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Find video protocols related to scientific articles indexed in Pubmed.
Inhibition of ER glucosidases impairs SARS-CoV and HCoV-NL63 spike protein-mediated entry by altering the glycan processing of ACE2.
Antimicrob. Agents Chemother.
PUBLISHED: 10-29-2014
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Endoplasmic reticulum (ER)-resident glucosidases I and II sequentially trim the three terminal glucose moieties on the N-linked glycans attached to nascent glycoproteins. These reactions are the first steps of N-linked glycan processing and are essential for proper folding and function of many glycoproteins. Because most of the viral envelope glycoproteins contain N-linked glycans, inhibition of ER glucosidases with derivatives of 1-deoxynojirimycin, i.e. iminosugars, efficiently disrupts the morphogenesis of a broad-spectrum of enveloped viruses. However, like viral envelope proteins, the cellular receptors of many viruses are also glycoproteins. It is, therefore, possible that inhibition of ER glucosidases not only compromises virion production, but may also disrupt expression and function of viral receptors and thus inhibit virus entry into host cells. Indeed, we demonstrated herein that iminosugar treatment altered the N-linked glycan structure of angiotensin-I converting enzyme 2 (ACE2), which did not affect its expression on cell surface and binding of severe acute respiratory syndrome coronavirus (SARS-CoV) spike glycoprotein. However, alteration of N-linked glycans of ACE2 impairs its ability to support the transduction of SARS-CoV and human coronavirus NL63 (HCoV-NL63) spike glycoprotein-pseudotyped lentiviral particles by disruption of the viral envelope protein triggered membrane fusion. Hence, in addition to reducing the production of infectious virions, inhibition of ER glucosidases also impairs the entry of selected viruses via a post receptor binding mechanism.
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[GSTP1 Ile105Val polymorphism confer susceptibility to oral cancer:a meta-analysis].
Shanghai Kou Qiang Yi Xue
PUBLISHED: 10-24-2014
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This meta-analysis was aimed to evaluate the association of glutathione S-transferase P1 (GSTP1) Ile105Val genetic polymorphism with susceptibility to oral cancer.
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The complete mitochondrial genome sequence of Hemibagrus nemurus (Siluriformes: Bagridae).
Mitochondrial DNA
PUBLISHED: 10-17-2014
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Abstract Hemibagrus nemurus (Valenciennes, 1840) is a kind of tropical freshwater catfish which is native to Asian waters. It is economically valued for its importance in fisheries and aquaculture. At present, there exist some confusion in species identification in Bagridae. In this paper, we sequenced and characterize the complete mitogenome of H. nemurus. The genome was 16,526?bp in length, and typically consists of 37 genes, including 13 protein-coding genes, 2 rRNAs, 22 tRNA, 1 origin of replication on the light-strand (OL) and a single large control region (CR). The gene organization is identical to that of a typical bony fish. The overall base composition was 31.5%, 26.6%, 26.7%, and 15.2% for A, T, C, and G, respectively, with a slight bias on AT content (58.1%). This result is expected to provide useful molecular data and contribute to further taxonomic and phylogenetic studies of Hemibagrus and Bagridae.
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Prediction of Drug Disposition in Diabetic Patients by Means of a Physiologically Based Pharmacokinetic Model.
Clin Pharmacokinet
PUBLISHED: 10-16-2014
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Accumulating evidence has shown that diabetes mellitus may affect the pharmacokinetics of some drugs, leading to alteration of pharmacodynamics and/or toxic effects. The aim of this study was to develop a novel physiologically based pharmacokinetic (PBPK) model for predicting drug pharmacokinetics in patients with type 2 diabetes mellitus quantitatively.
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A deeper understanding of the association between CTLA4 +49A/G and acute rejection in renal transplantation: an updated meta-analysis.
Ren Fail
PUBLISHED: 10-10-2014
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Abstract To reevaluate the association between the costimulatory molecule cytotoxic T lymphocyte-associated antigen4 (CTLA4) single nucleotide polymorphism (SNP) +49A/G and acute rejection (AR) in renal transplantation, nine studies published before June 2013 were analyzed. Meta-analysis and cumulative meta-analysis (metacum) were performed for each genotype in a random/fixed effect model. The combined odds ratios (OR) with 95% confidence intervals (CI) were calculated to estimate the strength of the association. In the sensitivity analysis, a single study involved in the meta-analysis was deleted each time to investigate the influence of the individual data sets on the pooled ORs. Meta-analysis regression was used for some influence factors, such as year of publication, total number in each group (AR group and control group), ethnicity, the ratio of GG to GA?+?AA, the ratio of G to A in CTLA4 +49A/G. Overall, a significant correlation was noted between the CTLA4 SNP (+49A/G) and the risk of AR (for GG vs. AG?+?AA: OR?=?1.35, 95% CI?=?1.05-1.73, p?=?0.02; for G vs. A: OR?=?1.21, 95% CI?=?1.03-1.42, p?=?0.02), especially in the Asian subgroup (for GG vs. AG?+?AA: OR?=?1.79, 95% CI?=?1.15-2.78, p?=?0.009; for G vs. A: OR?=?1.47, 95% CI?=?1.04-2.07, p?=?0.03). Of the influence factors, the ratio of GG to GA+AA (p?=?0.046) and the ratio of G to A (p?=?0.017) were significant factors. In conclusion, our results suggest that CTLA4 +49A/G contribute to the risk of AR following renal transplantation.
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Catabolism of (2E)-4-Hydroxy-2-nonenal via ?- and ?-1-Oxidation Stimulated by Ketogenic Diet.
J. Biol. Chem.
PUBLISHED: 10-01-2014
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Oxidative stress triggers the peroxidation of ?-6-polyunsaturated fatty acids to reactive lipid fragments, including (2E)-4-hydroxy-2-nonenal (HNE). We previously reported two parallel catabolic pathways of HNE. In this study, we report a novel metabolite that accumulates in rat liver perfused with HNE or 4-hydroxynonanoic acid (HNA), identified as 3-(5-oxotetrahydro-2-furanyl)propanoyl-CoA. In experiments using a combination of isotopic analysis and metabolomics studies, three catabolic pathways of HNE were delineated following HNE conversion to HNA. (i) HNA is ?-hydroxylated to 4,9-dihydroxynonanoic acid, which is subsequently oxidized to 4-hydroxynonanedioic acid. This is followed by the degradation of 4-hydroxynonanedioic acid via ?-oxidation originating from C-9 of HNA breaking down to 4-hydroxynonanedioyl-CoA, 4-hydroxyheptanedioyl-CoA, or its lactone, 2-hydroxyglutaryl-CoA, and 2-ketoglutaric acid entering the citric acid cycle. (ii) ?-1-hydroxylation of HNA leads to 4,8-dihydroxynonanoic acid (4,8-DHNA), which is subsequently catabolized via two parallel pathways we previously reported. In catabolic pathway A, 4,8-DHNA is catabolized to 4-phospho-8-hydroxynonanoyl-CoA, 3,8-dihydroxynonanoyl-CoA, 6-hydroxyheptanoyl-CoA, 4-hydroxypentanoyl-CoA, propionyl-CoA, and acetyl-CoA. (iii) The catabolic pathway B of 4,8-DHNA leads to 2,6-dihydroxyheptanoyl-CoA, 5-hydroxyhexanoyl-CoA, 3-hydroxybutyryl-CoA, and acetyl-CoA. Both in vivo and in vitro experiments showed that HNE can be catabolically disposed via ?- and ?-1-oxidation in rat liver and kidney, with little activity in brain and heart. Dietary experiments showed that ?- and ?-1-hydroxylation of HNA in rat liver were dramatically up-regulated by a ketogenic diet, which lowered HNE basal level. HET0016 inhibition and mRNA expression level suggested that the cytochrome P450 4A are main enzymes responsible for the NADPH-dependent ?- and ?-1-hydroxylation of HNA/HNE.
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Characterization of acid-and pepsin-soluble collagens from spines and skulls of skipjack tuna (Katsuwonus pelamis).
Chin J Nat Med
PUBLISHED: 09-30-2014
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Acid-soluble collagen (ASC) and pepsin-soluble collagen (PSC) from the spine (ASC-SP and PSC-SP) and skull (ASC-SK and PSC-SK) of the skipjack tuna, Katsuwonus pelamis, were successfully isolated and characterized. The yields of ASC-SP, PSC-SP, ASC-SK and PSC-SK were (2.47 ± 0.39)%, (5.62 ± 0.82)%, (3.57 ± 0.40)%, and (6.71 ± 0.81)%, respectively, on the basis of dry weight. The four collagens contained Gly (330.2-339.1 residues/1 000 residues) as the major amino acid, and their imino acid contents were between 168.8 and 178.2 residues/1 000 residues. Amino acid composition, SDS-PAGE, and FTIR investigations confirmed that ASC-SP and ASC-SK were mainly composed of type I collagen, and had higher contents of high-molecular weight cross-links than those of PSC-SK and PSC-SP. The FTIR investigation also certified all the collagens had triple helical structure. The denaturation temperatures of ASC-SK, PSC-SK, ASC-SP, and PSC-SP were 17.8, 16.6, 17.6, and 16.5 °C, respectively. All isolated collagens were soluble at acidic pH (1-5) and lost their solubilities when the NaCl concentration was above 2% (W/V). The isolated collagens from the spines and skulls of skipjack tuna could serve as an alternative source of collagens for further application in food, cosmetic, biomedical, and pharmaceutical industries.
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Characterization of the mitochondrial genome of the montane grasshopper, Qinlingacris elaeodes (Orthoptera: Catantopidae).
