bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tributyltin and dibutyltin alter secretion of tumor necrosis factor alpha from human natural killer cells and a mixture of T cells and natural killer cells
Authors: Hurt Kelsi , Hurd‐Brown Tasia , Whalen Margaret 
Published: October 2012

ABSTRACTButyltins (BTs) have been in widespread use. Tributyltin (TBT) has been used as a biocide in a variety of applications and is found in human blood samples. Dibutyltin (DBT) has been used as a stabilizer in polyvinyl chloride plastics and as a de‐worming agent in poultry. DBT, like TBT, is found in human blood. Human natural killer (NK) cells are the earliest defense against tumors and viral infections and secrete the cytokine tumor necrosis factor‐alpha (TNF‐α). TNF‐α is an important regulator of adaptive and innate immune responses. TNF‐α promotes inflammation and an association between malignant transformation and inflammation has been established. Previously, we have shown that TBT and DBT were able to interfere with the ability of NK cells to lyse tumor target cells. Here we show that BTs alter cytokine secretion by NK cells as well as a mixture of T and NK lymphocytes (T/NK cells). We examined 24‐, 48‐h and 6‐day exposures to TBT (200–2.5 nM) and DBT (5–0.05 μM) on TNF‐α secretion by highly enriched human NK cells and T/NK cells. The results indicate that TBT (200–2.5 nM) decreased TNF‐α secretion from NK cells. In the T/NK cells, 200 nM TBT decreased secretion whereas 100–5 nM TBT increased secretion of TNF‐α. NK cells or T/NK cells exposed to higher concentrations of DBT showed decreased TNF‐α secretion whereas lower concentrations showed increased secretion. The effects of BTs on TNF‐α secretion are seen at concentrations present in human blood. Copyright © 2012 John Wiley & Sons, Ltd.
Activation of nuclear estrogen receptors induced by low‐power laser irradiation via PI3‐K/Akt signaling cascade
Authors: Huang Lei , Tang Yonghong , Xing Da 
Published: October 2012

AbstractLow‐power laser irradiation (LPLI) has been shown to exert promotive effects on cell survival and proliferation through activation of various signaling pathways. Estrogen receptors (ERs, ERα, and ERβ) are ligand‐activated transcription factors, which regulate target gene expression, promote cell proliferation, and resist apoptosis. However, it is unclear whether LPLI could induce ligand‐independent activation of ERs. In the present study, we investigated the subcellular pools, nuclear redistribution, and transcriptional activity of ERs under LPLI (1.2 J/cm2, 633 nm) treatment using single‐molecule fluorescence imaging and dual‐luciferase reporter assay. We found that ERs were not only localized to nucleus, but also existed in mitochondria. Moreover, we found that LPLI induced nuclear redistribution and transcriptional activity of ERs in a ligand‐independent manner. Our further investigation showed that PI3‐K/Akt signaling cascade was involved in LPLI‐induced activation of ERs. Wortmannin, a PI3‐K inhibitor, or triciribine (API‐2), a specific Akt inhibitor, potently suppressed the nuclear redistribution and transcriptional activity of ERs induced by LPLI, revealing that PI3‐K/Akt signaling cascade was required for the activation of ERs induced by LPLI. Collectively, we demonstrated the first time that LPLI induced the ligand‐independent nuclear redistribution and transcriptional activity of ERs, which were dependent on the activity of PI3‐K/Akt. Our findings provide direct evidence for the molecular mechanisms of LPLI‐induced transcription factor activation. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.
A novel adipocytokine visfatin protects against H2O2‐induced myocardial apoptosis: A missing link between obesity and cardiovascular disease
Authors: Xiao Jing , Sun Bing , Li Ming , Wu Ying , Sun Xiao‐Bo 
Published: October 2012

