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Find video protocols related to scientific articles indexed in Pubmed.
Fluorofenidone Attenuates TGF-?1-Induced Lung Fibroblasts Activation via Restoring the Expression of Caveolin-1.
Shock
PUBLISHED: 11-14-2014
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Caveolin-1 plays an important role in the pathogenesis of idiopathic pulmonary fibrosis. We previously showed that fluorofenidone (FD), a novel pyridine agent, can attenuate bleomycin (BLM)-induced experimental pulmonary fibrosis and restore the production of caveolin-1. In this study, we explore mainly whether caveolin-1 plays a critical role in the anti-pulmonary fibrosis effects of FD in vitro. The normal human lung fibroblasts (NHLFs) were cultured with transforming growth factor?1(TGF-?1) and then were treated with FD. Subsequently, NHLFs transfected with cav-1-siRNA were treated with TGF-?1 and/or FD. The expressions of ?-smooth muscle actin (?-SMA), fibronectin, collagen I, caveolin-1, p-ERK, p-JNK, and p-P38 were measured by Western blot and/or real-time PCR. FD attenuated TGF-?1-induced expressions of ?-SMA, fibronectin and collagen I; inhibited phosphorylation of ERK, JNK, and P38; and restored caveolin-1 protein expression, but can not increase caveolin-1 mRNA level in vitro. After caveolin-1 was silenced, FD could not down-regulate TGF-?1-induced expressions of ?-SMA, fibronectin, collagen I expressions or phosphorylation of ERK, JNK, and P38. These studies demonstrate that FD, a potential anti-fibrotic agent, may attenuated TGF-?1-induced activation of NHLFs by restoring the expression of caveolin-1.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.
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Addition of optically pure H-phosphinate to ketones: selectivity, stereochemistry and mechanism.
Org. Biomol. Chem.
PUBLISHED: 10-20-2014
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Aromatic methyl ketones and cyclic asymmetric ketones underwent hydrophosphorylation with P-stereogenic H-P species in the presence of potassium carbonate to produce P,C-stereogenic tertiary ?-hydroxyl phosphinates in excellent yields with up to 99?:?1 dr. The diastereoselectivity was induced by a reversible conversion of less stable stereomer of product to that of a more stable one via an equilibrium, which was confirmed by aldehyde/ketone exchanging reaction. Toward the exchange, aliphatic or aldehyde carbonyl were more active than aromatic or ketone carbonyls, respectively. The stability difference between the two diastereomers was controlled by the sizes of substituents linking to phosphorus or ?-carbon.
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[Construction of prokaryotic expression vector for Ag85A-HA2 fusion gene and studies on the immunity efficacy of fusion protein against influenza A virus].
Sichuan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 10-08-2014
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To construct Ag85A-HA2 prokaryotic expression vector, express the fusion protein and study the immunity efficacy of fusion protein against influenza A virus.
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The Gateway Reflex, which is mediated by the inflammation amplifier, directs pathogenic immune cells into the CNS.
J. Biochem.
PUBLISHED: 10-06-2014
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The brain-blood barrier (BBB) tightly limits immune cell migration into the central nervous system (CNS), avoiding unwanted inflammation under the normal state. However, immune cells can traverse the BBB when inflammation occurs within the CNS, suggesting a certain signal that creates a gateway that bypasses the BBB might exist. We revealed the inflammation amplifier as a mechanism of this signal, and identified dorsal vessels of the fifth lumber (L5) spinal cord as the gateway. The inflammation amplifier is driven by a simultaneous activation of NF-?B and STATs in non-immune cells, causing the production of a large amount of inflammatory chemokines to open the gateway at L5 vessels. It was found that the activation of the amplifier can be modulated by neural activation and artificially operated by electric pulses followed by establishment of new gateways, Gateway Reflex, at least in mice. Furthermore, genes required for the inflammation amplifier have been identified and are highly associated with various inflammatory diseases and disorders in the CNS. Thus, physical and/or pharmacological manipulation of the inflammation amplifier holds therapeutic value to control neuro-inflammation.
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Losartan inhibits LPS + ATP-induced IL-1beta secretion from mouse primary macrophages by suppressing NALP3 inflammasome.
Pharmazie
PUBLISHED: 10-03-2014
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IL-1beta is a potent proinflammatory, pro-fibrogenetic and pro-athrosclerosis cytokine which has been shown to play an important role in an expanding number of noninfectious, chronic inflammatory conditions including cardiovascular disease, renal fibrosis, rheumatoid arthritis and even type 2 diabetes. Losartan is an angiotensin II receptor antagonist widely used for the treatment of hypertension, diabetic nephropathy and congestive heart failure. In this study, we attempted to clarify whether losartan has an inhibitory effect on IL-1beta. To further elucidate the molecular mechanism underlying the anti-IL-1beta property of losartan, we studied the LPS+ATP-induced activation of NALP3 inflammasome which controls the muturation and secretion of IL-1beta.
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[Clinical implication of urinary protein markers in diabetic nephropathy and interventional effects of Chinese herbal medicine].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 10-03-2014
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In clinic, some urinary protein makers can dynamically and noninvasively reflect the degree of renal tubular injury in patients with diabetic nephropathy (DN). These urinary biomarkers of tubular damage are broadly divided into two categories. One is newfound, including kidney injury molecule-1 (Kim-1), neutrophil getatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP) and cystatin C (CysC); the other one is classical, including beta2 microglobulin (beta2-MG), retinal binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG). It is reported that, the increases in urinary protein markers are not only closely related to the damage of tubular epithelial cells in DN patients, but also can be ameliorated by the treatment with Chinese herbal compound preparations or Chinese herbal medicine. Recently, although urinary proteomics are used in the protein separation and identification, the traditional associated detection of urinary protein markers is more practical in clinic. At present, it is possible that the associated detection of urinary biomarkers of glomerular and tubular damages may be a feasible measure to reveal the clinical significance of urinary protein markers in DN patients and the interventional effects of Chinese herbal medicine.
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Doxycycline as an Inhibitor of the Epithelial-to-Mesenchymal Transition and Vasculogenic Mimicry in Hepatocellular Carcinoma.
Mol. Cancer Ther.
PUBLISHED: 10-02-2014
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This study was conducted to examine the effects of doxycycline on the survival time and proliferation of hepatocellular carcinoma (HCC) in vivo and on the biological functions of HCC in vitro. This study was also designed to evaluate the effects of doxycycline on epithelial-to-mesenchymal transition (EMT)- and vasculogenic mimicry (VM)-related protein expression and on matrix metalloproteinase (MMP) and DNA methyltransferase (DNMT) activity in vitro. Human MHCC97H cells were injected into BALB/c mice, which were divided into treatment and control groups. Doxycycline treatment prolonged the mouse survival time and partly suppressed the growth of engrafted HCC tumor cells, with an inhibition rate of 43.39%. Higher amounts of VM and endothelium-dependent vessels were found in the control group than the treatment group. Immunohistochemistry indicated that epithelial (E)-cadherin expression was increased in the doxycycline-treated mice compared with the control group. In in vitro experiments, doxycycline promoted HCC cell adhesion but inhibited HCC cell viability, proliferation, migration, and invasion. Western blots, semi-quantitative RT-PCR, quantitative real-time PCR, and immunofluorescence demonstrated that doxycycline inhibited the degradation of the epithelial marker E-cadherin and downregulated the expression levels of EMT promoters, the mesenchymal marker vimentin, and the VM-associated marker vascular endothelial (VE)-cadherin. Furthermore, the activities of MMPs and DNMTs were examined in different groups via gelatin zymography and a DNMT activity assay kit. A methylation-specific polymerase chain reaction (MSP) was performed to assess the promoter methylation of CDH1 (the gene encoding E-cadherin). Doxycycline prolonged the mouse survival time by inhibiting EMT progression and VM formation.
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Asymmetric Synthesis of Planar Chiral Ferrocenes by Enantioselective Intramolecular C-H Arylation of N-(2-Haloaryl)ferrocenecarboxamides.
Org. Lett.
PUBLISHED: 09-29-2014
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The palladium-catalyzed intramolecular C-H arylation reaction of N-(2-bromoaryl)ferrocenecarboxamides furnishes planar chiral ferrocene derivatives. TADDOL-derived phosphoramide ligands induce enantioselectivities ranging from 91:9 to 98:2 er.
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[Synthesis of two-organic complexes and characterization of their adsorption behaviour of ten polycyclic aromatic hydrocarbons].
