bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNMT3a plays a role in switches between doxorubicin‐induced senescence and apoptosis of colorectal cancer cells
Authors: Zhang Yu , Gao Yanyan , Zhang Guoping , Huang Shuyan , Dong Zhixiong , Kong Chenfei , Su Dongmei , Du Juan , Zhu Shan , Liang Qian , Zhang Jianchao , Lu Jun , Huang Baiqu 
Published: April 2010

AbstractThe DNA‐damaging drug doxorubicin (Dox) induces cell senescence at concentrations significantly lower than those required for induction of apoptosis. At low Dox concentrations, tumor suppressor p53 is activated, which enhances the expression of p21Waf1/Cip1 (p21). At high concentrations, Dox activates p53 leading to apoptosis without enhancing p21 expression. The underlying mechanisms and factors that govern the differential effects of Dox in inducing senescence and apoptosis are unclear. Here, we report that the DNA methyltransferase (DNMT) DNMT3a was upregulated by Dox especially at concentrations that induced apoptosis in HCT116 colorectal cancer cells, and this process was regulated by p53. Meanwhile, p21 expression was significantly upregulated at senescence‐inducing concentrations and kept low on treatment with apoptosis‐inducing concentrations of Dox. The differential expression of DNMT3a and p21 in response to Dox suggests that DNMT3a may be a key factor in switches between Dox‐induced senescence and apoptosis. Moreover, when DNMT3a was silenced, treatment of HCT116 cells with apoptosis‐inducing concentration of Dox increased the percentage of cells undergoing senescence, accompanied by upregulation of p21. Contrarily, senescence‐inducing concentration of Dox promoted apoptosis rate, and p21 expression was repressed. Surprisingly, no changes in DNA methylation status at p21 promoter were detected at either ranges of Dox, although DNMT3a and HDAC1 were recruited to p21 promoter at apoptosis‐inducing Dox concentration, where they were present in the same complex. Overall, these data demonstrate that DNMT3a impacts the expression of p21 and plays a role in determining the Dox‐induced senescence and apoptosis in HCT116 cells.
Capecitabine plus oxaliplatin (XELOX) versus 5‐fluorouracil/leucovorin plus oxaliplatin (FOLFOX‐6) as first‐line treatment for metastatic colorectal cancer
Authors: Ducreux Michel , Bennouna Jaafar , Hebbar Mohamed , Ychou Marc , Lledo Gérard , Conroy Thierry , Adenis Antoine , Faroux Roger , Rebischung Christine , Bergougnoux Loic , Kockler Leila , Douillard Jean‐Yves 
Published: April 2010

AbstractA regimen consisting of 5‐fluorouracil/leucovorin plus oxaliplatin (FOLFOX‐6) is widely used in France in the first‐line treatment of metastatic colorectal cancer (MCRC). The aim of our study was to demonstrate the non‐inferiority of capecitabine plus oxaliplatin (XELOX) versus FOLFOX‐6 for this indication. Patients were randomly assigned to receive XELOX or FOLFOX‐6 for 6 months. The primary endpoint was overall response rate (ORR) in the per‐protocol (PP) population; however, progression‐free and overall survival (OS), time to response and response duration were also assessed. A total of 306 patients were enrolled (XELOX n = 156; FOLFOX‐6 n = 150). ORR was 42 and 46% with XELOX and FOLFOX‐6, respectively, in the PP population. The difference between groups was 4.7%; the upper limit of the unilateral 95% confidence interval (14.4%) was below the non‐inferiority margin of 15%. In the intent‐to‐treat population, median progression‐free survival was 8.8 months with XELOX and 9.3 months with FOLFOX‐6, and median OS was 19.9 and 20.5 months, respectively. XELOX patients had significantly more grade 3/4 thrombocytopenia (12% vs. 5%) and diarrhoea (14% vs. 7%), but significantly less grade 3/4 neutropenia (5% vs. 47%), febrile neutropenia (0% vs. 6%) and neuropathy (11% vs. 26%) than FOLFOX‐6 patients. We conclude that XELOX is non‐inferior in terms of efficacy to FOLFOX‐6 in the first‐line treatment of MCRC, but has a different toxicity profile.
Hyperhomocysteinemia, methylenetetrahydrofolate reductase c.677C>T polymorphism and risk of cancer: Cross‐sectional and prospective studies and meta‐analyses of 75,000 cases and 93,000 controls
Authors: Zacho Jeppe , Yazdanyar Shiva , Bojesen Stig E. , Tybjærg‐Hansen Anne , Nordestgaard Børge G. 
Published: April 2010

