bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of treatment approach on maternal and neonatal outcome in pregnant opioid‐maintained women
Authors: Metz Verena , Jagsch Reinhold , Ebner Nina , Würzl Johanna , Pribasnig Anna , Aschauer Constantin , Fischer Gabriele 
Published: August 2011

ABSTRACTObjectiveThe objective of this study is to compare maternal and neonatal outcome of opioid‐dependent women maintained on buprenorphine or methadone throughout pregnancy in a randomized double‐blind double‐dummy clinical trial (CT) with a comparison group undergoing a structured standard protocol (SP) at the Medical University of Vienna, Austria.MethodsOne hundred and fourteen subjects were included in the analysis, with 77 in SP (n = 51 methadone, n = 26 buprenorphine), and 37 in CT (n = 19 methadone, n = 18 buprenorphine), comparing maternal concomitant consumption during third trimester, demographic birth data, duration of treatment for neonatal abstinence syndrome (NAS), morphine dose for NAS treatment and length of hospital stay (LOS).ResultsBoth study groups yielded healthy neonates with no significant demographic differences and equivalently low rates of positive maternal urine toxicologies. However, NAS parameters were significantly better in CT regarding total medication dose administered to neonates (p = 0.014) and LOS (p = 0.015). Superior results were achieved in buprenorphine compared with methadone‐exposed neonates regarding gestational age at birth (p = 0.003), birth weight (p = 0.011), total morphine dose administered (p = 0.008), NAS treatment duration (p = 0.008) and LOS (p = 0.001).ConclusionsComparably favorable outcome for mothers and infants and efficacy and safety of opioid medications were shown in both treatment approaches. Neonatal care could benefit from transferring successful CT procedures into clinical practice. Copyright © 2011 John Wiley & Sons, Ltd.
The antitumor effect of a novel angiogenesis inhibitor (an octahydronaphthalene derivative) targeting both VEGF receptor and NF‐κB pathway
Authors: Watari Kosuke , Nakamura Mamiyo , Fukunaga Yuichi , Furuno Ayana , Shibata Tomohiro , Kawahara Akihiko , Hosoi Fumihito , Kuwano Takashi , Kuwano Michihiko , Ono Mayumi 
Published: August 2011

AbstractDevelopment of a novel type of angiogenesis inhibitor will be essential for further improvement of therapeutics against cancer patients. We examined whether an octahydronaphthalene derivative, AMF‐26, which was screened as an inhibitor of intercellular adhesion molecule‐1 (ICAM‐1) production stimulated by inflammatory stimuli in vascular endothelial cells, could block angiogenesis in response to vascular endothelial growth factor (VEGF) and/or inflammatory cytokines. Low dose AMF‐26 effectively inhibited the tumor necrosis factor‐α (TNF‐α)‐ or the interleukin‐1β (IL‐1β)‐induced production of ICAM‐1 in human umbilical vascular endothelial cells (HUVECs). We found that the TNF‐α‐induced phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B‐cells inhibitor, alpha (IκBα) and nuclear translocation of p65 were impaired by AMF‐26 in both endothelial cells and cancer cells. AMF‐26 was found to inhibit the phosphorylation of VEGF receptor 1 (VEGFR1), VEGFR2 and the downstream signaling molecules Akt, extracellular signal‐regulated kinase (ERK)1/2 stimulated by VEGF in HUVECs. Therefore, the VEGF‐induced proliferation, migration and tube formation of vascular endothelial cells was highly susceptible to inhibition by AMF‐26. Oral administration of AMF‐26 significantly blocked VEGF‐ or IL‐1β‐induced angiogenesis in the mouse cornea, and also tumor angiogenesis and growth. Together, our results indicate that AMF‐26 inhibits angiogenesis through suppression of both VEGFR1/2 and nuclear factor‐κB (NF‐κB) signaling pathways when stimulated by VEGF or inflammatory cytokines. AMF‐26 could be a promising novel candidate drug for cancer treatments.
Cavitand‐Based Coordination Cages: Achievements and Current Challenges
Authors: Pinalli Roberta , Boccini Francesca , Dalcanale Enrico 
Published: August 2011