Se Pu
PUBLISHED: 09-27-2014
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Metal-organic frameworks (MOFs) are concerned mainly due to the unusual properties for diverse analytical applications, such as high surface area, good thermal stability, inpore functionally and outer-surface modification. Two metal-organic complexes were prepared by two methods of hydrothermal synthesis and room temperature synthesis, separately. The compositions, structures, thermal stability and adsorption properties of the two complexes were characterized by X-ray powder diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and Brunauer-Emmett-Teller (BET) method, which indicated that the two complexes have not only good thermal stability but also good adsorption for polycyclic aromatic hydrocarbons (PAHs). PAHs enter into environment leading to pollution by industrial and agricultural production and life, rooting in the incomplete combustion or pyrolysis of organism. PAHs are strongly carcinogenic and mutagenic. Some PAHs are considered as endocrine disruptors, and maybe have biological effects on human health. Regulations have thus been formulated for monitoring and controlling PAHs by the United States Environmental Protection Agency (U.S. EPA) and other government agencies. Adsorption kinetic of PAHs on the two complexes could be well described by the pseudo-second order kinetic model, and the adsorption behaviors of the two complexes on PAHs are in accord with Langmuir model. In addition, the adsorption capacities increase with the increasing adsorbent dosage. It is proved by the FT-IR data that pi-pi interactions between the PAHs and the framework terephthalic acid molecules. Ten PAHs were adsorbed well on the two complexes which have good adsorptive selectivity. By further optimizing of the two complex materials, it is promising to use them as chromatographic stationary phases.
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Simulation and comparison of progression-free survival among patients with non-squamous non-small-cell lung cancer receiving sequential therapy.
Expert Rev Anticancer Ther
PUBLISHED: 09-25-2014
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Objectives: In recent years, the treatment landscape in advanced non-squamous non-small-cell lung cancer (nsNSCLC) has changed. New therapies (e.g., bevacizumab indicated in first line) have become available and other therapies (e.g., pemetrexed in first line and second line) moved into earlier lines in the treatment paradigm. While there has been an expansion of the available treatment options, it is still a key research question which therapy sequence results in the best survival outcomes for patients with nsNSCLC. Methods: A therapy-sequencing disease model that approximates treatment outcomes in up to five lines of treatment was developed for patients with nsNSCLC. The primary source of data for progression-free survival (PFS) and time to death was published pivotal trial data. All patients were treatment-naïve and in the PFS state, received first-line treatment with either bevacizumab-based therapy or doublet chemotherapy (including the option of pemetrexed + cisplatin). Patients would then progress to a subsequent line of therapy, remain in PFS or die. In case of progression, it was assumed that each survivor would receive a subsequent line of therapy, based on EMA licensed therapies. Weibull distribution curves were fitted to the data. Results: All bevacizumab-based first-line therapy sequences analyzed achieved total PFS of around 15 months. Bevacizumab + carboplatin + paclitaxel (first line) ? pemetrexed (second line) ? erlotinib (third line) ? docetaxel (fourth line) resulted in total mean PFS time of 15.7 months, for instance. Sequences with pemetrexed in combination with cisplatin in first line achieved total PFS times between 12.6 and 12.8 months with a slightly higher total PFS time achieved when assuming pemetrexed continuation therapy in maintenance after pemetrexed + cisplatin in first-line induction. Overall survival results followed the same trend as PFS. Conclusion: The model suggests that treatment-sequencing strategies starting with a bevacizumab-based combination in first line yield better survival outcomes than those starting with pemetrexed-based combinations, a result that is attributable to the possibility of one further line of treatment with first-line bevacizumab-based treatment sequences.
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Functional changes in pulmonary arterial endothelial cells associated with BMPR2 mutations.
PLoS ONE
PUBLISHED: 09-04-2014
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Pulmonary arterial hypertension (PAH) is a devastating disease characterized by abnormal remodeling of small, peripheral pulmonary arteries. Germline mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene are a major risk factor for developing PAH. At present, the correlation between the BMPR2 mutation and the patient's prognosis remains controversial despite several investigations. In this study, we explored the functional effects of four BMPR2 mutations to dissect the functional significance of the BMPR2 gene defect. Cellular immunofluorescence assay of four mutants (Tyr67Cys, Thr268fs, Ser863Asn, and Gln433X) revealed that the BMPR2 protein containing Thr268fs, Ser863Asn, or Gln433X exhibited abnormal subcellular localization. The BrdU incorporation and TUNEL assay suggested that any of the BMPR2 mutations Thr268fs, Ser863Asn, or Gln433X could improve endothelial cell apoptosis and decrease cell proliferation. All of the four mutants could inhibit nitric oxide (NO) synthesis in HLMVE cells, and ET-1 levels increased in the cells transfected with mutant Ser863Asn. Our results will improve the understanding of the genotype-phenotype correlations and mechanisms associated with BMPR2 mutations.
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Adaptable synthesis of C-lactosyl glycoclusters and their binding properties with galectin-3.
Org. Biomol. Chem.
PUBLISHED: 09-03-2014
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We report here the syntheses of mono- to tetravalent glycoclusters containing 1-methylene-C-?-lactose. The 1-methylene-C-?-lactose moiety has been synthesized from octa-acetyl-?-lactose using the key carbonyl insertion reaction and linked to a series of alkynlated scaffolds via CuAAC reaction to afford mono- to tetravalent glycoclusters. The binding affinities of the final products to galectin-3 were found in the range of 10-100 ?M.
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Vertically Architectured Stack of Multiple Graphene Field-Effect Transistors for Flexible Electronics.
Small
PUBLISHED: 08-13-2014
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Vertically architectured stack of multiple graphene field-effect transistors (GFETs) on a flexible substrate show great mechanical flexibility and robustness. The four GFETs are integrated in the vertical direction, and dually gated GFETs with graphene channel, PMMA dielectrics, and graphene gate electrodes are realized.
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[Effects of hormone treatment, light and temperatures on sprouting characteristics of Bupleurum chinense].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 07-22-2014
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Seeds of Bupleurum chinense cultivar, Zhongchai No. 1, were sowed in plastic pots which used the arable layer soil as the nursery bed and putted in the artificial climate incubator at various temperatures (15, 20, 25, 15-25 degrees C) and light (8,12 h) to germinate, respectively. The lower constant temperature (15 degrees ) and the higher constant temperature (25 "C) were not conducive to the sprouting characteristics of B. chinese. While they were able to enhance root activity to some extent; The seeding growth of B. chinese was significantly better in the variable temperature than correspondence in the constant temperature, significantly. The emergence speed, emergence index, vigor index and root activity of Bupleurum were improved under the 12 h of light-time, but the germination rate was not improved. The sprouting of Bupleurum's seeds could be improved to some extent by soaking with hormone, such as gibberellin, cytokinin, salicylic acid. Gibberellin promoted seeds' sprouting and seedings's root activity of Bupleurum, while salicylic acid increased the root activity of seeding. There is a significant influence of light, temperatures and hormone treatment on the germination of Zhongchai No. 1 seeds, and all three are remarkably interacted; It is beneficial to promote seed germination by the temperature (20 + 5) degrees C, lighting (8 h) and gibberellin concentration (10 x 10(-6)).
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High quality and large-scale manually operated monolayer graphene pasters.
Nanotechnology
PUBLISHED: 06-24-2014
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Graphene is a well-known material with various potential applications. Here we report the manufacture of high-quality and large-scale monolayer graphene pasters via polyvinyl butyral (PVB). These pasters have good self-supporting properties and overcome the drawback of weak mechanical strength of PMMA. Manual manipulations to monolayer graphene become realizable via graphene pasters. Graphene pasters can be quickly diverted onto any substrate with sufficient contact and greatly minimize the challenges in graphene transfer, measurements, and other applications. The improved transfer process via graphene pasters protects the integrity of monolayer graphene and introduces few cracks or tears into graphene. Large-scale monolayer graphene films diverted onto SiO2/Si by using graphene pasters maintain low resistivity and low Dirac point, while also exhibiting a higher magnetoresistance than traditional results. High magnetoresistance up to 600% and signs of saturation at high magnetic fields can be seen. Obvious negative magnetoresistance at low magnetic fields due to weak localization also can be observed. Graphene pasters can be used in many different domains and will promote future studies and applications of graphene.
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[Evaluation of Bupleuri Radix resources in Qingchuan based on DTOPSIS and grey related degree].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 06-21-2014
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In order to select high quality and suitable Bupleuri Radix varieties in Qingchuan, and establish a new comprehensive method to evaluation the quality of Bupleuri Radix, 12 characters of 14 samples were evaluated by DTOPSIS and grey related degree. The results showed that varieties No. 8 and No. 10 had high quality. DTOPSIS and grey related degree gave the uniformity result, and the biggest difference of value of Ci in DTOPSIS method was 46. 33% , but the biggest difference of the weighting correlation number( r (i)) in grey related degree was only 13.10%. The DTOPSIS combined with grey related degree can evaluate the quality of Bupleuri Radix comprehensively and objectively.
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Alternative splicing and immune response of Crassostrea gigas tumor necrosis factor receptor-associated factor 3.
Mol. Biol. Rep.