Mitochondrial DNA
PUBLISHED: 09-27-2014
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Abstract Qinlingacris elaeodes is the dominant grasshopper at an altitude of 3000 meters and above, and is a representative species of the genus Qinlingacris endemic to China. The sequenced mitochondrial genome of this grasshopper is 14,818?bp in length, including 13 protein-coding genes (ND1-6, COI-III, ATP6, ATP8, ND4L, CTYB), 21 transfer RNAs, and 2 ribosomal RNAs (12S and 16S). The orientation and gene order of these genes are identical to those found in the putative ancestral insect mitogenome. The 13 PCGs start with a typical ATN codon as their start codons. The usual TAA and TAG termination codons are found for 12 PCGs. However, the ND5 gene has an incomplete termination codon (T).
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An Iminocoumarin Sulfonamide Based Turn-On Fluorescent Probe for the Detection of Biothiols in Aqueous Solution.
Chem Asian J
PUBLISHED: 09-09-2014
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A new chemodosimeter for the highly selective sensing and imaging of biothiols was designed and realized in phosphate-buffered saline solution at pH?7.4 through a fluorescence "off-on" response. A unique mechanism featuring a two-step cascade (biothiols?H2 O) sequence for this remarkable recognition is disclosed for the first time.
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[Efficacy of inhaled nitric oxide in premature infants with hypoxic respiratory failure].
Zhongguo Dang Dai Er Ke Za Zhi
PUBLISHED: 08-21-2014
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To investigate the safety and efficacy of low-concentration inhaled nitric oxide (NO) in the treatment of hypoxic respiratory failure (HRF) among premature infants.
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Mipu1 Overexpression Protects Macrophages from oxLDL-Induced Foam Cell Formation and Cell Apoptosis.
DNA Cell Biol.
PUBLISHED: 08-20-2014
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Mipu1 (myocardial ischemic preconditioning upregulated protein 1) is a novel N-terminal Kruppel-associated box (KRAB)/C2H2 zinc finger superfamily protein, that displays a powerful effect in protecting H9c2 cells from oxidative stress-induced cell apoptosis. The present study aims to investigate the effect of Mipu1 overexpression on oxidized low-density lipoprotein (oxLDL)-induced foam cell formation, cell apoptosis, and its possible mechanisms. New Zealand healthy rabbits were used to establish atherosclerosis model, and serum levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were detected by an automatic biochemical analyzer. Sudan IV staining was used to detect atherosclerotic lesions. The RAW264.7 macrophage cell line was selected as the experimental material. Oil red O staining, high-performance liquid chromatography, and Dil-labeled lipoprotein were used to detect cholesterol accumulation qualitatively and quantitatively, respectively. Flow cytometry was used to determine cell apoptosis. Real-time quantitative PCR was used to detect the mRNA expression of the main proteins that are associated with the transport of cholesterol, such as ABCA1, ABCG1, SR-BI, and CD36. Western blot analysis was used to detect the protein expression of Mipu1. There were atherosclerotic lesions in the high-fat diet group with Sudan IV staining. High-fat diet decreased Mipu1 expression and increased CD36 expression significantly at the 10th week compared with standard-diet rabbits. Mipu1 overexpression decreased oxLDL-induced cholesterol accumulation, oxLDL uptake, cell apoptosis, and cleaved caspase-3. Mipu1 overexpression inhibited the oxLDL-induced CD36 mRNA and protein expression, but it did not significantly inhibit the mRNA expression of ABCA1, ABCG1, and SR-BI. Mipu1 overexpression inhibits oxLDL-induced foam cell formation and cell apoptosis. Mipu1 overexpression reduces the lipid intake of macrophages and might be associated with the downregulation of CD36 expression in the presence of oxLDL.
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The first report of a Pelecaniformes defensin cluster: Characterization of ?-defensin genes in the crested ibis based on BAC libraries.
Sci Rep
PUBLISHED: 07-10-2014
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Defensins play a key role in the innate immunity of various organisms. Detailed genomic studies of the defensin cluster have only been reported in a limited number of birds. Herein, we present the first characterization of defensins in a Pelecaniformes species, the crested ibis (Nipponia nippon), which is one of the most endangered birds in the world. We constructed bacterial artificial chromosome libraries, including a 4D-PCR library and a reverse-4D library, which provide at least 40 equivalents of this rare bird's genome. A cluster including 14 ?-defensin loci within 129?kb was assigned to chromosome 3 by FISH, and one gene duplication of AvBD1 was found. The ibis defensin genes are characterized by multiform gene organization ranging from two to four exons through extensive exon fusion. Splicing signal variations and alternative splice variants were also found. Comparative analysis of four bird species identified one common and multiple species-specific duplications, which might be associated with high GC content. Evolutionary analysis revealed birth-and-death mode and purifying selection for avian defensin evolution, resulting in different defensin gene numbers among bird species and functional conservation within orthologous genes, respectively. Additionally, we propose various directions for further research on genetic conservation in the crested ibis.
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Combined detection of serum UL16-binding protein 2 and macrophage inhibitory cytokine-1 improves early diagnosis and prognostic prediction of pancreatic cancer.
Oncol Lett
PUBLISHED: 07-08-2014
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Pancreatic cancer (PC) is the fourth leading cause of cancer-related mortality in the United States. There is no effective serum biomarker for the early diagnosis of PC at present. Although serum UL16-binding protein 2 (ULBP2) and macrophage inhibitory cytokine-1 (MIC-1) levels are reported to be elevated in PC patients, the diagnostic and prognostic value of ULBP2 and MIC-1 alone or in combination remains unknown. The aim of the present case-control study was to compare the diagnostic value of ULBP2, MIC-1 and carbohydrate antigen 19-9 (CA19-9) in 359 serum samples, consisting of 152 cases of PC, 20 cases of pre-pancreatic cancer, 91 cases of chronic pancreatitis (CP) and 96 normal controls (NC). All patients were followed up for a median of 2 years. It was found that the serum levels of ULBP2, MIC-1 and CA19-9 were significantly higher in the PC patients compared with those in the NC group. In distinguishing PC from the CP, the highest sensitivity and specificity were ULBP2 (0.878) and CA19-9 (0.816), respectively. The area under the receiver operating characteristic curve of ULBP2 was 0.923, which was the highest of the three biomarkers. MIC-1 was the optimal choice for the diagnosis of early-stage PC (area under the curve, 0.831). Overall, MIC-1 in combination with ULBP2 improved the diagnostic accuracy in differentiating PC from CP and NC. In addition, a higher level of MIC-1 was correlated with a poorer prognosis, as calculated by the Kaplan-Meier test (P=0.039). Patients with serum MIC-1 levels of ?1,932 ng/ml had a median survival time of 15.62±2.44 months (mean ± standard deviation) vs. 18.66±2.43 months in patients with a lower level of MIC-1. Overall, combined detection of serum MIC-1 and ULBP2 improved the diagnostic accuracy in differentiating PC from CP and NC, and serum MIC-1 level alone was a predictor of survival in the patients with PC.
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Characterization of the mitochondrial genome of the threatened alpine butterfly, Parnassius nomion (Lepidoptera: Papilionidae).
Mitochondrial DNA
PUBLISHED: 07-04-2014
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Abstract The sequenced mitochondrial genome of the threatened alpine butterfly Parnassius nomion includes 13 protein-coding genes (ND1-6, COI-III, ATP6, ATP8, ND4, ND4L, CTYB), 2 ribosomal RNAs (12?S and 16?S), 22 transfer RNAs, which is 14,547?bp in length. Its gene order and orientation are identical to the common type found in most of other completely sequenced lepidopteran mitogenomes. All protein-coding genes are initiated by ATN codons, except for COI, which uses CGA as its start codon. Eleven PCGs use the standard TAA as their termination codon, and COI, COII use the incomplete termination codon T.
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BRAF V600E mutation and KRAS codon 13 mutations predict poor survival in Chinese colorectal cancer patients.
BMC Cancer
PUBLISHED: 06-27-2014
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Mutations in KRAS, BRAF and PIK3CA are the most common somatic alterations found in the colorectal cancer (CRC) patients from Western countries; but their prevalence and prognostic value have not been adequately assessed in Asian patients. The aim of this study was to determine the mutation frequencies of these genes in Chinese CRC patients and to investigate their impact on prognosis.
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Effect of downregulated histone deacetylase 2 expression on cell proliferation and cell cycle in cervical cancer.
J BUON
PUBLISHED: 06-27-2014
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To investigate the effects and molecular mechanism of downregulated histone deacetylase 2 (HDAC2) expression on cell proliferation and cell cycle in cervical cancer Hela cells.
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Synthesis of chelating complexes through solid-state dehydrochlorination reactions via second-sphere-coordination interaction with metal chlorides: a combined experimental-molecular modeling study.
Inorg Chem
PUBLISHED: 06-24-2014
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We have applied crystal engineering as a tool to study the solid-state transformation from molecular salts to coordination complexes via mechanochemical dehydrochlorination reactions. The -(CH2)n- (n = 2, 3) alkyl chains were introduced into the bibenzylamine moiety to form the two nitrogen bases N,N,N',N'-tetrabenzylethylenediamine (L(1)) and N,N,N',N'-tetrabenzylpropydiamine (L(2)), which were self-assembled with tetrachlorometalates to form a series of supramolecular salts through second-sphere coordination. Single crystals of salts [L(1)]2H(+)·[CuCl4](2-)·solvent (1) and [L(2)]2H(+)·[XCl4](2-)·solvent (2-4; X = Cu, Hg, Zn) were obtained and their structures determined by single-crystal X-ray diffraction. The effect of different alkyl chains (two and three -CH2- units) on the solid-state reactivity showed that the chelating complexes resulting from the mechanochemical dehydrohalogenation reaction depend on the formation of quasi-chelating hydrogen-bonding salts. Quantum-mechanical calculations have been used to gain insight in this mechanochemical dehydrohalogenation reaction, demonstrating that not only is size matching between reactants is important but also conformational energies, intermolecular interactions, and the symmetry of frontier molecular orbitals play an important role.
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Levels of acylation stimulating protein and the complement component 3 precursor are associated with the occurrence and development of coronary heart disease.
