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Find video protocols related to scientific articles indexed in Pubmed.
NaDC3 Induces Premature Cellular Senescence by Promoting Transport of Krebs Cycle Intermediates, Increasing NADH, and Exacerbating Oxidative Damage.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 11-12-2014
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High-affinity sodium-dependent dicarboxylate cotransporter 3 (NaDC3) is a key metabolism-regulating membrane protein responsible for transport of Krebs cycle intermediates. NaDC3 is upregulated as organs age, but knowledge regarding the underlying mechanisms by which NaDC3 modulates mammalian aging is limited. In this study, we showed that NaDC3 overexpression accelerated cellular senescence in young human diploid cells (MRC-5 and WI-38) and primary renal tubular cells, leading to cell cycle arrest in G1 phase and increased expression of senescent biomarkers, senescence-associated ?-galactosidase and p16. Intracellular levels of reactive oxygen species, 8-hydroxy-2'-deoxyguanosine, malondialdehyde, and carbonyl were significantly enhanced, and activities of respiratory complexes I and III and ATP level were significantly decreased in NaDC3-infected cells. Stressful premature senescent phenotypes induced by NaDC3 were markedly ameliorated via treatment with the antioxidants Tiron and Tempol. High expression of NaDC3 caused a prominent increase in intracellular levels of Krebs cycle intermediates and NADH. Exogenous NADH and NAD(+) may aggravate and attenuate the aging phenotypes induced by NaDC3, respectively. These results suggest that NaDC3 can induce premature cellular senescence by promoting the transport of Krebs cycle intermediates, increasing generation of NADH and reactive oxygen species and leading to oxidative damage. Our results clarify the aging signaling pathway regulated by NaDC3.
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Ischemic Stroke Activates Hematopoietic Bone Marrow Stem Cells.
Circ. Res.
PUBLISHED: 11-02-2014
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Rationale: The mechanisms leading to an expanded neutrophil and monocyte supply after stroke are incompletely understood. Objective: To test the hypothesis that transient middle cerebral artery occlusion (tMCAO) in mice leads to activation of hematopoietic bone marrow stem cells. Methods and Results: Serial in vivo bioluminescence reporter gene imaging in mice with tMCAO revealed that bone marrow cell cycling peaked 4 days after stroke (p<0.05 versus pre tMCAO). FACS and cell cycle analysis showed activation of the entire hematopoietic tree, including myeloid progenitors. The cycling fraction of the most upstream hematopoietic stem cells increased from 3.34%±0.19 to 7.32±0.52 after tMCAO (p<0.05). In vivo microscopy corroborated proliferation of adoptively transferred hematopoietic progenitors in the bone marrow of mice with stroke. The hematopoietic system's myeloid bias was reflected by increased expression of myeloid transcription factors, including PU.1 (p<0.05), and by a decline in lymphocyte precursors. In mice after tMCAO, tyrosine hydroxylase levels in sympathetic fibers and bone marrow noradrenaline levels rose (p<0.05, respectively), associated with a decrease of hematopoietic niche factors that promote stem cell quiescence. In mice with genetic deficiency of the ?3 adrenergic receptor, hematopoietic stem cells did not enter the cell cycle in increased numbers after tMCAO (naive control, 3.23±0.22; tMCAO, 3.74±0.33, p=0.51). Conclusions: Ischemic stroke activates hematopoietic stem cells via increased sympathetic tone, leading to a myeloid bias of hematopoiesis and higher bone marrow output of inflammatory Ly6Chigh monocytes.
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Temporal Evolution of Photothermal-Induced Rayleigh Wave and Plate Deformation as an Interference in the Transient Kinetics of Photoinduced Carrier Recombination of Rutile Titanium Dioxide Single Crystal.
Appl Spectrosc
PUBLISHED: 10-31-2014
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The dynamic properties of photothermal processes occurring after the initial photogenerated carrier recombination in the flash photolysis of a semiconductor plate sample probed with a reflected infrared beam are reported in this work. Transient kinetics pertaining to the photothermal processes always appear as interfering signals in that of the photogenerated carrier recombination and should be distinguished and excluded. We observed that the photothermal-induced Rayleigh wave occurs immediately after the photogenerated carrier recombination that is then followed by the photothermal-induced flexural vibration of the sample substrate with a set of intrinsic frequencies as reported in our previous work (Appl. Spectrosc. 2013. 67(5): 506-512). When these two faster types of waves decay, the transient decaying signal from the plate deformation due to the inhomogeneous temperature field remains for much longer than 22 ms. Thus, all three types of the photothermal dynamic processes of different temporal properties induced by the pulsed laser on an absorbing semiconductor thin plate are clearly identified.
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Torsional energy levels of CH3OH(+)/CH3OD(+)/CD3OD(+) studied by zero-kinetic energy photoelectron spectroscopy and theoretical calculations.
J Chem Phys
PUBLISHED: 10-17-2014
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The torsional energy levels of CH3OH(+), CH3OD(+), and CD3OD(+) have been determined for the first time using one-photon zero kinetic energy photoelectron spectroscopy. The adiabatic ionization energies for CH3OH, CH3OD, and CD3OD are determined as 10.8396, 10.8455, and 10.8732 eV with uncertainties of 0.0005 eV, respectively. Theoretical calculations have also been performed to obtain the torsional energy levels for the three isotopologues using a one-dimensional model with approximate zero-point energy corrections of the torsional potential energy curves. The calculated values are in good agreement with the experimental data. The barrier height of the torsional potential energy without zero-point energy correction was calculated as 157 cm(-1), which is about half of that of the neutral (340 cm(-1)). The calculations showed that the cation has eclipsed conformation at the energy minimum and staggered one at the saddle point, which is the opposite of what is observed in the neutral molecule. The fundamental C-O stretch vibrational energy level for CD3OD(+) has also been determined. The energy levels for the combinational excitation of the torsional vibration and the fundamental C-O stretch vibration indicate a strong torsion-vibration coupling.
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Glipizide, an antidiabetic drug, suppresses tumor growth and metastasis by inhibiting angiogenesis.
Oncotarget
PUBLISHED: 10-09-2014
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Angiogenesis is involved in the development, progression and metastasis of various human cancers. Herein, we report the discovery of glipizide, a widely used drug for type 2 diabetes mellitus, as a promising anticancer agent through the inhibition of tumor angiogenesis. By high-throughput screening (HTS) of an FDA approved drug library utilizing our in vivo chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models, glipizide has been identified to significantly inhibit blood vessel formation and development. Moreover, glipizide was found to suppress tumor angiogenesis, tumor growth and metastasis using xenograft tumor and MMTV-PyMT transgenic mouse models. We further revealed that the anticancer capability of glipizide is not attributed to its antiproliferative effects, which are not significant against various human cancer cell lines. To investigate whether its anticancer efficacy is associated with the glucose level alteration induced by glipizide application, glimepiride, another medium to long-acting sulfonylurea antidiabetic drug in the same class, was employed for the comparison studies in the same fashion. Interestingly, glimepiride has demonstrated no significant impact on the tumor growth and metastasis, indicating that the anticancer effects of glipizide is not ascribed to its antidiabetic properties. Furthermore, glipizide suppresses endothelial cell migration and the formation of tubular structures, thereby inhibiting angiogenesis by up-regulating the expression of natriuretic peptide receptor A. These findings uncover a novel mechanism of glipizide as a potential cancer therapy, and also for the first time, provide direct evidence to support that treatment with glipizide may reduce the cancer risk for diabetic patients.
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[The modified extracorporeal photochemotherapy promotes apoptosis of spleen lymphocytes].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
PUBLISHED: 10-02-2014
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Objective To explore the efficacy of the modified extracorporeal photochemotherapy (ECP) in improving the apoptotic rate of lymphocytes in vitro. Methods The spleens which were obtained from liver transplantation donor under aseptic condition were used as experimental materials. Splenic lymphocytes (SPs) suspensions were prepared by modified and traditional ECP method, respectively. And then the isolated SPs were treated by the irradiation of 8-methoxypsoralen (8-MOP) combined with ultraviolet A (UVA) named PUVA, 8-MOP and UVA, and compared with a blank group meanwhile. The treated SPs were cultured overnight in an incubator at 37DegreesCelsius, in a humidified atmosphere of 50 mL/L CO2 for 6-8 hours. The morphological changes of cells were observed using an inverted microscope, the apoptotic rates of SPs were detected by flow cytometry, and the difference between groups was analyzed finally. Results The apoptotic rate at early stage and the total apoptotic rate of SPs prepared by the modified ECP method were respectively (95.33±3.03)% and (97.10±2.12)% after treated by PUVA, (23.39±4.55)% and (36.32±6.63)% after treated by 8-MOP, and (66.98±3.60)% and (68.65±4.35)% by UVA. Compared with control group (12.82±1.86% and 13.4±2.65%), there were statistically significant differences (P<0.01). The apoptotic rate at early stage and the total apoptotic rate of SPs prepared by the traditional ECP method were respectively (79.73±4.21)% and (82.70±4.13)%, (61.42±2.28)% and (68.91±2.18)%, (19.30±1.78)% and (28.06±1.88)%, (10.84±0.98)% and (12.77±1.22)%, and the statistical comparisons between groups also had significant difference (P<0.01). In addition, there was a significant difference in the early and total apoptosis between the modified and traditional ECP (P<0.01), but no obvious variation in the end-stage apoptosis in the two groups (P>0.05). Conclusion The modified ECP method can promote apoptosis of SPs in vitro conveniently, safely and efficiently, especially in the early stage. This can lay a foundation for the further study on dendritic cell immunomodulation induced by ECP method.