PUBLISHED: 06-19-2014
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Diverse alternative splicing isoforms play an important role in immune diversity and specificity. Their role in molluscan host-defense is however poorly understood. We characterized two alternative isoforms of tumor necrosis factor receptor-associated factor 3 (TRAF3) in the Pacific oyster, Crassostrea gigas, which were named CgTRAF3-S and CgTRAF3-L. An intron was retained in CgTRAF3-L, introducing a premature termination codon. Comparison and phylogenetic analysis revealed that CgTRAF3 shared a higher identity with other species, suggesting the conservation of the two gene transcripts. Quantitative real-time PCR was performed and the expression levels of CgTRAF3 isoforms were found to be significantly changed after Vibrio anguillarum and ostreid herpesvirus 1 challenges. These two isoforms represented contrary trends, indicating that CgTRAF3-L might function as a negative regulator of CgTRAF3-S. We also investigated the expression level of the transcripts of the two CgTRAF3 isoforms, following the silence of C. gigas mitochondrial anti-viral signaling protein like gene (CgMAVS-like). We concluded that CgTRAF3 might be involved in a MAVS-mediated immune signaling pathway. This study suggests that CgTRAF3 may be a response to bacterial and viral stimulation and that the two isoforms may be involved in immune response pathways. It is also possible that the two alternative splicing isoforms could be inter-coordinated and may promote survival of these oysters under immune stress conditions.
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A designed peptide targeting CXCR4 displays anti-acute myelocytic leukemia activity in vitro and in vivo.
Sci Rep
PUBLISHED: 06-05-2014
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Leukemia cells highly expressing chemokine receptor CXCR4 can actively response to stroma derived factor 1? (CXCL12), trafficking and homing to the marrow microenvironment, which causes poor prognosis and relapse. Here we demonstrate that a novel designed peptide (E5) targeting CXCR4 inhibits CXCL12- and stroma-induced activation in multiple acute myelocytic leukemia (AML) cell lines and displays anti-AML activity. We show that E5 has high affinity to multiple AML cells with high CXCR4 level in a concentration dependent manner. E5 significantly inhibits CXCL12- or murine stromal cell (MS-5)-induced migration of leukemia cells and prevents the cells from adhering to stromal cells. Mechanistic studies demonstrate that E5 down-regulates CXCL12-induced phosphorylation of Akt, Erk, and p38, which affects the cytoskeleton F-actin organization and ultimately results in the inhibition of CXCL12- and stroma-mediated leukemia cell responses. E5 can induce concentration-dependent apoptosis in the four AML cell lines tested while did not affect the viability of MS-5 or human umbilical vein cell (ea.hy926) even at 80?µM, both of which have a low level of CXCR4. In vivo experimental results show that immunocompromised mice transplanted with HL-60 cells survived longer when treated with E5 twice a week in comparison to those treated with cyclophosphamide.
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Engineered cytidine triphosphate synthetase with reduced product inhibition.
Protein Eng. Des. Sel.
PUBLISHED: 06-05-2014
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Cytidine triphosphate (CTP) synthetase (CTPS) (EC number 6.3.4.2) is a key enzyme involved in de novo synthesis of CTP. It catalyzes the rate-limiting step of the process due to the product inhibition effects on the enzyme. In this study, a novel CTPS from Corynebacterium glutamicum ATCC 13032 (CgCTPS) was cloned, expressed and characterized. A series of mutagenesis in its N-terminal ammonia ligase (ALase) domain was performed in order to reduce CTP product inhibition. All single mutation variants (D160E, E162A, E168K) lowered product inhibition by lowering the enzyme's binding affinity for CTP. The homology model of CgCTPS showed that D160E mutant caused steric hindrance for the pyrimidine ring of CTP stacking, E162A disrupted the hydrogen bond between CTP ribose and side chain and D168K caused minor localized structure perturbations of CTP binding pocket. The triple mutant of CTPS (D160E-E162A-E168K) with halved Km, doubled Vmax and the 23.5-fold increased IC50 for CTP shows a potential for use in industrial-scale CTP production by its better performance in enzyme kinetics and product inhibition.
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Fabrication and electrical properties of stacked graphene monolayers.
Sci Rep
PUBLISHED: 04-07-2014
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We develop a simple method to fabricate the two-stacked graphene monolayers and investigate the electronic transport in such a system. The independence of the two graphene monolayers gives rise to the asymmetric resistance-gate voltage curves and an eight-fold degeneracy of Landau level. The position of the maximum resistance of the transfer curves shifts towards higher gate voltage with increasing magnetic field, which is attributed to the magnetic field induced interlayer decoupling of the stacked graphene monolayers.
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A comparison between the pectoralis major myocutaneous flap and the free anterolateral thigh perforator flap for reconstruction in head and neck cancer patients: assessment of the quality of life.
J Craniofac Surg
PUBLISHED: 04-05-2014
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Our study investigated the quality of life (QoL) of Chinese patients after immediate reconstruction surgery on individuals with head and neck cancer. In addition, we compared the differences between pectoralis major myocutaneous flap (PMMF) and anterolateral thigh free flap (ALTFF). The University of Washington Quality of Life questionnaire, version 4, was used to assess the QoL. Assessments were performed at least 24 months postoperatively. A total of 110 patients' records were obtained. Among them, 86 patients completed a QoL questionnaire (78.2%). No significant differences could be found in age, primary site, T stage, N stage, and postoperative radiotherapy between PMMF and ALTFF groups. However, there were significant differences between both groups in sex, operation time, and complication. A matched analysis was performed to compare the differences in QoL between patients with head and neck cancers reconstructed with PMMF or ALTFF. Patients reconstructed with ALTFF had better shoulder but worse speech functions. There was a significant effect on the QoL of head and neck cancer patients who had undergone either PMMF or ALTFF reconstruction. The result of this study provide useful information for physicians and patients during their discussion of treatment modalities for head and neck cancers.
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Temporal variability in urinary levels of drinking water disinfection byproducts dichloroacetic acid and trichloroacetic acid among men.
Environ. Res.
PUBLISHED: 03-18-2014
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Urinary haloacetic acids (HAAs), such as dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), have been suggested as potential biomarkers of exposure to drinking water disinfection byproducts (DBPs). However, variable exposure to and the short elimination half-lives of these biomarkers can result in considerable variability in urinary measurements, leading to exposure misclassification. Here we examined the variability of DCAA and TCAA levels in the urine among eleven men who provided urine samples on 8 days over 3 months. The urinary concentrations of DCAA and TCAA were measured by gas chromatography coupled with electron capture detection. We calculated the intraclass correlation coefficients (ICCs) to characterize the within-person and between-person variances and computed the sensitivity and specificity to assess how well single or multiple urine collections accurately determined personal 3-month average DCAA and TCAA levels. The within-person variance was much higher than the between-person variance for all three sample types (spot, first morning, and 24-h urine samples) for DCAA (ICC=0.08-0.37) and TCAA (ICC=0.09-0.23), regardless of the sampling interval. A single-spot urinary sample predicted high (top 33%) 3-month average DCAA and TCAA levels with high specificity (0.79 and 0.78, respectively) but relatively low sensitivity (0.47 and 0.50, respectively). Collecting two or three urine samples from each participant improved the classification. The poor reproducibility of the measured urinary DCAA and TCAA concentrations indicate that a single measurement may not accurately reflect individual long-term exposure. Collection of multiple urine samples from one person is an option for reducing exposure classification errors in studies exploring the effects of DBP exposure on reproductive health.
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Screening for voltage-gated sodium channel interacting peptides.
Sci Rep
PUBLISHED: 03-18-2014
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The voltage-gated sodium channel (VGSC) interacting peptide is of special interest for both basic research and pharmaceutical purposes. In this study, we established a yeast-two-hybrid based strategy to detect the interaction(s) between neurotoxic peptide and the extracellular region of VGSC. Using a previously reported neurotoxin JZTX-III as a model molecule, we demonstrated that the interactions between JZTX-III and the extracellular regions of its target hNav1.5 are detectable and the detected interactions are directly related to its activity. We further applied this strategy to the screening of VGSC interacting peptides. Using the extracellular region of hNav1.5 as the bait, we identified a novel sodium channel inhibitor SSCM-1 from a random peptide library. This peptide selectively inhibits hNav1.5 currents in the whole-cell patch clamp assays. This strategy might be used for the large scale screening for target-specific interacting peptides of VGSCs or other ion channels.
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Ureic clearance granule, alleviates renal dysfunction and tubulointerstitial fibrosis by promoting extracellular matrix degradation in renal failure rats, compared with enalapril.
J Ethnopharmacol
PUBLISHED: 03-01-2014
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Chinese herbal compound prescription has a unique therapeutic action on chronic kidney disease (CKD) in China. In clinics, Uremic Clearance Granules (UCG), a compounded Chinese patent medicine, has been frequently used to treat chronic renal failure (CRF) patients for nearly 30 years, however, the deep therapeutic mechanisms involved in vivo remain a challenge. This study aims to demonstrate the effects and mechanisms of UCG on renal dysfunction and tubulointerstitial fibrosis by regulating extracellular matrix (ECM) degradation and transforming growth factor (TGF)-beta1/Smad signaling activity in vivo, compared with enalapril.
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Association of heme oxygenase-1 with the risk of polycystic ovary syndrome in non-obese women.
Hum. Reprod.
