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Find video protocols related to scientific articles indexed in Pubmed.
Antiviral medication use in a cohort of pregnant women during the 2009-2010 influenza pandemic.
J Obstet Gynaecol
PUBLISHED: 11-20-2014
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Preventing influenza-like illness (ILI) during pregnancy with antiviral medication use (AVMU) can mitigate serious health risks to mother and foetus. We report on AVMU in pregnant women in Ontario, Canada, and describe characteristics of AVMU during the 2009-2010 H1N1 pandemic. Rates and risk estimates of AVMU were compared across multiple categories and stratified across ILI infection status. Increased AVMU was observed in women with influenza infections, active smokers, those vaccinated against influenza, and those with pre-existing co-morbidities. Decreased AVMU was observed in women with multiple gestations, and those in neighbourhoods of high immigrant concentrations. Our stratified analysis indicated that the observed patterns differed by ILI infection status. We demonstrated that once infected, women across multiple groups were equally likely to use antiviral medications. In this report we also propose possible clinical explanations for the observed differences in AVMU, which will be useful in planning prevention initiatives for future pandemics.
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First Succinyl-Proteome Profiling of Extensively Drug-Resistant Mycobacterium tuberculosis Revealed Involvement of Succinylation in Cellular Physiology.
J. Proteome Res.
PUBLISHED: 11-04-2014
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Protein lysine succinylation, an emerging protein post-translational modification widespread among eukaryotic and prokaryotic cells, represents an important regulator of cellular processes. However, the extent and function of lysine succinylation in Mycobacterium tuberculosis, especially extensively drug-resistant strain, remain elusive. Combining protein/peptide prefractionation, immunoaffinity enrichment, and LC-MS/MS analysis, a total of 686 succinylated proteins and 1739 succinylation sites of M. tuberculosis were identified, representing the first global profiling of M. tuberculosis lysine succinylation. The identified succinylated proteins are involved in a variety of cellular functions such as metabolic processes, transcription, translation, and stress responses and exhibit different subcellular localization via GO, protein interaction network, and other bioinformatic analysis. Notably, proteins involved in protein biosynthesis and carbon metabolism are preferred targets of lysine succinylation. Moreover, two prevalent sequence patterns: EK(suc) and K*****K(suc), can be found around the succinylation sites. There are 109 lysine-succinylated homologues in E. coli, suggesting highly conserved succinylated proteins. Succinylation was found to occur at the active sites predicted by Prosite signature including Rv0946c, indicating that lysine succinylation may affect their activities. There is extensive overlapping between acetylation sites and succinylation sites in M. tuberculosis. Many M. tuberculosis metabolic enzymes and antibiotic resistance proteins were succinylated. This study provides a basis for further characterization of the pathophysiological role of lysine succinylation in M. tuberculosis.
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Architectural Design of Heterogeneous Metallic Nanocrystals-Principles and Processes.
Acc. Chem. Res.
PUBLISHED: 10-25-2014
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Conspectus Heterogeneous metal nanocrystals (HMNCs) are a natural extension of simple metal nanocrystals (NCs), but as a research topic, they have been much less explored until recently. HMNCs are formed by integrating metal NCs of different compositions into a common entity, similar to the way atoms are bonded to form molecules. HMNCs can be built to exhibit an unprecedented architectural diversity and complexity by programming the arrangement of the NC building blocks ("unit NCs"). The architectural engineering of HMNCs involves the design and fabrication of the architecture-determining elements (ADEs), i.e., unit NCs with precise control of shape and size, and their relative positions in the design. Similar to molecular engineering, where structural diversity is used to create more property variations for application explorations, the architectural engineering of HMNCs can similarly increase the utility of metal NCs by offering a suite of properties to support multifunctionality in applications. The architectural engineering of HMNCs calls for processes and operations that can execute the design. Some enabling technologies already exist in the form of classical micro- and macroscale fabrication techniques, such as masking and etching. These processes, when used singly or in combination, are fully capable of fabricating nanoscopic objects. What is needed is a detailed understanding of the engineering control of ADEs and the translation of these principles into actual processes. For simplicity of execution, these processes should be integrated into a common reaction system and yet retain independence of control. The key to architectural diversity is therefore the independent controllability of each ADE in the design blueprint. The right chemical tools must be applied under the right circumstances in order to achieve the desired outcome. In this Account, after a short illustration of the infinite possibility of combining different ADEs to create HMNC design variations, we introduce the fabrication processes for each ADE, which enable shape, size, and location control of the unit NCs in a particular HMNC design. The principles of these processes are discussed and illustrated with examples. We then discuss how these processes may be integrated into a common reaction system while retaining the independence of individual processes. The principles for the independent control of each ADE are discussed in detail to lay the foundation for the selection of the chemical reaction system and its operating space.
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[Treatment of combined hyperlipidemia patients by jiangzhi tongluo soft capsule combined atorvastatin calcium tablet: a clinical study].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 10-23-2014
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To evaluate the efficacy and safety of using Jiangzhi Tongluo Soft Capsule (JTSC) combined with Atorvastatin Calcium Tablet (ACT) or ACT alone in treatment of combined hyperlipidemia.
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Engineering the Work Function of Buckled Boron ?-Sheet by Lithium Adsorption: A First-Principles Investigation.
ACS Appl Mater Interfaces
PUBLISHED: 10-22-2014
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First-principles density functional theory calculations were performed to study the effect of Li adsorption on the structural and electronic properties, particularly the work function, of boron ?-sheet. The calculated binding energies indicated that boron ?-sheet could be well stabilized by the adsorption of Li atoms. Furthermore, the work functions of Li-adsorbed boron ?-sheets were observed to decrease drastically with increasing Li coverage. The work functions are lower than that of Mg and even, for some of them, lower than that of Ca, indicating a considerable potential application of Li-adsorbed boron ?-sheets as field-emission and electrode materials. Based on the calculated geometric and electronic structures, we discuss in details some possible aspects affecting the work function. The Li coverage dependence of the work functions of Li-adsorbed boron ?-sheets was further confirmed by electrostatic potential analyses. The relationship between the work function variation and the Fermi and vacuum energy level shifts was also discussed, and we observed that the variation of the work function is primarily associated with the shift of the Fermi energy level. It is the surface dipole formed by the interaction between adatoms and substrate that should be responsible for the observed variation of the work function, whereas the increasing negative charge and rumpling for boron ?-sheet only play minor roles. Additionally, the effect of Li adatoms on the work function of boron ?-sheet was confirmed to be much stronger than that of graphene or a graphene double layer.
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Rapid Charge-Discharge Property of Li4Ti5O12-TiO2 Nanosheet and Nanotube Composites as Anode Material for Power Lithium-Ion Batteries.
ACS Appl Mater Interfaces
PUBLISHED: 10-21-2014
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Well-defined Li4Ti5O12-TiO2 nanosheet and nanotube composites have been synthesized by a solvothermal process. The combination of in situ generated rutile-TiO2 in Li4Ti5O12 nanosheets or nanotubes is favorable for reducing the electrode polarization, and Li4Ti5O12-TiO2 nanocomposites show faster lithium insertion/extraction kinetics than that of pristine Li4Ti5O12 during cycling. Li4Ti5O12-TiO2 electrodes also display lower charge-transfer resistance and higher lithium diffusion coefficients than pristine Li4Ti5O12. Therefore, Li4Ti5O12-TiO2 electrodes display lower charge-transfer resistance and higher lithium diffusion coefficients. This reveals that the in situ TiO2 modification improves the electronic conductivity and electrochemical activity of the electrode in the local environment, resulting in its relatively higher capacity at high charge-discharge rate. Li4Ti5O12-TiO2 nanocomposite with a Li/Ti ratio of 3.8:5 exhibits the lowest charge-transfer resistance and the highest lithium diffusion coefficient among all samples, and it shows a much improved rate capability and specific capacity in comparison with pristine Li4Ti5O12 when charging and discharging at a 10 C rate. The improved high-rate capability, cycling stability, and fast charge-discharge performance of Li4Ti5O12-TiO2 nanocomposites can be ascribed to the improvement of electrochemical reversibility, lithium ion diffusion, and conductivity by in situ TiO2 modification.
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Bio-NCs - the marriage of ultrasmall metal nanoclusters with biomolecules.
Nanoscale
PUBLISHED: 10-01-2014
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Ultrasmall metal nanoclusters (NCs) have attracted increasing attention due to their fascinating physicochemical properties. Today, functional metal NCs are finding growing acceptance in biomedical applications. To achieve a better performance in biomedical applications, metal NCs can be interfaced with biomolecules, such as proteins, peptides, and DNA, to form a new class of biomolecule-NC composites (or bio-NCs in short), which typically show synergistic or novel physicochemical and physiological properties. This feature article focuses on the recent studies emerging at the interface of metal NCs and biomolecules, where the interactions could impart unique physicochemical properties to the metal NCs, as well as mutually regulate biological functions of the bio-NCs. In this article, we first provide a broad overview of key concepts and developments in the novel biomolecule-directed synthesis of metal NCs. A special focus is placed on the key roles of biomolecules in metal NC synthesis. In the second part, we describe how the encapsulated metal NCs affect the structure and function of biomolecules. Followed by that, we discuss several unique synergistic effects observed in the bio-NCs, and illustrate them with examples highlighting their potential biomedical applications. Continued interdisciplinary efforts are required to build up in-depth knowledge about the interfacial chemistry and biology of bio-NCs, which could further pave their ways toward biomedical applications.
