produce more P(3HB-co-4HB) from glucose but also allow convenient downstream separation from the fermentation broth.
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Development and validation of an ultra high performance liquid chromatography tandem mass spectrometry method for simultaneous determination of sulfonamides, quinolones and benzimidazoles in bovine milk.
J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.
PUBLISHED: 04-29-2014
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A simple, sensitive and reliable analytical method was developed for the simultaneous determination of 38 veterinary drugs (18 sulfonamides, 11 quinolones and 9 benzimidazoles) and 8 metabolites of benzimidazoles in bovine milk by ultra high performance liquid chromatography-positive electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). Samples were extracted with acidified acetonitrile, cleaned up with Oasis(®) MCX cartridges, and analyzed by LC-MS/MS on an Acquity UPLC(®) BEH C18 column with gradient elution. The method allows such multi-analyte measurements within a 13min runtime while the specificity is ensured through the MRM acquisition mode. The method was validated according to the European Commission Decision 2002/657/EC determining specificity, decision limit (CC?), detection capability (CC?), recovery, precision, linearity and stability. For compounds which have MRLs in bovine milk, the CC? values fall into a range from 11 to 115?g/kg, and the CC? values fall within a range of 12-125?g/kg. For compounds which have not MRLs in bovine milk, the CC? values fall into a range from 0.01 to 0.08?g/kg, and the CC? values fall within a range of 0.02-0.11?g/kg. The mean recoveries of the 46 analytes were between 87 and 119%. The calculated RSD values of repeatability and within-laboratory reproducibility experiments were below 11% and 15% for the 46 compounds, respectively. The method was demonstrated to be suitable for the simultaneous determination of sulfonamides, quinolones and benzimidazoles in bovine milk.
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The mechanism of anti-osteoporosis effects of 3-hydroxybutyrate and derivatives under simulated microgravity.
Biomaterials
PUBLISHED: 04-24-2014
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Skeletons have significant bone loss (osteoporosis) under microgravity environment. This study showed that microbial polyhydroxyalkanoates (PHA) degradation product, and also ketone body 3-hydroxybutyrate acid (3HB) and its derivative 3-hydroxybutyrate methyl ester (3HBME) inhibit the development of osteoporosis in mice maintained under simulated microgravity, helping preserve bone microstructure and mechanical property. Mice orally administrated with 3HB or 3HBME recovered much more quickly from osteoporosis resulted from simulated microgravity compared with the controls without 3HB or 3HBME treatments due to less calcium loss to the sera. It was known that abnormal activation of osteoclasts induced by microgravity led to bone tissue absorption and thus osteoporosis. In this study, it was found that 3HB or 3HBME down-regulated the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), which is the transcription factor of pre-osteoclast differentiation. When NFATc1 activation and downstream functions were inhibited, 3HB or 3HBME was able to strongly reduce pre-osteoclast differentiation. As a result, bone absorption was prevented. It was demonstrated that 100 mg/kg 3HB resulted in the most obvious effect on osteoporosis prevention. Based on these results, 3HB and 3HBME should be further developed as novel drug candidates against osteoporosis induced by microgravity.
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Increased levels of plasma CXC-Chemokine Ligand 10, 12 and 16 are associated with right ventricular function in patients with idiopathic pulmonary arterial hypertension.
Heart Lung
PUBLISHED: 04-16-2014
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To investigate plasma levels of CXC-Chemokine Ligand 10 (CXCL10), CXC-Chemokine Ligand 12 (CXCL12) and CXC-Chemokine Ligand 16 (CXCL16) in patients with idiopathic pulmonary arterial hypertension (IPAH).
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Establishment of a rat model of type II diabetic neuropathic pain.
Pain Med
PUBLISHED: 04-11-2014
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To establish a rat model of type II diabetic neuropathic pain.
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Picosecond pulsed electric fields induce apoptosis in a cervical cancer xenograft.
Mol Med Rep
PUBLISHED: 03-26-2014
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The aim of the present study was to evaluate the efficacy of picosecond pulsed electric fields (psPEF) on a cervical cancer xenograft. Human cervical cancer xenografts were established in nude mice by transplantation of HeLa cells, and the tumors were then treated with psPEF. The histological changes were observed by hematoxylin?eosin staining and transmission electron microscopy. The rate of tumor cell apoptosis was determined using a terminal deoxynucleotidyl?transferase?mediated dUTP nick end labeling assay. The mitochondrial transmembrane potential of the tumor cells was detected by laser scanning confocal microscopy, and the activity of caspase?3, ?8, ?9 and ?12 was determined. The inhibitory rate seven days post?psPEF treatment was also calculated. The results showed that exposure to psPEF led to an increased rate of apoptosis, collapse of mitochondrial transmembrane potential, and activation of caspases. The inhibitory rate was 9.11% at day 7. The results of the present study indicate that psPEF may induce apoptosis in a cervical cancer xenograft through the endoplasmic reticulum stress and caspase?dependent signaling pathways.
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ULK1 translocates to mitochondria and phosphorylates FUNDC1 to regulate mitophagy.
EMBO Rep.
PUBLISHED: 03-26-2014
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Autophagy eliminates dysfunctional mitochondria in an intricate process known as mitophagy. ULK1 is critical for the induction of autophagy, but its substrate(s) and mechanism of action in mitophagy remain unclear. Here, we show that ULK1 is upregulated and translocates to fragmented mitochondria upon mitophagy induction by either hypoxia or mitochondrial uncouplers. At mitochondria, ULK1 interacts with FUNDC1, phosphorylating it at serine 17, which enhances FUNDC1 binding to LC3. A ULK1-binding-deficient mutant of FUNDC1 prevents ULK1 translocation to mitochondria and inhibits mitophagy. Finally, kinase-active ULK1 and a phospho-mimicking mutant of FUNDC1 rescue mitophagy in ULK1-null cells. Thus, we conclude that FUNDC1 regulates ULK1 recruitment to damaged mitochondria, where FUNDC1 phosphorylation by ULK1 is crucial for mitophagy.
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CC chemokine ligand 18 correlates with malignant progression of prostate cancer.
Biomed Res Int
PUBLISHED: 03-14-2014
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CC chemokine ligand 18 (CCL18) promotes malignant behaviors of various human cancer types. However, its involvement in human prostate cancer has not been fully elucidated. The aim of this study was to investigate the role of CCL18 in PCa.
