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Find video protocols related to scientific articles indexed in Pubmed.
Energy metabolism targeted drugs synergize with photodynamic therapy to potentiate breast cancer cell death.
Photochem. Photobiol. Sci.
PUBLISHED: 11-03-2014
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Malignant cells are highly dependent on aerobic glycolysis, which differs significantly from normal cells (the Warburg effect). Interference of this metabolic process has been considered as an innovative method for developing selective cancer therapy. A recent study demonstrated that the glycolysis inhibitor 2-deoxyglucose (2-DG) can potentiate PDT efficacy, whereas the possible mechanisms have not been carefully investigated. This study firstly proved the general potentiation of PDT efficacy by 2-DG and 3-bromopyruvate (3-BP) in human breast cancer MDA-MB-231 cells, and carefully elucidated the underlying mechanism in the process. Our results showed that both 2-DG and 3-BP could significantly promote a PDT-induced cell cytotoxic effect when compared with either monotherapy. Synergistic potentiation of mitochondria- and caspase-dependent cell apoptosis was observed, including a mitochondrial membrane potential (MMP) drop, Bax translocation, and caspase-3 activation. Besides, ROS generation and the expression of oxidative stress related proteins such as P38 MAPK phosphorylation and JNK phosphorylation were notably increased after the combined treatments. Moreover, when pretreated with the ROS scavenger N-acetylcysteine (NAC), the ROS generation, the MMP drop, cell apoptosis and cytotoxicity were differently inhibited, suggesting that ROS was vertical in the pro-apoptotic process induced by 2-DG/3-BP combined with PDT treatment. These results indicate that the combination of glycolytic antagonists and PDT may be a promising therapeutic strategy to effectively kill cancer cells.
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Motor impulsivity during childhood and adolescence: A longitudinal biometric analysis of the go/no-go task in 9- to 18-year-old twins.
Dev Psychol
PUBLISHED: 10-28-2014
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In the present study, we investigated genetic and environmental effects on motor impulsivity from childhood to late adolescence using a longitudinal sample of twins from ages 9 to 18 years. Motor impulsivity was assessed using errors of commission (no-go errors) in a visual go/no-go task at 4 time points: ages 9-10, 11-13, 14-15, and 16-18 years. Significant genetic and nonshared environmental effects on motor impulsivity were found at each of the 4 waves of assessment with genetic factors explaining 22%-41% of the variance within each of the 4 waves. Phenotypically, children's average performance improved across age (i.e., fewer no-go errors during later assessments). Multivariate biometric analyses revealed that common genetic factors influenced 12%-40% of the variance in motor impulsivity across development, whereas nonshared environmental factors common to all time points contributed to 2%-52% of the variance. Nonshared environmental influences specific to each time point also significantly influenced motor impulsivity. Overall, results demonstrated that although genetic factors were critical to motor impulsivity across development, both common and specific nonshared environmental factors played a strong role in the development of motor impulsivity across age. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
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[Effects of extracts of Prunella Vulgaris L. on proteome of human lung adenocarcinoma cell line A549].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 10-22-2014
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To explore the effect of extracts of Prunella vulgaris L.on proteome of human lung adenocarcinoma cell line A549 by two-dimensional electrophoresis and mass spectrometry and elucidate the mechanism of anti-lung adenocarcinom effect of Prunella vulgaris L.at the level of proteome.
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Use and Prescription of Antibiotics in Primary Health Care Settings in China.
JAMA Intern Med
PUBLISHED: 10-07-2014
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Appropriate antibiotic use is a key strategy to control antibacterial resistance. The first step in achieving this is to identify the major problems in antibiotic prescription in health care facilities, especially in primary health care settings, which is where most patients receive medical care.
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Antitumor effect of sinoporphyrin sodium-mediated photodynamic therapy on human esophageal cancer eca-109 cells.
Photochem. Photobiol.
PUBLISHED: 10-07-2014
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The aim of this study was to evaluate the photodynamic effect of Sinoporphyrin sodium (DVDMS). In this study, Eca-109 cells were treated with DVDMS (5 ?g mL(-1) ) and subjected to photodynamic therapy (PDT). The uptake and subcellular localization of DVDMS were monitored by flow cytometry and confocal microscopy. The phototoxicity of DVDMS was studied by MTT assay. The morphological changes were observed by scanning electron microscopy (SEM). DNA damage, reactive oxygen species (ROS) generation and mitochondria membrane potential (MMP) changes were analyzed by flow cytometry. Studies demonstrated maximal uptake of DVDMS occurred within 3 h, with a mitochondrial subcellular localization. MTT assays displayed that DVDMS could be effectively activated by light and the phototoxicity was much higher than photofrin under the same conditions. In addition, SEM observation indicated that cells were seriously damaged after PDT treatment. Furthermore, activation of DVDMS resulted in significant increases in ROS production. The generated ROS played an important role in the phototoxicity of DVDMS. DVDMS-mediated PDT (DVDMS-PDT) also induced DNA damage and MMP loss. It is demonstrated that DVDMS-mediated PDT is an effective approach on cell proliferation inhibition of Eca-109 cells.
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Unusual, photo-induced self-assembly of azobenzene-containing amphiphiles.
Soft Matter
PUBLISHED: 10-04-2014
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Stimuli-responsive self-assembly is playing an increasingly important role in emerging applications, ranging from smart materials to biosensors. However, obtaining essential information for further development, such as molecular arrangement and interaction, is still experimentally challenging. A molecular-level understanding of the stimuli-responsive self-assembly is needed. Azobenzene-containing (azo-containing) amphiphiles organize into photo-responsive assemblies because of the cis-trans isomerization triggered by the irradiation of ultraviolet (UV) and visible light. In this study, we applied a coarse grained (CG) molecular dynamics (MD) simulation, with the necessary potential parameters fitted from theoretical calculation data, to study the photo-induced self-assembly of 4,4'-bis(hydroxymethyl)-azobenzene (AzoCO), a simple azo-containing amphiphile. An unusual "chaotic micelle" and "monolayer phase" were obtained with cis- and trans-AzoCO molecules, respectively. The structural information and formation mechanism were studied. The "chaotic micelle" possesses a chaotic but not a pure hydrophobic interior as commonly understood. Through comparative simulations, we found that the azo (-N[double bond, length as m-dash]N-) group of azobenzene plays a crucial role in the formation of the "chaotic micelle". The "monolayer phase" is arranged by abreast rod-like trans-AzoCO molecules; the axial symmetry of the trans-AzoCO molecule drives the formation of this structure. The novel "chaotic micelle" and "monolayer phase" have potential applications in nanotechnology and bioengineering. This work is expected to trigger further studies on stimuli-responsive phenomena and materials.
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A novel glucose 6-phosphate isomerase from Listeria monocytogenes.
Protein J.
PUBLISHED: 09-08-2014
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D-Arabinose 5-phosphate isomerases (APIs) catalyze the interconversion of D-ribulose 5-phosphate and D-arabinose 5-phosphate (A5P). A5P is an intermediate in the biosynthesis of 3-deoxy-D-manno-octulosonate (Kdo), an essential component of lipopolysaccharide, the lipopolysaccharide found in the outer membrane of Gram-negative bacteria. The genome of the Gram-positive pathogen Listeria monocytogenes contains a gene encoding a putative sugar isomerase domain API, Q723E8, with significant similarity to c3406, the only one of four APIs from Escherichia coli CFT073 that lacks a cystathionine-?-synthase domain. However, L. monocytogenes lacks genes encoding any of the other enzymes of the Kdo biosynthesis pathway. Realizing that the discovery of an API in a Gram-positive bacterium could provide insight into an alternate physiological role of A5P in the cell, we prepared and purified recombinant Q723E8. We found that Q723E8 does not possess API activity, but instead is a novel GPI (D-glucose 6-phosphate isomerase). However, the GPI activity of Q723E8 is weak compared with previously described GPIS. L. monocytogenes contains an ortholog of the well-studied two-domain bacterial GPI, so this maybe redundant. Based on this evidence glucose utilization is likely not the primary physiological role of Q723E8.
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Single Nanoparticle Detection and Sizing Using a Nanofiber Pair in an Aqueous Environment.
Adv. Mater. Weinheim
PUBLISHED: 08-28-2014
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Single nanoparticle detection and sizing is demonstrated using a nanofiber pair in an aqueous environment. The sizing of nanoparticles with a single radius (100 nm) and of mixed nanoparticles with different radii (100 nm and 170 nm) are both realized, and the experimental results agree well with predictions of Rayleigh-Gans scattering, by taking the inhomogeneous field distribution of the nanofibers into account.
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Comparison of protoporphyrin IX produced cell proliferation inhibition between human breast cancer MCF-7 and MDA-MB-231 cells.
