bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of long‐term late‐evening snack on health‐related quality of life in cirrhotic patients
Authors: Yamanaka‐Okumura Hisami , Nakamura Taki , Miyake Hidenori , Takeuchi Harumi , Katayama Takafumi , Morine Yuji , Imura Satoru , Shimada Mitsuo , Takeda Eiji 
Published: April 2010

Aim:  In patients with liver cirrhosis, abnormal energy metabolism induces low health‐related quality of life (HRQOL) scores. However, late‐evening snack (LES) prevents morning starvation in cirrhotic patients. Our aim is to assess the effect of long‐term LES on HRQOL in cirrhotic patients, using the 36‐item Short Form (SF‐36) health survey.Methods:  Thirty‐nine cirrhotic patients classified as Child–Pugh grade A were recruited. The patients were randomly divided into two groups: 24 were assigned to the non‐LES group and 15 to the LES group. SF‐36 scores, anthropometric data and serum biochemical parameters were examined in the non‐LES and LES groups at 0, 6 and 12 months.Results:  Neither anthropometric data nor laboratory data showed significant differences between the non‐LES and the LES groups at 0, 6 and 12 months. The role–emotional (RE) HRQOL scores at 6 months and mental health (MH) scores at 6 and 12 months were significantly reduced from the baseline level in the non‐LES group. In contrast, these scores remained unchanged in the LES group. General health perception (GH) scores at 12 months, RE at 6 months and MH at 6 and 12 months in the LES group were significantly higher than those of the non‐LES group.Conclusion:  Long‐term LES administration may be helpful in maintaining higher HRQOL in patients with cirrhosis.
Effect of chronic methylene blue administration on hypoxemia in rats with common bile duct ligation
Authors: Miyamoto Akiko , Katsuta Yasumi , Zhang Xue‐Jun , Li Hong‐Li , Ohsuga Masaru , Komeichi Hirokazu , Shimizu Shuji , Akimoto Toshio , Mizuno Kyoichi 
Published: April 2010

Aim: Acute administration of methylene blue (MB) can reverse hypoxemia in patients with hepatopulmonary syndrome (HPS). We evaluated the effect of chronic MB administration in common bile duct‐ligated rats, which develop HPS by 5 weeks after surgery.Methods: A total of 96 Sprague–Dawley rats were used, including 63 rats with common bile duct ligation (CBDL), 22 sham‐operated rats and 11 normal control rats. MB (6 mg/kg) was injected s.c. once a day for 4 weeks. Evaluation of hemodynamics and intrapulmonary vascular dilatation (IPVD), as well as blood sampling for arterial blood gas analysis, were done under conscious and unrestrained conditions. Hemodynamics were assessed by the reference sample method using141Ce‐microspheres (15 µm in diameter), and IPVD was also determined by i.v. injection of these microspheres. Histological examination of the lungs was done with hematoxylin–eosin staining and immunohistochemical staining for von Willebrand factor or vascular endothelial growth factor.Results: Both the arterial oxygen tension and alveolar–arterial oxygen difference were significantly improved in MB‐treated CBDL rats. The hyperdynamic circulation and splanchnic hyperemia seen in untreated CBDL rats were also alleviated by MB treatment. However, IPVD was not affected by MB. Histological examination of the lungs indicated that MB treatment reduced the proliferation of alveolar capillary vessels and angiogenesis, leading to improvement of arterial dysoxygenation. Hepatic synthetic and detoxification functions, as well as renal function, were not altered by MB treatment.Conclusion: Methylene blue may be a candidate treatment for HPS that does not cause deterioration of hepatic or renal function.
Iron redistribution as a therapeutic strategy for treating diseases of localized iron accumulationThis review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.
Authors: Kakhlon Or , Breuer William , Munnich Arnold , Cabantchik Z. Ioav 
Published: April 2010