Exp Ther Med
PUBLISHED: 06-23-2014
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The aim of the present study was to investigate whether acylation stimulating protein (ASP) and complement component 3 (C3) are associated with the occurrence and development of coronary heart disease (CHD). The participants of the study were divided into three groups, including the healthy control (n=42), metabolic syndrome (MS, n=56) and CHD (n=62) groups. An enzyme-linked immunosorbent assay was used to measure the ASP concentrations, while an immunoturbidimetric assay was employed to determine the C3 concentrations. In addition, coronary angiography was performed to determine the severity of coronary artery disease in the CHD group. The CHD group was divided into three subgroups, according to the final Gensini score of coronary artery stenosis for each patient (mild, ?20 points; moderate, 21-40 points; severe, >40 points). Western blotting and quantitative reverse transcription-polymerase chain reaction (RT-PCR) were performed to analyze the protein and mRNA expression levels of C3 in the CHD subgroups and the healthy control group. The concentrations of ASP and C3 in the CHD group were found to be significantly higher compared with the control and MS groups. In addition, the levels of ASP and C3 in the mild and moderate CHD subgroups were significantly higher compared with the healthy controls or mild CHD patients. Furthermore, the protein expression levels of C3 in the moderate and severe CHD patients were found to be significantly higher compared with the healthy individuals and the mild CHD patients. The quantitative RT-PCR results revealed that the mRNA expression levels of C3 in the moderate and severe CHD patients were significantly higher compared with the healthy control group and the mild CHD patients. Furthermore, the mean levels of C3 transcripts in the severe CHD patients were found to be higher compared with the moderate CHD subgroup (P<0.05). Therefore, ASP and C3 were found to be associated with the occurrence and development of CHD; thus, may be used as novel indexes for CHD.
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Modular isotopomer synthesis of ?-hydroxybutyric acid for a quantitative analysis of metabolic fates.
ACS Chem. Biol.
PUBLISHED: 06-19-2014
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Herein we report a study combining metabolomics and mass isotopomer analysis used for investigation of the biochemical fate of ?-hydroxybutyric acid (GHB). Using various (13)C incorporation labeling patterns into GHB, we have discovered that GHB is catabolized by previously unknown processes that include (i) direct ?-oxidation to acetyl-CoA and glycolate, (ii) ?-oxidation to 3-hydroxypropionyl-CoA and formate, and (iii) cleavage of C-4 to yield 3-hydroxypropionate and CO2. We further utilized the unique attributes of our labeling patterns and the resultant isotopomers to quantitate relative flux down the identified pathways.
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Characterization of the mitochondrial genome of the cabbage webworm, Hellula undalis (Lepidoptera: Pyralidae).
Mitochondrial DNA
PUBLISHED: 06-13-2014
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Abstract The sequenced mitochondrial genome of the cabbage webworm Hellula undalis includes 13 protein-coding genes (PCGs) (nad1-6, cox1-3, atp6, atp8, nad4L and cob), two ribosomal RNAs (12S and 16S) and 19 transfer RNAs, which is 14,678?bp in length. Its gene order and orientation are identical to the common types found in most of the other completely sequenced lepidopteran mitogenomes. Thirteen PCGs start with a typical ATN codon, while cox1 uses CGA as its start codon. Some PCGs use the standard TAA as their termination codon, while others use the incomplete termination codon T (cox1, cox2 and nad4).
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Prognostic function of Ki-67 for pathological complete response rate of neoadjuvant chemotherapy in triple-negative breast cancer.
Tumori
PUBLISHED: 05-24-2014
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Triple-negative breast cancer (TNBC) has fluctuating pathological complete response (pCR) rates to neoadjuvant chemotherapy (NAC) according to published reports. Biomarkers predicting pCR rates of NAC would improve TNBC patients' outcomes. We conducted a meta-analysis to estimate the prognostic function of Ki-67 in relation to pCR rates of NAC in TNBC.
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Estrogen regulation of the brain renin-angiotensin system in protection against angiotensin II-induced sensitization of hypertension.
Am. J. Physiol. Heart Circ. Physiol.
PUBLISHED: 05-23-2014
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This study investigated sex differences in the sensitization of angiotensin (ANG) II-induced hypertension and the role of central estrogen and ANG-(1-7) in this process. Male and female rats were implanted for telemetered blood pressure (BP) recording. A subcutaneous subpressor dose of ANG II was given alone or concurrently with intracerebroventricular estrogen, ANG-(1-7), an ANG-(1-7) receptor antagonist A-779 or vehicle for 1 wk (induction). After a 1-wk rest (delay), a pressor dose of ANG II was given for 2 wk (expression). In males and ovariectomized females, subpressor ANG II had no sustained effect on BP during induction, but produced an enhanced hypertensive response to the subsequent pressor dose of ANG II during expression. Central administration of estrogen or ANG-(1-7) during induction blocked ANG II-induced sensitization. In intact females, subpressor ANG II treatment produced a decrease in BP during induction and delay, and subsequent pressor ANG II treatment given during expression produced only a slight but significant increase in BP. However, central blockade of ANG-(1-7) by intracerebroventricular infusion of A-779 during induction restored the decreased BP observed in females during induction and enhanced the pressor response to the ANG II treatment during expression. RT-PCR analyses indicated that estrogen given during induction upregulated mRNA expression of the renin-angiotensin system (RAS) antihypertensive components, whereas both central estrogen and ANG-(1-7) downregulated mRNA expression of RAS hypertensive components in the lamina terminalis. The results indicate that females are protected from ANG II-induced sensitization through central estrogen and its regulation of brain RAS.
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Cadmium induces vascular permeability via activation of the p38 MAPK pathway.
Biochem. Biophys. Res. Commun.
PUBLISHED: 05-20-2014
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The vasculature of various organs is a targeted by the environmental toxin, cadmium (Cd). However, mechanisms leading to pathological conditions are poorly understood. In the present study, we examined the effect of cadmium chloride (CdCl2) on human umbilical vein endothelial cells (HUVECs). At 4 ?M, CdCl2 induced a hyper-permeability defect in HUVECs, but not the inhibition of cell growth up to 24h. This effect of CdCl2 was dependent on the activation of the p38 mitogen-activated protein kinase (MAPK) pathway. The p38 MAPK inhibitor SB203850 suppressed the CdCl2-induced alteration in trans-endothelial electrical resistance in HUVEC monolayers, a model measurement of vascular endothelial barrier integrity. SB203850 also inhibited the Cd-induced membrane dissociation of vascular endothelial (VE) cadherin and ?-catenin, the important components of the adherens junctional complex. In addition, SB203850 reduces the Cd-induced expression and secretion of tumor necrosis factor ? (TNF-?). Taken together, our findings suggest that Cd induces vascular hyper-permeability and disruption of endothelial barrier integrity through stimulation of p38 MAPK signaling.
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Suppression of histone deacetylation promotes the differentiation of human pluripotent stem cells towards neural progenitor cells.
BMC Biol.
PUBLISHED: 05-11-2014
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BackgroundEmerging studies of human pluripotent stem cells (hPSCs) raise new prospects for neurodegenerative disease modeling and cell replacement therapies. Therefore, understanding the mechanisms underlying the commitment of neural progenitor cell (NPCs) is important for the application of hPSCs in neurodegenerative disease therapies. It has been reported that epigenetic modifications of histones play important roles in neural differentiation, but the exact mechanisms in regulating hPSC differentiation towards NPCs are not fully elucidated.ResultsWe demonstrated that suppression of histone deacetylases (HDACs) promoted the differentiation of hPSCs towards NPCs. Application of HDAC inhibitors (HDACi) increased the expression of neuroectodermal markers and enhanced the neuroectodermal specification once neural differentiation was initiated, thereby leading to more NPC generation. Similarly, the transcriptome analysis showed that HDACi increased the expression levels of ectodermal markers and triggered the NPC differentiation related pathways, while decreased the expression levels of endodermal and mesodermal markers. Furthermore, we documented that HDAC3 but not HDAC1 or HDAC2 was the critical regulator participating in NPC differentiation, and knockdown of HDAC3¿s cofactor SMRT exhibited a similar effect as HDAC3 on NPC generation.ConclusionsOur study reveals that HDACs, especially HDAC3, negatively regulate the differentiation of hPSCs towards NPCs at an earlier stage of neural differentiation. Moreover, HDAC3 might function by forming a repressor complex with its cofactor SMRT during this process. Thus our findings uncover an important epigenetic mechanism of HDAC3 in the differentiation of hPSCs towards NPCs.
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Associations of nm23H1, VEGF-C, and VEGF-3 receptor in human prostate cancer.
Molecules
PUBLISHED: 05-06-2014
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We studied the expression of the non-metastatic clone 23 type 1 (nm23H1) gene, vascular endothelial growth factor (VEGF)-C, and its receptor VEGFR-3 using an in situ hybridization technique and immunohistochemical analyses with prostate cancer tissues and adjacent benign tissues of 52 human archival cases. The association between VEGF-C expression, microlymphatic count (MLC), and staining intensity for nm23H1 and VEGFR-3 was used to evaluate tumor metastasis and survival rate. MLC values were significantly higher in tumorous tissue than in non-cancerous tissue. VEGF-C mRNA, VEGFR-3, and nm23H1 were highly expressed in tumorous tissue. VEGFR-3 expression was greater in VEGF-C mRNA-positive tumors than in VEGF-C mRNA-negative tumors. The association of VEGFR-3 expression with VEGF-C mRNA and MLC suggested that the poor prognosis and tumor metastasis associated with VEGFR-3 expression may be due, in part, to its role in promoting angiogenesis. VEGF-C expression was significantly associated with tumor lymphangiogenesis, angiogenesis, and immune response as a potent multifunctional stimulating factor in prostate cancer. Expression of nm23H1 was significantly inversely correlated with lymph node metastasis. Furthermore, there was a strong negative correlation between the expression of nm23H1, VEGF-C mRNA, and MLC. These findings provide important information for prophylactic, diagnostic, and therapeutic strategies for prostate cancer.
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The concise synthesis of spiro-cyclopropane compounds via the dearomatization of indole derivatives.
