bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined supplementation of vanadium and fish oil suppresses tumor growth, cell proliferation and induces apoptosis in DMBA‐induced rat mammary carcinogenesis
Authors: Manna Sangita , Das Subhadeep , Chatterjee Mary , Janarthan M. , Chatterjee Malay 
Published: April 2011

AbstractThe anti‐cancer activity of vanadium and fish oil has been shown in a large number of studies. This study was undertaken to analyze the combined effect of vanadium and fish oil on 7,12‐dimethylbenz(α)anthracene (DMBA)‐induced mammary carcinogenesis in female Sprague–Dawley rats. The whole experiment was divided into three parts: (1) DNA strand breaks study, (2) morphological analysis, and (3) histological and immunohistochemical study. Rats were treated with DMBA (0.5 mg/0.2 ml corn oil/100 g body weight) by a tail vein injection. Rats received vanadium (w/v) as ammonium monovanadate at a concentration of 0.5 ppm (4.27 µmol/L) in the drinking water and given ad libitum and/or fish oil (0.5 ml/day/rat) by oral gavage. Histology, morphology, DNA strand breaks, cell proliferation, and apoptosis of the mammary tissue were assessed in this study. Treatment with vanadium or fish oil alone significantly reduced the DNA strand breaks, palpable mammary tumors, tumor multiplicity, and cell proliferation but the maximum protection effect was found in the group that received both vanadium and fish oil and the combination treatment offered an additive effect (P < 0.05). Furthermore, vanadium and fish oil significantly increased the TUNEL‐positive apoptotic cells (P < 0.05) but the increase was maximal with combination treatment and had an additive effect. These results affirm the benefits of administration of vanadium and fish oil in the prevention of rat mammary carcinogenesis which was associated with reduced DNA strand breaks, palpable mammary tumors and cell proliferation and increased TUNEL‐positive apoptotic cells. J. Cell. Biochem. 112: 2327–2339, 2011. © 2011 Wiley‐Liss, Inc.
The role of cognitions in imagery rescripting for posttraumatic nightmares
Authors: Long Mary E. , Davis Joanne L. , Springer Justin R. , Elhai Jon D. , Rhudy Jamie L. , Teng Ellen J. , Frueh B. Christopher 
Published: April 2011

AbstractDespite growing support for the use of imagery rescripting to treat posttraumatic nightmares (PTNMs), its underlying mechanisms have not been examined. This secondary data analysis piloted the proposal that modification of posttraumatic cognitions is a mechanism of change when using a manualized PTNM imagery rescripting intervention. Significant linear reductions in posttraumatic cognitions were observed from baseline through 6‐month follow‐up evaluations. Change in total negative cognitions was significantly correlated with change in posttraumatic stress disorder symptoms. Initial amount of change in subscale scores also predicted the amount of distal change observed at the 6‐month follow‐up. These findings provide preliminary evidence that trauma‐related cognitions may improve over time as a result of imagery rescripting. © 2011 Wiley Periodicals, Inc. J Clin Psychol 67:1–9, 2011.
Integrating post‐transcriptional regulation into the embryonic stem cell gene regulatory network
Authors: Cassar Paul A. , Stanford William L. 
Published: April 2011

AbstractStem cell behavior is orchestrated as a multilayered, concert of gene regulatory mechanisms collectively referred to as the gene regulatory network (GRN). Via cooperative mechanisms, transcriptional, epigenetic, and post‐transcriptional regulators activate and repress gene expression to finely regulate stem cell self‐renewal and commitment. Due to their tractability, embryonic stem cells (ESCs) serve as the model stem cell to dissect the complexities of the GRN, and discern its relation to stem cell fate. By way of high‐throughput genomic analysis, targets of individual gene regulators have been established in ESCs. The compilation of these discrete networks has revealed convergent, multi‐dimensional gene regulatory mechanisms involving transcription factors, epigenetic modifiers, non‐coding RNA (ncRNA), and RNA‐binding proteins. Here we highlight the seminal genomic studies that have shaped our understanding of the ESC GRN and describe alternate post‐transcriptional gene regulatory mechanisms that require in depth analyses to draft networks that fully model ESC behavior. J. Cell. Physiol. 227: 439–449, 2012. © 2011 Wiley Periodicals, Inc.
MicroRNA‐181b and microRNA‐9 mediate arsenic‐induced angiogenesis via NRP1
Authors: Cui Yi , Han Zhongji , Hu Yi , Song Ge , Hao Chanjuan , Xia Hongfei , Ma Xu 
Published: April 2011