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High glucose induces sumoylation of Smad4 via SUMO2/3 in mesangial cells.
Biomed Res Int
PUBLISHED: 02-27-2014
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Recent studies have shown that sumoylation is a posttranslational modification involved in regulation of the transforming growth factor-? (TGF-?) signaling pathway, which plays a critical role in renal fibrosis in diabetic nephropathy (DN). However, the role of sumoylation in the regulation of TGF-? signaling in DN is still unclear. In the present study, we investigated the expression of SUMO (SUMO1 and SUMO2/3) and Smad4 and the interaction between SUMO and Smad4 in cultured rat mesangial cells induced by high glucose. We found that SUMO1 and SUMO2/3 expression was significantly increased in the high glucose groups compared to the normal group (P < 0.05). Smad4 and fibronectin (FN) levels were also increased in the high glucose groups in a dose-dependent manner. Coimmunoprecipitation and confocal laser scanning revealed that Smad4 interacted and colocalized with SUMO2/3, but not with SUMO1 in mesangial cells. Sumoylation (SUMO2/3) of Smad4 under high glucose condition was strongly enhanced compared to normal control (P < 0.05). These results suggest that high glucose may activate TGF- ?/Smad signaling through sumoylation of Samd4 by SUMO2/3 in mesangial cells.
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Hemodynamic monitoring and management of patients undergoing high-risk surgery: a survey among Chinese anesthesiologists.
J Biomed Res
PUBLISHED: 02-19-2014
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Hemodynamic monitoring and optimization improve postoperative outcome during high-risk surgery. However, hemodynamic management practices among Chinese anesthesiologists are largely unknown. This study sought to evaluate the current intraoperative hemodynamic management practices for high-risk surgery patients in China. From September 2010 to November 2011, we surveyed anesthesiologists working in the operating rooms of 265 hospitals representing 28 Chinese provinces. All questionnaires were distributed to department chairs of anesthesiology or practicing anesthesiologists. Once completed, the 29-item questionnaires were collected and analyzed. Two hundred and 10 questionnaires from 265 hospitals in China were collected. We found that 91.4% of anesthesiologists monitored invasive arterial pressure, 82.9% monitored central venous pressure (CVP), 13.3% monitored cardiac output (CO), 10.5% monitored mixed venous saturation, and less than 2% monitored pulse pressure variation (PPV) or systolic pressure variation (SPV) during high-risk surgery. The majority (88%) of anesthesiologists relied on clinical experience as an indicator for volume expansion and more than 80% relied on blood pressure, CVP and urine output. Anesthesiologists in China do not own enough attention on hemodynamic parameters such as PPV, SPV and CO during fluid management in high-risk surgical patients. The lack of CO monitoring may be attributed largely to the limited access to technologies, the cost of the devices and the lack of education on how to use them. There is a need for improving access to these technologies as well as an opportunity to create guidelines and education for hemodynamic optimization in China.
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The proteasome inhibitor, MG132, attenuates diabetic nephropathy by inhibiting SnoN degradation in vivo and in vitro.
Biomed Res Int
PUBLISHED: 02-16-2014
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Transforming growth factor-? (TGF-?) has been shown to be involved in diabetic nephropathy (DN). The SnoN protein can regulate TGF-? signaling through interaction with Smad proteins. Recent studies have shown that SnoN is mainly degraded by the ubiquitin-proteasome pathway. However, the role of SnoN in the regulation of TGF- ?/Smad signaling in DN is still unclear. In this study, diabetic rats were randomly divided into a diabetic control group (DC group) and a proteasome inhibitor (MG132) diabetes therapy group (DT group). Kidney damage parameters and the expression of SnoN, Smurf2, and TGF-? were observed. Simultaneously, we cultured rat glomerular mesangial cells (GMCs) stimulated with high glucose, and SnoN and Arkadia expression were measured. Results demonstrated that 24-hour urine protein, ACR, BUN, and the expression of Smurf2 and TGF- ? were significantly increased (P < 0.05), whereas SnoN was significantly decreased in the DC group (P < 0.05). However, these changes diminished after treatment with MG132. SnoN expression in GMCs decreased significantly (P < 0.05), but Arkadia expression gradually increased due to high glucose stimulation (P < 0.05), which could be almost completely reversed by MG132 (P < 0.05). The present results support the hypothesis that MG132 may alleviate kidney damage by inhibiting SnoN degradation and TGF-? activation, suggesting that the ubiquitin-proteasome pathway may become a new therapeutic target for DN.
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A regulatory signaling loop comprising the PGAM5 phosphatase and CK2 controls receptor-mediated mitophagy.
Mol. Cell
PUBLISHED: 02-14-2014
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Mitochondrial autophagy, or mitophagy, is a major mechanism involved in mitochondrial quality control via selectively removing damaged or unwanted mitochondria. Interactions between LC3 and mitophagy receptors such as FUNDC1, which harbors an LC3-interacting region (LIR), are essential for this selective process. However, how mitochondrial stresses are sensed to activate receptor-mediated mitophagy remains poorly defined. Here, we identify that the mitochondrially localized PGAM5 phosphatase interacts with and dephosphorylates FUNDC1 at serine 13 (Ser-13) upon hypoxia or carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) treatment. Dephosphorylation of FUNDC1 catalyzed by PGAM5 enhances its interaction with LC3, which is abrogated following knockdown of PGAM5 or the introduction of a cell-permeable unphosphorylated peptide encompassing the Ser-13 and LIR of FUNDC1. We further observed that CK2 phosphorylates FUNDC1 to reverse the effect of PGAM5 in mitophagy activation. Our results reveal a mechanistic signaling pathway linking mitochondria-damaging signals to the dephosphorylation of FUNDC1 by PGAM5, which ultimately induces mitophagy.
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Additive manufacturing of poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate] scaffolds for engineered bone development.
