bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atorvastatin delays progression of pancreatic lesions to carcinoma by regulating PI3/AKT signaling in p48Cre/+ LSL‐KrasG12D/+ mice
Authors: Mohammed Altaf , Qian Li , Janakiram Naveena B. , Lightfoot Stan , Steele Vernon E. , Rao Chinthalapally V. 
Published: January 2012

AbstractPancreatic cancer is the one of most common causes of cancer deaths and has the worst prognosis. Clinical observational studies suggest that statins may reduce the risk of pancreatic cancer. The chemopreventive efficacy of the statin atorvastatin (Lipitor®) and the role of the phosphatidyl‐inositol 3‐kinase (PI3/AKT) signaling pathway were evaluated for the progression of pancreatic intraepithelial neoplasms (PanINs) to pancreatic ductal adenocarcinoma (PDAC) in conditional p48Cre/+‐LSL‐KrasG12D/+ transgenic mice. Six‐week‐old male p48Cre/+‐LSL‐KrasG12D/+ (20/group) mice were fed AIN‐76A diets containing 0, 200 and 400 ppm atorvastatin for 35 weeks. At termination, pancreata were evaluated histopathologically for PanINs and PDAC, and for various PI3/AKT signaling markers, and inflammatory cytokines, by immunohistochemistry/immunohistoflourscence, ELISA, Western blotting and/or reverse transcription‐PCR methods. Control diet‐fed mice showed 85% incidence of PDAC; whereas, mice fed with atorvastatin showed PDAC incidence of 65 and 35%, respectively (p < 0.0001). Similarly, significant suppression of PanIN‐3 (22.6%) was observed in mice fed 400 ppm atorvastatin. Importantly, pancreata from atorvastatin‐treated mice were ∼68% free from ductal lesions. Furthermore, pancreas of mice administered with atorvastatin had significantly reduced expressions levels of PCNA, p2X7, p‐ERK, RhoA, cyclin D1, survivin, Akt, pAKT, β‐catenin, cyclin E, cdK2 and caveolin‐1. Also, atorvastatin‐treated mice had shown dose‐dependent suppression of inflammatory cytokines and a significant increase in tunnel‐positive cells, p21 and PARP expression levels in pancreas. Atorvastatin significantly delays the progression of PanIN‐1 and ‐2 lesions to PanIN‐3 and PDAC by modulating PI3/AKT signal molecules in a preclinical model, suggesting potential clinical benefits of statins for high‐risk pancreatic cancer patients.
Heritability of chronic pain in 2195 extended families
Authors: Hocking L.J. ,   Generation Scotland, Morris A.D. , Dominiczak A.F. , Porteous D.J. , Smith B.H. 
Published: January 2012

AbstractChronic pain is pathological, persisting beyond normal tissue healing time. Previous work has suggested ∼50% variation in chronic pain development is heritable. No data are currently available on the heritability of pain categorized using the Chronic Pain Grade (CPG). Furthermore, few existing studies have accounted for potential confounders that may themselves be under genetic control or indeed ‘heritable’ non‐genetic traits. This study aimed to determine the relative contributions of genetic, measured and shared environmental and lifestyle factors to chronic pain. Chronic pain status was determined and CPG measured in participants from Generation Scotland: the Scottish Family Health Study, a large cohort of well‐characterized, extended families from throughout Scotland, UK. Heritability estimates (h
2) for ‘any chronic pain’ and ‘severe’ chronic pain (CPG 3 or 4) were generated using SOLAR software, with and without adjustment for shared household effects and measured covariates age, body mass index, gender, household income, occupation and physical activity. Data were available for 7644 individuals in 2195 extended families. Without adjustment, h
2 for ‘any chronic pain’ was 29% [standard errors (SE) 6%; p < 0.001], and for ‘severe’ chronic pain was 44% (SE 3%; p <0.001). After adjustment, ‘any chronic pain’ h
2 = 16% (SE 7%; p = 0.02) and ‘severe’ chronic pain h
2 = 30% (SE 13%; p = 0.007). Co‐heritability of both traits was 11% (SE 76%). This study supports the use of chronic pain as a phenotype in genetic studies, with adequate correction for confounders to specifically identify genetic risk factors for chronic pain.
Weight loss in obese older adults increases serum sclerostin and impairs hip geometry but both are prevented by exercise training
Authors: Armamento-Villareal Reina , Sadler Corinn , Napoli Nicola , Shah Krupa , Chode Suresh , Sinacore David R , Qualls Clifford , Villareal Dennis T 
Published: January 2012

