bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cigarette smoke‐induced skeletal muscle atrophy is associated with up‐regulation of USP‐19 via p38 and ERK MAPKs
Authors: Liu Qian , Xu Wei‐Guo , Luo Yong , Han Feng‐Feng , Yao Xiao‐Hong , Yang Tian‐Yun , Zhang Yue , Pi Wei‐Feng , Guo Xue‐Jun 
Published: April 2011

AbstractUbiquitin‐specific proteases (USPs) deubiquitinate ubiquitin–protein conjugates in the ubiquitin–proteasome system. Previous research shows that ubiquitin‐specific protease‐19 (USP‐19) is up‐regulated in mammalian skeletal muscle in some degradative conditions, such as including fasting, diabetes, dexamethasone treatment, and cancer, and its function is associated with muscle atrophy. However, it is still unclear whether USP‐19 is involved in muscle atrophy induced by chronic obstructive pulmonary disease. Rats exposed to chronic cigarette smoke and L6 myotubes incubated with cigarette smoke extract (CSE) were studied here. Using western blot analysis and quantitative real‐time polymerase chain reaction (qPCR), we observed over‐expression of USP‐19 and down‐regulation of myosin heavy chain (MHC) in both models. Moreover, CSE exposure inhibited myogenic differentiation and myotube formation in L6 myotubes. To explore the mechanism underlying these effects, we investigated the levels of phosphorylated mitogen‐activated protein kinases (MAPKs) and total MAPKs. Exposing myotubes to CSE resulted in the general activation of MAPKs such as p38, JNK, and ERK1/2. The ERK inhibitor PD98059 and the p38 inhibitor SB203580 significantly blocked the increase in USP‐19 gene expression induced by CSE. Our findings suggest that USP‐19 is associated with muscle atrophy in response to cigarette smoke and is a potential therapeutic target. CSE promotes myotube wasting in culture partly by inhibiting myogenic differentiation and acts via p38 and ERK MAPK to stimulate expression of USP‐19 in vitro. J. Cell. Biochem. 112: 2307–2316, 2011. © 2011 Wiley‐Liss, Inc.
TCERG1 inhibits C/EBPα through a mechanism that does not involve sequestration of C/EBPα at pericentromeric heterochromatin
Authors: Moazed Banafsheh , Banman Shanna L. , Wilkinson Grey A. , Roesler William J. 
Published: April 2011

AbstractTranscriptional elongation regulator 1 (TCERG1) is a nuclear protein that participates in multiple events that include regulating the elongation of RNA polymerase II and coordinating transcription and pre‐mRNA processing. More recently, we showed that TCERG1 is also a specific inhibitor of the transcription factor CCAAT enhancer binding protein α (C/EBPα). Interestingly, the inhibition of C/EBPα by TCERG1 is associated with the relocalization of TCERG1 from the nuclear speckle compartment to the pericentromeric regions where C/EBPα resides. In the present study, we examined additional aspects of C/EBPα‐induced redistribution of TCERG1. Using several mutants of C/EBPα, we showed that C/EBPα does not need to be transcriptionally competent or have anti‐proliferative activity to induce TCERG1 relocalization. Moreover, our results show that C/EBPα does not need to be localized to the pericentromeric region in order to relocalize TCERG1. This conclusion was illustrated through the use of a V296A mutant of C/EBPα, which is incapable of binding to the pericentromeric regions of heterochromatin and thus takes on a dispersed appearance in the nucleus. This mutant retained the ability to redistribute TCERG1, however in this case the redistribution was from the nuclear speckle pattern to the dispersed phenotype of C/EBPα V296A. Moreover, we showed that TCERG1 was still able to inhibit the activity of the V296A mutant. While we previously hypothesized that TCERG1 might inhibit C/EBPα by keeping it sequestered at the pericentromeric regions, our new findings indicate that TCERG1 can inhibit C/EBPα activity regardless of the latter's location in the nucleus. J. Cell. Biochem. 112: 2317–2326, 2011. © 2011 Wiley‐Liss, Inc.
Minimum MD simulation length required to achieve reliable results in free energy perturbation calculations: Case study of relative binding free energies of fructose‐1,6‐bisphosphatase inhibitors
Authors: Rathore R.S. , Aparoy P. , Reddanna P. , Kondapi A. K. , Rami Reddy M. 
Published: April 2011