AbstractFat accumulation in obese individuals worsens the clinical outcomes of cardiovascular disease (CVD). Paradoxically, increased circulating adipocytokines secreted from visceral fat may confer cardioprotective effects. Visfatin, a novel adipocytokine, has anti‐diabetic, anti‐tumor, and pro‐inflammatory properties. However, its effects on cardiomyocytes and the underlying mechanisms remain unknown. This article demonstrated that visfatin counteracted H2O2‐induced apoptotic damage in H9c2 cardiomyocytes in a time‐dependent manner. Qualitative immunofluorescence approaches demonstrated that visfatin pretreatment attenuated H2O2‐induced DNA fragmentation (TdT‐mediated dUTP‐biotin nick end‐labeling), phosphatidyl serine exposure (Annexin V/PI staining), and mitochondrial membrane potential (ΔΨm) depolarization (JC‐1 staining). Biochemical studies on cardiomyoctes showed improved cell viability and reduced caspase‐3 activation caused by visfatin pretreatment. Visfatin did not inhibit the death receptor‐dependent apoptotic pathways, as characterized by its absence in both Fas and TNFR1 down‐regulation. Instead, visfatin specifically suppressed the mitochondria‐dependent apoptotic pathways, as characterized by changed levels of p53 and its downstream Bcl‐2 family genes. Visfatin also up‐regulated the protein levels of phosphorylated AMPK, and the anti‐apoptotic action of visfatin was attenuated by the AMPK‐specific inhibitor compound C. These results suggested that visfatin plays a critical role in cardioprotection by suppressing myocardial apoptosis via AMPK activation. These findings may be the missing link between obesity and CVD. J. Cell. Physiol. 228: 495–501, 2013. © 2012 Wiley Periodicals, Inc.
α11β1 integrin‐mediated MMP‐13‐dependent collagen lattice contraction by fibroblasts: Evidence for integrin‐coordinated collagen proteolysis
Authors: Barczyk Malgorzata M. , Lu Ning , Popova Svetlana N. , Bolstad Anne Isine , Gullberg Donald 
Published: October 2012

AbstractWe have previously determined that integrin α11β1 is required on mouse periodontal ligament (PDL) fibroblasts to generate the force needed for incisor eruption. As part of the phenotype of α11−/− mice, the incisor PDL (iPDL) is thickened, due to disturbed matrix remodeling. To determine the molecular mechanism behind the disturbed matrix dynamics in the PDL we crossed α11−/− mice with the Immortomouse and isolated immortalized iPDL cells. Microarray analysis of iPDL cells cultured inside a 3D collagen gel demonstrated downregulated expression of a number of genes in α11‐deficient iPDL cells, including matrix metalloproteinase‐13 (MMP‐13) and cathepsin K. α11−/− iPDL cells in vitro displayed disturbed interactions with collagen I during contraction of attached and floating collagen lattices and furthermore displayed reduced MMP‐13 protein expression levels. The MMP‐13 specific inhibitor WAY 170523 and the Cathepsin K Inhibitor II both blocked part of the α11 integrin‐mediated collagen remodeling. In summary, our data demonstrate that in iPDL fibroblasts the mechanical strain generated by α11β1 integrin regulates molecules involved in collagen matrix dynamics. The positive regulation of α11β1‐dependent matrix remodeling, involving MMP‐13 and cathepsin K, might also occur in other types of fibroblasts and be an important regulatory mechanism for coordinated extracellular and intracellular collagen turnover in tissue homeostasis. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.
Variable velocity encoding in a three‐dimensional, three‐directional phase contrast sequence: Evaluation in phantom and volunteers
Authors: Nilsson Anders , Markenroth Bloch Karin , Carlsson Marcus , Heiberg Einar , Ståhlberg Freddy 
Published: October 2012

