bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pain‐releasing action of Platelet‐activating factor (PAF) antagonists in neuropathic pain animal models and the mechanisms of action
Authors: Motoyama N. , Morita K. , Kitayama T. , Shiraishi S. , Uezono Y. , Nishimura F. , Kanematsu T. , Dohi T. 
Published: January 2013

AbstractBackgroundPlatelet‐activating factor (PAF) has been implicated in the pathology of neuropathic pain. Previous studies reported that PAF receptor (PAF‐R) antagonists have varied anti‐allodynia effects by route of administration and nerve injury models in rats.MethodsThe present study elucidated the effectiveness of PAF antagonists against neuropathic pain in four different models of peripheral nerve injury and provided insights into the mode of anti‐allodynia action.ResultsPAF antagonists, TCV‐309, BN 50739 and WEB 2086 by intravenous (i.v.) and oral administration have potent and long‐lasting anti‐allodynia action in mice neuropathic pain models. Treatment with PAF antagonists before surgery delayed the initiation of allodynia until the effects of these treatments were abolished. Intrathecal (i.t.) injection of the PAF antagonists and siRNA against PAF receptor ameliorated allodynia. I.t. injection of the glycine receptor (GlyR)α3 siRNA reduced the anti‐allodynia effect of PAF antagonists. This evidence suggests that the anti‐allodynia effect of PAF antagonists is at least in part mediated by spinal relief of PAF‐induced dysfunction of GlyRα3. An analysis of the mode of anti‐allodynia action of TCV‐309 in vivo revealed a competitive action against PAF shortly after the injection of TCV‐309, converting to a non‐competitive action later.ConclusionsThe present results revealed the effectiveness in anti‐allodynia of PAF antagonists in different nerve injury models, and the unique mode of action; long‐lasting anti‐allodynia effects mediated by spinal GlyRα3 with a competitive manner at the initial stage and the following non‐competitive manner of inhibition.
3D interconnected porous HA scaffolds with SiO2additions: Effect of SiO2content and macropore size on the viability of human osteoblast cells
Authors: Nikom Jaru , Charoonpatrapong‐Panyayong Kanokwan , Kedjarune‐Leggat Ureporn , Stevens Ron , Kosachan Nudthakarn , Jaroenworaluck Angkhana 
Published: January 2013

Abstract3D interconnected porous scaffolds of HA and HA with various additions of SiO2were fabricated using a polymeric template technique, to make bioceramic scaffolds consisting of macrostructures of the interconnected macropores. Three different sizes of the polyurethane template were used in the fabrication process to form different size interconnected macropores, to study the effect of pore size on human osteoblast cell viability. The template used allowed fabrication of scaffolds with pore sizes of 45, 60, and 75 ppi, respectively. Scanning microscopy was used extensively to observe the microstructure of the sintered samples and the characteristics of cells growing on the HA surfaces of the interconnected macropores. It has been clearly demonstrated that the SiO2addition has influenced both the phase transformation of HA to TCP (β‐TCP and α‐TCP) and also affected the human osteoblast cell viability grown on these scaffolds. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Cucurbitane Triterpenoids from the Fruit Pulp of Momordica charantia and Their Cytotoxic Activity
Authors: Liao Yun‐Wen , Chen Chiy‐Rong , Chuu Jiunn‐Jye , Huang Hui‐Chi , Hsu Jue‐Liang , Huang Tzou‐Chi , Kuoe Yueh‐Hsiung , Chang Chi‐I 
Published: January 2013