Pharmazie
PUBLISHED: 08-28-2014
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Protoporphyrin IX (PpIX) is an effective hematoporphyrin derivative, widely adopted in photodynamic therapy (PDT) and sonodynamic therapy (SDT). As a sensitizer, PpIX could significantly enhance laser light or ultrasound causing tumor cell damage in PDT/SDT studies. However, the biological function of PpIX itself has not been carefully defined. Recently, studies indicate that PpIX alone can inhibit Hela cell proliferation, but the potential mechanism was unclear. Therefore, in the present study it was investigated whether the proliferation inhibition effect generally occurred in human breast cancer MCF-7 and MDA-MB-231 cells. Different sensitivities and the involved mechanisms were carefully explored. Our results show that PpIX preferentially accumulated and selectively caused cell damage in human breast cancer MCF-7 and MDA-MB-231 cells compared with mouse embryonic fibroblast NIH-3T3. In vitro, PpIX induced cell viability decrease, intracellular ROS (reactive oxygen species) generation, and DNA damage in a concentration-dependent and cell-specific manner. MCF-7 was more sensitive to PpIX than MDA-MB-231 cells at the same PpIX dose. Western blots showed obvious enhancement of P53, and PUMA in a concentration dependent manner in MCF-7 cells, but not in MDA-MB-231 cells. In cell-free system, we also found that PpIX could interact with some large biological molecules, such as calf thymus DNA, and induce hyperchromic effects in spectroscopic analysis. Our findings imply that DNA might be one of the main targets of PpIX, and PpIX alone can cause significant tumor cell damage through ROS generation, while P53 status may play an important role in these processes.
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Genetic landscape of esophageal squamous cell carcinoma.
Nat. Genet.
PUBLISHED: 08-24-2014
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Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers. We performed exome sequencing on 113 tumor-normal pairs, yielding a mean of 82 non-silent mutations per tumor, and 8 cell lines. The mutational profile of ESCC closely resembles those of squamous cell carcinomas of other tissues but differs from that of esophageal adenocarcinoma. Genes involved in cell cycle and apoptosis regulation were mutated in 99% of cases by somatic alterations of TP53 (93%), CCND1 (33%), CDKN2A (20%), NFE2L2 (10%) and RB1 (9%). Histone modifier genes were frequently mutated, including KMT2D (also called MLL2; 19%), KMT2C (MLL3; 6%), KDM6A (7%), EP300 (10%) and CREBBP (6%). EP300 mutations were associated with poor survival. The Hippo and Notch pathways were dysregulated by mutations in FAT1, FAT2, FAT3 or FAT4 (27%) or AJUBA (JUB; 7%) and NOTCH1, NOTCH2 or NOTCH3 (22%) or FBXW7 (5%), respectively. These results define the mutational landscape of ESCC and highlight mutations in epigenetic modulators with prognostic and potentially therapeutic implications.
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Total syntheses of parthenolide and its analogues with macrocyclic stereocontrol.
J. Med. Chem.
PUBLISHED: 08-20-2014
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The first total synthesis of parthenolide (1) is described. The key feature of this synthesis is the formation of a 10-membered carbocylic ring by a macrocyclic stereocontrolled Barbier reaction, followed by a photoinduced Z/E isomerization. The biological evaluation of a small library of parthenolide analogues (19, 33, and 34) disclosed a preliminary structure-activity relationship (SAR). The results revealed that the C1, C10 double bond configuration of parthenolide has little or no effect on the activity, and the C6 and C7 configurations of the lactone ring have a moderate impact on the activities against some cancer cell lines.
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TPX2 siRNA regulates growth and invasion of esophageal cancer cells.
Biomed. Pharmacother.
PUBLISHED: 07-09-2014
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Observe how specific small RNA interference (siRNA) aimed at TPX2 gene suppresses TPX2 gene expression in esophageal cancer EC9706 cells and the effect on esophageal cancer cell growth and invasion ability.
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Numerical investigations of the mechanical properties of a braided non-vascular stent design using finite element method.
Comput Methods Biomech Biomed Engin
PUBLISHED: 05-29-2014
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This paper discusses various issues relating to the mechanical properties of a braided non-vascular stent made of a Ni-Ti alloy. The design of the stent is a major factor which determines its reliability after implantation into a stenosed non-vascular cavity. This paper presents the effect of the main structural parameters on the mechanical properties of braided stents. A parametric analysis of a commercial stent model is developed using the commercial finite element code ANSYS. As a consequence of the analytical results that the pitch of wire has a greater effect than other structural parameters, a new design of a variable pitch stent is presented to improve mechanical properties of these braided stents. The effect of structural parameters on mechanical properties is compared for both stent models: constant and variable pitches. When the pitches of the left and right quarters of the stent are 50% larger and 100% larger than that of the central portion, respectively, the radial stiffness in the central portion increases by 10% and 38.8%, while the radial stiffness at the end portions decreases by 128% and 164.7%, the axial elongation by 25.6% and 56.6% and the bending deflection by 3.96% and 10.15%. It has been demonstrated by finite element analysis that the variable pitch stent can better meet the clinical requirements.
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Longitudinal alteration of amygdalar functional connectivity in mild cognitive impairment subjects revealed by resting-state FMRI.
Brain Connect
PUBLISHED: 05-22-2014
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Mild cognitive impairment (MCI) is considered to be the prodromal stage of Alzheimer's disease. The amygdala, which is considered to be a hub, has been shown to have widespread brain connections with many cortical regions. Longitudinal alterations in the functional connectivity of the amygdala remain unclear in MCI. We hypothesized that the impairment in the amygdala-cortical loop would be more severe in a follow-up MCI group than in a baseline MCI group and that these alterations would be related to the disease processes. To test this hypothesis, we used resting-state functional magnetic resonance imaging to investigate alterations in amygdalar connectivity patterns based on longitudinal data from 13 MCI subjects (8 males and 5 females). Compared to the baseline, decreases in functional connectivity were mainly found located between the amygdala and regions at the conjunction of the temporal-occipital system and the regions included in the default mode network in the follow-up MCI individuals. The alterations in the functional connectivity of the identified regions were validated in an independent dataset. Specifically, reduced amygdalar connectivity was significantly correlated with cognitive abilities. These findings indicate that impairments in the functional connectivity of the amygdala may be potential biomarkers of the progression of MCI.
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Protein kinase D1 is essential for Ras-induced senescence and tumor suppression by regulating senescence-associated inflammation.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 05-14-2014
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Oncogene-induced senescence (OIS) is an initial barrier to tumor development. Reactive oxygen species (ROS) is critical for oncogenic Ras OIS, but the downstream effectors to mediate ROS signaling are still relatively elusive. Senescent cells develop a senescence-associated secretory phenotype (SASP). However, the mechanisms underlying the regulation of the SASP are largely unknown. Here, we identify protein kinase D1 (PKD1) as a downstream effector of ROS signaling to mediate Ras OIS and SASP. PKD1 is activated by oncogenic Ras expression and PKD1 promotes Ras OIS by mediating inflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) via modulation of NF-?B activity. We demonstrate that ROS-protein kinase C? (PKC?)-PKD1 axis is essential for the establishment and maintenance of IL-6/IL8 induction. In addition, ablation of PKD1 causes the bypass of Ras OIS, and promotes cell transformation and tumorigenesis. Together, these findings uncover a previously unidentified role of ROS-PKC?-PKD1 pathway in Ras OIS and SASP regulation.
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Grey-matter volume as a potential feature for the classification of Alzheimer's disease and mild cognitive impairment: an exploratory study.
Neurosci Bull
PUBLISHED: 04-23-2014
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Specific patterns of brain atrophy may be helpful in the diagnosis of Alzheimer's disease (AD). In the present study, we set out to evaluate the utility of grey-matter volume in the classification of AD and amnestic mild cognitive impairment (aMCI) compared to normal control (NC) individuals. Voxel-based morphometric analyses were performed on structural MRIs from 35 AD patients, 27 aMCI patients, and 27 NC participants. A two-sample two-tailed t-test was computed between the NC and AD groups to create a map of abnormal grey matter in AD. The brain areas with significant differences were extracted as regions of interest (ROIs), and the grey-matter volumes in the ROIs of the aMCI patients were included to evaluate the patterns of change across different disease severities. Next, correlation analyses between the grey-matter volumes in the ROIs and all clinical variables were performed in aMCI and AD patients to determine whether they varied with disease progression. The results revealed significantly decreased grey matter in the bilateral hippocampus/parahippocampus, the bilateral superior/middle temporal gyri, and the right precuneus in AD patients. The grey-matter volumes were positively correlated with clinical variables. Finally, we performed exploratory linear discriminative analyses to assess the classifying capacity of grey-matter volumes in the bilateral hippocampus and parahippocampus among AD, aMCI, and NC. Leave-one-out cross-validation analyses demonstrated that grey-matter volumes in hippocampus and parahippocampus accurately distinguished AD from NC. These findings indicate that grey-matter volumes are useful in the classification of AD.
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Formation and soot combustion of honeycomb-like LaFeO3 microfibers.