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Protein-based fluorescent metal nanoclusters for small molecular drug screening.
Chem. Commun. (Camb.)
PUBLISHED: 09-26-2014
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A facile drug screening method based on synthesis of fluorescent gold nanoclusters inside albumin proteins loaded with small molecular drugs and comparing the relative fluorescence intensities of the resultant gold nanoclusters has been developed and successfully applied for the quantitative measurement of drug-protein binding constants.
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Crucial components of mycobacterium type II fatty acid biosynthesis (Fas-II) and their inhibitors.
FEMS Microbiol. Lett.
PUBLISHED: 09-02-2014
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Abundant mycolic acids are the hallmark of the mycobacterial cell wall. The biosynthesis of mycolic acids fulfilled by type I (Fas-I) and type II (Fas-II) synthase systems necessitates long chain fatty acids as the raw material. Fas-I is responsible for de novo fatty acid synthesis to form fatty acids 16-24 carbons in length and then elongated by the monofunctional enzymes of Fas-II to form long chain fatty acids, and further to form mycolic acids. Mutation of monofunctional enzymes can confer mycobacterial drug resistance. The key monofunctional enzymes of this system might represent new drug target candidates for antituberculosis drug development.
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Changes in the cellular proteins of A549 infected with hepatitis E virus by proteomics analysis.
BMC Vet. Res.
PUBLISHED: 08-30-2014
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Our understanding of Hepatitis E virus (HEV) has changed enormously over the past 30 years, from a waterborne infection causing outbreaks of acute hepatitis in developing countries to an infection of global distribution causing a range of hepatic and extra-hepatic illness. However, the key proteins playing important parts in the virus infection were still unknown. Understanding the changes of cellular proteins in these cells exposed to HEV is helpful for elucidating molecular mechanisms associated with function alterations of HEV-infected susceptible cells. In the present study, a comparative gel-based proteomic analysis was employed to study the changes in cellular proteins of A549 exposed to HEV in vitro to provide novel information for understanding the functional alterations of A549 induced by HEV infection.
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Counterion-Assisted Shaping of Nanocluster Supracrystals.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 08-29-2014
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Ag44 (p-MBA)30 (4-) (p-MBA=para-mercaptobenzoic acid) nanocluster (NC) supracrystals (SCs) with customizable shapes can be obtained by simply altering the type and concentration of the counterions of the p-MBA ligands in the dimethylsulfoxide (DMSO)/water crystallization system. Changing the counterion of the p-MBA ligand from H(+) to Cs(+) eliminates the directional hydrogen bonds in the SCs, resulting in the packing of deprotonated Ag44 (p-MBA)30 (4-) NCs into octahedral SCs, which is in stark contrast to the rhombohedral SCs that were formed by the packing of protonated Ag44 (p-MBA)30 (4-) NCs in previous studies. Furthermore, the double layer of deprotonated Ag44 (p-MBA)30 (4-) NCs is sensitive to charge screening induced by increasing the Cs(+) concentration, thereby providing a means to regulate the precipitation kinetics of the Ag44 (p-MBA)30 (4-) NCs for SC shape engineering. Slow precipitation kinetics was found to favor over-growth at the corners and edges of the octahedral SC nuclei, shaping the SCs into concave octahedra.
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An association between BDNF Val66Met polymorphism and impulsivity in methamphetamine abusers.
Neurosci. Lett.
PUBLISHED: 08-27-2014
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Recent studies showed an association between a functional polymorphism of BDNF gene (Val66Met) and the susceptibility to methamphetamine addiction. We hypothesized that this polymorphism was associated with methamphetamine abuse and impulsivity in methamphetamine-abuse patients. The polymorphism was genotyped in 200 methamphetamine-abuse patients and 219 healthy controls. The association of the Val66Met polymorphism of the BDNF gene and impulsivity in 138 methamphetamine abusers were assessed using Barratt Impulsivity Scale-11(BIS-11) Chinese version. The relationship between the polymorphism and age of onset of methamphetamine abuse was also examined. Our results showed no significant differences in genotype and allele distributions between the methamphetamine abusers and controls. Within the methamphetamine-abuse group, subjects carried the Met allele had significantly higher attentional impulsivity scores of BIS compared to those with the Val/Val genotype. The Met allele was also associated with earlier age onset of methamphetamine use. Our findings suggest that the BDNF Val66Met gene polymorphism may influence attentional impulsivity in methamphetamine abusers. Moreover, the BDNF Val66Met gene polymorphism may contribute to onset age of methamphetamine use.
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[Undergraduate teaching in life science exemplified by mycobacteriophages].
Yi Chuan
PUBLISHED: 08-22-2014
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An emerging theme of current biomedical study is a synthesis of multi-disciplinary tools to address the complex biological issues. This trend raised the bar for undergraduate teaching and learning. The phage is an ideal material for teaching reform. Inspired by the "phage hunter" project initiated by Pittsburgh University, we present our practice in translating the mycobacteriophage research achievements into undergraduate teaching experience during the last five years.
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A first-principles investigation of the stabilities and electronic properties of SrZrO3 (1?1?0) (1? × ?1) polar terminations.
J Phys Condens Matter
PUBLISHED: 08-20-2014
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The stabilities and electronic properties of SrZrO3 (1?1?0) (1? × ?1) polar terminations were investigated systematically by the first-principles density functional theory method. Five possible polar surfaces, i.e. O-deficient, O-rich, stoichiometric, SrO-rich and SrO-deficient ones, were considered. The calculated results indicated that the charge neutralization and polarity compensation condition could be achieved by charge redistributions of surface atoms. For the O-deficient (1?1?0) termination, some filled electronic states were separated from the original conduction bands, while a surface reconstruction was found for the O-rich (1?1?0) surface. The remaining three (1?1?0) terminations remained insulated. Furthermore, a stability diagram involving seven different terminations was constructed using the surface grand potential technique, in which the effect of the chemical environment was included. The calculated results indicated that three (1?1?0) (O-rich, SrO-rich and stoichiometric) and 2 (0?0?1) (ZrO2 and SrO) terminations could be stabilized in distinct areas, whereas the O-deficient surface was unstable within the whole region. Finally, we drew a comparison of stability behaviors between SrZrO3 (1?1?0) (1? × ?1) polar surfaces and the counterparts of ATiO3 (A = Ba, Pb, Sr) and BaZrO3 materials.
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Synthesis of optically active deuterated primary amines via reduction of N-tert-butanesulfinyl aldimines.
J. Org. Chem.
PUBLISHED: 08-11-2014
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Optically active deuterated primary amines have been obtained with 78-98% ee's from chiral N-tert-butanesulfinyl aldimines via reduction with N-Selectride and subsequent alcoholysis.
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Novel cyclopentadienyl tricarbonyl (99m)tc complexes containing 1-piperonylpiperazine moiety: potential imaging probes for sigma-1 receptors.
J. Med. Chem.
PUBLISHED: 08-11-2014
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We report the design, synthesis, and evaluation of a series of novel cyclopentadienyl tricarbonyl (99m)Tc complexes as potent ?1 receptor radioligands. Rhenium compounds 3-(4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl)propylcarbonylcyclopentadienyl tricarbonyl rhenium (10a) and 4-(4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl)butylcarbonylcyclopentadienyl tricarbonyl rhenium (10b) possessed high in vitro affinity for ?1 receptors and moderate to high selectivity for ?2 receptors and the vesicular acetylcholine transporter. Biodistribution studies in mice demonstrated high initial brain uptake for corresponding (99m)Tc derivatives [(99m)Tc]23 and [(99m)Tc]24 of 2.94 and 2.13% injected dose (ID)/g, respectively, at 2 min postinjection. Pretreatment of haloperidol significantly reduced the radiotracer accumulation of [(99m)Tc]23 or [(99m)Tc]24 in the brain. Studies of the cellular uptake of [(99m)Tc]23 in C6 and DU145 tumor cells demonstrated a reduction of accumulation by incubation with haloperidol, 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine (SA4503), or 1,3-di-o-tolyl-guanidine (DTG). Furthermore, blocking studies in C6 glioma-bearing mice confirmed the specific binding of [(99m)Tc]23 to ?1 receptors in the tumor.
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Recombination in truncated genome sequences of porcine circovirus type 2.
Arch. Virol.
PUBLISHED: 08-05-2014
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Porcine circovirus type 2 (PCV2) is the causal agent of a serious disease found in pigs. Here, we report the first detection of truncated genome sequences of PCV2 strain ZJ-R, with the genomic region encoding part of Rep and Cap with a nonviral insertion. To our knowledge, the genome of ZJ-R represents the first PCV2 DNA with a coding insertion. The PCV2 ZJ-R genome is 694 nucleotides long and has two main open reading frames. The whole genome sequence of ZJ-R may facilitate further study of the origin and evolution of PCV2.
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Pd-catalyzed [3+2] cycloaddition of ketoimines with alkynes via directed sp³ C-H bond activation.
Chem. Commun. (Camb.)
PUBLISHED: 07-31-2014
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The Pd(II)-catalyzed oxidative [3+2] cycloaddition of N-(2-pyridyl) ketoimines with internal alkynes has been developed. The transformation is tolerant of extensive substitution on halogen, alkene, alkyne, hydroxyl, aryl and acyl groups, and allows facile assembly of multisubstituted pyrroles.
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Mycobacterium biofilms: factors involved in development, dispersal, and therapeutic strategies against biofilm-relevant pathogens.
Crit. Rev. Eukaryot. Gene Expr.
