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Find video protocols related to scientific articles indexed in Pubmed.
DoGSD: the dog and wolf genome SNP database.
Nucleic Acids Res.
PUBLISHED: 11-19-2014
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The rapid advancement of next-generation sequencing technology has generated a deluge of genomic data from domesticated dogs and their wild ancestor, grey wolves, which have simultaneously broadened our understanding of domestication and diseases that are shared by humans and dogs. To address the scarcity of single nucleotide polymorphism (SNP) data provided by authorized databases and to make SNP data more easily/friendly usable and available, we propose DoGSD (http://dogsd.big.ac.cn), the first canidae-specific database which focuses on whole genome SNP data from domesticated dogs and grey wolves. The DoGSD is a web-based, open-access resource comprising ?19 million high-quality whole-genome SNPs. In addition to the dbSNP data set (build 139), DoGSD incorporates a comprehensive collection of SNPs from two newly sequenced samples (1 wolf and 1 dog) and collected SNPs from three latest dog/wolf genetic studies (7 wolves and 68 dogs), which were taken together for analysis with the population genetic statistics, Fst. In addition, DoGSD integrates some closely related information including SNP annotation, summary lists of SNPs located in genes, synonymous and non-synonymous SNPs, sampling location and breed information. All these features make DoGSD a useful resource for in-depth analysis in dog-/wolf-related studies.
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Genome Sequence of Tumebacillus flagellatus GST4, the First Genome Sequence of a Species in the Genus Tumebacillus.
Genome Announc
PUBLISHED: 11-15-2014
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We present here the first genome sequence of a species in the genus Tumebacillus. The draft genome sequence of Tumebacillus flagellatus GST4 provides a genetic basis for future studies addressing the origins, evolution, and ecological role of Tumebacillus organisms, as well as a source of acid-resistant amylase-encoding genes for further studies.
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Effectiveness and Safety of Lower Doses of Mifepristone Combined With Misoprostol for the Termination of Ultra-Early Pregnancy: A Dose-Ranging Randomized Controlled Trial.
Reprod Sci
PUBLISHED: 11-15-2014
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This study aimed to investigate the effectiveness and safety of lower doses of mifepristone combined with misoprostol for the termination of ultra-early pregnancy. A total of 2500 women with ultra-early pregnancy (amenorrhea ? 35 days) were randomly divided into 5 groups with gradually decreased dose of oral mifepristone from 150 to 50 mg followed by 200 µg of oral misoprostol 24 hours later. The primary end point was complete abortion without surgical intervention. Secondary end points were vaginal bleeding, return of menses, and side effects. Rates of complete abortion were high in all groups. Moreover, the lower doses of mifepristone led to shorter vaginal bleeding period, the return of menses on the expected date, and fewer side effects. Lower doses of mifepristone combined with 200 µg of misoprostol are as effective and safe as higher doses of this combination for the termination of ultra-early pregnancy with lower possibility of vaginal bleeding and side effects.
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Molecular Adhesion at Clay Nanocomposite Interfaces Depends on Counterion Hydration - Molecular Dynamics Simulation of Montmorillonite/Xyloglucan.
Biomacromolecules
PUBLISHED: 11-13-2014
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Nacre-mimetic clay/polymer nanocomposites with clay platelet orientation parallel to the film surface show interesting gas barrier and mechanical properties. In moist conditions, interfacial adhesion is lowered and mechanical properties are reduced. Molecular dynamic simulations (MD) have been performed to investigate the effects of counter ions on molecular adhesion at montmorillonite clay (Mnt)-xyloglucan (XG) interfaces. We focus on the role of both monovalent cations K+, Na+, Li+ and the divalent cation Ca2+ for the mediating and stabilizing the Mnt/XG complex formation. The conformation of adsorbed XG is strongly influenced by the choice of counterion, and so is the simulated work of adhesion. Free energy profiles that are used to estimate molecular adhesion show stronger interaction between XG and clay in the monovalent cation system than in divalent cation system, following a decreasing order of K-Mnt, Na-Mnt, Li-Mnt and Ca-Mnt. The Mnt clay hydrates differently in the presence of different counter ions, leading to a chemical potential of water that is highest in the case of K-Mnt, followed by Na-Mnt and Li-Mnt, and lowest in the case of Ca-Mnt. This means that water is most easily displaced from the interface in the case of K-Mnt, which contributes to the relatively high work of adhesion. In all systems, the penalty of replacing polymer with water at the interface gives a positive contribution to the work of adhesion of between 19% and 35%. Our work confirms the important role of counter ions in mediating the adsorption of biopolymer XG to Mnt clays and predicts potassium or sodium as the best choice of counter ions for a Mnt-based bio-composite design.
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CYP2J2 Attenuates Metabolic Dysfunction in Diabetic Mice by Reducing Hepatic Inflammation via the PPAR?
Am. J. Physiol. Endocrinol. Metab.
PUBLISHED: 11-13-2014
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Background and Purpose: Epoxyeicosatrienoic acids (EETs), arachidonic acid-derived cytochrome P450 (CYP) epoxygenase metabolites, have diverse biological effects including anti-inflammatory properties in the vasculature. Increasing evidence suggests that inflammation in type 2 diabetes is a key component in the development of insulin resistance. Experimental Approach: In this study, we investigated if CYP epoxygenase expression and exogenous EETs can attenuate insulin resistance in diabetic db/db mice and in cultured hepatic cells (HepG2). In vivo, CYP2J2 expression and the accompanying increase in EETs attenuated insulin resistance as determined by plasma glucose levels, glucose tolerance test, insulin tolerance test, and hyperinsulinemic-euglycemic clamp studies. Key Results: CYP2J2 expression reduced the production of pro-inflammatory cytokines in liver, including CRP, IL-6, IL-1? and TNF-?, and decreased the infiltration of macrophages in liver. CYP2J2 expression also decreased activation of pro-inflammatory signaling cascades by decreasing NF-?B and MAPK activation in hepatocytes. Interestingly, CYP2J2 expression and exogenous EET treatment increased glucose uptake and activated the insulin signaling cascade both in vivo and in vitro, suggesting that CYP2J2 metabolites play a role in glucose homeostasis. Furthermore, CYP2J2 expression up-regulated PPAR?, which has been shown to induce adipogenesis that attenuate dyslipidemias observed in diabetes. Conclusions & Implications: All the findings suggest that CYP2J2 expression attenuates the diabetic phenotype and insulin resistance via inhibition of NF-?B and MAPK signaling pathways, and activation of PPAR?.
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[Integrated regional network construction for ST-segment elevation myocardial infarction care].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 11-13-2014
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To investigate the feasibility of establishing an integrated regional network for ST-segment elevation myocardial infarction (STEMI) care in China and evaluate the implementation effect of this network.
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Regulation of cerebral CYP2D alters tramadol metabolism in the brain: interactions of tramadol with propranolol and nicotine.
Xenobiotica
PUBLISHED: 11-13-2014
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Abstract 1. Cytochrome P450 2D (CYP2D) protein is widely expressed across brain regions in human and rodents. We investigated the interactions between tramadol, a clinically used analgesic, and brain CYP2D regulators, by establishing concentration-time curves of tramadol and O-desmethyltramadol (M1) in rat cerebrospinal fluid (CSF) and plasma, as well as by analyzing the analgesia-time course of tramadol. 2. Propranolol (20??g, intracerebroventricular injection), CYP2D inhibitor, prolonged the elimination t1/2 of tramadol (40?mg/kg, intraperitoneal injection) in the CSF; meanwhile, lower Cmax and AUC0-? values of M1 were observed. Nicotine (1?mg base/kg, subcutaneous injection, seven days), brain CYP2D inducer, induced a shorter Tmax and elevated Cmax of M1 in CSF. No differences in the peripheral metabolism of tramadol were observed following propranolol and nicotine pretreatment. Nicotine increased areas under the analgesia-time curve (AUC) for 0-45?min and 0-90?min of tramadol, which was attenuated by propranolol administration. The analgesic actions of tramadol positively correlated with cerebral M1 concentration. 3. The results suggest that the regulation of brain CYP2D by xenobiotics may cause drug-drug interactions (DDIs) of tramadol. Brain CYPs may play an important role in DDIs of centrally active substances.
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Deficiency of Interferon-Gamma or Its Receptor Promotes Colorectal Cancer Development.
J. Interferon Cytokine Res.
PUBLISHED: 11-11-2014
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Genetic variations in interferon-gamma (IFN-?) and its receptor (IFN?R) subunits are closely associated with the risk of colorectal cancer (CRC) and survival after diagnosis. However, the role of loss of IFN-? or IFN?R function in the pathogenesis of CRC remains unclear. Here, we investigated the role of endogenous IFN-? deficiency in adenomatous polyposis coli (Apc)-mediated intestinal tumor by developing a variant of Apc(Min/+) mice. The Apc(Min/+)IFN-?(+/-) mice presented with increased number and size of adenomas, and 41.7% of these mice developed adenocarcinoma. Molecular analyses of the adenomas suggested that heterozygous deletion of IFN-? promoted EGFR/Erk1/2 and Wnt/?-catenin signaling. In vitro, IFN-? administration inhibited Apc-mutated HT-29 colon cancer cell proliferation and had no effect on the proliferation of HCT-116 colon cancer cells that express wild-type Apc. Besides, we challenged HT-29 cells with small interfering RNA targeting one of its receptor subunits IFN?R1. We found that knockdown of IFN?R1 in HT-29 cells stimulated cell proliferation and colony formation, which was also related to the regulation of EGFR/Erk1/2 and Wnt/?-catenin signaling. Thus, our results strongly support the notion that IFN-? and IFN?R1 act as a rate-limiting factor in the development of CRC, uncovering a novel role for them in cancer biology.
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Effects of Bisphenol S on the Structures and Activities of Trypsin and Pepsin.