PUBLISHED: 02-28-2014
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Is circulating heme oxygenase-1 (HO-1) associated with the risk of polycystic ovary syndrome (PCOS)?
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Size-Dependent Nonlinear Optical Properties of Atomically Thin Transition Metal Dichalcogenide Nanosheets.
Small
PUBLISHED: 02-27-2014
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Size-dependent nonlinear optical properties of modification-free transition metal dichalcogenide (TMD) nanosheets are reported, including MoS2 , WS2 , and NbSe2 . Firstly, a gradient centrifugation method is demonstrated to separate the TMD nanosheets into different sizes. The successful size separation allows the study of size-dependent nonlinear optical properties of nanoscale TMD materials for the first time. Z-scan measurements indicate that the dispersion of MoS2 and WS2 nanosheets that are 50-60 nm thick leads to reverse saturable absorption (RSA), which is in contrast to the saturable absorption (SA) seen in the thicker samples. Moreover, the NbSe2 nanosheets show no size-dependent effects because of their metallic nature. The mechanism behind the size-dependent nonlinear optical properties of the semiconductive TMD nanosheets is revealed by transient transmission spectra measurements.
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Fluorofenidone attenuates inflammation by inhibiting the NF-?B pathway.
Am. J. Med. Sci.
PUBLISHED: 02-19-2014
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Accumulated evidence indicates that inflammation plays a critical role in the progression of many renal diseases. Fluorofenidone (AKF-PD) has been shown to attenuate renal fibrosis in a number of experimental renal fibrosis models. The aim of this study was to assess the anti-inflammatory effect of AKF-PD.
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Antifatigue properties of dragonfly Pantala flavescens wings.
Microsc. Res. Tech.
PUBLISHED: 02-06-2014
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The wing of a dragonfly is thin and light, but can bear high frequent alternating stress and present excellent antifatigue properties. The surface morphology and microstructure of the wings of dragonfly Pantala flavescens were observed using SEM in this study. Based on the biological analysis method, the configuration, morphology, and structure of the vein were studied, and the antifatigue properties of the wings were investigated. The analytical results indicated that the longitudinal veins, cross veins, and membrane of dragonfly wing form a optimized network morphology and spacially truss-like structure which can restrain the formation and propagation of the fatigue cracks. The veins with multilayer structure present high strength, flexibility, and toughness, which are beneficial to bear alternating load during the flight of dragonfly. Through tensile-tensile fatigue failure tests, the results were verified and indicate that the wings of dragonfly P. flavescens have excellent antifatigue properties which are the results of the biological coupling and synergistic effect of morphological and structural factors.
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Fibulin-3 suppresses Wnt/?-catenin signaling and lung cancer invasion.
Carcinogenesis
PUBLISHED: 01-30-2014
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The 5 year survival rate of lung cancer is <20%, with most patients dying from distant metastasis. However, the molecular mechanisms underlying lung cancer invasion and metastasis have not been fully characterized. In this study, we found that fibulin-3, a fibulin family extracellular matrix protein, functions as a suppressor of lung cancer invasion and metastasis. Fibulin-3 was downregulated in large fractions of lung tumors and cell lines, and inhibited lung cancer cell invasion and the expression of matrix metalloproteinase-7 (MMP-7), a promoter of lung cancer invasion. The expression levels of fibulin-3 and MMP-7 were inversely correlated in lung tumors. Fibulin-3 inhibited extracellular signal-regulated kinase (ERK) to activate glycogen synthase kinase 3? and suppress Wnt/?-catenin signaling, which induces MMP-7 expression in lung cancer cells. Furthermore, fibulin-3 expression impeded the growth and metastasis of lung tumors in mice. Collectively, these results suggest that downregulation of fibulin-3 contributes to lung cancer invasion and metastasis by activating Wnt/?-catenin signaling and MMP-7 expression.
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Boron nitride film as a buffer layer in deposition of dielectrics on graphene.
Small
PUBLISHED: 01-24-2014
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As a two-dimensional material, graphene is highly susceptible to environmental influences. It is therefore challenging to deposit dielectrics on graphene without affecting its electronic properties. It is demonstrated that the effect of the dielectric deposition on graphene can be reduced by using a multilayer hexagonal boron nitride film as a buffer layer. Particularly, the boron nitride layer provides significant protection in magnetron sputtering deposition. It also enables growth of uniform and charge trapping free high-k dielectrics by atomic layer deposition. The doping effect of various deposition methods on graphene has been discussed.
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Combined effects of a high-fat diet and chronic valproic acid treatment on hepatic steatosis and hepatotoxicity in rats.
Acta Pharmacol. Sin.
PUBLISHED: 01-20-2014
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To investigate the potential interactive effects of a high-fat diet (HFD) and valproic acid (VPA) on hepatic steatosis and hepatotoxicity in rats.
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Significance of ER? expression in different molecular subtypes of breast cancer.
Diagn Pathol
PUBLISHED: 01-17-2014
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This study is to investigate the estrogen receptor ? (ER?) expression in molecular subtypes of breast cancer and clinic significance of ER? expression.
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Zinc oxide nanoparticles alter hatching and larval locomotor activity in zebrafish (Danio rerio).
J. Hazard. Mater.
PUBLISHED: 01-16-2014
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Zinc oxide nanoparticles (ZnO NP) are extensively used in various consumer products such as sunscreens and cosmetics, with high potential of being released into aquatic environments. In this study, fertilized zebrafish (Danio rerio) eggs were exposed to various concentrations of ZnO NP suspensions (control, 0.1, 0.5, 1, 5, and 10mg/L) or their respective centrifuged supernatants (0.03, 0.01, 0.08, 0.17, 0.75, and 1.21mg/L dissolved Zn ions measured) until reaching free swimming stage. Exposure to ZnO NP suspensions and their respective centrifuged supernatants caused similar hatching delay, but did not cause larval mortality or malformation. Larval activity level, mean velocity, and maximum velocity were altered in the groups exposed to high concentrations of ZnO NP (5-10mg/L) but not in the larvae exposed to the supernatants. To evaluate possible mechanism of observed effects caused by ZnO NP, we also manipulated the antioxidant environment by co-exposure to an antioxidant compound (N-acetylcysteine, NAC) or an antioxidant molecule suppressor (buthionine sulfoximine, BSO) with 5mg/L ZnO NP. Co-exposure to NAC did not alter the effects of ZnO NP on hatchability, but co-exposure to BSO caused further hatching delay. For larval locomotor activity, co-exposure to NAC rescued the behavioral effect caused by ZnO NP, but co-exposure to BSO did not exacerbate the effect. Our data indicated that toxicity of ZnO NP cannot be solely explained by dissolved Zn ions, and oxidative stress may involve in ZnO NP toxicity.
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Multi-channel recycling counter-current chromatography for natural product isolation: tanshinones as examples.
J Chromatogr A
PUBLISHED: 01-15-2014
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Recycling is a simple and efficient strategy for improving the peak resolution. In this work, a novel multi-channel recycling counter-current chromatography (CCC) was successfully established and three representative three-channel recycling CCC systems including 1R, 2R, and 3R CCC recycling on one, two, and three channel columns were developed for four typical tanshinones fractions. The results demonstrated that all recycling CCC separations were efficient for the isolation of targeted tanshinones. 1R CCC not only provided the single recycling separation, but also offered two parallel recycling separation or repeated preparation for multiple targets. 2R CCC provided the increased peak resolution and less risk of overlapping. 3R CCC offered versatile elution and recycling modes for multiple targets. Compared to 1R and 2R CCC, 3R CCC was easier to separate the more complex natural products with more targets in the complex natural extracts. In summary, the developed multi-channel recycling CCC systems including 1R, 2R, and 3R CCC were successful and efficient for resolving the complex natural tanshinones. To the best of our knowledge, this is the first document to report the multi-channel recycling CCC methods for the separation of tanshinones. They may be used as new multi-dimensional recycling CCC for targeted and non-targeted isolation of natural products. It may be widely used for current natural drug development and metabolome analysis.
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Induction of apoptosis through ER stress and TP53 in MCF-7 cells by the nanoparticle [Gd@C82(OH)22]n: A systems biology study.