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An In Situ Generated Achiral Cu(II)-Containing Polymer Complex Sensor for Enantioselective Recognition Induced from L-/D-Histidine Enantiomers.
Macromol Rapid Commun
PUBLISHED: 09-30-2014
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A novel achiral polymer P-1 is synthesized by the polymerization of (2,5-bis(octyloxy)-1,4-phenylene)diboronic acid (M-1) with pyridine-2,6-diylbis(methanylylidene)bis(4-iodoaniline) (M-2) via Pd-catalyzed Suzuki coupling reaction. The tridentate ligand in the main chain backbone can further coordinate with Cu(2+) to afford the corresponding achiral copper-containing polymer complex P-2, which selectively responds to L-/D-histidine with significant fluorescence enhancement over other amino acids. Interestingly, P-2 exhibits obvious CD response toward L- or D-histidine compared with its model compound MC, indicating that this kind Cu(II)-containing polymer complex sensor can be used as an effective chemosensor for enantioselective recognition of histidine enantiomers by means of CD spectroscopy.
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TOP2Ahigh is the phenotype of recurrence and metastasis whereas TOP2Aneg cells represent cancer stem cells in prostate cancer.
Oncotarget
PUBLISHED: 09-20-2014
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Recurrence and metastasis are the main causes of death for prostate cancer patients and cancer stem cells (CSCs) are proposed to play important roles in cancer recurrence and metastasis. It is generally thought that genes upregulated in recurrent/metastatic disease are likely biomarkers of CSCs. Hence we analyzed multiple microarray datasets on prostate tumor tissues to identify upregulated genes associated with cancer recurrence/metastasis, and tried to explore whether those genes were true biomarkers of prostate CSCs. Our results indicated that TOP2A was the most highly upregulated gene in recurrent/metastatic prostate cancer, and its high expression was positively correlated with poor prognosis in patients. Using a promoter reporter system, we unexpectedly discovered enrichment of CSCs in TOP2Aneg cells. Compared to TOP2Ahigh cells, TOP2Aneg cells formed spheres and tumors more efficiently, and became enriched in the presence of stresses. Analysis of cell divisions by time lapse imaging indicated that more slow-cycling cells were observed in TOP2Aneg cells while the proportion of abnormal divisions was higher in TOP2Ahigh cells. Our studies demonstrate that TOP2Ahigh is the phenotype of recurrence/metastasis but TOP2Aneg cells show slow cycling and have CSCs properties in prostate cancer, which has significant implications for prostate cancer therapy.
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Thermal transport along the dislocation line in silicon carbide.
Phys. Rev. Lett.
PUBLISHED: 09-18-2014
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We elucidate thermal conductivity along the screw dislocation line, which represents a transport direction inaccessible to classical theories. By using equilibrium molecular dynamics simulations, we uncover a Burgers vector dependent thermal conductivity reduction in silicon carbide. The effect is uncorrelated with the classical modeling and originates in the highly deformed core region, which represents a significant source of anharmonic phonon-phonon scattering. High strain reduces the phonon relaxation time, especially in the longitudinal acoustic branches, and creates an effective internal thermal resistance around the dislocation axis. Our results have implications for designing materials useful for high-temperature electronics and thermoelectric applications.
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Effect of eutrophication on mercury, selenium, and essential fatty acids in bighead carp (Hypophthalmichthys nobilis) from reservoirs of eastern China.
Sci. Total Environ.
PUBLISHED: 08-29-2014
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Analyses of the risks and benefits of consuming fish assess the content of beneficial fatty acids found in fish relative to harmful pollutants such as methylmercury (MeHg). Quantifying the effect of eutrophication on mercury (Hg), selenium (Se) and essential fatty acids (EFAs) in fish is necessary to determine how measures of risk vary with productivity. Total Hg and MeHg, Se and fatty acids, including the EFA eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), were analyzed in Bighead Carp (Hypophthalmichthys nobilis) dorsal muscle tissue from seven subtropical reservoirs of eastern China. Individual elements and fatty acids, as well as derived measures of risk (Se:Hg and hazard quotient, HQ(EFA)) were regressed against indicators of eutrophication, including total phosphorous (TP), chlorophyll-a (chl-a) and phytoplankton species composition. We found low MeHg concentrations (range=0.018-0.13 ?g/g ww) and Se concentrations (range=0.12-0.28 ?g/g ww), and Se:Hg molar ratios that were well above 1.0, indicating a low risk of Hg toxicity. Bighead Carp had a high content of total polyunsaturated fatty acids (?PUFAs=44.2-53.6%), which included both EPA (6.9-12.5%) and DHA (16.1-23.2%). However, fish had significantly lower Se:Hg molar ratios in reservoirs with high TP, and lower EPA content with increasing plankton density (i.e. higher chl-a). Phytoplankton species composition predicted Se concentrations, but not Hg concentrations or EFA content. Overall, Hg concentrations in Bighead Carp were very low relative to consumption guidelines, and Se concentrations were adequate to confer protective benefits against MeHg toxicity. Our findings suggest that changes to plankton species composition and density with eutrophication may result in fish of lower nutritional value and thus increase risks to fish consumers by changing the availability of Se and EPA relative to MeHg.
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Tetrasubstituted pyrazinones derived from the reaction of praziquantel with N-bromosuccinimide.
Tetrahedron Lett.
PUBLISHED: 08-16-2014
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When praziquantel was exposed to N-bromosuccinimide in the presence of ethanol, a tricyclic 3-bromo-1-ethoxy pyrazinone was formed. From this and the analogous 1,3-dibromopyrazinone, a small library of 3-alkylamino-1-ethoxy, 1,3-dialkoxy, 3-alkoxy-1-bromo, and 3-alkylamino-1-bromo substituted pyrazinones were synthesized in high yields.
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Gold-thiolate ring as a protecting motif in the Au20(SR)16 nanocluster and implications.
J. Am. Chem. Soc.
PUBLISHED: 08-15-2014
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Understanding how gold nanoclusters nucleate from Au(I)SR complexes necessitates the structural elucidation of nanoclusters with decreasing size. Toward this effort, we herein report the crystal structure of an ultrasmall nanocluster formulated as Au20(TBBT)16 (TBBT = SPh-t-Bu). The structure features a vertex-sharing bitetrahedral Au7 kernel and an unprecedented "ring" motif-Au8(SR)8. This large ring protects the Au7 kernel through strong Auring-Aukernel bonding but does not involve S-Aukernel bonding, in contrast to the common "staple" motifs in which the S-Aukernel bonding is dominant but the Austaple-Aukernel interaction is weak (i.e., aurophilic). As the smallest member in the TBBT "magic series", Au20(TBBT)16, together with Au28(TBBT)20, Au36(TBBT)24, and Au44(TBBT)28, reveals remarkable size-growth patterns in both geometric structure and electronic nature. Moreover, Au20(TBBT)16, together with the Au24(SR)20 and Au18(SR)14 nanoclusters, forms a "4e" nanocluster family, which illustrates a trend of shrinkage of bitetrahedral kernels from Au8(4+) to Au7(3+) and possibly to Au6(2+) with decreasing size.
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Potassium-sulfur batteries: a new member of room-temperature rechargeable metal-sulfur batteries.
Inorg Chem
PUBLISHED: 08-13-2014
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We report room-temperature rechargeable potassium-sulfur (K-S) batteries using ordered mesoporous carbon (CMK-3)/sulfur and polyanilime (PANI) coated CMK-3/sulfur composites as the cathode and metallic potassium as the anode. The electrochemical reaction mechanism was investigated by electrochemical tests, TEM, XRD, and Raman spectra. It was found that K-S batteries delivered two reduction peaks located at about 2.1 and 1.8 V and one oxidation peak at about 2.2 V, respectively. Meanwhile, K2S3 was the major discharge product that could be charged to reversibly form S and K ion. Through optimization of sulfur content, the CMK-3/sulfur composite with 40.8 wt % S displayed an initial discharge capacity of 512.7 mAh g(-1) and a capacity of 202.3 mAh g(-1) after 50 cycles at a current density of 50 mA g(-1). A coating of conductive polyanilime (PANI) on the CMK-3/sulfur composite is effective in enhancing the cycling performance. In comparison, PANI@CMK-3/sulfur composite showed a capacity of 329.3 mAh g(-1) after 50 cycles at 50 mA g(-1). The results shed light on the basic study of rechargeable K-S batteries.
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Delivering Sound Energy along an Arbitrary Convex Trajectory.
Sci Rep
PUBLISHED: 08-05-2014
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Accelerating beams have attracted considerable research interest due to their peculiar properties and various applications. Although there have been numerous research on the generation and application of accelerating light beams, few results have been published on the generation of accelerating acoustic beams. Here we report on the experimental observation of accelerating acoustic beams along arbitrary convex trajectories. The desired trajectory is projected to the spatial phase profile on the boundary which is discretized and sampled spatially. The sound field distribution is formulated with the Green function and the integral equation method. Both the paraxial and the non-paraxial regimes are examined and observed in the experiments. The effect of obstacle scattering in the sound field is also investigated and the results demonstrate that the approach is robust against obstacle scattering. The realization of accelerating acoustic beams will have an impact on various applications where acoustic information and energy are required to be delivered along an arbitrary convex trajectory.
