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Find video protocols related to scientific articles indexed in Pubmed.
Neuroprotective effects of the Buyang Huanwu decoction on functional recovery in rats following spinal cord injury.
J Spinal Cord Med
PUBLISHED: 10-21-2014
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Background The Buyang Huanwu decoction (BYHWD) is a traditional Chinese herbal prescription and has been used in China to treat spinal cord injury (SCI) for hundreds of years. Clinical trials have shown that BYHWD improves the outcome of SCI in clinical trials, but the mechanisms are not known. This study observed the neuroprotective effects of BYHWD on spinal nerve cells after SCI and investigated possible mechanisms. Materials and methods Forty female Wistar rats were randomized equally to four groups treated by sham injury, SCI, BYHWD, or methylprednisolone (MP). The Basso, Beattie, and Bresnahan (BBB) score was used to evaluate hind-limb locomotor function. Neuron apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling staining and caspase-3, Bax, and Bcl-2 mRNA and protein expression were evaluated by real-time quantitative polymerase chain reaction and Western blotting, respectively. Results In the sham group, walking was mildly abnormal after anesthesia but recovered completely in 2 days. The BBB score in the SCI model group was significantly different from that in the sham group. The BBB scores of rats in both the BYHWD and MP groups were significantly higher than scores of rats in the SCI group. BYHWD had an antiapoptosis effect, as shown by significant decreases in expression of caspase-3 and Bax and increase in Bcl-2 expression. Conclusion BYHWD treatment restored hind-limb motor function of rats with SCI. The neuroprotective effect of BYHWD was associated with modulation of the expression of apoptosis-related proteins.
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RP5-833A20.1/miR-382-5p/NFIA-Dependent Signal Transduction Pathway Contributes to the Regulation of Cholesterol Homeostasis and Inflammatory Reaction.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 09-30-2014
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Cardiovascular disease caused by atherosclerosis is the number one cause of death in Western countries and threatens to become the major cause of morbidity and mortality worldwide. Long noncoding RNAs are emerging as new players in gene regulation, but how long noncoding RNAs operate in the development of atherosclerosis remains unclear.
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Synthesis and molecular recognition studies on small-molecule inhibitors for thioredoxin reductase.
J. Med. Chem.
PUBLISHED: 09-24-2014
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Thioredoxin reductase (TrxR), which is overexpressed in many aggressive cancers, plays a crucial role in redox balance and antioxidant function, including defense of oxidative stress, control of cell proliferation, and regulation of cell apoptosis. Deactivation of TrxR can destroy the homeostasis of the cancer cells, inducing elevation of reactive oxygen species (ROS) levels and the oxidation of enzymatic substrates. Here, we synthesized and identified a new gold(I) small molecule (D9) that possesses two strong electron-donating moieties, i.e., 4-methylphenyl alkynyl and thionyldiphenyl phosphine, exhibiting an enhanced p-? conjunction effect. The resulting compound shows the increased soft Lewis acids and the stability of gold(I). And we demonstrated that D9 could efficiently and specifically inhibit the activity of TrxR in vitro and in vivo, and it could effectively avoid the ligand exchange with albumin that was one of the most abundant proteins in blood. We believe that these comprehensive studies on the relationship between the structure and performance will provide inspiring information on the precise synthesis and design of new compounds for targeting TrxR.
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Characterization of Five ?-Glycoside Hydrolases from Cellulomonas fimi ATCC 484.
J. Bacteriol.
PUBLISHED: 09-15-2014
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The Gram-positive bacterium Cellulomonas fimi produces a large array of carbohydrate-active enzymes. Analysis of the collection of carbohydrate-active enzymes from the recent genome sequence of C. fimi ATCC 484 shows a large number of uncharacterized genes for glycoside hydrolase (GH) enzymes potentially involved in biomass utilization. To investigate the enzymatic activity of potential ?-glucosidases in C. fimi, genes encoding several GH3 enzymes and one GH1 enzyme were cloned and recombinant proteins were expressed in Escherichia coli. Biochemical analysis of these proteins revealed that the enzymes exhibited different substrate specificities for para-nitrophenol-linked substrates (pNP), disaccharides, and oligosaccharides. Celf_2726 encoded a bifunctional enzyme with ?-d-xylopyranosidase and ?-l-arabinofuranosidase activities, based on pNP-linked substrates (CfXyl3A). Celf_0140 encoded a ?-d-glucosidase with activity on ?-1,3- and ?-1,6-linked glucosyl disaccharides as well as pNP-?-Glc (CfBgl3A). Celf_0468 encoded a ?-d-glucosidase with hydrolysis of pNP-?-Glc and hydrolysis/transglycosylation activities only on ?-1,6-linked glucosyl disaccharide (CfBgl3B). Celf_3372 encoded a GH3 family member with broad aryl-?-d-glycosidase substrate specificity. Celf_2783 encoded the GH1 family member (CfBgl1), which was found to hydrolyze pNP-?-Glc/Fuc/Gal, as well as cellotetraose and cellopentaose. CfBgl1 also had good activity on ?-1,2- and ?-1,3-linked disaccharides but had only very weak activity on ?-1,4/6-linked glucose.
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Adsorption of diethyl phthalate ester to clay minerals.
Chemosphere
PUBLISHED: 08-21-2014
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Phthalate esters are a group of plasticizers, which have been widely detected in China's agricultural and industrial soils. In this study, batch adsorption experiments were conducted to investigate the environmental effects on the adsorption of diethyl phthalate ester (DEP) to clay minerals. The results showed that DEP adsorption isotherms were well fitted with the Freundlich model; the interlayer spacing of K(+) saturated montmorillonite (K-mont) was the most important adsorption area for DEP, and di-n-butyl ester (DnBP) was limited to intercalate into the interlayer of K-mont due to the bigger molecular size; there was no significant effect of pH and ionic strength on DEP adsorption to K-mont/Ca-mont, but to Na-mont clay. The adsorption to kaolinite was very limited. Data of X-ray diffraction and FTIR spectra further proved that DEP molecules could intercalate into K-/Ca-mont interlayer, and might interact with clay through H-bonding between carbonyl groups and clay adsorbed water. Coated humic acid on clay surface would enhance DEP adsorption at low concentration, but not at high concentration (eg. Ce>0.26mM). The calculated adsorption enthalpy (?Hobs) and adsorption isotherms at varied temperatures showed that DEP could be adsorbed easier as more adsorbed. This study implied that clay type, compound structure, exchangeable cation, soil organic matter and temperature played important roles in phthalate ester's transport in soil.
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Heterochronic bilateral ectopic pregnancy after ovulation induction.
J Zhejiang Univ Sci B
PUBLISHED: 08-06-2014
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Ectopic pregnancy is identified with the widely-applied assisted reproductive technology (ART). Bilateral ectopic pregnancy is a rare form of ectopic pregnancy which is difficult to be diagnosed at the pre-operation stage. In this paper, we presented an unusual case of heterochronic bilateral ectopic pregnancy after stimulated intrauterine insemination (IUI), where there has been a delay of 22 d between the diagnoses of the two ectopic pregnancies. Literature was reviewed on the occurrence of bilateral ectopic pregnancy during the past four years in the MEDLINE database. We found 16 cases of bilateral ectopic pregnancy reported since 2008, and analyzed the characteristics of those cases of bilateral ectopic pregnancy. We emphasize that ovulation induction and other ARTs may increase the risk of bilateral ectopic pregnancy. Because of the difficulty in identification of bilateral ectopic pregnancy by ultrasonography, the clinician should be aware that the treatment of one ectopic pregnancy does not preclude the occurrence of a second ectopic pregnancy in the same patient and should pay attention to the intra-operation inspection of both side fallopian tubes in any ectopic pregnancy case.
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[Movement characteristics of Cyanobacteria under stress of water-lifting aeration].
Huan Jing Ke Xue
PUBLISHED: 07-25-2014
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In order to study the impact of algae control mixing technology on the distribution characteristics and movement of Cyanobacteria, the floating and subsiding velocity of Cyanobacteria in Taihu Lake was measured under different conditions such as different illuminance, temperature and pressure. The Cyanobacteria showed strong propensity of floating under the illuminance from 1500 1x to 6000 1x. The Cyanobacteria particle with floating velocity of more than 0.8 cm.min-1 accounted for 58% under the illuminance of 1 500 1x. The floating velocity slowed down when the illuminance was lower than 1 500 1x or higher than 6 000 1x. In the temperature range of 8 to 25 Celsius degree, the Cyanobacteria floated and the floating velocity increased with temperature. The Cyanobacteria floated under the pressure of 0- 0. 1 MPa and the floating velocity slowed down as the pressure increased. Most Cyanobacteria were suspended in the water when the pressure reached 0. 2-0. 3 MPa and only a small part of the Cyanobacteria floated or settled. When the pressure reached 0. 4-0. 6 MPa, the Cyanobacteria notably settled and the subsiding velocity increased with the increase of pressure. The Cyanobacteria particles with subsiding velocity of more than 1.0 cm.min-1 accounted for 52.5% when the pressure was 0. 6 MPa. Gas vesicles bursted when the gas vesicles of the Cyanobacteria could not bear the external pressure. The buoyancy of the Cyanobacteria diminished until the floating force became smaller than its weight, causing the particles of the Cyanobacteria to settle. Under normal atmospheric pressure, the particle diameter was positively correlated to the floating velocity, while negatively correlated to the density. Under high pressure, the particle diameter was positively correlated to the subsiding velocity and the density.