AbstractGlobal DNA hypomethylation associates with development of cancer. DNA hypomethylation also associates with hyperhomocysteinemia and MTHFR c.677C>T homozygosity, both of which may associate with increased risk of cancer. We tested the putative association of hyperhomocysteinemia with cancer and the association of the MTHFR c.677TC>T variant with hyperhomocysteinemia and with cancer. We performed a cross‐sectional study of 5,949 Danish general population adults, a prospective study of 9,235 Danish general population adults with up to 60 years of registry surveillance, and meta‐analyses of 231 studies including 74,671 cases and 93,344 controls. Cross‐sectionally, plasma homocysteine levels were 12.9 and 11.6 μmol/L in those with and without cancer (p < 0.0001). However, homocysteine levels increased with age and age‐adjusted odds ratio for any cancer in those with homocysteine levels >12.4 versus < 9.4 μmol/L did not differ from 1.0. In cancer‐free participants, plasma homocysteine levels were 14.7 and 11.7 μmol/L in MTHFR c.677C>T homozygtes and noncarriers (p < 0.0001). Prospectively, hazard ratios for any cancer and for cancer subtypes in MTHFR c.677C>T homozygotes versus noncarriers did not differ from 1.0. However, in meta‐analyses odds ratio for MTHFR c.677C>T homozygotes versus noncarriers were 1.07 (95% CI: 1.01–1.12) for any cancer, 1.77 (1.17–2.68) for esophagus cancer, 1.40 (1.19–1.66) for gastric cancer and 0.85 (0.77–0.94) for colorectal cancer. Increased plasma homocysteine levels are not associated with an increased age‐adjusted risk of any cancer. However, MTHFR c.677C>T homozygosity with lifelong hyperhomocysteinemia and hence hypomethylation associate with increased risk of esophagus and gastric cancer, and with decreased risk of colorectal cancer.
Berberine suppresses neuroinflammatory responses through AMP‐activated protein kinase activation in BV‐2 microglia
Authors: Lu Dah‐Yuu , Tang Chih‐Hsin , Chen Yi‐Hung , Wei I‐Hua 
Published: April 2010

AbstractThe AMPK cascade is a sensor of cellular energy change, which monitors the AMP/ATP ratio to regulate cellular metabolism by restoring ATP levels, but its regulation of neuroinflammation mechanism remains unclear. Berberine, one of the major constituents of Chinese herb Rhizoma coptidis, has been shown to improve several metabolic disorders, such as obesity and type II diabetes. However, the effect of berberine on neuroinflammatory responses in microglia are poorly understood. This study shows that berberine represses proinflammatory responses through AMP‐activated protein kinase (AMPK) activation in BV‐2 microglia. Our findings also demonstrate that berberine significantly down‐regulates LPS‐ or interferon (IFN)‐γ‐induced nitric oxide synthase (iNOS) and cyclo‐oxygenase‐2 (COX‐2) expression in BV‐2 microglia cells. Berberine also inhibited LPS‐ or IFN‐γ‐induced nitric oxide production. In addition, berberine effectively inhibited proinflammatory cytokines such as TNF‐α, IL‐1β, and IL‐6 expression. On the other hand, upon various inflammatory stimulus including LPS and IFN‐γ, berberine suppressed the phosphorylated of ERK but not p38 and JNK in BV‐2 microglia. AMPK activation is catalyzed by upstream kinases such as LKB1 and Ca2+/calmodulin‐dependent protein kinase kinase‐II (CaMKK II). Moreover, berberine induced LKB1 (Ser428), CaMKII (Thr286), and AMPK (Thr172) phosphorylation, but not AMPK (Ser485). Furthermore, the inhibitory effect of berberine on iNOS and COX‐2 expression was abolished by AMPK inhibition via Compound C, an AMPK inhibitor. Berberine‐suppressed ERK phosphorylation was also reversed by Compound C treatment. Our data demonstrate that berberine significantly induces AMPK signaling pathways activation, which is involved in anti‐neuroinflammation. J. Cell. Biochem. 110: 697–705, 2010. © 2010 Wiley‐Liss, Inc.
Smurf control in bone cells
Authors: Xing Lianping , Zhang Ming , Chen Di 
Published: April 2010