J. Agric. Food Chem.
PUBLISHED: 11-11-2014
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The effects of bisphenol S on the structures and activities of trypsin and pepsin were investigated by various methods like UV-visible absorbance, fluorescence, circular dichroism, and molecular docking. The secondary and tertiary structures of trypsin and pepsin were altered by bisphenol S binding, which resulted in the loosening of the skeletons of trypsin and pepsin. In addition, bisphenol S induced microenvironmental changes around tyrosine and tryptophan residues of trypsin and pepsin. The activity experimental results showed that the activity of pepsin decreases obviously with the increasing concentration of BPS, while the activity of trypsin does not change remarkably. The binding and thermodynamic parameters obtained by molecular docking and fluorescence spectroscopy showed that the bindings of bisphenol S to trypsin and pepsin were spontaneous processes and hydrogen bonding and hydrophobic interactions played a vital role in stabilizing the bisphenol S-trypsin and bisphenol S-pepsin complexes. The binding constants (KA) of bisphenol S with trypsin were 7.42 × 10(4) (298 K) and 5.91 × 10(4) L/mol (310 K), and those of pepsin were 5.78 × 10(4) (298 K) and 4.44 × 10(4) L/mol (310 K). Moreover, there was one main kind of binding site for bisphenol S on trypsin or pepsin.
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Pd(ii)-catalyzed C-H arylation of aryl and benzyl Weinreb amides.
Org. Biomol. Chem.
PUBLISHED: 11-08-2014
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The first example of palladium-catalyzed ortho-C-H arylation of aryl and benzyl Weinreb amides was developed, in which HOTf was used as a key promoter. This method exhibits good functional group tolerance, a broad substrate scope of both Weinreb amides and aryl iodides, high mono-selectivity and mild reaction conditions.
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Role of Retinoic Acid and Platelet-Derived Growth Factor Receptor crosstalk in the regulation of neonatal gonocyte and embryonal carcinoma cell differentiation.
Endocrinology
PUBLISHED: 11-08-2014
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Neonatal gonocytes are direct precursors of spermatogonial stem cells, the cell pool that supports spermatogenesis. Although unipotent in vivo, gonocytes express pluripotency genes common with embryonic stem cells. Previously, we found that all-trans retinoic acid (RA) induced the expression of differentiation markers and a truncated form of PDGFR? in rat gonocytes, as well as in F9 mouse embryonal carcinoma cells, an embryonic stem cell-surrogate that expresses somatic lineage markers in response to RA. The present study is focused on identifying the signaling pathways involved in RA-induced gonocyte and F9 cell differentiation. MEK1/2 activation was required during F9 cell differentiation towards somatic lineage, whereas its inhibition potentiated RA-induced Stra8 expression, suggesting that MEK1/2 acts as a lineage specification switch in F9 cells. In both cell types, RA increased the expression of the spermatogonial/pre-meiotic marker Stra8, which is in line with F9 cells being at a stage prior to somatic-germline lineage specification. Inhibiting PDGFR kinase activity reduced RA-induced Stra8 expression. Interestingly, RA increased the expression of PDGFR? variant forms in both cell types. Together, these results suggest a potential crosstalk between RA and PDGFR signaling pathways in cell differentiation. RAR? inhibition partially reduced RA effects on Stra8 in gonocytes, indicating that RA acts in part via RAR?. RA-induced gonocyte differentiation was significantly reduced by inhibiting SRC and JAK2/STAT5 activities, implying that these signaling molecules play a role in gonocyte differentiation. These results suggest that gonocyte and F9 cell differentiation is regulated via crosstalk between RA and PDGFRs using different downstream pathways.
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Decreasing electron flux through the cytochrome and/or alternative respiratory pathways triggers common and distinct cellular responses dependent on growth conditions.
Plant Physiol.
PUBLISHED: 11-08-2014
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Mitochondria have emerged as an important organelle for sensing and coping with stress, in addition to being the sites of important metabolic pathways. Here, responses to moderate light and drought stress were examined in different Arabidopsis thaliana mutant plants lacking a functional alternative oxidase (aox1a), those with reduced cytochrome electron transport chain capacity (rpoTmp), and double mutants impaired in both pathways (aox1a:rpoTmp). Under conditions considered optimal for growth, transcriptomes of aox1a and rpoTmp were distinct. Under adverse growth conditions, however, transcriptome changes in aox1a and rpoTmp displayed a highly significant overlap and were indicative of a common mitochondrial stress response and down-regulation of photosynthesis. This suggests that the role of mitochondria to support photosynthesis is provided through either the alternative pathway or the cytochrome pathway, and when either pathway is inhibited, as under environmental stress, a common, dramatic and succinct mitochondrial signal is activated to alter energy metabolism in both organelles. aox1a:rpoTmp double mutants grown under optimal conditions showed dramatic reductions in biomass production compared with aox1a and rpoTmp, and a transcriptome that was distinct from aox1a or rpoTmp. Transcript data indicating activation of mitochondrial biogenesis in aox1a:rpoTmp were supported by a proteomic analysis of over 200 proteins. Under optimal conditions, aox1a:rpoTmp plants appeared to switch on many of the typical mitochondrial stress regulators. Under adverse conditions aox1a:rpoTmp turned off these responses and display a biotic stress response. Taken together, these results highlight the diverse signaling pathways activated by the perturbation of mitochondrial function under different growth conditions.
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The Forest Filter Effect vs. Cold Trapping Effect on the Altitudinal Distribution of PCBs: A Case Study of Mt. Gongga, Eastern Tibetan Plateau.
Environ. Sci. Technol.
PUBLISHED: 11-08-2014
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High mountains are priority trapping zones of persistent organic pollutants (POPs) due to the cold condensation effect. Forest soils characterized by high organic carbon are important for terrestrial storage of POPs. To investigate the dominant factor controlling the altitudinal distribution of POPs in mountainous areas, we measured concentrations of polychlorinated biphenyls (PCBs) in different environmental matrices (surface soil, moss, and air) from nine elevations on the eastern slope of Mt. Gongga, the highest mountain in Sichuan Province on the Tibetan Plateau. The concentrations of 24 measured PCBs ranged from 41 to 510 pg/g dry weight (dw) (mean: 260 pg/g dw) in the surface soil, 280 to 1200 pg/g dw (mean: 740 pg/g dw) in moss, and 33 to 60 pg/m3 (mean: 47 pg/m3) in air. Soil organic carbon was a key determinant explaining 75% of the variation in concentration along the altitudinal gradient. Across all of the sampling sites, the average contribution of the forest filter effect (FFE) was greater than that of the mountain cold trapping effect based on principal components analysis and multiple linear regression. Our results deviate from the thermodynamic theory involving cold condensation at high altitudes of mountain areas and highlight the importance of the FFE.
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Heparin makes differences: a molecular dynamics simulation study on the human ?II-tryptase monomer.
Mol Biosyst
PUBLISHED: 11-05-2014
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Human ?-tryptase, an enzyme with trypsin-like activity in mast cells, is an important target for the treatment of inflammatory and allergy related diseases. Heparin has been inferred to play a vital role in the stabilization of the tryptase structure and the maintenance of its active form. Up to now, the structure-function relationship between heparin and the ?II-tryptase monomer has not been studied with atomic resolution due to the lack of a complex structure of tryptase and heparin. To this end, the exact effect of heparin bonding to the ?II-tryptase monomer structure has been investigated using molecular docking and molecular dynamics (MD) simulation. The MD simulation results combined with MM-GB/SA calculations showed that heparin stabilized the ?-tryptase structure mainly through salt bridge interaction. The averaged noncovalent interaction (aNCI) method was employed for the visualization of nonbonding interactions. A crucial loop, which is located in the core region of ?II-tryptase monomer structure, has been found. Arg188 and Asp189 from this loop act as a salt bridge intermediary between 4-mer heparin and 0GX. The observation of a salt bridge between Asp189 and P1 groups of 0GX confirms the supposed interaction between these two groups. These two residues have been proved to be responsible for the direction of the P1 group of 0GX. Our study revealed that how heparin affected the activity of the human ?II-tryptase monomer (hBTM) through salt bridge interactions. The knowledge of heparin binding characteristics and the key residue contributions in this study may enlighten further the inhibitor design of this enzyme and may also improve our understanding of inflammatory and allergy related diseases.
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Case-control study on prednisolone combined with ursodeoxycholic Acid and azathioprine in pure primary biliary cirrhosis with high levels of immunoglobulin g and transaminases: efficacy and safety analysis.
Medicine (Baltimore)
PUBLISHED: 11-04-2014
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To the best of our knowledge, this is the first study to address the use of glucocorticoids in the comparatively special population of pure primary biliary cirrhosis (PBC) patients who have high levels of immunoglobulin G (IgG) and transaminases but do not have PBC-autoimmune hepatitis overlap syndrome. Ursodeoxycholic acid (UDCA) is now assumed to be the standard therapy for PBC patients. However, patients treated with UDCA still have a risk of progression to cirrhosis and end-stage liver disease. The most recent European Association for the Study of the Liver guidelines of 2009 declared that further studies on glucocorticoid therapy in this disease should be a priority. Therefore, we designed this 3-year longitudinal retrospective study, which might provide deep insight into the treatment for PBC.The aim of this study was to assess whether the combination of prednisolone, UDCA, and azathioprine was superior to UDCA alone in these PBC patients.Sixty patients were enrolled in this study. Thirty-one patients underwent UDCA monotherapy, and 29 patients were treated with prednisolone, UDCA, and azathioprine. We analyzed their biochemistries, immune parameters, liver synthetic function, and noninvasive assessments of liver fibrosis, as well as treatment efficacy and adverse effects at baseline and at 1, 3, 6, 12, 24, and 36 months.Alkaline phosphatase (ALP), ?-glutamyl transpeptidase, alanine aminotransferase, and aspartate aminotransferase levels and the aspartate aminotransferase-to-platelet ratio index (APRI) and S-index improved dramatically in both groups, whereas IgG levels only decreased in the combination group (all P?
