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Find video protocols related to scientific articles indexed in Pubmed.
hARIP2 is a Putative Growth-promoting Factor Involved in Human Colon Tumorigenesis.
Asian Pac. J. Cancer Prev.
PUBLISHED: 11-07-2014
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Activin is a multifunctional growth and differentiation factor of the growth factor-beta (TGF-?) superfamily, which inhibits the proliferation of colon cancer cells. It induces phosphorylation of intracellular signaling molecules (Smads) by interacting with its type I and type II receptors. Previous studies showed that human activin receptor-interacting protein 2 (hARIP2) can reduce activin signaling by interacting with activin type II receptors; however, the activity of hARIP2 in colon cancer has yet to be detailed. In vitro, overexpression of hARIP2 reduced activin-induced transcriptional activity and enhanced cell proliferation and colony formation in human colon cancer HCT8 cells and SW620 cells. Also, hARIP2 promoted colon cancer cell apoptosis, suggesting that a vital role in the initial stage of colon carcinogenesis. In vivo, immunohistochemistry revealed that hARIP2 was expressed more frequently and much more intensely in malignant colon tissues than in controls. These results indicate that hARIP2 is involved in human colon tumorigenesis and could be a predictive maker for colon carcinoma aggressiveness.
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[Hyperspectral extraction of soil available nitrogen in Nan Mountain coal waste scenic spot of Jinhuagong Mine based on enter-PLSR].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 11-01-2014
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Soil available nitrogen content is an important index reflecting soil fertility. It provides dynamic information for land reclamation and ecological restoration if soil available nitrogen can be monitored and evaluated using hyperspectral technology. Facing the study blank of soil available nitrogen in National Mine Park and the deficiency of poor computational efficiency of partial least squares regression (PLSR) method, the present paper presents the relationship between soil spectrum and soil available nitrogen based on spectrum curves (ranging from 350 to 2 500 nm) of 30 salinized chestnut soil samples, which were collected from southern mountain coal waste scenic spot, located in Jinhuagong mine in Datong city, Shanxi Province, China (one part of Jinhuagong national mine park). Soil reflection spectrum was mathematically manipulated into first derivative and inverse-log spectral curves, then a corresponding estimation model was built and examined by PLSR and Enter-partial least squares regression (Enter-PLSR) based on characteristic absorption. The result indicated that Enter-PLSR corresponding estimation model greatly increased the computation efficiency by reducing the number of independent variables to 12 from 122 in case of a close accuracy of PLS corresponding estimation model. By using hyperspectral technology and Enter-PLSR method, the study blank of soil available nitrogen in National Mine Park was filled. At the same time, the computation efficiency problem of PLSR was resolved.
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Association of vitamin D receptor gene polymorphisms with the susceptibility to ulcerative colitis in patients from Southeast China.
J. Recept. Signal Transduct. Res.
PUBLISHED: 10-28-2014
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Abstract The association studies from different ethnic groups showed that vitamin D receptor (VDR) gene polymorphisms might be connected with the susceptibility to ulcerative colitis (UC); however, the conclusions were less consistent. Our study aimed to analyze the associations of UC with common mutations of VDR in Chinese patients. A total of 382 UC patients and 489 healthy controls were recruited. The genotypes of VDR FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) were examined by SNaPshot assays. Haplotype analysis was performed in all study subjects. After Bonferroni correction, the mutant alleles and genotypes of VDR FokI, BsmI, ApaI and TaqI did not statistically differ between UC patients and the controls (all p?>?0.0125). However, the mutant allele C and genotype TC?+?CC of FokI gene were significantly increased in patients with mild and moderate UC compared to those with severe UC (C allele: 54.1% versus 39.3%, OR?=?1.83, 95% CI: 1.21-2.75, p?=?0.004; TC?+?CC genotype: 81.6% versus 57.1%, OR?=?3.32, 95% CI: 1.83-6.06, p?
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Citrate-capped platinum nanoparticle as a smart probe for ultrasensitive mercury sensing.
Anal. Chem.
PUBLISHED: 10-27-2014
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An easily prepared platinum nanoparticle (PtNP) probe for the sensitive and selective detection of Hg(2+) ions is developed here. The PtNPs with an average size of approximately 2.5 nm were prepared by a reduction method with sodium borohydride and trisodium citrate serving as reductant and stabilizer, respectively. The resulting PtNPs could catalyze the reduction of Hg(2+) by surface-capping citrate. The effect of Hg(2+) uptake implies amalgam formation, which leads to remarkable inhibition of the peroxidase-like activity of citrate-capped PtNPs. On the basis of this effect, a colorimetric mercury sensor was established through the use of citrate-capped PtNPs to catalyze the colorimetric system of 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2. The high specificity of the Hg-Pt interaction provides the excellent selectivity for Hg(2+) over interfering metal ions. The sensitivity of this smart probe to Hg(2+) is extremely excellent with a limit of detection (LOD) as low as 8.5 pM. In view of these advantages, as well as the cost-effectiveness, minimized working steps, and naked-eye observation, we expect that this colorimetric sensor will be a promising candidate for the field detection of toxic Hg(2+) ions in environmental, biological, and food samples.
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[Risk factors of hepatolithasis-associated intrahepatic cholangiocarcinoma and the value of serum tumor-related makers in its diagnosis].
Sichuan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 10-08-2014
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To explore the risk factors of hepatolithasis-associated intrahepatic cholangiocarcinoma (HICC) and the clinical value of serum tumor-related markers for the detection of HICC.
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[Comparative study of Coptidis Rhizoma and Aconiti Kusnezoffii Radix on cell differentiation in lewis lung cancer].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 10-03-2014
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Coptidis Rhizoma and Aconiti Kusnezoffii Radix represent hot Chinese medicine and cold Chinese medicine respectively. The purpose of this study is to observe the differentiation effect of Coptidis Rhizoma and Aconiti Kusnezoffii Radix on lewis lung cancer and compare effect of hot Chinese medicine and cold Chinese medicine on tumor progression. In this study, the rat serum containing Coptidis Rhizoma or Aconiti Kusnezoffii Radix was prepared to treat lewis lung cancer cells in vitro, and effects of the serum containing Coptidis Rhizoma or Aconiti Kusnezoffii Radix on cell differentiation, proliferation, adhesion, succinic dehydrogenase (SDH) activity and gap-junction intercellular communication (GJIC) were investigated. In vivo, the subcutaneous implant model and pulmonary metastasis model of lewis lung cancer were established. Tumor bearing mice were taken water decoction of coptis chinensis or aconite by intragastric administration bid for four weeks, and the influences of coptis chinensis and aconite on tumor progression were evaluated by body temperature, blood oxygen saturation, red cell ATPase, blood rheology, intratumor hypoxia, capillary permeability and GJIC. The results showed that the serum containing aconite could induce cell differentiation, inhibit cell proliferation and migration, promote SDH activity and GJIC in lewis lung cancer cells. The serum containing Coptidis Rhizoma increased cell adhesion and decreased SDH activity and GJIC without cell differentiation although it also suppressed cell proliferation. Aconiti Kusnezoffii Radix water decoction could keep body temperature, blood oxygen saturation, red cell ATPase and blood rheology, and improve intratumor hypoxia, capillary permeability and GJIC in tumor bearing mice, which led to slower tumor growth and less metastasis. Coptidis Rhizoma water decoction decreased body temperature, blood oxygen saturation, red cell ATPase, blood rheology and GJIC, and promoted intratumor hypoxia and capillary permeability, which resulted to more tumor metastasis although it also prevented tumor growth. These results suggested that the hot Chinese medicine could induce tumor cell differentiation and prevent tumor poison invagination, which is better for tumor treatment than cold Chinese medicine.
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[Investigation and analysis of heavy metal pollution related to soil-Panax notoginseng system].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 10-03-2014
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In this study, five heavy metals contamination of soil and different parts of Panax notoginseng in the plantation area was investigated. Analysis of heavy metals correlation between the planting soil and P. notoginseng; and the absorption and accumulation characteristics and translocation of soil heavy metals by P. notoginseng plants was revealed.
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CARD9 mediates Dectin-1-induced ERK activation by linking Ras-GRF1 to H-Ras for antifungal immunity.
J. Exp. Med.
PUBLISHED: 09-29-2014
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Dectin-1 functions as a pattern recognition receptor for sensing fungal infection. It has been well-established that Dectin-1 induces innate immune responses through caspase recruitment domain-containing protein 9 (CARD9)-mediated NF-?B activation. In this study, we find that CARD9 is dispensable for NF-?B activation induced by Dectin-1 ligands, such as curdlan or Candida albicans yeast. In contrast, we find that CARD9 regulates H-Ras activation by linking Ras-GRF1 to H-Ras, which mediates Dectin-1-induced extracellular signal-regulated protein kinase (ERK) activation and proinflammatory responses when stimulated by their ligands. Mechanistically, Dectin-1 engagement initiates spleen tyrosine kinase (Syk)-dependent Ras-GRF1 phosphorylation, and the phosphorylated Ras-GRF1 recruits and activates H-Ras through forming a complex with CARD9, which leads to activation of ERK downstream. Finally, we show that inhibiting ERK activation significantly accelerates the death of C. albicans-infected mice, and this inhibitory effect is dependent on CARD9. Together, our studies reveal a molecular mechanism by which Dectin-1 induces H-Ras activation that leads to ERK activation for host innate immune responses against fungal infection.