PUBLISHED: 07-30-2014
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Many bacteria can develop biofilm (BF), a multicellular structure largely combining bacteria and their extracellular polymeric substances (EPS). The formation of biofilm results in an alternative existence in which microbes ensure their survival in adverse environments. Biofilm-relevant infections are more persistent, resistant to most antibiotics, and more recalcitrant to host immunity. Mycobacterium tuberculosis, the causative agent of tuberculosis, can develop biofilm, though whether M. tuberculosis can form biofilm within tuberculosis patients has yet to be determined. Here, we summarize the factors involved in the development and dispersal of mycobacterial biofilms, as well as underlying regulatory factors and inhibitors against biofilm to deepen our understanding of their development and to elucidate potential novel modes of action for future antibiotics. Key factors in biofilm formation identified as drug targets represent a novel and promising avenue for developing better antibiotics.
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Storage of Gold Nanoclusters in Muscle Leads to their Biphasic in Vivo Clearance.
Small
PUBLISHED: 07-25-2014
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Ultrasmall gold nanoclusters (Au NCs) show great potential in biomedical applications. Long-term biodistribution, retention, toxicity, and pharmacokinetics profiles are pre-requisites in their potential clinical applications. Here, the biodistribution, clearance, and toxicity of one widely used Au NC species-glutathione-protected Au NCs or GSH-Au NCs-are systematically investigated over a relatively long period of 90 days in mice. Most of the Au NCs are cleared at 30 days post injection (p.i.) with a major accumulation in liver and kidney. However, it is surprising that an abnormal increase of the Au amount in the heart, liver, spleen, lung, and testis is observed at 60 and 90 days p.i., indicating that the injected Au NCs form a V-shaped time-dependent distribution profile in various organs. Further investigations reveal that Au NCs are steadily accumulating in the muscle in the first 30 days p.i., and the as-stored Au NCs gradually release into the blood in 30-90 days p.i., which induces a re-distribution and re-accumulation of Au NCs in all blood-rich organs. Further hematology and biochemistry studies show that the re-accumulation of Au NCs still causes some liver toxicity at 30 days p.i. The muscle storage and subsequent release may give rise to the potential accumulation and toxicity risk of functional nanomaterials over long periods of time.
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Antidepressant-like effects of Chaihu-Shugan-San via SAPK/JNK signal transduction in rat models of depression.
Pharmacogn Mag
PUBLISHED: 07-24-2014
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Chaihu-Shugan-San (CHSGS), a traditional Chinese medicinal herbal formula, registered in Jingyue Quanshu, has been indicated that oral administration of the extract from it can remit depressive disorder. C-Jun amino-terminal kinase (JNK/SAPK) signal transduction plays a key role in the apoptosis of nerve cells, be reported closely correlated with depression. This study was designed to investigate CHSGS antidepressant-like effects in rat models of depression and probe its possible mechanism.
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Toward understanding the growth mechanism: tracing all stable intermediate species from reduction of Au(I)-thiolate complexes to evolution of Au?? nanoclusters.
J. Am. Chem. Soc.
PUBLISHED: 07-21-2014
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Despite 20 years of progress in synthesizing thiolated gold nanoclusters (Au NCs), the knowledge of their growth mechanism still lags behind. Herein the detailed process from reduction of Au(I)-thiolate complex precursors to the eventual evolution of and focusing to the atomically precise Au25 NCs was revealed for the first time by monitoring the time evolution of Au(I) precursor and Au NC intermediate species with ESI-MS. A two-stage, bottom-up formation and growth process was proposed: a fast stage of reduction-growth mechanism, followed by a slow stage of intercluster conversion and focusing. Balanced reactions of formation for each identified NC were suggested, backed by theoretical calculations of the thermodynamic driving force. This work advances one step further toward understanding the mechanism of formation and growth of thiolated Au NCs.
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Learning from nature: introducing an epiphyte-host relationship in the synthesis of alloy nanoparticles by co-reduction methods.
Chem. Commun. (Camb.)
PUBLISHED: 07-16-2014
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This communication reports an epiphytic co-reduction method which can overcome the common tendency of sequential deposition in the synthesis of alloy nanoparticles. In this method the reduction of one of the metals (the epiphyte-metal) is only turned-on and rendered more facile by the in situ generated fresh surfaces of the other metal (the host-metal).
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Modeling the interaction of interferon ?-1b to bovine serum albumin as a drug delivery system.
J Phys Chem B
PUBLISHED: 07-14-2014
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Protein-based nanoparticles represent a promising approach to carry polypeptide and protein drugs. Using both theory and experimentation, an interferon ?-1b (IFN) delivery system carried by bovine serum albumin (BSA) nanoparticles was designed. Theoretical results indicate the most probable binding site and interaction mechanism for IFN on BSA. IFN has a higher binding affinity with BSA compared with small chemical drugs. The drug loading is about 8 mg/g, significantly higher than those reported in other literature. The release profiles differ between the nanoparticles prepared by the incorporation method and the adsorption method. The adsorption of IFN on BSA nanoparticles is monolayer adsorption. The fact that IFN was carried successfully by BSA nanoparticles establishes a solid basis for expanding the drug loading field of BSA nanoparticles to proteins and polypeptides.
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Functional RsaI/PstI polymorphism in cytochrome P450 2E1 contributes to bladder cancer susceptibility: evidence from a meta-analysis.
Asian Pac. J. Cancer Prev.
PUBLISHED: 07-08-2014
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Cytochrome P450 2E1 (CYP2E1) might be involved in the development of bladder cancer. However, previous studies of any association between CYP2E1 RsaI/PstI polymorphism and bladder cancer risk have yielded conflicting results. In this study, we performed a more precise estimation of the relationship by a meta-analysis based on the currently available evidence from the literature.
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Cryptococcus inositol utilization modulates the host protective immune response during brain infection.
Cell Commun. Signal
PUBLISHED: 07-03-2014
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Background Cryptococcus neoformans is the most common cause of fungal meningitis among individuals with HIV/AIDS, which is uniformly fatal without proper treatment. The underlying mechanism of disease development in the brain that leads to cryptococcal meningoencephalitis remains incompletely understood. We have previously demonstrated that inositol transporters (ITR) are required for Cryptococcus virulence. The itr1a¿ itr3c¿ double mutant of C. neoformans was attenuated for virulence in a murine model of intra-cerebral infection; demonstrating that Itr1a and Itr3c are required for full virulence during brain infection, despite a similar growth rate between the mutant and wild type strains in the infected brain.ResultsTo understand the immune pathology associated with infection by the itr1a¿ itr3c¿ double mutant, we investigated the molecular correlates of host immune response during mouse brain infection. We used genome-wide transcriptome shotgun sequencing (RNA-Seq) and quantitative real-time PCR (qRT-PCR) methods to examine the host gene expression profile in the infected brain. Our results show that compared to the wild type, infection of mouse brains by the mutant leads to significant activation of cellular networks/pathways associated with host protective immunity. Most of the significantly differentially expressed genes (SDEG) are part of immune cell networks such as tumor necrosis factor-alpha (TNF-¿) and interferon-gamma (IFN-¿) regulon, indicating that infection by the mutant mounts a stronger host immune response compared to the wild type. Interestingly, a significant reduction in glucuronoxylomannan (GXM) secretion was observed in the itr1a¿ itr3c¿ mutant cells, indicating that inositol utilization pathways play a role in capsule production.ConclusionsSince capsule has been shown to impact the host response during Cryptococcus-host interactions, our results suggest that the reduced GXM production may contribute to the increased immune activation in the mutant-infected animals.
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Organocatalytic synthesis of optically active ?-branched ?-amino esters via asymmetric biomimetic transamination.
Org. Biomol. Chem.
PUBLISHED: 06-28-2014
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This paper describes an efficient asymmetric biomimetic transamination of ?-keto esters with a quinine-derived chiral base as the catalyst, giving a variety of ?-branched ?-amino esters in 50-96% yield and 87-95% ee.
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Ordered mesoporous black TiO(2) as highly efficient hydrogen evolution photocatalyst.
J. Am. Chem. Soc.
PUBLISHED: 06-23-2014
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Mesoporous TiO2 has gained increasing interest because of its outstanding properties and promising applications in a wide range of fields. Herein, we report the facile synthesis of ordered mesoporous black TiO2 (OMBT) materials, which exhibit excellent photocatalytic hydrogen evolution performances. In this case, the employment of a thermally stable and high-surface-area mesoporous TiO2 as the hydrogenation precursor is the key for fabricating the OMBT materials, which not only facilitate H2 gas diffusion into TiO2 and interaction with their structures but also maintain the ordered mesoporous structures as well as inhibit the phase transformation (from anatase to rutile) and crystal growth during hydrogenation at 500 °C. The resultant OMBT materials possess a relatively high surface area of ?124 m(2) g(-1) and a large pore size and pore volume of ?9.6 nm and 0.24 cm(3) g(-1), respectively. More importantly, the OMBT materials can extend the photoresponse from ultraviolet to visible and infrared light regions and exhibit a high solar-driven hydrogen production rate (136.2 ?mol h(-1)), which is almost two times as high as that of pristine mesoporous TiO2 (76.6 ?mol h(-1)).
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Novel Theranostic DNA Nanoscaffolds for the Simultaneous Detection and Killing of Escherichia coli and Staphylococcus aureus.