AbstractTwo new cucurbitane‐type triterpenes, 25‐methoxycucurbita‐5,23(E)‐diene‐3β,19‐diol (1) and 7β‐ethoxy‐3β‐hydroxy‐25‐methoxycucurbita‐5,23(E)‐dien‐19‐al (2), together with three known cucurbitane‐type triterpenes, 3β,7β,25‐trihydroxycucurbita‐5,23(E)‐dien‐19‐al (3), (23E)‐3β‐hydroxy‐7β,25‐dimethoxycucurbita‐5,23‐dien‐19‐al (4), and 3β‐hydroxy‐25‐methoxycucurbita‐6,23(E)‐dien‐19,5β‐olide (5), were isolated from the fruit pulp of Momordica charantia. The structures of two new compounds were elucidated on the basis of 1D and 2D NMR, MS, IR, optical rotation. Among these isolates, compounds 1, 2, and 5 showed slight cytotoxic activity against the SK‐Hep 1 cell line with IC50 values of 33.1, 24.3, and 38.7 μM, respectively.
TGFβ‐induced PI 3 kinase‐dependent Mnk‐1 activation is necessary for Ser‐209 phosphorylation of eIF4E and mesangial cell hypertrophy
Authors: Das Falguni , Ghosh‐Choudhury Nandini , Bera Amit , Kasinath Balakuntalam S. , Choudhury Goutam Ghosh 
Published: January 2013

AbstractTransforming growth factorβ (TGFβ)‐induced canonical signal transduction is involved in glomerular mesangial cell hypertrophy; however, the role played by the noncanonical TGFβ signaling remains largely unexplored. TGFβ time‐dependently stimulated eIF4E phosphorylation at Ser‐209 concomitant with enhanced phosphorylation of Erk1/2 (extracellular signal regulated kinase1/2) and MEK (mitogen‐activated and extracellular signal‐regulated kinase kinase) in mesangial cells. Inhibition of Erk1/2 by MEK inhibitor or by expression of dominant negative Erk2 blocked eIF4E phosphorylation, resulting in attenuation of TGFβ‐induced protein synthesis and mesangial cell hypertrophy. Expression of constitutively active (CA) MEK was sufficient to induce protein synthesis and hypertrophy similar to those induced by TGFβ. Pharmacological or dominant negative inhibition of phosphatidylinositol (PI) 3 kinase decreased MEK/Erk1/2 phosphorylation leading to suppression of eIF4E phosphorylation. Inducible phosphorylation of eIF4E at Ser‐209 is mediated by Mnk‐1 (mitogen‐activated protein kinase signal‐integrating kinase‐1). Both PI 3 kinase and Erk1/2 promoted phosphorylation of Mnk‐1 in response to TGFβ. Dominant negative Mnk‐1 significantly inhibited TGFβ‐stimulated protein synthesis and hypertrophy. Interestingly, inhibition of mTORC1 activity, which blocks dissociation of eIF4E‐4EBP‐1 complex, decreased TGFβ‐stimulated phosphorylation of eIF4E without any effect on Mnk‐1 phosphorylation. Furthermore, mutant eIF4E S209D, which mimics phosphorylated eIF4E, promoted protein synthesis and hypertrophy similar to TGFβ. These results were confirmed using phosphorylation deficient mutant of eIF4E. Together our results highlight a significant role of dissociation of 4EBP‐1‐eIF4E complex for Mnk‐1‐mediated phosphorylation of eIF4E. Moreover, we conclude that TGFβ‐induced noncanonical signaling circuit involving PI 3 kinase‐dependent Mnk‐1‐mediated phosphorylation of eIF4E at Ser‐209 is required to facilitate mesangial cell hypertrophy. J. Cell. Physiol. 228: 1617–1626, 2013. © 2013 Wiley Periodicals, Inc.
SIRT1 silencing confers neuroprotection through IGF‐1 pathway activation
Authors: Sansone Luigi , Reali Valentina , Pellegrini Laura , Villanova Lidia , Aventaggiato Michele , Marfe Gabriella , Rosa Roberta , Nebbioso Marcella , Tafani Marco , Fini Massimo , Russo Matteo A. , Pucci Bruna 
Published: January 2013