Defective iron utilization leading to either systemic or regional misdistribution of the metal has been identified as a critical feature of several different disorders. Iron concentrations can rise to toxic levels in mitochondria of excitable cells, often leaving the cytosol iron-depleted, in some forms of neurodegeneration with brain accumulation (NBIA) or following mutations in genes associated with mitochondrial functions, such as ABCB7 in X-linked sideroblastic anemia with ataxia (XLSA/A) or the genes encoding frataxin in Friedreich’s ataxia (FRDA). In anemia of chronic disease (ACD), iron is withheld by macrophages, while iron levels in extracellular fluids (e.g., plasma) are drastically reduced. One possible therapeutic approach to these diseases is iron chelation, which is known to effectively reduce multiorgan iron deposition in iron-overloaded patients. However, iron chelation is probably inappropriate for disorders associated with misdistribution of iron within selected tissues or cells. One chelator in clinical use for treating iron overload, deferiprone (DFP), has been identified as a reversed siderophore, that is, an agent with iron-relocating abilities in settings of regional iron accumulation. DFP was applied to a cell model of FRDA, a paradigm of a disorder etiologically associated with cellular iron misdistribution. The treatment reduced the mitochondrial levels of labile iron pools (LIP) that were increased by frataxin deficiency. DFP also conferred upon cells protection against oxidative damage and concomitantly mediated the restoration of various metabolic parameters, including aconitase activity. Administration of DFP to FRDA patients for 6 months resulted in selective and significant reduction in foci of brain iron accumulation (assessed by T2* MRI) and initial functional improvements, with only minor changes in net body iron stores. The prospects of drug-mediated iron relocation versus those of chelation are discussed in relation to other disorders involving iron misdistribution, such as ACD and XLSA/A.
Integrin β3 prevents apoptosis of HL-1 cardiomyocytes under conditions of oxidative stressThis article is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.
Authors: Shewchuk Lee J. , Bryan Sean , Ulanova Marina , Khaper Neelam 
Published: April 2010

Integrin receptors are essential in the regulation of vital cardiac functions, and impaired integrin activity has been associated with cardiac remodeling. Oxidative stress is known to be involved in apoptosis and cardiac remodeling and thus may profoundly influence cardiac function via integrin modulation. The aim of this study was to determine the expression pattern and functional role of integrins in HL-1 cardiomyocytes under conditions of oxidative stress. Gene expression was studied by end-point and real-time PCR; surface protein expression was studied by flow cytometry; integrin knockdown was accomplished by siRNA gene silencing; and apoptosis was studied by annexin V staining and active caspase-3/7 using flow cytometry. Among the various subunits under study (αv, α5, α6, and β1, β3, β4, and β5), the expression of β3 integrin was significantly increased at both the mRNA and protein levels in cardiomyocytes exposed to 100 µmol/L hydrogen peroxide for 3 h. Gene silencing of β3 integrin by using siRNA resulted in a 2-fold increase in cardiomyocyte apoptosis upon treatment with hydrogen peroxide. This increase in apoptosis, as measured by annexin V staining, correlated with an increase in active caspase-3/7. Integrin β3 plays a vital role in preventing cardiomyocyte apoptosis under conditions of oxidative stress.
Role of vasoactive peptides in high glucose-induced increased expression of Gαq/11 proteins and associated signaling in vascular smooth muscle cellsThis review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.
Authors: Descorbeth Magda , Anand-Srivastava Madhu B. 
Published: April 2010

We have recently shown that A10 vascular smooth muscle cells (VSMCs) exposed to high glucose exhibited enhanced expression of Gαq and PLCβ proteins. Since high glucose has been reported to increase the levels of vasoactive peptides and oxidative stress, the present study was undertaken to investigate the implication of angiotensin II (Ang II), endothelin (ET)-1, and oxidative stress in the high glucose-induced enhanced expression of Gαq/11 and PLCβ proteins and associated signaling in A10 VSMCs. The levels of Gαq, Gα11, PLCβ-1, and PLCβ-2 proteins, as determined by Western blotting, were significantly higher in A10 VSMCs exposed to high glucose than in control cells. The elevated levels were restored to control values by the antioxidant diphenyleneiodonium (DPI), as well as by the antagonist of Ang II AT1 receptor losartan and the antagonists of ETA and ETB receptors BQ123 and BQ788, respectively. In addition, ET-1-stimulated production of inositol trisphosphate (IP3), which was enhanced by high glucose, was also restored toward control levels by DPI. Furthermore, the enhanced production of superoxide anion (O2–), increased NADPH oxidase activity, and enhanced expression of p22phox and p47phox proteins induced by high glucose were restored to control levels by losartan, BQ123, and BQ788. These results suggest that through increased oxidative stress, high glucose-induced enhanced levels of endogenous Ang II and ET-1 may contribute to the increased levels of Gαq/11 and mediated signaling in A10 VSMCs.
Functional linkage as a direction for studies in oxidative stress: α-adrenergic receptorsThis review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.
Authors: Ziolkowski Natalia , Grover Ashok K. 
Published: April 2010