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Ox-LDL Upregulates CRP Expression Through the IGF2 Pathway in THP-1 Macrophages.
Inflammation
PUBLISHED: 07-04-2014
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C-reactive protein (CRP) is an acute-phase reactant protein that not only plays a predictive role in determining atherogenesis risk but also represents an active participant in atherogenesis onset and progression. Moreover, an increasing number of studies have reported that oxidized low-density lipoprotein (Ox-LDL) plays a significant role in the initiation and progression of atherosclerosis. However, the effect and underlying mechanism of Ox-LDL on CRP expression remains unclear. THP-1 macrophages were treated with 0, 25, 50, or 100 ?g/mL of Ox-LDL for 48 h, or 50 ?g/mL of Ox-LDL for 0, 12, 24, and 48 h, respectively. Messenger RNA (mRNA) and protein levels were measured by real-time quantitative PCR and Western blot analysis, respectively. We found that Ox-LDL markedly increased insulin-like growth factor 2 (IGF2) and CRP mRNA and protein levels in a dose- and time-dependent manner in THP-1 macrophages. Treatment with Ox-LDL increased CRP protein expression, and this effect was completely abolished by siRNA-mediated silencing of IGF2 in THP-1 macrophages. Moreover, treatment with pcDNA3.1-IGF2 significantly enhanced CRP protein expression in Ox-LDL-stimulated THP-1 macrophages. CRP expression is upregulated by Ox-LDL through the IGF2 pathway in THP-1 macrophages.
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Direct interaction of kindlin-3 with integrin ?IIb?3 in platelets is required for supporting arterial thrombosis in mice.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 06-26-2014
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Kindlin-3 is a critical supporter of integrin function in platelets. Lack of expression of kindlin-3 protein in patients impairs integrin ?IIb?3-mediated platelet aggregation. Although kindlin-3 has been categorized as an integrin-binding partner, the functional significance of the direct interaction of kindlin-3 with integrin ?IIb?3 in platelets has not been established. Here, we evaluated the significance of the binding of kindlin-3 to integrin ?IIb?3 in platelets in supporting integrin ?IIb?3-mediated platelet functions.
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[Research progress in human adenovirus].
Bing Du Xue Bao
PUBLISHED: 06-14-2014
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Human adenovirus (HAdV) is one of the most important pathogens in infants and young children with acute respiratory infections and other diseases. This article reviews the literature on HAdV, including its molecular biological characteristics, detection and typing, and pathogenic mechanism, the clinical features and epidemiological characteristics of HAdV-related diseases, and the prevention and control of HAdV infections. So far, 67 types of HAdV have been identified, including recombinant variants discovered in recent years. The major epidemic strains that cause acute respiratory infections are HAdV-3 and HAdV-7, both of which belong to the subgroup B. HAdV often leads to acute respiratory infections, but it also causes diseases of other systems. HAdV-related diseases have similar clinical manifestations as those caused by other respiratory viruses, but often accompanied by gastrointestinal symptoms. The pathogenic mechanism of HAdV remains unclear, especially for the new recombinant variants, due to few studies on their association with diseases. Because there are no prospective, large randomized controlled trials of HAdV infections, the treatment of HAdV infections is controversial. Vaccine is the most effective measure to reduce respiratory HAdV infections, but it is still not commercially available.
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Expression analysis of several antiviral related genes to BmNPV in different resistant strains of silkworm, Bombyx mori.
J. Insect Sci.
PUBLISHED: 05-30-2014
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Bombyx mori L. (Lepidoptera: Bombycidae) nucleopolyhedrovirus (BmNPV) is a highly pathogenic virus in the sericultural industry, often causing severe damage leading to large economic losses. The immune mechanisms of B. mori against this virus remain obscure. Previous studies had demonstrated Bmlipase-1, BmNox and Bmserine protease-2 showing antiviral activity in vitro, but data on the transcription levels of these proteins in different resistant strains were not reported. In order to determine the resistance level of the four different strains (P50, A35, A40, A53) and gain a better understanding of the mechanism of resistance to BmNPV in B. mori, the relative expression level of the genes coding the three antiviral proteins in larval haemolymph and midgut of different B. mori strains resistant to BmNPV was determined. The results showed that these genes expressed significantly higher in the resistant strains compared to the susceptible strain, and the differential expression levels were consistent with the LC50 values in different strains. The transcription level of the target genes almost all up-regulated in the larvae midgut and down-regulated in the haemolymph. The results indicate the correlation of these genes to BmNPV resistance in B. mori.
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[Temporal and spatial variations of soil NO(3-)-N in Orychophragmus violaceus/spring maize rotation system in North China].
Ying Yong Sheng Tai Xue Bao
PUBLISHED: 05-17-2014
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The February orchid (Orychophragmus violaceus)-spring maize rotation system is established to resolve the problems caused by the expansion of fallow fields in North China. Based on a site-specific experiment, temporal and spatial variations of soil NO(3-)-N were investigated during the period from February orchid incorporation to maize harvest. The results showed that the nitrate content in soil profiles not only showed a temporal characteristic, i. e., increasing at the beginning of the maize season and decreasing then after, but also showed a spatial characteristic, i. e., the gradual occurrence of the peak of nitrate content from shallower to deeper layer with the growth season of maize. Meanwhile, incorporation of February orchid could affect temporal and spatial variations of soil NO(3-)-N. February orchid planting reduced the soil NO(3-)-N accumulation in the profile of 0180 cm. After incorporation of February orchid, similar characteristics were observed at the seedling and bell stages of maize, i. e., the soil NO(3-)-N mainly stayed in the profile of 0-20 cm, and NO(3-)-N concentrations in the treatments with February orchid were higher in 0-100 cm layer and lower in 100-180 cm layer than those of the treatments without February orchid. After tasseling stage, opposite phenomena were found, and the soil NO(3-)-N content was all relative low. Overall, incorporation of February orchid could increase the storage capacity of soil NO(3-)-N in the profile of 0-180 cm.
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Analysis on the characteristics and prognosis of pulmonary neuroendocrine tumors.
Asian Pac. J. Cancer Prev.
PUBLISHED: 04-11-2014
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To retrospectively review the clinical characteristics and analyze the prognostic factors of Chinese patients with pulmonary neuroendocrine tumors.
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Activation of central angiotensin type 2 receptors by compound 21 improves arterial baroreflex sensitivity in rats with heart failure.
Am. J. Hypertens.
PUBLISHED: 03-31-2014
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In a previous study we demonstrated that central administration of compound 21 (C21), a nonpeptide AT2R agonist, inhibited sympathetic tone in normal rats. In this study, we hypothesized that C21 exerts a similar effect in rats with coronary ligation-induced heart failure (HF).
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Transneuronal tracing of central autonomic regions involved in cardiac sympathetic afferent reflex in rats.
J. Neurol. Sci.
PUBLISHED: 03-25-2014
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Stimulation of cardiac afferents (CA) increased sympathetic outflow and blood pressure. The goal of the current study is to determine the central autonomic nuclei involved in the regulation of cardiac sympathetic afferent reflex (CSAR) which has been proved in previously functional studies. Neuroanatomical method and pseudorabies virus (PRV) transynaptic retrograde trace technique will be performed to investigate the relationship between kidney and heart and the temporal order of the most PRV-labeled neurons in the central nervous system. Recombinant PRV expressing enhanced green fluorescence protein (EGFP) was injected into the left kidney of rats as a specific trans-synaptic retrograde tracer in neurons. After 2, 3, 4, 5, 6, 7, 8 or 9 days, brain, spinal cord and heart were collected for immunofluorescence staining. The temporal order of PRV labeled neurons was found in the ipsilateral intermediolateral nucleus (IML) of T8-T12 spinal segments on day 3; bilateral rostroventrolateral medulla (RVLM), paraventricular nucleus (PVN) and nucleus of the solitary tract (NTS) on day 4; and left and right ventricular walls and ventricular septum of the heart on day 9. In rats with renal denervation, no PRV-infected neurons or cardiomyocytes were found after PRV injection. In conclusion, PRV trans-synaptic retrograde trace confirms that CA, NTS, PVN, RVLM, IML and renal nerves do exist to be involved in the regulation of CSAR and there is a close relationship between heart and kidney. CA is mainly located in the left ventricular wall, right ventricular wall and ventricular septum.
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Ezrin is required for epithelial-mesenchymal transition induced by TGF-?1 in A549 cells.
Int. J. Oncol.
PUBLISHED: 03-23-2014
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Epithelial mesenchymal transition (EMT) has been shown to play a role in cellular differentiation during deve-lopment and tumor invasion. However, the precise molecular mechanisms of EMT are not fully elucidated. Previous studies suggested that the mechanism underlying the possible involvement of ezrin in EMT process might be different from that of moesin, another ERM protein. In our study, we examined the role of ezrin in actin filament reorganization and cell meta-stasis during TGF-?1-induced alveolar EMT. Suppressing ezrin expression limited morphological changes and actin filament remodeling, decreased cell migration and invasion during EMT. Immunofluorescence experiments indicated that EMT characteristics in lung cancer cells are associated to differential ezrin subcellular localization. We also found that podocalyxin interacted with ezrin after TGF-?1 induction. Therefore, ezrin is an important regulator of the EMT process, and its function might possibly be mediated by the ezrin-podocalyxin interaction during TGF-?1-induced alveolar EMT. Our finding provides important new insights into the mechanisms of action of the ERM proteins in the TGF-?1-induced alveolar EMT.