AbstractThe research results obtained in the self‐assembly of cavitand‐based coordination cages are presented. Cavitands are ideal multidentate ligands for the creation of coordination cages due to their structural rigidity, concave structure, and great versatility in terms of synthetic modularity. The introduction of the ligand moieties on the resorcinarene building block proceeds at the upper rim of the cavity, to take full advantage of the structural rigidity of the cavitand scaffold. Two different synthetic strategies are employed for the formation of multidentate cavitand ligands: (a) functionalization at the apical positions and (b) introduction of the ligands as bridging units. The key features to control the cage self‐assembly process emerging from this overview are the preorganization, for the cavitands, and kinetic versus thermodynamic stability of the resulting complexes, for the connecting metal. The versatility of this class of coordination cages is demonstrated by the formation of their heterotopic and heteronuclear versions, as well as their self‐assembly on gold and silicon surfaces. Desymmetrization of the cages is appealing because of the resulting differentiation of the inner cavities in terms of shape and interactivity, while surface self‐assembly represents an important opportunity to expand the application range of these objects.
The pathophysiology of early-stage chronic kidney disease–mineral bone disorder (CKD-MBD) and response to phosphate binders in the rat
Authors: Moe Sharon M , Radcliffe J Scott , White Kenneth E , Gattone Vincent H , Seifert Mark F , Chen Xianming , Aldridge Blaire , Chen Neal X 
Published: August 2011

Abstract
Chronic kidney disease–mineral bone disorder (CKD-MBD) is a systemic disorder that describes the complex bone and mineral abnormalities that occur in CKD. To understand the pathophysiology of CKD-MBD and determine whether the early use of phosphate binders would alter this physiology, we used a naturally occurring, slowly progressive model of CKD-MBD, the Cy/+ rat. Male Cy/+ rats were compared with their normal littermates at 20 weeks of age after 1 week of no phosphate binder, calcium carbonate, or sevelamer carbonate. The Cy/+ rat had renal function that was 50% of that of normal littermates, elevated parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23), decreased 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels, but normal calcium and phosphorus levels. There was a significant positive correlation of blood FGF23 and phosphorus levels and blood FGF23 and urine phosphorus levels. There was an inverse correlation between FGF23 and calcium levels. mRNA from the kidney demonstrated 50% reduction in klotho and Npt2a expression but no difference in CYP27B1. In the intestine, CKD animals had reduced active phosphate absorption in the jejunum using modified Ussing chambers and a reduction in Npt2b expression throughout the small intestine compared with normal littermates. In bone, mRNA expression of FGF23 was reduced (driven by lowering with phosphate binders), and TRAP expression was increased in CKD. By histology, there was increased osteoclast activity and number, and there were reductions in some measures of femoral neck mechanical strength. One week of phosphate binders reduced intestinal phosphate flux, serum phosphorus levels, and urinary phosphate excretion. These results demonstrate marked abnormalities in kidney, intestine, and bone in early CKD-MBD. While phosphate binders were effective in lowering urine phosphorus, they had little effect on end organs after 1 week of administration. © 2011 American Society for Bone and Mineral Research
The transcriptome of fracture healing defines mechanisms of coordination of skeletal and vascular development during endochondral bone formation
Authors: Grimes Rachel , Jepsen Karl J , Fitch Jennifer L , Einhorn Thomas A , Gerstenfeld Louis C 
Published: August 2011

Abstract
Fractures initiate one round of endochondral bone formation in which callus cells differentiate in a synchronous manner that temporally phenocopies the spatial variation of endochondral development of a growth plate. During fracture healing C57BL/6J (B6) mice initiate chondrogenesis earlier and develop more cartilage than bone, whereas C3H/HeJ (C3H) mice initiate osteogenesis earlier and develop more bone than cartilage. Comparison of the transcriptomes of fracture healing in these strains of mice identified the genes that showed differences in timing and quantitative expression and encode for the variations in endochondral bone development of the two mouse strains. The complement of strain-dependent differences in gene expression was specifically associated with ontologies related to both skeletal and vascular formation. Moreover, the differences in gene expression associated with vascular tissue formation during fracture healing were correlated with the underlying differences in development and function of the cardiovascular systems of these two strains of mice. Significant differences in gene expression associated with bone morphogenetic protein/transforming growth factor β (BMP/TGF-β) signal-transduction pathways were identified between the two strains, and a network of differentially expressed genes specific to the MAP kinase cascade was further defined as a subset of the genes of the BMP/TGF-β pathways. Other signal-transduction pathways that showed significant strain-specific differences in gene expression included the RXR/PPAR and G protein–related pathways. These data identify how bone and vascular regeneration are coordinated through expression of common sets of transcription and morphogenetic factors and suggest that there is heritable linkage between vascular and skeletal tissue development during postnatal regeneration. © 2011 American Society for Bone and Mineral Research
Exact and efficient calculation of lagrange multipliers in biological polymers with constrained bond lengths and bond angles: Proteins and nucleic acids as example cases
Authors: García‐Risueño Pablo , Echenique Pablo , Alonso J. L. 
Published: August 2011