Org. Lett.
PUBLISHED: 05-06-2014
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A concise synthesis of spiro-cyclopropane compounds from indole derivatives and sulfur ylides has been developed via a dearomatization strategy. Moreover, the spiro-cyclopropane compounds could be conveniently transformed to rearomatized indole derivatives in the presence of acids.
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Interferon induction of IFITM proteins promotes infection by human coronavirus OC43.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-21-2014
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IFNs are a family of cytokines that are essential for the antiviral response in vertebrates. Not surprisingly, viruses have adapted to encode virulence factors to cope with the IFN response. Intriguingly, we show here that all three types of interferons, IFN-?, IFN-?, and IFN-?, efficiently promote infection by a human coronavirus, HCoV-OC43, one of the major etiological agents of common cold, through the induction of IFN-inducible transmembrane (IFITM) proteins. IFITMs typically exert their antiviral function by inhibiting the entry of a broad spectrum of viruses into their host cells, presumably by trapping and degrading invading virions within the endocytic compartments. In contrast, HCoV-OC43 uses IFN-induced human IFITM2 or IFITM3 as an entry factor to facilitate its infection of host cells. Reverse genetics analyses suggest that the structural motifs critical for the IFITM proteins' enhancement of HCoV-OC43 infection are distinct from those required for inhibiting infection by other viruses. We also present evidence showing that IFITM family members work as homo- and hetero-oligomers to modulate virus entry. The observed enhancement of HCoV-OC43 infection by IFNs may underlie the propensity of the virus to invade the lower respiratory tract under inflammatory conditions.
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An interferon-beta promoter reporter assay for high throughput identification of compounds against multiple RNA viruses.
Antiviral Res.
PUBLISHED: 04-14-2014
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Virus infection of host cells is sensed by innate pattern recognition receptors (PRRs) and induces production of type I interferons (IFNs) and other inflammatory cytokines. These cytokines orchestrate the elimination of the viruses but are occasionally detrimental to the hosts. The outcomes and pathogenesis of viral infection are largely determined by the specific interaction between the viruses and their host cells. Therefore, compounds that either inhibit viral infection or modulate virus-induced cytokine response should be considered as candidates for managing virus infection. The aim of the study was to identify compounds in both categories, using a single cell-based assay. Our screening platform is a HEK293 cell-based reporter assay where the expression of a firefly luciferase is under the control of a human IFN-? promoter. We have demonstrated that infection of the reporter cell line with a panel of RNA viruses activated the reporter gene expression that correlates quantitatively with the levels of virus replication and progeny virus production, and could be inhibited in a dose-dependent manner by known antiviral compound or inhibitors of PRR signal transduction pathways. Using Dengue virus as an example, a pilot screening of a small molecule library consisting of 26,900 compounds proved the concept that the IFN-? promoter reporter assay can serve as a convenient high throughput screening platform for simultaneous discovery of antiviral and innate immune response modulating compounds. A representative antiviral compound from the pilot screening, 1-(6-ethoxybenzo[d]thiazol-2-yl)-3-(3-methoxyphenyl) urea, was demonstrated to specifically inhibit several viruses belonging to the family of flaviviridae.
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Literature review and clinical presentation of cervical spondylitis due to salmonella enteritidis in immunocompetent.
Asian Spine J
PUBLISHED: 04-08-2014
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A 48-year-old woman was presented to our clinic with some fever and neck pains for about one month. Based on the symptoms and results of image, an empirical diagnosis of tuberculous cervical spondylitis was made. The pain was not significantly decreased after anti-tuberculosis therapy. And, 3 weeks later, she was re-admitted to our hospital for the unbearable pain. An exploration of the C4/5 by the anterior medial approach was recommended to evaluate the germ and debridement. Bacteriological tests showed that the pathogen was Salmonella Enteritidis. The pain was relieved significantly after operation and sensitive antibiotic treatments. Infections with Salmonella Typhi or Salmonella Paratyphi have been well-documented, while there are few reports of cervical spondylitis caused by Salmonella Enteritidis. We reported a case of a healthy woman with whom pyogenic cervical spondylitis of Salmonella Enteritidis was corroborated and treated and reviewed according to previous reports about spondylitis caused by Salmonella Enteritidis in the literature.
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miR-22 inhibits proliferation and invasion in estrogen receptor ?-positive endometrial endometrioid carcinomas cells.
Mol Med Rep
PUBLISHED: 04-01-2014
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Endometrial endometrioid carcinomas (EECs) account for >80% of endometrial carcinomas (ECs). Continuous stimulation of the endometrium by estrogen is a risk factor for the tumorigenesis of estrogen receptor (ER) ?-positive EEC. MicroRNA-22 (miR-22) has been reported to be implicated in the regulation of various types of cancer and directly targets ER?. However, an exact regulatory mechanism between miR-22 and ER? in EEC has yet to be investigated. To the best of our knowledge, the present study demonstrated for the first time that the expression of miR-22 was significantly downregulated in ER?-positive EEC tissues and cell lines, RL95-2 and Ishikawa, when compared with that in normal endometrium and ER?-negative EEC samples. This indicated that miR-22 may be important in ER?-positive EEC, possibly through an estrogen-dependent mechanism. miR-22 mimics were then transfected into RL95-2 and Ishikawa cells, respectively, and revealed that the introduction of miR-22 markedly downregulated the mRNA and protein levels of ER?. Further investigation demonstrated that miR-22 was able to effectively reverse 17?-estradiol (E2)?induced cell proliferation, cell cycle progression and invasion of ER?-positive RL95-2 and Ishikawa cells, at least partially through inhibiting the expression of Cyclin D1 as well as the secretion of matrix metalloproteinase (MMP)-2 and MMP-9. In conclusion, the present study, to the best of our knowledge, was the first to reveal an inhibitory role of miR-22 in ER?-positive EEC tissues and cells, indicating that miR-22 may be a novel candidate for the endocrine therapy of ER?-positive EEC.
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Quantitative analysis of fitness costs associated with the development of resistance to the Bt toxin Cry1Ac in Helicoverpa armigera.
Sci Rep
PUBLISHED: 03-31-2014
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Transgenic Bacillus thuringiensis (Bt) crops play an increasing role in pest control, and resistance management is a major issue in large-scale cultivation of Bt crops. The fitness cost of resistance in targeted pests is considered to be one of the main factors delaying resistance when using the refuge strategy. By comparing 10 resistant Helicoverpa armigera (Hubner) strains, showing various resistance levels to Bt toxin (Cry1Ac), to a susceptible strain, we showed an increasing fitness cost corresponding with increasing levels of resistance. The relationship between overall fitness cost C and the resistance ratio Rr could be described by C = 24.47/(1 + exp([1.57 - Log10Rr]/0.2)). This model predicted that the maximum overall fitness cost would be ~24% (± 5.22) in the strains with the highest resistance level. The overall fitness cost was closely linked to egg hatching rate, fecundity, emergence rate, larval survival rate, and developmental duration of adults. Among fitness components measured, fecundity was the most sensitive trait linked to the resistance selection. To integrate the results into simulation models would be valuable in evaluating how variation in fitness cost may influence the development of resistance in pest populations, thus helping to develop enhanced refuge strategies.
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Development of an artificial compound eye system for three-dimensional object detection.
Appl Opt
PUBLISHED: 03-26-2014
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A compound eye has the advantages of a large field of view, high sensitivity, and compact structure, showing that it can be applicable for 3D object detection. In this work, an artificial compound eye system is developed for 3D object detection, consisting of a layer of lenslets and a prism-like beam-steering lens. A calibration method is developed for this system, with which the correspondences between incident light rays and the relevant image points can be obtained precisely using an active calibration pattern at multiple positions. Theoretically, calibration patterns at two positions are sufficient for system calibration, although more positions will increase the accuracy of the result. 3D positions of point objects are calculated to evaluate the system, which are obtained by the intersection of multiple incident light rays in the least-squares sense. Experimental results show that the system can detect an object with angular accuracy of better than 1 mrad, demonstrating the feasibility of the proposed compound eye system. With a 2D scanning device, the system can be extended for general object detection in 3D space.
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PDF and cAMP enhance PER stability in Drosophila clock neurons.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 03-18-2014
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The neuropeptide PDF is important for Drosophila circadian rhythms: pdf(01) (pdf-null) animals are mostly arrhythmic or short period in constant darkness and have an advanced activity peak in light-dark conditions. PDF contributes to the amplitude, synchrony, as well as the pace of circadian rhythms within clock neurons. PDF is known to increase cAMP levels in PDR receptor (PDFR)-containing neurons. However, there is no known connection of PDF or of cAMP with the Drosophila molecular clockworks. We discovered that the mutant period gene per(S) ameliorates the phenotypes of pdf-null flies. The period protein (PER) is a well-studied repressor of clock gene transcription, and the per(S) protein (PERS) has a markedly short half-life. The result therefore suggests that the PDF-mediated increase in cAMP might lengthen circadian period by directly enhancing PER stability. Indeed, increasing cAMP levels and cAMP-mediated protein kinase A (PKA) activity stabilizes PER, in S2 tissue culture cells and in fly circadian neurons. Adding PDF to fly brains in vitro has a similar effect. Consistent with these relationships, a light pulse causes more prominent PER degradation in pdf(01) circadian neurons than in wild-type neurons. The results indicate that PDF contributes to clock neuron synchrony by increasing cAMP and PKA, which enhance PER stability and decrease clock speed in intrinsically fast-paced PDFR-containing clock neurons. We further suggest that the more rapid degradation of PERS bypasses PKA regulation and makes the pace of clock neurons more uniform, allowing them to avoid much of the asynchrony caused by the absence of PDF.
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PDF neuron firing phase-shifts key circadian activity neurons in Drosophila.