AbstractPurpose:To evaluate accuracy and noise properties of a novel time‐resolved, three‐dimensional, three‐directional phase contrast sequence with variable velocity encoding (denoted 4D‐vPC) on a 3 Tesla MR system, and to investigate potential benefits and limitations of variable velocity encoding with respect to depicting blood flow patterns.Materials and Methods:A 4D PC‐MRI sequence was modified to allow variable velocity encoding (VENC) over the cardiac cycle in all three velocity directions independently. 4D‐PC sequences with constant and variable VENC were compared in a rotating phantom with respect to measured velocities and noise levels. Additionally, comparison of flow patterns in the ascending aorta was performed in six healthy volunteers.Results:Phantom measurements showed a linear relationship between velocity noise and velocity encoding. 4D‐vPC MRI presented lower noise levels than 4D‐PC both in phantom and in volunteer measurements, in agreement with theory. Volunteer comparisons revealed more consistent and detailed flow patterns in early diastole for the variable VENC sequences.Conclusion:Variable velocity encoding offers reduced noise levels compared with sequences with constant velocity encoding by optimizing the velocity‐to‐noise ratio (VNR) to the hemodynamic properties of the imaged area. Increased VNR ratios could be beneficial for blood flow visualizations of pathology in the cardiac cycle. J. Magn. Reson. Imaging 2012; 36:1450–1459. © 2012 Wiley Periodicals, Inc.
Enhancement of the liver and pancreas in the hepatic arterial dominant phase: Comparison of hepatocyte‐specific MRI contrast agents, gadoxetic acid and gadobenate dimeglumine, on 3 and 1.5 tesla MRI in the same patient
Authors: Kim Hee Jin , Kim Bong Soo , Kim Mi Jeong , Kim Seong Hyun , de Campos Rafael O.P. , Hernandes Mateus , Semelka Richard C. 
Published: October 2012

AbstractPurpose:To evaluate the relative enhancement of liver, pancreas, focal nodular hyperplasia (FNH), pancreas‐to‐liver index, and FNH‐to‐liver index in the hepatic arterial dominant phase (HADP) after injection of hepatocyte‐specific MRI contrast agents, gadoxetic acid and gadobenate dimeglumine, on 3 and 1.5 Tesla (T) MRI in the same patient.Materials and Methods:The MRI database was retrospectively searched to identify consecutive patients who underwent abdominal MRI at 3T and 1.5T systems, using both 0.025 mmol/kg gadoxetic acid‐enhanced and 0.05 mmol/kg gadobenate dimeglumine‐enhanced MRI at the same magnetic strength field system. 22 patients were identified, 10 were scanned at 3T system and 12 at 1.5T system. The enhancement of liver, pancreas, and FNH was evaluated quantitatively on MR images.Results:The relative enhancement of liver in HADP in the gadobenate dimeglumine‐enhanced group in all subjects was significantly higher than that in gadoxetic acid‐enhanced group (P = 0.023). The gadobenate dimeglumine‐enhanced group in HADP had better relative enhancement of pancreas and FNH, pancreas‐to‐liver index, and FNH‐to‐liver index than gadoxetic acid‐enhanced group, but the difference was not statistically significant.Conclusion:The 0.05 mmol/kg gadobenate dimeglumine‐enhanced abdominal MRI studies at 3T and 1.5T MR systems are superior in relative enhancement of the liver in HADP to 0.025 mmol/kg gadoxetic acid‐enhanced MRI. This type of assessment may provide comparative effectiveness data. J. Magn. Reson. Imaging 2013;37:903–908. © 2012 Wiley Periodicals, Inc.
Reduced‐cost microwave component modeling using space mapping‐enhanced electromagnetic‐based kriging surrogates
Authors: Koziel Slawomir , Bandler John W. , Cheng Qingsha S. 
Published: October 2012

ABSTRACTWe present a versatile technique for constructing fast microwave component models at a low computational cost. Our modeling procedure consists of two stages: (i) kriging interpolation of coarsely discretized electromagnetic simulation data of the device under consideration and (ii) enhancing the kriging model by using space mapping and a limited amount of high‐fidelity electromagnetic simulation data. The use of coarse discretization data allows for low‐cost model generation, whereas space mapping is a convenient way of ensuring its accuracy. Our approach can be applied to almost any type of microwave device; it can also work with other types of nonsmooth or costly low‐fidelity models. The operation and performance of our methodology is demonstrated using a variety of microwave components, including a microstrip filter, a planar ultrawideband antenna, and a microstrip‐to‐coplanar waveguide transition. Copyright © 2012 John Wiley & Sons, Ltd.
The effect direction plot: visual display of non‐standardised effects across multiple outcome domains
Authors: Thomson Hilary J , Thomas Sian 
Published: October 2012