Methods
PUBLISHED: 01-05-2014
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The nanoparticle gadolinium endohedral metallofullerenol [Gd@C82(OH)22]n is a new candidate for cancer treatment with low toxicity. However, its anti-cancer mechanisms remain mostly unknown. In this study, we took a systems biology view of the gene expression profiles of human breast cancer cells (MCF-7) and human umbilical vein endothelial cells (ECV304) treated with and without [Gd@C82(OH)22]n, respectively, measured by the Agilent Gene Chip G4112F. To properly analyze these data, we modified a suit of statistical methods we developed. For the first time we applied the sub-sub normalization to Agilent two-color microarrays. Instead of a simple linear regression, we proposed to use a one-knot SPLINE model in the sub-sub normalization to account for nonlinear spatial effects. The parameters estimated by least trimmed squares- and S-estimators show similar normalization results. We made several kinds of inferences by integrating the expression profiles with the bioinformatic knowledge in KEGG pathways, Gene Ontology, JASPAR, and TRANSFAC. In the transcriptional inference, we proposed the BASE2.0 method to infer a transcription factor's up-regulation and down-regulation activities separately. Overall, [Gd@C82(OH)22]n induces more differentiation in MCF-7 cells than in ECV304 cells, particularly in the reduction of protein processing such as protein glucosylation, folding, targeting, exporting, and transporting. Among the KEGG pathways, the ErbB signaling pathway is up-regulated, whereas protein processing in endoplasmic reticulum (ER) is down-regulated. CHOP, a key pro-apoptotic gene downstream of the ER stress pathway, increases to nine folds in MCF-7 cells after treatment. These findings indicate that ER stress may be one important factor that induces apoptosis in MCF-7 cells after [Gd@C82(OH)22]n treatment. The expression profiles of genes associated with ER stress and apoptosis are statistically consistent with other profiles reported in the literature, such as those of HEK293T and MCF-7 cells induced by the miR-23a?27a?24-2 cluster. Furthermore, one of the inferred regulatory mechanisms comprises the apoptosis network centered around TP53, whose effective regulation of apoptosis is somehow reestablished after [Gd@C82(OH)22]n treatment. These results elucidate the application and development of [Gd@C82(OH)22]n and other fullerene derivates.
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Anti-proliferative activities of sinigrin on carcinogen-induced hepatotoxicity in rats.
PLoS ONE
PUBLISHED: 01-01-2014
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Liver cancer is one of the leading causes of cancer death worldwide. A very high incidence of new liver cancer cases is diagnosed every year, and metastasis has been found to correlate to poor prognoses in humans. Better treatments for liver cancer are thus clearly needed. Sinigrin is one of the major ingredients present in Brassica nigra, which has been used in combination with other herbs for treatment of various diseases. The anti-proliferative activities of sinigrin were studied in a model of carcinogen-induced hepatotoxicity in rats. Rats were orally administered with sinigrin on a daily basis for three months before sacrifice. Sinigrin was found to significantly inhibit the proliferation of liver tumor cells; the number of surface tumors in the rat liver was dramatically reduced. Sinigrin induced apoptosis of liver cancer cells through up-regulation of p53 and down-regulation of Bcl-2 family members and caspases. Our findings indicated that the liver functions were gradually restored after treatment with sinigrin and that the agent did not cause liver toxicity. Cell cycle analysis indicated that sinigrin caused cell cycle arrest in G0/G1 phase. The results suggest that sinigrin exerts important anti-proliferative activities in carcinogen-induced hepatocarcinogenesis in rats, and highlight the potential of sinigrin as an anti-cancer agent for liver cancer.
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Effects of manure compost application on soil microbial community diversity and soil microenvironments in a temperate cropland in china.
PLoS ONE
PUBLISHED: 01-01-2014
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The long-term application of excessive chemical fertilizers has resulted in the degeneration of soil quality parameters such as soil microbial biomass, communities, and nutrient content, which in turn affects crop health, productivity, and soil sustainable productivity. The objective of this study was to develop a rapid and efficient solution for rehabilitating degraded cropland soils by precisely quantifying soil quality parameters through the application of manure compost and bacteria fertilizers or its combination during maize growth. We investigated dynamic impacts on soil microbial count, biomass, basal respiration, community structure diversity, and enzyme activity using six different treatments [no fertilizer (CK), N fertilizer (N), N fertilizer + bacterial fertilizer (NB), manure compost (M), manure compost + bacterial fertilizer (MB), and bacterial fertilizer (B)] in the plowed layer (0-20 cm) of potted soil during various maize growth stages in a temperate cropland of eastern China. Denaturing gradient electrophoresis (DGGE) fingerprinting analysis showed that the structure and composition of bacterial and fungi communities in the six fertilizer treatments varied at different levels. The Shannon index of bacterial and fungi communities displayed the highest value in the MB treatments and the lowest in the N treatment at the maize mature stage. Changes in soil microorganism community structure and diversity after different fertilizer treatments resulted in different microbial properties. Adding manure compost significantly increased the amount of cultivable microorganisms and microbial biomass, thus enhancing soil respiration and enzyme activities (p<0.01), whereas N treatment showed the opposite results (p<0.01). However, B and NB treatments minimally increased the amount of cultivable microorganisms and microbial biomass, with no obvious influence on community structure and soil enzymes. Our findings indicate that the application of manure compost plus bacterial fertilizers can immediately improve the microbial community structure and diversity of degraded cropland soils.
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Multi-walled carbon nanotubes impair Kv4.2/4.3 channel activities, delay membrane repolarization and induce bradyarrhythmias in the rat.
PLoS ONE
PUBLISHED: 01-01-2014
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The potential hazardous effects of multi-walled carbon nanotubes (MWCNTs) on cardiac electrophysiology are seldom evaluated. This study aimed to investigate the impacts of MWCNTs on the Kv4/Ito channel, action potential and heart rhythm and the underlying mechanisms.
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Can resistant coral-Symbiodinium associations enable coral communities to survive climate change? A study of a site exposed to long-term hot water input.
PeerJ
PUBLISHED: 01-01-2014
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Climate change has led to a decline in the health of corals and coral reefs around the world. Studies have shown that, while some corals can cope with natural and anthropogenic stressors either through resistance mechanisms of coral hosts or through sustainable relationships with Symbiodinium clades or types, many coral species cannot. Here, we show that the corals present in a reef in southern Taiwan, and exposed to long-term elevated seawater temperatures due to the presence of a nuclear power plant outlet (NPP OL), are unique in terms of species and associated Symbiodinium types. At shallow depths (<3 m), eleven coral genera elsewhere in Kenting predominantly found with Symbiodinium types C1 and C3 (stress sensitive) were instead hosting Symbiodinium type D1a (stress tolerant) or a mixture of Symbiodinium type C1/C3/C21a/C15 and Symbiodinium type D1a. Of the 16 coral genera that dominate the local reefs, two that are apparently unable to associate with Symbiodinium type D1a are not present at NPP OL at depths of <3 m. Two other genera present at NPP OL and other locations host a specific type of Symbiodinium type C15. These data imply that coral assemblages may have the capacity to maintain their presence at the generic level against long-term disturbances such as elevated seawater temperatures by acclimatization through successful association with a stress-tolerant Symbiodinium over time. However, at the community level it comes at the cost of some coral genera being lost, suggesting that species unable to associate with a stress-tolerant Symbiodinium are likely to become extinct locally and unfavorable shifts in coral communities are likely to occur under the impact of climate change.
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[Murine pulmonary fibrosis model induced by repeated low-dose intravenous injection and intratracheal instillation of bleomycin.]
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 12-31-2013
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Objective:To determine the characteristics and differences in bleomycin-induced lung fibrosis model by repeated low-dose intravenous injection and single dose intratracheal instillation of bleomycin. Methods: Forty male ICR (Institute for Cancer Research) mice were randomly divided into a model group I, a model group II, and 2 control groups (10 mice in each group). In model group I, bleomycin was injected intravenously at 10 mg/(kg.d) for 14 consecutive days; and in model group II, bleomycin was instilled intratracheally at 5 mg/kg. The 2 control groups were given isotonic saline solution. At the 28th day, the mice were sacrificed and the bronchoalveolar lavage fluid (BALF) was collected. The total cells and proteins in the BALF, pulmonary coefficient, and hydroxyproline (HYP) content were determined. The pathological changes were observed by the eosin staining and Massons trichrome staining. Results: 1) Both intravenous injection and intratracheal instillation of bleomycin resulted in severe and extensive inflammation and fibrosis in the lungs. The total cells and proteins in the BALF, HYP content, pulmonary coefficient and the pathological score of pulmonary fibrosis were all significantly increased in the 2 model groups (P<0.01). 2) Fibrosis was mainly under the pleura or around the vessel in model group I, and it was located near the bronehia and bronchioles in model group II. 3) The death rate was higher in the model group II than that in the model group I. 4) Proteins in the BALF were significantly higher in model group II than that in model group I (P<0.05). There was no difference in the total cells in the BALF, the pulmonary coefficient, the HYP content, and the pathological score of pulmonary fibrosis between the 2 groups (P>0.05). Conclusion: The pulmonary fibrosis model can be successfully established by intravenous injection or intratracheal instillation of bleomycin, but the sites of pulmonary fibrosis are different. The histological changes caused by the repeated low-dose intravenous injection of bleomycin is more similar to idiopathic pulmonary fibrosis than that by the single dose intratracheal instillation.
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Inflammation Amplifier, a New Paradigm in Cancer Biology.
Cancer Res.