ACS Appl Mater Interfaces
PUBLISHED: 06-19-2014
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A novel theranostic platform is made by utilizing a self-assembled DNA nanopyramid (DP) as scaffold for incorporation of both detection and therapeutic moieties to combat bacterial infection. Red-emissive glutathione-protected gold nanoclusters (GSH-Au NCs) were used for bacterial detection. Actinomycin D (AMD) that was intercalated on the DP scaffold was used as therapeutic agent. This results in the formation of theranostic DPAu/AMD. Model bacteria Escherichia coli and Staphylococcus aureus were found to be readily taken in the DPAu/AMD and be susceptible to its killing effect. In addition, DPAu/AMD was observed to outperform the free AMD in killing infectious bacteria. The degradation of the DP structure by DNase was found to be responsible for the release of AMD and the effective killing effect of the infectious bacteria. This novel strategy presents a basic platform for future improvements to detect infectious bacteria and treatment.
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Comparative genomics of Mycobacterium tuberculosis drug efflux pumps and their transcriptional regulators.
Crit. Rev. Eukaryot. Gene Expr.
PUBLISHED: 06-19-2014
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Efflux pump systems are important in general drug resistance. Understanding efflux pumps can inform drug target selection and novel antibiotics designs. In this review, we have summarized the physiological roles, types, and mechanisms of drug efflux pumps. Mycobacterium tuberculosis is the causative agent of tuberculosis, a global threat to public health, and the increasing resistance of this mycobacterium to antibiotics is alarming. Therefore, we have focused on the comparative genomics of efflux pumps and relevant transcriptional regulators of M. tuberculosis.
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Deep sequencing analysis of microRNA expression in porcine serum-induced hepatic fibrosis rats.
Ann Hepatol
PUBLISHED: 06-14-2014
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Recent studies have suggested miRNA dysregulation in liver tissue mediates the pathogenesis of various liver diseases especially liver fibrosis, but the microRNA changes during PS-induced hepatic fibrosis are still unknown. The purpose of this study was to screen the miRNA differences in rat liver fibrosis model and clarify the relationship of miRNAs with the development of PS-induced liver fibrosis.
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[Analysis and assessment of atmospheric pollution based on accumulation characterization of heavy metals in Platanus acerifolia leaves].
Huan Jing Ke Xue
PUBLISHED: 06-03-2014
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The present work was aimed to evaluate the heavy metal pollution in the atmosphere of Huainan City. We measured and clustered the accumulation of six heavy metals in Platanus acerifolia leaves in 20 sampling fields with six types of environmental conditions, and analyzed the EF value of heavy metal enrichment in the leaves. The results showed that the accumulations in Platanus acerifolia leaves varied according to different types of metals, following the order of Zn > Cu > Cr > Ni > Pb > Cd. Environmental conditions also had great influence on the accumulation of heavy metals. Cd and Cu were mostly found in cement plant and mine, respectively, and Cr, Ni, Pb and Zn were significant higher in main road, compared with other environmental conditions. The average values of EF for all the metals expect Cr in scenic and village area were over 1. The average values of EF for all the metals in mine, power plant, main road and cement plant were above 3. The overall pollution condition of heavy metals in Huainan City followed the order of Cd > Cu > Zn > Ni > Pb > Cr.
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Facile synthesis of water-soluble Au(25-x)Ag(x) nanoclusters protected by mono- and bi-thiolate ligands.
Chem. Commun. (Camb.)
PUBLISHED: 05-31-2014
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A series of water-soluble Au25-xAgx nanoclusters (NCs) protected by mono- and bi-thiolate ligands are synthesized via the NaOH-mediated NaBH4 reduction method. Compositions of both the metal core and the ligand shell can be tailored by varying the feeding ratios of metal precursors and hetero-ligands, further enriching the functionalities of the NCs.
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Prognostic value of pretreatment serum alkaline phosphatase in nasopharyngeal carcinoma.
Asian Pac. J. Cancer Prev.
PUBLISHED: 05-30-2014
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The prognostic value of serum alkaline phosphatase (S-ALP) has not been fully validated for nasopharyngeal carcinoma (NPC).
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D-serine plasma concentration is a potential biomarker of (R,S)-ketamine antidepressant response in subjects with treatment-resistant depression.
Psychopharmacology (Berl.)
PUBLISHED: 04-29-2014
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(R,S)-ketamine is a rapid and effective antidepressant drug that produces a response in two thirds of patients with treatment-resistant depression (TRD). The underlying biochemical differences between a (R,S)-ketamine responder (KET-R) and non-responder (KET-NR) have not been definitively identified but may involve serine metabolism.
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Association between Glutathione S-Transferase T1, M1, and P1 Genotypes and the Risk of Colorectal Cancer.
J. Korean Med. Sci.
PUBLISHED: 04-24-2014
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Glutathione S-transferases (GSTs) are enzymes which play an important role in the neutralization of toxic compounds and eradication of electrophilic carcinogens. Genetic polymorphisms within the genes encoding for GSTs may therefore cause variations in their enzyme activity, which may in turn influence the interindividual susceptibility to cancers. In this study, we aimed to investigate the association between genetic polymorphisms of GSTT1, GSTM1, and GSTP1 and the risk of colorectal cancer (CRC) in 264 cases and 317 controls in a Chinese population. Genotyping was performed by using multiplex PCR (for GSTT1 and GSTM1) and PCR-RFLP (for GSTP1) methods. The association between the polymorphic genotypes and CRC risk was evaluated by deriving odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis. Our results showed that individuals with GSTT1 and GSTM1 null genotypes exhibited a higher risk of CRC (GSTT1, OR,1.66; 95% CI, 1.20-2.31, P=0.003; GSTM1, OR,1.57; 95% CI,1.13-2.18, P=0.007), while no association was observed for GSTP1 (P heterozygous=0.790 or P variant=0.261). Furthermore, individuals who simultaneously carried the null genotypes for both GSTT1 and GSTM1 showed a stronger risk association (OR, 1.95; 95% CI, 1.33-2.85; P<0.001). In conclusion, the GSTT1 and GSTM1 polymorphisms, but not GSTP1, may modulate the CRC risk among Chinese.
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Rational design of multifunctional hetero-hexameric proteins for hydrogel formation and controlled delivery of bioactive molecules.
Adv Healthc Mater
PUBLISHED: 04-22-2014
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A hetero-hexameric protein system is developed in this study, which not only functions as cross-linkers for hydrogel formation but also offers docking sites for controlled delivery of bioactive molecules. First, a hexameric protein with two, four, and six tax-interacting protein-1 (TIP-1), respectively (named as 2T, 4T, and 6T), is designed and obtained. As the hexapeptide ligand (WRESAI) can specifically bind to TIP-1 with high affinity, the hexameric proteins of 2T, 4T, and 6T can be used to crosslink the self-assembling nanofibers of Nap-GFFYGGGWRESAI, leading to formation of injectable biohybrid hydrogels with tunable mechanical properties. Furthermore, a hetero-hexameric protein containing four TIP-1 and two C-terminal moiety of the pneumococcal cell-wall amidase LytA (C-LytA) proteins is designed and engineered (named as 4T2C). The 4T2C proteins can not only serve as cross-linkers for hydrogel formation but also provide docking sites for loading and controlled release of model drug Rhoda-GGK'. This study opens up new opportunities for further development of multifunctional hetero- recombinant protein-based hydrogels for biological applications.
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Luminescent properties of BaAl12O19:Tb, Dy phosphors prepared by sol-gel method.
J Nanosci Nanotechnol
PUBLISHED: 04-18-2014
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BaAl12O19:Tb, Dy phosphor was prepared by the sol-gel technique using citric acid as a complextant. XRD was used to characterize the relevant crystallization behavior of the phosphor. The luminescence properties and energy transfer between Tb3+ and Dy3+ were investigated. The results revealed that energy transfer exists between Dy3+ and Tb3+ at appropriate Tb3+ concentrations. The emission intensity of Tb3+ increases and energy transfer happens from Dy3+ to Tb3+ ions at the higher content of Tb3+ when Tb3+ and Dy3+ ions were co-doped. BaAl12O19 phosphors doped with Tb3+ or Dy3+ ions only were studied to compared with BaAl12O19:Tb, Dy phosphors. The results showed that the maximum excitation peak of BaAl12O19:Tb is 240 nm and the emission spectrum consists of four peaks at 490, 545, 590, and 625 nm, originating from 5D4 --> 7FJ (J = 6, 5, 4, 3) transitions of Tb3+ ion, respectively. The excitation peaks of BaAl12O19:Dy are at 291, 324 nm and the emissions of Dy3+ are at 370, 447 and 578 nm, originating from 4F9/2 --> 6P5/2, 4F9/2 --> 6H15/2 and 4F9/2 --> 6H13/2 transitions of Dy3+ ion, respectively.
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Near-infrared luminescence from Y2O3:Eu3+, Yb3+ prepared by sol-gel method.
J Nanosci Nanotechnol
PUBLISHED: 04-18-2014
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Eu3+ and Yb3+ codoped Y2O3 phosphors were synthesized by the sol-gel method. The phosphors possess absorption in the region of 300-550 nm, exhibiting an intense NIR emission of Yb3+ around 1000 nm, which is suitable for matching the maximum spectral response of c-Si solar cells. The optimum composition of Eu3+ and Yb3+ codoped Y2O3 was (Y1.94Yb0.04Eu0.02)2O3. It is observed that two-step energy transfer occurs from the 5D2 level of Eu3+ situated around (466 nm) exciting two neighboring Yb3+ ions to the 2F5/2 level (1000 nm). The down-conversion material based on Eu(3+)- Yb3+ couple may have great potential applications in c-Si solar cells to enhance their photovoltaic conversion efficiency via spectral modification.