AbstractThe homologous to the E6‐assosiated protein carboxyl terminus (HECT) domain E3 ubiquitin ligase Smurf1 is the first E3 ligase to be implicated in regulating bone cell function. The involvement of Smurf1 in multiple signaling pathways and pathological conditions is presently an area of extensive scientific interest. This review highlights recent works exploring Smurf‐regulated biological processes in bone cells and highlights recent discoveries surrounding the regulatory mechanisms modulating its catalytic activity and substrate recognition capability. Moreover, we discuss the relevance of targeting the HECT E3s through the development of small‐molecule inhibitors as an anticancer therapeutic strategy. J. Cell. Biochem. 110: 554–563, 2010. © 2010 Wiley‐Liss, Inc.
Synthesis and characterization of dexamethasone‐conjugated linear polyethylenimine as a gene carrier
Authors: Kim Hyunjung , Bae Yun Mi , Kim Hyun Ah , Hyun Hyesun , Yu Gwang Sig , Choi Joon Sig , Lee Minhyung 
Published: April 2010

AbstractLinear polyethylenimine (25 kDa, LPEI25k) has been shown to be an effective non‐viral gene carrier with higher transfection and lower toxicity than branched polyethylenimine (BPEI) of comparable molecular weight. In this study, dexamethasone was conjugated to LPEI25k to improve the efficiency of gene delivery. Dexamethasone is a synthetic glucocorticoid receptor ligand. Dexamethasone‐conjugated LPEI25k (LPEI–Dexa) was evaluated as a gene carrier in various cells. Gel retardation assays showed that LPEI–Dexa completely retarded plasmid DNA (pDNA) at a 0.75:1 weight ratio (LPEI/pDNA). LPEI–Dexa had the highest transfection efficiency at a 2:1 weight ratio (LPEI–Dexa/DNA). At this ratio, the size of the LPEI–Dexa/pDNA complex was approximately 125 nm and the zeta potential was 35 mV. LPEI–Dexa had higher transfection efficiency than LPEI and Lipofectamine 2000. In addition, the cytotoxicity of LPEI–Dexa was much lower than that of BPEI (25 kDa, BPEI25k). In conclusion, LPEI–Dexa has a high transfection efficiency and low toxicity and can therefore be used for non‐viral gene delivery. J. Cell. Biochem. 110: 743–751, 2010. © 2010 Wiley‐Liss, Inc.
Noradrenaline stimulates ATP release from DRG neurons by targeting β3 adrenoceptors as a factor of neuropathic pain
Authors: Kanno Takeshi , Yaguchi Takahiro , Nishizaki Tomoyuki 
Published: April 2010