J Nanosci Nanotechnol
PUBLISHED: 04-22-2014
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The nanocrystalline, honeycomb-like, perovskite LaFeO3 microfibers with a fibre diameter about 1-2 microm and channel sizes about 180-220 nm on the cross-section were prepared by the citrate-gel process. These microfibers were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and Brunauere-Emmette-Teller (BET) method. After calcined at a low temperature of 550 degrees C for 6 hours, the single phase of perovskite LaFeO3 microfibers is formed and the grain size increases from 27 to 38 nm with the calcination temperature increasing from 500 to 650 degrees C. The catalytic activity for soot combustion was analyzed by thermo-gravimetric method (TG), and the LaFeO3 microfibers calcined at 600 degrees C exhibits the highest catalytic activity for soot combustion, with a lowest T50 (393 degrees C) and T90 (434 degrees C). The formation mechanism of the honeycomb-like structure is analyzed and these honeycomb-like microfibers can be used as advanced catalysts, absorbents, filters and microreactors.
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Induction of autophagy in human neuroblastoma SH-SY5Y cells by tri-ortho-cresyl phosphate.
Mol. Cell. Biochem.
PUBLISHED: 04-13-2014
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Tri-ortho-cresyl phosphate (TOCP) is an organophosphorus ester and has been widely used in industry. It is found that TOCP induced delayed neurotoxicity in humans and sensitive animal species. However, the mechanism of TOCP-induced neural cytotoxicity remains unclear. In this study, we studied whether autophagy is involved in TOCP-induced neural cytotoxicity in human neuroblastoma SH-SY5Y cells. We found that 0.5 and 1.0 mM TOCP treatment significantly increased the ectopic accumulation of microtubule-associated protein 1 light chain 3 (LC3)-immunopositive puncta, Beclin 1, and LC3-II/LC3-I levels in SH-SY5Y cells in a dose-dependent manner. Notably, by monodansylcadaverine staining method, we found abundant punctate fluorescent acidic vesicular organelles in TOCP-treated cells. Furthermore, ultrastructural observation under the transmission electron microscope indicated that the cytoplasm was occupied by autophagosomes in TOCP-treated SH-SY5Y cells. Thus, these results suggest that TOCP may induce autophagy, and autophagy may be involved in the development of TOCP-induced neural cytotoxicity.
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Transport coefficients and entropy-scaling law in liquid iron up to Earth-core pressures.
J Chem Phys
PUBLISHED: 03-25-2014
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Molecular dynamics simulations were applied to study the structural and transport properties, including the pair distribution function, the structure factor, the pair correlation entropy, self-diffusion coefficient, and viscosity, of liquid iron under high temperature and high pressure conditions. Our calculated results reproduced experimentally determined structure factors of liquid iron, and the calculated self-diffusion coefficients and viscosity agree well with previous simulation results. We show that there is a moderate increase of self-diffusion coefficients and viscosity along the melting curve up to the Earth-core pressure. Furthermore, the temperature dependencies of the pair correlation entropy, self-diffusion, and viscosity under high pressure condition have been investigated. Our results suggest that the temperature dependence of the pair correlation entropy is well described by T(-1) scaling, while the Arrhenius law well describes the temperature dependencies of self-diffusion coefficients and viscosity under high pressure. In particular, we find that the entropy-scaling laws, proposed by Rosenfeld [Phys. Rev. A 15, 2545 (1977)] and Dzugutov [Nature (London) 381, 137 (1996)] for self-diffusion coefficients and viscosity in liquid metals under ambient pressure, still hold well for liquid iron under high temperature and high pressure conditions. Using the entropy-scaling laws, we can obtain transport properties from structural properties under high pressure and high temperature conditions. The results provide a useful ingredient in understanding transport properties of planet's cores.
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Combined subchronic toxicity of dichlorvos with malathion or pirimicarb in mice liver and serum: a metabonomic study.
Food Chem. Toxicol.
PUBLISHED: 03-22-2014
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Organophosphorus (OP) and carbamate (CM) pesticides are widely used in agriculture. These pesticides are highly toxic to humans and their residues in food pose potential threat to human health. In this study, we investigated the effect of subchronic low-level exposure of OPs (dichlorvos, DDVP; malathion, MAL), CM pirimicarb (PI), or their mixtures (DDVP+MAL, DDVP+PI) on mice liver. Metabonomic analysis based on (1)H nuclear magnetic resonance spectroscopy was carried out in combination with biochemical assays. Serum metabonomic analysis showed that levels of trimethylamine-N-oxide, lactate, acetone, very low- and low-density lipoprotein and 3-hydroxybutyrate changed after exposure to the pesticides. In the liver extracts, lactate, glucose, choline, glutathione, alanine, glutamine and isoleucine levels changed after the treatment by pesticides. Our results indicated that exposure to low dose DDVP, MAL and PI, either alone or in combination lead to alteration of liver glucose, fat and protein metabolism, energy metabolism and oxidative balance. This study also showed that metabonomics is of potential use in food toxicity study.
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Construction of genetically engineered bacteria that degrades organophosphorus pesticide residues and can be easily detected by the fluorescence.
Environ Technol
PUBLISHED: 03-21-2014
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Organophosphorus compounds (OPs) are widely used in agriculture and industry and there is increased concern about their toxicological effects in the environment. Bioremediation can offer an efficient and cost-effective option for the removal of OPs. Herein, we describe the construction of a genetically engineered microorganism (GEM) that can degrade OPs and be directly detected and monitored in the environment using an enhanced green fluorescent protein (EGFP) fusion strategy. The coding regions of EGFP, a reporter protein that can fluoresce by itself, and organophosphorus hydrolase (OPH), which has a broad substrate specificity and is able to hydrolyse a number of organophosphorus pesticides, were cloned into the expression vector pET-28b. The fusion protein of EGFP-OPH was expressed in E. coli BL21 (DE3) and the protein expression reached the highest level at 11 h after isopropyl beta-D-thiogalactopyranoside induction. The fluorescence of the GEM was detected by fluorescence spectrophotometry and microscopy, and its ability to degrade OPs was determined by OPH activity assay. Those GEM that express the fusion protein (EGFP and OPH) exhibited strong fluorescence intensity and also potent hydrolase activity, which could be used to degrade organophosphorus pesticide residues in the environment and can also be directly monitored by fluorescence.
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Sinoporphyrin sodium: a novel sensitizer in sonodynamic therapy.
Anticancer Drugs
PUBLISHED: 03-13-2014
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The aim of this paper was to investigate whether sinoporphyrin sodium (DVDMS) could be a novel sonosensitizer in sonodynamic therapy. We used two kinds of leukemia cells (K562, U937) as main tumor cell models and cells (peripheral blood mononuclear cells, spleen lymphocytes) separated from healthy ICR mice as normal cell models. The multivolume spectrophotometer system and fluorescence spectrophotometer were used to determine the spectral characteristics of DVDMS. The uptake of DVDMS by tumor cells and normal cells was measured by flow cytometry. The MTT assay was used to examine the cytotoxicity and sonotoxicity of DVDMS. The absorption spectra showed that DVDMS had five distinct peaks at 359, 514, 548, 580, and 631 nm, respectively, and the maximum peak was at ?359 nm. The fluorescence emission spectra showed that DVDMS fluorescence emission was at 642 nm. DVDMS showed an advantage of quick cellular uptake and selectively accumulated in tumor cells compared with normal healthy cells. The cytotoxicity of DVDMS by the MTT method was dose dependent, and DVDMS had little cytotoxicity to normal cells. The sonotoxicity of DVDMS showed that in the presence of DVDMS, under appropriate conditions, the cell-damaging effect of ultrasound was significantly enhanced. The present study showed that the newly synthesized sensitizer, DVDMS, under appropriate experiment conditions, can act as a potential sonosensitizer for tumors in sonodynamic therapy.
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Cytotoxic effect of protoporphyrin IX to human Leukemia U937 cells under ultrasonic irradiation.
Cell. Physiol. Biochem.
PUBLISHED: 03-11-2014
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Sonodynamic therapy (SDT) is an alternative strategy that manages malignancies via the generation of cytotoxic factors during ultrasound-activated sono-sensitive agents. However, the detailed mechanisms are not clear. This study was to identify the cytotoxic effects of ultrasound-activated protoporphyrin IX (PpIX) on U937 cells.
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Chloride intracellular channel 1 regulates colon cancer cell migration and invasion through ROS/ERK pathway.
World J. Gastroenterol.
PUBLISHED: 03-04-2014
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To investigate the mechanisms of chloride intracellular channel 1 (CLIC1) in the metastasis of colon cancer under hypoxia-reoxygenation (H-R) conditions.
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A new acidophilic endo-?-1,4-xylanase from Penicillium oxalicum: cloning, purification, and insights into the influence of metal ions on xylanase activity.