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miR-99a/100~125b tricistrons regulate hematopoietic stem and progenitor cell homeostasis by shifting the balance between TGF? and Wnt signaling.
Genes Dev.
PUBLISHED: 04-17-2014
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Although regulation of stem cell homeostasis by microRNAs (miRNAs) is well studied, it is unclear how individual miRNAs genomically encoded within an organized polycistron can interact to induce an integrated phenotype. miR-99a/100, let-7, and miR-125b paralogs are encoded in two tricistrons on human chromosomes 11 and 21. They are highly expressed in hematopoietic stem cells (HSCs) and acute megakaryoblastic leukemia (AMKL), an aggressive form of leukemia with poor prognosis. Here, we show that miR-99a/100?125b tricistrons are transcribed as a polycistronic message transactivated by the homeobox transcription factor HOXA10. Integrative analysis of global gene expression profiling, miRNA target prediction, and pathway architecture revealed that miR-99a/100, let-7, and miR-125b functionally converge at the combinatorial block of the transforming growth factor ? (TGF?) pathway by targeting four receptor subunits and two SMAD signaling transducers. In addition, down-regulation of tumor suppressor genes adenomatous polyposis coli (APC)/APC2 stabilizes active ?-catenin and enhances Wnt signaling. By switching the balance between Wnt and TGF? signaling, the concerted action of these tricistronic miRNAs promoted sustained expansion of murine and human HSCs in vitro or in vivo while favoring megakaryocytic differentiation. Hence, our study explains the high phylogenetic conservation of the miR-99a/100?125b tricistrons controlling stem cell homeostasis, the deregulation of which contributes to the development of AMKL.
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Prevalence and correlates of depressive symptoms during early methamphetamine withdrawal in Han Chinese population.
Drug Alcohol Depend
PUBLISHED: 04-02-2014
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Depression, a common comorbidity of drug abuse, is often a core component of withdrawal symptoms; however, risk factors associated with depressive symptoms during the acute stage of withdrawal among methamphetamine (METH) users are not well understood. This study investigated the correlations between several potential risk factors and depressive symptoms during acute METH withdrawal in a Han Chinese population.
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The influence of lysosomal stability of silver nanomaterials on their toxicity to human cells.
Biomaterials
PUBLISHED: 03-27-2014
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How silver nanomaterials (Ag NMs) could induce toxicity has been debated heatedly by many researchers. We utilized Ag nanoclusters (Ag NCs) with the same size and ligand protection but different core surface speciation. Ag(+)-rich NCs (Ag(+)-R NCs) and their counterpart, the reduced Ag(0)-rich NCs (Ag(0)-R NCs) are synthesized to represent possible dichotomous stages in silver nanomaterial degradation process. Here we show Ag(0)-R NCs induce higher cellular toxicity when compared to Ag(+)-R NCs. This cellular toxicity is brought about via the modulation of reactive oxygen species (ROS) in cells as a result of the more rapid release of Ag species from Ag(0)-R NCs and subsequent oxidation into Ag(+) in the lysosomal compartment. The weaker Ag(0)-R bond greatly potentiated the release of Ag species in the acidic and enzymatic processes within the lysosomes. Since lysosomes are absent in bacteria, increasing silver nanomaterials stability may lower toxicity in mammalian cells whilst not reducing their efficacy to fight bacteria; this redesign can result in a safer silver nanomaterial.
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A facile approach for crosslinker free nano self assembly of protein for anti-tumor drug delivery: factors' optimization, characterization and in vitro evaluation.
Eur J Pharm Sci
PUBLISHED: 03-23-2014
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We report crosslinker free self assembly of bovine serum albumin (BSA) and a hydrophobic payload paclitaxel (PTX), into nanoparticles by harnessing the temperature driven unfolding of protein. To systematically study the effects of various factors responsible for the key attributes of the nanoparticles, a Resolution IV design was used. 20 formulations were made with pH, temperature, time of heating before and after addition of drug, stirring rate, protein concentration, and protein to drug ratio selected as independent variables. Particle size, encapsulation efficiency, yield and zeta potential were the response variables. Perturbation and Pareto charts were used to single out the important factors, while, mathematical equations and 3D surface charts have been used to describe the relationship between dependent and independent variables. Nanoparticles with size of 188-482 nm were observed with a highly negative zeta potential of -39.5 to -21.9. Nanoparticles obtained had decent encapsulation efficiency (72.5-87.9%) with effective yield (80.0-93.8%). Validation of the mathematical models with 4 runs indicated the good prognostic ability of Resolution IV design. Spectroscopic studies suggested the non-covalent complexation between BSA and PTX as the possible mechanism of self assembly due to irreversible conformational changes in protein. Transmission Electron Microscopy (TEM) revealed spherical nanoparticles with a porous network of PTX-BSA. X-ray Diffraction (XRD) showed amorphous nature of nanoparticles. PTX release from the nanoparticles was found to be controlled release and followed Peppas-Sahlin model. In vitro cytotoxicity of PTX-BSA nanoparticles was comparable to that of Taxol after 48 h treatment. These findings suggest heat driven BSA self assembly as a viable approach to formulate cytotoxic drug carrying nanoparticles which could be efficiently used in anti-cancer therapy.
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X protein mutations in hepatitis B virus DNA predict postoperative survival in hepatocellular carcinoma.
Tumour Biol.
PUBLISHED: 03-21-2014
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Hepatitis B virus (HBV) DNA is prone to mutations because of the proofreading deficiencies of HBV polymerase. The postoperative prognostic value of HBV mutations in HBV X protein (HBx) gene was assessed in HBV associated hepatocellular carcinoma (HCC) patients. The HBx gene was amplified and sequenced, the HBV mutations was identified according to NCBI database ( http://www.ncbi.nlm.nih.gov/genome/5536 ). The relationship between the HBV mutations and HCC survival was compared. Survival curves were generated using the Kaplan-Meier method, and comparisons between the curves were made using the log-rank test. Multivariate survival analysis was performed using a Cox proportional hazards model. After adjusting for clinical characteristics, the following eight mutational sites were identified as statistically significant independent predictors of HCC survival: 1383, 1461, 1485, 1544, 1613, 1653, 1719, and 1753. In addition, the following four mutational sites were identified for their association with survival at a border-line significance level: 1527, 1637, 1674, and 1762/1764. A total of 12 mutations in HBx gene region were identified as independent predictors of postoperative survival in HCC patients. The analysis of HBV DNA mutations may help identify patient subgroups with poor prognosis and may help refine therapeutic decisions regarding HCC patients.
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PEGylated carboxymethyl chitosan/calcium phosphate hybrid anionic nanoparticles mediated hTERT siRNA delivery for anticancer therapy.
Biomaterials
PUBLISHED: 03-20-2014
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Lack of safe and effective delivery vehicle is the main obstacle for siRNA mediated cancer therapy. In this study, we synthesized a pH-sensitive polymer of PEG grafted carboxymethyl chitosan (PEG-CMCS) and developed anionic-charged hybrid nanoparticles of PEG-CMCS and calcium phosphate (CaP) for siRNA delivery through a single-step self-assembly method in aqueous condition. The formed nanoparticles with charge of around -8.25 mv and average diameter of 102.1 nm exhibited efficient siRNA encapsulation and enhanced colloidal and serum stability. The test in vitro indicated that the nanoparticles entered into HepG2 cells by endocytosis, and achieved endosomal escape of siRNA effectively due to the pH-responsive disassembly of nanoparticles and dissolution of CaP in the endosome. Reporter gene silencing assay showed that luciferase siRNA delivered by the anionic nanoparticles could achieve gene silencing efficacy comparable to that of conventional Lipofectamine 2000. Additionally, dramatic hTERT knockdown mediated by the anionic nanoparticles transfection induced significant apoptosis of HepG2 cells in vitro. After intravenous injection in tumor-bearing BALB/c nude mice, the nanoparticles specifically accumulated into tumor regions by EPR effect, leading to efficient and specific gene silencing sequentially. Most importantly, the nanoparticles carrying hTERT siRNA inhibited tumor growth significantly via silencing hTERT expression and inducing cells apoptosis in HepG2 tumor xenograft. Moreover, comprehensive safety studies of the nanoparticles confirmed their superior safety both in vitro and in vivo. We concluded that the PEG-CMCS/CaP hybrid anionic nanoparticles possessed potential as a safe and effective siRNA delivery system for anticancer therapy.
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Increased serum brain-derived neurotrophic factor levels during opiate withdrawal.
Neurosci. Lett.
PUBLISHED: 03-15-2014
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Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of opiate addiction. Both increased and decreased serum BDNF levels have been reported in heroin addicts. Moreover, the role of BDNF in heroin-dependent patients during withdrawal has not been studied. This study aimed to explore the differences in serum BDNF levels of heroin addicts and healthy controls, and investigate the changes of serum BDNF levels in heroin addicts at baseline and at one month after heroin cessation. Seventy-two heroin-dependent patients and ninety age- and gender-matched healthy controls were enrolled in this study. We measured serum BDNF levels at baseline (both heroin addicts and healthy controls) and one month after heroin cessation (heroin addicts only). A total of 37 (51.4%) heroin addicts completed the one-month study. We found that baseline serum BDNF levels were significantly higher in heroin addicts compared to controls (F=36.5, p=0.001). There was no difference in serum BDNF levels among heroin addicts at baseline and one month after heroin cessation (F=1.101, p=0.301). These results indicate that BDNF may play a critical role in the course of opiate addiction and withdrawal.