AbstractThe following study demonstrated that, in in vitro differentiated neurons, SIRT1 silencing induced an increase of IGF‐1 protein expression and secretion and of IGF‐1R protein levels which, in turn, prolonged neuronal cell survival in presence of an apoptotic insult. On the contrary, SIRT1 overexpression increased cell death. In particular, IGF‐1 and IGF‐1R expression levels were negatively regulated by SIRT1. In SIRT1 silenced cells, the increase in IGF‐1 and IGF‐1R expression was associated to an increase in AKT and ERK1/2 phosphorylation. Moreover, neuronal differentiation was reduced in SIRT1 overexpressing cells and increased in SIRT1 silenced cells. We conclude that SIRT1 silenced neurons appear more committed to differentiation and more resistant to cell death through the activation of IGF‐1 survival pathway. J. Cell. Physiol. 228: 1754–1761, 2013. © 2013 Wiley Periodicals, Inc.
RKIP: Much more than Raf Kinase inhibitory protein
Authors: Al‐Mulla Fahd , Bitar Milad S. , Taqi Zainab , Yeung Kam C. 
Published: January 2013

AbstractFrom its discovery as a phosphatidylethanolamine‐binding protein in bovine brain to its designation as a physiological inhibitor of Raf kinase protein, RKIP has emerged as a critical molecule for maintaining subdued, well‐orchestrated cellular responses to stimuli. The disruption of RKIP in a wide range of pathologies, including cancer, Alzheimer's disease, and pancreatitis, makes it an exciting target for individualized therapy and disease‐specific interventions. This review attempts to highlight recent advances in the RKIP field underscoring its potential role as a master modulator of many pivotal intracellular signaling cascades that control cellular growth, motility, apoptosis, genomic integrity, and therapeutic resistance. Specific biological and functional niches are highlighted to focus future research towards an enhanced understanding of the multiple roles of RKIP in health and disease. J. Cell. Physiol. 228: 1688–1702, 2013. © 2013 Wiley Periodicals, Inc.
Human Ng2+ adipose stem cells loaded in vivo on a new crosslinked hyaluronic acid‐lys scaffold fabricate a skeletal muscle tissue
Authors: Desiderio Vincenzo , De Francesco Francesco , Schiraldi Chiara , De Rosa Alfredo , La Gatta Annalisa , Paino Francesca , d'Aquino Riccardo , Ferraro Giuseppe Andrea , Tirino Virginia , Papaccio Gianpaolo 
Published: January 2013

AbstractMesenchymal stem cell (MSC) therapy holds promise for treating diseases and tissue repair. Regeneration of skeletal muscle tissue that is lost during pathological muscle degeneration or after injuries is sustained by the production of new myofibers. Human Adipose stem cells (ASCs) have been reported to regenerate muscle fibers and reconstitute the pericytic cell pool after myogenic differentiation in vitro. Our aim was to evaluate the differentiation potential of constructs made from a new cross‐linked hyaluronic acid (XHA) scaffold on which different sorted subpopulations of ASCs were loaded. Thirty days after engraftment in mice, we found that NG2+ ASCs underwent a complete myogenic differentiation, fabricating a human skeletal muscle tissue, while NG2− ASCs merely formed a human adipose tissue. Myogenic differentiation was confirmed by the expression of MyoD, MF20, laminin, and lamin A/C by immunofluorescence and/or RT‐PCR. In contrast, adipose differentiation was confirmed by the expression of adiponectin, Glut‐4, and PPAR‐γ. Both tissues formed expressed Class I HLA, confirming their human origin and excluding any contamination by murine cells. In conclusion, our study provides novel evidence that NG2+ ASCs loaded on XHA scaffolds are able to fabricate a human skeletal muscle tissue in vivo without the need of a myogenic pre‐differentiation step in vitro. We emphasize the translational significance of our findings for human skeletal muscle regeneration. J. Cell. Physiol. 228: 1762–1773, 2013. © 2013 Wiley Periodicals, Inc.
Gene therapy clinical trials worldwide to 2012 – an update
Authors: Ginn Samantha L. , Alexander Ian E. , Edelstein Michael L. , Abedi Mohammad R. , Wixon Jo 
Published: January 2013