Abstract
We reported that weight loss induces bone loss which is prevented by exercise training; however, the mechanism for this observation remains unclear. Sclerostin, an inhibitor of bone formation, has been found to increase in states of unloading and may mediate the changes in bone metabolism associated with weight loss and exercise. The objective of the study was to determine the effect of lifestyle intervention in obese older adults on sclerostin levels, and on hip geometry parameters. A total of 107 obese (body mass index [BMI] ≥ 30 kg/m2) older (≥65 years) adults were randomly assigned to control, diet, exercise, and combined diet-exercise for 1 year. Sclerostin levels were measured by ELISA at baseline, 6 months, and 12 months, while hip geometry parameters were obtained from bone mineral density (BMD) images done by dual-energy X-ray absorptiometry using hip structure analysis at baseline and 12 months. Both the diet and diet-exercise groups had significant decreases in body weight (−9.6% and −9.4%, respectively), whereas weight was stable in the exercise and control groups. Sclerostin levels increased significantly and progressively in the diet group (6.6% ± 1.7% and 10.5% ± 1.9% at 6 and 12 months, respectively, all p &lt; 0.05), whereas they were unchanged in the other groups; in particular, they were stable in the diet-exercise group (0.7% ± 1.6% and 0.4% ± 1.7% at 6 and 12 months, respectively, all p = 0.05). Hip geometry parameters showed significant decreases in cross-sectional area, cortical thickness, and BMD; and increases in buckling ratio at the narrow neck, intertrochanter, and femoral shaft. These negative changes on bone geometry were not observed in the diet-exercise group. Significant correlations between changes in sclerostin and changes in certain hip geometry parameters were also observed (p &lt; 0.05). In conclusion, the increase in sclerostin levels with weight loss that was prevented by exercise may partly mediate the negative effects of weight loss on bone metabolism and the osteoprotective effect of exercise training. © 2012 American Society for Bone and Mineral Research.
Sudan III dye strongly induces CYP1A1 mRNA expression in HepG2 cells
Authors: Ohno Marumi , Ikenaka Yoshinori , Ishizuka Mayumi 
Published: January 2012

AbstractSudan dyes possess a high affinity to the aryl hydrocarbon receptor (AHR) and potently induce its target genes, such as cytochrome P450 (CYP) 1A1, through unknown mechanisms. We investigated a detailed event occurring in cells after binding of Sudan dye to AHR in HepG2 cells. Treatment with 10 µM Sudan III caused rapid translocation of AHR into the nucleus and increased expression levels of human CYP1A1 mRNA by approximately 20‐fold after 16 and 24 h. The transactivation was due to the activation of a region located at −1137 to +59 bp from CYP1A1, in particular, four xenobiotic responsive elements (XREs) existing in the region. AHR and the Ah receptor nuclear translocator interacted with XRE sequences in a gel shift assay using nuclear extract from Sudan III‐‐treated HepG2 cells. Moreover, we suggest that constitutive androstane receptor could modify CYP1A1 transactivation by Sudan III. © 2012 Wiley Periodicals, Inc. J Biochem Mol Toxicol 26:16–22 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20408
Src modulates contractile vascular smooth muscle function via regulation of focal adhesions
Authors: Min Jianghong , Reznichenko Maya , Poythress Ransom H. , Gallant Cynthia M. , Vetterkind Susanne , Li Yunping , Morgan Kathleen G. 
Published: January 2012

AbstractSrc is a known regulator of focal adhesion turnover in migrating cells; but, in contrast, Src is generally assumed to play little role in differentiated, contractile vascular smooth muscle (dVSM). The goal of the present study was to determine if Src‐family kinases regulate focal adhesion proteins and how this might affect contractility of non‐proliferative vascular smooth muscle. We demonstrate here, through the use of phosphotyrosine screening, deconvolution microscopy imaging, and differential centrifugation, that the activity of Src family kinases in aorta is regulated by the alpha agonist and vasoconstrictor phenylephrine, and leads to focal adhesion protein phosphorylation and remodeling in dVSM. Furthermore, Src inhibition via morpholino knockdown of Src or by the small molecule inhibitor PP2 prevents phenylephrine‐induced adhesion protein phosphorylation, markedly slows the tissue's ability to contract, and decreases steady state contractile force amplitude. Significant vasoconstrictor‐induced and Src‐dependent phosphorylation of Cas pY‐165, FAK pY‐925, paxillin pY‐118, and Erk1/2 were observed. However, increases in FAK 397 phosphorylation were not seen, demonstrating differences between cells in tissue versus migrating, proliferating cells. We show here that Src, in a cause and effect manner, regulates focal adhesion protein function and, consequently, modulates contractility during the action of a vasoconstrictor. These data point to the possibility that vascular focal adhesion proteins may be useful drug discovery targets for novel therapeutic approaches to cardiovascular disease. J. Cell. Physiol. 227: 3585–3592, 2012. © 2012 Wiley Periodicals, Inc.
TGFβ1 inhibits lymphatic endothelial cell differentiation from mouse embryonic stem cells
Authors: Vittet Daniel , Merdzhanova Galina , Prandini Marie‐Hélène , Feige Jean‐Jacques , Bailly Sabine 
Published: January 2012