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[Insights into engineering of cellulosic ethanol].
Sheng Wu Gong Cheng Xue Bao
PUBLISHED: 09-13-2014
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For energy security, air pollution concerns, coupled with the desire to sustain the agricultural sector and revitalize the rural economy, many countries have applied ethanol as oxygenate or fuel to supplement or replace gasoline in transportation sector. Because of abundant feedstock resources and effective reduction of green-house-gas emissions, the cellulosic ethanol has attracted great attention. With a couple of pioneers beginning to produce this biofuel from biomass in commercial quantities around the world, it is necessary to solve engineering problems and complete the economic assessment in 2015-2016, gradually enter the commercialization stage. To avoid "competing for food with humans and competing for land with food", the 1st generation fuel ethanol will gradually transit to the 2nd generation cellulosic ethanol. Based on the overview of cellulosic ethanol industrialization from domestic and abroad in recent years, the main engineering application problems encountered in pretreatment, enzymes and enzymatic hydrolysis, pentose/hexose co-fermentation strains and processes, equipment were discussed from chemical engineering and biotechnology perspective. The development direction of cellulosic ethanol technology in China was addressed.
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C-type Lectin Receptor Dectin-3 Mediates Trehalose 6,6'-Dimycolate (TDM)-induced Mincle Expression through CARD9/Bcl10/MALT1-dependent Nuclear Factor (NF)-?B Activation.
J. Biol. Chem.
PUBLISHED: 09-08-2014
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Previous studies indicate that both Dectin-3 (also called MCL or Clec4d) and Mincle (also called Clec4e), two C-type lectin receptors, can recognize trehalose 6,6'-dimycolate (TDM), a cell wall component from mycobacteria, and induce potent innate immune responses. Interestingly, stimulation of Dectin-3 by TDM can also induce Mincle expression, which may enhance the host innate immune system to sense Mycobacterium infection. However, the mechanism by which Dectin-3 induces Mincle expression is not fully defined. Here, we show that TDM-induced Mincle expression is dependent on Dectin-3-mediated NF-?B, but not nuclear factor of activated T-cells (NFAT), activation, and Dectin-3 induces NF-?B activation through the CARD9-BCL10-MALT1 complex. We found that bone marrow-derived macrophages from Dectin-3-deficient mice were severely defective in the induction of Mincle expression in response to TDM stimulation. This defect is correlated with the failure of TDM-induced NF-?B activation in Dectin-3-deficient bone marrow-derived macrophages. Consistently, inhibition of NF-?B, but not NFAT, impaired TDM-induced Mincle expression, whereas NF-?B, but not NFAT, binds to the Mincle promoter. Dectin-3-mediated NF-?B activation is dependent on the CARD9-Bcl10-MALT1 complex. Finally, mice deficient for Dectin-3 or CARD9 produced much less proinflammatory cytokines and keyhole limpet hemocyanin (KLH)-specific antibodies after immunization with an adjuvant containing TDM. Overall, this study provides the mechanism by which Dectin-3 induces Mincle expression in response to Mycobacterium infection, which will have significant impact to improve adjuvant and design vaccine for antimicrobial infection.
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Uniaxial cyclic stretch promotes osteogenic differentiation and synthesis of BMP2 in the C3H10T1/2 cells with BMP2 gene variant of rs2273073 (T/G).
PLoS ONE
PUBLISHED: 09-05-2014
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Ossification of the posterior longitudinal ligament of the cervical spine (OPLL) is characterized by the replacement of ligament tissues with ectopic bone formation, and this result is strongly affected by genetic and local factors. Two single nucleotide polymorphisms (SNPs) of rs2273073 (T/G) and rs235768 (A/T) of bone morphogenetic protein 2 (BMP2) gene which are associated with OPLL have been reported in our previous report. In this study, we confirmed the connection in 18 case samples analysis of BMP2 gene in OPLL patients; additionally, it was also shown from the OPLL patients with ligament tissues that enchondral ossification and expression of BMP2 were significantly higher compared with the non-OPLL patients by histological examination, immunohistochemistry and Western blotting analysis. To investigate the underlying mechanism, we studied the effect of SNPs in cell model. The C3H10T1/2 cells with different BMP2 gene variants were constructed and then subjected to uniaxial cyclic stretch (0.5 Hz, 10% stretch). In the presence of mechanical stress, the expression of BMP2 protein in C3H10T1/2 cells transfected by BMP2 (rs2273073 (T/G)) and BMP2 (rs2273073 (T/G), rs235768 (A/T)) were significantly higher than the corresponding static groups (P<0.05). In conclusion, these results suggested that BMP2 gene variant of rs2273073 (T/G) could not only increase cell susceptibility to bone transformation similar to pre-OPLL change, but also increase the sensibility to mechanical stress which might play an important role during the progression of OPLL.
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Kinematic effect of Chinese herbal fomentation on patients with chronic neck pain.
Chin J Integr Med
PUBLISHED: 08-21-2014
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To clarify the effectiveness of Chinese herbal fomentation in treating chronic neck pain by means of changes in cervical kinematics.
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[Three-dimensional finite element analysis on mechanical behavior of the bone remodeling and bone integration between the bone-implant interface after hip replacement].
Zhongguo Gu Shang
PUBLISHED: 07-18-2014
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To discuss the primary stability of the fixed interface between the cementless prosthesis and femur, and its influence on bone ingrowth and secondary stability under the roughened surface and press fit of different prostheses by finite element analysis.
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A facile solvent-manipulated mesh for reversible oil/water separation.
ACS Appl Mater Interfaces
PUBLISHED: 07-11-2014
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A controllable oil/water separation mesh has been successfully developed and easily manipulated by immersion in a stearic acid ethanol solution and tetrahydrofuran with a very short period of time. The superhydrophilic and underwater superoleophobic mesh is first obtained via a one-step chemical oxidation and subsequently converts to superhydrophobic after it is immersed in an ethanol solution of stearic acid for 5 min. The surface wettability is regained to superhydrophilic quickly by immersion in tetrahydrofuran for 5 min. More importantly, the reversible superhydrophobic-and-superhydrophilic switching can be repeated multiple times with almost no visible morphology variation. Therefore, this approach provides potential application in controllable oil/water separation and opens up new perspectives in manipulation of various metallic oxide substrates.
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Electroporation Mediated Gene Delivery of Na+,K+-ATPase and ENaC Subunits to the Lung Attenuates Acute Respiratory Distress Syndrome in a Two-Hit Porcine Model.
Shock
PUBLISHED: 07-09-2014
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Acute Respiratory Distress Syndrome (ARDS) is a common cause of organ failure with an associated mortality rate of 40%. The initiating event is disruption of alveolar-capillary interface causing leakage of edema into alveoli. Hypothesis: Electroporation mediated gene delivery of epithelial sodium channel (ENaC) and Na,K-ATPase into alveolar cells would improve alveolar clearance of edema and attenuate ARDS.
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Kinematic study of the relation between the instantaneous center of rotation and degenerative changes in the cervical intervertebral disc.
Eur Spine J
PUBLISHED: 06-21-2014
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We located the instantaneous center of rotation (ICR) for the cervical spine at various ages and investigated age-related changes. We evaluated the impact of cervical disc degeneration on the ICR using a scoring system based on plain radiographs.
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Percutaneous needle aspiration versus catheter drainage in the management of liver abscess: a systematic review and meta-analysis.
HPB (Oxford)
PUBLISHED: 06-20-2014
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The aim of this study was to compare the effectiveness of percutaneous needle aspiration (PNA) and percutaneous catheter drainage (PCD) in the management of liver abscess.
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Re-print of "Histone extraction protocol from the two model diatoms Phaeodactylum tricornutum and Thalassiosira pseudonana".
Mar Genomics
PUBLISHED: 05-22-2014
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Post-translational modifications of histones affect many biological processes by influencing higher order chromatin structure that affects gene and genome regulation. It is therefore important to develop methods for extracting histones while maintaining their native post-translational modifications. While histone extraction protocols have been developed in multicellular and single celled organisms such as yeast and Arabidopsis, they are inefficient in diatoms that have a silica cell wall that is likely to hinder histone extraction. We report in this work a rapid and reliable method for extraction of large amounts of high quality histones from the two model diatoms Phaeodactylum tricornutum and Thalassiosira pseudonana. The protocol is an important enabling step permitting downstream applications such as western blotting and mass spectrometry.