AbstractNoradrenaline (NA), released in association with sympathetic nerve sprouting into the dorsal root ganglion (DRG) after peripheral nerve injury, may enhance neuropathic pain. ATP serves as a pain mediator; however, NA‐regulated ATP mobilizations in the DRG is far from understanding. In the present study, we analyzed ATP mobilizations in acutely dissociated rat DRG neurons by recording single‐channel currents through P2X receptor channels as an ATP biosensor in an outside‐out patch‐clamp configuration and by monitoring real‐time enzymatic NADPH fluorescent imaging, and examined the role for β3 adrenoceptors in allodynia using an in vivo rat model. We show here that NA stimulates ATP release from DRG neurons as mediated via β3 adrenoceptors linked to Gs protein involving PKA activation, to cause allodynia. This represents a fresh regulatory pathway for neuropathic pain relevant to noradrenergic transmission in the DRG. J. Cell. Physiol. 224: 345–351, 2010. © 2010 Wiley‐Liss, Inc.
Dysregulated calcium homeostasis and oxidative stress in chronic myeloid leukemia (CML) cells
Authors: Ciarcia Roberto , d'Angelo Danila , Pacilio Carmen , Pagnini David , Galdiero Massimiliano , Fiorito Filomena , Damiano Sara , Mattioli Eliseo , Lucchetti Chiara , Florio Salvatore , Giordano Antonio 
Published: April 2010

AbstractChronic myeloid leukemia (CML) is a hematopoietic stem cell disorder caused by the oncogenic activity of the Bcr‐Abl protein, a deregulated tyrosine kinase. Calcium may act directly on cellular enzymes and in conjunction with other cellular metabolites, such as cyclic nucleotides, to regulate cell functions. Alteration in the ionized calcium concentration in the cytosol has been implicated in the initiation of secretion, contraction, and cell proliferation as well as the production of reactive oxygen species (ROS) has been correlates with normal cell proliferation through activation of growth‐related signaling pathways. In this study we evaluated in peripheral blood leukocytes from CML patients the role of the balance between intracellular calcium and oxidative stress in CML disease in order to identify possible therapeutic targets in patients affected by this pathology. Our results demonstrated that peripheral blood mononuclear cells derived from CML patients displayed decreased intracellular calcium [Ca2+]i fluxes both after InsP3 as well as ATP and ionomycin (IONO) administration. CML cells showed lower levels of superoxide dismutase (SOD) activity and significantly higher malondialdehyde levels (MDA) than peripheral blood mononuclear cells derived from control patients. Finally we showed that resveratrol is able to down‐regulate InsP3 and ATP effects on intracellular calcium [Ca2+]i fluxes as well as the effects of ATP and IONO on oxidative stress in CML cells. J. Cell. Physiol. 224: 443–453, 2010. © 2010 Wiley‐Liss, Inc.
Role of proteoglycans and glycosaminoglycans in the pathogenesis of Alzheimer's disease and related disorders: Amyloidogenesis and therapeutic strategies—A review
Authors: Ariga Toshio , Miyatake Tadashi , Yu Robert K. 
Published: April 2010

AbstractThe extracellular accumulation of amyloid β proteins (Aβs) in neuritic plaques is one of the hallmarks of Alzheimer's disease (AD). The binding of Aβs to extracellular membranes (ECMs) is a critical step in developing AD. Aβs bind to many biomolecules, including lipids, proteins, and proteoglycans (PGs). PGs play several roles in amyloid formation, including promoting the aggregation of Aβs into insoluble amyloid fibrils, which contributes to the increased neurotoxicity of Aβs. Although Aβs readily self‐aggregate to form amyloid fibrils in vitro, their binding to PGs and heparin enhances amyloid aggregation and fibril formation. The sulfate moiety in glycosaminoglycans (GAGs), the carbohydrate portion of PGs, is necessary for the formation of amyloid fibrils; no fibrils are observed in the presence of hyaluronic acid (HA), a nonsulfated GAG. PGs and Aβs are known to colocalize in senile plaques (SPs) and neurofibrillary tangles (NFTs) in the AD brain. The binding site of PGs to Aβs has been identified in the 13–16‐amino‐acid region (His‐His‐Gln‐Lys) of Aβs and represents a unique target site for inhibition of amyloid fibril formation; His13 in particular is an important residue critical for interaction with GAGs. The sulfate moieties of GAGs play a critical role in the binding to Aβs and enhance Aβ fibril formation. Low‐molecular‐weight heparins (LMWHs) can reverse the process of amyloidosis to inhibit fibril formation by blocking the formation of β‐plated structures, suggesting a possible therapeutic approach using LMWHs to interfere with the interaction between PGs and Aβs and to arrest or prevent amyloidogenesis. © 2010 Wiley‐Liss, Inc.
The inhibitory neurotransmitter glycine modulates macrophage activity by activation of neutral amino acid transporters
Authors: Carmans Sofie , Hendriks Jerome J.A. , Thewissen Kristof , Van den Eynden Jimmy , Stinissen Piet , Rigo Jean‐Michel , Hellings Niels 
Published: April 2010