AbstractThe lymphatic vasculature is essential for the maintenance of tissue fluid, immune surveillance, and dissemination of metastasis. Recently, several models for lymphatic vascular research and markers specific for lymphatic endothelium have been characterized. Despite these significant achievements, our understanding of the early lymphatic development is still rather limited. The purpose of the study was to further define early lymphatic differentiation regulatory pathways. In the present study, we have developed conditions leading to lymphatic endothelial cell differentiation under both serum‐rich and serum‐free conditions, using the coculture system of Flk‐1‐positive vascular precursors derived from murine embryonic stem (ES) cells grown on an OP9 stromal cell layer. In this work, we also identified Transforming Growth Factor‐β1 (TGFβ1) as a negative regulator of lymphvasculogenesis from ES‐derived vascular progenitors. Finally, we could show that TGFβ1 addition decreases COUP‐TFII and Sox18 mRNA levels, which are two transcription factors known to be involved in early lymphatic endothelial differentiation. Taken together these findings support the concept that manipulating the TGFβ signaling pathway may represent an interesting target to favor lymphatic endothelial cell expansion for cell replacement strategies. J. Cell. Physiol. 227: 3593–3602, 2012. © 2012 Wiley Periodicals, Inc.
Endothelium‐specific overexpression of human vascular endothelial growth factor‐D in mice leads to increased tumor frequency and a reduced lifespan
Authors: Kotimaa Antti A. , Zainana Anna‐Mari , Pulkkinen Eveliina , Huusko Jenni , Heinonen Suvi E. , Kholová Ivana , Stedt Hanna , Lesch Hanna P. , Ylä‐Herttuala Seppo 
Published: January 2012

AbstractBackgroundVascular endothelial growth factors (VEGFs) are central mediators in vascular development and lymphangiogenesis. VEGF‐D contributes to the growth and formation of blood and lymphatic vessels, although its biological role is still somewhat unclear.MethodsTransgenic mice, which express the mature form of human VEGF‐D under endothelium‐specific Tie1 promoter, were produced by the lentiviral perivitelline‐injection method. The mice were followed up to generation F5 and the effect of the transgene was analyzed.ResultsTransgenic mice had a high expression of human (h)VEGF‐D in the endothelium in several tissues, such as kidney, liver, lung and spleen. However, transgenic mice developed tumors in lungs, kidneys, liver, mammary glands and lymph nodes upon aging and their mortality was also increased as a result of other pathological conditions. Hind limb ischemia was surgically induced in these mice and they were analyzed 1, 2 and 3 weeks after the ischemia operation. No significant differences were found in hVEGF‐D mRNA expression, the number of capillaries or tissue repair between ischemic transgenic mice and transgene negative littermates.ConclusionsIt is concluded that targeted unregulated long‐term expression of hVEGF‐D in endothelium may not be useful and reduces the life span of transgenic mice. Copyright © 2012 John Wiley & Sons, Ltd.
The flavonoid monoHER prevents monocrotaline‐induced hepatic sinusoidal injury in rats
Authors: Ezzat Tarek , van den Broek Maartje A.J. , Davies Nathan , Dejong Cornelis H.C. , Bast Aalt , Malagó Massimo , Dhar Dipok K. , Olde Damink Steven W.M. 
Published: January 2012