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Protein Phosphatase 2C of Toxoplasma Gondii Interacts with Human SSRP1 and Negatively Regulates Cell Apoptosis.
Biomed. Environ. Sci.
PUBLISHED: 03-20-2014
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The protozoan Toxoplasma gondii expresses large amounts of a 37 kDa Type 2C serine-threonine phosphatase, the so-called TgPP2C which has been suggested to contribute to parasite growth regulation. Ectopic expression in mammalian cells also indicated that the enzyme could regulate growth and survival. In this study, we aimed to investigate the interaction of TgPP2C with human SSRP1 (structure-specific recognition protein 1) and the effects of TgPP2C on cell viability.
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Dihydrocapsaicin down-regulates apoM expression through inhibiting Foxa2 expression and enhancing LXR? expression in HepG2 cells.
Lipids Health Dis
PUBLISHED: 03-13-2014
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Apolipoprotein M (apoM), as a novel apolipoprotein which is mainly expressed in liver and kidney tissues, is associated with development and progression of atherosclerosis and diabetes. Our group have recently shown that Dihydrocapsaicin(DHC)can significantly decrease atherosclerotic plaque formation in apoE-/- mice. However, the effect and possible mechanism of DHC on apoM expression remain unclear.
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The role of the globular heads of the C1q receptor in HPV-16 E2-induced human cervical squamous carcinoma cell apoptosis via a mitochondria-dependent pathway.
J Transl Med
PUBLISHED: 02-27-2014
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Human papillomavirus type-16 (HPV-16) E2 protein acts as a transcriptional modulator and plays a key role in regulating many biological responses. The purpose of this study was to investigate the relationship between HPV-16 E2, the receptor for the globular heads of human C1q (gC1qR) gene expression, mitochondrial dysfunction and apoptosis regulation in human cervical squamous carcinoma cells (C33a and SiHa).
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The highly conserved negatively charged Glu141 and Asp145 of the G-protein-coupled receptor RXFP3 interact with the highly conserved positively charged arginine residues of relaxin-3.
Amino Acids
PUBLISHED: 02-20-2014
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Relaxin-3 is a newly identified insulin/relaxin superfamily peptide that plays a putative role in the regulation of food intake and stress response by activating its cognate G-protein-coupled receptor RXFP3. Relaxin-3 has three highly conserved arginine residues, B12Arg, B16Arg and B26Arg. We speculated that these positively charged arginines may interact with certain negatively charged residues of RXFP3. To test this hypothesis, we first replaced the negatively charged residues in the extracellular domain of RXFP3 with arginine, respectively. Receptor activation assays showed that arginine replacement of Glu141 or Asp145, especially Glu141, significantly decreased the sensitivity of RXFP3 to wild-type relaxin-3. In contrast, arginine replacement of other negatively charged extracellular residues had little effect. Thus, we deduced that Glu141 and Asp145, locating at the extracellular end of the second transmembrane domain, played a critical role in the interaction of RXFP3 with relaxin-3. To identify the ligand residues interacting with the negatively charged EXXXD motif of RXFP3, we replaced the three conserved arginines of relaxin-3 with negatively charged glutamate or aspartate, respectively. The mutant relaxin-3s retained the native structure, but their binding and activation potencies towards wild-type RXFP3 were decreased significantly. The compensatory effects of the mutant relaxin-3s towards mutant RXFP3s suggested two probable interaction pairs during ligand-receptor interaction: Glu141 of RXFP3 interacted with B26Arg of relaxin-3, meanwhile Asp145 of RXFP3 interacted with both B12Arg and B16Arg of relaxin-3. Based on these results, we proposed a relaxin-3/RXFP3 interaction model that shed new light on the interaction mechanism of the relaxin family peptides with their receptors.
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MMP-2/9-oriented combinations enhance antitumor efficacy of EGFR/HER2-targeting fusion proteins and gemcitabine.
Oncol. Rep.
PUBLISHED: 02-17-2014
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To increase the antitumor efficacy, in the present study, we proposed several settings of matrix metalloproteinase (MMP)-2/9-oriented combinations that comprise the MMP-2/9-targeting fusion protein dFv-LDP and the MMP inhibitor doxycycline (DOX) in association with EGFR/HER2-bispecific fusion protein Ec-LDP-Hr, its enediyne-energized analogue Ec-LDP-Hr-AE, and gemcitabine (GEM). The expressions of various fusion proteins were detected by western blot analysis. Proliferation and migration inhibition of cells were determined by MTT and Transwell assay, respectively. The binding capability of dFv-LDP and Ec-LDP-Hr to cancer cells was examined by ELISA, cell immunofluorescence coimmunoprecipitation and confocal assays. Animal experiments were set to investigate the antitumor efficacy of various combinations against colorectal carcinoma HCT-15 xenograft in athymic mice. These two targeting proteins dFv-LDP and Ec-LDP-Hr had strong binding capabilities and antiproliferation effects on various cancer cell lines. Enhanced therapeutic efficacy in vivo was observed in the MMP-2/9-targeting fusion protein dFv-LDP integrated combinations including: i) dFv-LDP and Ec-LDP-Hr, ii) dFv-LDP and enediyne-energized fusion protein Ec-LDP-Hr-AE, iii) dFv-LDP and Ec-LDP-Hr-AE plus DOX, and iv) dFv-LDP and GEM plus DOX against colorectal cancer HCT-15 xenograft in athymic mice. In setting iii, DOX (20 mg/kg), dFv-LDP (20 mg/kg) and Ec-LDP-Hr-AE (0.3 mg/kg) alone suppressed tumor growth by 35, 49.7 and 67.5%, respectively. The combination of dFv-LDP and Ec-LDP-Hr-AE was 75.1%. Furthermore, this combination plus DOX showed stronger efficacy with an inhibitory rate of 82.7%. In setting iv, the combination of dFv-LDP and GEM suppressed tumor growth by 66.3%. Notably, the tumor inhibitory rate of the dFv-LDP/GEM/DOX combination reached 85.5%, producing initial shrinkage after the first administration. The MMP-2/9-oriented combination strategy that employs the MMP-2/9-targeting antibody-based fusion protein and the small molecular inhibitor DOX as the basic composed agents may enhance antitumor efficacy in association with the EGFR/HER2-targeting fusion protein and GEM. This multiple targeting approach may be useful for enhancing antitumor efficacy against colorectal cancer.
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Tet and TDG mediate DNA demethylation essential for mesenchymal-to-epithelial transition in somatic cell reprogramming.
Cell Stem Cell
PUBLISHED: 02-13-2014
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Tet-mediated DNA oxidation is a recently identified mammalian epigenetic modification, and its functional role in cell-fate transitions remains poorly understood. Here, we derive mouse embryonic fibroblasts (MEFs) deleted in all three Tet genes and examine their capacity for reprogramming into induced pluripotent stem cells (iPSCs). We show that Tet-deficient MEFs cannot be reprogrammed because of a block in the mesenchymal-to-epithelial transition (MET) step. Reprogramming of MEFs deficient in TDG is similarly impaired. The block in reprogramming is caused at least in part by defective activation of key miRNAs, which depends on oxidative demethylation promoted by Tet and TDG. Reintroduction of either the affected miRNAs or catalytically active Tet and TDG restores reprogramming in the knockout MEFs. Thus, oxidative demethylation to promote gene activation appears to be functionally required for reprogramming of fibroblasts to pluripotency. These findings provide mechanistic insight into the role of epigenetic barriers in cell-lineage conversion.
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A lincRNA-DYNLRB2-2/GPR119/GLP-1R/ABCA1-dependent signal transduction pathway is essential for the regulation of cholesterol homeostasis.
J. Lipid Res.
PUBLISHED: 02-03-2014
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Accumulated evidence shows that G protein-coupled receptor 119 (GPR119) plays a key role in glucose and lipid metabolism. Here, we explored the effect of GPR119 on cholesterol metabolism and inflammation in THP-1 macrophages and atherosclerotic plaque progression in apoE(-/-) mice. We found that oxidized LDL (Ox-LDL) significantly induced long intervening noncoding RNA (lincRNA)-DYNLRB2-2 expression, resulting in the upregulation of GPR119 and ABCA1 expression through the glucagon-like peptide 1 receptor signaling pathway. GPR119 significantly decreased cellular cholesterol content and increased apoA-I-mediated cholesterol efflux in THP-1 macrophage-derived foam cells. In vivo, apoE(-/-) mice were randomly divided into two groups and infected with lentivirus (LV)-Mock or LV-GPR119 for 8 weeks. GPR119-treated mice showed decreased liver lipid content and plasma TG, interleukin (IL)-1?, IL-6, and TNF-? levels, whereas plasma levels of apoA-I were significantly increased. Consistent with this, atherosclerotic lesion development was significantly inhibited by infection of apoE(-/-) mice with LV-GPR119. Our findings clearly indicate that, Ox-LDL significantly induced lincRNA-DYNLRB2-2 expression, which promoted ABCA1-mediated cholesterol efflux and inhibited inflammation through GPR119 in THP-1 macrophage-derived foam cells. Moreover, GPR119 decreased lipid and serum inflammatory cytokine levels, decreasing atherosclerosis in apoE(-/-) mice. These suggest that GPR119 may be a promising candidate as a therapeutic agent.