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Discovery of FDA-Approved Drugs as Inhibitors of Fatty Acid Binding Protein 4 Using Molecular Docking Screening.
J Chem Inf Model
PUBLISHED: 11-04-2014
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We first identified fluorescein, ketazolam, antrafenine, darifenacin, fosaprepitant, paliperidone, risperidone, pimozide, trovafloxacin, and levofloxacin as inhibitors of fatty acid binding protein 4 using molecular docking screening from FDA-approved drugs. Subsequently, the biochemical characterizations showed that levofloxacin directly inhibited FABP4 activity in both the in vitro ligand displacement assay and cell-based function assay. Furthermore, levofloxacin did not induce adipogenesis in adipocytes, which is the major adverse effect of FABP4 inhibitors.
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Assessing the adequacy of the HL7/LOINC Document Ontology Role axis.
J Am Med Inform Assoc
PUBLISHED: 10-30-2014
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The healthcare landscape is changing, driven by innovative care models and the emergence of new roles that are inter-professional in nature. Currently, the HL7/LOINC Document Ontology (DO) aids the use and exchange of clinical documents using a multi-axis structure of document attributes for Kind of Document, Setting, Role, Subject Matter Domain, and Type of Service. In this study, the adequacy of the Role axis for representing the type of author documenting care was assessed. Experts used a master list of 220 values created from seven resources and established mapping guidelines. Baseline certification, licensure, and didactic training were identified as key parameters that define roles and hence often need to be pre-coordinated. DO was inadequate in representing 82% of roles, and this gap was primarily due to lack of granularity in DO. Next steps include refinement of the proposed schema for the Role axis and dissemination within the larger standards community.
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[Chromomycin A(2) induces apoptosis of HepG2 cells in vitro].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 10-28-2014
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To study the effect of chromomycin A(2) in inducing apoptosis of HepG2 cells and explore the molecular mechanism.
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miR-382 inhibits tumor growth and enhance chemosensitivity in osteosarcoma.
Oncotarget
PUBLISHED: 10-27-2014
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Dysregulation of miRNAs is involved in osteosarcoma (OS). Here, we demonstrate that miR-382 is decreased in specimens of OS patients with a poor chemoresponse compared to those with a good chemoresponse. In addition, our clinical data show that decreased miR-382 was associated with poor survival in OS patients. Overexpression of miR-382 inhibited cell growth and chemoresistance by targeting KLF12 and HIPK3, respectively. In contrast, inhibition of miR-382 or overexpression of target genes stimulated OS cell growth and chemoresistance both in vitro and in vivo. Taken together, these findings suggest that miR-382 is a tumor suppressor miRNA and induction of miR-382 is a potential strategy to inhibit OS progression.
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Core-Shell Nanoparticles Based on Pullulan and Poly(?-amino) Ester for Hepatoma-Targeted Codelivery of Gene and Chemotherapy Agent.
ACS Appl Mater Interfaces
PUBLISHED: 10-27-2014
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This study designs a novel nanoparticle system with core-shell structure based on pullulan and poly(?-amino) ester (PBAE) for the hepatoma-targeted codelivery of gene and chemotherapy agent. Plasmid DNA expressing green fluorescent protein (pEGFP), as a model gene, was fully condensed with cationic PBAE to form the inner core of PBAE/pEGFP polycomplex. Methotrexate (MTX), as a model chemotherapy agent, was conjugated to pullulan by ester bond to synthesize polymeric prodrug of MTX-PL. MTX-PL was then adsorbed on the surface of PBAE/pEGFP polycomplex to form MTX-PL/PBAE/pEGFP nanoparticles with a classic core-shell structure. MTX-PL was also used as a hepatoma targeting moiety, because of its specific binding affinity for asialoglycoprotein receptor (ASGPR) overexpressed by human hepatoma HepG2 cells. MTX-PL/PBAE/pEGFP nanoparticles realized the efficient transfection of pEGFP in HepG2 cells and exhibited significant inhibitory effect on the cell proliferation. In HepG2 tumor-bearing nude mice, MTX-PL/PBAE/pEGFP nanoparticles were mainly distributed in the tumor after 24 h postintravenous injection. Altogether, this novel codelivery system with a strong hepatoma-targeting property achieved simultaneous delivery of gene and chemotherapy agent into tumor at both cellular and animal levels.
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Changes of the Abdomen in Patients with Ankylosing Spondylitis Kyphosis.
Spine
PUBLISHED: 10-25-2014
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Study Design. A retrospective clinical study.Objective. To investigate changes of the abdomen in patients with ankylosing spondylitis kyphosis.Summary of Background Date. Since 1945, many authors had reported the good clinical and radiographic outcomes and and higher patient satisfaction rates of spinal osteotomy techniques. However, to our knowledge, whether the visceral and diaphragmatic compression that results from the inferior edge of the thoracic cage is relieved by the surgery have not yet been reported.Materials and Methods. From July 2010 to July 2013, 26 patients (24 male, and 2 female) in our department with severe ankylosing spondylitis kyphosis underwent pedicle subtraction osteotomy were studied. Preoperative and postoperative computed tomographic scan, three dimensional reconstruction and preoperative pulmonary function test were performed. Via those tests the minimum distance on the median sagittal plane of the abdomen (MD), the acreage of the abdominal median sagittal plane (AMSP), the diaphragm angle on median sagittal plane(DA) can be gained. A paired sample t test was performed to determine the differences between the preoperative and postoperative AMSPA and MD and DA, respectively. Postoperative-MD/preoperative-MD and postoperative-AMSPA/preoperative-AMSPA and GK were also analyzed by performing independent sample t test for the two groups.Results. The DA has changed significantly in all the patients. There was significant change of both MD and AMSPA in patients whose abdominal wall were folded into abdomen, while neither MD nor AMSPA in patients without the factor. CONCLUSION:To a certain degree, the diaphragmatic compression and the visceral compression could be compensated for by turning to flattening or even developing into kyphosis of the lumbar lordosis before surgery, which could be corrected by a spinal osteotomy. Sagittal rotation of diaphragm in ankylosing spondylitis kyphosis could also be improved by a spinal osteotomy.
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[Recent Research Progress on the Relation of B-ALL Associated Cytogenetic and Molecular Genetic Abnormalities with B-ALL Prognosis].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 10-24-2014
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In recent years, standardized treatment based on the risk stratification has been applied to clinical diagnosis and treatment of leukemia, which significantly improves the remission rate of ALL. However, relapse after remission remains an important challenge for long term efficacy. Chromosomal karyotype analysis is often used clinically to study the genetic features of ALL. As leukemia-specific markers, the cytogenetic and molecular genetic abnormalities can be used to evaluate prognosis and make an effective and optimal therapy. Furthermore, they are also used to track minimal residual disease. Therefore, the cytogenetic and molecular genetic abnormalities may become a monitor and a new target for the treatment of leukemia. This review briefly introduces the structure and physiological function of B-ALL associated cytogenetic and molecular genetic abnormalities, focusing on their prognostic effect on B-ALL.
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Multi-source development of an integrated model for family health history.
J Am Med Inform Assoc
PUBLISHED: 10-23-2014
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To integrate data elements from multiple sources for informing comprehensive and standardized collection of family health history (FHH).
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[Effect of qubi recipe on changes of oxygen free radical metabolism and hypoxia-inducible factor-1alpha in collagen-induced arthritis rats].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 10-23-2014
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To observe the effect of Qubi Recipe (QR) on the expression of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and hypoxia-inducible factor (HIF)-1alpha in rats with type II collagen-I induced arthritis (CIA), and to explore its therapeutic roles and mechanism.
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[Expression of Fascin-1 protein in breast cancer and its clinicopathologic correlation].
Zhonghua Bing Li Xue Za Zhi
PUBLISHED: 10-21-2014
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To study the expression of fascin-1 protein in breast cancer and to evaluate its correlation with clinicopathologic features of the tumor.
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[Low fat milk powder containing esterified plant sterols improves the blood lipid profile of adults with hypercholesterolemia].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 10-21-2014
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To observe the impact of plant sterol esters (PSE) mixed in low fat milk powder (2.5 g of PSE/day) on plasma cholesterol levels in hypercholesterolemic subjects during a 6-week intervention period.
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[The rheology properties of common hydrophilic gel excipients].
Yao Xue Xue Bao
PUBLISHED: 10-18-2014
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To investigate theological properties of common hydrophilic gel excipients such as Carbopol based on viscosity, the viscosity was determined by rotation method and falling-ball method. Linear regression was made between ln(eta) and concentration, the slope of which was used to explore the relation between viscosity and concentration of different excipients. The viscosity flow active energy (E(eta)) was calculated according to Arrhenius equation and was used to investigate the relation between viscosity and temperature of different excipients. The results showed that viscosities measured by two methods were consistent. Concentration of guargum (GG) and hydroxypropylmethyl cellulose (HPMC) solution had a great influence on the viscosity, k > 5; while concentration of polyvinylpyrrolidone-K30 (PVP-K30) and polyethylene glycol 6000 (PEG6000) exerted a less effect on viscosity, k < 0.2; viscosity flow active energy of different excipients were close, which ranged from 30 to 40 kJ x mol(-1). Therefore, theological properties study could provide the basis for application of excipients and establish a foundation for the research of relation between excipients structure, property and function.
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Effect of Nicorandil in patients with heart failure: a systematic review and meta-analysis.