PUBLISHED: 12-20-2013
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Tumor-associated inflammation can induce various molecules expressed from the tumors themselves or surrounding cells to create a microenvironment that potentially promotes cancer development. Inflammation, particularly chronic inflammation, is often linked to cancer development, even though its evolutionary role should impair nonself objects including tumors. The inflammation amplifier, a hyperinducer of chemokines in nonimmune cells, is the principal machinery for inflammation and is activated by the simultaneous stimulation of NF-?B and STAT3. We have redefined inflammation as local activation of the inflammation amplifier, which causes an accumulation of various immune cells followed by dysregulation of local homeostasis. Genes related to the inflammation amplifier have been genetically associated with various human inflammatory diseases. Here, we describe how cancer-associated genes, including interleukin (IL)-6, Ptgs2, ErbB1, Gas1, Serpine1, cMyc, and Vegf-?, are strongly enriched in genes related to the amplifier. The inflammation amplifier is activated by the stimulation of cytokines, such as TNF-?, IL-17, and IL-6, resulting in the subsequent expression of various target genes for chemokines and tumor-related genes like BCL2L11, CPNE7, FAS, HIF1-?, IL-1RAP, and SOD2. Thus, we conclude that inflammation does indeed associate with the development of cancer. The identified genes associated with the inflammation amplifier may thus make potential therapeutic targets of cancers. Cancer Res; 74(1); 1-7. ©2013 AACR.
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Free fibula flap: assessment of quality of life of patients with head and neck cancer who have had defects reconstructed.
J Craniofac Surg
PUBLISHED: 11-14-2013
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This study investigated the quality of life (QoL) of patients with head and neck cancer undergoing immediate reconstruction of the mandible with free fibula flap. From March 2006 to January 2011, the QoL of 42 patients was assessed using the Medical Outcomes Study Short Form 36 and the University of Washington QoL (version 4) questionnaires. The assessments were performed at least 24 months after surgery. A total of 31 of the 42 questionnaires (73.8%) were returned. The length of harvested fibula varied from 17.5 to 26.1 cm. In the Short Form 36, the lowest-scoring domain was vitality, whereas the highest scores occurred in physical role. According to the University of Washington QoL, the key domains affected by surgery are chewing, speech, and appearance. The domain of pain has the best score. There was a significant effect on the QoL of patients with head and neck cancer with resections of the mandible who had undergone free fibula flap reconstruction. Data from this study may provide useful information for physicians and patients, which may be of value during discussion of treatment modalities for head and neck cancers.
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[Regulative mechanism of renal inflammatory-related p38MAPK signaling pathway in diabetic nephropathy and interventional effects of Chinese herbal medicine].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 11-09-2013
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It is reported, in the process of diabetic nephropathy (DN), inflammatory-related p38 mitogen-activated protein kinase (MAPK) signaling pathway has a close relationship with renal injury. On the one hand,many factors in the upstream including hyperglycemia, abnormal hemodynamics, oxidative stress, and pro-inflammatory cytokines could activate p38MAPK signaling pathway. On the other hand,the activated p38MAPK signaling pathway could lead to renal damage via activating inflammatory cells, inducing the expression of inflammatory mediators, and intervening cytokines production. CHM could intervene p38MAPK signaling pathway through multi-ways, including inhibiting inflammatory cytokines expression, regulating phosphorylated p38MAPK (p-p38MAPK) expression, and reducing fibrogenic factors expression.
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Three new iridoid glycosides from the fruit of gardenia jasminoides var. radicans.
Chem. Pharm. Bull.
PUBLISHED: 10-04-2013
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Three new iridoid glycosides, 6?-O-trans-feruloylgenipin gentiobioside (1), 2-O-trans-p-coumaroylgardoside (2), 2-O-trans-feruloylgardoside (3), were isolated from the fruit of Gardenia jasminoides var. radicans MAKINO (Rubiaceae). The structures of these compounds were elucidated on the basis of MS, NMR spectra analysis, glycoside hydrolysis, and sugar derivatization coupled with HPLC analysis.
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[Visual detection of HIV-1 by reverse transcription loop-mediated isothermal amplification with the hydroxynaphthol blue dye].
Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi
PUBLISHED: 09-19-2013
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A reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for rapid visual detection of HIV-1.
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Comprehensive multi-channel multi-dimensional counter-current chromatography for separation of tanshinones from Salvia miltiorrhiza Bunge.
J Chromatogr A
PUBLISHED: 09-17-2013
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Multi-dimensional chromatography offers the increased resolution and peak capacity by coupling of multiple columns with the same or different separation mechanisms. In this work, a novel multi-channel multi-dimensional counter-current chromatography (CCC) has been successfully constructed and used for several two-dimensional (2D) and three-dimensional (3D) CCC separations including 2D A×B/A×C, A×B-C and A-B×C, and 3D A×B×C systems. These 2D and 3D CCC systems were further applied to separate the bioactive tanshinones from the extract of Tanshen (or Danshen, Salvia miltiorrhiza Bunge), a famous Traditional Chinese Medicine (TCM). As a result, the developed 2D and 3D CCC methods were successful and efficient for resolving the tanshinones from complex extracts. Compared to the 1D multiple columns CCC separation, the 2D and 3D CCC decrease analysis time, reduce solvent consumption and increase sample throughput significantly. It may be widely used for current drug development, metabolomic analysis and natural product isolation.
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The effect of serum in culture on RNAi efficacy through modulation of polyplexes size.
Biomaterials
PUBLISHED: 08-28-2013
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Serum in the culture medium is one crucial factor that compromises RNAi efficiency of non-viral vectors. However, mechanistic roles of serum in siRNA delivery remain unknown. In this work, we took one cationic polymer, pullulan chemically modified by spermine (termed as pullulan-spermine, Ps), as a siRNA carrier model to investigate the effects of serum on key steps in siRNA delivery including formation of Ps and siRNA polyplexes (Ps-siRNA), cellular uptake, lysosomal escape, and cytotoxicity. We demonstrate that low serum concentration (1.25% and 2.5%) in culture medium results in large particles of Ps-siRNA, while high serum concentration (10%-40%) leads to small particles of Ps-siRNA. The larger particles initiated the internalization of siRNA more effectively in comparison to the smaller ones. The engulfed Ps-siRNA particles mainly locate in lysosomes. The large particles exhibited stronger abilities of destabilizing lysosomes than that of the small particles as large Ps-siRNA particles contain more amines and subsequently elicit a stronger proton sponge effect which results in more effective lysosomal escape of siRNA. Despite the lower RNAi efficiency, the small particle of Ps-siRNA in the high serum medium generates much lower cytotoxicity. These findings explain why serum significantly affects RNAi and also propose a strategy for improving RNAi efficiency and safety by modulating serum concentration and enhancing lysosomal destabilization.
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Low-dose of multi-glycoside of Tripterygium wilfordii Hook. f., a natural regulator of TGF-?1/Smad signaling activity improves adriamycin-induced glomerulosclerosis in vivo.
J Ethnopharmacol
PUBLISHED: 08-25-2013
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Transforming growth factor (TGF)-?1/Smad signaling pathway plays a critical role in the prolonged glomerulosclerosis (GS), which is an important determinant during the progression in chronic kidney disease (CKD). For recent 30 years, multi-glycoside of Tripterygium wilfordii Hook. f. (GTW), an extract from Chinese herbal medicine has been proved clinically effective in improving GS in CKD in China. However, therapeutic mechanisms involved in vivo are still unclear. In this study, we aimed to explain the dose-effects and molecular mechanisms of GTW on GS by regulating TGF-?1/Smad signaling activity in adriamycin (ADR)-induced nephropathy (ADRN).
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Interaction of stable colloidal nanoparticles with cellular membranes.
Biotechnol. Adv.
PUBLISHED: 08-05-2013
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Due to their ultra-small size, inorganic nanoparticles (NPs) have distinct properties compared to the bulk form. The unique characteristics of NPs are broadly exploited in biomedical sciences in order to develop various methods of targeted drug delivery, novel biosensors and new therapeutic pathways. However, relatively little is known in the negotiation of NPs with complex biological environments. Cell membranes (CMs) in eukaryotes have dynamic structures, which is a key property for cellular responses to NPs. In this review, we discuss the current knowledge of various interactions between advanced types of NPs and CMs.
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Vertical graphene spin valve with Ohmic contacts.
Nanoscale
PUBLISHED: 08-01-2013
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Evident spin valve signals are observed in Co/graphene/Co sandwich structures with both monolayer and two-layer graphene stacks at temperatures from 1.5 K to 300 K. All the devices demonstrate linear current-voltage curves, indicating that an Ohmic property is dominating rather than a tunneling effect. The vertical graphene spin valves have potential applications in high-density non-volatile memories.
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A continuous, real-time water quality monitoring system for the coral reef ecosystems of Nanwan Bay, Southern Taiwan.
Mar. Pollut. Bull.
PUBLISHED: 07-31-2013
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The coral reef ecosystems of Nanwan Bay, Southern Taiwan are undergoing degradation due to anthropogenic impacts, and as such have resulted in a decline in coral cover. As a first step in preventing the continual degradation of these coral reef environments, it is important to understand how changes in water quality affect these ecosystems on a fine-tuned timescale. To this end, a real-time water quality monitoring system was implemented in Nanwan Bay in 2010. We found that natural events, such as cold water intrusion due to upwelling, tended to elicit temporal shifts in coral spawning between 2010 and 2011. In addition, Degree Heating Weeks (DHWs), a commonly utilized predictor of coral bleaching, were 0.92 and 0.59 in summer 2010 and 2011, respectively. Though this quantity of DHW was below the presumed stress-inducing value for these reefs, a rise in DHWs in the future may stress the resident corals.