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EBV-driven LMP1 and IFN-? up-regulate PD-L1 in nasopharyngeal carcinoma: Implications for oncotargeted therapy.
Oncotarget
PUBLISHED: 07-20-2014
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PD-L1 expression is a feature of Epstein-Barr virus (EBV) associated malignancies such as nasopharyngeal carcinoma (NPC). Here, we found that EBV-induced latent membrane protein 1 (LMP1) and IFN-? pathways cooperate to regulate programmed cell death protein 1 ligand (PD-L1). Expression of PD-L1 was higher in EBV positive NPC cell lines compared with EBV negative cell lines. PD-L1 expression could be increased by exogenous and endogenous induction of LMP1 induced PD-L1. In agreement, expression of PD-L1 was suppressed by knocking down LMP1 in EBV positive cell lines. We further demonstrated that LMP1 up-regulated PD-L1 through STAT3, AP-1, and NF-?B pathways. Besides, IFN-? was independent of but synergetic with LMP1 in up-regulating PD-L1 in  NPC. Furthermore, we showed that PD-L1 was associated with worse disease-free survival in NPC patients. These results imply that blocking both the LMP1 oncogenic pathway and PD-1/PD-L1 checkpoints may be a promising therapeutic approach for EBV positive NPC patients.
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Photodissociation dynamics of superexcited O?: dissociation channels O(?S) vs. O(³S).
J Chem Phys
PUBLISHED: 07-10-2014
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The photodissociation dynamics of O2, O2 + h? ? O((3)P) + O(2p(3)((4)S)3s, (3)S/(5)S), has been studied by combining the XUV laser pump / UV laser probe and velocity map imaging methods in the photon energy range 14.64-15.20 eV. The fragment yield spectra of O((3)S) and O((5)S) and their velocity map images have been recorded using the state-selective (1+1) REMPI method to detect the fragments. The fragment yield spectra show resolved fine structure that arises from the predissociated Rydberg states I, I' and I? ((3)?(? = 0,1,2)). The branching ratios between the two decay channels have been measured by one-photon ionization of the fragments O((3)S) and O((5)S) simultaneously. It is surprising to find that the dissociation cross sections for the production of O((5)S) are larger than, or comparable to, those of O((3)S) for the I and I' states, while the cross sections for the production of O((5)S) are smaller than those of O((3)S) for the I? state. All fragments O((5)S) arise from perpendicular transitions, which provides direct experimental evidence about the symmetry assignments of the states I, I' and I? excited in this energy region. Although most of the fragments O((3)S) arise from perpendicular transitions, some of them are from parallel transitions. Based on the calculated ab initio potential energy curves, we propose that the neutral dissociation into O((3)P) + O((3)S) occurs mainly via the interaction of the Rydberg states I, I', and I? with the vibrational continuum of the diabatic 8(3)?(u) state (1?(u)?¹(a??(u))3s?(g), ³?(u)), while the neutral dissociation into O((3)P) + O((5)S) occurs mainly via the interaction of Rydberg states I, I', and I? with the diabatic 7(3)?(u) (1?(g)?¹(X²?(g))3p?(u), ³?(u)).
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MUC1 Aptamer-Based Near-Infrared Fluorescence Probes for Tumor Imaging.
Mol Imaging Biol
PUBLISHED: 07-10-2014
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DNA aptamer (APT) is able to bind to Mucin 1 (MUC1) specifically. The possibility of APT acting as a moiety to construct tumor-targeting probes was investigated.
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Neochromine S5 improves contact hypersensitivity through a selective effect on activated T lymphocytes.
Biochem. Pharmacol.
PUBLISHED: 07-02-2014
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Strategy on activated T cells is an effective treatment for T cell mediated diseases. By using a synthesized chromone derivative, we examined its effects on the activated T cells. This compound, (Z)-1,3-dihydroxy-9-methyl-13H-benzo[b]chromeno[3,2-f][1,4]oxazepin-13-one (neochromine S5), exhibited immunosuppressive activity in vitro and in vivo. Interestingly, neochromine S5 selectively inhibited proliferation and induced apoptosis in T lymphocytes activated by concanavalin A (Con A) in a dose-dependent manner but not in naïve T lymphocytes, distinct from quercetin. This compound triggered mitochondrial apoptotic pathway including cleavage of caspase 3, caspase 9 and PARP, downregulation of bcl-2 and release of cytochrome c in activated T cells, but did not affect ER stress or Fas signals. In addition, neochromine S5 downregulated the expression of CD25 and CD69 and the production of inflammatory cytokines, including TNF?, IFN? and IL-2, improved ear swelling in mice with contact hypersensitivity, reduced CD4(+) T cells infiltration, and increased apoptosis of isolated T lymphocytes from peripheral lymph nodes. Moreover, neochromine S5 showed no effect on the weight of mice and their immune organs, while dexamethasone caused a significant weight loss. Taken together, our results suggest that neochromine S5 exerts a unique anti-inflammatory activity mainly through a selective effect on activated T cells, which is different from the current immunosuppressant, dexamethasone.
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Application of a glycaemic control optimization programme in patients with stress hyperglycaemia.
Nurs Crit Care
PUBLISHED: 06-25-2014
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This study investigated the clinical effects of a blood glycaemic control optimization programme (BGCOP) in patients with stress hyperglycaemia post hepatobiliary or pancreatic surgery.
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The sheep genome illuminates biology of the rumen and lipid metabolism.
Science
PUBLISHED: 06-07-2014
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Sheep (Ovis aries) are a major source of meat, milk, and fiber in the form of wool and represent a distinct class of animals that have a specialized digestive organ, the rumen, that carries out the initial digestion of plant material. We have developed and analyzed a high-quality reference sheep genome and transcriptomes from 40 different tissues. We identified highly expressed genes encoding keratin cross-linking proteins associated with rumen evolution. We also identified genes involved in lipid metabolism that had been amplified and/or had altered tissue expression patterns. This may be in response to changes in the barrier lipids of the skin, an interaction between lipid metabolism and wool synthesis, and an increased role of volatile fatty acids in ruminants compared with nonruminant animals.
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Peripherally Cross-Linking the Shell of Core-Shell Polymer Micelles Decreases Premature Release of Physically Loaded Combretastatin A4 in Whole Blood and Increases its Mean Residence Time and Subsequent Potency Against Primary Murine Breast Tumors After IV Administratio
Pharm. Res.
PUBLISHED: 06-01-2014
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Determine the feasibility and potential benefit of peripherally cross-linking the shell of core-shell polymer micelles on the premature release of physically loaded hydrophobic drug in whole blood and subsequent potency against solid tumors.
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Hydrogenated uniform Pt clusters supported on porous CaMnO(3) as a bifunctional electrocatalyst for enhanced oxygen reduction and evolution.
Adv. Mater. Weinheim
PUBLISHED: 05-13-2014
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Hydrogenated uniform Pt clusters supported on porous CaMnO3 nanocomposites are synthesized and investigated as a new electrocatalytic material for oxygen reduction and evolution reactions. Due to the synergistic effect of Pt and CaMnO3, the nanocomposites exhibit superior activity and durability to the benchmark Pt/C catalyst.
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Autofocused 3D Classification of Cryoelectron Subtomograms.
Structure
PUBLISHED: 04-28-2014
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Classification of subtomograms obtained by cryoelectron tomography (cryo-ET) is a powerful approach to study the conformational landscapes of macromolecular complexes in situ. Major challenges in subtomogram classification are the low signal-to-noise ratio (SNR) of cryo-tomograms, their incomplete angular sampling, the unknown number of classes and the typically unbalanced abundances of structurally distinct complexes. Here, we propose a clustering algorithm named AC3D that is based on a similarity measure, which automatically focuses on the areas of major structural discrepancy between respective subtomogram class averages. Furthermore, we incorporate a spherical-harmonics-based fast subtomogram alignment algorithm, which provides a significant speedup. Assessment of our approach on simulated data sets indicates substantially increased classification accuracy of the presented method compared to two state-of-the-art approaches. Application to experimental subtomograms depicting endoplasmic-reticulum-associated ribosomal particles shows that AC3D is well suited to deconvolute the compositional heterogeneity of macromolecular complexes in situ.
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Identification of novel predictive markers for the prognosis of pancreatic ductal adenocarcinoma.
Cancer Invest.
PUBLISHED: 04-18-2014
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This study demonstrated that klotho gene expression was significantly lower whereas miR-504 and phospho-IGF-1R levels were significantly higher in PDAC than in normal pancreatic tissues. miR-504 level significantly correlated with klotho mRNA and promoter methylation level in PDACs. Loss of Klotho protein expression, klotho promoter hypermethylation, high miR-504 levels, and high phospho-IGF-1R levels significantly correlated with poor survival, high clinical and pathological stages in PDAC patients. The demethylation reagent and miR-504 inhibitor increased klotho gene expression, invasion, and migration in BxPC-3 and Panc-1 cells. Klotho is a tumor suppressor whose expression in PDAC correlated with progression and prognosis of PDAC.
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Thermal-triggerd proteinquake leads to disassembly of DegP hexamer as an imperative activation step.