Cardiovasc Ther
PUBLISHED: 10-17-2014
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BACKGROUND AND PURPOSE: It is unclear whether nicorandil, a metabolic therapeutic drug, can be applied clinically to therapy of heart failure (HF). This meta-analysis evaluated therapeutic effects of nicorandil on HF patients. EXPERIMENTAL APPROACH: We performed a systematic review and meta-analysis of published studies evaluating effect of nicorandil on HF patients. Studies were stratified according to controlled versus uncontrolled designs and analyzed using random-effects meta-analysis models. KEY RESULTS: We identified total 20 studies with total 1222 patients. In 5 randomized controlled studies, nicorandil treatment resulted in reduction in all-cause mortality and hospitalization for cardiac causes (HR: 0.35, p<0.001), and improved cardiac pump function (SMD: 0.31, p=0.02). In 15 observational studies, nicorandil therapy increases cardiac pump function (SMD: 0.75, p<0.001), improves NYHA functional class (WMD: -1.33, p<0.001), decreases PCWP (WMD: -6.86mmHg, p<0.001), and pulmonary arterial pressure (SMD: -0.84, p<0.001). CONCLUSIONS & IMPLICATIONS: use of nicorandil in HF patients exerts substantial beneficial effects, suggesting that it may be an additional therapeutic agent for HF. This article is protected by copyright. All rights reserved.
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Hyaluronic Acid Oligosaccharide Modified Redox-Responsive Mesoporous Silica Nanoparticles for Targeted Drug Delivery.
ACS Appl Mater Interfaces
PUBLISHED: 10-15-2014
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A redox-responsive delivery system based on colloidal mesoporous silica (CMS) has been developed, in which 6-mercaptopurine (6-MP) was conjugated to vehicles by cleavable disulfide bonds. The oligosaccharide of hyaluronic acid (oHA) was modified on the surface of CMS by disulfide bonds as a targeting ligand and was able to increase the stability and biocompatibility of CMS under physiological conditions. In vitro release studies indicated that the cumulative release of 6-MP was less than 3% in the absence of glutathione (GSH), and reached nearly 80% within 2 h in the presence of 3 mM GSH. Confocal microscopy and fluorescence-activated cell sorter (FACS) methods were used to evaluate the cellular uptake performance of fluorescein isothiocyanate (FITC) labeled CMS, with and without oHA modification. The CMS-SS-oHA exhibited a higher cellular uptake performance via CD44 receptor-mediated endocytosis in HCT-116 (CD44 receptor-positive) cells than in NIH-3T3 (CD44 receptor-negative) cells. 6-MP loaded CMS-SS-oHA exhibited greater cytotoxicity against HCT-116 cells than NIH-3T3 cells due to the enhanced cell uptake behavior of CMS-SS-oHA. This study provides a novel strategy to covalently link bioactive drug and targeting ligand to the interiors and exteriors of mesoporous silica to construct a stimulus-responsive targeted drug delivery system.
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PPARD rs2016520 Polymorphism Affects Repaglinide Response in Chinese Han Patients with Type 2 Diabetes Mellitus.
Clin. Exp. Pharmacol. Physiol.
PUBLISHED: 10-15-2014
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Repaglinide is a short-acting insulin secretagogue, which often results in considerable inter-individual variability in therapeutic efficacy when widely used in clinical setting. Among various reasons under discussion is genetic polymorphism, especially the genes related to insulin secretion and resistance. Recent studies have described the importance of PPARD in regulating the secretion and resistance of insulin. However, little is known as to the impacts of PPARD genetic polymorphism on the efficacy of repaglinide. Therefore, the current study was designed to investigate the associations of PPARD rs2016520 polymorphism with T2DM susceptibility and repaglinide therapeutic efficacy in Chinese Han T2DM patients. A total of 338 T2DM patients and 200 healthy subjects were genotyped for PPARD rs2016520 polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Eighty-four patients with the same genotypes of CYP2C8*3 139Arg and OATP1B1 521TT were randomized to orally take repaglinide for eight weeks. Then the pharmacodynamic parameters of repaglinide and biochemical indicators were determined before and after repaglinide treatment. No significant difference was found in either allelic frequency (P = 0.298) or genotype distribution (P = 0.151) of PPARD rs2016520 between T2DM patients and healthy subjects. But T2DM patients carrying genotype TC exhibited a significantly lower increase in PINS (mU/l) than those with wild-type TT (P < 0.05). These findings suggest that PPARD rs2016520 polymorphism may influence the therapeutic effect of repaglinide rather than T2DM susceptibility in Chinese Han T2DM patients. This article is protected by copyright. All rights reserved.
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Gene expression patterns, and protein metabolic and histological analyses for muscle development in Peking duck.
Poult. Sci.
PUBLISHED: 10-13-2014
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In this study, we aimed to use duck breast muscle and leg muscle, the 2 main productive muscle organs, as a model to elucidate the molecular mechanism controlling how the 2 muscles have different deposition capabilities, and to analyze the mechanisms facilitating duck muscle development posthatching. Peking duck breast muscle and leg muscle were collected 3, 7, and 16 wk posthatching. The morphology of the myofibers was observed by paraffin sectioning the muscles. The expression of genes involved in protein metabolism [mammalian target of rapamycin (mTOR), RPS6-p70-protein kinase (S6K), forkhead box O1 (FoxO1), muscle RING finger 1 (MuRF1), and atrogin-1 (MAFbx)] was detected using real-time quantitative PCR and Western blot assays, and the results indicated that breast muscle had a stronger capacity for both protein synthesis and protein degradation compared with leg muscle. Satellite cell frequency declined during muscle development in both tissues, and the expression of Pax3/7, satellite cell marker genes, was not significantly different between breast muscle and leg muscle. No notable apoptosis was observed in either tissue. The results of this study suggest that protein metabolism signaling is the main reason promoting duck skeletal muscle mass gain.
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Postoperative cognitive dysfunction: current developments in mechanism and prevention.
Med. Sci. Monit.
PUBLISHED: 10-13-2014
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Postoperative cognitive dysfunction (POCD) is a subtle disorder of thought processes, which may influence isolated domains of cognition and has a significant impact on patient health. The reported incidence of POCD varies enormously due to lack of formal criteria for the assessment and diagnosis of POCD. The significant risk factors of developing POCD mainly include larger and more invasive operations, duration of anesthesia, advanced age, history of alcohol abuse, use of anticholinergic medications, and other factors. The release of cytokines due to the systemic stress response caused by anesthesia and surgical procedures might induce the changes of brain function and be involved in the development of postoperative cognitive dysfunction. The strategies for management of POCD should be a multimodal approach involving close cooperation between the anesthesiologist, surgeon, geriatricians, and family members to promote early rehabilitation and avoid loss of independence in these patients.
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Angiographic correlation and synergistic effect of coronary artery stenosis and cerebral artery stenosis: a retrospective study.
Med. Sci. Monit.
PUBLISHED: 10-12-2014
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Comorbidity of coronary artery stenosis (CoAS) and cerebral artery stenosis (CeAS) is relatively common, but little is known about their angiographic correlation and synergistic effect.
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PRDM1 expression on the epithelial component but not on ectopic lymphoid tissues of Warthin tumour.
Oral Dis
PUBLISHED: 10-04-2014
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To determine the role of PRDM1, a key molecule for modulating the immune cells, in warthin tumour (WT) pathogenesis.
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[Determination of myclobutanil 25% WG degradation dynamics in ginseng root, stem, leaf and soil by HPLC-MS/MS].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 10-04-2014
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A high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) method was developed for determining degradation dynamics and final residues of myclobutanil 25% WG in ginseng root, stem, leaf and soil. The samples were extracted with acetonitrile, cleaned-up with primary secondary amine (PSA) solid phase extraction cartridge, separated by Kromasil Eternity-5-C18 (2.1 mm x 150 mm, 5 microm) column with a gradient of acetonitrile and 0.1% formate in water as mobile phases, and analyzed with the multiple reaction monitoring (MRM) in positive ion mode by employing the external standard method. The average recoveries and the relative standard derivations (RSDs) of myclobutanil at the spiked level of 0.01-0.20 mg x kg(-1) were 80.9%-90.7% and 5.54%-9.29%, respectively, and the limit of quantification (LOQ) was 0.005 mg x kg(-1). The method with good reproducible, high precision and low detection limit could meet the requirements of residual analysis on ginseng production. The half-lives of myclobutanil were from 6.25 days to 9.94 days in ginseng root, stem, leaf and soil at spraying dosage of 1 152 g x hm(-2) The final residues were below 0.060 1 mg x kg(-1) in root, below 0.081 7 mg x kg(-1) in stem, 0.006 0-0.102 2 mg x kg(-1) in leaf and below 0.037 6 mg x kg(-1) in soil at spraying dosage range from 576 to 1 152 g x hm(-2). It is recommended that the MRLs of myclobutanil in dried ginseng may be suggested to be 0.10 mg x kg(-1) temporarily, and the preharvest interval was set at 35 days.
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[Sulfation of naringenin by Mucor sp].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 10-03-2014
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Naringenin (1) was transformed to three metabolites (2-4) by Mucor sp. Based on LCMS(n)-IT-TOF and NMR spectroscopic data, 2-4 were identified as naringenin-7-O-sulphate, naringenin-4'-O-sulphate, and naringenin-5-O-sulphate, respectively. These results might provide hints to the mammalian/human metabolism of naringenin.
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[Determination of polysaccharides content of Gentiana farreri from different producing areas based on anthrone-sulfuric acid method].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 10-03-2014
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Study a method for the detemination of the content of polysaccharides in Gentiana farreri, and analysis of the content of polysaccharides from different producing areas. The results showed that using the anthrone-sulfuric acid method, simple operation, accurate result. Sample was measured at 620 nm absorbance after anthrone-sulfuric acid color, at this wavelength, solution absorption and glucose showed a good linear relationship; The linearity was in the range of 0.01-0.07 g x L(-1) (r = 0.996 7). The recovery rate was 99.41%, with RSD of 2.0%. Considering the experimental conditions, to determine the solid-liquid ratio 1:60, extracting time 50 min, concentration of ethanol 80%. The mass fraction of polysaccharides was the highest to reached 0.743% in G. farreri from Gansu Xiahe. This experiment has laid a good foundation for further study on G. farreri.
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S-1 as Monotherapy or in Combination With Leucovorin as Second-Line Treatment in Gemcitabine-Refractory Advanced Pancreatic Cancer: A Randomized, Open-Label, Multicenter, Phase II Study.
