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Find video protocols related to scientific articles indexed in Pubmed.
An Overview of Hedgehog Signaling in Fibrosis.
Mol. Pharmacol.
PUBLISHED: 11-13-2014
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The Hedgehog (Hh) signaling plays an important role during embryogenesis and tissue regeneration. Recently, studies revealed that over-activated Hh signaling leads to fibrogenesis in many types of tissues. The activation of Hh signaling is involved in epithelial-mesenchymal transition (EMT) and excessive extracellular matrix deposition. Blockade of Hh signaling abolishes the induction of EMT and ameliorates tissue fibrosis. Therefore, new therapeutic targets to alleviate fibrosis based on the Hh signaling have attracted a great deal of attention. This is a new strategy for treating fibrosis and other related diseases. In this review, we will discuss the crucial role of Hh signaling in fibrogenesis to provide a better understanding of their relationship and to encourage the study of novel targeted therapies.
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A study of the kinetics and isotherms for Cr(VI) adsorption in a binary mixture of Cr(VI)-Ni(II) using hierarchical porous carbon obtained from pig bone.
Water Sci. Technol.
PUBLISHED: 09-27-2014
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Cr(VI) adsorption in a binary mixture Cr(VI)-Ni(II) using the hierarchical porous carbon prepared from pig bone (HPC) was investigated. The various factors affecting adsorption of Cr(VI) ions from aqueous solutions such as initial concentration, pH, temperature and contact time were analyzed. The results showed excellent efficiency of Cr(VI) adsorption by HPC. The kinetics and isotherms for Cr(VI) adsorption from a binary mixture Cr(VI)-Ni(II) by HPC were studied. The adsorption equilibrium described by the Langmuir isotherm model is better than that described by the Freundlich isotherm model for the binary mixture in this study. The maximum adsorption capacity was reliably found to be as high as 192.68 mg/g in the binary mixture at pH 2. On fitting the experimental data to both pseudo-first- and second-order equations, the regression analysis of the second-order equation gave a better R² value.
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Perylene-cored star-shaped polycations for fluorescent gene vectors and bioimaging.
ACS Appl Mater Interfaces
PUBLISHED: 09-09-2014
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Two star polycations, poly(2-aminoethyl methacrylate) (PAEMA, P1) and poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA, P2), have been synthesized with perylene diimide (PDI) as the central fluorophore. (1)H NMR and (13)C NMR are used to confirm the successful synthesis of a macromolecular initiator. Using ATRP strategy, P1 and P2 are obtained with narrow molecular weight distribution. The star polymers have good fluorescence properties in aqueous solution, which provides fluorescent tracing and imaging during gene delivery. Both P1 and P2 can efficiently condense DNA into stable nanoparticles. Transfection studies demonstrate that P1 and P2 deliver DNA into live cells with higher efficiency and lower cytotoxicity than polyethylenimine (PEI, 25 kDa). P2 shows higher capacity for gene delivery than P1 due to its better buffering and faster rate of cellular internalization.
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Hepatic stellate cell is activated by microRNA-181b via PTEN/Akt pathway.
Mol. Cell. Biochem.
PUBLISHED: 08-23-2014
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Activation of hepatic stellate cells (HSCs) is an essential event in the initiation and progression of liver fibrosis. MicroRNAs have been shown to play a pivotal role in regulating HSC functions such as cell proliferation, differentiation, and apoptosis. Recently, miR-181b has been reported to promote HSCs proliferation by targeting p27. But whether alpha-smooth muscle actin (?-SMA) or collagens could be promoted by miR-181b in activated HSCs is still not clear. Therefore, the understanding of the role of miR-181b in liver fibrosis remains limited. Our results showed that miR-181b expression was increased much higher than miR-181a expression in vitro in transforming growth factor-?1-induced HSC activation as well as in vivo in carbon tetrachloride-induced rat liver fibrosis. Of note, overexpression of miR-181b significantly increased the expressions level of ?-SMA and type I collagen, and further promoted HSCs proliferation. Furthermore, phosphatase and tensin homologs deleted on chromosome 10 (PTEN), a negative regulator of PI3K/Akt pathway, were confirmed as a direct target of miR-181b. We demonstrated that miR-181b could suppress PTEN expression and increase Akt phosphorylation in HSCs. Interestingly, the effects of miR-181b on the activation of HSCs were blocked down by Akt inhibitor LY294002. Our results revealed a profibrotic role of miR-181b in HSC activation and demonstrated that miR-181b could activate HSCs, at least in part, via PTEN/Akt pathway.
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Induction of TRPV5 expression by small activating RNA targeting gene promoter as a novel approach to regulate cellular calcium transportation.
Life Sci.
PUBLISHED: 08-17-2014
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Promoter-targeted small activating RNAs (saRNAs) have been shown to be able to induce target gene expression, a mechanism known as RNA activation (RNAa). The present study tested whether saRNA can induce the overexpression of TRPV5 in human cells derived from the kidney and subsequently manipulate cell calcium uptake.
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Systemic gene silencing in plants triggered by fluorescent nanoparticle-delivered double-stranded RNA.
Nanoscale
PUBLISHED: 07-28-2014
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A cationic fluorescence nanoparticle efficiently enters plants with high transfection efficacy. Applying a mixture of G2/dsRNA to the model plant, Arabidopsis root, leads to significant reduction in the expression of important developmental genes and results in apparent phenotypes. This study reports a non-viral gene nanocarrier which triggers gene silencing in plants and leads to systemic phenotypes.
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Effect of tacrolimus in idiopathic membranous nephropathy: a meta-analysis.
Chin. Med. J.
PUBLISHED: 07-22-2014
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The efficacy and safety of immunosuppression for idiopathic membranous nephropathy (IMN) are still controversial. Recent studies showed tacrolimus is effective in the treatment of IMN. To evaluate the efficacy and safety of tacrolimus (TAC) for IMN, we conducted a meta-analysis of published medical literatures.
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The effect of oligonucleotide probes substituted by deoxyinosines on the specificity of SNP detection on the DNA microarray.
Electrophoresis
PUBLISHED: 07-06-2014
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One of the main factors that can affect the quality of microarray results is the microarray hybridization specificity. The key factor that affects hybridization specificity is the design of the probes. In this paper, we described a novel oligonucleotide probe containing deoxyinosines aimed at improving DNA hybridization specificity. We compared different probes to determine the distance between deoxyinosine base and SNPs site and the number of deoxyinosine bases. The new probe sequences contained two set of deoxyinosines (each set had two deoxyinosines), in which the interval between SNP site and each set of deoxyinosines was two bases. The new probes could obtain the highest hybridization specificity. The experimental results showed that probes containing deoxyinosines hybridized effectively to the perfectly matched target and improved the hybridization specificity of DNA microarray. By including a simple washing step after hybridization, these probes could distinguish matched targets from single-base-mismatched sequences perfectly. For the probes containing deoxyinosines, the fluorescence intensity of a match sequence was more than 8 times stronger than that of a mismatch. However, the intensity ratio was only 1.3 times or less for the probes without deoxyinosines. Finally, using hybridization of the polymerase chain reaction (PCR) product microarrays, we successfully genotyped single-nucleotide polymorphism (SNP) of 140 samples using these new labeled probes. Our results show that this is a useful new strategy for modifying oligonucleotide probes for use in DNA microarray analysis. This article is protected by copyright. All rights reserved.
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Resveratrol inhibits epithelial-mesenchymal transition and renal fibrosis by antagonizing the hedgehog signaling pathway.
Biochem. Pharmacol.
PUBLISHED: 07-03-2014
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Epithelial-to-mesenchymal transition (EMT), a biologic process in which tubular cells lose their epithelial phenotypes and acquire new characteristic features of mesenchymal properties, is increasingly recognized as an integral part of renal tissue fibrogenesis. Recent studies indicate that resveratrol, a botanical compound derived mainly from the skins of red grapes, may have anti-fibrotic effects in many tissues, but the potential molecular mechanism remains unknown. In the present study, we identified that resveratrol inhibits the induction of EMT and deposition of extracellular matrix (ECM) through antagonizing the hedgehog pathway in vitro and in vivo. In rats with unilateral ureteral obstruction (UUO), administration of resveratrol (20mg/kg/day) significantly reduced serum creatinine. Resveratrol also decreased expression of TGF-?1, and inhibited the phenotypic transition from epithelial cells to mesenchymal cells, and the deposition of ECM in UUO rats. In cultured renal tubular epithelial cells (NRK-52E), TGF-?1-induced EMT and ECM synthesis was abolished with the treatment of resveratrol. The induction of EMT was associated with the activation of the hedgehog pathway. Resveratrol treatment markedly inhibited the over-activity of the hedgehog pathway in the obstructed kidney and in TGF-?1-treated NRK-52E cells, resulted in reduction of cellular proliferation, EMT and ECM accumulation. Thus, these results suggest that resveratrol is able to inhibit EMT and fibrosis in vivo and in vitro through antagonizing the hedgehog pathway, and resveratrol may have therapeutic potential for patients with fibrotic kidney diseases.