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Using gold nanorods core/silver shell nanostructures as model material to probe biodistribution and toxic effects of silver nanoparticles in mice.
Nanotoxicology
PUBLISHED: 07-29-2013
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Abstract The aim of this work was to probe the biodistribution and toxic effects of silver nanoparticles (NPs) with powerful anti-bacterial and anti-virus activities. For this purpose, novel silver NPs with gold nanorod (NR) core and silver shell (Au@Ag NRs) were developed and employed as a model material. The inner gold core provided an excellent internal reference for tracking the NRs in vivo. After subcutaneous injection of Au@Ag NRs, silver and gold contents in the subcutis and organs were examined by inductively coupled plasma mass spectrometry at different time points within 28 days. Histological analysis, physiological function and complement faction 3 (C3) and 5a (C5a) measurement were performed over time to reveal the toxic effect of Au@Ag NRs in vivo. Experimental results showed that majority of the Au@Ag NRs remained in the injection site except for a small amount migrating into the lymph nodes. The silver shell was dissolved in the subcutaneous tissue and released silver ions rapidly, which resulted in detectable silver accumulation in most of the organs. The accumulated silver ions in the kidney not only interacted with the kidney cells membrane but also induced a rapid increase of complement fraction C3 followed by a significant consumption and C3a and C5a production significantly in the serum, which resulted in kidney oxidative damage and eventually led to the morphological changes and filtration function impairment of the glomerulus. The released silver ions also caused oxidative injury of subcutaneous tissue in the injection site.
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Berberine Protects against Palmitate-Induced Endothelial Dysfunction: Involvements of Upregulation of AMPK and eNOS and Downregulation of NOX4.
Mediators Inflamm.
PUBLISHED: 07-23-2013
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Endothelial dysfunction is a critical factor during the initiation of cardiovascular complications in diabetes. Berberine can ameliorate endothelial dysfunction induced by diabetes. However, the underlying mechanisms remain unclear. The aim of this study was to investigate the protective effect and mechanism of berberine on palmitate-induced endothelial dysfunction in human umbilical vein endothelial cells (HUVECs). The cell viability of HUVECs was determined by MTT assays. Nitric oxide (NO) level and production of reactive oxygen species (ROS) were determined in supernatants or in the cultured HUVECs. The mRNA level of endothelial nitric oxide synthase (eNOS) was measured by RT-PCR, and the protein levels of eNOS, p-eNOS, Akt, p-Akt, AMPK, p-AMPK, and NADPH oxidase (NOX4) were analyzed. The results demonstrated that berberine significantly elevated NO levels and reduced the production of ROS. The expressions of eNOS were significantly increased, while NOX4 protein expression was decreased in berberine-treated HUVECs. Moreover, berberine upregulated the protein expression of AMPK and p-AMPK in palmitate-treated HUVECs, but had no effect on the levels of Akt. Therefore, berberine ameliorates palmitate-induced endothelial dysfunction by upregulating eNOS expression and downregulating expression of NOX4. This regulatory effect of berberine may be related to the activation of AMPK.
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Biological characterizations of [Gd@C82(OH)22]n nanoparticles as fullerene derivatives for cancer therapy.
Integr Biol (Camb)
PUBLISHED: 06-26-2013
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Malignant tumor disease is one of the leading causes of human death in many countries. Currently, chemotherapy is considered highly efficient for cancer treatment. However, the clinical application of conventional chemotherapeutic agents is limited because of their high toxicity. With the development of nanotechnology, engineered nanomaterials have been widely and increasingly used in biomedical fields such as biomedicine. Thus, the use of engineered nanomaterials has become a promising approach to cancer treatment. Many newly fabricated nanomaterials with unique characteristics exhibit favorable therapeutic and diagnostic properties, implying their enormous potential as biomedical candidates. [Gd@C(82)(OH)(22)](n) is a new type of metallofullerenol nanoparticle with high anti-tumor activity but low toxicity. In this article, the properties and biological effects of [Gd@C(82)(OH)(22)](n) are summarized, and their possible mechanisms are analyzed.
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[The establishment of a new resequencing pathogen microarray-based assay for detecting unexplained respiratory tract infections].
Bing Du Xue Bao
PUBLISHED: 06-14-2013
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Resequencing Pathogen Microarray (RPM) is a new pathogen detection and identification technology based on DNA microarray. In order to apply RPM in the detection of unexplained infection and as a result, to improve the emergency response capacity, a new RPM-based respiratory pathogens detection assay was developed to simultaneously detect 19 common respiratory viruses, 9 influenza A viruses (Flu A),11 human rhinoviruses(HRV), 28 enteroviruses and 18 rare respiratory viruses. The specificity of multiplex system was examined by confirmed positive specimens for 16 common respiratory virus. The sensi-tivity was evaluated by serial ten-fold dilutions of plasmids or in vitro-transcribed RNA. RPM could detect and differentiate 16 virus types/subtypes at 10 - 1 000 copies/reaction level. Nucleic acids of 8 throat swabs with unexplained respiratory tract infections were pooled and detected by the new assay. The RPM result was verified by common PCR followed by sequencing as well as PLEX-ID (Abbott). Except for a false-positive of PIV1, no difference among the three assays was found. These results indicate the assay based on the new RPM is a highly sensitive, high throughput test for the detection of respiratory virus infections, which is significant for the management of emergent and epidemic infectious disease.
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Super-paramagnetic responsive nanofibrous scaffolds under static magnetic field enhance osteogenesis for bone repair in vivo.
Sci Rep
PUBLISHED: 06-12-2013
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A novel nanofibrous composite scaffold composed of super-paramagnetic ?-Fe2O3 nanoparticles (MNP), hydroxyapatite nanoparticles (nHA) and poly lactide acid (PLA) was prepared using electrospinning technique. The scaffold well responds extern static magnetic field with typical saturation magnetization value of 0.049?emu/g as well as possesses nanofibrous architecture. The scaffolds were implanted in white rabbit model of lumbar transverse defects. Permanent magnets are fixed in the rabbit cages to provide static magnetic field for the rabbits post surgery. Results show that MNP incorporated in the nanofibers endows the scaffolds super-paramagnetic responsive under the applied static magnetic field, which accelerates new bone tissue formation and remodeling in the rabbit defect. The scaffold also exhibits good compatibility of CK, Cr, ALT and ALP within normal limits in the serum within 110 days post implantation. In conclusion, the super-paramagnetic responding scaffold with applying of external magnetic field provides a novel strategy for scaffold-guided bone repair.
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[Molecular mechanisms of renal extracellular matrix degradation and interventional effects of Chinese herbal medicine].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 05-30-2013
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The reduction of extracellular matrix (ECM) degradation in kidney is taken as the morphological features and pathological base in renal injury in chronic kidney disease (CKD). ECM degradation is controlled by the catabolic enzyme systems in glomerulus and renal interstitium, in which matrix metalloproteinases (MMPs) play a key role. The expression and activity of MMPs are regulated by the classical pathway, such as the genic transcription, the activation of zymogen, and the specific inhibitor. The previous studies showed that, Uremic Clearance granule, as a representation, and other prescriptions of Chinese herbal medicine, as well as some extracts from Chinese herbal medicine could intervene the pathway of ECM degradation through promoting the degradation of ECM components, affecting the expression of catabolic enzymes, regulating the genetic transcription of MMPs, and inhibiting the relative signaling transduction of MMPs.
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Graphene plasmon enhanced photoluminescence in ZnO microwires.
Nanoscale
PUBLISHED: 05-23-2013
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We report the temperature dependent photoluminescence (PL) properties of monolayer graphene-Au-nanoparticle-ZnO (GAZ) microwire hybrid structures. By comparing with the bare ZnO wire without coverage of graphene, a three times enhancement of PL was found in the GAZ hybrid structures. The enhancement is attributed to the coupling between the PL photons from ZnO and the graphene surface plasmons with ~1-2 nm Au as a corrugated surface. Our results may be valuable for designing graphene-ZnO hybrid based optical and photoelectrical devices.
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Hyper-methylated miR-203 dysregulates ABL1 and contributes to the nickel-induced tumorigenesis.
Toxicol. Lett.
PUBLISHED: 05-17-2013
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Nickel compounds have been found to be carcinogenic based upon epidemiological, animal and cell culture studies. Previous studies suggest that epigenetic mechanisms play a role in Nickel-induced carcinogenesis such as DNA methylation and histone modification. In this study, we investigated the role of microRNAs (miRNAs) in nickel-induced carcinogenesis. The expression of several miRNAs which may function as tumor suppressor genes revealed a strong downregulation of miR-203 in Ni3S2-transformed 16HBE cells (NSTCs). Meanwhile, we observed hypermethylation of CpGs in miR-203 promoter and first exon area, and proved that the hyper-methylated miR-203 was involved in the Nickel-induced tumorigenesis. Moreover, we identified that miR-203 may suppress the tumorigenesis at least in part through negatively regulating its target gene ABL1. Our findings indicate that DNA methylation-associated silencing of tumor suppressor miRNAs contributes to the development of Nickel-induced cancer.