Sci Rep
PUBLISHED: 04-11-2014
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The Escherichia coli DegP has been reported to function both as molecular chaperone and protease for the quality control of outer membrane protein biogenesis. Activation of the inactive DegP hexamers was believed to occur via their disassembly into trimeric units and subsequent reassembly into larger oligomers (12-mers and 24-mers). Here, we analyzed the thermal stability and the unfolding dynamics of the different secondary structure components of the DegP hexamers using Fourier transform infrared spectroscopy and temperature-jump nanosecond time-resolved IR difference absorbance spectroscopy. We found that the interfacial secondary structure components possess a degreed thermal stability, with the disassembly of the DegP hexamers follows a "proteinquake" manner, such that the fully exposed parts of the interfacial ?-sheets serving as the temperature sensor and epicenter to drive the sequential unfolding/disassembly process that finishes within about 134?ns at room temperature.
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New parasitoid-predator associations: female parasitoids do not avoid competition with generalist predators when sharing invasive prey.
Naturwissenschaften
PUBLISHED: 04-03-2014
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Optimal habitat selection is essential for species survival in ecosystems, and interspecific competition is a key ecological mechanism for many observed species association patterns. Specialized animal species are commonly affected by resource and interference competition with generalist and/or omnivorous competitors, so avoidance behavior could be expected. We hypothesize that specialist species may exploit broad range cues from such potential resource competitors (i.e., cues possibly common to various generalist and/or omnivorous predators) to avoid costly competition regarding food or reproduction, even in new species associations. We tested this hypothesis by studying short-term interactions between a native larval parasitoid and a native generalist omnivorous predator recently sharing the same invasive host/prey, the leaf miner Tuta absoluta. We observed a strong negative effect of kleptoparasitism (food resource stealing) instead of classical intraguild predation on immature parasitoids. There was no evidence that parasitoid females avoided the omnivorous predator when searching for oviposition sites, although we studied both long- and short-range known detection mechanisms. Therefore, we conclude that broad range cue avoidance may not exist in our biological system, probably because it would lead to too much oviposition site avoidance which would not be an efficient and, thus, beneficial strategy. If confirmed in other parasitoids or specialist predators, our findings may have implications for population dynamics, especially in the current context of increasing invasive species and the resulting creation of many new species associations.
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[The research of clinical pathological features of ALK positive lung cancer in 525 patients and the discussion of detection methods].
Zhongguo Fei Ai Za Zhi
PUBLISHED: 03-27-2014
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The fusion (rearrangement) of anaplastic lymphoma kinase (ALK) gene has been identified as an import factor to the tumorigenesis and development of lung cancer. ALK tyrosine kinase inhibitors (ALK-TKIs) have been proved to have good effects to ALK positive lung cancers. The increasement of the relevance ratio of ALK will be very important to patients. The aim of this study is to investigate the clinical pathological features of ALK positive lung cancer, and the roles of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in screening and confirming the ALK positive cases in the testing flow of ALK.
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Predictive factors for the sensitivity of radiotherapy and prognosis of esophageal squamous cell carcinoma.
Int. J. Radiat. Biol.
PUBLISHED: 03-20-2014
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To identify predictive biomarkers for radiosensitization and prognosis of esophageal squamous cell carcinoma (ESCC).
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The roles of miR-200c in colon cancer and associated molecular mechanisms.
Tumour Biol.
PUBLISHED: 03-18-2014
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The expression of miR-200c has been widely reported to be elevated in tumor tissues and sera of patients with colorectal cancer (CRC) and has been found to correlate with poor prognosis. However, how miR-200c regulates the apoptosis, survival, invasion, metastasis, and tumor growth in colon cancer cells remains to be fully elucidated. This study seeks to further investigate the role of miR-200c in colon cancer development. The expression of miR-200c in tumor and peritumoral tissues of 101 colon cancer patients was measured by real-time PCR. miR-200c expression in HCT-116 and HT-29 colon cancer cells was silenced by adenovirus-carried expression of antisense mRNA against miR-200c. The protein levels of PTEN, p53 Ser(15), PP1, and activated caspase-3 in HCT-116 and HT-29 cells were measured by Western blot. This study demonstrated that the expression of miR-200c was significantly higher in tumor tissues than in peritumoral tissues of colon cancer patients. The elevated miR-200c expression significantly correlated with the TNM stage, lymph node metastasis, and invasion of colon cancer. Silencing miR-200c expression significantly induced cell apoptosis, inhibited long-term survival, invasion, and metastasis, and delayed xenograft tumor growth. Importantly, silencing miR-200c expression sensitized the therapeutic effect of Ara-C (Cytarabine). The effects of silencing miR-200c expression were associated with upregulation of PTEN protein and p53 Ser(15) phosphorylation levels in HCT-116 cells and PTEN protein expression in HT-29 cells. In conclusion, miR-200c functions as an oncogene in colon cancer cells through regulating tumor cell apoptosis, survival, invasion, and metastasis as well as xenograft tumor growth through inhibition of PTEN expression and p53 phosphorylation.
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A nutrient mixture reduces the expression of matrix metalloproteinases in an animal model of spinal cord injury by modulating matrix metalloproteinase-2 and matrix metalloproteinase-9 promoter activities.
Exp Ther Med
PUBLISHED: 03-07-2014
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This study aimed to determine whether a novel nutrient mixture (NM), composed of lysine, ascorbic acid, proline, green tea extracts and other micronutrients, attenuates impairments induced by spinal cord injury (SCI) and to investigate the related molecular mechanisms. A mouse model of SCI was established. Thirty-two mice were divided into four groups. The sham group received vehicle only. The SCI groups were treated orally with saline (saline group), a low dose (500 ?g 3 times/day) of NM (NM-LD group) or a high dose (2,000 ?g 3 times/day) of NM (NM-HD group). The levels of mouse hindlimb movement were determined every day in the first week post-surgery. The protein expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 were determined by western blotting. Wild-type and mutant MMP-2- and MMP-9-directed luciferase constructs were generated and their luciferase activities were determined. NM significantly facilitated the recovery of hindlimb movement of the mice in comparison to that in the saline group. The expression levels of MMP-2 in the NM-LD and NM-HD groups were decreased by ~50% compared with the saline group as indicated by western blotting results. The expression levels of MMP-9 in the NM-LD and NM-HD groups were decreased to ~25 and ~10%, respectively. These results suggest that NM significantly inhibits the expression of MMP-2 and MMP-9 proteins. Reverse transcription quantitative polymerase chain reaction results indicated that NM reduced the levels of MMP-2 and MMP-9 mRNA. Furthermore, the luciferase results indicated that site-directed mutagenesis comprising a -1306 C to T (C/T) base change in the MMP-2 promoter and a -1562 C/T base change in the MMP-9 promoter abolished the inhibitory effects of NM on MMP-2 and MMP-9 promoters. These results suggest that NM attenuates SCI-induced impairments in mice movement by negatively affecting the promoter activity of MMP-2 and MMP-9 genes and thus decreasing the expression of MMP-2 and MMP-9 proteins.
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Effect of ozonide OZ418 against Schistosoma japonicum harbored in mice.
Parasitol. Res.
PUBLISHED: 03-04-2014
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The in vitro and in vivo efficacies of ozonide carboxylic acid OZ418 against Schistosoma japonicum were investigated. For in vitro experiments, juvenile (14-day-old) and adult schistosomes were collected from mice infected with 80-100?S. japonicum cercariae for 14 and 35 days post-infection and the worms were maintained in Roswell Park Memorial Institute (RPMI) 1640 supplemented by 10% calf serum. Against 35-day-old adult S. japonicum, OZ418 resulted in weakened worm motor activity, injury to the worm body, emergence of vacuoles along the worm surface, and death. A similar outcome was seen in 14-day-old juvenile S. japonicum exposed to OZ418. Ineffective concentrations (1, 5, and 10 ?g/mL) of OZ418 also interacted with hemin to significantly increase the killing effect against adult schistosomes. The LC50 value of OZ418 against juvenile (14-day-old) and adult schistosomes were identical--16.2 ?g/mL, whereas the corresponding LC95 values were 30.7 and 22.7 ?g/mL, respectively. Treatment of adult and juvenile (14-day-old) S. japonicum-infected mice with single 200-400-mg/kg oral doses of OZ418 produced total worm burden reductions of 68.5-84.1 and 37.5-50.9%, respectively. Further study showed that in mice infected with various stages of schistosomes and treated with a single oral OZ418 400 mg/kg, poor efficacy was seen in the 3-h-old juvenile worm group, while 14-day-old and 21-day-old juvenile worm groups exhibited less efficacy with total worm burden reductions of 42.6-52.4%. On the other hand, similar and higher total worm burden reductions (64.2-76.0%) were seen in the 7-day-old juvenile worm group and 28-day-old as well as 35-day-old adult worm groups. Furthermore, the mean worm burden reductions of the 7-day-old juvenile worm group and 35-day-old adult worm group were statistically significantly higher than that of the 14-day-old or 21-day-old juvenile worm group (P?
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?-MnO2 nanostructures directly grown on Ni foam: a cathode catalyst for rechargeable Li-O2 batteries.
Nanoscale
PUBLISHED: 03-01-2014
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A sponge-like ?-MnO2 nanostructure was synthesized by direct growth of ?-MnO2 on Ni foam through a facile electrodeposition route. When applied as a self-supporting, binder-free cathode material for rechargeable nonaqueous lithium-oxygen batteries, the ?-MnO2/Ni electrode exhibits considerable high-rate capability (discharge capacity of ?6300 mA h g(-1) at a current density of 500 mA g(-1)) and enhanced cyclability (exceeding 120 cycles) without controlling the discharge depth. The superior performance is proposed to be associated with the 3D nanoporous structures and abundant oxygen defects as well as the absence of side reactions related to carbon-based conductive additives and binders.