J. Ind. Microbiol. Biotechnol.
PUBLISHED: 02-20-2014
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A new acidophilic xylanase (XYN11A) from Penicillium oxalicum GZ-2 has been purified, identified and characterized. Synchronized fluorescence spectroscopy was used for the first time to evaluate the influence of metal ions on xylanase activity. The purified enzyme was identified by MALDI TOF/TOF mass spectrometry, and its gene (xyn11A) was identified as an open reading frame of 706 bp with a 68 bp intron. This gene encodes a mature protein of 196 residues with a predicted molecular weight of 21.3 kDa that has the 100 % identity with the putative xylanase from the P. oxalicum 114-2. The enzyme shows a structure comprising a catalytic module family 10 (GH10) and no carbohydrate-binding module family. The specific activities were 150.2, 60.2, and 72.6 U/mg for beechwood xylan, birchwood xylan, and oat spelt xylan, respectively. XYN11A exhibited optimal activity at pH 4.0 and remarkable pH stability under extremely acidic condition (pH 3). The specific activity, K m and V max values were 150.2 U/mg, 30.7 mg/mL, and 403.9 ?mol/min/mg for beechwood xylan, respectively. XYN11A is a endo-?-1,4-xylanase since it release xylobiose and xylotriose as the main products by hydrolyzing xylans. The activity of XYN11A was enhanced 155 % by 1 mM Fe(2+) ions, but was inhibited strongly by Fe(3+). The reason of enhancing the xylanase activity of XYN11A with 1 mM Fe(2+) treatment may be responsible for the change of microenvironment of tryptophan residues studied by synchronous fluorescence spectrophotometry. Inhibition of the xylanase activity by Fe(3+) was first time demonstrated to associate tryptophan fluorescence quenching.
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PTEN interacts with histone H1 and controls chromatin condensation.
Cell Rep
PUBLISHED: 02-14-2014
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Chromatin organization and dynamics are integral to global gene transcription. Histone modification influences chromatin status and gene expression. PTEN plays multiple roles in tumor suppression, development, and metabolism. Here, we report on the interplay of PTEN, histone H1, and chromatin. We show that loss of PTEN leads to dissociation of histone H1 from chromatin and decondensation of chromatin. PTEN deletion also results in elevation of histone H4 acetylation at lysine 16, an epigenetic marker for chromatin activation. We found that PTEN and histone H1 physically interact through their C-terminal domains. Disruption of the PTEN C terminus promotes the chromatin association of MOF acetyltransferase and induces H4K16 acetylation. Hyperacetylation of H4K16 impairs the association of PTEN with histone H1, which constitutes regulatory feedback that may reduce chromatin stability. Our results demonstrate that PTEN controls chromatin condensation, thus influencing gene expression. We propose that PTEN regulates global gene transcription profiling through histones and chromatin remodeling.
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Removal and mechanism of Cu (II) and Cd (II) from aqueous single-metal solutions by a novel biosorbent from waste-activated sludge.
Environ Sci Pollut Res Int
PUBLISHED: 01-25-2014
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The removal and mechanism of Cu(2+) and Cd(2+) from aqueous single-metal solutions were investigated by using a novel biosorbent from waste-activated sludge. A series of adsorption experiments was designed to disclose the effects of the key factors on the adsorption capacity of the biosorbent for the metal ions. The mass ratio of the biosorbent to metal ion was optimized as 2 to balance the adsorption capacity and the removal efficiency. A right shaking speed (150 r/min) not only ensured enough contact frequency between the sorbent and the adsorbate but also reduced the mass transfer resistance. The natural pH value (about 5.5) of the metal solutions benefited a high adsorption capacity of the biosorbent and avoided the consumption of acid or base for pH adjustment. The adsorption reactions belonged to the endothermic process between 15 and 45 °C. As the scanning electron microscopy (SEM) images showed, the meshy structure with long chains and many branches was ideal for the biosorbent to quickly capture the metal ions. The energy-dispersive X-ray (EDX) spectra confirmed that the adsorbed metal ions lay in the precipitates of the adsorption reactions. According to the FTIR analyses, the functional groups responsible for Cu(2+) adsorption majorly consisted of O-H, N-H, COOH, CONH2, and the groups containing sulfur and phosphorus, while those for Cd(2+) adsorption contained O-H, N-H, COOH, and CONH2. The differences in the responsible functional groups explained the phenomenon that the adsorption capacity of the biosorbent for Cu(2+) was higher than that for Cd(2+).
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Involvement of mitochondrial and reactive oxygen species in the sonodynamic toxicity of chlorin e6 in human leukemia K562 cells.
Ultrasound Med Biol
PUBLISHED: 01-22-2014
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It is well accepted that sonodynamic therapy (SDT) exerts cytotoxicity and anti-tumor activity in many human tumors through the induction of cell apoptosis. The aim of the work described here was to study the effect of chlorin e6 (Ce6)-mediated SDT on human chronic myelogenous leukemia K562 cells. Our results indicate that Ce6-mediated SDT can suppress the viability of K562 cells. SDT caused apoptosis as analyzed by annexin V-phycoerythrin/7-amino-actinomycin D staining as well as cleavage of caspase 3 and the polypeptide poly(ADP-ribose) polymerase. After SDT exposure, loss of mitochondrial membrane potential, translocation of Bax from cytoplasm to mitochondria and activation of caspase 9 indicated that the mitochondrial-related apoptotic pathway might be activated. This process was accompanied by rapid generation of reactive oxygen species (ROS). Scavenging of ROS significantly blocked caspase-3 expression and the killing effect of SDT on K562 cells. Stress-activated protein kinases c-jun NH2-terminal kinase (JNK) and the p38 mitogen-activated protein kinase were activated after SDT treatment. Together, these findings indicate that Ce6-mediated SDT triggers mitochondria- and caspase-dependent apoptosis; oxidative injury may play a vital role in apoptotic signaling cascades.
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Activation of microbubbles by low-level therapeutic ultrasound enhances the antitumor effects of doxorubicin.
Eur Radiol
PUBLISHED: 01-20-2014
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To prove that DNA damage, intracellular reactive oxygen species (ROS) generation and loss of mitochondrial membrane potential (MMP) are contributing factors for the inhibition of cell proliferation induced by doxorubicin (DOX) administration combined with microbubble-assisted low-level therapeutic ultrasound (US) in K562 cells.
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ERK inhibitor U0126 enhanced SDT-induced cytotoxicity of human leukemia U937 cells.
Gen. Physiol. Biophys.
PUBLISHED: 01-13-2014
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This study was to investigate the cell killing effect of chlorin-e6 (Ce6) mediated sonodynamic therapy (SDT) on human leukemia U937 cells and explore the role of ERK signal pathway in the process. The ultrastructure changes of U937 cells induced by ultrasonic irradiation were evaluated by scanning electron microscope (SEM) and transmission electron microscope (TEM). The viability of cells was evaluated by viacount assay. Apoptosis was analyzed using ?ow cytometer as well as ?uorescence microscopy with 4'-6-diamidino-2-phenylindole (DAPI) staining. Western blotting was used to analyze the expression of mitogen-activated protein kinase (MAPK). Intracellular reactive oxygen species (ROS) and mitochondria membrane potential (MMP) levels were also analyzed by ?ow cytometer after exposure. Our experiments showed that several distinct sonochemical effects were found after Ce6-mediated SDT treatment. Western blotting analysis indicated that the MAPK were activated. Especially, pre-treatment with ERK inhibitor U0126 could additionally enhance SDT-induced cell viability loss, early- and late-apoptotic rate, chromatin condensation, DNA fragmentation and caspase-3 activation. Besides, a mass of ROS accumulation and a conspicuous loss of mitochondrial membrane potential were detected in U937 cells. These ?ndings suggested ERK signal pathway may deliver a survival signal which counteracts SDT-induced cell death, while combination with U0126 could significantly potentiate the SDT-induced cytotoxic effect in U937 cells.
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PTEN?, a PTEN isoform translated through alternative initiation, regulates mitochondrial function and energy metabolism.
Cell Metab.
PUBLISHED: 01-07-2014
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PTEN is one of the most frequently mutated genes in human cancer. It is known that PTEN has a wide range of biological functions beyond tumor suppression. Here, we report that PTEN?, an N-terminally extended form of PTEN, functions in mitochondrial metabolism. Translation of PTEN? is initiated from a CUG codon upstream of and in-frame with the coding region of canonical PTEN. Eukaryotic translation initiation factor 2A (eIF2A) controls PTEN? translation, which requires a CUG-centered palindromic motif. We show that PTEN? induces cytochrome c oxidase activity and ATP production in mitochondria. TALEN-mediated somatic deletion of PTEN? impairs mitochondrial respiratory chain function. PTEN? interacts with canonical PTEN to increase PINK1 protein levels and promote energy production. Our studies demonstrate the importance of eIF2A-mediated alternative translation for generation of protein diversity in eukaryotic systems and provide insights into the mechanism by which the PTEN family is involved in multiple cellular processes.
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Genome-wide study reveals an important role of spontaneous autoimmunity, cardiomyocyte differentiation defect and anti-angiogenic activities in gender-specific gene expression in Keshan disease.
Chin. Med. J.
PUBLISHED: 01-04-2014
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Keshan disease (KD) is an endemic cardiomyopathy in China. The etiology of KD is still under debate and there is no effective approach to preventing and curing this disease. Young women of child-bearing age are the most frequent victims in rural areas. The aim of this study was to determine the differences between molecular pathogenic mechanisms in male and female KD sufferers.
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Altered functional connectivity of the marginal division in Alzheimer's disease.