Oncologist
PUBLISHED: 10-01-2014
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In this study, we compared the efficacy and safety of the oral fluoropyrimidine S-1 as monotherapy or in combination with leucovorin as the second-line treatment for patients with metastatic pancreatic cancer whose disease had progressed on gemcitabine treatment.
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Coordination complex pyrolyzation for the synthesis of nanostructured GeO2 with high lithium storage properties.
Chem. Commun. (Camb.)
PUBLISHED: 09-30-2014
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A new (NH4)3H(Ge7O16)(H2O)2.72 precursor-pyrolyzation approach was designed and developed for the facile synthesis of nanostructured GeO2, avoiding the use of any hazardous or expensive germanium compounds. The products show promising anode application in lithium ion batteries with high capacity and excellent cycling stability.
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Hyaluronan Synthase 2 Protects Skin Fibroblasts against Apoptosis Induced by Environmental Stress.
J. Biol. Chem.
PUBLISHED: 09-29-2014
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A balanced turnover of dermal fibroblasts is crucial for structural integrity and normal function of the skin. During recovery from environmental injury (such as UV exposure and physical wounding), apoptosis is an important mechanism regulating fibroblast turnover. We are interested in the role that hyaluronan (HA), an extracellular matrix molecule synthesized by HA synthase enzymes (Has), plays in regulating apoptosis in fibroblasts. We previously reported that Has1 and Has3 double knock-out (Has1/3 null) mice show accelerated wound closure and increased numbers of fibroblasts in the dermis. In the present study, we report that HA levels and Has2 mRNA expression are higher in cultured Has1/3 null primary skin fibroblasts than in wild type (WT) cells. Apoptosis induced by two different environmental stressors, UV exposure and serum starvation (SS), was reduced in the Has1/3 null cells. Hyaluronidase, added to cultures to remove extracellular HA, surprisingly had no effect upon apoptotic susceptibility to UVB or SS. However, cells treated with 4-methylumbelliferone to inhibit HA synthesis were sensitized to apoptosis induced by SS or UVB. When fibroblasts were transfected with Has2-specific siRNA that lowered Has2 mRNA and HA levels by 90%, both Has1/3 null and WT cells became significantly more sensitive to apoptosis. The exogenous addition of high molecular weight HA failed to reverse this effect. We conclude that Has1/3 null skin fibroblasts (which have higher levels of Has2 gene expression) are resistant to stress-induced apoptosis.
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Involvement of NLRP3 inflammasome in CVB3-induced viral myocarditis.
Am. J. Physiol. Heart Circ. Physiol.
PUBLISHED: 09-26-2014
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Viral myocarditis, which is most prevalently caused by coxsackievirus B3 (CVB3) infection, is a serious clinical condition characterized by cardiac inflammation. Inflammasome plays an essential role in the regulation of diverse inflammatory responses by serving as a platform for caspase-1 activation and caspase-1-dependent proteolytic maturation and secretion of IL-1?. Although inflammasome has been reported to be crucial for the development of many inflammatory diseases, its role in the pathogenesis of viral myocarditis is still elusive. The present study aims to investigate whether CVB3 infection activates inflammasome and whether the activation of inflammasome contributes to CVB3-induced myocarditis. Our results showed that CVB3 infection induced inflammasome activation both in vitro and in vivo. With the inhibition of inflammasome activation, the severity of CVB3-induced myocarditis was significantly alleviated as evidenced by less weight loss, decreased serological indexes of creatine kinase and creatinekinase-MB activities, as well as less severe myocardial injury. Of importance, echocardiography results showed that inhibition of inflammasome activation also efficiently improved cardiac function as revealed by enhanced left ventricular ejection fraction and left ventricular fractional shortening. Despite that CVB3 infection significantly increased the expression of both retinoic acid-inducible gene 1 and NOD-like receptor family, pyrin domain containing 3 (NLRP3) in cardiac myocytes, CVB3-induced inflammasome activation was NLRP3-, but not retinoic acid-inducible gene 1, dependent. Further study showed that reactive oxygen species production and K(+) efflux were critical for the activation of NLRP3 inflammasome upon CVB3 infection. Collectively, our study demonstrated a crucial role of the NLRP3 inflammasome in the pathogenesis of CVB3-induced myocarditis, and modulation of inflammasome activation might represent a promising therapeutic strategy for viral myocarditis.
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Fast convolution method and its application in mask optimization for intensity calculation using basis expansion.
IEEE Trans Image Process
PUBLISHED: 09-24-2014
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Finer grid representation is required for a more accurate description of mask patterns in inverse lithography techniques, thus resulting in a large-size mask representation and heavy computational cost. To mitigate the computation problem caused by intensive convolutions in mask optimization, a new method called convolution using basis expansion (CBE) is discussed in this paper. Matrices defined in fine grid are projected on coarse gird under a base matrix set. The new matrices formed by the expansion coefficients are used to perform convolution on the coarse grid. The convolution on fine grid can be approximated by the sum of a few convolutions on coarse grid following an interpolation procedure. The CBE is verified by random matrix convolutions and intensity calculation in lithography simulation. Results show that the use of the CBE method results in similar image quality with significant running speed enhancement compared with traditional convolution method.
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The Mitochondrial Protein Import Component, TRANSLOCASE OF THE INNER MEMBRANE17-1, Plays a Role in Defining the Timing of Germination in Arabidopsis.
Plant Physiol.
PUBLISHED: 09-24-2014
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In Arabidopsis (Arabidopsis thaliana), small gene families encode multiple isoforms for many of the components of the mitochondrial protein import apparatus. There are three isoforms of the TRANSLOCASE OF THE INNER MEMBRANE17 (Tim17). Transcriptome analysis indicates that AtTim17-1 is only detectable in dry seed. In this study, two independent transfer DNA insertional mutant lines of tim17-1 exhibited a germination-specific phenotype, showing a significant increase in the rate of germination. Microarray analyses revealed that Attim17-1 displayed alterations in the temporal sequence of transcriptomic events during germination, peaking earlier compared with the wild type. Promoter analysis of AtTim17-1 further identified an abscisic acid (ABA)-responsive element, which binds ABA-responsive transcription factors, acting to repress the expression of AtTim17-1. Attim17-1 dry seeds contained significantly increased levels of ABA and gibberellin, 2- and 5-fold, respectively. These results support the model that mitochondrial biogenesis is regulated in a tight temporal sequence of events during germination and that altering mitochondrial biogenesis feeds back to alter the germination rate, as evidenced by the altered levels of the master regulatory hormones that define germination.
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Torsion sensors of high sensitivity and wide dynamic range based on a graphene woven structure.
Nanoscale
PUBLISHED: 09-24-2014
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Due to its unique electromechanical properties, nanomaterial has become a promising material for use in the sensing elements of strain sensors. Tensile strain is the type of deformation most intensively studied. Torsion is another deformation occurring in everyday life, but is less well understood. In the present study a torsion sensor was prepared by wrapping woven graphene fabrics (GWFs) around a polymer rod at a specific winding angle. The GWF sensor showed an ultra-high sensitivity with a detection limit as low as 0.3 rad m(-1), indicating its potential application in the precise measurement of low torsions. The GWFs were pre-strained before wrapping on polydimethylsiloxane (PDMS) to improve the tolerance of the sensor to high torsion. The microstructure of the GWFs at different torsion levels was monitored using an optical microscope. The results demonstrated the formation of GWF waves and cracks under high torsion, a critical factor in determining the electromechanical properties of a GWF sensor.
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Aflatoxin B? degradation by a Pseudomonas strain.
Toxins (Basel)
PUBLISHED: 09-23-2014
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Aflatoxin B1 (AFB1), one of the most potent naturally occurring mutagens and carcinogens, causes significant threats to the food industry and animal production. In this study, 25 bacteria isolates were collected from grain kernels and soils displaying AFB1 reduction activity. Based on its degradation effectiveness, isolate N17-1 was selected for further characterization and identified as Pseudomonas aeruginosa. P. aeruginosa N17-1 could degrade AFB?, AFB? and AFM? by 82.8%, 46.8% and 31.9% after incubation in Nutrient Broth (NB) medium at 37 °C for 72 h, respectively. The culture supernatant of isolate N17-1 degraded AFB? effectively, whereas the viable cells and intra cell extracts were far less effective. Factors influencing AFB1 degradation by the culture supernatant were investigated. Maximum degradation was observed at 55 °C. Ions Mn²? and Cu²? were activators for AFB1 degradation, however, ions Mg²?, Li?, Zn²?, Se²?, Fe³? were strong inhibitors. Treatments with proteinase K and proteinase K plus SDS significantly reduced the degradation activity of the culture supernatant. No degradation products were observed based on preliminary LC-QTOF/MS analysis, indicating AFB? was metabolized to degradation products with chemical properties different from that of AFB?. The results indicated that the degradation of AFB? by P. aeruginosa N17-1 was enzymatic and could have a great potential in industrial applications. This is the first report indicating that the isolate of P. aeruginosa possesses the ability to degrade aflatoxin.
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[Biological characteristics of cleft palate relevant gene thyroid transcription factor-2 transgenic mice].
Hua Xi Kou Qiang Yi Xue Za Zhi
PUBLISHED: 09-23-2014
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The aim of this study is to establish a transgenic mouse model for cleft palate relevant gene thyroid transcription factor-2 (TTF-2), which can be used to study palatal shelf development when the expression pattern and regular activation of TTF-2 is altered.
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Ginsenoside?Rg5 induces apoptosis and DNA damage in human cervical cancer cells.