The α-adrenergic receptors (adrenoceptors) are activated by the endogenous agonists epinephrine and norepinephrine. They are G protein-coupled receptors that may be broadly classified into α1(subclasses α1A, α1B, α1D) and α2(subclasses α2A, α2B, α2C). The α1-adrenoceptors act by binding to Gαqsubunits of the G proteins, causing activation of phospholipase C (PLC). PLC converts phosphatidylinositol 4,5-bisphosphate into inositol trisphosphate (IP3) and diacylglycerol (DAG), which have downstream effects on cytosolic Ca2+concentration. The α2-adrenoceptors bind to Gαithus inhibiting adenylyl cyclase and decreasing cAMP levels. DAG alters protein kinase C activity and cAMP activates protein kinase A. The downstream pathways of the two receptors may also interact. Activation of α1- and α2-adrenoceptors in vascular smooth muscle results in vasoconstriction. However, the densities of individual receptor subclasses vary between vessel beds or between vessels of various sizes within the same bed. In vasculature, the densities of adrenoceptor subclasses differ between conduit arteries and arterioles. These differences, along with differences in coupling mechanisms, allow for fine regulation of arterial blood flow. This diversity is enhanced by interactions resulting from homo- and heterodimer formation of the receptors, metabolic pathways, and kinases. Reactive oxygen species generated in pathologies may alter α1- and α2-adrenoceptor cascades, change vascular contractility, or cause remodeling of blood vessels. This review emphasizes the need for understanding the functional linkage between α-adrenoceptor subtypes, coupling, cross talk, and oxidative stress in cardiovascular pathologies.
MULTIVARIATE TECHNIQUES FOR IDENTIFYING DIFFRACTIVE INTERACTIONS AT THE LHC
Authors: KUUSELA MIKAEL , LÄMSÄ JERRY W. , MALMI ERIC , MEHTÄLÄ PETTERI , ORAVA RISTO 
Published: April 2010

Close to one half of the LHC events are expected to be due to elastic or inelastic diffractive scattering. Still, predictions based on extrapolations of experimental data at lower energies differ by large factors in estimating the relative rate of diffractive event categories at the LHC energies. By identifying diffractive events, detailed studies on proton structure can be carried out.The combined forward physics objects: rapidity gaps, forward multiplicity and transverse energy flows can be used to efficiently classify proton–proton collisions. Data samples recorded by the forward detectors, with a simple extension, will allow first estimates of the single diffractive (SD), double diffractive (DD), central diffractive (CD), and nondiffractive (ND) cross-sections. The approach, which uses the measurement of inelastic activity in forward and central detector systems, is complementary to the detection and measurement of leading beam-like protons.In this investigation, three different multivariate analysis approaches are assessed in classifying forward physics processes at the LHC. It is shown that with gene expression programming, neural networks and support vector machines, diffraction can be efficiently identified within a large sample of simulated proton–proton scattering events. The event characteristics are visualized by using the self-organizing map algorithm.
THE ALL-SILICON STRIP CMS TRACKER: MICROTECHNOLOGY AT THE MACROSCALE
Authors: MANNELLI M. 
Published: April 2010