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Key role of persistent free radicals in hydrogen peroxide activation by biochar: implications to organic contaminant degradation.
Environ. Sci. Technol.
PUBLISHED: 01-21-2014
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We investigated the activation of hydrogen peroxide (H2O2) by biochars (produced from pine needles, wheat, and maize straw) for 2-chlorobiphenyl (2-CB) degradation in the present study. It was found that H2O2 can be effectively activated by biochar, which produces hydroxyl radical ((•)OH) to degrade 2-CB. Furthermore, the activation mechanism was elucidated by electron paramagnetic resonance (EPR) and salicylic acid (SA) trapping techniques. The results showed that biochar contains persistent free radicals (PFRs), typically ? 10(18) unpaired spins/gram. Higher trapped [(•)OH] concentrations were observed with larger decreases in PFRs concentration, when H2O2 was added to biochar, indicating that PFRs were the main contributor to the formation of (•)OH. This hypothesis was supported by the linear correlations between PFRs concentration and trapped [(•)OH], as well as kobs of 2-CB degradation. The correlation coefficients (R(2)) were 0.723 and 0.668 for PFRs concentration vs trapped [(•)OH], and PFRs concentration vs kobs, respectively, when all biochars pyrolyzed at different temperatures were included. For the same biochar washed by different organic solvents (methanol, hexane, dichloromethane, and toluene), the correlation coefficients markedly increased to 0.818-0.907. Single-electron transfer from PFRs to H2O2 was a possible mechanism for H2O2 activation by biochars, which was supported by free radical quenching studies. The findings of this study provide a new pathway for biochar implication and insight into the mechanism of H2O2 activation by carbonaceous materials (e.g., activated carbon and graphite).
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Quality control and identification of steroid saponins from Dioscorea zingiberensis C. H. Wright by fingerprint with HPLC-ELSD and HPLC-ESI-Quadrupole/Time-of-fight tandem mass spectrometry.
J Pharm Biomed Anal
PUBLISHED: 01-15-2014
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In this study, a fingerprint of steroid saponins, the major bioactive constituents in the crude extracts from Dioscorea zingiberensis C. H. Wright (DZW), has been established for the first time by combined use of the following two methods: high-performance liquid chromatography coupled with evaporative light scattering detector (HPLC-ELSD) and the simultaneous characterization of the steroid saponins by high-performance liquid chromatography coupled with electrospray ionization-mass spectrometry and quadrupole tandem time-of-fight mass analyzers detection (HPLC-ESI-Q/TOF). All HPLC analyses were carried out on a Welchrom C18 column (250mm×4.6mm I.D., 5?m) with a mobile phase composed of water and acetonitrile under gradient elution. There were 68 common characteristic peaks in the fingerprints, in which 12 of them were confirmed by comparing their mass spectra and retention times with those of the reference compounds. In order to identify other unknown peaks, their fragmentation behaviors characteristic of the major groups of steroid saponins from DZW with six types of aglycone skeletons were discussed in detail, and possible MS/MS fragmentation pathways were proposed for aiding the structural identification of these components. According to the summarized fragmentation patterns, these peaks were tentatively assigned by matching their empirical molecular formula with those of the published compounds, or by elucidating their quasi-molecular ions and fragment ions referring to available literature information when the reference standards were unavailable. As a result, 22 new steroid saponins were found in DZW for the first time. In addition, the quantitative analysis of the nine (except for the reference compounds A, B, and C) known peaks was accomplished at the same time which indicated that there was a great variability in the amount of these active compounds in different batches in the crude extracts. This approach could demonstrate that the fingerprint could be considered to be a suitable tool to comprehensively improve the quality control of DZW. The identification and structural elucidation of the peaks in the fingerprint may provide important experimental data for further pharmacological and clinical researches.
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Modeling urban growth by the use of a multiobjective optimization approach: Environmental and economic issues for the Yangtze watershed, China.
Environ Sci Pollut Res Int
PUBLISHED: 01-07-2014
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Urban growth is an unavoidable process caused by economic development and population growth. Traditional urban growth models represent the future urban growth pattern by repeating the historical urban growth regulations, which can lead to a lot of environmental problems. The Yangtze watershed is the largest and the most prosperous economic area in China, and it has been suffering from rapid urban growth from the 1970s. With the built-up area increasing from 23,238 to 31,054 km(2) during the period from 1980 to 2005, the watershed has suffered from serious nonpoint source (NPS) pollution problems, which have been mainly caused by the rapid urban growth. To protect the environment and at the same time maintain the economic development, a multiobjective optimization (MOP) is proposed to tradeoff the multiple objectives during the urban growth process of the Yangtze watershed. In particular, the four objectives of minimization of NPS pollution, maximization of GDP value, minimization of the spatial incompatibility between the land uses, and minimization of the cost of land-use change are considered by the MOP approach. Conventionally, a genetic algorithm (GA) is employed to search the Pareto solution set. In our MOP approach, a two-dimensional GA, rather than the traditional one-dimensional GA, is employed to assist with the search for the spatial optimization solution, where the land-use cells in the two-dimensional space act as genes in the GA. Furthermore, to confirm the superiority of the MOP approach over the traditional prediction approaches, a widely used urban growth prediction model, cellular automata (CA), is also carried out to allow a comparison with the Pareto solution of MOP. The results indicate that the MOP approach can make a tradeoff between the multiple objectives and can achieve an optimal urban growth pattern for Yangtze watershed, while the CA prediction model just represents the historical urban growth pattern as the future growth pattern. Moreover, according to the spatial clustering index, the urban growth pattern predicted through MOP is more reasonable. In summary, the proposed model provides a set of Pareto urban growth solutions, which compromise environmental and economic issues for the Yangtze watershed.
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Role of H2O2 dynamics in brassinosteroid-induced stomatal closure and opening in Solanum lycopersicum.
Plant Cell Environ.
PUBLISHED: 01-07-2014
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Brassinosteroids (BRs) are essential for plant growth and development; however, their roles in the regulation of stomatal opening or closure remain obscure. Here, the mechanism underlying BR-induced stomatal movements is studied. The effects of 24-epibrassinolide (EBR) on the stomatal apertures of tomato (Solanum lycopersicum) were measured by light microscopy using epidermal strips of wild type (WT), the abscisic acid (ABA)-deficient notabilis (not) mutant, and plants silenced for SlBRI1, SlRBOH1 and SlGSH1. EBR induced stomatal opening within an appropriate range of concentrations, whereas high concentrations of EBR induced stomatal closure. EBR-induced stomatal movements were closely related to dynamic changes in H(2)O(2) and redox status in guard cells. The stomata of SlRBOH1-silenced plants showed a significant loss of sensitivity to EBR. However, ABA deficiency abolished EBR-induced stomatal closure but did not affect EBR-induced stomatal opening. Silencing of SlGSH1, the critical gene involved in glutathione biosynthesis, disrupted glutathione redox homeostasis and abolished EBR-induced stomatal opening. The results suggest that transient H(2)O(2) production is essential for poising the cellular redox status of glutathione, which plays an important role in BR-induced stomatal opening. However, a prolonged increase in H(2)O(2) facilitated ABA signalling and stomatal closure.
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Structure-activity relationship of Baifuzi-cerebrosides on BKCa channel activation.
Eur J Med Chem
PUBLISHED: 01-03-2014
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Our previous study reported that a mixture of cerebrosides from traditional Chinese medicine Baifuzi could activate BKCa channel. It is curious to know the effect of each single cerebroside on the channel. Here we isolated 5 pure cerebrosides from the mixture and determined their chemical structures. The most potent one increased the single channel open probability 6 folds with EC50 value of 1.0 ?M. The structure-activity relationship revealed that acyl chain length of cerebrosides has potent effect, while configuration of double bond at C8-C9 on their long chain base has weak effect on the channel activity. Thus, this research provides a guide for design and synthesis of a lead cerebroside with more potent effect on the BKCa channel.
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The coordination polymer poly[[aqua(?-oxalato)[1H-1,2,4-triazole-5(4H)-thione]cadmium(II)] monohydrate].
Acta Crystallogr C Struct Chem
PUBLISHED: 01-02-2014
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The title complex, {[Cd(C2O4)(C2H3N3S)(H2O)]·H2O}n, has a two-dimensional metal-organic framework, with the Cd(II) cation coordinated by three oxalate ligands, a 1H-1,2,4-triazole-5(4H)-thione (H2trzS) ligand and a water molecule. The CdO6S and oxalate units form an extended two-dimensional layered structure, with the terminal H2trzS ligands bonded to the Cd(II) sites through the thione S atoms. Hydrogen-bond interactions exist between adjacent layers.