AbstractBackgroundSinusoidal obstruction syndrome (SOS) occurs in 50–70% of patients after oxaliplatin treatment for hepatic colorectal metastasis. SOS is associated with portal hypertension and is caused by oxidative damage to endothelial cells and matrix metalloproteinase (MMP) induction. We studied the effect of a flavonoid (monoHER) on SOS prevention.MethodsA monocrotaline (MTC) SOS model was used in rats, with pre‐treatment of monoHER. We studied hepatocellular damage and MMP expression. The potential inhibition of oxaliplatin cytotoxicity by monoHER was tested in vitro in colorectal cancer cell lines.ResultsMonoHER ameliorated the increase in portal pressure after MCT (72 hr: 7.3 ± 2.7 mmHg vs. 11.4 ± 3.0 mmHg, P = 0.016 MCT + monoHER vs. MCT, P < 0.01). MonoHER prevented hepatocellular damage (ALT: 48 hr 42.2 ± 3.1 IU/L vs. 253.4 ± 171.7 IU/L, P = 0.034; 72 hr: 46.2 ± 4.3 IU/L vs. 311.9 ± 163.6 IU/L, MCT + monoHER vs. MCT, P < 0.01). The liver damage score was lower in the monoHER group (72 hr: 4.8 ± 3.6 vs. 10.3 ± 0.5, MCT‐monoHER vs. MCT, P < 0.01) associated with less inflammatory cell infiltration. Livers of MCT treated rats had higher expression of MMP‐9 when compared to monoHER pairs at 24 hr (P = 0.016) and 72 hr (P < 0.001). MonoHER had no effect on in vitro proliferation of colorectal cancer cells when used either alone or in combination with oxaliplatin.ConclusionsMonoHER prevented MCT induced portal hypertension and hepatic injury in rats. J. Surg. Oncol. 2012; 106:72–78. © 2012 Wiley Periodicals, Inc.
Brain metastasis from colorectal cancer: Prognostic factors and survival
Authors: Noura Shingo , Ohue Masayuki , Shingai Tatsushi , Fujiwara Ayako , Imada Shinya , Sueda Toshinori , Yamada Terumasa , Fujiwara Yoshiyuki , Ohigashi Hiroaki , Yano Masahiko , Ishikawa Osamu 
Published: January 2012

AbstractBackgroundColorectal cancer (CRC) rarely metastasizes to the brain, and the incidence rate has been reported to be 1–2%. Unfortunately, the median survival for patients with brain metastasis (BM) from CRC is short. In this study, we retrospectively investigated the BM from CRC and examined the prognostic factors.MethodsWe retrospectively analyzed 29 CRC patients who developed BM; the lesions were diagnosed synchronously in 1 patient and metachronously in 28 patients.ResultsAfter BM, the median survival time was 7.4 months. In the groups of patients who underwent surgical resection and radiation therapy, the median survival times were 8.3 and 7.4 months, respectively. The difference between the two groups was not statistically significant. The curability of the therapy for BM, number of BM, number of metastatic organs including the brain, and the CEA level at the time of treatment of the BM were significantly associated with the cancer‐specific survival (P = 0.0044, 0.0229, 0.0019, and 0.0205, respectively).ConclusionsThe prognosis of patients with BM from CRC was associated with the curability of the therapy for BM, number of metastatic organs, and the serum CEA level. The modality of treatment had no significant impact on the outcome. J. Surg. Oncol. 2012; 106:144–148. © 2012 Wiley Periodicals, Inc.
The study of tribological properties of laser‐textured surface of 2024 aluminium alloy under boundary lubrication
Authors: Hu Tianchang , Hu Litian 
Published: January 2012

ABSTRACTThe tribological property of aluminium alloy is critical for its reliable operation in practical applications. In this paper, the tribological performance of laser‐textured 2024 aluminium alloy is studied in unidirectional sliding tests under boundary lubrication. The dimples were produced on the aluminium alloy surface by using a pulse Nd : YAG laser. The topographical microstructures of these laser‐induced textures were characterised by optical and scanning electron microscopy. In comparison with untextured surfaces, a significant improvement in friction behaviour was observed for the textured surfaces. The influences of dimples density on the tribological properties were investigated. Two types of oil with different viscosities were evaluated as lubricants. It was found that the beneficial effects of laser surface texturing are more pronounced at higher speed and load with higher viscosity oil. The optimum dimples density of 8.5% was found to have a lower friction coefficient. On basis of the experimental results, the mechanism of friction reduction and anti‐wear is proposed. Copyright © 2012 John Wiley & Sons, Ltd.
Synthesis and characterisation of HSIBR used as viscosity index improver for lubricants
Authors: Li Wei , Li Yang , Hu Yanming , Wang Yurong 
Published: January 2012