AbstractEnvironmental exposure to inorganic arsenic compounds has been reported to have serious health effects on humans. Recent studies reported that arsenic targets endothelial cells lining blood vessels, and endothelial cell activation or dysfunction, may underlie the pathogenesis of arsenic‐induced diseases and developmental toxicity. It has been reported that microRNAs (miRNAs) may act as an angiogenic switch by regulating related genes. The present study was designed to test the hypothesis that arsenite‐regulated miRNAs play pivotal roles in arsenic‐induced toxicity. Fertilized eggs were injected via the yolk sac with 100 nM sodium arsenite at Hamburger–Hamilton (HH) stages 6, 9, and 12, and harvested at HH stage 18. To identify the individual miRNAs and mRNAs that may regulate the genetic network, the expression profiles of chick embryos were analyzed by microarray analysis. Microarray analyses revealed that the expression of a set of miRNAs changed after arsenite administration, especially miRNA‐9, 181b, 124, 10b, and 125b, which exhibited a massive decrease in expression. Integrative analyses of the microarray data revealed that several miRNAs, including miR‐9 and miR‐181b, might target several key genes involved in arsenic‐induced developmental toxicity. A luciferase reporter assay confirmed neuropilin‐1 (Nrp1) as a target of mir‐9 and mir‐181b. Data from the transwell migration assay and the tube‐formation assay indicated that miR‐9 and mir‐181b inhibited the arsenic‐induced EA.hy926 cell migration and tube formation by targeting NRP1. Our study demonstrates that the environmental toxin, sodium arsenite, induced angiogenesis by altering the expression of miRNAs and their cognate mRNA targets. J. Cell. Physiol. © 2011 Wiley Periodicals, Inc.
Homeodomain transcription factors regulate BMP‐2‐induced osteoactivin transcription in osteoblasts
Authors: Singh Maneet , Del Carpio‐Cano Fabiola E. , Monroy M. Alexandra , Popoff Steven N. , Safadi Fayez F. 
Published: April 2011

AbstractOsteoactivin (OA) is required for the differentiation of osteoblast cells. OA expression is stimulated by bone morphogenetic protein‐2 (BMP‐2). BMP‐2 recruits homeodomain transcription factors Dlx3, Dlx5, and Msx2 to selectively activate or repress transcription of osteogenic genes and hence tightly regulate their transcription during osteoblast differentiation. Considering the key roles of Dlx3, Dlx5, and Msx2 in osteoblast differentiation, here we hypothesize that homeodomain proteins regulate BMP‐2‐induced OA transcription during osteoblast differentiation. Four classical homeodomain binding sites were identified in the proximal 0.96 kb region of rat OA promoter. Deletions and mutagenesis studies of the OA promoter region indicated that all four homeodomain binding sites are crucial for BMP‐2‐induced OA promoter activity. Simultaneous disruption of homeodomain binding sites at −852 and −843 of the transcription start site of OA gene significantly decreased the BMP‐2‐induced OA transcription and inhibited binding of Dlx3, Dlx5, and Msx2 proteins to the OA promoter. Dlx3 and Dlx5 proteins were found to activate the OA transcription, whereas, Msx2 suppressed BMP‐2‐induced OA transcription. Using chromatin immunoprecipitation assays, we demonstrated that the OA promoter is predominantly occupied by Dlx3 and Dlx5 during the proliferation and matrix maturation stages of osteoblast differentiation, respectively. During the matrix mineralization stage, BMP‐2 robustly enhanced the recruitment of Dlx5 and to a lesser extent of Dlx3 and Msx2 to the OA promoter region. Collectively, our results show that the BMP‐2‐induced OA transcription is differentially regulated by Dlx3, Dlx5, and Msx2 during osteoblast differentiation. J. Cell. Physiol. 227: 390–399, 2012. © 2011 Wiley Periodicals, Inc.
Hypoxia enhances cancer cell invasion through relocalization of the proprotein convertase furin from the trans‐golgi network to the cell surface
Authors: Arsenault Dominique , Lucien Fabrice , Dubois Claire M. 
Published: April 2011