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Lgr5 over-expression is positively related to the tumor progression and HER2 expression in stage pTNM IV colorectal cancer.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Recent studies display that Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) appears to involve the initiation of colorectal cancer (CRC). However, its role in the progression of CRC is not clear at present. In the present study, the expression of Lgr5, HER2, VEGF, and Ki-67 was detected by immunohistochemistry in primary cancer tissue and the matched normal mucosa, metastatic lymph node and distant metastatic tissues in 42 CRC cases staged as pTNM IV. The correlation of Lgr5 over-expression with the CRC progression, survival time, and expression of HER2, VEGF, and Ki-67 was evaluated. Moreover, the Lgr5 expression at the invasive front or residual cancer cells around coagulation necrosis was compared with that at the center of CRC in 51 paraffin embedded tissues. The results revealed that Lgr5 over-expression was more frequently found in the metastatic tissues of both lymph nodes and distant area when compared with primary CRC tissue (P<0.05). Additionally, cancer cells in the invasive front and residual cancer cells around or among the coagulation necrosis presented stronger Lgr5 immunoreactivity than that at tumor center (P<0.05), and strong positive staining was often observed in tumor budding cells. While, HER2 over-expression was detected in 28.9% (IHC 3+) and 42.1% (IHC 3+/2+) of CRC patients, neither Lgr5 nor HER2 expression was significantly related to the prognosis of CRC patients, though there was a positive correlation between Lgr5 and HER2 (P<0.05) or Ki-67 expression (P<0.05). In conclusions, Lgr5 over-expression might involve the proliferation, invasion, and distant and regional metastasis of CRC cells, and has potential positive relation to HER2 expression.
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An agomir of miR-144-3p accelerates plaque formation through impairing reverse cholesterol transport and promoting pro-inflammatory cytokine production.
PLoS ONE
PUBLISHED: 01-01-2014
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ATP-binding cassette transporter A1 (ABCA1) mediates the efflux of cholesterol and phospholipids to lipid-poor apolipoproteins, which then form nascent HDL, a key step in the mechanism of reverse cholesterol transport (RCT). While a series of microRNAs (miRNAs) have been identified as potent post-transcriptional regulators of lipid metabolism, their effects on ABCA1 function and associated mechanisms remain unclear.
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Nur77 decreases atherosclerosis progression in apoE(-/-) mice fed a high-fat/high-cholesterol diet.
PLoS ONE
PUBLISHED: 01-01-2014
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It is clear that lipid disorder and inflammation are associated with cardiovascular diseases and underlying atherosclerosis. Nur77 has been shown to be involved in inflammatory response and lipid metabolism.
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[Molecular and epidemiological study of human adenovirus among infants with diarrhea in Nanjing].
Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi
PUBLISHED: 12-11-2013
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To study the prevalence, clinic features and epidemiologic characteristics of human adenovirus diarrhea in Nanjing.
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How well do various health outcome definitions identify appropriate cases in observational studies?
Drug Saf
PUBLISHED: 10-30-2013
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Observational data can be useful for drug safety research, but accurate measurement of adverse health outcomes is paramount. Best practices for identifying important health outcomes of interest (HOI) are needed.
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Hyperammonaemia induces hepatic injury with alteration of gene expression profiles.
Liver Int.
PUBLISHED: 10-13-2013
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Hyperammonaemia is a serious metabolic disorder commonly observed in patients with hepatic failure. However, it is unknown whether hyperammonaemia has a direct adverse effect on the hepatocytes and thereby serves as both a cause and effect of hepatic failure.
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[Hyperammonemia-induced hepatic injury in rats: Characterization of a new animal model].
Zhonghua Gan Zang Bing Za Zhi
PUBLISHED: 09-17-2013
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To establish an accurate new rat model of hyperammonemia-induced liver injury for use in studies of the molecular mechanisms underlying acute liver failure (ALF).
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Ascorbic acid enhances Tet-mediated 5-methylcytosine oxidation and promotes DNA demethylation in mammals.
J. Am. Chem. Soc.
PUBLISHED: 07-01-2013
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DNA hydroxymethylation and its mediated DNA demethylation are critical for multiple cellular processes, for example, nuclear reprogramming, embryonic development, and many diseases. Here, we demonstrate that a vital nutrient ascorbic acid (AA), or vitamin C (Vc), can directly enhance the catalytic activity of Tet dioxygenases for the oxidation of 5-methylcytosine (5mC). As evidenced by changes in intrinsic fluorescence and catalytic activity of Tet2 protein caused by AA and its oxidation-resistant derivatives, we further show that AA can uniquely interact with the C-terminal catalytic domain of Tet enzymes, which probably promotes their folding and/or recycling of the cofactor Fe(2+). Other strong reducing chemicals do not have a similar effect. These results suggest that AA also acts as a cofactor of Tet enzymes. In mouse embryonic stem cells, AA significantly increases the levels of all 5mC oxidation products, particularly 5-formylcytosine and 5-carboxylcytosine (by more than an order of magnitude), leading to a global loss of 5mC (?40%). In cells deleted of the Tet1 and Tet2 genes, AA alters neither 5mC oxidation nor the overall level of 5mC. The AA effects are however restored when Tet2 is re-expressed in the Tet-deficient cells. The enhancing effects of AA on 5mC oxidation and DNA demethylation are also observed in a mouse model deficient in AA synthesis. Our data establish a direct link among AA, Tet, and DNA methylation, thus revealing a role of AA in the regulation of DNA modifications.
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RNAi screening identifies GSK3? as a regulator of DRP1 and the neuroprotection of lithium chloride against elevated pressure involved in downregulation of DRP1.
Neurosci. Lett.
PUBLISHED: 06-27-2013
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Elevated intraocular pressure (IOP) is considered as the major risk factor for the loss of retinal ganglion cells (RGCs) and their axons in glaucoma. Emerging evidence suggests elevated IOP can induce Drp1 upregulation and mitochondrial fission, which is involved in cell death. However, the underlying mechanism for these effects remains unknown. The present study used RNAi screening to investigate the effects of 24 kinases associated with mitochondrial activities on DRP1 expression under hydrostatic pressure. We identified, for the first time, that glycogen synthase kinase 3 beta (GSK3?) knockdown suppressed the upregulation of DRP1 induced by elevated pressure. Use of the pharmacological inhibitor of GSK3? inhibitor, lithium chloride (LiCl), confirmed this result. Furthermore, we demonstrated that one of the mechanisms of lithium chloride neuroprotection might be via inhibition of mitochondrial fission through downregulation of Drp1.
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Decreased Tim-3 and its correlation with Th1 cells in patients with immune thrombocytopenia.
Thromb. Res.
PUBLISHED: 06-08-2013
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Here we evaluate the expression of Tim-3 in CD4+ T cells from patients with immune thrombocytopenia (ITP). We also counted platelets and evaluated plasma IFN-?, IL-18 and IL-4 levels in patients with active ITP (n=26), patients with ITP in remission (n=23) and in healthy subjects (n=34) by enzyme linked immunosorbent assay (ELISA). Using real-time quantitative polymerase chain reaction (RT-PCR), the mRNA expression of IL-18, IFN-?, IL-4, T-box (T-bet) and Tim-3 was studied in the blood. The CD4+ Tim-3+ cells in blood were evaluated by flow cytometry and are expressed as a percentage of the total number of CD4+ cells. The Tim-3 positive cells within the circulating CD4+ population of newly diagnosed patients were significantly decreased compared to controls. However, T-bet, IL-18 and IFN-? levels were significantly elevated in patients. Tim-3 mRNA expression was significantly lower in the peripheral mononuclear cells (PBMCs) of ITP patients compared to controls. The decreased levels of Tim-3 during active stages of disease suggest a possible role in the pathogenesis and course of ITP and restoration of Tim-3 may be a reasonable therapeutic strategy for ITP.
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[Comparative study on pharmacokinetics of senkyunolide I after administration of simple recipe and compound recipe in rats].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 05-15-2013
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To develop a LC-MS method for the determination of senkyunolide I (SI) in rat plasma, in order to observe whether there is significant change in the pharmacokinetics parameters of complex prescriptions of Huoluoxiaolingdan (HLXL) and single herbal extracts from Ligusticum chuanxiong Hort. in rats, and assess the effect of other components in HLXL on the pharmacokinetics of SI.
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[Study on the levels of DA and metabolite in striatum in rats with Parkinsons disease treated by BDNF gene modified bone mesenchymal stem cells].
Zhongguo Ying Yong Sheng Li Xue Za Zhi
PUBLISHED: 05-14-2013
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To investigate the effects of dopamine (DA) and metabolite in striatum of Parkinsons disease (PD) rats treated by bone mesenchymal stem cells (MSCs) modified by plasmid pIRESneo-EGFP-BDNF.
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A tubular one-dimensional polymer constructed from alternating clusters of europium(III)-water and copper(I) chloride bridged by 4-(pyridin-4-yl)benzoate.
Acta Crystallogr C
PUBLISHED: 05-05-2013
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A new 3d-4f heterometallic polymer, poly[[aqua-?3-chlorido-[?3-4-(pyridin-4-yl)benzoato]tris[?2-4-(pyridin-4-yl)benzoato]dicopper(I)erbium(III)] dihydrate], {[Cu2Er(C12H8NO2)4Cl(H2O)]·2H2O}n, was synthesized by the hydrothermal reaction of Er2O3, CuCl2·2H2O and 4-(pyridin-4-yl)benzoic acid in the presence of HClO4. The asymmetric unit contains one Er(3+) cation, two Cu(+) cations, one Cl(-) anion, four deprotonated 4-(pyridin-4-yl)benzoate ligands, one coordinated aqua ligand and two solvent water molecules. This tubular one-dimensional polymer is constructed from alternating clusters of europium(III)-water and copper(I) chloride bridged by 4-(pyridin-4-yl)benzoate ligands. Extensive hydrogen-bonding interactions involving both the coordinated and the solvent water molecules provide further stabilization to the structure.