Mol Med Rep
PUBLISHED: 09-18-2014
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Panax ginseng is traditionally used as a remedy for cancer, inflammation, stress and aging, and ginsenoside?Rg5 is a major bioactive constituent of steamed ginseng. The present study aimed to evaluate whether ginsenoside?Rg5 had any marked cytotoxic, apoptotic or DNA?damaging effects in human cervical cancer cells. Five human cervical cancer cell lines (HeLa, MS751, C33A, Me180 and HT?3) were used to investigate the cytotoxicity of ginsenoside?Rg5 using a 3?(4,5?dimethylthiazol?2?yl)?2,5?diphenyltetrazolium bromide assay. Additionally, the effects of ginsenoside?Rg5 on the apoptosis of HeLa and MS751 cells were detected using DNA ladder assays and flow cytometry. DNA damage was assessed in the HeLa and MS751 cells using alkaline comet assays and by detection of ?H2AX focus formation. The HeLa and MS751 cells were significantly more sensitive to ginsenoside?Rg5 treatment compared with the C?33A, HT?3 and Me180 cells. As expected, ginsenoside?Rg5 induced significant concentration? and time?dependent increases in apoptosis. In addition, ginsenoside?Rg5 induced significant concentration?dependent increases in the level of DNA damage compared with the negative control. Consistent with the comet assay data, the percentage of ?H2AX?positive HeLa and MS751 cells also revealed that ginsenoside?Rg5 caused DNA double?strands to break in a concentration?dependent manner. In conclusion, ginsenoside?Rg5 had marked genotoxic effects in the HeLa and MS751 cells and, thus, demonstrates potential as a genotoxic or cytotoxic drug for the treatment of cervical cancer.
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Molecular characterization and different expression patterns of the FABP gene family during goat skeletal muscle development.
Mol. Biol. Rep.
PUBLISHED: 09-18-2014
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The FABP (adipocyte fatty acid-binding protein) genes play an important role in intracellular fatty acid transport and considered to be candidate genes for fatness traits in domestic animal. In this study, we cloned the cDNA sequences of goat FABP family genes and their expression patterns were detected by semi-quantitative RT-PCR and quantitative real time RT-PCR. Expression analysis showed that goat FABP1 gene was predominantly expressed in liver, kidney and large intestine. While FABP4 was widely expressed in many tissues with a high expression level was observed in the fat, skeletal muscle, stomach and lung. Notably, FABP2 gene was expressed specifically in small intestine. Moreover, goat FABP3 was expressed at 60 day with the highest level, then significantly (p < 0.01) decreased at the 90 day. No significant expression differences were observed in longissimus dorsi muscles among 3 day, 30 day and 60 day. Goat FABP4 was expressed at 3 day with the lowest level, then significantly (p < 0.01) increased to a peak at the 60 day. In addition, a significant relationship between FABP3 mRNA expression levels and intramuscular fat (IMF) content was observed. These results suggest that the FABP3 and FABP4 may be important genes for meat quality and provides useful information for further studies on their roles in skeletal muscle IMF deposit.
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Construction of special eye models for investigation of chromatic and higher-order aberrations of eyes.
Biomed Mater Eng
PUBLISHED: 09-18-2014
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An achromatic element eliminating only longitudinal chromatic aberration (LCA) while maintaining transverse chromatic aberration (TCA) is established for the eye model, which involves the angle formed by the visual and optical axis. To investigate the impacts of higher-order aberrations on vision, the actual data of higher-order aberrations of human eyes with three typical levels are introduced into the eye model along visual axis. Moreover, three kinds of individual eye models are established to investigate the impacts of higher-order aberrations, chromatic aberration (LCA+TCA), LCA and TCA on vision under the photopic condition, respectively. Results show that for most human eyes, the impact of chromatic aberration on vision is much stronger than that of higher-order aberrations, and the impact of LCA in chromatic aberration dominates. The impact of TCA is approximately equal to that of normal level higher-order aberrations and it can be ignored when LCA exists.
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[Construction and characterization of liposomal magnetofection system in pig kidney cells].
Sheng Wu Gong Cheng Xue Bao
PUBLISHED: 09-13-2014
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Magnetic nano gene vector is one of the non-viral gene vectors, modified by functional group to bind cationic transfect reagents. Coupling magnetofection with the universal lipofection we developed a novel somatic cell transfection method as the so-called liposomal magnetofection (LMF). This approach is potential to provide somatic cell cloning with stable genetic cell lines to cultivate transgenic animals. In order to construct such liposomal magnetic gene vectors complexes system, we used nano magnetic gene vector to combine with liposomal cationic transfect reagents by molecular self-assembly. This vectors system successfully carried exogenous gene and then transfected animal somatic cells. Here, we conducted atomic force microscopy (AFM), zeta potential-diameter analysis and other characterization experiments to investegate the size distribution and morphology of magnetic nanoparticles, the way of the vectors to load and concentrate DNA molecules. Our data reveal that, the LMF of Pig Kidney cells exhibited higher transfection efficiency comparing with the transfection mediated by the commercial lipofectamine2000. Moreover, LMF method overcomes the constraint of transient expression mediated by lipofection. Meanwhile, MTT assay showed low cytotoxicity of LMF. Hence, LMF is a feasible, low cytotoxic and effective method of cell transfection.
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A Small-Molecule Modulator of the Tumor-Suppressor miR34a Inhibits the Growth of Hepatocellular Carcinoma.
Cancer Res.
PUBLISHED: 09-12-2014
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Small molecules that restore the expression of growth-inhibitory microRNAs (miRNA) downregulated in tumors may have potential as anticancer agents. miR34a functions as a tumor suppressor and is downregulated or silenced commonly in a variety of human cancers, including hepatocellular carcinoma (HCC). In this study, we used an HCC cell-based miR34a luciferase reporter system to screen for miR34a modulators that could exert anticancer activity. One compound identified as a lead candidate, termed Rubone, was identified through its ability to specifically upregulate miR34a in HCC cells. Rubone activated miR34a expression in HCC cells with wild-type or mutated p53 but not in cells with p53 deletions. Notably, Rubone lacked growth-inhibitory effects on nontumorigenic human hepatocytes. In a mouse xenograft model of HCC, Rubone dramatically inhibited tumor growth, exhibiting stronger anti-HCC activity than sorafenib both in vitro and in vivo. Mechanistic investigations showed that Rubone decreased expression of cyclin D1, Bcl-2, and other miR34a target genes and that it enhanced the occupancy of p53 on the miR34a promoter. Taken together, our results offer a preclinical proof of concept for Rubone as a lead candidate for further investigation as a new class of HCC therapeutic based on restoration of miR34a tumor-suppressor function. Cancer Res; 74(21); 6236-47. ©2014 AACR.
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Spectrum-Effect Relationships as a Systematic Approach to Traditional Chinese Medicine Research: Current Status and Future Perspectives.
Molecules
PUBLISHED: 09-05-2014
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Component fingerprints are a recognized method used worldwide to evaluate the quality of traditional Chinese medicines (TCMs). To foster the strengths and circumvent the weaknesses of the fingerprint technique in TCM, spectrum-effect relationships would complementarily clarify the nature of pharmacodynamic effects in the practice of TCM. The application of the spectrum-effect relationship method is crucial for understanding and interpreting TCM development, especially in the view of the trends towards TCM modernization and standardization. The basic requirement for using this method is in-depth knowledge of the active material basis and mechanisms of action. It is a novel and effective approach to study TCMs and great progress has been made, but to make it more accurate for TCM research purposes, more efforts are needed. In this review, the authors summarize the current knowledge about the spectrum-effect relationship method, including the fingerprint methods, pharmacodynamics studies and the methods of establishing relationships between the fingerprints and pharmacodynamics. Some speculation regarding future perspectives for spectrum-effect relationship approaches in TCM modernization and standardization are also proposed.
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Urotensin II increases foam cell formation by repressing ABCA1 expression through the ERK/NF-?B pathway in THP-1 macrophages.
Biochem. Biophys. Res. Commun.
PUBLISHED: 09-03-2014
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Foam cell formation in the arterial wall plays a key role in the development of atherosclerosis. Recent studies showed that Urotensin II (U II) is involved in the pathogenesis of atherosclerosis. Here we examined the effects of human U II on ATP-binding cassette transporter A1 (ABCA1) expression and the underlying mechanism in THP-1 macrophages.
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CRKL protein overexpression enhances cell proliferation and invasion in pancreatic cancer.
Tumour Biol.
PUBLISHED: 09-02-2014
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CRKL is an adapter protein which is overexpressed in many malignant tumors and plays crucial roles in tumor progression. However, expression pattern and biological roles of CRKL in pancreatic cancer have not been examined. In the present study, we found that CRKL expression in pancreatic cancer specimens was higher than that in normal pancreatic tissues. Colony formation assay and Matrigel invasion assay showed that the overexpression of CRKL in Bxpc3 and Capan2 cell lines with low endogenous expression increased cell proliferation and invasion. Flow cytometry showed that CRKL promoted cell proliferation by facilitating cell cycle. Further analysis of cell cycle- and invasion-related molecules showed that CRKL upregulated cyclin D1, cyclin A, matrix metalloproteinase 2 (MMP2) expression, and phosphorylated extracellular signal (ERK)-regulated kinase. In conclusion, our study demonstrated that CRKL was overexpressed in human pancreatic cancers and contributed to pancreatic cancer cell proliferation and invasion through ERK signaling.
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Identification of a small molecule signaling factor that regulates the biosynthesis of the antifungal polycyclic tetramate macrolactam HSAF in Lysobacter enzymogenes.
Appl. Microbiol. Biotechnol.
PUBLISHED: 09-01-2014
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Lysobacter species are emerging as new sources of antibiotics. The regulation of these antibiotics is not well understood. Here, we identified a small molecule metabolite (LeDSF3) that regulates the biosynthesis of the antifungal antibiotic heat-stable antifungal factor (HSAF), a polycyclic tetramate macrolactam with a structure and mode of action distinct from the existing antifungal drugs. LeDSF3 was isolated from the culture broth of Lysobacter enzymogenes, and its chemical structure was established by NMR and MS. The purified compound induced green fluorescence in a reporter strain of Xanthomonas campestris, which contained a gfp gene under the control of a diffusible signaling factor (DSF)-inducible promoter. Exogenous addition of LeDSF3 in L. enzymogenes cultures significantly increased the HSAF yield, the transcription of HSAF biosynthetic genes, and the antifungal activity of the organism. The LeDSF3-regulated HSAF production is dependent on the two-component regulatory system RpfC/RpfG. Moreover, LeDSF3 upregulated the expression of the global regulator cAMP receptor-like protein (Clp). The disruption of clp led to no HSAF production. Together, the results show that LeDSF3 is a fatty acid-derived, diffusible signaling factor positively regulating HSAF biosynthesis and that the signaling is mediated by the RfpC/RpfG-Clp pathway. These findings may facilitate the antibiotic production through applied genetics and molecular biotechnology in Lysobacter, a group of ubiquitous yet underexplored microorganisms.
