bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organic‐solvent extraction of model biomaterials for use in the in vitro chromosome aberration test
Authors: Matsuoka Atsuko , Haishima Yuji , Hasegawa Chie , Matsuda Yoshie , Tsuchiya Toshie 
Published: October 2007

AbstractWe prepared polyurethane (PU) containing 0.4% or 4% 4,4′‐methylenedianiline (MDA) as model materials to investigate the effectiveness of sample preparation by organic‐solvent extraction for the in vitro chromosome aberration (CA) test. MDA itself (0.4 mg/mL) was positive only in the presence of an exogenous metabolizing system (S9 mix). The culture medium extract of PU containing 4% MDA (PU/4% MDA) was negative with and without S9 mix. Methanol and acetone extracts, on the other hand, induced structural CAs without S9 mix, which we did not expect because MDA requires S9 mix for activity. On chemical analysis, however, we found that the ratio of MDA extracted by the organic solvents to that extracted by the culture medium of PU/4% MDA was about 15:1. Interestingly, oligomers consisting of poly(tetramethyleneglycol) derivatives (OTMG) were also extracted by the organic solvents. The data suggest that the induction of structural CAs in the absence of S9 mix may have been partly due to synergism of MDA and OTMG. CA tests of MDA and PTMG‐1000 in combination confirmed that to be the case. Thus, organic‐solvent extraction may be more effective than medium extraction in evaluating the biological safety of biomaterials. Detailed chemical analysis of extracts was performed. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Wear‐corrosion performance of Si‐DLC coatings on Ti‐6Al‐4V substrate
Authors: Kim Jung‐Gu , Lee Kwang‐Ryeol , Yang Seok‐Jo 
Published: October 2007

AbstractSi‐incorporated diamond‐like carbon (Si‐DLC) coatings ranging from 0 to 2 at % Si were deposited on Ti‐alloy substrate by means of radio frequency plasma‐assisted chemical vapor deposition (r.f. PACVD) technique, using a mixture of benzene (C6H6) and silane (SiH4) as the reaction gas. The synergy in wear and corrosion of Si‐DLC coatings was investigated by tribological and electrochemical techniques. The electrolyte used in this test to simulate the corrosive environment of body fluid was a 0.89 wt % NaCl solution of pH 7.4 at 37°C. This study provides quantitative data for the assessment of the effect of Si incorporation on the synergistic effect between wear and corrosion in the simulated body fluid environment. In conclusion, tribological and electrochemical measurements showed that the Si‐DLC films could improve wear‐corrosion resistance in the simulated body fluid environment owing to the lower friction coefficient, corrosion rate, delamination area, and water uptake. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Characterization of porous injectable poly‐(propylene fumarate)‐based bone graft substitute
Authors: Kim Choll W. , Talac Robert , Lu Lichun , Moore Michael J. , Currier Bradford L. , Yaszemski Michael J. 
Published: October 2007

AbstractThe use of bone grafts for orthopedic applications have increased steadily over the past decade. With improvements in surgical technique, combined with an increasing aged population requiring orthopedic treatment, the need for bone grafts substitutes have also increased. To be useful clinically, the bone graft substitute must be biocompatible, bioabsorbable, and have convenient handling properties. In addition, it must possess a microarchitecture that allows cellular ingrowth and remodeling while simultaneously providing mechanical strength. Poly(propylene fumarate) (PPF) has been investigated as an injectable, biodegradable scaffold for orthopedic applications. Various methods to create a porous, interconnected polymer scaffold are available. The foaming technique is a convenient method to accomplish this task. Reactions between bicarbonate salts and weak acids generate CO2 gas, causing a bubbling reaction during the polymerization process. This technique allows the porosity of the scaffold to be modulated. Image analysis and mechanical testing of porous PPF fabricated using the foaming technique shows that a highly porous, interconnected scaffold can be produced. At ∼50% porosity, the scaffold has excellent handling properties, contains pore sizes ranging from 50 to 500 μm with an elastic modulus ranging from 20 to 40 MPa. The foaming technique provides an additional method by which clinically useful polymers can be fabricated for use in various bone tissue engineering applications. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Is HMGB1 an osteocyte alarmin?
Authors: Bidwell Joseph P. , Yang Jieping , Robling Alexander G. 
Published: October 2007