The CMS silicon strip tracker is the largest device of its kind ever built, and is the first instance of a large collider detector relying exclusively on this all-silicon technology for tracking. With an instrumented surface of over 200 m2, and over nine million readout channels, it is two orders of magnitude larger than the silicon vertex detectors of the LEP experiments, and 30–40 times larger than the silicon inner detectors of the CDF and D0 experiments at the Tevatron. It makes use of microelectronics technology, but deploys it at the macroscale. The photograph below shows the completed CMS silicon tracker, ready for installation in the experiment, side by side with the silicon strip vertex detector of the OPAL experiment at LEP. Approximately a decade and more than two orders of magnitude in scale separate these two silicon strip detectors. [Formula: see text] In the following we motivate the choice of an all-silicon tracker for the CMS experiment, and discuss the reasons for the major design choices that define the system.
Adipose-Derived Mesenchymal Stem Cells as Stable Source of Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Delivery for Cancer Therapy
Authors: Grisendi Giulia , Bussolari Rita , Cafarelli Luigi , Petak Istvan , Rasini Valeria , Veronesi Elena , De Santis Giorgio , Spano Carlotta , Tagliazzucchi Mara , Barti-Juhasz Helga , Scarabelli Laura , Bambi Franco , Frassoldati Antonio , Rossi Giulio , Casali Christian , Morandi Uliano , Horwitz Edwin M. , Paolucci Paolo , Conte PierFranco , Dominici Massimo 
Published: April 2010

Abstract
Adipose-derived mesenchymal stromal/stem cells (AD-MSC) may offer efficient tools for cell-based gene therapy approaches. In this study, we evaluated whether AD-MSC could deliver proapoptotic molecules for cancer treatment. Human AD-MSCs were isolated and transduced with a retroviral vector encoding full-length human tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), a proapoptotic ligand that induces apoptosis in a variety of human cancers but not normal tissues. Although several studies have documented the antitumor activity of recombinant human TRAIL, its use in vivo is limited by a short half-life in plasma due to a rapid clearance by the kidney. We found that these limitations can be overcome using stably transduced AD-MSC, which could serve as a constant source of TRAIL production. AD-MSC armed with TRAIL targeted a variety of tumor cell lines in vitro, including human cervical carcinoma, pancreatic cancer, colon cancer, and, in combination with bortezomib, TRAIL-resistant breast cancer cells. Killing activity was associated with activation of caspase-8 as expected. When injected i.v. or s.c. into mice, AD-MSC armed with TRAIL localized into tumors and mediated apoptosis without significant apparent toxicities to normal tissues. Collectively, our results provide preclinical support for a model of TRAIL-based cancer therapy relying on the use of adipose-derived mesenchymal progenitors as cellular vectors. Cancer Res; 70(9); 3718–29. ©2010 AACR.
Activation of Endothelial Ras Signaling Bypasses Senescence and Causes Abnormal Vascular Morphogenesis
Authors: Bajaj Anshika , Zheng Qingxia , Adam Alejandro , Vincent Peter , Pumiglia Kevin 
Published: April 2010

Abstract
Angiogenesis is crucial for embryogenesis, reproduction, and wound healing and is a critical determinant of tumor growth and metastasis. The multifunctional signal transducer Ras is a proto-oncogene and frequently becomes mutated in a variety of human cancers, including angiosarcomas. Regulation of Ras is important for endothelial cell function and angiogenesis. Hyperactivation of Ras is linked with oncogene-induced senescence in many cell types. Given links between vascular malformations and angiosarcoma with activated Ras signaling, we sought to determine the consequence of sustained Ras activation on endothelial cell function. We find that sustained Ras activation in primary endothelial cells leads to prolonged activation of progrowth signaling, accompanied by a senescence bypass, enhanced proliferation, autonomous growth, and increased survival. Moreover, Ras severely compromises the ability of these cells to organize into vascular structures, instead promoting formation of planar endothelial sheets. This abnormal phenotype is regulated by phosphoinositide 3-kinase signaling, highlighting the therapeutic potential of agents targeting this axis in dealing with vascular morphogenic disorders and vascular normalization of tumors. Cancer Res; 70(9); 3803–12. ©2010 AACR.
Xg Expression in Ewing's Sarcoma Is of Prognostic Value and Contributes to Tumor Invasiveness
Authors: Meynet Ophélie , Scotlandi Katia , Pradelli Emmanuelle , Manara Maria C. , Colombo Mario P. , Schmid-Antomarchi Heidy , Picci Piero , Bernard Alain , Bernard Ghislaine 
Published: April 2010