J Tissue Eng Regen Med
PUBLISHED: 02-13-2014
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A wide range of poly(hydroxyalkanoate)s (PHAs), a class of biodegradable polyesters produced by various bacteria grown under unbalanced conditions, have been proposed for the fabrication of tissue-engineering scaffolds. In this study, the manufacture of poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate] (or PHBHHx) scaffolds, by means of an additive manufacturing technique based on a computer-controlled wet-spinning system, was investigated. By optimizing the processing parameters, three-dimensional scaffolds with different internal architectures were fabricated, based on a layer-by-layer approach. The resulting scaffolds were characterized by scanning electron microscopy, which showed good control over the fibre alignment and a fully interconnected porous network, with porosity in the range 79-88%, fibre diameter 47-76?µm and pore size 123-789?µm. Moreover, the resulting fibres presented an internal porosity connected to the external fibre surface as a consequence of the phase-inversion process governing the solidification of the polymer solution. Scaffold compressive modulus and yield stress and strain could be varied in a certain range by changing the architectural parameters. Cell-culture experiments employing the MC3T3-E1 murine pre-osteoblast cell line showed good cell proliferation after 21?days of culture. The PHBHHx scaffolds demonstrated promising results in terms of cell differentiation towards an osteoblast phenotype. Copyright © 2014 John Wiley & Sons, Ltd.
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Accidental degeneracy of double Dirac cones in a phononic crystal.
Sci Rep
PUBLISHED: 02-12-2014
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Artificial honeycomb lattices with Dirac cone dispersion provide a macroscopic platform to study the massless Dirac quasiparticles and their novel geometric phases. In this paper, a quadruple-degenerate state is achieved at the center of the Brillouin zone in a two-dimensional honeycomb lattice phononic crystal, which is a result of accidental degeneracy of two double-degenerate states. In the vicinity of the quadruple-degenerate state, the dispersion relation is linear. Such quadruple degeneracy is analyzed by rigorous representation theory of groups. Using k·p method, a reduced Hamiltonian is obtained to describe the linear Dirac dispersion relations of this quadruple-degenerate state, which is well consistent with the simulation results. Near such accidental degeneracy, we observe some unique properties in wave propagating, such as defect-insensitive propagating character and the Talbot effect.
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Leukemia propagating cells rebuild an evolving niche in response to therapy.
Cancer Cell
PUBLISHED: 01-31-2014
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Residence of cancer-propagating cells (CPCs) within preferential microenvironmental niches has a major part in evading therapy. However, the nature of niches involved and the mechanisms protecting CPCs remain largely unknown. We addressed these issues in mouse transplantation models of acute lymphoblastic leukemia (ALL). When the engrafted leukemic cells substantially damaged adjacent microenvironment in the bone marrow (BM), after chemotherapy small foci of CPCs were retained, surrounded by sheaths of supporting cells that comprise a protective niche. We investigated patients' BM biopsies and found evidence of a similar process in patients receiving induction therapy. The efficacy of chemotherapy was enhanced by interfering with the niche formation or function. We therefore identified a therapy-induced niche that protects CPCs.
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Elevated plasma YKL-40 as a prognostic indicator in patients with idiopathic pulmonary arterial hypertension.
Respirology
PUBLISHED: 01-27-2014
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Pulmonary vascular remodelling and inflammation have been implicated in pulmonary arterial hypertension (PAH). YKL-40, a marker of tissue remodelling and inflammation, has recently been recognized as a risk predictor of cardiovascular and inflammatory diseases. The study aimed to investigate a potential role of YKL-40 in predicting prognosis in idiopathic PAH (IPAH).
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Polyhydroxyalkanoates, challenges and opportunities.
Curr. Opin. Biotechnol.
PUBLISHED: 01-15-2014
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Microbial polyhydroxyalkanoates (PHA) have been developed as biodegradable plastics for the past many years. However, PHA still have only a very limited market. Because of the availability of large amount of shale gas, petroleum will not raise dramatically in price, this situation makes PHA less competitive compared with low cost petroleum based plastics. Therefore, two strategies have been adopted to meet this challenge: first, the development of a super PHA production strain combined with advanced fermentation processes to produce PHA at a low cost; second, the construction of functional PHA production strains with technology to control the precise structures of PHA molecules, this will allow the resulting PHA with high value added applications. The recent systems and synthetic biology approaches allow the above two strategies to be implemented. In the not so distant future, the new technology will allow PHA to be produced with a competitive price compared with petroleum-based plastics.
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Pyrroloquinoline quinone protects mouse brain endothelial cells from high glucose-induced damage in vitro.
Acta Pharmacol. Sin.
PUBLISHED: 01-14-2014
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To investigate the effects of pyrroloquinoline quinone (PQQ), an oxidoreductase cofactor, on high glucose-induced mouse endothelial cell damage in vitro.
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Impulsive control for synchronizing delayed discrete complex networks with switching topology.
Neural Comput Appl
PUBLISHED: 01-14-2014
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In this paper, global exponential synchronization of a class of discrete delayed complex networks with switching topology has been investigated by using Lyapunov-Ruzimiki method. The impulsive scheme is designed to work at the time instant of switching occurrence. A time-varying delay-dependent criterion for impulsive synchronization is given to ensure the delayed discrete complex networks switching topology tending to a synchronous state. Furthermore, a numerical simulation is given to illustrate the effectiveness of main results.
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Entecavir vs lamivudine therapy for naïve patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure.
World J. Gastroenterol.
PUBLISHED: 01-13-2014
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To investigate the short-term and long-term efficacy of entecavir versus lamivudine in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure (ACLF).
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MG132 ameliorates kidney lesions by inhibiting the degradation of Smad7 in streptozotocin-induced diabetic nephropathy.
J Diabetes Res
PUBLISHED: 01-05-2014
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Smad7 is the main negative regulatory protein in the transforming growth factor-? (TGF-?) downstream signaling pathway, which plays an important role in diabetic nephropathy (DN) and may be related to the ubiquitin proteasome pathway (UPP).
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Mechanisms for steep pulse irreversible electroporation technology to kill human large cell lung cancer cells L9981.
Int J Clin Exp Med
PUBLISHED: 01-01-2014
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To explore the mechanisms for steep pulse irreversible electroporation technology to kill the lung cancer cell L9981. The apoptosis, cells mitochondrial membrane potential, internal PH changes and the intra-cellular calcium ions concentration were detected after steep pulses acted on the human large cell lung cancer cell L9981. Apoptosis test results indicated that cancer cells mainly experienced necrosis and apoptosis. Along with the increase of electric parameters, the proportion of the necrotic cells increased rapidly; the detection of cells mitochondrial membrane potential indicated that membrane potential occurred depolarization. Steep pulse can cause cancer cells to produce death and apoptosis .The PH value indicated that intracellular PH level down jumped. Internal PH became more acidic and led to cell death. The detection of intra-cellular calcium ions concentration showed that the number of free calcium significantly increased, and this change had killing effects on cell death and apoptosis. Steep pulse could induce cell apoptosis.