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Optimization of medium composition for cis,cis-muconic acid production by a Pseudomonas sp. mutant using statistical methods.
Prep. Biochem. Biotechnol.
PUBLISHED: 08-29-2014
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cis,cis-Muconic acid (CCMA) is used as a platform chemical for the production of several high-value compounds. For this article, an optimization strategy has been used to optimize medium composition for CCMA production from fairly cheap benzoate by Pseudomonas sp. 1167. The effect of different concentrations of medium components on CCMA production was studied. CCMA yields obtained from Plackett-Burman design (PBD) showed wide variation (3.95-5.87 g/L), and the first-order model indicated that (NH(4))(2)SO(4) (P < 0.01) and K(2)HPO(4) · 3H(2)O (P < 0.02) were the significant components for CCMA production. Then the optimization was performed by steepest ascent design (SAD) and central composite design (CCD), and a validation experiment was conducted to verify the predicted value. The optimal medium composition was: 12 g/L sodium benzoate, 2.5 g/L sodium succinate, 0.7932 g/L (NH(4))(2)SO(4), 1.5612 g/L K(2)HPO(4) · 3H(2)O, 1.2 g/L MgSO(4) · 7H(2)O, 0.4 g/L yeast extract, 0.08 g/L FeCl(3) · 6H(2)O, and 0.08 g/L ethylenediamine tetraacetic acid (EDTA). Under these conditions, a maximum of 7.18 g/L CCMA was produced per 12 g/L benzoate with a highly efficient process within 11 hr and a molecular conversion yield of 61%. Altogether, our results provide valuable insights into nutritional supplementation of CCMA production by using statistical methods, which may benefit a cost-competitive industrial fed-batch fermentation process using a cheap substrate.
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Homogeneity of the Vaginal Microbiome at the Cervix, Posterior Fornix, and Vaginal Canal in Pregnant Chinese Women.
Microb. Ecol.
PUBLISHED: 08-25-2014
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The vaginal microbiome is an emerging concern in prenatal health. Because the sampling process of vaginal microbiota may pose potential risks for pregnant women, the choice of sampling site should be carefully considered. However, whether the microbial diversity is different across various sampling sites has been controversial. In the present study, three repeated swabs were collected at the cervix (C), posterior fornix (P), and vaginal canal (V) from 34 Chinese women during different pregnancy stages, and vaginal species were determined using the Illumina sequencing of 16S rRNA tag sequences. The identified microbiomes were classified into four community state types (CSTs): CST I (dominated by L. crispatus), CST II (dominated by L. gasseri), CST III (dominated by L. iners), and CST IV-A (characterized by a low abundance of Lactobacillus, but with proportions of various species previously shown to be associated with bacterial vaginosis). All individuals had consistent CST at the three sampling sites regardless of pregnancy stage and CST group. In addition, there was little heterogeneity across community structures within each individual, as determined by LEfSe, indicating high vaginal microbiome homogeneity at the three sampling sites. The present study also revealed different beta diversity during pregnancy stages. The vaginal microbiome variation among women during trimester T1 (9?±?2.6 weeks) is larger than that of non-pregnant women and women from other trimesters, as demonstrated by the UniFrac distance (P?
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Exploring the interactions of decabrominateddiphenyl ether and tetrabromobisphenol A with human serum albumin.
Environ. Toxicol. Pharmacol.
PUBLISHED: 08-23-2014
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Decabrominateddiphenyl ether (deca-BDE) and tetrabromobisphenol A (TBBPA) are known as brominated flame-retardants, which are commonly found in the environment. The binding mechanisms of deca-BDE and TBBPA with human serum albumin (HSA) are still unknown. In this report, the interactions of deca-BDE and TBBPA with HSA were investigated using different spectroscopic methods and molecular modeling. The experimental results indicated the formation of complexes between deca-BDE/TBBPA and HSA with different affinity. These interactions affected the secondary structure of HSA. Thermodynamic investigations revealed that hydrophobic forces mainly drove the binding interactions of deca-BDE/TBBPA with HSA. For TBBPA, hydrogen-bonding interactions were also involved in the binding process of TBBPA with HSA. According to the analysis of experimental and theoretical data, we concluded that the binding site of deca-BDE to HSA located in the subdomain IB, while TBBPA was near to subdomain IIA and Trp-214. The binding interactions of deca-BDE and TBBPA with the most prominent carrier protein in the human circulatory system could influence mechanisms of their biochemical processes. Thus, these binding interactions can play central roles in studying the distribution and toxicity mechanisms of brominated flame-retardants.
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Rapid and sensitive detection of Listeria monocytogenes by cross-priming amplification of lmo0733 gene.
FEMS Microbiol. Lett.
PUBLISHED: 08-22-2014
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Listeria monocytogenes is a food-borne pathogen that causes severe opportunistic infection in humans and animals. This study reports the development of single cross-priming amplification (S-CPA) and double CPA (D-CPA) assays targeting species-specific gene lmo0733 for identifying L. monocytogenes strains. The CPA assays were performed at a constant temperature 64 °C using seven specific primers and evaluated for specificity and sensitivity. The color change of positive amplification was directly observed by Loopamp(®) Fluorescent Detection Reagent (FD), and the DNA products were visualized as a ladder-like banding pattern on 2.5% gel electrophoresis. Moreover, the positive reactions were also detected by real-time measurement of turbidity. 50 L. monocytogenes and 46 non-L. monocytogenes strains were used for the method verification, and the specificity was 100%. The limit of detection (LoD) of the S-CPA and D-CPA assays was 2.5 pg DNA per reaction and 10-fold more sensitive than PCR. A total of 60 pork samples were tested for L. monocytogenes using the S-CPA assay developed in the study, and the accuracy of the S-CPA and the culture-biotechnical method was 100% identical. The results suggested that the S-CPA assay was a rapid, sensitive, and valuable tool for detection of L. monocytogenes in food products.
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Fast quantification of endogenous carbohydrates in plasma using hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry.
J Sep Sci
PUBLISHED: 08-19-2014
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Objective: Endogenous carbohydrates in biosamples are frequently highlighted as the most differential metabolites in many metabolomics studies. A simple, fast, simultaneous quantitative method for 16 endogenous carbohydrates in plasma has been developed using hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry. Method: In order to quantify 16 endogenous carbohydrates in plasma, various conditions, including columns, chromatographic conditions, mass spectrometry conditions, and plasma preparation methods, were investigated. Different conditions in this quantified analysis were performed and optimized. The reproducibility, precision, recovery, and stability of the method were verified. Result: The results indicated that a methanol/acetonitrile (50:50, v/v) mixture could effectively and reproducibly precipitate rat plasma proteins. Cold organic solvents coupled with vortex for 1 min and incubated at -20°C for 20 min were the most optimal conditions for protein precipitation and extraction. The results, according to the linearity, recovery, precision, and stability, showed that the method was satisfactory in the quantification of endogenous carbohydrates in rat plasma. Conclusion: The quantified analysis of endogenous carbohydrates in rat plasma performed excellently in the sensitivity, high throughput and simple sample preparation, which met the requirement of quantification in specific expanded metabolomic studies after the global metabolic profiling research. This article is protected by copyright. All rights reserved.
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Proteasome inhibitor lactacystin enhances cisplatin cytotoxicity by increasing endoplasmic reticulum stress?associated apoptosis in HeLa cells.
Mol Med Rep
PUBLISHED: 08-08-2014
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Cisplatin is commonly used as a therapeutic agent, despite its known adverse side effects and the occurrence of drug resistance. The development of novel methods for combination therapy with cisplatin is required in order to circumvent these limitations of cisplatin alone. The proteasome inhibitor lactacystin (LAC) has been indicated to produce anti?tumor effects, and has previously been used as an antitumor agent in cancer treatment research; however, its effects in combination with cisplatin treatment are unknown. In the current study, the effects of LAC in combination with cisplatin treatment were investigated in HeLa human cervical cancer (HCC) cells. The results demonstrated that cisplatin treatment inhibited cell growth and induced cell apoptosis. HeLa cell exposure to cisplatin induced endoplasmic reticulum (ER) stress?associated apoptosis, and LAC treatment increased levels of cell apoptosis and the activation of caspase?3. Specifically, LAC treatment increased the cisplatin?induced expression of PDI, GRP78, CHOP, cleaved caspase?4 and cleaved caspase?3. Together, these data indicate that LAC is able to enhance cisplatin cytotoxicity by increasing ER stress?associated apoptosis in HeLa cells.
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[Impact of introduction of O2 on the welding arc of gas pool coupled activating TIG].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 08-07-2014
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In the present paper, Boltzmann plot method was applied to analyze the temperature distributions of the are plasma when the gas pool coupled activating TIG welding was at different coupling degrees with the outer gas being O2. Based on this study of temperature distributions, the changing regularities of are voltage and are appearance were studied. The result shows that compared with traditional TIG welding, the introduction of O2 makes the welding arc constricted slightly, the temperature of the are center build up, and the are voltage increase. When argon being the inner gas, oxygen serving as the outer gas instead of argon makes the are constricted more obviously. When the coupling degree increases from 0 to 2, the temperature of the are center and the are voltage both increase slightly. In the gas pool coupled activating TIG welding the are is constricted not obviously, and the reason why the weld penetration is improved dramatically in the welding of stainless steel is not are constriction.