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Comparative population genomics reveals the domestication history of the peach, Prunus persica, and human influences on perennial fruit crops.
Genome Biol.
PUBLISHED: 02-25-2014
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Recently, many studies utilizing next generation sequencing have investigated plant evolution and domestication in annual crops. Peach, Prunus persica, is a typical perennial fruit crop that has ornamental and edible varieties. Unlike other fruit crops, cultivated peach includes a large number of phenotypes but few polymorphisms. In this study, we explore the genetic basis of domestication in peach and the influence of humans on its evolution.
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Pentamethoxyflavanone regulates macrophage polarization and ameliorates sepsis in mice.
Biochem. Pharmacol.
PUBLISHED: 02-18-2014
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Macrophages, owning variable phenotypes and diverse functions, were becoming the target cells in inflammatory, infectious and autoimmune diseases. In the present study, we evaluated the effect of 5,7,3',4',5'-pentamethoxyflavanone (abbreviated as PMFA), a kind of flavonoid, on macrophage polarization, and investigated the underlying mechanism. We found that PMFA significantly inhibited M1 macrophage polarization and diminished the proinflammatory cytokines, meanwhile it greatly enhanced M2 macrophage related molecules. Moreover, PMFA facilitated the phenotype shift from M1 to M2. However, PMFA only slightly inhibited the activation of T and B cells. Further researches showed that the mechanisms can be attributed to PMFA's down-regulation on p-STAT1 and up-regulation on p-STAT6, the pivotal regulatory molecules for M1 and M2 polarization, respectively. In addition, PMFA ameliorated LPS- and cecal ligation and puncture (CLP)-induced sepsis in mice, as assessed by the raise of survival rate, descend of tissue damage and bronchoalveolar lavage fluid (BALF) cytokines. PMFA significantly decreased the expression of IL-1?, IL-6 and TNF-? and reduced the infiltration of M1 macrophages in lung. As expected, adoptive transfer of PMFA-pretreated M1 macrophages significantly increased survival rate of LPS-challenged mice compared with control mice. Taken together, the results indicate that PMFA regulates macrophage polarization via targeting the STAT1/STAT6 signals and its potential use in treatment of inflammatory disease.
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A fast tumor-targeting near-infrared fluorescent probe based on bombesin analog for in vivo tumor imaging.
Contrast Media Mol Imaging
PUBLISHED: 02-14-2014
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Bombesin (BBN), an analog of gastrin-releasing peptide (GRP), of which the receptors are over-expressed on various tumor cells, is able to bind to GRP receptor specifically. In this study, a near-infrared fluorescent dye (MPA) and polyethylene glycol (PEG) were conjugated to BBN analog to form BBN[7-14]-MPA and BBN[7-14]-SA-PEG-MPA. The successful synthesis of the two probes was proved by the characterization via sodium dodecylsulfate-polyacrylamide gel electrophoresis, infrared and optical spectra. Cellular uptakes studies indicated that BBN-based probes were mediated by gastrin-releasing peptide receptors (GRPR) on tumor cells and the PEG modified probe had higher affinity. The dynamic distribution and clearance investigations showed that the BBN-based probes were eliminated by the liver-kidney pathway. Furthermore, both of the BBN-based probes displayed tumor-targeting ability in GRPR over-expressed tumor-bearing mice. The PEG modified probe exhibited faster and higher tumor targeting capability than BBN[7-14]-MPA. The results implied that BBN[7-14]-SA-PEG-MPA could act as an effective fluorescence probe for tumor imaging.
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Involvement of miR-29b signaling in the sensitivity to chemotherapy in patients with ovarian carcinoma.
Hum. Pathol.
PUBLISHED: 02-05-2014
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Although the molecular mechanisms driving chemoresistance and relapse of ovarian cancer have been widely studied, the key molecules have not been identified. In this study, the expression of miR-29b messenger RNA (mRNA) and its targeted genes, myeloid cell leukemia sequence 1, mitogen-activated protein kinase 10 (MAPK10), and autophagy-related protein 9A (ATG9A), were investigated in ovarian carcinomas, and their associations with clinicopathological characteristics and survival of patients with ovarian cancer were analyzed. The protein expression of MCL1, MAPK10, and ATG9A was measured using immunohistochemistry. miR-29b mRNA and ATG9A gene mRNA levels were measured by real-time polymerase chain reaction. Results demonstrated that the percentage of MCL1, MAPK10, and ATG9A protein-positive cases were significantly higher, whereas miR-29b was significantly lower in ovarian serous, mucinous, and clear cell carcinomas than that in normal tissues. MAPK10 was significantly associated with higher histopathologic grading. The percentage of positive myeloid cell leukemia sequence 1, ATG9A, and MAPK10 protein expression and low miR-29b mRNA expression were significantly higher in cases with clinical stage III and IV ovarian cancer than in cases with clinical stage II ovarian cancer. High ATG9A protein and low miR-29b mRNA expression were significantly associated with relapse. Univariate Kaplan-Meier analysis showed a negative correlation between MAPK10 or ATG9A protein expression and overall as well as progression-free survival, whereas a positive correlation was observed between miR-29b mRNA expression and overall as well as progression-free survival. Multivariate Cox regression analysis showed that elevated MAPK10 or ATG9A protein and lowered miR-29b mRNA expression in ovarian carcinoma was an independent poor prognostic predictor. Our study suggested that miR-29b mRNA, MAPK10 protein expression, and ATG9A protein expression are closely related to chemosensitivity of ovarian carcinoma.
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Therapeutic effect of the treatment for colorectal cancer with adenoviral vectors mediated estrogen receptor ? gene therapy combined with thermotherapy.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 02-04-2014
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Our preliminary study on repressing colorectal tumors by recombinant adenoviruses (Ads) delivering the human ER? gene (Ad-ER?) has achieved positive result.
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Monocyte chemotactic protein-1 -2518 gene polymorphism and susceptibility to spinal tuberculosis.
Arch. Med. Res.
PUBLISHED: 01-27-2014
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Monocyte chemotactic protein-1 (MCP-1) gene polymorphisms play important roles in regulating immunological reactions and may be associated with pulmonary tuberculosis. However, the relationship between the MCP-1 -2518 gene polymorphism and susceptibility to spinal tuberculosis remains unknown. We undertook this study to investigate the relationships between MCP-1 promoter 2518 genotype frequency and allele polymorphisms and susceptibility to spinal tuberculosis in a Chinese Han population.
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Effects of oxysophoridine on amino acids after cerebral ischemic injury in mice.
Ann Indian Acad Neurol
PUBLISHED: 01-26-2014
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Our previous studies demonstrated that oxysophoridine (OSR) had neuroprotective effects on mice through antioxidant and anti-apoptotic mechanisms. In this study, we investigated whether OSR could influence the release of amino acids in ischemic mice brains.
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An investigation of symptom burden and quality of life in Chinese chemo-naïve advanced lung cancer patients by using the Instrument-Cloud QOL System.
Lung Cancer
PUBLISHED: 01-18-2014
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This study was designed to assess the disease-related symptom burden and quality of life (QOL) in Chinese chemo-naïve advanced lung cancer patients.
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Magnetic resonance spectroscopy at term-equivalent age in extremely preterm infants: association with cognitive and language development.
Pediatr. Neurol.
PUBLISHED: 01-17-2014
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Proton magnetic resonance spectroscopy can be used to assess brain integrity and maturation with age.
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Oleate promotes differentiation of chicken primary preadipocytes in vitro.
Biosci. Rep.
PUBLISHED: 01-09-2014
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In addition to providing energy and constituting cell membrane, fatty acids also play an important role in adipocyte differentiation and lipid metabolism. As an important member of monounsaturated fatty acids, oleate, together with other components, is widely used to induce chicken preadipocyte differentiation. However, it is not clear whether oleate alone can induce chicken preadipocyte differentiation. In the present study, four different treatments were designed to test this question: basal medium, IDX[1] (insulin, dexamethasone and 3-isobutyl-1-methylxanthine), oleate, and IDX plus oleate. Cytoplasmic lipid droplet accumulation and mRNA expression for adipogenesis-related genes were monitored. After treatment of oleate on chicken preadipocytes, apparent lipid droplet formation and lipid accumulation were observed, accompanied by increasing expression of peroxisome proliferator-activated receptor-? (PPAR?) and adipocyte fatty acid-binding protein (AFABP), but decreasing level of GATA binding protein 2 (GATA2). In contrast, for cells cultured in basal medium with or without IDX supplementation, lipid droplet barely occurred. These results suggest that exogenous oleate alone can act as an inducer of preadipocyte differentiation into adipocytes.
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Activity of diimidazoline amides against African trypanosomiasis.
Bioorg. Med. Chem. Lett.
PUBLISHED: 01-09-2014
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We identified several diimidazoline mono- and diamides that were as potent as pentamidine against Trypanosoma brucei rhodesiense in vitro. All of these were also less cytotoxic than pentamidine, but none was as effective as the latter in a T. brucei rhodesiense-infected mouse model. A single imidazoline may be sufficient for high antitrypanosomal activity provided that a second weak base functional group is present.