AbstractTo date, over 1800 gene therapy clinical trials have been completed, are ongoing or have been approved worldwide. Our database brings together global information on gene therapy clinical trials from official agency sources, published literature, conference presentations and posters kindly provided to us by individual investigators or trial sponsors.This review presents our analysis of clinical trials that, to the best of our knowledge, have been or are being performed worldwide. As of our June 2012 update, we have entries on 1843 trials undertaken in 31 countries. We have analysed the geographical distribution of trials, the disease indications (or other reasons) for trials, the proportions to which different vector types are used, and which genes have been transferred. Details of the analyses presented, and our searchable database are available on The Journal of Gene Medicine Gene Therapy Clinical Trials Worldwide website at: http://www.wiley.co.uk/genmed/clinical. We also provide an overview of the progress being made in clinical trials of gene therapy approaches around the world and discuss the prospects for the future. Copyright © 2013 John Wiley & Sons, Ltd.
Diesel‐lubricated ta‐C coatings
Authors: Makowski S. , Weihnacht V. , Leson A. 
Published: January 2013

ABSTRACTSamples coated with tetrahedral amorphous carbon were investigated in two different oscillating test setups regarding their friction and wear properties. As lubricants petrodiesel, rapeseed methyl ester biodiesel and a mixture thereof were used. Compared with a petrodiesel‐lubricated uncoated system, friction was reduced for more than 50% when a tetrahedral amorphous carbon coating was applied and biodiesel added to the lubricant. Impurities of monoglycerides are assumed to be the cause for the friction‐modifying effect. Copyright © 2013 John Wiley & Sons, Ltd.
Roles of phosphorylated JNK in esophageal squamous cell carcinomas of kazakh ethnic
Authors: Qin Xu , Zheng Shutao , Liu Tao , Liu Qing , Liang Meng , Li Xiuling , Sheyhidin Ilyar , Lu Xiaomei 
Published: January 2013

AbstractThe c‐Jun NH2‐terminal kinase (JNK) signal pathway has been implicated in the growth, cellular proliferation, and apoptosis in many kinds of carcinomas. However, the role of JNK in the development of esophageal squamous cell carcinomas (ESCCs) is unknown. To investigate the role of JNK in ESCC, in vitro, esophageal cancer cell line Eca109 was pretreated using SP600125, JNK specific inhibitor, then was subjected to MTT assay to examine cellular proliferation, flow cytometric analysis to detect apoptosis and cell cycle, and wound healing assay to evaluate cell migration. Meanwhile, the mRNA and protein expression of JNK in Eca109 cells pretreated with SP600125 were examined by real‐time quantitative reverse transcription PCR (qRT‐PCR) and Western blotting, respectively. In vivo, 12 paired of fresh ESCC and normal adjacent tissues (NAT) from Kazakh patients were used to validate the expression of JNK by qRT‐PCR and Western blotting. Furthermore, to reconfirm the expression trend of activation JNK (p‐JNK), enlarged 72 paired of Kazakh's ESCC and NAT were subjected to immunohistochemistry. Our results showed that the suppression of p‐JNK could lead to apoptosis and reduce proliferation in Eca109 cells. However, there was an elevated expression of p‐JNK protein in NAT compared with ESCC tissues, and there was significant difference between p‐JNK expression and pathological differentiation (P < 0.05) in Kazakh populations. Together, all the data we obtained in the present study indicated that the p‐JNK MAPK pathway was involved in pathogenesis of Kazakh's ESCC, and played a different roles in carcinogenesis and development of Kazakh's ESCC. © 2013 Wiley Periodicals, Inc.
Dual involvements of cyclooxygenase and nitric oxide synthase expressions in ketamine‐induced ulcerative cystitis in rat bladder
Authors: Chuang Shu‐Mien , Liu Keh‐Min , Li Yi‐Lun , Jang Mei‐Yu , Lee Hei‐Hwa , Wu Wen‐Jeng , Chang Wei‐Chiao , Levin Robert M. , Juan Yung‐Shun 
Published: January 2013