AbstractThe death of osteocytes, the terminally differentiated cells of the osteoblast lineage that are embedded in bone and regulate remodeling, is significant to both normal and pathological bone resorption. Apoptotic osteocytes putatively release a clarion signal that enhances the development of the bone‐resorbing osteoclasts and targets their migration to the breach in the osteocyte network. This phenomenon is thought to underlie normal repair of bone microdamage and contribute to the etiologies of inflammatory bone loss. The chromatin protein high mobility group box 1 protein (HMGB1) has been identified as an “alarmin” in other tissues. An alarmin is an endogenous molecule released by dead and dying cells that alert the innate immune system to damage and the need for tissue repair. Wang and colleagues presented evidence in a landmark 1999 study showing that released HMGB1 is a lethal mediator of sepsis. Extracellular HMGB1 is a ligand for the toll‐like receptors (TLRs) and for the receptor for advanced glycation end products (RAGE) all of which amplify inflammation. Recent studies by our lab and others have shown that HMGB1 is a bone‐active cytokine. It is released by apoptotic osteoblasts in vitro, including the MLO‐Y4 osteocyte‐like cells. Extracellular HMGB1 enhances the expression of RANKL, TNFα, and IL6 in osteoblastogenic bone marrow stromal cell cultures, and it is chemotactic to osteoclasts. In this prospectus we will review HMGB1 activity at the immune‐bone interface and propose a role for HMGB1 as an osteocyte alarmin and mediator of normal remodeling and inflammatory bone loss. J. Cell. Biochem. 103: 1671–1680, 2008. © 2007 Wiley‐Liss, Inc.
Activation or inactivation of cardiac Akt/mTOR signaling diverges physiological from pathological hypertrophy
Authors: Kemi Ole Johan , Ceci Marcello , Wisloff Ulrik , Grimaldi Serena , Gallo Paolo , Smith Godfrey L , Condorelli Gianluigi , Ellingsen Oyvind 
Published: October 2007

AbstractCardiomyocyte hypertrophy differs according to the stress exerted on the myocardium. While pressure overload‐induced cardiomyocyte hypertrophy is associated with depressed contractile function, physiological hypertrophy after exercise training associates with preserved or increased inotropy. We determined the activation state of myocardial Akt signaling with downstream substrates and fetal gene reactivation in exercise‐induced physiological and pressure overload‐induced pathological hypertrophies. C57BL/6J mice were either treadmill trained for 6 weeks, 5 days/week, at 85–90% of maximal oxygen uptake (VO2max), or underwent transverse aortic constriction (TAC) for 1 or 8 weeks. Total and phosphorylated protein levels were determined with SDS‐PAGE, and fetal genes by real‐time RT‐PCR. In the physiologically hypertrophied heart after exercise training, total Akt protein level was unchanged, but Akt was chronically hyperphosphorylated at serine 473. This was accompanied by activation of the mammalian target of rapamycin (mTOR), measured as phosphorylation of its two substrates: the ribosomal protein S6 kinase‐1 (S6K1) and the eukaryotic translation initiation factor‐4E binding protein‐1 (4E‐BP1). Exercise training did not reactivate the fetal gene program (β‐myosin heavy chain, atrial natriuretic factor, skeletal muscle actin). In contrast, pressure overload after TAC reactivated fetal genes already after 1 week, and partially inactivated the Akt/mTOR pathway and downstream substrates after 8 weeks. In conclusion, changes in opposite directions of the myocardial Akt/mTOR signal pathway appears to distinguish between physiological and pathological hypertrophies; exercise training associating with activation and pressure overload associating with inactivation of the Akt/mTOR pathway. J. Cell. Physiol. 214: 316–321, 2008. © 2007 Wiley‐Liss, Inc.
Extremely low‐frequency electromagnetic fields promote in vitro neurogenesis via upregulation of Cav1‐channel activity
Authors: Piacentini Roberto , Ripoli Cristian , Mezzogori Daniele , Azzena Gian Battista , Grassi Claudio 
Published: October 2007