AbstractIn an attempt to establish the criteria for the length of simulation to achieve the desired convergence of free energy calculations, two studies were carried out on chosen complexes of FBPase‐AMP mimics. Calculations were performed for varied length of simulations and for different starting configurations using both conventional‐ and QM/MM‐FEP methods. The results demonstrate that for small perturbations, 1248 ps simulation time could be regarded a reasonable yardstick to achieve convergence of the results. As the simulation time is extended, the errors associated with free energy calculations also gradually tapers off. Moreover, when starting the simulation from different initial configurations of the systems, the results are not changed significantly, when performed for 1248 ps. This study carried on FBPase‐AMP mimics corroborates well with our previous successful demonstration of requirement of simulation time for solvation studies, both by conventional and ab initio FEP. The establishment of aforementioned criteria of simulation length serves a useful benchmark in drug design efforts using FEP methodologies, to draw a meaningful and unequivocal conclusion. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Detecting coached feigning using the test of Memory Malingering (TOMM) and the structured inventory of Malingered Symptomatology (SIMS)
Authors: Jelicic Marko , Ceunen Erik , Peters Maarten J.V. , Merckelbach Harald 
Published: April 2011

AbstractUndergraduate students were administered the Test of Memory Malingering (TOMM) and the Structured Inventory of the Malingered Symptomatology (SIMS) and asked to respond honestly, or instructed to feign cognitive dysfunction due to head injury. Before both instruments were administered, symptom‐coached feigners were provided with some information about brain injury, while feigners who received a mix of symptom‐coaching and test‐coaching were given the same information plus advice on how to defeat symptom validity tests. Results show that, although the accuracy of both instruments appears to be somewhat reduced by a mix of symptom coaching and test coaching, the TOMM and SIMS are relatively resistant to different kinds of coaching. © 2011 Wiley Periodicals, Inc. J Clin Psychol 67:1–6, 2011.
Targeting mitochondria as a therapeutic target in cancer
Authors: Wenner Charles E. 
Published: April 2011

AbstractKnowledge of re‐programming in cancer cells with metabolic differences from their normal counterparts has resulted in new examination of therapeutic approaches. Several studies of the role of tumor mitochondria in cancer have led to the development of non‐genotoxic therapies which target mitochondrial proteins, function. The now well‐established functions of mitochondria in apoptosis provide novel targets for tumor cell suicide. Mitochondria serve as a central hub for responses to cellular stress as well as injury. The alterations in cancer cells which result in protection from apoptosis can be targeted to inhibit proliferation. Because of the reprogramming of cancer cell metabolism involving increased glycolysis, it appears that blocking InsP3R Ca2+ release or adaptive pathways in response to hypoxia by targeting HIF‐1 or metabolic enzymes encoded by the HIF‐1 gene represents a feasible therapeutic approach to cancer. A very early in vitro event found in tumor cells following resveratrol addition is an increase in intracellular Ca2+, measurable within seconds. Ca2+ release is also observed with non‐toxic flavonoids and a goal to identify the sentinel targets of resveratrol as a model compound involved in calcium activation seems worthwhile. New findings of the relationship between autophagy and apoptosis are discussed. The contribution of reactive oxygen species (ROS) generated by mitochondria is also considered. New data as to how cyclophilins and VDAC are involved in mitochondrial hexokinase protection of factors that induce apoptosis are reviewed. In addition, chemotherapeutic approaches based on Akt‐activated mTORC1 are described, and their relationship to the role of aerobic glycolysis in this protection. J. Cell. Physiol. © 2011 Wiley Periodicals, Inc.
High expression of ubiquitin conjugates and NF‐κB in unstable human intracranial atherosclerotic plaques
Authors: Sun Ruihong , Xiao Ling , Duan Shurong 
Published: April 2011