AbstractAimsThe aims of the present study were to investigate voiding patterns, tissue constituents and the expressions of cyclooxygenase‐2 (COX‐2) and nitric oxide synthase (NOS) involved in ketamine‐induced ulcerative cystitis in rat urinary bladder.MethodsThirty Sprague–Dawley rats were distributed into three groups which received saline or ketamine (25 mg/kg/day) for a period of 14 and 28 days. In each group, cystometry was performed weekly and the concentration of ketamine and its metabolites (norketamine) was assayed. Paraffin‐embedded sections were stained with Masson's trichrome stain, and ketamine‐induced morphological changes were examined. Western blot analyses were carried out to examine the expressions of COX‐2 and different NOS isoforms in bladder tissues. Immunofluorescence study was done to evaluate the expressions of COX‐2 and macrophage infiltration (stained with ED‐1 macrophage cell surface antigen) within the bladder.ResultsKetamine treatment resulted in bladder hyperactivity and the non‐voiding contractions were significantly increased. The urine concentrations of ketamine and norketamine were much higher in ketamine‐treated group. Moreover, ulcerated urothelium and mononuclear cell infiltration were noted in ketamine‐treated group. These alterations in urodynamic functions and tissue constituents were accompanied by increases in the expression of COX‐2. Two NOS isoforms (iNOS and eNOS) were also overexpressed, but no significant change was observed for nNOS. COX‐2 positive stained cells were significantly increased. Meanwhile, increased amounts of ED‐1 positive stained macrophages were present and most of COX‐2 expressed cells were co‐stained with ED‐1 in the early stage of ketamine treatment.ConclusionsKetamine treatment affected bladder tissues by enhancing interstitial fibrosis and accelerating macrophages infiltration. Ketamine also initiated the up‐regulations of COX‐2 and iNOS and eNOS expressions. These up‐regulated enzymes might play an important role in contributing to ketamine‐induced alterations in micturition patterns and ulcerative cystitis. Neurourol. Urodynam. 32:1137–1143, 2013. © 2013 Wiley Periodicals, Inc.
Robust network design: Formulations, valid inequalities, and computations
Authors: Koster Arie M.C.A. , Kutschka Manuel , Raack Christian 
Published: January 2013

AbstractTraffic in communication networks fluctuates heavily over time. Thus, to avoid capacity bottlenecks, operators highly overestimate the traffic volume during network planning. In this article we consider telecommunication network design under traffic uncertainty, adapting the robust optimization approach of Bertsimas and Sim [Oper Res 52 (2004), 35–53]. We present two different mathematical formulations for this problem, provide valid inequalities, study the computational implications, and evaluate the realized robustness. To enhance the performance of the mixed‐integer programming solver, we derive robust cutset inequalities generalizing their deterministic counterparts. Instead of a single cutset inequality for every network cut, we derive multiple valid inequalities by exploiting the extra variables available in the robust formulations. We show that these inequalities define facets under certain conditions and that they completely describe a projection of the robust cutset polyhedron if the cutset consists of a single edge. For realistic networks and live traffic measurements, we compare the formulations and report on the speed‐up achieved by the valid inequalities. We study the “price of robustness” and evaluate the approach by analyzing the real network load. The results show that the robust optimization approach has the potential to support network planners better than present methods. © 2013 Wiley Periodicals, Inc. NETWORKS, 2013
A particle‐based method for mechanical analyses of planar fiber‐based materials
Authors: Persson J. , Isaksson P. 
Published: January 2013