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[Correlation of chromosome karyotype with dyshaematopoiesis and reticulin in myelodysplastic syndrome].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 05-01-2013
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This study was purposed to explore the correlation of chromosome karyotype with dyshaematopoiesis and reticulin in myelodysplastic syndrome (MDS). The data of 202 MDS patients diagnosed and treated in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed in term of chromosome karyotype, dyshaematopoiesis and reticulin detection results. The chromosome karyotypes were categorized according to the International Prognostic Scoring System (IPSS). The results showed that there was a positive correlation between chromosome karyotype grading and number of lineages with dyshaematopoiesis (r = 0.443, P < 0.05). The detected rates of multilineage dyshaematopoiesis in patients with good, intermediate and poor chromosome karyotypes were 44.4%, 71.4% and 96.3% respectively. There was a positive correlation between chromosome karyotype grading and reticulin grading (r = 0.451, P < 0.05). The positive rates of reticulin in patients with good grading, intermediate and poor chromosome karyotypes were 36.8%, 64.3% and 92.6% respectively. The detected rate of multilineage dyshaematopoiesis, number of lineages with dyshaematopoiesis, the positive rate of reticulin and reticulin grade in patients with poor karyotypes were higher than those in patients with intermediate or good chromosome karyotypes (separately P < 0.01). The above data in patients with intermediate chromosome karyotypes were higher than those in patients with good chromosome karyotypes (separately P < 0.01). It is concluded that the chromosome karyotype grading positively correlates with the number of lineages with dyshaematopoiesis and reticulin grading. When the chromosome karyotype changed from good to poor, the detected rate of multilineage dyshaematopoiesis, number of lineages with dyshaematopoiesis, positive rate of reticulin and reticulin grading became higher and higher.
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Developing an expert panel process to refine health outcome definitions in observational data.
J Biomed Inform
PUBLISHED: 04-30-2013
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Drug safety surveillance using observational data requires valid adverse event, or health outcome of interest (HOI) measurement. The objectives of this study were to develop a method to review HOI definitions in claims databases using (1) web-based digital tools to present de-identified patient data, (2) a systematic expert panel review process, and (3) a data collection process enabling analysis of concepts-of-interest that influence panelists determination of HOI.
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Activation of persulfate by quinones: free radical reactions and implication for the degradation of PCBs.
Environ. Sci. Technol.
PUBLISHED: 04-26-2013
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There has been considerable interest in the use of persulfate for in situ chemical oxidation of organic contaminants in soils, sediments, and groundwater. Since humic acid (HA) exists ubiquitously in these environmental compartments, its redox active functional moieties, such as quinones, may play an important role in the oxidation processes of persulfate treatments. Understanding the effects of HA, especially the quinone functional groups on the degradation of pollutants by persulfate and the production of sulfate radicals (SO4(•-)) from persulfate, is beneficial for devising effective and economically feasible remediation strategies. In this study, the effects of model quinone compounds and HA on the degradation of 2,4,4-trichlorobiphenyl (PCB28) by persulfate and the production of SO4(•-) from persulfate were investigated. It was found that quinones and HA can efficiently activate persulfate for the degradation of PCB28. The mechanism of persulfate activation was elucidated by quenching and electron paramagnetic resonance (EPR) studies. The results indicated that production of SO4(•-) from persulfate and quinones was semiquinone radical-dependent. The effects of quinone concentrations were also studied. The findings of this study elucidated a new pathway of persulfate activation, which could degrade environmental contaminants efficiently and provide useful information for the remediation of contaminated soil and water by persulfate.
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Optimized expression, purification and characterization of a family 11 xylanase (AuXyn11A) from Aspergillus usamii E001 in Pichia pastoris.
J. Sci. Food Agric.
PUBLISHED: 04-07-2013
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Xylanases have attracted much attention because of their potential applications. Unfortunately, the commercialization of xylanases is limited by their low catalytic activities. The aim of this study was to improve the activity of a xylanase by optimization of the expression conditions and to investigate its characterization.
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The Globular Heads of the C1q Receptor Regulate Apoptosis in Human Extravillous Cytotrophoblast-derived Transformed Cells via a Mitochondria-dependent Pathway.
Am. J. Reprod. Immunol.
PUBLISHED: 03-28-2013
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The receptor for the globular head of human C1q (gC1qR) predominantly localizes to the mitochondrial matrix. gC1qR mediates many biological responses, including growth perturbations, morphological abnormalities and the initiation of apoptosis. The purpose of this study was to investigate the relationship between gC1qR expression, mitochondrial dysfunction and the regulation of apoptosis in human extravillous cytotrophoblast (EVCT)-derived transformed cell lines (HTR-8/SVneo and HPT-8).
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Integrity of kindlin-2 FERM subdomains is required for supporting integrin activation.
Biochem. Biophys. Res. Commun.
PUBLISHED: 03-22-2013
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Kindlin family members are essential for supporting integrin activation by functionally cooperating with the talin head domain. Both the talin head and kindlin are FERM domain-containing proteins that can simultaneously interact with the integrin ? cytoplasmic tails. While the talin head is well studied, the molecular basis of kindlins interaction with integrin during integrin activation is still poorly understood. Here we defined the subdomain boundaries in kindlin-2 and evaluated their contribution to integrin activation and recognition. We found that each subdomain in kindlin-2 was required for co-activating the integrin ?IIb?3 together with the talin head (inside-out signaling) and for enhancing integrin ?IIb?3-mediated cell spreading (outside-in signaling). To evaluate the involvement of the kindlin-2 subdomains in integrin interaction, we developed a FACS-based binding assay and found that an intact FERM domain in kindlin-2 was required for the interaction. Taking all together, these findings suggest that the integrity of kindlin-2 subdomains is a prerequisite for supporting integrin recognition and for subsequent integrin activation.
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CSP typing of Chinese Aspergillus fumigatus isolates: identification of additional CSP types.
Med. Mycol.
PUBLISHED: 03-19-2013
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Cell surface protein (CSP) typing is a typing strategy that employs comparative DNA sequence analysis of the 12-mer tandem repeat region of the AFUA_3G08890 gene. The CSP typing scheme and modified nomenclature was applied to a collection of 162 clinical Aspergillus fumigatus isolates from China. A total of 16 CSP variants were observed, including five that were newly reported, indicating that phylogeographic differences may exist between the Chinese and the previously studied Australian, European and North American A. fumigatus populations. However, the most common CSP variants observed in this study are consistent with those in previous studies.
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Genome-wide profiling of 5-formylcytosine reveals its roles in epigenetic priming.
Cell
PUBLISHED: 02-19-2013
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TET proteins oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). 5fC and 5caC are excised by mammalian DNA glycosylase TDG, implicating 5mC oxidation in DNA demethylation. Here, we show that the genomic locations of 5fC can be determined by coupling chemical reduction with biotin tagging. Genome-wide mapping of 5fC in mouse embryonic stem cells (mESCs) reveals that 5fC preferentially occurs at poised enhancers among other gene regulatory elements. Application to Tdg null mESCs further suggests that 5fC production coordinates with p300 in remodeling epigenetic states of enhancers. This process, which is not influenced by 5hmC, appears to be associated with further oxidation of 5hmC and commitment to demethylation through 5fC. Finally, we resolved 5fC at base resolution by hydroxylamine-based protection from bisulfite-mediated deamination, thereby confirming sites of 5fC accumulation. Our results reveal roles of active 5mC/5hmC oxidation and TDG-mediated demethylation in epigenetic tuning at regulatory elements.
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The role of globular heads of the C1q receptor in HPV 16 E2-induced human cervical squamous carcinoma cell apoptosis is associated with p38 MAPK/JNK activation.
J Transl Med
PUBLISHED: 02-07-2013
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Human papillomavirus type 16 (HPV 16) E2 protein is a multifunctional DNA-binding protein. HPV 16 E2 regulates many biological responses, including DNA replication, gene expression, and apoptosis. The purpose of this study was to investigate the relationship among the receptor for globular heads of the human C1q (gC1qR) gene expression, HPV 16 E2 transfection and apoptosis regulation in human cervical squamous carcinoma cells (C33a and SiHa).
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Expert panel assessment of acute liver injury identification in observational data.
Res Social Adm Pharm
PUBLISHED: 01-25-2013
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Observational data are useful for studying drug safety; however, to be effective, accurate outcome measurement is paramount.
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Dynamic expression of microRNAs during the differentiation of human embryonic stem cells into insulin-producing cells.