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Choline and acetylcholine detection based on peroxidase-like activity and protein antifouling property of platinum nanoparticles in bovine serum albumin scaffold.
Biosens Bioelectron
PUBLISHED: 05-16-2014
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Platinum nanoparticles (PtNPs) in the scaffold of bovine serum albumin (BSA) through biomineralization are found to possess excellent peroxidase-like activity that can catalyze N-ethyl-N-(3-sulfopropyl)-3-methylaniline sodium salt (TOPS) coupled with 4-amino-antipyrine (4-AAP) by the action of hydrogen peroxide to give an obvious purple product. Based on this phenomenon, acetylcholinesterase (AChE) and choline oxidase (ChOx) are used to catalyze ACh and choline to form the active product H2O2 and the as-produced H2O2 is detected optically. Owning to the protection effect of the protein shell, BSA-PtNPs turn out to be very stable and preserve the catalytic activity in the presence of protein and even in the real plasma samples. This protein antifouling property makes the BSA-PtNPs suitable for a wide range of applications in sensors for biological samples. Choline in infant formula and ACh in plasma have been successfully detected.
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[Expressions and correlation of HPA, CK2beta and HIF-1alpha in nasopharyngeal carcinoma].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 05-16-2014
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To investigate the expression of HPA, CK2beta and HIF-1alpha gene in nasopharyngeal carcinoma (NPC) tissues, and the correlation between their expression with the clinical characteristics of NPC and the relativity of HPA, CK2beta and HIF-1alpha gene in NPC tissues.
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Tumor vasculature targeted photodynamic therapy for enhanced delivery of nanoparticles.
ACS Nano
PUBLISHED: 05-12-2014
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Delivery of nanoparticle drugs to tumors relies heavily on the enhanced permeability and retention (EPR) effect. While many consider the effect to be equally effective on all tumors, it varies drastically among the tumors' origins, stages, and organs, owing much to differences in vessel leakiness. Suboptimal EPR effect represents a major problem in the translation of nanomedicine to the clinic. In the present study, we introduce a photodynamic therapy (PDT)-based EPR enhancement technology. The method uses RGD-modified ferritin (RFRT) as "smart" carriers that site-specifically deliver (1)O2 to the tumor endothelium. The photodynamic stimulus can cause permeabilized tumor vessels that facilitate extravasation of nanoparticles at the sites. The method has proven to be safe, selective, and effective. Increased tumor uptake was observed with a wide range of nanoparticles by as much as 20.08-fold. It is expected that the methodology can find wide applications in the area of nanomedicine.
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[Clinical apprehension on application of Tri-lock BPS total hip arthroplasty].
Zhongguo Gu Shang
PUBLISHED: 04-24-2014
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To study short-term results and clinical application of Tri-lock BPS in total hip arthoplasty.
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Inflammatory T cell responses rely on amino acid transporter ASCT2 facilitation of glutamine uptake and mTORC1 kinase activation.
Immunity
PUBLISHED: 03-24-2014
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Glutamine has been implicated as an immunomodulatory nutrient, but how glutamine uptake is mediated during T cell activation is poorly understood. We have shown that naive T cell activation is coupled with rapid glutamine uptake, which depended on the amino acid transporter ASCT2. ASCT2 deficiency impaired the induction of T helper 1 (Th1) and Th17 cells and attenuated inflammatory T cell responses in mouse models of immunity and autoimmunity. Mechanistically, ASCT2 was required for T cell receptor (TCR)-stimulated activation of the metabolic kinase mTORC1. We have further shown that TCR-stimulated glutamine uptake and mTORC1 activation also required a TCR signaling complex composed of the scaffold protein CARMA1, the adaptor molecule BCL10, and the paracaspase MALT1. This function was independent of IKK kinase, a major downstream target of the CARMA1 complex. These findings highlight a mechanism of T cell activation involving ASCT2-dependent integration of the TCR signal and a metabolic signaling pathway.
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MAPK phosphotase 5 deficiency contributes to protection against blood-stage Plasmodium yoelii 17XL infection in mice.
J. Immunol.
PUBLISHED: 03-14-2014
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Cell-mediated immunity plays a crucial role in the development of host resistance to asexual blood-stage malaria infection. However, little is known of the regulatory factors involved in this process. In this study, we investigated the impact of MAPK phosphotase 5 (MKP5) on protective immunity against a lethal Plasmodium yoelii 17XL blood-stage infection using MKP5 knockout C57BL/6 mice. Compared with wild-type control mice, MKP5 knockout mice developed significantly lower parasite burdens with prolonged survival times. We found that this phenomenon correlated with a rapid and strong IFN-?-dependent cellular immune response during the acute phase of infection. Inactivation of IFN-? by the administration of a neutralizing Ab significantly reduced the protective effects in MKP5 knockout mice. By analyzing IFN-? production in innate and adaptive lymphocyte subsets, we observed that MKP5 deficiency specifically enhanced the IFN-? response mediated by CD4+ T cells, which was attributable to the increased stimulatory capacity of splenic CD11c+ dendritic cells. Furthermore, following vaccination with whole blood-stage soluble plasmodial Ag, MKP5 knockout mice acquired strongly enhanced Ag-specific immune responses and a higher level of protection against subsequent P. yoelii 17XL challenge. Finally, we found the enhanced response mediated by MKP5 deficiency resulted in a lethal consequence in mice when infected with nonlethal P. yoelii 17XNL. Thus, our data indicate that MKP5 is a potential regulator of immune resistance against Plasmodium infection in mice, and that an understanding of the role of MKP5 in manipulating anti-malaria immunity may provide valuable information on the development of better control strategies for human malaria.
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Primary hepatic sarcomatoid carcinoma: clinical features and prognosis of 28 resected cases.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 03-03-2014
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Primary hepatic sarcomatoid carcinoma (SC) is an extremely rare malignancy composed of both carcinomatous and spindle cell sarcomatous components. Our aim was to clarify the clinical features and prognosis of patients with this disease.
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In situ growth of porous platinum nanoparticles on graphene oxide for colorimetric detection of cancer cells.
Anal. Chem.
PUBLISHED: 02-20-2014
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A green approach is proposed for in situ growth of porous platinum nanoparticles on graphene oxide (PtNPs/GO). The resulting nanocomposite has been proven to function as peroxidase mimetics that can catalyze the reaction of peroxidase substrate in the presence of hydrogen peroxide. On the basis of the peroxidase-like activity, we used the PtNPs/GO as a signal transducer to develop a colorimetric assay for the direct detection of cancer cells. By using folic acid as a recognition element, a total of 125 cancer cells (MCF-7) can be distinguished by naked-eye observation. We envision that this nanomaterial could be used as a power tool for a wide range of potential applications in biotechnology and medicine.
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Fluorescent hydrogen peroxide sensor based on cupric oxide nanoparticles and its application for glucose and L-lactate detection.
Biosens Bioelectron
PUBLISHED: 02-18-2014
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A novel fluorescent hydrogen peroxide sensor was developed based on the peroxidase-like activity of cupric oxide nanoparticles. Cupric oxide nanoparticles effectively catalyzed the decomposition of hydrogen peroxide into hydroxyl radicals. Then terephthalic acid was oxidized by hydroxyl radical to form a highly fluorescent product. The linear range of hydrogen peroxide estimated to be 5.0 × 10(-6)-2.0 × 10(-4)M with a detection limit of 3.4 × 10(-7)M. Moreover, this detection system enabled the sensing of analytes which can enzymatically generate hydrogen peroxide. By coupling the oxidation of glucose or L-lactate catalyzed by their corresponding oxidase enzymes with terephthalic acid oxidation catalyzed by cupric oxide nanoparticles, sensitive assays of glucose and l-lactate with detection limits of 1.0 × 10(-6) and 4.5 × 10(-8)M were realized. The successful applications of this approach in human serum samples have also been demonstrated.
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Prediction of protein S-nitrosylation sites based on adapted normal distribution bi-profile Bayes and Chou's pseudo amino acid composition.
Int J Mol Sci
PUBLISHED: 02-14-2014
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Protein S-nitrosylation is a reversible post-translational modification by covalent modification on the thiol group of cysteine residues by nitric oxide. Growing evidence shows that protein S-nitrosylation plays an important role in normal cellular function as well as in various pathophysiologic conditions. Because of the inherent chemical instability of the S-NO bond and the low abundance of endogenous S-nitrosylated proteins, the unambiguous identification of S-nitrosylation sites by commonly used proteomic approaches remains challenging. Therefore, computational prediction of S-nitrosylation sites has been considered as a powerful auxiliary tool. In this work, we mainly adopted an adapted normal distribution bi-profile Bayes (ANBPB) feature extraction model to characterize the distinction of position-specific amino acids in 784 S-nitrosylated and 1568 non-S-nitrosylated peptide sequences. We developed a support vector machine prediction model, iSNO-ANBPB, by incorporating ANBPB with the Chou's pseudo amino acid composition. In jackknife cross-validation experiments, iSNO-ANBPB yielded an accuracy of 65.39% and a Matthew's correlation coefficient (MCC) of 0.3014. When tested on an independent dataset, iSNO-ANBPB achieved an accuracy of 63.41% and a MCC of 0.2984, which are much higher than the values achieved by the existing predictors SNOSite, iSNO-PseAAC, the Li et al. algorithm, and iSNO-AAPair. On another training dataset, iSNO-ANBPB also outperformed GPS-SNO and iSNO-PseAAC in the 10-fold crossvalidation test.