SUMMARYA new discrete element model to deal with rapid deformation and fracture of flat fibrous materials is derived. The method is based on classical mechanical theories and is a combination of traditional particle dynamics and nonlinear engineering beam theory. It is assumed that a fiber can be seen as a beam that is represented by discrete particles, which are moving according to Newton's laws of motion. Damage is dealt with by fracture of fiber‐segments and fiber–fiber bonds when the potential energy of a segment or bond exceeds the critical fracture energy. This allows fractures to evolve as a result of material properties only. To validate the model, four examples are shown and compared with analytical results found in literature. Copyright © 2013 John Wiley & Sons, Ltd.
The effect of surface treatments on the mechanical properties of basalt‐reinforced epoxy composites
Authors: Varley Russell J. , Tian Wendy , Leong K.H. , Leong Alan Y. , Fredo Flavio , Quaresimin Marino 
Published: January 2013

AbstractBasalt fiber is an emerging alternative reinforcement to glass or carbon depending upon the application. An important contributing parameter to ultimate performance of any composite is the fiber–‐matrix interface, to which toughness and compressive strength are intimately related. To better understand this matrix fiber interaction in controlling properties, we compared different modification strategies and the impact upon the properties of composites. Strategies focussing upon mechanical interlocking through increased surface roughness and covalent chemical bonding using sol/get methods were explored. Combined methods were also used to explore synergistic behavior as well as the use of aliphatic triethylenetetramine (TETA) to react with any covalently attached epoxy groups. Results from single ply composites showed that when the properties were fiber or fiber/matrix dominated, the sol/gel or epoxy silane method gave the largest improvement in ultimate tensile strength increasing 66% and 27% for uni‐weave 0° and 45° laminas. The combined surface modification methods exhibited increases of 45% and 13% for the same laminas. When properties were matrix dominated, the combined strategies produced the highest improvements in ultimate tensile strength of about 55% compared with 37% for sol/gel modification. For 16‐ply plain weave laminates, epoxy silane surface treatments produced the greatest improvements in compressive and interlaminar shear strengths, increasing 52% and 21%, respectively. This correlated with fiber‐ and fiber/matrix‐dominated results from single ply laminas. The combined treatment using TETA however decreased shear and compressive strength by about 20%, while scanning electron microscopy (SEM) evaluation and dynamic mechanical thermal analysis (DMTA) attributed this to increased resin ductility and plasticization. © 2013 Society of Plastics Engineers
Nearly a third of abnormalities found after first‐trimester screening are different than expected:10‐year experience from a single center
Authors: Alamillo Christina M. L. , Krantz David , Evans Mark , Fiddler Morris , Pergament Eugene 
Published: January 2013

ABSTRACTObjectiveThis study aimed to assess the efficacy of first‐trimester aneuploidy screening in a single clinical setting.MethodsMaternal age, nuchal translucency, and maternal serum levels of pregnancy‐associated plasma protein A and free beta human chorionic gonadotrophin comprised first‐trimester risk assessment for Down syndrome and trisomies 13/18. Means, screen positive rates, detection rates, and predictive values were calculated for Down syndrome and trisomies 13/18.ResultsOf the 23 329 first‐trimester screenings, 6.3% were screen positive: 5.7% for Down syndrome only, 0.4% for trisomies 13/18 only, and 0.3% for Down syndrome and trisomies 13/18. An abnormal karyotype was present in 3.9% of screen positives for Down syndrome, 13.8% of screen positives for trisomies 13/18, and 45.9% of screen positives for both Down syndrome and trisomies 13/18. Of the 97 pregnancies found to have an abnormal karyotype, 29.9% had chromosome abnormalities other than trisomy 13, 18, or 21, with expected clinical outcomes ranging from likely benign to uniformly lethal.ConclusionAs expected, first‐trimester screening is effective for detecting aneuploidy for chromosomes 13, 18, and 21; however, a significant number of chromosomally abnormal pregnancies initially identified by first‐trimester screening have a different karyotype. With the possible exception of 47,XYY and 45,X, the dataset suggested that these different chromosome complements were likely to be randomly distributed. Nevertheless, prior to diagnostic testing, prospective parents should be counseled concerning the possibility of a chromosome abnormality other than the trisomies 13, 18, or 21. © 2013 John Wiley & Sons, Ltd.