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M2-polarized macrophages contribute to the decreased sensitivity of EGFR-TKIs treatment in patients with advanced lung adenocarcinoma.
Med. Oncol.
PUBLISHED: 06-23-2014
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Previous study has revealed that tumor-associated macrophages (TAMs) correlate with response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC). In the present study, we further determined that M2-TAMs, but not M1-TAMs, are related to the treatment response to EGFR-TKIs in advanced NSCLC and may be an independent predictor of survival. Eighty-eight advanced lung adenocarcinoma patients treated with a second-line EGFR-TKI were involved in this study. M2-TAMs counts but not M1-TAMs were significantly higher in patients with progressive disease than in those without (P < 0.001). A trend also remained in patients with known EGFR status (n = 61) and those with mutant EGFR (n = 49). High M2-TAMs counts were shown to be significantly related to poor progression-free survival (PFS) and overall survival (OS) in all patients, or subsets of patients with known EGFR status or patients with EGFR mutation (all P < 0.05). Multivariate Cox analyses showed that high M2-TAMs counts and EGFR mutations were both independent factors associated with PFS and OS (P < 0.05). Overall, we revealed that M2- but not M1-TAMs are related to the response of EGFR-TKIs treatment irrespective of EGFR mutation and can independently predict survival in advanced lung adenocarcinoma treated with a second-line EGFR-TKI.
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Parameterized hilbert-type integral inequalities in the whole plane.
ScientificWorldJournal
PUBLISHED: 06-21-2014
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By the use of the way of real analysis, we estimate the weight functions and give some new Hilbert-type integral inequalities in the whole plane with nonhomogeneous kernels and multiparameters. The constant factors related to the hypergeometric function and the beta function are proved to be the best possible. We also consider the equivalent forms, the reverses, and some particular cases in the homogeneous kernels.
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Reversion of trichostatin A resistance via inhibition of the Wnt signaling pathway in human pancreatic cancer cells.
Oncol. Rep.
PUBLISHED: 06-16-2014
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Drug resistance is a major impediment to successful chemotherapy in pancreatic cancer (PC) patients. We investigated the effect of Wnt/?-catenin signaling inhibition by wnt-c59 on chemoresistance in a trichostatin A-resistant Panc-1 cell line (Panc-1/TSA). Panc-1/TSA cells were treated with the Wnt/??catenin signaling inhibitor wnt-c59 (10 µmol?·?l-1) and/or trichostatin A (TSA; 10 µmol?·?l-1) for 24 h. CCK-8 assay was utilized to analyze the interactive effect of TSA and wnt-c59 on induction of apoptosis of the Panc-1/TSA cells. Cell apoptosis was measured by flow cytometry. Real-time PCR and western blotting were used to assess Wnt/?-catenin signaling, epithelial-mesenchymal transition (EMT) and multidrug resistance (MDR). Real-time cell analysis (RTCA) was used to detect the cell migration ability. After wnt-c59 treatment for 24 h, relative genes and transcriptional targets of Wnt/?-catenin signaling were downregulated (P<0.05). CCK-8 assay indicated that the combination of TSA and wnt-c59 had a synergistic effect on induction of Panc-1/TSA cell apoptosis. As detected by FACS, cell apoptosis rates increased significantly (P<0.05). The results of RTCA showed that the cell indices of the control group, wnt-c59 group, TSA group and TSA+wnt-c59 combination group were 1.2842±0.0257, 1.2155±0.0282, 1.2533±0.0194 and 0.8541±0.0250, respectively. In accordance, MMP-9 protein in the wnt-c59 treatment groups was decreased compared to the non-wnt-c59 treatment groups. Meanwhile, E-cadherin protein was upregulated and vimentin protein was downregulated, both of which are characteristic markers of EMT. Chemoresistant gene MDR1 and P-glycoprotein (P-gp) in the wnt-c59 treatment groups had a reduced expression compared to the non-wnt-c59 treatment groups. This study revealed that TSA sensitivity, migration ability, and the EMT phenotype in Panc-1/TSA cells were reversed following Wnt/?-catenin signaling inhibition.
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Distinguishing cytosine methylation using electrochemical, label-free detection of DNA hybridization and ds-targets.
Biosens Bioelectron
PUBLISHED: 06-08-2014
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In this communication we report on two important effects related to the detection of DNAs. Firstly, we investigate the sensor response to target DNA when the target is in a double stranded (ds) form and compare the response to single stranded (ss) target DNA. The importance in evaluating such an effect lies in the fact that most biological DNA targets are found in ds form. Secondly, we use synthetic ds targets to investigate the effect of DNA methylation on the sensor response. DNA methylation is known to affect functional properties of DNA and is related to a number of diseases, including various cancers. In these studies, we utilize our previously developed sensor platform, which is based on the use of a glassy carbon electrode-confined conducting polymer that is covalently modified with DNA probe sequences. The signal detection methodology we use is measuring a change in the reaction kinetics of ferro-ferricyanide redox couple at the electrode upon hybridization by means of electrical impedance spectroscopy (EIS). Additionally, EIS is utilized to study the kinetics of the hybridization of the conducting polymer-bound probe with methylated vs. non-methylated ds-DNA. Preliminary results are proving valuable as a guide to the future design of sensors for gene methylation.
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Investigation of the epidermal growth factor receptor mutation rate in non-small cell lung cancer patients and the analysis of associated risk factors using logistic regression.
Oncol Lett
PUBLISHED: 04-30-2014
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The aim of the present study was to investigate the mutation rate of the epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) patients and to apply logistic regression analysis to investigate the factors associated with EGFR gene mutation to provide data for the treatment of NSCLC. Paraffin tissue, bronchoscopy or pleural effusion specimens were collected from 176 NSCLC patients following pathological diagnosis. The EGFR gene exon 19 delL747-S75linss and delL747-S752ins deletion mutations, and the exon 20 T790M and exon 21 L858R mutations were identified using amplification refractory mutation system analysis. The clinical data and laboratory results of the patients were collected, and the total mutation rate of the EGFR gene in exons 19, 20 and 21 in the 176 NSCLC patients was found to be 48.3% (85/176). In addition, the EGFR gene mutation rate in adenocarcinoma was found to be significantly higher than that in squamous cell and large cell carcinoma (?(2)=12.454; P=0.002). Furthermore, the mutation rate was found to be significantly higher in females than in males (?(2)=13.78; P=0.001). The rate of exon 19 mutation was 21.0% (37/176), whereas the rate of exon 20 T90M mutation was 1.7% (3/176) and that of exon 21 L858R mutation was 29.0% (51/176). The logistic regression analysis revealed that the female gender, adenocarcinoma, distant metastasis and chemotherapy are factors associated with EGFR gene mutation (P<0.05). The female gender resulted in an increased incidence (2.438 times that of males) of EGFR mutation. Similarly, adenocarcinoma, distant metastasis and chemotherapy exhibited an increase in EGFR mutation risk (by 2.571, 2.810 and 0.367 times, respectively). The rate of EGFR mutation was high in the NSCLC patients, predominantly in exons 21 and 19. Therefore, these factors (female gender, adenocarcinoma, distant metastasis and chemotherapy) may increase the probability of EGFR gene mutations.
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Effects of vegetative propagule pressure on the establishment of an introduced clonal plant, Hydrocotyle vulgaris.
Sci Rep
PUBLISHED: 04-24-2014
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Some introduced clonal plants spread mainly by vegetative (clonal) propagules due to the absence of sexual reproduction in the introduced range. Propagule pressure (i.e. total number of propagules) may affect the establishment and thus invasion success of introduced clonal plants, and such effects may also depend on habitat conditions. A greenhouse experiment with an introduced plant, Hydrocotyle vulgaris was conducted to investigate the role of propagule pressure on its invasion process. High (five ramets) or low (one ramet) propagule pressure was established either in bare soil or in an experimental plant community consisting of four grassland species. H. vulgaris produced more total biomass under high than under low propagule pressure in both habitat conditions. Interestingly, the size of the H. vulgaris individuals was smaller under high than under low propagule pressure in bare soil, whereas it did not differ between the two propagule pressure treatments in the grassland community. The results indicated that high propagule pressure can ensure the successful invasion in either the grass community or bare soil, and the shift in the intraspecific interaction of H. vulgaris from competition in the bare soil to facilitation in the grassland community may be a potential mechanism.
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E2F1 acts as a negative feedback regulator of c-Myc?induced hTERT transcription during tumorigenesis.