AbstractWe previously reported that exposure to extremely low‐frequency electromagnetic fields (ELFEFs) increases the expression and function of voltage‐gated Ca2+ channels and that Ca2+ influx through Cav1 channels plays a key role in promoting the neuronal differentiation of neural stem/progenitor cells (NSCs). The present study was conducted to determine whether ELFEFs influence the neuronal differentiation of NSCs isolated from the brain cortices of newborn mice by modulating Cav1‐channel function. In cultures of differentiating NSCs exposed to ELFEFs (1 mT, 50 Hz), the percentage of cells displaying immunoreactivity for neuronal markers (β‐III‐tubulin, MAP2) and for Cav1.2 and Cav1.3 channels was markedly increased. NSC‐differentiated neurons in ELFEF‐exposed cultures also exhibited significant increases in spontaneous firing, in the percentage of cells exhibiting Ca2+ transients in response to KCl stimulation, in the amplitude of these transients and of Ca2+ currents generated by the activation of Cav1 channels. When the Cav1‐channel blocker nifedipine (5 µM) was added to the culture medium, the neuronal yield of NSC differentiation dropped significantly, and ELFEF exposure no longer produced significant increases in β‐III‐tubulin‐ and MAP2‐immunoreactivity rates. In contrast, the effects of ELFEFs were preserved when NSCs were cultured in the presence of either glutamate receptor antagonists or Cav2.1‐ and Cav2.2‐channel blockers. ELFEF stimulation during the first 24 h of differentiation caused Cav1‐dependent increases in the number of cells displaying CREB phosphorylation. Our data suggest that ELFEF exposure promotes neuronal differentiation of NSCs by upregulating Cav1‐channel expression and function. J. Cell. Physiol. 215: 129–139, 2008. © 2007 Wiley‐Liss, Inc.
Adrenomedullin is anti‐apoptotic in osteoblasts through CGRP1 receptors and MEK‐ERK pathway
Authors: Uzan Benjamin , Villemin Aude , Garel Jean‐Michel , Cressent Michèle 
Published: October 2007

AbstractAdrenomedullin (ADM) has been shown to mediate multifunctional responses in cell culture and animal system such as regulation of growth and apoptosis. ADM stimulates the proliferation of osteoblasts in vitro and promotes bone growth in vivo. The ability of ADM to influence osteoblastic cell number through inhibition of apoptosis has not yet been studied. To address this question we have investigated its effect on the apoptosis of serum‐deprived osteoblastic cells using mouse MC3T3‐E1 cells which express both ADM and ADM receptors. Treatment with ADM significantly blunted apoptosis, evaluated by caspase‐3 activity, DNA fragmentation quantification and annexin V‐FITC labeling. This effect was abolished by the subtype‐1 CGRP receptor antagonist, CGRP(8–37). Both ADM and its specific receptor antagonist, the (22–52) ADM fragment exhibited a similar anti‐apoptotic effect. Thus, our data suggest that ADM exerts anti‐apoptotic effects through CGRP1 receptors. This was substantiated by a similar protective effect of CGRP on MC3T3‐E1 cells apoptosis. Accordingly, neutralization of endogenous ADM by a specific antibody enhanced apoptosis. Finally, the selective inhibitor of MAPK kinase (MEK), PD98059, abolished the apoptosis protective effect of ADM and prevented ADM activation of ERK1/2. These data show that ADM acts as a survival factor in osteoblastic cells via a CGRP1 receptor‐MEK‐ERK pathway, which provides further understanding on the physiological function of ADM in osteoblasts. J. Cell. Physiol. 215: 122–128, 2008. © 2007 Wiley‐Liss, Inc.
GHRH proliferative action on somatotrophs is cell‐type specific and dependent on Pit‐1/GHF‐1 expression
Authors: Solloso A , Barreiro L , Seoane R , Nogueira E , Cañibano C , Alvarez C.V. , Zalvide J , Diéguez C , Pombo C.M. 
Published: October 2007