Curr Alzheimer Res
PUBLISHED: 01-02-2014
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The marginal division (MrD) is a neostriatum subregion that links the limbic system and basal nucleus of Meynert; it is an important subcortical center that is involved in learning and memory. Alzheimer's disease (AD) is a neurodegenerative disorder and the most common cause of dementia in the elderly. AD clinically manifests as gradually progressive cognitive decline with behavioral disorders. Prior to full dementia, AD patients typically experience a transient state, i.e., mild cognitive impairment (MCI). Amnestic MCI individuals, but not all MCI individuals, frequently convert to AD dementia. To specify whether and how the functional relationships between the MrD and other brain regions change during AD, functional connectivity was assessed using resting-state functional MRI data and associated neuropsychological tests in AD and MCI patients (amnestic-type). Compared with normal controls, a different decreased functional connectivity pattern was observed between the MrD and caudate, the amygdala/parahippocampal region, the inferior frontal gyrus, the superior temporal gyrus, and the cerebellum for AD/MCI patients. Moreover, the functional connectivity between the MrD and the identified regions was significantly correlated with the neuropsychological scores among the MCI and AD subjects. Our results suggest that the MrD functional network is disrupted during AD.
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Compositions and Anti-Tumor Activity of Pyropolyporus fomentarius Petroleum Ether Fraction In Vitro and In Vivo.
PLoS ONE
PUBLISHED: 01-01-2014
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The chemical compositions and anti-tumor activities of the petroleum ether fraction (PE), from mushroom Pyropolyporus fomentarius, were studied. Upon gas chromatography-mass spectrometry (GC-MS) analysis, nine major constituents were identified in the fraction. In vitro, the PE showed cytotoxic activity against murine sarcoma S180 (S180) cells in a dose- and time-dependent manner, and the cytotoxic effects were associated with apoptosis. The mitochondrial membrane potential loss and the intracellular ROS generation were greatly increased in the Pyropolyporus fomentarius PE treated group, suggesting cell apoptosis, induced by the PE in S180 cells, might be mitochondria dependent and ROS mediated. Consistent with in vitro findings, the in vivo study showed that the Pyropolyporus fomentarius PE was also effective in inhibiting the tumor growth induced by S180 cells and had lower immune organ toxicity. We found that the Pyropolyporus fomentarius PE has significant anti-tumor activity and great potential in screening anti-tumor drugs.
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Sinoporphyrin sodium, a novel sensitizer, triggers mitochondrial-dependent apoptosis in ECA-109 cells via production of reactive oxygen species.
Int J Nanomedicine
PUBLISHED: 01-01-2014
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Sonodynamic therapy (SDT) is a promising method that uses ultrasound to activate certain chemical sensitizers for the treatment of cancer. The purpose of this study was to investigate the sonoactivity of a novel sensitizer, sinoporphyrin sodium (DVDMS), and its sonotoxicity in an esophageal cancer (ECA-109) cell line.
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Investigating migration inhibition and apoptotic effects of Fomitopsis pinicola chloroform extract on human colorectal cancer SW-480 cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Fomitopsis pinicola (Sw. Ex Fr.m) Karst (FPK) which belongs to the Basidiomycota fungal class is one of the most popular medical fungi in China. It has been used for many diseases: cancer, heart diseases, diabetes and so on. However, little study on the pro-apoptotic effect and migration inhibition of FPK chloroform extract (FPKc) has been reported and the possible involved mechanism has not been illuminated.
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Different miRNA expression profiles between human breast cancer tumors and serum.
Front Genet
PUBLISHED: 01-01-2014
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A bunch of microRNAs (miRNAs) have been demonstrated to be aberrantly expressed in cancer tumor tissue and serum. The miRNA signatures identified from the serum samples could serve as potential noninvasive diagnostic markers for breast cancer. The role of the miRNAs in cancerigenesis is unclear. In this study, we generated the expression profiles of miRNAs from the paired breast cancer tumors, normal, tissue, and serum samples from eight patients using small RNA-sequencing. Serum samples from eight healthy individuals were used as normal controls. We identified total 174 significantly differentially expressed miRNAs between tumors and the normal tissues, and 109 miRNAs between serum from patients and serum from healthy individuals. There are only 10 common miRNAs. This suggests that only a small portion of tumor miRNAs are released into serum selectively. Interestingly, the expression change pattern of 28 miRNAs is opposite between breast cancer tumors and serum. Functional analysis shows that the differentially expressed miRNAs and their target genes form a complex interaction network affecting many biological processes and involving in many types of cancer such as prostate cancer, basal cell carcinoma, acute myeloid leukemia, and more.
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Characterization of nitrite degradation by Lactobacillus casei subsp. rhamnosus LCR 6013.
PLoS ONE
PUBLISHED: 01-01-2014
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Nitrites are potential carcinogens. Therefore, limiting nitrites in food is critically important for food safety. The nitrite degradation capacity of Lactobacillus casei subsp. rhamnosus LCR 6013 was investigated in pickle fermentation. After LCR 6013 fermentation for 120 h at 37°C, the nitrite concentration in the fermentation system was significantly lower than that in the control sample without the LCR 6013 strain. The effects of NaCl and Vc on nitrite degradation by LCR 6013 in the De Man, Rogosa and Sharpe (MRS) medium were also investigated. The highest nitrite degradations, 9.29 mg/L and 9.89 mg/L, were observed when NaCl and Vc concentrations were 0.75% and 0.02%, respectively in the MRS medium, which was significantly higher than the control group (p ? 0.01). Electron capture/gas chromatography and indophenol blue staining were used to study the nitrite degradation pathway of LCR 6013. The nitrite degradation products contained N2O, but no NH4(+). The LCR 6013 strain completely degraded all NaNO2 (50.00 mg/L) after 16 h of fermentation. The enzyme activity of NiR in the periplasmic space was 2.5 times of that in the cytoplasm. Our results demonstrated that L. casei subsp. rhamnosus LCR 6013 can effectively degrade nitrites in both the pickle fermentation system and in MRS medium by NiR. Nitrites are degraded by the LCR 6013 strain, likely via the nitrate respiration pathway (NO2(-)>NO->N2O->N2), rather than the aammonium formation pathway (dissimilatory nitrate reduction to ammonium, DNRA), because the degradation products contain N2O, but not NH4(+).
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Anti-cancer effect and the underlying mechanisms of gypenosides on human colorectal cancer SW-480 cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Gypenosides (Gyp), the main components from Gynostemma pentaphyllum Makino, are widely used in traditional Chinese medicine. The present study aimed to investigate the anti-cancer effect and the underlying mechanisms of Gyp on human colorectal cancer cells SW-480.
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Dimeric Ube2g2 simultaneously engages donor and acceptor ubiquitins to form Lys48-linked ubiquitin chains.
EMBO J.
PUBLISHED: 12-23-2013
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Cellular adaptation to proteotoxic stress at the endoplasmic reticulum (ER) depends on Lys48-linked polyubiquitination by ER-associated ubiquitin ligases (E3s) and subsequent elimination of ubiquitinated retrotranslocation products by the proteasome. The ER-associated E3 gp78 ubiquitinates misfolded proteins by transferring preformed Lys48-linked ubiquitin chains from the cognate E2 Ube2g2 to substrates. Here we demonstrate that Ube2g2 synthesizes linkage specific ubiquitin chains by forming an unprecedented homodimer: The dimerization of Ube2g2, mediated primarily by electrostatic interactions between two Ube2g2s, is also facilitated by the charged ubiquitin molecules. Mutagenesis studies show that Ube2g2 dimerization is required for ER-associated degradation (ERAD). In addition to E2 dimerization, we show that a highly conserved arginine residue in the donor Ube2g2 senses the presence of an aspartate in the acceptor ubiquitin to position only Lys48 of ubiquitin in proximity to the donor E2 active site. These results reveal an unanticipated mode of E2 self-association that allows the E2 to effectively engage two ubiquitins to specifically synthesize Lys48-linked ubiquitin chains.
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Effect of shape and severity of vertebral fractures on the outcomes of kyphoplasty.
Acta Orthop Belg
PUBLISHED: 12-20-2013
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The aim of this retrospective study was to evaluate the effect of shape and severity of osteoporotic vertebral fractures on the clinical and surgical outcomes of kyphoplasty. Ninety-four patients with single level vertebral fractures were enrolled. Fractures were divided into two types according to the shape of the fractured vertebrae: wedge type (n = 54) or biconcave type (n = 40). All fractures were further classified into 3 grades (grade 1-3) according to their severity. The Visual Analog Score for back pain improved significantly in the "wedge" and in the "biconcave" group: there was no significant difference between groups. Wedge type fractures had a significantly greater correction of anterior vertebral height and kyphotic angle than biconcave type fractures (p < 0.01). Biconcave type fractures had a significantly greater correction of the middle vertebral height (p < 0.01), but had a higher risk of intradiscal cement leakage (p = 0.03). Rates of cement leakage in grade 1, grade 2, and grade 3 fractures were 12.8%, 25.8%, and 50.0%, respectively : there was a gradually higher risk of cement leakage as the severity of compression increased (p < 0.01).