Elife
PUBLISHED: 03-13-2014
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Our experiments address two long-standing models for the function of the Drosophila brain circadian network: a dual oscillator model, which emphasizes the primacy of PDF-containing neurons, and a cell-autonomous model for circadian phase adjustment. We identify five different circadian (E) neurons that are a major source of rhythmicity and locomotor activity. Brief firing of PDF cells at different times of day generates a phase response curve (PRC), which mimics a light-mediated PRC and requires PDF receptor expression in the five E neurons. Firing also resembles light by causing TIM degradation in downstream neurons. Unlike light however, firing-mediated phase-shifting is CRY-independent and exploits the E3 ligase component CUL-3 in the early night to degrade TIM. Our results suggest that PDF neurons integrate light information and then modulate the phase of E cell oscillations and behavioral rhythms. The results also explain how fly brain rhythms persist in constant darkness and without CRY.
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Protective effect of polysaccharides from Sargassum horneri against oxidative stress in RAW264.7 cells.
Int. J. Biol. Macromol.
PUBLISHED: 03-09-2014
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This study was designed to investigate chemical composition and the protective effects of polysaccharides isolated from Sargassum horneri against hydrogen peroxide (H2O2)-induced oxidative injury in RAW264.7 cells. Results showed that isolated polysaccharides (SHSc) and the major fractions (SHS1, SHS0.5) contained sulfate ester, and SHS1 was high fucose-containing sulfated polysaccharide. After preincubation with three isolated polysaccharides, RAW264.7 cells viability were significantly restored and decreased in cellular LDH release (P<0.05). SHS1 and SHS0.5 decreased intracellular ROS level, intracellular NO and malonic dialdehyde (MDA) level (P<0.05), restoring activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) (P<0.05), decreasing inducible nitric oxide synthase (iNOS) (P<0.05). Moreover, preincubation of SHS1 with RAW264.7 cells resulted in the increase of the gene expression level of endogenous antioxidant enzymes such as MnSOD and GSH-Px (P<0.05). These results clearly showed that SHSc and its fractions could attenuate H2O2-induced stress injury in RAW264.7 cells, and a similar efficiency in protecting RAW264.7 cells against H2O2-induced oxidative injury between SHS1 and Vitamin C. Taken together, our findings suggested that SHS1 can effectively protect RAW264.7 cells against oxidative stress by H2O2, which might be used as a potential natural antioxidant in the functional food and pharmaceutical industries.
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Functional role of asparaginyl endopeptidase ubiquitination by TRAF6 in tumor invasion and metastasis.
J. Natl. Cancer Inst.
PUBLISHED: 03-07-2014
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Asparaginyl endopeptidase (AEP) has been implicated in human cancer development. However, the molecular mechanisms underlying AEP regulation, including the role of pro-AEP activation, remain elusive.
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Idiopathic mesenteric phlebosclerosis associated with long-term use of medical liquor: two case reports and literature review.
World J. Gastroenterol.
PUBLISHED: 02-27-2014
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A 62-year-old woman was admitted to our hospital in 2011 because of recurrent abdominal pain, nausea and constipation for six months. Computed tomography enterography (CTE) showed tortuous thread-like calcifications in the ileocolic vein and right colic vein, while colonoscopy revealed purple-blue mucosa extending from the cecum to the splenic flexure. Based on the results of these tests, the patient was diagnosed with idiopathic mesenteric phlebosclerosis (IMP). She had a history of Chinese medical liquor intake for one and a half years and her symptoms subsided after conservative treatment. In 2013, a 63-year-old male patient who presented with recurrent lower right abdominal pain, bloating, melena and diarrhea for fifteen months was admitted to our institution. Colonoscopy and CTE led to the diagnosis of IMP. He also used Chinese medical liquor for approximately 12 years. The patient underwent total colectomy and the postoperative course was uneventful. We searched for previously published reports on similar cases and analyzed the clinical data of 50 cases identified in PubMed. As some of these patients admitted use of Chinese medicines, we hypothesize that Chinese medicines may play a role in the pathogenesis of IMP.
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Trastuzumab monotherapy for bone marrow metastasis of breast cancer: A case report.
Oncol Lett
PUBLISHED: 02-26-2014
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The current study presents the case of a 41-year-old female patient who received modified radical mastectomy and adjuvant chemotherapy and radiotherapy for infiltrating ductal cancer of the left breast. The pathological stage of the disease was IIA. In addition, the patient was negative for the estrogen and progesterone receptors, and human epidermal growth factor receptor-2 gene amplification was identified. At one year following surgery, the patient presented with severe pancytopenia and pain at multiple sites all over the body. Furthermore, the patient's Eastern Cooperative Oncology Group performance status score was 3 and numeric rating scale pain score was 8. The bone marrow puncture indicated bone marrow metastatic cancer, and the positron emission tomography/computed tomography (CT) indicated multiple internal organ metastases and osseous metastasis. Chemotherapy treatment posed great risks due to the patient's poor performance status and severe bone marrow suppression. Therefore, trastuzumab monotherapy was administered at a loading dose of 8 mg/kg and a maintenance dose of 6 mg/kg every three weeks. Following four doses of trastuzumab treatment, the patient's performance status significantly improved and the peripheral blood cell counts had returned to within the normal ranges. Taxol was added to the trastuzumab treatment and seven cycles were completed. No metastatic cancer cells were found in the subsequent bone marrow smear test; however, CT showed metastatic foci in the left lung. Furthermore, the enlarged lymph nodes had subsided and the tumor in the right appendix region had decreased in size by 50%. The patient's disease condition was maintained stable for 11 months.
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HPV16E7 silencing enhances susceptibility of CaSki cells to natural killer cells.
Mol Med Rep
PUBLISHED: 02-07-2014
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The aim of the present study was to investigate the cytotoxicity of natural killer (NK) cells to CaSki cells following knockdown of the E7 protein of the human papillomavirus type 16 (HPV16E7). Recombinant adenovirus-short hairpin-E7 protein of the human panillomavirus type 16 (Ad?sh?HPV16E7) was constructed and used to infect CaSki cells. The expression of HPV16E7 in CaSki cells was assessed using western blot analysis. The expression of cell surface molecule major histocompatibility complex?I (MHC?I) in CaSki cells infected with Ad?sh?HPV16E7 was examined using flow cytometry. The cytotoxicity of NK cells isolated and expanded from healthy volunteers on Ad?sh?HPV16E7?infected CaSki cells was assessed using the lactate dehydrogenase (LDH) release assay. Ad?sh?HPV16E7 was successfully constructed and able to inhibit HPV16E7 the expression in CaSki cells. The expression of major histocompa-tibility complex I (MHC?I), a surface molecule, in CaSki cells was increased after infection with Ad?sh?HPV16E7. Compared with the controls, the cytotoxicity of NK cells on CaSki cells, which were infected with Ad?sh?HPV16E7, was decreased (p<0.05). In conclusion, HPV16E7 suppresses the expression of MHC?I on CaSki cells to evade cytotoxic T?cell (CTL) response. However, it was possible to enhance the cytotoxicity of expanded NK cells to cervical cancer cells or HPV16?infected cells in vitro, indicating that NK cells may be used for immunotherapy of cervical cancer.
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Glutathionylated 4-hydroxy-2-(E)-alkenal enantiomers in rat organs and their contributions toward the disposal of 4-hydroxy-2-(E)-nonenal in rat liver.
Free Radic. Biol. Med.
PUBLISHED: 02-05-2014
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The major route for elimination of 4-hydroxy-2-(E)-nonenal (4-HNE) has long been considered to be through glutathionylation and eventual excretion as a mercapturic acid conjugate. To better quantitate the glutathionylation process, we developed a sensitive LC-MS/MS method for the detection of glutathione (GSH) conjugates of 4-hydroxy-2-(E)-alkenal enantiomers having a carbon skeleton of C5 to C12. The newly developed method enabled us to quantify 4-hydroxy-2-(E)-alkenal-glutathione diastereomers in various organs, i.e., liver, heart, and brain. We identified the addition of iodoacetic acid as a critical step during sample preparation to avoid an overestimation of glutathione-alkenal conjugation. Specifically, we found that in the absence of a quenching step reduced GSH and 4-hydroxy-2-(E)-alkenals react very rapidly during the extraction and concentration steps of sample preparation. Rat liver perfused with d11-4-hydroxy-2-(E)-nonenal (d11-4-HNE) revealed enantioselective conjugation with GSH and transportation out of the liver. In the d11-4-HNE-perfused rat livers, the amount of d11-(S)-4-HNE-GSH released from the rat liver was higher than that of d11-(R)-4-HNE-GSH, and more d11-(R)-4-HNE-GSH than d11-(S)-4-HNE-GSH remained in the perfused liver tissues. Overall, the glutathionylation pathway was found to account for only 8.7% of the disposition of 4-HNE, whereas catabolism to acetyl-CoA, propionyl-CoA, and formate represented the major detoxification pathway.
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The complete mitochondrial genome of the longhorn beetle, Massicus raddei.
Mitochondrial DNA
PUBLISHED: 02-05-2014
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Abstract We sequenced the complete mitochondrial genome of Massicus raddei, which is the first beetle sequenced in Cerambycinae to date. The complete mitochondrial genome is 15,585?bp in length with an A?+?T content of 71.82%, and contains 13 protein-coding genes, 2 rRNAs, 22 tRNAs and a control region. The gene order and orientation are similar to that of typical insect species. These data will provide useful molecular information for phylogenetic relationships among the suborders of Coleoptera. By using 13 protein-coding genes as phylogenetic markers, the results support that the suborder Archostemata is a sister group to the remaining beetles and the most primitive suborder in any case; the suborder Myxophaga is sister to the suborder Adephaga.
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Association of GLP-1 secretion with anti-hyperlipidemic effect of ginsenosides in high-fat diet fed rats.
Metab. Clin. Exp.
PUBLISHED: 01-13-2014
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Ginsenosides, major bioactive constituents in Panax ginseng, have been shown to exert anti-hyperlipidemia effects. However, the underlying mechanism was not well-elucidated due to the low bioavailability of ginsenosides. Glucagon-like peptide-1 (GLP-1) was considered to be a critical regulator of energy homeostasis. Our previous studies have showed that ginseng total saponins (GTS) exhibited antidiabetic effects partly via modulating GLP-1 release. The aim of this study was to investigate the potential role of GLP-1 in anti-hyperlipidemia effect of GTS in rats fed with high-fat diet.