AbstractGlycine, an important inhibitory neurotransmitter in the mammalian central nervous system (CNS), has been shown to modulate peripheral immune cell responses. In that respect, glycine levels are increased in several neuroinflammatory disorders, such as amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). In this study, we show that glycine modulates macrophage effector functions implicated in CNS inflammation and in other, related inflammatory conditions. We demonstrate that glycine does not affect the production of reactive oxygen species but stimulates myelin phagocytosis and the production of the proinflammatory mediators nitric oxide (NO) and tumor necrosis factor (TNF)‐α by rat macrophages. These effects of glycine are not mediated by the glycine receptor (GlyR) or by glycine transporters (GlyTs), as neither the GlyR antagonist strychnine nor the antagonist of GlyT1 (ALX5407) reverses the observed effects. In contrast, 2‐aminoisobutyric acid, a substrate of neutral amino acid transporters (NAATs), inhibits the glycine‐mediated enhancement of myelin phagocytosis as well as of NO and TNF‐α production. In conclusion, our findings demonstrate that glycine modulates macrophage function through activation of NAATs. Glycine may thereby influence immunological processes in inflammatory diseases involving macrophage activation and demyelination, including MS and related conditions associated with altered glycine levels. © 2010 Wiley‐Liss, Inc.
Preferential inhibition by antidiarrheic 2‐methoxy‐4‐methylphenol of Ca2+ influx across acquired N‐methyl‐D‐aspartate receptor channels composed of NR1/NR2B subunit assembly
Authors: Nakamichi Noritaka , Fukumori Ryo , Takarada Takeshi , Kambe Yuki , Yamamoto Tomomi , Matsushima Nobuyuki , Moriguchi Nobuaki , Yoneda Yukio 
Published: April 2010

AbstractIn our previous studies, particular phenolic ingredients, such as 2‐methoxy‐4‐methylphenol (2M4MP), of the antidiarrheic drug wood creosote significantly prevented cell death by both hydrogen peroxide and glutamate in cultured rat hippocampal neurons. In this study, we further evaluated the pharmacological properties of 2M4MP on Ca2+ influx across native and acquired N‐methyl‐D‐aspartate (NMDA) receptor (NMDAR) channels. The addition of 2M4MP significantly prevented the loss of cellular viability and the increase in intracellular free Ca2+ levels as determined by Fluo‐3 in cultured rat hippocampal neurons briefly exposed to NMDA. Brief exposure to NMDA also led to a marked increase in mitochondrial free Ca2+ levels determined by Rhod‐2, in addition to intracellular free Ca2+ levels, in HEK293 cells expressing either NR1/NR2A or NR1/NR2B subunit channels. The further addition of the general NMDAR channel blocker dizocilpine similarly inhibited the increase of intracellular Ca2+ levels by NMDA in both types of acquired NMDAR channels, whereas the NR2B subunit selective antagonist ifenprodil drastically inhibited the increase by NMDA in HEK293 cells expressing NR1/NR2B, but not NR1/NR2A, subunits. Similarly, 2M4MP significantly and selectively inhibited the NMDA‐induced influx of Ca2+ across acquired NR1/NR2B channels in a concentration‐dependent manner. Moreover, prior daily oral administration of 2M4MP significantly reduced the infarct volume in the ipsilateral cerebral hemisphere in rats with middle cerebral artery occlusion 1 day after reperfusion. These results suggest that 2M4MP may protect neurons from excitotoxicity through preferential inhibition of Ca2+ influx across NMDAR channels composed of NR1/NR2B subunits. © 2010 Wiley‐Liss, Inc.
Morphometric and anthropometric analysis of Killian's triangle
Authors: Anagiotos Andreas , Preuss Simon Florian , Koebke Juergen 
Published: April 2010