AbstractEwing's sarcoma (EWS) is an aggressive tumor of children and young adults that requires intensive treatment. The search for new prognostic factors is very important to choose the most appropriate therapy and to better understand the biology of the disease for the development of new therapeutic tools. We found that Xg, a thus far poorly described molecule and member of the CD99 family, is expressed in EWS cell lines and EWS primary tumors. Immunohistochemical analysis confirmed the expression of Xg in 24% of patients. We found that Xg expression in EWS defines a subgroup of patients with worse prognosis compared with those with Xg-negative localized tumors, indicating a clinical relevance of Xg expression in EWS. Forced expression of Xg in an EWS cell line upregulated cell migration and invasion in vitro. Furthermore, knockdown of Xg expression with specific short hairpin RNA significantly reduced migration and invasion of EWS cells. Consistent with these data, in vivo xenotransplant studies in nude mice revealed that Xg expression increased the incidence and the number of metastases of EWS cells. Thus, Xg expression is associated with lower overall survival in EWS patients with localized tumors and is implicated in metastasis. Cancer Res; 70(9); 3730–8. ©2010 AACR.
Signal Transducers and Activators of Transcription-3 Binding to the Fibroblast Growth Factor Receptor Is Activated by Receptor Amplification
Authors: Dudka Anna A. , Sweet Steve M.M. , Heath John K. 
Published: April 2010

Abstract
Fibroblast growth factor receptors (FGFR) are cell surface tyrosine kinases that function in cell proliferation and differentiation. Aberrant FGFR signaling occurs in diverse cancers due to gene amplification, but the associated oncogenic mechanisms are poorly understood. Using a proteomics approach, we identified signal transducers and activators of transcription-3 (STAT3) as a receptor-binding partner that is mediated by Tyr677 phosphorylation on FGFR. Binding to activated FGFR was essential for subsequent tyrosine phosphorylation and nuclear translocation of STAT3, along with activation of its downstream target genes. Tyrosine phosphorylation of STAT3 was also dependent on concomitant FGFR-dependent activity of SRC and JAK kinases. Lastly, tyrosine (but not serine) phosphorylation of STAT3 required amplified FGFR protein expression, generated either by enforced overexpression or as associated with gene amplification in cancer cells. Our findings show that amplified FGFR expression engages the STAT3 pathway, and they suggest therapeutic strategies to attack FGFR-overexpressing cancers. Cancer Res; 70(8); 3391–401. ©2010 AACR.
A Unique Pharmacophore for Activation of the Nuclear Orphan Receptor Nur77 In vivo and In vitro
Authors: Liu Jing-jing , Zeng Hui-ni , Zhang Lian-ru , Zhan Yan-yan , Chen Yan , Wang Yuan , Wang Juan , Xiang Shao-hua , Liu Wen-jun , Wang Wei-jia , Chen Hang-zi , Shen Yue-mao , Su Wen-jin , Huang Pei-qiang , Zhang Hong-kui , Wu Qiao 
Published: April 2010

Abstract
Nur77 is a steroid orphan receptor that plays a critical role in regulating proliferation, differentiation, and apoptosis, including acting as a switch for Bcl-2 function. We previously reported that the octaketide cytosporone B (Csn-B) is a natural agonist for Nur77. In this study, we synthesized a series of Csn-B analogues and performed a structure-activity analysis that suggested criteria for the development of a unique pharmacophore to activate Nur77. The components of the pharmacophore necessary for binding Nur77 included the benzene ring, the phenolic hydroxyl group, and the acyl chain of the Csn-B scaffold, whereas the key feature for activating the biological function of Nur77 was the ester group. Csn-B analogues that bound Nur77 tightly not only stimulated its transactivation activity but also initiated mitochondrial apoptosis by means of novel cross-talk between Nur77 and BRE, an antiapoptotic protein regulated at the transcriptional level. Notably, the derivative n-amyl 2-[3,5-dihydroxy-2-(1-nonanoyl)phenyl]acetate exhibited greater antitumor activity in vivo than its parent compounds, highlighting particular interest in this compound. Our findings describe a pathway for rational design of Csn-B–derived Nur77 agonists as a new class of potent and effective antitumor agents. Cancer Res; 70(9); 3628–37. ©2010 AACR.