Visual display of reported impacts is a valuable aid to both reviewers and readers of systematic reviews. Forest plots are routinely prepared to report standardised effect sizes, but where standardised effect sizes are not available for all included studies a forest plot may misrepresent the available evidence. Tabulated data summaries to accompany the narrative synthesis can be lengthy and inaccessible. Moreover, the link between the data and the synthesis conclusions may be opaque.This paper details the preparation of visual summaries of effect direction for multiple outcomes across 29 quantitative studies of the health impacts of housing improvement. A one page summary of reported health outcomes was prepared to accompany a 10 000‐word narrative synthesis. The one page summary included details of study design, internal validity, sample size, time of follow‐up, as well as changes in intermediate outcomes, for example, housing condition. This approach to visually summarising complex data can aid the reviewer in cross‐study analysis and improve accessibility and transparency of the narrative synthesis where standardised effect sizes are not available. Copyright © 2012 John Wiley & Sons, Ltd.
Effect of Crystallization Kinetics on Microstructure and Charge Transport of Polythiophenes
Authors: Vakhshouri Kiarash , Gomez Enrique D. 
Published: October 2012

AbstractWe have examined the effects of crystallization kinetics of poly(3‐hexylthiophene) and poly[2,5‐bis(3‐hexadecylthiophen‐2‐yl)thieno(3,2‐b)thiophene] on microstructure and charge transport. Rapid crystallization increases the density of tie molecules in polythiophenes. As a consequence, ordered regions are better connected resulting in higher charge carrier mobilities. Our results suggest that controlling the crystallization kinetics might be an important factor for maximizing the charge mobility in semicrystalline polythiophene thin films.
Smart Poly(N‐isopropylacrylamide) Containing Iridium(III) Complexes as Water‐Soluble Phosphorescent Probe for Sensing and Bioimaging of Homocysteine and Cysteine
Authors: Liu Shujuan , Qiao Weili , Cao Guoyi , Chen Yang , Ma Yun , Huang Yanqin , Liu Xiangmei , Xu Wenjuan , Zhao Qiang , Huang Wei 
Published: October 2012

AbstractHomocysteine (Hcy) and cysteine (Cys) are two important kinds of amino acids in human bodies. Herein, we synthesized an iridium(III) complex‐functionalized poly(N‐isopropylacrylamide) and its hydrogel, which could be used as the excellent phosphorescent bioprobe for sensing Hcy and Cys. Their detection can be realized in aqueous system through the variations in absorption and photoluminescence spectra. Furthermore, living cell imaging experiments demonstrate that the phosphorescent bioprobe is membrane permeable and can monitor the changes of Hcy and Cys within living cells. In addition, the probe is also thermoresponsive, and its photoluminescence intensified with increasing temperature. These results suggests that this bioprobe has promising application in biomedical fields.
Dysregulation of FURIN by prostaglandin‐endoperoxide synthase 2 in lung epithelial NCI‐H292 cells
Authors: Brant Kelly A. , Leikauf George D. 
Published: October 2012