AbstractArteries from the first segment of the middle cerebral and adjacent normal blood vessel specimens were collected from 19 patients who had died from cerebral infarction. According to morphologic examination the atherosclerotic plaque present was classified as stable or unstable. The expression of ubiquitin conjugates and nuclear factor kappa B (NF‐κB) was assessed and found significantly higher in plaques than normal tissue and higher in unstable plaques than in stable plaques. Ubiquitin conjugates and NF‐κB were positively correlated with each other. It was concluded that the ubiquitin proteasome system and NF‐κB possibly play a role in the development of atherosclerotic plaques in intracranial arteries. J. Cell. Physiol. 227: 784–788, 2012. © 2011 Wiley Periodicals, Inc.
Tumorigenic polyploid cells contain elevated ROS and ARE selectively targeted by antioxidant treatment
Authors: Roh Meejeon , van der Meer Riet , Abdulkadir Sarki A. 
Published: April 2011

AbstractPolyploidy has been linked to tumorigenicity mainly due to the chromosomal aberrations. Elevated reactive oxygen species (ROS) generation, on the other hand, has also been associated with oncogenic transformation in most cancer cells. However, a possible link between ploidy and ROS is largely unexplored. Here we have examined the role of ROS in the tumorigenicity of polyploid cells. We show that polyploid prostate and mammary epithelial cells contain higher levels of ROS due to their higher mitochondrial contents. ROS levels and mitochondrial mass are also higher in dihydrocytochalasin B (DCB)‐induced polyploid cells, suggesting that higher levels of ROS observed in polyploid cell can occur due to cytokinesis failure. Interestingly, polyploid cells were more sensitive to the inhibitory effect of the antioxidant, N‐Acetyl‐L‐cysteine (NAC), than control diploid cells. Treatment of polyploid/diploid cells with NAC led to the selective elimination of polyploid cells over time and abrogated the tumorigenicity of polyploid cells. This effect was partially mediated via the Akt signaling pathway. We next explored a possible role for ROS in promoting chromosomal instability by analyzing the effects of ROS on the mitotic stage of the cell cycle. Enhancing ROS levels by treating cells with hydrogen peroxide delayed not only entry into and but also exit from mitosis. Furthermore, increasing ROS levels significantly increased taxol resistance. Our results indicated that increased ROS in polyploid cells can contribute to tumorigenicity and highlight the therapeutic potential of antioxidants by selectively targeting the tumorigenic polyploid cells and by reversing taxol resistance. J. Cell. Physiol. 227: 801–812, 2012. © 2011 Wiley Periodicals, Inc.
PML as a potential predictive factor of oxaliplatin/fluoropyrimidine‐based first line chemotherapy efficacy in colorectal cancer patients
Authors: Vincenzi Bruno , Santini Daniele , Perrone Giuseppe , Graziano Francesco , Loupakis Fotios , Schiavon Gaia , Frezza Anna Maria , Ruzzo Anna Maria , Rizzo Sergio , Crucitti Pierfilippo , Galluzzo Sara , Zoccoli Alice , Rabitti Carla , Muda Andrea Onetti , Russo Antonio , Falcone Alfredo , Tonini Giuseppe 
Published: April 2011