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Urine interleukin-18 in prediction of acute kidney injury: a systemic review and meta-analysis.
J. Nephrol.
PUBLISHED: 02-10-2014
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Interleukin-18 (IL-18) mediates ischemic acute tubular necrosis; it has been proved as a rapid, reliable, and affordable test marker for the early detection of acute kidney injury (AKI), but its predictive accuracy varies greatly.
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Expression patterns of WNT/?-CATENIN signaling molecules during human tooth development.
J. Mol. Histol.
PUBLISHED: 02-07-2014
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The WNT/?-CATENIN signaling has been demonstrated to play critical roles in mouse tooth development, but little is known about the status of these molecules in human embryonic tooth. In this study, expression patterns of WNT/?-CATENIN signaling components, including WNT ligands (WNT3, WNT5A), receptors (FZD4, FZD6, LRP5), transducers (?-CATENIN), transcription factors (TCF4, LEF1) and antagonists (DKK1, SOSTDC1) were investigated in human tooth germ at the bud, cap and bell stages by in situ hybridization. All these genes exhibited similar but slightly distinct expression patterns in human tooth germ in comparison with mouse. Furthermore the mRNA expression of these genes in incisors and molars at the bell stage was also examined by real-time PCR. Our results reveal the status of active WNT/?-CATENIN signaling in the human tooth germ and suggest these components may also play an essential role in the regulation of human tooth development.
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miR-145 sensitizes ovarian cancer cells to paclitaxel by targeting Sp1 and Cdk6.
Int. J. Cancer
PUBLISHED: 01-27-2014
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Multidrug resistance (MDR) remains a major obstacle to effective chemotherapy treatment in ovarian cancer. In our study, paclitaxel-resistant ovarian cancer patients and cell lines had decreased miR-145 levels and expressed high levels of Sp1 and Cdk6. Introducing miR-145 into SKOV3/PTX and A2780/PTX cells led to a reduction in Cdk6 and Sp1 along with downregulation of P-gp and pRb. These changes resulted in increased accumulation of antineoplastic drugs and G1 cell cycle arrest, which rendered the cells more sensitive to paclitaxel in vitro and in vivo. These effects could be reversed by reintroducing Sp1 or Cdk6 into cells expressing high levels of miR-145, resulting in restoration of P-gp and pRb levels. Furthermore, we confirmed that both Cdk6 and Sp1 are targets of miR-145. Intriguingly, demethylation with 5-aza-dC led to reactivation of miR-145 expression in drug-resistant ovarian cancer cell lines, which also resulted in increased sensitivity to paclitaxel. Collectively, these findings begin to elucidate the role of miR-145 as an important regulator of chemoresistance in ovarian cancer by controlling both Cdk6 and Sp1.
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Degradation of Acid Orange 7 in aqueous solution by dioxygen activation in a pyrite/H?O/O? system.
Environ Sci Pollut Res Int
PUBLISHED: 01-22-2014
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Increasing attention has been paid to pyrite due to its ability to generate hydroxyl radicals in air-saturated solutions. In this study, the mineral pyrite was studied as a catalyst to activate molecular oxygen to degrade Acid Orange 7 (AO7) in aqueous solution. A complete set of control experiments were conducted to optimize the reaction conditions, including the dosage of pyrite, the AO7 concentration, as well as the initial pH value. The role of reactive oxygen species (ROS) generated by pyrite in the process was elucidated by free radical quenching reactions. Furthermore, the concentrations of Fe(II) and total Fe formed were also measured. The mechanism for the production of ROS in the pyrite/H2O/O2 system was that H2O2 was formed by hydrogen ion and superoxide anion (O2(·-)) which was produced by the reaction of pyrite activating O2 and then reacted with Fe(II) dissolved from pyrite to produce (·)OH through Fenton reaction. The findings suggest that pyrite/H2O/O2 system is potentially practical in pollution treatment. Moreover, the results provide a new insight into the understanding of the mechanism for degradation of organic pollutants by pyrite.
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Tissue factor expression and methylation regulation in differentiation of embryonic stem cells into trophoblast.
Asian Pac J Trop Med
PUBLISHED: 01-10-2014
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To explore tissue factor (TF) expression and methylation regulation in differentiation of human embryonic stem cells (hESCs) into trophoblast.
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Th17 cell expansion in gastric cancer may contribute to cancer development and metastasis.
Immunol. Res.
PUBLISHED: 01-10-2014
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Th0 cells differentiate into Th1 or Th2 depending on multiple transcription factors acting on specific time points to regulate gene expression. Th17 cells, a subset of IL-17-producing T cells distinct from Th1 or Th2 cells has been described as key players in inflammation and autoimmune diseases as well as cancer development. In the present study, 66 patients with gastric cancer were included; the expression level of Th1- and Th17-related IFN-?, IL-17, T-bet, ROR?t in gastric cancer tissues and peripheral blood mononuclear cell (PBMC) were detected, analyzed the relationship between Th17 or Th1 infiltration and metastasis and explored the possible mechanism. Our results showed that IL-17 and ROR?t expression were significantly increased in gastric cancer tissues and PBMC, especially, in metastasis patients; plasma IL-17 also increased; furthermore, the mRNA and protein levels of IL-1?, IL-21 and TGF-? were up-regulated. All the data indicated that Th17 was infiltrated the cancer tissue; IL-1?, IL-21 and TGF-? were also involved in gastric cancer development by promoting Th17 cell generation. From the above data, we speculated that Th17 cell expansion in gastric cancer may contribute to cancer development and metastasis.
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Electrochemical immunosensor for detection of topoisomerase based on graphene-gold nanocomposites.
Talanta
PUBLISHED: 01-09-2014
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A facile electrochemical immunosensor based on graphene-three dimensional nanostructure gold nanocomposites (G-3D Au) using simple and rapid one-step electrochemical co-reduction technique was developed for sensitive detection of topoisomerase. The resultant G-3D Au nanocomposites were characterized by scanning electron microscopy, cyclic voltammetry and electrochemical impedance spectroscopy, and then were used as a substrate for construction of the "sandwich-type" immunosensor. Amperometric current-time curve was employed to monitor the immunoreaction on the protein modified electrode. The proposed method could respond to topoisomerase with a linear calibration range from 0.5 ng mL(-1) to 50 ng mL(-1) with a detection limit of 10 pg mL(-1). This new biosensor exhibited a fast amperometric response, high sensitivity and selectivity, and was successfully used in determining the topoisomerase which was added in human serum with a relative standard deviation (n=5)<5%. The immunosensor served as a significant step toward the practical application of the immunosensor in clinical diagnosis and prognosis monitor.
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A conserved tetrameric interaction of cry toxin helix ?3 suggests a functional role for toxin oligomerization.
Biochim. Biophys. Acta
PUBLISHED: 01-03-2014
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Crystal (Cry) toxins are widely used for insect control, but their mechanism of toxicity is still uncertain. These toxins can form lytic pores in vitro, and water soluble tetrameric pre-pore intermediates have been reported. Even the precise oligomeric state of the toxin in membranes, trimeric or tetrameric, is still a debated issue. Based on previous reports, we have assumed that interactions between toxin monomers in solution are at least partly mediated by domain I, and we have analyzed in silico the homo-oligomerization tendencies of the domain I ?-helices individually. Using many homologous sequences for each ?-helix, our strategy allows selection of evolutionarily conserved interactions. These interactions appeared only in helices ?3 and ?5, but only ?3 produced a suitably oriented or ?-helical sample in lipid bilayers, forming homotetramers in C14-betaine, and allowing determination of its rotational orientation in lipid bilayers using site-specific infrared dichroism (SSID). The determined orientation in the tetrameric model is in agreement with only one of the evolutionarily conserved models. In addition mutation R99E, which was found to inhibit oligomerization experimentally, greatly destabilized the tetramer in molecular dynamic simulations. In this model, helix 3 is able to form inter-monomer interactions without significant rearrangements of domain I, which is compatible with the available crystal structure of Cry toxins in solution. The model presented here at least partially explains the reported tetrameric oligomerization of Cry toxins in solution and the inhibition of this oligomerization by a synthetic ?3 peptide.
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C-type lectin receptors differentially induce th17 cells and vaccine immunity to the endemic mycosis of North America.