AbstractTo accelerate molecular dynamics simulations, it is common to impose holonomic constraints on the hardest degrees of freedom. In this way, the time step used to integrate the equations of motion can be increased, thereby allowing longer total simulation times. The imposition of such constraints results in an aditional set of Nc equations (the equations of constraint) and unknowns (their associated Lagrange multipliers), whose solution is closely related to any algorithm implementing the constraints in Euclidean coordinates. In this work, it is shown that, due to the essentially linear structure of typical biological polymers the algebraic equations that need to be solved involve a matrix which is not only sparse, but also banded if the constraints are indexed in a skilful way. This allows the Lagrange multipliers to be obtained through a noniterative procedure, which can be considered exact up to machine precision, and which takes O(Nc) operations, instead of the usual O(N) for generic molecular systems. We develop the formalism, and describe the appropriate indexing for a number of model molecules. Finally, we provide a numerical example of the technique in a series of polyalanine peptides of different lengths. Although a use of the Lagrange multipliers without any modification in the solution of the underlying ordinary differential equations yields unstable integration algorithms, the central role of these quantities makes their efficient calculation useful for the improvement of methods that correctly enforce the exact satisfaction of the constraints at each time step. We provide several examples of this. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Bond indices in solids: Extended analytical model
Authors: Ponec Robert 
Published: August 2011

AbstractThe analytical model suggested some time ago for the calculation of bond indices in infinite periodical structures was reconsidered and extended so as to provide not only realistic estimate of the extent of electron sharing localized among individual pairs of the atoms in the lattice but also to detect the eventual presence of multicenter bonding in metallic solids. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Beneficial effects of fenofibrate in retinal pigment epithelium by the modulation of stress and survival signaling under diabetic conditions
Authors: Miranda Soledad , González‐Rodríguez Águeda , García‐Ramírez Marta , Revuelta‐Cervantes Jesús , Hernández Cristina , Simó Rafael , Valverde Ángela M. 
Published: August 2011

AbstractIn this study, we found an imbalance between stress‐mediated and survival signaling and elevated apoptotic markers in retinal pigment epithelium (RPE) from diabetic patients. Since fenofibric acid (FA) treatment reduces the progression of diabetic retinopathy (DR), we investigated the effect of hyperglycemia and hypoxia, two components of the diabetic milieu, on stress, apoptosis, and survival pathways in ARPE‐19 cells (immortalized human RPE cell line) and whether FA is able to prevent the deleterious effects induced by these conditions. ARPE‐19 cells cultured in high‐glucose (HG) medium or under hypoxia (1% oxygen)‐induced phosphorylation of the stress‐activated kinases JNK and p38 MAPK. This effect was increased by the combination of both conditions. Likewise, hyperglycemia and hypoxia triggered the phosphorylation of the endoplasmic reticulum (ER) stress markers PERK and eIF2α and the induction of the pro‐apoptotic transcription factor CHOP. Under these experimental conditions, reactive oxygen species (ROS) were elevated and the integrity of tight junctions was disrupted. Conversely, ARPE‐19 cells treated with FA were protected against these deleterious effects induced by hyperglycemia and hypoxia. FA increased insulin‐like growth factor I receptor (IGF‐IR)‐mediated survival signaling in cells cultured under hyperglycemia and hypoxia, thereby suppressing caspase‐3 activation and down‐regulation of BclxL. Moreover, FA increased LC3‐II, an autophagy marker. In conclusion, our results demonstrated that FA elicits a dual protective effect in RPE by down‐regulation of stress‐mediated signaling and induction of autophagy and survival pathways. These molecular mechanisms could be involved in the beneficial effects of fenofibrate reported in clinical trials. J. Cell. Physiol. 227: 2352–2362, 2012. © 2011 Wiley Periodicals, Inc.
Proliferation of rat small hepatocytes requires follistatin expression
Authors: Ooe Hidekazu , Chen Qijie , Kon Junko , Sasaki Kazunori , Miyoshi Hiroyuki , Ichinohe Norihisa , Tanimizu Naoki , Mitaka Toshihiro 
Published: August 2011