Gene
PUBLISHED: 01-07-2013
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Human embryonic stem (hES) cells with the capacity of self-renewal and multilineage differentiation are promising sources for generation of pancreatic islet cells for cell replacement therapy in diabetes. Here we induced hES cells into insulin-producing cells (IPCs) in a stepwise process which recapitulated islet organogenesis by directing cells through the stages resembling definitive endoderm, gut-tube endoderm, pancreatic precursor and cells that expressed pancreatic endocrine hormones. The dynamic expression of microRNAs (miRNAs) during the differentiation was analyzed and was compared with that in the development of human pancreatic islets. We found that the dynamic expression patterns of miR-375 and miR-7 were similar to those seen in the development of human fetal pancreas, whereas the dynamic expression of miR-146a and miR-34a showed specific patterns during the differentiation. Furthermore, the expression of Hnf1? and Pax6, the predicted target genes of miR-375 and miR-7, was reciprocal to that of miR-375 and miR-7. Over-expression of miR-375 down-regulated the expression of gut-endoderm/pancreatic progenitor specific markers Hnf1? and Sox9. Therefore, the miRNAs may directly or indirectly regulate the expression of pancreatic islet organogenesis-specific transcription factors to control the differentiation and maturation of pancreatic islet cells.
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Angiotensin type 2 receptors in the intermediolateral cell column of the spinal cord: negative regulation of sympathetic nerve activity and blood pressure.
Int. J. Cardiol.
PUBLISHED: 01-03-2013
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Our previous study demonstrated that AT2R in brainstem nuclei participated in the regulation of sympathetic outflow and cardiovascular function. However, the functional significance of AT2R in the intermediolateral cell column (IML) of the thoracic spinal cord in normal rats remains elusive. We hypothesized that AT2R activation in the IML exerts a sympatho-inhibitory effect.
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Fusing a carbohydrate-binding module into the Aspergillus usamii ?-mannanase to improve its thermostability and cellulose-binding capacity by in silico design.
PLoS ONE
PUBLISHED: 01-01-2013
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The AuMan5A, an acidophilic glycoside hydrolase (GH) family 5 ?-mannanase derived from Aspergillus usamii YL-01-78, consists of an only catalytic domain (CD). To perfect enzymatic properties of the AuMan5A, a family 1 carbohydrate-binding module (CBM) of the Trichoderma reesei cellobiohydrolase I (TrCBH I), having the lowest binding free energy with cellobiose, was selected by in silico design, and fused into its C-terminus forming a fusion ?-mannanase, designated as AuMan5A-CBM. Then, its encoding gene, Auman5A-cbm, was constructed as it was designed theoretically, and expressed in Pichia pastoris GS115. SDS-PAGE analysis displayed that both recombinant AuMan5A-CBM (reAuMan5A-CBM) and AuMan5A (reAuMan5A) were secreted into the cultured media with apparent molecular masses of 57.3 and 49.8 kDa, respectively. The temperature optimum of the reAuMan5A-CBM was 75°C, being 5°C higher than that of the reAuMan5A. They were stable at temperatures of 68 and 60°C, respectively. Compared with reAuMan5A, the reAuMan5A-CBM showed an obvious decrease in K m and a slight alteration in V max. In addition, the fusion of a CBM of the TrCBH I into the AuMan5A contributed to its cellulose-binding capacity.
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Facile synthesis of acid-labile polymers with pendent ortho esters.
Biomacromolecules
PUBLISHED: 12-28-2011
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This work presents a facile approach for preparation of acid-labile and biocompatible polymers with pendent cyclic ortho esters, which is based on the efficient and mild reactions between cyclic ketene acetal (CKA) and hydroxyl groups. Three CKAs, 2-ethylidene-1,3-dioxane (EDO), 2-ethylidene-1,3-dioxolane (EDL), and 2-ethylidene-4- methyl-1,3-dioxolane (EMD) were prepared from the corresponding cyclic vinyl acetals by catalytic isomerization of the double bond. The reaction of CKAs with different alcohols and diols was examined using trace of p-toluenesulfonic acid as a catalyst. For the monohydroxyl alcohols, cyclic ortho esters were formed by simple addition of the hydroxyl group toward CKAs with ethanol showing a much greater reactivity than iso-propanol. When 1,2- or 1,3-diols were used to react with the CKAs, we observed the isomerized cyclic ortho esters besides the simple addition products. Biocompatible polyols, that is, poly(2-hydroxyethyl acrylate) (PHEA) and poly(vinyl alcohol) (PVA) were then modified with CKAs, and the degree of substitution of the pendent ortho esters can be easily tuned by changing feed ratio. Both the small molecule ortho esters and the CKA-modified polymers demonstrate the pH-dependent hydrolysis profiles, which depend also on the chemical structure of the ortho esters as well as the polymer hydrophobicity.
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[Severe sepsis as an initial presentation in children with Wernicke s encephalopathy: report of a case and literature review].
Zhonghua Er Ke Za Zhi
PUBLISHED: 11-19-2011
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Wernickes encephalopathy (WE) is an acute neuropsychiatric syndrome resulting from thiamine deficiency, which is associated with significant morbidity and mortality. The disorder is still greatly underdiagnosed in children because of either a relatively non-specific clinical presentation in some cases or unrecognized clinical setting. The aim of this literature review was to provide knowledge of pediatric WE in an effort to assist in early diagnosis, thereby reducing the morbidity and mortality.
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Endocrine disruptors, polychlorinated biphenyls-induced gC1qR-dependent apoptosis in human trophoblast cell line HTR-8/SVneo.
Reprod Sci
PUBLISHED: 11-18-2011
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Although an association exists between exposure to polychlorinated biphenyls (PCBs) and spontaneous miscarriage, the mechanisms underlying this phenomenon remain unclear. In this study, PCBs content in plasma was detected by gas chromatography-mass spectrometry (GC-MS) and decidua tissues were examined for the expression of globular heads of C1q receptor (gC1qR) using Western blot in patients who underwent induced abortion and spontaneous abortion. Results showed increased PCBs content and gC1qR expression in patients who experienced spontaneous abortion. In vitro, Western blot analysis demonstrated significantly higher caspase 3 expression and apoptotic cell counts in green fluorescent protein (GFP)-gC1qR vector group. Additionally, gC1qR and caspase 3 showed decreased expression following PCBs plus gC1qR small interfering RNA (siRNA) treatment. The percentage of apoptotic cells increased in cells treated with PCBs alone or PCB plus negative siRNA. These data suggest that maternal exposure to PCBs is associated with adverse pregnancy outcomes and that upregulation of gC1qR is important for PCBs-mediated trophoblast cell apoptosis.
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Ghrelin promotes differentiation of human embryonic stem cells into cardiomyocytes.
Acta Pharmacol. Sin.
PUBLISHED: 08-01-2011
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Ghrelin is involved in regulating the differentiation of mesoderm-derived precursor cells. The aim of this study was to investigate whether ghrelin modulated the differentiation of human embryonic stem (hES) cells into cardiomyocytes and, if so, whether the effect was mediated by growth hormone secretagogue receptor 1? (GHS-R1?).
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SOD1 overexpression in paraventricular nucleus improves post-infarct myocardial remodeling and ventricular function.
Pflugers Arch.
PUBLISHED: 06-05-2011
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Excessive sympathetic activation contributes to the progression of chronic heart failure. Reactive oxygen species in paraventricular nucleus (PVN) play an important role in the enhanced sympathetic outflow. This study was designed to determine whether superoxide dismutase 1 (SOD1) overexpression in the PVN attenuated the sympathetic activation and cardiac dysfunction in rats after an episode of myocardial infarction (MI). Adenoviral vectors containing human SOD1 (Ad-SOD) or null adenoviral vectors (Ad-null) were immediately microinjected into the PVN of rats with coronary artery ligation or sham operation. At the eighth week, the SOD1 protein level and activity in the PVN increased while the superoxide anions in the PVN decreased in Ad-SOD rats. The SOD1 overexpression in the PVN prevented the increases in left ventricular end-diastolic pressure and volume, and the decreases in ejection fraction and peak velocities of contraction in MI rats. In addition, there was an attenuation of renal sympathetic nerve activity, cardiac sympathetic afferent reflex and plasma norepinephrine level in MI rats. Furthermore, the SOD1 overexpression in the PVN reduced cardiomyocyte size, collagen deposition and the TUNEL-positive cardiomyocytes in MI rats. These results indicate that the SOD1 overexpression in the PVN attenuates the excessive sympathetic activation, myocardial remodeling, cardiomyocyte apoptosis and ventricular dysfunction in MI rats.
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M2-polarized tumor-associated macrophages are associated with poor prognoses resulting from accelerated lymphangiogenesis in lung adenocarcinoma.
Clinics (Sao Paulo)
PUBLISHED: 05-29-2011
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Tumor-associated macrophages have been implicated in promoting tumor growth, progression and metastasis. However, the activated phenotype (M1 or M2) of tumor-associated macrophages remains unknown in solid tumors. Therefore, this study examined the density and prognostic significance of M2-polarized tumor-associated macrophages in lung adenocarcinoma.
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The role of gC1qR in regulating survival of human papillomavirus 16 oncogene-transfected cervical cancer cells.
Int. J. Oncol.