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PpIX induces mitochondria-related apoptosis in murine leukemia L1210 cells.
Drug Chem Toxicol
PUBLISHED: 12-16-2013
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Abstract Context: Protoporphyrin IX (PpIX), a well-known sensitizer that can enhance laser light or ultrasound induced cytotoxicity in photodynamic and sonodynamic therapy. However, PpIX alone could effectively cause anti-tumor effect and the underlying mechanisms are rarely been reported. Therefore, this study was to investigate the possible mechanism by which PpIX revealed anti-proliferative effect on murine leukemia L1210 cells. Materials and methods: The accumulation of PpIX in L1210 cells and normal peripheral blood mononuclear cells (PBMCs) was evaluated with flow cytometry. The subcellular localization of PpIX and apoptosis-inducing factor (AIF) translocation were determined by confocal microscope. The cell viability was examined by MTT assay. Annexin V-PE/7-AAD and DAPI staining were used to detect apoptotic cells. The mitochondrial membrane potential (MMP) changes were tested by rhodamine123 staining. DNA damage was measured by comet assay. Results: PpIX preferentially accumulated in L1210 cells compared to PBMCs and PpIX mainly located in the mitochondria of L1210 cells. PpIX at a concentration of 1?µg/ml or above exerted significant anti-tumor effect and the cell viability loss presented PpIX dose-dependent manner. Typical apoptotic features such as chromatin condensation were observed by DAPI staining. Annexin V-PE/7-AAD analysis showed 5?µg/ml PpIX could induce about 24% cell apoptosis, which was inhibited by cyclosporin A (CsA), an inhibitor of mitochondrial permeability transition pore. In addition, the PpIX caused MMP loss, AIF translocation to nucleus and serious DNA damage were also suppressed by CsA. Conclusion: The results indicate mitochondria-dependent apoptosis were involved in PpIX caused cell damage on L1210 cells.
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Efficacy of Chlorin e6-Mediated Sono-Photodynamic Therapy on 4T1 Cells.
Cancer Biother. Radiopharm.
PUBLISHED: 11-09-2013
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Abstract Purpose: The present study aims to investigate the antitumor effect and possible mechanisms of chlorin e6 (Ce6)-mediated sono-photodynamic therapy (Ce6-SPDT) on murine 4T1 mammary cancer cells in vitro. Materials: Cellular uptake and intracellular distribution of Ce6 in 4T1 cells were detected by flow cytometry and confocal microscope. Cells after loading with 1??g/mL Ce6 were exposed to ultrasound at 1.0?MHz for up to 1 minute with an intensity of 0.36?W/cm(2) and laser light with total radiation dose of 1.2?J/cm(2). Cell viability and clonogenicity were determined by MTT assay and colony formation assay. Apoptosis was analyzed by DAPI staining, Western blots were used to detect the activity of Caspase-3. DNA damage, mitochondrial membrane potential (MMP), and intracellular reactive oxygen species (ROS) of 4T1 cells were also evaluated by flow cytometry. FD500 was employed to detect changes of membrane permeability after ultrasound. Results: Ce6 rapidly entered 4T1 cells within 4 hours after it has been added and displayed a mitochondria-localization pattern. Compared with sonodynamic therapy (SDT) and photodynamic therapy (PDT) alone, the combined SPDT treatment further enhanced cell viability loss, DNA damage, and clonogenicity inhibition. DAPI staining and western blots analysis reflected that cells with apoptotic morphological characteristics and the activity of Caspase-3 were apparently increased in the combined group. Besides, SPDT caused obvious MMP loss and intracellular ROS generation at early 1 hour post treatment. Interestingly, the SPDT induced cell viability loss and cell apoptosis was greatly inhibited by pre-treatment with ROS scavenger N-acetylcysteine and Caspase inhibitor z-VAD-fmk. FD500 detection showed that ultrasound enhanced cell membrane permeability, implying much higher uptake of Ce6 might be involved in PDT therapy by pre-ultrasound treatment. Conclusions: The findings demonstrated that Ce6-mediated SPDT enhanced the antitumor efficacy on 4T1 cells compared with SDT and PDT alone, a Caspase-dependent apoptosis and loss of MMP, generation of ROS may be involved.
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A highly efficient and enantioselective intramolecular Cannizzaro reaction under TOX/Cu(II) catalysis.
J. Am. Chem. Soc.
PUBLISHED: 10-30-2013
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An asymmetric intramolecular Cannizzaro reaction of aryl and alkyl glyoxals with alcohols has been realized with an unprecedented high level of enantioselectivity, on the basis of a newly developed congested TOX ligand and a gradual liberation protocol of active glyoxals from glyoxal monohydrates. Preliminary results suggested a mechanism of enantioselective addition of alcohols to glyoxals contributing most to the stereoselectivity, other than by the dynamic kinetic resolution of hemiacetal intermediates.
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Parkin overexpression ameliorates hippocampal long-term potentiation and ?-amyloid load in an Alzheimers disease mouse model.
Hum. Mol. Genet.
PUBLISHED: 10-08-2013
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Alzheimers disease (AD) is a progressive neurodegenerative disorder characterized by a severe decline of memory performance. A widely studied AD mouse model is the APPswe/PSEN1?E9 (APP/PS1) strain, as mice exhibit amyloid plaques as well as impaired memory capacities. To test whether restoring synaptic plasticity and decreasing ?-amyloid load by Parkin could represent a potential therapeutic target for AD, we crossed APP/PS1 transgenic mice with transgenic mice overexpressing the ubiquitin ligase Parkin and analyzed offspring properties. Overexpression of Parkin in APP/PS1 transgenic mice restored activity-dependent synaptic plasticity and rescued behavioral abnormalities. Moreover, overexpression of Parkin was associated with down-regulation of APP protein expression, decreased ?-amyloid load and reduced inflammation. Our data suggest that Parkin could be a promising target for AD therapy.
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Protection-group-free semisyntheses of parthenolide and its cyclopropyl analogue.
J. Org. Chem.
PUBLISHED: 09-27-2013
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Parthenolide showed extensive bioactivities including selective eradication of AML stem cells. Herein we report protection-free semisyntheses of parthenolide and its cyclopropyl analogue (compound 10) from the abundant natural product costunolide with an overall yield of 55 and 60%, respectively. Compound 10 was more stable than parthenolide, and it maintained comparable activities against AML cell lines and AML stem cells. Therefore, compound 10 might be a superior small molecule than parthenolide as a tool for investigation of cancer stem cell biology.
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[Isolation and characterization of a highly efficient BBP-degrading bacterium].
Huan Jing Ke Xue
PUBLISHED: 09-14-2013
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A bacterial strain HS-B1 which can utilize n-butyl benzyl phthalate as the sole source of carbon and energy was isolated from contaminated sludge in the Jinsha River of Hubei Province. Based on its morphology, physiological characteristic and 16S rDNA sequence analysis, HS-B1 was identified as Acinetobacter sp.. Shake flask experiments indicated the optimum pH, temperature for growth and BBP biodegradation by HS-B1 was found to be 8.0 and 35 degrees C, respectively. When using 0.10 mmol x L(-1) non-ionic surfactant Tween-80 as co-solvent to increase the apparent solubility of BBP in water, HS-B1 was able to completely degrade 1 000 mg x L(-1) BBP within 48 hours. Diversity of degradable substrates also showed that HS-B1 can efficiently utilize many other phthalate esters such as dimethyl phthalate and diethyl phthalate. It revealed that the strain HS-B1 has special application potential in dealing with the pollution caused by phthalate esters.
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[Application of Ni-Ti patellar concentrator combined with Herbert screw and wirerope for the treatment of comminuted patellar inferior pole fractures].
Zhongguo Gu Shang
PUBLISHED: 09-11-2013
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To evaluate the surgical techniques and clinical effect of Ni-Ti patellar concentrator combined with Herbert screw and wirerope in treating comminuted patellar inferior pole fractures.
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Production of furfural from xylose, xylan and corncob in gamma-valerolactone using FeCl3·6H2O as catalyst.
Bioresour. Technol.
PUBLISHED: 08-30-2013
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An efficient and simple one-pot monophasic reaction system with small carbon footprint for converting xylose, xylan and corncob into furfural was developed in gamma-valerolactone (GVL, an ideal sustainable solvent derived from lignocelluloses) by using FeCl3·6H2O as catalyst. Good yields of furfural from xylose were obtained, and the system was shown to work for xylan and corncob as well. A surprisingly high furfural yield of 79.6% from untreated corncob was achieved at 458K for 100min. Contrary to what was generally believed, the addition of water, reduced the rate of the reactions, but showed positive effect on preventing the furfural from degradation in GVL. Besides, the C6 sugars (glucose and cellulose) afforded 11.4-24.5% furfural yields when employing this catalytic approach. The reaction system proposed in this manuscript showed great potential for optimizing the catalytic process in furfural production.
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DNA damage and cell cycle arrest induced by protoporphyrin IX in sarcoma 180 cells.
Cell. Physiol. Biochem.