J. Immunol.
PUBLISHED: 01-03-2014
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Vaccine immunity to the endemic mycoses of North America requires Th17 cells, but the pattern recognition receptors and signaling pathways that drive these protective responses have not been defined. We show that C-type lectin receptors exert divergent contributions to the development of antifungal Th17 cells and vaccine resistance against Blastomyces dermatitidis, Histoplasma capsulatum, and Coccidioides posadasii. Acquired immunity to B. dermatitidis requires Dectin-2, whereas vaccination against H. capsulatum and C. posadasii infection depends on innate sensing by Dectin-1 and Dectin-2, but not Mincle. Tracking Ag-specific T cells in vivo established that the Card9 signaling pathway acts indispensably and exclusively on differentiation of Th17 cells, while leaving intact their activation, proliferation, survival, and migration. Whereas Card9 signaling is essential, C-type lectin receptors offer distinct and divergent contributions to vaccine immunity against these endemic fungal pathogens. Our work provides new insight into innate immune mechanisms that drive vaccine immunity and Th17 cells.
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Activation of the Transcription Factor c-Maf in T Cells Is Dependent on the CARMA1-IKK? Signaling Cascade.
Sci Signal
PUBLISHED: 12-19-2013
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The proto-oncogene c-Maf is a transcription factor that plays a critical role in the differentiation of various T helper (TH) cell subsets. The amount of c-Maf increases after stimulation of the T cell receptor (TCR), which results in the production of multiple cytokines. We showed that two essential regulators of the transcription factor nuclear factor ?B (NF-?B), the scaffold protein CARMA1 and the kinase IKK? [inhibitor of NF-?B (I?B) kinase ?], are also critical for the activation of c-Maf. Although CARMA1 deficiency did not affect the TCR-dependent increase in c-Maf abundance in T cells, CARMA1-dependent activation of the IKK complex was required for the nuclear translocation of c-Maf and its binding to the promoters of its target genes. Consistent with a role for c-Maf in the development of T follicular helper (TFH) cells, which provide help to B cells in the germinal centers of the spleen, CARMA1- or IKK?-deficient mice immunized with peptide antigen had defects in the generation of TFH cells, formation of germinal centers, and production of antigen-specific antibodies. Together, these data suggest a mechanism by which c-Maf is regulated during T cell activation and differentiation.
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Epithelial Growth Factor Receptor-Activated Nuclear Factor ?B Signaling and Its Role in Epithelial Growth Factor Receptor-Associated Tumors.
Cancer J
PUBLISHED: 11-26-2013
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Dysregulated epithelial growth factor receptor (EGFR) signaling is directly associated with a number of cancers, such as brain, lung, and breast cancer. The downstream signaling pathways activated by EGFR have been extensively studied, such as PI3K/AKT pathway, MAPK (mitogen-activated protein kinase) pathway, and STAT (signal transducer and activator of transcription) pathway. There are growing numbers of evidence suggesting that EGFR activates nuclear factor ?B (NF-?B), which is a key transcription factor controlling a variety of cellular functions. However, relatively less is known about the signal transduction mechanism that links EGFR to NF-?B activation. Here, we discuss recent progress in EGFR-induced NF-?B pathways, including the identification of CARMA3-Bcl10-MALT1 complex and protein kinase C[Latin Small Letter Open E] as 2 essential signaling components linking EGFR to the activation of I?B? kinase. In addition, we discuss the multifunctional roles of NF-?B in EGFR-associated tumors, including proliferation, tumor invasiveness, metabolism, tumor-promoting microenvironment, and EGFR tyrosine kinase inhibitor resistance.
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One-stage versus two-stage management for concomitant gallbladder stones and common bile duct stones in patients with obstructive jaundice.
Am Surg
PUBLISHED: 10-30-2013
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No consensus exists regarding the optimal management of concomitant gallbladder stones and common bile duct stones (CBDS). Previous studies showed a significant association between the presence of obstructive jaundice and increased risk of postoperative complications and conversion to open surgery. This retrospective study evaluated the effectiveness and safety of one-stage (laparoscopic cholecystectomy [LC] plus laparoscopic common bile duct exploration) management versus two-stage (preoperative endoscopic retrograde cholangiopancreatography/endoscopic sphincterotomy + LC) management for patients with obstructive jaundice, concomitant gallbladder stones, and CBDS. One-stage management (n = 88) or two-stage management (n = 122) was used for 210 eligible patients between January 2009 and March 2011. Both types of management proved to be effective and safe. No significant difference was observed in terms of stone clearance from the common bile duct (CBD), postoperative morbidity, mortality, or conversion to open surgery. However, one-stage management was more cost-effective and decreased the number of procedures. In addition, postoperative hospital stay and operative time were shorter for patients who received one-stage management. Especially for patients with CBD greater than 1 cm in diameter, one-stage management is a better choice.
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Autotaxin-lysophosphatidic Acid signaling axis mediates tumorigenesis and development of acquired resistance to sunitinib in renal cell carcinoma.
Clin. Cancer Res.
PUBLISHED: 10-11-2013
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Sunitinib is currently considered as the standard treatment for advanced renal cell carcinoma (RCC). We aimed to better understand the mechanisms of sunitinib action in kidney cancer treatment and in the development of acquired resistance.
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An IMPLICATION logic gate based on citrate-capped gold nanoparticles with thiocyanate and iodide as inputs.
Analyst
PUBLISHED: 09-20-2013
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Herein we developed an IMPLICATION logic gate based on citrate-capped AuNPs by employing thiocyanate (SCN(-)) and iodide (I(-)) as inputs, and devised a colorimetric sensor for the determination of I(-) with good selectivity and sensitivity. To the best of our knowledge, this is the first example in which two species of anions serve as inputs to obtain visually observed Boolean outputs. Under the optimum conditions, 0.8 ?M I(-) could induce a significant color change and be recognized by the naked eye. The detection limit is 50 nM by using UV-vis spectroscopy.
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[A case of imported schistosomiasis haematobia first reported in Fujian Province].
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi
PUBLISHED: 09-13-2013
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The first case of imported schistosomiasis haematobia in Fujian Province was detected and the patient was cured following treatment with praziquantel.
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[A missense SNP in the codon of ADD1 phosphorylation site associated with non-cardia gastric cancer susceptibility in a Chinese population].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 08-30-2013
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This study investigated the association between a missense SNP in the codon of ADD1 phosphorylation site and the susceptibility of non-cardia gastric cancer in a Chinese population.
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[Impact of CCND1 A870G polymorphism on acute adverse events in postoperative rectal cancer patients treated with adjuvant concurrent chemoradiotherapy].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 08-30-2013
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The purpose of this study was to investigate the association between single nucleotide polymorphism (SNP) of CCND1 A870G and acute adverse events (AEs) in postoperative rectal cancer patients who received capecitabine-based postoperative chemoradiotherapy (CRT).
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In vitro and in vivo therapeutic efficacy of carfilzomib in mantle cell lymphoma: targeting the immunoproteasome.
Mol. Cancer Ther.
PUBLISHED: 08-29-2013
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Mantle cell lymphoma (MCL) remains incurable due to its inevitable pattern of relapse after treatment with current existing therapies. However, the promise of a cure for MCL lies in the burgeoning area of novel agents. In this study, we elucidated the therapeutic effect and mechanism of carfilzomib, a novel long-acting second-generation proteasome inhibitor, in MCL cells. We found that carfilzomib induced growth inhibition and apoptosis in both established MCL cell lines and freshly isolated primary MCL cells in a dose-dependent manner. In contrast, carfilzomib was less toxic to normal peripheral blood mononuclear cells from healthy individuals. The carfilzomib-induced apoptosis of MCL cells was mediated by the activation of JNK, Bcl-2, and mitochondria-related pathways. In addition, carfilzomib inhibited the growth and survival signaling pathways NF-?B and STAT3. Interestingly, we discovered that expression of immunoproteasome (i-proteasome) subunits is required for the anti-MCL activity of carfilzomib in MCL cells. In MCL-bearing SCID mice/primary MCL-bearing SCID-hu mice, intravenous administration of 5 mg/kg carfilzomib on days 1 and 2 for 5 weeks slowed/abrogated tumor growth and significantly prolonged survival. Our preclinical data show that carfilzomib is a promising, potentially less toxic treatment for MCL. Furthermore, an intact i-proteasome, especially LMP2, appears to be necessary for its anti-MCL activity, suggesting that i-proteasome could serve as a biomarker for identifying patients who will benefit from carfilzomib.
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Histone extraction protocol from the two model diatoms Phaeodactylum tricornutum and Thalassiosira pseudonana.
Mar Genomics
PUBLISHED: 07-29-2013
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Post-translational modifications of histones affect many biological processes by influencing higher order chromatin structure that affects gene and genome regulation. It is therefore important to develop methods for extracting histones while maintaining their native post-translational modifications. While histone extraction protocols have been developed in multicellular and single celled organisms such as yeast and Arabidopsis, they are inefficient in diatoms that have a silica cell wall that is likely to hinder histone extraction. We report in this work a rapid and reliable method for extraction of large amounts of high quality histones from the two model diatoms Phaeodactylum tricornutum and Thalassiosira pseudonana. The protocol is an important enabling step permitting downstream applications such as western blotting and mass spectrometry.