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Involvement of transient receptor potential melastatin-8 (TRPM8) in menthol-induced calcium entry, reactive oxygen species production and cell death in rheumatoid arthritis rat synovial fibroblasts.
Eur. J. Pharmacol.
PUBLISHED: 01-07-2014
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Rheumatoid arthritis is most prominently characterized by synoviocyte hyperplasia which therefore serves as an important target for clinical therapy. In the present study, it was observed that menthol, the specific agonist of transient receptor potential melastatin subtype 8 (TRPM8), could induce sustained increases of cytosolic calcium concentration ([Ca(2+)]c) in synoviocytes isolated from collagen-induced arthritis rats in dose-dependent manner, which was evidently blocked by applying an extracellular Ca(2+)-free buffer. Menthol-induced [Ca(2+)]c increase was also significantly inhibited by potent TRPM8 antagonist capsazepine (CZP), indicating that this [Ca(2+)]c elevation was mostly attributed to TRPM8-mediated Ca(2+) entry. Besides, RT-PCR indeed demonstrated presence of TRPM8 in the synoviocytes. Meanwhile, it was found that menthol evoked production of intracellular reactive oxygen species, which could be abolished by Ca(2+) free solutions or CZP. Further experiments showed that menthol reduced the cell numbers and survival of synoviocytes. This reduction was associated with apoptosis as suggested by mitochondrial membrane depolarization, nuclear condensation and a caspase 3/7 apoptotic assay. Menthol-induced death and apoptosis of synoviocytes both were obviously inhibited by CZP, intracellular calcium chelator BAPTA-AM, and reactive oxygen species inhibitor diphenylene iodonium, respectively. Taken together, our data indicated that menthol resulted in synoviocyte death associated with apoptosis via calcium entry and reactive oxygen species production depending on TRPM8 activation.
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Ultrasound guidance for radial artery catheterization: an updated meta-analysis of randomized controlled trials.
PLoS ONE
PUBLISHED: 01-01-2014
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Since a previous meta-analysis reported that ultrasound guidance was associated with a higher first-attempt success rate in catheterization of the radial artery, a number of randomized controlled trials (RCTs) have reported inconsistent results. The aim of the present study is to conduct an updated meta-analysis to clarify the role of ultrasound guidance for radial artery catheterization.
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Risk of treatment-related deaths with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a meta-analysis of 41 randomized controlled trials.
Onco Targets Ther
PUBLISHED: 01-01-2014
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Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) have widely been used in advanced cancer. However, these drugs may also lead to serious adverse events. The present meta-analysis aimed to determine the overall incidence and risk of deaths due to VEGFR-TKIs with more detailed subgroup analysis.
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Effective compounds screening from Rabdosia serra (Maxim) Hara against HBV and tumor in vitro.
Int J Clin Exp Med
PUBLISHED: 01-01-2014
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The aim of this study was to screen and investigate the anti-HBV and anti-tumor activities of separated compounds from Rabdosia serra (Maxim.) Hara to lay the basis for further isolate active entity. Three kinds of extractions from Rabdosia serra using different solvents (petroleum ether, acetidin, butyl alcohol) were prepared and used to analyze their anti-HBV activity in HepG2.2.15 cells for further separation. The cytotoxicity of each extraction was tested by MTT assay, the levels of HBsAg, HBeAg and HBV DNA in supernatants from HepG2.2.15 cells were detected by ELISA and real-time quantitative polymerase chain reaction (PCR). Then, the most effective extraction was further separated, the anti-HBV activities of separated compounds were also tested by MTT and ELISA, and three compounds with highest cytotoxicity were selected to further identify their anti-tumor activities on MCF-7, BGC-823 and HepG2 cells. Acetidin extraction C2 had the most effective anti-HBV activity that was used to be further separated, it led to statistically significant reduction in HBsAg and HBeAg secretion and HBV DNA. The separation of C2 resulted in 14 compounds, A3 and A5 markedly inhibited HBsAg secretion, while A9 inhibited HBeAg secretion in a dose-dependent manner with higher TI comparing with C2. A6, A7, A11 had different anti-tumor activity against different tumor cells. These data showed that the extraction and their separated effective compounds had strong inhibitory effect on HBV replication so as to have anti-HBV activity, and further separation and purification could enhance anti-HBV activity. Meanwhile, some compounds have high cytotoxicities on different tumor cells. Our study could provide a theoretical basis for the next clinical use and the development of potential and efficient drugs for HBV and tumor therapy from Rabdosia serra.
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Lycium barbarum polysaccharide prevents focal cerebral ischemic injury by inhibiting neuronal apoptosis in mice.
PLoS ONE
PUBLISHED: 01-01-2014
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To investigate the neuroprotective effect of Lycium barbarum polysaccharide (LBP) on focal cerebral ischemic injury in mice and to explore its possible mechanism.
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Network meta-analysis of erlotinib, gefitinib, afatinib and icotinib in patients with advanced non-small-cell lung cancer harboring EGFR mutations.
PLoS ONE
PUBLISHED: 01-01-2014
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Several EGFR-tyrosine kinase inhibitors (EGFR-TKIs) including erlotinib, gefitinib, afatinib and icotinib are currently available as treatment for patients with advanced non-small-cell lung cancer (NSCLC) who harbor EGFR mutations. However, no head to head trials between these TKIs in mutated populations have been reported, which provides room for indirect and integrated comparisons.
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Using focus groups to design a psychoeducation program for patients with schizophrenia and their family members.
Int J Clin Exp Med
PUBLISHED: 01-01-2014
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The purpose of this project was to determine what factors to be considered in planning a psychoeducation program to better meet the needs of patients with schizophrenia and their family members.
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Glial choristoma of the middle ear.
Ear Nose Throat J
PUBLISHED: 12-25-2013
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Glial choristomas are isolated masses of mature brain tissue that are found outside the spinal cord or cranial cavity. These masses are rare, especially in the middle ear. We describe the case of an 81-year-old man who presented with left-sided chronic otitis media, mastoiditis, hearing loss, tinnitus, and aural fullness. He was found to have a glial choristoma of the middle ear on the left. Otologic surgeons should be aware of the possibility of finding such a mass in the middle ear and be familiar with the differences in treatment between glial choristomas and the more common encephaloceles.
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Inhibition of Cell Proliferation and Increase of Chemosensitivity by Simultaneous Knockdown of XIAP and Survivin in Pancreatic Carcinoma Cells.
Oncol. Res.
PUBLISHED: 12-17-2013
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At present, classic therapies provide limited benefits to the survival of patients with pancreatic cancer. However, clinically available gene therapy strategies have not been well established. This study investigates the effect of shRNA-mediated inhibition of XIAP and survivin expression on the proliferation, apoptosis, and chemosensitivity of pancreatic cancer cells. Stable inhibition of XIAP and survivin expression in SW1990 and Panc-1 pancreatic cancer cells was established by lentivirus-carried shRNAs. The mRNA and protein expression of XIAP and survivin were detected by real-time PCR and Western blot, respectively. Cell proliferation was measured by MTT assay, and apoptosis was detected by caspase-3/7 activity and Hoechst33342 staining. The lentivirus-carried shRNA significantly inhibited XIAP and survivin expression. Simultaneous inhibition of XIAP and survivin expression in pancreatic cells significantly reduced cell proliferation, increased caspase-3/7 activity, and increased cell sensitization to 5-FU and gemcitabine treatments compared to inhibition of XIAP or survivin expression alone. However, simultaneous silencing of XIAP and survivin showed no significant difference in inducing cell apoptosis compared to silencing of XIAP or survivin expression alone. Simultaneous inhibition of XIAP and survivin expression may be an effective strategy for gene therapy of pancreatic cancer.
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Mercury biomagnification in subtropical reservoir fishes of eastern China.
Ecotoxicology
PUBLISHED: 12-04-2013
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Little is known about mercury (Hg) biomagnification in the subtropics, aquatic systems with high species diversity resulting in complex food webs. High atmospheric Hg emissions and ubiquitous reservoir fisheries may lead to elevated Hg bioaccumulation in Chinese freshwater fishes. However, stocking practices using fast-growing species can result in low fish total Hg (THg) concentrations. Here, we describe Hg transfer within the fish food web of a large subtropical reservoir, Qiandao Hu (Xinanjiang reservoir) situated in eastern China. We measured food web Hg biomagnification and THg concentrations in 33 species of stocked and wild fishes. Mercury concentrations in most fishes were low, though we also found high Hg concentrations in wild top predators. The food web structure, assessed using stable isotopes of carbon (?(13)C) and nitrogen (?(15)N), demonstrated a high degree of omnivory and a long food chain. THg concentrations were highly correlated with fish ?(15)N values. The regression of log10THg against ?(15)N revealed the overall Hg biomagnification rate was low. This study shows that where long food chains exist in subtropical reservoirs, elevated Hg accumulation in top predators can occur despite a low Hg biomagnification rate.
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Size effect of lithium peroxide on charging performance of Li-O2 batteries.
Nanoscale
PUBLISHED: 11-12-2013
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We report herein that the particle size of Li2O2, which is the discharged product of a Li-O2 battery, remarkably influences the charging performance. As the particle size decreases, the average voltage of charge plateaus is lowered due to reduced electrode polarization and enhanced kinetics of the oxidation reaction of Li2O2.
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Synthesis of a Au44(SR)28 nanocluster: structure prediction and evolution from Au28(SR)20, Au36(SR)24 to Au44(SR)28.
Chem. Commun. (Camb.)