PUBLISHED: 08-26-2013
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Porphyrin derivatives have been widely used in photodynamic therapy as effective sensitizers. Protoporphyrin IX (PpIX), a well-known hematoporphyrin derivative component, shows great potential to enhance light induced tumor cell damage. However, PpIX alone could also exert anti-tumor effects. The mechanisms underlying those direct effects are incompletely understood. This study thus investigated the putative mechanisms underlying the anti-tumor effects of PpIX on sarcoma 180 (S180) cells.
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Efficacy of combined therapy with paclitaxel and low-level ultrasound in human chronic myelogenous leukemia cell line K562.
J Drug Target
PUBLISHED: 08-19-2013
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Sonochemotherapy, which applies ultrasound in cancer chemotherapy, has been proven to be a promising therapeutic modality by some previous researches.
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Self-assembly of various Au nanocrystals on functionalized water-stable PVA/PEI nanofibers: A highly efficient surface-enhanced Raman scattering substrates with high density of "hot" spots.
Biosens Bioelectron
PUBLISHED: 08-17-2013
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We have demonstrated a facile approach for the fabrication of flexible and reliable sulfydryl functionalized PVA/PEI nanofibers with excellent water stability for the self-assembly of Au nanocrystals, such as Au nanoparticles (AuNPs), Au nanoflowers (AuNFs) and Au nanorods (AuNRs), used as the highly efficient surface-enhanced Raman scattering (SERS) substrates for the detection of rhodamine B (RhB). Various methods were employed to cross-link the PVA nanofibers with better morphology and porous structures after immersing in water for desired times. Various SERS-active Au nanocrystals, such as AuNPs, AuNFs, and AuNRs have been successfully synthesized. After the grafting of MPTES on the cross-linked PVA/PEI nanofibers, the Au nanocrystals can easily be self-assembled on the surfaces of the nanofibers because of the strong interactions of the Au-S chemical bondings. The Au nanocrystals self-assembled throughout the PVA/PEI nanofibers used as SERS substrates all exhibit enhanced SERS signals of RhB compared with their individual nanocrystals. It is mainly due to the close interparticle distance, mutual orientation and high density of "hot" spots, that can strongly affect the overall optical response and the SERS enhancement. By changing the amounts of the self-assembled AuNFs on the nanofibers, we can control the density of the "hot" spots. With the increased amounts of the AuNFs throughout the nanofibers, the SERS substrates show enhanced Raman signals of the RhB, indicating that the increased density of "hot" spots can directly lead to the SERS enhancement. The AuNFs/(PVA/PEI) SERS substrates show good sensitivity, reliability and low detection limit (10(-9)M). The presented approach can be broadly applicable to the assembly of different types of plasmonic nanostructures and these novel materials with strong SERS enhancement can be applied in bioanalysis and biosensors.
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Impaired functional connectivity of the thalamus in Alzheimer s disease and mild cognitive impairment: a resting-state FMRI study.
Curr Alzheimer Res
PUBLISHED: 07-28-2013
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The current study evaluated whether the functional connectivity pattern of the thalamo-cortical network in patients with Alzheimer s disease (AD) and mild cognitive impairment (MCI) would show disease severityrelated alterations.
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Association between TLR4 polymorphism and periodontitis susceptibility: a meta-analysis.
Crit. Rev. Eukaryot. Gene Expr.
PUBLISHED: 07-25-2013
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TLR4 has been implicated in periodontal disease, but the association between the TLR4 Asp299Gly and Thr399Ile polymorphisms and the risk of periodontal disease remains unclear. Therefore, the aim of this study was to investigate the association between the TLR4 Asp299Gly and Thr399Ile polymorphism and periodontal disease. A search of electronic databases identified previous studies evaluating the association of the polymorphisms of TLR4 and periodontitis risk. The association was evaluated by odds ratio (OR) and its 95% confidence interval (CI). The results showed that TLR4 Asp299Gly and Thr399Ile were not associated with a significant risk of periodontitis (OR = 0.96, 95% CI = 0.80-1.16 for G versus A; OR = 1.39, 95% CI = 0.82-2.36 for AG/GG versus AA; OR = 1.05, 95% CI = 0.52-2.15 for T versus C; OR = 0.76, 95% CI = 0.55-1.04 for CT/TT versus CC). In the stratified analyses, there was no significantly increased risk for the studies of chronic periodontitis and aggressive periodontitis. Our meta-analysis revealed that the two common TLR4 polymorphisms, Asp299Gly and Thr399Ile, have no association with the likelihood of periodontitis. In a subgroup analysis by ethnicity and periodontitis type, the results also did not show any association. However, there was a significant increased risk for periodontitis in recessive models of Asp299Gly. The effect of genetic networks and their mutual interactions in the TLR4 signaling pathway on periodontitis susceptibility needs further study.
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Protoporphyrin IX-mediated sonodynamic action induces apoptosis of K562 cells.
Ultrasonics
PUBLISHED: 07-14-2013
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The present study aims to investigate apoptosis of human leukemia K562 cells induced by protoporphyrin IX (PpIX)-mediated sonodynamic therapy (PpIX-SDT).
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Involvement of MAPK activation and ROS generation in human leukemia U937 cells undergoing apoptosis in response to sonodynamic therapy.
Int. J. Radiat. Biol.
PUBLISHED: 07-08-2013
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To elucidate the underlying events in Chlorin e6 (Ce6)-mediated sonodynamic therapy (SDT) (Ce6-SDT)-induced apoptosis of human leukemia cell line U937.
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The effects of Ce6-mediated sono-photodynamic therapy on cell migration, apoptosis and autophagy in mouse mammary 4T1 cell line.
Ultrasonics
PUBLISHED: 06-30-2013
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Sono-Photodynamic therapy (SPDT) is an alternative therapy which claims to enhance the anti-cancer effects by combining sonodynamic therapy (SDT) with photodynamic therapy (PDT). In the present study, we investigated the effects of chlorin e6 (Ce6) mediated SPDT on migration, apoptosis and autophagy in mouse mammary 4T1 cancer cells, and its underlying mechanisms.
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[Screening of differentially expressed proteins in serum from subjects with Keshan disease by two-dimensional electrophoresis and mass and mass spectrometry].
Wei Sheng Yan Jiu
PUBLISHED: 06-29-2013
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To screen differentially expressed proteins in serum in patients with Keshan disease (KD), peripheral blood protein expression spectrum between subjects with Keshan disease and health controls were compared.
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Porous Cu/Ce-K-O nanocomposites for simultaneous removal of soot and NO(x) from diesel exhaust emission.
J Nanosci Nanotechnol
PUBLISHED: 06-15-2013
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The porous xCu/(1 - x)Ce-K-O (x = 0.1-0.4) nanocomposites were prepared by the citrate-gel thermal decomposition and reduction process. The effect of nanosized metallic Cu on their microstructure and catalytic properties was investigated by XRD, SEM, BET, TG analysis. With Cu content increasing, the grain size of metallic Cu is increased from 40 nm to 62 nm, whilst the grain size of CeO2 decreases from 38 nm to 20 nm. While, their specific surface area (S(BET)) and average pore size (P(ave)) show an increasing trend with the Cu content increase in the nanocomposites. The catalytic activity for soot combustion is influenced by the Cu content, with a lowest T20 (216 degrees C) and T50 (357 degrees C) for xCu/(1 - x)Ce-K-O (x = 0.3) nanocomposite catalyst. The catalytic performance for the optimal xCu/(1 - x)Ce-K-O (x = 0.3) nanocomposite coated honeycomb ceramic device was evaluated under the practical diesel exhaust emissions at the temperature range of 200-400 degrees C. This 10 wt.% catalyst-loaded honeycomb ceramic device confirms a high catalytic activity and stability for simultaneous removal of soot and NO(x), largely,due to the porous structure and synergistic effect of nano Cu and nano ceria in the catalyst.
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Catalytic activity of nanocrystalline porous La0.8K0.2Fe(1-x)Mn(x)O3 for simultaneous removal of soot and nitrogen oxides.
J Nanosci Nanotechnol
PUBLISHED: 06-15-2013
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The nanocrystalline, porous, perovskite La0.8K0.2Fe(1-x)Mn(x)O3 (x = 0-0.5) catalysts were prepared by the citrate-gel process. All the perovskite catalysts can effectively catalyze the soot combustion and among them the La0.8K0.2Fe0.7Mn0.3O3 catalyst exhibits the highest catalytic activity, with a lowest T50 (366 degrees C). This optimized La0.8K0.2Fe0.7Mn0.3O3 catalyst then was coated onto a honeycomb ceramic by the citrate-gel assisted dip-coating method and its catalytic performance was evaluated by the bench test in the practical exhaust emission. It is proved that the La0.8K0.2Fe0.7Mn0.3O3-coated honeycomb ceramic device simultaneously has a effective capture of soot particulates and a good absorption of NO(x) from the exhaust emission at a low temperature and begins to efficiently catalyze oxidization reactions of the soot particulates at around 230 degrees C, and conversion of NO(x) at about 290 degrees C, with a conversion rate of 16.6% at 400 degrees C. This catalytic performance enhancement for simultaneous removal of soot and NO(x) can be largely attributed to the synergistic effect of Fe and Mn, pore structure of a large channel with various small pores connected, and microstructural characteristics of La0.8K0.2Fe0.7Mn0.3O3 catalyst. The catalytic mechanism of capture-oxidation-reduction is rationally proposed.