AbstractTumor hypoxia is strongly associated with malignant progression such as increased cell invasion and metastasis. Although the invasion‐related genes affected by hypoxia have been well described, the contribution of post‐transcriptional mechanisms such as protein trafficking and proprotein processing associated with the hypoxic response remains poorly understood. The proprotein convertase furin, the major processing enzyme of the secretory pathway, resides in the trans‐Golgi network and most studies support a model where endogenous substrates are processed by furin within this compartment. Here, we report that hypoxia triggered an unexpected relocalization of furin from the trans‐Golgi network to endosomomal compartments and the cell surface in cancer cells. Exposing these cells back to normoxic conditions reversed furin redistribution, suggesting that the tumor microenvironment modulates furin trafficking in a highly regulated manner. Assessment of the mechanisms involved revealed that both Rab4GTPase‐dependent recycling and interaction of furin with the cytoskeletal anchoring protein, filamin‐A, are essential for the cell surface relocalization of furin. Interference with the association of furin with filamin‐A, prevented cell surface relocalization of furin and abolished the ability of cancer cells to migrate in response to hypoxia. Our observations support the notion that hypoxia promotes the formation of a peripheral processing compartment where furin translocates for enhanced processing of proproteins involved in tumorigenesis. J. Cell. Physiol. 227: 789–800, 2012. © 2011 Wiley Periodicals, Inc.
Nestin expression is lost in ventricular fibroblasts during postnatal development of the rat heart and re‐expressed in scar myofibroblasts
Authors: Béguin Pauline C. , Gosselin Hugues , Mamarbachi Maya , Calderone Angelino 
Published: April 2011

AbstractStudies have reported that the intermediate filament protein nestin was expressed in various non‐stem/progenitor cells during development, downregulated during postnatal growth and re‐expressed following injury. The present study tested the hypothesis that an analogous paradigm was prevalent for ventricular fibroblasts. In the neonatal rat heart, nestin protein levels were significantly higher than the adult heart and the isolation of cardiac cells revealed a selective expression in ventricular fibroblasts. In adult ventricular fibroblasts, nestin protein expression was markedly lower compared to neonatal ventricular fibroblasts. Following ischemic damage to the rat heart, nestin staining was detected in a subpopulation of scar myofibroblasts (37%) and the percentage of immunoreactive cells was greater than adult ventricular fibroblasts (7%) but significantly lower than neonatal ventricular fibroblasts (86%). Moreover, dissimilar rates of 3H‐thymidine uptake were observed among the fibroblast populations and may be related in part to the disparate percentage of nestin(+) cells. To assess the role of nestin in DNA synthesis, neonatal ventricular fibroblasts were infected with a lentivirus containing a shRNAmir directed against the intermediate filament protein. The partial depletion of nestin expression in neonatal ventricular fibroblasts significantly reduced basal DNA synthesis, in the absence of an apoptotic response. Thus, postnatal development of the rat heart was associated with a selective loss of nestin expression in ventricular fibroblasts and subsequent induction in a subpopulation of myofibroblasts following ischemic injury. The re‐expression of nestin in scar myofibroblasts may represent an adaptive response to enhance their proliferative rate and accelerate the healing process. J. Cell. Physiol. 227: 813–820, 2012. © 2011 Wiley Periodicals, Inc.
Involvement of TACE/ADAM17 and ADAM10 in etoposide‐induced apoptosis of germ cells in rat spermatogenesis
Authors: Lizama Carlos , Rojas‐benitez Diego , Antonelli Marcelo , Ludwig Andreas , Moreno Ricardo D. 
Published: April 2011