Oncol. Rep.
PUBLISHED: 04-09-2014
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Since induction of hTERT expression and subsequent telomerase activation play a critical role in the multistep process of tumorigenesis, a better understanding of hTERT regulation may provide not only a rationale for the molecular basis of cancer progression but also a path to the development of cancer prevention. The c-Myc oncoprotein can function effectively in activating the transcriptional expression of hTERT through E-box elements on its promoter. E2F transcription factor 1 (E2F1) was found to be a repressor of hTERT transcription by directly binding to its promoter, thereby inhibiting hTERT protein expression. For the extensively crosstalk between c-Myc and E2F1 signals, which is now known to be vital to cell fate, we speculated that E2F1 may play a negative regulatory role in c-Myc-induced hTERT transcription. In the present study, we chose to use human embryonic fibroblast cells as an experimental model system, and present evidence that the E2F1 transcription factor constitutes a negative regulatory system to limit c-Myc transcriptional activation of hTERT in normal cells. Furthermore, we demonstrated that upregulation of the miR-17-92 cluster (miR-20a/miR-17-5p) is involved in the regulation of E2F1-mediated negative feedback of the c-Myc/hTERT pathway. Our results not only reveal novel insights into how normal cells control the transmission of c-Myc-mediated oncogenic signals, but also further establish E2F1 as an important molecular target for cancer therapy.
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Comparative ultrastructure analysis of radiation-induced radioresistant laryngeal cancer hep-2 cell line.
Ultrastruct Pathol
PUBLISHED: 03-31-2014
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Radioresistance is one of the main reasons for the failure of radiotherapy in laryngeal cancer. However, the mechanisms of radioresistance of tumor cells have remained elusive. This study was conducted to identify the ultrastructural changes of radiation-induced radioresistant laryngeal cancer hep-2 cell line. First, a radioresistant hep-2R cell line was generated after prolonged exposure to ?-rays for 60 Gy (6 Gy/day, 2 days/week) and was confirmed by clonogenic assay. Next, the ultrastructural differences between hep-2R cells and hep-2 cells were compared by transmission electron microscopy. Finally, the results showed that hep-2R cells showed significant resistance to radiation compared with parental hep-2 cells. Increased cell nucleus atypia, more rough endoplasmic reticulum and less mitochondria were observed in hep-2R cells. The amount of microvilli of hep-2R was similar to hep-2 cell. In summary, these ultrastructural differences revealed the morphological mechanism that hep-2R cells had stronger radioresistance than hep-2 cells.
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Effect of Sedum sarmentosum BUNGE extract on aristolochic acid-induced renal tubular epithelial cell injury.
J. Pharmacol. Sci.
PUBLISHED: 03-27-2014
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Aristolochic acid (AA) is known as a potent mutagen that induces significant cytotoxic and mutagenic effects on renal tubular epithelial cells. Clinically, the persistent injury of AA results in the infiltration of inflammatory cells, epithelial-to-mesenchymal transition (EMT), and renal tubulointerstitial fibrosis. There are no truly effective pharmaceuticals. In this study, we investigated the potential role of the extract of Sedum sarmentosum Bunge (SSB), a traditional Chinese herbal medicine, on rat tubuloepithelial (NRK-52E) cells after AA injury in vitro. Evidence revealed that AA induced mitochondrial-pathway-mediated cellular apoptosis, accompanied by cell proliferation in a feedback mechanism. Treatment with SSB also induced cells to enter early apoptosis, but inhibited cell proliferation. In cultured NRK-52E cells, AA induced the imbalance of MMP-2/TIMP-2 and promoted EMT and ECM accumulation. SSB treatment significantly alleviated AA-induced NRK-52E cells fibrosis-like appearance, inhibited the induction of EMT, and deposition of ECM. SSB also decreased the activity of the NF-?B signaling pathway, resulting in down-regulated expression of NF-?B-controlled chemokines and pro-inflammatory cytokines, including MCP-1, MIF, and M-CSF, which may regulate the macrophage-mediated inflammatory reaction during renal fibrosis in vivo. Therefore, these findings suggest that SSB exerts protective effects against AA-induced tubular epithelial cells injury through suppressing the synthesis of inflammatory factors, EMT, and ECM production.
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A risk evaluation model of cervical cancer based on etiology and human leukocyte antigen allele susceptibility.
Int. J. Infect. Dis.
PUBLISHED: 02-27-2014
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There are no reliable risk factors to accurately predict progression to cervical cancer in patients with chronic cervicitis infected with human papillomavirus (HPV). The aim of this study was to create a validated predictive model based on the risk factors for cervical cancer. A model to estimate the risk of cervical cancer may help select patients for intervention therapy in order to reduce the occurrence of cervical cancer after HPV infection.
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HER2 expression in primary gastric cancers and paired synchronous lymph node and liver metastases. A possible road to target HER2 with radionuclides.
Tumour Biol.
PUBLISHED: 02-03-2014
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Resistance has been reported to human epidermal growth factor receptor 2 (HER2)-targeted therapy with the tyrosine kinase inhibitor lapatinib and the antibody trastuzumab in metastatic gastric cancer. An alternative or complement might be to target the extracellular domain of HER2 with therapy-effective radionuclides. The fraction of patients with HER2 expression in primary tumors and major metastatic sites, e.g., lymph nodes and liver, was analyzed to evaluate the potential for such therapy. Samples from primary tumors and lymph node and liver metastases were taken from each patient within a few hours, and to our knowledge, such sampling is unique. The number of analyzed cases was therefore limited, since patients that had received preoperative radiotherapy, chemotherapy, or HER2-targeted therapy were excluded. From a large number of considered patients, only 29 could be included for HER2 analysis. Intracellular mutations were not analyzed since they are assumed to have no or minor effect on the extracellular binding of molecules that deliver radionuclides. HER2 was positive in nearly 52 % of the primary tumors, and these expressed HER2 in corresponding lymph node and liver metastases in 93 and 100 % of the cases, respectively. Similar values for primary tumors and also good concordance with metastases have been indicated in the literature. Thus, relevant radionuclides and targeting molecules for nuclear medicine-based noninvasive, whole-body receptor analysis, dose planning, and therapy can be applied for many patients; see "Discussion" Hopefully, more patients can then be treated with curative instead of palliative intention.
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Formyl peptide receptor suppresses melanoma development and promotes NK cell migration.
Inflammation
PUBLISHED: 01-23-2014
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In order to understand how tumor cells can escape immune surveillance mechanisms and thus develop antitumor therapies, it is critically important to investigate the mechanisms by which the immune system interacts with the tumor microenvironment. In our current study, wild-type mice were inoculated with melanoma cell line B16-F10 (1?×?10(6)/mouse) and treated with the formyl peptide receptor (FPR) agonist WKYMVm or the FPR antagonist WRW(4). Growth of melanoma cell line B16-F10 was significantly inhibited in WKYMVm-treated mice and markedly promoted in WRW(4)-treated mice compared with control. Decreased number of myeloid-derived suppressor cells (MDSCs) and increased NK cell infiltration in tumor tissues were detected from WKYMVm-treated mice. Next, we showed that depletion of NK cell significantly increased tumor development in B16 tumor-bearing mice compared with the control group, and the suppressed tumor-developing effect of WKYMVm in B16 melanoma was abrogated with NK cell depletion. We also found that WKYMVm stimulates chemotactic migration in NK cells via the FPR family, and this was dependent on extracellular signal-related kinase (ERK) activation. Moreover, in our further experiment, we showed that the increased infiltration of NK cell and promoted NK cell chemotaxis in B16 melanoma induced by WKYMVm were both abolished with ERK inhibitor PD98059 administration. In conclusion, the FPR family promoted NK cell migration through ERK activation and inhibited B16 melanoma growth in a murine model.
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Elevated dopamine induces minimal hepatic encephalopathy by activation of astrocytic NADPH oxidase and astrocytic protein tyrosine nitration.
Int. J. Biochem. Cell Biol.
PUBLISHED: 01-20-2014
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We previously demonstrated that dopamine (DA) overload may be a key mechanism behind development of minimal hepatic encephalopathy (MHE) in rats. It has been shown that low-grade cerebral oedema and oxidative stress play important roles in the pathogenesis of MHE. In the current study, DA-triggered oxidative injury in cerebral cortex was studied.
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Matrix metalloproteinase-9 overexpression is closely related to poor prognosis in patients with colon cancer.
World J Surg Oncol
PUBLISHED: 01-18-2014
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Matrix metalloproteinase-9 (MMP-9) is an important member of the matrix metalloproteinase family and is considered to be involved in the invasion and metastasis of cancer cells. This study analyzed the expression of MMP-9 in colon cancer patients and the relationship between this expression and clinicopathological features and survival.