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Hypoxia enhances chondrogenesis and prevents terminal differentiation through PI3K/Akt/FoxO dependent anti-apoptotic effect.
Sci Rep
PUBLISHED: 06-10-2013
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Hypoxia, a common environmental condition, influences cell signals and functions. Here, we compared the effects of hypoxia (1% oxygen) and normoxia (air) on chondrogenic differentiation of human mesenchymal stem cells (MSCs). For in vitro chondrogenic differentiation, MSCs were concentrated to form pellets and subjected to conditions appropriate for chondrogenic differentiation under normoxia and hypoxia, followed by the analysis for the expression of genes and proteins of chondrogenesis and endochondral ossification. MSCs induced for differentiation under hypoxia increased in chondrogenesis, but decreased in endochondral ossification compared to those under normoxia. MSCs induced for differentiation were more resistant to apoptosis under hypoxia compared to those under normoxia. The hypoxia-dependent protection of MSCs from chondrogenesis-induced apoptosis correlated with an increase in the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/FoxO pathway. These results suggest that the PI3K/Akt/FoxO survival pathway activated by hypoxia in MSCs enhances chondrogenesis and plays an important role in preventing endochondral ossification.
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Protective effect of polypeptides from larva of housefly (Musca domestica) on hydrogen peroxide-induced oxidative damage in HepG2 cells.
Food Chem. Toxicol.
PUBLISHED: 05-25-2013
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Housefly (Musca domestica) is an important medical insect and its larva is an ideal high protein food source. We isolated from housefly larvae the polypeptides hydrolyzed by neutral protease (PHNP), and investigated the protective effect of PHNP on hydrogen peroxide (H?O?)-induced oxidative damage in HepG2 cells. Cells exposed to H?O? showed a marked decrease in proliferation and intracellular superoxide dismutase (SOD) activity, and a significant increase in reactive oxygen species (ROS) level and malondialdehyde (MDA) content. H?O? also caused apoptosis and mitochondrial dysfunction including mitochondrial fragmentation and the loss of mitochondrial membrane potential. Pretreatment with PHNP at concentrations of 2.5, 5, 10 ?g/mL blocked these H?O?-induced cellular events in a dose-dependent manner. The effect of PHNP at 10 ?g/mL is equal to that of ascorbic acid at 10 ?M. In summary, PHNP has a protective effect against H?O?-induced oxidative injury in cells due to its ability to decrease intracellular ROS and elevate antioxidant enzyme activities.
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Comparison between sonodynamic and photodynamic effect on MDA-MB-231 cells.
J. Photochem. Photobiol. B, Biol.
PUBLISHED: 05-17-2013
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Photodynamic therapy (PDT) and sonodynamic therapy (SDT) are therapeutic modalities for tumors. In this study we investigated the combined cytotoxic effect of 0.36W/cm(2) and 0.72W/cm(2) ultrasound with various Ce6 concentrations (1, 2, 5, 10?g/ml), and that of 1?g/ml Ce6 with different laser light dose (650nm; 10.4mW/cm(2); 0.3, 0.6, 1.2 and 2.5J/cm(2)) on MDA-MB-231 cells. Both high reactive oxygen species (ROS) production and a decline in mitochondrial membrane potential (MMP) were detected with high Ce6 concentrations (5 and 10?g/ml) combined with 0.72W/cm(2) ultrasound and 1.2, 2.5J/cm(2) laser light with 1?g/ml Ce6. In addition, cell membrane integrity was evaluated by using propidium iodide (PI), revealing membrane damage was aggravated with the increasing ultrasound intensity, but no significant difference on cell membrane integrity could be observed after PDT treatment. These results suggest ROS may play an important role both in SDT and PDT. Besides, mitochondria may be an initial target in PDT while SDT can cause multi-site damages in MDA-MB-231 cells.
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Tumor cell growth inhibitory activity and structure-activity relationship of polyoxygenated steroids from the gorgonian Menella kanisa.
Steroids
PUBLISHED: 05-17-2013
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Fourteen new polyoxygenated steroids (6, 9, 14-18, 20-23, 25-27) having carbon skeletons of cholestane, ergostane, and 24-norcholestane, were isolated together with thirteen known analogues (1-5, 7, 8, 10-13, 19, 24) from the South China Sea gorgonian Menella kanisa. The structures of the new compounds were elucidated by detailed analysis of spectroscopic data and comparisons with reported data. This is the first report of chemical investigation on the title gorgonian. Compounds 12 and 13 were reported for the first time from natural sources. These compounds exhibited different levels of growth inhibition activity against A549 and MG-63 cell lines in bioassay in vitro. Preliminary structure-activity analysis revealed an important role of side chain in the activity. A substitution of a 5?-hydroxy or an oxidation of 6?-hydroxy to a ketone carbonyl group may decrease the activity whereas the contribution of the 1-ketone group remains uncertain.
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The ethyl acetate fraction of Polytrichum commune L.ex Hedw induced cell apoptosis via reactive oxygen species in L1210 cells.
J Ethnopharmacol
PUBLISHED: 05-16-2013
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Polytrichum commune L.ex Hedw is a traditional Chinese herb for treatment of fever, hemostatic, uterine prolapse and especially for leukemia. Previous studies indicated its anti-leukemia effect but the potential mechanisms have not been fully explained.
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Transcriptional directionality of the human insulin-degrading enzyme promoter.
Mol. Cell. Biochem.
PUBLISHED: 04-23-2013
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Unidirectional promoters dominate among mammalian genomes. However, the mechanism through which the transcriptional directionality of promoters is accomplished remains to be clarified. Insulin-degrading enzyme (IDE) is a ubiquitously expressed zinc metalloprotease, whose promoter contains a CpG island. We previously showed that the basal promoter region of mouse IDE has bidirectional transcriptional activity, but an upstream promoter element blocks its antisense transcription. Therefore, we wonder whether the human IDE promoter contains an analogous element. Similarly, the basal promoter region of human IDE (-102 ~ +173 and -196 ~ +173 relative to the transcription start site) showed bidirectional transcriptional activity. However, the region from -348 to +173 could only be transcribed from the normal orientation, implying that an upstream promoter element between -348 and -196 blocks the antisense transcription of the human IDE promoter. Through promoter deletion and mutagenesis analysis, we mapped this element precisely and found that the upstream promoter element locates between -318 and -304. Furthermore, the transcription-blocking elements in the mouse and human IDE promoters inhibited the transcription of the SV40 promoter when put downstream of it. In conclusion, we identify an upstream promoter element which blocks the antisense transcription of the human IDE promoter. Our studies are helpful to clarify the transcriptional directionality of promoters.
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[Relationship of ionized calcium and 25-(OH) D in serum with obesity].
Wei Sheng Yan Jiu
PUBLISHED: 04-20-2013
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To investigate the relationship of ionized calcium and 25-(OH) D level in serum with obesity in order to provide theoretical basis for preventing obesity-related diseases.
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Comparison of vertebroplasty and kyphoplasty in the treatment of osteoporotic vertebral compression fractures with intravertebral clefts.
Eur J Orthop Surg Traumatol
PUBLISHED: 04-19-2013
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Few studies have compared the surgical outcomes of vertebroplasty (VP) and kyphoplasty (KP) in the treatment of osteoporotic vertebral compression fractures (VCFs) with intravertebral clefts.
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Association between CD14 gene polymorphism and periodontitis: a meta-analysis.
Crit. Rev. Eukaryot. Gene Expr.
PUBLISHED: 04-16-2013
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This meta-analysis aimed to analyze the association between CD14 C-159T and C-260T polymorphisms and periodontitis risks because previous results have been conflicting. We used 12 eligible case-control studies involving 1435 cases and 1446 controls to evaluate this association. Compared with the common CD14 C-159T and C-260T genotypes, there was no significant association of T alleles and the CT/TT genotypes polymorphism with periodontitis risk (odds ratio [OR], 1.03; 95% confidence interval [CI], 0.83-1.27 for C vs. T; OR, 1.07; 95% CI, 0.83-1.38 for CT/TT vs. CC). A similar result was found in a subgroup analysis by ethnicity and periodontitis type. An enhanced risk for periodontitis was demonstrated in the comparison of subjects carrying the CT genotype versus CC homozygotes (overall OR, 1.681; 95% CI, 1.048-2.695; P for heterogeneity=0.367; I2=2.00%) for the C-260T genotype. Our meta-analysis revealed that the 2 common CD14 polymorphisms, C-159T and C-260T, have no association with the likelihood of periodontitis. In subgroup analysis by ethnicity and periodontitis type, the results also did not show any association. The effect of genetic networks and their mutual interactions in the CD14 signaling pathway on susceptibility to periodontitis need to be studied further.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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