AbstractBecause proprotein convertases (PCSKs) activate growth factors and matrix metalloproteinase, these enzymes have been implicated in non‐small cell lung cancer tumor progression and aggressiveness. Previous studies indicate that one PCSK member, FURIN is overexpressed in NSCLC, but little is known regarding the mechanisms driving PCSKs expression during malignant change. We sought to determine whether prostaglandin‐endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) (PTGS2) (aka COX2), whose expression is also frequently increased in NSCLC, differentially regulates PCSK expression and activity between normal (NHBE) and NSCLC epithelial cells (NCI‐H292, NCI‐H441, A549). NSCLC cells exhibit significantly greater cell‐associated and secreted PCSK activity as compared with NHBE. The heightened activity is consistent with increased FURIN, PCSK4, and PCSK6 protein in the NCSLC cells. Inhibition of PTGS2 activity using NS‐398 and siRNA decreased FURIN mRNA, protein, activity along with cell proliferation in NCI‐H292 cells but not NHBE cells. NSCLC also expressed elevated levels of the transcription factor E2F1. When NCI‐H292 cells were transfected with E2F1 siRNA, both PTGS2 expression and PCSK activity were attenuated, arguing a pivotal role for E2F1 in the differential regulation of PCSKs by PTGS2. Our results highlight a novel role for PTGS2 in NSCLC and may provide a mechanism, whereby PTGS2 inhibitors suppress lung cancer cell growth. © 2012 Wiley Periodicals, Inc.
Tumor‐associated mutations in O6‐methylguanine DNA‐methyltransferase (MGMT) reduce DNA repair functionality
Authors: Lamb Kristy L. , Liu Yanfeng , Ishiguro Kimiko , Kwon Youngho , Paquet Nicolas , Sartorelli Alan C. , Sung Patrick , Rockwell Sara , Sweasy Joann B. 
Published: October 2012

AbstractMGMT is the primary vehicle for cellular removal of alkyl lesions from the O‐6 position of guanine and the O‐4 position of thymine. While key to the maintenance of genomic integrity, MGMT also removes damage induced by alkylating chemotherapies, inhibiting the efficacy of cancer treatment. Germline variants of human MGMT are well‐characterized, but somatic variants found in tumors were, prior to this work, uncharacterized. We found that MGMT G132R, from a human esophageal tumor, and MGMT G156C, from a human colorectal cancer cell line, are unable to rescue methyltransferase‐deficient Escherichia coli as well as wild type (WT) human MGMT after treatment with a methylating agent. Using pre‐steady state kinetics, we biochemically characterized these variants as having a reduced rate constant. G132R binds DNA containing an O6‐methylguanine lesion half as tightly as WT MGMT, while G156C has a 40‐fold decrease in binding affinity for the same damaged DNA versus WT. Mammalian cells expressing either G132R or G156C are more sensitive to methylating agents than mammalian cells expressing WT MGMT. G132R is slightly resistant to O6‐benzylguanine, an inhibitor of MGMT in clinical trials, while G156C is almost completely resistant to this inhibitor. The impared functionality of expressed variants G132R and G156C suggests that the presence of somatic variants of MGMT in a tumor could impact chemotherapeutic outcomes. © 2012 Wiley Periodicals, Inc.
Genetic alterations of RDINK4/ARF enhancer in human cancer cells
Authors: Li Junan , Knobloch Thomas J. , Poi Ming J. , Zhang Zhaoxia , Davis Andrew T. , Muscarella Peter , Weghorst Christopher M. 
Published: October 2012

AbstractRecent identification of an enhancer element, RDINK4/ARF (RD), in the prominent INK4/ARF locus provides a novel mechanism to simultaneously regulate the transcription of p15INK4B (p15), p14ARF, and p16INK4A (p16) tumor suppressor genes. While genetic inactivation of p15, p14ARF, and p16 in human tumors has been extensively studied, little is known about genetic alterations of RD and its impact on p15, p14ARF, and p16 in human cancer. The purpose of this study was to investigate the potential existence of genetic alterations of RD in human cancer cells. DNAs extracted from 17 different cancer cell lines and 31 primary pheochromocytoma tumors were analyzed for deletion and mutation of RD using real‐time PCR and direct DNA sequencing. We found that RD was deleted in human cancer cell lines and pheochromocytoma tumors at frequencies of 41.2% (7/17) and 13.0% (4/31), respectively. While some of these RD deletion events occurred along with deletions of the entire INK4/ARF locus, other RD deletion events were independent of genetic alterations in p15, p14ARF, and p16. Furthermore, the status of RD was poorly associated with the expression of p15, p14ARF, and p16 in tested cancer cell lines and tumors. This study demonstrates for the first time that deletion of the RD enhancer is a prevalent event in human cancer cells. Its implication in carcinogenesis remains to be further explored. © 2012 Wiley Periodicals, Inc.
G‐A variant in miR‐200c binding site of EFNA1 alters susceptibility to gastric cancer
Authors: Li Yingfei , Nie Yuqiang , Cao Jie , Tu Sanfang , Lin Yong , Du Yanlei , Li Yuyuan 
Published: October 2012