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Sedum sarmentosum Bunge extract exerts renal anti-fibrotic effects in vivo and in vitro.
Life Sci.
PUBLISHED: 01-03-2014
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Sedum sarmentosum Bunge, a traditional Chinese herbal medicine, has a wide range of clinical effects, including anti-oxidation, anti-inflammation, and anti-cancer properties. In this study, we determined whether S. sarmentosum Bunge Extract (SSBE) has anti-fibrotic effects on renal tissues.
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Surgical management of urolithiasis in patients after urinary diversion.
PLoS ONE
PUBLISHED: 01-01-2014
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To present our experience in surgical management of urolithiasis in patients after urinary diversion.
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Spatial and temporal variations of ecosystem service values in relation to land use pattern in the loess plateau of china at town scale.
PLoS ONE
PUBLISHED: 01-01-2014
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Understanding the relationship between land use change and ecosystem service values (ESVs) is the key for improving ecosystem health and sustainability. This study estimated the spatial and temporal variations of ESVs at town scale in relation to land use change in the Loess Plateau which is characterized by its environmental vulnerability, then analyzed and discussed the relationship between ESVs and land use pattern. The result showed that ESVs increased with land use change from 1982 to 2008. The total ESVs increased by 16.17% from US$ 6.315 million at 1982 to US$ 7.336 million at 2002 before the start of the Grain to Green project, while increased significantly thereafter by 67.61% to US$ 11.275 million at 2008 along with the project progressed. Areas with high ESVs appeared mainly in the center and the east where largely distributing orchard and forestland, while those with low ESVs occurred mainly in the north and the south where largely distributing cropland. Correlation and regression analysis showed that land use pattern was significantly positively related with ESVs. The proportion of forestland had a positive effect on ESVs, however, that of cropland had a negative effect. Diversification, fragmentation and interspersion of landscape positively affected ESVs, while land use intensity showed a negative effect. It is concluded that continuing the Grain to Green project and encouraging diversified agriculture benefit to improve the ecosystem service.
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Regional arterial infusion with lipoxin A4 attenuates experimental severe acute pancreatitis.
PLoS ONE
PUBLISHED: 01-01-2014
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Investigate the therapeutic effect of regional arterial infusion (RAI) with Aspirin-Triggered Lipoxin A4 (ATL) in experimental severe acute pancreatitis (SAP) in rats.
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Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells.
Int J Nanomedicine
PUBLISHED: 01-01-2014
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Gold nanoparticles (GNPs) can potentially be used in biomedical fields ranging from therapeutics to diagnostics, and their use will result in increased human exposure. Many studies have demonstrated that GNPs can be deposited in the kidneys, particularly in renal tubular epithelial cells. Chronic hypoxic is inevitable in chronic kidney diseases, and it results in renal tubular epithelial cells that are susceptible to different types of injuries. However, the understanding of the interactions between GNPs and hypoxic renal tubular epithelial cells is still rudimentary. In the present study, we characterized the cytotoxic effects of GNPs in hypoxic renal tubular epithelial cells.
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Decreased intratumoral Foxp3 Tregs and increased dendritic cell density by neoadjuvant chemotherapy associated with favorable prognosis in advanced gastric cancer.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Although neoadjuvant chemotherapy (NACT) has been increasingly used to improve the outcome of advanced gastric cancer (GC) for decades, its precise efficacy has been difficult to evaluate yet. Abundant studies have investigated the predictive factors that represent the effect of NACT on advanced GC. In the present study, the intratumoral infiltration of regulatory T cells (Tregs) and dendritic cells (DCs) response to NACT in advanced GC and their correlation with prognosis were evaluated. Infiltration of Tregs (marked by Foxp3) and DCs (marked by S-100) in 102 advanced GC specimens with or without NACT was measured using immunohistochemical method. Intratumoral infiltration of Foxp3 Tregs was significantly lower and DC density was significantly higher in NACT group than that in nNACT group (P=0.007, P=0.002, respectively). Infiltration of Foxp3 Tregs was significantly associated with tumor invasion depth (P<0.001). The DC density was significantly correlated with histopathologic type (P=0.035), invasion depth (P=0.002), TNM stage (P=0.018), and lymph node metastasis (P<0.001). There was no significant difference of patient's OS between NACT and nNACT groups (P=0.452); however, patients treated with NACT had longer OS with lower infiltration of Foxp3 Tregs (P<0.001) and higher infiltration of DCs (P=0.010). Univariate and multivariate analyses indicated that infiltration of Foxp3 Tregs and DCs were independent prognostic factors (P=0.002, P=0.003, respectively). The results demonstrated that NACT could decrease intratumoral Foxp3 Tregs infiltration and increase DCs density, and that infiltration of Foxp3 Tregs and DCs may serve as novel prognostic biomarkers of human GC.
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Antitumor efficacy of ?-solanine against pancreatic cancer in vitro and in vivo.
PLoS ONE
PUBLISHED: 01-01-2014
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?-solanine, a steroidal glycoalkaloid in potato, was found to have proliferation-inhibiting and apoptosis-promoting effect on multiple cancer cells, such as clone, liver, melanoma cancer cells. However, the antitumor efficacy of ?-solanine on pancreatic cancer has not been fully evaluated. In this study, we inquired into the anti-carcinogenic effect of ?-solanine against human pancreatic cancer cells. In the present study, we investigated the anti-carcinogenic effect of ?-solanine against human pancreatic cancer cells. In vitro, ?-solanine inhibited proliferation of PANC-1, sw1990, MIA PaCa-2 cells in a dose-dependent manner, as well as cell migration and invasion with atoxic doses. The expression of MMP-2/9, extracellular inducer of matrix metalloproteinase (EMMPRIN), CD44, eNOS and E-cadherin were suppressed by ?-solanine in PANC-1 cells. Moreover, significantly decreased vascular endothelial growth factor (VEGF) expression and tube formation of endothelial cells were discerned following ?-solanine treatment. Suppressed phosphorylation of Akt, mTOR, and Stat3, and strengthen phosphorylation of ?-catenin was found, along with markedly decreased tran-nuclear of NF-?B, ?-catenin and TCF-1. Following the administration of ?-solanine (6 µg/g for 2 weeks) in xenograft model, tumor volume and weight were decreased by 61% and 43% (p<0.05) respectively, showing decreased MMP-2/9, PCNA and VEGF expression. In conclusion, ?-solanine showed beneficial effects on pancreatic cancer in vitro and in vivo, which may via suppressing the pathway proliferation, angiogenesis and metastasis.
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Sevelamer carbonate lowers serum phosphorus effectively in haemodialysis patients: a randomized, double-blind, placebo-controlled, dose-titration study.
Nephrol. Dial. Transplant.
PUBLISHED: 10-22-2013
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Hyperphosphataemia in patients with advanced chronic kidney disease (CKD) is associated with adverse outcomes, including vascular calcification and higher mortality rates. While phosphate lowering is an integral aspect of CKD management, the efficacy and safety of phosphate binders in a contemporary cohort of Chinese haemodialysis patients (who have different genetics and dietary patterns than other populations) has not been previously described. Moreover, sparse data are available on strategies for optimal dose titration when transitioning from a calcium-based to a polymer-based phosphate binder.
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Urinary stone analysis on 12,846 patients: a report from a single center in China.
Urolithiasis
PUBLISHED: 09-24-2013
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We reported a retrospective review of the urinary stone compositions in 12,846 patients. Data on urinary stone compositions analyzed between January 2003 and December 2012 in our center were collected. Infrared spectroscopy was used for stone analysis. Predominant stone component was recorded. Patients were divided into four age groups: 0-18, 19-40, 41-60, and 61-92, and five categories by components. In order to determine the change of stone characteristics with respect to time, data were also divided into two periods, 2003-2007 and 2008-2012. A total of 12,846 stones were included in this study. The age of the patients ranged from 1 to 92 years with 7,736 males and 5,110 females. Stone made of single component was rare, 2.61 %. Calcium oxalate stone was the most common component at 82.56 %. Calcium oxalate and uric acid stones were more common in male than in female. The incidence of calcium phosphate stones and uric acid stones had increased during the past 5 years, while calcium oxalate stones decreased. We found the highest incidence of stone disease in the 41-60 years old group and the lowest in the 1-18 years old for both genders. Calcium oxalate was the dominant component in every group but was more prevalent in 19-40 years group. The percentage of magnesium ammonium phosphate stone and uric acid stone increased with age.
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Lipoxin A4 attenuation of endothelial inflammation response mimicking pancreatitis-induced lung injury.