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Tumor suppressor TSLC1 inhibits growth, proliferation, invasiveness and angiogenesis in nude mice xenografted tumor of Eca109 cells.
Int J Clin Exp Med
PUBLISHED: 01-01-2014
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Tumor suppressor in lung cancer 1 (TSLC1) is a novel tumor suppressor gene whose inactivation is implicated in the occurrence, invasion, metastasis and prognosis of esophageal cancer. TSLC1 was studied by comparing the tumor formation of TSLC1 transfectant and control cells in nude mice. Compared with blank group and mock group, tumor size and infiltrating range of transfected group was less, differentiation of tumor tissue was slightly better, and differences of tumor angiogenesis was worse. There was no obvious difference between blank group and mock group. We have shown TSLC1 gene inhibited the growth proliferation, infiltration and angiogenesis of Eca109 cells.
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Synergistic and antagonistic effects of salinity and pH on germination in switchgrass (Panicum virgatum L.).
PLoS ONE
PUBLISHED: 01-01-2014
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The effects of salt-alkaline mixed stress on switchgrass were investigated by evaluating seed germination and the proline, malondialdehyde (MDA) and soluble sugar contents in three switchgrass (Panicum virgatum L.) cultivars in order to identify which can be successfully produced on marginal lands affected by salt-alkaline mixed stress. The experimental conditions consisted of four levels of salinity (10, 60, 110 and 160 mM) and four pH levels (7.1, 8.3, 9.5 and 10.7). The effects of salt-alkaline mixed stress with equivalent coupling of the salinity and pH level on the switchgrass were explored via model analyses. Switchgrass was capable of germinating and surviving well in all treatments under low-alkaline pH (pH?8.3), regardless of the salinity. However, seed germination and seedling growth were sharply reduced at higher pH values in conjunction with salinity. The salinity and pH had synergetic effects on the germination percentage, germination index, plumular length and the soluble sugar and proline contents in switchgrass. However, these two factors exhibited antagonistic effects on the radicular length of switchgrass. The combined effects of salinity and pH and the interactions between them should be considered when evaluating the strength of salt-alkaline mixed stress.
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Percutaneous endoscopic interlaminar discectomy for pediatric lumbar disc herniation.
Childs Nerv Syst
PUBLISHED: 01-01-2014
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Percutaneous endoscopic interlaminar discectomy (PEID) is a widely used minimally invasive procedure which shows satisfying outcomes in the adult population. However, pediatric lumbar disc herniations (PLDH) occur in growing spines and are less related to degeneration, which makes them different from the adult disc herniations. This study evaluates the clinical outcomes of PEID in treating PLDH.
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[Clinical outcomes of percutaneous kyphoplasty under local anesthesia for osteoporotic vertebral compression fractures].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 12-24-2013
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To analyze the clinical outcomes of percutaneous kyphoplasty under local anesthesia for osteoporotic vertebral compression fractures.
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Chloroboron (III) subnaphthalocyanine as an electron donor in bulk heterojunction photovoltaic cells.
Nanotechnology
PUBLISHED: 11-06-2013
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In this work, chloroboron (III) subnaphthalocyanine (SubNc) was used as an electron donor, combined with a [6,6]-phenyl-C71-butyric acid methyl ester (PC70BM) or fullerene C70 acceptor in bulk heterojunction photovoltaic cells. In spite of the limited solubility of SubNc in organic solvents, the solution processed device exhibited an efficiency of 4.0% under 1 sun, AM1.5G solar irradiation at room temperature, and 5.0% at 80?° C due to the temperature-dependence of the carrier mobilities. SubNc:C70 bulk heterojunctions were also fabricated via thermal co-evaporation, demonstrating an efficiency of 4.4%. This result shows that SubNc is a promising material for photovoltaic applications via various processing techniques, such as vacuum deposition and wet coating.
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[Clinical features of adult patients with Eisenmenger syndrome associated with different types of congenital heart disease].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 09-14-2013
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To explore the clinical features and hemodynamics of adult patients with Eisenmenger syndrome in different types of congenital heart diseases (CHD).
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Phosphoproteomics study on the activated PKC?-induced cell death.
J. Proteome Res.
PUBLISHED: 09-10-2013
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The proteolytic activation of protein kinase C? (PKC?) generates a catalytic fragment called PKC?-CF, which induces cell death. However, the mechanisms underlying PKC?-CF-mediated cell death are largely unknown. On the basis of an engineering leukemic cell line with inducible expression of PKC?-CF, here we employ SILAC-based quantitative phosphoproteomics to systematically and dynamically investigate the overall phosphorylation events during cell death triggered by PKC?-CF expression. Totally, 3000 phosphorylation sites were analyzed. Considering the fact that early responses to PKC?-CF expression initiate cell death, we sought to identify pathways possibly related directly with PKC? by further analyzing the data set of phosphorylation events that occur in the initiation stage of cell death. Interacting analysis of this data set indicates that PKC?-CF triggers complicated networks to initiate cell death, and motif analysis and biochemistry verification reveal that several kinases in the downstream of PKC? conduct these networks. By analysis of the specific sequence motif of kinase-substrate, we also find 59 candidate substrates of PKC? from the up-regulated phosphopeptides, of which 12 were randomly selected for in vitro kinase assay and 9 were consequently verified as substrates of PKC?. To our greatest understanding, this study provides the most systematic analysis of phosphorylation events initiated by the cleaved activated PKC?, which would vastly extend the profound understanding of PKC?-directed signal pathways in cell death. The MS data have been deposited to the ProteomeXchange with identifier PXD000225.
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Assessment of the associations between three VEGF polymorphisms and risk of prostate cancer.
Tumour Biol.