AbstractGerm cell apoptosis is important to regulate sperm production in the mammalian testis, but the molecular mechanisms underlying apoptosis are still poorly understood. We have recently shown that in vitro, etoposide induces upregulation of TACE/ADAM17 and ADAM10, two membrane‐bound extracellular metalloproteases. Here we show that in vivo these enzymes are involved in etoposide‐, but not in heat shock‐, induced apoptosis in rat spermatogenesis. Germ cell apoptosis induced by DNA damage was associated with an increase in protein levels and cell surface localization of TACE/ADAM17 and ADAM10. On the contrary, apoptosis of germ cells induced by heat stress, another cell death stimulus, did not change levels or localization of these proteins. Pharmacological in vivo inhibition of TACE/ADAM17 and ADAM10 prevents etoposide‐induced germ cell apoptosis. Finally, Gleevec (STI571) a pharmacological inhibitor of p73, a master gene controlling apoptosis induced by etoposide, prevented the increase of TACE/ADAM17 levels. Our results strongly suggest that TACE/ADAM17 participates in in vivo apoptosis of male germ cells induced by DNA damage. J. Cell. Physiol. 227: 829–838, 2012. © 2011 Wiley Periodicals, Inc.
Cross‐circulation and cell distribution kinetics in parabiotic mice
Authors: Gibney Barry C. , Chamoto Kenji , Lee Grace S. , Simpson Dinee C. , Miele Lino F. , Tsuda Akira , Konerding Moritz A. , Wagers Amy , Mentzer Steven J. 
Published: April 2011

AbstractBlood‐borne nucleated cells participate not only in inflammation, but in tissue repair and regeneration. Because progenitor and stem cell populations have a low concentration in the blood, the circulation kinetics and tissue distribution of these cells is largely unknown. An important approach to tracking cell lineage is the use of fluorescent tracers and parabiotic models of cross‐circulation. Here, we investigated the cross‐circulation and cell distribution kinetics of C57/B6 GFP+/wild‐type parabionts. Flow cytometry analysis of the peripheral blood after parabiosis demonstrated no evidence for a “parabiotic barrier” based on cell size or surface characterstics; all peripheral blood cell subpopulations in this study reached equilibrium within 14 days. Whole blood fluorescence analysis indicated that the mean exchange flow rate was 16 µl/h or 0.66% of the circulating blood volume per hour. Studies of peripheral lymphoid organs indicated differential cell distribution kinetics. Some subpopulations, such as CD8+ and CD11c+, equilibrated in both lymph nodes and spleen indicating a residence time <28 days; in contrast, other lymphocyte subpopulations, such as B220+ and CD4+ cells, had not yet reached equilibrium at 28 days. We conclude that parabiosis can provide important insights into defining tissue distribution, residence times, and recirculating pools using fluorochrome markers of cell lineage. J. Cell. Physiol. 227: 821–828, 2012. © 2011 Wiley Periodicals, Inc.
Phosphorylation of histone H1 by P‐TEFb is a necessary step in skeletal muscle differentiation
Authors: O'Brien Siobhan K. , Knight Kendall L. , Rana Tariq M. 
Published: April 2011