AbstractPML regulates a wide range of pathways involved in tumorigenesis, such as apoptosis, which is also one of the main mechanisms through which oxaliplatin and fluoropyrimidine exert their antineoplastic activity. The present study aims to investigate PML expression as a predictive factor of oxaliplatin/fluoropyrimidine therapy efficacy. Seventy‐four metastatic colorectal cancer patients who received oxaliplatin/floropyrimidine‐based first line therapy have been included in this retrospective study. PML expression was assessed by immunohistochemistry. PML down‐regulation was detected in 39 (52.7%) patients (14 complete and 25 partial PML loss). RR was significantly lower (25.6%) in patients with PML down‐regulation than in patients with preserved PML expression (60%) (P = 0.006). Median TTP was 5.5 months when PML was down‐regulated versus 11.9 months in case of preserved PML expression (P < 0.0001). A statistical significant difference was also detected in OS (15.6 and 24.5 months, respectively, P = 0.003). The impact of PML down‐regulation on TTP and OS was statistically significant also in a multivariate model. This study represents the first evidence of a possible correlation between PML protein expression and outcome of metastatic colorectal cancer patients treated with oxaliplatin/fluoropyrimidine‐based first line therapy. J. Cell. Physiol. 227: 927–933, 2012. © 2011 Wiley Periodicals, Inc.
Functional redundancy of type II BMP receptor and type IIB activin receptor in BMP2‐induced osteoblast differentiation
Authors: Liu Hongbin , Zhang Rongrong , Chen Di , Oyajobi Babatunde O. , Zhao Ming 
Published: April 2011

AbstractSignaling pathways for bone morphogenetic proteins (BMPs) are important in osteoblast differentiation. Although the precise function of type I BMP receptors in mediating BMP signaling for osteoblast differentiation and bone formation has been characterized previously, the role of type II BMP receptors in osteoblasts is to be well clarified. In this study, we investigated the role of type II BMP receptor (BMPR‐II) and type IIB activin receptor (ActR‐IIB) in BMP2‐induced osteoblast differentiation. While osteoblastic 2T3 cells expressed BMPR‐II and ActR‐IIB, loss‐of‐function studies, using dominant negative receptors and siRNAs, showed that BMPR‐II and ActR‐IIB compensated each other functionally in mediating BMP2 signaling and BMP2‐induced osteoblast differentiation. This was evidenced by two findings. First, unless there was loss of function of both type II receptors, isolated disruption of either BMPR‐II or ActR‐IIB did not remove BMP2 activity. Second, in cells with loss of function of both receptors, restoration of function of either BMPR‐II or ActR‐IIB by transfection of the wild‐type forms, restored BMP2 activity. These findings suggest a functional redundancy between BMPR‐II and ActR‐IIB in osteoblast differentiation. Results from experiments to test the effects of transforming growth factor β (TGF‐β), activin, and fibroblast growth factor (FGF) on osteoblast proliferation and differentiation suggest that inhibition of receptor signaling by double‐blockage of BMPR‐II and ActR‐IIB is BMP‐signaling specific. The observed functional redundancy of type II BMP receptors in osteoblasts is novel information about the BMP signaling pathway essential for initiating osteoblast differentiation. J. Cell. Physiol. 227: 952–963, 2012. © 2011 Wiley Periodicals, Inc.
Allodynic skin in post‐herpetic neuralgia: Histological correlates
Authors: Buonocore Michelangelo , Gatti Anna Maria , Amato Georgia , Aloisi Anna Maria , Bonezzi Cesare 
Published: April 2011