PUBLISHED: 08-22-2013
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Vascular endothelial growth factor (VEGF) plays a crucial role in the regulation of angiogenesis and is involved in the development and metastasis of common cancers. There were several case-controls studies published to assess the associations of VEGF polymorphisms with risk of prostate cancer, but the findings were inconsistent. We performed a meta-analysis to provide a comprehensive assessment of the associations of three VEGF polymorphisms with risk of prostate cancer. The pooled odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated to assess the associations. Eleven individual case-control studies with a total of 5,209 cases of prostate cancer and 5,233 controls were finally included into our meta-analysis. Overall, VEGF rs833061 polymorphism was not associated with risk of prostate cancer (T versus C, OR?=?1.14, 95 % CI 0.91-1.44, P?=?0.26; TT versus CC, OR?=?1.09, 95 % CI 0.67-1.76, P?=?0.74; TT versus CC/CT: OR?=?1.46, 95 % CI 0.67-3.18, P?=?0.34; TT/CT versus CC, OR?=?1.08, 95 % CI 0.82-1.43, P?=?0.59). VEGF rs3025039 polymorphism was also not associated with risk of prostate cancer (T versus C, OR?=?1.03, 95 % CI 0.91-1.16, P?=?0.66; TT versus CC, OR?=?1.82 95 % CI 0.16-20.53, P?=?0.63; TT versus CC/CT, OR?=?2.00, 95 % CI 0.18-22.41, P?=?0.57; TT/CT versus CC, OR?=?0.72, 95 % CI 0.38-1.36, P?=?0.31). VEGF rs2010963 polymorphism was not associated with risk of prostate cancer under three models (C versus G, OR?=?1.17, 95 % CI 0.92-1.48, P?=?0.20; CC versus GG, OR?=?2.28, 95 % CI 0.90-5.75, P?=?0.08; CC versus GG/GC, OR?=?1.57, 95 % CI 0.67-3.68, P?=?0.30). In conclusison, current data suggest that those three VEGF polymorphisms are not obviously associated with risk of prostate cancer.
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Preventive and therapeutic effects of adenanthin on experimental autoimmune encephalomyelitis by inhibiting NF-?B signaling.
J. Immunol.
PUBLISHED: 08-22-2013
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Adenanthin, a diterpenoid isolated from the leaves of Isodon adenanthus, has been reported to possess antileukemic activity through targeting peroxiredoxin I/II. However, its other potential activities remain to be explored. Using myelin oligodendrocyte glycoprotein (MOG)35-55-induced experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, we report in this study that adenanthin exerts efficaciously preventive and therapeutic effects on EAE accompanied by significant restriction of infiltration of inflammatory cells and demyelination in CNS. Adenanthin-presented immunomodulatory effects on EAE are correlated with suppressed proliferation of MOG35-55-reactive T cells, decreased Th1 and Th17 cells, increased regulatory T cell populations, decreased production of serum proinflammatory cytokines, and reduced stimulatory capacity of APCs, which might be mediated by its inhibitory action on NF-?B signaling pathway. Our results propose that, as a novel NF-?B inhibitor, adenanthin has potent immunomodulatory activity for the treatment of multiple sclerosis and possibly other autoimmune disorders.
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Antisense reduction of tau in adult mice protects against seizures.
J. Neurosci.
PUBLISHED: 08-02-2013
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Tau, a microtubule-associated protein, is implicated in the pathogenesis of Alzheimers Disease (AD) in regard to both neurofibrillary tangle formation and neuronal network hyperexcitability. The genetic ablation of tau substantially reduces hyperexcitability in AD mouse lines, induced seizure models, and genetic in vivo models of epilepsy. These data demonstrate that tau is an important regulator of network excitability. However, developmental compensation in the genetic tau knock-out line may account for the protective effect against seizures. To test the efficacy of a tau reducing therapy for disorders with a detrimental hyperexcitability profile in adult animals, we identified antisense oligonucleotides that selectively decrease endogenous tau expression throughout the entire mouse CNS--brain and spinal cord tissue, interstitial fluid, and CSF--while having no effect on baseline motor or cognitive behavior. In two chemically induced seizure models, mice with reduced tau protein had less severe seizures than control mice. Total tau protein levels and seizure severity were highly correlated, such that those mice with the most severe seizures also had the highest levels of tau. Our results demonstrate that endogenous tau is integral for regulating neuronal hyperexcitability in adult animals and suggest that an antisense oligonucleotide reduction of tau could benefit those with epilepsy and perhaps other disorders associated with tau-mediated neuronal hyperexcitability.
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Whole-genome sequencing identifies a recurrent functional synonymous mutation in melanoma.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 07-30-2013
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Synonymous mutations, which do not alter the protein sequence, have been shown to affect protein function [Sauna ZE, Kimchi-Sarfaty C (2011) Nat Rev Genet 12(10):683-691]. However, synonymous mutations are rarely investigated in the cancer genomics field. We used whole-genome and -exome sequencing to identify somatic mutations in 29 melanoma samples. Validation of one synonymous somatic mutation in BCL2L12 in 285 samples identified 12 cases that harbored the recurrent F17F mutation. This mutation led to increased BCL2L12 mRNA and protein levels because of differential targeting of WT and mutant BCL2L12 by hsa-miR-671-5p. Protein made from mutant BCL2L12 transcript bound p53, inhibited UV-induced apoptosis more efficiently than WT BCL2L12, and reduced endogenous p53 target gene transcription. This report shows selection of a recurrent somatic synonymous mutation in cancer. Our data indicate that silent alterations have a role to play in human cancer, emphasizing the importance of their investigation in future cancer genome studies.
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High glucose induces activation of NF-?B inflammatory signaling through I?B? sumoylation in rat mesangial cells.
Biochem. Biophys. Res. Commun.
PUBLISHED: 07-11-2013
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The posttranslational modification of proteins by small ubiquitin-like modifiers (SUMOs) has emerged as an important regulatory mechanism for the alteration of protein activity, stability, and cellular localization. The latest research demonstrates that sumoylation is extensively involved in the regulation of the nuclear factor ?B (NF-?B) pathway, which plays a critical role in the regulation of inflammation and contributes to fibrosis in diabetic nephropathy (DN). However, the role of sumoylation in the regulation of NF-?B signaling in DN is still unclear. In the present study, we cultured rat glomerular mesangial cells (GMCs) stimulated by high glucose and divided GMCs into six groups: normal glucose group (5.6mmol/L), high glucose groups (10, 20, and 30mmol/L), mannitol group (i.e., osmotic control group), and MG132 intervention group (30mmol/L glucose with MG132, a proteasome inhibitor). The expression of SUMO1, SUMO2/3, I?B?, NF-?Bp65, and monocyte chemotactic protein 1 (MCP-1) was measured by Western blot, reverse-transcription polymerase chain reaction, and indirect immunofluorescence laser scanning confocal microscopy. The interaction between SUMO1, SUMO2/3, and I?B? was observed by co-immunoprecipitation. The results showed that the expression of SUMO1 and SUMO2/3 was dose- and time-dependently enhanced by high glucose (p<0.05). However, the expression of I?B? sumoylation in high glucose was significantly decreased compared with the normal glucose group (p<0.05). The expression of I?B? was dose- and time-dependently decreased, and NF-?Bp65 and MCP-1 were increased under high glucose conditions, which could be mostly reversed by adding MG132 (p<0.05). The present results support the hypothesis that high glucose may activate NF-?B inflammatory signaling through I?B? sumoylation and ubiquitination.