AbstractPositive transcription elongation factor b (P‐TEFb), the complex of Cyclin T1 and CDK9, activates the transcription of many viral and eukaryotic genes at the point of mRNA elongation. The activity of P‐TEFb has been implicated in the differentiation of a number of cell types, including skeletal muscle. In order to promote transcription, P‐TEFb hyperphosphorylates RNA Pol II, thereby increasing its processivity. Our previous work identified histone H1 as a P‐TEFb substrate during HIV‐1 and immediate‐early transcription. Here, we examine the role of P‐TEFb phosphorylation of histone H1 during differentiation, using the myoblast cell line C2C12 as a model for skeletal muscle differentiation. We found that H1 phosphorylation is elevated in differentiating C2C12, and this phosphorylation is sensitive to P‐TEFb inhibition. H1 phosphorylation was also necessary for the induction of three muscle marker genes that require P‐TEFb for expression. Additionally, ChIP experiments demonstrate that H1 dissociates from muscle differentiation marker genes in C2C12 cells under active P‐TEFb conditions. We determine that both P‐TEFb activity and H1 phosphorylation are necessary for the full differentiation of C2C12 myoblasts into myotubes. J. Cell. Physiol. 227: 383–389, 2012. © 2011 Wiley Periodicals, Inc.
Functional regulation of HIF‐1α under normoxia—is there more than post‐translational regulation?
Authors: Kuschel A. , Simon P. , Tug S. 
Published: April 2011

AbstractThe hypoxia‐inducible factor‐1 (HIF‐1) is an oxygen‐regulated transcriptional activator playing a pivotal role in mammalian physiology and disease pathogenesis, e.g., HIF‐1 is indispensable in a broad range of developmental stages in different tumors. Its post‐translational regulation via PHDs under the influence of hypoxia is widely investigated and accepted. Different non‐hypoxic stimuli such as lipopolysaccharides (LPS), thrombin, and angiotensin II (Ang II), have been proven to enhance HIF‐1 levels through activation of regulative mechanisms distinct from protein stabilization. Some of these stimuli specifically regulate HIF‐1α at the transcriptional, post‐transcriptional, or translational level, whereas others additionally influence post‐translational modifications. Thus, it is difficult for the investigators to discern the impact of the different mechanisms leading to functional HIF‐1 protein. Nevertheless, profound knowledge of additional regulatory networks appears to depict new therapeutic opportunities and thus is an interesting and important field for further investigations. J. Cell. Physiol. 227: 514–524, 2012. © 2011 Wiley Periodicals, Inc.
Nicotinamide inhibits the early stage of carcinogen‐induced hepatocarcinogenesis in mice and suppresses human hepatocellular carcinoma cell growth
Authors: Park Soo Young , Lee Kyoung Bun , Lee Min‐Jae , Bae Suk‐Chul , Jang Ja‐June 
Published: April 2011

AbstractHepatocellular carcinoma (HCC) can cause severe complications, resulting in a high incidence of recurrence after treatment of the primary tumor. Recently, we have shown that nicotinamide effectively inhibits the growth and progression of bladder tumors by up‐regulating RUNX3 and p300 expression. Therefore, in this study, the efficacy and inhibitory mechanisms of nicotinamide against HCC were investigated in mice and HCC cell lines, respectively. To evaluate the inhibitory effects of nicotinamide on HCC development, mice were injected with diethylnitrosamine (DEN) and simultaneously treated with 1% nicotinamide. Also, the effect of nicotinamide on human HCC cell lines was assessed by measuring caspase activity, cell proliferation, and DNA content using immunoblot analysis and reverse‐transcriptase polymerase chain reaction. It was found that nicotinamide significantly inhibited the development of pre‐neoplastic lesions (foci and adenomas) during the early stages of HCC. Furthermore, nicotinamide inhibited cell proliferation and induced mitochondria‐mediated apoptosis in HCC cell lines. It also increased the expression of p21, and the expression and acetylation of p53. These results strongly suggest that nicotinamide inhibits the progression of early‐stage HCC and may contribute to the induction of apoptosis and the inhibition of proliferation of HCC cells. Taken together, the results of this study indicate that nicotinamide is a potential chemopreventive agent, i.e., it may prevent the progression of early HCC development and/or the recurrence of HCC after primary treatment. J. Cell. Physiol. 227: 899–908, 2012. © 2011 Wiley Periodicals, Inc.
Indomethacin enhances learning and memory potential by interacting with CaMKII
Authors: Kanno Takeshi , Yaguchi Takahiro , Nagata Tetsu , Shimizu Tadashi , Tanaka Akito , Nishizaki Tomoyuki 
Published: April 2011