Exp. Biol. Med. (Maywood)
PUBLISHED: 09-02-2013
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Lipoxins (LXs) and their analogues are known to display potent anti-inflammatory actions. Previously, we reported that lipoxin A4 (LXA4) possessed powerful anti-inflammatory properties in acute pancreatitis in rats and that it may ameliorate the concomitant acute lung injury by reducing cytokine generation and inhibiting neutrophil activation. Considering that the vascular endothelium plays an important role during adherence, migration and activation of leukocytes, the present study was designed to investigate the effects of LXA4 on the inflammatory response induced by tumor necrosis factor ? (TNF-?) in human pulmonary microvascular endothelial cells (HPMECs) and explore the potential mechanisms involved in these processes. We found that LXA4 markedly down-regulated the expression of monocyte chemotactic protein-1 (MCP-1), E-selectin, and interleukin-6 (IL-6) mRNA, as well as intercellular adhesion molecule-1 (ICAM-1) in TNF-?-exposed HPMECs. Moreover, LXA4 inhibited the phosphorylation and nuclear translocation of nuclear factor-?B/p65 (NF-?B/p65) and phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) in HPMECs following TNF-? stimulation. Heme oxygenase-1 (HO-1), a cytoprotective enzyme, was up-regulated by LXA4 in both non- and TNF-?-stimulated HPMECs. In conclusion, the protective effects of LXA4 to ALI may be executed through inhibition inflammation pathways of NF-?B and p38 MAPK and up-regulation of cytoprotective HO-1.
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Anti-fatigue effect of ginsenoside Rb1 on postoperative fatigue syndrome induced by major small intestinal resection in rat.
Biol. Pharm. Bull.
PUBLISHED: 08-06-2013
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Ginsenoside Rb1 (GRb1), one of the principle active ingredients of Panax ginseng, exerts multiple pharmacological activities to fight fatigue. In the present study, we investigate the anti-fatigue effect of GRb1 on postoperative fatigue syndrome (POFS) in a rat model induced by major small intestinal resection. GRb1 (10 mg/kg) was administrated intraperitoneally once daily for 1, 3, 7, and 10 d from the operation day. Anti-fatigue effect was assessed by grasping test and biochemical parameters in blood or skeletal muscle were determined by autoanalyzer or commercially available kits. Transmission electron microscope was applied to observe the ultra microstructure of skeletal muscles. The results revealed that GRb1 significantly enhanced rat maximum grip strength with POFS. Similarly, negative alterations in biochemical parameters (lactic acid, hepatic glycogen, muscle glycogen and malondialdehyde) of POFS rats were improved by GRb1. In addition, GRb1 also increased the activity of lactate dehydrogenase and superoxide dismutase in POFS. No significant differences of levels of blood urea nitrogen and ultra microstructure of skeletal muscles were found between the POFS and GRb1 treatment rats. The potent anti-fatigue effect of GRb1 on POFS might be achieved through improvement of energy metabolism and suppression of skeletal muscle oxidative stress.
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Curcumin up-regulates phosphatase and tensin homologue deleted on chromosome 10 through microRNA-mediated control of DNA methylation - a novel mechanism suppressing liver fibrosis.
FEBS J.
PUBLISHED: 07-24-2013
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Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) has been reported to play a role in the suppression of activated hepatic stellate cells (HSCs). Moreover, it has been demonstrated that hypermethylation of the PTEN promoter is responsible for the loss of PTEN expression during HSC activation. Methylation is now established as a fundamental regulator of gene transcription. MicroRNAs (miRNAs), which can control gene expression by binding to their target genes for degradation and/or translational repression, were found to be involved in liver fibrosis. However, the mechanism responsible for miRNA-mediated epigenetic regulation in liver fibrosis still remained unclear. In the present study, curcumin treatment significantly resulted in the inhibition of cell proliferation and an increase in the apoptosis rate through the up-regulation of PTEN associated with a decreased DNA methylation level. Only DNA methyltransferase 3b (DNMT3b) was reduced in vivo and in vitro after curcumin treatment. Further studies were performed aiming to confirm that the knockdown of DNMT3b enhanced the loss of PTEN methylation by curcumin. In addition, miR-29b was involved in the hypomethylation of PTEN by curcumin. MiR-29b not only was increased by curcumin in activated HSCs, but also was confirmed to target DNMT3b by luciferase activity assays. Curcumin-mediated PTEN up-regulation, DNMT3b down-regulation and PTEN hypomethylation were all attenuated by miR-29b inhibitor. Collectively, it is demonstrated that curcumin can up-regulate miR-29b expression, resulting in DNMT3b down-regulation in HSCs and epigenetically-regulated PTEN involved in the suppression of activated HSCs. These results indicate that miRNA-mediated epigenetic regulation may be a novel mechanism suppressing liver fibrosis.
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Identification of a 5-gene signature for clinical and prognostic prediction in gastric cancer patients upon microarray data.
Med. Oncol.
PUBLISHED: 07-01-2013
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In this study, we aimed to investigate the clinical and prognostic value of a 5-gene expression signature model for gastric cancer patients upon microarray data. A total of 158 gastric cancer patients were selected, with 33 cases used for microarray analysis as training set and 125 cases for validation real-time quantitative polymerase chain reaction analysis as test set. Unsupervised clustering algorithms and supervised clustering algorithm were used to identify differentially expressed genes. Gene ontology analyses were used to determine functional prediction of gene biomarkers and receiver operating characteristic analyses to verify the specificity and sensitivity of the evaluation. Moreover, the correlation between clinicopathological characteristics and 5-gene expression was evaluated. The results showed that there were poor disease progression and clinic prognosis in the patients with proximal gastric cancer compared with distal gastric cancer, including differentiation grade (P = 0.001), depth of tumor invasion (P < 0.01), lymph node metastasis (P < 0.01), UICC stage (P < 0.01), and survival status (P < 0.01). Furthermore, a 5-gene signature, including cordon-bleu protein-like 1, damage-specific DNA binding protein 1, BCL2-like 13, nuclear receptor coactivator-6, and F-box leucine-rich protein 11, was identified based on the combination of multiple bioinformatics algorithm. The expression of 5-gene signature (HR = 2.35; 95 % confidence interval 1.24-5.06; P = 0.026) and UICC stage (HR = 5.35; 95 % confidence interval 1.36-19.15; P = 0.032) was independent prognostic factors for overall survival in the survival multivariate analysis. Over-expression of the 5-gene signature in patients with proximal gastric cancer is strongly associated with disease progression and poor prognosis, suggesting that might be potential prognostic predictors in gastric cancer.
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[Expression of chemokine CXCL14 in primary osteosarcoma and its association with prognosis].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 06-28-2013
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To detect the expression of CXCL14 in human osteosarcoma cell lines and tissues and investigate its association with the prognosis of the patients.
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Mitochondrial dysfunction is an early event in aldosterone-induced podocyte injury.
Am. J. Physiol. Renal Physiol.
PUBLISHED: 06-12-2013
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We previously showed that mitochondrial dysfunction (MtD) is involved in an aldosterone (Aldo)-induced podocyte injury. Here, the potential role of MtD in the initiation of podocyte damage was investigated. We detected the dynamic changes of urinary protein, urinary F2-isoprostane and renal malondialdehyde levels, kidney ultrastructure morphology, mitochondrial DNA (mtDNA) copy number, mitochondrial membrane potential (??m), and nephrin and podocin expressions in Aldo-infused mice. Aldo infusion first induced renal oxidative stress, as evidenced by increased levels of urinary F2-isoprostane and renal malondialdehyde, and MtD, as demonstrated by reduced mtDNA, ??m, and ATP production. Later, at 5 days after Aldo infusion, proteinuria and podocyte injury began to appear. In cultured podocytes, Aldo or hydrogen peroxide (H2O2) induced MtD after 2-8 h of treatment, whereas the podocyte damage, as shown by decreased nephrin and podocin expressions, occurred later after 12 h of treatment. Thus Aldo treatment both in vitro and in vivo indicated that MtD occurred before podocyte damage. Additionally, MtDNA depletion by ethidium bromide or mitochondrial transcription factor A (TFAM) RNAi induced MtD, further promoting podocyte damage. TFAM expression was found to be reduced in Aldo-infused mice and Aldo-treated podocytes. Adenoviral vector-mediated overexpression of TFAM prevented Aldo-induced MtD and protected against podocyte injury. Together, these findings support MtD as an early event in podocyte injury, and manipulation of TFAM may be a novel strategy for treatment of glomerular diseases such as podocytopathy.
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Gas6/Axl mediates tumor cell apoptosis, migration and invasion and predicts the clinical outcome of osteosarcoma patients.
Biochem. Biophys. Res. Commun.