AbstractTo investigate the mechanisms by which the hypothalamic peptide GHRH influences cell division, we analyzed its effects on the proliferation of two different cell lines: CHO‐4, an ovary‐derived cell line, and GH3, a pituitary‐derived cell line. We found that GHRH induces the proliferation of pituitary‐derived cells but inhibits the proliferation of ovary‐derived cells. We further characterized this dual effect of GHRH to find that the cytoplasmic signals induced by this hormone are similar in both cell lines. Moreover, in CHO‐4 cells GHRH stimulates two well‐known positive cell cycle regulators, c‐myc and cyclin D1, but is unable to induce the degradation of the negative cell cycle regulator p27Kip1. Significantly, when the Pit‐1/GHF‐1 gene is exogenously expressed in CHO‐4 cells, the negative effect of GHRH on the proliferation of these cells is attenuated. Furthermore, when the levels of Pit‐1 are downregulated by siRNA in GH3‐GHRHR cells, the positive effects of GHRH on the proliferation of these cells are diminished. These findings add to our understanding of the molecules involved in the regulation of cell proliferation by GHRH, as we demonstrate for the first time that Pit‐1 is not only required to drive the expression of the GHRH receptor, as previously described, but is also needed for the downstream effects that occur after its activation to modulate cell proliferation. These data suggest that the regulation of cell proliferation in response to a specific growth factor depends in certain cell populations on the presence of a tissue‐specific transcription factor. J. Cell. Physiol. 215: 140–150, 2008. © 2007 Wiley‐Liss, Inc.
All‐trans retinoic acid prevents angiotensin II‐ and mechanical stretch‐induced reactive oxygen species generation and cardiomyocyte apoptosis
Authors: Choudhary Rashmi , Baker Kenneth M. , Pan Jing 
Published: October 2007

AbstractCardiomyocyte apoptosis has an important role in the transition from compensatory cardiac remodeling to heart failure. All‐trans retinoic acid (RA), a bioactive vitamin A derivative, prevents stretch‐ and angiotensin II (Ang II)‐induced cardiac hypertrophy. However, the anti‐apoptotic potential of RA in the heart remains unexplored. Here, we demonstrate that stretch‐ and Ang II‐induced apoptosis is prevented by RA in neonatal cardiomyocytes. RA improved mitochondrial function by inhibiting the stretch‐ and Ang II‐induced reduction in mitochondrial membrane potential, cytochrome c release and by increasing the Bcl2/Bax ratio. RA inhibited stretch‐ and Ang II‐induced intracellular reactive oxygen species (ROS) generation and upregulated the SOD2 level. Hydrogen peroxide‐induced increases in the number of TUNEL‐positive cells and percentage of Annexin V positive cells, were dose‐dependently inhibited by RA. The thiol antioxidant, N‐acetyl cysteine (NAC), completely inhibited stretch‐ and Ang II‐induced apoptosis. Using diazoxide (mitochondrial ATP‐sensitive K+ channel opener) and SDS (NADPH oxidase activator), we confirmed that RA suppressed both mitochondrial‐ and NADPH oxidase‐derived ROS. We also observed that both RAR and RXR were involved in preventing Ang II‐ and stretch‐induced ROS production and apoptosis, by using selective retinoid receptor agonists and antagonists. Our data provide the first evidence that RA prevents Ang II and stretch induced apoptosis, by inhibiting ROS generation and increasing the anti‐oxidant defense system, suggesting that RA‐mediated signaling may provide a new therapeutic target for the prevention of the cardiac remodeling process. J. Cell. Physiol. 215: 172–181, 2008. © 2007 Wiley‐Liss, Inc.
Transcriptional responses of human epidermal keratinocytes to cytokine interleukin‐1
Authors: Yano Shoichiro , Banno Tomohiro , Walsh Rebecca , Blumenberg Miroslav 
Published: October 2007