AbstractThe present study examined the effect of indomethacin (IM), a cyclooxygenase inhibitor, on learning and memory functions. IM activated Ca2+/calmodulin‐dependent protein kinase II (CaMKII) in cultured rat hippocampal neurons. IM (100 µM) significantly increased the rate of spontaneous AMPA receptor‐mediated miniature excitatory postsynaptic currents elicited from CA1 pyramidal neurons of rat hippocampal slices, without affecting the amplitude, and enhanced extracellular high K+ (20 mM)‐induced glutamate release from rat hippocampal slices, indicating that IM stimulates presynaptic glutamate release. Those IM effects were clearly inhibited by the CaMKII inhibitor KN‐93. IM persistently facilitated synaptic transmission monitored from the CA1 region of rat hippocampal slices in a concentration (1–100 µM)‐dependent manner that was also abolished by KN‐93. In the water maze test, IM (1 mg/kg, i.p.) enhanced spatial learning and memory ability for normal rats, and ameliorated scopolamine‐induced spatial learning and memory impairment or age‐related spatial learning and memory deterioration for senescence‐accelerated mouse‐prone 8 mice. In the test to learn 15 numbers consisting of three patterns of five digit number for healthy human subjects, oral intake with IM (25 mg/kg) significantly raised the scores of correct number arrangements that subjects memorized 5 min and 3 days after the test. The results of the present study indicate that IM could enhance learning and memory potential by facilitating hippocampal synaptic transmission as a result from stimulating presynaptic glutamate release under the control of CaMKII. J. Cell. Physiol. 227: 919–926, 2012. © 2011 Wiley Periodicals, Inc.
Identification of a functional estrogen‐responsive enhancer element in the promoter 2 of PRDM2 gene in breast cancer cell lines
Authors: Abbondanza Ciro , De Rosa Caterina , D'Arcangelo Andrea , Pacifico Marianna , Spizuoco Clorinda , Piluso Giulio , Di Zazzo Erika , Gazzerro Patrizia , Medici Nicola , Moncharmont Bruno , Alfredo Puca Giovanni 
Published: April 2011

AbstractThe retinoblastoma protein‐interacting zinc‐finger (RIZ) gene, also known as PRDM2, encodes two protein products, RIZ1 and RIZ2, differing for the presence of a 202 aa domain, called PR domain, at the N‐terminus of the RIZ1 molecule. While the histone H3 K9 methyltransferase activity of RIZ1 is associated with the negative control of cell proliferation, no information is currently available on either expression regulation of the RIZ2 form or on its biological activity. RIZ proteins act as ER co‐activators and promote optimal estrogen response in female reproductive tissues. In estrogen‐responsive cells, 17‐β estradiol modulates RIZ gene expression producing a shift in the balanced expression of the two forms. Here, we demonstrate that an estrogen‐responsive element (ERE) within the RIZ promoter 2 is regulated in a ligand‐specific manner by ERα, through both the AF1 and AF2 domains. The pattern of ERα binding, histone H4 acetylation, and histone H3 cyclical methylation of lysine 9 was comparable to other estrogen‐regulated promoters. Association of topoisomerase IIβ with the RIZ promoter 2 confirmed the transcriptional activation induced by estrogen. We hypothesize that RIZ2, acting as a negative regulator of RIZ1 function, mediates the proliferative effect of estrogen through regulation of survival and differentiation gene expression. J. Cell. Physiol. 227: 964–975, 2012. © 2011 Wiley Periodicals, Inc.