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LIM kinase 1 is required for insulin?dependent cell growth of osteosarcoma cell lines.
Mol Med Rep
PUBLISHED: 05-09-2013
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Osteosarcoma is a type of malignant bone tumor with high metastasis and poor prognosis. Previous studies have demonstrated the involvement of LIM kinase 1 (LIMK1) in the proliferation of osteosarcoma cells. LIMK1 is overexpressed in human osteosarcoma tissues and cell lines. To further study LIMK1-associated mechanisms, we used shRNA targeted to the LIMK1 gene to block its expression in the osteosarcoma cell lines MG63 and U2OS. Insulin promoted the proliferation of MG63 cells in a time- and dose-dependent manner, however, this insulin induced proliferation was significantly inhibited by transfection of shRNA targeted to the LIMK1 gene, as well as by the PI3K inhibitor LY294002, but not by the mitogen?activated protein kinase (MAPK) inhibitor PD98059. The level of cofilin phosphorylation was increased significantly following stimulation of insulin for 24 h, indicating the activation of LIMK1. MG63 cell proliferation was also significantly inhibited by 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) in a time-dependent manner. Furthermore, 1,25(OH)2D3 negated the inhibitory effect of LIMK1 shRNA, indicating that LIMK1 is important in the inhibitory pathway of 1,25(OH)2D3. The present study confirms that LIMK1 is important in regulating osteosarcoma cell proliferation via the insulin/PI3K/LIMK1 signaling pathway, thus the development of gene therapy for osteosarcoma targeting LIMK1 is warranted.
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Preparation and biocompatibility evaluation of polyurethane filled with multiwalled carbon nanotubes.
J Nanosci Nanotechnol
PUBLISHED: 05-08-2013
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Biocompatibility has been one of the most crucial performances that determine the clinical application potentials of biomaterials and implants. As carbon is one inner substance and possesses clinical accepted blood compatibility, carbon nanotubes may bring improved hemocompatibility of polymeric materials when used as fillers. In this work, a kind of composite composed of polyurethane and multiwalled carbon nanotubes has been developed using a customized sol-gel technique. The cytotoxicity of the composite was evaluated by examining viability of the endothelium cells seeded on the composite or cultured with composite extraction using MTS assay and Environmental Scanning Electronic Microscope. Tissue compatibility was evaluated by subcutaneous implantation of the composite film in the paraspinal skin incision of rat. Dynamic clotting test of the composite were conducted to evaluate blood compatibility. Experiments results revealed that multiwalled carbon nanotubes were well dispersed into the polyurethane matrix. More functional endothelial cell grew on the composite than polyurethane. When implanted subcutaneously, the composite did not induce long-term inflammation in the implanted sites and exhibited good tissue compatibility. The dynamic clotting test showed that the composite had longer clotting time than PU, indicating that anti-coagulant property of the composite was improved.
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High-dose accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine and carboplatin chemotherapy in locally advanced non-small-cell lung cancer: a feasibility study.
Radiat Oncol
PUBLISHED: 05-05-2013
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Increasing the radiotherapy dose can result in improved local control for non-small-cell lung cancer (NSCLC) and can thereby improve survival. Accelerated hypofractionated radiotherapy can expose tumors to a high dose of radiation in a short period of time, but the optimal treatment regimen remains unclear. The purpose of this study was to evaluate the feasibility of utilizing high-dose accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine (NVB) and carboplatin (CBP) chemotherapy for the treatment of local advanced NSCLC.
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The preliminary exploration of 64-slice volume computed tomography in the accurate measurement of pleural effusion.
Acta Radiol
PUBLISHED: 04-30-2013
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Using computed tomography (CT) to rapidly and accurately quantify pleural effusion volume benefits medical and scientific research. However, the precise volume of pleural effusions still involves many challenges and currently does not have a recognized accurate measuring.
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Bony palmar ridges of the phalanges of the human fingers.
Surg Radiol Anat
PUBLISHED: 04-17-2013
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On imaging studies, bony ridges can be seen at the palmar aspect of the phalanges of the fingers. Our purpose was to address the following: (1) which structures insert on to the ridges and what is the histological appearance? (2) Is there a difference between the different fingers? (3) Is there a correlation between the ridges and age?
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Skp2 regulates subcellular localization of PPAR? by MEK signaling pathways in human breast cancer.
Int J Mol Sci
PUBLISHED: 03-20-2013
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Nuclear hormone receptor family member PPAR? plays an important role in mammary gland tumorigenesis. Previous studies have shown PPAR? has cytoplasmic activities upon tetradecanoyl phorbol acetate (TPA) stimulation. However, the clinical pathological significance of cytoplasmic PPAR? is not completely understood in human breast cancer. Skp2 is oncogenic, and its frequent amplification and overexpression correlated with the grade of malignancy. In this study, the role of cytoplasmic PPAR? and Skp2 expression was investigated in human breast cancer progression. Therefore, immunohistochemical analysis was performed on formalin-fixed paraffin sections of 70 specimens. Furthermore, Western blot and immunofluorescence microscopy analysis were used to study the relationship between expression of cytoplasmic PPAR? and Skp2 expression in human breast cancer cells in vitro. Results showed that the expression of cytoplasmic PPAR? was positively correlated with Skp2 expression (p < 0.05), and correlated significantly with estrogen receptor (p = 0.026) and pathological grade (p = 0.029), respectively. In addition, Skp2 overexpression can provoke cytoplasmic localization of PPAR? upon MEK1-dependent mechanisms in human breast cancer cells by nuclear-cytosolic fractionation technology and immunofluorescence microscopy analysis. Using RNA interference technology, we also found that down-regulated Skp2 reduced the phosphorylation level of MEK1 and significantly reversed TPA-induced nuclear export of PPAR? in MDA-MB-231 cells. The changes in the subcellular localization of PPAR? may represent a novel target for selective interference in patients with breast cancer.
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Evaluation of reproductive and developmental toxicities of Pu-erh black tea (Camellia sinensis var. assamica) extract in Sprague Dawley rats.
J Ethnopharmacol
PUBLISHED: 03-18-2013
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Pu-erh black tea, which is obtained by first parching crude green tea leaves and followed by secondary fermentation with microorganisms, has been believed to be beneficial beverages for health in PR China. But its potential toxicity when administered at a high dose as concentrated extract has not been completely investigated.
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Fabrication of microlens arrays by localized hydrolysis in water droplet microreactors.
ACS Appl Mater Interfaces
PUBLISHED: 03-07-2013
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We report a facile self-assembly strategy for fabricating TiO2 microlens arrays by localized hydrolysis of TiCl4 precursor in water droplets. Microcontact printing was used to define hydrophilic areas on a substrate for space resolved hydrolytic reaction. The water droplets served as the templates, reactant, and microreactors. Highly ordered TiO2 microlens arrays could be produced, which exhibit excellent ability to focus light. Because both size and shape of the final TiO2 microlens can be controlled by the printed chemical pattern and the precursor concentration, it is possible to define TiO2 microlens arrays with different imaging properties. This new method shows attractive features of simplicity, low cost, and requires no heating process, hence is suitable for a range of applications.
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Pharmacokinetic interactions between 20(S)-ginsenoside Rh2 and the HIV protease inhibitor ritonavir in vitro and in vivo.
Acta Pharmacol. Sin.
PUBLISHED: 02-23-2013
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20(S)-Ginsenoside Rh2 (Rh2) has shown potent inhibition on P-glycoprotein (P-gp), while most HIV protease inhibitors are both substrates and inhibitors of P-gp and CYP3A4. The aim of this study was to investigate the potential pharmacokinetic interactions between Rh2 and the HIV protease inhibitor ritonavir.
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Design, synthesis and cytotoxicity of cell death mechanism of rotundic acid derivatives.
Bioorg. Med. Chem. Lett.
PUBLISHED: 02-22-2013
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In the present investigation, 16 new rotundic acid (RA) derivatives modified at the C-3, C-23 and C-28 positions were synthesized. The cytotoxicities of the derivatives were evaluated against HeLa, A375, HepG2, SPC-A1 and NCI-H446 human tumor cell lines by MTT assay. Among these derivatives, compounds 4-7 exhibited stronger cell growth inhibitory than RA and compound 4 was found to be the best inhibition activity on five human tumor cell lines with IC50 <10 ?M. The apoptosis mechanism of compound 4 in HeLa cells was investigated by western blot analysis. The results indicated that compound 4 could induce apoptosis through increasing protein expression of cleaved caspase-3 and Bax, and decreasing protein expression of Bcl-2. In summary, the present work suggests that compound 4 might serve as an effective chemotherapeutic candidate.
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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.