PUBLISHED: 05-03-2013
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Dysregulation of the receptor tyrosine kinase Axl and its ligand Gas6 has been shown to promote multiple tumorigenic processes, as well as to correlate with worse prognosis in many different tumor types. However, studies of Axl expression and function in osteosarcoma have rarely been reported. In this study, we report that activated Axl is highly expressed in osteosarcoma cells, and this expression is significantly correlated with the recurrence and lung metastasis of osteosarcoma patients. High expression of activated Axl was an independent predictor for worse prognosis in osteosarcoma. Additionally, we confirmed a strong positive correlation between P-Axl and MMP-9 expression in those osteosarcoma patients. In osteosarcoma cell lines MG63 and U2OS, 200 ng/ml rhGas6 could cause obvious increase of P-Axl expression within 30 min, consistent with the expression of P-AKT. In both of the cell lines, Axl activated by rhGas6 could protect the tumor cells from apoptosis caused by serum starvation, and promote tumor cells migration and invasion in vitro. Together with previous data, these studies suggest that activated Axl participate in the progression of osteosarcoma by resisting tumor cells apoptosis and promoting their migration and invasion, which may be linked to the expression of MMP-9. In the mechanism, AKT signaling pathway may contribute to the function of P-Axl in osteosarcoma rather than ERK pathway.
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FTY720 prevents progression of renal fibrosis by inhibiting renal microvasculature endothelial dysfunction in a rat model of chronic kidney disease.
J. Mol. Histol.
PUBLISHED: 04-18-2013
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Recent studies have shown that chronic endothelial dysfunction can impair multiple aspects of renal physiology and, in turn, contribute to renal fibrosis. Sphingosine 1-phosphate (S1P) has been highlighted as an endothelial barrier-stabilizing mediator. The aim of our study was to investigate the effect of FTY720, an S1P analog, on the progression of renal fibrosis by inhibiting renal microvasculature endothelial dysfunction in a rat model of chronic kidney disease. Thirty male Sprague-Dawley rats were used in this study. Seven days after surgery, we placed the animals into three groups: sham surgery; 5/6 nephrectomized (Nx) rats; and 5/6Nx + FTY720 (1 mg/kg/day). All of the animals were sacrificed 12 weeks after surgery. We obtained and analyzed blood and kidney tissue samples from all of the groups. Glomerular capillary density and peritubular capillary (PTC) density were determined by CD31 immunostaining. The expression of transforming growth factor beta 1 (TGF-?1), collagen IV, fibronectin, endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) were analyzed by immunohistochemistry, reverse transcription-polymerase chain reaction and western blotting. The 5/6Nx group exhibited increased blood urea nitrogen and serum creatinine, visible renal histological changes, pro-fibrotic molecule (TGF-?1) and production of extracellular matrix proteins such as collagen IV and fibronectin and decreased glomerular and PTC density, compared to the sham controls (P < 0.01). We observed that treatment with FTY720 reduced these abnormalities. Furthermore, the level of NO, the expression levels of eNOS and VEGF were downregulated in the kidney tissue in 5/6Nx rats, FTY720 treatment significantly attenuated this decrease. FTY720 prevents the progression of renal fibrosis by inhibiting renal microvasculature endothelial dysfunction in a rat model of chronic kidney disease.
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Fluorescent water-soluble perylenediimide-cored cationic dendrimers: synthesis, optical properties, and cell uptake.
Chem. Commun. (Camb.)
PUBLISHED: 03-25-2013
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Different generations of perylenediimide-cored dendrimers with peripheral amine groups were synthesized. All these water-soluble dendrimers could rapidly internalize into live cells with high efficacy of gene transfection and low cytotoxicity. Increasing dendrimer generation increased their ability for gene transfection.
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Fluorescent nanoparticle delivered dsRNA toward genetic control of insect pests.
Adv. Mater. Weinheim
PUBLISHED: 03-15-2013
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A fluorescent cationic core-shell nanoparticle efficiently enters into cells with high transfection efficacy. A FNP/CHT10-dsRNA complex is orally fed to insect pests and knocks down a midgut-specific chitinase gene of the Asian corn borer, which leads to death. This is the first report on the genetic control of insect pests through a non-viral gene delivery system to knock down key developmental gene expression.
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Association study of OPRM1 polymorphisms with Schizophrenia in Han Chinese population.
BMC Psychiatry
PUBLISHED: 03-12-2013
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The expression of ?-opioid receptor has important role in cognitive dysfunction in Schizophrenia (SZ). The results of studies about the association of polymorphisms of ?-opioid receptor gene (OPRM1) with SZ were inconsistent.
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Expression status of fatty acid synthase (FAS) but not HER2 is correlated with the differentiation grade and prognosis of esophageal carcinoma.
Hepatogastroenterology
PUBLISHED: 02-20-2013
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Fatty acid synthase (FAS) and human epidermal growth factor receptor 2 (HER2) are overexpressed in a series of cancers. However, few studies have investigated the potential role of FAS and HER2 in esophageal carcinoma. The aim of this study was to evaluate the expression of FAS and HER2 and the possible link between FAS/HER2 expression and the pathological prognostic variables.
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A polytriazole synthesized by 1,3-dipolar polycycloaddition showing aggregation-enhanced emission and utility in explosive detection.
Macromol Rapid Commun
PUBLISHED: 02-18-2013
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The metal-free click polymerizations (MFCPs) of activated alkynes and azides have become a powerful technique for the preparation of functional polytriazoles. Recently, a new MFCP of activated azide and alkyne has been established, but no functional polytriazole is prepared. In this paper, polytriazole PIa with aggregation-enhanced emission (AEE) characteristics is prepared by this efficient polymerization in excellent yield (97.9%). PIa is thermally stable, with 5% loss of its weight at temperature as high as 440 °C. Thanks to its unique AEE feature of PIa, its nanoaggregates can be used to detect explosives with a superamplification quenching effect.
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The efficiency of continuous regional intra-arterial infusion in the treatment of infected pancreatic necrosis.
Pancreatology
PUBLISHED: 02-15-2013
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Our aim was to investigate the efficiency of continuous regional intra-arterial infusion (CRAI) with antisecretory agents and antibiotics in the treatment of infected pancreatic necrosis.
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Lung cancer screening: from imaging to biomarker.
Biomark Res
PUBLISHED: 01-16-2013
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Despite several decades of intensive effort to improve the imaging techniques for lung cancer diagnosis and treatment, primary lung cancer is still the number one cause of cancer death in the United States and worldwide. The major causes of this high mortality rate are distant metastasis evident at diagnosis and ineffective treatment for locally advanced disease. Indeed, approximately forty percent of newly diagnosed lung cancer patients have distant metastasis. Currently, the only potential curative therapy is surgical resection of early stage lung cancer. Therefore, early detection of lung cancer could potentially increase the chance of cure by surgery and underlines the importance of screening and detection of lung cancer. In the past fifty years, screening of lung cancer by chest X-Ray (CXR), sputum cytology, computed tomography (CT), fluorescence endoscopy and low-dose spiral CT (LDCT) has not improved survival except for the recent report in 2010 by the National Lung Screening Trial (NLST), which showed a 20 percent mortality reduction in high risk participants screened with LDCT compared to those screened with CXRs. Furthermore, serum biomarkers for detection of lung cancer using free circulating DNA and RNA, exosomal microRNA, circulating tumor cells and various lung cancer specific antigens have been studied extensively and novel screening methods are being developed with encouraging results. The history of lung cancer screening trials using CXR, sputum cytology and LDCT, as well as results of trials involving various serum biomarkers, are reviewed herein.
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Transcriptomic evidence for the expression of horizontally transferred algal nuclear genes in the photosynthetic sea slug, Elysia chlorotica.
Mol. Biol. Evol.
PUBLISHED: 12-23-2011
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Analysis of the transcriptome of the kleptoplastic sea slug, Elysia chlorotica, has revealed the presence of at least 101 chloroplast-encoded gene sequences and 111 transcripts matching 52 nuclear-encoded genes from the chloroplast donor, Vaucheria litorea. These data clearly show that the symbiotic chloroplasts are translationally active and, of even more interest, that a variety of functional algal genes have been transferred into the slug genome, as has been suggested by earlier indirect experiments. Both the chloroplast- and nuclear-encoded sequences were rare within the E. chlorotica transcriptome, suggesting that their copy numbers and synthesis rates are low, and required both a large amount of sequence data and native algal sequences to find. These results show that the symbiotic chloroplasts residing inside the host molluscan cell are maintained by an interaction of both organellar and host biochemistry directed by the presence of transferred genes.
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Comparison of the two major classes of assembly algorithms: overlap-layout-consensus and de-bruijn-graph.