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[The effect of continuous renal replacement therapy on the outcome of severe pneumonia in patients receiving long-term immunosuppressants].
Zhonghua Jie He He Hu Xi Za Zhi
PUBLISHED: 07-17-2013
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To investigate the effect of continuous renal replacement therapy (CRRT) on the outcome of severe pneumonia in patients receiving long-term immunosuppressants.
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Ferritin nanocages to encapsulate and deliver photosensitizers for efficient photodynamic therapy against cancer.
ACS Nano
PUBLISHED: 07-11-2013
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Photodynamic therapy is an emerging treatment modality that is under intensive preclinical and clinical investigations for many types of disease including cancer. Despite the promise, there is a lack of a reliable drug delivery vehicle that can transport photosensitizers (PSs) to tumors in a site-specific manner. Previous efforts have been focused on polymer- or liposome-based nanocarriers, which are usually associated with a suboptimal PS loading rate and a large particle size. We report herein that a RGD4C-modified ferritin (RFRT), a protein-based nanoparticle, can serve as a safe and efficient PS vehicle. Zinc hexadecafluorophthalocyanine (ZnF16Pc), a potent PS with a high (1)O2 quantum yield but poor water solubility, can be encapsulated into RFRTs with a loading rate as high as ~60 wt % (i.e., 1.5 mg of ZnF16Pc can be loaded on 1 mg of RFRTs), which far exceeds those reported previously. Despite the high loading, the ZnF16Pc-loaded RFRTs (P-RFRTs) show an overall particle size of 18.6 ± 2.6 nm, which is significantly smaller than other PS-nanocarrier conjugates. When tested on U87MG subcutaneous tumor models, P-RFRTs showed a high tumor accumulation rate (tumor-to-normal tissue ratio of 26.82 ± 4.07 at 24 h), a good tumor inhibition rate (83.64% on day 12), as well as minimal toxicity to the skin and other major organs. This technology can be extended to deliver other metal-containing PSs and holds great clinical translation potential.
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USP18 inhibits NF-?B and NFAT activation during Th17 differentiation by deubiquitinating the TAK1-TAB1 complex.
J. Exp. Med.
PUBLISHED: 07-01-2013
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Reversible ubiquitin modification of cell signaling molecules has emerged as a critical mechanism by which cells respond to extracellular stimuli. Although ubiquitination of TGF-?-activated kinase 1 (TAK1) is critical for NF-?B activation in T cells, the regulation of its deubiquitination is unclear. We show that USP18, which was previously reported to be important in regulating type I interferon signaling in innate immunity, regulates T cell activation and T helper 17 (Th17) cell differentiation by deubiquitinating the TAK1-TAB1 complex. USP18-deficient T cells are defective in Th17 differentiation and Usp18(-/-) mice are resistant to experimental autoimmune encephalomyelitis (EAE). In response to T cell receptor engagement, USP18-deficient T cells exhibit hyperactivation of NF-?B and NFAT and produce increased levels of IL-2 compared with the wild-type controls. Importantly, USP18 is associated with and deubiquitinates the TAK1-TAB1 complex, thereby restricting expression of IL-2. Our findings thus demonstrate a previously uncharacterized negative regulation of TAK1 activity during Th17 differentiation, suggesting that USP18 may be targeted to treat autoimmune diseases.
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Early airway pressure release ventilation prevents ARDS-a novel preventive approach to lung injury.
Shock
PUBLISHED: 06-05-2013
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Acute respiratory distress syndrome (ARDS) afflicts 200,000 patients annually with a mortality rate of 30% to 60% despite wide use of low tidal volume (LTV) ventilation, the present standard of care. High-permeability alveolar edema and instability occur early in the development of ARDS, before clinical signs of lung injury, and represent potential targets for therapy. We hypothesize that early application of a protective ventilation strategy (airway pressure release ventilation [APRV]) will stabilize alveoli and reduce alveolar edema, preventing the development of ARDS. Yorkshire pigs (30-40 kg) were anesthetized and subjected to two-hit injury: (a) intestinal ischemia-reperfusion, (b) peritoneal sepsis, or sham surgery. Following surgery, pigs were randomized into APRV (n = 4), according to current published guidelines for APRV; LTV ventilation (n = 3), using the current published ARDS Network guidelines (6 mL/kg); or sham (n = 5). The clinical care of all pigs was administered per the Surviving Sepsis Campaign guidelines. Animals were killed, and necropsy performed at 48 h. Arterial blood gases were measured to assess for the development of clinical lung injury. Lung tissue epithelial cadherin (E-cadherin) was measured to assess alveolar permeability. Bronchoalveolar lavage fluid (BALF) surfactant protein A was measured to assess alveolar stability. Lung edema content and histopathology were analyzed at 48 h. Airway pressure release ventilation pigs did not develop ARDS. In contrast, pigs in the LTV ventilation met ARDS criteria (PaO2/FIO2 ratio) (APRV: baseline = 471 ± 16; 48 h = 392 ± 8; vs. LTV ventilation: baseline = 551 ± 28; 48 h = 138 ± 88; P < 0.001). Airway pressure release ventilation preserved alveolar epithelial integrity demonstrated by higher levels of E-cadherin in lung tissue as compared with LTV ventilation (P < 0.05). Surfactant protein A levels were higher in BALF from the APRV group, suggesting APRV preserved alveolar stability. Quantitative histologic scoring showed improvements in all stigmata of ARDS in the APRV group versus the LTV ventilation (P < 0.05). Airway pressure release ventilation had significantly lower lung edema (wet-dry weight) than LTV ventilation (P < 0.05). Protective ventilation with APRV immediately following injury prevents development of ARDS. Reduction in lung edema, preservation of lung E-cadherin, and surfactant protein A abundance in BALF suggest that APRV attenuates lung permeability, edema, and surfactant degradation. Protective ventilation could change the clinical paradigm from supportive care for ARDS with LTV ventilation to preventing development of ARDS with APRV.
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RGD-modified apoferritin nanoparticles for efficient drug delivery to tumors.
ACS Nano
PUBLISHED: 06-04-2013
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Ferritin (FRT) is a major iron storage protein found in humans and most living organisms. Each ferritin is composed of 24 subunits, which self-assemble to form a cage-like nanostructure. FRT nanocages can be genetically modified to present a peptide sequence on the surface. Recently, we demonstrated that Cys-Asp-Cys-Arg-Gly-Asp-Cys-Phe-Cys (RGD4C)-modified ferritin can efficiently home to tumors through RGD-integrin ?v?3 interaction. Though promising, studies on evaluating surface modified ferritin nanocages as drug delivery vehicles have seldom been reported. Herein, we showed that after being precomplexed with Cu(II), doxorubicin can be loaded onto RGD modified apoferritin nanocages with high efficiency (up to 73.49 wt %). When studied on U87MG subcutaneous tumor models, these doxorubicin-loaded ferritin nanocages showed a longer circulation half-life, higher tumor uptake, better tumor growth inhibition, and less cardiotoxicity than free doxorubicin. Such a technology might be extended to load a broad range of therapeutics and holds great potential in clinical translation.
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Insights into the role of DNA methylation in diatoms by genome-wide profiling in Phaeodactylum tricornutum.
Nat Commun
PUBLISHED: 05-31-2013
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DNA cytosine methylation is a widely conserved epigenetic mark in eukaryotes that appears to have critical roles in the regulation of genome structure and transcription. Genome-wide methylation maps have so far only been established from the supergroups Archaeplastida and Unikont. Here we report the first whole-genome methylome from a stramenopile, the marine model diatom Phaeodactylum tricornutum. Around 6% of the genome is intermittently methylated in a mosaic pattern. We find extensive methylation in transposable elements. We also detect methylation in over 320 genes. Extensive gene methylation correlates strongly with transcriptional silencing and differential expression under specific conditions. By contrast, we find that genes with partial methylation tend to be constitutively expressed. These patterns contrast with those found previously in other eukaryotes. By going beyond plants, animals and fungi, this stramenopile methylome adds significantly to our understanding of the evolution of DNA methylation in eukaryotes.
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C-type lectin receptors Dectin-3 and Dectin-2 form a heterodimeric pattern-recognition receptor for host defense against fungal infection.