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Genomic study of polyhydroxyalkanoates producing Aeromonas hydrophila 4AK4.
Appl. Microbiol. Biotechnol.
PUBLISHED: 06-25-2013
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The complete genome of Gram-negative Aeromonas hydrophila 4AK4 that has been used for industrial production of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) was sequenced and annotated. Its chromosome is 4,527,993 bp in size encoding 4,272 genes, including 28 rRNA genes and 104 tRNA genes. Comparative analysis indicated that genome of A. hydrophila 4AK4 was similar to that of the A. hydrophila ATCC 7966(T), an intensively studied aeromonad for its pathogenicity related to its genomic information. Genes possibly coming from other species or even other genus were identified in A. hydrophila 4AK4. A large number of putative virulent genes were predicted. However, a cytotonic enterotoxin (Ast) is absent in A. hydrophila 4AK4, allowing the industrial strain to be different from other A. hydrophila strains, indicating possible reduced virulence of strain 4AK4, which is very important for industrial fermentation. Genes involved in polyhydroxyalkanoate (PHA) metabolism were predicted and analyzed. The resulting genomic information is useful for improved production of PHA via metabolic engineering of A. hydrophila 4AK4.
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Prostanoid therapy for pulmonary arterial hypertension: a meta-analysis of survival outcomes.
Eur. J. Clin. Pharmacol.
PUBLISHED: 06-10-2013
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Prostanoids have played an important role in the treatment of pulmonary arterial hypertension (PAH). However, whether prostanoid therapy provides a survival advantage is still not clear. The aim of this meta-analysis was to evaluate the efficacy and safety of prostanoids in PAH, focusing on the improvement in overall survival.
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3-hydroxybutyrate methyl ester as a potential drug against Alzheimers disease via mitochondria protection mechanism.
Biomaterials
PUBLISHED: 05-30-2013
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Alzheimers disease (AD) is induced by many reasons, including decreased cellular utilization of glucose and brain cell mitochondrial damages. Degradation product of microbially synthesized polyhydroxybutyrate (PHB), namely, 3-hydroxybutyrate (3HB), can be an alternative to glucose during sustained hypoglycemia. In this study, the derivative of 3HB, 3-hydroxybutyrate methyl ester (HBME), was used by cells as an alternative to glucose. HBME inhibited cell apoptosis under glucose deprivation, rescued activities of mitochondrial respiratory chain complexes that were impaired in AD patients and decreased the generation of ROS. Meanwhile, HBME stabilized the mitochondrial membrane potential. In vivo studies showed that HBME crossed the blood brain barrier easier compared with charged 3HB, resulting in a better bioavailability. AD mice treated with HBME performed significantly better (p < 0.05) in the Morris water maze compared with other groups, demonstrating that HBME has a positive in vivo pharmaceutical effect to improve the spatial learning and working memory of mice. A reduced amyloid-? deposition in mouse brains after intragastric administration of HBME was also observed. Combined with the in vitro and in vivo results, HBME was proposed to be a drug candidate against AD, its working mechanism appeared to be mediated by various effects of protecting mitochondrial damages.
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Somatic Mutations in MAP3K5 Attenuate Its Proapoptotic Function in Melanoma through Increased Binding to Thioredoxin.
J. Invest. Dermatol.
PUBLISHED: 05-07-2013
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Patients with advanced metastatic melanoma have poor prognosis and the genetics underlying its pathogenesis are poorly understood. High-throughput sequencing has allowed comprehensive discovery of somatic mutations in cancer samples. Here, on analysis of our whole-genome and whole-exome sequencing data of 29 melanoma samples, we identified several genes that harbor recurrent nonsynonymous mutations. These included MAP3K5 (mitogen-activated protein kinase kinase kinase-5), which in a prevalence screen of 288 melanomas was found to harbor a R256C substitution in 5 cases. All MAP3K5-mutated samples were wild type for BRAF, suggesting a mutual exclusivity for these mutations. Functional analysis of the MAP3K5 R256C mutation revealed attenuation of MKK4 (mitogen-activated protein kinase kinase 4) activation through increased binding of the inhibitory protein thioredoxin (TXN/TRX-1/Trx), resulting in increased proliferation and anchorage-independent growth of melanoma cells. This mutation represents a potential target for the design of new therapies to treat melanoma.Journal of Investigative Dermatology advance online publication, 10 October 2013; doi:10.1038/jid.2013.365.
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Expression of SOCSs in human prostate cancer and their association in prognosis.
Mol. Cell. Biochem.
PUBLISHED: 05-02-2013
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Suppressors of cytokine signaling (SOCS) proteins have been identified as negative feedback regulators of cytokine-mediated signaling in various tissues, and demonstrated to play critical roles in tumorigenesis and tumor development of different cancers. The involvement of SOCSs in human prostate cancer (PCa) has not been fully elucidated. Thus, the aim of this study is to investigate the expression patterns and the clinical significance of SOCSs in PCa. The expression changes of SOCSs at mRNA and protein levels in human PCa tissues compared with adjacent benign prostate tissues were, respectively, detected by using real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) and immunohistochemistry analyses. The associations of SOCSs expression with clinicopathological features and clinical outcome of PCa patients were further statistically analyzed. Among SOCSs, both QRT-PCR and immunohistochemistry analyses found that SOCS2 expression was upregulated (at mRNA level: change ratio = 1.98, P = 0.031; at protein level: 5.12 ± 0.60 vs. 2.68 ± 0.37, P = 0.016) and SOCS6 expression was downregulated (at mRNA level: change ratio = -1.65, P = 0.008; at protein level: 3.03 ± 0.32 vs. 4.0.72 ± 0.39, P = 0.004) in PCa tissues compared with those in non-cancerous prostate tissues. In addition, the upregulation of SOCS2 in PCa tissues was correlated with the lower Gleason score (P < 0.001), the absence of metastasis (P < 0.001) and the negative PSA failure (P = 0.009); the downregulation of SOCS6 tended to be found in PCa tissues with the higher Gleason score (P = 0.016), the advanced pathological stage (P = 0.007), the positive metastasis (P = 0.020), and the positive PSA failure (P = 0.032). Furthermore, both univariate and multivariate analyses showed that the downregulation of SOCS2 was an independent predictor of shorter biochemical recurrence-free survival. Our data offer the convincing evidence for the first time that the dysregulation of SOCS2 and SOCS6 may be associated with the aggressive progression of PCa. SOCS2 may be potential markers for prognosis in PCa patients.