AbstractMicroRNAs (miRNAs) post‐transcriptionally modulate gene expression by binding to complementary sites at 3′‐untranslated regions (3′UTRs) of their target messenger RNAs (mRNAs). Genetic variations in miRNA binding sites may alter individual susceptibilities to many cancers. However, whether miRNA binding site single nucleotide polymorphisms (SNPs) interfere with gastric cancer (GC) susceptibility has not been reported. In this case–control study including 525 GC patients and 501 controls, we selected three miRNA binding site SNPs located in 3′UTRs of genes involved in GC to investigated their associations with GC susceptibility. We identified that rs12904 in ephrin‐A1 (EFNA1) gene was significantly associated with risk of GC, with the OR for carrying AG or GG genotype being 0.65 (P = 0.002, OR 0.65; 95% CI, 0.50–0.85) compared with AA genotype. Specifically, we found that rs12904 is in strong linkage disequilibrium (LD) with rs4072037, a susceptibility variant reported by previous genome‐wide association study (GWAS). No significant associations were observed for the other two SNPs (rs699517 in TYMS and rs1042542 in BIRC5). Furthermore, luciferase assays indicated EFNA1 as the target of hsa‐miR‐200c and rs12904 G > A change resulted in altered regulation of luciferase expression. In addition, rs12904 AA genotype was associated with increased expression of EFNA1 mRNA compared with AG or GG genotype in the cancer tissues from 48 patients. Taken together, these findings indicate that the miR‐200c binding site SNP (rs12904 G > A) in the 3′UTR of EFNA1 can modulate EFNA1 expression and is associated with GC susceptibility. Larger replication studies are needed to confirm our findings. © 2012 Wiley Periodicals, Inc.
Inhibition of the focal adhesion kinase and vascular endothelial growth factor receptor‐3 interaction leads to decreased survival in human neuroblastoma cell lines
Authors: Beierle Elizabeth A. , Ma Xiaojie , Stewart Jerry E. , Megison Michael , Cance William G. , Kurenova Elena V. 
Published: October 2012

AbstractNeuroblastoma continues to be a devastating childhood solid tumor and is responsible for over 15% of all childhood cancer‐related deaths. Focal adhesion kinase (FAK) and vascular endothelial growth factor receptor‐3 (VEGFR‐3) are protein tyrosine kinases that are overexpressed in a number of human cancers, including neuroblastoma. These two kinases can directly interact and provide survival signals to cancer cells. In this study, we utilized siRNA to VEGFR‐3 to demonstrate the biologic importance of this kinase in neuroblastoma cell survival. We also used confocal microscopy and immunoprecipitation to show that FAK and VEGFR‐3 bind in neuroblastoma. Finally, employing a 12‐amino‐acid peptide (AV3) specific to VEGFR‐3, we showed that the colocalization between FAK and VEGFR‐3 could be disrupted, and that disruption resulted in decreased neuroblastoma cell survival. These studies provide insight to the FAK–VEGFR‐3 interaction in neuroblastoma and demonstrate its importance in this tumor type. Focusing upon the FAK–VEGFR‐3 interaction may provide a novel therapeutic target for the development of new strategies for treatment of neuroblastoma. © 2012 Wiley Periodicals, Inc.