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Increased Macrophage Activation Inhibited by Tacrolimus in the Kidney of Diabetic Rats.
Nephron Exp. Nephrol.
PUBLISHED: 08-06-2014
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Background/Aims: Accumulating evidence suggests that macrophage-induced inflammation may be the mechanism of development and progression of diabetic nephropathy. A previous study by our group has shown that tacrolimus, like cyclosporin A, has a renoprotective effect in diabetic rats. The present study aimed to elucidate the underlying molecular events. Methods: Diabetic rats were induced by using streptozotocin. Diabetic rats were subjected to oral tacrolimus treatment at a dose of 0.5 or 1.0 mg/kg daily for 4 weeks. Body weight, blood glucose, hemoglobin A1c (HbA1c) and renal pathology were assessed, followed by analyses of renal calcineurin (CaN) expression, changes in renal macrophage infiltration, proliferation and activation, and detection of renal TLR2+ and TLR4+ as well as NF-?B-p-p65+ in macrophages. Results: Diabetic rats had a reduced body weight and increased blood glucose and HbA1c levels, whereas tacrolimus treatment did not affect body weight or blood glucose and HbA1c. Increased relative kidney weight was only significantly reduced by tacrolimus treatment at a dose of 1.0 mg/kg, while the elevated albumin excretion rate was markedly attenuated after treatment with tacrolimus (0.5 and 1.0 mg/kg) in diabetic rats. Elevated glomerular volume was significantly attenuated by tacrolimus treatment with 0.5 and 1.0 mg/kg, and increased indices for tubulointerstitial injury were only ameliorated by tacrolimus treatment with 1.0 mg/kg. Western blot data showed that expression of CaN protein was induced 2.4-fold in the kidneys of positive control diabetic rats, whereas tacrolimus treatment at 0.5 and 1.0 mg/kg doses reduced the increased expression of CaN protein by 38.0 and 73.2%, respectively. Histologically there was a marked accumulation of ED-1+ cells (macrophages) in diabetic kidneys and tacrolimus treatment failed to inhibit it. In contrast, tacrolimus treatment at 0.5 and 1.0 mg/kg doses significantly inhibited the elevated ED-1+/PCNA+ cells and ED-1+/iNOS+ cells in the kidneys of diabetic rats, while tacrolimus treatment at a dose of 0.5 or 1.0 mg/kg significantly suppressed the increased ED-1+/TLR2+ cells, ED-1+/TLR4+ cells and ED-1+/NF-?B-p-p65+ cells in the kidneys of diabetic rats. Conclusion: The data from the current study demonstrated that tacrolimus could ameliorate early renal injury through a mechanism to suppress macrophage activation. © 2014 S. Karger AG, Basel.
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Analyses of functional and oncologic outcomes following supracricoid partial laryngectomy.
Eur Arch Otorhinolaryngol
PUBLISHED: 08-05-2014
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To review the functional and oncologic outcomes of patients who received supracricoid partial laryngectomy (SCPL) with cricohyoidoepiglottopexy (CHEP) or cricohyoidopexy (CHP) in our institution. A total of 208 patients who received SCPL with CHEP or CHP from our institution from 1995 to 2007 were involved. Among them, 190 cases were patients with squamous cell carcinoma of the larynx (T1-T4, N0-N2), 14 cases were patients with recurrent larynx cancer and 4 cases were patients with laryngeal stenosis. Forty-four patients also received unilateral neck dissection, and 41 patients received a bilateral neck dissection. All patients were assessed at functional outcome and complications of their treatment. Also, the oncologic outcomes, such as disease-specific survival, total survival, and local recurrence, were measured for patients with tumor. Decannulation was achieved in nearly all patients, with the average time to decannulation being 20 ± 11.52 days in CHEP patients and 28 ± 8.92 days in CHP patients (P < 0.05). The average nasogastric tubes were removed, days postoperation, was 18 ± 7.39 days in CHEP patients and 25 ± 13.87 days in CHP patients (P < 0.05). The 5-year local recurrence rate was 5.77 %, the 5-year disease-specific survival was 82.7 %, and the 5-year overall survival was 84.1 %. The patients with CHEP had a better recovery than the patients with CHP. SCPL was a well-tolerated procedure with generally good functional outcomes for patients with advanced laryngeal cancer, also for some patients with laryngeal stenosis.
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Compound bioflocculant and polyaluminum chloride in kaolin-humic acid coagulation: Factors influencing coagulation performance and floc characteristics.
Bioresour. Technol.
PUBLISHED: 07-25-2014
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The objective of this study was to investigate the influence of coagulant dosage and pH on coagulation performance and floc properties using polyaluminum chloride (PAC) and compound bioflocculant (CBF) dual-coagulant in kaolin-humic acid (HA) treatment. Results showed that as PAC dosage rose, comparatively better coagulation efficiencies and floc characteristics were achieved due to stronger charge neutralization and sweeping effect. Addition of CBF could enhance coagulation performance and floc properties, including size, strength and recoverability, except fractal dimension. Solution pH had a significant effect on coagulation efficiencies and flocs formation. Under acidic condition, flocs showed higher strength and recoverability but lower fractal dimension, where charge neutralization was the foremost mechanism. More compact flocs were generated under alkaline condition due to the sweeping effect of hydrolyzed Al species.
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Exenatide can inhibit calcification of human VSMCs through the NF-kappaB/RANKL signaling pathway.
Cardiovasc Diabetol
PUBLISHED: 07-21-2014
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BackgroundArterial calcification is an important pathological change of diabetic vascular complication. Osteoblastic differentiation of vascular smooth muscle cells (VSMCs) plays an important cytopathologic role in arterial calcification. The glucagon-like peptide-1 receptor agonists (GLP-1RA), a novel type of antidiabetic drugs, exert cardioprotective effects through the GLP-1 receptor (GLP-1R). However, the question of whether or not GLP-1RA regulates osteoblastic differentiation and calcification of VSMCs has not been answered, and the associated molecular mechanisms have not been examined.MethodsCalcifying VSMCs (CVSMCs) were isolated from cultured human arterial smooth muscle cells through limiting dilution and cloning. The extent of matrix mineralization was measured by Alizarin Red S staining. Protein expression and phosphorylation were detected by Western blot. Gene expression of receptor activator of nuclear factor-¿B ligand (RANKL) was silenced by small interference RAN (siRNA).ResultsExenatide, an agonist of GLP-1 receptor, attenuated ß-glycerol phosphate (ß-GP) induced osteoblastic differentiation and calcification of human CVSMCs in a dose- and time-dependent manner. RANKL siRNA also inhibited osteoblastic differentiation and calcification. Exenatide decreased the expression of RANKL in a dose-dependent manner. 1,25 vitD3 (an activator of RANKL) upregulated, whereas BAY11-7082 (an inhibitor of NF-¿B) downregulated RANKL, alkaline phosphatase (ALP), osteocalcin (OC), and core binding factor ¿1 (Runx2) protein levels and reduced mineralization in human CVSMCs. Exenatide decreased p-NF-¿B and increased p-AMPK¿ levels in human CVSMCs 48 h after treatment. Significant decrease in p-NF-¿B (p-Ser276, p-Ser536) level was observed in cells treated with exenatide or exenatide¿+¿BAY11-7082.ConclusionGLP-1RA exenatide can inhibit human VSMCs calcification through NF-¿B/ RANKL signaling.
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Floc properties and membrane fouling of polyferric silicate chloride and polyferric chloride: the role of polysilicic acid.
Environ Sci Pollut Res Int
PUBLISHED: 07-21-2014
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Impact of polysilicic acid (pSi) in polyferric silicate chloride (PFSiC) on coagulation-ultrafiltration process was investigated in comparison with polyferric chloride (PFC). The Fe(III) species distribution in PFSiC and PFC was measured by a timed complexation spectroscopy method. Characteristics of flocs produced by PFSiC and PFC were studied using a laser diffraction particle sizing device. Moreover, membrane fouling was evaluated using a dead-end batch ultrafiltration unit under two operation modes, coagulation-ultrafiltration (C-UF) and coagulation-sedimentation-ultrafiltration (CSUF). The results indicated that PFSiC with various Si/Fe ratios had better turbidity removal efficiency but inferior organic matter removal. Flocs formed by PFSiC were larger than those by PFC. In case of PFSiC, floc size increased with Si/Fe ratio increasing. PFSiC with various Si/Fe ratios resulted in more compact and weaker flocs than PFC. Ultrafiltration experiments indicated that under C-UF mode, PFSiC with Si/Fe ratios of 0.07 and 0.10 presented better membrane performance than PFC. Under CSUF mode, addition of pSi could alleviate membrane fouling.
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Structural covariance networks across healthy young adults and their consistency.
J Magn Reson Imaging
PUBLISHED: 07-12-2014
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To investigate structural covariance networks (SCNs) as measured by regional gray matter volumes with structural magnetic resonance imaging (MRI) from healthy young adults, and to examine their consistency and stability.
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Immunohistochemical detection of the BRAF V600E mutation in melanoma patients with monoclonal antibody VE1.
Pathol. Int.
PUBLISHED: 07-08-2014
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A novel mutation-specific monoclonal antibody VE1 was generated to detect BRAF V600E mutation with immunohistochemistry. This study aims to investigate the sensitivity and specificity of immunohistochemistry compared with conventional Sanger sequencing and to evaluate whether IHC would become the routine screening method of BRAF V600E mutation. A total of 84 cases of melanoma lesion specimens were selected to make the tissue microarray and to perform IHC with VE1 antibody. Simultaneously Sanger sequencing was applied to test and verify. VE1 has a high specificity (100%) and sensitivity (72.2%), and the concordance between the two techniques is excellent (93.8% cases coherent and kappa?=?0.801). As a rapid, cost-effective method, IHC may become the routine diagnostic means for the detection of BRAF V600E mutation of malignant melanomas in the near future, and the recommended detection process is initial immunohistochemical staining for positive cases, followed by molecular techniques for negative or ambiguous cases.
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