PUBLISHED: 04-28-2011
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Human papillomavirus 16 (HPV-16) is strongly associated with the development of 50% of cervical cancers. The E6 and E7 proteins encoded by high-risk HPV types are associated with the immune evasion of cervical cancer cells, but the mechanism is poorly understood. The purpose of this study was to investigate whether cells transfected with E6 and E7 expression constructs reduce the expression of the globular heads of the C1q receptor (gC1qR), a mitochondrial surface protein overexpressed in certain cancer cells. First, C-33A cells were transiently transfected with the HPV-16 E6 and E7 oncogenes which resulted in gC1qR inhibition and a reduction in apoptosis. Second, gC1qR overexpression in cells showed that caspase-3 activation and mitochondrial dysfunction were involved in gC1qR-induced apoptosis. Cells transfected with a GFP-gC1qR vector resulted in upregulated gC1qR protein and a gradual increase in the generation of reactive oxygen species (ROS). Additionally, ROS generation and increased Ca2+ influx in mitochondria resulted in the loss of the mitochondrial transmembrane potential. Interestingly, when gC1qR was overexpressed in C-33A cells, apoptosis was significantly inhibited when cells were treated with metformin, which may protect mitochondrial function. These data suggest that gC1qR could play an important role in HPV-16-induced cervical cancer immune evasion depending on its level of expression and subcellular localisation.
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Small interfering RNA targeting integrin-linked kinase inhibited the growth and induced apoptosis in human bladder cancer cells.
Int. J. Biochem. Cell Biol.
PUBLISHED: 04-01-2011
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Integrin-linked kinase (ILK), an intracellular serine/threonine kinase, is implicated in cell growth and survival, cell-cycle progression, tumor angiogenesis, and cell apoptosis. Recent studies showed that the expression and activity of ILK increased significantly in many types of solid tumors. However, the exact molecular mechanism of ILK underlie tumor has not been fully ascertained. The purpose of our study was to determine whether knockdown of ILK would inhibit cell growth and induce apoptosis in bladder cancer cells using a plasmid vector based small interfering RNA (siRNA). The experiments showed that knockdown of ILK could remarkably inhibit cell proliferation and growth, regulate cell cycle and induce apoptosis of bladder cancer BIU-87 and EJ cells. We demonstrated that knockdown of ILK inhibited phosphorylation of downstream signaling targets protein kinase B/Akt, glycogen synthase kinase 3-beta (GSK-3?), and reduced expression of ?-catenin in BIU-87 as well as EJ cells by Western blot and Immunofluorescence analysis. In addition, down-regulation of ILK also could increase expression of Ribonuclease inhibitor (RI), an important acidic cytoplasmic protein with many functions. BALB/C nude mice injected with the BIU-87 cells transfected ILK siRNA showed a significant inhibition of the tumor growth with lighter tumor weight, lower microvessels density and higher apoptosis rate than those in the other two control groups. In conclusion, these results suggest that ILK might be involved in the development of bladder cancer, and could be served as a novel potential therapy target for human bladder cancer. Our study may be of biological and clinical importance.
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Activation of central angiotensin type 2 receptors suppresses norepinephrine excretion and blood pressure in conscious rats.
Am. J. Hypertens.
PUBLISHED: 03-10-2011
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We have previously documented the finding that central angiotensin type 2 receptors (AT2R) negatively modulate sympathetic outflow and arterial blood pressure (BP). In this study, we investigated the effects of intracerebroventricular (icv) infusion of Compound 21 (C21), the first selective nonpeptide AT2R agonist, on norepinephrine (NE) excretion and BP in rats.
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Open-framework aluminoborates co-templated by two types of primary amines.
Dalton Trans
PUBLISHED: 02-14-2011
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A series of open-framework aluminoborates (ABOs), [CH(3)NH(3)][(CH(3)CH(2))(2)NH(2)][Al(B(5)O(10))] (1), [CH(3)CH(2)NH(3)][(CH(3)CH(2))(2)NH(2)][Al(B(5)O(10))] (2), [CH(3)CH(2)NH(3)][(CH(3))(2)NH(2)](H(2)O)(0.5)[Al(B(5)O(10))] (3) and [CH(3)NH(3)][CH(3)CH(2)NH(3)](H(2)O)(2)[Al(B(5)O(10))] (4) have been made co-templated by two types of primary amines under solvothermal conditions and characterized by elemental analysis, IR, TGA, UV-Vis, powder XRD, single crystal XRD and NLO determination, respectively. These four ABOs display two structural types: 1, 2 and 3 are isostructural and exhibit CrB(4) topology, showing three different layers along three different directions; while 4 contains 8-, 14-ring layers, which are packed along the [001] direction to form a noncentrosymmetric 3D framework with 8-, 14-ring channels, showing second harmonic generation (SHG) response that is about 0.5 times that of KDP (KH(2)PO(4)). The electronic structure calculations for 1 and 4 also have been performed.
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c-Src in paraventricular nucleus modulates sympathetic activity and cardiac sympathetic afferent reflex in renovascular hypertensive rats.
Pflugers Arch.
PUBLISHED: 02-01-2011
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Enhanced cardiac sympathetic afferent reflex (CSAR) contributes to sympathetic activation in renovascular hypertension. The study was to determine whether c-Src in paraventricular nucleus (PVN) is involved in the enhanced CSAR and sympathetic activation in hypertensive rats induced by two-kidney one-clip (2K1C). At the end of the fourth week after 2K1C surgery, renal sympathetic nerve activity (RSNA) was recorded in anesthetized rats with baroreceptor denervation and vagotomy. The CSAR was evaluated by the RSNA response to epicardial application of capsaicin. In the PVN, c-Src activity was higher in 2K1C rats than sham-operated (Sham) rats while c-Src expression was not. Epicardial application of capsaicin or PVN microinjection of angiotensin II (Ang II) increased c-Src activity more in 2K1C than Sham rats. PVN microinjection of selective Src family kinase inhibitor 4-Amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazol [3,4-D] pyrimidine (PP2) or 2,3-Dihydro-N,N-dimethyl-2-oxo-3-[(4,5,6,7-tetrahydro-1 H-indol-2-yl)methylene]-1 H-indole-5-sulfonamide (SU6656) abolished the CSAR and decreased RSNA more in 2K1C than Sham rats. The Ang II-induced RSNA and CSAR enhancement was abolished by PP2 or SU6656 pretreatment in 2K1C and Sham rats. NAD(P)H oxidase activity and superoxide anion level in PVN were higher in 2K1C rats, which was attenuated by PP2 but increased by epicardial application of capsaicin or PVN microinjection of Ang II. The effects of capsaicin or Ang II were abolished by PP2. These results indicate that c-Src in the PVN is involved in the enhanced CSAR and sympathetic activation in renovascular hypertension, and mediates the excitatory effects of Ang II in the PVN on the CSAR and sympathetic activity via NAD(P)H oxidase-derived generation of superoxide anions.
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Reprogramming of mouse and human somatic cells by high-performance engineered factors.
EMBO Rep.
PUBLISHED: 01-15-2011
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Reprogramming somatic cells to become induced pluripotent stem cells (iPSCs) by using defined factors represents an important breakthrough in biology and medicine, yet remains inefficient and poorly understood. We therefore devised synthetic factors by fusing the VP16 transactivation domain to OCT4 (also known as Pou5f1), NANOG and SOX2, respectively. These synthetic factors could reprogramme both mouse and human fibroblasts with enhanced efficiency and accelerated kinetics. Remarkably, Oct4-VP16 alone could efficiently reprogramme mouse embryonic fibroblasts (MEFs) into germline-competent iPSCs. Furthermore, episomally delivered synthetic factors could reproducibly generate integration-free iPSCs from MEFs with enhanced efficiency. Our results not only demonstrate the feasibility of engineering more potent reprogramming factors, but also suggest that transcriptional reactivation of OCT4 target genes might be a rate-limiting step in the conversion of somatic cells to pluripotent cells. Synthetic factor-based reprogramming might lead to a paradigm shift in reprogramming research.
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Dynamic integration of reward and stimulus information in perceptual decision-making.
PLoS ONE
PUBLISHED: 01-11-2011
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In perceptual decision-making, ideal decision-makers should bias their choices toward alternatives associated with larger rewards, and the extent of the bias should decrease as stimulus sensitivity increases. When responses must be made at different times after stimulus onset, stimulus sensitivity grows with time from zero to a final asymptotic level. Are decision makers able to produce responses that are more biased if they are made soon after stimulus onset, but less biased if they are made after more evidence has been accumulated? If so, how close to optimal can they come in doing this, and how might their performance be achieved mechanistically? We report an experiment in which the payoff for each alternative is indicated before stimulus onset. Processing time is controlled by a "go" cue occurring at different times post stimulus onset, requiring a response within msec. Reward bias does start high when processing time is short and decreases as sensitivity increases, leveling off at a non-zero value. However, the degree of bias is sub-optimal for shorter processing times. We present a mechanistic account of participants performance within the framework of the leaky competing accumulator model [1], in which accumulators for each alternative accumulate noisy information subject to leakage and mutual inhibition. The leveling off of accuracy is attributed to mutual inhibition between the accumulators, allowing the accumulator that gathers the most evidence early in a trial to suppress the alternative. Three ways reward might affect decision making in this framework are considered. One of the three, in which reward affects the starting point of the evidence accumulation process, is consistent with the qualitative pattern of the observed reward bias effect, while the other two are not. Incorporating this assumption into the leaky competing accumulator model, we are able to provide close quantitative fits to individual participant data.
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What is Visualize?

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

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

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