PUBLISHED: 11-05-2013
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We report the synthesis of a Au44(SR)28 nanocluster (SR = 4-tert-butylbenzenethiolate). Based on the structural rules learned from the known Au28(SR)20 and Au36(SR)24 structures, we propose a plausible structure for Au44(SR)28, which is predicted to comprise a six-interpenetrating cuboctahedral Au36 kernel protected by four dimeric staples and sixteen bridging thiolates, i.e. Au36[Au2(SR)3]4(SR)16.
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Thermal responsive micelles for dual tumor-targeting imaging and therapy.
Nanoscale
PUBLISHED: 10-30-2013
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Two kinds of thermally responsive polymers P(FAA-NIPA-co-AAm-co-ODA) and P(FPA-NIPA-co-AAm-co-ODA) containing folate, isopropyl acrylamide and octadecyl acrylate were fabricated through free radical random copolymerization for targeted drug delivery. Then the micelles formed in aqueous solution by self-assembly and were characterized in terms of particle size, lower critical solution temperature (LCST) and a variety of optical spectra. MTT assays demonstrated the low cytotoxicity of the control micelle and drug-loaded micelle on A549 cells and Bel 7402 cells. Then fluorescein and cypate were used as model drugs to optimize the constituents of micelles for drug entrapment efficiency and investigate the release kinetics of micelles in vitro. The FA and thermal co-mediated tumor-targeting efficiency of the two kinds of micelles were verified and compared in detail at cell level and animal level, respectively. These results indicated that the dual-targeting micelles are promising drug delivery systems for tumor-targeting therapy.
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Predicting distant metastasis and chemoresistance using plasma miRNAs.
Med. Oncol.
PUBLISHED: 10-22-2013
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In the clinic, predicting metastasis and chemoresistance takes high priority, but has not been well established. This study seeks to investigate whether dynamically monitoring serum microRNAs (miRNAs) can help predict metastasis, chemoresistance, and prognosis of colorectal cancer. Serum miR-155, miR-200c, and miR-210 levels in 15 patients with colon cancer were measured by real-time PCR at different time points post surgery and chemotherapy for 3 years. Significant increases in miR-155, miR-200c, and miR-210 levels were observed in the serum and tumor tissues of colon cancer patients compared to that of healthy subjects. After surgery and chemotherapy, the serum levels of these miRNAs in patients with good prognosis returned to normal levels found in healthy controls during the 3-year follow-up. In patients with recurrence and distant metastasis, serum miR-155, miR-200c, and miR-210 levels remained at an elevated level or became elevated again after a short period of decline. In patients with good response to chemotherapy for metastatic tumors, re-elevation of miR-155 was not significant compared to miR-200c and miR-210. In contrast, miR-155 re-elevated more significantly in patients not sensitized to chemotherapy than miR-200c and miR-210. Our study suggests that re-elevation or sustained elevation of serum miR-155 level after surgery and chemotherapy is a sign of chemoresistance in colon cancer, while high and/or re-elevated miR-155, miR-200c, and miR-210 levels implicate local recurrence and distant metastasis as well as poor prognosis.
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Quaternary Zn-Ag-In-Se quantum dots for biomedical optical imaging of RGD-modified micelles.
ACS Appl Mater Interfaces
PUBLISHED: 10-16-2013
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Exploring the synthesis of new biocompatible quantum dots (QDs) helps in overcoming the intrinsic toxicity of the existing QDs composed of highly toxic heavy metals (e.g., Cd, Hg, Pb, etc.) and is particularly interesting for the future practical application of QDs in biomedical imaging. Hence, in this report, a new one-pot approach to oil-soluble (highly toxic heavy metal-free) highly luminescent quaternary Zn-Ag-In-Se (ZAISe) QDs was designed. Their photoluminescence (PL) emission could be systematically tuned from 660 to 800 nm by controlling the Ag/Zn feed ratio, and their highest PL quantum yield is close to 50% after detailed optimization. Next, by using biodegradable RGD peptide (arginine-glycine-aspartic acid)-modified N-succinyl-N-octyl-chitosan (RGD-SOC) micelles as a water transfer agent, the versatility of these quaternary ZAISe QDs for multiscale bioimaging of micelles (namely, in vitro and in vivo evaluating the tumor targeting of drug carriers) was further explored, as a promising alternative for Cd- and Pb-based QDs.
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Mapping the disease gene in two congenital motor nystagmus families.
Clin. Experiment. Ophthalmol.
PUBLISHED: 10-08-2013
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Congenital nystagmus (CN) is a hereditary disease characterized by bilateral ocular oscillations that occur within the first 6 month of life.(1) Congenital motor nystagmus (CMN) is a subtype of CN that is usually diagnosed after sensory defect nystagmus has been ruled out.(2) Although several inheritance patterns for CMN have been proposed, no causative gene has been identified in most of the reported linkage loci. In this study, two families with CMN (nys-01, nys-02) were investigated for four generations. Family nys-01 included 15 individuals with CMN, 22 normal individuals and 15 spouses, while family nys-02 included 9 individuals with CMN, 9 normal individuals and 8 spouses. This study was approved by the Ethics committee of Nanhua University. The criteria used in this study to diagnose CMN were reported previously(3.)
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Iterative reconstruction of cryo-electron tomograms using nonuniform fast Fourier transforms.
J. Struct. Biol.
PUBLISHED: 09-30-2013
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Algorithms for three-dimensional (3D) reconstruction of objects based on their projections are essential in various biological and medical imaging modalities. In cryo-electron tomography (CET) a major challenge for reconstruction is the limited range of projection angles, which manifests itself as a "missing wedge" of data in Fourier space making the reconstruction problem ill-posed. Here, we apply an iterative reconstruction method that makes use of nonuniform fast Fourier transform (NUFFT) to the reconstruction of cryo-electron tomograms. According to several measures the reconstructions are superior to those obtained using conventional methods, most notably weighted backprojection. Most importantly, we show that it is possible to fill in partially the unsampled region in Fourier space with meaningful information without making assumptions about the data or applying prior knowledge. As a consequence, particles of known structure can be localized with higher confidence in cryotomograms and subtomogram averaging yields higher resolution densities.
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Efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors for Chinese patients with squamous cell carcinoma of lung harboring EGFR mutation.
J Thorac Dis
PUBLISHED: 09-24-2013
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Epidermal growth factor receptor (EGFR) mutation mostly occurred in lung adenocarcinoma, rarely in squamous cell carcinoma (SQCC). EGFR mutation rate in SQCC varied in previous reports, and the efficacy of EGFR tyrosine kinase inhibitors (TKIs) in SQCC harboring EGFR mutation has not yet been fully evaluated. The aim of this study was to investigate the efficacy EGFR-TKIs for Chinese patients with SQCC of lung harboring EGFR mutation.
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Emodin inhibits ATP-induced IL-1? secretion, ROS production and phagocytosis attenuation in rat peritoneal macrophages via antagonizing P2X7 receptor.
Pharm Biol
PUBLISHED: 09-12-2013
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Abstract Context: Previous in vitro studies have demonstrated that emodin (1,3,8-trihydroxy-6-methyl-anthraquinone), an anthraquinone derivative from the rhizome of Rheum palmatum L., can inhibit the activation of P2X7 receptors (P2X7R) as a potential antagonist. However, the effects of emodin on P2X7R-related inflammatory processes remain unclear. Objective: This study aimed to investigate the effects of emodin on different inflammation responses of macrophages induced by ATP, the natural ligand of P2X7R. Materials and methods: Rat peritoneal macrophages were treated with millimolar ATP and emodin (0.1, 0.3,?1,?3,?10?µM) or brilliant blue G (BBG, 0.1,?1,?10?µM). Cytosolic Ca(2+) concentration ([Ca(2+)]c) was detected by fluorescent Ca(2+) imaging. Interleukin-1? (IL-1?) release was measured by rat IL-1? ELISA kits. Reactive oxygen species (ROS) generation was examined by dihydroethidium (DHE) fluorescent staining. Phagocytic activity was tested by neutral red uptake assay. Results: We found that the [Ca(2+)]c increase evoked by ATP (5?mM) was inhibited by emodin, in a dose-dependent manner with IC50 of 0.5??M. Furthermore, emodin reduced the IL-1? release induced by ATP (2?mM) in lipopolysaccharide (LPS)-activated macrophages, with an IC50 of 1.6??M. Emodin also strongly suppressed the ROS production and phagocytosis attenuation triggered by ATP (1?mM), with IC50 values of 1??M and 0.7??M, respectively. Besides, BBG, a specific antagonist of P2X7R, exhibited similar suppressive effects on these inflammation responses. Conclusion: These results showed the inhibitory effects of emodin on ATP-induced [Ca(2+)]c increase, IL-1? release, ROS production and phagocytosis attenuation in rat peritoneal macrophages, by inhibiting the activation of P2X7R.
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Ion-pair dissociation dynamics of O2 in the range 17.2-17.5 eV studied by XUV laser and velocity map imaging method.