AbstractSmall hepatocytes (SHs) are a subpopulation of hepatocytes that have high growth potential in culture and can differentiate into mature hepatocytes (MHs). The activin (Act)/follistatin (Fst) system critically contributes to homeostasis of cell growth in the normal liver. ActA and ActB consist of two disulfide‐linked Inhibin (Inh)β subunits, InhβA and InhβB, respectively. Fst binds to Act and blocks its bioactivity. In the present study we carried out the experiments to clarify how Fst regulates the proliferation of SHs. The gene expression was analyzed using DNA microarray analysis, reverse transcription‐polymerase chain reaction (RT‐PCR) and real‐time PCR, and protein expression was examined by western blots, immunocytochemistry, and enzyme‐linked immunosorbent assay. RT‐PCR showed that Fst expression was high in SHs and low in MHs. Although the ActA expression was opposite to that of Fst, ActB expression was high in SHs and low in MHs and increased with time in culture. Fst protein was detected in the cytoplasm of SHs and secreted into the culture medium. ActB protein was also secreted into the medium. Although the exogenous administration of ActA and ActB apparently suppressed the proliferation of SHs, apoptosis of SHs was not induced by treatment with ActA or ActB. On the other hand, Fst treatment did not affect the colony formation of SHs but prevented the inhibitory effect of ActA. Neutralization by the anti‐Fst antibody resulted in the suppression of DNA synthesis in SHs, and small hairpin RNA against Fst suppressed the expansion of SH colonies. In conclusion, Fst expression is necessary for the proliferation of SHs. J. Cell. Physiol. 227: 2363–2370, 2012. © 2011 Wiley Periodicals, Inc.
Growth inhibition of human hepatocellular carcinoma cells by overexpression of G‐protein‐coupled receptor kinase 2
Authors: Wei Zhengyu , Hurtt Reginald , Ciccarelli Michele , Koch Walter J. , Doria Cataldo 
Published: August 2011

AbstractHepatocellular carcinoma (HCC) is one of the deadliest forms of human liver cancer and does not respond well to conventional therapies. Novel effective treatments are urgently in need. G‐protein‐coupled kinase 2 (GRK2) is unique serine/threonine kinase that involves in many signaling pathways and regulates various essential cellular processes. Altered levels of GRK2 have been linked with several human diseases including cancer. In this study, we investigated a novel approach for HCC treatment by inducing overexpression of GRK2 in human HCC cells. We found that overexpression of GRK2 through recombinant adenovirus transduction inhibits the growth of human HCC cells. BrdU incorporation assay showed that the growth inhibition caused by elevated GRK2 level was due to reduced cell proliferation but not apoptosis. To examine the anti‐proliferative function of increased GRK2 level, we performed cell cycle analysis using propidium iodide staining. We found that the proliferation suppression was associated with G2/M phase cell cycle arrest by the wild‐type GRK2 but not its kinase‐dead K220R mutant. Furthermore, increased levels of wild‐type GRK2 induced upregulation of phosphor‐Ser15 p53 and cyclin B1 in a dose‐dependent manner. Our data indicate that the anti‐proliferative function of elevated GRK2 is associated with delayed cell cycle progression and is GRK2 kinase activity‐dependent. Enforced expression of GRK2 in human HCC by molecular delivery may offer a potential therapeutic approach for the treatment of human liver cancer. J. Cell. Physiol. 227: 2371–2377, 2012. © 2011 Wiley Periodicals, Inc.
PTHrP(1‐34)‐mediated repression of the PHEX gene in osteoblastic cells involves the transcriptional repressor E4BP4
Authors: Pellicelli Martin , Taheri Maryam , St‐Louis Mathieu , Bériault Véronique , Desgroseillers Luc , Boileau Guy , Moreau Alain 
Published: August 2011