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Determination of a novel carbamate AChE inhibitor meserine in mouse plasma, brain and rat plasma by LC-MS/MS: application to pharmacokinetic study after intravenous and subcutaneous administration.
J Pharm Biomed Anal
PUBLISHED: 03-12-2014
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In this paper a simple and sensitive method for determination of a novel phenylcarbamate AChE inhibitor, meserine, in mouse plasma, brain and rat plasma was evaluated using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Separation was achieved on an Alltech Alltima-C18 column (150mm×2.1mm, 3?m, Deerfield, IL, USA) with isocratic elution at a flow rate of 0.35ml/min. Detection was performed under the multiple reaction monitoring (MRM) mode using an electrospray ionization (ESI) in the positive ion mode. The protein precipitation and liquid-liquid extraction methods were used for the pretreatment of plasma and brain homogenates, respectively. The calibration curves of meserine showed good linearity over the concentration range of 0.5-1000ng/ml for mouse and rat plasma and 0.5-500ng/ml for mouse brain. The intra- and inter-day precision were less than 9.34% and the accuracy was from 95.34% to 107.78% for QC samples. The validated method was successfully applied to a preclinical pharmacokinetic study of meserine in mice and rats after intravenous and subcutaneous administration. The results showed that this novel drug could easily cross the blood-brain barrier to reach the site of drug action. Meserine was rapidly absorbed with a high subcutaneous absolute bioavailability (>90%).
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Understanding the thermal and mechanical stabilities of olivine-type LiMPO4 (M = Fe, Mn) as cathode materials for rechargeable lithium batteries from first principles.
ACS Appl Mater Interfaces
PUBLISHED: 03-11-2014
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To elucidate the microscopic origin of the difference behaviors, first-principles calculations were performed to investigate the thermal and mechanical stabilities of LixFePO4 and LixMnPO4. The calculated free energies suggested that LiFePO4 and LiMnPO4 are thermal stable with respect to relevant oxides both in their pristine and fully delithiated states. According to the calculations, it can be identified that the shear deformations are more easier to occur with respect to the volume compressions in LixFePO4 and LixMnPO4, and this phenomenon is related to M-O(I) and M-O(II) bonds. Typically for MnPO4, Li(+) extraction from the host structures further weakens the Mn-O(I) bonds by about 33%, and it thus becomes very brittle. The shear anisotropy (AG) of MnPO4 is abnormally large and has already reached 19.05 %, which is about 6 times as large as that of FePO4. Therefore, shear deformations and dislocations occur easily in MnPO4. Moreover, as the Mn-O(I) bonds in MnPO4 are mainly spread within the {101} and {1?01} crystal planes, the relevant slip systems thus allow the recombination of bonds at the interfaces, leading to the experimentally observed phase transformation. It can be concluded that mechanical reason will play an important role for the poor cycling performance of MnPO4.
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Kidney-specific drug delivery system for renal fibrosis based on coordination-driven assembly of catechol-derived chitosan.
Biomaterials
PUBLISHED: 03-06-2014
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Renal fibrosis is a common progressive kidney disease, and there is a lack of efficient treatment for the condition. In this study, we designed a kidney-specific nanocomplex by forming coordination-driven assembly from catechol-derived low molecular weight chitosan (HCA-Chi), metal ions and active drug molecules. The coordination activities of various metals and ligands, cytotoxicity, immunogenicity and biodistribution of HCA-Chi were investigated. Autofluorescent doxorubicin (DOX) was selected to fabricate HCA-Chi-Cu-DOX ternary nanocomplex for investigating cellular uptake behavior, transmembrane and targeting properties. The nanodevice demonstrated satisfactory stability under normal physiological conditions and pH-responsive drug release in acidic environments. Uptake of HCA-Chi-Cu-DOX by HK-2 cells was dependent on exposure time, concentration, and temperature, and was inhibited by blockers of megalin receptor. Tissue distribution showed that HCA-Chi-Cu-DOX nanocomplex was specifically accumulated in kidney with a renal relative uptake rate (r(e)) of 25.6. When active anti-fibrosis compound emodin was installed in HCA-Chi-Zn-emodin and intravenously injected to the ureter obstructed mice, obvious attenuation of fibrotic progression was exhibited. It was concluded that HCA-Chi coordination-driven nanocomplex showed special renal targeting capacity and could be utilized to develop drug delivery systems for treating renal fibrosis.
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Relationships of alpha-SMA-positive fibroblasts and SDF-1-positive tumor cells with neoangiogenesis in nasopharyngeal carcinoma.
Biomed Res Int
PUBLISHED: 02-28-2014
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Nasopharyngeal carcinoma (NPC) is one of the most prevalent malignant tumors with poor prognosis in Southern China and Southeast Asia. Angiogenesis-related molecules can be promising therapeutic targets in NPC. To investigate the relationships of cancer-associated fibroblasts (CAFs) and chemokine-related molecules with neoangiogenesis, we compared immunohistochemical analyses of alpha-smooth-muscle actin (?-SMA), stroma-derived factor-1 (SDF-1), and its receptor CXCR4 in primary NPC specimens and chronic nasopharyngitis tissues. In addition, we examined the expression of vascular endothelial growth factor (VEGF-A), and CD133- and VEGF- receptor-2 (VEGFR-2) double positive cells, as endothelial progenitor cells (EPCs). We also assessed CD34-positive microvessels. Significantly higher expression of ? -SMA was observed in fibroblasts in NPC stroma. The immunoreactive intensities of SDF-1 and CXCR4 were significantly higher in NPC cells. CXCR4-positive cells and CD133/VEGFR-2- double positive cells were observed in the stroma surrounding cancer nests, and VEGF was detected in both cancer and stromal cells. Microvessel density was significantly higher in the stroma of NPC tissues compared to chronic nasopharyngitis tissues. Our data suggest that CAFs and NPC tumor cells may enhance neoangiogenesis in a VEGF- and SDF-1-dependent manner by recruiting EPCs from the bone marrow into tumor stroma.
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A survey of the frequency of aminoglycoside antibiotic-resistant genotypes and phenotypes in Escherichia coli in broilers with septicaemia in Hebei, China.
Br. Poult. Sci.
PUBLISHED: 02-28-2014
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1. The aim of this study was to investigate the occurrence of aminoglycoside resistance and the prevalence of 6 important modifying enzyme genes, i.e. (strA, strB, aph(3')-IIa, aac(3)-IIa, aac(6')-Ib and ant(3")-Ia), in Escherichia coli strains in broilers with septicaemia in Hebei, China. 2. A total of 111 clinical isolates of E. coli were collected from 46 large-scale farms. Antimicrobial susceptibility tests, using the Kirby-Bauer disc diffusion method, were performed on all 111 isolates. In addition, all were screened for the presence of modifying enzyme genes using the polymerase chain reaction (PCR). 3. The results show that the rates of resistance were as follows: streptomycin: 97.3%, kanamycin: 97.0%, gentamicin: 95.5%, neomycin: 50.5%, amikacin: 46.0%, spectinomycin: 22.5%. Of the genes examined, strB (73.9%) was the most frequently identified gene in the phenotypic resistant isolates, followed in order by: ant(3")-Ia, aac(3)-IIa, aac(6')-Ib, aph(3')-IIa and strA. 4. It is concluded that aminoglycoside resistance in E. coli from broilers with septicaemia remains a serious problem in Hebei, China. This emphasises the need to ban the non-therapeutic use of antibiotics, discourage their misuse and to be continually vigilant by providing appropriate scientific and technological support for the poultry industry.
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Role of mitochondrial electron transport chain dysfunction in Cr(VI)-induced cytotoxicity in L-02 hepatocytes.
Cell. Physiol. Biochem.
PUBLISHED: 02-20-2014
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Hexavalent chromium [Cr(VI)] and its compounds (e.g. chromates), which are extensively used in numerous industrial processes including leather tanning and steel manufacturing, are considered as priority pollutants. There is growing evidence supporting that Cr(VI) could be a human carcinogen that induces primary liver cancer after oral exposure, and this sheds light on the importance of the investigation of Cr(VI)-induced hepatotoxicity. Although it is known that mitochondria are major targets for heavy metals, the mechanisms of electron transfer chain (ETC) dysfunction involved in Cr(VI)-induced cytotoxicity are unclear.
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Transforming growth factor ß inhibits heme oxygenase-1 expression in lung fibroblast through NF-B dependent pathway.
Pharmacology
PUBLISHED: 02-14-2014
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Heme oxygenase-1 (HO-1) contributes to the pathogenesis of pulmonary fibrosis. However, the expression of HO-1 in fibroblasts under fibrotic conditions has not been studied.
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Toxicity profiling of water contextual zinc oxide, silver, and titanium dioxide nanoparticles in human oral and gastrointestinal cell systems.
Environ. Toxicol.