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Identification of a negative feedback loop in biological oxidant formation fegulated by 4-hydroxy-2-(E)-nonenal.
Redox Biol
PUBLISHED: 01-01-2014
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4-Hydroxy-2-(E)-nonenal (4-HNE) is one of the major lipid peroxidation product formed during oxidative stress. At high concentrations, 4-HNE is cytotoxic and exerts deleterious effects that are often associated with the pathology of oxidative stress-driven disease. Alternatively, at low concentrations it functions as a signaling molecule that can activate protective pathways including the antioxidant Nrf2-Keap1 pathway. Although these biphasic signaling properties have been enumerated in many diseases and pathways, it has yet to be addressed whether 4-HNE has the capacity to modulate oxidative stress-driven lipid peroxidation. Here we report an auto-regulatory mechanism of 4-HNE via modulation of the biological oxidant nitric oxide (NO). Utilizing LPS-activated macrophages to induce biological oxidant production, we demonstrate that 4-HNE modulates NO levels via inhibition of iNOS expression. We illustrate a proposed model of control of NO formation whereby at low concentrations of 4-HNE a negative feedback loop maintains a constant level of NO production with an observed inflection at approximately 1 µM, while at higher 4-HNE concentrations positive feedback is observed. Further, we demonstrate that this negative feedback loop of NO production control is dependent on the Nrf2-Keap1 signaling pathway. Taken together, the careful regulation of NO production by 4-HNE argues for a more fundamental role of this lipid peroxidation product in normal physiology.
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An EGFR/HER2-Bispecific and enediyne-energized fusion protein shows high efficacy against esophageal cancer.
PLoS ONE
PUBLISHED: 01-01-2014
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Esophageal cancer is one of the most common cancers, and the 5-year survival rate is less than 10% due to lack of effective therapeutic agents. This study was to evaluate antitumor activity of Ec-LDP-Hr-AE, a recently developed bispecific enediyne-energized fusion protein targeting both epidermal growth factor receptor (EGFR) and epidermal growth factor receptor 2 (HER2), on esophageal cancer. The fusion protein Ec-LDP-Hr-AE consists of two oligopeptide ligands and an enediyne antibiotic lidamycin (LDM) for receptor binding and cell killing, respectively. The current study demonstrated that Ec-LDP-Hr had high affinity to bind to esophageal squamous cell carcinoma (ESCC) cells, and enediyne-energized fusion protein Ec-LDP-Hr-AE showed potent cytotoxicity to ESCC cells with differential expression of EGFR and HER2. Ec-LDP-Hr-AE could cause significant G2-M arrest in EC9706 and KYSE150 cells, and it also induced apoptosis in ESCC cells in a dosage-dependent manner. Western blot assays showed that Ec-LDP-Hr-AE promoted caspase-3 and caspase-7 activities as well as PARP cleavage. Moreover, Ec-LDP-Hr-AE inhibited cell proliferation via decreasing phosphorylation of EGFR and HER2, and further exerted inhibition of the activation of their downstream signaling molecules. In vivo, at a tolerated dose, Ec-LDP-Hr-AE inhibited tumor growth by 88% when it was administered to nude mice bearing human ESCC cell KYSE150 xenografts. These results indicated that Ec-LDP-Hr-AE exhibited potent anti-caner efficacy on ESCC, suggesting it could be a promising candidate for targeted therapy of esophageal cancer.
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Population explosion in the yellow-spined bamboo locust Ceracris kiangsu and inferences for the impact of human activity.
PLoS ONE
PUBLISHED: 01-01-2014
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Geographic distance and geographical barriers likely play a considerable role in structuring genetic variation in species, although some migratory species may have less phylogeographic structure on a smaller spatial scale. Here, genetic diversity and the phylogenetic structure among geographical populations of the yellow-spined bamboo locust, Ceracris kiangsu, were examined with 16S rDNA and amplified fragment length polymorphisms (AFLPs). In this study, no conspicuous phylogeographical structure was discovered from either Maximum parsimony (MP) and Neighbor-joining (NJ) phylogenetic analyses. The effect of geographical isolation was not conspicuous on a large spatial scale.At smaller spatial scales local diversity of some populations within mountainous areas were detected using Nei's genetic distance and AMOVA. There is a high level of genetic diversity and a low genetic differentiation among populations in the C. kiangsu of South and Southeast China. Our analyses indicate that C. kiangsu is a monophyletic group. Our results also support the hypothesis that the C. kiangsu population is in a primary differentiation stage. Given the mismatch distribution, it is likely that a population expansion in C. kiangsu occurred about 0.242 Ma during the Quaternary interglaciation. Based on historical reports, we conjecture that human activities had significant impacts on the C. kiangsu gene flow.
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[Autologous cytokine-induced killer cells therapy on the quality of life of patients with breast cancer after adjuvant chemotherapy: a prospective study].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 12-30-2013
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To explore the effect of autologous cytokine-induced killer cells on the quality of life in patient with breast cancer who have already finished the adjuvant chemotherapy.
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Novel approach in LC-MS/MS using MRM to generate a full profile of acyl-CoAs; discovery of acyl-dephospho-CoAs.
J. Lipid Res.
PUBLISHED: 12-23-2013
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A metabolomics approach to selectively profile all acyl-CoAs was developed using a programmed multiple reaction monitoring (MRM) method in LC-tandem mass spectrometry and was employed in the analysis of various rat organs. The programmed MRM method possessed ~300 mass ion transitions with the mass difference of 507 between precursor ion (Q1) and product ion (Q3), and precursor ion started from m/z 768 and progressively increased to 1054 by one mass unit at each step. Acyl-dephospho-CoAs resulting from the dephosphorylation of acyl-CoAs were identified by accurate mass spectrometry and fragmentation. Acyl-dephospho-CoAs were also quantitatively scanned by MRM method with the mass difference of 427 between Q1 and Q3 mass ions. Acyl-CoAs and dephospho-CoAs were assayed with limit of detection (LOD) ranging from 2 to 133 nM. The accuracy of assay was demonstrated by high recovery values (80~114%) for a range of spiked concentrations. The distribution of acyl-CoAs reflects the metabolic status of each organ. The physiological role of dephosphorylation of acyl-CoAs remains to be further characterized. The methodology described herein provides a novel strategy in metabolomics studies to quantitative and qualitative profiles all potential acyl-CoAs and acyl-dephospho-CoAs.
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Topical skin targeting effect of penetration modifiers on hairless mouse skin, pig abdominal skin and pig ear skin.
Drug Deliv
PUBLISHED: 12-17-2013
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Abstract Objective: This study was to investigate the topical skin targeting effects and mechanism of combination penetration modifiers of 1,2-hexanediol (or 1,2-heptanediol) and 1,4-cyclohexanediol on transdermal absorption of metronidazole (MTZ) in different skin models. Methods: Six formulations were applied to pig abdominal skin and pig ear skin models, respectively, and the results were compared with the previous data on hairless mouse skin worked out by our laboratory. Four parameters (flux, Tlag, Q24 and targeting ratio) were used to evaluate permeability and targeting effect in skin. Results: The combined penetration modifiers played a general role on decreasing permeability without reducing skin retention. The most significant skin permeability decrement to MTZ was pig abdominal skin (permeability decrement was ?20% for hairless mouse skin, 60% for pig abdominal skin and 40% for pig ear skin, respectively) while the strongest skin targeting effect appeared in hairless mouse skin (targeting ratios were 1.79 for hairless mouse skin, 1.24 for pig abdominal skin and 1.05 for pig ear skin, respectively) under the role of penetration modifiers. Conclusions: Thickness of stratum corneum (SC) was the major factor impact on skin targeting effect. Selection criteria of skin models also have been discussed in this study.
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The Henry Reaction in [Bmim][PF6]-based Microemulsions Promoted by Acylase.
Molecules
PUBLISHED: 10-21-2013
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An environmentally-friendly, enzyme-promoted procedure for the Henry reaction was first studied using water-in-[Bmim][PF6] microemulsions as reaction medium. The Amano acylase from Aspergillus oryzae showed better catalytic activity for the addition reactions of nitromethane with a series of aromatic aldehydes, and a highest yield of 90% was obtained.
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Phosphine-free synthesis from 1D Pb(OH)Cl nanowires to 0D and 1D PbSe nanocrystals.
ACS Appl Mater Interfaces
PUBLISHED: 10-10-2013
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In this paper, we report a new phosphine-free, low-cost, low-temperature colloidal method of controlled synthesis of PbSe nanocrystals in both zero-dimension (0D) and one-dimension (1D). Different from the widely used "hot injection" method and "nonprecursor injection" method, the novelty of this new method is that it does not require a nucleation process. Instead, high-quality presynthesized 1D Pb(OH)Cl nanowires (?80 to ?160 nm in diameter) can be directly used as a Pb precursor and reacted with a Se precursor to form monodisperse dot-shaped 0D cubic PbSe and 1D orthorhombic PbSe nanowires. 0D cubic PbSe nanocrystals begin to form at elevated temperatures after the Se precursor is added to react with Pb(OH)Cl nanowires. By prolonging the reaction time for 3 h, good self-assembled 0D cubic PbSe nanocrystals can be synthesized with an average diameter of about 15 nm. Furthermore, such method has been demonstrated to synthsize high-quality 1D PbSe nanowires successfully with temperature as low as 110 °C. 1D PbSe nanowires possess a mean diameter of 15-24 nm with the shortest and longest length from 600 nm to 5 ?m. The only sharp and strong peak, which is consistent with characteristic peaks of orthorhombic PbSe, indicates that the nanowires elongation axis is in the [111] direction, and 0D cubic PbSe nanocrystals change to 1D orthorhombic PbSe nanowires completely.