Brief Funct Genomics
PUBLISHED: 12-19-2011
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Since the completion of the cucumber and panda genome projects using Illumina sequencing in 2009, the global scientific community has had to pay much more attention to this new cost-effective approach to generate the draft sequence of large genomes. To allow new users to more easily understand the assembly algorithms and the optimum software packages for their projects, we make a detailed comparison of the two major classes of assembly algorithms: overlap-layout-consensus and de-bruijn-graph, from how they match the Lander-Waterman model, to the required sequencing depth and reads length. We also discuss the computational efficiency of each class of algorithm, the influence of repeats and heterozygosity and points of note in the subsequent scaffold linkage and gap closure steps. We hope this review can help further promote the application of second-generation de novo sequencing, as well as aid the future development of assembly algorithms.
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Antisense oligonucleotide targeting matrix metalloproteinase-7 (MMP-7) changes the ultrastructure of human A549 lung adenocarcinoma cells.
Ultrastruct Pathol
PUBLISHED: 10-07-2011
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Antisense oligonucleotide (ASODN) targeting specific gene can be capable of potently downregulating proliferation and invasion in human cancer cells. However, the underlying mechanisms are less well defined. Here the authors show that matrix metalloproteinase-7 (MMP-7) ASODN changes the ultrastructure of human A549 lung adenocarcinoma cells. Transfection of MMP-7 ASODN significantly lowered the expression of MMP-7 protein in A549 cells. Decreased microvilli, endoplasmic reticulum dilation, swelling of mitochondria, and formation of apoptotic bodies were observed by transmission electron microscope. Collectively, the findings identified the morphological mechanism that MMP-7 ASODN inhibited proliferation and invasion in A549 cells.
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Sirolimus damages podocytes in rats with protein overload nephropathy.
J. Nephrol.
PUBLISHED: 09-23-2011
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Conversion from calcineurin inhibitors (CNIs) to sirolimus could significantly improve long-term graft survival after kidney transplantation. Proteinuria was found in some recipients after the switch, which could be alleviated by an angiotensin II receptor blocker (ARB). But the mechanisms for this have remained unclear. In this study, we utilized a rat model with protein overload nephropathy to explore the mechanisms of sirolimus-related proteinuria.
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MPYS is required for IFN response factor 3 activation and type I IFN production in the response of cultured phagocytes to bacterial second messengers cyclic-di-AMP and cyclic-di-GMP.
J. Immunol.
PUBLISHED: 08-03-2011
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Cyclic-di-GMP and cyclic-di-AMP are second messengers produced by bacteria and influence bacterial cell survival, differentiation, colonization, biofilm formation, virulence, and bacteria-host interactions. In this study, we show that in both RAW264.7 macrophage cells and primary bone marrow-derived macrophages, the production of IFN-? and IL-6, but not TNF, in response to cyclic-di-AMP and cyclic-di-GMP requires MPYS (also known as STING, MITA, and TMEM173). Furthermore, expression of MPYS was required for IFN response factor 3 but not NF-?B activation in response to these bacterial metabolites. We also confirm that MPYS is required for type I IFN production by cultured macrophages infected with the intracellular pathogens Listeria monocytogenes and Francisella tularensis. However, during systemic infection with either pathogen, MPYS deficiency did not impact bacterial burdens in infected spleens. Serum IFN-? and IL-6 concentrations in the infected control and MPYS(-/-) mice were also similar at 24 h postinfection, suggesting that these pathogens stimulate MPYS-independent cytokine production during in vivo infection. Our findings indicate that bifurcating MPYS-dependent and -independent pathways mediate sensing of cytosolic bacterial infections.
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Progress towards elucidating the mechanisms of self-incompatibility in the grasses: further insights from studies in Lolium.
Ann. Bot.
PUBLISHED: 07-27-2011
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Self-incompatibility (SI) in flowering plants ensures the maintenance of genetic diversity by ensuring outbreeding. Different genetic and mechanistic systems of SI among flowering plants suggest either multiple origins of SI or considerable evolutionary diversification. In the grasses, SI is based on two loci, S and Z, which are both polyallelic: an incompatible reaction occurs only if both S and Z alleles are matched in individual pollen with alleles of the pistil on which they alight. Such incompatibility is referred to as gametophytic SI (GSI). The mechanics of grass GSI is poorly understood relative to the well-characterized S-RNase-based single-locus GSI systems (Solanaceae, Rosaceae, Plantaginaceae), or the Papaver recognition system that triggers a calcium-dependent signalling network culminating in programmed cell death. There is every reason to suggest that the grass SI system represents yet another mechanism of SI. S and Z loci have been mapped using isozymes to linkage groups C1 and C2 of the Triticeae consensus maps in Secale, Phalaris and Lolium. Recently, in Lolium perenne, in order to finely map and identify S and Z, more closely spaced markers have been developed based on cDNA and repeat DNA sequences, in part from genomic regions syntenic between the grasses. Several genes tightly linked to the S and Z loci were identified, but so far no convincing candidate has emerged.
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Draft genome sequence of pigeonpea (Cajanus cajan), an orphan legume crop of resource-poor farmers.
Nat. Biotechnol.
PUBLISHED: 07-19-2011
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Pigeonpea is an important legume food crop grown primarily by smallholder farmers in many semi-arid tropical regions of the world. We used the Illumina next-generation sequencing platform to generate 237.2 Gb of sequence, which along with Sanger-based bacterial artificial chromosome end sequences and a genetic map, we assembled into scaffolds representing 72.7% (605.78 Mb) of the 833.07 Mb pigeonpea genome. Genome analysis predicted 48,680 genes for pigeonpea and also showed the potential role that certain gene families, for example, drought tolerance-related genes, have played throughout the domestication of pigeonpea and the evolution of its ancestors. Although we found a few segmental duplication events, we did not observe the recent genome-wide duplication events observed in soybean. This reference genome sequence will facilitate the identification of the genetic basis of agronomically important traits, and accelerate the development of improved pigeonpea varieties that could improve food security in many developing countries.
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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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Glutathione S-transferases T1 null genotype is associated with susceptibility to aristolochic acid nephropathy.
Int Urol Nephrol
PUBLISHED: 04-07-2011
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This study aims to determine whether six polymorphisms of the genes involved in drug metabolism are associated with susceptibility to the development and progression of aristolochic acid nephropathy (AAN).
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Cordyceps sinensis extracts attenuate aortic transplant arteriosclerosis in rats.
J. Surg. Res.
PUBLISHED: 02-14-2011
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Transplant arteriosclerosis is a hallmark of chronic rejection and is still the major limiting factor affecting the success of long-term organ transplants. Development of transplant arteriosclerosis is refractory to conventional immunosuppressive drugs, and adequate therapy is not yet available. The aim of this study was to determine the role of Cordyceps sinensis extracts in reducing the formation of transplant arteriosclerosis in a rat aortic transplant model.
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Statistical phase-shifting step estimation algorithm based on the continuous wavelet transform for high-resolution interferometry metrology.
Appl Opt
PUBLISHED: 02-02-2011
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We propose a statistical phase-shifting estimation algorithm for temporal phase-shifting interferometry (PSI) based on the continuous wavelet transform (CWT). The proposed algorithm explores spatial information redundancy in the intraframe interferogram dataset using the phase recovery property on the power ridge of the CWT. Despite the errors introduced by the noise of the interferogram, the statistical part of the algorithm is utilized to give a sound estimation of the phase-shifting step. It also introduces the usage of directional statistics as the statistical model, which was validated, so as to offer a better estimation compared with other statistical models. The algorithm is implemented in computer codes, and the validations of the algorithm were performed on numerical simulated signals and actual phase-shifted moiré interferograms. The major advantage of the proposed algorithm is that it imposes weaker conditions on the presumptions in the temporal PSI, which, under most circumstances, requires uniform and precalibrated phase-shifting steps. Compared with other existing deterministic estimation algorithms, the proposed algorithm estimates the phase-shifting step statistically. The proposed algorithm allows the temporal PSI to operate under dynamic loading conditions and arbitrary phase steps and also without precalibration of the phase shifter. The proposed method can serve as a benchmark method for comparing the accuracy of the different phase-step estimation methods.
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Mitochondrial dysfunction mediates aldosterone-induced podocyte damage: a therapeutic target of PPAR?.
Am. J. Pathol.