AbstractObjectives/Hypothesis:To determine the prevalence and the morphometric characteristics of Killian's triangle and to examine their relationship with the anthropometric features of the person.Study Design:Prospective.Methods:The hypopharyngeal wall was examined on 47 human cadavers. After a standardized method of dissection, the muscular structures of the hypopharyngeal wall were demonstrated and the existence or absence of Killian's triangle was determined. The triangle was examined in regard to its morphometric characteristics. In addition, anthropometric examinations of the whole body and of the head and neck regions on these cadavers were done, and the results were compared with the features of Killian's dehiscence.Results:A triangle of Killian was present on 60% (9/15) of the males and on 34% (11/32) of the females. The mean height for the males was 7 mm and for the females 4 mm, and the width was on average 16 mm and 12 mm, respectively. The dimensions of the triangle were correlated significantly with the dimensions of the body and with the length and the descensus of the larynx.Conclusions:The frequency and the dimensions of Killian's triangle appear to be greater in males than in females. Furthermore, the morphometric characteristics of the dehiscence show a correlation with the anthropometric features of the person. These findings can be an explanation for the higher incidence of Zenker's diverticulum with men and for the geographical differences of the diverticulum's frequency. Laryngoscope, 2010
Rheological study of solidified lubricant oils under very high pressure by observing microsphere deformation and viscosity prediction
Authors: Nakamura Yuichi , Takimoto Akira , Matsui Masahito 
Published: April 2010

AbstractThe rheological properties of solidified lubricant oils under pressure were evaluated by observing large plastic deformation of metal microspheres, occurring due to non‐hydrostatic pressurisation in the oils when using a diamond‐anvil cell pressure‐generating apparatus. Defining the solidification pressure as the onset pressure of plastic deformation of aluminum sphere obtained solidification pressures for traction oils were about 0.5 GPa, whereas those for mineral and synthetic oils ranged from 1.2 to 2 GPa. By substituting the solidification pressures and pressure–viscosity coefficients in the Barus equation, viscosities at the solidification pressure were obtained. The values were different for each oil and were within the order of 106–108 Pas. Based on several assumptions, shear stresses of the solidified oils could be estimated up to 5 GPa from the deformed Cu spheres. The shear stresses for a traction oil were almost equal to the mean shear stress obtained from a traction test between 1.0 and 1.7 GPa. Copyright © 2010 John Wiley & Sons, Ltd.
Experimental measuring procedure for the friction torque in rolling bearings
Authors: Cousseau Tiago , Graça Beatriz , Campos Armando , Seabra Jorge 
Published: April 2010

AbstractThe reduction of the power loss generated in mechanical transmissions and the use of low friction biodegradable lubricants has been attracting considerable attention in recent times. Therefore, it is necessary to develop methods to test and evaluate the performance of such lubricants and compare them with conventional ones.In this sense, a Four‐Ball Machine was modified allowing the test of rolling bearings. A 51107 thrust ball bearing was used to test two different greases and the corresponding base oils. Friction torque and operating temperatures were continuously monitored to quantify the power loss and the heat evacuation for each lubricant tested. Copyright © 2010 John Wiley & Sons, Ltd.