PUBLISHED: 02-13-2014
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Engineered nanoparticles (ENPs) are increasingly detected in water supply due to environmental release of ENPs as the by-products contained within the effluent of domestic and industrial run-off. The partial recycling of water laden with ENPs, albeit at ultra-low concentrations, may pose an uncharacterized threat to human health. In this study, we investigated the toxicity of three prevalent ENPs: zinc oxide, silver, and titanium dioxide over a wide range of concentrations that encompasses drinking water-relevant concentrations, to cellular systems representing oral and gastrointestinal tissues. Based on published in silico-predicted water-relevant ENPs concentration range from 100 pg/L to 100 µg/L, we detected no cytotoxicity to all the cellular systems. Significant cytotoxicity due to the NPs set in around 100 mg/L with decreasing extent of toxicity from zinc oxide to silver to titanium dioxide NPs. We also found that noncytotoxic zinc oxide NPs level of 10 mg/L could elevate the intracellular oxidative stress. The threshold concentrations of NPs that induced cytotoxic effect are at least two to five orders of magnitude higher than the permissible concentrations of the respective metals and metal oxides in drinking water. Based on these findings, the current estimated levels of NPs in potable water pose little cytotoxic threat to the human oral and gastrointestinal systems within our experimental boundaries. © 2014 Wiley Periodicals, Inc. Environ Toxicol, 2014.
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A miR-SNP of the KRT81 gene is associated with the prognosis of non-Hodgkin's lymphoma.
Gene
PUBLISHED: 02-05-2014
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MicroRNA (miRNA), which plays an important role in tumorigenesis, can regulate post-transcriptional gene expression by binding to the 3' untranslated regions (3'-UTRs) of messenger RNAs and repressing its translation. Several single nucleotide polymorphisms (SNPs) are considered to have significant impacts on susceptibility of the role these genetic polymorphisms in development of carcinogenesis through that mechanism. But few of them focus their impact on non-Hodgkin's lymphoma (NHL). Therefore, we conducted this study to investigate the associations between the genetic variants and cancer risk or cancer outcome. MiRNA-related single nucleotide polymorphism (miR-SNP) sites rs3660 of KRT81, rs1044129 of RYR3, rs4901706 of f101, and rs1053667 of KIAA0423 were selected and analyzed in 210 patients in NHL to evaluate their association with cancer risk and prognosis. The results indicated that none of them is associated with the cancer risk in NHL. Otherwise KRT81 rs3660 GG type is associated with a shorter survival time (p=0.012), after being assessed by multivariate Cox analyses, its effect on prognosis was verified (p=0.003). It suggests that KRT81 rs3660 GG type is an independent prognostic marker in NHL.
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(Pb,Cd)-O covalency in PbTiO3-CdTiO3 with enhanced negative thermal expansion.
Phys Chem Chem Phys
PUBLISHED: 02-05-2014
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Recently experiments have found that negative thermal expansion is a common phenomenon in PbTiO3-based materials, and their negative thermal expansion is affected by various substitutions. Interestingly, Cd substitution in PbTiO3 has a unique effect in enhancing negative thermal expansion compared with any other A-site substitutions. Therefore, studying Cd substitution in PbTiO3, the role of which still remains unclear, would bring us deeper understanding on the nature of the negative thermal expansion of PbTiO3-based materials. Structure calculations, density of states, Bader analysis and the minimum electron density of Pb1-xCdxTiO3 supercells have been reported on the chemical bond through first-principles calculations here. We found that the hybridization between (Pb,Cd)-O orbitals exists in tetragonal phase. Furthermore, the hybridization between Cd-O orbitals is stronger than that between Pb-O orbitals, and Cd-O covalency promotes the average A-site hybridization. Simultaneously, the average bulk coefficient of thermal expansion is negative and inversely proportional to the Cd substitution amount. So, (Pb,Cd)-O covalency in the tetragonal Pb1-xCdxTiO3 is responsible for the nature of enhanced negative thermal expansion in accordance with our previous experimental investigations.
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Palmatine inhibits growth and invasion in prostate cancer cell: Potential role for rpS6/NF?B/FLIP.
Mol. Carcinog.
PUBLISHED: 02-03-2014
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Novel agents are desperately needed for improving the quality of life and 5-year survival to more than 30% for metastatic castrate-resistant prostate cancer. Previously we showed that Nexrutine, Phellodendron amurense bark extract, inhibits prostate tumor growth in vitro and in vivo. Subsequently using biochemical fractionation we identified butanol fraction contributes to the observed biological activities. We report here that palmatine, which is present in the butanol fraction, selectively inhibits growth of prostate cancer cells without significant effect on non-tumorigenic prostate epithelial cells. By screening receptor tyrosine kinases in a protein kinase array, we identified ribosomal protein S6, a downstream target of p70S6K and the Akt/mTOR signaling cascade as a potential target. We further show that palmatine treatment is associated with decreased activation of NF?B and its downstream target gene FLIP. These events led to inhibition of invasion. Similar results were obtained using parent extract Nexrutine (Nx) suggesting that palmatine either in the purified form or as one of the components in Nx is a potent cytotoxic agent with tumor invasion inhibitory properties. Synergistic inhibition of rpS6/NF?B/FLIP axis with palmatine may have therapeutic potential for the treatment of prostate cancer and possibly other malignancies with their constitutive activation. These data support a biological link between rpS6/NF?B/FLIP in mediating palmatine-induced inhibitory effects and warrants additional preclinical studies to test its therapeutic efficacy. © 2014 Wiley Periodicals, Inc.
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miR-1207-5p and miR-1266 suppress gastric cancer growth and invasion by targeting telomerase reverse transcriptase.
Cell Death Dis
PUBLISHED: 02-01-2014
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hTERT is the catalytic subunit of the telomerase complex. Elevated expression of hTERT is associated with the expansion and metastasis of gastric tumor. In this study, we aimed to identify novel tumor suppressor miRNAs that restrain hTERT expression. We began our screen for hTERT-targeting miRNAs with a miRNA microarray. miRNA candidates were further filtered by bioinformatic analysis, general expression pattern in different cell lines, gain-of-function effects on hTERT protein and the potential of these effects to suppress hTERT 3' untranslated region (3'UTR) luciferase activity. The clinical relevance of two miRNAs (miR-1207-5p and miR-1266) was evaluated by real-time RT-PCR. The effects of these miRNAs on cell growth, cell cycle and invasion of gastric cancer cells were measured with CCK-8, flow cytometry and transwell assays. Finally, the ability of these miRNAs to suppress the transplanted tumors was also investigated. Fourteen miRNAs were identified using a combination of bioinformatics and miRNA microarray analysis. Of these fourteen miRNAs, nine were expressed at significantly lower levels in hTERT-positive cell lines compared with hTERT-negative cell lines and five could downregulate hTERT protein expression. Only miR-1207-5p and miR-1266 interacted with the 3' UTR of hTERT and the expression levels of these two miRNAs were significantly decreased in gastric cancer tissues. These two miRNAs also inhibited gastric tumor growth in vitro and in vivo. Altogether, miR-1207-5p and miR-1266 were determined to be hTERT suppressors in gastric cancer, and the delivery of these two miRNAs represents a novel therapeutic strategy for gastric cancer treatment.
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Activation of Autophagy Protects Against ROS-Mediated Mitochondria-Dependent Apoptosis in L-02 Hepatocytes Induced by Cr(VI).
Cell. Physiol. Biochem.
PUBLISHED: 01-24-2014
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Background: Hexavalent chromium (Cr(VI)) overdose causes hepatocellular injuries by inducing mitochondrial damage and subsequent apoptosis in animals and humans. Autophagy can selectively remove damaged organelles, especially impaired mitochondria, and in turn, protects against mitochondria-dependent cell death. The present study was designed to explore the effects of autophagy on the Cr(VI)-induced hepatotoxicity. Methods: L-02 hepatocytes were incubated with different concentrations of Cr(VI) for 24h and several indicators for evaluating mitochondrial damage and hepatocellular apoptosis were measured. Then effects of ROS scavenger NAC on ROS production and calcium overload during Cr(VI)-induced hepatotoxicity were examined. Finally, the study further investigated the role of autophagy played in repairing mitochondrial damage and subsequent hepatocyte injuries. Results: After exposed to different concentrations of Cr(VI) for 24h, cell viability, mitochondria membrane potential, ATP content were significantly decreased and caspase-3 activities and apoptosis rates increased in L-02 hepatocytes. The treatment of NAC reduced ROS formation and Ca(2+) content, restored CRAC channel activities and further diminished mitochondrial injuries. Furthermore, autophagy inducer, rapamycin is beneficial for repairing mitochondrial function and limiting hepatocytes damage, and pharmacological inhibition of autophagy by 3-methyladenine further exacerbated Cr(VI)-induced hepatotoxicity. Conclusions: ROS production is a critical reason for Cr(VI)-induced mitochondria-dependent apoptosis. And activation of autophagy could repair mitochondria function to protect hepatocytes potentially by removing damaged mitochondria. © 2014 S. Karger AG, Basel.
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Characterization of a novel mutation in the overlap of tlyA and ppnK involved in capreomycin resistance in Mycobacterium.
IUBMB Life
PUBLISHED: 01-21-2014
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Capreomycin (CAP) is an important second-line drug for multidrug-resistant tuberculosis. To further define the drug resistance mechanism of CAP, a Mycobacterium smegmatis transposon mutant library was constructed using Tn5 transposon for screening isolates with enhanced CAP resistance. A mutant (named C4) with fourfold increased CAP resistance was isolated and characterized. Tn5 was found to be inserted into MSMEG_0841, an annotated pseudogene. However, knockout demonstrated that MSMEG_0841 was not responsible for CAP resistance. We further sequenced the whole genome of C4 and found an A to G substitution in the overlap region between tlyA and ppnK, which leads a stop codon mutation in upstream tlyA and a T2A mutation in downstream ppnK. Mutation in the overlap might confer the dysfuction of both genes. tlyA is a known gene involved in CAP action. Overexpression of ppnK in both Escherichia coli and M. smegmatis confer subtle susceptible to CAP. Taken together, our study found that a novel mutation involved in CAP resistance.