PUBLISHED: 01-05-2011
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Aldosterone (Aldo) causes podocyte damage by an unknown mechanism. We examined the role of mitochondrial dysfunction (MtD) in Aldo-treated podocytes in vitro and in vivo. Exposure of podocytes to Aldo reduced nephrin expression dose dependently, accompanied by increased production of reactive oxygen species (ROS). The ROS generation and podocyte damage were abolished by the mitochondrial (mt) respiratory chain complex I inhibitor rotenone. Pronounced MtD, including reduced mt membrane potential, ATP levels, and mtDNA copy number were seen in Aldo-treated podocytes and in the glomeruli of Aldo-infused mice. The mineralocorticoid receptor antagonist eplerenone significantly inhibited Aldo-induced MtD. The MtD was associated with higher levels of ROS, reduction in the activity of complexes I, III, and IV, and expression of the peroxisome proliferator-activated receptor-? (PPAR?) coactivator-1? and mt transcription factor A. Both the PPAR? agonist rosiglitazone and PPAR? overexpression protected against podocyte injury by preventing MtD and oxidative stress, as evidenced by reduced ROS production, by maintenance of mt morphology, by restoration of mtDNA copy number, by decrease in mt membrane potential loss, and by recovery of mt electron transport function. The protective effect of rosiglitazone was abrogated by the specific PPAR? small interference RNA, but not a control small interference RNA. We conclude that MtD is involved in Aldo-induced podocyte injury, and that the PPAR? agonist rosiglitazone may protect podocytes from this injury by improving mitochondrial function.
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The protective effects of Lipoxin A4 during the early phase of severe acute pancreatitis in rats.
Scand. J. Gastroenterol.
PUBLISHED: 10-18-2010
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Our aim was to investigate the protective effects of a Lipoxin A(4) analogue (LXA4) in the early phase of acute pancreatitis in rats.
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[The cell-free protein synthesis-based protein microarray technology].
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi
PUBLISHED: 07-27-2010
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The major bottle-neck in the way of constructing high density protein microarray is the availability and stability of proteins. The traditional methods of generating protein arrays require the in-vivo expression, purification and immobilization of hundreds or thousands of proteins. The cell-free protein array technology employs cell-free expression systems to produce proteins directly onto surface from co-distributed or pre-arrayed DNA or RNA, thus avoiding the laborious and often costly processes of protein preparation in the traditional approach. Here we provide an overview of recently developed novel technology in cell free based protein microarray and their applications in protein interaction analysis, in antibody specificity and vaccine screening, and in biomarker assay.
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Angiotensin II mediates the high-glucose-induced endothelial-to-mesenchymal transition in human aortic endothelial cells.
Cardiovasc Diabetol
PUBLISHED: 06-17-2010
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Substantial evidence suggests that high glucose (HG) causes endothelial cell damage; however, the potential mechanism therein has yet to be clarified. The aim of this study was to investigate the influence of HG on the endothelial-to-mesenchymal transition (EndMT) and its relevance to the activation of the renin-angiotensin system.
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Nasopharyngeal carcinoma risk by histologic type in central China: impact of smoking, alcohol and family history.
Int. J. Cancer
PUBLISHED: 06-06-2010
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The role of cigarette smoking, alcohol use, family history of cancer and the interaction of cigarettes and family history in the etiology of Nasopharyngeal carcinoma (NPC) in general and within each histologic type are unclear. We conducted a case-control study among 1,044 Han Chinese patients with NPC and 1,095 Han Chinese cancer-free control subjects. Logistic regression was used to analyze the association between histologic type of NPC and cigarette smoking, alcohol drinking and family history. The results indicated that NPC was significantly associated with cigarette smoking [adjusted odds ratio (OR) = 2.97, 95% confidence interval (CI), 2.38-3.70], and the association exhibited a dose-response relationship for intensity, duration, and cumulative consumption of cigarettes (p(trend) < 0.0001 for intensity, duration and cumulative consumption of cigarettes). Positive family history of cancer led to a significant 12-fold elevated risk of NPC (adjusted OR = 12.95, 95% CI, 7.12-23.54) and acted jointly with cigarettes in contributing to NPC risk (adjusted OR = 56.68, 95% CI, 17.25-186.19). The association of NPC risk with cigarettes was stronger for nonkeratinizing carcinoma than for keratinizing squamous cell carcinoma (KSCC), whereas family history was more closely associated with KSCC. NPC risk was not associated with alcohol consumption. Our study demonstrated that cigarette smoking and family history of cancer could serve independently and jointly as risk factors for etiology of NPC and might affect the risk of histology-specific NPC differently. This knowledge may help facilitate comprehension of NPC etiology in general as well as within each histologic type, and thereby improve prevention efforts.
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A canine portal hypertension model induced by intra-portal administration of Sephadex microsphere.
J. Gastroenterol. Hepatol.
PUBLISHED: 05-25-2010
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Big animal models of portal hypertension are important for the research into this disease. The aim of this study was to establish a canine portal hypertension model by intra-portal administration of microspheres.
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Loss of Reprimo and S100A2 expression in human gastric adenocarcinoma.
Diagn. Cytopathol.
PUBLISHED: 05-01-2010
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Reprimo and S100A2 are two newly identified candidate tumor-suppressor genes, which play an important role in the regulation of p53-dependent cell cycle. In this study, we examined the expressions of Reprimo and S100A2 in surgical specimens of gastric adenocarcinoma and correlated these results with pathological and clinical parameters. Tissues were obtained from 100 gastric adenocarcinoma patients that underwent curative gastrectomy. Reprimo and S100A2 expressions were evaluated by immunohistochemical analysis. Loss of Reprimo and S100A2 expressions occurred in 65 and 52% of the patients, respectively. Loss of Reprimo expression was significantly correlated with the depth of tumor invasion (P = 0.000), lymphatic vessel invasion (P = 0.006), and lymph node metastasis (P = 0.000). Loss of S100A2 expression was significantly associated with histological type (P = 0.009), depth of invasion (P = 0.033), lymphatic vessel invasion (P = 0.01), and lymph node metastasis (P = 0.001). In addition, there was a significant positive association between the expressions of Reprimo and S100A2 (P < 0.01). The results suggest that loss of Reprimo and S100A2 expressions occurs frequently in gastric adenocarcinomas. The expressions of Reprimo and S100A2 may be potential biomarkers for gastric adenocarcinomas detection.
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Blockade of gammac signals in combination with donor-specific transfusion induces cardiac allograft acceptance in murine models.
J. Huazhong Univ. Sci. Technol. Med. Sci.
PUBLISHED: 04-23-2010
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The gammac cytokines play an important role in proliferation and survival of T cells. Blocking the gammac signals can cause the activated donor-reactive T cells losing the ability to proliferate, and getting into apoptosis pathway, which contributes to induction of the peripheral tolerance. In this study, we induced the transplant tolerance through blocking the gammac in combination with donor-specific transfusion (DST) in the cardiac transplantation. Following DST, on the day 2, 4 and 6, C57BL/6 recipients received anti-gammac monoclonal antibodies (mAbs) injection, and those in control group were not given anti-gammac mAbs. On the day 7, Balb/c cardiac allografts were transplanted. All recipients in experimental group accepted cardiac allografts over 30 days, and two of them accepted allografts without rejection until sacrifice on the 120 day. Animals only receiving DST rejected grafts within 5 days, and the mice receiving cardiac transplantation alone rejected grafts within 9 days. Our study showed that blockade of gammac signaling combined with DST significantly prolonged allograft survival, which was probably associated with inhibition of antigen-specific T-cell proliferation and induction of apoptosis.
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Operation for huge subclavian artery aneurysm: a case report.
J Thorac Dis
PUBLISHED: 04-05-2010
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Subclavian artery aneurysm is extremely rare, and further aneurysm compressing trachea and leading to breathing difficulty is more exceptional. The most common causes of subclavian artery aneurysm are atherosclerosis, trauma and post-stenotic dilated aneurysm secondary to thoracic outlet syndrome, besides, the rare causes include infective, syphilitic media necrosis and so on. We present a case report in which the patient presented with sever dyspnea due to compression of trachea by a 7 cm large subclavian artery aneurysm. After operation, the patient improved symptomatically. The blood pressure remained stable, blood circulation of right upper extremity was fine, and pulse was improved comparing with that before operation. Chest film confirmed tumor shrank and depressed trachea improved significantly. The patient was discharged 14 days later and continued anticoagulant therapy after discharge. Follow up one month later after the operation revealed breathing difficulty disappeared, and patient was with normal right upper extremity movement and good blood circulation.
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Identification of genes expressed during the self-incompatibility response in perennial ryegrass (Lolium perenne L.).
Plant Mol. Biol.
PUBLISHED: 05-16-2009
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Self-incompatibility (SI) in Lolium perenne is controlled gametophytically by the S-Z two-locus system. S and Z loci mapped to L. perenne linkage groups 1 and 2, respectively, with their corresponding putative-syntenic regions on rice chromosome 5 (R5) and R4. None of the gene products of S and Z have yet been identified. SI cDNA libraries were developed to enrich for SI expressed genes in L. perenne. Transcripts were identified from the SI libraries that were orthologous to sequences on rice R4 and R5. These represent potential SI candidate genes. Altogether ten expressed SI candidate genes were identified. A rapid increase in gene expression within two minutes after pollen-stigma contact was revealed, reaching a maximum between 2 and 10 min. The potential involvement of these genes in the SI reactions is discussed.
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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.