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Arterial compression of nerve is the primary cause of trigeminal neuralgia.
Neurol. Sci.
PUBLISHED: 04-11-2013
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Whether arterial or venous compression or arachnoid adhesions are primarily responsible for compression of the trigeminal nerve in patients with trigeminal neuralgia is unclear. The aim of this study was to determine the causes of trigeminal nerve compression in patients with trigeminal neuralgia. The surgical findings in patients with trigeminal neuralgia who were treated by micro vascular decompression were compared to those in patients with hemifacial spasm without any signs or symptoms of trigeminal neuralgia who were treated with microvascular decompression. The study included 99 patients with trigeminal neuralgia (median age, 57 years) and 101 patients with hemifacial spasm (median age, 47 years). There were significant differences between the groups in the relationship of artery to nerve (p < 0.001) and the presence of arachnoid adhesions (p < 0.001) but no significant difference in relationship of vein to nerve. After adjustment for age, gender, and other factors, patients with vein compression of nerve or with artery compression of nerve were more likely to have trigeminal neuralgia (OR = 5.21 and 42.54, p = 0.026 and p < 0.001, respectively). Patients with arachnoid adhesions were less likely to have trigeminal neuralgia (OR = 0.15, p = 0.038). Arterial compression of the trigeminal nerve is the primary cause of trigeminal neuralgia and therefore, decompression of veins need not be a priority when performing microvascular dissection in patients with trigeminal neuralgia.
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The Effect of Created Local Hyperosmotic Microenvironment in Microcapsule for the Growth and Metabolism of Osmotolerant Yeast Candida krusei.
Biomed Res Int
PUBLISHED: 04-02-2013
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Candida krusei is osmotolerant yeast used for the production of glycerol. Addition of osmolyte such as NaCl into culture medium can increase the production of glycerol from glucose, but osmolytes may burden the glycerol separation. A coencapsulation method was suggested to create local extracellular hyperosmotic stress for glycerol accumulation. Firstly, the influence of osmotic stress induced by the addition of PEG4000 on growth and metabolism of free cell was studied in detail. Glycerol accumulation could be improved by employing PEG4000 as osmoregulator. Secondly, cells and PEG4000 were coentrapped in NaCS/PDMDAAC capsules to create local hyperosmotic stress. The effects of local hyperosmotic microenvironment on the cell growth and metabolism were studied. The coentrapment method increased the glycerol concentration by 25%, and the glycerol concentration attained 50?gL(-1) with productivity of 18.8?gL(-1)Day(-1) in shake flask. More importantly, the glycerol could be directly separated from the encapsulated cells. The entrapped cells containing PEG4000 were also cultivated for 15 days in an airlift reactor. The yield and productivity were ca. 35% and 21?gL(-1)Day(-1), respectively.
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Thermodynamics of the enantiomers of amino acid and monosaccharide binding to fullerenol used as an artificial sweet taste receptor model.
Food Chem
PUBLISHED: 03-29-2013
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Fullerenol was used as sweet taste receptor model to investigate the binding affinities of structurally related pairs of enantiomers by isothermal titration calorimetry (ITC). It reveals that amino acid binding with fullerenol are enthalpy-cost and entropically-driven processes, whereas enthalpy contributes to monosaccharide binding to fullerenol. Spontaneous binding of amino acids was found through two sequential steps in which the sweeter enantiomer displays larger binding constants. Association of the d-form of fructose and l-form galactose with fullerenol suggested that, the higher the perceived sweetness intensity of the enantiomer, the larger was the binding constant with respect to their antipodes. Further investigation by molecular dynamic simulation showed that the binding energy and the perceived sweetness intensity were well correlated. The preliminary results of this biomimetic research cover the lack of information about the thermodynamic basis of sweet sensation and the underlying principles of sweetness differences between the enantiomers of amino acids and monosaccharides.
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Notch Signaling Molecules Activate TGF- ? in Rat Mesangial Cells under High Glucose Conditions.
J Diabetes Res
PUBLISHED: 03-17-2013
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The involvement of the Notch signaling pathway in the cellular differentiation of the mammalian kidney is established. Recently, the dysregulation of Notch signaling molecules has been identified in acute and chronic renal injuries, fibrosis models, and diabetic kidney biopsies. The canonical Notch ligand , Jagged1, is upregulated in a transforming growth factor-beta- (TGF- ? -) dependent manner during chronic kidney disease. TGF- ? , a central mediator of renal fibrosis, also is a major contributor to the development of diabetic nephropathy. To explore the roles and possible mechanisms of Notch signaling molecules in the pathogenesis of diabetic nephropathy, we exposed cultured rat mesangial cells to a ? -secretase inhibitor (DAPT) or high glucose and measured the expression of Notch signaling molecules and the fibrosis index. Notch pathway-related molecules, TGF- ? , and fibronectin increased with exposure to high glucose and decreased with DAPT treatment. Our results suggest that the Notch signaling pathway may precipitate diabetic nephropathy via TGF- ? activation.
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MicroRNA-335 acts as a candidate tumor suppressor in prostate cancer.
Pathol. Oncol. Res.
PUBLISHED: 02-11-2013
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MicroRNA-335 (miR-335) acts as a tumor suppressor or a tumor promoter in different human malignancies. However, the involvement of miR-335 in prostate cancer (PCa) is still unclear. The purpose of this study was to investigate the functional and clinical significance of miR-335 in PCa. miR-335 expression in 3 PCa cell lines (LNCaP/DU145/PC3) and in 20 clinical PCa tissues were detected by real-time quantitative reverse transcriptase-PCR compared with corresponding controls. The function of miR-335 was investigated for cell proliferation, invasion and migration in PCa cells transfected with agents containing EGFP-miR-335 expression vector. Additionally, miR-335 expression in 104 clinical PCa tissues was detected by in situ hybridization. Its assocaitions with clinicopathological features and prognosis in patients with PCa were also determined. miR-335 was significantly down-regulated in PCa cell lines than in the normal prostate cell line (P?