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p75 neurotrophin receptor positive dental pulp stem cells: new hope for patients with neurodegenerative disease and neural injury.
Shanghai Kou Qiang Yi Xue
PUBLISHED: 10-09-2013
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Neurodegenerative diseases and neural injury are 2 of the most feared disorders that afflict humankind by leading to permanent paralysis and loss of sensation. Cell based treatment for these diseases had gained special interest in recent years. Previous studies showed that dental pulp stem cells (DPSCs) could differentiate toward functionally active neurons both in vitro and in vivo, and could promote neuranagenesis through both cell-autonomous and paracrine neuroregenerative activities. Some of these neuroregenerative activities were unique to tooth-derived stem cells and superior to bone marrow stromal cells. However, DPSCs used in most of these studies were mixed and unfractionated dental pulp cells that contain several types of cells, and most were fibroblast cells while just contain a small portion of DPSCs. Thus, there might be weaker ability of neuranagenesis and more side effects from the fibroblast cells that cannot differentiate into neural cells. p75 neurotrophin receptor (p75NTR) positive DPSCs subpopulation was derived from migrating cranial neural crest cells and had been isolated from DPSCs, which had capacity of differentiation into neurons and repairing neural system. In this article, we hypothesize that p75NTR positive DPSCs simultaneously have greater propensity for neuronal differentiation and fewer side effects from fibroblast, and in vivo transptantation of autologous p75NTR positive DPSCs is a novel method for neuranagenesis. This will bring great hope to patients with neurodegenerative disease and neural injury.
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Off-on-off fluorescent chemosensor for pH measurement with a terbium(iii) complex based on a tripodal salicylic-acid derivative.
Org. Biomol. Chem.
PUBLISHED: 09-24-2013
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New Tb(iii) and Eu(iii) complexes have been synthesized as potential pH probes using a tripodal substituted-salicylic ligand (H3). Among them, this carboxylate ligand is found to be a good sensitizer for Tb(iii) emission owing to the superior match of the triplet energy level of the ligand with the (5)D4 emitting level of Tb(iii). The resulting · complex exhibited high sensitivity in the physiological pH range with significant "off-on-off" fluorescence changes in aqueous solution. Furthermore, this unique rare-earth complex has been successfully used to monitor pH variations within HeLa cells and with filter papers.
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Clinical character of pediatric head and neck rhabdomysarcomas: a 7-year retrospective study.
Asian Pac. J. Cancer Prev.
PUBLISHED: 09-03-2013
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The rhabdomysarcoma (RMS) is most common soft tissue carcinoma in children, mostly found in the head and neck with high degree of malignancy. The current study aimed to summarize clinical data and evaluate treatment outcome of cases in a single hospital.
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Alpha-interferon suppresses hepadnavirus transcription by altering epigenetic modification of cccDNA minichromosomes.
PLoS Pathog.
PUBLISHED: 09-01-2013
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Covalently closed circular DNA (cccDNA) of hepadnaviruses exists as an episomal minichromosome in the nucleus of infected hepatocyte and serves as the transcriptional template for viral mRNA synthesis. Elimination of cccDNA is the prerequisite for either a therapeutic cure or immunological resolution of HBV infection. Although accumulating evidence suggests that inflammatory cytokines-mediated cure of virally infected hepatocytes does occur and plays an essential role in the resolution of an acute HBV infection, the molecular mechanism by which the cytokines eliminate cccDNA and/or suppress its transcription remains elusive. This is largely due to the lack of convenient cell culture systems supporting efficient HBV infection and cccDNA formation to allow detailed molecular analyses. In this study, we took the advantage of a chicken hepatoma cell line that supports tetracycline-inducible duck hepatitis B virus (DHBV) replication and established an experimental condition mimicking the virally infected hepatocytes in which DHBV pregenomic (pg) RNA transcription and DNA replication are solely dependent on cccDNA. This cell culture system allowed us to demonstrate that cccDNA transcription required histone deacetylase activity and IFN-? induced a profound and long-lasting suppression of cccDNA transcription, which required protein synthesis and was associated with the reduction of acetylated histone H3 lysine 9 (H3K9) and 27 (H3K27) in cccDNA minichromosomes. Moreover, IFN-? treatment also induced a delayed response that appeared to accelerate the decay of cccDNA. Our studies have thus shed light on the molecular mechanism by which IFN-? noncytolytically controls hepadnavirus infection.
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Adsorption of drugs on nanodiamond: toward development of a drug delivery platform.
Mol. Pharm.
PUBLISHED: 08-28-2013
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Nanodiamond particles produced by detonation synthesis and having ?5 nm diameter possess unique properties, including low cell toxicity, biocompatibility, stable structure, and highly tailorable surface chemistry, which render them an attractive material for developing drug delivery systems. Although the potential for nanodiamonds in delivery and sustained release of anticancer drugs has been recently demonstrated, very little is known about the details of adsorption/desorption equilibria of these and other drugs on/from nanodiamonds with different purity, surface chemistry, and agglomeration state. Since adsorption is the basic mechanism most commonly used for the loading of drugs onto nanodiamond, the fundamental studies into the details of adsorption and desorption on nanodiamond are critically important for the rational design of the nanodiamond drug delivery systems capable of targeted delivery and triggered release, while minimizing potential leaks of dangerous drugs. In this paper we report on a physical-chemical study of the adsorption of doxorubicin and polymyxin B on nanodiamonds, analyzing the role of purification and surface chemistry of the adsorbent.
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An endovascular treatment of a thoracic aortic injury caused by a misplaced pedicle screw: Case report and review of the literature.
J. Formos. Med. Assoc.
PUBLISHED: 07-15-2013
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Aortic injuries are devastating complications after spinal surgery. We here would like to share our experience with a successful endovascular treatment of an iatrogenic thoracic aortic injury caused by misplaced pedicle screw after spinal surgery.
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Robust and durable superhydrophobic cotton fabrics for oil/water separation.
ACS Appl Mater Interfaces
PUBLISHED: 07-12-2013
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By introducing the incorporation of polyaniline and fluorinated alkyl silane to the cotton fabric via a facile vapor phase deposition process, the fabric surface possessed superhydrophobicity with the water contact angle of 156° and superoleophilicity with the oil contact angle of 0°. The as-prepared fabric can be applied as effective materials for the separation of water and oil mixture with separation efficiency as high as 97.8%. Compared with other materials for oil/water separation, the reported process was simple, time-saving, and repeatable for at least 30 times. Moreover, the obtained fabric kept stable superhydrophobicity and high separation efficiency under extreme environment conditions of high temperature, high humidity, strong acidic or alkaline solutions, and mechanical forces. Therefore, this reported fabric has the advantages of scalable fabrication, high separation efficiency, stable recyclability, and excellent durability, exhibiting the strong potential for industrial production.
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Molecular characterization of the major histocompatibility complex class Ia gene in the black-spotted frog, Pelophylax nigromaculata.
Biochem. Genet.
PUBLISHED: 07-09-2013
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The genes of the major histocompatibility complex (MHC) are attractive candidates for investigating the link between adaptive variation and individual fitness. We improved rapid amplification of cDNA ends to obtain the whole coding sequence of the MHC class Ia gene of the black-spotted frog (Pelophylax nigromaculata), the most common amphibian in China. We also used genome walking to characterize the partial introns adjacent to exon 3 of the MHC Ia gene. Based on the sequences obtained, we designed locus-specific primers to investigate the molecular polymorphisms of this species in southeast China. The MHC class Ia gene showed a high level of genetic diversity, indicating that this species retains a relatively high potential for survival, despite a population decline among frog species in general and many other amphibians.
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[Mechanism of MBL inhibiting the LPS-induced DC maturation].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 07-03-2013
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The study was aimed to investigate the mechanism of mannan-binding lectin (MBL) on bacterial lipopolysaccharide (LPS)-induced human peripheral blood monocyte-derived dendritic cell (DC) maturation. The monocytes were prepared from the peripheral blood of healthy adult volunteers. The immature dendritic cells (imDC) were induced by 5-day-culture in medium supplemented with rhGM-CSF and rhIL-4. FACS was used to investigate the interaction of MBL with imDC and the impact of MBL on LPS binding to imDC. ELISA and Western blot was used to analyze the interaction of MBL with soluble TLR4 ectodomain protein (sTLR4); Western blot was used to detect LPS-induced NF-?B translocation in imDC. The results showed that MBL could directly bind to imDC in the presence of calcium. sTLR4 protein or LPS could competitively inhibit the binding of MBL to imDC. ELISA and Western blot showed that MBL could evidently bind to sTLR4 protein in a concentration-dependent manner. FACS showed that MBL could competitively inhibit the binding of LPS to imDC by binding to imDC directly. Western blot showed that MBL decreased LPS-induced NF-?B translocation in imDC. It is concluded that MBL may competitively inhibit the binding of LPS to imDC by binding to TLR4 expressed on imDC, resulted in inhibition of LPS-induced DC maturation, suggesting that MBL can regulate DC maturation through ligand-binding. This study provides the good foundation to clarify the mechanism of MBL inhibiting the LPS-induced DC maturation.
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Short neuropeptide F is a sleep-promoting inhibitory modulator.
Neuron
PUBLISHED: 07-02-2013
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To advance the understanding of sleep regulation, we screened for sleep-promoting cells and identified neurons expressing neuropeptide Y-like short neuropeptide F (sNPF). Sleep induction by sNPF meets all relevant criteria. Rebound sleep following sleep deprivation is reduced by activation of sNPF neurons, and flies experience negative sleep rebound upon cessation of sNPF neuronal stimulation, indicating that sNPF provides an important signal to the sleep homeostat. Only a subset of sNPF-expressing neurons, which includes the small ventrolateral clock neurons, is sleep promoting. Their release of sNPF increases sleep consolidation in part by suppressing the activity of wake-promoting large ventrolateral clock neurons, and suppression of neuronal firing may be the general response to sNPF receptor activation. sNPF acutely increases sleep without altering feeding behavior, which it affects only on a much longer time scale. The profound effect of sNPF on sleep indicates that it is an important sleep-promoting molecule.