Immunity
PUBLISHED: 05-23-2013
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C-type lectin receptors (CLRs) play critical roles as pattern-recognition receptors (PRRs) for sensing Candida albicans infection, which can be life-threatening for immunocompromised individuals. Here we have shown that Dectin-3 (also called CLECSF8, MCL, or Clec4d), a previously uncharacterized CLR, recognized ?-mannans on the surfaces of C. albicans hyphae and induced NF-?B activation. Mice with either blockade or genetically deleted Dectin-3 were highly susceptible to C. albicans infection. Dectin-3 constantly formed heterodimers with Dectin-2, a well-characterized CLR, for recognizing C. albicans hyphae. Compared to their respective homodimers, Dectin-3 and Dectin-2 heterodimers bound ?-mannans more effectively, leading to potent inflammatory responses against fungal infections. Together, our study demonstrates that Dectin-3 forms a heterodimeric PRR with Dectin-2 for sensing fungal infection and suggests that different CLRs may form different hetero- and homodimers, which provide different sensitivity and diversity for host cells to detect various microbial infections.
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Ubiquitin-specific protease 25 regulates TLR4-dependent innate immune responses through deubiquitination of the adaptor protein TRAF3.
Sci Signal
PUBLISHED: 05-16-2013
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Protein ubiquitination plays a critical role in Toll-like receptor (TLR) signaling and innate immunity. Although several E3 ubiquitin ligases have been identified downstream of TLRs, the regulation of protein deubiquitination in TLR-triggered innate immune responses is poorly understood. We identified ubiquitin-specific protease 25 (USP25) as a regulator of TLR signaling. USP25 was recruited to the TLR4 signaling complex, and it associated with the adaptor proteins tumor necrosis factor receptor-associated factor 3 (TRAF3) and TRAF6 after stimulation of TLR4 with its ligand lipopolysaccharide (LPS). USP25 specifically reversed the Lys(48)-linked ubiquitination of TRAF3 that was mediated by the E3 ubiquitin ligase cIAP2 (cellular inhibitor of apoptosis 2). Deficiency in USP25 enhanced the extent of ubiquitination of TRAF3 and accelerated its degradation after TLR4 activation, which potentiated TLR4-induced activation of NF-?B (nuclear factor ?B) and MAPK (mitogen-activated protein kinase) signaling, but inhibited activation of the transcription factor IRF3 (interferon regulatory factor 3). USP25-deficient mice exhibited increased susceptibility to LPS-induced septic shock compared to their wild-type counterparts, which was associated with enhanced production of proinflammatory cytokines and decreased production of interferon-?. Thus, by inhibiting the degradation of TRAF3 during TLR4 activation, USP25 enables a balanced innate immune response.
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Differential regulation of c-Jun protein plays an instrumental role in chemoresistance of cancer cells.
J. Biol. Chem.
PUBLISHED: 05-15-2013
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The chemotherapeutic drug cisplatin (cis-diamminedichloroplatinum(II) (CDDP)) is widely used in the treatment of human cancers. However, the mechanism underlying intrinsic tumor resistance to CDDP remains elusive. Here, we demonstrate that treatment with CDDP resulted in down-regulation of c-Jun expression via caspase-9-dependent cleavage of c-Jun at Asp-65 and MEKK1-mediated ubiquitylation and degradation of c-Jun in CDDP-sensitive cancer cells. In contrast, activation of JNK2 (but not JNK1) phosphorylated and up-regulated the expression of c-Jun in CDDP-resistant cells. Activated c-Jun bound to the promoter regions of the MDR1 gene and promoted the expression of MDR1. Expression of a cleavage-resistant c-Jun mutant (D65A) suppressed CDDP-induced apoptosis of CDDP-sensitive cells, whereas depletion of JNK2, c-Jun, or MDR1 in CDDP-resistant cancer cells promoted apoptosis upon CDDP treatment. In addition, mammary gland tumors induced by polyomavirus middle T antigen in JNK2(-/-) mice were more sensitive to CDDP compared with those in JNK2(+/+) mice. These findings highlight the instrumental role of c-Jun in the resistance of tumors to treatment with CDDP and indicate that c-Jun is a molecular target for improving cancer therapy.
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Adenine phosphoribosyl transferase 1 is a key enzyme catalyzing cytokinin conversion from nucleobases to nucleotides in Arabidopsis.
Mol Plant
PUBLISHED: 05-08-2013
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In plants, the cytokinin metabolic processes, including cytokinin biosynthesis, interconversion, inactivation, and degradation, play critical roles in the regulation of cytokinin homeostasis and plant development. Purine metabolic enzymes have been implied to catalyze the cytokinin interconversion in previous works. In this study, we report that Adenine Phosphoribosyl Transferase 1 (APT1) is the causal gene of the high-dose cytokinin-resistant mutants. APT1 catalyzes the cytokinin conversion from free bases to nucleotides, and is functionally predominant among the five members of the Arabidopsis Adenine Phosphoribosyl Transferase family. Loss of APT1 activity in plants leads to excess accumulation of cytokinin bases, thus evoking myriad cytokinin-regulated responses, such as delayed leaf senescence, anthocyanin accumulation, and downstream gene expression. Thus, our study defines APT1 as a key metabolic enzyme participating in the cytokinin inactivation by phosphoribosylation.
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Committed changes in tropical tree cover under the projected 21st century climate change.
Sci Rep
PUBLISHED: 05-03-2013
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Warming and drought pose a serious threat to tropical forest. Yet the extent of this threat is uncertain, given the lack of methods to evaluate the forest tree cover changes under future climate predicted by complex dynamic vegetation models. Here we develop an empirical approach based on the observed climate space of tropical trees to estimate the maximum potential tropical tree cover (MPTC) in equilibrium with a given climate. We show that compared to present-day (2000-2009) conditions, MPTC will be reduced by 1 to 15% in the tropical band under equilibrium future (2090-2099) climate conditions predicted by 19 IPCC climate models. Tropical forests are found to regress or disappear mainly in the current transition zones between forest and savanna ecosystems. This climate pressure on tropical forests, added to human-caused land use pressure, poses a grand challenge to the sustainability of the worlds largest biomass carbon pool.
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Trimeric G protein-CARMA1 axis links smoothened, the hedgehog receptor transducer, to NF-?B activation in diffuse large B-cell lymphoma.
Blood
PUBLISHED: 04-30-2013
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Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. Aberrant activation of Hedgehog (Hh) and nuclear factor (NF)-?B pathways is ubiquitously observed and known to mediate tumor growth, survival, and chemoresistance in DLBCL. Here, we find that activation of Hh signaling is positively correlated with NF-?B pathway in DLBCL tumors, and that smoothened (SMO), the signal transducer subunit of Hh pathway, contributes to NF-?B activation through recruiting G protein subunits G?i and G?12 to activate PKC?/CARMA1/TRAF6/NEMO signaling axis followed by assembling of the CARMA1/BCL10/MALT1/TRAF6 complex to SMO. Moreover, functional inhibition of SMO enhances the cytotoxic effects of NF-?B inhibitor. Altogether, our study reveals a noncanonical Hh signaling pathway in which SMO activates trimeric G proteins and CARMA1-associated signaling complex, leading to NF-?B activation. This signaling cascade contributes to the survival of DLBCL and may serve as a potential target for combination therapies in DLBCL.
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Cord factor and peptidoglycan recapitulate the Th17-promoting adjuvant activity of mycobacteria through mincle/CARD9 signaling and the inflammasome.
J. Immunol.
PUBLISHED: 04-29-2013
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Although adjuvants are critical vaccine components, their modes of action are poorly understood. In this study, we investigated the mechanisms by which the heat-killed mycobacteria in CFA promote Th17 CD4(+) T cell responses. We found that IL-17 secretion by CD4(+) T cells following CFA immunization requires MyD88 and IL-1?/IL-1R signaling. Through measurement of Ag-specific responses after adoptive transfer of OTII cells, we confirmed that MyD88-dependent signaling controls Th17 differentiation rather than simply production of IL-17. Additional experiments showed that CFA-induced Th17 differentiation involves IL-1? processing by the inflammasome, as mice lacking caspase-1, ASC, or NLRP3 exhibit partially defective responses after immunization. Biochemical fractionation studies further revealed that peptidoglycan is the major component of heat-killed mycobacteria responsible for inflammasome activation. By assaying Il1b transcripts in the injection site skin of CFA-immunized mice, we found that signaling through the adaptor molecule caspase activation and recruitment domain 9 (CARD9) plays a major role in triggering pro-IL-1? expression. Moreover, we demonstrated that recognition of the mycobacterial glycolipid trehalose dimycolate (cord factor) by the C-type lectin receptor mincle partially explains this CARD9 requirement. Importantly, purified peptidoglycan and cord factor administered in mineral oil synergized to recapitulate the Th17-promoting activity of CFA, and, as expected, this response was diminished in caspase-1- and CARD9-deficient mice. Taken together, these findings suggest a general strategy for the rational design of Th17-skewing adjuvants by combining agonists of the CARD9 pathway with inflammasome activators.
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The effect of combined antihypertensive treatment (felodipine with either irbesartan or metoprolol) on erectile function: a randomized controlled trial.
Cardiology
PUBLISHED: 03-26-2013
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This study aimed to determine whether combining a calcium channel blocker with either an angiotensin II receptor blocker or a ?-blocker would have similar effects on sexual function in men with hypertension.