AbstractPHosphate‐regulating gene with homology to Endopeptidase on the X chromosome (PHEX) has been identified as the gene mutated in X‐linked hypophosphatemia (XLH) syndrome, the most prevalent form of rickets in humans. The predominant expression of PHEX in bones and teeth, and the defective mineralization of these tissues in XLH patients indicate that PHEX is an important regulator of mineralization. Parathyroid hormone (PTH) and PTH‐related protein (PTHrP) are known to regulate the expression of numerous genes in osteoblastic cells through activation of the protein kinase A pathway, including repression of PHEX. PTH also activates the transcriptional repressor E4BP4 through the same pathway, suggesting that PTH or PTHrP‐mediated repression of PHEX expression could involve E4BP4. To evaluate this possibility, we treated UMR‐106 osteoblastic cells with PTHrP(1‐34), and used RT‐PCR and immunoblotting to analyze PHEX and E4BP4 expression. E4BP4 mRNA and protein levels were rapidly increased in cells treated with PTHrP(1‐34), with a concomitant decrease in PHEX expression. This downregulation of PHEX could be reproduced by overexpression of E4BP4. Moreover, PTHrP(1‐34)‐mediated PHEX repression was blocked when cells were transfected with a siRNA targeting E4BP4 mRNA. Finally, DNA pull‐down and luciferase assays showed that two E4BP4 response elements located in PHEX promoter were functional. These results underline the important role of E4BP4 in osteoblastic cells and further define the repression mechanism of PHEX gene by PTHrP(1‐34). J. Cell. Physiol. 227: 2378–2387, 2012. © 2011 Wiley Periodicals, Inc.
Diverse effects of type II collagen on osteogenic and adipogenic differentiation of mesenchymal stem cells
Authors: Chiu Li‐Hsuan , Yeh Tien‐Shun , Huang Huei‐Mei , Leu Sy‐Jye , Yang Charng‐Bin , Tsai Yu‐Hui 
Published: August 2011

AbstractType II collagen is known to modulate chondrogenesis of mesenchymal stem cells (MSCs). In this study, MSCs from human bone marrow aspirates were used to study the modulating effects of type II collagen on MSC differentiation during the early stages of osteogenesis and adipogenesis. With osteogenic induction, MSCs cultured on the type II collagen‐coated surface showed an enhanced calcium deposition level with increasing mRNA expressions of RUNX2, osteocalcin, and alkaline phosphatase. A synthetic integrin binding peptide, which specifically interacts with the I‐domain of α1β1/α2β1 integrins significantly blocks the mineralization‐enhancing effect of type II collagen. MSCs attached on the type II collagen‐coated plates exhibited expanded cell morphology with increasing spreading area, and the pretreatment of cells with integrin α1β1 or α2β1‐blocking antibody reduced the effect. The phosphorylation levels of FAK, ERK, and JNK significantly increased in the MSCs that attached on the type II collagen‐coated plates. On the contrary, the mineralization‐enhancing effect of type II collagen was diminished by JNK and MEK inhibitors. Furthermore, type II collagen blocked the adipogenic differentiation of MSCs, and this effect is rescued by JNK and MEK inhibitors. In conclusion, type II collagen facilitates osteogenesis and suppresses adipogenesis during early stage MSC differentiation. Such effects are integrin binding‐mediated and conducted through FAK–JNK and/or FAK–ERK signaling cascades. These results inspire a novel strategy encompassing type II collagen in bone tissue engineering. J. Cell. Physiol. 227: 2412–2420, 2012. © 2011 Wiley Periodicals, Inc.
STAT5 isoforms regulate colorectal cancer cell apoptosis via reduction of mitochondrial membrane potential and generation of reactive oxygen species
Authors: Du Wan , Wang Ying‐Chao , Hong Jie , Su Wen‐Yu , Lin Yan‐Wei , Lu Rong , Xiong Hua , Fang Jing‐Yuan 
Published: August 2011

AbstractAlthough the two isoforms of signal transducer and activator of transcription 5 (STAT5) protein, STAT5a and STAT5b, have 94% sequence identity, they are encoded by different genes. Previous studies have been unable to define clearly the roles of the STAT5 genes in colorectal cancer (CRC). To investigate the role of STAT5 isoforms in CRC oncogenesis, immunohistochemical staining was performed. Colorectal adenocarcinomas showed higher expression of STAT5a/5b than normal colonic mucosa (P < 0.05), and STAT5b expression was significantly higher than that of STAT5a in colorectal adenocarcinoma tissue (P < 0.05). Furthermore, STAT5b expression was significantly associated with TNM stage. To delineate the roles of STAT5a/5b in CRC carcinogenesis, we studied CRC cells depleted of each isoform by treating the cells with small interfering RNA. Both STAT5a and STAT5b were found to be involved in cell growth, cell cycle progression, and apoptosis of CRC cells, and exerted their effects via the regulation of downstream targets of the STAT genes. However, STAT5b influenced CRC cell apoptosis more than STAT5a (P < 0.05), reducing mitochondrial membrane potential and generating reactive oxygen species. In conclusion, both isoforms of STAT5 are involved in the growth and cell cycle progression of CRC cells, STAT5b could play a more important role than STAT5a in the clinicopathological characteristics of CRC and CRC cell apoptosis. J. Cell. Physiol. 227: 2421–2429, 2012. © 2011 Wiley Periodicals, Inc.