ABSTRACTSelf‐prepared styrene–isoprene–butadiene rubber (SIBR) was anionically synthesised and modified by a hydrogenation reaction. The hydrogenated SIBR (HSIBR) was used as a viscosity index improver in lubricants due to its improved thermal and oxidative resistance. The precursors and corresponding hydrogenated polymers were characterised by size‐exclusion chromatography, Fourier transform infrared, proton nuclear magnetic resonance (1H‐NMR) spectroscopy, differential scanning calorimetry and thermal gravimetric analysis. Moreover, the efficiencies of HSIBR as viscosity index improvers for SAE 5W‐30 multigrade oils (150N HG base oil) were studied. The results confirm that adding 1 wt.% of HSIBR markedly increases the specific viscosity of base oil, increases the viscosity index (119 for base oil) up to a value between 158 and 164 and maintains the shear stability well. Furthermore, the HSIBR‐containing oil possesses a high high‐temperature and high‐shear viscosity without destroying its low‐temperature fluidity. Copyright © 2012 John Wiley & Sons, Ltd.
Perfluorophenyl‐Terpyridine Ruthenium Complex as Monomer for Fast, Efficient, and Mild Metallopolymerizations
Authors: Wild Andreas , Winter Andreas , Hager Martin D. , Görls Helmar , Schubert Ulrich S. 
Published: January 2012

AbstractHerein, the new concept of thiol‐para‐fluorine “click” chemistry is employed for the formation of ruthenium(II) bisterpyridine metallopolymers in a fast and efficient manner. In general, the assembly of comparable metallopolymers requires high temperatures and long reaction times. In contrast to established methods, when utilizing a pentafluorophenyl‐substituted homoleptic RuII bisterpyridine complex, as a monomer, thiol‐functionalized organic spacer units can easily be introduced at low temperatures and in very short reaction times. Furthermore, alternating arrangements of different metal ions (e.g., RuII and FeII) in metallopolymers can be achieved.
Skeletal muscle 1H MRSI before and after prolonged exercise. II. visibility of free carnitine
Authors: Boss Andreas , Kreis Roland , Saillen Pierre , Zehnder Monica , Boesch Chris , Vermathen Peter 
Published: January 2012

AbstractCarnitine (Car) buffers excess acetyl‐CoA through the formation of acetylCar (AcCar). AcCar's acetyl group (AG‐AcCar) gives rise to a peak at 2.13 ppm in 1H MR spectra of skeletal muscle, whereas the trimethylammonium (TMA) groups of both, AcCar and Car, are thought to contribute to the TMA peak at 3.23 ppm. Surprisingly, in previous studies both resonances, AG‐AcCar and TMA, increased after exercise. The aim of this study was to assess if the exercise‐related TMA increase correlated with AcCar production. Magnetic resonance spectroscopic imaging (pulse repetition time/echo time = 1200/35 ms) was performed before and after prolonged exercise in the lower leg and thigh of eight runners and eight cyclists, respectively. TMA and AG‐AcCar increased after exercise (P < 0.001). TMA's increase correlated with the AG‐AcCar increase (R2 = 0.73, P < 0.001, lower leg; R2 = 0.28, P < 0.001, thigh). The correlation of ΔTMA with ΔAG‐AcCar suggests that the TMA increase is due to AcCar formation. As total Car (Car + AcCar) remains unchanged with exercise, these findings suggest that the contribution of free Car to the TMA peak is limited and, therefore, is partly invisible in muscle 1H MR spectra. This indicates that the biochemically relevant cytosolic content of free Car is considerably lower than the overall concentration determined by radioisotopic assays, a potentially important result with respect to regulation of substrate oxidation. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
Suppression of effects of gradient imperfections on imaging with alternate ascending/descending directional navigation
Authors: Park Sung‐Hong , Zhao Tiejun , Kim Jung‐Hwan , Boada Fernando E. , Bae Kyongtae Ty 
Published: January 2012

AbstractAlternate ascending/descending directional navigation (ALADDIN) is a new imaging technique that provides interslice perfusion‐weighted and magnetization transfer (MT) asymmetry images. In this article, we investigated the effects of gradient imperfections on ALADDIN MT asymmetry (MTA) signals. Subtraction artifacts increasing with readout offsets were detectable in ALADDIN MTA images from an agarose phantom but not from a water phantom. Slice‐select offsets had no significant effect on the artifacts in MTA. The artifacts were suppressed by averaging signals over the readout gradient polarities independent of scan parameters. All these results suggested that the subtraction artifacts were induced by readout eddy currents. With suppression of the artifacts, ALADDIN signals in human brain and skeletal muscle varied less with scan conditions. Percent signal changes of MTA in human skeletal muscle (0.51 ± 0.11%, N = 3) were about 30% of those in white matter. The new averaging scheme will allow for more accurate MTA imaging with ALADDIN, especially at off‐center positions. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.