AbstractInterleukin‐1 is a proinflammatory and immunomodulatory cytokine that plays a crucial role in inflammatory diseases of the skin, including bacterial infections, bullous diseases, UV damage, and especially psoriasis. To characterize the molecular effects of IL‐1 in epidermis, we defined the transcriptional changes in human epidermal keratinocytes 1, 4, 24, and 48 h after treatment with IL‐1α. IL‐1 significantly regulated 388 genes, including genes associated with proteolysis, adhesion, signal transduction, proliferation, and epidermal differentiation. IL‐1 induces many genes that have antimicrobial function. Secreted cytokines, chemokines, growth factors, and their receptors are the prominent targets of IL‐1 regulation, including IL‐8, IL‐19, elafin, C3, and S100A proteins, which implicate IL‐1 in the pathogenesis of inflammatory diseases. IL‐1 induced not only proliferation‐associated genes but also differentiation marker genes such as transglutaminase‐1 and involucrin, which suggests that IL‐1 plays an important role in the aberrant proliferation and differentiation seen in psoriasis. Correlation of IL‐1 regulated genes with the TNFα and IFNγ regulated ones showed more similarities between IL‐1 and TNFα than IL‐1 and IFNγ, whereas Oncostatin‐M (OsM) affected a largely unrelated set of genes. IL‐1 regulates many genes previously shown to be specifically over‐expressed in psoriasis. In summary, IL‐1 regulates a characteristic set of genes that define its specific contribution to inflammation and aberrant differentiation in skin diseases. J. Cell. Physiol. 214:1–13, 2008. © 2007 Wiley‐Liss, Inc.
Etoposide‐resistant HT‐29 human colon carcinoma cells during glucose deprivation are sensitive to piericidin A, a GRP78 down‐regulator
Authors: Hwang Ji‐Hwan , Kim Ju‐Young , Cha Mi‐Ran , Ryoo In‐Ja , Choo Soo‐Jin , Cho Sung‐Min , Tsukumo Yoshinori , Tomida Akihiro , Shin‐Ya Kazuo , Hwang Yong‐Il , Yoo Ick‐Dong , Park Hae‐Ryong 
Published: October 2007

AbstractGlucose deprivation, a pathophysiological cell condition, causes up‐regulation of GRP78 and induction of etoposide resistance in human cancer cells. The induction of drug resistance can be partly explained by the fact that GRP78 can block activation of caspase‐7 induced by treatment with etoposide. Therefore, downregulating GRP78 expression may be a novel strategy anticancer drug development. Based on that premise, we established a screening program for anticancer agents that exhibit preferential cytotoxic activity for etoposide‐resistant cancer cells under glucose‐deprived conditions. We recently isolated an active compound, AR‐054, from the culture broth of Streptomyces sp., which prevents stress‐induced etoposide resistance in vitro. AR‐054 was identified as piericidin A, a prototypical compound, by ESI‐MS analysis and various NMR spectroscopic methods. Here, we showed that piericidin A suppressed the accumulation of GRP78 protein and was also highly toxic to etoposide‐resistant HT‐29 cells, with IC50 values for colony formation of 6.4 and 7.7 nM under 2‐deoxyglucose supplemented and glucose‐deprived conditions, respectively. Interestingly, piericidin A had no effect under normal growth conditions. Therefore, we suggest that piericidin A prevents up‐regulation of GRP78, and exhibits cytotoxicity in glucose‐deprived HT‐29 cells that are resistant to etoposide. J. Cell. Physiol. 215: 243–250, 2008. © 2007 Wiley‐Liss, Inc.
Evidence that 3‐hydroxy‐3‐methylglutaric acid promotes lipid and protein oxidative damage and reduces the nonenzymatic antioxidant defenses in rat cerebral cortex
Authors: Leipnitz Guilhian , Seminotti Bianca , Haubrich Josué , Dalcin Manuela B. , Dalcin Karina B. , Solano Alexandre , de Bortoli Giorgia , Rosa Rafael B. , Amaral Alexandre U. , Dutra‐Filho Carlos S. , Latini Alexandra , Wajner Moacir 
Published: October 2007