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The pharmacokinetic study of sinomenine, paeoniflorin and paeonol in rats after oral administration of a herbal product Qingfu Guanjiesu capsule by HPLC.
Biomed. Chromatogr.
PUBLISHED: 01-06-2014
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An accurate and reliable high-performance liquid chromatography-diode array detector (HPLC-DAD) method was developed and validated for determination of sinomenine (SI), paeoniflorin (PF) and paeonol (PA), which was further applied to assess the pharmacokinetics of SI, PF and PA in an anti-arthritic herbal product, Qingfu Guanjieshu (QFGJS) capsule, in rats. Successful separation was achieved with a C18 column and a mobile phase composed of acetonitrile and aqueous phase (containing 0.1% formic acid, adjusted with triethylamine to pH 3.5 ± 0.2). The method was validated with excellent precision, accuracy, recovery and stability in calibration ranges from 0.06 to 11.62 µg/mL for SI, from 0.09 to 35.70 µg/mL for PF, and from 0.15 to 4.53 µg/mL for PA (with r(2) > 0.999 for all three compounds). Our results showed that absorption of PF after administration of QFGJS was similar to that after oral administration of PF alone; the absorption of SI was decreased while the absorption of PA was increased after giving QFGJS orally compared with pure compounds. We may conclude that pharmacokinetic studies of complex herbal products are not only necessary but also feasible by using representative bioactive chemicals as indicators of establishing quality control standards and of determining pharmacokinetic behavior of herbal medicines. Copyright © 2014 John Wiley & Sons, Ltd.
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How Noise and Language Proficiency Influence Speech Recognition by Individual Non-Native Listeners.
PLoS ONE
PUBLISHED: 01-01-2014
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This study investigated how speech recognition in noise is affected by language proficiency for individual non-native speakers. The recognition of English and Chinese sentences was measured as a function of the signal-to-noise ratio (SNR) in sixty native Chinese speakers who never lived in an English-speaking environment. The recognition score for speech in quiet (which varied from 15%-92%) was found to be uncorrelated with speech recognition threshold (SRTQ/2), i.e. the SNR at which the recognition score drops to 50% of the recognition score in quiet. This result demonstrates separable contributions of language proficiency and auditory processing to speech recognition in noise.
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A four actin-binding protein signature model for poor prognosis of patients with esophageal squamous cell carcinoma.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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The actin cytoskeleton is a dynamic structure with actin-binding proteins (ABPs) playing an essential role in the regulation of migration, differentiation and signal transduction in all eukaryotic cells. We examined the relationship between altered expression of four ABPs and clinical parameters in esophageal squamous cell carcinoma (ESCC). To this end, we analyzed 152 formalin-fixed and paraffin-embedded esophageal curative resection specimens by immunohistochemistry for tensin, profilin-1, villin-1 and talin. A molecular predictor model, based on the combined expression of the four proteins, was developed to correlate the expression pattern of the four ABPs with clinical factors and prognosis of ESCC. According to the results, weak significance was found for tensin in lymph node metastasis (P=0.033), and profilin-1 in pTNM stage (P=0.031). However, our four-protein model showed strong correlation with the 5-year overall survival rate (P=0.002). Similarly, Kendall's tau-b test also showed the relationship between the collective expression pattern of the four ABPs with lymph node metastasis (P=0.005) and pTNM stage (P=0.001). Our results demonstrate that the collective protein expression pattern of four actin-binding proteins could be a biomarker to estimate the prognosis of ESCC patients.
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Prognostic value of pretreatment serum levels of lactate dehydrogenase in nonmetastatic nasopharyngeal carcinoma: single-site analysis of 601 patients in a highly endemic area.
Onco Targets Ther
PUBLISHED: 01-01-2014
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Numerous studies have generated promising but incomplete evidence for the prognostic value of pretreatment serum levels of lactate dehydrogenase (S-LDH) in nasopharyngeal carcinoma (NPC).
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Celecoxib ameliorates non-alcoholic steatohepatitis in type 2 diabetic rats via suppression of the non-canonical Wnt signaling pathway expression.
PLoS ONE
PUBLISHED: 01-01-2014
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Our aim was to test whether pharmacological inhibition of cycloxygenase-2 (COX-2) reverses non-alcoholic steatohepatitis (NASH) in type 2 diabetes mellitus (T2DM) rats via suppression of the non-canonical Wnt signaling pathway expression. Twenty-four male Sprague-Dawley rats were randomly distributed to two groups and were fed with a high fat and sucrose (HF-HS) diet or a normal chow diet, respectively. After four weeks, rats fed with a HF-HS diet were made diabetic with low-dose streptozotocin. At the 9(th) week the diabetic rats fed with a HF-HS diet or the non-diabetic rats fed with a normal chow diet were further divided into two subgroups treated with vehicle or celecoxib (a selective COX-2 inhibitor, 10 mg/Kg/day, gavage) for the last 4 weeks, respectively. At the end of the 12(th) week, rats were anesthetized. NASH was assessed by histology. Related cytokine expression was measured at both the protein and gene levels through immunohistochemistry (IHC), Western blot and real-time PCR. T2DM rats fed with a HF-HS diet developed steatohepatitis and insulin resistance associated with elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin levels and the non-alcoholic fatty liver disease (NAFLD) activity score (NAS). The expression of Wnt5a, JNK1, NF-?B p65, and COX-2 were all significantly increased in the T2DM-NASH group compared with the control and control-cele group. Hepatic injury was improved by celecoxib in T2DM-NASH-Cele group indicated by reduced serum ALT and AST levels and hepatic inflammation was reduced by celecoxib showed by histology and the NAFLD activity score (NAS). Serum related metabolic parameters, HOMA-IR and insulin sensitivity index were all improved by celecoxib. The expression of Wnt5a, JNK1, NF-?B p65, and COX-2 expression were all suppressed by celecoxib in T2DM-NASH-Cele group. The results of the present study indicated that celecoxib ameliorated NASH in T2DM rats via suppression of the non-canonical Wnt5a/JNK1 signaling pathway expression.
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Progress of FtsZ Inhibitors as Novel Antibiotics Leads.
Crit. Rev. Eukaryot. Gene Expr.
PUBLISHED: 11-26-2013
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Bacterial cell division is an attractive target for new antibiotics. FtsZ is a major cytoskeletal protein widespread among archaea and bacteria. FtsZ has a filament-forming GTPase and a structural homologue of eukaryotic tubulin. FtsZ has been validated as a target for antibiotics. This review summarizes the chemical features, binding sites, mechanisms of action, and minimum inhibitory concentration of FtsZ inhibitors.
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Bacteriophage Inspired Antibiotics Discovery against Infection Involved Biofilm.
Crit. Rev. Eukaryot. Gene Expr.
PUBLISHED: 11-26-2013
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Bacterial biofilm profoundly influences the fate of bacteria within and the outcome of related infection, and is closely associated with antibiotics resistance and bacterial persistence. Bacteriophages represent a new promising alternative to combat biofilm-related infection. The interplay between phages and biofilms is complex. Some phages or their components can inhibit the host bacteria biofilm via diverse mechanisms, while other phages can facilitate the host biofilm formation through phage-mediated lysis and extracellular DNA release. In this paper, we summarize the role of bacteriophages in the biofilm formation, and the application of phages to the control of bacterial persisters and infectious biofilms, in particular, the phage-inspired antibiotics discovery.
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Emerging biomedicines based on bacteriophages.
Crit. Rev. Eukaryot. Gene Expr.
PUBLISHED: 11-26-2013
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Bacteriophage is bacterial virus widespread in the biosphere. Bacteriophages and their encoded endolysin (or lysin), holin, and other small proteins are intensively pursed as novel therapeutic agents to complement and tackle the increasing antibiotics resistance. Moreover, the delivery system based on bacteriophage and the diagnostic method based on engineered bacteriophage were also promising new avenues to drug delivery and diagnosis.
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Engineering ultrasmall water-soluble gold and silver nanoclusters for biomedical applications.
Chem. Commun. (Camb.)
PUBLISHED: 11-21-2013
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Gold and silver nanoclusters or Au/Ag NCs with core sizes smaller than 2 nm have been an attractive frontier of nanoparticle research because of their unique physicochemical properties such as well-defined molecular structure, discrete electronic transitions, quantized charging, and strong luminescence. As a result of these unique properties, ultrasmall size, and good biocompatibility, Au/Ag NCs have great potential for a variety of biomedical applications, such as bioimaging, biosensing, antimicrobial agents, and cancer therapy. In this feature article, we will first discuss some critical biological considerations, such as biocompatibility and renal clearance, of Au/Ag NCs that are applied for biomedical applications, leading to some design criteria for functional Au/Ag NCs in the biological settings. According to these biological considerations, we will then survey some efficient synthetic strategies for the preparation of protein- and peptide-protected Au/Ag NCs with an emphasis on our recent contributions in this fast-growing field. In the last part, we will highlight some potential biomedical applications of these protein- and peptide-protected Au/Ag NCs. It is believed that with continued efforts to understand the interactions of biomolecule-protected Au/Ag NCs with the biological systems, scientists can largely realize the great potential of Au/Ag NCs for biomedical applications, which could finally pave their way towards clinical use.
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What is Visualize?

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

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

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