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Antimicrobial and antioxidant activities of Cichorium intybus root extract using orthogonal matrix design.
J. Food Sci.
PUBLISHED: 02-08-2013
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Solvent, impregnation time, sonication repetitions, and ultrasonic power were important factors in the process of ultrasound-assisted extraction from chicory (Cichorium intybus) root, while there were no studies about optimizing these 4 factors for extract yield, total phenolic content (TPC), antioxidant, antibacterial, and antifungal activity of the extracts using orthogonal matrix design. The present research demonstrated that the solvent composition played a significant role in the improving extract yield, TPC, antioxidant, and antibacterial activities. The other 3 factors had inequable effect on different purposes, ultrasonic power could improve TPC and antioxidant activity, but long time of extraction lowered antioxidant activity. The TPC increased from 22.34 to 27.87 mg GAE (gallic acid equivalents)/100 g (dry extracts) with increasing solvent polarity. The half inhibition concentration (IC(50,) ?g/mL) of the radical scavenging activity of the chicory extracts ranged from 281.00 to 983.33 ?g/mL. The content of caffeoylquinic acids of root extract, which was extracted by the optimal combination was 0.104%. Several extracts displayed antibacterial activities against Escherichia coli, Staphylococcus aureus, Bacillus thuringiensis, Bacillus subtilis, and Salmonella typhi, while Penicillium sp. and Aspergillus sp. resisted against all the extracts. Combination of 70% ethanol v/v, 24-h impregnation time, 3 sonication rounds, and 300-W ultrasonic input power was found to be the optimal combination for the chicory extract yield, TPC, antioxidant activity, and antibacterial activity.
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Coalescence of Pickering emulsion droplets induced by an electric field.
Phys. Rev. Lett.
PUBLISHED: 02-05-2013
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Combining high-speed photography with electric current measurement, we investigate the electrocoalescence of Pickering emulsion droplets. Under a high enough electric field, the originally stable droplets coalesce via two distinct approaches: normal coalescence and abnormal coalescence. In the normal coalescence, a liquid bridge grows continuously and merges two droplets together, similar to the classical picture. In the abnormal coalescence, however, the bridge fails to grow indefinitely; instead, it breaks up spontaneously due to the geometric constraint from particle shells. Such connecting-then-breaking cycles repeat multiple times, until a stable connection is established. In depth analysis indicates that the defect size in particle shells determines the exact merging behaviors: when the defect size is larger than a critical size around the particle diameter, normal coalescence will show up, while abnormal coalescence will appear for coatings with smaller defects.
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Improved process for the production of cellulose sulfate using sulfuric acid/ethanol solution.
Carbohydr Polym
PUBLISHED: 01-23-2013
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An improved process for production of cellulose sulfate (CS) was developed by using sulfuric acid/ethanol solution as sulfonating agent and Na2SO4 as water absorbent. The FTIR, SEM and TG analysis were used to characterize the CS prepared. The total degree of substitution and viscosity of the product solution (2%, w/v) were ranging from 0.28 to 0.77 and from 115 to 907 mPa s, respectively, by changing the process parameters such as the amount of Na2SO4, the reaction time, the temperature, the sulfuric acid/alcohol ratio and liquid/solid ratio. The results indicated that the product with DS (0.28-0.77) and ?2% (115-907) mPa s could be produced by using this improved process and more cellulose sulfate could be produced when cellulose was sulfonated for 3-4 h at -2 °C in sulfuric acid/ethanol (1.4-1.6) solution with addition of 0.8 g Na2SO4. The (13)C NMR indicated that the sulfate group of CS produced using sulfuric acid/ethanol solution was at C6 position.
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Non-invasive continuous blood pressure monitoring: a review of current applications.
Front Med
PUBLISHED: 01-23-2013
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Blood pressure monitoring has come a long way from the initial observations made by Reverend Hales in the 18th century. There are none that deny the importance of monitoring perioperative blood pressure; however, the limited ability of the current prevalent technology (oscillometric blood pressure monitoring) to offer continuous blood pressure measurements leaves room for improvement. Invasive monitoring is able to detect beat-to-beat blood pressure measurement, but the risks inherent to the procedure make it unsuitable for routine use except when this risk is outweighed by the benefits. This review focuses on the discoveries which have led up to the current blood pressure monitoring technologies, and especially the creation of those offering non-invasive but continuous blood pressure monitoring capabilities, including their methods of measurement and limitations.
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Picosecond pulsed electric fields induce apoptosis in HeLa cells via the endoplasmic reticulum stress and caspase-dependent signaling pathways.
Int. J. Oncol.
PUBLISHED: 01-16-2013
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The non-invasive treatment of tumors with preserved fertility holds great promise. The application of pulsed electric field (PEF) is a new biomedical engineering technique for tumor therapy. Picosecond pulsed electric fields (psPEF) can be transferred to target deep tissue non-invasively and precisely; however, research of the biological effects of psPEF on cells is limited. Electric theory predicts that when the pulse duration decreases to nanoseconds and picoseconds, it will mainly affect organelles and lead to intracellular electromanipulations. Previous studies have shown that psPEF targets the mitochondria and induces apoptosis through a mitochondrial-mediated pathway in HeLa cells. The endoplasmic reticulum is also involved in the intrinsic pathways of apoptosis. In the present study, HeLa cells were exposed to psPEF to investigate the underlying mechanisms of apoptosis. MTT assay demonstrated that psPEF displayed strong growth inhibitory effects on HeLa cells. Treatment with psPEF led to marked cell apoptosis and cell cycle arrest at the G2/M phase. In addition, psPEF affected the phosphorylation levels of endoplasmic reticulum sensors and upregulated the expression of glucose-regulated protein 78 (GRP78), glucose-regulated protein 94 (GRP94) and CCAAT enhancer-binding protein (C/EBP) homologous protein (CHOP). These changes were accompanied by the elevation of intracellular Ca2+ concentrations. Furthermore, the activation of caspase-12, -9 and -3, led to the release of cytochrome c, as well as the upregulation of Bax and the downregulation of Bcl-2, as observed in the HeLa cells. Taken together, these data suggest that psPEF is an efficient apoptosis-inducing agent for HeLa cells, which exerts its effects, at least partially, via the endoplasmic reticulum stress and caspase-dependent signaling pathways.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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

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