AbstractIn the present work we investigated the in vitro effect of 3‐hydroxy‐3‐methylglutarate (HMG) that accumulates in 3‐hydroxy‐3‐methylglutaryl‐CoA lyase deficiency (HMGLD) on important parameters of oxidative stress in rat cerebral cortex. It was observed that HMG induced lipid peroxidation by significantly increasing chemiluminescence and levels of thiobarbituric acid‐reactive substances (TBA‐RS). This effect was prevented by the antioxidants α‐tocopherol, melatonin, N‐acetylcysteine, and superoxide dismutase plus catalase, suggesting that free radicals were involved in the lipid oxidative damage. On the other hand, HMG did not change TBA‐RS levels in intact or disrupted mitochondrial preparations, indicating that generation of oxidants by this organic acid was dependent on cytosolic mechanisms. HMG also induced protein oxidative damage in cortical supernatants, which was reflected by increased carbonyl content and sulfhydryl oxidation. Furthermore, HMG significantly reduced the nonenzymatic antioxidant defenses total‐radical trapping antioxidant potential, total antioxidant reactivity, and reduced glutathione (GSH) levels in rat cerebral cortex. HMG‐induced GSH reduction was totally blocked by melatonin pretreatment. We also verified that the decrease of GSH levels provoked by HMG in cortical supernatants was not due to a direct oxidative effect of this organic acid, because exposition of commercial GSH and purified membrane protein‐bound thiol groups to HMG in the absence of cortical supernatants did not decrease the reduced sulfhydryl groups. Finally, the activities of the main antioxidant enzymes were not altered by HMG exposure. Our data indicate that oxidative stress elicited in vitro by HMG may possibly contribute at least in part to the pathophysiology of the brain injury in HMGLD. © 2007 Wiley‐Liss, Inc.
Eicosapentaenoic acid stimulates the expression of myelin proteins in rat brain
Authors: Salvati Serafina , Natali Francesco , Attorri Lucilla , Di Benedetto Rita , Leonardi Fabiana , Di Biase Antonella , Ferri Federica , Fortuna Stefano , Lorenzini Paola , Sanchez Massimo , Ricceri Laura , Vitelli Luigi 
Published: October 2007

AbstractWe have previously demonstrated that, in C6 glioma cells, eicosapentaenoic acid (EPA) stimulates the expression of proteolipid protein (PLP) via cAMP‐mediated pathways. In this study, we investigated whether n‐3 polyunsaturated fatty acids can affect myelinogenesis in vivo. A single dose of either EPA or docosahexaenoic acid (DHA) was injected intracerebroventricularly into 2‐day‐old rats, which were then killed after 3 days post‐injection (p.i.). Total RNA was isolated from the medulla, cerebellum, and cortex, and the expression of myelin‐specific mRNAs was analyzed by real‐time PCR. The levels of PLP, myelin basic protein, and myelin oligodendrocyte protein mRNAs increased in nearly all brain regions of DHA‐ and EPA‐treated animals, but the effect was more pronounced in EPA‐treated rats. The enhancement in PLP transcript levels was followed by an increase in PLP translation in EPA‐treated rats. A further indicator of accelerated myelination was the increase in 2′‐3′‐cyclic nucleotide 3′‐phosphodiesterase (CNPase) protein levels. In EPA‐treated rats, the increased expression of myelin genes coincided with a decrease of cAMP‐response element‐binding protein (CREB)‐DNA binding in the cerebellum and cortex (1 hr p.i.). After 16 hr, this effect was still present in the same cerebral regions even though the decrease in EPA‐treated rats was less pronounced than in controls. The down‐regulation of CREB activity was due to a decrease in the levels of CREB phosphorylation. In conclusion, our data suggest that EPA stimulates the expression of specific myelin proteins through decreased CREB phosphorylation. These results corroborate the clinical studies of the n‐3 PUFA beneficial effects on several demyelinating diseases. © 2007 Wiley‐Liss, Inc.