AbstractMost post‐herpetic neuralgia (PHN) patients suffer from tactile allodynia (pain evoked by lightly touching the skin) and it is frequently the dominant clinical manifestation. The pathophysiology of tactile allodynia in PHN patients is poorly understood and this is one of the major limits to the development of appropriate therapies. Epidermal nerve fibres (ENFs) are free nerve endings of small‐diameter A‐delta and C primary afferents, which can easily be assessed by neurodiagnostic skin biopsy (NSB). The aim of this study was to establish the correlation between the residual epidermal innervation of the allodynic skin and the intensity of tactile allodynia in that area. Twenty‐five patients (13 males and 12 females) with PHN were enrolled. Eighteen patients had PHN in the thoracic dermatome, four in the cervical, two in the trigeminal and one in the lumbar. The severity of allodynia evoked by a paintbrush was graded according to an eleven‐point numerical scale. A skin biopsy was obtained from the maximal allodynia area and from the contralateral skin. Nerve fibres were labelled with indirect immunofluorescence. Results showed that epidermal innervation was lower in the allodynic skin than in the contralateral skin, although there was great variability among patients. There was no correlation between severity of allodynia and epidermal innervation of the PHN skin. In conclusion, the present study further indicates peripheral nervous system involvement in PHN but does not support a direct correlation between epidermal innervation changes and tactile allodynia. J. Cell. Physiol. 227: 934–938, 2012. © 2011 Wiley Periodicals, Inc.
Distinct cellular responses induced by saporin and a transferrin–saporin conjugate in two different human glioblastoma cell lines
Authors: Cimini A. , Mei S. , Benedetti E. , Laurenti G. , Koutris I. , Cinque B. , Cifone M.G. , Galzio R. , Pitari G. , Di Leandro L. , Giansanti F. , Lombardi A. , Fabbrini M.S. , Ippoliti R. 
Published: April 2011

AbstractGlioblastoma multiforme (GBM) is the most common primary brain tumour in adults, with a median survival of ∼12–18 months post‐diagnosis. GBM usually recurs within 12 months post‐resection, with poor prognosis. Thus, novel therapeutic strategies to target and kill GBM cells are urgently needed. The marked difference of tumour cells with respect to normal brain cells renders glioblastoma a good candidate for selective targeted therapies. Recent experimental strategies focus on over expressed cell surface receptors. Targeted toxins represent a new class of selective molecules composed by a potent protein toxin and a carrier ligand. Targeted toxins approaches against glioblastoma were under investigation in phase I and II clinical trials with several immunotoxins (IT)/ligand toxins such as IL4‐Pseudomonas aeruginosa exotoxin A (IL4‐PE, NBI‐3001), tumour growth factor fused to PE38, a shorter PE variant, (TGF)alpha‐TP‐38, IL13‐PE38, and a transferrin‐C diphtheriae toxin mutant (Tf‐CRM107). In this work, we studied the effects of the plant ribosome‐inactivating saporin and of its chimera transferrin–saporin against two different GBM cell lines. The data obtained here indicate that cell proliferation is affected by the toxin treatments but that different mechanisms are used, directly linked to the presence of an active or inactive p53. A model is proposed for these alternative intracellular pathways. J. Cell. Physiol. 227: 939–951, 2012. © 2011 Wiley Periodicals, Inc.
Resveratrol suppresses tumorigenicity and enhances radiosensitivity in primary glioblastoma tumor initiating cells by inhibiting the STAT3 axis
Authors: Yang Yi‐Ping , Chang Yuh‐Lih , Huang Pin‐I , Chiou Guang‐Yuh , Tseng Ling‐Ming , Chiou Shih‐Hwa , Chen Ming‐Hsiung , Chen Ming‐Teh , Shih Yang‐Hsin , Chang Chin‐Hong , Hsu Chuan‐Chih , Ma Hsin‐I , Wang Chin‐Tien , Tsai Lo‐Lin , Yu Cheng‐Chia , Chang Charn‐Jung 
Published: April 2011

AbstractGlioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. Patients diagnosed with GBM have a poor prognosis, and it has been reported that tumor malignancy and GBM recurrence are promoted by STAT3 signaling. As resveratrol (RV), a polyphenol in grapes, is reported to be a potent and non‐toxic cancer‐preventive compound, the aim of this study was to investigate the therapeutic effect and molecular mechanisms of RV on GBM‐derived radioresistant tumor initiating cells (TIC). Firstly, our results showed that primary GBM‐CD133+ TIC presented high tumorigenic and radiochemoresistant properties as well as increased protein levels of phosphorylated STAT3. We consistently observed that treatment with shRNA‐STAT3 (sh‐STAT3) or AG490, a STAT3 inhibitor, significantly inhibited the cancer stem‐like cell properties and radioresistance of GBM‐CD133+ in vitro and in vivo. Furthermore, treatment of GBM‐CD133+ with 100 µM RV induced apoptosis and enhanced radiosensitivity by suppressing STAT3 signaling. Microarray results suggested that RV or AG490 inhibited the stemness gene signatures of GBM‐CD133+ and facilitated the differentiation of GBM‐CD133+ into GBM‐CD133− or astrocytoma cells. Finally, xenotransplant experiments indicated that RV or sh‐STAT3 therapy could significantly improve the survival rate and synergistically enhance the radiosensitivity of radiation‐treated GBM‐TIC. In summary, RV can reduce in vivo tumorigenicity and enhance the sensitivity of GBM‐TIC to radiotherapies through the STAT3 pathway. J. Cell. Physiol. 227: 976–993, 2012. © 2011 Wiley Periodicals, Inc.
Recent advances in computational analysis of mass spectrometry for proteomic profiling
Authors: Sun Clement S. , Markey Mia K. 
Published: April 2011

AbstractThe proteome, defined as an organism's proteins and their actions, is a highly complex end‐effector of molecular and cellular events. Differing amounts of proteins in a sample can be indicators of an individual's health status; thus, it is valuable to identify key proteins that serve as ‘biomarkers’ for diseases. Since the proteome cannot be simply inferred from the genome due to pre‐ and posttranslational modifications, a direct approach toward mapping the proteome must be taken. The difficulty in evaluating a large number of individual proteins has been eased with the development of high‐throughput methods based on mass spectrometry (MS) of peptide or protein mixtures, bypassing the time‐consuming, laborious process of protein purification. However, proteomic profiling by MS requires extensive computational analysis. This article describes key issues and recent advances in computational analysis of mass spectra for biomarker identification. Copyright © 2011 John Wiley & Sons, Ltd.
Formation of metal complex ions from amino acid in the presence of Li+, Na+ and K+ by electrospray ionization: metal replacement of hydrogen in the ligands
Authors: Jang Soonmin , Ju Song Min , Kim Hyunsik , Choi Sung‐Seen 
Published: April 2011

AbstractAlkali metal cations easily form complexes with proteins in biological systems; understanding amino acid clusters with these cations can provide useful insight into their behaviors at the molecular level including diagnosis and therapy of related diseases. For the purpose of characterization of basic interaction between amino acids and alkali metal, each of the 20 naturally occurring amino acids were ionized in the presence of lithium, sodium and potassium cations by electrospray ionization, and the resulting product ions were analyzed. We focus our attention on the gas phase alkali metal ion‐proton exchanged complexes in current study, specifically complexes with serine, threonine, asparagine and glutamine, which share characteristic pattern unlike other amino acids. All amino acids generated [M + H]+ and [M + Na]+ ions, where M stands for the neutral amino acid. Serine, threonine, asparagine and glutamine generated cluster ions of [nM − nH + (n + 1)Na]+ and [nM − (n − 1)H + (n − 1)Na + K]+, where n = 1–7. While the (M − H + Li) and (M − H + K) species were not observed, the neutral (M − H + Na) species formed by proton–sodium cation exchange had a highly stable cyclic structure with ketone and amine ligand sites, suggesting that (M − H + Na) serves as a building block in cluster ion formation. Cluster ion intensity distributions of [nM − nH + (n + 1)Na]+ and [nM − (n − 1)H + (n − 1)Na + K]+ showed a magic number at n = 3 and 4, respectively. Extensive B3LYP‐DFT quantum mechanical calculations were carried out to elucidate the geometry and energy of the cluster ions, and they provided a reasonable explanation for the stability and structure of the cluster ions. Copyright © 2011 John Wiley & Sons, Ltd.