J Chem Phys
PUBLISHED: 09-07-2013
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The ion-pair dissociation dynamics of O2, O2 + hv ? O(+)((4)S) + O(-)((2)P(1/2, 3/2)), in the photon energy range 17.20-17.50 eV has been studied using extreme ultraviolet laser and velocity map imaging method. The ion-pair yield spectrum and the fine structure resolved photofragment O(-)((2)P(j)) velocity map images have been recorded. The branching ratios between the two spin-orbit components O(-)((2)P(3/2)) and O(-)((2)P(1/2)) and the corresponding anisotropy parameters describing their angular distributions have been determined. It is found that the fragments O(-)((2)P(1/2)) are all from parallel transitions, while the fragments O(-)((2)P(3/2)) are from both parallel and perpendicular transitions. The main products for most of the excitation photon energies are O(-)((2)P(1/2)). The dissociation dynamics has been discussed based on the ab initio potential energy curves of the ion-pairs. The major peaks in the ion-pair yield spectrum have been assigned based on the angular distribution of the photofragments. The experimental results suggest that the so-called strong and weak series of Rydberg states converging to O2(+)b(4)?g(-) should have symmetries of (3)?u(-) and (3)?u, respectively. In addition to the Rydberg states converging to O2(+)b(4)?g(-), the Rydberg states converging to O2(+)A(2)?u should also play a role in the ion-pair dissociation of O2.
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Tunneling splittings in vibronic energy levels of CH3F+ (X2E) studied by high resolution photoelectron spectroscopy and ab initio calculation.
J Chem Phys
PUBLISHED: 08-17-2013
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The energy levels of CH3F(+) (X(2)E), which show strong vibronic coupling effect (Jahn-Teller effect), have been measured up to 3500 cm(-1) above the ground vibrational state using one-photon zero-kinetic energy photoelectron spectroscopic method. Theoretical calculations have also been performed to calculate the spin-vibronic energy levels using a diabatic model and ab initio adiabatic potential energy surfaces (APESs) including the energy gradients and derivative couplings between the APESs. The calculations showed that the tunneling splittings of the vibrational energy levels occur due to the deep potential energy wells formed by the Jahn-Teller deformation. The calculated spin-vibronic energy levels are in good agreement with the experimental data. For example, the energy splitting for the first excited vibrational energy level is calculated as 111 cm(-1) that is confirmed by the experimental value. The experimental spectrum was assigned based on the fundamental vibrational modes calculated at the energy minimum. The fundamental vibrational modes related to the H-C-F bending, H-C-H bending, C-F stretching, and C-H stretching vibrations have been observed.
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Amino ozonides exhibit in vitro activity against Echinococcus multilocularis metacestodes.
Int. J. Antimicrob. Agents
PUBLISHED: 08-16-2013
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Artemisinin is an antimalarial sesquiterpene lactone that contains a 1,2,4-trioxane heterocycle. Dihydroartemisinin and artesunate demonstrated activity against Echinococcus multilocularis metacestodes in vitro but were not effective in a mouse model. In this study, the in vitro effects of a small library of synthetic ozonides (1,2,4-trioxolanes) were investigated. Initial compound screening against E. multilocularis metacestodes was performed at 20?M, and selected ozonides were further assessed in dose-response studies in metacestode cultures and mammalian cells. Transmission electron microscopy (TEM) was employed to characterise compound-induced structural alterations. At 20?M, the most potent ozonides (OZ401, OZ455, OZ491 and OZ494) led to death of ca. 60-100% of the parasites. Subsequent dose-response experiments demonstrated that OZ401, OZ455 and OZ491, which contain an aminopropylether substructure, were the most potent, with 50% inhibitory concentrations ranging from 11?M to 14?M. Cytotoxicity for these three ozonides, assessed in human foreskin fibroblasts, rat hepatoma cells and green monkey epithelial kidney (Vero) cells, was evident only at high concentrations. TEM demonstrated that OZ401 and OZ491 treatment induced considerable metabolic impairment in metacestodes at 1 day post exposure. At Day 3 post exposure, the germinal layer was severely distorted, although some intact cells were still visible, demonstrating that not all cell types in the parasite tissue were equally affected. Complete destruction of the germinal layer was noted at 5 days post exposure. Synthetic ozonides could represent interesting leads that will be further investigated in a suitable in vivo model of E. multilocularis infection.
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Coherent photon interference elimination and spectral correction in femtosecond time-resolved fluorescence non-collinear optical parametric amplification spectroscopy.
Rev Sci Instrum
PUBLISHED: 08-02-2013
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We report an improved setup of femtosecond time-resolved fluorescence non-collinear optical parametric amplification spectroscopy (FNOPAS) with a 210 fs temporal response. The system employs a Cassegrain objective to collect and focus fluorescence photons, which eliminates the interference from the coherent photons in the fluorescence amplification by temporal separation of the coherent photons and the fluorescence photons. The gain factor of the Cassegrain objective-assisted FNOPAS is characterized as 1.24 × 10(5) for Rhodamine 6G. Spectral corrections have been performed on the transient fluorescence spectra of Rhodamine 6G and Rhodamine 640 in ethanol by using an intrinsic calibration curve derived from the spectrum of superfluorescence, which is generated from the amplification of the vacuum quantum noise. The validity of spectral correction is illustrated by comparisons of spectral shape and peak wavelength between the corrected transient fluorescence spectra of these two dyes acquired by FNOPAS and their corresponding standard reference spectra collected by the commercial streak camera. The transient fluorescence spectra of the Rhodamine 6G were acquired in an optimized phase match condition, which gives a deviation in the peak wavelength between the retrieved spectrum and the reference spectrum of 1.0 nm, while those of Rhodamine 640 were collected in a non-optimized phase match condition, leading to a deviation in a range of 1.0-3.0 nm. Our results indicate that the improved FNOPAS can be a reliable tool in the measurement of transient fluorescence spectrum for its high temporal resolution and faithfully corrected spectrum.
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The cyclophilin CYP20-2 modulates the conformation of BRASSINAZOLE-RESISTANT1, which binds the promoter of FLOWERING LOCUS D to regulate flowering in Arabidopsis.
Plant Cell
PUBLISHED: 07-29-2013
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Brassinosteroids (BRs) regulate many physiological processes during plant development, including flowering. However, little is known about the components of BR signaling that mediate flowering. Here, we report that BRASSINAZOLE-RESISTANT1 (BZR1), the conformation of which is altered by a cyclophilin (CYP20-2), binds cis-elements in the FLOWERING LOCUS D (FLD) promoter to regulate flowering. Both bzr1-1D and fld-4 showed delayed flowering. Electrophoretic mobility shift assay and chromatin immunoprecipitation revealed that BZR1 bound to a putative BR response cis-element and suppressed the expression of FLD. Overexpression of FLD partially rescued the late flowering of pBZR1:mBZR1(Pro234-Leu)-CFP (mx3). Yeast two-hybrid and pull-down assays demonstrated that BZR1 interacts with CYP20-2. Arabidopsis thaliana CYP20-2 had greater peptidyl-prolyl cis-trans isomerase activity than did wheat (Triticum aestivum) CYP20-2. Fourier transform infrared spectroscopy revealed conformation changes in BZR1, dependent on interaction with CYP20-2. Due to differences in activity and substrate preference between CYP20-2 proteins from wheat and Arabidopsis, At-CYP20-2-overexpressing lines showed earlier flowering, whereas Ta CYP20-2 lines flowered later. Immunoblot and chromatin immunoprecipitation assays showed that histone H3 trimethyl Lys4 and H3 acetylation levels were negatively correlated with the transcription of FLD (a putative histone demethylase) in various lines. Therefore, a conformational change of BZR1 mediated by CYP20-2 causes altered flowering through modulation of FLD expression.
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Whole transcriptome sequencing reveals genes involved in plastid/chloroplast division and development are regulated by the HP1/DDB1 at an early stage of tomato fruit development.
Planta
PUBLISHED: 07-24-2013
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The phenotype of tomato high pigment-1 (hp1) mutant is characterized by overproduction of pigments including chlorophyll and carotenoids during fruit development and ripening. Although the increased plastid compartment size has been thought to largely attribute to the enhanced pigmentation, the molecular aspects of how the HP1/DDB1 gene manipulates plastid biogenesis and development are largely unknown. In the present study, we compared transcriptome profiles of immature fruit pericarp tissue between tomato cv. Ailsa Craig (WT) and its isogenic hp1 mutant. Over 20 million sequence reads, representing > 1.6 Gb sequence data per sample, were generated and assembled into 21,972 and 22,167 gene models in WT and hp1, respectively, accounting for over 60 % official gene models in both samples. Subsequent analyses revealed that 8,322 and 7,989 alternative splicing events, 8833 or 8510 extended 5-UTRs, 8,263 or 8,939 extended 3-UTRs, and 1,136 and 1,133 novel transcripts, exist in WT and hp1, respectively. Significant differences in expression level of 880 genes were detected between the WT and hp1, many of which are involved in signaling transduction, transcription regulation and biotic and abiotic stresses response. Distinctly, RNA-seq datasets, quantitative RT-PCR analyses demonstrate that, in hp1 mutant pericarp tissue at early developmental stage, an apparent expression alteration was found in several regulators directly involved in plastid division and development. These results provide a useful reference for a more accurate and more detailed characterization of the molecular process in the development and pigmentation of tomato fruits.
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Hypoperfusion and T1-hypointense lesions in white matter in multiple sclerosis.
Mult. Scler.
PUBLISHED: 07-08-2013
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Longitudinal magnetic resonance imaging (MRI) studies show that a fraction of the multiple sclerosis (MS) T2-lesions contain T1-hypointense components that may persist to represent severe, irreversible tissue damage. It is not known why certain lesions convert to persistent T1-hypointense lesions.
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