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Colorimetric sensor based on dual-functional gold nanoparticles: analyte-recognition and peroxidase-like activity.
Food Chem
PUBLISHED: 03-22-2013
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A novel colorimetric sensor based on the interaction ability with specific analytes and peroxidase-like activity of gold nanoparticles was established in this work. Combining the high-affinity binding between bare gold nanoparticles and melamine with signal amplification procedure based on the catalytic activity of gold nanoparticles for oxidation of TMB, melamine with the concentration as low as 0.02 mg/L can be easily distinguished by naked-eye observation. Such system can be adapted through carefully-controlled surface modifications of gold nanoparticles for determination of other targets.
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Single-incision laparoscopic appendectomy vs conventional laparoscopic appendectomy: systematic review and meta-analysis.
World J. Gastroenterol.
PUBLISHED: 02-21-2013
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To assess the differences in clinical benefits and disadvantages of single-incision laparoscopic appendectomy (SILA) and conventional laparoscopic appendectomy (CLA).
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MicroRNA-335 acts as a candidate tumor suppressor in prostate cancer.
Pathol. Oncol. Res.
PUBLISHED: 02-11-2013
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MicroRNA-335 (miR-335) acts as a tumor suppressor or a tumor promoter in different human malignancies. However, the involvement of miR-335 in prostate cancer (PCa) is still unclear. The purpose of this study was to investigate the functional and clinical significance of miR-335 in PCa. miR-335 expression in 3 PCa cell lines (LNCaP/DU145/PC3) and in 20 clinical PCa tissues were detected by real-time quantitative reverse transcriptase-PCR compared with corresponding controls. The function of miR-335 was investigated for cell proliferation, invasion and migration in PCa cells transfected with agents containing EGFP-miR-335 expression vector. Additionally, miR-335 expression in 104 clinical PCa tissues was detected by in situ hybridization. Its assocaitions with clinicopathological features and prognosis in patients with PCa were also determined. miR-335 was significantly down-regulated in PCa cell lines than in the normal prostate cell line (P?
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Expression and distribution of dendritic cells in nasal polyps.
Exp Ther Med
PUBLISHED: 02-08-2013
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The aim of the present study was to investigate the expression, distribution and function of dendritic cells (DCs) and to study their role in nasal polyps. The study involved 55 participants, 45 of whom had nasal polyps and were the study group and 10 who had normal inferior turbinates and were the control group. Immunohistochemical staining was used to visualize the expression and distribution of the S-100 protein. A double immunostaining method was used to visualize the CD1a and CD40 expression and the images were analyzed with Axioplan 2 microscopy. The expression level of the S-100 protein in the nasal polyps was higher than that in the normal inferior turbinates with a significant difference (P<0.01). The distribution area, number and density of the double stained cells in the nasal polyps were all greater than in the normal inferior turbinates (P<0.01). The S-100 protein and double stained cells were mainly located in the lamina propria below the mucous membrane. The present study demonstrates that DCs are involved in the pathogenesis of nasal polyps and the presence of CD40-positive DCs suggests that this was related to the reciprocal interaction between the DCs and T lymphocytes.
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Evaluation of terrestrial carbon cycle models for their response to climate variability and to CO2 trends.
Glob Chang Biol
PUBLISHED: 02-08-2013
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The purpose of this study was to evaluate 10 process-based terrestrial biosphere models that were used for the IPCC fifth Assessment Report. The simulated gross primary productivity (GPP) is compared with flux-tower-based estimates by Jung et al. [Journal of Geophysical Research 116 (2011) G00J07] (JU11). The net primary productivity (NPP) apparent sensitivity to climate variability and atmospheric CO2 trends is diagnosed from each model output, using statistical functions. The temperature sensitivity is compared against ecosystem field warming experiments results. The CO2 sensitivity of NPP is compared to the results from four Free-Air CO2 Enrichment (FACE) experiments. The simulated global net biome productivity (NBP) is compared with the residual land sink (RLS) of the global carbon budget from Friedlingstein et al. [Nature Geoscience 3 (2010) 811] (FR10). We found that models produce a higher GPP (133 ± 15 Pg C yr(-1) ) than JU11 (118 ± 6 Pg C yr(-1) ). In response to rising atmospheric CO2 concentration, modeled NPP increases on average by 16% (5-20%) per 100 ppm, a slightly larger apparent sensitivity of NPP to CO2 than that measured at the FACE experiment locations (13% per 100 ppm). Global NBP differs markedly among individual models, although the mean value of 2.0 ± 0.8 Pg C yr(-1) is remarkably close to the mean value of RLS (2.1 ± 1.2 Pg C yr(-1) ). The interannual variability in modeled NBP is significantly correlated with that of RLS for the period 1980-2009. Both model-to-model and interannual variation in model GPP is larger than that in model NBP due to the strong coupling causing a positive correlation between ecosystem respiration and GPP in the model. The average linear regression slope of global NBP vs. temperature across the 10 models is -3.0 ± 1.5 Pg C yr(-1) °C(-1) , within the uncertainty of what derived from RLS (-3.9 ± 1.1 Pg C yr(-1) °C(-1) ). However, 9 of 10 models overestimate the regression slope of NBP vs. precipitation, compared with the slope of the observed RLS vs. precipitation. With most models lacking processes that control GPP and NBP in addition to CO2 and climate, the agreement between modeled and observation-based GPP and NBP can be fortuitous. Carbon-nitrogen interactions (only separable in one model) significantly influence the simulated response of carbon cycle to temperature and atmospheric CO2 concentration, suggesting that nutrients limitations should be included in the next generation of terrestrial biosphere models.
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Comparison of the efficacy of ondansetron and granisetron to prevent postoperative nausea and vomiting after laparoscopic cholecystectomy: a systematic review and meta-analysis.
Surg Laparosc Endosc Percutan Tech
PUBLISHED: 02-07-2013
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Our purpose was to assess the prophylactic antiemetic effects of ondansetron versus granisetron for laparoscopic cholecystectomy.
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Global priority conservation areas in the face of 21st century climate change.
PLoS ONE
PUBLISHED: 01-24-2013
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In an era when global biodiversity is increasingly impacted by rapidly changing climate, efforts to conserve global biodiversity may be compromised if we do not consider the uneven distribution of climate-induced threats. Here, via a novel application of an aggregate Regional Climate Change Index (RCCI) that combines changes in mean annual temperature and precipitation with changes in their interannual variability, we assess multi-dimensional climate changes across the "Global 200" ecoregions - a set of priority ecoregions designed to "achieve the goal of saving a broad diversity of the Earths ecosystems" - over the 21(st) century. Using an ensemble of 62 climate scenarios, our analyses show that, between 1991-2010 and 2081-2100, 96% of the ecoregions considered will be likely (more than 66% probability) to face moderate-to-pronounced climate changes, when compared to the magnitudes of change during the past five decades. Ecoregions at high northern latitudes are projected to experience most pronounced climate change, followed by those in the Mediterranean Basin, Amazon Basin, East Africa, and South Asia. Relatively modest RCCI signals are expected over ecoregions in Northwest South America, West Africa, and Southeast Asia, yet with considerable uncertainties. Although not indicative of climate-change impacts per se, the RCCI-based assessment can help policy-makers gain a quantitative and comprehensive overview of the unevenly distributed climate risks across the G200 ecoregions. Whether due to significant climate change signals or large uncertainties, the ecoregions highlighted in the assessment deserve special attention in more detailed impact assessments to inform effective conservation strategies under future climate change.
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A sandwich-type DNA biosensor based on electrochemical co-reduction synthesis of graphene-three dimensional nanostructure gold nanocomposite films.
Anal. Chim. Acta
PUBLISHED: 01-08-2013
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A novel electrochemical DNA biosensor based on graphene-three dimensional nanostructure gold nanocomposite modified glassy carbon electrode (G-3D Au/GCE) was fabricated for detection of survivin gene which was correlated with osteosarcoma. The G-3D Au film was prepared with one-step electrochemical coreduction with graphite oxide and HAuCl4 at cathodic potentials. The active surface area of G-3D Au/GCE was 2.629cm(2), which was about 3.8 times compared to that of a Au-coated GCE under the same experimental conditions, and 8.8 times compared to a planar gold electrode with a similar geometric area. The resultant nanocomposites with high conductivity, electrocatalysis and biocompatibility were characterized by scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). A "sandwich-type" detection strategy was employed in this electrochemical DNA biosensor and the response of this DNA biosensor was measured by CV and amperometric current-time curve detection. Under optimum conditions, there was a good linear relationship between the current signal and the logarithmic function of complementary DNA concentration in a range of 50-5000fM with a detection limit of 3.4fM. This new biosensor exhibited a fast amperometric response, high sensitivity and selectivity and has been used in a polymerase chain reaction assay of real-life sample with a satisfactory result.
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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.