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Central endogenous angiotensin-(1-7) protects against aldosterone/NaCl-induced hypertension in female rats.
Am. J. Physiol. Heart Circ. Physiol.
PUBLISHED: 06-28-2013
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In comparison to male rodents, females are protected against angiotensin (ANG) II- and aldosterone (Aldo)-induced hypertension. However, the mechanisms underlying this protective effect are not well understood. ANG-(1-7) is formed from ANG II by angiotensin-converting enzyme 2 (ACE2) and has an antihypertensive effect in the central nervous system (CNS). The present study tested the hypothesis that central ANG-(1-7) plays an important protective role in attenuating the development of Aldo/NaCl-hypertension in female rats. Systemic infusion of Aldo into intact female rats with 1% NaCl as their sole drinking fluid resulted in a slight increase in blood pressure (BP). Intracerebroventricular (icv) infusion of A-779, an ANG-(1-7) receptor (Mas-R) antagonist, significantly augmented the pressor effects of Aldo/NaCl. In contrast, systemic Aldo/NaCl induced a significant increase in BP in ovariectomized (OVX) female rats, and central infusion of ANG-(1-7) significantly attenuated this Aldo/NaCl pressor effect. The inhibitory effect of ANG-(1-7) on the Aldo/NaCl pressor effect was abolished by concurrent infusion of A-779. RT-PCR analyses showed that there was a corresponding change in mRNA expression of several renin-angiotensin system components, estrogen receptors and an NADPH oxidase subunit in the lamina terminalis. Taken together these results suggest that female sex hormones regulate an antihypertensive axis of the brain renin-angiotensin system involving ACE2/ANG-(1-7)/Mas-R that plays an important counterregulatory role in protecting against the development of Aldo/NaCl-induced hypertension.
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SU6668 suppresses proliferation of triple negative breast cancer cells through down-regulating MTDH expression.
Cancer Cell Int.
PUBLISHED: 06-25-2013
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The multiple tyrosine kinase inhibitors SU6668 have a promising therapeutic effect on the progression of hematological malignancies and some solid tumors. Here, we determined its effect on triple negative breast cancer (TNBC) cells and explored the potential molecular mechanism.
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Application of chiral N-tert-butylsulfinyl vinyl aziridines in Rh(I) catalyzed 1,4-addition of aryl boronic acids to cyclic enones.
Chem. Commun. (Camb.)
PUBLISHED: 06-13-2013
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Chiral N-tert-butylsulfinyl vinyl aziridine ligands prepared from a readily available (R)-tert-butanesulfinamide have been applied in the rhodium-catalyzed asymmetric 1,4-addition of aryl boronic acids to cyclic enones, which gives high yields and excellent enantioselectivities.
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Computer-assisted orthognathic surgery combined with fibular osteomyocutaneous flap reconstruction to correct facial asymmetry and maxillary defects secondary to maxillectomy in childhood.
J Craniofac Surg
PUBLISHED: 05-30-2013
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Maxillectomy in childhood not only causes composite primary defects but also secondary malformation of the middle and lower face. In the case presented, we introduced computer-assisted planning and simulation of orthognathic surgery combined with fibular osteomyocutaneous flap reconstruction to correct complex craniofacial deformities. Virtual orthognathic surgery and maxillary reconstruction surgery were undertaken preoperatively. LeFort I osteotomy, with bilateral sagittal split ramus osteotomy and lower border ostectomy, was performed to correct malocclusion and facial asymmetry. Maxillary reconstruction was accomplished using a fibular osteomyocutaneous flap. The patient recovered uneventfully with an adequate aesthetic appearance on 3D computed tomography. Our experience indicates that orthognathic surgery combined with fibular osteomyocutaneous flap reconstruction can used to correct complex facial asymmetry and maxillary defects secondary to maxillectomy. Computer-assisted simulation enables precise execution of the reconstruction. It shortens the free flap ischemia time and reduces the risks associated with microsurgery.
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PKM2 Regulates Chromosome Segregation and Mitosis Progression of Tumor Cells.
Mol. Cell
PUBLISHED: 05-17-2013
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Tumor-specific pyruvate kinase M2 (PKM2) is instrumental in both aerobic glycolysis and gene transcription. PKM2 regulates G1-S phase transition by controlling cyclin D1 expression. However, it is not known whether PKM2 directly controls cell-cycle progression. We show here that PKM2, but not PKM1, binds to the spindle checkpoint protein Bub3 during mitosis and phosphorylates Bub3 at Y207. This phosphorylation is required for Bub3-Bub1 complex recruitment to kinetochores, where it interacts with Blinkin and is essential for correct kinetochore-microtubule attachment, mitotic/spindle-assembly checkpoint, accurate chromosome segregation, cell survival and proliferation, and active EGF receptor-induced brain tumorigenesis. In addition, the level of Bub3 Y207 phosphorylation correlated with histone H3-S10 phosphorylation in human glioblastoma specimens and with glioblastoma prognosis. These findings highlight the role of PKM2 as a protein kinase controlling the fidelity of chromosome segregation, cell-cycle progression, and tumorigenesis.
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Patterns of genetic differentiation at MHC class I genes and microsatellites identify conservation units in the giant panda.
BMC Evol. Biol.
PUBLISHED: 05-15-2013
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Evaluating patterns of genetic variation is important to identify conservation units (i.e., evolutionarily significant units [ESUs], management units [MUs], and adaptive units [AUs]) in endangered species. While neutral markers could be used to infer population history, their application in the estimation of adaptive variation is limited. The capacity to adapt to various environments is vital for the long-term survival of endangered species. Hence, analysis of adaptive loci, such as the major histocompatibility complex (MHC) genes, is critical for conservation genetics studies. Here, we investigated 4 classical MHC class I genes (Aime-C, Aime-F, Aime-I, and Aime-L) and 8 microsatellites to infer patterns of genetic variation in the giant panda (Ailuropoda melanoleuca) and to further define conservation units.
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Effects of legumain as a potential prognostic factor on gastric cancers.
Med. Oncol.
PUBLISHED: 05-11-2013
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Although legumain has been found to be a prognostic factor in both breast cancer and colorectal cancer, its effects on gastric cancer are unknown. In this study, we investigated effects of legumain on gastric cancer and the correlation between legumain expression and prognosis of gastric cancer patients. SGC7901 cells were transduced with legumain cDNA (SGC7901-hLeg) for overexpression of legumain or with legumain shRNA to knock down legumain. In vitro tumor migration was examined by wound healing assay. Furthermore, a tumorigenicity and metastasis mouse model was used to examine legumain function in vivo; asparaginyl endopeptidase inhibitor (AEPI, an inhibitor of legumain) was injected to the mice (i.p.) to evaluate its therapeutic effect. Tissue microarray analysis from 112 gastric cancer patients was performed to evaluate the association between legumain expression and the cumulative survival time. Legumain was highly expressed in gastric cancer patients and some gastric cancer cell lines. Legumain promoted gastric cell migration in vitro and promoted gastric tumor growth and metastasis in vivo, and these effects were reversed by knockdown of legumain with shRNA or treated with AEPI. In gastric cancer clinical samples, legumain expression in tumor was significantly higher than in non-tumor and was negatively associated with the cumulative survival rate. In conclusion, legumain was highly expressed in gastric adenocarcinoma; legumain promoted gastric cancer tumorigenesis and metastasis in vitro and in vivo. Legumain expression in tumor was a poor prognostic factor for gastric cancer patients, and legumain could be a potential target molecule for gastric cancer therapy in clinic.
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[Research of Dangua Recipe on intervening the glycolipid metabolism and oxidative stress in diabetic rats with atherosclerosis].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 05-08-2013
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To explore the effects of Dangua Recipe (DGR) on glycolipid metabolism, serum reactive oxygen species (ROS) level, nuclear factor kappa B (NF-kappaB) positive expression and its mRNA expression level in the thoracic aorta of diabetic rats with atherosclerosis, thus revealing its partial mechanisms for intervening chronic diabetic complications.
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Copolymerization of isoprene and nonconjugated ?,?-dienes by half-sandwich scandium catalysts with and without a coordinative side arm.
Chem Asian J
PUBLISHED: 04-30-2013
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A series of half-sandwich scandium-dialkyl complexes that bear various auxiliary ligands have been examined for the copolymerization of isoprene (IP) with nonconjugated ?,?-dienes such as 1,5-hexadiene (HD) and 1,6-heptadiene (HPD). Significant ligand influence on the catalytic activity and selectivity has been observed. The thf-coordinated complex [(C5Me4SiMe3)Sc(CH2SiMe3)2(thf)] (2) and the methoxy side arm containing the half-sandwich complex [(C5Me4C6H4OMe-o)Sc(CH2SiMe3)2] (3), in combination with an equivalent of [Ph3C][B(C6F5)4], can serve as excellent catalysts for the random cyclocopolymerizations of IP with HD and HPD. The resulting random HD-IP copolymers contain five-membered-ring methylene-1,3-cyclopentane (MCP), 3,4-polyisoprene (3,4-IP), and 1,4-polyisoprene (1,4-IP) units with controllable HD incorporation in a range of 17-82 mol%. The random HPD-IP copolymers possess six-membered-ring methylene-1,3-cyclohexane (MCH), 1,4-IP, and 3,4-IP units with HPD incorporation in a range of 11-55 mol%. By use of a catalyst that bears a phosphine oxide group [{C5Me4SiMe2CH2P(O)Ph2}Sc(CH2SiMe3)2] (5), the alternating copolymerizations of IP with HD and HPD have been achieved for the first time in which HD and HPD are completely cyclized to the MCP and MCH units, respectively. More remarkably, in the alternating copolymerization of HPD and IP by 5, the regio- and stereospecific cis-MCH selectivity reached as high as 99%. The microstructures and compositions of these copolymers showed significant influences on their mechanical properties.
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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.